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{
"abstract": "BACKGROUND\nLupus nephritis (LN) has a considerable impact on the morbidity and mortality of systemic lupus erythematosus (SLE) patients. Long-term comparative outcome data from the Indian subcontinent on treatment regimens with cyclophosphamide (CYP) and mycophenolate mofetil (MMF) are sparse. We assessed renal and patient survival for these patients in terms of the types of induction - CYP or MMF - and the two maintenance therapies - MMF or azathioprine (AZA).\n\n\nMETHODS\nWe retrospectively analysed outcomes of 100 LN patients, 67 treated with CYP (26 class III, 25 class IV, 6 class III + V and 10 class IV + V; 40 Euro lupus regimen and 27 National Institutes of Health regimen) and 33 treated with a MMF-based regimen with steroids between July 2008 and June 2018. Data regarding demographic, clinical and histopathological features and the treatment given to all patients were extracted. Outcomes between the two regimens CYP and MMF were compared in terms of remission, dialysis and patient survival.\n\n\nRESULTS\nThe clinical characteristics were similar in both groups, except that the activity index was higher in CYP patients (6.13 ± 4.48 vs. 4.61 ± 2.80). However, the chronicity index was similar. The overall remission rate was 70% at the end of induction. The rates of complete remission, partial remission and non-responders in the CYP group were 46.2%, 23.9% and 29.9%, respectively. However, in the MMF group, the corresponding rates were 57.6%, 12.1% and 30.3%, respectively. The 1-, 2-, 3-, 4-, 5- and 10-year patient survival rates in the CYP group were 89.5%, 86.2%, 86.2%, 83.8%, 83.8% and 83.8%, respectively. In the MMF induction group, the corresponding rates were 93.9%, 93.9%, 89%, 89%, 89% and 89%, respectively. At the end of the study, rates of end-stage renal disease in the MMF group and CYP group were 7.5% and 12.1%, respectively. The death-censored and non-censored renal survival rates were also similar in the long term. With regard to maintenance therapy, 3/56 (5.3%) in the MMF group and 7/34 (20.5%) in the AZA group experienced doubling of serum creatinine (p = 0.03).\n\n\nCONCLUSIONS\nLong-term outcomes in terms of patient and renal survival of LN patients treated with CYP and MMF induction are similar. Doubling of serum creatinine occurred more with AZA-based maintenance therapy than with MMF-based maintenance therapy. Most deaths occurred during induction, and sepsis was the most common cause of death.",
"affiliations": "Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Pathology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.;Department of Nephrology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.",
"authors": "Prasad|Narayan|N|https://orcid.org/0000-0001-9801-0474;Kurian|Jithu|J|;Agarwal|Vikas|V|;Bhadauria|Dharmendra|D|;Behera|Manas|M|;Yacha|Monika|M|;Kushwaha|Ravi|R|;Agrawal|Vinita|V|;Jain|Manoj|M|;Gupta|Amit|A|",
"chemical_list": "D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid; D001379:Azathioprine; D011241:Prednisone",
"country": "England",
"delete": false,
"doi": "10.1177/0961203320926256",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0961-2033",
"issue": "29(8)",
"journal": "Lupus",
"keywords": "Systemic lupus erythematosus; lupus nephritis; outcomes; patient survival; renal survival",
"medline_ta": "Lupus",
"mesh_terms": "D000328:Adult; D001379:Azathioprine; D003520:Cyclophosphamide; D018572:Disease-Free Survival; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D007194:India; D007262:Infusions, Intravenous; D007668:Kidney; D007676:Kidney Failure, Chronic; D008181:Lupus Nephritis; D060046:Maintenance Chemotherapy; D008297:Male; D009173:Mycophenolic Acid; D011241:Prednisone; D012074:Remission Induction; D012189:Retrospective Studies; D055815:Young Adult",
"nlm_unique_id": "9204265",
"other_id": null,
"pages": "845-853",
"pmc": null,
"pmid": "32437258",
"pubdate": "2020-07",
"publication_types": "D003160:Comparative Study; D016428:Journal Article",
"references": null,
"title": "Long-term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil.",
"title_normalized": "long term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil"
} | [
{
"companynumb": "NVSC2020IN151467",
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},
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}
],
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"reaction": [
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"reactionmeddrapt": "Osteonecrosis",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Product use in unapproved indication",
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}
],
"summary": null
},
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"literaturereference": "PRASAD N, KURIAN J, AGARWAL V, BHADAURIA D, BEHERA M, YACHA M ET AL.. LONG-TERM OUTCOMES OF LUPUS NEPHRITIS TREATED WITH REGIMENS BASED ON CYCLOPHOSPHAMIDE AND MYCOPHENOLATE MOFETIL. LUPUS. 2020?1-9",
"literaturereference_normalized": "long term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil",
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},
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"receivedate": "20200603",
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},
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"reaction": [
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "23.0",
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},
{
"reactionmeddrapt": "Pancreatitis",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PRASAD N, KURIAN J, AGARWAL V, BHADAURIA D, BEHERA M, YACHA M ET AL.. LONG-TERM OUTCOMES OF LUPUS NEPHRITIS TREATED WITH REGIMENS BASED ON CYCLOPHOSPHAMIDE AND MYCOPHENOLATE MOFETIL. LUPUS. 2020?1-9",
"literaturereference_normalized": "long term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil",
"qualification": "3",
"reportercountry": "IN"
},
"primarysourcecountry": "IN",
"receiptdate": "20200602",
"receivedate": "20200602",
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},
{
"companynumb": "NVSC2020IN151462",
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{
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},
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"drugindication": "LUPUS NEPHRITIS",
"drugintervaldosagedefinition": "804",
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"medicinalproduct": "MYCOPHENOLATE MOFETIL."
}
],
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"reaction": [
{
"reactionmeddrapt": "End stage renal disease",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PRASAD N, KURIAN J, AGARWAL V, BHADAURIA D, BEHERA M, YACHA M ET AL.. LONG-TERM OUTCOMES OF LUPUS NEPHRITIS TREATED WITH REGIMENS BASED ON CYCLOPHOSPHAMIDE AND MYCOPHENOLATE MOFETIL. LUPUS. 2020?1-9",
"literaturereference_normalized": "long term outcomes of lupus nephritis treated with regimens based on cyclophosphamide and mycophenolate mofetil",
"qualification": "3",
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},
"primarysourcecountry": "JP",
"receiptdate": "20200602",
"receivedate": "20200602",
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},
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"transmissiondate": "20200714"
}
] |
{
"abstract": "A 48-year-old woman was diagnosed with idiopathic pulmonary arterial hypertension (PAH) and administered PAH-specific therapies, including bosentan. Four years after the initiation of treatment with bosentan, liver dysfunction appeared, and ambrisentan was substituted for bosentan. One-and-a half years later, a second episode of liver dysfunction occurred. The pathological findings of a liver biopsy specimen were not definitive, although drug-induced hepatotoxicity caused by ambrisentan was considered. However, the patient's liver dysfunction did not improve even after the discontinuation of ambrisentan. Finally, we diagnosed her with autoimmune hepatitis (AIH). Providing careful observation with a suspicion of AIH is important when treating PAH patients with autoantibodies.",
"affiliations": "Department of Respirology, Graduate School of Medicine, Chiba University, Japan.",
"authors": "Naito|Akira|A|;Terada|Jiro|J|;Tanabe|Nobuhiro|N|;Sugiura|Toshihiko|T|;Sakao|Seiichiro|S|;Kanda|Tatsuo|T|;Yokosuka|Osamu|O|;Tatsumi|Koichiro|K|",
"chemical_list": "D065128:Endothelin Receptor Antagonists; D010666:Phenylpropionates; D011724:Pyridazines; D013449:Sulfonamides; C467894:ambrisentan; D000077300:Bosentan",
"country": "Japan",
"delete": false,
"doi": "10.2169/internalmedicine.53.1362",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0918-2918",
"issue": "53(7)",
"journal": "Internal medicine (Tokyo, Japan)",
"keywords": null,
"medline_ta": "Intern Med",
"mesh_terms": "D001706:Biopsy; D000077300:Bosentan; D003937:Diagnosis, Differential; D004359:Drug Therapy, Combination; D065128:Endothelin Receptor Antagonists; D065627:Familial Primary Pulmonary Hypertension; D005260:Female; D005500:Follow-Up Studies; D019693:Hepatitis, Autoimmune; D006801:Humans; D008875:Middle Aged; D010666:Phenylpropionates; D011724:Pyridazines; D013449:Sulfonamides; D014057:Tomography, X-Ray Computed; D018616:Ultrasonography, Doppler, Duplex",
"nlm_unique_id": "9204241",
"other_id": null,
"pages": "771-5",
"pmc": null,
"pmid": "24694495",
"pubdate": "2014",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Autoimmune hepatitis in a patient with pulmonary arterial hypertension treated with endothelin receptor antagonists.",
"title_normalized": "autoimmune hepatitis in a patient with pulmonary arterial hypertension treated with endothelin receptor antagonists"
} | [
{
"companynumb": "JP-PFIZER INC-2018487111",
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{
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],
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"reaction": [
{
"reactionmeddrapt": "Syncope",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hepatic function abnormal",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "NAITO, A.. AUTOIMMUNE HEPATITIS IN A PATIENT WITH PULMONARY ARTERIAL HYPERTENSION TREATED WITH ENDOTHELIN RECEPTOR ANTAGONISTS. INTERNAL MEDICINE. 2014?53 (7):771-775",
"literaturereference_normalized": "autoimmune hepatitis in a patient with pulmonary arterial hypertension treated with endothelin receptor antagonists",
"qualification": "3",
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},
"primarysourcecountry": "JP",
"receiptdate": "20181207",
"receivedate": "20181207",
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"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190205"
}
] |
{
"abstract": "The therapeutic approach for relapsed/refractory acute lymphoblastic leukemia (ALL) remains to be a challenge. The patient was diagnosed as B-cell ALL at 6 months of age and relapsed for the second time following repeat allogeneic hematopoietic stem cell transplantation (one after first complete remission [CR1] and the other after CR2). During blinatumomab monotherapy, he developed an extramedullary relapse. Finally, the combined therapy with clofarabine, donor lymphocyte infusion, and blinatumomab induced CR of the bone marrow and extramedullary relapse. Unfortunately, the patient developed central nervous system relapse, however, this case showed a promising potential for combination therapy with clofarabine, donor lymphocyte infusion, and blinatumomab in relapsed/refractory B-cell ALL.",
"affiliations": "Department of Pediatrics, Seoul National University College of Medicine.;Department of Pediatrics, Seoul National University College of Medicine.;Department of Pediatrics, Seoul National University College of Medicine.;Department of Pediatrics, Seoul National University College of Medicine.;Department of Pediatrics, Seoul National University College of Medicine.;Department of Pediatrics, Seoul National University College of Medicine.;Department of Pediatrics, Seoul National University College of Medicine.",
"authors": "Choi|Ho Jung|HJ|;Choi|Jung Yoon|JY|;Kim|Bo Kyung|BK|;An|Hong Yul|HY|;Hong|Kyung Taek|KT|;Shin|Hee Young|HY|;Kang|Hyoung Jin|HJ|",
"chemical_list": "D018033:Antibodies, Bispecific; D003561:Cytarabine; C510808:blinatumomab; D005047:Etoposide; D000077866:Clofarabine; D003520:Cyclophosphamide",
"country": "United States",
"delete": false,
"doi": "10.1097/MPH.0000000000001789",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1077-4114",
"issue": "43(2)",
"journal": "Journal of pediatric hematology/oncology",
"keywords": null,
"medline_ta": "J Pediatr Hematol Oncol",
"mesh_terms": "D018033:Antibodies, Bispecific; D000971:Antineoplastic Combined Chemotherapy Protocols; D001782:Blood Donors; D000077866:Clofarabine; D003131:Combined Modality Therapy; D003520:Cyclophosphamide; D003561:Cytarabine; D019008:Drug Resistance, Neoplasm; D005047:Etoposide; D006801:Humans; D007223:Infant; D017710:Lymphocyte Transfusion; D008297:Male; D009364:Neoplasm Recurrence, Local; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma; D011379:Prognosis; D012189:Retrospective Studies",
"nlm_unique_id": "9505928",
"other_id": null,
"pages": "e280-e283",
"pmc": null,
"pmid": "32251153",
"pubdate": "2021-03-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Combination Therapy With Chemotherapy, Donor Lymphocyte Infusion With Concurrent Blinatumomab in Relapsed/Refractory Acute Precursor B-Lymphoblastic Leukemia.",
"title_normalized": "combination therapy with chemotherapy donor lymphocyte infusion with concurrent blinatumomab in relapsed refractory acute precursor b lymphoblastic leukemia"
} | [
{
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},
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"drugindication": "PRECURSOR B-LYMPHOBLASTIC LYMPHOMA REFRACTORY",
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"activesubstancename": "FILGRASTIM"
},
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"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "UNK UNK, QD",
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"drugindication": "NEUTROPHIL COUNT ABNORMAL",
"drugintervaldosagedefinition": "804",
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"medicinalproduct": "FILGRASTIM"
},
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"actiondrug": null,
"activesubstance": {
"activesubstancename": "ETOPOSIDE"
},
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"medicinalproduct": "ETOPOSIDE."
},
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"activesubstancename": "CYTARABINE"
},
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"drugdosagetext": "50 MICROGRAM",
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"drugindication": "LEUKAEMIC INFILTRATION EXTRAMEDULLARY",
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"drugstructuredosageunit": "004",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "CYTARABINE."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CYCLOPHOSPHAMIDE"
},
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"drugcharacterization": "2",
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"drugdosagetext": "40 MILLIGRAM/SQ. METER, D0 TO D4",
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"drugstructuredosageunit": "009",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "CYCLOPHOSPHAMIDE."
},
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "BLINATUMOMAB"
},
"drugadditional": null,
"drugadministrationroute": "042",
"drugauthorizationnumb": "125557",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": "5 MICROGRAM/SQ. METER, QD, DAY 0 TO DAY 6",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "B PRECURSOR TYPE ACUTE LEUKAEMIA",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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"drugrecurrence": null,
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"drugstructuredosagenumb": "5",
"drugstructuredosageunit": "010",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "BLINCYTO"
}
],
"patientagegroup": "2",
"patientonsetage": "19",
"patientonsetageunit": "802",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Febrile neutropenia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Tonic convulsion",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Cytokine release syndrome",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Central nervous system leukaemia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "B precursor type acute leukaemia",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Acute graft versus host disease",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Leukaemic infiltration extramedullary",
"reactionmeddraversionpt": "23.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KANG H.J.? CHOI H.J.? CHOI J.Y. ET AL.. COMBINATION THERAPY WITH CHEMOTHERAPY, DONOR LYMPHOCYTE INFUSION WITH CONCURRENT BLINATUMOMAB IN RELAPSED/REFRACTORY ACUTE PRECURSOR B-LYMPHOBLASTIC LEUKEMIA. JOURNAL OF PEDIATRIC HEMATOLOGY/ONCOLOGY. 2020?1-4",
"literaturereference_normalized": "combination therapy with chemotherapy donor lymphocyte infusion with concurrent blinatumomab in relapsed refractory acute precursor b lymphoblastic leukemia",
"qualification": "1",
"reportercountry": "KR"
},
"primarysourcecountry": "KR",
"receiptdate": "20200430",
"receivedate": "20170605",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13611711,
"safetyreportversion": 6,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200713"
}
] |
{
"abstract": "BACKGROUND\nThis study quantified risks of cardiovascular, cerebrovascular, and mortality events among patients with migraine receiving prophylaxis.\n\n\nMETHODS\nPatients with migraine aged 18-65 years were identified from 2010 through 2015 within a United States administrative claims database. Topiramate initiators during follow-up were propensity score-matched separately to anticonvulsant, cardiovascular treatment, antidepressant, and other prophylactic treatment initiators. Incident outcomes were identified, and hazard ratios were calculated comparing outcome occurrence among topiramate initiators relative to each comparator. A case-control analysis was nested within the full migraine cohort, and odds ratios quantified the association between outcomes and use or non-use of individual prophylactic treatments (anticonvulsants, serotonin norepinephrine reuptake inhibitors, beta blockers, antihypertensives, tricyclic antidepressants, and other prophylactic treatments).\n\n\nRESULTS\nThe cohort included 119,243 patients with migraine. The matched topiramate initiators had a lower mortality risk versus antidepressant (hazard ratio: 0.44, 95% CI: 0.24, 0.83) and anticonvulsant initiators (hazard ratio: 0.45, 95% CI: 0.25, 0.84). In the case-control analysis, increased risks of several outcomes were observed with all prophylactic treatments relative to non-use of that treatment (odds ratios range from 1.54 to 7.90, and 95% CIs exclude 1.0) except for topiramate and calcium channel blockers.\n\n\nCONCLUSIONS\nAlthough increased risks for several outcomes were observed with certain prophylactic treatments, the treatments other than topiramate likely represent markers for outcome risk factors that developed or progressed after cohort entry, rather than being a direct effect of the treatments. Factors including migraine severity, frequency, and other treatment indications should be considered in future migraine prophylactic treatment safety assessments.",
"affiliations": "Optum Epidemiology, Ann Arbor, MI, US.;Amgen, Inc., Thousand Oaks, CA, US.;Optum Epidemiology, Boston, MA, US.;Amgen, Inc., Thousand Oaks, CA, US.;Optum Epidemiology, Ann Arbor, MI, US.;Amgen, Inc., Thousand Oaks, CA, US.;Institute of Public Health, Charité - Universitätsmedizin Berlin, Berlin, Germany.;Optum Epidemiology, Boston, MA, US.",
"authors": "Hoffman|Veena|V|https://orcid.org/0000-0003-4932-0892;Xue|Fei|F|;Ezzy|Stephen M|SM|;Yusuf|Akeem|A|;Green|Edward|E|;Eisele|Osa|O|;Kurth|Tobias|T|https://orcid.org/0000-0001-7169-2620;Seeger|John D|JD|",
"chemical_list": "D000700:Analgesics",
"country": "England",
"delete": false,
"doi": "10.1177/0333102419856630",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0333-1024",
"issue": "39(12)",
"journal": "Cephalalgia : an international journal of headache",
"keywords": "Migraine; cardiovascular events; cerebrovascular events; mortality; prophylactic treatment",
"medline_ta": "Cephalalgia",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D000700:Analgesics; D002318:Cardiovascular Diseases; D016022:Case-Control Studies; D002561:Cerebrovascular Disorders; D015331:Cohort Studies; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D008881:Migraine Disorders; D012307:Risk Factors; D055815:Young Adult",
"nlm_unique_id": "8200710",
"other_id": null,
"pages": "1544-1559",
"pmc": null,
"pmid": "31195804",
"pubdate": "2019-10",
"publication_types": "D016428:Journal Article; D064888:Observational Study",
"references": null,
"title": "Risk of cardiovascular and cerebrovascular events and mortality in patients with migraine receiving prophylactic treatments: An observational cohort study.",
"title_normalized": "risk of cardiovascular and cerebrovascular events and mortality in patients with migraine receiving prophylactic treatments an observational cohort study"
} | [
{
"companynumb": "US-JNJFOC-20170821522",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "TOPIRAMATE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "020505",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MIGRAINE PROPHYLAXIS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TOPIRAMATE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Ischaemic stroke",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Myocardial infarction",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Transient ischaemic attack",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Myocardial ischaemia",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Haemorrhagic stroke",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Angina unstable",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HOFFMAN V, XUE F, EZZY S, YUSU A, GREEN E, EISELE O, KURTH T, SEEGER J. RISK OF CARDIOVASCULAR AND CEREBROVASCULAR EVENTS AND MORTALITY IN PATIENTS WITH MIGRAINE RECEIVING PROPHYLACTIC TREATMENTS: AN OBSERVATIONAL COHORT STUDY. CEPHALALGIA. 2019 OCT?39(12):1544-1559.",
"literaturereference_normalized": "risk of cardiovascular and cerebrovascular events and mortality in patients with migraine receiving prophylactic treatments an observational cohort study",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20200103",
"receivedate": "20170831",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 13925409,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20200409"
}
] |
{
"abstract": "BACKGROUND\nParathyroidectomy is associated with renal functional losses in transplant patients; cinacalcet offers an attractive alternative.\n\n\nMETHODS\nWe performed a prospective observational study in 58 patients with persisting hyperparathyroidism after renal transplantation (Ca≥2.6 mmol/L) and impaired renal transplant function (estimated glomerular filtration rate [eGFR] <50 mL/min). The patients received 30 to 90 mg cinacalcet for 12 months with the target to normalize serum Ca. We measured parathyroid hormone (PTH), serum Ca, serum phosphorus, alkaline phosphatase, bone-specific alkaline phosphatase, osteocalcin, and telopeptide at 0, 1, 2, 3, 6, 9, and 12 months of cinacalcet treatment. Fractional excretion of calcium and phosphorus (n=24) were monitored at 0 and 1 month.\n\n\nRESULTS\nAt inclusion, creatinine was 181±70 μmol/L, eGFR 43±19 mL/min, PTH 371±279 pg/mL, and Ca 2.73±0.22 mmol/L. We observed nephrocalcinosis in 58% of biopsied patients at enrollment. After cinacalcet, Ca decreased significantly and normalized at nearly any measurement. Phosphorus increased significantly at months 1, 9, and 12. PTH decreased significantly, but only at months 9 and 12 and did not normalize. Bone-specific alkaline phosphatase increased significantly (>normal) by month 12. eGFR decreased and serum creatinine increased at all time points. The Δ(creatinine) % increase correlated significantly with the Δ(PTH) % decrease at month 1 and 12. Telopeptide and alkaline phosphatase correlated with PTH and telopeptide also correlated with serum creatinine.\n\n\nCONCLUSIONS\nCalcium-phosphorus homeostasis in hypercalcemic renal transplant patients normalizes under cinacalcet and PTH decreases, albeit not to normal. The renal functional decline could be PTH mediated, analogous to the effects observed after parathyroidectomy.",
"affiliations": "Department of Nephrology, Hannover Medical School, Carl-Neuberg Strasse 1, Hannover, Germany. [email protected]",
"authors": "Schwarz|Anke|A|;Merkel|Saskia|S|;Leitolf|Holger|H|;Haller|Hermann|H|",
"chemical_list": "D009281:Naphthalenes; D010281:Parathyroid Hormone; D010758:Phosphorus; D003404:Creatinine; D002118:Calcium; D000069449:Cinacalcet",
"country": "United States",
"delete": false,
"doi": "10.1097/TP.0b013e3182079431",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0041-1337",
"issue": "91(5)",
"journal": "Transplantation",
"keywords": null,
"medline_ta": "Transplantation",
"mesh_terms": "D000368:Aged; D001706:Biopsy; D001842:Bone and Bones; D002118:Calcium; D000069449:Cinacalcet; D003404:Creatinine; D005260:Female; D005919:Glomerular Filtration Rate; D006706:Homeostasis; D006801:Humans; D006961:Hyperparathyroidism; D007668:Kidney; D007676:Kidney Failure, Chronic; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D009281:Naphthalenes; D009397:Nephrocalcinosis; D010281:Parathyroid Hormone; D010758:Phosphorus; D011446:Prospective Studies",
"nlm_unique_id": "0132144",
"other_id": null,
"pages": "560-5",
"pmc": null,
"pmid": "21192318",
"pubdate": "2011-03-15",
"publication_types": "D016430:Clinical Trial; D016428:Journal Article",
"references": null,
"title": "The effect of cinacalcet on bone remodeling and renal function in transplant patients with persistent hyperparathyroidism.",
"title_normalized": "the effect of cinacalcet on bone remodeling and renal function in transplant patients with persistent hyperparathyroidism"
} | [
{
"companynumb": "DE-AMGEN-DEUSP2020018768",
"fulfillexpeditecriteria": "2",
"occurcountry": "DE",
"patient": {
"drug": [
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "SIROLIMUS"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "SIROLIMUS."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CINACALCET HYDROCHLORIDE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "021688",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "UNKNOWN FORMULATION",
"drugdosagetext": "30-90 MILLIGRAM, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HYPERPARATHYROIDISM",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "CINACALCET HCL"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "MYCOPHENOLATE MOFETIL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
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"drugcharacterization": "2",
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "MYCOPHENOLATE MOFETIL."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "CYCLOSPORINE"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
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{
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{
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{
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{
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{
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{
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],
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},
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] |
{
"abstract": "Instituting drug holidays for chronic opioid using patients is becoming commonplace for pain practitioners initiating procedures such as intrathecal pump or spinal cord stimulator trials. As such, pain practitioners need to be adept in their management of acute opioid withdrawal. Successfully weaning an opioid dependent patient off of chronic opioids requires a thorough knowledge of the available adjuvants to assist in this process. However, that selection can become exhausted by adjuvant side effects or by ineffective attenuation of opioid withdrawal symptoms. In that case, novel drugs, or novel application of currently available medications must be sought after to assist in the drug holiday. We present a case in which refractory muscle spasms secondary to opioid withdrawal were successfully treated with an over-the-counter supplement that is not typically used for the attenuation of opioid withdrawal symptoms. In a patient intolerant to the side effects of clonidine, we were able to successfully wean chronic opiates by treating refractory muscle spasms with the serotonin precursor, 5-hydroxytryptophan (5-HTP). We hypothesize that our success with this medication gives further credence to the role of serotonin in opioid withdrawal somatic symptomatology, and supports the need for future research to clarify the role of serotonin precursors or serotonin modulating drugs as potential alternatives in those unable to follow standard treatment protocols.",
"affiliations": "The University of Texas Health Science Center at Houston Houston, TX; 2The University of Texas Medical Branch at Galveston, Galveston, TX.",
"authors": "Dais|Jennifer|J|;Khosia|Ankur|A|;Doulatram|Gulshan|G|",
"chemical_list": "D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D006916:5-Hydroxytryptophan; D003000:Clonidine",
"country": "United States",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1533-3159",
"issue": "18(3)",
"journal": "Pain physician",
"keywords": null,
"medline_ta": "Pain Physician",
"mesh_terms": "D006916:5-Hydroxytryptophan; D000316:Adrenergic alpha-Agonists; D000701:Analgesics, Opioid; D001416:Back Pain; D003000:Clonidine; D005260:Female; D006801:Humans; D007278:Injections, Spinal; D008875:Middle Aged; D007319:Sleep Initiation and Maintenance Disorders; D013035:Spasm; D013375:Substance Withdrawal Syndrome; D016896:Treatment Outcome",
"nlm_unique_id": "100954394",
"other_id": null,
"pages": "E417-20",
"pmc": null,
"pmid": "26000689",
"pubdate": "2015",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "The Successful Treatment of Opioid Withdrawal-Induced Refractory Muscle Spasms with 5-HTP in a Patient Intolerant to Clonidine.",
"title_normalized": "the successful treatment of opioid withdrawal induced refractory muscle spasms with 5 htp in a patient intolerant to clonidine"
} | [
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"medicinalproduct": "CLONAZEPAM."
}
],
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},
{
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},
{
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}
],
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},
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},
"serious": 1,
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"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20171127"
}
] |
{
"abstract": "Altered biodistribution can be a source of diagnostic error in the interpretation of nuclear medicine studies. This case reports an instance of increased liver and spleen uptake with 99mTc-dimercaptosuccinic acid believed to be a result of chlorhexidine-mediated colloid labeling. This finding underscores the principle that certain constituents of antiseptics may adversely affect the purity of radiopharmaceuticals during their preparation.",
"affiliations": "Department of Radiology, Medical University of South Carolina, Charleston, South Carolina.;Department of Radiology, Medical University of South Carolina, Charleston, South Carolina.;Department of Radiology, Medical University of South Carolina, Charleston, South Carolina [email protected].",
"authors": "Krull|Veronica|V|;Kocher|Madison R|MR|;Rieter|William J|WJ|",
"chemical_list": "D000891:Anti-Infective Agents, Local; D003102:Colloids; D019275:Radiopharmaceuticals; D019783:Technetium Tc 99m Dimercaptosuccinic Acid",
"country": "United States",
"delete": false,
"doi": "10.2967/jnmt.120.258020",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0091-4916",
"issue": "49(3)",
"journal": "Journal of nuclear medicine technology",
"keywords": "99mTc-DMSA; antiseptic; chlorhexidine; colloid; liver-spleen",
"medline_ta": "J Nucl Med Technol",
"mesh_terms": "D000891:Anti-Infective Agents, Local; D003102:Colloids; D008099:Liver; D019275:Radiopharmaceuticals; D013154:Spleen; D019783:Technetium Tc 99m Dimercaptosuccinic Acid; D014018:Tissue Distribution",
"nlm_unique_id": "0430303",
"other_id": null,
"pages": "290-291",
"pmc": null,
"pmid": "33722920",
"pubdate": "2021-09",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Antiseptic-Mediated Colloid Labeling as a Potential Source of Abnormal Liver and Spleen Uptake with 99mTc-Dimercaptosuccinic Acid.",
"title_normalized": "antiseptic mediated colloid labeling as a potential source of abnormal liver and spleen uptake with 99mtc dimercaptosuccinic acid"
} | [
{
"companynumb": "US-GE HEALTHCARE LIFE SCIENCES-2021CSU001561",
"fulfillexpeditecriteria": "2",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "SUCCIMER"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "017944",
"drugbatchnumb": "NOT REPORTED",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "KIT FOR RADIOPHARMACEUTICAL PREPARATION",
"drugdosagetext": "UNK, SINGLE",
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"drugindication": "RADIOISOTOPE SCAN",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "DMSA"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CHLORHEXIDINE"
},
"drugadditional": "3",
"drugadministrationroute": "050",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "TO STERILIZE THE RUBBER STOPPER ON THE DMSA VIAL",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "INFECTION PROPHYLAXIS",
"drugintervaldosagedefinition": null,
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"medicinalproduct": "CHLORHEXIDINE"
},
{
"actiondrug": "6",
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"activesubstancename": "SUCCIMER"
},
"drugadditional": null,
"drugadministrationroute": null,
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"drugbatchnumb": null,
"drugcharacterization": "1",
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"drugcumulativedosageunit": null,
"drugdosageform": "KIT FOR RADIOPHARMACEUTICAL PREPARATION",
"drugdosagetext": null,
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"drugenddateformat": null,
"drugindication": "KIDNEY SMALL",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "DMSA"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "TECHNETIUM TC-99M"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
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"medicinalproduct": "TECHNETIUM TC 99M"
},
{
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"activesubstance": {
"activesubstancename": "POLYETHYLENE GLYCOL 3350"
},
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"drugadministrationroute": null,
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"drugbatchnumb": null,
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
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"drugdosagetext": "UNK, PRN",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "GLYCOLAX"
}
],
"patientagegroup": null,
"patientonsetage": "13",
"patientonsetageunit": "801",
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Radioisotope scan abnormal",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Product contamination",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "No adverse event",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KRULL V, KOCHER MR AND RIETER WJ. ANTISEPTIC?MEDIATED COLLOID LABELING AS A POTENTIAL SOURCE OF ABNORMAL LIVER AND SPLEEN UPTAKE WITH 99MTC?DIMERCAPTOSUCCINIC ACID.. J OF NUCLEAR MEDICINE TECHNOLOGY. 2021",
"literaturereference_normalized": "antiseptic mediated colloid labeling as a potential source of abnormal liver and spleen uptake with 99mtc dimercaptosuccinic acid",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210623",
"receivedate": "20210623",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19454384,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 2,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20210717"
}
] |
{
"abstract": "Melanoma can be classified based on the detection of relevant oncogenic driver mutations. These mutations partially determine a patient's treatment options. MEK inhibitors have demonstrated little efficacy in patients with NRAS-mutated melanoma owing to primary and secondary resistance. We report two patients with NRAS-mutant metastatic melanoma with long-term response to intermittent MEK-inhibitor binimetinib therapy. Intermittent dosing schedules could play a key role in preventing resistance to targeted therapy. This article highlights the efficacy of an intermittent dosing schedule, toxicities associated with binimetinib, and possible mechanisms preventing resistance in targeted therapy. Intermittent MEK-inhibitor therapy may be considered in patients with NRAS-mutated melanoma that have failed all standard therapies. KEY POINTS: Melanomas harbor NRAS mutations in 10%-30% of the cases. These mutations promote hyperactivation of the MAPK pathway, leading to proliferation and prolonged survival of tumor cells. Currently, drugs directly targeting NRAS are not available. Downstream inhibition of the MAPK pathway can be considered as a therapeutic option after immunotherapeutic failure. Intermittent administration of kinase inhibitors might be the way to partially overcome the development of drug resistance by (a) inducing a fitness deficit for drug-resistant cells on treatment break, (b) increasing the immunogenicity, and (c) inducing apoptosis and cell cycle arrest. It also enhances expression of numerous immunomodulating molecules, and reduction of immunosuppressive factors, which suggests better access of the immune system to the tumor.",
"affiliations": "Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.;Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.;Department of Private Ophthalmic Practice in Cooperation with the Skin Cancer Unit, University Hospital of Zurich, Zurich, Switzerland.;Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.;Department of Dermatology, University Hospital of Zurich, Zurich, Switzerland.",
"authors": "Matter|Alexandra Valeska|AV|;Micaletto|Sara|S|;Urner-Bloch|Ursula|U|;Dummer|Reinhard|R|;Goldinger|Simone M|SM|0000-0002-7995-7301",
"chemical_list": "D001562:Benzimidazoles; D008565:Membrane Proteins; D047428:Protein Kinase Inhibitors; C581313:binimetinib; D048493:Proto-Oncogene Proteins B-raf; D020558:GTP Phosphohydrolases; C579846:NRAS protein, human",
"country": "United States",
"delete": false,
"doi": "10.1634/theoncologist.2019-0656",
"fulltext": "\n==== Front\nOncologist\nOncologist\n10.1002/(ISSN)1549-490X\nONCO\ntheoncologist\nThe Oncologist\n1083-7159 1549-490X John Wiley & Sons, Inc. Hoboken, USA \n\n32886824\n10.1634/theoncologist.2019-0656\nONCO13512\n17\n29\nPrecision Medicine Clinic: Molecular Tumor Board\nPrecision Medicine Clinic: Molecular Tumor Board\n\nLong‐Term Response to Intermittent Binimetinib in Patients with NRAS‐Mutant Melanoma\nIntermittent MEK Inhibitors in NRAS MelanomaMatter, Micaletto, Urner‐Bloch et al.Matter Alexandra Valeska \n1\n Micaletto Sara \n1\n Urner‐Bloch Ursula \n2\n Dummer Reinhard \n1\n\n3\n\n†\[email protected] Goldinger Simone M. https://orcid.org/0000-0002-7995-7301\n1\n\n3\n\n†\n \n1 \nDepartment of Dermatology, University Hospital of Zurich\nZurich\nSwitzerland\n\n\n2 \nDepartment of Private Ophthalmic Practice in Cooperation with the Skin Cancer Unit, University Hospital of Zurich\nZurich\nSwitzerland\n\n\n3 \nFaculty of Medicine, University of Zurich\nZurich\nSwitzerland\n\n* \nCorrespondence: Reinhard Dummer, M.D., Department of Dermatology, University Hospital of Zurich, Gloriastrasse 31, 8091 Zürich, Switzerland. Telephone: 41 (44) 255 2507; e‐mail: [email protected]\n† Contributed equally\n\n\n21 9 2020 \n11 2020 \n25 11 10.1002/onco.v25.11e1593 e1597\n10 11 2019 18 8 2020 © 2020 The Authors. The Oncologist published by Wiley Periodicals LLC on behalf of AlphaMed Press.This is an open access article under the terms of the http://creativecommons.org/licenses/by-nc-nd/4.0/ License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.Abstract\nMelanoma can be classified based on the detection of relevant oncogenic driver mutations. These mutations partially determine a patient's treatment options. MEK inhibitors have demonstrated little efficacy in patients with NRAS‐mutated melanoma owing to primary and secondary resistance. We report two patients with NRAS‐mutant metastatic melanoma with long‐term response to intermittent MEK‐inhibitor binimetinib therapy. Intermittent dosing schedules could play a key role in preventing resistance to targeted therapy. This article highlights the efficacy of an intermittent dosing schedule, toxicities associated with binimetinib, and possible mechanisms preventing resistance in targeted therapy. Intermittent MEK‐inhibitor therapy may be considered in patients with NRAS‐mutated melanoma that have failed all standard therapies.\n\nKey Points\n\nMelanomas harbor NRAS mutations in 10%–30% of the cases. These mutations promote hyperactivation of the MAPK pathway, leading to proliferation and prolonged survival of tumor cells.\n\nCurrently, drugs directly targeting NRAS are not available. Downstream inhibition of the MAPK pathway can be considered as a therapeutic option after immunotherapeutic failure.\n\nIntermittent administration of kinase inhibitors might be the way to partially overcome the development of drug resistance by (a) inducing a fitness deficit for drug‐resistant cells on treatment break, (b) increasing the immunogenicity, and (c) inducing apoptosis and cell cycle arrest. It also enhances expression of numerous immunomodulating molecules, and reduction of immunosuppressive factors, which suggests better access of the immune system to the tumor.\n\n\n\n\nCase reports for two patients with NRAS‐mutant metastatic melanoma are presented, highlighting toxicities associated with binimetinib, as well as the efficacy of an intermittent dosing schedule and possible mechanisms preventing resistance in targeted therapy.\n\n source-schema-version-number2.0cover-dateNovember 2020details-of-publishers-convertorConverter:WILEY_ML3GV2_TO_JATSPMC version:5.9.3 mode:remove_FC converted:07.11.2020\nDisclosures of potential conflicts of interest may be found at the end of this article.\n==== Body\nPatient Stories\nPatient 1\nA 71‐year‐old female presented with multiple subcutaneous in‐transit metastases on the shin after resection of a melanoma on her right lower leg (Breslow 1.1 mm). Her sentinel lymph nodes were negative. Several surgical procedures were performed because of local relapses. The mutational analysis of an in‐transit metastasis by polymerase chain reaction (PCR) and sequencing analysis detected a NRAS mutation (p.Q61R in Exon 3). Despite treatment with anti–cytotoxic T‐lymphocyte–associated protein 4 (CTLA‐4) antibodies (ipilimumab 200 mg intravenously, four infusions), the disease progressed (locoregional lymph node involvement and in‐transit soft tissue metastasis up to 4.5 cm in size). As anti–programmed cell death protein 1 (PD‐1) blockade was not available at the time, the patient was enrolled in a clinical trial investigating binimetinib (45‐mg tablets p.o. b.i.d.; NCT01763164) in March 2015. Binimetinib was stopped after 6 weeks of treatment owing to myalgia and severe creatine phosphokinase (CPK) elevation grade (G) 3. The patient also developed acneiform dermatitis G2, bilateral retinopathy G1, and eye pressure elevation G2. All adverse events (AEs) resolved when binimetinib was withheld. On resumption of binimetinib, the same AEs recurred after 3–6 weeks. Consequently, a dose reduction (30 mg b.i.d.) and intermittent treatment (3 weeks on and 10 days off) schedule was trialed. On this regimen, CPK elevation fluctuated between G1 and G3. The acneiform dermatitis peaked to G2 at the end of each treatment phase but settled between dosing. Both retinopathy and elevated eye pressure were never symptomatic but present on ophthalmic review. A combination of a beta‐blocker and a carbonic anhydrase inhibitor (cosopt eye drops) led to improvement of the eye pressure. The patient did not experience myalgia.\n\nPatient 2\nA 75‐year‐old male presented with a melanoma (Breslow 0.95 mm) on the trunk. He developed right axillary lymph node metastasis developed right lymph node metastasis axillary in December 2013. Mutational analysis by PCR and sequencing revealed a NRAS mutation (p.Q61K in Exon 3). Within 6 months, the patient developed hilar lymph node metastasis of 3.4 cm, lung and soft tissue metastases (stage IV disease) (Figure 1). In July 2014, binimetinib (45‐mg tablets b.i.d.) was started (NCT01763164). Immunotherapy was kept as salvage therapy. Four weeks into therapy, treatment had to be suspended because of CPK elevation G4. The patient experienced facial acneiform dermatitis G2 and retinopathy G1, but no myalgias. A 2‐weeks‐on and 1‐week‐off schedule with reduced dose (30 mg b.i.d.) was commenced. With this regimen, CPK elevation was between G1 and G3, acneiform dermatitis between G1 and G2, and the retinopathy between G0 and G1. Within the first year of treatment, the tumor burden continuously decreased with overall partial response. By April 2017, all lesions had disappeared or shrunk to a maximum of 5 mm and remained stable. In August 2018, binimetinib was ceased owing to right central retinal vein thrombosis. The visual disturbance improved and eventually returned to normal with two intravitreal anti–vascular endothelial growth factor injections and eye pressure–reducing drops (dorzolamide and timolol).\n\nFigure 1 Representative transverse chest computed tomography sections of Patient 2. Left hilar metastasis measuring 3.4 × 2.6 cm at baseline (A) showing complete remission under intermittent therapy with binimetinib (B). Mediastinal metastasis of 1.5 × 1 cm adjacent to the esophagus (C) was not detectable at the end of therapy in August 2018 (D).\n\nMolecular Tumor Board\nMelanoma and Tumor Biology\nDevelopment of melanoma can be triggered by activating oncogenes or inactivating tumor‐suppressor genes through specific mutations. Some of the most important signaling pathways involved in the pathogenesis of melanoma include MAPK, PI3K/PTEN/AKT, and MITF [1].\n\nCutaneous melanomas can be divided into four genomic subtypes: BRAF, RAS, NF1, and triple‐WT melanomas [2].\n\nIn The Cancer Genome Atlas (TCGA), NRAS somatic mutations were present in 28% of the analyzed samples [2]. NRAS and BRAF mutations are thought to be often mutually exclusive. However, the presence of both mutations in one cell line was proved [3]. Either of them is sufficient to promote hyperactivation of the MAPK pathway, leading to proliferation and prolonged survival of tumor cells.\n\nGenotyping Results and Interpretation of the Molecular Results\nIn the presented cases, NRAS mutations (p.Q61K in Exon 3 and p.Q61R in Exon 3) were detected by both PCR and sequencing. BRAF mutation was not present.\n\nThe most common NRAS mutation in melanoma (occurring in more than 80% of NRAS‐mutated samples) is a substitution of glutamine with arginine or lysine at position p.61 (NRASQ61R/K/L) as a result of the c.181C > A transversion (38%) of the c.182A > G transition (34%) or of the c.182A > T transversion (10%) in exon 3 of the gene, respectively [4]. Codon 61 mutations are associated with locking of the RAS protein into its activating conformation and impaired GTPase activity [5], leading to activated RAS signaling (MAPK pathway) with consecutive cell growth, motility, and survival, thereby enhancing tumor growth [6]. NRAS mutation not only activates the MAPK pathway, but can also trigger activation of the phosphatidylinositol 3‐kinase/protein kinase B (PI3K/AKT) pathway and other survival signaling pathways [7].\n\nFunctional and Clinical Significance of NRAS Mutation in Melanoma\n\nNRAS mutation is considered the second most common oncogenic driver mutation in melanoma. Compared with BRAF‐mutated or WT NRAS melanoma, there are conflicting data regarding the importance of NRAS mutations in outcomes to new therapies, particularly checkpoint inhibitors.\n\nPotential Strategies to Target the Pathway and Implications for Clinical Practice\nCurrently, there are no drugs that target NRAS. Downstream inhibition of the MAPK pathway can be considered as a therapeutic option after immunotherapeutic failure.\n\nBinimetinib, a selective inhibitor of mitogen‐activated protein kinase (MEK1 and 2), demonstrated some benefit in patients with NRAS‐mutated melanoma (median progression‐free survival [PFS] 3.7 months, 95% confidence interval [CI] 2.5–5.4) [8]. In the pivotal trial comparing dacarbazine and binimetinib, median PFS for patients with MEK inhibitor–treated NRAS‐mutant melanoma was 2.8 months (95% CI 2.8–3.6) versus 1.5 months (95% CI 1.5–1.7) in the dacarbazine group [9]. Unfortunately, most patients develop resistance within the first year [10].\n\nCommon AEs of MEK inhibitors include diarrhea (G1–2 39%, G3–4 1%), acneiform dermatitis (G1–2 33%, G3–4 3%), increased CPK (G1–2 23%, G3–4 19%), and various ocular events such as retinal pigment epithelial detachment (retinopathy; G1–2 32%, G3–4 1%) and retinal vein occlusion (G1–4 2%) [9].\n\nIn view of the modest outcomes and the AEs, MEK inhibitors are not routinely used for NRAS‐mutant melanomas.\n\nDespite low clinical efficacy, we report two cases of long‐term response to binimetinib treated with an intermittent dosing schedule. Intermittent dosing was well tolerated and toxicity was manageable. Yaeger et al. also reported long‐term response to intermittent MEK‐inhibitor treatment in a patient with melanoma with RAF1 mutation [11].\n\n\nIntermittent MEK Inhibition as a Possible Mechanism Preventing Resistance\n\nMost tyrosine kinase–resistant tumor cells remain dependent on MAPK pathway signaling and rely on ERK (extracellular signal‐regulated kinase) reactivation [12, 13]. Although reliant on oncogenes (MAPK pathway and ERK signaling), resistant tumor cells experience a fitness deficit in the absence of the drug. They can induce apoptosis and cell cycle arrest [13]. This is observed with both inhibition and hyperactivation of the MAPK pathway leading to an excessive MEK–ERK signaling [14]. It seems that melanoma cells require a specific level of activated ERK for optimal tumor growth. Drug‐resistant tumor cells have a selective disadvantage in the absence of the drug, leading to regrowth of drug‐sensitive tumor cells during drug holiday [15]. Moreover, MITF (microphthalmia‐associated transcription factor), an important regulator of melanoma cell proliferation and survival, is strongly linked to the MAPK pathway. In MEK inhibitor–resistant melanoma cells, MITF expression can be highly upregulated, whereas strong activation of MAPK signaling will reduce MITF protein levels through degradation [16].\n\nWe propose that the dosing interval during intermittent therapy targets drug‐sensitive tumor cells and the off interval drives drug‐resistant tumor cells into cell cycle arrest and apoptosis.\n\nDifferent data support the strategy of intermittent dosing for MEK‐inhibitor therapy. First, MEK inhibitors lead to an initial increase of HLA‐1 and HLA‐2, enhanced expression of numerous immunomodulating molecules, and reduction of immunosuppressive factors such as IL1A, IL8, programmed death‐ligand 1 (PD‐L1), and others [17]. Higher immunogenicity at the beginning of treatment would suggest more efficient antitumor response. Second, after a longer exposure to MEK inhibitor, melanoma cells can switch phenotype into more invasive cell behavior. Zipser et al. demonstrated a phenotype switch in MITF‐expressing tumor cells with an activated MAPK pathway after 2 weeks of treatment. This was characterized by a change in morphology, increased invasiveness, and a decline in expression of melanocytic differentiation antigens. [18] Third, Deken et al. reported a high influx of T cells within the first week and lesser presence of T cells later on in a mouse model treated with kinase inhibitors [19]. An enrichment of tumor‐infiltrating, antigen‐specific CD8+ effector T cells in the MEK inhibitor–treated mice has also been demonstrated [20]. Consequently, this implies a more effective access of the immune system to the tumor at the beginning of the treatment.\n\nThese alterations give reasonable justification to assume that immunogenicity could be elevated at the beginning of MAPK pathway inhibition and reduced after long‐term exposure. Intermittent administration of kinase inhibitors may overcome this problem [21]. Consistent with our hypothesis, Choi et al. recently demonstrated that pulsatile, rather than continuous, treatment with MEK inhibitors in murine models can maintain T‐cell activity better and prolong survival in KRAS mutant cancer. This effect is further enhanced when combined with immunotherapy [22].\n\nContinuous MEK‐inhibitor administration combined with anti–PD‐L1 inhibitor atezolizumab failed in a recent clinical study in humans [23]. Based on our experience, this study protocol should be repeated with an intermittent MEK‐inhibitor dosing.\n\nAnother strategy to optimize tumor apoptosis is a combination of MEK inhibitors and CDK4/6 inhibitors. Teh et al. demonstrated in an in vivo study a more effective tumor inhibition with less toxicity on an intermittent dosing schedule (in this case continuous MEK inhibition with intermittent CDK4/6 inhibition) than alternative scheduling options [24].\n\nPatient Update\nPatient 1\nThe patient's tumor burden steadily decreased in the first 6 months of treatment and remained stable for more than 4 years. Side effects were well tolerated with the intermittent dosing schedule. In April 2019, two progressive nodules were detected on the right shin leading to end of treatment because of progressive disease. A next‐generation sequencing–based test (FoundationOne CDx, Foundation Medicine Inc. Cambridge, MA, USA) of the excised metastasis confirmed NRAS Q61R mutation as well as CDKN2A/B loss, EED R441 alteration, MTAP loss, and TERT promoter alteration 1146 C > T. The tumor mutational burden was intermediate with 11 mutations per megabase. NRAS mutations with CDKN2A/B loss and TERT promoter alterations are likely present at baseline based on their high prevalence in primary samples [2]. Whereas the role of MTPA loss in melanoma is not clearly characterized, the EED R441 alteration might favor resistance by EZH2‐mediated epigenetic changes [25]. But as no serial biopsies were performed, we can only speculate on the resistance mechanisms.\n\nImmunotherapy with anti–PD1‐inhibitor nivolumab (six infusions of 240 mg intravenously every 2 weeks) was started in June 2019. Despite this, the patient's condition progressed. Combined intermittent binimetinib (Mektovi Pfizer, New York) with nivolumab initiated in September 2019 finally resulted in complete metabolic response by June 2020.\n\nPatient 2\nNo further therapy was required as regular imaging by positron emission tomography–computed tomography demonstrated complete metabolic response. This prolonged response is unusual in the landscape of targeted therapy. Supportive factors might be the small tumor burden and normal LDH at therapy start, as well as favorable organ involvement (lymph node, lung) [9].\n\nConclusion\n\nNRAS‐mutated melanomas have fewer treatment options compared with BRAF‐mutated melanomas. We report two patients with NRAS‐mutant melanoma with long‐term response on an intermittent MEK‐inhibitor treatment with reduced dosing. Both patients did not develop resistance for more than 3 years, and the regimen was well tolerated with manageable side effects. Intermittent therapy may be key to achieving better responses, reducing side effects, and delaying drug resistance. Larger‐cohort studies are required to investigate these findings.\n\nAuthor Contributions\n\nConception/design: Reinhard Dummer, Simone M. Goldinger\n\n\nProvision of study material or patients: Alexandra Valeska Matter, Sara Micaletto, Ursula Urner‐Bloch, Reinhard Dummer\n\n\nCollection and/or assembly of data: Alexandra Valeska Matter, Sara Micaletto, Ursula Urner‐Bloch, Reinhard Dummer, Simone M. Goldinger\n\n\nData analysis and interpretation: Alexandra Valeska Matter, Sara Micaletto, Ursula Urner‐Bloch, Reinhard Dummer, Simone M. Goldinger\n\n\nManuscript writing: Alexandra Valeska Matter, Simone M. Goldinger\n\n\nFinal approval of manuscript: Alexandra Valeska Matter, Sara Micaletto, Ursula Urner‐Bloch, Reinhard Dummer, Simone M. Goldinger\n\nDisclosures\n\nRichard Dummer: Novartis, Merck Sharp & Dohme, Bristol‐Myers Squibb, Roche, Amgen, Takeda, Pierre Fabre, Sun Pharma, Sanofi, Catalym, Second Genome (C/A). The other authors indicated no financial relationships.\n\n(C/A) Consulting/advisory relationship; (RF) Research funding; (E) Employment; (ET) Expert testimony; (H) Honoraria received; (OI) Ownership interests; (IP) Intellectual property rights/inventor/patent holder; (SAB) Scientific advisory board\n\nGlossary of Genomic Terms and Nomenclature\nAKTprotein kinase B\n\nBRAFv‐raf murine sarcoma viral oncogene homolog B\n\nCDKN2A/Bcyclin‐dependent kinase inhibitor 2A/B\n\nEEDembryonic ectoderm development\n\nERKextracellular signal‐regulated kinase\n\nHLAhuman leukocyte antigens, also called major histocompatibility complex (MHC)\n\nKRASKirsten rat sarcoma viral oncogene homolog\n\nMAPKmitogen‐activated protein kinases\n\nMEKmitogen‐activated protein kinase kinase\n\nMITFmicrophthalmia transcription factor\n\nMTAPmethylthioadenosine phosphorylase\n\nNRASneuroblastoma RAS viral oncogene homolog\n\nNF1neurofibromin 1\n\nRASrat sarcoma\n\nPI3Kphosphatidylinositol 3‐kinase/ protein kinase B\n\nPTENphosphatase and tensin homologue\n\nTCGAThe Cancer Genome Atlas\n\nTERTtelomerase reverse transcriptase\n\nWTwildtype\n==== Refs\nReferences\n1 \n\nLugovic‐Mihic \nL \n, \nCesic \nD \n, \nVukovic \nP \n et al. Melanoma development: Current knowledge on melanoma pathogenesis\n. Acta Dermatovenerol Croat \n2019 ;27 :163 –168\n.31542060 \n2 \nCancer Genome Atlas Network \n. Genomic classification of cutaneous melanoma\n. Cell \n2015 ;161 :1681 –1696\n.26091043 \n3 \n\nRaaijmakers \nMI \n, \nWidmer \nDS \n, \nNarechania \nA \n et al. Co‐existence of BRAF and NRAS driver mutations in the same melanoma cells results in heterogeneity of targeted therapy resistance\n. Oncotarget \n2016 ;7 :77163 –77174\n.27791198 \n4 \n\nSarkisian \nS \n, \nDavar \nD \n. MEK inhibitors for the treatment of NRAS mutant melanoma\n. Drug Des Devel Ther \n2018 ;12 :2553 –2565\n.\n5 \n\nFedorenko \nIV \n, \nGibney \nGT \n, \nSmalley \nKS \n. NRAS mutant melanoma: Biological behavior and future strategies for therapeutic management\n. Oncogene \n2013 ;32 :3009 –3018\n.23069660 \n6 \n\nColicelli \nJ \n. Human RAS superfamily proteins and related GTPases\n. Sci STKE \n2004 ;2004 :Re13 .15367757 \n7 \n\nReddy \nBY \n, \nMiller \nDM \n, \nTsao \nH \n. Somatic driver mutations in melanoma\n. Cancer \n2017 ;123 :2104 –2117\n.28543693 \n8 \n\nAscierto \nPA \n, \nSchadendorf \nD \n, \nBerking \nC \n et al. MEK162 for patients with advanced melanoma harbouring NRAS or Val600 BRAF mutations: A non‐randomised, open‐label phase 2 study\n. Lancet Oncol \n2013 ;14 :249 –256\n.23414587 \n9 \n\nDummer \nR \n, \nSchadendorf \nD \n, \nAscierto \nPA \n et al. Binimetinib versus dacarbazine in patients with advanced NRAS‐mutant melanoma (NEMO): A multicentre, open‐label, randomised, phase 3 trial\n. Lancet Oncol \n2017 ;18 :435 –445\n.28284557 \n10 \n\nLong \nGV \n, \nWeber \nJS \n, \nInfante \nJR \n et al. Overall survival and durable responses in patients with BRAF V600‐mutant metastatic melanoma receiving dabrafenib combined with trametinib\n. J Clin Oncol \n2016 ;34 :871 –878\n.26811525 \n11 \n\nYaeger \nR \n. Intermittent treatment with MEK inhibitors in patients with oncogenic RAF‐driven tumors: A potential strategy to manage toxicity and maintain efficacy\n. JCO Precis Oncol \n2018 ;2 :1 –2\n.30949620 \n12 \n\nLim \nSY \n, \nMenzies \nAM \n, \nRizos \nH \n. Mechanisms and strategies to overcome resistance to molecularly targeted therapy for melanoma\n. Cancer \n2017 ;123 :2118 –2129\n.28543695 \n13 \n\nDas Thakur \nM \n, \nSalangsang \nF \n, \nLandman \nAS \n et al. Modelling vemurafenib resistance in melanoma reveals a strategy to forestall drug resistance\n. Nature \n2013 ;494 :251 –255\n.23302800 \n14 \n\nDeng \nQ \n, \nLiao \nR \n, \nWu \nBL \n et al. High intensity RAS signaling induces premature senescence by activating p38 pathway in primary human fibroblasts\n. J Biol Chem \n2004 ;279 :1050 –1059\n.14593117 \n15 \n\nDas Thakur \nM \n, \nStuart \nDD \n. The evolution of melanoma resistance reveals therapeutic opportunities\n. Cancer Res \n2013 ;73 :6106 –6110\n.24097822 \n16 \n\nWellbrock \nC \n, \nArozarena \nI \n. Microphthalmia‐associated transcription factor in melanoma development and MAP‐kinase pathway targeted therapy\n. Pigment Cell Melanoma Res \n2015 ;28 :390 –406\n.25818589 \n17 \n\nLiu \nL \n, \nMayes \nPA \n, \nEastman \nS \n et al. The BRAF and MEK inhibitors dabrafenib and trametinib: Effects on immune function and in combination with immunomodulatory antibodies targeting PD‐1, PD‐L1, and CTLA‐4\n. Clin Cancer Res \n2015 ;21 :1639 –1651\n.25589619 \n18 \n\nZipser \nMC \n, \nEichhoff \nOM \n, \nWidmer \nDS \n et al. A proliferative melanoma cell phenotype is responsive to RAF/MEK inhibition independent of BRAF mutation status\n. Pigment Cell Melanoma Res \n2011 ;24 :326 –333\n.21176117 \n19 \n\nDeken \nMA \n, \nGadiot \nJ \n, \nJordanova \nES \n et al. Targeting the MAPK and PI3K pathways in combination with PD1 blockade in melanoma\n. Oncoimmunology \n2016 ;5 :e1238557.28123875 \n20 \n\nEbert \nPJR \n, \nCheung \nJ \n, \nYang \nY \n et al. Map kinase inhibition promotes T cell and anti‐tumor activity in combination with PD‐L1 checkpoint blockade\n. Immunity \n2016 ;44 :609 –621\n.26944201 \n21 \n\nDummer \nR \n, \nRamelyte \nE \n, \nSchindler \nS \n et al. MEK inhibition and immune responses in advanced melanoma\n. Oncoimmunology \n2017 ;6 :e1335843.28919996 \n22 \n\nChoi \nH \n, \nDeng \nJ \n, \nLi \nS \n et al. Pulsatile MEK inhibition improves anti‐tumor immunity and T cell function in murine KRAS mutant lung cancer\n. Cell Rep \n2019 ;27 :806 –819\n e805.30995478 \n23 \n\nArance \nAM \n, \nGogas \nH \n, \nDreno \nB \n et al. LBA69Combination treatment with cobimetinib (C) and atezolizumab (A) vs pembrolizumab (P) in previously untreated patients (pts) with BRAFV600 wild type (WT) advanced melanoma: Primary analysis from the phase III IMspire170 trial\n. Ann Oncol \n2019 ;30 .\n24 \n\nTeh \nJLF \n, \nCheng \nPF \n, \nPurwin \nTJ \n et al. In vivo E2F reporting reveals efficacious schedules of MEK1/2‐CDK4/6 targeting and mTOR‐S6 resistance mechanisms\n. Cancer Discov \n2018 ;8 :568 –581\n.29496664 \n25 \n\nZingg \nD \n, \nDebbache \nJ \n, \nSchaefer \nSM \n et al. The epigenetic modifier EZH2 controls melanoma growth and metastasis through silencing of distinct tumour suppressors\n. Nat Commun \n2015 ;6 :6051 .25609585\n\n",
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"title": "Long-Term Response to Intermittent Binimetinib in Patients with NRAS-Mutant Melanoma.",
"title_normalized": "long term response to intermittent binimetinib in patients with nras mutant melanoma"
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}
],
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}
},
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{
"abstract": "A 53-year-old man was diagnosed with prostate cancer with multiple bone metastasis. Therefore androgen deprivation therapy was initiated. After treatment with denosumab injection for bone metastasis, hypocalcemia and hypophosphatemia occurred. Despite treatment for hypocalcemia with vitamin D and calcium lactate,his serum calcium and phosphate levels were refractory to treatment. The etiology of hypophosphatemia was investigated,and the level of serum fibroblast growth factor 23 (FGF23) was abnormally elevated. Three months after the first measurement of FGF23,the patient died of prostate cancer. Severe hypophosphatemia is a typical manifestation of tumor-induced hypophosphatemic osteomalacia (TIO),which is a paraneoplastic condition, mediated by FGF23 overexpression in most cases. His osteoblastic metastasis,however,did not meet the disease criteria of osteomalacia. Several reports have suggested that excessive FGF23 may mediate both severe hypophosphatemia and aggressive castrationresistant prostate cancer characteristics. Management of serum FGF23 may be a novel therapeutic strategy for castration-resistant prostate cancer with hypophosphatemia.",
"affiliations": "The Department of Urology, Sapporo Medical Center, NTT East Corporation･The Department of Urology, Sapporo Medical University.;The Department of Endocrinology, Sapporo Medical Center, NTT East Corporation.;The Department of Endocrinology, Sapporo Medical Center, NTT East Corporation.;The Department of Urology, Sapporo Medical Center, NTT East Corporation.;The Department of Urology, Sapporo Medical University.",
"authors": "Nishida|Sachiyo|S|;Shigesawa|Ikumi|I|;Nagai|Satoshi|S|;Itoh|Naoki|N|;Masumori|Naoya|N|",
"chemical_list": "D000726:Androgen Antagonists; C000717427:FGF23 protein, human; D005346:Fibroblast Growth Factors; D000089703:Fibroblast Growth Factor-23",
"country": "Japan",
"delete": false,
"doi": "10.14989/ActaUrolJap_67_1_47",
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"issn_linking": "0018-1994",
"issue": "67(1)",
"journal": "Hinyokika kiyo. Acta urologica Japonica",
"keywords": null,
"medline_ta": "Hinyokika Kiyo",
"mesh_terms": "D000726:Androgen Antagonists; D000089703:Fibroblast Growth Factor-23; D005346:Fibroblast Growth Factors; D006801:Humans; D006996:Hypocalcemia; D017674:Hypophosphatemia; D008297:Male; D008875:Middle Aged; D011471:Prostatic Neoplasms",
"nlm_unique_id": "0421145",
"other_id": null,
"pages": "47-51",
"pmc": null,
"pmid": "33535298",
"pubdate": "2021-01",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "A Case of Prostate Cancer with Multiple Bone Metastasis with High FGF23 Value Indicated by Intractable Hypocalcemia and Hypophosphatemia.",
"title_normalized": "a case of prostate cancer with multiple bone metastasis with high fgf23 value indicated by intractable hypocalcemia and hypophosphatemia"
} | [
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{
"abstract": "A man in his fifties with diabetes had a past history of myocardial infarction and ventricular septal perforation. He underwent hemodialysis about a year ago and was taking amiodarone. He presented with sores and purpura on the lower limbs.-Skin biopsy showed immunofluorescence-negative leukocytoclastic vasculitis. Skin lesions were treated with ointments, which ameliorated the symptoms to some extent, but ulceration relapsed and deteriorated in both number and size. Calciphylaxis was suspected, and a second skin biopsy was performed. No calcium detection,on the arteries was observed, but leukocytoclastic vasculitis was seen. Antineutrophil cytoplasmic antibody-related vasculitis, cryoglobulin vasculitis, or anti-phospholipid syndrome were ruled out by negative findings for autoantibodies. Although he was treated with 30 mg prednisolone, his systemic condition deteriorated, and he died of disseminated intravascular coagulation. Autopsy findings showed no vasculitis in the lung, kidney or intestine, and perimyocardial patch infection was observed.Although calciphylaxis was clinically suspected, his condition was diagnosed finally as cutaneous small-vessel vasculitis.",
"affiliations": null,
"authors": "Nakamura|Hironori|H|;Anayama|Mariko|M|;Makino|Yasushi|Y|;Nagasawa|Masaki|M|",
"chemical_list": "D019268:Antibodies, Antineutrophil Cytoplasmic; D011239:Prednisolone",
"country": "Japan",
"delete": false,
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"issue": "59(2)",
"journal": "Nihon Jinzo Gakkai shi",
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"medline_ta": "Nihon Jinzo Gakkai Shi",
"mesh_terms": "D019268:Antibodies, Antineutrophil Cytoplasmic; D001344:Autopsy; D001706:Biopsy; D002115:Calciphylaxis; D006801:Humans; D008297:Male; D008875:Middle Aged; D011239:Prednisolone; D014657:Vasculitis; D018366:Vasculitis, Leukocytoclastic, Cutaneous",
"nlm_unique_id": "7505731",
"other_id": null,
"pages": "85-91",
"pmc": null,
"pmid": "30549918",
"pubdate": "2017",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Premature diagnosis of calciphylaxis without pathological indications finally diagnosed as cutaneous small-vessel vasculitis: a post-mortem case report.",
"title_normalized": "premature diagnosis of calciphylaxis without pathological indications finally diagnosed as cutaneous small vessel vasculitis a post mortem case report"
} | [
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"literaturereference": "NAKAMURA H, ANAYAMA M, MAKINO Y, NAGASAWA M.. PREMATURE DIAGNOSIS OF CALCIPHYLAXIS WITHOUT PATHOLOGICAL INDICATIONS FINALLY DIAGNOSED AS CUTANEOUS SMALL-VESSEL VASCULITIS: A POST-MORTEM CASE REPORT. [JAPANESE].. JAPANESE JOURNAL OF NEPHROLOGY. 2017;59(2):85-91",
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"abstract": "BACKGROUND\nValproic acid (VPA) is an effective antiepileptic drug widely used worldwide. Despite several studies indicating the usefulness of intravenous L-carnitine in the treatment of VPA poisoning, this drug is not readily available in Iran. The aim of this study was to determine whether supportive care without antidote would result in acceptable outcomes in VPA poisoned patients.\n\n\nMETHODS\nIn an observational, retrospective, single-center case series, all patients >12-year-old with VPA overdose who had referred to a tertiary center between 2009 and 2013 were consecutively enrolled. Patients' demographic and presenting features, physical examinations, clinical management, laboratory data, and outcomes were recorded.\n\n\nRESULTS\nA total of 316 patients were enrolled with pure VPA toxicity. The most common presenting signs/symptoms were drowsiness, nausea and vomiting, vertigo, and headache. In the course of the disease, 14 patients (4.4%) were intubated and three (0.9%) required hemodialysis with mean dialysis sessions of two. Fourteen patients were admitted to Intensive Care Unit, and seizures occurred in five. The initial level of consciousness was lower in patients with poor outcome. The median ingested dose of VPA in patients who required dialysis was significantly higher (20 vs. 6 g; P = 0.006). Multivariate analyses revealed that coma on presentation was associated with a worse outcome (P = 0.001; odds ratio = 61.5, 95% CI = 5.8-646.7).\n\n\nCONCLUSIONS\nPrognosis of VPA poisoned patients appears to be good even with supportive care. According to our study, older age, ingestion of higher amounts of VPA and lower PCO2, HCO3, base excess, and CPK levels prone the patients to more severe toxicities in univariate analysis, but the main poor prognostic factor is coma on presentation in multivariate analysis.",
"affiliations": "Toxicological Research Center, Department of Clinical Toxicology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Excellence Center of Clinical Toxicology, Shahid Beheshti University of Medical Sciences, Iranian Ministry of Health, Tehran, Iran.;Toxicological Research Center, Department of Clinical Toxicology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Emergency Medicine Management Research Center, Iran University of Medical Sciences, Tehran, Iran ; Department of Emergency Medicine, Firouzgar Hospital, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.;Toxicological Research Center, Department of Clinical Toxicology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Excellence Center of Clinical Toxicology, Shahid Beheshti University of Medical Sciences, Iranian Ministry of Health, Tehran, Iran.;Emergency Medicine Management Research Center, Iran University of Medical Sciences, Tehran, Iran ; Department of Emergency Medicine, Firouzgar Hospital, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.;Department of Emergency Medicine, Firouzgar Hospital, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran.;Department of Internal Medicine, Hematology, and Oncology, Alborz University of Medical Sciences, Karaj, Iran.;Toxicological Research Center, Department of Clinical Toxicology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran ; Excellence Center of Clinical Toxicology, Shahid Beheshti University of Medical Sciences, Iranian Ministry of Health, Tehran, Iran.",
"authors": "Shadnia|Shahin|S|;Amiri|Hasan|H|;Hassanian-Moghaddam|Hossein|H|;Rezai|Mahdi|M|;Vasei|Zohreh|Z|;Ghodrati|Nillofar|N|;Zamani|Nasim|N|",
"chemical_list": null,
"country": "India",
"delete": false,
"doi": "10.4103/1735-1995.166211",
"fulltext": "\n==== Front\nJ Res Med SciJ Res Med SciJRMSJournal of Research in Medical Sciences : The Official Journal of Isfahan University of Medical Sciences1735-19951735-7136Medknow Publications & Media Pvt Ltd India JRMS-20-65610.4103/1735-1995.166211Original ArticleFavorable results after conservative management of 316 valproate intoxicated patients Shadnia Shahin 12Amiri Hasan 134Hassanian-Moghaddam Hossein 12Rezai Mahdi 34Vasei Zohreh 4Ghodrati Nillofar 5Zamani Nasim 121 Toxicological Research Center, Department of Clinical Toxicology, Loghman Hakim Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran2 Excellence Center of Clinical Toxicology, Shahid Beheshti University of Medical Sciences, Iranian Ministry of Health, Tehran, Iran3 Emergency Medicine Management Research Center, Iran University of Medical Sciences, Tehran, Iran4 Department of Emergency Medicine, Firouzgar Hospital, Faculty of Medicine, Iran University of Medical Sciences, Tehran, Iran5 Department of Internal Medicine, Hematology, and Oncology, Alborz University of Medical Sciences, Karaj, IranAddress for correspondence: Dr. Hossein Hassanian-Moghaddam, Loghman Hakim Clinical Research Development Center, South Karegar Ave, Kamali Street, Tehran, Iran. E-mail: [email protected] 2015 20 7 656 661 13 5 2015 29 6 2015 06 8 2015 Copyright: © 2015 Journal of Research in Medical Sciences2015This is an open access article distributed under the terms of the Creative Commons Attribution-NonCommercial-ShareAlike 3.0 License, which allows others to remix, tweak, and build upon the work non-commercially, as long as the author is credited and the new creations are licensed under the identical terms.Background:\nValproic acid (VPA) is an effective antiepileptic drug widely used worldwide. Despite several studies indicating the usefulness of intravenous L-carnitine in the treatment of VPA poisoning, this drug is not readily available in Iran. The aim of this study was to determine whether supportive care without antidote would result in acceptable outcomes in VPA poisoned patients.\n\nMaterials and Methods:\nIn an observational, retrospective, single-center case series, all patients >12-year-old with VPA overdose who had referred to a tertiary center between 2009 and 2013 were consecutively enrolled. Patients’ demographic and presenting features, physical examinations, clinical management, laboratory data, and outcomes were recorded.\n\nResults:\nA total of 316 patients were enrolled with pure VPA toxicity. The most common presenting signs/symptoms were drowsiness, nausea and vomiting, vertigo, and headache. In the course of the disease, 14 patients (4.4%) were intubated and three (0.9%) required hemodialysis with mean dialysis sessions of two. Fourteen patients were admitted to Intensive Care Unit, and seizures occurred in five. The initial level of consciousness was lower in patients with poor outcome. The median ingested dose of VPA in patients who required dialysis was significantly higher (20 vs. 6 g; P = 0.006). Multivariate analyses revealed that coma on presentation was associated with a worse outcome (P = 0.001; odds ratio = 61.5, 95% CI = 5.8-646.7).\n\nConclusion:\nPrognosis of VPA poisoned patients appears to be good even with supportive care. According to our study, older age, ingestion of higher amounts of VPA and lower PCO2, HCO3, base excess, and CPK levels prone the patients to more severe toxicities in univariate analysis, but the main poor prognostic factor is coma on presentation in multivariate analysis.\n\nAnticonvulsantsantiepileptic drugsoverdosesuicidepoisoningvalproic acid\n==== Body\nINTRODUCTION\nValproic acid (VPA) or valproate is an effective antiepileptic drug widely used all over the world and approved for the treatment of both partial and generalized seizures.[1234] It is also used to treat bipolar and schizoaffective disorders, social phobias, neuropathic pain, and for prophylaxis or treatment of migraine headaches.[23] The usual daily dose of 1-2 g in adults and 15-60 mg/kg in children is generally recommended. Serum valproate levels range from 50 μg/mL to 125 μg/mL, although a level more than 100 μg/mL in acute ingestion may be considered to be toxic and in levels higher than this cutoff point, hemodialysis may contribute to VPA elimination.[256]\n\nWhen serum VPA level is over 100-150 μg/mL, protein sites are saturated leading to increased levels of the free drug.[235] VPA enhances gamma-aminobutyric acid synthesis and release in some specific areas of the brain that can control seizure onset and propagation.[26] Furthermore, VPA reduces the release of the epileptogenic acid and changes dopaminergic and serotoninergic neurotransmissions.[27] As VPA use has increased, reports on both accidental and intentional intoxications are increasing.[236]\n\nVPA overdose usually causes mild and self-limited central nervous system depression. However, serious adverse effects and even death have been reported.[89] In addition to central nervous system depression, VPA toxicity may cause cerebral edema, hyperammonemia, and hepatotoxicity.[710]\n\nRecent articles have shown that hepatotoxicity induced by VPA can be managed by L-carnitine. L-carnitine also increases the survival rate of these patients, especially in cases referred with coma, rising ammonia level, or VPA levels greater than 450 μg/mL.[31112] However, some experts believe that L-carnitine has no specific therapeutic effect in acute overdose.[13] Despite several studies indicating the usefulness of intravenous L-carnitine in the treatment of VPA poisoning, this drug is not readily available in Iran. Many patients with severe acute VPA toxicity are supportively treated. The objective of this study was, therefore, to determine whether supportive care without antidote would result in acceptable outcome in acutely VPA poisoned patients and to find out the factors associated with poorer outcomes.\n\nMATERIALS AND METHODS\nAfter approval of the Ethical Committee of Human Research of the Clinical Research Development Center, all patients >12-year-old with acute VPA overdose who had been referred to Loghman-Hakim Hospital between 2009 and 2013 were consecutively enrolled. Those with multidrug ingestions were excluded [Figure 1]. In this observational, retrospective, single-center case series, patients were identified using the International Classification of Disease Codes (ICD10 codes version 2010). Those with code T42-6 (poisoning chapter; poisoning by antiepileptics, sedative-hypnotics, and antiparkinsonism drugs), X41 (accidental poisoning by and exposure to antiepileptics), X61 (intentional self-poisoning by and exposure to antiepileptics), and Y11 (antiepileptic poisoning, undetermined intent) were evaluated.\n\nFigure 1 Selection and outcome of participants recruited in the study\n\nPatients’ demographic and presenting features, physical examinations, laboratory data, treatment modalities, and outcomes were recorded. On arrival, vital signs and laboratory findings, as well as those after initial stabilization (averagely 6 h after admission), were checked. The time elapsed between ingestion and presentation, as well as the ingested amount, was also recorded based on the patients’ report or hospital admission. Severe toxicity was defined as the need for intubation and/or hemodialysis or death during hospitalization and those with poor prognosis were considered to have severe toxicity in the current study. Severity of poisoning was also determined based on the ingested dose as follow: Severe toxicity (>28 g or ~400 mg/kg), probable moderate toxicity (>14 g or ~200 mg/kg), probable mild toxicity (>1.8 g), and probable nontoxic ingestion (<1.8 g).[1314] Patients with severe toxicity were compared to the remainder in order to determine the independent variables which would cause a worse outcome. The normal range of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALK/P), and carnitine phosphokinase were considered to be 5-40 IU/L, 7-56 IU/L, 44-147 IU/L, and 140-280 IU/L, respectively.[15]\n\nAll the patients had received standard care, including airway management, intravenous fluid resuscitation, gastrointestinal lavage, activated charcoal and sorbitol, and Intensive Care Unit (ICU) care/hemodialysis if indicated. As we did not access the serum level of VPA in all cases (just in 19.6%) and L-carnitine was also unavailable, we treated the patients conservatively and dialyzed them when they did not respond to conservative treatment. Activated charcoal was given within the 1st h postingestion, if the time of overdose was known. Intravenous L-carnitine was not prescribed to any patient because it is not available in Iran. This study was approved by the institutional review board.\n\nStatistical analysis was performed by Statistical Package for Social Sciences (SPSS) version 18.0 (SPSS Inc., Chicago, IL, USA) using Shapiro-Wilk, Chi-square and Fisher's exact tests, Wilcoxon signed-rank test, Mann-Whitney U-test, Kruskal-Wallis H-test, and binomial logistic regression test. Statistical significance was set at P < 0.05.\n\nRESULTS\nOf a total of 715 patients, 316 were enrolled as pure VPA toxicity [Figure 1] with a female to male ratio of 2.55. The median (interquartile range [IQR]) age was 23 (18, 30 [range; 10-66 years]). The median (IQR) ingested dose of VPA was 600 (400, 1000 mg [range; 400-4000 mg]). However, the exact intake dose of 44 patients (13.9%) was unknown. In 286 patients (90.5%), the exact time of ingestion was reported by the patients themselves or their accompanying relatives. Median (IQR) time elapsed between drug ingestion and hospital presentation was 4 (2, 7 h [range; 1-72 h]). All the patients had deliberately poisoned themselves as confirmed by psychiatric assessments. Gastric lavage and/or activated charcoal administration were performed in 178 (56.3%) patients. The most common underlying diseases were epilepsy (56 patients), psychosis (32 patients), depression (24 patients), and migraine headaches (13 patients). However, 166 (52.5%) intoxicated cases did not have any underlying diseases. The most common presenting signs/symptoms were drowsiness (70 patients, 22.2%), nausea and vomiting (60 patients, 19.1%), vertigo (43 patients, 13.6%), and headache (34 patients, 10.8%).\n\nIn 223 cases (70.6%), electrocardiograms (ECGs) were normal on presentation. The most common ECG abnormalities included sinus tachycardia (46 patients, 14.6%) followed by sinus bradycardia (16 patients, 5.1%). In the course of the disease, 14 patients (4.4%) were intubated and three (0.9%) required hemodialysis with the mean dialysis sessions of two. ICU admission was needed in 14 patients (4.4%). Mean ICU stay was 80 ± 57 h while the median (IQR) hospital stay was 15 (12, 24) h. Seizures occurred in five patients (1.4 %) during hospitalization, none of whom had a history of epilepsy. The average ingested dose of VPA was 6.5 ± 6.3 g (range, 2-16 g). There was no association between the occurrence of seizures and poor outcomes (P = 0.204, Fisher's exact test).\n\nThe initial level of consciousness was lower in patients with poor outcomes. On the other hand, only 0.7% of the patients who discharged without any complications had been admitted to an emergency department in coma. Table 1 shows the comparison between the patients with fair and poor outcomes. A total of 7.6% and 1.4% of the patients had abnormal AST and ALT on admission with no significant association between these tests and patients’ outcome. ALK/P was abnormal in 56% of the patients who had the documented levels of this test in their files and was not significantly different between those with fair and poor outcomes. None of the patients with nontoxic ingestions (<1.8 g) had abnormal AST, ALT, or ALK/P. Table 2 shows that although there was a significant correlation between probable mild/moderate/severe toxicity based on the ingested dose and poor outcome (P < 0.005), such a significant relation was not found between VPA level and outcome (P = 0.404, Kruskal-Wallis test). Table 3 shows the characteristics of 14 patients with poor outcomes.\n\nTable 1 Comparison between the patients with good and poor outcome\n\nTable 2 Correlation of ingested dose and poor outcome in 272 patients with known ingested dose\n\nTable 3 On-arrival characteristics of 14 intubated patients\n\nThe median ingested dose of VPA in patients who required dialysis was significantly higher (20 vs. 6 g; P = 0.006). However, median VPA serum concentration failed to show such significant difference between the two groups (150 vs. 117 μg/mL; P = 0.182). Ammonia level was not measured in any of the patients who underwent dialysis.\n\nEvaluation of the platelets using Wilcoxon signed-rank test showed no evidence to approve thrombocytopenia as an indicator of severe valproate toxicity. On the other hand, pH, PCO2, HCO3, and liver function tests (AST, ALT, and ALK/P) evaluated in the patients with poor outcomes showed no statistically significant difference between these parameters on admission and before death or discharge (Wilcoxon signed-rank test). Multivariate analysis revealed that coma on presentation was associated with the worst outcome (P = 0.001; odds ratio = 61.5; 95% CI = 5.8-646.7).\n\nDISCUSSION\nThere is no controlled, randomized trial that delineate the therapeutic and prophylactic roles of L-carnitine and the optimal regimen of its administration in VPA toxicity. To compare treatment with or without L-carnitine, the only way is to review those studies that used this antidote and compare final outcomes with the ones which did not use it.\n\nValproate is widely prescribed for the treatment of epilepsy with few side effects although its toxicity has been steadily increasing in frequency worldwide.[13616171819] Our previous data from 2003 showed that in 6 months only 51 pure VPA toxicity cases had been admitted to our center.[20] In the current study, 316 cases were hospitalized in 36 months which again confirms this claim. The frequency of anticonvulsant and benzodiazepine toxicities were almost constant between 2006 and 2011 (F [5-2.70] = 0.22, P = 0.93).[21]\n\nVPA is generally well tolerated, but rare serious adverse events may occur in some patients receiving it, including hemorrhagic pancreatitis, bone marrow suppression, hepatotoxicity, and VPA-induced encephalopathy.[2] Our data showed no sign of bone marrow suppression including thrombocytopenia in our patients during hospitalization. The same results were found by Isbister et al.[16] On the other hand, while liver function tests did not significantly affect the patients’ outcome, ALK/P was interestingly high in the majority of the patients with ingestion of toxic doses (56%).\n\nInitial vital signs were shown to have no significant effect on the final outcome of the patients. In univariate analysis, the only independent factors which correlated with poorer outcome were older age, higher ingested doses, coma on presentation, lower PCO2, HCO3, base excess, and CPK, and not surprisingly, prolonged hospital stay [Table 1]. Unlike Spiller et al. and Thanacoody studies, we could not find any association between serum VPA level and outcome.[822] This may be due to different presentation and sampling times.\n\nAlthough it is claimed that the massive overdoses (>400 mg/kg) of valproate are potentially life-threatening and can lead to poor outcomes, we had some patients presenting with mild overdoses who developed hepatotoxicity, loss of consciousness, and even death. Overall, the outcome is good in VPA toxicity and the number of patients with poor outcome is quite few (4.4%) and death is uncommon (0.6%). Most studies on VPA toxicity are case reports. Isbister et al. reported a fatal case of VPA toxicity among 79 cases; however, it was a mixed ingestion of drugs.[16] We had no deaths in our previous study in 51 pure VPA toxicity cases.[20]\n\nPublished evidence on the efficacy and safety of L-carnitine for acute VPA overdose is not enough.[12] Perrott et al. stated that it was reasonable to consider L-carnitine for patients with acute VPA overdose and decreased level of consciousness.[23] Mock and Schwetschenau concluded that oral levocarnitine was safe and effective in VPA-induced encephalopathy.[24] L-carnitine has also been used with questionable benefit in the setting of acute VPA-induced hepatitis.[25] In a recent study, Lheureux and Hantson mentioned that early intravenous L-carnitine improved survival in severe VPA-induced hepatotoxicity.[1] In our study, intravenous L-carnitine was not used and conservative management had arguably resulted in the similar results. We are not yet able to decline or confirm the usefulness of L-carnitine in acute VPA toxicity although it seems a safe antidote.[1113182324]\n\nIn terms of hemodialysis, we were not dependent on ammonia level.[22] Hemodialysis was done in three patients unresponsive to supportive care and the progress of the loss of consciousness and probable encephalopathy. None of them had a serum VPA more than 850 μg/mL which was considered for HD by previous studies.[1622] One of the dead cases was dialyzed one time and we think that early HD might have saved his life. L-carnitine may be used in this situation as well, but the formation of ammonia is higher due to higher VPA concentrations. Some authors suggest measuring ammonia during VPA toxicity treatment.[25]\n\nSTRENGTH AND LIMITATIONS\nTo the best of our knowledge, this is the largest single-center study on pure VPA toxicity. The retrospective nature of this study along with missing data, lab tests, valproate level (measured in 62 cases), and ammonia level (measured in only three cases) were definitely the main limitations of this study. The valproate level was not measured on arrival in all the cases; thus there was no correlation between ingested dose and valproate level. Inability to follow all outpatients in order to measure the probable late consequences of VPA toxicity is another potential limitation.\n\nCONCLUSIONS\nThe prognosis of patients with acute VPA toxicity appears to be good even with supportive care. According to our study, the main poor prognostic factor is coma in the multivariate analysis which may be seen after the ingestion of doses as low as 6 g. In univariate analysis, older age and ingestion of higher amounts of VPA prone the patients to more severe toxicities. Lower PCO2, HCO3, BE, and CPK are other variables which can be used to predict the outcome of toxicity.\n\nFinancial support and sponsorship\nNil.\n\nConflicts of interest\nThere are no conflicts of interest.\n\nAUTHOR'S CONTRIBUTION\nSS and HA designed the study. NGh and MR acquiesced the data. NZ, ZV and HHM drafted the article, HHM analysed and interpreted the data. All authors made substantial contribution for final approval of the current article.\n\nAcknowledgments\nThis study was supported by Clinical Research and Development Center of Loghman Hakim Hospital, Shahid-Beheshti University of Medical Sciences, Tehran, Iran.\n==== Refs\nREFERENCES\n1 Lheureux PE Hantson P Carnitine in the treatment of valproic acid-induced toxicity Clin Toxicol (Phila) 2009 47 101 11 19280426 \n2 Lheureux PE Penaloza A Zahir S Gris M Science review: Carnitine in the treatment of valproic acid-induced toxicity — What is the evidence? Crit Care 2005 9 431 40 16277730 \n3 Russell S Carnitine as an antidote for acute valproate toxicity in children Curr Opin Pediatr 2007 19 206 10 17496767 \n4 Löscher W Valproate: A reappraisal of its pharmacodynamic properties and mechanisms of action Prog Neurobiol 1999 58 31 59 10321796 \n5 Meek MF Broekroelofs J Yska JP Egbers PH Boerma EC van der Voort PH Valproic acid intoxication: Sense and non-sense of haemodialysis Neth J Med 2004 62 333 6 15635819 \n6 Crudup JB III Hartley BI Keel BR Panda M Recognizing and treating valproic acid toxicity: A case report J Med Cases 2011 2 185 7 \n7 Katiyar A Aaron C Case files of the children's hospital of Michigan regional poison control center: The use of carnitine for the management of acute valproic acid toxicity J Med Toxicol 2007 3 129 38 18072149 \n8 Spiller HA Krenzelok EP Klein-Schwartz W Winter ML Weber JA Sollee DR Multicenter case series of valproic acid ingestion: Serum concentrations and toxicity J Toxicol Clin Toxicol 2000 38 755 60 11192462 \n9 Ellenhorn M Diagnosis and treatment of human poisoning Medical Toxicology 1997 Baltimore Williams and Wilkins 609 10 \n10 Berthelot-Moritz F Chadda K Chanavaz I Leroy JP Droy JM Bonmarchand G Fatal sodium valproate poisoning Intensive Care Med 1997 23 599 9201541 \n11 De Vivo DC Bohan TP Coulter DL Dreifuss FE Greenwood RS Nordli DR Jr L-carnitine supplementation in childhood epilepsy: Current perspectives Epilepsia 1998 39 1216 25 9821988 \n12 Chan YC Tse ML Lau FL Two cases of valproic acid poisoning treated with L-carnitine Hum Exp Toxicol 2007 26 967 9 18375641 \n13 LoVecchio F Shriki J Samaddar R L-carnitine was safely administered in the setting of valproate toxicity Am J Emerg Med 2005 23 321 2 15915405 \n14 Smith FR Boots M Sodium valproate and bone marrow suppression Ann Neurol 1980 8 197 9 6775583 \n15 Limdi JK Hyde GM Evaluation of abnormal liver function tests Postgrad Med J 2003 79 307 12 12840117 \n16 Isbister GK Balit CR Whyte IM Dawson A Valproate overdose: A comparative cohort study of self poisonings Br J Clin Pharmacol 2003 55 398 404 12680889 \n17 Johannessen CU Johannessen SI Valproate: Past, present, and future CNS Drug Rev 2003 9 199 216 12847559 \n18 Sztajnkrycer MD Valproic acid toxicity: Overview and management J Toxicol Clin Toxicol 2002 40 789 801 12475192 \n19 Roberge RJ Francis EH 3rd Use of naloxone in valproic acid overdose: Case report and review J Emerg Med 2002 22 67 70 11809558 \n20 Hassanian-Moghaddam H Zarei MR Kargar M Sarjami S Rasouli MR Factors associated with nonbenzodiazepine antiepileptic drug intoxication: Analysis of 9,809 registered cases of drug poisoning Epilepsia 2010 51 979 83 20384729 \n21 Hassanian-Moghaddam H Zamani N Rahimi M Shadnia S Pajoumand A Sarjami S Acute adult and adolescent poisoning in Tehran, Iran; the epidemiologic trend between 2006 and 2011 Arch Iran Med 2014 17 534 8 25065275 \n22 Thanacoody RH Extracorporeal elimination in acute valproic acid poisoning Clin Toxicol (Phila) 2009 47 609 16 19656009 \n23 Perrott J Murphy NG Zed PJ L-carnitine for acute valproic acid overdose: A systematic review of published cases Ann Pharmacother 2010 44 1287 93 20587742 \n24 Mock CM Schwetschenau KH Levocarnitine for valproic-acid-induced hyperammonemic encephalopathy Am J Health Syst Pharm 2012 69 35 9 22180549 \n25 Bohan TP Helton E McDonald I König S Gazitt S Sugimoto T Effect of L-carnitine treatment for valproate-induced hepatotoxicity Neurology 2001 56 1405 9 11376200\n\n",
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},
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{
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{
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{
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},
{
"reactionmeddrapt": "Intentional overdose",
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},
{
"reactionmeddrapt": "Tachycardia",
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"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Liver function test abnormal",
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"reactionoutcome": "5"
}
],
"summary": null
},
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"literaturereference_normalized": "favorable results after conservative management of 316 valproate intoxicated patients",
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},
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{
"companynumb": "IR-UNICHEM LABORATORIES LIMITED-UCM201511-000866",
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{
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},
{
"reactionmeddrapt": "Electrocardiogram QT prolonged",
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},
{
"reactionmeddrapt": "Toxicity to various agents",
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"reactionoutcome": "6"
}
],
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},
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},
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},
{
"companynumb": "IR-MYLANLABS-2015M1036890",
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{
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},
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"medicinalproduct": "VALPROATE"
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],
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"reaction": [
{
"reactionmeddrapt": "Electrocardiogram QT prolonged",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Intentional overdose",
"reactionmeddraversionpt": "18.1",
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}
],
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"literaturereference_normalized": "favorable results after conservative management of 316 valproate intoxicated patients",
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},
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}
] |
{
"abstract": "Bleeding disorders are commonly associated with hemato-oncologic diseases. We report a 68 years old male with a chronic myelomonocytic leukemia derived from a long lasting mielodysplastic syndrome that did not respond to treatment with Azacitidine. The patient was hospitalized due to tonic clonic seizures. A CAT scan showed a hematoma in the frontal lobe. A new assessment of hemostasis revealed an isolated deficiency of Factor X. We speculate that this deficit could be secondary to consumption due to the chronic Myelomonocytic Leukemia.",
"affiliations": null,
"authors": "Zelada|Javier|J|;Cantó|Gabriela|G|;Berkovits|Alejandro|A|;Diocares|Gonzalo|G|;López|Adriana|A|",
"chemical_list": "D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine",
"country": "Chile",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0034-9887",
"issue": "143(11)",
"journal": "Revista medica de Chile",
"keywords": null,
"medline_ta": "Rev Med Chil",
"mesh_terms": "D000368:Aged; D000964:Antimetabolites, Antineoplastic; D001374:Azacitidine; D005171:Factor X Deficiency; D005625:Frontal Lobe; D006406:Hematoma; D006801:Humans; D015477:Leukemia, Myelomonocytic, Chronic; D007962:Leukocytes; D008297:Male; D009000:Monocytes; D012640:Seizures",
"nlm_unique_id": "0404312",
"other_id": null,
"pages": "1490-3",
"pmc": null,
"pmid": "26757875",
"pubdate": "2015-11",
"publication_types": "D002363:Case Reports; D004740:English Abstract; D016428:Journal Article",
"references": null,
"title": "Isolated factor X deficiency in chronic myelomonocytic leukemia: Report of one case.",
"title_normalized": "isolated factor x deficiency in chronic myelomonocytic leukemia report of one case"
} | [
{
"companynumb": "CL-CELGENE-CHL-2016015341",
"fulfillexpeditecriteria": "1",
"occurcountry": "CL",
"patient": {
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{
"actiondrug": "5",
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"medicinalproduct": "THALOMID"
},
{
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"activesubstancename": "HUMAN PLASMA"
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"medicinalproduct": "FRESH FROZEN PLASMA"
}
],
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"patientonsetage": "68",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Coagulation factor X level abnormal",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Haematoma",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Generalised tonic-clonic seizure",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Microangiopathy",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Chronic myeloid leukaemia",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2011"
}
},
"primarysource": {
"literaturereference": "ZELADA J. ISOLATED FACTOR X DEFICIENCY IN CHRONIC MYELOMONOCYTIC LEUKEMIA REPORT OF ONE CASE. REVISTA MEDICA DE CHILE. 2015?143:.",
"literaturereference_normalized": "isolated factor x deficiency in chronic myelomonocytic leukemia report of one case",
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}
] |
{
"abstract": "Depression and anxiety disorders are frequently seen in the postpartum period. Primary pharmacological agents for these disorders are antidepressants, especially selective serotonin reuptake inhibitors. Despite no adverse reports, data on safety for the maternal use of fluvoxamine on breastfed infants are limited. This case report presents diarrhea and vomiting in the breastfed baby of a woman using fluvoxamine at 50 mg/d.",
"affiliations": "Department of Psychiatry, Meram Faculty of Medicine, Necmettin Erbakan University, Konya, Turkey [email protected].",
"authors": "Uguz|Faruk|F|",
"chemical_list": "D017367:Serotonin Uptake Inhibitors; D016666:Fluvoxamine",
"country": "United States",
"delete": false,
"doi": "10.1177/0890334415582207",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0890-3344",
"issue": "31(3)",
"journal": "Journal of human lactation : official journal of International Lactation Consultant Association",
"keywords": "antidepressants; breastfeeding; postnatal depression; postpartum depression",
"medline_ta": "J Hum Lact",
"mesh_terms": "D000328:Adult; D001942:Breast Feeding; D019052:Depression, Postpartum; D003967:Diarrhea; D005260:Female; D016666:Fluvoxamine; D006801:Humans; D007223:Infant; D017367:Serotonin Uptake Inhibitors; D014839:Vomiting",
"nlm_unique_id": "8709498",
"other_id": null,
"pages": "371-3",
"pmc": null,
"pmid": "25896469",
"pubdate": "2015-08",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Gastrointestinal Side Effects in the Baby of a Breastfeeding Woman Treated with Low-Dose Fluvoxamine.",
"title_normalized": "gastrointestinal side effects in the baby of a breastfeeding woman treated with low dose fluvoxamine"
} | [
{
"companynumb": "TR-MYLANLABS-2017M1003921",
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{
"actiondrug": "6",
"activesubstance": {
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},
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"drugauthorizationnumb": "075889",
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},
{
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},
{
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},
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"medicinalproduct": "PAROXETINE."
}
],
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"reaction": [
{
"reactionmeddrapt": "Agitation",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Exposure during breast feeding",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Diarrhoea",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Vomiting",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Insomnia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "UGUZ F. GASTROINTESTINAL SIDE EFFECTS IN THE BABY OF A BREASTFEEDING WOMAN TREATED WITH LOW-DOSE FLUVOXAMINE. J-HUM-LACT 2015;31(3):371-373.",
"literaturereference_normalized": "gastrointestinal side effects in the baby of a breastfeeding woman treated with low dose fluvoxamine",
"qualification": "1",
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},
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"receiptdate": "20170127",
"receivedate": "20170127",
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},
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"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
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"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20170428"
},
{
"companynumb": "TR-LUPIN PHARMACEUTICALS INC.-2017-00648",
"fulfillexpeditecriteria": "1",
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"patient": {
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{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "SERTRALINE HYDROCHLORIDE"
},
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"drugauthorizationnumb": "077670",
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"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "MAJOR DEPRESSION",
"drugintervaldosagedefinition": null,
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"medicinalproduct": "SERTRALINE"
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "PAROXETINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "204134",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
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"drugindication": "MAJOR DEPRESSION",
"drugintervaldosagedefinition": null,
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"drugtreatmentdurationunit": null,
"medicinalproduct": "PAROXETINE."
}
],
"patientagegroup": null,
"patientonsetage": "40",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Anxiety",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Vomiting",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Insomnia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Tachycardia",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Nausea",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
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"abstract": "BACKGROUND\nPatients with chronic Strongyloides stercoralis infection are usually asymptomatic; therefore, their condition is easily overlooked. In immunosuppressed patients, mortality is high because of disseminated infection and hyperinfection. This report describes a fatal S stercoralis hyperinfection in a patient with nephrotic syndrome after treatment with steroids.\nA 70-year-old male presented with a history of progressive edema, skin infection, persistent fever, cough, intermittent abdominal pain, and progressive respiratory failure after steroid treatment.\n\n\nMETHODS\nNephrotic syndrome; cellulitis; S stercoralis hyperinfection; Klebsiella pneumonia.\n\n\nMETHODS\nDuring the first hospital admission, the patient was administered full-dose glucocorticoid and antibiotic therapy after suffering from cellulitis. During the second admission, he was diagnosed and treated for normal digestive discomfort and a bacterial infection. The patient had progressive respiratory failure and was placed on a ventilator. He was immediately treated with albendazole when S stercoralis was found in samples of his sputum and feces.\n\n\nRESULTS\nThe patient died despite treatment with albendazole and antibiotic therapy.\n\n\nCONCLUSIONS\nIt is essential to consider the possibility of S stercoralis infection in immunosuppressed patients with nephrotic syndrome. Given the lack of classic manifestations and high mortality rate of advanced disease, continuous monitoring, early diagnosis, and proper treatment are imperative.",
"affiliations": "Department of Nephrology, the Second Affiliated Hospital (Xinqiao Hospital), Army Military Medical University (Third Military Medical University), Chongqing, China.",
"authors": "Wang|Wei-Li|WL|;Zhang|Qi-Wu|QW|;Tang|Sha|S|;Chen|Feng|F|;Zhang|Jing-Bo|JB|",
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"fulltext": "\n==== Front\nMedicine (Baltimore)Medicine (Baltimore)MEDIMedicine0025-79741536-5964Wolters Kluwer Health 31804353MD-D-19-0156410.1097/MD.0000000000018247182473400Research ArticleClinical Case ReportCo-infection with Strongyloides stercoralis hyperinfection syndrome and Klebsiella in a nephrotic syndrome patient A case reportWang Wei-Li MDZhang Qi-Wu MDTang Sha MDChen Feng MDZhang Jing-Bo MD∗NA. Department of Nephrology, the Second Affiliated Hospital (Xinqiao Hospital), Army Military Medical University (Third Military Medical University), Chongqing, China.∗ Correspondence: Jing-Bo Zhang, Department of Nephrology, the Second Affiliated Hospital (Xinqiao Hospital), Army Military Medical University (Third Military Medical University), Chongqing, 400037, China (e-mail: [email protected]).12 2019 10 12 2019 98 49 e182479 3 2019 26 10 2019 7 11 2019 Copyright © 2019 the Author(s). Published by Wolters Kluwer Health, Inc.2019This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0Abstract\nRationale:\nPatients with chronic Strongyloides stercoralis infection are usually asymptomatic; therefore, their condition is easily overlooked. In immunosuppressed patients, mortality is high because of disseminated infection and hyperinfection. This report describes a fatal S stercoralis hyperinfection in a patient with nephrotic syndrome after treatment with steroids.\n\nPatient concerns:\nA 70-year-old male presented with a history of progressive edema, skin infection, persistent fever, cough, intermittent abdominal pain, and progressive respiratory failure after steroid treatment.\n\nDiagnosis:\nNephrotic syndrome; cellulitis; S stercoralis hyperinfection; Klebsiella pneumonia.\n\nInterventions:\nDuring the first hospital admission, the patient was administered full-dose glucocorticoid and antibiotic therapy after suffering from cellulitis. During the second admission, he was diagnosed and treated for normal digestive discomfort and a bacterial infection. The patient had progressive respiratory failure and was placed on a ventilator. He was immediately treated with albendazole when S stercoralis was found in samples of his sputum and feces.\n\nOutcomes:\nThe patient died despite treatment with albendazole and antibiotic therapy.\n\nLessons:\nIt is essential to consider the possibility of S stercoralis infection in immunosuppressed patients with nephrotic syndrome. Given the lack of classic manifestations and high mortality rate of advanced disease, continuous monitoring, early diagnosis, and proper treatment are imperative.\n\nKeywords\nhyperinfection syndromeimmunosuppressed patientsnephrotic syndromeStrongyloides stercoralisOPEN-ACCESSTRUE\n==== Body\n1 Introduction\nStrongyloides stercoralis is an intestinal parasite that spawns larvae in the soil and mainly infects humans. Most cases of S stercoralis are distributed in tropical, subtropical, and temperate regions.[1] From 1973 to 2013, 330 cases were reported in China, mainly in the southern regions.[2] Those chronically infected with S stercoralis are usually asymptomatic and are easily overlooked by healthcare workers. The immunosuppressed population is more vulnerable to disseminated infection and is more likely to develop hyperinfection. Many studies on S stercoralis have focused on organ transplant recipients and patients with malignant tumors, since these individuals often receive multi-target immunosuppression treatment and therefore have severe immunodeficiency. We reviewed the literature and report a case of a fatal S stercoralis hyperinfection in a patient with nephrotic syndrome.\n\n2 Case report\nA 70-year-old male suffered progressive generalized edema after consuming stale crabs, with only mild abdominal discomfort and no fever or other symptoms. Before this, he was healthy and did not have a history of digestive diseases, diabetes, or chronic obstructive pulmonary disease. The man was a native of Chongqing, the subtropical area in southwest China. He used to be a soldier; he fought in the Vietnam War and joined the police force after returning to his hometown.\n\nIn the hospital, his initial vitals were BP 108/78 mmHg, HR 111, respiratory rate 22, and oxygen saturation 98%. Initial laboratories included white blood cells 13.32 × 109/L (neutrophils% 77.5%; lymphocytes% 13.31%; eosinophils% 0.5%), normal hemoglobin and platelets, albumin (ALB) 14.5 g/L, globulin (GLB) 19.9 g/L, alanine aminotransferase (ALT) 78.7 IU/L, aspartate aminotransferase (AST) 90.9 IU/L, creatinine (Cr) 134 μmol/L, 24-hour urine protein 9.61 g, and negative antinuclear antibody spectrum (ANAs) and anti-neutrophil cytoplasmic antibodies (ANCA). Chest X-ray showed mild emphysema but no sign of infection. The patient was diagnosed with nephrotic syndrome but was unable to undergo pathological biopsy due to a renal cyst. He was administered full-dose glucocorticoid therapy alone, with no other immunosuppression. Three weeks later, while still under this treatment, the patient suffered lower limb cellulitis. His procalcitonin (PCT) was 0.3 ng/ml, and he was administrated mupirocin ointment and IV cefuroxime. After those treatments, his status improved and he continued to take oral glucocorticoids after discharge from the hospital.\n\nHowever, over the next ten days, the patient seemed to get worse and had to return to the hospital due to persistent fever, cough, and intermittent abdominal pain. Initial vitals on admission were temperature 37.8 °C, BP 90/60 mmHg, HR 125, respiratory rate 26, and oxygen saturation 95%. Laboratory tests showed white blood cells 12.36 × 109/L (neutrophils %: 83.5%; eosinophils %: 0.7%). Sputum smear and culture were negative. Imaging examinations included CT scans of the chest, which reported interstitial pneumonia (Fig. 1), and the abdomen, which reported no specific findings. The patient was diagnosed with normal gastrointestinal discomfort and pulmonary bacterial infection. A proton pump inhibitor, cefoperazone sodium, and sulbactam sodium were administered. However, the patient then started display hemoptysis, passed occult blood-positive stool, and gradually fell into a state of hyperpyrexia and drowsiness. Soon, Klebsiella pneumoniae (which was sensitized to the previous antibiotic), and unexpectedly, a large number of S. stercoralis larvae (Fig. 2) were found in repeated sputum specimens. Meanwhile, the parasite was also found in a repeated brown stool specimen. Blood samples showed eosinophils% reached 18.1% and PCT was 1.01 ng/ml. Because ivermectin is not available in our region, albendazole (400 mg/day) was administered for 3 consecutive days but there was no progress. Subsequently, a mechanical ventilator was administered due to continued severe hypoxia and respiratory failure. The patient was unable to maintain his blood pressure and eventually died after co-infection with S stercoralis hyperinfection and the K pneumoniae found 1 week later. The course of this case has been summarized in Figure 3. The authorized relative of patient has provided informed consent for publication of the case.\n\nFigure 1 A chest computed tomography showing interstitial pneumonia.\n\nFigure 2 A large number of Strongyloides stercoralis are found in the sputum (A), and are further identified as filariform larvae (B).\n\nFigure 3 The course of the disease. Lines showed as fold the upper reference limit indicate WBC absolute count, neutrophil %, eosinophil % and procalcitonin, respectively. WBC, white blood cell.\n\n3 Discussion\nInfection with S stercoralis is often initiated through contact with soil contaminated with infectious larvae that penetrate the skin and migrate via the circulatory system to the lung, where they are expectorated and travel through the trachea to be swallowed back down to the gastrointestinal tract.[3,4] This migration is usually clinically asymptomatic and therefore often goes unnoticed by the host. After migration, the larvae mature into adult roundworms and release eggs in the gastrointestinal tract. Some eggs are excreted and some transform into infectious larvae and re-infect the host in a process called autoinfection. An infected patient may survive without any symptoms for decades if his or her immune system is not compromised. However, a patient who has received steroid therapy is more susceptible to fatal dissemination and hyperinfection.[5,19]\n\nThe innate and adaptive immune system, both profoundly modulated by strongyloidiasis, are vital to the prevention of S stercoralis disseminated infection. Larval migration and proliferation are facilitated due to varying degrees of inhibition in an immunosuppressed host. As part of the innate immune system, eosinophils play a prominent role in parasitic infections and have been confirmed to kill worms and act as antigen-presenting cells (APCs) for the initiation of Th2 immune responses in strongyloidiasis.[20] Recently findings proved that neutrophil and mast cell activation may play another important role in defending against S stercoralis infection.[21] Studies on adaptive immunity in strongyloidiasis have reported that the CD4+ T cell subsets Th1, Th2 and Th17 showed susceptibility or resistance to infection.[22]\n\nFurther migration of larvae causes noticeable symptoms, mainly in gastrointestinal tract and lung, including emesis, diarrhea, abdominal pain, wheezing, and hemoptysis.[4] Some patients diagnosed with strongyloidiasis can develop hyperinfection syndrome, wherein larvae proliferation spirals out of control, resulting in disseminated larval infection. This result is especially common if the patient has received immunosuppressants such as steroids and chemotherapeutics or has become immunocompromised by virtue of chronic strongyloidiasis. Hyperinfection can cause multiple organ failure and death. The mortality rate of S stercoralis hyperinfection ranges from 87% to 100%.[5,6] In this case, our patient was administered prednisone. He subsequently suffered a persistent fever, hemoptysis, and abdominal pain. The chest CT showed interstitial pneumonia and both S. stercoralis and K pneumoniae were found in the sputum. In the end, he developed severe hypoxia and respiratory failure. It is easy to ignore and difficult to diagnose strongyloidiasis before finding evidence of parasitic pathogens. Many patients are either asymptomatic or exhibit non-specific symptoms that are indistinguishable from those of other diseases. Although eosinophilic infiltration is associated with parasitic infections and the ratio of eosinophils increased dramatically when our patient was confirmed to be infected with S stercoralis, this indicator is highly variable and is not a reliable tool for prediction or diagnosis.[7] Serological IgG testing of larval antigens has a sensitivity of approximately 80% and a specificity of 97%,[8] but it is less often used in clinical practice. Therefore, parasite detection remains the gold standard for diagnosis. In the treatment of strongyloidiasis, ivermectin 200 μg/kg orally daily for 2 weeks is recommended, as it is well tolerated with few side effects.[7,9] Because ivermectin was absent in our region, albendazole was a reasonable alternative. Nevertheless, cure rates for albendazole are lower than ivermectin,[10] therefore ivermectin should be administered as a first-line treatment whenever possible. Furthermore, Henriquez-Camacho et al showed that although the parasitological cure of ivermectin and albendazole is similar, ivermectin results in more people cured than albendazole.[9]\n\nIn the 8 reported cases of nephrotic syndrome associated with strongyloidiasis (Table 1), the initial presentation was related to the features of nephrotic syndrome. In most patients, clinical features of strongyloidiasis manifested within 1 or 2 months of receiving steroid treatment. Unlike patients who must undergo multi-target immunosuppression after a kidney transplant[11] or for malignant tumors,[12] steroid alone was the main treatment for these eight patients. Eosinophils were high in 6 of 8 cases, and 3 cases had a concomitant bacterial infection. In our case, the patient suffered cellulitis during treatment, which made him more susceptible to infection after immunosuppressive therapy. In addition to his immunosuppression, the patient's travel to Vietnam also put him at high risk of S stercoralis hyperinfection.\n\nTable 1 Clinical characteristics of patients in eight reported cases of nephrotic syndrome associated with strongyloidiasis.\n\nDue to the non-specific nature of strongyloidiasis symptoms, of strongyloidiasis it is easy to neglect parasitic infection and therefore delay screening and treatment. This is especially true if there is an accompanying bacterial infection. Hence, ongoing monitoring of any new or progressive symptoms, eosinophil ratio, and repeated examination samples will contribute to timely diagnosis and treatment of strongyloidiasis and will decrease the risk of hyperinfection. Finally, re-establishing immune homeostasis may play a crucial part in the survival of immunosuppressed patients.\n\nAcknowledgments\nWe thank Dr. Peng Tang for providing photos and videos of clinical samples.\n\nAuthor contributions\nInvestigation: Qiwu Zhang, Feng Chen.\n\nProject administration: weili wang, Jingbo Zhang.\n\nResources: Feng Chen.\n\nSupervision: Sha Tang.\n\nWriting – original draft: weili wang.\n\nWriting – review & editing: weili wang, Qiwu Zhang, Sha Tang, Jingbo Zhang.\n\nweili wang orcid: 0000-0002-3502-2360.\n\nAbbreviations: ALT = alanine aminotransferase, ANAs = antinuclear antibody spectrum, ANCA = anti-neutrophil cytoplasmic antibodies, APCs = antigen-presenting cells, AST = aspartate aminotransferase, BP = blood pressure, CT = computed tomography, HR = heart rate, PCT = procalcitonin.\n\nHow to cite this article: Wang WL, Zhang QW, Tang S, Chen F, Zhang JB. Co-infection with Strongyloides stercoralis hyperinfection syndrome and Klebsiella in a nephrotic syndrome patient: a case report. Medicine. 2019;98:49(e18247).\n\nW-LW and Q-WZ contributed equally to this work.\n\nInformed written consent was obtained from the authorized relative of the patient for publication of this case report and accompanying images.\n\nThe authors have no conflicts of interests to disclose.\n==== Refs\nReferences\n[1] Olsen A van Lieshout L Marti H \nStrongyloidiasis-the most neglected of the neglected tropical diseases? \nTrans R Soc Trop Med Hyg \n2009 ;103 :967 –72 .19328508 \n[2] Wang C Xu J Zhou X \nStrongyloidiasis: an emerging infectious disease in China . Am J Trop Med Hyg \n2013 ;88 :420 –5 .23468357 \n[3] Greaves D Coggle S Pollard C \nStrongyloides stercoralis infection . BMJ \n2013 ;347 :f4610 .23900531 \n[4] Mejia R Nutman TB \nScreening, prevention, and treatment for hyperinfection syndrome and disseminated infections caused by Strongyloides stercoralis . Curr Opin Infect Dis \n2012 ;25 :458 –63 .22691685 \n[5] Lam CS Tong MK Chan KM \nDisseminated strongyloidiasis: a retrospective study of clinical course and outcome . Eur J Clin Microbiol Infect Dis \n2006 ;25 :14 –8 .16418832 \n[6] Croker C Reporter R Redelings M \nStrongyloidiasis-related deaths in the United States, 1991-2006 . Am J Trop Med Hyg \n2010 ;83 :422 –6 .20682893 \n[7] Sims H Erber WN \nInvestigation of an incidental finding of eosinophilia . BMJ \n2011 ;342 :d2670 .21593088 \n[8] van Doorn HR Koelewijn R Hofwegen H \nUse of enzyme-linked immunosorbent assay and dipstick assay for detection of Strongyloides stercoralis infection in humans . J Clin Microbiol \n2007 ;45 :438 –42 .17151215 \n[9] Henriquez-Camacho C Gotuzzo E Echevarria J \nIvermectin versus albendazole or thiabendazole for Strongyloides stercoralis infection . Cochrane Database Syst Rev \n2016 ;18 :CD007745 .\n[10] Suputtamongkol Y Premasathian N Bhumimuang K \nEfficacy and safety of single and double doses of ivermectin versus 7-day high dose albendazole for chronic strongyloidiasis . PLoS Negl Trop Dis \n2011 ;5 :e1044 .21572981 \n[11] Rego Silva J Macau RA Mateus A \nSuccessful treatment of strongyloides stercoralis hyperinfection in a kidney transplant recipient: case report . Transplant Proc \n2018 ;50 :861 –6 .29661454 \n[12] Glenn K Lindholm DA Meis G \nCase report: a case of recurrent strongyloides stercoralis colitis in a patient with multiple myeloma . Am J Trop Med Hyg \n2017 ;97 :1619 –22 .29140233 \n[13] Abdullah A Winnicka L Raghu C \nDisseminated strongyloidiasis in association with nephrotic syndrome . Case Rep Nephrol Dial \n2018 ;8 :155 –60 .30197904 \n[14] Wong TY Szeto CC Lai FF \nNephrotic syndrome in strongyloidiasis: remission after eradication with anthelmintic agents . Nephron \n1998 ;79 :333 –6 .9678435 \n[15] Miyazaki M Tamura M Kabashima N \nMinimal change nephrotic syndrome in a patient with strongyloidiasis . Clin Exp Nephrol \n2010 ;14 :367 –71 .20224878 \n[16] Seet RC Lau LG Tambyah PA \nStrongyloides hyperinfection and hypogammaglobulinemia . Clin Diagn Lab Immunol \n2005 ;12 :680 –2 .15879034 \n[17] Mitsunaga M Miyauchi N Akiyama Y \nA case of strongyloidiasis hyperinfection during oral corticosteroid therapy associated with a nephrotic patient infected with HTLV-1 . Nihon Ronen Igakkai Zasshi \n2003 ;40 :397 –401 .12934572 \n[18] Yee YKLC Yung CY Que TL \nStrongyloidiasis as a possible cause of nephrotic syndrome . Am J Kidney Dis \n1999 ;33 :e4 .\n[19] Mobley CM Dhala A Ghobrial RM \nStrongyloides stercoralis in solid organ transplantation: early diagnosis gets the worm . Curr Opin Organ Transplant \n2017 ;22 :336 –44 .28562417 \n[20] Huang L Gebreselassie NG Gagliardo LF \nEosinophils mediate protective immunity against secondary nematode infection . J Immunol \n2015 ;194 :283 –90 .25429065 \n[21] Rajamanickam A Munisankar S Bhootra Y \nElevated systemic levels of eosinophil, neutrophil, and mast cell granular proteins in strongyloides stercoralis infection that diminish following treatment . Front Immunol \n2018 ;9 :207 .29479356 \n[22] Anuradha R Munisankar S Dolla C \nParasite antigen-specific regulation of Th1, Th2, and Th17 responses in strongyloides stercoralis infection . J Immunol \n2015 ;195 :2241 –50 .26202988\n\n",
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"abstract": "Drug reaction with eosinophilia and systemic symptoms (DRESS) is a severe adverse drug reaction that can affect any age group. We carried out a prospective study of the clinicoepidemiologic aspects of DRESS in children. We prospectively studied all patients ages 12 years and younger admitted to the departments of pediatrics and dermatology at a tertiary care hospital over a 3-year period with probable or definite DRESS, defined based on the RegiSCAR scoring system. A total of 11 patients were studied. Lamotrigine (four patients) and pencillins (three patients) were the most common offending drugs. Not adhering to the standard guidelines of introduction and gradual titration of lamotrigine to therapeutic dose may have increased the chance of lamotrigine-induced DRESS. A short latent period between the onset of drug intake and drug reaction was noted in DRESS induced by antibiotics.",
"affiliations": "Department of Dermatology, Government Medical College, Kozhikode, Kozhikode, Kerala, India.;Department of Pediatrics, Government Medical College, Kozhikode, Kozhikode, Kerala, India.;Department of Dermatology, Government Medical College, Kozhikode, Kozhikode, Kerala, India.;Department of Dermatology, Government Medical College, Kozhikode, Kozhikode, Kerala, India.;Department of Dermatology, Government Medical College, Kozhikode, Kozhikode, Kerala, India.;Department of Pediatrics, Government Medical College, Kozhikode, Kozhikode, Kerala, India.;Department of Pediatrics, Government Medical College, Kozhikode, Kozhikode, Kerala, India.;Department of Dermatology, Government Medical College, Kozhikode, Kozhikode, Kerala, India.",
"authors": "Sasidharanpillai|Sarita|S|;Sabitha|Sasidharanpillai|S|;Riyaz|Najeeba|N|;Binitha|Manikoth P|MP|;Muhammed|Kunnummal|K|;Riyaz|Arakkal|A|;Jayakrishnan|Machinary P|MP|;Reyila|Vengarakath P|VP|",
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] |
{
"abstract": "OBJECTIVE\nTo investigate patient-reported visual function among individuals taking pentosan polysulfate (PPS) for interstitial cystitis.\n\n\nMETHODS\nA 27-item online survey was distributed to an international mailing list of individuals with interstitial cystitis in November 2018. Demographic characteristics, PPS exposure history, subjective visual function, and previous macular diagnoses were queried. The impact of PPS use, grouped by tertile of cumulative exposure, on visual function and macular diagnoses was assessed with multivariate logistic regression.\n\n\nRESULTS\nThe survey was completed by 912 respondents. Eight hundred and sixty-one (96.4%) were women, and the median age was 55 [interquartile range (IQR), 45-64 years]. Among PPS users, the median exposure was 547.5 g (IQR, 219-1,314 g). Respondents in the highest PPS exposure tertile were more likely to report difficulty with reading small print [adjusted odds ratio 2.29, 95% confidence interval (CI) 1.15-4.57] and to have a diagnosis of macular degeneration and/or pigmentary maculopathy (adjusted odds ratio 2.41, 95% CI 1.44-4.03) than unexposed respondents.\n\n\nCONCLUSIONS\nIn this large sample of individuals with interstitial cystitis, those in the highest PPS exposure category were more likely to have difficulties reading small print and to report a previous diagnosis of macular disease. Further study of objective measures of visual function in PPS users is warranted.",
"affiliations": "Emory University School of Medicine, Atlanta, Georgia.;Department of Family and Preventive Medicine, Emory University School of Medicine, Atlanta, Georgia; and.;Department of Ophthalmology, Emory University School of Medicine, Atlanta, Georgia.",
"authors": "Uner|Ogul E|OE|;Shah|Megha K|MK|;Jain|Nieraj|N|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1097/IAE.0000000000003078",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0275-004X",
"issue": "41(7)",
"journal": "Retina (Philadelphia, Pa.)",
"keywords": null,
"medline_ta": "Retina",
"mesh_terms": null,
"nlm_unique_id": "8309919",
"other_id": null,
"pages": "1562-1569",
"pmc": null,
"pmid": "33332810",
"pubdate": "2021-07-01",
"publication_types": "D016428:Journal Article",
"references": "31004677;21220632;31486843;21683389;31725711;14816304;32085877;25245489;9146008;7688432;21945281;6191049;29972328;25623737;9145997;29801663",
"title": "PENTOSAN POLYSULFATE AND VISION: Findings from an International Survey of Exposed Individuals.",
"title_normalized": "pentosan polysulfate and vision findings from an international survey of exposed individuals"
} | [
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"activesubstancename": "PENTOSAN POLYSULFATE SODIUM"
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"reactionmeddrapt": "Maculopathy",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
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},
"primarysource": {
"literaturereference": "E UNER O, JAIN N, SHAH M, E UNER O. PENTOSAN POLYSULFATE AND VISION: FINDINGS FROM AN INTERNATIONAL SURVEY OF EXPOSED INDIVIDUALS. RETINA PUBLISH AHEAD OF PRINT.",
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{
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},
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"reactionmeddraversionpt": "23.1",
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},
{
"reactionmeddrapt": "Retinal dystrophy",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Optic disc drusen",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Retinal pigment epitheliopathy",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Retinal disorder",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Stargardt^s disease",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Cone dystrophy",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
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"transmissiondate": "20210114"
}
] |
{
"abstract": "An 18 month-old boy underwent endoscopic foreign body removal under anesthesia on an outpatient basis and the operation took approximately 5 minutes. Stridor developed in both lung fields 6 hours after emergence from anesthesia, and severe croup developed, with cyanosis of the lips and aggravated stridor 20 hours after the end of the procedure. The croup resolved with oxygen therapy, intravenous dexamethasone, and epinephrine nebulization therapy. In this report, we suggest that thorough investigations of the patient's past history, including history of any airway problems, and careful monitoring after emergence from anesthesia be done in order to decide the proper discharge time of the patient. Further, proper prophylaxis following risk stratification is important, especially in patients at high risk of postoperative airway obstruction.",
"affiliations": "Department of Anesthesiology and Pain Medicine, Keimyung University School of Medicine, Daegu, Korea.;Department of Anesthesiology and Pain Medicine, Keimyung University School of Medicine, Daegu, Korea.;Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Daegu, Korea.",
"authors": "Kim|Hyun Jee|HJ|;Son|Je Do|JD|;Kwak|Kyung-Hwa|KH|",
"chemical_list": null,
"country": "Korea (South)",
"delete": false,
"doi": "10.4097/kjae.2014.67.4.287",
"fulltext": "\n==== Front\nKorean J AnesthesiolKorean J AnesthesiolKJAEKorean Journal of Anesthesiology2005-64192005-7563The Korean Society of Anesthesiologists 10.4097/kjae.2014.67.4.287Case ReportUnexpected and severe postintubation croup after a very short day surgery in a pediatric patient: a case report Kim Hyun Jee 1Son Je Do 1Kwak Kyung-Hwa 21 Department of Anesthesiology and Pain Medicine, Keimyung University School of Medicine, Daegu, Korea.2 Department of Anesthesiology and Pain Medicine, Kyungpook National University School of Medicine, Daegu, Korea.Corresponding author: Hyun Jee Kim, M.D., Ph.D., Department of Anesthesiology and Pain Medicine, Keimyung University School of Medicine, 56, Dalseong-ro, Jung-gu, Daegu 700-712, Korea. Tel: 82-53-250-7232, Fax: 82-53-250-7240, [email protected] 2014 27 10 2014 67 4 287 289 22 3 2013 13 6 2013 13 6 2013 Copyright © the Korean Society of Anesthesiologists, 20142014This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.An 18 month-old boy underwent endoscopic foreign body removal under anesthesia on an outpatient basis and the operation took approximately 5 minutes. Stridor developed in both lung fields 6 hours after emergence from anesthesia, and severe croup developed, with cyanosis of the lips and aggravated stridor 20 hours after the end of the procedure. The croup resolved with oxygen therapy, intravenous dexamethasone, and epinephrine nebulization therapy. In this report, we suggest that thorough investigations of the patient's past history, including history of any airway problems, and careful monitoring after emergence from anesthesia be done in order to decide the proper discharge time of the patient. Further, proper prophylaxis following risk stratification is important, especially in patients at high risk of postoperative airway obstruction.\n\nAmbulatory surgical proceduresCroup\n==== Body\nA very brief time of surgery may make clinicians tend to overlook prophylaxis of anesthetic complications. Prophylaxis of postextubation airway obstruction in high-risk patients is always important, especially in pediatric patients. The incidence of postintubation croup is known to be 0.1-1% [1]. Postintubation croup shows characteristic symptoms and signs such as inspiratory wheezing, barking cough, hoarseness, and inspiratory dyspnea, and is likely to develop from immediately after extubation to 3 hours after. Symptoms that require treatment usually become clear within the first hour after extubation [2]. The authors report a case of a pediatric patient who experienced severe croup 20 hours after simple endoscopic foreign body removal under short-term general anesthesia.\n\nCase Report\nAn 18-month-old male patient, weighing 12 kg, was scheduled for removal of foreign body of the upper gastrointestinal tract using endoscopy under anesthesia on an outpatient basis. The patient was delivered vaginally at 39 weeks gestational age, weighing 3,180 g. He was diagnosed with a tracheoesophageal fistula and went through tracheoesophageal fistula ligation and end-to-end anastomosis 2 days after birth. On his 25th day, he was diagnosed with infantile hypertrophic pyloric stenosis and underwent pyloromyotomy. 40 days after birth, esophageal stricture was found and tracheal dilation with ballooning was done by endoscopy.\n\nPreoperative evaluation showed no abnormality in the physical examination, electrocardiagraphy, and chest X-ray. A general anesthesia was planned with endotracheal intubation, given the the patient's past medical history and age. For premedication, glycopyrrolate 0.05 mg was injected intramuscularly 30 minutes before the operation. Anesthesia was induced with intravenous thiopental 60 mg, and then manual ventilation via a face mask with sevoflurane 8% and O2 100% was applied. While trying to intubate the patient with a tracheal tube of internal diameter 4.0 mm, resistance was felt right after the tube was passed through the vocal cords, so we replaced the tracheal tube with one with an internal diameter of 3.5 mm, and then intubation was completed successfully. The cuff on the tracheal tube was not inflated. Sevoflurane 2.0-2.5 vol%, and N2O 1.5 L/min, O2 1.5 L/min were used for maintenance and N2O was stopped as soon as the foreign body was pulled out. During the endoscopic procedure, the heart rate was maintained at 110-130 beats/min, SpO2 100%, systolic blood pressure 70-85 mmHg, end-tidal CO2 (ETCO2) 32-38 mmHg, and body temperature 37.0℃. Endoscopic removal of the foreign body, which seemed to be some kind of food material, took approximately 5 minutes. During the procedure, the patient recovered spontaneous breathing, and extubation was done right after the procedure was completed. Supportive ventilation via a face mask was given until the patient recovered consciousness. The patient was transferred to the ward after observation for 20 minutes in the recovery room. The heart rate was 110 beats/min, respiratory rate was 28 /min, and body temperature was 37.3N2 when the patient arrived in the ward.\n\n6 hours after the procedure, the general condition of the patient was unremarkable except that his body temperature was slightly high and there was mild stridor in both upper lung fields. Dexamethasone 5 mg was injected intramuscularly owing to the absence of an IV line and the discharge plan was canceled. Tepid massage was performed and the body temperature fell from 37.4 to 37.0N2. While sleeping, the patient had dyspnea and cyanosis of the lips and the stridor in both upper lung fields became worse 20 hours after the procedure. The SpO2 at that time was 70%. A mask of O2 7 L/min, dexamethasone 2.5 mg intravenous, and epinephrine 1 : 1,000 2.5 ml nebulization for 10 minutes were used for treatment. SpO2 rose to 100% 20 minutes after treatment and the patient was transferred to the intensive care unit (ICU). Heart rate was 170 beats/min, respiratory rate was 46 /min, and temperature was 36.9N2 right after arriving in the ICU. After 6 hours of oxygen therapy, he was transferred to the general ward, with stable vital signs, and he was discharged without any symptoms the next day.\n\nDiscussion\nRisk factors for postintubation croup are age between 1 and 4 years, anesthetic time longer than 1 hour, coughing on the endotracheal tube, traumatic intubation, tight-fitting endotracheal tube, changes in position during surgery, patient position other than supine, and repeated attempts to intubate [1]. In this case, the patient's past history of a tracheoesophageal fistula operation could have caused tracheal narrowing. Further, leakage was not found until the airway pressure was 25 cmH2O. Consequently, the risk factors of postoperative airway obstruction in this case are the age of 2, repeated intubation attempts, and a tight-fitting endotracheal tube. Recently, cuffed tracheal tubes are thought to be acceptable for use in pediatric patients except for premature babies and newborns [1,3]. We used a cuffed tracheal tube but the cuff was not inflated as adequate airway pressure and tidal volume were achieved without inflation. In adult patients, the risk factors of laryngeal injury or edema are longer duration of intubation, lack of use of neuromuscular blocking agents, smaller patient's height/tracheal tube size ratio, absence of tube leak, and female gender [4,5]. But the sensitivity of the air-leak test in predicting post-extubation laryngeal edema in pediatric patients is low [6].\n\nTo prevent coughing while intubated, asleep extubation or a painkiller given before extubation is used. Other than that, lidocaine 1.5 mg/kg with close monitoring can be used for smooth extubation. In this case, extubation was done smoothly without coughing while the patient was still asleep. Administration of multiple doses of dexamethasone prior to extubation can be helpful for children with multiple airway manipulations who have been intubated for more than 24 hours [7]. Although we did not expect postoperative airway complications in this patient owing to the brief duration of the procedure, if dexamethasone had been administered prophylactically, postroperative croup may not have developed or may not have been as severe. That is to say, early identification of patients with an increased risk of developing laryngeal edema that can evolve into respiratory failure can facilitate prevention or early treatment of this condition.\n\nThe croup scoring system most commonly used is the Westley clinical score [8]. In this patient, a score of mild severity was applicable at 6 hours after the surgery, and a score of high severity was relevant at 20 hours. The treatment modalities are dexamethasone and nebulized epinephrine. The most commonly studied dexamethasone dose is 0.6 mg/kg; however, a dose as low as 0.15 mg/kg may be just as effective, and oral dosing of dexamethasone has a similar effect as intramuscular administration [9]. As dexamethasone's half-life is 36-54 hours, serum dexamethasone levels which were at therapeutic levels and epinephrine nebulization must have resolved the upper airway obstruction when severe croup developed in this case. Other than dexamethasone, the inhalant form of budesonide is helpful in acute exacerbation of croup because it causes strong vasocontriction with fast action, and furthermore, its systemic effects are minimal [1,10].\n\nShort and simple procedures are appropriate for ambulatory surgery setting. Because airway problems in pediatric patients are an important and emergent problem, thorough investigation of a past history of airway problems and careful observation after emergence from general anesthesia should be done in order to decide when the patient should be discharged. Moreover, proper prophylaxis such as dexamethasone administration is important in pediatric patients who have risk factors for postoperative airway obstruction even if they have very brief surgery.\n\nAcknowledgments\nThis work was supported by the Bisa Research Grant of Keimyung University in 2013.\n==== Refs\n1 Coté CJ Lerman J Todres ID A practice of anesthesia for infants and children 4th ed Philadelphia WB Saunders 2009 250 253 \n2 Wetchler BV Outpatient anesthesia. What are the problems in the recovery room? Can J Anaesth 1991 38 890 894 1742824 \n3 Newth CJ Rachman B Patel N Hammer J The use of cuffed versus uncuffed endotracheal tubes in pediatric intensive care J Pediatr 2004 144 333 337 15001938 \n4 Tadié JM Behm E Lecuyer L Benhmamed R Hans S Brasnu D Post-intubation laryngeal injuries and extubation failure: a fiberoptic endoscopic study Intensive Care Med 2010 36 991 998 20237758 \n5 Wittekamp BH van Mook WN Tjan DH Zwaveling JH Bergmans DC Clinical review: post-extubation laryngeal edema and extubation failure in critically ill adult patients Crit Care 2009 13 233 20017891 \n6 Mhanna MJ Zamel YB Tichy CM Super DM The \"air leak\" test around the endotracheal tube, as a predictor of postextubation stridor, is age dependent in children Crit Care Med 2002 30 2639 2643 12483052 \n7 Lukkassen MA Markhorst DG Does dexamethasone reduce the risk of extubation failure in ventilated children? Arch Dis Child 2006 91 791 793 16923866 \n8 Westley CR Cotton EK Brooks JG Nebulized racemic epinephrine by IPPB for the treatment of croup: a double-blind study Am J Dis Child 1978 132 484 487 347921 \n9 Kliegman RM Stanton BF St. Geme JW Schor NF Behrman RE Nelson Textbook of Pediatrics 19th ed Philadelphia Elsevier Sanunders 2011 1445 1448 \n10 Choi BH Son KB Shim JY Hong S-J Prospective Randomized Study Comparing L-epinephrine and Budesonide Aerosols in the Treatment of Moderate to Severe Croup J Korean Pediatr Soc 1999 42 40 46\n\n",
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"abstract": "We conducted a prospective phase II trial of pentostatin, cyclophosphamide and rituximab as initial therapy for patients with previously untreated advanced stage low-grade or indolent B-cell lymphomas (iNHLs). Of 83 evaluable patients, 91·6% attained an overall response and 86·8% a complete or unconfirmed complete response. The 3-year progression-free survival (PFS) and overall survival rates were 73% and 93%, respectively. The 3-year PFS rate was significantly different for different diagnoses (P = 0·01): 83% [95% confidence interval (CI): 0·72, 0·96] for follicular lymphomas, 73% (95% CI: 0·54, 1·0) for marginal zone lymphomas and 61% (95% CI: 0·46, 0·81) for small lymphocytic lymphomas. The most common adverse events were haematological. Of 509 cycles of chemotherapy administered, grade 3 or 4 neutropenia was reported in 68 cycles (13% of cycles administered) and most frequently occurred during cycles 4-6. This is the first report demonstrating the effectiveness of pentostatin, cyclophosphamide and rituximab in patients with previously untreated iNHLs, including those over 60 years of age.",
"affiliations": "Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Biostatistics, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Hematopathology, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.;Department of Lymphoma and Myeloma, The University of Texas MD Anderson Cancer Center, Houston, TX, USA.",
"authors": "Samaniego|Felipe|F|;Hagemeister|Fredrick|F|;Romaguera|Jorge E|JE|;Fanale|Michelle A|MA|;Pro|Barbara|B|;McLaughlin|Peter|P|;Rodriguez|M Alma|MA|;Neelapu|Sattva S|SS|;Fayad|Luis|L|;Younes|Anas|A|;Feng|Lei|L|;Berkova|Zuzana|Z|;Khashab|Tamer|T|;Sehgal|Lalit|L|;Vega-Vasquez|Francisco|F|;Kwak|Larry W|LW|",
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"title": "Pentostatin, cyclophosphamide and rituximab for previously untreated advanced stage, low-grade B-cell lymphomas.",
"title_normalized": "pentostatin cyclophosphamide and rituximab for previously untreated advanced stage low grade b cell lymphomas"
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{
"abstract": "Tuberculosis (TB) has become a global concern due to its increasing incidence, particularly in immunocompromised patients, closely following the migratory patterns of populations. TB pyomyositis is a rare extrapulmonary manifestation of TB. Its clinical presentation varies and requires a high degree of suspicion for early diagnosis. We present three patients diagnosed with TB pyomyositis: a 46-year-old man with dermatomyositis (DM) and hepatitis B who presented with fever, muscle weakness, and an abscess at the right proximal arm; a 71-year-old immunocompetent male, with a past medical history of tuberculous lymphadenopathy in childhood, who presented with a 2-month history of fever and pain at the right thigh, and a 44-year-old woman with systemic lupus erythematosus (SLE) on prednisone and methotrexate who presented with skin eruption at her thighs mimicking lupus panniculitis. In all three patients, Mycobacterium tuberculosis was identified as the causative agent. The lack of specific signs, the false negative tuberculin skin test in some cases, and the unfamiliarity of many clinicians with this entity can cause diagnostic delays. Prompt diagnosis requires a high index of suspicion especially in immunocompromised patients with fever.",
"affiliations": "Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, 41 110, Greece.;Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, 41 110, Greece.;Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, 41 110, Greece.;Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, 41 110, Greece.;Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, 41 110, Greece.;Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, 41 110, Greece.;Department of Rheumatology, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, 41 110, Greece.;Department of Orthropaedic Surgery and Musculoskeletal Trauma, Faculty of Medicine, School of Health Sciences, University of Thessaly, Larissa, 41 110, Greece. [email protected].",
"authors": "Simopoulou|Theodora|T|;Varna|Areti|A|;Dailiana|Zoe|Z|;Katsiari|Christina|C|;Alexiou|Ioannis|I|;Basdekis|Georgios|G|;Malizos|Konstantinos N|KN|;Sakkas|Lazaros I|LI|",
"chemical_list": null,
"country": "Germany",
"delete": false,
"doi": "10.1007/s10067-014-2564-8",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0770-3198",
"issue": "35(4)",
"journal": "Clinical rheumatology",
"keywords": "Muscle abscess; Mycobacterium; Pyomyositis; Tuberculosis",
"medline_ta": "Clin Rheumatol",
"mesh_terms": "D000038:Abscess; D000328:Adult; D000368:Aged; D003882:Dermatomyositis; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D008180:Lupus Erythematosus, Systemic; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009132:Muscles; D009169:Mycobacterium tuberculosis; D052880:Pyomyositis; D016896:Treatment Outcome; D014376:Tuberculosis",
"nlm_unique_id": "8211469",
"other_id": null,
"pages": "1105-10",
"pmc": null,
"pmid": "24609759",
"pubdate": "2016-04",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": "2294789;12473721;21454737;11242210;12826705;23905092;14939816;19885661;10348455;23919207;426186;7562766;18039359;18780002;21732022;22081197;7548524;11417755;10809836;13714049;10930768;16145077;11721168",
"title": "Tuberculous pyomyositis: a re-emerging entity of many faces.",
"title_normalized": "tuberculous pyomyositis a re emerging entity of many faces"
} | [
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{
"abstract": "Neuropsychological services are considered an essential component of specialized epilepsy centers. In such a multidisciplinary setting, neuropsychologists interact regularly with other professionals involved in epilepsy patients' care. For these other professionals, this article provides an overview of the background of neuropsychologists, the services they provide, and how their findings contribute to the evaluation of the epilepsy patient. Two case examples are included to illustrate how neuropsychological evaluations are employed in the epilepsy monitoring unit setting.",
"affiliations": null,
"authors": "Kirlin|Kristin A|KA|;Locke|Dona E C|DE|",
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"country": "United States",
"delete": false,
"doi": "10.1080/21646821.2014.11106810",
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"issn_linking": "2164-6821",
"issue": "54(3)",
"journal": "The Neurodiagnostic journal",
"keywords": null,
"medline_ta": "Neurodiagn J",
"mesh_terms": "D004827:Epilepsy; D006801:Humans; D008991:Monitoring, Physiologic; D009483:Neuropsychological Tests; D009484:Neuropsychology",
"nlm_unique_id": "101573167",
"other_id": null,
"pages": "289-98",
"pmc": null,
"pmid": "25351036",
"pubdate": "2014-09",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "The role of neuropsychology on an epilepsy monitoring unit: a peek behind the \"do not disturb\" sign.",
"title_normalized": "the role of neuropsychology on an epilepsy monitoring unit a peek behind the do not disturb sign"
} | [
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"abstract": "Stenotrophomonas maltophila (S.maltophila) is an aerobic Gram-negative bacillus that is a frequent colonizer of fluids used in the hospital setting. The organism is known to cause life threatening infections in immuno-compromised patients especially in those who are neutropenic, on chemotherapy or on broad spectrum antibiotics. We report a case of ventilator associated pneumonia caused by Stenotrophomonas maltophila in a two-month old infant who later developed multi organ dysfunction syndrome. In seriously ill paediatric patients, S.maltophila should also be considered as a possible pathogen for Ventilator-Associated Pneumonia (VAP), hence empiric antibiotic choice should include antimicrobials that are active against S. maltophila. An early identification and treatment of VAP with Multi-Drug Resistant (MDR) strains with appropriate antibiotics has a significant impact on morbidity and mortality.",
"affiliations": "Associate Professor, Department of Microbiology, MediCiti Institute of Medical Sciences (MIMS) , Hyderabad, Telangana, India .;Head of Department, Department of Microbiology, Pathcare Labs , Hyderabad, Telangana, India .;Associate Professor, Department of Pediatrics, MIMS , Hyderabad, Telangana, India .;Assistant Professor, Department of Pediatrics, MIMS , Hyderabad, Telangana, India .;Assistant Professor, Department of Pediatrics, MIMS , Hyderabad, Telangana, India .",
"authors": "Angaali|Neelima|N|;Roy|Nina Dutta|ND|;Chitgupikar|Sudharshan Raj|SR|;Subramanian|Preeti|P|;Pabbati|Jaya Lakshmi|JL|",
"chemical_list": null,
"country": "India",
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"doi": "10.7860/JCDR/2016/19822.8411",
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"issn_linking": "0973-709X",
"issue": "10(9)",
"journal": "Journal of clinical and diagnostic research : JCDR",
"keywords": "Cefotaxime; Endo Tracheal Aspirate; Hypotension; Multi Drug Resistant Strains",
"medline_ta": "J Clin Diagn Res",
"mesh_terms": null,
"nlm_unique_id": "101488993",
"other_id": null,
"pages": "DD01-DD03",
"pmc": null,
"pmid": "27790437",
"pubdate": "2016-09",
"publication_types": "D002363:Case Reports",
"references": "15095221;11555535;9041440;19219287;15699079;22645207;589735;18579427;17219003;17334747;12536991;9476869;25029020",
"title": "Ventilator Associated Pneumonia in an Infant Caused by Stenotrophomonas maltophila - A Case Report.",
"title_normalized": "ventilator associated pneumonia in an infant caused by stenotrophomonas maltophila a case report"
} | [
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{
"abstract": "The aim of this cohort study was to determine the characteristics and clinical outcome of 287 patients with drug-induced liver injury (DILI) in a Chinese hospital.Between January 2008 and January 2013, individuals who were diagnosed with DILI were selected. The complete medical records of each case were reviewed, and factors for the outcome of patients with DILI were extracted and analyzed using univariate and multivariate analysis.Two hundred eighty-seven cases identified as DILI were included in the study. A total of 105 different drugs were considered to be related to the hepatotoxicity. The main causative group of drugs was Chinese herb (n = 111). Liver failure developed in 9 (3.1%) patients, and 2 died (0.7%). Overall, complete recovery occurred in 92 (32.1%) patients. Univariate analysis and binary logistic regression analysis identified the digestive symptoms, jaundice, total bilirubin (TBIL), and direct bilirubin (DBIL) as independent factors for the non-recovery of DILI. Then the prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, was built by using binary logistic regression analysis again. Receiver operating characteristic curve validated the strong power (area under the curve (AUC) = 0.907) of prediction model for predicting the DILI non-recovery.DILI is an important cause of liver test abnormalities, and Chinese herb represented the most common drug group. The factors such as digestive symptoms, jaundice, TBIL, and DBIL have effect on DILI outcomes. The prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, established in this study is really an excellent predictive tool for non-recovery of DILI patients.",
"affiliations": "Department of Infectious Diseases and Hepatology, Huashan Hospital, Fudan University, Shanghai, China.",
"authors": "Chen|Sheng-Sen|SS|;Yu|Kang-Kang|KK|;Huang|Chong|C|;Li|Ning|N|;Zheng|Jian-Ming|JM|;Bao|Su-Xia|SX|;Chen|Ming-Quan|MQ|;Zhang|Wen-Hong|WH|",
"chemical_list": "D004365:Drugs, Chinese Herbal",
"country": "United States",
"delete": false,
"doi": "10.1097/MD.0000000000004683",
"fulltext": "\n==== Front\nMedicine (Baltimore)Medicine (Baltimore)MEDIMedicine0025-79741536-5964Wolters Kluwer Health 2755997610.1097/MD.0000000000004683046834500Research ArticleObservational StudyThe characteristics and clinical outcome of drug-induced liver injury in a Chinese hospital A retrospective cohort studyChen Sheng-Sen MDYu Kang-Kang PhDHuang Chong PhDLi Ning PhDZheng Jian-Ming MDBao Su-Xia PhDChen Ming-Quan MD, PhD∗Zhang Wen-Hong MD, PhD∗Tarantino. Giovanni Department of Infectious Diseases and Hepatology, Huashan Hospital, Fudan University, Shanghai, China.∗ Correspondence: Ming-Quan Chen, Department of Infectious Diseases and Hepatology of Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China (e-mail: [email protected]), Wen-Hong Zhang, Department of Infectious Diseases and Hepatology of Huashan Hospital, Fudan University, 12 Middle Urumqi Road, Shanghai 200040, China (e-mail: [email protected]).8 2016 26 8 2016 95 34 e46831 4 2016 7 7 2016 3 8 2016 Copyright © 2016 the Author(s). Published by Wolters Kluwer Health, Inc. All rights reserved.2016This is an open access article distributed under the Creative Commons Attribution-NonCommercial-NoDerivatives License 4.0, where it is permissible to download, share and reproduce the work in any medium, provided it is properly cited. The work cannot be changed in any way or used commercially. http://creativecommons.org/licenses/by-nc-nd/4.0Supplemental Digital Content is available in the text\n\nAbstract\nThe aim of this cohort study was to determine the characteristics and clinical outcome of 287 patients with drug-induced liver injury (DILI) in a Chinese hospital.\n\nBetween January 2008 and January 2013, individuals who were diagnosed with DILI were selected. The complete medical records of each case were reviewed, and factors for the outcome of patients with DILI were extracted and analyzed using univariate and multivariate analysis.\n\nTwo hundred eighty-seven cases identified as DILI were included in the study. A total of 105 different drugs were considered to be related to the hepatotoxicity. The main causative group of drugs was Chinese herb (n = 111). Liver failure developed in 9 (3.1%) patients, and 2 died (0.7%). Overall, complete recovery occurred in 92 (32.1%) patients. Univariate analysis and binary logistic regression analysis identified the digestive symptoms, jaundice, total bilirubin (TBIL), and direct bilirubin (DBIL) as independent factors for the non-recovery of DILI. Then the prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, was built by using binary logistic regression analysis again. Receiver operating characteristic curve validated the strong power (area under the curve (AUC) = 0.907) of prediction model for predicting the DILI non-recovery.\n\nDILI is an important cause of liver test abnormalities, and Chinese herb represented the most common drug group. The factors such as digestive symptoms, jaundice, TBIL, and DBIL have effect on DILI outcomes. The prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, established in this study is really an excellent predictive tool for non-recovery of DILI patients.\n\nKeywords\nacute liver failuredrug-induced liver injuryhepatotoxicityrecoverytoxic hepatitisOPEN-ACCESSTRUE\n==== Body\n1 Introduction\nDrug-induced liver injury (DILI) is a serious common health problem in the general population.[1,2] It is the most common cause of acute liver failure (ALF) in the United States, accounting for more than 50% of cases;[3] thus DILI has been attracting increased attention over the past years.[4] The symptoms of DILI range from mildly elevated liver enzymes to severe hepatic damage requiring liver transplantation with poor transplant-free survival of the respective cases.[5] The epidemiology of DILI in the general population has not been well studied. According to reporting systems, the incidence rate of DILI in France and Spain was 14 and 34 cases per 100,000 individuals per year, respectively.[6,7] However, this number is likely underestimated because of the several limitations of the reporting systems.\n\nTo date, case reports and cohort studies have revealed numerous drugs that may cause hepatic damage. But only a minority of these medications have a dose-related and thus predictable hepatotoxicity,[8] as most of them display an idiosyncratic mode, either immune-mediated or metabolic.[9] Therefore, more studies are needed in order to quantify the risk of different drugs. In China, because of the huge population and multitude of drugs available, especially, the vast number of Chinese herbal medicines, DILI is becoming an increasingly serious health problem.[10] Many studies in China have revealed the drugs that lead to DILI and also involved the relevant clinical features and outcomes of DILI;[10–12] nevertheless, the results of these studies cannot well explain the relationships between clinical characteristics and outcomes of DILI. To further clarify the causes, clinical features, and outcomes of DILI in hospitalized patients, we conducted this study by retrospectively collecting the 5-year data of hospitalized patients diagnosed with DILI.\n\n2 Materials and methods\n2.1 Hospital\nHuashan Hospital, one of the accredited agencies of Joint Commission International (JCI), is a tertiary hospital with 1216 beds and annual admission rate of about 20,000 patients. The hospital's hepatology department has 60 faculties and 120 inpatient beds, with an average annual admission of 3300 patients.\n\n2.2 Patients\nBetween January 2008 and January 2013, a total of 287 consecutive patients diagnosed with DILI who were seen at Department of Infectious Diseases and Hepatology, Huashan Hospital, were retrospectively analyzed. The data were collected from hospitalized patients. A history, including the presence of medical illness, present and previous drug use, herbal remedies and mushroom intake, alcohol abuse, and drug addiction, was obtained for all patients and family members, if available. The final diagnoses and reasons for the inclusion and exclusion of the cases are shown in Fig. 1. Criteria for inclusion were age above 14 years; absence of confounding disease including acute (not the chronic) viral hepatitis (hepatitis A, B, C virus, cytomegalovirus, herpes simplex virus, and Epstein–Barr virus); convincing evidence of absent or minimal alcohol consumption, < 15 g alcohol/day for women and <20 g alcohol/day for men; exclusion of other forms of liver disease including autoimmune, metabolic liver disease such as hemochromatosis, Wilson disease, α-1 antitrypsin deficiency, and biliary obstruction; exclusion of renal diseases and severe heart diseases (mild and moderate heart diseases included); and elevation of alanine aminotransferase (ALT) or aspartate aminotransferase (AST) threefold above upper limit of normal (ULN) or an elevation of total bilirubin (TBIL) higher than 2 mg dL−1. Liver biopsies were available for evaluation in 36 patients with DILI.\n\nFigure 1 Flowchart summarizing the patient enrollment. ALT = alanine aminotransferase, AST = aspartate aminotransferase, DILI = drug-induced liver injury, NAFLD = nonalcoholic fatty liver disease, ULN = upper limit of normal.\n\n2.3 Data collection and abstraction\nData were abstracted and recorded in a standard form by 2 investigators and then reviewed in duplicate by another 3 investigators, all of whom accepted training to familiarize themselves with the performance of the data form at the commencement of the study. We recorded data as follows: general information (sex, age, occupation, height, weight, etc.), the comorbidity, and complications; diagnosis at admission and discharge, disease history (including history of allergies), and drinking history; information about the drug suspected to have caused the liver injury; symptoms and signs; results of biochemical examinations, including ALT, AST, serum TBIL, direct bilirubin (DBIL), alkaline phosphatase (ALP), gamma-glutamyl transpeptidase (GGT), creatinine (Cr), and blood routine examination results the first time DILI was diagnosed; results of laboratory tests for other liver diseases (including hepatitis A, B, C, D, E virus, cytomegalovirus, Epstein–Barr virus, and herpes virus infection, Wilson disease, autoimmune hepatitis, etc.); imaging and endoscopic results; and severity and outcome of DILI.\n\n2.4 Ethics statements\nAll data were anonymously analyzed without individual patient consent due to the retrospective nature of the study. This study protocol was approved by the institutional review boards at Fudan University and Huashan Hospital.\n\n2.5 Definition\nAfter the data were collected, we rediagnosed all the patients according to the American College of Gastroenterology (ACG) clinical guidelines for the diagnosis and management of idiosyncratic DILI.[13] The diagnosis of DILI was based on the patient's history, clinical and biochemical characteristics, and histologic criteria, when available. The diagnosis was based on clinical suspicion, exclusion of other forms of liver disease, and consideration of the relationships between suspicious drug intake and onset of liver test abnormalities. Patients with underlying liver disease such as in inactive hepatitis B virus (HBV) carrier or nonalcoholic fatty liver disease (NAFLD) having normal liver tests were included into the study if they developed superimposed DILI. HBV-DNA levels in inactive HBV carriers with elevated liver enzymes were also checked using polymerase chain reaction to rule out HBV reactivation.\n\nThe definition and pattern of DILI (hepatocellular, cholestatic, or mixed) were characterized based on the International Consensus Meeting criteria for liver injury.[14,15] Hepatocellular pattern of DILI was defined as the ratio (R) of serum ALT (as a multiple of its ULN) to serum ALP (as a multiple of its ULN) greater than 5, cholestatic as R less than 2, and mixed as R greater than 2 to less than 5.[14,15] Interval between suspicious drug intake and DILI recognition was defined as the time to onset from the beginning of the drug/herb.\n\nThe most widely accepted definition of ALF includes evidence of coagulation abnormality, usually an International Normalized Ratio (INR) ≥1.5, and any degree of mental alteration (encephalopathy) in a patient without preexisting cirrhosis and with an illness of <26 weeks’ duration.[16,17] Patients with DILI were defined as recovery when abnormal liver tests had returned to normal within 3 months for hepatocellular pattern of injury or within 6 months for cholestatic or mixed pattern of injury; if no recovery was observed and patients also did not develop into ALF, the patients were defined as chronicity.[7] Then ALF and chronicity patients were included into non-recovery group in this study.\n\n2.6 Statistical analyses\nKruskal–Wallis test was used for group comparisons and Fisher exact test for categorical variables. Mean ± SD was given for continuous measurements. Frequencies and percentiles were given for categorical data. Influence of cancer, infection, antineoplastic agents, and antibiotics on the patterns of liver injury was assessed by using multinomial logistic regression analysis. Binary logistic regression was used to evaluate the factors associated with clinical outcome of DILI. Odds ratios (ORs) and 95% confidence intervals (CIs) of ORs were given. In addition, the predictive accuracy of TBIL, DBIL, and DBIL/TBIL for patients’ outcome was assessed by receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC). A prediction model built by using significant variables obtained from binary logistic regression with P < 0.05. Then predictive power of the prediction model was also validated by ROC curve analysis. The optimal cutoff value was determined to maximize the sum of sensitivity and specificity. Differences were reported as statistically significant if the P value was less than 0.05. The data analyses were performed using SPSS 21.0 (IBM Corp., Armonk, NY) and Stata 12.0 (StataCorp., College Station, Texas).\n\n3 Results\n3.1 Study population\nFrom January 2008 to January 2013, a total of 7374 new patients with liver test abnormalities were seen in our hospital. Of those, a total of 287 patients (male/female: 123/164; mean age: 50.70 ± 16.98 years, range: 14 to 81 years) (3.9%) fulfilled the criteria of DILI; female sex was slightly predominant (57.1%); and 45 (15.7%) had known underlying liver disease with NAFLD and inactive HBV carrier status. A total of 105 different drugs were potential candidates for the hepatotoxicity. Cholestatic pattern of liver injury was most commonly observed (100 of 287, 34.8%) followed by mixed pattern (98 of 287, 34.1%) and hepatocellular pattern (89 of 287, 31.0%). The median interval between suspicious drug intake and DILI recognition was 30 days (interquartile range: 18 to 87 days). The interval period showed no significant difference among these 3 patterns (P = 0.870). Digestive symptoms (44.9%), dark urine (39.4%), fatigue (37.3%), and jaundice (16.4%) were the most frequent symptoms during admission. Digestive symptoms were more frequently associated with the hepatocellular pattern of injury (P = 0.027) and jaundice seemed related to the cholestatic pattern of injury (P = 0.035). No significant differences were observed between groups in terms of patient age, sex, and the presence of preexisting chronic liver disease (P > 0.05). The demographics and clinical and laboratory characteristics of the 287 patients with DILI are shown in Table 1. As regards comorbidities, 42 patients had infection, 38 had cancer (detailed information about cancer can be seen in Table S1), 28 had hypertension, 22 had autoimmune disease, 19 had diabetes mellitus, and 19 had hyperlipidemia. Among these complications, only cancer and infection were significantly different in 3 DILI patterns (P = 0.046 and P = 0.045).\n\nTable 1 Characteristics of patients with DILI based on the type of liver damage.\n\n3.2 Drug causality assessment in individual cases\nIn a total of 287 cases, the drug relationship according to the updated CIOMS scale was judged as at least “possible.” A total of 105 different drugs or herbs were identified in these 287 patients as being related to liver injury. Table S2 exhibits the drug or herbs assessed as “possible,” “probable,” and “highly probable.” Altogether, drugs of Chinese herbs (38.7%), antineoplastic agents (9.1%), nonsteroidal anti-inflammatory drugs (NSAIDs) (8.7%), and antibiotics (8.4%) were the groups represented the most (Table 1, Table S2). Additionally, as shown in Table 1, Chinese herbs (P = 0.041) and antineoplastic agents (P = 0.002) were significantly correlated with patterns of DILI, while antibiotics showed no relationship with 3 DILI patterns. Moreover, the multinomial logistic regression analysis, in which the factors such as antineoplastic agents, antibiotics, cancer, and infection were respectively included, was performed to deeply confirm whether these 4 variables were independent factors which affect the patterns of DILI. Finally, our results showed that antineoplastic agents, antibiotics, cancer, and infection were all not correlated with DILI patterns (Fig. 2 and Table S3).\n\nFigure 2 Influence of cancer, infection, antineoplastic agents, and antibiotics on the patterns of liver injury was evaluated by multinomial logistic regression analysis. 1 = hepatocellular vs mixed, 2 = cholestatic vs hepatocellular, 3 = mixed vs cholestatic.\n\n3.3 Clinical characteristics of patients with ALF\nAcute liver failure (ALF) based on American Association for the Study of Liver Diseases (AASLD) criteria[16] developed in 9 patients. Among these 9 patients, cholestatic was the most common pattern of injury (6 patients), 2 (1 hepatocellular pattern and 1 cholestatic pattern injury) died in the hospital, 3 were auto-discharged, and the remaining 4 patients (3 cholestatic pattern of injury and 1 mixed pattern of injury) became chronicity. All of the patients with ALF ranged from 16 to 62 years, 5 were male and 4 were female, and 3 had preexisting liver disease. Table S4 shows detailed information of the 9 patients with ALF.\n\n3.4 Univariate analysis and binary logistic regression analysis for factors associated with DILI outcomes\nIt is shown in Table 2 (univariate analysis) that non-recovery (including ALF and chronicity) developed in 195 patients (67.9%) (male/female: 81/114; mean age: 49.24 ± 16.79 years). Recovery occurred in 92 (32.1%) hospitalized patients within a mean of 20.38 ± 14.44 days (range: 7 to 180 days) after discontinuation of the implicated drug. Significant relationship was found between the characteristics (age, jaundice, ALP, TBIL, DBIL, hospitalization costs, diabetes, pattern of liver injury, and antineoplastic agents) and the development of different outcomes (P < 0.05). Other factors showed no association with patients’ outcomes (Table 2).\n\nTable 2 The association between patients’ outcomes and clinical characteristics (univariate analysis).\n\nIn order to further investigate independent factors associated with prognosis of DILI patients, multivariate binary logistic regression analysis was performed, and the results (Fig. 3 and Table 3) showed that presence of digestive symptoms and jaundice on admission were associated with non-recovery (digestive symptoms: OR = 1.626, P = 0.002; jaundice: OR = 2.447, P = 0.039), which means patients with digestive symptoms (nausea/vomiting/anorexia/abdominal discomfort) and jaundice were more likely to become non-recovery compared with patients without digestive symptoms and jaundice. It is also clear from Table 3 and Fig. 3 that TBIL and DBIL were the independent factors related with DILI prognosis (ORTBIL = 1.011, βTBIL = 0.011, PTBIL = 0.002; ORDBIL = 1.013, βDBIL = 0.013, PDBIL = 0.011), suggesting that individuals with non-recovery had higher level of TBIL and DBIL.\n\nFigure 3 Factors associated with non-recovery of drug-induced liver injury (DILI) patients after adjusting the confounders. 1 to 12 represent the serial numbers.\n\nTable 3 Factors for non-recovery studied by binary logistic regression.\n\n3.5 ROC curve assesses efficacy of TBIL, DBIL, and DBIL/TBIL for predicting DILI non-recovery\nWe considered non-recovery (yes vs not) as final diagnosis; TBIL, DBIL, and DBIL/TBIL were respectively regarded as diagnostic indicators. Then ROC curves were plotted by SPSS 21.0 to evaluate the predictive power of TBIL (Fig. 4A), DBIL (Fig. 4B), and DBIL/TBIL (Fig. 4C) for DILI patients’ non-recovery. The AUCs of the 3 ROC curves were 0.625, 0.621, and 0.615, severally (Fig. 4), and the 3 AUCs all were less than 0.70, indicating that TBIL, DBIL, and DBIL/TBIL did not have strong predictive power for DILI patients’ prognosis.\n\nFigure 4 Receiver operating characteristic (ROC) curves with TBIL (A), DBIL (B), and DBIL/TBIL (C) for predicting the non-recovery in drug-induced liver injury (DILI) patients. P value was calculated by the Delong test. DBIL = direct bilirubin, TBIL = total bilirubin.\n\n3.6 Prediction model establishment\nAfter plotting ROC curves, the independent factors such as digestive symptoms, jaundice, TBIL, and DBIL were together included into the binary logistic regression model again. Next, we built a prediction model and got the prediction probability for forecasting the clinical outcomes of DILI patients (each patient had a prediction probability, the details can be seen in Table S5). Then we took the prediction probability as test variable and the actual classification of clinical outcome as state variable (non-recovery vs recovery), and finally the ROC curve was plotted again by using SPSS 21.0 to determine predictive power of the prediction model. As shown in Fig. 5, the AUC of this model for predicting non-recovery was 0.907, and optimal cutoff prediction probability was 0.558, suggesting that DILI patient whose prediction probability is greater than 0.558 can be considered as non-recovery outcome according to the result of ROC curve (Fig. 5).\n\nFigure 5 Receiver operating characteristic (ROC) curve for determining the predictive power of the prediction model including digestive symptoms, jaundice, TBIL, and DBIL. P value was calculated by the Delong test. DBIL = direct bilirubin, TBIL = total bilirubin.\n\n4 Discussion\nEstablishing a diagnosis of DILI in an individual with elevated liver injury tests is often compelled because of the complete definition criteria of DILI. In fact, misdiagnosis and missed diagnosis for hospitalized patients are common, and there are still no standard diagnostic criteria for DILI in China. Most of the diagnoses are based on the physicians’ individual ability and experience, and the Roussel Uclaf Causality Assessment Method (RUCAM) causality assessment[18] is seldom used. Therefore, in this study, DILI diagnosis in each case was made on the basis of clinical assessment, biochemical parameters, and histologic evaluation when available. Complete recovery after the implicated drug withdrawal is an important diagnostic criterion for DILI. We also ruled out other causes of liver injury in the final analysis. As seen in Table 1, female sex showed slight predominance, cholestatic pattern of liver injury was most commonly observed (34.8%), followed by mixed pattern (34.1%), which was conflicted with other studies that showed hepatocellular as the most commonly observed pattern in individuals with DILI.[3,7] Hundreds of drugs available on the market have been implicated in hepatotoxicity. Antibiotics and NSAID are the most widely used medications worldwide.[1,6] As seen from our investigation, Chinese herbs represented the main causative group, followed by antineoplastic agents, NSAIDs, and antibiotics (Table 1), which is inconsistent with the results reported in earlier studies.[3,7,19] Therefore, the cholestatic pattern of liver injury was predominant in our series maybe due to the most common drug leading to the DILI. As the main causative group in our study, Chinese herbs were relevant with 3 DILI patterns (Table 1, P = 0.041) and they may lead the cholestatic pattern of liver injury to become predominant. However, the mechanism of how Chinese herbs affect the pattern of DILI still remains unknown and needs to be further studied.\n\nIn addition, epidemiological studies have established that increasing BMI (kg/m2) is associated with increased all-cause mortality,[20,21] and obesity is designated as a disease by American Medical Association. The prevalence of obesity is increasing worldwide in both developed and developing nations,[22] and the China Health and Nutrition Survey[23] reports that adult overweight prevalence nearly tripled from 1991 (11.7%) to 2009 (29.2%), leading to increasing concern in the public. Chinese herbal medicine is broadly accepted as safe and effective medication in China for the treatment of various ailments including obesity. They are believed to have effects on weight loss and other components of the metabolic syndrome, but good quality data on efficacy and side effects are lacking.[24,25] So obese patients are likely to take these so-called “safe” and “natural” products for losing weight, and a part of them may result in liver injury.[26]\n\nSeveral antibiotics have the potential to cause liver injury. The exact incidence of antibiotic-related liver injury is unknown. In this study, the percentage of antibiotic-related liver injury was 8.4% (24/287). Antibiotic-induced liver injury represents all patterns of liver injury and one antibiotic may cause more than one pattern of injury.[27,28] Several reasons can explain antibiotics as common implicated drug group related to hepatotoxicity, such as the high consumption of antibiotics in the general population, lax prescription policies concerning antibiotics in most countries including China, and also infection and inflammation increase the susceptibility of the liver to some drugs.[29] NSAIDs is also a common cause of DILI in our study, which was similar to the results reported in the Western countries and the United States.[3,6,7] Also, in this analysis, antineoplastic agents (26/287) seemed to be one main cause of DILI, the reason for this may be the increased incidence of cancer in China.[30] Furthermore, data of Table 1 reveal that antineoplastic agents, cancer, and infection have influence on the patterns of DILI. However, the comorbidity may be just the condition which drug was used (cancer: antineoplastic agent; infection: antibiotics) rather than itself that make different patterns of DILI. Therefore, we performed multinomial logistic regression analysis to confirm the influence of cancer, infection, antineoplastic agents, and antibiotics on the patterns of liver injury, and the results indicated that these 4 factors were not correlated with DILI patterns (Fig. 2 and Table S3).\n\nThe manifestation was mild in most of the patients, and some patients were even asymptomatic. Besides, the liver function of the patients rapidly improved after the hepatotoxic drugs were discontinued. These findings suggest that early detection of abnormal liver function and timely discontinuation of the drugs are very imperative. ALF developed in approximately 3.1% (9/287) of individuals with DILI in this study, and cholestatic pattern of injury was predominant (6/9) in patients with ALF (Table S4). Earlier studies conducted in Spain and in the United States[3,7] were evaluated to identify the risk factors for the development of ALF in individuals with DILI. Female sex, pattern of liver injury, and serum bilirubin level on admission were identified as risk factors for the development of ALF in the Spain Cohort study,[7] but not in the US study.[3] In this study, because of the limitation of the ALF patients’ number (only 9), the risk factors for the development of ALF were really hard to identify. The data from Spain[7] showed that the mortality rate of DILI was approximately 5.38% and the recovery patients accounted for the most percentage in the DILI series. Whereas, according to our research, the mortality rate of DILI was merely 0.697% (2/287), which showed the favorable prognosis and all of the mortality was liver related. Moreover, the number of recovery patients was lower than non-recovery patients in this study. Thus, compared with the Western series, our DILI series had low complete recovery and low mortality, and this phenomenon may be attributed to the different race of the patients in the Western and our study. The property difference between the Western and Chinese patients may lead to the different clinical outcomes. The influence of racial difference on the prognosis of DILI patients needs to be identified by a multiethnic study in the future.\n\nIn our research, 15.7% (45/287) of DILI individuals had preexisting liver disease. NAFLD and inactive HBV carrier status were the most common diagnoses among these preexisting liver diseases. It has been reported that NAFLD conveys a nearly fourfold increase of DILI risk in middle-aged patients,[31] which deserves great attention by physicians when treating NAFLD patients to avoid drugs with potential hepatotoxicity. Our data also demonstrated that preexisting liver disease in patients with DILI did not affect the patients’ prognosis (non-recovery vs recovery) (Table 2). Additionally, it can be seen from this study that non-recovery developed in 67.9% (195/287) of the individuals, and overall complete recovery occurred in 92 patients (32.1%) (Table 2). Although predictable factors associated with the clinical outcomes of DILI patients have been investigated in many countries,[3,6,7,19,32] the reliable data from China still seem lacking. Therefore, in this investigation, we further explored the risk factors related to DILI outcomes (non-recovery vs recovery). On our univariate analysis, the presence of jaundice on admission, age, ALP, TBIL, DBIL, hospitalization costs, diabetes, pattern of liver injury, and antineoplastic agents were associated with non-recovery or recovery of DILI patients (Table 2).\n\nAs univariate analysis (Fisher exact test and Kruskal–Wallis test) could hardly manage the interference existed among these variables, in order to identify the independent factors for recovery and non-recovery, a multivariate analysis must be used to determine the authenticity and validity of the prognostic factors detected from the univariate analysis. After that, binary logistic regression analysis was performed and the results demonstrated that digestive symptoms, jaundice, TBIL, and DBIL were independent factors for the non-recovery and recovery. As shown in Table 3 and Fig. 3, the groups with digestive symptoms and jaundice may have 1.626 and 2.447 times possibility of DILI non-recovery compared with their counterpart groups without digestive symptoms and jaundice. As TBIL and DBIL were continuous variables, the odds ratio just represented that the possibility of non-recovery or recovery change n-fold with one unit. Thereby, to further investigate the role of TBIL and DBIL in predicting DILI outcomes, we combined TBIL and DBIL together, and took DBIL/TBIL as a new factor for the prognosis of DILI patients. TBIL, DBIL, and DBIL/TBIL were respectively regarded as test variable, and then 3 ROC curves were plotted to evaluate the predictive power of these 3 variables (TBIL, DBIL, and DBIL/TBIL) for DILI patients’ outcomes (non-recovery vs recovery). Regrettably, the results from the ROC curve analyses indicated that TBIL (AUC = 0.625), DBIL (AUC = 0.621) and DBIL/TBIL (AUC = 0.615) did not have strong power for predicting non-recovery of DILI patients (Fig. 4). In order to seek a reliable method to predict the non-recovery of DILI patients, we ultimately developed a prediction model composed of the 4 variables (digestive symptoms, jaundice, TBIL, and DBIL) by using binary logistic regression analysis again. The strong power of the prediction model for predicting the non-recovery of DILI patients can be described by the ROC curve (AUC = 0.907, P < 0.001) (Fig. 5). The cutoff value of prediction probability (0.558) was also determined by ROC curve. Notably, the patient with prediction probability greater than 0.558 was considered as non-recovery in our study.\n\nIn conclusion, on the basis of the results of this study, DILI is one of the important causes of liver test abnormalities. Chinese herbal medicine was the main cause of DILI in hospitalized patients in China, followed by antineoplastic agents, NSAIDs, and antibiotics. Digestive symptoms, jaundice, TBIL, and DBIL were identified as independent factors associated with recovery and non-recovery. Furthermore, the prediction model, including digestive symptoms, jaundice, TBIL, and DBIL, firstly built in our study can be an excellent tool to predict non-recovery in DILI patients.\n\nSupplementary Material\nSupplemental Digital Content\n Abbreviations: ALF = acute liver failure, ALP = alkaline phosphatase, ALT = alanine aminotransferase, AST = aspartate aminotransferase, DBIL = direct bilirubin, DILI = drug-induced liver injury, GGT = gamma-glutamyl transpeptidase, NAFLD = nonalcoholic fatty liver disease, NSAIDs = nonsteroidal anti-inflammatory drugs, RUCAM = Roussel Uclaf Causality Assessment Method, TBIL = total bilirubin, ULN = upper limit of normal.\n\nAuthorship: All authors substantially contributed to conception (SSC, KKY) and design (SSC, MQC), or analysis (SSC) and interpretation of data (CH, NL, JMZ, SXB); drafting the manuscript (SSC) or revising it critically for important intellectual content (SSC); and final approval of the submitted manuscript (all authors). SSC and MQC had full access to all the data in the study and take responsibility for the accuracy and integrity of the data analysis.\n\nFunding/support: This study was not supported by any foundation.\n\nThe authors have no conflicts of interest to disclose.\n\nSupplemental digital Content is available for this article.\n==== Refs\nReferences\n1 Andres E \nDrug-induced hepatotoxicity . N Engl J Med \n2003 ; 349 :1974 –1976 .14626266 \n2 Grant LM Rockey DC \nDrug-induced liver injury . Curr Opin Gastroenterol \n2012 ; 28 :198 –202 .22450893 \n3 Chalasani N Fontana RJ Bonkovsky HL \nCauses, clinical features, and outcomes from a prospective study of drug-induced liver injury in the United States . Gastroenterology \n2008 ; 135 :1924 –1934 .e4 .18955056 \n4 Hayashi PH Fontana RJ \nClinical features, diagnosis, and natural history of drug-induced liver injury . Semin Liver Dis \n2014 ; 34 :134 –144 .24879979 \n5 Reuben A Koch DG Lee WM \nDrug-induced acute liver failure: results of a U.S. multicenter, prospective study . Hepatology \n2010 ; 52 :2065 –2076 .20949552 \n6 Sgro C Clinard F Ouazir K \nIncidence of drug-induced hepatic injuries: a French population-based study . Hepatology \n2002 ; 36 :451 –455 .12143055 \n7 Andrade RJ Lucena MI Fernandez MC \nDrug-induced liver injury: an analysis of 461 incidences submitted to the Spanish registry over a 10-year period . Gastroenterology \n2005 ; 129 :512 –521 .16083708 \n8 Ostapowicz G Fontana RJ Schiodt FV \nResults of a prospective study of acute liver failure at 17 tertiary care centers in the United States . Ann Intern Med \n2002 ; 137 :947 –954 .12484709 \n9 Hussaini SH Farrington EA \nIdiosyncratic drug-induced liver injury: an overview . Expert Opin Drug Saf \n2007 ; 6 :673 –684 .17967156 \n10 Ou P Chen Y Li B \nCauses, clinical features and outcomes of drug-induced liver injury in hospitalized patients in a Chinese tertiary care hospital . Springer Plus \n2015 ; 4 :802 .26702391 \n11 Zhou Y Yang L Liao Z \nEpidemiology of drug-induced liver injury in China: a systematic analysis of the Chinese literature including 21,789 patients . Eur J Gastroenterol Hepatol \n2013 ; 25 :825 –829 .23510965 \n12 Shang P Xia Y Liu F \nIncidence, clinical features and impact on anti-tuberculosis treatment of anti-tuberculosis drug induced liver injury (ATLI) in China . PLoS One \n2011 ; 6 :e21836 .21750735 \n13 Chalasani NP Hayashi PH Bonkovsky HL \nACG Clinical Guideline: the diagnosis and management of idiosyncratic drug-induced liver injury . Am J Gastroenterol \n2014 ; 109 :950 –966 .quiz 967 .24935270 \n14 Watkins PB Seeff LB \nDrug-induced liver injury: summary of a single topic clinical research conference . Hepatology \n2006 ; 43 :618 –631 .16496329 \n15 Benichou C \nCriteria of drug-induced liver disorders. Report of an international consensus meeting . J Hepatol \n1990 ; 11 :272 –276 .2254635 \n16 Polson J Lee WM \nAASLD position paper: the management of acute liver failure . Hepatology \n2005 ; 41 :1179 –1197 .15841455 \n17 Lee WM Stravitz RT Larson AM \nIntroduction to the revised American Association for the Study of Liver Diseases Position Paper on acute liver failure 2011 . Hepatology \n2012 ; 55 :965 –967 .22213561 \n18 Danan G \nCausality assessment of drug-induced liver injury. Hepatology Working Group . J Hepatol \n1988 ; 7 :132 –136 .3053889 \n19 Bjornsson E Kalaitzakis E Av KV \nLong-term follow-up of patients with mild to moderate drug-induced liver injury . Aliment Pharmacol Ther \n2007 ; 26 :79 –85 .17555424 \n20 Adams KF Schatzkin A Harris TB \nOverweight, obesity, and mortality in a large prospective cohort of persons 50 to 71 years old . N Engl J Med \n2006 ; 355 :763 –778 .16926275 \n21 Calle EE Thun MJ Petrelli JM \nBody-mass index and mortality in a prospective cohort of U.S. adults . N Engl J Med \n1999 ; 341 :1097 –1105 .10511607 \n22 Scully T \nPublic health: society at large . Nature \n2014 ; 508 :S50 –S51 .24740125 \n23 Yan S Li J Li S \nThe expanding burden of cardiometabolic risk in China: the China Health and Nutrition Survey . Obes Rev \n2012 ; 13 :810 –821 .22738663 \n24 Yin J Zhang H Ye J \nTraditional Chinese medicine in treatment of metabolic syndrome . Endocr Metab Immune Disord Drug Targets \n2008 ; 8 :99 –111 .18537696 \n25 Zhou Q Chang B Chen XY \nChinese herbal medicine for obesity: a randomized, double-blinded, multicenter, prospective trial . Am J Chin Med \n2014 ; 42 :1345 –1356 .25406653 \n26 Tarantino G \nDrug-induced liver injury due to “natural products” used for weight loss: a case report . World J Gastroenterol \n2009 ; 15 :2414 .19452589 \n27 Polson JE \nHepatotoxicity due to antibiotics . Clin Liver Dis \n2007 ; 11 :549 –561 .vi .17723919 \n28 Larrey D \nEpidemiology and individual susceptibility to adverse drug reactions affecting the liver . Semin Liver Dis \n2002 ; 22 :145 –155 .12016546 \n29 Ganey PE Luyendyk JP Maddox JF \nAdverse hepatic drug reactions: inflammatory episodes as consequence and contributor . Chem Biol Interact \n2004 ; 150 :35 –51 .15522260 \n30 Chen W Zheng R Baade PD \nCancer statistics in China, 2015 . CA Cancer J Clin \n2016 ; 66 :115 –132 .26808342 \n31 Tarantino G Conca P Basile V \nA prospective study of acute drug-induced liver injury in patients suffering from non-alcoholic fatty liver disease . Hepatol Res \n2007 ; 37 :410 –415 .17539815 \n32 Suk KT Kim DJ Kim CH \nA prospective nationwide study of drug-induced liver injury in Korea . Am J Gastroenterol \n2012 ; 107 :1380 –1387 .22733303\n\n",
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"abstract": "BACKGROUND\nInhaled nitric oxide (iNO) has been approved for the treatment of persistent pulmonary hypertension of the newborn (PPHN) in term and near-term newborns. Its role in the management of persistent pulmonary hypertension in preterm infants is not clear. Although guidelines do not exist, some studies have shown that iNO could be used as a rescue therapy in preterm neonate with severe pulmonary hypertension.\n\n\nMETHODS\nWe describe the case of a preterm neonate, born at 30 + 1 weeks of gestation, with hypoxic respiratory failure not responding to maximal conventional therapy. On the third day of life echocardiography showed severe pulmonary hypertension with right to left shunt and therapy with iNO was started. We achieved a rapid improvement in clinical conditions and pulmonary pressure normalized after 42 h of treatment.\n\n\nCONCLUSIONS\nMoving on a case by case basis, treatment with iNO should be considered as a rescue therapy in preterm newborns with acute hypoxic respiratory failure caused by severe pulmonary hypertension.",
"affiliations": "Dipartimento di Scienze per la Promozione della Salute e Materno Infantile \"Giuseppe D'Alessandro\", University of Palermo, Palermo, Italy. [email protected].;Dipartimento di Scienze per la Promozione della Salute e Materno Infantile \"Giuseppe D'Alessandro\", University of Palermo, Palermo, Italy.;Unità Operativa di Neonatologia e Terapia Intensiva Neonatale, AOOR Villa Sofia-Cervello, Palermo, Italy.;Unità Operativa di Neonatologia e Terapia Intensiva Neonatale, AOOR Villa Sofia-Cervello, Palermo, Italy.;Unità Operativa di Neonatologia e Terapia Intensiva Neonatale, AOOR Villa Sofia-Cervello, Palermo, Italy.",
"authors": "Busè|Martina|M|http://orcid.org/0000-0003-0825-9159;Graziano|Francesco|F|;Lunetta|Fabio|F|;Sulliotti|Giorgio|G|;Duca|Vincenzo|V|",
"chemical_list": "D001993:Bronchodilator Agents; D009569:Nitric Oxide",
"country": "England",
"delete": false,
"doi": "10.1186/s13052-018-0494-9",
"fulltext": "\n==== Front\nItal J PediatrItal J PediatrItalian Journal of Pediatrics1824-7288BioMed Central London 49410.1186/s13052-018-0494-9Case ReportInhaled nitric oxide as a rescue therapy in a preterm neonate with severe pulmonary hypertension: a case report http://orcid.org/0000-0003-0825-9159Busè Martina [email protected] 1Graziano Francesco [email protected] 1Lunetta Fabio [email protected] 2Sulliotti Giorgio [email protected] 2Duca Vincenzo [email protected] 21 0000 0004 1762 5517grid.10776.37Dipartimento di Scienze per la Promozione della Salute e Materno Infantile “Giuseppe D’Alessandro”, University of Palermo, Palermo, Italy 2 Unità Operativa di Neonatologia e Terapia Intensiva Neonatale, AOOR Villa Sofia-Cervello, Palermo, Italy 15 5 2018 15 5 2018 2018 44 552 2 2018 8 5 2018 © The Author(s). 2018Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nInhaled nitric oxide (iNO) has been approved for the treatment of persistent pulmonary hypertension of the newborn (PPHN) in term and near-term newborns. Its role in the management of persistent pulmonary hypertension in preterm infants is not clear. Although guidelines do not exist, some studies have shown that iNO could be used as a rescue therapy in preterm neonate with severe pulmonary hypertension.\n\nCase presentation\nWe describe the case of a preterm neonate, born at 30 + 1 weeks of gestation, with hypoxic respiratory failure not responding to maximal conventional therapy. On the third day of life echocardiography showed severe pulmonary hypertension with right to left shunt and therapy with iNO was started. We achieved a rapid improvement in clinical conditions and pulmonary pressure normalized after 42 h of treatment.\n\nConclusions\nMoving on a case by case basis, treatment with iNO should be considered as a rescue therapy in preterm newborns with acute hypoxic respiratory failure caused by severe pulmonary hypertension.\n\nKeywords\nInhaled nitric oxidePreterm neonatePulmonary hypertensionissue-copyright-statement© The Author(s) 2018\n==== Body\nBackground\nPersistent pulmonary hypertension of the newborn (PPHN) is a serious cardio-respiratory complication of the transition to extrauterine life. PPHN occurs mainly in term neonates, but it has also been detected in preterm neonates [1].\n\nInhaled nitric oxide (iNO) has been approved for the treatment of PPHN in term and near-term newborns. It was demonstrated that its selective vasodilatory action on the pulmonary circulation improves oxygenation and reduces the need for extracorporeal membrane oxygenation [2–7].\n\nHowever, its role in the management of hypoxic respiratory failure due to pulmonary hypertension in preterm infants is not clear. Guidelines or standardized protocols do not exist, but some studies have shown that iNO could be used as a rescue therapy in preterm neonate with severe pulmonary hypertension who are not responding to maximal conventional therapy [8–13].\n\nIn the present paper, we describe the case of a preterm neonate, born at 30 + 1 weeks of gestation (WG), with severe pulmonary hypertension treated with inhaled nitric oxide.\n\nCase presentation\nWe report on the case of a female neonate born at 30 + 1 WG by emergency caesarean section for preterm premature rupture of membranes (PPROM). She is the first born of a bichorionic and biamniotic twin pregnancy. At born: Apgar score 1′ 5, 5′ 8, birth weight 1380 g. She first needed nasal continuous positive airway pressure (CPAP), followed by orotracheal intubation. A dose of surfactant was administered, then the neonate was immediately transferred to our Neonatal Intensive Care Unit (NICU).\n\nUpon arrival to our NICU, the patient appeared suffering, hypotonic with reduced reactivity; oxygen saturation was 93–94% (inspired oxygen concentration (FiO2) 0.45) during synchronized intermittent positive pressure ventilation (SIPPV) and the abdomen appeared globose but treatable. She had emission of meconium with blood; blood and blood cores were suctioned from the oral cavity and stomach. Arterial blood gas analysis and routine investigations were normal. The coagulation was disrupted with prolonged prothrombin time and partial thromboplastin time and reduced antithrombin III activity (17%). This was corrected by administration of antithrombin III.\n\nIn the following hours the patient’s respiratory state deteriorated. Chest X-ray revealed the presence of pulmonary infiltrates, mainly to the left lung, and a second dose of surfactant was administered. Cranial ultrasound was normal. Echocardiography showed patent ductus arteriosus (PDA) and tricuspid insufficiency (PAPs 40–45 mmHg), but treatment was not started because of bleeding disorders.\n\nOn the second day of life echocardiography was repeated, showing PDA with pulsatile flow. The coagulation was normalized so we could start treatment with ibuprofen (first dose 10 mg/Kg). Broad-spectrum antibiotics were initiated.\n\nOn the third day of life the patient’s general conditions further deteriorated. Oxygen saturation was 80% during synchronized intermittent mandatory ventilation (SIMV) with FiO2 0.80–0.90. We observed a severe respiratory acidosis (pH 6.93, pCO2 75 mmHg, bicarbonate 11 mmol/l, base excess − 15.9 mmol/l). A third dose of surfactant and sodium bicarbonate were administered; simultaneously continuous dopamine infusion was started. The oxygenation index (OI), calculated as FiO2 x Mean Airway Pressure × 100/PaO2 (mmHg), was 16. Echocardiography showed severe pulmonary hypertension (PAPs 77–80 mmHg) with right to left shunt (Fig. 1). Given the critical condition of the infant and the finding of severe pulmonary hypertension, we decided to stop ibuprofen and start therapy with iNO. iNO was started at the dose of 10 p.p.m. and the neonate was ventilated in SIPPV (FiO2 0.95). After 1 h iNO was increased to 15 p.p.m. and conventional mechanical ventilation was switched to high frequency oscillation ventilation (HFOV). Eight hours after starting treatment, oxygen saturation and blood gas parameters were improving and we reduced iNO to 13, 10 and 7.5 p.p.m. gradually. At the same time conventional mechanical ventilation was restarted and FiO2 was progressively reduce to 0.50.Fig. 1 Doppler ultrasound showing severe pulmonary hypertension: velocity of tricuspid regurgitant jet up to 4.1 m/sec\n\n\n\nAfter 42 h of treatment echocardiography showed normal pulmonary pressure and PDA with almost totally left to right shunt (Fig. 2a and b). Oxygenation index was 9. iNO was progressively stopped, reaching the complete suspension after 50 h from the start of treatment. The patient continued conventional mechanical ventilation (SIMV), gradually lowering the FiO2, and at 60 h from iNO suspension she was extubated.Fig. 2 a Echocardiography showing prevalence of right heart chambers. b Doppler ultrasound: sisto-diastolic flow with almost totally left to right shunt\n\n\n\nCranial ultrasound performed at 32 + 5 WG was normal. Follow-up echocardiography was performed, the last (at 34 WG) showing normal pulmonary pressure, no shunts and closed ductus arteriosus.\n\nDiscussion and conclusions\nAlthough iNO has been approved for the treatment of PPHN in term and near-term newborns, the efficacy of this therapy for acute hypoxic respiratory failure owing to PPHN in premature neonates is not clear. Different studies have shown that iNO could be used as a rescue therapy in preterm neonates with severe pulmonary hypertension [8, 9]. In particular, it seems that the response to iNO improves significantly with increasing gestational age: neonates born ≥ 29 WG have a significantly greater response compared to neonates < 29 WG [10]. The most recent studies conclude that iNO therapy can improve the oxigenation in very preterm infants with PPHN, but it is not recommended for the routinely treatment and should be considered carefully. Moreover, they suggest that FiO2 > 0.65, echocardiographic diagnosis of PPHN, and birth weight > 750 g independently predict a beneficial effect of iNO in very preterm infants with RDS [12].\n\nIt is difficult to establish the cause of pulmonary hypertension in our patient, but it probably results from significant alteration of lung flows (with increased vasoconstrictive component) secondary to a maternal factors such as PPROM [10]. However, we cannot exclude that the administration of ibuprofen for PDA closure was the trigger that led to the onset of pulmonary hypertension. In fact, pulmonary hypertension is a rare but potentially lethal side effect in preterm infants receiving ibuprofen for PDA closure [14, 15].\n\nAfter the finding of severe pulmonary hypertension, we started iNO therapy and we achieved a rapid improvement in clinical conditions. Treatment with iNO lasted a total of 50 h; the maximum dose reached was 15 p.p.m. During treatment the maximum value of methemoglobin was 1,4%. It is also important to note how the patient’s conditions improved when iNO has been associated with HFOV rather than with conventional mechanical ventilation, confirming the effectiveness of the association between iNO and HFOV for the treatment of PPHN.\n\nOur NICU does not have a standard protocol regarding the use of iNO in preterm infants. At the discretion of the clinical team, and moving on a case by case basis, iNO therapy is used in preterm neonates with PPHN when even maximal conventional therapy (FiO2 0.80–0.90) is not working.\n\nIn conclusion, our experience confirms that treatment with iNO should be considered as a rescue therapy in preterm newborns with acute hypoxic respiratory failure caused by severe pulmonary hypertension. Further studies and clinical trials are needed to better determine the real efficacy of this therapy in preterm and extremely preterm infants and to define guidelines and standard protocols.\n\nAbbreviations\nCPAPContinuous positive airway pressure\n\nFiO2Inspired oxygen concentration\n\nHFOVHigh frequency oscillation ventilation\n\niNOInhaled nitric oxide\n\nNICUNeonatal intensive care unit\n\nOIOxygenation index\n\nPDAPatent ductus arteriosus\n\nPPHNPersistent pulmonary hypertension of the newborn\n\nPPROMPreterm premature rupture of membranes\n\nSIMVSynchronized intermittent mandatory ventilation\n\nSIPPVSynchronized intermittent positive pressure ventilation\n\nWGWeeks of gestation\n\nAcknowledgements\nWe would like to thank the patient family, and all the participants of this study.\n\nFunding\nThe authors declare no funding for this work.\n\nAuthors’ contributions\nAll authors contributed in the same way to collect, analyze and interpret data and write the manuscript; all authors read and approved the final draft.\n\nEthics approval and consent to participate\nNot applicable.\n\nConsent for publication\nWritten informed consent was obtained from the patient’s parents.\n\nCompeting interests\nThe authors declare that they have no competing interests.\n\nPublisher’s Note\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n1. Walther FJ Benders MJ Leighton JO Persistent pulmonary hypertension in premature neonates with severe respiratory distress syndrome Pediatrics 1992 90 6 899 904 1437431 \n2. Roberts JD Polaner DM Zapol WM Lang P Inhaled nitric oxide in persistent pulmonary hypertension of the newborn Lancet 1992 340 8823 818 819 10.1016/0140-6736(92)92686-A 1357245 \n3. Neonatal Inhaled Nitric Oxide Study Group Inhaled nitric oxide in full-term and nearly full-term infants with hypoxic respiratory failure N Engl J Med 1997 336 9 597 604 10.1056/NEJM199702273360901 9036320 \n4. Roberts JD Jr Fineman JR Morin FC Shaul PW Rimar S Schreiber MD The Inhaled Nitric Oxide Study group Inhaled nitric oxide and persistent pulmonary hypertension of the newborn N Engl J Med 1997 336 9 605 610 10.1056/NEJM199702273360902 9032045 \n5. Al-Alaiyan S Neiley E Inhaled nitric oxide in persistent pulmonary hypertension of the newborn refractory to high-frequency ventilation Crit Care 1999 3 1 7 10.1186/cc299 11056716 \n6. Clark RH Kueser TJ Walker MW Southgate WM Huckaby JL Perez JA Roy BJ Keszler M Kinsella JP Low-dose nitric oxide therapy for persistent pulmonary hypertension of the newborn N Engl J Med 2000 342 7 469 474 10.1056/NEJM200002173420704 10675427 \n7. Barrington KJ, Finer N, Pennaforte T, Altit G. Nitric oxide for respiratory failure in infants born at or near term: The Cochrane Library; 2017.\n8. Kinsella JP Cutter GR Walsh WF Gerstmann DR Bose CL Hart C Sekar KC Auten RL Bhutani VK Gerdes JS George TN Southgate WM Carriedo H Couser RJ Mammel MC Hall DC Pappagallo M Sardesai S Strain JD Baier M Abman SH Early inhaled nitric oxide therapy in premature newborns with respiratory failure N Engl J Med 2006 355 4 354 364 10.1056/NEJMoa060442 16870914 \n9. Donohue PK Gilmore MM Cristofalo E Wilson RF Weiner JZ Lau BD Robinson KA Allen MC Inhaled nitric oxide in preterm infants: a systematic review Pediatrics 2011 127 2 e414 e422 10.1542/peds.2010-3428 21220391 \n10. Kumar VH Hutchison AA Lakshminrusimha S Morin FC Wynn RJ Ryan RM Characteristics of pulmonary hypertension in preterm neonates J Perinatol 2007 27 4 214 219 10.1038/sj.jp.7211673 17330053 \n11. Barrington KJ, Finer N, Pennaforte T. Inhaled nitric oxide for respiratory failure in preterm infants. Cochrane Database Syst Rev. 2017;\n12. Dani C Corsini I Cangemi J Vangi V Pratesi S Nitric oxide for the treatment of preterm infants with severe RDS and pulmonary hypertension Pediatr Pulmonol 2017 52 11 1461 1468 10.1002/ppul.23843 29058384 \n13. Baczynski M, Ginty S, Weisz DE, McNamara PJ, Kelly E, Shah P, Jain A. 2017. Short-term and long-term outcomes of preterm neonates with acute severe pulmonary hypertension following rescue treatment with inhaled nitric oxide. Archives of disease in childhood-fetal and neonatal edition, fetalneonatal-2016.\n14. Gournay V Savagner C Thiriez G Kuster A Roze JC Pulmonary hypertension after ibuprofen prophylaxis in very preterm infants Lancet 2002 359 9316 1486 1488 10.1016/S0140-6736(02)08424-6 11988250 \n15. Bellini C Campone F Serra G Pulmonary hypertension following L-lysine ibuprofen therapy in a preterm infant with patent ductus arteriosus Can Med Assoc J 2006 174 13 1843 1844 10.1503/cmaj.051446 16785458\n\n",
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"abstract": "Objective We herein present a case involving a prevertebral abscess complicated by a spinal epidural abscess (SEA) secondary to intradiscal oxygen-ozone chemonucleolysis for treatment of a cervical disc herniation. Methods A 67-year-old woman with a history of intradiscal oxygen-ozone chemonucleolysis developed numbness and weakness in her right upper and bilateral lower extremities followed by urinary retention. Her symptoms did not respond to intravenous antibiotics alone. Magnetic resonance imaging of the cervical region revealed an extensive SEA anterior to the spinal cord, spinal cord myelopathy due to anterior compression by the lesion, and a prevertebral abscess extending from C2 to T1. She underwent surgical drainage and irrigation. Results The patient was successfully treated with surgical drainage and systemic antibiotic therapy without kyphosis. Streptococcus intermedius was detected within the abscess. All clinical symptoms except for the sensory deficit in the left leg were relieved. Conclusions The safety of intradiscal oxygen-ozone therapy requires further assessment. High-dose intravenous antibiotics should be initiated empirically at the earliest possible stage of prevertebral and epidural abscesses. Surgical drainage may be a rational treatment choice for patients with a prevertebral abscess complicated by an SEA and spinal cord myelopathy.",
"affiliations": "1 Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.;1 Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.;2 Department of Radiology, Tianjin Medical University General Hospital Tianjin, China.;1 Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.;1 Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China.",
"authors": "Yang|Chun-Sheng|CS|http://orcid.org/0000-0003-0846-2851;Zhang|Lin-Jie|LJ|;Sun|Zhi-Hua|ZH|;Yang|Li|L|;Shi|Fu-Dong|FD|",
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"fulltext": "\n==== Front\nJ Int Med ResJ. Int. Med. ResIMRspimrThe Journal of International Medical Research0300-06051473-2300SAGE Publications Sage UK: London, England 2958451210.1177/030006051876418610.1177_0300060518764186Case ReportsAcute prevertebral abscess secondary to intradiscal oxygen–ozone chemonucleolysis for treatment of a cervical disc herniation http://orcid.org/0000-0003-0846-2851Yang Chun-Sheng 1Zhang Lin-Jie 1Sun Zhi-Hua 2Yang Li 1Shi Fu-Dong 13\n1 Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, Tianjin, China\n2 Department of Radiology, Tianjin Medical University General Hospital Tianjin, China\n3 Department of Neurology, Barrow Neurological Institute, St. Joseph’s Hospital and Medical Center, Phoenix, AZ, USAChun-Sheng Yang, Department of Neurology, Tianjin Neurological Institute, Tianjin Medical University General Hospital, 154 Anshan Road, Heping District, Tianjin 300052, China. Email: [email protected] 3 2018 6 2018 46 6 2461 2465 16 1 2018 19 2 2018 © The Author(s) 20182018SAGE PublicationsCreative Commons Non Commercial CC BY-NC: This article is distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 License (http://www.creativecommons.org/licenses/by-nc/4.0/) which permits non-commercial use, reproduction and distribution of the work without further permission provided the original work is attributed as specified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Objective\nWe herein present a case involving a prevertebral abscess complicated by a spinal epidural abscess (SEA) secondary to intradiscal oxygen–ozone chemonucleolysis for treatment of a cervical disc herniation.\n\nMethods\nA 67-year-old woman with a history of intradiscal oxygen–ozone chemonucleolysis developed numbness and weakness in her right upper and bilateral lower extremities followed by urinary retention. Her symptoms did not respond to intravenous antibiotics alone. Magnetic resonance imaging of the cervical region revealed an extensive SEA anterior to the spinal cord, spinal cord myelopathy due to anterior compression by the lesion, and a prevertebral abscess extending from C2 to T1. She underwent surgical drainage and irrigation.\n\nResults\nThe patient was successfully treated with surgical drainage and systemic antibiotic therapy without kyphosis. Streptococcus intermedius was detected within the abscess. All clinical symptoms except for the sensory deficit in the left leg were relieved.\n\nConclusions\nThe safety of intradiscal oxygen–ozone therapy requires further assessment. High-dose intravenous antibiotics should be initiated empirically at the earliest possible stage of prevertebral and epidural abscesses. Surgical drainage may be a rational treatment choice for patients with a prevertebral abscess complicated by an SEA and spinal cord myelopathy.\n\nOxygen–ozonecervical disc herniationprevertebral abscessspinal epidural abscessintravenous antibioticssurgical drainageNational Natural Science Foundation of Chinahttps://doi.org/10.13039/50110000180981571172Tianjin Research Program of Application Foundation and Advanced Technology15JCYBJC49800\n==== Body\nIntroduction\nPrevertebral abscesses are rare but potentially life-threatening. Infections of the prevertebral space always result from infective spondylodiscitis or penetrating injuries to the posterior pharyngeal wall.1 Intradiscal injection of oxygen–ozone (O2-O3) gas can be used to treat disc herniation. The main mechanism of action is dehydration by reduction of proteoglycans and a subsequent decrease in the hernia volume.2,3 Percutaneous techniques can minimize the invasive nature of surgery and decrease complications such as postsurgical infection. However, the safety profile of O2-O3 chemonucleolysis remains controversial. We herein present a case of an acute prevertebral abscess secondary to intradiscal O2-O3 chemonucleolysis for treatment of a cervical disc herniation in a patient who subsequently recovered well without cervical instability or progressive kyphosis. This case is being reported to alert clinicians to the potential complications associated with O2-O3 therapy and the need for caution when considering this treatment.\n\nCase report\nThe present study was approved by the ethics committee of Tianjin Medical University General Hospital. Written informed consent was obtained from the patient.\n\nA 67-year-old woman developed pain and numbness in her left hand and was diagnosed with cervical disc herniation. She received a percutaneous intradiscal injection of an O2-O3 gas mixture at C5 to C6 in another hospital 2 weeks before admission (Figure 1(a)). Her symptoms were partially relieved after the treatment. However, 3 days later she developed fever and chills. Her body temperature ranged from 37°C to 39°C. Her white blood cell count was 27.79 × 109/L with predominant neutrophilia (87.3%). She was diagnosed with an upper respiratory tract infection and received intravenous levofloxacin for 1 week in another clinic. Her fever and chills vanished. However, she subsequently presented to our hospital with a 4-day history of numbness and weakness in her right upper and bilateral lower extremities as well as urinary retention.\n\nFigure 1. Magnetic resonance imaging (MRI) and computed tomography findings. (a) Cervical sagittal T2-weighted MRI performed in another hospital before intradiscal oxygen–ozone (O2-O3) injection shows disc herniation at C5 to C6 (white arrow). (b) Cervical MRI performed before admission reveals an increased soft tissue density along the entire extent of the prevertebral region of the neck with hyperintensity in the spinal cord from C2 to C7 (white arrows). (c, d) Enhanced cervical MRI reveals an extensive spinal epidural abscess extending from C2 to C6 anterior to the spinal cord. Additionally, spinal cord myelopathy is present from C3 to C6 due to anterior compression by the lesion, and a prevertebral abscess with hypointense content and homogeneous enhancement of the wall and septa is present. There is no evidence of an air–fluid level, vertebral erosion, or foreign body (white arrows). (e) Cervical computed tomography shows a prevertebral abscess from C2 from T1 (white arrow). (f) Repeat cervical MRI after drainage shows a significant decrease in the hyperintensity and size of the cervical prevertebral and epidural spaces (white arrows). (g, h) MRI shows hyperintensity in the spinal cord at C4 to C5 after the 2-month and 1-year follow-ups (white arrow).\n\nThe patient was afebrile with a normal pulse, blood pressure, and respiratory rate. Clinical examination revealed weakness in the right upper limb (Medical Research Council [MRC] grade 2/5) and bilateral lower limbs (MRC grade 3–4/5) and normal reflexes with sensory deficit below T6 on the left side. Babinski’s sign was positive. There was no evidence of any neck swelling. She had no history of tuberculosis or diabetes.\n\nLaboratory testing revealed a normal white blood cell count and an elevated erythrocyte sedimentation rate and C-reactive protein concentration. The patient’s fasting and postprandial blood glucose levels were both normal. Lumbar puncture results showed an elevated white cell count (60 × 106/L) with predominant lymphocythemia and elevated protein (2.34 g/L), but decreased glucose and chloride concentrations. Blood and cerebrospinal fluid cultures were negative. Cervical magnetic resonance imaging (MRI) revealed an increased soft tissue density along the entire extent of the prevertebral region of the neck with hyperintensity in the spinal cord from C2 to C7 (Figure 1(b)).\n\nThe patient was started on intravenous ceftriaxone; however, her symptoms were not relieved. One week later, enhanced cervical MRI revealed an extensive spinal epidural abscess (SEA) extending from C2 to C6 anterior to the spinal cord, spinal cord myelopathy from C3 to C6, and a prevertebral abscess with hypointense contents and homogeneous enhancement of the wall and septa (Figure 1(c), (d)). The patient was switched from intravenous ceftriaxone to intravenous vancomycin. Two days later, she developed neck pain and dysphagia. Cervical computed tomography showed a prevertebral abscess from C2 from T1 (Figure 1(e)). She underwent surgical drainage under general anesthesia with endotracheal intubation. A 6-cm transverse incision was made at the level of the thyroid cartilage, and 60 mL of frank pus was drained from the abscess. A negative-pressure drain was inserted into the space and secured in place for constant postoperative drainage of the abscess and irrigation of the space with antiseptic solution. The pus was sent for Gram staining, aerobic bacterial culture and sensitivity, and acid-fast bacilli (AFB) staining and culture. Gram staining and culture revealed growth of Streptococcus intermedius sensitive to cefotaxime and vancomycin. Acid-fast bacilli staining and culture were negative. Cervical MRI carried out 12 days later showed a significant decrease in the hyperintensity and size of the cervical prevertebral and epidural spaces (Figure 1(f)). The patient was discharged after 16 days of intravenous antibiotic therapy and was advised to undergo 4 weeks of treatment with an oral antibiotic. At the 2-month follow-up, physical examination revealed no weakness but hypoesthesia in the right leg. MRI showed hyperintensity in the spinal cord from C4 to C5 (Figure 1(g)). Both the sensory and MRI abnormalities persisted after 1 year (Figure 1(h)).\n\nDiscussion\nOzone chemonucleolysis for disc herniations has been performed for more than 20 years. Muto et al.2 reported no neurological or infectious complications during follow-up. However, severe infection has been reported in rare cases.3,4 Prevertebral abscesses are extremely uncommon. In developing countries, however, the lack of primary healthcare, antibiotic abuse, and high level of antibiotic-resistant infections have been recognized as prime contributing factors to both deep neck infections and death.5 Deep neck infections, including prevertebral abscesses, are infections within the potential spaces and fascial planes of the head and neck. Most of these infections are of odontogenic origin. However, prevertebral infections usually result from infective spondylodiscitis and penetrating injuries to the posterior pharyngeal wall.1 The patient in the present case had no predisposing risk factors, such as diabetes, malignancy, or human immunodeficiency virus infection. Streptococcus intermedius, a bacterial species native to the mouth, nasopharynx, and esophagus, was isolated from the abscess. Considering the negative blood culture and no evidence of gastrointestinal disease, the most likely route was transesophageal puncture during chemonucleolysis, similar to a previously reported case.3 Andrés-Cano et al.3 and Bo et al.4 each reported a case of a cervical spondylodiscitis with an associated SEA secondary to O2-O3 therapy for cervical disc herniation. Both patients subsequently developed cervical instability with progressive kyphosis after abscess drainage and decompressive laminectomy, which required spinal stabilization with instrumentation. In the present case, we selected surgical drainage to protect the intervertebral disc and maintain the spinal stability. A nasogastric tube was inserted into the space and secured in place for constant postoperative drainage of the abscess and irrigation of the space with antiseptic solution. The patient had been started on intravenous vancomycin before the operation. All of these procedures effectively controlled the infection. Our patient did not develop cervical instability. However, the T2 hyperintensity in the spinal cord on MRI did not resolve. This imaging abnormality indicated the presence of ischemic myelopathy, which caused the residual sensory deficit in her left leg.\n\nThe optimal application of conservative versus surgical management of SEAs remains controversial.6,7 In the present case, the SEA complicated with a deep neck infection made treatment more challenging. Broad-spectrum antibiotic therapy is essential at the time of presentation of deep neck abscess, and treatment should subsequently be updated based on culture and sensitivity. Unfortunately, a blood culture was not done before the initiation of antibiotic therapy because the physician did not correlate the patient’s symptoms with the invasive injection. Moreover, inappropriate use of antibiotics before admission changed the clinical presentation of the infections, making the symptoms elusive.\n\nIn conclusion, this case indicates that the safety of intradiscal O2-O3 therapy requires further assessment. Even a minimally invasive injection can cause severe complications in rare cases. Surgical drainage should be performed to relieve compression from prevertebral and epidural abscess formation if the patient exhibits a decline in neurologic function or airway obstruction.\n\nDeclaration of conflicting interest\nThe authors declare that there is no conflict of interest.\n\nFunding\nThis work was supported by the National Natural Science Foundation of China (grant number: 81571172) and the Tianjin Research Program of Application Foundation and Advanced Technology (grant number: 15JCYBJC49800).\n==== Refs\nReferences\n1 Hedge A Mohan S Lim WE. \nInfections of the deep neck spaces. \nSingapore Med J \n2012 ; \n53 : 305 –311 .22584969 \n2 Muto M Ambrosanio G Guarnieri G et al \nLow back pain and sciatica: treatment with intradiscal-intraforaminal O2-O3 injection. Our experience \nRadiol Med \n2008 ; \n113 : 695 –706 .18594765 \n3 Andrés-Cano P Vela T Cano C et al \nCervical spondylodiscitis after oxygen-ozone therapy for treatment of a cervical disc herniation: a case report and review of the literature. \nHSS J \n2016 ; \n12 : 278 –283 .27703423 \n4 Bo W Longyi C Jian T et al. \nA pyogenic discitis at c3-c4 with associated ventral epidural abscess involving c1-c4 after intradiscal oxygen-ozone chemonucleolysis: a case report. \nSpine (Phila Pa 1976) \n2009 ; \n34 : E298 –E304 .19365239 \n5 Bhandarkar AM Pillai S Venkitachalam S et al. \nAcute prevertebral abscess secondary to infected pancreatic pseudocyst . BMJ Case Rep \n2014 ; \n2014 .\n6 Alton TB Patel AR Bransford RJ et al \nIs there a difference in neurologic outcome in medical versus early operative management of cervical epidural abscesses? \nSpine J \n2015 ; \n15 : 10 –17 .24937797 \n7 Ghobrial GM Franco D Theofanis T et al \nCervical spondylodiscitis: presentation, timing, and surgical management in 59 patients. \nWorld Neurosurg \n2017 ; \n103 : 664 –670 .28457929\n\n",
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"keywords": "Oxygen–ozone; cervical disc herniation; intravenous antibiotics; prevertebral abscess; spinal epidural abscess; surgical drainage",
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"mesh_terms": "D000038:Abscess; D000368:Aged; D000900:Anti-Bacterial Agents; D002574:Cervical Vertebrae; D019299:Decompression, Surgical; D020802:Epidural Abscess; D005260:Female; D006801:Humans; D007404:Intervertebral Disc Chemolysis; D007405:Intervertebral Disc Displacement; D008279:Magnetic Resonance Imaging; D010100:Oxygen; D010126:Ozone; D013122:Spinal Diseases; D013290:Streptococcal Infections; D034367:Streptococcus intermedius; D007507:Therapeutic Irrigation",
"nlm_unique_id": "0346411",
"other_id": null,
"pages": "2461-2465",
"pmc": null,
"pmid": "29584512",
"pubdate": "2018-06",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "28457929;19365239;24937797;22584969;24408943;27703423;18594765",
"title": "Acute prevertebral abscess secondary to intradiscal oxygen-ozone chemonucleolysis for treatment of a cervical disc herniation.",
"title_normalized": "acute prevertebral abscess secondary to intradiscal oxygen ozone chemonucleolysis for treatment of a cervical disc herniation"
} | [
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"literaturereference": "LITERATURE REFERENCE: YANG C?S, ZHANG L?J, SUN Z?H, YANG L, SHI F?D. ACUTE PREVERTEBRAL ABSCESS?SECONDARY TO INTRADISCAL OXYGEN?OZONE CHEMONUCLEOLYSIS FOR TREATMENT OF A CERVICAL DISC?HERNIATION. J INT MED RES. 2018 JUN?46(6):2461?5.",
"literaturereference_normalized": "acute prevertebral abscess secondary to intradiscal oxygen ozone chemonucleolysis for treatment of a cervical disc herniation",
"qualification": "3",
"reportercountry": "CN"
},
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"receiptdate": "20180712",
"receivedate": "20180712",
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},
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"transmissiondate": "20181010"
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{
"abstract": "BACKGROUND\nThis monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany.\n\n\nRESULTS\n46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed.\n\n\nCONCLUSIONS\nOur data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.",
"affiliations": "Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Pediatrics III, University Children's Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, Medical Faculty, University Hospital Essen, 45147 Essen, Germany.;Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;MVZ Dr. Eberhard & Partner, 44137 Dortmund, Germany.;Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.;Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany.",
"authors": "Proske|Pia|P|0000-0002-2757-7825;Distelmaier|Laura|L|;Aramayo-Singelmann|Carmen|C|;Koliastas|Nikolaos|N|;Iannaccone|Antonella|A|;Papathanasiou|Maria|M|;Temme|Christian|C|;Klump|Hannes|H|0000-0003-3536-1212;Lenz|Veronika|V|;Koldehoff|Michael|M|0000-0002-8738-5884;Carpinteiro|Alexander|A|;Reinhardt|Hans Christian|HC|;Köninger|Angela|A|;Röth|Alexander|A|;Yamamoto|Raina|R|;Dührsen|Ulrich|U|;Alashkar|Ferras|F|0000-0001-7530-8892",
"chemical_list": null,
"country": "Switzerland",
"delete": false,
"doi": "10.3390/jpm11090870",
"fulltext": "\n==== Front\nJ Pers Med\nJ Pers Med\njpm\nJournal of Personalized Medicine\n2075-4426\nMDPI\n\n10.3390/jpm11090870\njpm-11-00870\nArticle\nPregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?\nhttps://orcid.org/0000-0002-2757-7825\nProske Pia 1\nDistelmaier Laura 12\nAramayo-Singelmann Carmen 3\nKoliastas Nikolaos 4\nIannaccone Antonella 4\nPapathanasiou Maria 5\nTemme Christian 6\nhttps://orcid.org/0000-0003-3536-1212\nKlump Hannes 6\nLenz Veronika 6\nhttps://orcid.org/0000-0002-8738-5884\nKoldehoff Michael 1\nCarpinteiro Alexander 17\nReinhardt Hans Christian 1\nKöninger Angela 48\nRöth Alexander 1\nYamamoto Raina 9\nDührsen Ulrich 1\nhttps://orcid.org/0000-0001-7530-8892\nAlashkar Ferras 1*\nCeci Adriana Academic Editor\nKountouris Petros Academic Editor\n1 Department of Hematology and Stem Cell Transplantation, West German Cancer Center, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany; [email protected] (P.P.); [email protected] (L.D.); [email protected] (M.K.); [email protected] (A.C.); [email protected] (H.C.R.); [email protected] (A.R.); [email protected] (U.D.)\n2 Vivantes, MVZ Neukölln, 12351 Berlin, Germany\n3 Department of Pediatrics III, University Children’s Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany; [email protected]\n4 Department of Gynecology and Obstetrics, University of Duisburg-Essen, 45147 Essen, Germany; [email protected] (N.K.); [email protected] (A.I.); [email protected] (A.K.)\n5 Department of Cardiology and Vascular Medicine, West German Heart and Vascular Center, Medical Faculty, University Hospital Essen, 45147 Essen, Germany; [email protected]\n6 Institute for Transfusion Medicine, University Hospital Essen, University of Duisburg-Essen, 45147 Essen, Germany; [email protected] (C.T.); [email protected] (H.K.); [email protected] (V.L.)\n7 Institute for Molecular Biology, University of Duisburg-Essen, 45147 Essen, Germany\n8 Hospital of the Order of St. John of God Regensburg, Clinic for Gynaecology and Obstetrics, 93049 Regensburg, Germany\n9 MVZ Dr. Eberhard & Partner, 44137 Dortmund, Germany; [email protected]\n* Correspondence: [email protected]\n30 8 2021\n9 2021\n11 9 87029 7 2021\n27 8 2021\n© 2021 by the authors.\n2021\nhttps://creativecommons.org/licenses/by/4.0/ Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).\nBackground: This monocentric study conducted at the University Hospital of Essen aims to describe maternal and fetal/neonatal outcomes in sickle cell disease (SCD) documented between 1996 to 2021 (N = 53), reflecting the largest monocentric analysis carried out in Germany. Methods/Results: 46 pregnancies in 22 patients were followed. None of the patients died. In total, 35% (11/31) of pregnancies were preterm. 15 pregnancies in eight patients were conceived on hydroxycarbamide (HC), of which nine had a successful outcome and three were terminated prematurely. There was no difference regarding the rate of spontaneous abortions in patients receiving HC compared to HC-naive patients prior to conception. In patients other than HbS/C disease, pregnancies were complicated by vaso-occlusive crises (VOCs)/acute pain crises (APCs) (96%, 23/24); acute chest syndrome (ACS) (13%, 3/24), transfusion demand (79%, 19/24), urinary tract infections (UTIs) (42%, 10/24) and thromboembolic events (8%, 2/24). In HbS/C patients complications included: VOCs/APCs (43%, 3/7; ACS: 14%, 1/7), transfusion demand (14%, 1/7), and UTIs (14%, 1/7). Independent of preterm deliveries, a significant difference with respect to neonatal growth in favor of neonates from HbS/C mothers was observed. Conclusion: Our data support the results of previous studies, highlighting the high rate of maternal and fetal/neonatal complications in pregnant SCD patients.\n\npregnancy\nsickle cell disease\nvaso-occlusive (VOC)\ntransfusion\ncomplications\ngenotype–phenotype correlation and patient stratification\npatient registries and standardization\n==== Body\npmc1. Introduction\n\nOver the last years, sickle cell disease (SCD)-related maternal and neonatal mortality has decreased significantly. This can be ascribed to the availability of evidence-based clinical practice guidelines (CPGs) and preventive measures, antenatal counseling and implementation of newborn screening [1,2]. However, pregnancy in patients with SCD still remains associated with both maternal morbidity and fetal/neonatal morbidity and mortality [3,4]. The observation of increased maternal morbidity is supported by the fact that care in SCD throughout pregnancy and in the postpartum period is mainly restricted to supportive measures in addition to transfusion therapy. The reason is that therapeutic modalities require immediate discontinuation due to the fear of possible complications that could particularly endanger fetal well-being [5,6,7]. Therefore, it is not surprising that sickle cell-associated complications (e.g., anemia, vaso-occlusive crises (VOCs), including acute chest syndrome (ACS), pre-existing cardio-pulmonary and renal complications) often deteriorate in pregnant SCD patients, resulting in frequent inpatient admissions for medical care. In addition, infectious complications, thromboembolic events (TEs), and preeclampsia can further complicate pregnancy and the postpartum period [8].\n\nErythrocyte sickling may contribute to micro-vascular placental pathology, increasing the risk for decreased placental circulatory blood flow, (acute) fetal hypoxemia, and placental thromboses, all of which are closely associated with a high incidence of perinatal complications. Those can be spontaneous abortions, stillbirths, or an increased rate of preterm deliveries with low gestational weight in neonates. Often, there is an imperative need for cesarean deliveries [8].\n\nThe prevalence of SCD and the number of affected children born in Germany is presently unknown. Notwithstanding that reliable epidemiological data are lacking, it is estimated that approximately 3000 to 5000 affected children and adults currently live in Germany. According to conservative estimates, approximately 70 to 150 affected children are born in Germany each year. Furthermore, due to increased immigration within the past years, more children affected by SCD will be born within the next years [9].\n\nHere we report pregnancy outcomes in patients with SCD registered at the Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Germany. To the best of our knowledge, this is the first large German monocentric observational study addressing this clinically important topic in a considerable number of patients.\n\n2. Materials and Methods\n\n2.1. Study Design and Participants\n\nThis is a single-center observational study of pregnancies in women with homozygous SCD (HbSS) or compound heterozygous states, such as HbS/C, HbS/β-thalassemia, or HbS/O-Arab (±co-inheritance of heterozygous α-thalassemia, if tested) who were in part or entirely monitored at the Department of Hematology and Stem Cell Transplantation, University Hospital Essen, Germany, allowing a prospective follow-up. Pregnancies before referral to our department were recorded retrospectively, based on patients’ information and medical reports. Data from patients delivering outside of Germany were generally not available. Carrier states for SCD were excluded. The study was approved by the Ethics Committee of the University of Duisburg-Essen and conducted in accordance with the Declaration of Helsinki.\n\n2.2. Disease-Related Definitions, Methods, and Treatments\n\nSCD was diagnosed according to international standards at the Hemoglobin Laboratory of the University Hospital Ulm and starting from 2017 at the Medical Care Center Dr. Eberhard and Partner Dortmund via molecular globin gene genetic analyses by polymerase chain reaction (PCR), sequencing and/or multiplex ligation-dependent probe amplification (MLPA).\n\n2.3. Sickle Cell-Associated Definitions\n\nAn acute pain crisis (APC) or uncomplicated VOC was defined as an acute onset of pain for which there was no other medical explanation other than vaso-occlusion and which required analgetic treatment (enteral or parenteral), irrespective if the event required hospitalization or was managed at home. ACS or splenic sequestration were referred to as complicated VOCs. ACS was defined based on the finding of a new pulmonary infiltrate in the presence of other signs and symptoms: chest pain, a temperature of ≥38.5 °C, tachypnea, wheezing or cough. Splenic sequestration was defined on the basis of left upper quadrant pain, an enlarged spleen, and an acute decrease in hemoglobin (Hb) concentration (e.g., a decrease in Hb of 2 g/dL from baseline).\n\n2.4. Pregnancy-Related Definitions\n\nSpontaneous abortion and stillbirth were defined as unsuccessful pregnancy outcomes before or after gestational week (GW) 22. Preterm delivery was defined as delivery before GW 37. Preterm premature rupture of membranes (PPROM) was classified if PROM occurred before GW 37.\n\n2.5. Treatments\n\nTreatment with hydroxycarbamide (HC) was recommended according to international guidelines and prescribed, if desired. In all HC-treated patients, therapy was discontinued with establishment of pregnancy due to possible teratogenicity [10,11]. Prior to pregnancy, none of the patients were treated with crizanlizumab. In patients allowing for pre-conceptional care (PCC), HC was aimed to be discontinued at least three months before conception under close follow-up, if feasible.\n\nFolic acid (5 mg daily) was routinely supplemented. Iron supplementation was restricted to patients with iron deficiency. Extended red blood cell (RBC) phenotyping, including full Rhesus (C, D, E, c, and e), Kell typing (K, k) and screening for other blood group antigens [Kp(a), Kp(b), Duffy (Fy(a), Fy(b)), Kidd (Jk(a), Jk(b)), M, N, S, s, Lewis (Le(a), Le(b)), Lu(a), Lu(b)] was routinely performed. Partners of patients were encouraged to undertake genetic counseling.\n\nIn patients with past pregnancies not yet treated at our center, extended RBC phenotyping was performed on the date of their first visit. RBC transfusions were restricted to patients with symptomatic anemia, a peri- or antenatal Hb concentration <7 g/dL, or in pregnant patients with SCD- or fetal-related complications. A RBC exchange (RCE) was recommended for the treatment of severe VOCs (i.e., severe pain crises and/or ACS). Low-molecular-weight-heparins (LMWHs) were prescribed to patients with prior TEs, in the event of inpatient admission, and were routinely applied in the postpartum period. The duration of thromboprophylaxis was at the discretion of the treating physician, based on the individual risk profile and mode of delivery.\n\n2.6. Statistical Analysis\n\nDue to the small sample size, statistical analysis was not carried out except for maternal and neonatal outcomes using paired Student’s t-test and two-tailed Mann-Whitney U test. Differences between groups were considered to be significant at a p value of < 0.05. Statistical analyses were performed with GraphPad Prism 6.\n\n3. Results\n\nIn total, 53 pregnancies in 22 females were recorded (HbSS (15/22; 68%)), HbS/β-thalassemia (2/22; 9%), HbS/C (4/22; 18%), and HbS/O-Arab (1/22; 5%) ± co-inheritance of heterozygous α-thalassemia) (Table 1). Prior to first presentation, seven gravidities occurred outside Germany, of which five were first-time pregnancies. The median age at first conception was 24 years (range, 14–39; N = 22). Four patients had one, six had two, and eleven had ≥3 pregnancies. No twin pregnancies were observed. In two patients the diagnosis of SCD was established after first gestation (Pat. 2 and 10).\n\nFifteen conceptions occurred in eight of the 22 patients under HC treatment (median maximum HC dosage: 20 mg/kg body weight (BW) (range, 8–35)), with three documented pregnancies in three patients and two in one patient. Antenatal counseling allowing for adequate time of HC discontinuation was possible in only one patient (Pat. 8).\n\nAt first presentation, alloimmunization to RBC antigens was observed in two patients (Pat. 1: anti-K and 16: anti-M, and -E). Both of which had a medical history of repeated RBC transfusions.\n\n3.1. Maternal, Fetal, and Neonatal Outcomes\n\nNone of the patients died. In total, 31 of the 53 (58%) documented pregnancies in 22 patients had a successful outcome (median age at conception: 26 years, range 14–39) with 26 deliveries observed in Germany (Table 2). Excluding elective (N = 9) or medical-induced abortions (N = 2), 74% (31/42) of pregnancies were successful. Ten pregnancies in eight patients resulted in spontaneous abortions, including one patient requiring in-vitro fertilization (IVF) (28 years of age (median), range 20–33).\n\nOverall, patient age was independent with respect to pregnancy outcome (successful versus unsuccessful), irrespective (prior) HC exposure: overall: p = 0.7477; severe genotypes: p = 0.4697. Preterm deliveries (35% (11/31)) were secondary to premature rupture of membranes (PROM), HELLP syndrome (hemolysis, elevated liver enzymes, low platelets), placenta insufficiency or abruption, pathologic fetal cardiotocographs (CTGs) and doppler indices, amniotic infection syndrome (AIS), maternal urosepsis, fetal subdural hematoma, spontaneous onset of labor in a multigravida patient, or due to a combination of two causes. Medical data concerning the reasons for preterm deliveries in patients giving birth outside Germany were in general not available.\n\nIn HC-pre-treated patients, nine of the 15 documented pregnancies had a successful outcome. Three pregnancies were terminated prematurely by elective abortions and three pregnancies resulted in spontaneous abortions, compared to six spontaneous abortions of the 22 pregnancies in patients with no prior exposure to HC. None of the patients with HbS/C disease experienced spontaneous abortions/stillbirths or received HC prior to pregnancy (median age at conception: 28 years, range 17–35).\n\nThe rate of spontaneous abortions in patients with severe genotypes, if excluding the one patient requiring IVF (independent risk factor), was independent of prior HC treatment (HC-treated: 25% (3/12); HC-naive: 27% (6/22)). Of note, two pregnancies in one patient were conceived under HC (Pat. 16).\n\nThe histological evaluation of the placenta from the one patient who experienced a stillbirth was not available. In patients suffering from recurrent (≥2) miscarriages (N = 3), only one (Pat. 19) was tested for other causes of loss of pregnancy. In another patient (Pat. 11), the diagnosis of delta-storage pool disease was confirmed during her fourth pregnancy.\n\n3.2. Gestational-, Peri-, and Postpartum Phase in Patients with Severe Genotypes (HbSS, HbS/β-Thalassemia, and HbS/O-Arab Disease)\n\nIn patients with severe genotypes and successful pregnancies (N = 24), APCs or VOCs were described by all patients during gestation, except for one carrying the HbSS genotype (96%, 23/24). These events predominately occurred during the second and third trimester, requiring in part (recurrent) inpatient admissions (54%, (13/24)) for (parenteral) analgetic treatment, and/or RBC transfusion support secondary to VOCs, or because of (infectious-related) hemolytic and/or symptomatic anemia. Throughout the observation time, two complicated VOCs (ACS) were observed in one HC-naive HbSS patient (Pat. 4) during her two successive pregnancies (GW 15 and 29 + 3) necessitating manual RCE. An additional ACS was observed in the postpartum period in a second HbSS patient (Pat. 11) (ACS rate in patients with severe disease-associated genotypes: 13% (3/24)).\n\nRBC transfusions were necessary in 75% (18/24) of the patients. One HC-naive patient treated in Italy presenting with recurrent VOCs (including ACS) prior to pregnancy, received serial prophylactic (exchange) blood transfusions (SP(E)BTs) for four years which were continued throughout pregnancy and thereafter every three weeks (Pat. 15). In another pre-conceptionally HC-treated patient (Pat. 8), SPBTs (every three weeks, starting from GW 20) were indicated due to suspicious doppler indices and symptomatic/hemolytic anemia.\n\nOne possible delayed hemolytic transfusion reaction (DHTR) with diagnosis of an alloantibody against the S-antigen (DD hyper-hemolytic VOC) despite transfusion of extended-phenotyped and matched RBCs was observed in one HbSS patient (Pat. 16, GW 29) already expressing irregular antibodies against erythrocytic antigens (anti-E, anti-M). To avoid further RBC transfusions, resumption of HC (20 mg/kg BW) in combination with erythropoietin (EPO) in GW 34 prior to delivery in GW 35 + 2 was indicated. Due to transfusion-dependent anemia in her subsequent pregnancy despite continuation of EPO, resumption of HC (15 mg/kg BW; GW 30) was mandatory prior to delivery (GW 34 + 4). In the presence of HC, breastfeeding was avoided in this patient.\n\nOverall, thromboembolic complications were seen in two patients (left DVT (Pat. 19; GW 26) and pulmonary embolism in the context of ACS during puerperium (Pat. 11)). Infectious complications were restricted to (recurrent) urinary tract infections (UTIs) and documented in ten out of the 24 successful pregnancies (42%), including maternal urosepsis in third trimester (GW 28) in one patient (Pat. 11).\n\nThe peripartum complications included P(P)ROM in five pregnancies, possibly associated with or occurred independently to placental abruption, cervical insufficiency, or amniotic infection syndrome (AIS). One patient suffered from HELLP syndrome. VOCs/APCs and/or RBC transfusion demand in the peripartum period were observed in five of the pregnancies (21%). A caesarean section (CS) secondary to pregnancy-, including active-phase arrest and/or pathologic doppler indices (N = 4), or SCD-related complications was mandatory in 42% (10/24) of patients for whom medical data were available, resulting in an overall CS rate of 67% (16/24). In the postpartum period, RBC transfusions were required in four patients. Postpartum cardiomyopathy was seen in one patient (Pat. 11).\n\nFollowing delivery, HC was re-initiated, if breastfeeding was not desired. In breasfeeding patients, treatment was re-initiated as soon as weaning was ensured.\n\n3.3. Gestational-, Peri-, and Postpartum Phase in Patients with HbS/C Disease\n\nIn the four patients with HbS/C disease, recurrent VOCs/APCs were observed in two patients. Both patients had a medical history of VOCs/APCs, however, none of them resulted in inpatient admission during pregnancy. One of the pregnancies was further complicated by transfusion demand for RBCs due to symptomatic anemia unrelated to a VOC/APC. Peripartum (SCD-associated) complications were observed in one of the pregnancies and required inpatient admission due to a VOC (pyelonephritis) in the third trimester of pregnancy which progressed to an ACS, requiring CS. AIS was seen in one of the four patients. In the postpartum period, only in one of the two patients with past VOCs/APCs during gestational phase were VOCs/APCs also documented, respectively. Throughout observation time, no serious infectious- or TE complications were observed.\n\nThree of the overall seven successful pregnancies in the other two HbS/C patients were uneventful (43%, 3/7), despite documented VOCs/APCs prior to conception in one of them.\n\n3.4. Neonatal Outcomes\n\nIn patients with severe genotypes, median GW at delivery was 37 weeks (range 29–40; N = 24) compared to 38 weeks (range, 37–40; N = 6/7) in HbS/C patients. Preterm neonates defined as <37 weeks of completed gestational age, were observed in 42% (10/24) of deliveries in patients with severe genotypes. In comparison, the rate of preterm neonates from mothers with HbS/C disease for whom gestational age was available was 14% (1/7). Median overall birth weight of neonates of mothers with severe disease-associated genotypes was 2570 g (range, 946–3090 g; N = 19) (median (overall) height: 47 cm (range, 36–50; N = 17)); median (overall) head circumference: 32 cm (range, 27.2–34.5; N = 17).\n\nExcluding preterm neonates (N = 8), data of neonatal outcomes were available from 12 neonates of HbSS patients. Median birth weight in these neonates was 2677 g (range, 1980–2090); height (median): 47.5 cm (range, 46–50); and head circumference (median): 32 cm (range, 30–34.5; N = 21)). Neonates from mothers with HbS/C disease born >37 GW displayed a median birth weight of 3370 g (range, 2890–4330), a height (median) of 55 cm (range, 51–60); and head circumference (median) of 35 cm (range, 34–36.5). Thus, there were statistically significant differences with respect to neonatal growth in favor of neonates from HbS/C mothers (Figure 1). A preterm CS (GW 29 + 5) in one patient with HbSS-α+-thalassemia and platelet delta-storage pool disease was required in the context of right-sided subdural fetal hematoma (1.5 × 7 cm) with midline shift and ventricular enlargement of the lateral ventricles.\n\n4. Discussion\n\nPregnancy in SCD is associated with a high incidence of adverse events as highlighted by past meta-analyses implicating the importance of an interdisciplinary therapeutic approach by national reference centers to ensure maternal and fetal/neonatal well-being [4,12]. The results of our single-center study are in partial agreement with previous studies.\n\nBefore commenting on the findings in our patients, we have to point out on the low number of patients with severe genotypes receiving HC, given the overall benefit regarding reduction in morbidity and mortality rates in HC-treated SCD patients [13,14,15]. The low number was based on the following notion: some of the patients rejected treatment because of individual concerns. Others were not taken care by a medical reference center prior to pregnancy and, thus, had only very limited access to antenatal care. These patients presented at our department at a late stage of pregnancy which may be attributed to their refugee status, often requiring direct hospitalization due to SCD-associated complications. Furthermore, despite the rising prevalence of SCD in Germany due to recent immigration, SCD is still considered a rare disease compared to other countries. Nevertheless, as the present analysis summarizes outcomes over a period of two decades, our results support the findings of other studies stating an overall improved maternal and neonatal outcome over the past decades [3,16,17].\n\nIn a meta-analysis published by Oteng-Ntim et al. (2015), the authors estimated a sixfold increased risk of maternal mortality in HbSS females compared to non-affected persons [4]. However, mortality rates vary depending on the particular analyses, the time of data collection, and may likely be associated with a poorer health care system as compared to Europe. Even though, no increased maternal mortality is observed in developing countries with substantial experience, as published by Babah et al. (2019) [18].\n\nAlthough a low prevalence of HC-induced teratogenicity can be assumed following exposure during pregnancy, treatment is supposed to be withheld three months before conception, if feasible [19]. Of note, in all our documented pregnancies (except one) with prior maternal HC exposure (treatment duration: ≥1 year), treatment was stopped only after diagnosis of pregnancy within the 1st trimester, indicating that all fetuses were exposed to HC during organogenesis (3rd to 8th week after conception). In these patients no obvious difference with regard to fetal mortality was observed (i.e., spontaneous abortions compared to HC-naive mothers) and neonatal development was not associated with any adverse events throughout observation time. Furthermore, in one of our patients with known alloantibodies and severe transfusion-dependent anemia, HC was needed to be reinitiated in the 3rd trimester of pregnancy up to four weeks prior to delivery during her two consecutive pregnancies resulting in no adverse fetal outcome. Our observations are therefore in line with the results observed in the European non-interventional, multicentric, prospective Escort-HU study. Hence, in some patients not suitable for SP(E)BT, HC (±EPO) may remain the only therapeutic option to ensure maternal and fetal well-being. Noteworthy, HC might even be considered safe in some patients if treated throughout the entire pregnancy. However, decision should be based on a case-by-case discussion and cannot be generally recommended due to the potential harmful effects [20].\n\nWhether or not SPBTs are beneficial in pregnant SCD patients remains a matter of debate [21,22,23,24]. Importantly, transfusion techniques and timing of SP(E)BT vary throughout the different studies probably explaining the contradictory results. Our study was not designed to answer this important topic. However, we did observe a high demand for RBC transfusions, especially in HbSS patients. Taking the risk of alloimmunization into account, transfusions were restricted to patients presenting either with symptomatic/hemolytic anemia or to those with other SCD-associated or obstetric complications.\n\nAlloimmunization is a multifactorial process and presents one of the most clinically relevant complications in the context of pregnancy. The incidence of alloimmunization is highest in SCD patients, with a reported rate of up to 47% [25]. Most of the alloantibodies are formed against Rhesus- (Rh-) and Kell- (K-) antigens [1,26]. It is assumed that this is due to the much larger variety of Rh-antigens found outside of Europe, particularly Africa, which differ from the common variants of European blood donors [1]. We observed alloimmunization in two out of eight HbSS patients with a history of periodic blood transfusions. Our low rate may be related to extended red cell antigen typing which may lower the rate of alloimmunization, although this has not yet been clearly proven [27]. Nevertheless, even in patients with a history of low exposure to allogeneic RBCs, alloimmunization can still occur at a relatively high rate, as reported for Ugandan sickle cell patients (with 6.1% alloimmunization) [28]. Although extended RBC matching has not been formally proven to contribute to a reduction of alloimmunization rates, it can speed up identification of the specificity of alloantibodies in the case of a positive antibody screen and also helps to select compatible RBCs [27]. Furthermore, some clinically significant alloantibodies can be difficult to detect because they evanesce over time and drop below the detection threshold in the immunohematology laboratory [29]. This potentiates the risk for severe transfusion-associated complications after antigen-re-exposure by transfusion of antigen-positive red blood cells. Such a booster can particularly lead to DHTRs [30]. It also emphasizes the importance of extended RBC antigen characterization (serologically and/or genetically) of donors and recipients, especially in European countries with a low disease prevalence to decrease the risk of potential transfusion reactions [31]. Particularly intrauterine transfusions can efficiently trigger alloimmunization against RBC antigens and against HLA molecules. As a matter of fact, alloimmunization against additional RBC antigens has been reported to occur in up to 25% of women already expressing an alloantibody. In contrast to transfusions in adults, extended antigen matching of donor cells (including Duffy-, Kidd-, and S-antigens) prior to intrauterine transfusion was shown to decrease the formation of alloantibodies in the mothers by 60% [32,33].\n\nIn summary, pregnant mothers suffering from SCD who have experienced severe SCD-related complications, either preceding the current pregnancy or during a previous pregnancy, may be considered for SP(E)BTs. This is the case if a high-risk exists for both, the mother and the fetus (e.g., twin pregnancies), or in patients encountering SCD-associated complications during the current pregnancy, in patients receiving HC before the gravidity, or in patients already receiving a chronic transfusion program [27]. A switch to SP(E)BTs may be worth to be considered in patients receiving crizanlizumab prior to or in the context of pregnancy for prevention of recurrent VOCs. Whether outcome might be favored by early initiation of SPEBT as described by Vianello et al. (2018) may be answered by the TAPS-2 study, as placental damage in SCD might even occur early in pregnancy [34,35].\n\nBecause not all documented pregnancies were monitored at our department, we included a patient survey. Pregnancies in our patients with successful outcomes were accompanied by a high rate of vaso-occlusive events (VOEs), especially in HbSS patients (96%) compared to HbS/C disease, requiring in part, if severe, recurrent inpatient admissions for medical care. Of note, the patient query revealed that not all of them seeked advice of their treating physicians during a painful crisis. This may offer an explanation for the overall higher VOC/APC rates described in our patients unlike other studies. Nevertheless, routine counselling was associated with a sense of security according to the patient survey, as these patients could directly contact their attending physician in the event of impending complications, if desired.\n\nComplicated VOEs (ACS) requiring inpatient admission for partial RCE and intravenous anti-infective treatment were observed for four pregnancies (13%, 4/31), including a patient with HbS/C disease. Thus, patients with HbS/C disease also are at increased risk for serious complications when being pregnant or in the postpartum period. Nevertheless, a higher rate of complications was seen in patients with genotypes mediating severe disease.\n\nSpecial attention should also be paid to the high number of elective abortions in our study. Reasons for medical abortions were related to age at time of conception, socio-economic factors, including uncertain partnerships, or disease-related stressors, implicating the importance of early psycho-social support in patients with SCD.\n\nAcknowledgments\n\nWe thank all our patients for participation in this study.\n\nAuthor Contributions\n\nConceptualization, F.A.; Data curation, F.A.; Formal analysis, P.P. and F.A.; Investigation, P.P., R.Y. and F.A.; Methodology, R.Y. and F.A.; Project administration, F.A.; Supervision, F.A.; Validation, P.P., L.D., C.A.-S., N.K., A.I., M.P., C.T., H.K., V.L., M.K., A.C., H.C.R., A.K., A.R., R.Y., U.D. and F.A.; Visualization, F.A.; Writing—original draft, P.P. and F.A.; Writing—review & editing, H.K., H.C.R., A.K., A.R., U.D. and F.A. All authors have read and agreed to the published version of the manuscript.\n\nFunding\n\nFA was supported as a Clinician Scientist within the University Medicine Essen Academy (UMEA) program, funded by the German Research Foundation (DFG; grant FU356/12-1) and the Faculty of Medicine, University of Duisburg-Essen, Germany.\n\nInstitutional Review Board Statement\n\nThe study involving human participants was reviewed and approved by retrospective analysis and use of data was approved by the Ethical Committee of the Faculty of Medicine at the University Hospital of Duisburg-Essen (21-10031-BO; 5/6/2021) and the study was conducted in accordance to the Declaration of Helsinki.\n\nInformed Consent Statement\n\nThe patients/participants provided their written informed consent to participate in this study.\n\nData Availability Statement\n\nAll datasets generated for this study are included in the article.\n\nConflicts of Interest\n\nAll authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\n\nFigure 1 Neonatal status (Birth weight (g), height (cm), and head circumference (cm)) from women with HbSS (N = 12) versus HbS/C disease (N = 5) ±co-inheritance of heterozygous α-thalassemia, excluding preterm neonates.\n\njpm-11-00870-t001_Table 1 Table 1 Maternal characteristics, including antenatal, peri-, and postpartum complications in SCD patients (N = 22).\n\nPatient-ID\tGenotype ((Genetic) Origin)\tGravida (G), Para (P); Age (Years)\tBefore Conception\tGestation Period\tCountry (Abortion/Stillbirth/Delivery)\tPeripartum Period\tPostpartum Period\t\nSCD-Associated Complication (HC Dosage; Alloantibodies)\tSCD-Associated Complications\tSCD-Associated Complications\tSCD-Associated Complications\t\nExclusively succesful pregnancy outcomes\t\n1\tHbSS-α+-thalassemia (Nigeria)\tG1, P0; 39\trecurrent VOCs/APCs, intermittent transfusion demand for RBCs (hemolytic/symtpomatic anemia, VOCs) (HC: 8 mg/kg BW; alloantibodies: anti-K)\tVOCs, transfusion demand for RBCs (hemolytic/symptomatic anemia)\tGermany\t-\t-\t\n2\tHbSS (Togo)\tG1, P0; 32\trecurrent APCs\tAPCs, transfusion demand for RBCs (hemolytic/symptomatic anemia; 1 unit)\tGermany\tCS secondary to birth arrest in the active-phase arrest\tTransfusion demand for RBCs (2 units) due to symptomatic anemia (Hb 5.6 g/dL); Wound infection of the cesarean scar\t\nG2, P1; 38\trecurrent APCs, st. p. cholecystectomy (cholecystolithiasis)\tAPCs\tGermany\tAPCs\t-\t\n3\tHbSS (Guinea)\tG1, P0; 14\t-\tVOCs/APCs\tGuinea\tNDA\t-\t\nG2, P1; 20\tAPCs (childhood), st. p. left hip joint endoprosthesis (left femoral head necrosis), st. p. cholecystectomy (cholecystolithiasis); HBV/HDV infection\tVOCs, requiring inpatient admissions, UTIs\tGermany\tPROM, AIS\t-\t\n4\tHbSS (Turkey)\tG1, P0; 24\trecurrent VOCs/APCs; intermittent transfusion demand for RBCs (hemolytic/symtpomatic anemia/VOCs), right femoral head necrosis, st. p. cholecystectomy (cholecystolithiasis)\tVOCs, including ACS (RBC-exchange transfusion (GW 15)), requiring inpatient admissions, recurrent transfusion demand for RBCs (hemolytic/symptomatic anemia), UTIs\tGermany\tAIS (GW 37)\tTransfusion demand for RBCs (2 units) (symptomatic anemia (Hb 6.5 g/dL))\t\nG2, P1; 27\tVOCs, including ACS (RCE (GW 29+3)), requiring inpatient admissions, transfusion demand for RBCs (hemolytic/symptomatic anemia), UTIs\tGermany\t-\t-\t\n5\tHbSS\n(Guinea)\tG1, P0; 17 (Germany: GW 30; refugee status)\trecurrent VOCs/APCs, intermittent transfusion demand for RBCs (hemolytic/symtpomatic anemia, VOCs (Guinea))\tGW 30: VOC, requiring inpatient admission, transfusion demand for RBCs (hemolytic/symptomatic anemia), UTI\tGermany\t-\t-\t\n6\tHbSS\n(Nigeria)\tG1, P0; 26 (refugee status)\t-\t-\tGermany\tCS secondary to active-phase arrest, transfusion demand for RBCs (hemolytic/symptomatic anemia; 2 units)\t-\t\nG2, P1; 28\tsplenic sequestration (RBC transfusion), cholecystolithiasis (HC 15 mg/kg BW)\tVOCs/APCs, requiring inpatient admissions, transfusion demand for RBCs (hemolytic/symptomatic anemia), UTIs\tGermany\ttransfusion demand for RBCs (PROM/hemolytic/symptomatic anemia; 2 units)\t-\t\n7\tHbSS\n(Togo)\tG1, P0; 17\trecurrent VOCs/APCs, including ACS, intermittent transfusion demand for RBCs (hemolytic/symptomatic anemia, VOCs), cholecystolithiasis (27 mg/kg BW)\tVOCs, requiring inpatient admissions (GW 9 and 27), transfusion demand for pRBCs (hemolytic/symptomatic anemia; 1 unit (GW 9)), UTI\tGermany\tCervical insufficiency\t-\t\n8\tHbS/β-thalassemia (Syria)\tG1, P0; 33\trecurrent VOCs/APCs, including ACS (pulmonary embolism); st. p. splenectomy (transfusion demand for pRBCs, hemolytic/symptomatic anemia, VOCs (Syria)), cholecystolithiasis (HC: 20 mg/kg BW)\tTransfusion demand for RBCs (hemolytic/symptomatic anemia; Hb <7 g/dl; 5 units, GW 20, 25, 30 (borderline doppler indices; intrauterine growth restriction), APC\tGermany\tCS (secondary to pathologic CTG and doppler indices, placental insufficiency)\tTransfusion demand for RBCs (2 units) due to symptomatic anemia (Hb 8.5 g/dL)\t\n9\tHbS/C\n(Ghana)\tG1, P0; 30\t-\t-\tGermany\t-\t-\t\nG2, P1; 31\t-\t-\tGermany\t-\t-\t\nG3, P2; 32\t-\t-\tGermany\tAIS\t-\t\n10\tHbS/C\n(Ghana)\tG1, P0; 35\tAPCs\tAPCs\tGermany\t-\t-\t\nSuccessful and unsuccessful pregnancy outcomes\t\n11\tHbSS-α+-thalassemia (Angola);\nDelta-storage pool disease\n(Diagnosis: 4th pregnancy)\tG1, P0; 20\tVOCs/APCs, intermittent transfusion demand for RBCs (hemolytic/symptomatic anemia, VOCs) (childhood), cholecystolithiasis, st. p. splenectomy\t-\tGermany (spontaneous abortion, GW 6)\t\nG2, P0; 21\t-\tGermany (spontaneous abortion, GW 11)\t\nG3, P0; 22\tVOCs/APCs, transfusion demand for RBCs (1 unit)\tGermany\tVOC, transfusion demand for RBCs (hemolytic/symptomatic anemia; 1 unit)\t-\t\nG4, P1; 25\tVOCs/APCs, requiring inpatient admission (GW 26, 28), transfusion demand for RBCs (hemolytic/symptomatic anemia; 6 units); UTI-> urosepsis (GW 28)\tGermany\tCS (fetal subdural hematoma; GW 29 + 5); re-sectio (hematoma evacuation); re-re-sectio (post-bleeding); re-re-re-sectio (hysterectomy); re-re-re-re-sectio (hematoma evacuation); re-re-re-re-re-sectio (post-bleeding); hemorrhagic shock; DIC; ACS (pulmonary embolism); transfusion demand for RBCs (overall: 49 pRBC units) and platetes (16 units); postpartum cardiomyopathy (HFrEF; EF 20–35%)\t\n12\tHbSS-α+-thalassemia (Nigeria)\tG1, P0; 27\tVOCs/APCs\tAPCs\tNigeria\t-\t-\t\nG2, P1; 30\tAPCs\tGermany (elective abortion)\t\nG2, P1; 33\tAPCs\tGermany (spontaneous abortion)\t\n13\tHbSS-α+-thalassemia\n(Zaire)\tG1, P0; 17\tVOCs/APCs, transfusion demand for RBCs (hemolytic symptomatic anemia, VOCs); st. p. splenectomy; st. p. cholecystectomy (cholecystolithiasis), infections (HC: 35 mg/kg BW)\t-\tGermany (elective abortion)\t\nG2, P0; 19\tVOCs/APCs, transfusion demand for RBCs (hemolytic symptomatic anemia, VOCs), left DVT (HC: 25 mg/kg BW)\tVOCs/APCs, requiring inpatient admissions (GW 16, 32), transfusion demand for pRBCs (hemolytic/symptomatic anemia; 6 units), febrile UTIs\tGermany\tPROM, CS secondary to active-phase arrest\tTransfusion demand for RBCs (hemolytic/symptomatic anemia; 1 unit)\t\nG3, P1; 22\tVOCs/APCs, including ACSs (3rd ACS: vvECMO), transfusion demand for RBCs (hemolytic/symptomatic anemia, VOCs), gram-negative port infection (HC: 25 mg/kg BW)\tVOCs/APCs, requiring inpatient admissions (GW 8, 11, 24, 29, 33), transfusion demand for RBCs (hemolytic/symptomatic anemia; 4 units)\tGermany\tPROM\t-\t\n14\tHbSS\n(Dominican Republic)\tG1, P0; 18\tVOCs/APCs, including ACS, intermittent transfusion demand for RBCs (hemolytic/symptomatic anemia, VOCs), infections, cholecystolithiasis\tVOCs/APCs, transfusion demand for RBCs (hemolytic/symptomatic anemia; 3 units)\tDominican Republic\t-\t-\t\nG2, P1; 21\t-\tDominican Republic (spontaneous abortion)\t\nG3, P1; 25\tVOCs/APCs, transfusion demand for RBCs (hemolytic/symptomatic anemia; 2 units)\tDominican Republic\t-\t-\t\nG4, P2; 30\t-\tGermany (spontaneous abortion)\t\n15\tHbSS\n(Congo)\tG1, P0; 24\tVOCs/APCs, including ACS; 4 yr. history of transfusion therapy (20–24th years of age; Italy)\tVOCs/APCs, requiring inpatient admissions (SP(E)BT, every 3 weeks)\tItaly\t-\tContinuation of transfusion therapy\t\nG2, P1; 29\tVOCs/APCs (HC: 20 mg/kg BW)\tVOCs, requiring inpatient admissions, transfusion demand for RBCs (hemolytic/symptomatic anemia; 3 units)\tGermany\tHELLP-Syndrome\t-\t\nG3, P2; 32\tVOCs/APCs (HC: 20 mg/kg BW)\t-\tGermany (spontaneous abortion)\t\n16\tHbSS\n(Angola)\tG1, P0; 20\tVOCs/APCs, transfusion demand for RBCs (hemolytic/symptomatic anemia) (Angola/Belgium) (HC: 15 mg/kg BW; alloantibodies: anti- E, -M)\t-\tBelgium (sponatenous abortion)\t\nG2, P1; 22 (Germany: GW 29, refugee status)\tVOCs/APCs, requiring inpatient admissions (GW 29), transfusion demand for RBCs (hemolytic/symptomatic anemia; 2 units), possible DHTR (Anti-S) following RBC transfusion in the context of a VOC (DD febrile hyperhemolytic VOC (UTI)) (re-start HU (20 mg/kg BW), GW 34 + EPO)\tGermany\tvaginal bleedings (GW 35), PPROM\t\t\nG3, P2; 24\tVOCs/APCs, including ACS, transfusion demand for RBCs (hemolytic/symptomatic anemia) (HC: 20 mg/kg BW + EPO; alloantibodies: anti- E, -M, -S)\tVOCs/APCs, requiring inpatient admissions (GW 13 and 17) (infectious-related), transfusion demand for RBCs (hemolytic/symptomatic anemia; 5 units) (EPO throughout pregnancy; re-start HU GW 30; 15 mg/kg BW)\tGermany\t-\t-\t\n17\tHbS/C-α+-thalassemia\n(Ghana)\tG1, P0; 17\tVOCs/APCs\t-\tGermany (elective abortion)\t\nG2, P0; 22\t-\tGermany\t-\t-\t\n18\tHbS/C\n(Nigeria)\tG1, P0; 24\tVOCs/APCs\t-\tGermany (elective abortion)\t\nG2, P0; 26\tAPCs, transfusion demand for RBCs (hemolytic/symptomatic anemia; 2 units)\tGermany\t-\tAPCs\t\nG3, P1; 28\tAPCs\tGermany\tVOC-infectious related (UTI -> pyelonephritis) -> ACS\t-\t\n19\tHbS/O-Ara\n(Kenya)\tG1, P0; 28\trecurrent VOCs (child- and adulthood), including recurrent ACSs (childhood) and transfusion demand for RBCs (symptomatic/hemolytic anemia, VOCs)\tDVT\tGermany (stillbirth, GW 26)\t\nG2, P0; 28\t-\tGermany (spontaneous abortion, GW 11)\t\nG3, P0; 29\tVOCs\tGermany\tPlacental abruption\t-\t\nUnsuccessful pregnancy outcomes\t\n20\tHbSS-α+-thalassemia\n(Suriname)\tG1, P0; 31\tVOCs/APCs (childhood)\t-\tGermany (ectopic pregnancy (IVF); medical abortion)\t\nG3, P0; 32\t-\t-\tGermany (spontaneous abortion, (IVF))\t\nG3, P0; 32\t-\t-\tGermany (ectopic pregnancy (IVF); medical abortion)\t\n21\tHbSS\n(Congo)\tG1, P0; 22\tRecurrent VOCs/APCs, including ACS, intermittent transfusion demand for RBCs (hemolytic/symptomatic anemia, VOCs; 8 units), right femoral head necrosis\t-\tGermany (elective abortion)\t\nG2, P0; 24\trecurrent VOCs/APCs, intermittent transfusion demand for RBCs (hemolytic/symptomatic anemia; 2 units), st. p. right hip joint endoprothesis (right femoral head necrosis), left humerus head necrosis (HC: 16 mg/kg BW)\t-\tGermany (elective abortion)\t\nG3, P0; 28\trecurrent VOCs/APCs, including ACS, intermittent transfusion demand for RBCs (hemolytic/symptomatic anemia; 2 units) (HC: 21 mg/kg BW)\t-\tGermany (elective abortion)\t\nG4, P0; 28\trecurrent VOCs/APCs (HC: 25 mg/kg BW)\t-\tGermany (spontaneous abortion)\t\n22\tHbS-β-thalassemia\n(Cuba)\tG1, P0; 18\trecurrent VOCs/APCs, including ACS, st. p. splenectomy (splenic sequestration), transfusion demand for RBCs (hemolytic/symptomatic anemia, VOCs)\t-\tGermany (elective abortion)\t\nG2, P0; 39\trecurrent VOCs/APCs, including ACS, bi-femoral head necrosis (st. p. femoral head cannulation)\t-\tGermany (elective abortion)\t\nAbbreviations: ACS, acute chest syndrome; AIS, amniotic infection syndrome; APCs, acute pain crises; BW, body weight; CS, caesarean section; DHTR, delayed hemolytic transfusion reaction; DIC, disseminated intravascular coagulation; DVT, deep venous thrombosis; EPO, erythropoietin; GW, gestational week; Hb, hemoglobin; HC, hydroxycarbamide; HELLP, hemolysis, elevated liver enzymes, low platelets; HFrEF, heart failure with reduced ejection fraction; NDA, no data available; P(P)ROM, preterm (premature) rupture of membranes; RBC, red blood cells; SP(E)BT, serial prophylactic (exchange) blood transfusions; UTIs, urinary tract infections; VOCs, vaso-occlusive crises.\n\njpm-11-00870-t002_Table 2 Table 2 Delivery and neonatal status in women with SCD (N = 31).\n\nPatient-ID/Genotype (Mother)\tPregnancy\tDelivery\tNewborn\t\nTime a\tType\tCountry (Birth)\tApgar Score b\tApH\tVpH\tBE (mmol/l)\tWeight (g)\tHeight (cm)\tHead\nCircumference (cm)\t\nHbSS (±α+-thalassemia)\t\n1\t1st\t38 + 4\tCS\tGermany\t9/10/10\t7.25\t7.3\t−1.2\t3090\t50\t34\t\n2\t1st\t39 + 1\tCS\tGermany\t8/10/10\t7.16\t-\t−11.5\t2620\t48\t33\t\n2nd\t38 + 1\tCS\tGermany\t9/10/10\t7.25\t-\t−6.7\t2730\t50\t33.5\t\n3\t1st\t36\tCS\tGuinea\t-\t-\t-\t-\t-\t-\t-\t\n2nd\t37 + 1\tVD\tGermany\t9/10 /10\t7.2\t-\t-\t2710\t48\t32\t\n4\t1st\t37 + 5\tCS\tGermany\t9/10/10\t7.32\t7.38\t-\t2610\t47\t34.5\t\n2nd\t39 + 5\tVD\tGermany\t9/10/10\t7.29\t7.36\t-\t2770\t46\t33.5\t\n5\t1st\t37 + 5\tVD\tGermany\t6/7/8\t7.19\t-\t−10\t1980\t46\t31\t\n6\t1st\t38 + 3\tCS\tGermany\t7/9/10\t7.29\t-\t−5.8\t2570\t47\t33\t\n2nd\t35 + 1\tCS\tGermany\t7/8/9\t7.34\t7.37\t-\t1900\t40\t31\t\n7\t1st\t37 + 1\tVD\tGermany\t9/10/10\t7.10\t7.27\t11\t2185\t46\t32\t\n11\t3rd\t37 + 5\tCS\tGermany\t9/10/10\t7.33\t7.37\t0.4\t2750\t48\t30\t\n4th\t29 + 5\tCS\tGermany\t7/8/8\t7.37\t-\t-\t1600\t41\t29\t\n12\t1st\t36\tCS\tNigeria\t-\t-\t-\t-\t-\t-\t-\t\n13\t2nd\t38 + 6\tCS\tGermany\t9/10/10\t7.32\t7.37\t−2.4\t2845\t47\t33\t\n3rd\t37 + 7\tVD\tGermany\t9/10/10\t7.29\t7.31\t-\t2645\t50\t34\t\n14\t1st\t39\tVD\tDominican Republic\t-\t-\t-\t-\t-\t-\t-\t\n3rd\t40\tCS\tDominican Republic\t-\t-\t-\t-\t-\t-\t-\t\n15\t1st\t32\tCS\tItaly\t-\t-\t-\t-\t-\t-\t-\t\n2nd\t34 + 1\tCS\tGermany\t8/8/9\t7.3\t7.37\t\t2320\t-\t-\t\n16\t2nd\t35 + 2\tVD\tGermany\t10/10/10\t7.27\t7.28\t−5.6\t2540\t46\t32\t\n3rd\t34 + 4\tVD\tGermany\t7/8/9\t7.22\t7.26\t−4.5\t2300\t42\t31\t\nHbS/β-thalassemia\t\n8\t1st\t30 + 5\tCS\tGermany\t-\t7.21\t-\t-\t946\t36\t27.2\t\nHbS/C\t\n9\t1st\t39 + 0\tVD\tGermany\t9/10/10\t7.35\t-\t-\t4140\t55\t36.5\t\n2nd\t38\tVD\tGermany\t-\t-\t-\t-\t-\t-\t-\t\n3rd\t40 + 6\tVD\tGermany\t9/10/10\t7.29\t-\t−2.4\t4330\t55\t36\t\n10\t1st\t35 + 6\tVD\tGermany\t9/10/10\t7.38\t-\t-\t2550\t48\t29.5\t\n17\t1st\t40 + 0\tVD\tGermany\t10/10/10\t7.28\t7.35\t−3\t3370\t60\t34\t\n18\t2nd\t38 + 5\tVD\tGermany\t9/10/10\t7.29\t-\t-\t3050\t50\t35\t\n3rd\t37 + 3\tCS\tGermany\t7/9/10\t7.31\t7.33\t−2.6\t2890\t51\t34\t\nHbS/O-Arab\t\n19\t3rd\t29 + 2\tCS\tGermany\t7/8/9\t7.32\t\t\t1140\t\t\t\nAbbreviations:a: Gestational week plus days; b: After 1, 5, and 10 min; CS, caesarean section; VD, vaginal delivery; ApH, arterial pH; VpH, venous pH; BE, base excess.\n\nPublisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n\n1. Vichinsky E.P. Earles A. Johnson R.A. Hoag M.S. Williams A. Lubin B. Alloimmunization in Sickle Cell Anemia and Transfusion of Racially Unmatched Blood N. Engl. J. Med. 1990 322 1617 1621 10.1056/NEJM199006073222301 2342522\n2. Piel F.B. Steinberg M.H. Rees D.C. Sickle Cell Disease N. Engl. J. Med. 2017 376 1561 1573 10.1056/NEJMra1510865 28423290\n3. Smith J. Espeland M. Bellevue R. Bonds D. Brown A. Koshy M. Pregnancy in Sickle Cell Disease: Experience of the Cooperative study of sickle cell disease Obstet. Gynecol. 1996 87 199 204 10.1016/0029-7844(95)00367-3 8559523\n4. Oteng-Ntim E. Meeks D. Seed P.T. Webster L. Howard J. Doyle P. Chappell L.C. Adverse maternal and perinatal outcomes in pregnant women with sickle cell disease: Systematic review and meta-analysis Blood 2015 125 3316 3325 10.1182/blood-2014-11-607317 25800049\n5. EU/3/16/1769|European Medicines Agency Available online: https://www.ema.europa.eu/en/medicines/human/orphan-designations/eu3161769 (accessed on 29 June 2021)\n6. Adakveo|European Medicines Agency Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/adakveo (accessed on 29 June 2021)\n7. Ballas S.K. The Evolving Pharmacotherapeutic Landscape for the Treatment of Sickle Cell Disease Mediterr. J. Hematol. Infect. Dis. 2020 12 e2020010 10.4084/mjhid.2020.010 31934320\n8. Smith-Whitley K. Complications in pregnant women with sickle cell disease Hematology 2019 1 359 366 10.1182/hematology.2019000039 31808864\n9. Lobitz S. Perspektive: Neugeborenen -screening auf Sichelzellkrankheiten in Deutschland Kinder Jugendmed. 2017 17 82 86 10.1055/s-0038-1629406\n10. Wong T.E. Brandow A.M. Lim W. Lottenberg R. Update on the use of hydroxyurea therapy in sickle cell disease Blood 2014 124 3850 3857 10.1182/blood-2014-08-435768 25287707\n11. Siklos|European Medicines Agency Available online: https://www.ema.europa.eu/en/medicines/human/EPAR/siklos (accessed on 29 June 2021)\n12. Boafor T.K. Olayemi E. Galadanci N. Hayfron-Benjamin C. Dei-Adomakoh Y. Segbefia C. Kassim A.A. Aliyu M.H. Galadanci H. Tuuli M.G. Pregnancy outcomes in women with sickle-cell disease in low and high income countries: A systematic review and meta-analysis BJOG Int. J. Obstet. Gynaecol. 2016 123 691 698 10.1111/1471-0528.13786\n13. Bakanay S.M. Dainer E. Clair B. Adekile A. Daitch L. Wells L. Holley L. Smith D. Kutlar A. Mortality in sickle cell patients on hydroxyurea therapy Blood 2005 105 545 547 10.1182/blood-2004-01-0322 15454485\n14. Ballas S.K. Barton F.B. Waclawiw M.A. Swerdlow P. Eckman J.R. Pegelow C.H. Koshy M. Barton B.A. Bonds D.R. Hydroxyurea and sickle cell anemia: Effect on quality of life Health Qual. Life Outcomes 2006 4 59 10.1186/1477-7525-4-59 16942629\n15. Voskaridou E. Christoulas D. Bilalis A. Plata E. Varvagiannis K. Stamatopoulos G. Sinopoulou K. Balassopoulou A. Loukopoulos D. Terpos E. The effect of prolonged administration of hydroxyurea on morbidity and mortality in adult patients with sickle cell syndromes: Results of a 17-year, single-center trial (LaSHS) Blood 2010 115 12 2354 10.1182/blood-2009-05-221333\n16. Jain D. Atmapoojya P. Colah R. Lodha P. Sickle cell disease and Pregnancy Mediterr. J. Hematol. Infect. Dis. 2019 11 2019040 10.4084/mjhid.2019.040 31308916\n17. Sun P.M. Wilburn W. Raynor B. Jamieson D. Sickle cell disease in pregnancy: Twenty years of experience at Grady Memorial Hospital, Atlanta, Georgia Am. J. Obstet. Gynecol. 2001 184 6 1127 10.1067/mob.2001.115477\n18. Babah O.A. Aderolu M.B. Oluwole A.A. Afolabi B.B. Towards zero mortality in sickle cell pregnancy: A prospective study comparing haemoglobin SS and AA women in Lagos, Nigeria Niger. Postgrad. Med. J. 2019 26 1 7 10.4103/npmj.npmj_177_18 30860192\n19. Gellen-Dautremer J. Le Jeune S. Receveur M.-C. Foïs E. Hydroxyurea Exposure throughout Pregnancy in Patients with Sickle-Cell Disease: 4 Case Reports from European Non-Interventional, Multicentric, Prospective Escort-HU Study Blood 2019 134 1027 10.1182/blood-2019-126529\n20. Galactéros F. Cannas G. Bartolucci P. Voskaridou E. Joseph L. Bernit E. Gellen-Dautremer J. Charneau C. Ngo S. Habibi A. Outcomes of Pregnancies in Patients with Sickle-Cell Disease: Update from European Non-Interventional, Multicentric, Prospective Escort-HU Study Blood 2019 134 891 10.1182/blood-2019-125812\n21. Malinowski A.K. Shehata N. D’Souza R. Kuo K.H.M. Ward R. Shah P.S. Murphy K. Prophylactic transfusion for pregnant women with sickle cell disease: A systematic review and meta-analysis Blood 2015 126 2424 2435 10.1182/blood-2015-06-649319 26302758\n22. Elenga N. Adeline A. Balcaen J. Vaz T. Calvez M. Terraz A. Accrombessi L. Carles G. Pregnancy in Sickle Cell Disease Is a Very High-Risk Situation: An Observational Study Obstet. Gynecol. Int. 2016 2016 9069054 10.1155/2016/9069054 27403164\n23. Whittington J.R. Magann E.F. Ounpraseuth S.T. Chang J.N. Whitcombe D.D. Morrison J.C. Evidence for Prophylactic Transfusion during Pregnancy for Women with Sickle Cell Disease South. Med. J. 2021 114 231 236 10.14423/SMJ.0000000000001233 33787937\n24. Driss F. Tertian G. Becquemont L. Haddad B. Cynober T. Raphael M. Tchernia G. Prise en charge des grossesses à risque chez les femmes drépanocytaires: Intérêt d’une stratégie préventive par des transfusions de globules rouges ou des échanges érythrocytaires automatisés Transfus. Clin. Biol. 2007 14 386 392 10.1016/j.tracli.2007.10.002 18035571\n25. Chou S.T. Jackson T. Vege S. Smith-Whitley K. Friedman D.F. Westhoff C.M. High prevalence of red blood cell alloimmunization in sickle cell disease despite transfusion from Rh-matched minority donors Blood 2013 122 1062 1071 10.1182/blood-2013-03-490623 23723452\n26. Sippert E. Fujita C.R. Variant RH alleles and Rh immunisation in patients with sickle cell disease Blood Transfus. 2015 13 72 10.2450/2014.0324-13 24960646\n27. Chou S.T. Alsawas M. Fasano R.M. Field J.J. Hendrickson J.E. Howard J. Kameka M. Kwiatkowski J.L. Pirenne F. Shi P.A. American Society of Hematology 2020 guidelines for sickle cell disease: Transfusion support Blood Adv. 2020 28 327 355 10.1182/bloodadvances.2019001143 31985807\n28. Natukunda B. Schonewille H. Ndugwa C. Brand A. Red blood cell alloimmunization in sickle cell disease patients in Uganda Transfusion 2010 50 20 25 10.1111/j.1537-2995.2009.02435.x 19821949\n29. Tormey C.A. Stack G. The persistence and evanescence of blood group alloantibodies in men Transfusion 2009 49 505 512 10.1111/j.1537-2995.2008.02014.x 19040411\n30. Nickel R.S. Hendrickson J.E. Fasano R.M. Meyer E.K. Winkler A.M. Yee M.M. Lane P.A. Jones Y.A. Pashankar F.D. New T. Impact of red blood cell alloimmunization on sickle cell disease mortality: A case series Transfusion 2016 56 107 114 10.1111/trf.13379 26509333\n31. Costa D.C.D. Pellegrino J. Jr. Guelsin G.A.S. Ribeiro K.A.R. Gilli S.C.O. Castilho L. Molecular matching of red blood cells is superior to serological matching in sickle cell disease patients Rev. Bras. Hematol. Hemoter. 2013 35 35 38 10.5581/1516-8484.20130012 23580882\n32. Schonewille H. Prinsen-Zander K.J. Reijnart M. Van De Watering L. Zwaginga J.-J. Meerman R.H. Van Kamp I.L. Brand A. Extended matched intrauterine transfusions reduce maternal Duffy, Kidd, and S antibody formation Transfusion 2015 55 2912 2919 10.1111/trf.13231 26173835\n33. Hendrickson J.E. Tormey C.A. Understanding red blood cell alloimmunization triggers Hematology 2016 2016 446 451 10.1182/asheducation-2016.1.446 27913514\n34. Oakley L.L. Awogbade M. Brien S. Briley A. Chorozoglou M. Drasar E. Johns J. Rhodes E. Robinson V. Seed P. Serial prophylactic exchange blood transfusion in pregnant women with sickle cell disease (TAPS-2): Study protocol for a randomised controlled feasibility trial Trials 2020 21 1 11 10.1186/s13063-020-4212-8 31898511\n35. Vianello A. Vencato E. Cantini M. Zanconato G. Manfrin E. Zamo A. Zorzi F. Mazzi F. Martinelli N. Cavaliere E. Improvement of maternal and fetal outcomes in women with sickle cell disease treated with early prophylactic erythrocytapheresis Transfusion 2018 58 2192 2201 10.1111/trf.14767 29984534\n\n",
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"title": "Pregnancies and Neonatal Outcomes in Patients with Sickle Cell Disease (SCD): Still a (High-)Risk Constellation?",
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}
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"reaction": [
{
"reactionmeddrapt": "Premature baby",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
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{
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"summary": null
},
"primarysource": {
"literaturereference": "Proske P, Distelmaier L, Aramayo-Singelmann C, Koliastas N, Iannaccone A, Papathanasiou M, et al. Pregnancies and neonatal outcomes in patients with sickle cell disease (SCD): Still a (high-)risk constellation?. Journal of Personalized Medicine. 2021;11(9):1-17",
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"qualification": "3",
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},
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"receivedate": "20211213",
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},
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"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
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"seriousnessdeath": 2,
"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "DE-BRISTOL-MYERS SQUIBB COMPANY-BMS-2021-133685",
"fulfillexpeditecriteria": "1",
"occurcountry": "DE",
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{
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"reactionmeddrapt": "Premature delivery",
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},
{
"reactionmeddrapt": "Maternal exposure before pregnancy",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Intentional product use issue",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Proske P, Distelmaier L, Aramayo-Singelmann C, Koliastas N, Iannaccone A, Papathanasiou M, et al. Pregnancies and neonatal outcomes in patients with sickle cell disease (SCD): Still a (high-)risk constellation?. Journal of Personalized Medicine. 2021;11(9):1-17",
"literaturereference_normalized": "pregnancies and neonatal outcomes in patients with sickle cell disease scd still a high risk constellation",
"qualification": "3",
"reportercountry": "DE"
},
"primarysourcecountry": "DE",
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"receivedate": "20211213",
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},
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"seriousnessdisabling": 2,
"seriousnesshospitalization": 2,
"seriousnesslifethreatening": 2,
"seriousnessother": 1,
"transmissiondate": "20220303"
},
{
"companynumb": "DE-BRISTOL-MYERS SQUIBB COMPANY-BMS-2021-133676",
"fulfillexpeditecriteria": "1",
"occurcountry": "DE",
"patient": {
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{
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"activesubstancename": "HYDROXYUREA"
},
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}
],
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"reaction": [
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"reactionmeddrapt": "Abortion spontaneous",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Maternal exposure before pregnancy",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Intentional product use issue",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Proske P, Distelmaier L, Aramayo-Singelmann C, Koliastas N, Iannaccone A, Papathanasiou M, et al. Pregnancies and neonatal outcomes in patients with sickle cell disease (SCD): Still a (high-)risk constellation?. Journal of Personalized Medicine. 2021;11(9):1-17",
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"qualification": "3",
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},
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}
] |
{
"abstract": "Although eribulin mesylate(ERI)has been approved for metastatic breast cancer, its efficacy and safety in combination with other chemotherapeutic agents have not been established. To investigate the tolerability of combination therapy with ERI and gemcitabine(GEM), we conducted a phase I clinical study in Japanese patients with metastatic breast cancer. The initial doses(Level 0)of ERI and GEM were 1.1mg/m2 and 800 mg/m2, respectively. When tolerability to Level 0 doses was confirmed, the doses were escalated to 1.4mg/m2 for ERI and 800 mg/m2 for GEM(Level 1). Seven patients were enrolled in this study; 3 patients received Level 0 doses and the other 4 patients received Level 1 doses. A dose limiting toxicity(DLT)was found in only 1 patient of the Level 1 group(Grade 3 oral mucositis). However, Grade 3 or higher hematological toxicities, including neutropenia, frequently occurred, and hence, this combination therapy was not conducted as scheduled. Thus, maximum tolerated dose(MTD)and recommended dose(RD)for phase II trials were not evaluated in this study. Drugdrug interactions between ERI and GEM were not observed. In conclusion, it was difficult to continue the combination therapy for patients with advanced recurrent breast cancer due to hematological toxicities. There is little possibility for the combination therapy with ERI and GEM at the specific doses to be regarded as a new treatment option for Japanese patients.",
"affiliations": "Dept. of Breast and Endocrine Surgery, Nagoya City University Hospital.",
"authors": "Kondo|Naoto|N|;Kashiwaba|Masahiro|M|;Goto|Risa|R|;Hattori|Masaya|M|;Iwata|Hiroji|H|",
"chemical_list": "D005663:Furans; D007659:Ketones; D003841:Deoxycytidine; C056507:gemcitabine; C490954:eribulin",
"country": "Japan",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0385-0684",
"issue": "45(8)",
"journal": "Gan to kagaku ryoho. Cancer & chemotherapy",
"keywords": null,
"medline_ta": "Gan To Kagaku Ryoho",
"mesh_terms": "D000328:Adult; D000368:Aged; D000971:Antineoplastic Combined Chemotherapy Protocols; D001943:Breast Neoplasms; D003841:Deoxycytidine; D004334:Drug Administration Schedule; D005260:Female; D005663:Furans; D006801:Humans; D007659:Ketones; D008875:Middle Aged; D009362:Neoplasm Metastasis",
"nlm_unique_id": "7810034",
"other_id": null,
"pages": "1165-1170",
"pmc": null,
"pmid": "30158412",
"pubdate": "2018-08",
"publication_types": "D017426:Clinical Trial, Phase I; D016428:Journal Article",
"references": null,
"title": "A Phase I Combination Dose-Escalation Study of Eribulin Mesylate and Gemcitabine in Japanese Patients with Metastatic Breast Cancer.",
"title_normalized": "a phase i combination dose escalation study of eribulin mesylate and gemcitabine in japanese patients with metastatic breast cancer"
} | [
{
"companynumb": "JP-PFIZER INC-2018376582",
"fulfillexpeditecriteria": "1",
"occurcountry": "JP",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "GEMCITABINE HYDROCHLORIDE"
},
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"drugadministrationroute": "041",
"drugauthorizationnumb": "078339",
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"drugdosagetext": "800 MG/M2, CYCLIC (LEVEL 0, OVER 30 MINUTES, ON DAY 1 AND DAY 8)",
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"drugindication": "BREAST CANCER METASTATIC",
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"medicinalproduct": "GEMCITABINE HYDROCHLORIDE."
},
{
"actiondrug": "1",
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"activesubstancename": "ERIBULIN"
},
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"drugdosagetext": "1.1 MG/M2, CYCLIC (LEVEL 0, OVER TWO TO FIVE MINUTES, ON DAY 1 AND DAY 8 )",
"drugenddate": null,
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"drugindication": "BREAST CANCER METASTATIC",
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"medicinalproduct": "ERIBULIN MESILATE"
}
],
"patientagegroup": null,
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"reaction": [
{
"reactionmeddrapt": "Neutropenia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Leukopenia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Neuropathy peripheral",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KONDO, N.. A PHASE I COMBINATION DOSE?ESCALATION STUDY OF ERIBULIN MESYLATE AND GEMCITABINE IN JAPANESE PATIENTS WITH METASTATIC BREAST CANCER. JAPANESE JOURNAL OF CANCER AND CHEMOTHERAPY. 2018?45(8):1165?1170",
"literaturereference_normalized": "a phase i combination dose escalation study of eribulin mesylate and gemcitabine in japanese patients with metastatic breast cancer",
"qualification": "3",
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},
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"receivedate": "20180919",
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},
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},
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"seriousnesscongenitalanomali": null,
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"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
},
{
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"patient": {
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{
"actiondrug": "1",
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},
"drugadditional": null,
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"drugcharacterization": "1",
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"drugdosagetext": "1.4 MG/M2, CYCLIC (LEVEL 1)",
"drugenddate": null,
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"drugindication": "BREAST CANCER METASTATIC",
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"drugstructuredosagenumb": "1.4",
"drugstructuredosageunit": "009",
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"medicinalproduct": "ERIBULIN MESILATE"
},
{
"actiondrug": "1",
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},
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"drugadministrationroute": "041",
"drugauthorizationnumb": "078339",
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"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
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"drugdosageform": null,
"drugdosagetext": "800 MG/M2, CYCLIC (LEVEL 1)",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "BREAST CANCER METASTATIC",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "800",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "GEMCITABINE HYDROCHLORIDE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Neutropenia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Neuropathy peripheral",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Leukopenia",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KONDO, N.. A PHASE I COMBINATION DOSE?ESCALATION STUDY OF ERIBULIN MESYLATE AND GEMCITABINE IN JAPANESE PATIENTS WITH METASTATIC BREAST CANCER. JAPANESE JOURNAL OF CANCER AND CHEMOTHERAPY. 2018?45(8):1165?1170",
"literaturereference_normalized": "a phase i combination dose escalation study of eribulin mesylate and gemcitabine in japanese patients with metastatic breast cancer",
"qualification": "3",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20180920",
"receivedate": "20180920",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15407675,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
}
] |
{
"abstract": "BACKGROUND\nAcute localized exanthematous pustulosis (ALEP) is a rare variant of acute generalized exanthematous pustulosis and is also defined by diagnostic criteria established by the EuroSCAR study group. Some twenty cases of ALEP have been described in the literature.\n\n\nMETHODS\nA 61-year-old woman suddenly developed erythematous and edematous lesions after subcutaneous heparin calcium injections in the thighs, with bullous detachment at the center of the lesions and multiple vesicles and non-follicular pustules on the edges. These lesions were centered around the injection points. There were no other skin lesions and no lesions on the oral mucosa, and the patient was apyrexial. The skin biopsy revealed an intracorneal pustule with spongiosis, as well as a prominent infiltrate of lymphocytes, neutrophils and eosinophils in the dermis, with no necrotic keratinocytes. We confirmed a definite diagnosis of ALEP, with a score of 10/12 according to the EuroSCAR criteria. A favorable outcome was quickly obtained after discontinuation of heparin injections, with only post-inflammatory pigmented macules.\n\n\nCONCLUSIONS\nThis case shows that heparin calcium can lead to ALEP, thus contraindicating further administration of this substance. Other causative factors consist chiefly of systemic antibiotics, spider bites and exposure to certain plants. This case is remarkable in terms of the limitation of lesions to heparin calcium injection sites.",
"affiliations": "Clinique dermatologique, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg cedex, France. Electronic address: [email protected].;Clinique dermatologique, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg cedex, France.;Clinique dermatologique, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg cedex, France.;Clinique dermatologique, hôpitaux universitaires de Strasbourg, 1, place de l'Hôpital, 67091 Strasbourg cedex, France.",
"authors": "Osché|M|M|;Gusdorf|L|L|;Cribier|B|B|;Scrivener|J-N|JN|",
"chemical_list": "D000925:Anticoagulants; C006871:calcium heparin; D006493:Heparin",
"country": "France",
"delete": false,
"doi": "10.1016/j.annder.2019.09.607",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0151-9638",
"issue": "147(3)",
"journal": "Annales de dermatologie et de venereologie",
"keywords": "Acute localized exanthematous pustulosis; Cutaneous drug reaction; Heparin; Heparin calcium; Héparine; Héparine calcique; Héparine non fractionnée; Pustulose exanthématique aiguë localisée; Toxidermie; Unfractionated heparin",
"medline_ta": "Ann Dermatol Venereol",
"mesh_terms": "D056150:Acute Generalized Exanthematous Pustulosis; D000925:Anticoagulants; D001706:Biopsy; D004804:Eosinophils; D005260:Female; D006493:Heparin; D006801:Humans; D007279:Injections, Subcutaneous; D008214:Lymphocytes; D008875:Middle Aged; D009504:Neutrophils; D012867:Skin",
"nlm_unique_id": "7702013",
"other_id": null,
"pages": "207-211",
"pmc": null,
"pmid": "32029300",
"pubdate": "2020-03",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "Acute localized exanthematous pustulosis following heparin calcium injections.",
"title_normalized": "acute localized exanthematous pustulosis following heparin calcium injections"
} | [
{
"companynumb": "FR-HONG KONG KING-FRIEND INDUSTRIAL COMPANY-2020NKF00003",
"fulfillexpeditecriteria": "1",
"occurcountry": "FR",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": "1",
"drugadministrationroute": "058",
"drugauthorizationnumb": "211005",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "INJECTION",
"drugdosagetext": "IN THIGHS",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "HEPARIN"
}
],
"patientagegroup": null,
"patientonsetage": "61",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Acute generalised exanthematous pustulosis",
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"abstract": "Post-operative delirium (POD) represents a unique challenge in the care of any surgical patient but is especially challenging in neurosurgical inpatient management due to a host of potentially significant predisposing factors. Patients undergoing stereoencephalography (SEEG) for diagnosis of drug resistant epilepsy are at unique risk due to safety concerns, yet POD has been underdiscussed in this population. Patients should be counseled pre-operatively about their risk and subsequent steps be taken post-operatively. We present two cases of POD status-post SEEG and propose a mechanism by which future post-operative care be coordinated by the physician, patient, and patient's family.",
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"fulltext": "\n==== Front\nEpilepsy Behav Rep\nEpilepsy Behav Rep\nEpilepsy & Behavior Reports\n2589-9864\nElsevier\n\nS2589-9864(21)00012-5\n10.1016/j.ebr.2021.100438\n100438\nCase Report\nManagement of post-operative delirium following stereoelectroencephalography electrode placement for drug resistant epilepsy: Lessons learned from two case reports\nBelanger Katherine [email protected]\na⁎\nGrassia Fabio ab\nKortz Michael W. b\nThompson John A. abc\nDeStefano Sam ac\nOjemann Steven abc\na School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO 80217, USA\nb Department of Neurosurgery, University of Colorado Anschutz Medical Campus, Aurora, CO 80217, USA\nc Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, CO 80217, USA\n⁎ Corresponding author at: 2136 Spruce St, Denver, CO 80238, USA. [email protected]\n22 3 2021\n2021\n22 3 2021\n16 10043816 1 2021\n3 3 2021\n9 3 2021\n© 2021 The Author(s)\n2021\nhttps://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).\nHighlights\n\n• Post-operative delirium poses unique challenges in neurosurgical patients.\n\n• Substance use is a modifiable risk factor for post-operative delirium after SEEG.\n\n• SEEG patients have increased risk of harm when experiencing post-operative delirium.\n\nPost-operative delirium (POD) represents a unique challenge in the care of any surgical patient but is especially challenging in neurosurgical inpatient management due to a host of potentially significant predisposing factors. Patients undergoing stereoencephalography (SEEG) for diagnosis of drug resistant epilepsy are at unique risk due to safety concerns, yet POD has been underdiscussed in this population. Patients should be counseled pre-operatively about their risk and subsequent steps be taken post-operatively. We present two cases of POD status-post SEEG and propose a mechanism by which future post-operative care be coordinated by the physician, patient, and patient’s family.\n\nKeywords\n\nEpilepsy\nStereoencephalography\nDelirium\nNeurosurgery\nCase report\n==== Body\nIntroduction\n\nPost-operative delirium (POD) is an acute, fluctuating disruption in attention and cognition that is associated with altered perception, inappropriate behavior, changes in awareness, and disorganized thinking [1], [2], [3]. Often expression of POD cannot be explained by a pre-existing disorder and can impair ability to comply with medical care [4], [5]. Diagnosis and treatment are complicated by a multitude of interactions between pre-operative vulnerabilities with intra-operative and post-operative precipitating factors [6], [7].\n\nPatients undergoing neurosurgical interventions are at unique risk for POD [4]. They require frequent neurologic checks, have baseline deficits with neurologic and metabolic derangements, and neurosurgical related brain injury [2], [5], [8]. In this population factors such as age, functional and neurologic impairment, and structural comorbidities of the brain (epilepsy, ischemia, etc.) have all been shown to be predisposing factors to delirium [3], [9].\n\nPatients undergoing neural implantation are particularly vulnerable to POD. Research investigating POD in Parkinson’s patients with deep brain stimulation (DBS) electrodes suggest that there is a direct psychotropic effect of surgical implantation of electrodes that contributes to POD [10]. Yet, there has been little research in patients undergoing stereoelectroencephalography (SEEG) surgery, where depth electrodes are implanted directly into the brain for localization of epileptic foci. Hyperactive delirium is of particular interest in this population because of the potential for self-harm.\n\nAlthough there is substantial risk, by aborting the SEEG procedure before epileptic foci localization, patients cannot undergo a subsequent surgical procedure aimed at seizure control, typically their last remaining option. Thus, pre-operative risk mitigation and discussing the potential for POD can allow therapeutic alignment between patient, family and treatment team about delirium management. This paper reviews two cases of POD in patients undergoing SEEG neuromonitoring and proposes how to mitigate complications post-operatively if a patient becomes acutely delirious.\n\nCase reports\n\nCase 1\n\nA 20-year-old female patient presented to the University of Colorado Neurology Department in 2015 with a 4-year history of drug resistant focal epilepsy. She subsequently underwent three phase 1 video-EEG (VEEG) sessions in the epilepsy monitoring unit (EMU) over a seven-month span. During the first session, the patient had an altercation with her parents and asked for security to escort them from her room. She then was adamant about leaving herself. She had completed the VEEG session but her final magnetic resonance imaging (MRI) had to be completed as an outpatient. Two subsequent phase 1 evaluations were without further altercations. VEEG helped localize seizure onset to the right posterior temporal lobe along with MRI findings of heterotopic gray matter along the right hippocampus and medial right temporal lobe.\n\nIn 2019 the patient presented to the University of Colorado Neurology Department for surgical consideration. A multi-disciplinary team recommended phase 2 invasive neuromonitoring using SEEG to further localize seizure onset. Psychiatric evaluation was performed prior to surgery and the patient was deemed an appropriate surgical candidate. Electrodes were implanted in the temporal occipital pole, anterior temporal pole, amygdala, anterior, middle and posterior hippocampus, posterior periventricular nodular heterotopia, temporal occipital junction and insula.\n\nOn post-operative day 1, the patient demonstrated severe agitation. She attempted to remove her electrodes and slam her head against the bed aiming at the surgical site. The patient was physically restrained by multiple individuals and given 5 mg Haldol and 4 mg Ativan to sedate and calm her.\n\nAn emergent consultation with psychiatry deemed the patient lacked decision making capacity and was a potential active harm to herself and staff. The treatment teams deemed it prudent to remove electrodes over safety concerns. The family and patient showed unwillingness to consent for explantation surgery. Ultimately consent was obtained, though family expressed a strong preference the electrodes remain. Legal counsel advised the neurosurgical team to not remove the electrodes unless necessary. Thus, the patient and family were advised that the next incident of any agitation/antagonism would result in immediate removal.\n\nThe patient was left in the intensive care unit (ICU) for better control of environment. She was given a sitter for monitoring and safety. She had successful capture of seizures and was explanted uneventfully on hospital day 23 without further incident.\n\nCase 2\n\nA 34-year-old male presented to the University of Colorado Neurology Department in 2018 with a 12-year history of drug resistant focal epilepsy. He was scheduled for a phase 1 EMU study which was rescheduled on the day of admission as the patient believed he was only having a half day test opposed to a multi-day study. His reasoning for rescheduling was that he was “not in the right mental space to tolerate the test”. He was later admitted for his phase 1 evaluation in the EMU using VEEG and completed the study with no disturbances. The pre-surgical hypothesis was left temporal lobe, non-lesional epilepsy with no obvious anatomical abnormalities on MRI.\n\nIn 2019 a multi-disciplinary team recommended SEEG to further localize seizures for potential surgical intervention. Prior to surgery the patient was evaluated by psychiatry and deemed an appropriate surgical candidate.\n\nWhile under observation in the EMU after electrode implantation, the patient had multiple episodes of agitation suspected to be secondary to nicotine and marijuana withdrawal and expressed interest in leaving against medical advice (AMA). During these episodes he threatened to pull out his electrodes. He was counseled on the adverse and potentially life-threatening outcome of electrode tampering and subsequent ineligibility for future epilepsy surgery. Psychiatry noted that during periods of agitation the patient lacked capacity to understand the consequences of leaving the hospital with electrodes in place. He was given 2 mg Ativan once and put on Quetiapine 25 mg on post-operative day 1 in response. The patient went on to have multiple target seizures and was successfully explanted on hospital day four.\n\nFollowing explantation, the patient was still severely agitated and expressed interest in leaving the hospital. He was counseled on the post-operative risks and informed that leaving AMA would prevent future surgical interventions due to concern over treatment compliance. The patient was able to calm down, though had repeated cycles of agitation where he threatened to leave until discharged 24 h later.\n\nDiscussion\n\nWell known risk factors for POD include increased age, cognitive impairment, substance abuse, and many others [11], [9]. These vulnerabilities interact with intra-, peri-, and post-operative factors to result in an acutely delirious state [12], [13], [5]. In particular, it has been proposed that there is a direct psychotropic effect of intracranial electrodes that contributes to POD [10]. Thus, patients following SEEG placement are a particularly vulnerable population, but no guidance exists on POD in this population.\n\nPre-operative substance use is a modifiable risk factor for POD. In our two case reports, both patients had significant substance use with abstinence contributing to agitation while hospitalized. Additionally, both of these patients had documented issues tolerating previous phase 1 studies and difficulty abstaining from substances for recommended periods of time (e.g. prior to WADA testing). More thorough documentation of these occurrences may enlighten the care team to the possibility of such situations during phase 2 studies. We propose detailed documentation regarding prior studies, duration of substance abstinence prior to hospitalization and patient tolerance of the prior monitoring to be part of the discussion at epilepsy surgery patient care conferences.\n\nAs well, patients and families need to be informed of the potential of POD and the risk it poses to a patient before electrode placement. Identification of surrogate decision makers and assent for electrode removal if needed for safety concerns can be obtained pre-operatively. Thus, patients and families are able to make better informed decisions and allows for alignment of the patient, family and treatment team on the surgical treatment plan.\n\nPost-operatively, if a patient develops POD re-orientation and modification of risk factors is necessary. As well, decision making capacity should be evaluated using standard hospital protocol. If the patient lacks decision making capacity then the pre-determined medical durable power of attorney (MDPOA) should be reached for treatment discussion. If the MDPOA is not available or no one is designated, legal should be involved, particularly if there is a disagreement about explantation over safety concerns between the treatment team and patient/family. Escalation to this point is hoped to be avoided by the pre-emptive conversations and decrease in substance use before surgery.\n\nAs demonstrated in these case reports, patients that have hyperactive delirium after SEEG can pose unique risk of harm to themselves. By having an external conduit via the electrodes, pulling at the electrodes and aggressive movement of the head can result in neurologic damage that can have devastating consequences. Thus, we propose several steps that can mitigate the risk of POD and lessen the decision making burden post-operatively in the event the patient becomes delirious.\n\nConclusion\n\nPatients undergoing SEEG neuromonitoring for drug resistant epilepsy are at particular risk of POD and have unique safety concerns. Yet, there is a paucity of literature about POD in patients undergoing SEEG monitoring. Thus, we propose several steps pre-operatively that can help reduce the risk of POD and ways post-operatively that POD can be mitigated and addressed by the treatment team.\n\nFunding\n\nNo funding was received for this research\n\nDeclarations of interest\n\nNone.\n\nEthical approval\n\nAll procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.\n\nInformed consent\n\nFor this type of study formal consent is not required.\n\nContributions\n\nAll authors contributed to the article’s conception and design. Material preparation, data collection, and analysis were performed by K. Belanger, F. Grassia and S. DeStefano. The first draft of the manuscript was written by K. Belanger and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.\n\nConflict of interest\n\nAll authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers' bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge or beliefs) in the subject matter or materials discussed in this manuscript.\n==== Refs\nReferences\n\n1 Bilotta F. Lauretta M.P. Borozdina A. Mizikov V.M. Rosa G. Postoperative delirium: risk factors, diagnosis and perioperative care Minerva Anestesiol 79 9 2013 1066 1076 23511351\n2 Rudolph J.L. Marcantonio E.R. Postoperative delirium: acute change with long-term implications Anesth Analg 112 5 2011 1202 1211 21474660\n3 Stienen M.N. Delirium in neurosurgery Acta Neurochir 161 7 2019 1305 1306 31062179\n4 Morshed R.A. Young J.S. Safaee M. Sankaran S. Berger M.S. McDermott M.W. Delirium risk factors and associated outcomes in a neurosurgical cohort: a case-control study World Neurosurg 126 2019 e930 e936 30872201\n5 Rengel K.F. Pandharipande P.P. Hughes C.G. Postoperative delirium La Presse Médicale 47 4 2018 e53 e64 29680484\n6 Brown E.G. Josephson S.A. Anderson N. Reid M. Lee M. Douglas V.C. Evaluation of a multicomponent pathway to address inpatient delirium on a neurosciences ward BMC Health Services Res 18 1 2018 106\n7 Inouye S.K. Bogardus S.T. Charpentier P.A. Leo-Summers L. Acampora D. Holford T.R. A multicomponent intervention to prevent delirium in hospitalized older patients New Engl J Med 340 9 1999 669 676 10053175\n8 Wang J. Ji Y. Wang N. Chen W. Bao Y. Qin Q. Establishment and validation of a delirium prediction model for neurosurgery patients in intensive care Int J Nurs Pr 26 4 2020\n9 Zipser C.M. Deuel J. Ernst J. Schubert M. von Känel R. Böttger S. The predisposing and precipitating risk factors for delirium in neurosurgery: a prospective cohort study of 949 patients Acta Neurochir 161 7 2019 1307 1315 31106393\n10 Carlson J.D. Neumiller J.J. Swain L.D.W. Mark J. McLeod P. Hirschauer J. Postoperative delirium in Parkinson’s disease patients following deep brain stimulation surgery J Clin Neurosci 21 7 2014 1192 1195 24518269\n11 Greene N.H. Attix D.K. Weldon B.C. Smith P.J. Mcdonagh D.L. Monk T.G. Measures of executive function and depression identify patients at risk for postoperative delirium J Am Soc Anesthesiol 110 4 2009 788 795\n12 Maldonado J.R. Acute brain failure: pathophysiology, diagnosis, management, and sequelae of delirium Crit Care Clin 33 3 2017 461 519 28601132\n13 Matano F. Mizunari T. Yamada K. Kobayashi S. Murai Y. Morita A. Environmental and clinical risk factors for delirium in a neurosurgical center: a prospective study World Neurosurg 103 2017 424 430 28412481\n\n",
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"abstract": "BACKGROUND\nOmalizumab is indicated to treat chronic spontaneous urticaria (CSU) refractory to antihistamines. We aim to describe the experience of our department in the treatment of CSU with omalizumab.\n\n\nMETHODS\nRetrospective review of the clinical records of patients.\n\n\nRESULTS\nSix patients (5 females, median age 33 years) treated with omalizumab for a median of 17.5 months were evaluated. All patients had improvement of symptoms after the first dose. In one case, the treatment was suspended after 7 months, but in 9 weeks there was recurrence of symptoms. The main side effect was headache in the drug administration's day. Currently, all patients maintain therapy with omalizumab and are clinically stable.\n\n\nCONCLUSIONS\nOmalizumab proved to be an effective and safe drug for the treatment of patients with refractory CSU.",
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{
"abstract": "Small bowel adenocarcinomas are remarkable for their rarity, difficult diagnosis and poor prognosis. Here we report an unusual case of a 33-year-old patient in whom infiltrative adenocarcinoma of the small bowel was diagnosed after a 10-year history of Crohn's disease. In most previously reported cases, detection of Crohn's disease was subsequent to that of carcinoma of the small bowel or the patients involved had an even longer history of the disease. Our literature review suggests that the risk of small bowel adenocarcinoma is higher in patients with Crohn's disease than in the overall population. We present details on epidemiology as well as clinical and diagnostic aspects of this rare disease entity.",
"affiliations": "Department of Gastroenterology and Hepatology, Anichstrasse 35, A-6020 Innsbruck, Austria. [email protected]",
"authors": "Kronberger|Irmgard E|IE|;Graziadei|Ivo W|IW|;Vogel|Wolfgang|W|",
"chemical_list": "D000894:Anti-Inflammatory Agents, Non-Steroidal; D019804:Mesalamine; D001379:Azathioprine",
"country": "United States",
"delete": false,
"doi": "10.3748/wjg.v12.i8.1317",
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"issn_linking": "1007-9327",
"issue": "12(8)",
"journal": "World journal of gastroenterology",
"keywords": null,
"medline_ta": "World J Gastroenterol",
"mesh_terms": "D000230:Adenocarcinoma; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001379:Azathioprine; D003424:Crohn Disease; D006801:Humans; D007078:Ileal Neoplasms; D015994:Incidence; D008297:Male; D019804:Mesalamine; D011379:Prognosis; D012307:Risk Factors; D012737:Sex Factors; D012907:Smoking; D013997:Time Factors",
"nlm_unique_id": "100883448",
"other_id": null,
"pages": "1317-20",
"pmc": null,
"pmid": "16534894",
"pubdate": "2006-02-28",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": "3158499;7040175;1948581;1499440;1358741;8348849;8253348;7910274;8918446;8980937;9207270;9386295;9500769;9619392;9759659;10366146;10372277;10574144;10665347;11009523;11241255;11247898;11303390;11424324;12144571;12169995;12408504;12432298;12486941;12653953;12901893;12907319;12950413;12950415;14641202;14648412;14716243;14743885;14984375;15046221;15058524;15106148;15037927;15143222;15168828;15181618;15256978;15274064;15300912;15326402;15359211;15508068;4696534;4761532;1155482;949714;598065;2824276",
"title": "Small bowel adenocarcinoma in Crohn's disease: a case report and review of literature.",
"title_normalized": "small bowel adenocarcinoma in crohn s disease a case report and review of literature"
} | [
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},
{
"reactionmeddrapt": "Product use in unapproved indication",
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},
{
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},
{
"reactionmeddrapt": "Abdominal distension",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Small intestine adenocarcinoma",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Malabsorption",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Anaemia",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 200306"
}
},
"primarysource": {
"literaturereference": "KRONBERGER IE, GRAZIADEI IW, VOGEL W. SMALL BOWEL ADENOCARCINOMA IN CROHN?S DISEASE: A CASE REPORT AND REVIEW OF LITERATURE. WORLD JOURNAL OF GASTROENTEROLOGY. 2006?12(8):1317-20",
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] |
{
"abstract": "Ciprofloxacin is a commonly used antibiotic. Renal side effects are rare and are usually immune mediated. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of crystal nephropathy in a young woman treated with ciprofloxacin and a nonsteroidal anti-inflammatory drug.",
"affiliations": "Department of Nephrology, Hedi Chaker Hospital; Renal Pathology Unit UR 12 ES 14, Faculty of Medicine, Sfax, Tunisia. [email protected].",
"authors": "Kammoun|Khawla|K|;Jarraya|Faical|F|;Makni|Saloua|S|;Ben Mahmoud|Lobna|L|;Kharrat|Mahmoud|M|;Ben Hmida|Mohamed|M|;Zeghal|Khaled|K|;Boudawara|Tahia|T|;Hachicha|Jamil|J|",
"chemical_list": "D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D008528:Mefenamic Acid; D002939:Ciprofloxacin",
"country": "Iran",
"delete": false,
"doi": null,
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"issn_linking": "1735-8582",
"issue": "8(3)",
"journal": "Iranian journal of kidney diseases",
"keywords": null,
"medline_ta": "Iran J Kidney Dis",
"mesh_terms": "D000293:Adolescent; D000900:Anti-Bacterial Agents; D000894:Anti-Inflammatory Agents, Non-Steroidal; D002939:Ciprofloxacin; D003460:Crystallization; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007674:Kidney Diseases; D008528:Mefenamic Acid; D014552:Urinary Tract Infections",
"nlm_unique_id": "101316967",
"other_id": null,
"pages": "240-2",
"pmc": null,
"pmid": "24878949",
"pubdate": "2014-05",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Ciprofloxacin-induced crystal nephropathy.",
"title_normalized": "ciprofloxacin induced crystal nephropathy"
} | [
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{
"abstract": "BACKGROUND\nJuvenile dermatomyositis is a rare condition, but it is the most common idiopathic inflammatory myopathy in pediatric patients.\n\n\nOBJECTIVE\nTo study the clinical manifestations, investigations, treatment, clinical course, and outcomes of juvenile dermatomyositis in Thai children.\n\n\nMETHODS\nThis retrospective study included juvenile dermatomyositis patients treated at Siriraj Hospital, a 2,300-bed national tertiary referral center in Bangkok, Thailand, from 1994 to 2019.\n\n\nRESULTS\nThirty patients (22 females and 8 males) were included with a female to male ratio of 2.7:1. Median age at diagnosis was 5.1 years (range, 2.6-14.8 years). Median duration of illness before diagnosis was 6.5 months (range, 0.3-84.0 months). Acute and subacute onset occurred in the majority of patients. Presenting symptoms included muscle weakness in 27/30 (90%), skin rash in 26/30 (86.7%), muscle pain in 17/26 (65.4%), and arthralgia in 4/18 (22.2%) of patients. Dermatologic examination revealed Gottron's rash, heliotrope rash, and periungual telangiectasia in 25/30 (83.3%), 21/30 (70.0%), and 15/24 (62.5%) of patients, respectively. Interestingly, scalp dermatitis was found in 8/21 (38.1%) of patients. The most commonly used treatment regimen in this series was a combination of prednisolone and methotrexate. During the median follow-up of 3.1 years (range, 0.0-18.5 years), only one-third of patients were seen to have monocyclic disease. Extraskeletal osteosarcoma at a previous lesion of calcinosis cutis was observed in one patient at 12 years after juvenile dermatomyositis onset.\n\n\nCONCLUSIONS\nThis was a retrospective single-center study, and our results may not be generalizable to other healthcare settings. Prospective multicenter studies are needed to confirm the findings of this study.\n\n\nCONCLUSIONS\njuvenile dermatomyositis usually poses a diagnostic and therapeutic challenge, which can be compounded by the ethnic variations in the clinical presentation, as observed in this study. Asian patients tend to present with acute or subacute onset of disease, and arthralgia and/or arthritis are less common than in Caucasian patients. Scalp dermatitis is not uncommon in pediatric juvenile dermatomyositis patients. An association between juvenile dermatomyositis and malignancy, though rare, can occur.",
"affiliations": "Division of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.;Division of Rheumatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.;Division of Neurology, Department of Pediatrics, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.;Division of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.;Division of Dermatology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.",
"authors": "Nitiyarom|Rattanavalai|R|;Charuvanij|Sirirat|S|;Likasitwattanakul|Surachai|S|;Thanoophunchai|Chaiwat|C|;Wisuthsarewong|Wanee|W|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0378-6323",
"issue": null,
"journal": "Indian journal of dermatology, venereology and leprology",
"keywords": "JDM; Juvenile dermatomyositis; Thai; calcinosis cutis; children; osteosarcoma; pediatric",
"medline_ta": "Indian J Dermatol Venereol Leprol",
"mesh_terms": null,
"nlm_unique_id": "7701852",
"other_id": null,
"pages": "1-9",
"pmc": null,
"pmid": "34491668",
"pubdate": "2021-08-24",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Juvenile dermatomyositis in Thai children: Retrospective review of 30 cases from a tertiary care center.",
"title_normalized": "juvenile dermatomyositis in thai children retrospective review of 30 cases from a tertiary care center"
} | [
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{
"abstract": "Twenty patients with carbapenem-resistant Enterobacteriaceae infections were treated with meropenem-vaborbactam. Thirty-day clinical success and survival rates were 65% (13/20) and 90% (18/20), respectively. Thirty-five percent of patients had microbiologic failures within 90 days. One patient developed a recurrent infection due to meropenem-vaborbactam-nonsusceptible, ompK36 porin mutant Klebsiella pneumoniae.",
"affiliations": "Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.;Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.;Antibiotic Management Program, University of Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA.;Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.;Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.;Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.;Hackensack-Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA.;Hackensack-Meridian Health Center for Discovery and Innovation, Nutley, New Jersey, USA.;Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.;Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.;Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA.",
"authors": "Shields|Ryan K|RK|;McCreary|Erin K|EK|;Marini|Rachel V|RV|;Kline|Ellen G|EG|;Jones|Chelsea E|CE|;Hao|Binghua|B|;Chen|Liang|L|;Kreiswirth|Barry N|BN|;Doi|Yohei|Y|;Clancy|Cornelius J|CJ|;Nguyen|M Hong|MH|",
"chemical_list": "D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001897:Boronic Acids; C000626994:vaborbactam; D001618:beta-Lactamases; D000077731:Meropenem",
"country": "United States",
"delete": false,
"doi": "10.1093/cid/ciz1131",
"fulltext": null,
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"issue": "71(3)",
"journal": "Clinical infectious diseases : an official publication of the Infectious Diseases Society of America",
"keywords": "KPC; meropenem; porin; resistance; vaborbactam",
"medline_ta": "Clin Infect Dis",
"mesh_terms": "D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001897:Boronic Acids; D000073182:Carbapenem-Resistant Enterobacteriaceae; D004756:Enterobacteriaceae Infections; D006801:Humans; D007711:Klebsiella pneumoniae; D000077731:Meropenem; D008826:Microbial Sensitivity Tests; D001618:beta-Lactamases",
"nlm_unique_id": "9203213",
"other_id": null,
"pages": "667-671",
"pmc": null,
"pmid": "31738396",
"pubdate": "2020-07-27",
"publication_types": "D016428:Journal Article; D052061:Research Support, N.I.H., Extramural; D013485:Research Support, Non-U.S. Gov't",
"references": "26349830;31660388;30397063;28827415;28848018;29133570;30099490;23459476;28559250;30863839;26133566;30617090;29507064;27624958;29038260;30188993;29020404;29486041;28031201;30578403;30270406",
"title": "Early Experience With Meropenem-Vaborbactam for Treatment of Carbapenem-resistant Enterobacteriaceae Infections.",
"title_normalized": "early experience with meropenem vaborbactam for treatment of carbapenem resistant enterobacteriaceae infections"
} | [
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{
"abstract": "We report a case of intentional overdose in a 29-year-old male with two of the newer anti-epileptic agents, lamotrigine and pregabalin. To our knowledge, this case report details the highest plasma levels of lamotrigine ever recorded in the literature. The patient presented with seizures and a reduced level of consciousness. Management of these and subsequent complications centres on supportive care in the high dependency and intensive therapy units.",
"affiliations": "Department of Anaesthetics and Intensive Care, Gloucestershire Royal Hospital, Gloucester, UK. [email protected]",
"authors": "Braga|A J|AJ|;Chidley|K|K|",
"chemical_list": "D000927:Anticonvulsants; D014227:Triazines; D000069583:Pregabalin; D005680:gamma-Aminobutyric Acid; D000077213:Lamotrigine",
"country": "England",
"delete": false,
"doi": "10.1111/j.1365-2044.2006.04913.x",
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"issn_linking": "0003-2409",
"issue": "62(5)",
"journal": "Anaesthesia",
"keywords": null,
"medline_ta": "Anaesthesia",
"mesh_terms": "D000328:Adult; D000927:Anticonvulsants; D062787:Drug Overdose; D006801:Humans; D000077213:Lamotrigine; D008297:Male; D000069583:Pregabalin; D012640:Seizures; D013406:Suicide, Attempted; D014227:Triazines; D014474:Unconsciousness; D005680:gamma-Aminobutyric Acid",
"nlm_unique_id": "0370524",
"other_id": null,
"pages": "524-7",
"pmc": null,
"pmid": "17448068",
"pubdate": "2007-05",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Self-poisoning with lamotrigine and pregabalin.",
"title_normalized": "self poisoning with lamotrigine and pregabalin"
} | [
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"abstract": "Phyllodes tumors of the breast are biphasic tumors consisting from an epithelial component and a mesenchymal component. Usually, the mesenchymal component of the tumor is the one who dictates the malignancy of the biphasic proliferation. Presence of the malignancy of the both, epithelial [under the form of invasive carcinoma or ductal carcinoma in situ (DCIS)] and mesenchymal components is very rare. Most of the data available from the literature refers to single case presentations. This paper presents the experience of Prof. Dr. Ion Chiricuţă Oncological Institute (IOCN), Cluj-Napoca, Romania, with the malignant phyllodes tumors with both epithelial and mesenchymal components showing malignancy. Over two decades (1999-2018), four cases of malignant phyllodes tumors with concomitant epithelial and mesenchymal malignancy were found and presented as a case series. Two out of four cases were malignant phyllodes tumors harboring invasive breast carcinomas (one case with associated DCIS and one case of pure invasive carcinoma) and two cases were malignant phyllodes tumors with the epithelial component showing DCIS. Average follow-up period was 67 months (from 39 to 132 months) with a disease-free survival of 58 months.",
"affiliations": "Department of Surgical and Gynecological Oncology, Prof. Dr. Ion Chiricuţă Oncological Institute, Cluj-Napoca, Romania; [email protected].",
"authors": "Nistor-Ciurba|Codruţ Cosmin|CC|;Şomcutian|Oana|O|;Lisencu|Ioan Cosmin|IC|;Ignat|Florin Laurenţiu|FL|;Lazăr|Gabriel Lucian|GL|;Eniu|Dan Tudor|DT|",
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"fulltext": "\n==== Front\nRom J Morphol Embryol\nRom J Morphol Embryol\nRJME\nRomanian Journal of Morphology and Embryology\n1220-0522 2066-8279 Academy of Medical Sciences, Romanian Academy Publishing House, Bucharest \n\n32747903\n610120129135\n10.47162/RJME.61.1.14\nOriginal Paper\nMalignant phyllodes tumors of the breast associating malignancy of both mesenchymal and epithelial components (invasive or in situ ductal carcinoma)\nNistor-Ciurba Codruţ-Cosmin 12 Şomcutian Oana 3 Lisencu Ioan Cosmin 12 Ignat Florin Laurenţiu 12 Lazăr Gabriel Lucian 12 Eniu Dan Tudor 12 1 Discipline of Surgical and Gynecological Oncology, Department of Oncology, Iuliu Haţieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania\n2 Department of Surgical and Gynecological Oncology, Prof. Dr. Ion Chiricuţă Oncological Institute, Cluj-Napoca, Romania\n3 Department of Pathology, Prof. Dr. Ion Chiricuţă Oncological Institute, Cluj-Napoca, Romania\nCorresponding Author: Ioan Cosmin Lisencu\nMD, PhD, Department of Surgical and Gynecological OncologyProf. Dr. Ion Chiricuţă Oncological Institute34–36 Republicii Street400015 Cluj-NapocaRomania+40264–598 [email protected]\nJan-Mar 2020 \n02 6 2020 \n61 1 129 135\n07 1 2020 02 6 2020 Copyright © 2020, Academy of Medical Sciences, Romanian Academy Publishing House, Bucharest2019This is an open-access article distributed under the terms of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License, which permits unrestricted use, adaptation, distribution and reproduction in any medium, non-commercially, provided the new creations are licensed under identical terms as the original work and the original work is properly cited.Phyllodes tumors of the breast are biphasic tumors consisting from an epithelial component and a mesenchymal component. Usually, the mesenchymal component of the tumor is the one who dictates the malignancy of the biphasic proliferation. Presence of the malignancy of the both, epithelial [under the form of invasive carcinoma or ductal carcinoma in situ (DCIS)] and mesenchymal components is very rare. Most of the data available from the literature refers to single case presentations. This paper presents the experience of Prof. Dr. Ion Chiricuţă Oncological Institute (IOCN), Cluj-Napoca, Romania, with the malignant phyllodes tumors with both epithelial and mesenchymal components showing malignancy. Over two decades (1999–2018), four cases of malignant phyllodes tumors with concomitant epithelial and mesenchymal malignancy were found and presented as a case series. Two out of four cases were malignant phyllodes tumors harboring invasive breast carcinomas (one case with associated DCIS and one case of pure invasive carcinoma) and two cases were malignant phyllodes tumors with the epithelial component showing DCIS. Average follow-up period was 67 months (from 39 to 132 months) with a disease-free survival of 58 months.\n\nphyllodes tumorbreast cancerinvasive carcinomaductal carcinoma in situ\n==== Body\nIntroduction\nBreast phyllodes tumors are rare biphasic (mesenchymal with a typical leaf-like architecture and epithelial) tumors of the breast usually classified in benign, borderline and malignant according to the World Health Organization (WHO) classification of breast tumors [1], on the basis of features like stromal overgrowth, atypia, infiltrative borders, mitosis rate, presence of necrosis [1,2]. Usually is the mesenchymal component the one to dictate the malignancy of the tumor [1,2]. Presence of the malignancy of both epithelial [under the form of invasive carcinoma or ductal carcinoma in situ (DCIS)] and mesenchymal components at the same time is an even rarer finding. That is why most of the literature data refers to single case presentations [3,4,5,6] or small series presentations [7,8,9,10] but also that is why it is a challenging diagnostic for the pathologists [1,2, 11]. It is believed that malignancy of the epithelial component of phyllodes tumor occurs in less than 1% of all phyllodes tumors [8].\n\nWe could not find any Romanian prior experience with such cases or series.\n\nAim\n\nCurrent paper presents the experience of Prof. Dr. Ion Chiricuţă Oncological Institute (IOCN), Cluj-Napoca, Romania, with the cases of malignant phyllodes tumors of the breast harboring malignancy of both mesenchymal and epithelial components of the tumor.\n\nPatients, Materials and Methods\nTo obtain data about all the cases of malignant phyllodes tumors, the Digital Database of the Department of Pathology from IOCN was searched for malignant phyllodes tumors, from the beginning (1999) of our digital records to 31.12.2018. A total of 114 distinct cases of malignant phyllodes tumors were found. The search was done for both International Classification of Diseases for Oncology (ICD–O) C50 and ICD–O 9020/3 codes.\n\nAll the reports were reviewed and for five cases, we found coexistence of malignant phyllodes tumors and invasive carcinoma or DCIS in the same breast.\n\nThe remaining five cases were reviewed; after each case was reviewed by a senior pathologist to reconfirm the diagnosis, according to current WHO classifications, four cases were reconfirmed. These four cases form the series we present in this article.\n\nAll cases have written consent obtained during hospitalization for publishing data (information and photos) from their medical files.\n\nAll data presented in this article was obtained from IOCN Institutional Cancer Registry.\n\nPresent study has the authorization for publication obtained from the Ethics Committee of IOCN, available at the editor.\n\nResults \nWe present here four cases of malignant phyllodes tumors that showed malignant transformations in both epithelial and mesenchymal structures. The age of the patients ranged from 45 to 75 years and average age at presentation was 60.25 years. Average follow-up was 67 months (39 to 132 months). The main characteristics of the patients in our group are presented in Table 1.\n\nTable 1 Main descriptive features of the cases \n\n\nFeature\n\n\n\t\nCase No. 1\n\n\n\t\nCase No. 2\n\n\n\t\nCase No. 3\n\n\n\t\nCase No. 4\n\n\n\t\n\nAge [years]\n\n\n\t\n50\n\n\n\t\n71\n\n\n\t\n45\n\n\n\t\n75\n\n\n\t\n\nDimension [cm]\n\n\n\t\n11\n\n\n\t\n5\n\n\n\t\n6\n\n\n\t\n4\n\n\n\t\n\nGrade of mesenchymal component\n\n\n\t\n2\n\n\n\t\n1\n\n\n\t\n1\n\n\n\t\n2\n\n\n\t\n\nNo. of mitoses/10 HPFs\n\n\n\t\n25\n\n\n\t\n12\n\n\n\t\n13\n\n\n\t\n20\n\n\n\t\n\nDifferentiation\n\n\n\t\nChondrosarcoma\n\n\n\t\n–\n\n\n\t\n–\n\n\n\t\n–\n\n\n\t\n\nEpithelial component malignancy\n\n\n\t\nIDC + DCIS\n\n\n\t\nIDC\n\n\n\t\nDCIS\n\n\n\t\nIDC + DCIS\n\n\n\t\n\nGrade of epithelial component\n\n\n\t\n3\n\n\n\t\n1\n\n\n\t\n2\n\n\n\t\n2\n\n\n\t\n\nType of epithelial component\n\n\n\t\nNST\n\n\n\t\nNST\n\n\n\t\nSolid, cribiform\n\n\n\t\nNST\n\n\n\t\n\nER [%]\n\n\n\t\n0\n\n\n\t\n98\n\n\n\t\n10\n\n\n\t\n0\n\n\n\t\n\nPR [%]\n\n\n\t\n0\n\n\n\t\n98\n\n\n\t\n10\n\n\n\t\n0\n\n\n\t\n\nKi67 [%]\n\n\n\t\n45\n\n\n\t\n10\n\n\n\t\n–\n\n\n\t\n35\n\n\n\t\n\nFollow-up [months]\n\n\n\t\n132\n\n\n\t\n39\n\n\n\t\n41\n\n\n\t\n56\n\n\n\t\n\nDFS [months]\n\n\n\t\n132\n\n\n\t\n39\n\n\n\t\n27\n\n\n\t\n34\n\n\n\t\n\nDeath from tumor [months]\n\n\n\t\n–\n\n\n\t\n–\n\n\n\t\n–\n\n\n\t\n56\n\n\n\t\nHPFs: High-power fields; ER: Estrogen receptor; PR: Progesterone receptor; DFS: Disease-free survival; IDC: Invasive ductal carcinoma; DCIS: Ductal carcinoma in situ; NST: No special type \n\nFor a better understanding of our series, we decided to briefly present every case.\n\nCase No. 1\n\nPatient, MA, 50-year-old, from a town in Cluj County (Romania), presented in June 2000 in IOCN with a left breast tumor of 12/10 cm.\n\nShe had no family history of cancers or other significant illness.\n\nShe had no surgical antecedents and no important comorbidities, apart from moderate high blood pressure controlled with medication (Captopril).\n\nThe patient discovered the tumor three weeks ahead of the presentation at IOCN by palpation, as a mass in the left breast, of about 7 cm, and she decided to go to her family doctor after two weeks when she found that the tumor was growing rapidly. She was directed to IOCN.\n\nAt presentation, patient was in good health, with no important comorbidities, no known allergies, premenopausal. Clinical exam revealed a 12/10 cm tumor of the left breast deforming the whole breast, polylobate, partially well delimited, without skin ulceration but with skin adhesion, mobile on the pectoral plane, without axillary adenopathy. The contralateral breast and axilla and both supraclavicular areas were without pathological changes.\n\nWith clinical suspicion of malignant phyllodes tumor, a mammogram was done and revealed a bulky nodular opacity of 10 cm diameter of the left breast, partial well delimited, with intraductal microcalcifications in the tumor. The mammogram was interpreted as highly suspect of malignancy and a biopsy was requested.\n\nAn excisional biopsy was performed, with an intra-operative on ice pathological examination confirming malignancy. In the same surgical session, left modified Madden mastectomy has been carried out. Postoperative evolution was simple with no complication.\n\nDefinitive pathological report showed a giant tumor of 11/8 cm with microscopic structure of a malignant phyllodes tumor with chondrosarcomatous differentiation associating areas of intraductal breast carcinoma. The mesenchymal component was G2, with 25 mitoses/10 high-power fields (HPFs), while the epithelial component was G3, estrogen receptor (ER) and progesterone receptor (PR) negative, with a 45% Ki67 factor. No axillary nodes metastasis (N 0/22) was found (Figure 1, a and b).\n\nFigure 1 (a) Chondrosarcomatous differentiation within the malignant mesenchymal component; (b) The malignant mesenchymal component represented by an atypical fusocellular population, located in the immediate vicinity of the epithelial component that has the appearance of DCIS. HE staining: (a) ×100; (b) ×40. DCIS: Ductal carcinoma in situ; HE: Hematoxylin–Eosin\n\nComputed tomography (CT) scan showed no distant metastasis and Therapeutic Decision Committee recommended adjuvant chemo-radiotherapy, which the patient fulfilled until November 2000. She presented for the follow-up visits for 11 years (132 months) with no recurrence during the follow-up period and then she was lost from surveillance.\n\nCase No. 2\n\nPatient, TA, 71-year-old, from a village of Suceava County (Romania), presented in IOCN in early November 2014 with a right breast tumor of 5/5 cm.\n\nThe patient had no family history of cancers. Her surgical history included only an appendectomy in the childhood and a laparoscopic cholecystectomy in 2007. She had no oncological antecedents and she had no significant prior illness and no known allergies.\n\nThe patient found the tumor two weeks before the presentation in IOCN, by palpation. She presented to her family doctor who directed her in our Service.\n\nAt presentation, clinical exam found a 5/5 cm polylobate mass of inhomogeneous consistency, with preserved mobility against the pectoralis plane, with incomplete skin adhesion in the upper and central quadrants (12.00 hours) of the right breast. No axillary or supraclavicular palpable nodes were noted. Left breast and axilla were normal.\n\nBreast ultrasound (US) examination and mammogram have described a 5/5 cm mass, at the junction of the superior quadrants of the right breast (12.00 hours) partially well delimitated, partial seeming invasive, polylobate, inhomogeneous, with calcifications within the tumor, tending to extend to the overlying skin. With high suspicion of a malignant phyllodes tumor, the lesion had been classified as Breast Imaging-Reporting and Data System (BI-RADS) 5, demanding biopsy confirmation.\n\nTru-Cut® biopsy has been done at the time of first presentation and three weeks later, the pathological report showed the presence of a malignant phyllodes tumor associated with a ductal invasive of no special type (NST) carcinoma G1 Nottingham (nuclear grade 1, mitotic grade 1, tube formation 1) without in situ component (Figure 2, a and b).\n\nThe invasive component was described as ER+++ (98%) and PR+++ (98%), with human epidermal growth factor receptor 2 (Her2) 1+ score and a Ki67 index of <10%, cytokeratin (CK) AE1/AE3 and E-cadherin positive. There was no sign of lymphatic or perineural invasion.\n\nThe malignant mesenchymal component of the phyllodes tumor was described by immunohistochemistry (IHC) as smooth muscle actin (SMA) and cluster of differentiation (CD) 10 focally positive, CD34 and p63 positive (Figure 2c); CK AE1/AE3, c-kit, desmin, myoglobin, CK high molecular weight (CKHMW) were negative. It was considered a G1 malignant mesenchymal component with 12 mitoses/10 HPFs.\n\nFigure 2 (a) Mesenchymal–epithelial biphasic aspect: the fusocellular component is predominant and has condensation around the epithelial component; (b) Tubular structures devoid of myoepithelial cells, arranged in a desmoplastic stroma and accompanied by the hypercellular mesenchymal contingent; (c) Microscopic image with epithelial, tubular structures, positive for anti-p63 antibody. HE staining: (a and b) ×100. Anti-p63 antibody immunostaining: (c) ×200. HE: Hematoxylin–Eosin\n\nAs a result of this pathological report, the patient returned in December 2014, a thorax–abdomen–pelvis CT scan excluded distant metastasis and a modified right radical mastectomy was performed with simple, favorable evolution, the definitive pathological report describing a 5/4 cm tumor with the same features with a posterior resection margin of less than 1 mm, with 16 negative axillary lymph nodes (N 0/16).\n\nTherapeutic Decision Committee indicated hormonal therapy and external breast irradiation. The patient underwent the radiotherapy three months after the definitive surgical treatment and presented for the follow-up visits 39 months after the surgery. During this period of time, she also received hormonal treatment. She was lost from follow-up after 39 months, with no signs of loco-regional or distant recurrence for 39 months after the surgical treatment.\n\nCase No. 3\n\nPatient, AM, 39-year-old, from a village of Tulcea County (Romania), presented in IOCN Outpatient Service, in June 2010, with a 7/7 cm left breast tumor discovered by the patient (inspection and palpation) two months before the presentation.\n\nThe patient had no family history of cancers and also no relatives with serious medical conditions. She was in good health; from her medical history, we can mention only a uterine fibromatosis and polycystic kidney. She had no prior surgical treatments and she was not known with allergies.\n\nTwo months before the presentation, she observed a mass deforming her left breast and at palpation, she describes the tumor as about 6/6 cm. A few weeks after, she visited her family doctor, who sent her for breast US and mammographic investigations. Both described a 6/6 cm well delimited left breast mass at the junction of the superior quadrants with no skin or pectoral invasion. The tumor was polylobate, inhomogeneous, with a structural mix of fluid and solid parts, with some calcifications in the solid component. It was interpreted as a possible phyllodes tumor and she was referred to IOCN. No other breast tumor was found bilaterally and no axillary adenopathy was found bilateral.\n\nClinical examination at presentation found a still mobile on the pectoral plane, 7/7 cm mass, inhomogeneous, polylobate, with different consistencies within the tumor (fluid and solid). The tumor was also mobile against the overlaying skin. No other tumor was found in the breasts bilaterally and there was no supraclavicular or axillary (bilateral) lymphadenopathy.\n\nWith the suspicion of a phyllodes tumor, an excisional biopsy was performed with an intraoperative ice and definitive pathological result of a borderline phyllodes tumor, with maximum five mitoses/10 HPFs. The exuberant epithelial component showed areas of ductal typical hyperplasia.\n\nShe refused any further re-excision and come only for one follow-up visit, at three months.\n\nAfter six years, she presented again in the IOCN Outpatient Service, in September 2016, with a left breast mass of about 10/7 cm, involving the central and upper quadrants of the left breast, with no supraclavicular or axillary (bilateral) adenopathy. The tumor was worst delimited than first time, also presented mixed consistency, with alternation of solid and liquid areas, but still was mobile on the pectoral plane. No axillary or supraclavicular (bilateral) adenopathies were noted. Right breast was normal.\n\nThe tumor was first noticed by the patient three months before the presentation by palpation as a 5 cm diameter mass at that time. When she realized that the tumor was growing fast, she presented in IOCN.\n\nThe mammogram showed a 10/7 cm left breast mass, partial well delimited, partial invasive, inhomogeneous, with mixed structure (fluid and solid) with microcalcifications within the tumor.\n\nAn excision was performed (patient refused core biopsy). Pathological report stated malignant phyllodes tumor, with 12–13 mitoses/10 HPFs in the most active areas of the malignant mesenchymal component, with invasion front, necrosis and infarction on about 25% of the section surface, with the typical leaf-like feature. No differentiation of the mesenchymal component was noted. As for the mesenchymal component, a G2 malignancy was assigned (Figure 3, a and b).\n\nFigure 3 (a) Epithelial contingent represented by ductal structures with DCIS lesions with cribriform and solid architecture; (b) DCIS lesions with micropapillary architecture, surrounded by a hypercellular mesenchymal contingent, composed of fusiform cells, with mild, mitotically-active atypia. HE staining: (a) ×40; (b) ×100. DCIS: Ductal carcinoma in situ; HE: Hematoxylin–Eosin\n\nWithin the tumor foci, solid, moderate grade (G2) DCIS were found in the epithelial component. Those were ER+ (10%) and PR+ (10%), p63 positive and CK5 negative.\n\nFor our study, we considered this moment, of the first diagnosis of malignant phyllodes tumor associated with DCIS, as the T0 moment for the follow-up.\n\nThe patient was recalled for further treatment (mastectomy/irradiation) but she refused and she did not came for follow-up visits until January 2019 when, after 27 months, she presented with a big 9/8 cm tumor in the same left breast, entirely deforming the upper and central quadrants of the breast. From the anamneses, we found out that the tumor reappeared 3–4 months before the presentation. The tumor had the same clinical features, inhomogeneous, polylobate, mobile on the pectoralis plane but tending to be invaded by the overlying skin and the surrounding fat tissue. No left axillary or supraclavicular adenopathy were found. Right breast, axilla and supraclavicular area were normal.\n\nBilateral mammogram showed a bulky 90/80 mm left breast opacity partially well delimited, partially irregular, tending to invade the surrounding tissues, with round calcifications within the tumor. No lymphadenopathies were noted.\n\nCT scan was normal, with no distant metastasis.\n\nA left mastectomy with sentinel node biopsy was performed in January 2019, with simple favorable evolution. The pathological report stated a 6/6 cm bulky, polylobate, friable tumor, with a minimum 1 cm resection margin (posterior) of sane tissue.\n\nThe fibroepithelial proliferation had a mitotic index of 10–11 mitoses/10 HPFs and showed leaf-like features, invasion front, necrosis (approximately 25% of the section surface), foci of DCIS solid and cribriform, moderate nuclear grade (G2) inside the tumor but this time also in the vicinity of the tumor. Sentinel lymph node biopsy showed no sign of malignity in the Hematoxylin–Eosin (HE) and IHC staining (for CK AE1/AE3).\n\nGiven the result, no further treatment was recommended and the patient, this time, presented for the follow-up visits, with no signs of distant or loco-regional recurrences.\n\nCase No. 4\n\nPatient, TS, 75-year-old, from a small town in Cluj County (Romania), presented in IOCN Outpatient Service, in July 2014, with a left breast, 4/3 cm, mass.\n\nThe patient discovered the mass a few weeks ago by palpation, she presented to her family doctor who directed her to IOCN Outpatient Service.\n\nFrom her medical history is to be retained a Parkinson’s disease, stage IIIC (very high-risk) hypertension under treatment and atrial fibrillation (under treatment). In addition, she had multiple allergies. She had no relatives with cancer history.\n\nClinical examination found a 4/3 cm mass in the left breast, partially well delimited, partial imprecise delimited, invasive in the surrounding tissues, mobile on the thoracic wall, not invading the pectoralis plane, with partial adhesion to the overlying skin, situated in the superior-external quadrant of the left breast. Also, a 1.5 cm high consistency, mobile, left axillary adenopathy was noted. No supraclavicular (bilateral) adenopathy was found. Right breast and axilla were normal.\n\nA mammogram and a breast US examination were performed, showing a BI-RADS 5, 4/3 cm left breast tumor in the outer-external quadrant, partially well delimited, partially imprecise delimited, inhomogeneous, polylobate, seeming to invade the surrounding tissues in some parts. Microcalcifications were present inside the tumor, especially in a 2/1.5 cm area, which seemed to be more speculate, solid and invasive. Also, the left adenopathy was described.\n\nCT scan showed no distant metastasis.\n\nA core biopsy was performed with pathological result of phyllodes tumor, with not much information due to the relative small specimens and recommendation for excisional biopsy, which was performed in August 2014 with intraoperative, at ice, pathological exam showing malignancy (malignant phyllodes tumor associated with carcinoma). A left radical modified Madden mastectomy was performed in the same operative session, with simple, favorable evolution.\n\nThe pathological report revealed a 4/3 cm tumor consisting from a malignant phyllodes tumor associated with invasive breast carcinoma NST (2/1.7 cm epithelial component) Nottingham II (histological grade 2, nuclear grade 2, mitotic grade 1) and moderate grade (G2) solid DCIS associated on approximately 5% of the sections (Figure 4, a and b).\n\nFigure 4 (a) Typical biphasic aspect with the predominance of the mesenchymal, hypercellular contingent, with nuclear atypia and mitotic activity; (b) Image of malignant epithelial component represented by a proliferation of epithelial cells with moderate atypia, arranged in trabeculae and focally drawing glandular lumens. HE staining: (a) ×100; (b) ×40\n\nWithin the tumor, necrosis was focal; no angiolymphatic or perineural invasion was noted.\n\nThe epithelial component was a triple negative (ER 0%, PR 0%, Her2 – 0) breast cancer, with a Ki67 proliferation index of 35%.\n\nThe malignant mesenchymal component had the following IHC features: SMA, CD10, CKHMW, CK AE1/AE3, p63 and CK5/6 focal positive, CD34 and c-kit negative. Mitotic index was 20 mitoses/10 HPFs in the most active parts of the mesenchymal component.\n\nNo axillary metastasis was found among the 24 axillary lymph nodes examined (N 0/24).\n\nTherapeutic Decision Committee indicated external radiotherapy, which was delivered in November 2014. The patient presented for follow-up since May 2017 when a 4/3.5 cm was found in the right breast associated with a 2 cm right axillary adenopathy. Until that time, no loco-regional or distant relapse was found. A two-dimensional (2D) + three-dimensional (3D) mammogram was performed showing a highly suggestive for malignancy (BI-RADS 5) right breast mass and a image-guided core biopsy has been performed, confirming the malignancy of the lesion as invasive ductal carcinoma of the breast NST G3 with ER 40%, PR 40%, Ki67 index 30%, Her2 – 0.\n\nDue to the existing, accentuated cardiac comorbidity (left ventricle G3 failure, atrial fibrillation with high transmission rate, which could not be converted, stage 3 hypertension), the patient refused surgery, chemotherapy was not possible and hormonal treatment (Anastrozole) has begun. CT scan and whole body scintigraphy at that time revealed no distant metastasis. Under hormone treatment, the cancer progressed rapidly and in three months, the appearance was of inflammatory carcinoma. Although palliative irradiation of the right breast and axilla was delivered and hormonal treatment changed for Exemestane, the evolution was unstoppable, in April 2019 the patient was diagnosed with metastatic bilateral pleurisy, multiple lung and bone (spine and rips) metastasis and died in May 2019, 56 months after the initial treatment.\n\nDiscussion\nAlthough phyllodes tumors mainly affect women in their 40’s [12,13], in our series, the association of malignancy of both components of a phyllodes tumor seems to arise slightly later; only one of the cases was 45-year-old at the moment of diagnostic; average age was 60.25 years, with two cases over 70 years (71 and 75 years old, respectively). This is in accordance with data published by some authors [7,8].\n\nTo date, only a few studies in literature published data about malignant phyllodes tumor of the breast associating malignancy of both mesenchymal and epithelial components. A simple search of PubMed® returns 1126 items for “malignant phyllodes tumor of the breast” but only 35 items when searching for “malignant phyllodes tumor of the breast associated with breast carcinoma”. Some of them are larger studies on phyllodes tumors of all types (benign, borderline and malignant – from the mesenchymal component appearance) and report cases of malignant phyllodes tumors from Singapore [9] presented six cases of malignant epithelial components through phyllodes tumors and the last malignancy of both phyllodes components [7, 9, 14].\n\nA study from British Columbia, Canada [7], presented three cases and another one, from China (South China and Hong Kong) [14], presented six cases of malignant epithelial component of phyllodes tumors, three of them also associating malignancy of the mesenchymal component in the same breast.\n\nCanadian study [7] presented a higher incidence of malignancy of epithelial component among phyllodes tumors (6%) compared to other studies (1%) [8,9, 14]. Our series is between the two limits (four cases out of 114, meaning 3.508%).\n\nThere is no current proven data about certain types of stromal malignant differentiations to be more often associated with the coexistence of the malignancy of the epithelial component in a malignant phyllodes tumor, although the chondrosarcomatous differentiation is the most common type of mesenchymal differentiation found in malignant phyllodes tumors [1,2, 11,12]. In our series, also, the only type of differentiation found was the chondrosarcomatous differentiation, present in one case.\n\nCurrent data in the literature stated that surgical treatment is the main treatment for the malignant phyllodes tumors of the breast. It may be either local excision, with >10 mm clear margins or mastectomy [12, 14,15,16,17,18]. For the tumors with malignancy only of the mesenchymal component, the axillary lymph nodes dissection is not indicated [12, 15,16,17,18]. Due to the association of malignancy of the epithelial component, verifying the axillary status either by sentinel lymph nodes biopsy or axillary lymph nodes dissection is mandatory.\n\nIn our series, both cases with invasive breast carcinoma benefited from homolateral axillary lymphadenectomy, both with negative nodes (N 0/16, N 0/24) and one of the cases with DCIS benefited of sentinel node biopsy meanwhile the other had axillary lymphadenectomy (N 0/22).\n\nBoth cases with the malignant epithelial component consisting in invasive breast carcinoma were treated by radical modified mastectomy; also, one of the cases in which the epithelial component was DCIS was primary treated by mastectomy. Also, the second case with DCIS was recalled for further treatment but the patient did not show.\n\nIf clear margins of 10 mm or more cannot be achieved, adjuvant radiotherapy is to be delivered [12, 15,16,17,18,19]. Also, association of the malignancy of the epithelial component indicates the radiotherapy in cases of conservative surgical treatment or in case of axillary lymph nodes involvement.\n\nIn our study, three of the cases benefited from radiotherapy due to close margins (<10 mm) even after mastectomy.\n\nThe use of chemotherapy in malignant phyllodes tumors is usually reserved for the metastatic cases [16, 18, 20], but association of the malignancy of the epithelial component may render adjuvant chemotherapy necessary after surgical treatment as an appropriate indication for the malignancy of the epithelial component.\n\nDepending of the ER and PR status, hormonal treatment may be mandatory for the carcinomatous component of the tumor and, also, depending of the Her2 status, specific anti Her2 treatment may be required. In our study, both ER- and PR positive cases were assigned for hormonal therapy. No case was Her2+, so no anti-Her2 treatment has been given.\n\nAlthough some authors indicate that carcinomas arising from the epithelial component of a malignant phyllodes tumor will behave less aggressive [21], in our study the epithelial component was present in both recurrences (one local recurrence and the other distant metastasis).\n\nUnfortunately, occurrence of metastasis usually signals imminence of death [12,13, 22], with a median of seven months of survival after metastasis appearance. The only case in our series with distant metastasis had a five months survival after metastasis diagnostic.\n\nConclusions\nCurrent paper presents the experience of a tertiary health care institution in the management of malignant phyllodes tumors associating the malignancy of both mesenchymal and epithelial components in the form of a four cases series. Apart from the rarity of these tumors, real challenges arise for the whole team involved in the management of such cases, from diagnostic to treatment due to concomitant association of two different malignancies in the same tumor. Of course, the small number of cases is the weak point of present study but given the rarity of these tumors, this might one of the biggest series published to date.\n\nConflict of interests\nAll authors have no conflicts of interest to declare.\n==== Refs\nReferences\n1 World Health Organization (WHO) Classification of tumours of the breast Lakhani SR Ellis IO Schnitt SJ Tan PH van de Vijver MJ WHO Classification of Tumours 4 2012 Lyon, France International Agency for Research on Cancer (IARC) Press 4 143 147 \n2 Pathology and genetics of tumours of the breast and female genital organs Tavassoli FA Devilee P WHO Classification of Tumours 2003 Lyon, France IARC Press 99 103 \n3 Lester J Stout AP Cystosarcoma phyllodes Cancer 1954 7 2 335 353 13141227 \n4 Kodama T Kameyama K Mukai M Sugiura H Ikeda T Okada Y Invasive lobular carcinoma arising in phyllodes tumor of the breast Virchows Arch 2003 442 6 614 616 12743817 \n5 Macher-Goeppinger S Marme F Goeppert B Penzel R Schirmacher P Sinn HP Aulmann S Invasive ductal breast cancer within a malignant phyllodes tumor: case report and assessment of clonality Hum Pathol 2010 41 2 293 296 19896695 \n6 Sugie T Takeuchi E Kunishima F Yotsumoto F Kono Y A case of ductal carcinoma with squamous differentiation in malignant phyllodes tumor Breast Cancer 2007 14 3 327 332 17690514 \n7 Widya RL Rodrigues MF Truong PT Watson PH Weir LM Knowling MA Wai ES Malignant epithelial transformation in phyllodes tumor: a population-based case series Cureus 2017 9 11 e1815 e1815 29312836 \n8 Tan PH Jayabaskar T Chuah KL Lee HY Tan Y Hilmy M Hung H Selvarajan S Bay BH Phyllodes tumors of the breast: the role of pathologic parameters Am J Clin Pathol 2005 123 4 529 540 15743740 \n9 Sin EIL Wong CY Yong WS Ong KW Madhukumar P Tan VKM Thike AA Tan PH Tan BKT Breast carcinoma and phyllodes tumour: a case series J Clin Pathol 2016 69 4 364 369 26670744 \n10 Sun L Zhu R Ginter P Malik M Sung KJ Hughes JM Siegel B Tsai J Coexisting DCIS and phyllodes breast tumors in young Chinese women: case series Int J Surg Case Rep 2019 56 13 16 30798095 \n11 Tan BY Acs G Apple SK Badve S Bleiweiss IJ Brogi E Calvo JP Dabbs DJ Ellis IO Eusebi V Farshid G Fox SB Ichihara S Lakhani SR Rakha EA Reis-Filho JS Richardson AL Sahin A Schmitt FC Schnitt SJ Siziopikou KP Soares FA Tse GM Vincent-Salomon A Tan PH Phyllodes tumours of the breast: a consensus review Histopathology 2016 68 1 5 21 26768026 \n12 Mituś J Reinfuss M Mituś JW Jakubowicz J Blecharz P Wysocki WM Skotnicki P Malignant phyllodes tumor of the breast: treatment and prognosis Breast J 2014 20 6 639 644 25227987 \n13 Mituś JW Blecharz P Reinfuss M Kulpa JK Skotnicki P Wysocki WM Changes in the clinical characteristics, treatment options, and therapy outcomes in patients with phyllodes tumor of the breast during 55 years of experience Med Sci Monit 2013 19 1183 1187 24356679 \n14 Co M Tse GM Chen C Wei J Kwong A Coexistence of ductal carcinoma within mammary phyllodes tumor: a review of 557 cases from a 20-year region-wide database in Hong Kong and Southern China Clin Breast Cancer 2018 18 3 e421 e425 28689011 \n15 Onkendi EO Jimenez RE Spears GM Harmsen WS Ballman KV Hieken TJ Surgical treatment of borderline and malignant phyllodes tumors: the effect of the extent of resection and tumor characteristics on patient outcome Ann Surg Oncol 2014 21 10 3304 3309 25034817 \n16 Adesoye T Neuman HB Wilke LG Schumacher JR Steiman J Greenberg CC Current trends in the management of phyllodes tumors of the breast Ann Surg Oncol 2016 23 10 3199 3205 27334214 \n17 Guillot E Couturaud B Reyal F Curnier A Ravinet J Laé M Bollet M Pierga JY Salmon R Fitoussi A Breast Cancer Study Group of the Institut Curie Management of phyllodes breast tumors Breast J 2011 17 2 129 137 21251125 \n18 National Comprehensive Cancer Network. Phyllodes tumor (version 3.2019) Available from:\nhttps://www.nccn.org/professionals/physician_gls/pdf/breast.pdf. [ Accesed 19.11.2019]\n \n19 Zeng S Zhang X Yang D Wang X Ren G Effects of adjuvant radiotherapy on borderline and malignant phyllodes tumors: a systematic review and meta-analysis Mol Clin Oncol 2015 3 3 663 671 26137284 \n20 Yamamoto S Yamagishi S Kohno T Tajiri R Gondo T Yoshimoto N Kusano N Effective treatment of a malignant breast phyllodes tumor with doxorubicin-ifosfamide therapy Case Rep Oncol Med 2019 2019 2759650 2759650 31316848 \n21 Shin YD Lee SK Kim KS Park MJ Kim JH Yim HS Choi YJ Collision tumor with inflammatory breast carcinoma and malignant phyllodes tumor: a case report and literature review World J Surg Oncol 2014 12 5 5 24400686 \n22 Lin CC Chang HW Lin CY Chiu CF Yeh SP The clinical features and prognosis of phyllodes tumors: a single institution experience in Taiwan Int J Clin Oncol 2013 18 4 614 620 22773245\n\n",
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"abstract": "Glioblastoma is the most common adult primary brain tumor that occurs in the central nervous system and is characterized by rapid growth and diffuse invasiveness with respect to the adjacent brain parenchyma, which renders surgical resection inefficient. Although it is a highly infiltrative tumor, it is rarely disseminated beyond the central nervous system, wherein extracranial metastasis is a unique but rare manifestation of this kind of tumor. It is very common for acquired immunodeficiency syndrome (AIDS) patients to be infected with the human immunodeficiency virus (HIV), which suggests that a possible association between HIV infection and tumor development exists. In this paper, we present a new case of a young patient's HIV-associated glioblastoma, with glioblastoma metastasis within the T9 vertebral body and lymph nodes in the anterior neck tissue. Initially, the patient was diagnosed with a grade III plastic astrocytoma. The patient lived a normal life for a year while being treated with temozolomide, radiotherapy, and highly active antiretroviral therapy. However, the tumor quickly evolved into a glioblastoma. We believe that the drastic progression of the tumor from a grade III anaplastic astrocytoma to a metastatic glioblastoma is due to the HIV infection that the patient had acquired, which contributed to a weakened immune system, thus accelerating progression of the cancer.",
"affiliations": "Hospital São Vicente de Paulo, Rua Gonçalves Crespo, 430 Tijuca - Rio de Janeiro, RJ, Brazil.;Instituto Estadual do Cérebro Paulo Niemeyer, Rua do Rezende 156, Rio de Janeiro, RJ, Brazil.;Instituto Estadual do Cérebro Paulo Niemeyer, Rua do Rezende 156, Rio de Janeiro, RJ, 20231-092, Brazil.",
"authors": "Rodrigues|Leonardo Fonseca|LF|;Camacho|Aline Helen da Silva|AHDS|;Spohr|Tania Cristina Leite de Sampaio E|TCLSE|https://orcid.org/0000-0001-8691-5962",
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"fulltext": "\n==== Front\nTher Adv Med Oncol\nTher Adv Med Oncol\nTAM\nsptam\nTherapeutic Advances in Medical Oncology\n1758-8340 1758-8359 SAGE Publications Sage UK: London, England \n\n10.1177/1758835920923432\n10.1177_1758835920923432\nCase Report\nSecondary glioblastoma metastasis outside the central nervous system\nin a young HIV-infected patient\nRodrigues Leonardo Fonseca Hospital São Vicente de Paulo, Rua Gonçalves\nCrespo, 430 Tijuca – Rio de Janeiro, RJ, Brazil\n Camacho Aline Helen da Silva Instituto Estadual do Cérebro Paulo Niemeyer,\nRua do Rezende 156, Rio de Janeiro, RJ, Brazil\nInstituto Nacional do Câncer, Divisão de\nAnatomia-Patológica, Rua Cordeiro da Graça, 156, Rio de Janeiro, RJ,\nBrazil\n https://orcid.org/0000-0001-8691-5962Spohr Tania Cristina Leite de Sampaio e Instituto Estadual do Cérebro Paulo Niemeyer,\nRua do Rezende 156, Rio de Janeiro, RJ, 20231-092, Brazil\nPrograma de Pós-Gradução em Anatomia Patológica,\nHospital Universitário Clementino Fraga Filho, Universidade Federal do Rio\nde Janeiro, Rio de Janeiro, Brazil\n [email protected]\n18 5 2020 \n2020 \n12 175883592092343217 10 2019 10 4 2020 © The Author(s), 20202020SAGE Publications Ltd unless otherwise noted.\nManuscript content on this site is licensed under Creative Commons\nLicensesThis article is distributed under the terms of the Creative Commons\nAttribution-NonCommercial 4.0 License (https://creativecommons.org/licenses/by-nc/4.0/) which\npermits non-commercial use, reproduction and distribution of the work\nwithout further permission provided the original work is attributed as\nspecified on the SAGE and Open Access pages (https://us.sagepub.com/en-us/nam/open-access-at-sage).Glioblastoma is the most common adult primary brain tumor that occurs in the\ncentral nervous system and is characterized by rapid growth and diffuse\ninvasiveness with respect to the adjacent brain parenchyma, which renders\nsurgical resection inefficient. Although it is a highly infiltrative tumor, it\nis rarely disseminated beyond the central nervous system, wherein extracranial\nmetastasis is a unique but rare manifestation of this kind of tumor. It is very\ncommon for acquired immunodeficiency syndrome (AIDS) patients to be infected\nwith the human immunodeficiency virus (HIV), which suggests that a possible\nassociation between HIV infection and tumor development exists. In this paper,\nwe present a new case of a young patient’s HIV-associated glioblastoma, with\nglioblastoma metastasis within the T9 vertebral body and lymph nodes in the\nanterior neck tissue. Initially, the patient was diagnosed with a grade III\nplastic astrocytoma. The patient lived a normal life for a year while being\ntreated with temozolomide, radiotherapy, and highly active antiretroviral\ntherapy. However, the tumor quickly evolved into a glioblastoma. We believe that\nthe drastic progression of the tumor from a grade III anaplastic astrocytoma to\na metastatic glioblastoma is due to the HIV infection that the patient had\nacquired, which contributed to a weakened immune system, thus accelerating\nprogression of the cancer.\n\nAIDSglioblastomaHIVmetastasiscover-dateJanuary-December 2020typesetterts1\n==== Body\nBackground\nGliomas are tumors derived from the neoplastic transformation of glial cells and are\nthe most common form of brain tumors.1 The type of gliomas originating from glial cells and their precursors are\nalso known as astrocytomas.2 Further, astrocytic tumors are classified histologically and molecularly\nbased on the World Health Organization’s criteria. They are known as grade III and\nIV astrocytomas or glioblastomas and are considered to be malignant.1 The median survival period of patients with grade III anaplastic astrocytoma\nis 3 years.2 Moreover, glioblastoma are the most malignant and aggressive brain tumors,\nwith a poor prognosis.3,4\nOn the other hand, the median survival period of patients with glioblastoma is\n14–16 months, which is 2 years less than of 10–15% of those patients with access to\nthe gold standard treatment available nowadays.5\n\nIn 1983, the human immunodeficiency virus (HIV), which causes acquired immune\ndeficiency syndrome (AIDS), was discovered. The virus replicates in TCD4+\ncells, resulting in a progressive decline in T cell immunity.6 The replication of HIV may, among other things, contribute to chronic\ninflammation and lead to progression of AIDS, resulting in the eventual death of the patient.6 More than half of patients with AIDS demonstrate some kind of neurological\ndisorder, especially in the 10% of those diagnosed with brain tumors, including\nglioblastoma.7,8\nSome reports, however, suggest that there is an increased possibility of\nglioblastoma occurring at a younger age in the HIV-infected population compared with\nthe general healthy population.9 Since the introduction of highly active antiretroviral therapy in 1998, a\nsubstantial decrease in HIV/AIDS-associated mortality has been reported.10 However, when treated via highly active antiretroviral\ntherapy, patients develop a chronic immune activation that contributes to the\nprogression of cancers by stimulating the production of nitrogen species and\nreactive oxygen, ensuring cell proliferation, along with an enhanced secretion of\npro-carcinogenic chemokines, cytokines, and related mechanisms.11,12 Moreover, the\nimmune cell functions of the patients undergoing highly active antiretroviral\ntherapy are not fully recovered and may become impaired, even after a year of\neffective therapy, a phenomenon that contributes to the formation of neoplasms.13\n\nIn the current report, we present a new case of a young patient’s HIV-associated\nglioblastoma with glioblastoma metastasis at the T9 vertebral body and lymph nodes\nin the anterior neck tissue.\n\nCase presentation\nHistory and case evolution\nA 32-year-old, seemingly healthy, man presented an acute syncope while practicing\nphysical activities, followed by hemiplegia on the right side, right labial\ncommissure deviation, and disorientation. At the emergency unit, his brain\ncomputed tomography scan showed a intraparenchymal hematoma in the left basal\nganglia, measuring 3.8 × 3.1 × 2.8 cm3, with edema in a small area that induced a contralateral deviation in the\nmidline structures. The patient was a former smoker who had stopped smoking for\na month, and therefore, at that time, was likely to have suffered a hemorrhagic\nstroke. A cerebral arteriography further showed occlusion of the middle cerebral\nartery. During clinical evaluation at the hospital, laboratory tests showed that\nthe patient was HIV1 positive. At the time, his CD4 count was 333 and his viral\nload was 7792 copies/ml without any associated co-morbidity (hepatitis B and C,\ncytomegalovirus, toxoplasmosis, and fluorescent treponemal antibody absorption\ntest results were found to be negative). Further, the patient started highly\nactive antiretroviral therapy during his hospitalization. Magnetic resonance\nimaging of his brain showed an expansive lesion in the periventricular region\nand in the internal capsule on the left side, with extension to the thalamus,\ninferior to the cerebral peduncle, along with the corona radiate and a semi-oval\nwhite center at the top left, measuring about 4.5 × 4.0 × 4.6 cm3. The tumor mass presented a heterogeneous signal intensity on T1 and T2,\nwith a large amount of blood residue and hypo-intense signal on conducting\nsusceptibility-weighted imaging, with heterogeneous and irregular enhanced\ncontrast. Moreover, there was a central lesion area with a necrotic aspect,\nwithout the contrast being enhanced or diffusion restriction being encountered\nin the uppermost portion of the lesion. These findings suggested an associated\nneoplasm in the same area where the hemorrhagic changes were found (Figure 1).\n\nFigure 1. Magnetic resonance imaging of the brain when the tumor was diagnosed. In\n(A) and (B), we can see the first magnetic resonance imaging that the\npatient underwent when he discovered the grade III anaplastic\nastrocytoma. In (C) and (D), we can view the perfusion magnetic\nresonance imaging with the surrounding edema and the peripheral contrast\nhypercapnia, indicating a malignant neoplasm. In (E) we can observe a\nhematoxylin and eosin staining of the first resection of the central\nnervous system lesion. Here, we can note the gemistocytic astrocyte’\nproliferation, with mild-to-moderate pleomorphism. In (F) and (G), we\ncan observe the first magnetic resonance imaging the patient underwent,\nwhich suggests the grade III anaplastic astrocytoma had already\nprogressed to a glioblastoma.\n\nThe patient underwent a stereotactic biopsy of the supposed neoplasm 2 months\nafter his stroke, when he was diagnosed with an anaplastic astrocytoma. The\nneoplasia could not be completely resected owing to its location. In addition to\nthe administration of antiviral drugs for HIV, the patient started chemotherapy\nwith temozolomide, and underwent five cycles of 30 Gy radiotherapy, leading a\nnormal life for a year.\n\nAt 1 year and 7 months following disease onset, the patient developed chronic\ndorsalgia, which worsened after physical therapy. A magnetic resonance imaging\nof the thoracic spine indicated a pathological fracture of the 9th thoracic\nvertebral body, along with spinal cord compression. The patient underwent a\nsurgical procedure in order to decompress his spinal cord with laminectomy and\npartial corpectomy, followed by pedicular screw stabilization. The biopsy of the\nninth thoracic vertebral body mass led to the diagnosis of glioblastoma\nmetastasis in this vertebral body. Moreover, a month prior to the spine surgery,\na mass was noted in the patient’s anterior neck tissue, which was also analyzed\nvia magnetic resonance imaging. Therefore, he was asked to\nundergo a lymph node biopsy, which also showed glioblastoma metastasis (Figure 2).\n\nFigure 2. Magnetic resonance imaging of the thoracic spine and neck. In (A), we can\nsee the magnetic resonance imaging of the thoracic spine, wherein a\npathologic fracture of the ninth thoracic vertebral body was diagnosed\nwith spinal cord compression. The biopsy of the T9 vertebral body mass\ndiagnosed glioblastoma metastasis in this vertebral body. In (B), we can\nview the magnetic resonance imaging of the neck, wherein we can observe\nan augmentation in the anterior neck tissue; the lymph node biopsy,\ntogether with immunohistochemistry studies, also diagnosed with\nmetastasis from the glioblastoma. In (C), we can note neoplastic\ngemistocytic proliferation infiltrating the skin. In (D), the neoplastic\ncells diffuse the glial fibrillary acidic protein positivity, whereas\n(E) shows Ki-67positive cells.\n\nAt 3 months after his first spine surgery, the patient reported acute anterior\nthoracic and rib pain, despite a series of spine radiotherapy sessions, and in\naddition to several chemotherapy cycles. The new thoracic spine magnetic\nresonance imaging showed a recurrence of spinal cord compression on the same\nsite as before, with foramen stenosis resulting from the regrowth of the tumor\nmass in the vertebral body. Subsequently, the patient underwent a new palliative\nsurgical procedure to decompress the spinal cord, along with the debridement of\nthe spine canal, as a result of which we managed to isolate his cancer cells\n(Figure 3). At that\ntime, a thoracic computed brain tomography scan showed multiple lytic lesions on\nthe ribs and the scapula, whereas the thoracic magnetic resonance imaging showed\nextensive edema on the same sites, suggesting permeating lesions (secondary\nimplants). Towards the end of his life, the patient presented metastatic masses\nin the cervical area (ribs, scapula, and neck) and in the spine, wherein an\nextracranial tumor emerged from the first biopsy path, all of which were\ncompatible with the glioblastoma metastasis. After palliative spine surgery, the\npatient developed liver insufficiency as well as pneumonia, and was thus treated\nwith antibiotics. After 2 weeks of palliative treatment, the patient died as a\nconsequence of his disease.\n\nFigure 3. Characterization of glioblastoma cells isolated from the spinal cord\nmetastasis. In (A) and (B), we can observe the met-GBM18 primary cells\nthat were isolated from the patient in his last surgery for\ndecompression, and stained for glial fibrillary acidic protein as well\nas S100β in order to confirm their glial origins. In (C), we can view a\ncell staining for SOX-2, which is a stem cell marker demonstrating that\nthis cell line has properties identical to cancer stem cells. In (D), we\ncan see a cell staining for vimentin, which demonstrates that this cell\nline possesses epithelial–mesenchymal transition properties that are\nclosely related to its capacity to migrate and undergo metastasis. In\n(E), we can note a cell staining for nestin, demonstrating its neural\norigin. In (F), we cannot observe any staining for HIV, as expected.\n\nHIV, human immunodeficiency virus.\n\nPathological description of the clinical case and methodology\nRepresentative sections of the patient’s stereotactic biopsy were stained with\nhematoxylin and eosin; a small area with a diffuse and rich proliferation of\ngemistocytic astrocytes could be observed (Figure 1E). Endothelial proliferation was\nobserved, after which single-labeled immunoperoxidase staining was performed\nusing standard procedures. For this purpose, the following primary antibodies\nwere used: monoclonal anti-glial fibrillary acidic protein (GFAP EP672Y, Cell\nMarque; 1:500), mouse monoclonal anti-IDH-1R132H/DIA-H09 (Optistain; 1:300), and\nmonoclonal anti-Ki67 (SP6, Cell Marque; 1:5000). The immunohistochemistry showed\ndiffuse positivity for the glial fibrillary acidic protein, was IDH-1R132H\nnegative, and displayed a proliferation index of 8% (Ki–67) (Figure 2C–E). In addition, the\ndiagnosis showed a grade III anaplastic astrocytoma (World Health Organization).\nThe vertebral body and the resections of the lymph nodes depicted the same\nhistology as that of diffuse gemistocytic astrocyte and cell pleomorphism.\nHowever, in these samples, we could still identify necrosis. Again, the\ndiagnosis showed metastatic glioblastoma.\n\nWhen the patient underwent a palliative spine surgery for decompression 2 years\nafter disease onset, his metastatic glioblastoma (met-GBM18) cells were\nisolated, established, and characterized in our laboratory (Figure 3). This study was approved by the\nClinical Research Ethics Committee of Instituto Estadual do Cérebro Paulo\nNiemeyer (CAAE:90670018.4.0000.8110). The cells were cultured in Dulbecco’s\nModified Eagle Medium/Nutrient Mixture F-12, supplemented with 10% fetal bovine\nserum, and maintained at 37°C in an atmosphere containing 95% air and 5%\nCO2. For immunofluorescence, the met-GBM18 cells were cultured on\ncoverslips in 24-well plates as described previously.14 The cells were subsequently stained using standard procedures. In\nsummary, the following primary antibodies were used: polyclonal rabbit anti-GFAP\n(Dako, Carpinteria, CA, USA; 1:200), polyclonal rabbit S100 (Dako; 1:400),\nanti-SOX-2 (Cell Signaling Technology, Danvers, MA, USA; 1:400), monoclonal\nmouse anti-Vimentin Clone V9 (Dako; 1:100), Anti-Nestin Antibody (Millipore,\nBedford, MA, USA; 1:200), and anti-HIV-1 p24 monoclonal mouse (NIH AIDS reagent\nprogram, NIH, Bethesda, MD, USA; 1:1000). As a control for the nonspecific\nbinding of secondary antibodies, primary antibodies were omitted. The secondary\nantibodies were goat anti-rabbit IgG or goat anti-mouse IgG, conjugated with\nAlexa Fluor 488 (1:750). The nuclei were stained with\n4′,6-diamidino-2-phenylindole (DAPI). In all cases, no reactivity was observed\nwhen the primary antibody was absent. The cell preparations were mounted\ndirectly on the ProLong® Gold Antifade reagent and visualized in a DMi8 advanced\nfluorescence microscope (Leica Microsystems, Wetzlar, Germany).\n\nDiscussion\nIn this paper, we have reported the case of a 32-year-old patient who presented\nsyncope while engaging in physical activities. Only after the patient had been\nhospitalized did post laboratory tests indicate that he was HIV1 positive. Owing to\nthis condition, it was not clear whether the initial ischemia could have been caused\nby a neoplasm. After a biopsy, a grade III anaplastic astrocytoma was diagnosed,\nwhich was unfortunately considered inoperable due to its location. The patient\nstarted chemotherapy with temozolomide and underwent five cycles of 30 Gy\nradiotherapy, thereby leading a normal life for a year. However, the grade III\nanaplastic astrocytoma quickly evolved into a metastatic glioblastoma in the spinal\ncord and the anterior neck tissue. The patient’s general condition worsened rapidly\nafter the glioblastoma diagnosis, and he died a year later.\n\nHIV is a neurotrophic virus that usually targets macrophages and microglia within the\ncentral nervous system.15,16 It does not manifest itself in glial tumors, as per the\nanalysis of immunohistochemistry.17 This corroborates our findings, as we could not observe the same after\nconducting immunocytochemistry staining for HIV on the cells we isolated from the\npatient after his last surgery for spinal cord decompression. It is believed that\nthe HIV virus has an indirect effect on glial cell transformation, facilitating\neither the activation of oncogenes or the inactivation of tumor suppressors.18 Although HIV has already been demonstrated in astrocytes in\nvitro,15,19 it is also known that astrocytes cannot maintain HIV\nreplication and gene expression owing to the limitations of the HIV life cycle.20 The resistance of astrocytes to HIV-mediated cytotoxicity, in conjunction\nwith the persistence of HIV in a host genome, helps in the transformation of\nastrocytes during infection.15 Further, it is believed that astrocytes can serve as essential HIV\nrepositories, and act as potential mediators of HIV-induced neuronal damage.21\n\nMoreover, the tumor microenvironment is fundamental to controlling the progression\nto, and development of, cancer. The immune system plays a pivotal role in this\nregard. Immune surveillance within the CNS is crucial to maintaining healthy brain\nfunctions. It is well known that HIV-positive patients possess an unhealthy immune\nsystem that cannot control tumorigenesis properly, thus causing a faster progression\nof cancer and/or a more frequent clinical presentation of tumors at a younger age.9 It has also been demonstrated that HIV infection promotes the secretion of\nseveral cytokines, such as interleukin-1, interleukin-6, interleukin-8, and tumor\nnecrosis alpha, all of which aid in the progression of the glioma.15 The overexpression of transforming growth factor-beta by macrophages in the\nbrains of HIV patients plays an important role in maintaining this immunosuppressive\nmicro environment, in addition to helping with astrocytoma and glioblastoma progression.15 We already know that favoring brain tissue does not express transforming\ngrowth factor-beta.15 Some reports suggest that there is a link between the development of\nastrocytomas and/or glioblastomas and reduced immune surveillance.22,23 Furthermore, a\nprevious study demonstrated a correlation of 40% between patients with advanced\ncancer and AIDS.24 In addition, it was recently demonstrated that patients with HIV-glioma have\na worse prognosis than glioblastoma patients without HIV. Indeed, HIV is also\nassociated with an increased incidence of glioblastoma inpatients.9,25 Currently, cancer therapy is\nfocused on immunotherapy based on immune checkpoints blockade, to favor the immune\nsystem and eventually help tumor regression.26 A systematic review recently described that HIV-infected patients in an\nadvanced-stage of cancer (melanoma or non-small cell lung cancer) tolerated immune\ncheckpoint inhibitory therapy well, i.e. the presence of HIV infection appears not\nto affect the efficacy of immune checkpoint inhibitor therapy. However, the\ncorrelation between safety and efficacy of immune checkpoint inhibitor therapy and\nHIV load, CD4 cell count, tumor mutation burden, or programmed cell death-ligand 1\nexpression has not yet been evaluated.27\n\nIn our research, we believe that our patient developed a glioblastoma from a\ngrade III anaplastic astrocytoma rapidly because he was found to be HIV-positive;\nthis was discovered only 2 days after being hospitalized, following a syncope that\nled to a hemiplegia on the right side of his body. As he was an ex-smoker who had\nstopped smoking for only a month, the first diagnostic hypothesis was stroke. At the\ntime, his CD4 count was 333 and viral load was 7792 copies/mL without any associated\nco-morbidity. The patient was subsequently administered highly active antiretroviral\ntherapy during his hospitalization. However, he died 2 years and 3 months after he\nexperiencing the syncope. We believe his immune system became compromised due to his\nHIV infection, which drove the transformation of glial cells into a grade III\nanaplastic astrocytoma. Furthermore, we argue that HIV infection also contributed to\nthe rapid evolution of the disease into a glioblastoma, thus also causing the\npatient to present different metastasic foci. It is already known that patients with\nhigh-grade gliomas after radiation and temozolomide treatment have a CD4 count\nreduction (below 300 cells/mm3).28 However, the development of extracranial metastasis is rare. Moreover,\nimmunocompetent patients rarely develop glioblastoma metastasis, being, therefore,\nconsidered marginal donors for organ transplant. On the other hand, studies have\ndemonstrated that patients who received organs from those patients died of\nglioblastoma metastasis, probably due to an immunosuppressed immune system.29 We believe that our patient’s immune system was probably as equally\ncompromised as the immune system of a transplant patient, as he was taking a number\nof drugs such as temozolomide (in the first 1.5 years) and irinotecan, together with\nbevacizumab (in the last year), in addition to oxcarbazepine, clobazam,\ncotrimoxazole, and dexamethasone. Apart from these drugs, he was also being treated\nwith radiotherapy and highly active antiretroviral therapy. This combination of\ndrugs along with the treatments he received caused his immune system to\ncollapse.\n\nWe would like to thank Professors Vivaldo Moura Neto and Leila Chimelli for their\ncareful reading of the manuscript and all the support they have provided for our\nproject. We are also grateful to Professor Rodrigo Martinez (in\nmemoriam) for his help in searching the patient’s clinical history. We\nalso wish to thank Aytel Marcelo Teixeira da Fonseca for all the support and\ninformation that helped us elucidate this case in detail.\n\nAuthor contributions: The manuscript was conceptualized, written and edited by TCLSS. LFR evaluated and\nparticipated in the palliative surgical procedure to decompress the spinal cord.\nAHSC made the pathological description of the case and analyzed all biopsies.\nThe work was supervised by TCLSS. All authors read and approved the final\nsubmitted version of the manuscript.\n\nAvailability of data and material: All data generated or analyzed during this study are included in this published\narticle.\n\nConflict of interest statement: The authors declare that there is no conflict of interest.\n\nEthics approval: The submission of this case report was approved by the Clinical Research Ethics\nCommittee of Instituto Estadual do Cérebro Paulo Niemeyer\n(CAAE:10611219.3.0000.8110).\n\nEthics approval for the isolation of patient cells was obtained from the Clinical\nResearch Ethics Committee of Instituto Estadual do Cérebro Paulo Niemeyer\n(CAAE:90670018.4.0000.8110), as we have established a cell line for future\nstudies.\n\nFunding: The authors disclosed receipt of the following financial support for the\nresearch, authorship, and/or publication of this article: This research would\nnot have been possible without the support extended by the National Institute\nfor Translational Neuroscience (INNT), Ministry of Science and Technology,\nBrazil. We are also indebted to the Support and Evaluation of Graduate Education\n(CAPES) Foundation (Ministry of Education, Brazil), the National Council for\nScientific and Technological Development (CNPq), the Foundation Carlos Chagas\nFilho Research Support of the State of Rio de Janeiro (FAPERJ), the Ary Frauzino\nFoundation for Cancer Research, and the Pro-Health Charitable Association of\nSocial and Hospital Assistance and Hospital Psiquiátrico Espírita Mahatma\nGandhi, Brazil (Pró-Saúde Associação Beneficente de Assistência Social e\nHospitalar).\n\nInformed consent: Written informed consent for publication of this case report and for the\nisolation of cells to establish a new cell line for future research was obtained\nfrom the patient’s legally authorized representative rather than from the\npatient himself. Although the patient was capable of understanding his actions\nand making a reasoned decision, he was unable to sign as he was disabled due to\nillness.\n\nORCID iD: Tania Cristina Leite de Sampaio e Spohr \nhttps://orcid.org/0000-0001-8691-5962\n==== Refs\nReferences\n1 \nLouis DN Perry A Reifenberger G , et al\nThe 2016 World Health\nOrganization classification of tumors of the central nervous system: a\nsummary\n. Acta Neuropathol \n2016 ; 131 :\n803 –820\n.27157931 \n2 \nDong X Noorbakhsh A Hirshman BR , et al\nSurvival trends of grade I,\nII, and III astrocytoma patients and associated clinical practice patterns\nbetween 1999 and 2010: a SEER-based analysis\n.\nNeuro-Oncology Pract \n2014 ; 3 :\n29 –38\n.\n3 \nLomax AJ Yannakou CK Rosenthal MA \nSpinal cord metastasis in a patient treated with\nbevacizumab for glioblastoma\n. Target Oncol \n2013 ; 8 :\n153 –155\n.23430346 \n4 \nRavindran K Gaillard F Lasocki A \nDistant spread of a supratentorial glioblastoma\nto the spinal cord\n. J Clin Neurosci \n2017 ; 38 :\n56 –57\n.28089418 \n5 \nStupp R Mason WP van den Bent MJ , et al\nRadiotherapy plus\nconcomitant and adjuvant temozolomide for glioblastoma\n.\nN Engl J Med \n2005 ; 352 :\n987 –996\n.15758009 \n6 \nDeeks SG \nImmune dysfunction, inflammation, and\naccelerated aging in patients on antiretroviral therapy\n.\nTop HIV Med \n2009 ; 17 :\n118 –123\n.19890183 \n7 \nValentín-Guillama G López S Kucheryavykh YV , et al\nHIV-1 envelope protein gp120\npromotes proliferation and the activation of glycolysis in glioma\ncell\n. Cancers (Basel) \n2018 ; 10 : 301 .\n8 \nChaudhry NS Ahmad FU Blieden C , et al Brainstem anaplastic glioma in patients\nwith AIDS: a case report and review of the literature Case Reports 2013;\n2013 : bcr2012008384.\n9 \nHall JR Short SC \nManagement of glioblastoma multiforme in HIV\npatients: a case series and review of published studies\n.\nClin Oncol \n2009 ; 21 :\n591 –597\n.\n10 \nPalella FJ Delaney KM Moorman AC , et al\nDeclining morbidity and\nmortality among patients with advanced human immunodeficiency virus\ninfection\n. N Engl J Med \n1998 ; 338 :\n853 –860\n.9516219 \n11 \nAppay V Sauce D \nImmune activation and inflammation in HIV-1\ninfection: causes and consequences\n. J\nPathol \n2008 ; 214 :\n231 –241\n.18161758 \n12 \nGrivennikov SI Greten FR Karin M \nImmunity, inflammation, and\ncancer\n. Cell \n2010 ; 140 :\n883 –899\n.20303878 \n13 \nCorbeau P Reynes J \nImmune reconstitution under antiretroviral\ntherapy: the new challenge in HIV-1 infection\n.\nBlood \n2011 ; 117 :\n5582 –5590\n.21403129 \n14 \nSpohr TCL Dezonne RS Rehen SK , et al\nAstrocytes treated by\nlysophosphatidic acid induce axonal outgrowth of cortical progenitors\nthrough extracellular matrix protein and epidermal growth factor signaling\npathway\n. J Neurochem \n2011 ; 119 :\n113 –123\n.21834854 \n15 \nMoulignier A Mikol J Pialoux G , et al\nCerebral glial tumors and\nhuman immunodeficiency virus-1 infection: more than a coincidental\nassociation\n. Cancer \n1994 ; 74 :\n686 –692\n.8033048 \n16 \nGasnault J Roux FX Vedrenne C \nCerebral astrocytoma in association with HIV\ninfection\n. J Neurol Neurosurg Psychiatry \n1988 ; 51 :\n422 –424\n.3361334 \n17 \nBlumenthal DT Raizer JJ Rosenblum MK , et al\nPrimary intracranial\nneoplasms in patients with HIV\n. Neurology \n1999 ; 52 :\n1648 –1651\n.10331693 \n18 \nChoy W Lagman C Lee SJ , et al\nImpact of human\nimmunodeficiency virus in the pathogenesis and outcome of patients with\nglioblastoma multiforme\n. Brain Tumor Res\nTreat \n2016 ; 4 :\n77 –86\n.27867916 \n19 \nBrack-Werner R Kleinschmidt A Ludvigsen A , et al\nInfection of human brain\ncells by HIV-1: Restricted virus production in chronically infected human\nglial cell lines\n. AIDS \n1992 ; 6 :\n273 –285\n.1373627 \n20 \nVincendeau M Kramer S Hadian K , et al\nControl of HIV replication\nin astrocytes by a family of highly conserved host proteins with a common\nRev-interacting domain (Risp)\n. AIDS \n2010 ; 24 :\n2433 –2442\n.20827171 \n21 \nLiu Y Liu H Kim BO , et al\nCD4-independent infection of\nastrocytes by human immunodeficiency virus type 1: requirement for the human\nmannose receptor\n. J Virol \n2004 ; 78 :\n4120 –4133\n.15047828 \n22 \nVannemreddy PSSV Fowler M Polin RS , et al\nGlioblastoma multiforme in a\ncase of acquired immunodeficiency syndrome: investigating a possible\noncogenic influence of human immunodeficiency virus on glial\ncells\n. J Neursurg \n2000 ; 92 :\n161 –164\n.\n23 \nMatias D Balça-Silva J da Graça GC , et al\nMicroglia/astrocytes–glioblastoma crosstalk: crucial\nmolecular mechanisms and microenvironmental factors\n.\nFront Cell Neurosci \n2018 ; 12 :\n1 –22\n.29386999 \n24 \nPeters BS Beck EJ Coleman DG , et al\nChanging disease patterns in\npatients with AIDS in a referral centre in the United Kingdom: the changing\nface of AIDS\n. BMJ \n1991 ; 302 :\n203 –207\n.1998759 \n25 \nWang T Gao T Niu X , et al\nClinical characteristics and\nprognistics analysis of glioma with HIV patients\n.\nWorld Neurosurg \n2018 ; 114 :\ne218 –e223\n.29524717 \n26 \nUrbanavicius D Alvarez T Such GK , et al\nThe potential of\nnanoparticle vaccines as a treatment for cancer\n. Mol\nImmunol \n2018 ; 98 :\n2 –7\n.29395251 \n27 \nCook MR Kim C \nSafety and efficacy of immune checkpoint\ninhibitor therapy in patients with HIV infection and advanced-stage cancer:\na systematic review\n. JAMA Oncol \n2019 ; 5 :\n1049 –1053\n.30730549 \n28 \nGrossman SA Ye X Lesser G , et al\nImmunosuppression in\npatients with high-grade gliomas treated with radiation and\ntemozolomide\n. Clin Cancer Res \n2011 ; 5473 –5481\n.21737504 \n29 \nJimsheleishvili S Alshareef AT Papadimitriou K , et al\nExtracranial glioblastoma in\ntransplant recipients\n. J Cancer Res Clin\nOncol \n2014 ; 140 :\n801 –807\n.24595597\n\n",
"fulltext_license": "CC BY-NC",
"issn_linking": "1758-8340",
"issue": "12()",
"journal": "Therapeutic advances in medical oncology",
"keywords": "AIDS; HIV; glioblastoma; metastasis",
"medline_ta": "Ther Adv Med Oncol",
"mesh_terms": null,
"nlm_unique_id": "101510808",
"other_id": null,
"pages": "1758835920923432",
"pmc": null,
"pmid": "32489434",
"pubdate": "2020",
"publication_types": "D002363:Case Reports",
"references": "29395251;24595597;19589665;30123112;30200472;27867916;10616096;18161758;1373627;1998759;20827171;8033048;30730549;15047828;9516219;29524717;21834854;23386496;3361334;23430346;31579519;28089418;21737504;19890183;10331693;20303878;27157931;15758009;21403129",
"title": "Secondary glioblastoma metastasis outside the central nervous system in a young HIV-infected patient.",
"title_normalized": "secondary glioblastoma metastasis outside the central nervous system in a young hiv infected patient"
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"abstract": "Diffuse alveolar hemorrhage (DAH) is rarely seen in patients with systemic lupus erythematosus (SLE), often associated with a poor outcome. It almost affects young women and it is an unusual initial manifestation of SLE. We report a case of SLE presenting with DAH. The patient was a male. He had no history of photosensitivity, malar rash, discoid rash, arthritis, and oral ulcer. Antinuclear antibody, and anti-double stranded DNA (dsDNA) were positive with very high titers, and serum complement levels (C3, C4) were low. He also had renal dysfunction and pericardial effusion. He was diagnosed as DAH due to SLE. He had to undergo hemodialysis for several weeks. DAH and renal dysfunction were improved with intensive treatment including corticosteroid, cyclophosphamide, and mycophenolate mophetil.",
"affiliations": "Department of Nephrology, Gulhane School of Medicine, Ankara, Turkey. [email protected]",
"authors": "Sengul|Erkan|E|;Eyıleten|Tayfun|T|;Ozcan|Ayhan|A|;Yılmaz|Mahmut Ilker|MI|;Yenıcesu|Mujdat|M|",
"chemical_list": "D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D003520:Cyclophosphamide; D009173:Mycophenolic Acid",
"country": "Germany",
"delete": false,
"doi": "10.1007/s00296-009-1227-6",
"fulltext": null,
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"issn_linking": "0172-8172",
"issue": "31(8)",
"journal": "Rheumatology international",
"keywords": null,
"medline_ta": "Rheumatol Int",
"mesh_terms": "D003520:Cyclophosphamide; D003937:Diagnosis, Differential; D005938:Glucocorticoids; D006470:Hemorrhage; D006801:Humans; D007166:Immunosuppressive Agents; D008171:Lung Diseases; D008180:Lupus Erythematosus, Systemic; D008297:Male; D009173:Mycophenolic Acid; D011650:Pulmonary Alveoli; D006435:Renal Dialysis; D016896:Treatment Outcome; D055815:Young Adult",
"nlm_unique_id": "8206885",
"other_id": null,
"pages": "1085-7",
"pmc": null,
"pmid": "19908046",
"pubdate": "2011-08",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "9229363;11260619;15190526;9193454;11035681;17933839;17377738;11334313;10639536",
"title": "Diffuse alveolar hemorrhage as an unusual presentation of systemic lupus erythematosus.",
"title_normalized": "diffuse alveolar hemorrhage as an unusual presentation of systemic lupus erythematosus"
} | [
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{
"abstract": "Nocardia fusca was first described in 1983; however, to date, no report of human infection has been done. In this work, we report the first case of N. fusca isolation during an episode of acute exacerbation in a patient with chronic obstructive pulmonary disease. The extent of the role of N. fusca as human pathogen still has to be determined.",
"affiliations": "University Hospital Donostia, Donostia, Gipuzkoa, Spain.;University Hospital Donostia, Donostia, Gipuzkoa, Spain.",
"authors": "Ercibengoa Arana|María|M|;Marimón Ortiz de Zarate|José María|JM|",
"chemical_list": "D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin",
"country": "England",
"delete": false,
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"issn_linking": "1757-790X",
"issue": "2015()",
"journal": "BMJ case reports",
"keywords": null,
"medline_ta": "BMJ Case Rep",
"mesh_terms": "D000208:Acute Disease; D000368:Aged; D000900:Anti-Bacterial Agents; D002939:Ciprofloxacin; D003937:Diagnosis, Differential; D006801:Humans; D008297:Male; D009615:Nocardia; D009617:Nocardia Infections; D029424:Pulmonary Disease, Chronic Obstructive; D016896:Treatment Outcome",
"nlm_unique_id": "101526291",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "26038381",
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"references": "18427245;8381805;19593231;24594890;21402847;17374898;22656187;10531644;10586501;16891489;16614249;23966490;24853015",
"title": "First report of Nocardia fusca isolated in humans.",
"title_normalized": "first report of nocardia fusca isolated in humans"
} | [
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{
"abstract": "Methemoglobinemia is caused due to an increase in methemoglobin in the blood, impairing oxygen transfer to tissues. Acquired methemoglobinemia is caused by various drugs like local anesthetics, antibiotics, nitrates, nitrites, and food additives. We present a case of a 73-year-old male who presented with cyanosis, altered mental status, and hypoxia following transesophageal echocardiography. Arterial blood gas analysis revealed methemoglobinemia. He had been given topical lidocaine and benzocaine spray before the procedure. He improved after the administration of methylene blue. The case highlights the importance of considering methemoglobinemia in patients presenting with cyanosis, altered mental status, and hypoxia after endoscopic procedures.",
"affiliations": "Department of Internal Medicine, Mount Sinai Hospital, Chicago, USA.;Department of Medicine, Mount Sinai Hospital, Chicago, USA.;Department of Internal Medicine, Mount Sinai Hospital, Chicago, USA.;Department of Emergency Medicine, Palpa Hospital, Palpa, NPL.;Department of Internal Medicine, Mount Sinai Hospital, Chicago, USA.",
"authors": "Mir|Wasey Ali Yadullahi|WAY|;Shrestha|Dhan B|DB|;Reddy|Vijay Ketan|VK|;Gaire|Suman|S|;Verda|Larissa|L|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.7759/cureus.18580",
"fulltext": "\n==== Front\nCureus\nCureus\n2168-8184\nCureus\n2168-8184\nCureus Palo Alto (CA)\n\n10.7759/cureus.18580\nAnesthesiology\nInternal Medicine\nHematology\nA Case Report of Acute Transient Encephalopathy Following a Trans-esophageal Echocardiography\nMuacevic Alexander\nAdler John R\nMir Wasey Ali Yadullahi 1\nShrestha Dhan B 2\nReddy Vijay Ketan 1\nGaire Suman 3\nVerda Larissa 1\n1 Department of Internal Medicine, Mount Sinai Hospital, Chicago, USA\n2 Department of Medicine, Mount Sinai Hospital, Chicago, USA\n3 Department of Emergency Medicine, Palpa Hospital, Palpa, NPL\nDhan B. Shrestha [email protected]\n7 10 2021\n10 2021\n13 10 e185807 10 2021\nCopyright © 2021, Mir et al.\n2021\nMir et al.\nhttps://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\nThis article is available from https://www.cureus.com/articles/66688-a-case-report-of-acute-transient-encephalopathy-following-a-trans-esophageal-echocardiography\nMethemoglobinemia is caused due to an increase in methemoglobin in the blood, impairing oxygen transfer to tissues. Acquired methemoglobinemia is caused by various drugs like local anesthetics, antibiotics, nitrates, nitrites, and food additives. We present a case of a 73-year-old male who presented with cyanosis, altered mental status, and hypoxia following transesophageal echocardiography. Arterial blood gas analysis revealed methemoglobinemia. He had been given topical lidocaine and benzocaine spray before the procedure. He improved after the administration of methylene blue. The case highlights the importance of considering methemoglobinemia in patients presenting with cyanosis, altered mental status, and hypoxia after endoscopic procedures.\n\nbenzocaine\nlocal anesthetics\nmethemoglobinemia\ntransesophageal echocardiography\nlidocaine\ncyanosis\nhypoxia\nThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\npmcIntroduction\n\nMethemoglobinemia is a rare condition of the blood associated with an increase in the proportion of methemoglobin, which affects the oxygen-carrying capacity of the blood. There are two types of methemoglobinemia, congenital and acquired. Congenital/inherited methemoglobinemia is caused by a genetic deficiency of an enzyme cytochrome B5 reductase or a hemoglobin protein defect (Hemoglobin M disease). The acquired form is associated with exposure to certain chemicals/medications like local anesthetics (benzocaine, prilocaine, lidocaine); antibiotics (dapsone, sulfonamides, chloroquine); nitrates (salts, nitroglycerin); nitrites (nitroprusside, nitrous oxide, food additives); nitrobenzene (used in lubricating oils, dyes), and many others [1,2].\n\nWe present a case of methemoglobinemia following topical lidocaine and benzocaine spray for transesophageal echocardiography.\n\nCase presentation\n\nA 73-year-old African American male presented to the hospital for lower back pain and symptoms of urinary tract infection and a chronic great toe wound with discharge. His history was significant for type 2 diabetes mellitus, hypertension, and coronary artery disease, post-stenting five years ago.\n\nHis blood culture collected at the time of hospital admission was positive for Streptococcus dysgalactiae. Other significant laboratory findings at the time of admission were a complete blood count of 17000/mm3, hemoglobin of 13 gm/dL, the random blood sugar of 212 mg/dL, blood urea/creatinine of 13/1.37 mg/dL, and raised inflammatory markers (erythrocyte sedimentation rate [ESR]: 140 mm/hr, c-reactive protein [CRP]: 299 mg/L). The patient was started on vancomycin and cefepime based on his blood culture report. Right hallux wound incision and drainage had Streptococcus dysgalactiae, Staphylococcus capre, and methicillin-resistant Staphylococcus aureus, then MRI confirmed right hallux osteomyelitis. He underwent right hallux amputation. Further workup showed that patient had a spinal abscess, which developed due to the seeding of bacteria from his toe infection. He underwent bilateral laminectomy and decompression with drainage of the abscess.\n\nA transthoracic echocardiogram done to rule out infective endocarditis showed no vegetations. Due to high suspicion of infective endocarditis, transesophageal echocardiography was also performed using benzocaine 20% spray to the back of the throat before procedure initiation. In addition, the patient was given 1 mg of midazolam and 25 mcg of fentanyl for pre-procedure sedation. Within minutes after the procedure, the patient was cyanotic, diaphoretic, confused, and developed a facial droop on the operating table. Code Stroke was called. Vitals were blood pressure 99/56, heart rate 106, respiratory rate 30, saturating 76% on room air. He was started on supplemental O2 with a non-rebreather mask. He was intermittently bagged with saturation improving to 85% on 100% O2 with on and off improvement in mental status and facial droop resolved. The decision was made not to intubate the patient, and an arterial blood gas analysis (ABG) was done, which showed chocolate-brown colored blood and a partial pressure of oxygen (PaO2) of 185 mmHg with 70% methemoglobin (ABG-pH/PaO2/PaCO2/HCO3: 7.48/185/37/27.6). The patient was immediately given 1 mg/kg of methylene blue and transferred to the intensive care unit (ICU). Within 15 minutes, the patient was improving, with improved cyanosis, mental status, and improving diaphoresis. One hour repeat ABG showed methemoglobin levels of 31. Poison control was called, and they recommended methemoglobin levels less than 30, with a goal of less than 20, and resolution of symptoms. In the following hour, the attending toxicologist recommended re-dosing with another 1 mg/kg for a total of 2 mg/kg (100 mg) methylene blue for persistently elevated methemoglobin levels greater than the goal level. The repeat ABG after the second dosing of methylene blue showed methemoglobin levels less than 10. The toxicologist recommended following the methemoglobin levels on Arco oximetry ABG. His final ABG showed a methemoglobin level of 2.6 and saturation maintained with oxygen supplementation via nasal cannula. The patient was discharged the next day to a rehabilitation center with antibiotics.\n\nWe report this case to draw attention to rare circumstances of methemoglobinemia following the use of local anesthetics. This may not be considered and missed during code scenarios due to uncommon encounters, a general lack of awareness, and limited availability of standard co-oximetry for an accurate diagnosis.\n\nDiscussion\n\nA transesophageal echocardiogram (TEE) is used for better visualization of posterior cardiac structures not clearly visualized by transthoracic echocardiography. It is a safe procedure, and only a few significant complications have been reported. The major complications include esophageal perforation, gastrointestinal bleeding, pharyngeal hematoma, and methemoglobinemia [3-5].\n\nMethemoglobinemia following TEE is due to local anesthetic spray use. In a retrospective study for all adverse events following benzocaine use, 132 of 198 cases (66.7%) were related to methemoglobinemia, which involved 107 serious events (81.1%) and even two deaths (1.5%). More than 90% of these cases were related to benzocaine spray use. Most of these cases of benzocaine-related methemoglobinemia happened in the inpatient setting following procedures needing endoscopy of any kind [6]. The incidence of methemoglobinemia was 0.067% in a series of over 28,000 TEEs performed in a center [7].\n\nRisk factors for developing methemoglobinemia following medication use depends on several factors which affect the drug concentration (both levels and time taken to clear) in the blood: elderly, glucose 6-phosphate dehydrogenase (G6PD) deficiency, high doses, prolonged use, concomitant use of multiple oxidant drugs (lidocaine + benzocaine), route of administration, concomitant problems (heart, lung, liver, kidney), sepsis, and shock. Methemoglobinemia can present early or might take time to manifest after drug exposure (ranging from one to 10 hours). This is because some of the above medications need to transform into toxic metabolites before symptoms manifest [1].\n\nClinical presentation depends on the severity of methemoglobinemia. According to the increasing level of methemoglobin in the blood, the symptoms are cyanosis, chocolate-colored blood, headache, anxiety, tachycardia, dizziness, changes in mental status, tachypnea, and syncope arrhythmias, seizures, coma, and death [2]. Our patient presented with altered mental status, cyanosis, and hypoxia following TEE. Refractory hypoxemia, cyanosis, and chocolate-colored blood following any procedure or after the use of topical anesthetics are highly suggestive of methemoglobinemia.\n\nThe gold standard for diagnosis remains co-oximetry, but some blood gas analyzers give methemoglobin levels as well. Traditional pulse oximetry is unreliable in diagnosing methemoglobinemia. It cannot distinguish oxyhemoglobin from abnormal hemoglobin like methemoglobin, sulfhemoglobin, and carboxyhemoglobin which bind and carry oxygen to varying extents but do not release it to the tissues [2,8]. Oxygen saturation gap (difference between oxygen saturation measured by pulse oximeter and saturations by blood gas analysis) >5% indicates the presence of abnormal hemoglobin [9].\n\nTreatment of severe methemoglobinemia with methylene blue is done only if the patient is symptomatic or methemoglobin >30% [6]. Care is needed with methylene blue as it is known to cause hemolysis in toxic doses or G6PD-deficient individuals [10-12]. However, most patients respond rapidly to the treatment, as seen in our patient.\n\nConclusions\n\nTopical anesthetic use is associated with methemoglobinemia. In addition, episodes of methemoglobinemia are reported after TEE. Therefore, it is crucial to keep methemoglobinemia very high in differential in cases of cyanosis, altered mental status, and hypoxia after application of local anesthetics. In addition, it is imperative to differentiate methemoglobinemia from other complications of TEE in such patients.\n\nWe want to acknowledge our patient without whom this report would not have been possible. Additionally, we would like to thank all the treating healthcare personnel involved in patient care.\n\nHuman Ethics\n\nThe authors have declared that no competing interests exist.\n\nConsent was obtained or waived by all participants in this study\n==== Refs\nReferences\n\n1 Drugs may be induced methemoglobinemia J Hematol Thromboemb Dis Alanazi MQ 6 2017\n2 Methemoglobinemia Ludlow JT Wilkerson RG Nappe TM Treasure Island StatPearls Publishing 2021 https://www.ncbi.nlm.nih.gov/books/NBK537317/\n3 Clinical features of complications from transesophageal echocardiography: a single-center case series of 10,000 consecutive examinations J Am Soc Echocardiogr Min JK Spencer KT Furlong KT DeCara JM Sugeng L Ward RP Lang RM 925 929 18 2005 16153515\n4 Review of complications in a series of patients with known gastro-esophageal varices undergoing transesophageal echocardiography J Am Soc Echocardiogr Spier BJ Larue SJ Teelin TC 396 400 22 2009 19231133\n5 Upper airway obstruction after transesophageal echocardiography J Am Soc Echocardiogr Saphir JR Cooper JA Kerbavez RJ Larson SF Schiller NB 977 978 10 1997 9440076\n6 Reported adverse event cases of methemoglobinemia associated with benzocaine products Arch Intern Med Moore TJ Walsh CS Cohen MR 1192 1196 164 2004 15197044\n7 Benzocaine-induced methemoglobinemia based on the Mayo Clinic experience from 28 478 transesophageal echocardiograms: incidence, outcomes, and predisposing factors Arch Intern Med Kane GC Hoehn SM Behrenbeck TR Mulvagh SL 1977 1982 167 2007 17923598\n8 An atypical case of methemoglobinemia due to self-administered benzocaine Case Rep Emerg Med Nappe TM Pacelli AM Katz K 670979 2015 2015 25874137\n9 Mind the gap J Emerg Med Akhtar J Johnston BD Krenzelok EP 131 132 33 2007 17692762\n10 Studies of the efficacy and potential hazards of methylene blue therapy in aniline-induced methaemoglobinaemia Br J Haematol Harvey JW Keitt AS 29 41 54 1983 6849836\n11 Failure of methylene blue treatment in toxic methemoglobinemia. Association with glucose-6-phosphate dehydrogenase deficiency Ann Intern Med Rosen PJ Johnson C McGehee WG Beutler E 83 86 75 1971 5091568\n12 Rasburicase-induced methemoglobinemia in a patient with glucose-6-phosphate dehydrogenase deficiency Curr Drug Saf Khan M Paul S Farooq S Oo TH Ramshesh P Jain N 13 18 12 2017 28078984\n\n",
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"title": "A Case Report of Acute Transient Encephalopathy Following a Trans-esophageal Echocardiography.",
"title_normalized": "a case report of acute transient encephalopathy following a trans esophageal echocardiography"
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"abstract": "BACKGROUND\nUstekinumab is a fully human IgG1κ monoclonal antibody that blocks the biologic activity of interleukin-12/23. Ustekinumab is approved for treatment of plaque psoriasis and has been shown to be effective for induction and maintenance of clinical response in anti-TNF resistant Crohn's disease (CD). The aim of the study was to describe the real-life experience with open-label use of ustekinumab in anti-TNF resistant CD patients.\n\n\nMETHODS\nA retrospective observational open-label study. Clinical response was defined by physician's global assessment combined with decision to continue therapy. The clinical response was evaluated at 3, 6, 12months and last follow-up.\n\n\nRESULTS\nThirty-eight patients were included in the study. Initial clinical response was achieved in 28/38 (73.7%) of the patients. Among the initial responders, 80% with follow-up data maintained their response for 6months. At 12months of follow-up, 88.9% of patients responding at 6months maintained their response. At the last follow-up (7.9±5.2 mo) 27/38 (71%) of the patients were responding, and 73.3% were able to discontinue corticosteroids. Dose escalation was required in 47.7% of the patients and was successful in 61.1% of them.\n\n\nCONCLUSIONS\nIn this real-life cohort of severe anti-TNF resistant CD, an initial clinical response to subcutaneous ustekinumab was observed in 73.7% of the patients. The initial response was successfully maintained in the majority of patients for up to 12months. Subcutaneous ustekinumab is an effective therapeutic option in this challenging patient cohort. The optimal dosing and injection schedule remain to be established in future studies.",
"affiliations": "Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada. Electronic address: [email protected].;Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada.;Division of Gastroenterology, Jewish General Hospital, Montreal, Quebec, Canada.;Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada.;Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada.;Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada.;Division of Gastroenterology, Jewish General Hospital, Montreal, Quebec, Canada.;Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada.;Division of Gastroenterology, Jewish General Hospital, Montreal, Quebec, Canada.;Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada.",
"authors": "Kopylov|U|U|;Afif|W|W|;Cohen|A|A|;Bitton|A|A|;Wild|G|G|;Bessissow|T|T|;Wyse|J|J|;Al-Taweel|T|T|;Szilagyi|A|A|;Seidman|E|E|",
"chemical_list": "D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D014409:Tumor Necrosis Factor-alpha; D000069549:Ustekinumab",
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"medline_ta": "J Crohns Colitis",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents; D061067:Antibodies, Monoclonal, Humanized; D002170:Canada; D003424:Crohn Disease; D004351:Drug Resistance; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007279:Injections, Subcutaneous; D008297:Male; D008875:Middle Aged; D019233:Retreatment; D012189:Retrospective Studies; D014409:Tumor Necrosis Factor-alpha; D000069549:Ustekinumab; D055815:Young Adult",
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"pages": "1516-22",
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"pmid": "24996483",
"pubdate": "2014-11",
"publication_types": "D016428:Journal Article; D064888:Observational Study; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Subcutaneous ustekinumab for the treatment of anti-TNF resistant Crohn's disease--the McGill experience.",
"title_normalized": "subcutaneous ustekinumab for the treatment of anti tnf resistant crohn s disease the mcgill experience"
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"abstract": "BACKGROUND\nReported cases of potassium overdoses have shown that this condition could generate several morbidities, mainly related to cardiac dysrhythmias even with fatal outcomes in some cases. Potassium salts in extended release tablets could form pharmacobezoars if a large amount is ingested. In relation to the above, when the patient has a pharmacobezoar, clinical findings may be delayed and may persist. The techniques available for removal of a pharmacobezoar are whole bowel irrigation (WBI), endoscopy or in some surgery [1]. Endoscopy as a decontamination method has shown promising results.\n\n\nMETHODS\nA 42 year old woman, who intentionally ingested 100 tablets of extended release potassium chloride, 50 mg of clonazepam and an undisclosed amount of ethanol, presented with metabolic acidosis, hyperlactatemia and sinus tachycardia 2 h after ingestion. Gastric lavage and activated charcoal were applied initially, specific measures were not necessary. However, a transcutaneous pacemaker was placed. Because of her background, we considered a pharmacobezoar and an endoscopy were performed to remove 99 tablets of potassium that were isolated or forming concretions.\n\n\nCONCLUSIONS\nThe readily available techniques to remove a pharmacobezoar are whole bowel irrigation (WBI) and endoscopy; nevertheless there is not a consensus about their relative merits. Our patient was treated by endoscopy because we found on the X-ray a conglomerate of radiopaque images suggesting a pharmacobezoar. In this case we did not have any adverse effect.\n\n\nCONCLUSIONS\nWe consider that endoscopy could be an effective and safe method to remove a drug bezoar from the stomach in uncomplicated patients.",
"affiliations": "Jefe del Centro Toxicológico Hospital Angeles Lomas, Vialidad de la Barranca No. 14, Colonia Valle de las Palmas, Huixquilucan, Estado de México CP 52787, Mexico.;Adscrito al Centro Toxicológico Hospital Angeles Lomas, Vialidad de la Barranca No. 14, Colonia Valle de las Palmas, Huixquilucan, Estado de México CP 52787, Mexico.;Adscrito al Centro Toxicológico Hospital Angeles Lomas, Vialidad de la Barranca No. 14, Colonia Valle de las Palmas, Huixquilucan, Estado de México CP 52787, Mexico.;Adscrito al Centro Toxicológico Hospital Angeles Lomas, Vialidad de la Barranca No. 14, Colonia Valle de las Palmas, Huixquilucan, Estado de México CP 52787, Mexico.;Residente de Toxicología Hospital Angeles Lomas, Vialidad de la Barranca No. 14, Colonia Valle de las Palmas, Huixquilucan, Estado de México CP 52787, Mexico.",
"authors": "Guillermo|Pérez Tuñón Jorge|PTJ|;Carlos|Pérez Hernández Juan|PHJ|;Ivonne|Bautista Albiter Mayré|BAM|;Herminio|Terán Flores|TF|;Rubén|Ramírez Pérez|RP|",
"chemical_list": null,
"country": "Ireland",
"delete": false,
"doi": "10.1016/j.toxrep.2014.04.002",
"fulltext": "\n==== Front\nToxicol RepToxicol RepToxicology Reports2214-7500Elsevier S2214-7500(14)00014-610.1016/j.toxrep.2014.04.002Case ReportExtended release potassium salts overdose and endoscopic removal of a pharmacobezoar: A case report Guillermo Pérez Tuñón Jorge [email protected][email protected]⁎Carlos Pérez Hernández Juan [email protected] Bautista Albiter Mayré [email protected] Terán Flores [email protected]én Ramírez Pérez [email protected] Jefe del Centro Toxicológico Hospital Angeles Lomas, Vialidad de la Barranca No. 14, Colonia Valle de las Palmas, Huixquilucan, Estado de México CP 52787, Mexicob Adscrito al Centro Toxicológico Hospital Angeles Lomas, Vialidad de la Barranca No. 14, Colonia Valle de las Palmas, Huixquilucan, Estado de México CP 52787, Mexicoc Residente de Toxicología Hospital Angeles Lomas, Vialidad de la Barranca No. 14, Colonia Valle de las Palmas, Huixquilucan, Estado de México CP 52787, Mexico⁎ Corresponding author. Tel.: +52 1 55 52465056; mobile: +52 1 55 19177028 [email protected][email protected] Mobile: +52 1 55 48706380.\n\n2 Mobile: +52 1 722 5189242.\n\n3 Mobile: +52 1 55 39896337.\n\n4 Mobile: +52 1 55 45832697.\n\n22 5 2014 2014 22 5 2014 1 209 213 7 2 2014 4 4 2014 4 4 2014 © 2014 The Authors2014This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/3.0/).Background\nReported cases of potassium overdoses have shown that this condition could generate several morbidities, mainly related to cardiac dysrhythmias even with fatal outcomes in some cases.\n\nPotassium salts in extended release tablets could form pharmacobezoars if a large amount is ingested. In relation to the above, when the patient has a pharmacobezoar, clinical findings may be delayed and may persist.\n\nThe techniques available for removal of a pharmacobezoar are whole bowel irrigation (WBI), endoscopy or in some surgery [1]. Endoscopy as a decontamination method has shown promising results.\n\nCase report\nA 42 year old woman, who intentionally ingested 100 tablets of extended release potassium chloride, 50 mg of clonazepam and an undisclosed amount of ethanol, presented with metabolic acidosis, hyperlactatemia and sinus tachycardia 2 h after ingestion. Gastric lavage and activated charcoal were applied initially, specific measures were not necessary. However, a transcutaneous pacemaker was placed. Because of her background, we considered a pharmacobezoar and an endoscopy were performed to remove 99 tablets of potassium that were isolated or forming concretions.\n\nDiscussion\nThe readily available techniques to remove a pharmacobezoar are whole bowel irrigation (WBI) and endoscopy; nevertheless there is not a consensus about their relative merits. Our patient was treated by endoscopy because we found on the X-ray a conglomerate of radiopaque images suggesting a pharmacobezoar. In this case we did not have any adverse effect.\n\nConclusions\nWe consider that endoscopy could be an effective and safe method to remove a drug bezoar from the stomach in uncomplicated patients.\n\nKeywords\nPharmacobezoarEndoscopyExtended release potassium salts\n==== Body\n1 Background\nExtended release potassium salts are indicated in induced or acquired hypokalemic conditions. The potassium overdose could generate hyperkalemic states, especially if the patient has impaired renal function or if there has been a large ingestion of salts (toxic dosage: 2 mEq/kg) [1]. When a patient presents a large ingestion of extended release potassium tablets, clinical manifestations could be delayed even more than 24 h and concretions could be formed in the stomach. Concretions complicates the decontamination by gastric lavage, so that after this procedure in these patients, it is possible to find tablets remaining in the stomach, even in 88.2% of cases [2].\n\nThe great absorption that follows to a massive ingestion of potassium salts causes myocardial conduction disturbances and metabolic acidosis.\n\nThe correct technique for gastrointestinal decontamination in cases of massive overdose of extended-release tablets is not well established, nowadays, toxicologists continue to consider use of whole bowel irrigation (WBI), endoscopy or even surgery to evacuate tablet remaining from the stomach [1].\n\n2 Case report\nA 42 year old woman with history of borderline personality disorder and a suicide attempt with potassium salts (50 tablets) one year earlier presented to the emergency room after intake of 100 tablets of extended release potassium chloride (1000 mEq), 50 mg of liquid clonazepam, and an undisclosed amount of ethanol at home.\n\nShe recognized this as a new suicide attempt and presented with somnolence, tachycardia and exhalation of ethanol odor 2 h after ingestion. Her vital signs were: blood pressure 130/90 mm Hg, pulse was 97 beats/min, respirations were 22 breaths/min, temperature was 36.5 °C, and oxygen saturation was 98% on room air.\n\nA 12 lead electrocardiogram demonstrated sinus tachycardia with normal QRS duration and unaltered T-waves. Potassium level was 3.9 mmol/L, blood gas analysis revealed pH 7.25, HCO3 17.5 mEq/L and lactate 4.9 mmol/L. A standard toxicological screen was negative for all agents. Ethanol level was 90.80 mg/dl. Finally a plain film of the abdomen showed multiple opacities in the region of the stomach (Fig. 1). Other agents, including acetaminophen and salicylates were reported to be absent.Fig. 1 Abdominal radiography with multiple radioopacities in the stomach (red arrow).\n\n\n\nA venous access was placed. After that, a gastric lavage with a 20-french orogastric tube (maximum size in our hospital) was performed. However, no tablets were recovered during this procedure. Also, a single dose of activated charcoal was performed in order to treat a possible coingestant. Anti-hyperkalemic measures were not necessary at that time. However, a transcutaneous pacemaker was placed.\n\nGiven her background and the gastric lavage that was ineffective, an abdominal radiography was performed in order to identify the location of the tablets. The radiography showed multiple radiopacities in the stomach and the possibility of a pharmacobezoar was considered. Consultation with the gastroenterology service was done to request an endoscopy for removal of the suspected pharmacobezoar. A total of 99 of the 100 tablets that were either isolated or forming concretions were removed with an endoscopic basket (Fig. 2, Fig. 3).Fig. 2 Endoscopic removal of the tablets.\n\nFig. 3 Removed tablets.\n\n\n\nAfter gastric decontamination, clinical outcome was satisfactory, pharmacological correction of acidosis was not needed and she did not develop hyperkalemia or cardiovascular impairments. The patient was intubated for the procedure and extubated 18 h later. After that, she was discharged to the psychiatry service 48 h later.\n\n3 Discussion\nThe potassium excess could be absorbed by the intracellular compartment to maintain serum levels under 5.5 mEq/L, but unfortunately this mechanism is saturable [3]. In this context, potassium serum levels over 6.0 mEq/L should be considered risky and need to be treated immediately [4], [5]. Although there is no clear relationship between the serum level and heart rhythm disturbances, we know that the risk of dysrhythmias is increased if rapid absorption of potassium occurs [1], [4], [6], [7].\n\nMany drugs are capable to form concretions as in the case of amitriptyline, salicylates, carbamazepine, iron, potassium salts and other extended release preparations, with or without an enteric coat [8], [9], [10], [11].\n\nThe gastric decontamination is an essential procedure in the treatment of patients with an oral drug overdose; however, the appropriate technique to remove a bezoar is still controversial.\n\nThe gastric lavage and activated charcoal administration have both been demonstrated to be poorly effective on patients with pharmacobezoars. Moreover, in Mexico there are no orogastric tubes with a recommended diameter to remove extended release tablets (36–40 Fr).\n\nNowadays, the available techniques to remove pharmacobezoars include: WBI (only small size bezoars), endoscopy and surgical extraction. In this context, the main factors to consider before selecting a decontamination technique are: drug toxicity, pharmacobezoar size and location, clinical condition of the patient and availability of the resources (polyethylene glycol, operating room, etc.) [10].\n\nDespite the fact that WBI has been demonstrated in some reports be safe and to improve the clinical condition of these patients, at this time there is no strong evidence of its efficacy. It requires several hours to clarify the effluent, also, it is necessary to have a normal bowel function and it could not be effective if a big bezoar exists in the stomach. In the case of perforation, intestinal occlusion, active bleeding, hemodynamic instability or vomiting, the WBI are contraindicated [12]. Also, in the case of a potassium salts overdose, one of the most important causes of morbidity is the cardiac rhythm disturbance with hemodynamic instability, which limits the use of WBI.\n\nWe considered the high risk of massive absorption with hemodynamic implications and started management with airway protection, placement of a pacemaker and decontamination by endoscopy [13]. Furthermore, our patient had a history of a previous suicide attempt with 50 tablets of extended release potassium salts. She developed hyperkalemia, metabolic acidosis and hyperacute T waves, and was hospitalized seven days in an intensive care unit. In the second attempt, even though the patient increased the ingestion to 100 tablets of the same drug, she did not develop any complication and was discharged two days after ingestion. We strongly concur that if a pharmacobezoar is suspected endoscopy should be considered in order to avoid a massive absorption [10], [14], [21].\n\nOn the other hand, the multiple introductions of the endoscope could increase the risk of airway injuries and aspiration of gastric content [15]. Despite that, in our case, the equipment was introduced eighteen times and no complications were presented. For this reason, we consider the endoscopic removal of bezoars a therapeutical option for uncomplicated patients and should be performed early if the medical center is short of appropriate orogastric tubes [1], [16].\n\nGunja [17] describes a case of a patient who ingested 100 tablets of extended release potassium chloride with severe hyperkalemia 5 h after the ingestion [17]. Also, Saxena [18] describes a case of a woman who ingested 16 mEq/Kg of potassium salts and developed severe hyperkalemia with cardiac arrest in the first hour after the ingestion. Finally, Colledge [19] reported another case with an intake of approximately 100 tablets with hyperkalemia and ventricular tachycardia demonstrating the effects of a rapid absorption in massive ingestions of potassium salts. In our case, due to the early endoscopic removal of tablets, the patient did not increase potassium serum levels and complications were not registered.\n\n4 Conclusions\nThis was a case of intentional potassium, ethanol and clonazepam overdose resulting in mild metabolic acidosis, hyperlactatemia and sinus tachycardia at 2 h after ingestion, without hyperkalemia and after utilizing endoscopy in order to remove 100 isolated tablets and forming pharmacobezoars. In this case, the bezoar formation could lead to massive absorption of potassium and increase the risk of hyperkalemic disturbances. In addition to standard treatments for hyperkalemia, this case report demonstrates the benefit from endoscopy in extended-release potassium bezoar formation, considering the hospital resources, time from the ingestion and clinical status of the patient. Also, this study asks whether endoscopy should be used as an initial measure of decontamination in patients who have ingested a large quantity of tablets, particularly in centers where there is a lack of adequate tubes for gastric lavage (Table 1).Table 1 Case development.\n\nTime\tSerumpotassium, blood gas\tTherapeutics\t\nArrival\tK 3.9 mmol/L\tParenteral solutions\t\npH 7.25, HCO3 17, Lact 4.9 mmol/L\tNot Anti hyperkalemic measures. Transcutaneouspacemaker\t\n\tEndoscopy\t\n\n\n\t\n5 h\n(after endoscopy)\tK 3.5 mmol/L\tNot Anti hyperkalemicmeasures\t\npH 7.39, HCO3 18.3, Lact 0.6 mmol/L\t\t\n\n\n\t\n8 h\tK 3.4 mmol/L\tNot Anti hyperkalemicmeasures\t\n\n\n\t\n18 h\tK 4.3 mmol/L\tNot Anti hyperkalemic measures. Transcutaneous pacemaker was removed\t\n\n\nWe concur that in selected cases endoscopy could be used instead of gastric lavage as first decontamination measure, although, a clinical guideline for the use of endoscopy as a decontamination method still need to be created.\n\nCases of extended release potassium salts reported are summarized below (Table 2).Table 2 Reported cases.\n\nReport\tPatient\tTime (intake)\tExtended release KCl\tFindings\tSerum K\tTherapy\t\nCharles et al. (1978)\t32, F\t18 h\t47 tabs (8 mmol)\tDiarrhea, death\t10.8 mmol/l\n(intraocular)\t0\t\nIllingworth (1980) [22]\t36, M\t5 h\tUnknown\nTabs, 8 mmol\tWide complex tachycardia (125×)\t8.9 mml/l\t5, 6, 7, 9, 10\t\nColledge et al. (1988)\t24, F\t2 h\t100 tabs\tHyperacute T waves, sinus tachycardia 110×. Ventricular tachycardia\n\t6.4 mmol/l\t1, 5, 6, 7\t\nSteedman (1988) [25]\n\t27, F\t12 h\t60 tabs (8 mmol)\t1st degree AV blockade, QRS widening and hyperacute T waves\t9.1 mmol/l\t5, 6, 7, 9,12\t\nPeeters et al. (1998)\t62, F\t?\t300 tabs (2.4 mmol)\tAbdominal distension. One month later gastric necrosis\tNot report\t3\t\n58, M\t5 h\t20 tabs of extended release KCl (630 mg). Bendoflurazide and phenylbutazone\tLeft ventricular heart failure\t8 mmol/l\t1, 6, 9, 10\t\n26, M\t3.5 h\t10 tabsdextropropoxyphene – acetaminophen\n40 tabs of extended release KCl (8 mmol)\tUnaltered EKG. Nausea and vomiting, Asystole, death in gastric lavage\t9.3 mmol/l\t1\t\n2 months\nM\t24 h\t5 tabs (8 mmol)\tDeath\t10.1 mmol/l\t0\t\nWhitaker et al. (2000) [26]\t30 months\nM\n\t30 min\t32 tabs\tTachycardia (155×) 1st degree AV blockade. Hyperacute T waves\t9.2 mmol/l\t2, 5, 6, 9, 10\t\nSu (2001) [27]\t50, F\t1 h\t100 tabs (10 mEq)\nAlprazolam and ibuprofen\tHyperacute T waves\t8.2 mmol/l\t1, 2, 4, 5, 6, 7, 9, 13\t\n17 a, M\t10 h\t20–30 tabs (10 mEq)\tTachycardia, nausea, vomiting and diarrhea\t5.5 mmol/l\t2\t\nWan (2007) [24]\t86, M\tChronic\t70 tabs (8 mmol)\tAsthenia and adinamia\t6.8 mmol/l\t2, 5, 6, 7\t\nGunja (2011)\t42, F\t90 min\t40 tabs (8 mmol)\tTachycardia (100×)\t5.5 mmol/l\t6, 2\t\n42, F\t5 h\t100 tab (8 mmol)\tTachycardia (124×)\t8.5 mmol/l\t5, 6, 7, 4\t\n6, M\t2 h\t10–20 tab (8 mmol)\tPlane T waves\t7.6 mmol/l\t4, 5, 6, 7, 8.\t\nSaxena (1988)\t46, F\t1 h\t100 tab (8 mmol)\tCardiac arrest\t9.6 mmol/l\t1, 5, 6, 7, 9, 11, 14.\t\nBriggs Albert et al. (2013) [28]\t44, F\t75 min\t30 tab (20 mEq)\tMildly peaked T waves\t7.3 mmol/L\t2, 3, 5, 6, 7, 8.\t\nPérez et al. (2013)\t42, F\t2 h\t100 tab (10 mEq)\tMetabolic acidosis, hyperlactatemia and sinus tachycardia with normal T waves\t3.9 mmol/L\t1, 3, 11\t\n1: gastric lavage; 2: whole bowel irrigation; 3: endoscopy; 4: hemodialysis; 5: calcium; 6: insulin/glucose; 7: sodium bicarbonate; 8: β-2 agonist; 9: ion exchange resin; 10: furosemide; 11: activated charcoal; 12: mannitol; 13: cardiac pacemaker and 14: advanced cardiac resuscitation.\n\n\n\nConflict of interest\nThe authors declare that they have no competing interests.\n\nAppendix A Supplementary data\nThe following are the supplementary data to this article: Transparency document\n \n\nAcknowledgement\nSpecial thanks to Dr. Carlos Mitrani Boyle, gastroenterologist and endoscopist who performed the procedure.\n\nAvailable online 22 May 2014\n\nAppendix A Supplementary data associated with this article can be found, in the online version, at doi:10.1016/j.toxrep.2014.04.002.\n==== Refs\nReferences\n1 Buckley N.A. Dawson A.H. Reith A.D. Controlled release drugs in overdose Drug Saf. 12 1995 73 84 7741985 \n2 Saetta J.P. Quinton D.N. Residual gastric content after gastric lavage and ipecacuanha-induced emesis in self-poisoned patients: an endoscopic study J. R. Soc. Med. 84 1991 35 38 1671603 \n3 Timothy J.S. Robert W.W. Disorders of Potassium Emerg. Med. Clin. N. Am. 23 2005 723 747 \n4 Gennari F.J. Disorders of potassium homeostasis: hypokalemia and hyperkalemia Crit. Care Clin. 18 2002 273 288 12053834 \n5 Perazella M.A. Mahnensmith R.L. Hyperkalemia in the elderly: drugs exacerbate impaired potassium homeostasis J. Gen. Intern. Med. 12 1997 646 656 9346463 \n6 Acker C.G. Johnson J.P. Palevsky P.M. Hyperkalemia in hospitalized patient: cause, adequacy of treatment, and results of an attempt to improve physician compliance with published therapy guidelines Arch. Intern. Med. 158 1998 917 924 9570179 \n7 Charytan D. Goldfarb D.S. Indications for hospitalization of patients with hyperkalemia Arch. Intern. Med. 160 2000 1605 1611 10847253 \n8 Taylor J.R. Streetman D.S. Castle S.S. Medication bezoars: a literature review and report of a case Ann. Pharmacother. 32 1998 940 946 9762382 \n9 Peeters J.W.P.M. Van Der Werf S.D.J. Gastric stenosis after potassium chloride ingestion Endoscopy 30 1998 110 \n10 Höjer J. Personne M. Endoscopic removal of slow reléase clomipramine bezoars in two cases of acute poisoning Clin. Toxicol. 46 2008 317 319 \n11 Robert R. Frat J.-P. Veinstein A. Rouffineau J. Protective effect of medication bezoar after a massive beta-blocker, digoxin, and amitriptyline poisoning Clin. Toxicol. 43 2005 381 382 \n12 American Academy of Clinical Toxicology European Association of Poison Centers and Clinical Toxicologists. position paper: whole bowel irrigation Clin. Toxicol. 42 2004 843 854 \n13 Whang R. Hyperkalaemia: diagnosis and treatment Am. J. Med. Sci. 272 1976 19 29 961713 \n14 Savitt D.L. Hawkins H.H. Roberts J.R. The radiopacity of ingested medications Ann. Emerg. Med. 16 1987 331 339 3813170 \n15 Ng H.W. Tse M.L. Lau F.L. Chu W. Endoscopic removal of iron bezoar following acute overdose Clin Toxicol. 46 2008 913 915 \n16 Geng W.L. Chen C.H. Tseng Y.J. Zong H.D. Pharmacobezoar of the esophagus Clin. Toxicol. 49 2011 348 349 \n17 Gunja N. Decontamination and enhanced elimination in sustained-release potassium chloride poisoning Emerg. Med. Australas 23 2011 769 772 22151677 \n18 Saxena K. Death from potassium chloride overdose Postgrad. Med. 84 97-8 1988 101 102 \n19 Colledge N.R. Northridge B. Fraser D.M. Survival after massive overdose of slow release potassium Scott. Med. J. 33 1988 279 3175610 \n21 Schwerk C. Schulz M. Schwerk N. Blüher S. Kiess W. Siekmeyer W. Etilefrin hydrochloride tablet ingestion: successful therapy by endoscopic removal of tablet conglomerate Klin. Padiatr. 221 2009 93 96 19199226 \n22 Illingworth N.R. Rapid poisoning with slow-release potassium Br. Med. J. 1980 485 486 \n24 Wan C.K. Tong H.K. A case of slow release potassium chloride overdose Hong Kong J. Emerg. Med. 14 2007 169 173 \n25 Steedman D.J. Poisoning with sustained release potassium Arch. Emerg. Med. 5 1988 206 211 3233133 \n26 Whitaker R.J. Maguire J.E. Slow-release potassium overdose: clinical features and the role of wholebowel lavage in management Emerg. Med. 12 2000 218 225 \n27 Su M. Stork C. Ravuri S. Lavoie T. Sustained-release potassium chloride overdose Clin. Toxicol. 39 2001 641 648 \n28 Briggs A.L. Deal L.L. Endoscopic removal of pharmacobezoar in case of intentional potassium overdose J. Emerg. Med. 08 2013 1 4\n\n",
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"title": "Extended release potassium salts overdose and endoscopic removal of a pharmacobezoar: A case report.",
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"abstract": "BACKGROUND\nIn the field of oncofertility, patients with breast cancer are often administered letrozole as an adjuvant drug before and after oocyte retrieval to prevent an increase in circulating estradiol.\n\n\nMETHODS\nWe report a case of abdominal hemorrhage due to an ovarian rupture in a 29-year-old Japanese patient who restarted letrozole 2 days after an oocyte retrieval procedure in which 14 mature oocytes were retrieved. The patient had sought embryo cryopreservation as a fertility preservation option before undergoing treatment for recurrent breast cancer. A day after restarting letrozole treatment, the patient unexpectedly developed severe abdominal pain. Laparoscopic hemostasis was performed to manage the ovarian swelling and hemorrhage.\n\n\nCONCLUSIONS\nThe ovaries can be restimulated by restart letrozole after an oocyte retrieval procedure. Therefore, reproductive-medicine practitioners should understand the potential complications of letrozole administration in such cases and take steps to ensure that they are minimized.",
"affiliations": "Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan. [email protected].;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.;Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama, 350-3550, Japan.",
"authors": "Huang|Haipeng|H|;Takai|Yasushi|Y|;Samejima|Kouki|K|;Gomi|Yosuke|Y|;Narita|Tatsuya|T|;Ichinose|Shunichiro|S|;Itaya|Yukiko|Y|;Ono|Yosihisa|Y|;Matsunaga|Sigetaka|S|;Saitoh|Masahiro|M|;Seki|Hiroyuki|H|",
"chemical_list": "D000077289:Letrozole",
"country": "England",
"delete": false,
"doi": "10.1186/s13256-021-02938-8",
"fulltext": "\n==== Front\nJ Med Case Rep\nJ Med Case Rep\nJournal of Medical Case Reports\n1752-1947\nBioMed Central London\n\n2938\n10.1186/s13256-021-02938-8\nCase Report\nSevere hemoperitoneum resulting from restart of letrozole after oocyte retrieval procedure: a case report\nHuang Haipeng [email protected]\n\nTakai Yasushi [email protected]\n\nSamejima Kouki [email protected]\n\nGomi Yosuke [email protected]\n\nNarita Tatsuya [email protected]\n\nIchinose Shunichiro [email protected]\n\nItaya Yukiko [email protected]\n\nOno Yosihisa [email protected]\n\nMatsunaga Sigetaka [email protected]\n\nSaitoh Masahiro [email protected]\n\nSeki Hiroyuki [email protected]\n\ngrid.410802.f 0000 0001 2216 2631 Department of Obstetrics and Gynecology, Saitama Medical Center, Saitama Medical University, 1981 Kamoda, Kawagoe City, Saitama 350-3550 Japan\n27 6 2021\n27 6 2021\n2021\n15 32726 3 2021\n1 6 2021\n© The Author(s) 2021\nhttps://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.\nBackground\n\nIn the field of oncofertility, patients with breast cancer are often administered letrozole as an adjuvant drug before and after oocyte retrieval to prevent an increase in circulating estradiol.\n\nCase presentation\n\nWe report a case of abdominal hemorrhage due to an ovarian rupture in a 29-year-old Japanese patient who restarted letrozole 2 days after an oocyte retrieval procedure in which 14 mature oocytes were retrieved. The patient had sought embryo cryopreservation as a fertility preservation option before undergoing treatment for recurrent breast cancer. A day after restarting letrozole treatment, the patient unexpectedly developed severe abdominal pain. Laparoscopic hemostasis was performed to manage the ovarian swelling and hemorrhage.\n\nConclusions\n\nThe ovaries can be restimulated by restart letrozole after an oocyte retrieval procedure. Therefore, reproductive-medicine practitioners should understand the potential complications of letrozole administration in such cases and take steps to ensure that they are minimized.\n\nKeywords\n\nBreast cancer\nFertility preservation\nHemoperitoneum\nLaparoscopic surgery\nLetrozole\nOvarian hemorrhage\nissue-copyright-statement© The Author(s) 2021\n==== Body\nBackground\n\nIncidence of breast cancer in adolescent and young adult women is on the rise both in Japan and worldwide [1, 2]. It is also the most common disease for which patients seek assisted reproductive technology procedures for fertility preservation. In the case of hormone-dependent tumors, the use of the aromatase inhibitor, letrozole, as an adjuvant is recommended to prevent an increase in the circulating concentration of estradiol (E2) [3]. Moreover, Rodgers et al. concluded that letrozole does not diminish total oocyte yield [4]. Current recommendations for fertility preservation in women with E2-responsive breast cancer advise a second course of letrozole after oocyte retrieval to keep serum E2 levels low [5]. This regimen is known to significantly reduce the circulating concentration of E2 after oocyte retrieval [6]. However, letrozole has also been reported to have ovary-stimulating effects, even if administered in the luteal phase of the menstrual cycle [7]. Here, we report a case of abdominal hemorrhage due to ovarian rupture in a patient who restarted letrozole after an oocyte retrieval procedure.\n\nCase presentation\n\nThe patient was a 29-year-old nulligravid Japanese woman with no history of infertility, who was seeking fertility preservation in advance of chemotherapy for breast cancer that developed shortly after her marriage. Her body mass index (BMI) was 19.4 (height 157 cm, weight 48 kg). Although she had a history of asthma, she had been incident-free for more than 2 years. She had been diagnosed with breast cancer 3 years previously and was treated by partial resection of the left mammary gland. The excised mass had a positive margin and was identified as ductal carcinoma in situ based on histopathological findings: Estrogen receptor (ER) (+), Progesterone receptor (PR) (+), HER2 (1+), and Ki67 (10%). These findings prompted the doctors to perform a left total mastectomy, which yielded an excised mass with a negative margin. The patient tested negative for lymph-node metastasis. She declined postoperative chemotherapy and radiation therapy because of a strong desire to bear children. Follow-up tests every 3 months revealed no evidence of disease until 31 months after the total mastectomy, when subcutaneous recurrence was discovered in the left chest. The mass was surgically removed, and identified as an invasive ductal carcinoma based on histopathological findings: Nottingham Grade (NG) 1, ER (8) PR (8) HER2 (2+) fluorescence in situ hybridization (FISH) (2.54) Ki67 (10–20%). The patient was then scheduled for 6 months of chemotherapy consisting of cyclophosphamide and HER2-targeted therapy and trastuzumab starting roughly 2 months after tumor excision. Chemotherapy was followed by hormone therapy for a minimum of 3 years. The patient was referred to Saitama Medical Center after expressing the desire, during counseling, to preserve her fertility prior to starting chemotherapy.\n\nThe patient’s family history of multiple breast cancer reported for both her mother and grandmother led us to suspect hereditary breast and ovarian cancer syndrome, and therefore, she was referred to a genetic counselor before beginning any fertility treatment. Blastocyst cryopreservation was selected as the treatment option for fertility preservation after the ovaries were verified to be cancer-free.\n\nHer blood tests showed normal levels of infertility-related biomarkers [anti-Müllerian hormone (AMH): 2.90 ng/mL, Base E2: 42.7 pg/mL, follicle-stimulating hormone (FSH): 5.8 mU/mL, luteinizing hormone (LH): 4.1 mU/mL] and no signs of coagulation abnormalities. Her menstrual cycle was 30 days. Her ultrasound did not reveal any characteristics of polycystic ovary syndrome. Her Pap test result was negative for intraepithelial lesions or malignancy (NILM) according to the Bethesda classification. The results of her husband’s semen analysis were normal (semen volume: 3.8 mL, sperm count: 43 million, motility: 69%).\n\nThe woman commenced oral letrozole (5.0 mg/day) on day 5 of her cycle, and started self-injecting recombinant FSH (225 IU/day) the next day. As expected, her circulating hormone levels were slightly elevated 6 days after FSH administration, [E2: 469 pg/mL, LH: 3.1 mIU/m, FSH: 19.3 mU/mL, progesterone (P4): 0.54 ng/mL], and the dominant follicle had a diameter of 16 mm. Daily administration of ganirelix (0.25 mg/day) was started on the same day. After 11 days of FSH administration, the dominant follicle had increased in size to 22 mm, and hormone levels were further elevated (E2: 1550 pg/mL, LH: 1.6 mIU/m, FSH: 16.4 mU/mL, P4: 2.23 ng/mL). At this point, we decided to proceed with the oocyte retrieval, expecting to harvest 16 eggs of suitable size (> 14 mm). Final oocyte maturation was triggered by administering two 300 μg doses of a gonadotropin releasing hormone (GnRH) agonist 1 hour apart (buserelin nasal spray 0.2 mg, Nasanyl; Pfizer, Tokyo, Japan). After 36 hours, 15 oocytes were retrieved, including 14 mature metaphase II (MII) eggs and one immature germinal vesicle (GV). The MII oocytes were fertilized before cryopreservation [split insemination: seven in vitro fertilization (IVF), seven intracytoplasmic sperm injection (ICSI)], preserving only the good-quality embryos; the lone GV oocyte was cryopreserved unfertilized.\n\nTo prevent any delays in her cancer treatment due to ovarian hyperstimulation syndrome (OHSS), the patient started taking oral cabergoline (0.5 mg) after oocyte retrieval. Only mild ovarian swelling (right: 57 × 50 mm, left: 58 × 46 mm) and mild ascites were observed on a follow-up visit 2 days later, after 52 hours of the oocyte retrieval procedure (Figs. 1, 2). She did not complain of tenderness during the pelvic examination. As the patient experienced only minor abdominal pain after oocyte retrieval, analgesic use was considered unnecessary. On the same day, she was restarted on letrozole (5.0 mg/day) to prevent the increase of circulating E2, since her tumor was E2 receptor-positive. The next day, 76 hours after the oocyte retrieval procedure, she unexpectedly developed severe abdominal pain and was urgently admitted to our hospital.Fig. 1 Ultrasonography showing mild ascites 2 days after oocyte retrieval\n\nFig. 2 Ovarian ultrasonography showing mild ovarian swelling 2 days after oocyte retrieval\n\nOn admission, the patient complained of abdominal distension and lower abdominal and lower back pain. Her blood biochemistry profile was as follows: white blood cell (WBC): 8200/μL, hemoglobin (Hb): 14.2 g/dL, hematocrit (Hct): 40.1%, C-reactive protein (CRP): 0.02 mg/dL, total protein (TP): 7.2 g/dL, albumin (Alb): 4.5 g/dL, Creatinine (Cre): 0.53 mg/dL, Uric Acid (UA): 4.8 mg/dL, activated partial thromboplastin time (APTT): 31.7 seconds, prothrombin time (PT): 12.0 seconds, PT%: 107, D-dimer: 0.78 μg/mL. Ultrasonography revealed bilateral exacerbation of ovarian swelling (right: 105 × 49 mm, left: 70 × 60 mm;) and increased (moderate) ascitic volume (Fig. 3). Ovarian torsion was suspected based on tenderness and swelling noted in the left ovary.Fig. 3 Ovarian ultrasonography 3 days after oocyte retrieval (1 day after restarted letrozole). The ultrasonograph shows bilateral exacerbation of ovarian swelling and increased ascitic volume\n\nAn emergency laparoscopic surgery was performed to confirm the diagnosis. The left ovary was enlarged and had ruptured at what was apparently an aspiration site from oocyte retrieval. Hemoperitoneum, caused by continued abnormal bleeding from the same site, was also observed (Fig. 4). Laparoscopic hemostasis was performed. A day later, her blood biochemistry profile showed normal findings with a slight reduction in hemoglobin (WBC: 9400/μL, Hb: 12.7 g/dL, Hct: 36.4%, TP: 6.3 g/dL, Alb: 3.9 g/dL, Cre: 0.48 mg/dL, APTT: 30.7 seconds, PT: 12.9 seconds, PT%: 93). The patient’s general condition after the intervention was good. She was discharged from the hospital 4 days later (that is, 7 days after oocyte retrieval) after bilateral shrinkage of the ovarian swelling was confirmed by ultrasonography (right: 46 × 44 mm, left: 42 × 42 mm; Fig. 5), and no worsening of OHSS symptoms in the past week of daily oral cabergoline (0.5 mg) was noted.Fig. 4 Intraoperative findings. Left: ruptured ovary; right: blood pooling in the pelvic cavity\n\nFig. 5 Ovarian ultrasonography before discharge, showing bilateral shrinkage of the ovarian swelling to ~ 4.5 cm size\n\nDiscussion and conclusions\n\nThe incidence of severe hemoperitoneum was 0.08% in 2007, decreasing 0.29-fold by 2015 in Japan [8]. Severe hemoperitoneum symptoms usually appear within 24 hours after oocyte retrieval procedures [9].\n\nLetrozole is an oral medication frequently used in the field of oncofertility, and few reports of complications or side effects have been published. Despite showing no signs of abnormality during a follow-up examination 2 days, that is, 52 hours, after the oocyte retrieval procedure, our patient unexpectedly experienced ovarian swelling after 76 hours of the oocyte retrieval procedure within 24 hours of restarting letrozole, which apparently caused ovarian rupture and persistent ovarian hemorrhage. Given the clinical findings and time line, the ovulation-stimulating effects of letrozole clearly contributed to the swelling observed [7]. However, as ovarian swelling is also a hallmark symptom of OHSS, this syndrome may also have played a role. We believe this case serves as a timely warning that should encourage practitioners to exercise caution when considering letrozole administration after oocyte retrieval.\n\nAdjuvant letrozole is effective in preventing OHSS [10, 11]. In one randomized clinical trial [12] either aspirin or letrozole was taken orally for 5 consecutive days after ovulation was induced using an hCG trigger, and letrozole resulted in a lower incidence of OHSS compared with aspirin. However, 25% of the letrozole group experienced moderate or higher OHSS, and, just as concerning, patients treated with letrozole had higher serum vascular endothelial growth factor (VEGF) levels than those not treated with it. Similar research has shown increased levels of VEGF and decreased levels of pigment epithelium-derived factor (a potent angiogenesis inhibitor) in the follicular fluid of patients treated with letrozole [13]. Factors such as these could have led to the abnormal ovarian bleeding observed in our patient in the days following oocyte retrieval.\n\nThe adjuvant use of letrozole after oocyte retrieval suppresses circulating E2 and may reduce the likelihood of OHSS. Nonetheless, our experience here suggests that letrozole treatment can also lead to ovarian restimulation, causing ovarian rupture and persistent ovarian hemorrhage.\n\nIn conclusion, the use of letrozole has become essential to oocyte retrieval protocols for E2-receptor-positive breast-cancer patients seeking fertility preservation. This case report highlights a potential complication associated with letrozole treatment in such patients. Therefore, when considering letrozole administration in anticipation of subsequent oncotherapy, reproductive medicine practitioners should consider its potential complications and take appropriate steps to ensure that they are minimized.\n\nAbbreviations\n\nE2 Estradiol\n\nNILM Negative for intraepithelial lesions or malignancy\n\nMII Metaphase II\n\nGV Germinal vesicle\n\nOHSS Ovarian hyperstimulation syndrome\n\nVEGF Vascular endothelial growth factor\n\nAcknowledgements\n\nWe would like to thank Editage for English language editing.\n\nAuthors’ contributions\n\nHH was a major contributor in writing the manuscript. YT was involved in drafting and revising the manuscript. KS, YG, TN, SI, YI, YO, SM, and MS were involved in revising the manuscript. HS contributed to the study concept and design. All the authors read and approved the final manuscript.\n\nFunding\n\nThis report received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.\n\nAvailability of data and materials\n\nNot applicable.\n\nDeclarations\n\nEthics approval and consent to participate\n\nEthical approval was waived by the ethical committee of Saitama Medical University, Saitama Medical Center.\n\nConsent for publication\n\nWritten informed consent was obtained from the patient to publish this case report and any accompanying images. A copy of the written consent is available for review from the Editor-in-Chief of this journal.\n\nCompeting interests\n\nHH, YT, KS, YG, TN, SI, YI, YO, SM, MS, and HS declare that they have no conflicts of interest.\n\nPublisher's Note\n\nSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n==== Refs\nReferences\n\n1. Johnson RH Chien FL Bleyer A Incidence of breast cancer with distant involvement among women in the United States, 1976 to 2009 JAMA 2013 309 800 805 10.1001/jama.2013.776 23443443\n2. Merlo DF Ceppi M Filiberti R Bocchini V Znaor A Gamulin M Breast cancer incidence trends in European women aged 20–39 years at diagnosis Breast Cancer Res Treat 2012 134 363 370 10.1007/s10549-012-2031-7 22456983\n3. Kasum M von Wolff M Franulic D Čehić E Klepac-Pulanić T Orešković S Fertility preservation options in breast cancer patients Gynecol Endocrinol 2015 31 11 846 851 26370157\n4. Rodgers RJ Reid GD Koch J Deans R Ledger WL Friedlander M The safety and efficacy of controlled ovarian hyperstimulation for fertility preservation in women with early breast cancer: a systematic review Hum Reprod 2017 32 1033 1045 10.1093/humrep/dex027 28333356\n5. Oktay K Hourvitz A Sahin G Oktem O Safro B Cil A Letrozole reduces estrogen and gonadotropin exposure in women with breast cancer undergoing ovarian stimulation before chemotherapy J Clin Endocrinol Metab 2006 91 3885 3890 10.1210/jc.2006-0962 16882752\n6. Cheng ZX Kong G Zhang CL Zhao YN Letrozole versus gonadotropin-releasing hormone antagonist during luteal phase in the prevention of ovarian hyperstimulation syndrome: a randomized controlled trial Zhonghua Fu Chan Ke Za Zhi 2020 55 9 14 32074767\n7. Kuang Y Chen Q Hong Q Lyu Q Fu Y Ai A Luteal-phase ovarian stimulation case report: three-year follow-up of a twin birth J Fertiliz. 2013 1 106\n8. Kuroda K Nagai S Ikemoto Y Matsumura Y Ochiai A Nojiri S Incidences and risk factors of moderate-to-severe ovarian hyperstimulation syndrome and severe hemoperitoneum in 1,435,108 oocyte retrievals Reprod Biomed Online 2021 42 1 125 132 10.1016/j.rbmo.2020.09.001 33051135\n9. Nouri K Walch K Promberger R Kurz C Tempfer CB Ott J Severe haematoperitoneum caused by ovarian bleeding after transvaginal oocyte retrieval: a retrospective analysis and systematic literature review Reprod Biomed Online 2014 29 6 699 707 10.1016/j.rbmo.2014.08.008 25444503\n10. Tshzmachyan R Hambartsoumian E The role of Letrozole (LE) in controlled ovarian stimulation (COS) in patients at high risk to develop ovarian hyper stimulation syndrome (OHSS). A prospective randomized controlled pilot study J Gynecol Obstet Hum Reprod 2020 49 101643 10.1016/j.jogoh.2019.101643 31563697\n11. Kamath MS Maheshwari A Bhattacharya S Lor KY Gibreel A Oral medications including clomiphene citrate or aromatase inhibitors with gonadotropins for controlled ovarian stimulation in women undergoing in vitro fertilisation Cochrane Database Syst Rev. 2017 11 8528\n12. Mai Q Hu X Yang G Luo Y Huang K Yuan Y Effect of letrozole on moderate and severe early-onset ovarian hyperstimulation syndrome in high-risk women: a prospective randomized trial Am J Obstet Gynecol 2017 216 42 10.1016/j.ajog.2016.08.018 27555316\n13. Haas J Bassil R Gonen N Meriano J Jurisicova A Casper RF The VEGF and PEDF levels in the follicular fluid of patients co- treated with LETROZOLE and gonadotropins during the stimulation cycle Reprod Biol Endocrinol 2018 16 54 10.1186/s12958-018-0367-5 29843716\n\n",
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"issue": "15(1)",
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"keywords": "Breast cancer; Fertility preservation; Hemoperitoneum; Laparoscopic surgery; Letrozole; Ovarian hemorrhage",
"medline_ta": "J Med Case Rep",
"mesh_terms": "D000328:Adult; D001943:Breast Neoplasms; D005260:Female; D059247:Fertility Preservation; D006465:Hemoperitoneum; D006801:Humans; D000077289:Letrozole; D009364:Neoplasm Recurrence, Local; D054315:Oocyte Retrieval; D010062:Ovulation Induction",
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{
"abstract": "BACKGROUND\nThere is evidence that sugammadex can facilitate extubation post-surgery and attenuate postoperative pulmonary complications resulting from postoperative residual neuromuscular blockade. However, it may induce adverse effects, including bronchospasm, laryngospasm, bradycardia, hypotension, and cardiac arrest. Here, we present a case of sugammadex-induced bradycardia and hypotension.\nAn 82-year-old female received video-assisted thoracic surgery decortication and wedge resection of the lung for empyema. Post-surgery, she developed bradycardia, hypotension, hypoxia, and weakness.\nThe patient was suspected to have sugammadex-induced bradycardia, hypotension, hypoxia and weakness.\n\n\nMETHODS\nThe patient received immediate treatment with atropine (0.5 mg) for bradycardia. Glycopyrrolate (0.1 mg) and neostigmine (1 mg) were administered to improve the train-of-four (TOF) ratio.\n\n\nRESULTS\nFollowing initial management, we observed improvement in the hemodynamics of the patient. She was discharged without any sequelae.\n\n\nCONCLUSIONS\nSugammadex-induced bradycardia or cardiac arrest are rare; however, anesthesiologists must consider the possibility of the occurrence of such events and initiate appropriate management measures. Immediate treatment with atropine and inotropic or vasopressors is warranted if the patient presents with bradycardia.",
"affiliations": "Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan.;Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan.;Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan.;Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan.;Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan.;Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.",
"authors": "Teng|I-Chia|IC|;Chang|Ying-Jen|YJ|;Lin|Yao-Tsung|YT|;Chu|Chin-Chen|CC|;Chen|Jen-Yin|JY|;Wu|Zhi-Fu|ZF|0000-0001-6376-9085",
"chemical_list": "D000077122:Sugammadex",
"country": "United States",
"delete": false,
"doi": "10.1097/MD.0000000000026796",
"fulltext": "\n==== Front\nMedicine (Baltimore)\nMedicine (Baltimore)\nMEDI\nMedicine\n0025-7974\n1536-5964\nLippincott Williams & Wilkins Hagerstown, MD\n\nMD-D-21-03029\n10.1097/MD.0000000000026796\n26796\n3300\nResearch Article\nClinical Case Report\nSugammadex induced bradycardia and hypotension\nA case report and literature review\nTeng I-Chia MD a\nChang Ying-Jen MD a\nLin Yao-Tsung MD ab\nChu Chin-Chen MD, PhD a\nChen Jen-Yin MD, PhD a\nWu Zhi-Fu MD cd∗\nSaranathan. Maya\na Department of Anesthesiology, Chi Mei Medical Center, Tainan City, Taiwan\nb Department of Food Science and Technology, Chia Nan University of Pharmacy and Science, Tainan, Taiwan\nc Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan\nd Department of Anesthesiology, Tri-Service General Hospital and National Defense Medical Center, Taipei, Taiwan.\n∗ Correspondence: Zhi-Fu Wu, Department of Anesthesiology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung 807, Taiwan (e-mail: [email protected]).\n30 7 2021\n30 7 2021\n100 30 e267962 5 2021\n14 6 2021\n12 7 2021\nCopyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.\n2021\nhttps://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0\n\nAbstract\n\nRationale:\n\nThere is evidence that sugammadex can facilitate extubation post-surgery and attenuate postoperative pulmonary complications resulting from postoperative residual neuromuscular blockade. However, it may induce adverse effects, including bronchospasm, laryngospasm, bradycardia, hypotension, and cardiac arrest. Here, we present a case of sugammadex-induced bradycardia and hypotension.\n\nPatient concerns:\n\nAn 82-year-old female received video-assisted thoracic surgery decortication and wedge resection of the lung for empyema. Post-surgery, she developed bradycardia, hypotension, hypoxia, and weakness.\n\nDiagnoses:\n\nThe patient was suspected to have sugammadex-induced bradycardia, hypotension, hypoxia and weakness.\n\nInterventions:\n\nThe patient received immediate treatment with atropine (0.5 mg) for bradycardia. Glycopyrrolate (0.1 mg) and neostigmine (1 mg) were administered to improve the train-of-four (TOF) ratio.\n\nOutcomes:\n\nFollowing initial management, we observed improvement in the hemodynamics of the patient. She was discharged without any sequelae.\n\nLessons:\n\nSugammadex-induced bradycardia or cardiac arrest are rare; however, anesthesiologists must consider the possibility of the occurrence of such events and initiate appropriate management measures. Immediate treatment with atropine and inotropic or vasopressors is warranted if the patient presents with bradycardia.\n\nKeywords\n\nbradycardia\ncardiac arrest\nhypotension\nsugammadex\nOPEN-ACCESSTRUE\n==== Body\n1 Introduction\n\nNeuromuscular blocking agents are often employed to facilitate intubation, mechanical ventilation, and favorable surgical conditions. However, postoperative pulmonary complications, such as pulmonary hemorrhage, difficulty breathing, reintubation, and prolongation of the patient's length of stay could be attributed to postoperative residual neuromuscular blockade.[1,2]\n\nReversal agents are used to speed up recovery time from neuromuscular blockade and prevent postoperative residual neuromuscular blockade.[3] In contrast to acetylcholinesterase inhibitors, sugammadex has been demonstrated to shorten extubation time, resulting in improved operating room turnover in clinical anesthesia settings and attenuation of postoperative pulmonary complications.[4,5] However, sugammadex has been associated with several adverse effects, including bronchospasm,[6] pulmonary edema,[6] desaturation, hypotension, laryngospasm,[7] bradycardia, and cardiac arrest.[8–16] Here, we present a case of sugammadex-induced bradycardia, hypotension, and hypoxia in a patient following video-assisted thoracic surgery decortication and wedge resection of the lung. In addition, we analyzed adult cases of bradycardia or hypotension following sugammadex administration between January 2014 and January 2021 with a detailed literature review as well.\n\n2 Case presentation\n\nThe patient was an 82-year-old woman (146 cm, 44 kg) diagnosed with hypertensive heart disease with no known history of allergy. Upon being diagnosed with empyema, she was scheduled for video-assisted thoracic surgery decortication and wedge resection of the lung. Pre-procedural electrocardiography revealed a normal sinus rhythm. Cardiac echocardiography showed a left ventricular ejection fraction of 71% and impaired left ventricular relaxation. Abnormal laboratory data demonstrated a white blood cell count of 15500/uL and C-reactive protein level of 220.7 mg/L. Vital signs were unremarkable except for oxygen saturation being around 90% to 95% on room air.\n\nRoutine monitoring included electrocardiography (lead II), noninvasive blood pressure, pulse oximetry, end-tidal carbon dioxide measurement, entropy, and the use of neuromuscular transmission monitors (NMTM). General anesthesia was induced with thiamylal (225 mg), rocuronium (50 mg), lidocaine (40 mg), fentanyl (75 mg), and glycopyrrolate (0.1 mg). The patient was intubated with a 32 Fr left double-lumen tube, and inspected using a fiberoptic bronchoscope. Following tracheal intubation, a right radial arterial line and central venous catheter were inserted. Anesthesia was maintained with sevoflurane (0.5–0.9), minimum alveolar concentration and propofol (20 mL/h) ti4trated to effect under entropy. In addition, the patient received a continuous dose of rocuronium (15–10 mg/h) under NMTM. Ventilation was adjusted to maintain an end-tidal carbon dioxide of 35 to 45 mmHg. The surgery was completed uneventfully in 2 hours and 40 minutes. At the completion of the procedure, arterial blood pressure of the patient was estimated to be 124/85 mmHg; heart rate, 65 beats per minute (bpm); SpO2, 99%; NMTM count, 4; and train-of-four (TOF) ratio, 64. The patient regained consciousness and spontaneous breathing. A dose of 200 mg sugammadex was next administered. One minute following sugammadex administration, the patient developed sinus bradycardia with 34 bpm without diffuse ST depression, hypotension (67/34 mmHg), hypoxia (SpO2: 65%), with an NMTM count of 0, and TOF ratio of 0. The patient was immediately administered atropine (0.5 mg) intravenously, following which her hemodynamics improved, with a corresponding heart rate of 65 bpm, SBP of 89/50 mmHg, and SpO2 of 93%. Subsequent administration of glycopyrrolate (0.1 mg) and neostigmine (1 mg) improved the TOF ratio to 69. Arterial blood gas values were as follows: pH, 7.291; PaO2, 75 mmHg; PaCO2, 51.4 mmHg; HCO3−, 22.8 mmol/L; lactate, 1.1 mmol/L; hemoglobin, 12.6 g/dL; and hematocrit, 36.7%. The anesthesiologist replaced the double-lumen tube with a single-lumen 4endotracheal tube, following which the patient was transferred to the intensive care unit for further care. The patient was extubated and discharged 4 and 10 days post-surgery, respectively, without any sequelae.\n\n3 Discussion\n\nPubMed and Cochrane Database were searched for the terms “sugammadex AND (bradycardia operating room cardiac arrest)” in January 2021. Articles between January 2014 and January 2021 were included regardless of the type of publication or journal. The full text of the articles was retrieved. The authors assessed the articles using the following set of criteria:\n\n1. the article is written in English;\n\n2. the study is a case report or case series;\n\n3. the study includes a description of the dose of sugammadex used, its adverse effects, and the treatment strategy;\n\n4. the subjects are adult patients.\n\nInformation such as the type of publication (case report), year of publication, description of adverse effects, treatment administered for the reaction, and patient outcome were extracted from the articles. The results have been summarized in Table 1.\n\nTable 1 Literature review of reported cases of sugammadex induced bradycardia or cardiac arrest.\n\n\tPatient Information\t\t\t\t\t\nAuthors\tDose of Sugammadex\tSigns and symptoms\tManagement\tOutcome\tMechanism\t\nObara et al[12]\t73 y/oMale77 kg, 178 cmSugammadex 200 mg (2.60 mg/kg)\t• Hypotension: SBP unmeasurable (6 min after sugammadex)• ECG: ST depression, polymorphic ventricular premature contraction, and then cardiac arrest• Unconscious• Flushed on entire body trunk and lower limbs\t• Fluid resuscitation• Phenylephrine 0.1 mg for 2 times• Epinephrine 0.1 mg• Suspecting primary cardiac ischemia, lidocaine (100 mg over 2 min) and nicorandil (2 mg/h) were also administered to prevent further progression of cardiac ischemia and arrhythmia• Re-intubation• CPR 10 min: epinephrine 3 mg i.v., defibrillations 2 times for VF• Suspecting an allergic reaction, methylprednisolone 1 g, hydroxyzine hydrochloride 50 mg, and a large volume of fluids\t• SBP 70 mmHg, sinus heart rhythm 110 bpm• ICU• Consciousness recover 1 hr. after shock• The serum tryptase level 3 h. after the event was elevated to 9.6 μg/L (normal range, 1.2–5.7)• Skin prick test: positive reaction of sugammadex\tAnaphylaxis\t\nBhavani et al[8]\t41 y/oMale72 kgSugammadex 300 mg (4.17 mg/kg)\tCase 1• Bradycardia (HR: 25 bpm) (2 min after sugammadex)• No palpable peripheral pulses\t• CPR• Epinephrine 1 mg i.v.• Re-intubation• Ventilation with 100% O2\t• Spontaneous cardiac activity• ICU• Tryptase concentration drawn shortly after resuscitation: 1.7 mg litre1 (normal < 11)• Cardiac enzymes, troponins: normal• ECG: no evidence of ischemia• Die on 15th day\tUnknown\t\n\t60 y/oFemale88 kgSugammadex 200 mg (2.27 mg/kg)\tCase 2• Bradycardia (HR: 30 bpm) (1 min after sugammadex)• Asystole• Hypotension• No palpable pulse\t• CPR• Epinephrine 30 mg i.v.\t• Spontaneous circulation and normal hemodynamics at the end of the 5th cycle CPR• Re-intubated during CPR• Extubated 15 min later• Discharged 48 hrs. later\tUnknown\t\nSanoja and Toth[14]\t60 y/oMale82 kgBMI 28.4Sugammadex 200 mg (2.4 mg/kg)\t• Bradycardia (HR: 35 bpm) (< 1 mins after sugammadex)• MAP dropped to mid-30s• No rash or urticaria• Bilateral breath sounds clear• Peak airway pressure remained 18 cmH2O; end-tidal CO2: 38 mmHg• End-tidal CO2 fell to 10 mm Hg• Carotid pulses (-)• PEA\t• Atropine 1 mg (no effect)• CPR• Epinephrine 1 mg every 3 minutes for a total of 7 mg• Calcium chloride 1 gm until return of spontaneous circulation\t• Spontaneous circulation, with HR > 100 bpm and MAP > 90 mm Hg• ICU• Transthoracic echocardiogram, electrocardiogram, chest X-ray, computed tomography chest, urine toxicology: all unremarkable• Tryptase level: not obtained (owing to a lack of signs or symptoms of allergic reaction)• Discharged on day 7 with no discernible sequelae\tUnknown\t\nYanai and Ariyos[15]\t71 y/oFemale65 kgSugammadex 200 mg (3.08 mg/kg)\tEpisode 1• Desaturation (2 min after sugammadex)• VF• No rash on the skin\t• Mask ventilation• CPR and defibrillation• Re-intubated 18 mins after resuscitation\t• Unconscious (GCS: E1VTM1) without sedation• BP 100/60 mmHg, HR 100 bpm• RR 20 beats/min with spontaneous breathing• SpO2 level was 100% while breathing 100% oxygen• 12-lead ECG: sinus tachycardia without specific ST segment elevation or depression• TTE: normal EF with no regional wall motion abnormalities• Blood tests, chest X-ray, brain CT scan, contrast-enhanced CT scans of chest and abdomen → no remarkable findings• Troponin I level 1 hr. after cardiac arrest: 0.219 ng/mL (ref: 0–0.028 ng/mL)• ICU, discharged from ICU on day 14• Coronary CT angiography on day 45 → no marked coronary artery disease• Transferred to a rehabilitation hospital on day 61\tKounis Syndrome (Anaphylaxis)\t\n\t71 y/oFemale65 kgSugammadex 130 mg (2 mg/kg)\tEpisode 2• Blood pressure drop suddenly• Bradycardia (without mention of HR)• PEA4\t• Noradrenaline i.v. drip\t• Spontaneous circulation after 13 min of resuscitation• ECG: diffuse ST depression• TTE: diffused, severely depressed left ventricular wall motion• Coronary angiogram: multiple spasms in RCA, resolved via intracoronary administration of nitroglycerin• Troponin I: 0.245 ng/mL• At 72 mins, tryptase level 81.2 μg/L (ref: 1.2–5.7 μg/mL)• ICU: 40 mg methylprednisolone i.v. and continuous infusion of nicorandil• Recovered by day 3 and so was extubated• Discharged from ICU on day 5• Skin prick test: positive reaction to sugammadex• Discharged to a rehabilitation hospital on day 26\tKounis Syndrome (Anaphylaxis)\t\nYoshida et al[16]\t50 y/oFemale79.2 kg, 156 cmSugammadex 200 mg (2.53 mg/kg)\t• Bradycardia (HR from 87 bpm to 36 bpm) (1 min after sugammadex)• Hypotension (41/20 mmHg)• ST depression in lead II• Lack of signs suggesting allergic reactions, such as skin rash or urticaria\t• Atropine 0.5 mg i.v. (hemodynamics did not improve)• Adrenaline 0.5 mg i.v. 2 min after atropine• Trachea intubated\t• ICU (approximately 1 hr. after bradycardia occurred)• HR 130 bpm and BP 100/54 mmHg• Spontaneous breathing with low tidal volume leading to hypercapnia (end-tidal CO2 58 mmHg) and alveolar hypoventilation (SpO2 93% [FiO2 1.0])• Bilateral breath sounds clear• Normal systolic function of both ventricles• BIS: 70–80• ECG: down sloping ST depression in leads II, III, aVF, and V3–6, as well as ST elevation in lead aVR, were noted, MI was considered• Serum tryptase, histamine were not assessed• Extubated 9 hrs after admitted to ICU• Discharged on POD 8\tUnknown\t\nMirza et al[11]\t82 y/oMale68.97 kgSugammadex 200 mg (2.9 mg/kg)\t• Bradycardia (without mention of HR)• Asystole• PEA• Ventricular rhythms\t• Glycopyrrolate 0.2 mg• Ephedrine 10 mg• Multiple doses of epinephrine• CPR• Defibrillation• Norepinephrine infusion\t• Death\tUnknown\t\nCarmen et al[10]\t80 y/oMale55 kg, 158 cmSugammadex 200 mg (3.64mg/kg)\t• Severe bradycardia (HR < 35 bpm) (1 minute after sugammadex)• SBP < 50 mmHg• Asystole and cardiac arrest\t• Total of 10 mg ephedrine i.v.• Atropine 1 mg i.v.• CPR for 1 min, restoring spontaneous cardiac activity\t• ICU• Cardiac enzymes and troponins: normal• ECG and transthoracic echocardiography: not show any pathological sign• Spontaneous respiration during the following 3 days in ICU• Discharged uneventfully on postoperative day 10\tUnknown\t\nMurat Bilgi et al[9]\t56y/oMale77 kg, 163 cmSugammadex 200 mg (2.6 mg/kg)\t• Bradycardia (HR 35 bpm) (2 min after sugammadex)• BP: 124/81 mmHg• SpO2 99%, airway pressure 20 cmH2O, end tidal CO2 42 mmHg• After 0.5 mg i.v. atropine, HR increased to 55 bpm, then decreased to 30–35 bpm again\t• Atropine 0.5 mg i.v.• Total dose of 2 mg atropine\t• HR 63 bpm• Adequate spontaneous respiration• Vital findings stable for 1 hr• Discharged\tUnknown\t\nEvangelia Samara et al[13]\t54y/oMale175 cm, 75 kgSugammadex 200 mg (2.7 mg/kg)\t• Unresponsive• Apnea• Pulseless• Asystole• SpO2 45%\t• CPR (after 5 mins of CPR, EtCO2: 15 mmHg)• Epinephrine 8 mg• Amiodarone 450 mg• Defibrillated 6 times• Re-intubation\t• Sinus rhythm (after 40 mins)• Discharged after 2 more days\tUnknown\t\nBedirli et al[17]\t22y/oFemale213 cm, 85 kgSugammadex 340 mg (4 mg/kg)\t• Bradycardia (HR 43 bpm) (Immediately after sugammadex administration)• Hypotension (43/25 mmHg)• Arrhythmia: PVC and bigeminy with the heart rate of 125 beats/min occurred• Face and upper body were flushed• Airway pressure: 40 cmH2O• Bronchospasm was diagnosed by wheezing• Peripheral oxygen saturation: 86%\t• Ephedrine 10 mg i.v.• Rapid infusion of lactated Ringer's solution• Epinephrine 50-μg i.v.• Lidocaine 60 mg i.v.• Epinephrine 50-μg i.v. was repeated• Methylprednisolone 125 mg i.v.• Famotidine 20 mg i.v.• Pheniramine maleat i.v.• Continuous infusion of norepinephrine 0.04 μg/kg/min for 12 h\t• BP: 90/50 mm Hg• Extubated (3 hrs after sugammadex administration)• ICU• Serum Ig E, tryptase levels assessed 3 and 24 hrs after the onset of anaphylactic reaction: within normal range• Discharged to home with normal ECG\tAnaphylaxis\t\nOur case\t82y/oFemale 146 cm, 44 kgSugammadex 200 mg (4.55 mg/kg)\t• Bradycardia (34 bpm without diffuse ST depression) (1 min after sugammadex)• Hypotension (67/34 mmHg)• Hypoxia (SpO2: 65%)• NMTM count: 0• TOF ratio: 0\t• Atropine 0.5 mg i.v.• Glycopyrrolate 0.1 mg and neostigmine 1 mg\t• ICU• Extubated and discharged 4 and 10 d after surgery without any sequel\tUnknown\t\n\nWe came across 11 cases of bradycardia and/or cardiac arrest.[8–17] These cases were further categorized into cardiac events associated with bradycardia (9 out of 11),[8–11,14–17] cardiac arrest/asystole (5 out of 11),[8,10–13] hypotension (7 out of 11),[8,10,12,14–17] and desaturation (3 out of 11).[13,15,17] Amongst bradycardia patients, a total of 8 out of 9 cases returned to spontaneous circulation following initial treatment.[8–10,14–17] Desaturation was observed in 3 out of 11 cases; mask ventilation, cardiopulmonary resuscitation, defibrillation, and reintubation were performed in some of these cases.[13,15] In summary, cardiopulmonary collapse was reported in 8 out of 11 cases, wherein cardiopulmonary resuscitation was performed;[8,10–15] however, 2 cases resulted in death.[8,11] Case 1 reported by Bhavani et al[8] returned to spontaneous circulation following resuscitation; however, the patient died on the 15th day after being transferred to the ICU. Mirza et al[11] reported the death of another patient because of failure of resuscitation. In our case, the patient presented with bradycardia, hypotension, hypoxia, and weakness.\n\nDifferent management practices were adopted according to clinical symptoms and signs. A total of nine cases were reported to have bradycardia. Therefore, atropine (4 out of 11)[9,10,14,16] or glycopyrrolate (1 out of 11)[11] were administered. Although the mechanism of anticholinergic agents remains unknown, and their effects are limited, the use of anticholinergic agents to treat s44ugammadex-induced bradycardia is still being considered in some case reports.[18] However, some patients did not respond to anticholinergic agents such as atropine.[16]\n\nIn cases where hypotension was reported, vasopressors with epinephrine, norepinephrine, or ephedrine were administered.[8,10–17] Additionally, other drugs, including lidocaine, calcium, and nicorandil, were administered to prevent further progression of cardiac ischemia and arrhythmia. Vasopressors have been preferred over anticholinergic agents for the treatment of sugammadex-induced bradycardia owing to the absence of known muscarinic effects of sugammadex[19] and inadequate response to atropine.[16] In our case, hypotension and bradycardia were effectively treated via administration of ephedrine and atropine.\n\nThe etiology of cardiac and pulmonary adverse effects in all the other cases is unknown. Two cases were suspected to be associated with hypersensitivity to sugammadex, as indicated by serum tryptase level and/or skin prick test.[12,15] Another case was clinically diagnosed with hypersensitivity to sugammadex with tryptase and IgE levels within the normal range.[17] These patients immediately experienced erythema, hypotension, or desaturation following the administration of sugammadex. Therefore, anaphylactic medications, such as methylprednisolone, and antihistamine drugs with hydroxyzine pamoate were administered.[12,17]\n\nPühringer et al[18] reported that hypotension was observed in a study involving large doses of sugammadex. However, at three different doses of sugammadex (2, 4, and 16 mg/kg) in pooled phase I-III patients, the incidence of marked bradycardia was found to be 1%, 1%, and 5%, respectively.[6] Upon reviewing these 11 cases, we found that the dose of sugammadex ranged from 2.08 to 4.17 mg/kg.[8–17] In our case, the dosage of sugammadex used was 4.55 mg/kg. Therefore, the correlation between the dose of sugammadex and severity of bradycardia needs to be further investigated.\n\nFrom 2014 to December 31, 2020, a total of 282 cases of major cardiac events were reported following sugammadex/sugammadex sodium/bridion administration as per the Food and Drug Administration Adverse Event Reporting System database. These events include bradycardia (n = 160), cardiac arrest (n = 110), cardiorespiratory arrest (n = 16), hypotension (n = 83), and decreased oxygen saturation (n = 55).[20] However, in this study, we have investigated only 11 case reports from previous literature.[8–17] Therefore, the incidence of adverse effects associated with sugammadex could have been underestimated.\n\n4 Conclusions\n\nAlthough sugammadex-induced bradycardia or cardiac arrest are rare, anesthesiologists should consider the possibility of the occurrence of such events. Immediate treatment with atropine and inotropic or vasopressors is recommended in such cases. Furthermore, advanced cardiac life support is required if initial management fails to manage the adverse effects.\n\nAuthor contributions\n\nInvestigation: I-Chia Teng, Yao-Tsung Lin, Zhi-Fu Wu.\n\nSupervision: Chin-Chen Chu, Jen-Yin Chen.\n\nWriting – original draft: I-Chia Teng, Zhi-Fu Wu.\n\nWriting – review & editing: Ying-Jen Chang, Zhi-Fu Wu.\n\nAbbreviations: bpm = beats per minute, NMTM = neuromuscular transmission monitors, TOF = train-of-four.\n\nHow to cite this article: Teng IC, Chang YJ, Lin YT, Chu CC, Chen JY, Wu ZF. Sugammadex induced bradycardia and hypotension: a case report and literature review. Medicine. 2021;100:30(e26796).\n\nWritten informed consent was obtained from the patient for publication of the case details.\n\nThe authors have no conflicts of interests to disclose.\n\nData sharing not applicable to this article as no datasets were generated or analyzed during the current study.\n\nBIS = Bispectral index, BMI = body mass index, BP = bold pressure, bpm = beats per minute, CPR = cardiopulmonary resuscitation, CT = computed tomography, ECG = electrocardiogram, EF = ejection fraction, EtCO2 = end-tidal carbon dioxide, GCS = Glasgow Coma Scale, hr = hour, HR = heart rate, hrs = hours, ICU = intensive care unit, iv = intravenous, MAP = mean arterial pressure, MI = myocardial ischemia, mins = minutes, PEA = pulseless electrical activity, POD = post operation day, PVC = Premature ventricular contraction, RCA = right coronary artery, ref = reference, RR = respiratory rate, SBP = systolic blood pressure, TTE = transesophageal echocardiography, VF = ventricular fibrillation, y/o = year-old.\n==== Refs\nReferences\n\n[1] Bevan DR Donati F Kopman AF . Reversal of neuromuscular blockade. Anesthesiology 1992;77 :785–805.1416176\n[2] Murphy GS Brull SJ . Residual neuromuscular block: lessons unlearned. Part I: definitions, incidence, and adverse physiologic effects of residual neuromuscular block. Anesth Analg 2010;111 :120–8.20442260\n[3] Chang YJ Hung KC Wang LK . A real-time artificial intelligence-assisted system to predict weaning from ventilator immediately after lung resection surgery. Int J Env Res Pub HE 2021;18 :2713.\n[4] Kheterpal S Vaughn MT Dubovoy TZ . Sugammadex versus neostigmine for reversal of neuromuscular blockade and postoperative pulmonary complications (STRONGER): a multicenter matched cohort analysis. Anesthesiology 2020;132 :1371–81.32282427\n[5] Park ES Lim BG Lee WJ Lee IO . Sugammadex facilitates early recovery after surgery even in the absence of neuromuscular monitoring in patients undergoing laryngeal microsurgery: a single-center retrospective study. BMC Anesthesiol 2016;16 :48.27484887\n[6] Fabian AI Csernoch V Tassonyi E Fedor M Fülesdi B . The effect of magnesium on the reversal of rocuronium-induced neuromuscular block with sugammadex: an ex vivo laboratory study. BMC Anesthesiol 2019;19 :64.31043175\n[7] Wu TS Tseng WC Lai HC Huang YH Wu ZF . Sugammadex and laryngospasm. J Clin Anesth 2019;56 :52.30690311\n[8] Bhavani SS . Severe bradycardia and asystole after sugammadex. Br J Anaesth 2018;121 :95–6.29935601\n[9] Bilgi M Demirhan A Akkaya A . Sugammadex associate persistant bradycardia. Int J Med Sci Public Health 2014;3 :372–4.\n[10] Fierro C Medoro A Mignogna D . Severe hypotension, bradycardia and asystole after sugammadex administration in an elderly patient. Medicina (Kaunas) 2021;57 :79.33477765\n[11] Mirza K Landoski K Thakar D . Sugammadex-associated hypotension, bradycardia, asystole, and death. Case Rep Anesthesiol 2020;2020 :8767195.32566314\n[12] Obara S Kurosawa S Honda J Oishi R Iseki Y Murakawa M . Cardiac arrest following anaphylaxis induced by sugammadex in a regional hospital. J Clin Anesth 2018;44 :62–3.29145023\n[13] Samara E Iatrelli I Georgakis T Tzimas P . Cardiac arrest after administration of sugammadex as neuromuscular blockade reversal agent and full recovery from anesthesia. J Anaesthesiol Clin Pharmacol 2020;36 :268–9.33013047\n[14] Sanoja IA Toth KS . Profound bradycardia and cardiac arrest after sugammadex administration in a previously healthy patient: a case report. A A Pract 2019;12 :22–4.30004912\n[15] Yanai M Ariyoshi K . Two cardiac arrests that occurred after the administration of sugammadex: a case of kounis syndrome. Case Rep Emerg Med 2020;2020 :6590101.32128264\n[16] Yoshida T Sumi C Uba T Miyata H Umegaki T Kamibayashi T . A rare case of atropine-resistant bradycardia following sugammadex administration. JA Clin Rep 2020;6 :18.32124089\n[17] Bedirli N Işik B Bashiri M Pampal K Kurtipek O . Clinically suspected anaphylaxis induced by sugammadex in a patient with Weaver syndrome undergoing restrictive mammoplasty surgery: a case report with the literature review. Medicine (Baltimore) 2018;97 :e9661.29505006\n[18] Pühringer FK Rex C Sielenkämper AW . Reversal of profound, high-dose rocuronium-induced neuromuscular blockade by sugammadex at two different time points: an international, multicenter, randomized, dose-finding, safety assessor-blinded, phase II trial. Anesthesiology 2008;109 :188–97.18648227\n[19] Booij LH van Egmond J Driessen JJ de Boer HD . In vivo animal studies with sugammadex. Anaesthesia 2009;64 :38–44.19222430\n[20] Cohen JC Latchford KJ . Sugammadex in ontario hospitals: access and institutional policies. J Eval Clin Pract 2020;26 :50–5.31012211\n\n",
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},
{
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},
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"medicinalproduct": "FENTANYL"
},
{
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"activesubstancename": "GLYCOPYRROLATE"
},
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"drugtreatmentdurationunit": null,
"medicinalproduct": "GLYCOPYRROLATE"
},
{
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"activesubstance": {
"activesubstancename": "SEVOFLURANE"
},
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"drugdosagetext": "0.5-0.9",
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"drugindication": "Maintenance of anaesthesia",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "SEVOFLURANE"
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
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"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
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"drugdosageform": null,
"drugdosagetext": "20 ML/H",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "Maintenance of anaesthesia",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
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"drugtreatmentdurationunit": null,
"medicinalproduct": "PROPOFOL"
}
],
"patientagegroup": null,
"patientonsetage": "82",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": "44",
"reaction": [
{
"reactionmeddrapt": "Hypoxia",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Bradycardia",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Hypotension",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Asthenia",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Incorrect dose administered",
"reactionmeddraversionpt": "25.0",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 20200824"
}
},
"primarysource": {
"literaturereference": "Teng IC, Chang YJ, Lin YT, Chu CC, Chen JY, Wu ZF. Sugammadex induced bradycardia and hypotension: A case report and literature review. Medicine. 2021;100 (30):1-6",
"literaturereference_normalized": "sugammadex induced bradycardia and hypotension a case report and literature review",
"qualification": "1",
"reportercountry": "TW"
},
"primarysourcecountry": "TW",
"receiptdate": "20220407",
"receivedate": "20201002",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 18340522,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
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"seriousnessother": 1,
"transmissiondate": "20220721"
}
] |
{
"abstract": "Citalopram is a selective serotonin reuptake inhibitor with a favorable cardiac-safety profile. Corrected QT interval (QTc) prolongation and cardiac arrhythmias have not been previously reported in association with citalopram use except in the presence of overdose, abnormal electrolyte values, or renal or liver failure. Herein, we report the case of a 40-year-old woman with mental depression who presented with a prolonged QTc interval and torsades de pointes after the initiation of citalopram at therapeutic doses. The QTc interval improved when citalopram therapy was discontinued. We recommend that clinicians investigate the family history for sudden deaths and perform baseline electrocardiography before prescribing citalopram. We also recommend routine electrocardiographic testing during citalopram therapy, and that patients with long QT syndrome avoid taking citalopram.",
"affiliations": "Department of Cardiovascular Medicine, The Cardiac Center of Creighton University, Omaha, Nebraska 68131, USA. [email protected]",
"authors": "Deshmukh|Anand|A|;Ulveling|Kyle|K|;Alla|Venkata|V|;Abuissa|Hussam|H|;Airey|Kelly|K|",
"chemical_list": "D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D017367:Serotonin Uptake Inhibitors; D015283:Citalopram; D008803:Mianserin; D000078785:Mirtazapine",
"country": "United States",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0730-2347",
"issue": "39(1)",
"journal": "Texas Heart Institute journal",
"keywords": "Citalopram/adverse effects/therapeutic use; depression/drug therapy; long QT syndrome/chemically induced/diagnosis/physiopathology; serotonin uptake inhibitors/adverse effects/therapeutic use; torsades de pointes/chemically induced/diagnosis/physiopathology",
"medline_ta": "Tex Heart Inst J",
"mesh_terms": "D000328:Adult; D018687:Antidepressive Agents, Second-Generation; D000929:Antidepressive Agents, Tricyclic; D015283:Citalopram; D003863:Depression; D057915:Drug Substitution; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System; D006801:Humans; D008803:Mianserin; D000078785:Mirtazapine; D011237:Predictive Value of Tests; D017367:Serotonin Uptake Inhibitors; D013997:Time Factors; D016171:Torsades de Pointes",
"nlm_unique_id": "8214622",
"other_id": null,
"pages": "68-70",
"pmc": null,
"pmid": "22412232",
"pubdate": "2012",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "10391413;9174567;9274602;11391127;19540606;21295285;17919753;10664899;11852052;8709713",
"title": "Prolonged QTc interval and torsades de pointes induced by citalopram.",
"title_normalized": "prolonged qtc interval and torsades de pointes induced by citalopram"
} | [
{
"companynumb": "US-LUNDBECK-DKLU3040374",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "CITALOPRAM HYDROBROMIDE"
},
"drugadditional": "1",
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"drugauthorizationnumb": "020822",
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"drugcharacterization": "1",
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"drugdosageform": null,
"drugdosagetext": "OVERDOSE: 80MG DAILY",
"drugenddate": null,
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"drugindication": "Depression",
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"medicinalproduct": "CITALOPRAM HYDROBROMIDE"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Long QT syndrome congenital",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Syncope",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Torsade de pointes",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Inappropriate schedule of product administration",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Prescribed overdose",
"reactionmeddraversionpt": "24.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "Deshmukh A, Ulveling K, Alla V, Abuissa H, Airey K. Prolonged QTc Interval and Torsades de Pointes Induced by Citalopram. Texas Heart Institute Journal. 2012;39(1):68-70",
"literaturereference_normalized": "prolonged qtc interval and torsades de pointes induced by citalopram",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20211112",
"receivedate": "20211112",
"receiver": {
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},
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},
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"seriousnesslifethreatening": 1,
"seriousnessother": 1,
"transmissiondate": "20220303"
}
] |
{
"abstract": "Colchicine poisoning is a rare event. It is characterized by multiorgan involvement and by poor prognosis associated with overdose. In this article we present four children with colchicine poisoning to emphasize that colchicine poisoning has a large spectrum in childhood. The children's ages ranged between 1 year and 3.5 years. The ingested dosage of colchicine was between 0.37 and 1.72 mg/kg. Most of the findings of colchicine poisoning such as gastrointestinal symptoms, hepatotoxicity, cardiotoxicity, bone marrow suppression, hypocalcaemia and hair loss were diagnosed in our patients. Two children receiving 0.37 mg/kg and 1 mg/kg colchicine and admitted 13 and 19 hours after poisoning, respectively, died. Our findings suggest that in addition to amounts of the drug, mortality was also related to the duration between drug ingestion and admission to hospital.",
"affiliations": "Department of Pediatrics, Faculty of Medicine, Yüzüncü Yil University, Van, Turkey. [email protected]",
"authors": "Ataş|Bülent|B|;Caksen|Hüseyin|H|;Tuncer|Oğuz|O|;Kirimi|Ercan|E|;Akgün|Cihangir|C|;Odabaş|Dursun|D|",
"chemical_list": "D003078:Colchicine",
"country": "England",
"delete": false,
"doi": "10.1191/0960327104ht457sc",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0960-3271",
"issue": "23(7)",
"journal": "Human & experimental toxicology",
"keywords": null,
"medline_ta": "Hum Exp Toxicol",
"mesh_terms": "D002675:Child, Preschool; D003078:Colchicine; D062787:Drug Overdose; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male",
"nlm_unique_id": "9004560",
"other_id": null,
"pages": "353-6",
"pmc": null,
"pmid": "15311853",
"pubdate": "2004-07",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Four children with colchicine poisoning.",
"title_normalized": "four children with colchicine poisoning"
} | [
{
"companynumb": "TR-TAKEDA-2017TUS005785",
"fulfillexpeditecriteria": "1",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "COLCHICINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
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"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
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"drugdosageform": "TABLET",
"drugdosagetext": "10 MG, UNK",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
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"drugstartdateformat": null,
"drugstructuredosagenumb": "10",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
}
],
"patientagegroup": null,
"patientonsetage": "27",
"patientonsetageunit": "802",
"patientsex": "2",
"patientweight": "10.8",
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Drug administered to patient of inappropriate age",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ATAS B, CAKSEN H, TUNCER O, KIRIMI E, AKGUN C AND ODABAS D. FOUR CHILDREN WITH COLCHICINE POISONING. HUMAN + EXPERIMENTAL TOXICOLOGY. 2004;23(7):353-356",
"literaturereference_normalized": "four children with colchicine poisoning",
"qualification": "1",
"reportercountry": "TR"
},
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"receiptdate": "20170317",
"receivedate": "20170317",
"receiver": {
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},
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},
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"transmissiondate": "20170428"
},
{
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"patient": {
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{
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},
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"drugdosagetext": "25 MG, UNK",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
}
],
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"reaction": [
{
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"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ATAS B, CAKSEN H, TUNCER O, KIRIMI E, AKGUN C AND ODABAS D. FOUR CHILDREN WITH COLCHICINE POISONING. HUMAN + EXPERIMENTAL TOXICOLOGY. 2004;23(7):353-356",
"literaturereference_normalized": "four children with colchicine poisoning",
"qualification": "1",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20170320",
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},
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},
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"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20170429"
},
{
"companynumb": "TR-TAKEDA-2017TUS005787",
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"patient": {
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{
"actiondrug": "5",
"activesubstance": {
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},
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"drugdosagetext": "6 MG, UNK",
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"medicinalproduct": "COLCHICINE."
}
],
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"reaction": [
{
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"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
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},
"primarysource": {
"literaturereference": "ATAS B, CAKSEN H, TUNCER O, KIRIMI E, AKGUN C AND ODABAS D. FOUR CHILDREN WITH COLCHICINE POISONING. HUMAN + EXPERIMENTAL TOXICOLOGY. 2004;23(7):353-356",
"literaturereference_normalized": "four children with colchicine poisoning",
"qualification": "1",
"reportercountry": "TR"
},
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"receivedate": "20170317",
"receiver": {
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},
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},
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"seriousnessother": null,
"transmissiondate": "20170428"
},
{
"companynumb": "TR-TAKEDA-2017TUS005721",
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"patient": {
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{
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"activesubstance": {
"activesubstancename": "COLCHICINE"
},
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"drugdosagetext": "3 MG, UNK",
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"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
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"drugstructuredosagenumb": "3",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "COLCHICINE."
}
],
"patientagegroup": null,
"patientonsetage": "12",
"patientonsetageunit": "802",
"patientsex": "2",
"patientweight": "7.9",
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Product use issue",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Overdose",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ATAS B, CAKSEN H, TUNCER O, KIRIMI E, AKGUN C AND ODABAS D. FOUR CHILDREN WITH COLCHICINE POISONING. HUMAN + EXPERIMENTAL TOXICOLOGY. 2004;23(7):353-356",
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"qualification": "1",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20170317",
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"receiver": {
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},
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"safetyreportversion": 1,
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},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
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"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20170428"
}
] |
{
"abstract": "BACKGROUND\nPatients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radical resection and adjuvant chemotherapy. This study investigated the treatment efficacy and toxicity of neoadjuvant chemoradiotherapy in patients with LACC.\n\n\nMETHODS\nWe retrospectively reviewed 36 patients with LACC preoperatively treated with chemotherapy and radiotherapy. Patients were administered chemoradiotherapy, which comprised radiotherapy and neoadjuvant chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks.\n\n\nRESULTS\nMedian age was 64 years (45-86 years) and median follow-up period was 23.5 months (5.0-49.1 months). Seven (19.4%) patients developed grade 3 or 4 adverse events during neoadjuvant concurrent chemoradiotherapy. Pathologic responses were not evaluated in two patients who did not undergo radical resection. Of the 34 patients who underwent surgery, nine (26.4%) achieved a pathologic complete response (pCR). The 2-year estimated overall survival and disease-free survival rates were 88.7% and 73.6%, respectively.\n\n\nCONCLUSIONS\nOur results demonstrated that neoadjuvant chemoradiotherapy is feasible and safe. A prominent pCR rate with an acceptable toxicity profile suggests that the multimodality therapy might be a treatment option for patients with LACC.",
"affiliations": "Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.;Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.;Department of Surgery, Division of General and Digestive Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.;Department of Surgery, Division of Colorectal Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung, 807, Taiwan.;Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.;Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.;Department of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.;Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan. [email protected].",
"authors": "Huang|Chun-Ming|CM|;Huang|Ming-Yii|MY|;Ma|Cheng-Jen|CJ|;Yeh|Yung -Sung|Y-|;Tsai|Hsiang-Lin|HL|;Huang|Ching-Wen|CW|;Huang|Chih-Jen|CJ|;Wang|Jaw-Yuan|JY|http://orcid.org/0000-0002-7705-2621",
"chemical_list": "D009944:Organoplatinum Compounds; D002955:Leucovorin; D005472:Fluorouracil",
"country": "England",
"delete": false,
"doi": "10.1186/s13014-017-0790-3",
"fulltext": "\n==== Front\nRadiat OncolRadiat OncolRadiation Oncology (London, England)1748-717XBioMed Central London 79010.1186/s13014-017-0790-3ResearchNeoadjuvant FOLFOX chemotherapy combined with radiotherapy followed by radical resection in patients with locally advanced colon cancer Huang Chun-Ming [email protected] 12Huang Ming-Yii [email protected] 13Ma Cheng-Jen [email protected] 456Yeh Yung –Sung [email protected] 5678Tsai Hsiang-Lin [email protected] 2569Huang Ching-Wen [email protected] 2569Huang Chih-Jen [email protected] 13http://orcid.org/0000-0002-7705-2621Wang Jaw-Yuan [email protected]@cc.kmu.edu.tw 25691011121 0000 0000 9476 5696grid.412019.fDepartment of Radiation Oncology, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 2 0000 0000 9476 5696grid.412019.fGraduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 3 0000 0000 9476 5696grid.412019.fDepartment of Radiation Oncology, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 4 0000 0000 9476 5696grid.412019.fDepartment of Surgery, Division of General and Digestive Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 5 0000 0000 9476 5696grid.412019.fDepartment of Surgery, Division of Colorectal Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100 Tzyou 1st Road, Kaohsiung, 807 Taiwan 6 0000 0000 9476 5696grid.412019.fGraduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 7 0000 0000 9476 5696grid.412019.fDepartment of Surgery, Division of Trauma and Critical Care, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 8 0000 0000 9476 5696grid.412019.fDepartment of Emergency Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan 9 0000 0000 9476 5696grid.412019.fDepartment of Surgery, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 10 0000 0000 9476 5696grid.412019.fCenter for Biomarkers and Biotech Drugs, Kaohsiung Medical University, Kaohsiung, Taiwan 11 0000 0000 9476 5696grid.412019.fResearch Center for Environmental Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan 12 0000 0000 9476 5696grid.412019.fResearch Center for Natural Products & Drug Development, Kaohsiung Medical University, Kaohsiung, Taiwan 7 3 2017 7 3 2017 2017 12 4816 12 2016 22 2 2017 © The Author(s). 2017\nOpen AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.Background\nPatients with locally advanced colon cancer (LACC) have a relatively poor prognosis despite radical resection and adjuvant chemotherapy. This study investigated the treatment efficacy and toxicity of neoadjuvant chemoradiotherapy in patients with LACC.\n\nMethods\nWe retrospectively reviewed 36 patients with LACC preoperatively treated with chemotherapy and radiotherapy. Patients were administered chemoradiotherapy, which comprised radiotherapy and neoadjuvant chemotherapy involving a 5-fluorouracil, leucovorin, and oxaliplatin regimen every 2 weeks.\n\nResults\nMedian age was 64 years (45–86 years) and median follow-up period was 23.5 months (5.0–49.1 months). Seven (19.4%) patients developed grade 3 or 4 adverse events during neoadjuvant concurrent chemoradiotherapy. Pathologic responses were not evaluated in two patients who did not undergo radical resection. Of the 34 patients who underwent surgery, nine (26.4%) achieved a pathologic complete response (pCR). The 2-year estimated overall survival and disease-free survival rates were 88.7% and 73.6%, respectively.\n\nConclusions\nOur results demonstrated that neoadjuvant chemoradiotherapy is feasible and safe. A prominent pCR rate with an acceptable toxicity profile suggests that the multimodality therapy might be a treatment option for patients with LACC.\n\nKeywords\nColon cancerOxaliplatinChemoradiotherapyPathologic complete responsehttp://dx.doi.org/10.13039/501100004663Ministry of Science and Technology, TaiwanMOST105-2325-B-037-001Wang Jaw-Yuan http://dx.doi.org/10.13039/100008903Ministry of Health and WelfareMOHW105-TDU-B-212-134007Wang Jaw-Yuan issue-copyright-statement© The Author(s) 2017\n==== Body\nBackground\nWorldwide, colorectal cancer is the third most commonly diagnosed cancer in men and the second most commonly diagnosed cancer in women [1]. In Taiwan, colorectal cancer is the most common cancer, with a rapid increase in its prevalence, and is the third leading cause of cancer-related death [2]. Complete tumor removal surgery with a margin negative resection (R0) is the only curative modality for localized colon cancer. However, treatment results for locally advanced colon cancer (LACC), which is clinically defined as a primary tumor that directly invades adjacent structures or by the presence of extensive nodal involvement that renders curative resection infeasible, remain disappointing despite recent developments in surgery with subsequent adjuvant chemotherapy [3, 4]. The 5-year survival rates for patients with stage IIC, IIIB, and IIIC LACC were reported to be 37.3%, 46.3 and 28%, respectively [5], which has prompted researchers to investigate new treatment approaches for LACC in order to resolve the problems of markedly low survival rates resulting from tumor invasion to adjacent organs or extensive lymph node metastasis.\n\nNeoadjuvant concurrent chemoradiotherapy (CCRT) instead of initial surgery is the current standard treatment for locally advanced rectal cancer, which has been well-established by randomized trials [6, 7]. The Chinese FOWARC randomized phase III trial demonstrated that patients with locally advanced rectal cancer treated with neoadjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX)-based CCRT achieved a higher pathologic complete response (pCR) rate than those treated with fluorouracil-based CCRT or perioperative FOLFOX alone [8]. However, the role of radiotherapy in the treatment of LACC remains unclear. Although benefits of postoperative radiotherapy have been reported in selected groups of patients with LACC [9, 10], the intergroup 0130 trial demonstrated that there was no difference in overall survival and disease-free survival between LACC patients receiving postoperative chemotherapy alone and those receiving postoperative CCRT [11]. In addition, hematologic toxicity was higher in the CCRT group. However, the intergroup 0130 trial has been criticized for its slow accrual and a large number of ineligible patients. For neoadjuvant CCRT in patients with LACC invading adjacent organs or extensive lymph node metastasis, the advantages of neoadjuvant CCRT have been reported in limited case reports and two small case series [12–15]. On the basis of our previous reports, which indicated that neoadjuvant FOLFOX-based CCRT resulted in a pCR rate of up to 31.6% in patients with locally advanced rectal cancer [16], we adopted the same treatment modality in patients with LACC to potentially improve their oncologic outcomes.\n\nThe present study investigated the treatment efficacy, toxicity and short-term oncologic outcome of neoadjuvant FOLFOX-based CCRT in patients with LACC.\n\nMethods\nThe present study included 36 consecutive patients who received a histopathological diagnosed of colon adenocarcinoma and were treated with neoadjuvant CCRT followed by radical resection with curative intent in a single institute between January 2012 and June 2016. Multidisciplinary cancer conferences have recommended that patients with potentially suitable for incomplete resection of LACC should receive neoadjuvant CCRT. The potential for incomplete resection was defined by a T3 tumor with extramural extension of >5 mm or a T4 tumor diagnosed by imaging studies. Other inclusion criteria were colon cancer located above 15 cm from the anal verge, an Eastern Cooperative Oncology Group score of 0–2, and no evidence of distant metastasis at diagnosis. The exclusion criteria were a history of previous or synchronous malignancies other than nonmelanoma skin cancer and the presence of serious medical comorbidities that may influence treatment compliance. Medical records were reviewed to analyze the treatment efficacy, toxicity and short-term oncologic outcomes. The present study was approved by the Institutional Ethics Committee of our hospital. Pretreatment evaluation entailed a complete medical history review and physical examination, colonoscopy, tumor biopsy, chest radiography, abdominal and pelvic computed tomography (CT) with or without magnetic resonance imaging, carcinoembryonic antigen (CEA) level assessment, and routine laboratory tests.\n\nPreoperative treatment\nThe concurrent chemotherapy regimen was a biweekly schedule of FOLFOX. Each cycle of FOLFOX consisted of oxaliplatin (85 mg/m2) and folinic acid (400 mg/m2) infusion on day 1 followed by a 46-h infusion of 5-fluorouracil (5-FU, 2800 mg/m2) repeated every 2 weeks. All patients received concurrent chemotherapy and radiotherapy. After completion of radiotherapy, all patients received chemotherapy twice weekly until surgery. Patients underwent surgery about 4 weeks after completing preoperative chemotherapy.\n\nAll patients underwent a planning CT in the supine position and were immobilized with custom thermoplastic immobilization devices before initiating radiotherapy. Target volumes were delineated according to the International Commission on Radiation Units and Measurements reports 50 and 62 [17]. The gross tumor volume (GTV) was defined as the macroscopic tumor and enlarged lymph nodes visible on diagnostic CT images. The clinical target volume (CTV) was the GTV plus a 15- to 20-mm margin, and the planning target volume was the CTV plus a 10- to 15-mm margin. Organs at risk (OAR), namely kidney, small bowel, liver, and spinal cord, were contoured. A radiation dose of 45–50.4 Gy was administered in 25–28 fractions. The dose constraints for OARs were as follows: the V30 of the liver was kept at <30%; the mean dose and V20 of the kidneys were restricted to <15 Gy and <30%, respectively; the volume of small bowel receiving >50 Gy was limited to <1 cc; and the maximal dose to the spinal cord was restricted to <45 Gy.\n\nSurgery and pathology review\nPatients underwent elective surgery at >6 weeks after completion of radiotherapy. The pathologic tumor (T) and nodal (N) stages (ypT and ypN, respectively) of the tumor, histological grade, lymphovascular invasion, perineural invasion, tumor regression grade (TRG), and status of the circumferential, proximal, and distal resection margins were documented. The tumor response after CCRT was assessed according to the American Joint Committee on Cancer (AJCC) system as follows [18]: Grade 0, no residual cancer cells; Grade 1, single cell or small group of cancer cells (major regression); Grade 2, residual cancer with desmoplastic response (moderate regression); and Grade 3, minimal evidence of tumor response. A circumferential resection margin (CRM) of <1 mm was defined as an involved CRM [19]. A pCR was defined as the absence of viable cancer cells in the pathological specimens, including primary tumor and lymph nodes (ypT0N0), after neoadjuvant CCRT.\n\nPostoperative chemotherapy\nFifteen patients received an adjuvant chemotherapy regimen of FOLFOX. Adjuvant UFUR (tegafur and uracil) and capecitabine were administered in 11 and 5 patients, respectively; 3 patients did not receive postoperative chemotherapy. Two patients were transferred to the folinic acid, 5-FU, and irinotecan (FOLFIRI) regimen after laparotomy because of a poor response to the FOLFOX-based CCRT and the development of distant metastasis.\n\nToxicity evaluation and follow-up\nDuring CCRT and in postoperative follow-up, acute adverse events at each visit were graded according to the Common Terminology Criteria for Adverse Events (CTCAE), version 3.0 (http://ctep.cancer.gov/reporting/ctc.html). Late radiation toxicity was scored using the Radiation Therapy Oncology Group Late Radiation Morbidity Scoring System. After surgery, patients were followed monthly for 6 months and subsequently once every 2–3 months to date.\n\nEndpoints and statistics\nThe pCR rate was the primary endpoint of the study. Secondary endpoints were multimodality therapy-associated toxicities, TGR, and R0 resection rate. Downstaging was determined according to the response between the clinical T or N stage before neoadjuvant CCRT and the postoperative pathological T or N stage.\n\nDescriptive statistics are presented as proportions and medians. The chi-squared test and Fisher’s exact test were used to compare the categorical data, and normally distributed continuous variables were analyzed using the Student t test. Disease-free survival (DFS) was measured from the date of onset of CCRT to the date of any type of recurrence or last follow-up. Overall survival (OS) was defined as the time from the onset of CCRT until death due to any cause or until the final follow-up. Survival rates were estimated using the Kaplan–Meier method. Data analyses were performed using JMP software (version 9.0, SAS Institute Inc., Cary, NC, USA).\n\nResults\nThe median age was 64 years (45–86 years). Most tumor locations were the sigmoid colon (58.4%) followed by the ascending colon. Four patients received three-dimensional conformal radiotherapy using either three or four fields. Volumetric-modulated arc therapy (VMAT) and helical tomotherapy were administered to 22 and 10 patients, respectively. Table 1 lists the patient and treatment characteristics.Table 1 Patient and treatment characteristics (N = 36)\n\nAge, median (years, range)\t64 (45–86)\t\nGender\t\n Male\t20 (55.6)\t\n Female\t16 (44.4)\t\nLocation\t\n Sigmoid colon\t21 (58.4)\t\n Ascending colon\t12 (33.3)\t\n Transverse colon\t3 (8.3)\t\nClinical tumor depth\t\n T3\t13 (36.1)\t\n T4a\t13 (36.1)\t\n T4b\t10 (27.8)\t\nClinical lymph node metastasis\t\n N0\t1 (2.7)\t\n N1\t16 (44.5)\t\n N2\t19 (52.8)\t\nUICC staging\t\n IIC\t1 (2.7)\t\n IIIB\t15 (41.7)\t\n IIIC\t20 (55.6)\t\nPretreatment CEA (ng/mL)\t\n ≦ 5\t19 (52.8)\t\n > 5\t17 (47.2)\t\nIleosotmy/colostomy prior to therapy\t\n Yes\t19 (52.7)\t\n No\t17 (47.3)\t\nRadiotherapy (dose/fractions)\t\n 45 Gy/25\t6 (16.7)\t\n 50 Gy/25\t25 (69.5)\t\n 50.4Gy/28\t4 (11.1)\t\n 46.8Gy/26\t1 (2.7)\t\nPost-operative chemotherapy\t\n FOLFOX\t15 (41.7)\t\n UFUR\t11 (30.6)\t\n Capecitabine\t5 (13.9)\t\n FOLFIRI\t2 (5.4)\t\n None\t3 (8.4)\t\nBMI kg/m2 (median) (range)\t22.4 (14.8–41.8)\t\nRT-Surgery interval week (median) (range)\t11 (6–25)\t\nData are presented as n (%), unless otherwise indicated\n\n\nCEA carcinoembryonic antigen, FOLFOX fluorouracil, leucovorin, and oxaliplatin, UFUR Tegafur and Uracil, FOLFIRI fluorouracil, leucovorin, and irinotecan, UICC Union for International Cancer Control, BMI body mass index, RT radiotherapy\n\n\n\n\nAcute toxicity and treatment compliance\nTable 2 presents the acute adverse events during neoadjuvant CCRT. Overall, seven (19.4%) of the 36 patients experienced grade 3 or 4 adverse events during neoadjuvant CCRT. Leukopenia was defined according to the CTCAE, version 3.0, and leucopenia (83.2%) was the most common adverse event; however, most events (69.4%) were of grade 1 or 2 and were manageable in all patients. For non-hematologic toxicity, fatigue and nausea were the leading side effects caused by CCRT. Moreover, there were no grade 4 adverse events or neoadjuvant CCRT-related deaths.Table 2 Toxicities during neoadjuvant treatment (N = 36)\n\nToxicity\tGrade 1\tGrade 2\tGrade 3\t\nNo.\t%\tNo.\t%\tNo.\t%\t\nAll\t28\t77.8\t30\t83.3\t7\t19.4\t\nFatigue\t22\t61.1\t0\t0.0\t0\t0.0\t\nHematologic\t\n Hemoglobin\t11\t30.5\t10\t27.7\t6\t16.7\t\n Leukocytes\t6\t16.7\t19\t52.7\t5\t13.8\t\nGastrointestinal\t\n Nausea\t14\t38.8\t4\t11.1\t1\t2.7\t\n Vomiting\t3\t8.3\t5\t13.8\t0\t0.0\t\n Diarrhea\t11\t30.5\t6\t16.7\t1\t2.7\t\nParesthesia\t10\t27.7\t7\t19.4\t0\t0.0\t\nOral mucositis\t6\t16.7\t2\t5.5\t0\t0.0\t\nDermatitis\t8\t22.2\t2\t5.5\t0\t0.0\t\n\n\n\nOf all the patients, only one did not complete the prescribed radiation course (50.4 Gy); radiotherapy was interrupted at 46.8 Gy with two fractions remaining because of grade 3 diarrhea and grade 2 vomiting. The patient with sigmoid colon cancer did not complete the radiotherapy during the study period; however, he finally underwent surgery 51 days after completion of radiotherapy. The median radiotherapy duration was 35 days (32–49 days). Two patients temporarily discontinued preoperative chemotherapy because of neutropenic fever (n = 1) and grade 3 diarrhea with dehydration (n = 1), and both of the two patients continued scheduled preoperative chemotherapy after management of those adverse events.\n\nSurgery and pathologic response\nThe median interval between radiotherapy completion and surgery was 11 weeks (6–25 weeks). All but two patients underwent surgery after neoadjuvant CCRT. Of the 34 patients receiving surgery, sigmoidectomy was performed in 17 (50%), right hemicolectomy in 12 (35.3%), and left hemicolectomy in five (14.7%) patients. Multivisceral resection was performed in 6 patients: 2 patients underwent colectomy plus partial cystectomy; 2 patients underwent colectomy plus resection of small intestine; 1 patient underwent colectomy plus partial gastrectomy; 1 patient underwent colectomy plus extensive resection of visceral peritoneum. Of the 4 patients diagnosed with bladder invasion, 2 received a partial cystectomy and 2 underwent a simple colectomy while preserve the bladder intact. Two patients did not undergo radical resection after neoadjuvant therapy. One patient with sigmoid colon cancer accompanied by uterus and left ureter invasion did not undergo radical resection after neoadjuvant treatment because of tumor invasion to the common iliac artery, which was observed during the surgery. Therefore, the tumor was not resected and the patient was administered 10 cycles of FOLFOX. Thereafter, FOLFIRI was administered as a second-line chemotherapy, and the patient’s condition was stable for 15 months at the final follow-up. The other patient with ascending colon cancer, T4aN2bM0, developed peritoneal carcinomatosis, which was revealed by CT images, after completion of the neoadjuvant FOLFOX-based CCRT; therefore, surgery was not performed. Two cycles of the FOLFIRI regimen were administered to the patients for disease control; however, the patient died because of tumor progression at 7 months after diagnosis.\n\nTable 3 lists the pathologic results and treatment efficacy. Final pathologic analysis revealed that of the 34 patients, nine (26.4%) achieved ypT0 (no viable tumor in the primary site) and 28 (82.4%) achieved ypN0. The median number of lymph nodes retrieved was 11 (3–26). The resection margin was free of cancer cells in 31 (91.2%) of the 34 patients. Using a univariate analysis of the correlation between positive surgical margins and clinicopathologic features, the unfavorable tumor regression (TRG 3–4 versus TRG 0–1; p = 0.030), CEA level > 5 (p = 0.041), and ypT4 disease (p = 0.042) were associated with positive surgical margins. Of the 34 patients who underwent surgery, pCR, major regression (TRG 1), and moderate regression (TRG 2) were achieved in 9 (26.4%), 11 (32.4%), and 7 patients (20.6%), respectively, and 14 patients (41.2%) downstaged to the ypT0-2 stage. Comparison between the changes in the clinical and pathologic stages revealed that TN downstaging was achieved in 29 (85.3%) of the 34 patients; primary tumor and nodal downstaging were achieved in 24 (70.6%) and 31 (91.2%) of the 34 patients, respectively.Table 3 Pathological results and tumor response to neoadjuvant treatment (N = 34)b\n\n\n\tNo. (%)\t\nypT\t\n 0\t9 (26.4)\t\n 1\t0 (0)\t\n 2\t5 (14.7)\t\n 3\t17 (50.0)\t\n 4\t3 (8.9)\t\nypN\t\n 0\t28 (82.4)\t\n 1\t5 (14.7)\t\n 2\t1 (2.9)\t\nMedian number of resected nodesa\n\t11 (3–26)\t\nMedian number of involved nodesa\n\t0 (0–6)\t\nLymph node with extranodal involvement\t4 (11.7)\t\nLymphovascular invasion\t\n Yes\t5 (14.7)\t\n No\t29 (85.3)\t\nPerineural invasion\t\n Yes\t2 (5.9)\t\n No\t32 (94.1)\t\nTumor differentiation\t\n Well\t2 (5.9)\t\n Moderately\t28 (82.4)\t\n Poorly\t4 (11.7)\t\nResection margin (CRM)\t\n Negative\t31 (91.2)\t\n Positive\t3 (8.8)\t\nPathologic complete response\t\n Yes\t9 (26.4)\t\n No\t25 (73.6)\t\nTumor regression grade\t\n 0\t9 (26.4)\t\n 1\t11 (32.4)\t\n 2\t7 (20.6)\t\n 3\t7 (20.6)\t\nypT0-2 vs. ypT3-4\t\n ypT0-2\t14 (41.2)\t\n ypT3-4\t20 (58.8)\t\nPathologic T stage\t\n Downstaging\t24 (70.6)\t\n Stable\t10 (29.4)\t\n Progressive\t0 (0)\t\nPathologic N stage\t\n Downstaging\t31 (91.2)\t\n Stable\t3 (8.8)\t\n Progressive\t0 (0)\t\nPathologic TN stage\t\n Downstaging\t29 (85.3)\t\n Stable\t5 (14.7)\t\n Progressive\t0 (0)\t\n\naMedian (range)\n\n\nbTwo patients (T4bN2M0 and T4aN2M0) did not receive surgical resection due to unresectable tumor despite chemoradiotherapy\n\n\nypT postoperative pathologic tumor stage, ypN postoperative pathologic nodal stage, CRM circuferential resection margin\n\n\n\n\nTable 4 summarizes the pathologic evaluation of primary tumor after neoadjuvant CCRT compared with that of the initial clinical stage. Of the 23 patients with clinical T4 tumors, five (21.7%) achieved ypT0 after intensified neoadjuvant CCRT, and clinical T4 tumors in eight patients (34.8%) were downstaged to ypT0-2.Table 4 Comparison of clinical staging to pathologic T and N staging (N = 34)a\n\n\nClinical staging\tPathologic T staging\typN negative\typN positive\tTotal\t\nypT0\typT1\typT2\typT3\typT4a\typT4b\t\t\ncT3\t4 (11.8)\t\t2 (5.9)\t7 (20.6)\t\t\t-\t-\t13 (38.2)\t\ncT4a\t4 (11.8)\t\t1 (2.9)\t6 (17.6)\t1 (3.0)\t\t-\t-\t12 (35.3)\t\ncT4b\t1 (3.0)\t\t2 (5.9)\t4 (11.8)\t\t2 (5.9)\t-\t-\t9 (26.5)\t\ncN negative\t-\t-\t-\t-\t-\t-\t1 (3.0)\t0\t1 (3.0)\t\ncN positive\t-\t-\t-\t-\t-\t-\t27 (79.4)\t6 (17.6)\t33 (97.0)\t\nTotal\t9 (26.5)\t0\t5 (14.7)\t17 (50)\t1 (3.0)\t2 (5.9)\t28 (82.4)\t6 (17.6)\t34 (100)\t\n\nc clinical (in this case evaluated by imaging), ypT pathologic T-stage posttreatment, ypN pathologic N-stage posttreatment\n\n\naTwo patients (T4bN2M0 and T4aN2M0) did not receive surgical resection due to unresectable tumor despite chemoradiotherapy\n\n\n\n\nPostoperative complications\nSurgical mortality was not observed within 30 days after surgery. Of the 34 patients, five (14.7%) experienced postoperative complications requiring medical or surgical interventions. One patient developed a wound abscess on a previous drainage site, which resulted in a postoperative enterocutaneous fistula at 3 weeks, and this healed following antibiotic treatment. Another patient developed an intra-abdominal infection because of anastomotic leakage at 1 month after right hemicolectomy and temporary ileostomy closure; this patient finally recovered after undergoing another ileostomy along with antibiotic treatment. Two patients required surgical interventions because of adhesion ileus; one patient underwent enterolysis 1 month after left hemicolectomy and the other required segmental resection of small bowel at 32 months after extended left hemicolectomy. One patient developed a postoperative chronic rectovaginal fistula at 7 months and died of tumor progression.\n\nFailure patterns and survival data\nMedian follow-up period was 23.5 months (5.0–49.1 months). The 2-year estimated OS and DFS rates were 88.7 and 73.6%, respectively (Fig. 1). Of the 34 patients who completed neoadjuvant CCRT and radical resection, four (11.8%) experienced local recurrence and five (14.7%) developed distant metastasis. The most common first site of distant failure was lung metastasis (n = 2), followed by liver metastasis (n = 1), retroperitoneal lymph node metastasis (n = 1), and adrenal gland metastasis (n = 1). Univariate analysis of the correlation between local recurrence and clinicopathologic features, we found that positive surgical margins (p = 0.003), unfavorable tumor regression (TRG 3–4 versus TRG 0–1; p = 0.022), and ypT4 disease (p = 0.055) were associated with local recurrence.Fig. 1 Overall and disease-free survival rates. a Overall survival rate and (b) disease-free survival rate in patients with locally advanced colon cancer receiving neoadjuvant chemoradiation and radical resection\n\n\n\n\nDiscussion\nAccording to our review of relevant literature, the present clinical study used the largest sample for investigating the role of combined neoadjuvant oxaliplatin-based chemoradiotherapy in the treatment of primary LACC [20]. Our data demonstrated that the intensified multimodality approach resulted in an excellent pCR rate of 26.4% with an acceptable toxicity profile. However, this multimodal therapy should be used cautiously in clinical practice because of the limited sample size and short follow-up period of the present study. Our results, nevertheless, suggest that intensified neoadjuvant CCRT should be considered as a treatment option for patients with LACC, particularly those with potentially threatened surgical resection margins.\n\nEvidence has indicated that nodal involvement is a major predictor of oncologic outcomes in patients with colorectal cancer [21, 22]. In our study, 82.4% of the patients did not develop nodal diseases after neoadjuvant CCRT. Furthermore, in a surgical series, pathologically positive nodal involvement was observed in approximately 69% patients with LACC [23]. The high pN0 rate in our study may be attributable to the marked influence of the neoadjuvant CCRT. For locally advanced rectal cancer, the neoadjuvant CCRT has been associated with nodal downstaging and a decrease in the pathologic lymph node harvest [16, 24]. Our findings reveal a similar effect of the neoadjuvant CCRT on eradication of lymph node metastasis in LACC. However, OS and DFS rates did not differ significantly between the patients with and without nodal metastasis.\n\nEvidence has demonstrated that patients with locally advanced rectal cancer who achieved a pCR to neoadjuvant CCRT exhibited excellent tumor control and survival rates [25]. Moreover, numerous studies have added oxaliplatin into neoadjuvant fluorouracil-base treatment to enhance pCR rates. Of the six large phase III trials (ACCORD 12/0405-Prodige 2, STAR-01, National Surgical Adjuvant Breast and Bowel Project R04, CAO/ARO/AIO-04, and PETTAC6), only CAO/ARO/AIO-04 demonstrated that the addition of oxaliplatin improved DFS and a pCR rate [26–30]. Garcia-Aguilar et al. reported that extending FOLFOX chemotherapy after neoadjuvant CCRT and before surgery in locally advanced rectal cancer resulted in a pCR arte of 38% [31]. The FOWARC trial demonstrated that FOLFOX chemotherapy administered concurrently with and following radiotherapy resulted in a higher pCR rate than fluorouracil-based CCRT or perioperative FOLFOX alone [8]. Our prior study also showed similar results to FOWARC trial [16]. However, the correlation between a pCR and clinical outcome in colon cancer has been rarely reported. To date, several studies have investigated the role of neoadjuvant chemotherapy in patients with LACC; however, the benefits of combined radiotherapy and chemotherapy for primary LACC have been rarely evaluated. Only a Canadian group reported that of the total 33 patients with LACC that were treated with neoadjuvant concurrent 5-FU and radiotherapy, only one patient (3%) achieved a pCR [14]. The FOxTROT trial assessed the role of neoadjuvant chemotherapy in LACC management by evaluating the efficacy and safety of the preoperative FOLFOX-based chemotherapy in a randomized controlled manner; two patients (2%) of the neoadjuvant group reported pCRs [32]. Furthermore, a phase II trial demonstrated that three (4.2%) of the 71 operated patients achieved a pCR after three cycles of neoadjuvant XELOX [capecitabine (2000 mg/m2) orally administered on days 1–14 (q3w) and oxaliplatin (130 mg/m2) intravenously infused on day 1 (q3w)] [33]. Arredondo et al. investigated 65 patients with LACC treated with either neoadjuvant XELOX- or FOLFOX-based chemotherapy; three patients (4.6%) had a pCR [34]. In the present study, patients with LACC were administered with neoadjuvant FOLFOX-based CCRT that resulted in a pCR rate of 26.4%, which was higher than that reported in other neoadjuvant studies (2–4.6%) [14, 33, 34].\n\nThe prognosis in patients with LACC remains discouraging even with the current standard treatment of radical resection followed by adjuvant chemotherapy. Danielle et al. analyzed the Surveillance, Epidemiology, and End Results Program database (1988–2008) and reported that the 5-year OS rates of patients with 7th AJCC stages IIC, IIIB, and IIIC were 54.6%, 59.0, 47.9%, respectively [35]. Therefore, treatment strategies should be modified to improve the oncologic outcomes in patients with LACC. Neoadjuvant CCRT is the standard of care in patients with locally advanced rectal cancer [6]. Although several studies have reported promising results for the neoadjuvant chemotherapy, we aimed to use an intensified multimodality approach of combined chemotherapy and radiotherapy in patients with LACC, particularly in those with clinical T4 tumors. Arredondo et al. investigated the efficacy and safety of neoadjuvant chemotherapy and reported that only 12 patients (18.5%) had T4 tumors [34]. Jakobsen et al. conducted a phase II trial in patients with LACC treated with neoadjuvant chemotherapy and reported that 11 (15%) patients developed T4 tumors [33]. Furthermore, the phase III FOxTROT trial reported on 30 patients (30%) with T4 tumors [32]. In our study, the proportion of patients with a T4 tumor was 63.9% (23 of the 36 patients), which is higher than that reported in other studies. The prognosis of a T4 colon cancer remains the worst, and T4 tumors have been closely associated with an involved resection margin [35, 36]. Therefore, we aimed to maximally treat LACC with a combination of radiotherapy and chemotherapy and obtained a R0 resection rate of 91.2%. Of the 23 patients with cT4 tumors in the present study, two (8.7%) did not undergo surgery because of a poor response to neoadjuvant CCRT, and 18 (85.7%) of the 21 patients received radical resection of cT4 tumors obtained R0 resections in our study.\n\nSeveral studies have investigated the efficacy and safety of neoadjuvant chemotherapy for LACC [33, 37, 38]. The inclusion criteria for neoadjuvant chemotherapy was T4 or T3 with extramural extension >5 mm. By contrast, the eligibility for neoadjuvant CCRT was the tumor extensively involved other organs/structures on imaging studies or the tumor considered to be unresectable after exploratory laparotomy. Qiu et al. delivered neoadjuvant CCRT for 21 patients with unresectable locally advanced sigmoid colon cancer [20]. Of the 19 patients with clinical T4 diseases, seven patients achieved a pCR after CCRT. The results were similar to our study, in which five patients achieved a pCR after neoadjuvant CCRT among the 23 patients with clinical T4 tumors. For tolerability, both neoadjuvant chemotherapy and neoadjuvant CCRT were well-tolerable in patients with LACC, but toxicity was generally higher in neoadjuvant CCRT [14, 20, 32, 33]. Therefore, clinical T4 tumors, especially unresectable mass or tumors extensively involved adjacent structures, are potential indications for neoadjuvant CCRT. In addition, patients with a locally extensive T3 tumor or patients unable to tolerate CCRT may be candidates for neoadjuvant chemotherapy. However, the indications for neoadjuvant CCRT or chemotherapy need to be validated in more prospective randomized studies.\n\nIn en bloc multivisceral resections for primary locally advanced colorectal cancer, R0 resection rates ranged from 40 to 93%, with high postoperative complications (11%–40%) and a nonnegligible mortality up to 9% [36, 39, 40]. Cukier et al. analyzed the oncologic outcomes of neoadjuvant CCRT followed by multivisceral resection for primary LACC and reported a R0 resection rate of 100%, with a postoperative complication rate of 36% and zero surgical mortality [14]. Qiu et al. found that neoadjuvant CCRT can effectively reduce the peripheral tumor infiltration and thereby decrease the necessity for multivisceral resection. Therefore, neoadjuvant CCRT may decrease postoperative complications caused by multivisceral resection [20]. In the present study, the R0 resection rate was 91.2% with a postoperative complication rate of 14.7% and without surgical mortality, despite the intensified neoadjuvant CCRT. Our results suggested that neoadjuvant CCRT followed by radical resection does not increase a postoperative complication rate compared to resection alone (11%–40%).\n\nHowever, the eligibility criterion of patients with LACC suitable for a neoadjuvant CCRT remains debatable. Moreover, the risk of overtreatment must be minimized because of occasional discrepancies between the clinical and pathologic stages. CT images have been primarily examined to select patients eligible to receive neoadjuvant therapy for colon cancer, and the accuracy of CT staging has improved. Numerous studies have demonstrated that CT can identify T3 tumors with extramural extension or T4 tumors, which are candidates for neoadjuvant therapy [28, 34, 37]. In contrast to tumor depth prediction, accurate nodal status prediction through CT remains difficult. Therefore, we assessed the CT images and T stage to guide neoadjuvant CCRT.\n\nCukier et al. reported that 9% of the patients with LACC experienced grade 3 or higher grades of adverse events during 5-FU-based CCRT [14]. In the present study, we used oxaliplatin and 5-FU in the neoadjuvant setting to maximize the effect of CCRT on LACC, and 19.4% of patients experienced grade 3 adverse events during neoadjuvant CCRT. Of all the patients, only one patient did not complete the prescribed radiation course, although FOLFOX-based CCRT had a relatively higher toxicity rate than that in 5-FU-based CCRT. However, the incidence of grade 3 or 4 adverse events reported in the present study were considerably lower than those reported in our previous studies or in other studies investigating the influence of FOLFOX-based CCRT in patients with rectal cancer, which ranged from 24% to 40% [16, 28, 37]. In our study, 88.9% of the patients received intensity-modulated radiotherapy with either VMAT or tomotherapy, which might partly contribute to the improved toxicity profiles because of normal organ sparing [41].\n\nThe present study has some limitations. First, because of the relatively small sample and short follow-up period, long-term efficacy and adverse events could not be addressed. Second, this was a retrospective study; therefore, the sampling may have been affected by selection bias. Third, the postoperative chemotherapy regimens were varied in our study, which might contribute to disease control and survival.\n\nConclusions\nOur results demonstrate that neoadjuvant chemoradiotherapy is feasible and safe. A high pCR and R0 resection rate with an acceptable toxicity profile suggests that multimodality therapy is a treatment option for patients with LACC. Additional prospective randomized studies are warranted to validate our results.\n\nAbbreviations\n5-FU5-fluorouracil\n\nAJCCAmerican Joint Committee on Cancer\n\nCCRTConcurrent chemoradiotherapy\n\nCEACarcinoembryonic antigen\n\nCRMCircumferential resection margin\n\nCTComputed tomography\n\nCTCAECommon Terminology Criteria for Adverse Events\n\nCTVClinical target volume\n\nDFSDisease-free survival\n\nFOLFIRIfolinic acid, 5-fluorouracil, and irinotecan\n\nFOLFOX5-fluorouracil, leucovorin, and oxaliplatin\n\nGTVGross tumor volume\n\nLACCLocally advanced colon cancer\n\nNNodal\n\nOAROrgans at risk\n\nOSOverall survival\n\npCRPathologic complete response\n\nR0Margin negative resection\n\nTTumor\n\nTRGTumor regression grade\n\nUFURTegafur and uracil\n\nVMATVolumetric-modulated arc therapy\n\nWe thank Kaohsiung Medical University Hospital (KMUH104-4 M44, KMUHS10522, KMUHS10505, KMUHS10418, KMUHGCRC2016002) for assistance.\n\nFunding\nThis work was supported by grants from the Excellence for Cancer Research Center.\n\nGrant through funding by the Ministry of Science and Technology (MOST105-2325-B-037-001) and the Ministry of Health and Welfare (MOHW105-TDU-B-212-134007), Health and welfare surcharge of tobacco products, Taiwan, Republic of China. The study was supported by Kaohsiung Medical University “Aim for the top University Grant, grant no. KMU-TP105C01, KMU-TP105C11, KMU-TP106005, KMU-TP105A11, KMU-TP105A12, KMU-DK106005, SH000113 (Give2Asia) and the Grant of Biosignature in Colorectal Cancers, Academia Sinica, Taiwan.\n\nAvailability of data and materials\nAll data and materials have been presented in the manuscript.\n\nAuthors’ contributions\nCMH and JYW participated in the design of the study, performed the statistical analysis and interpretation of data, and drafted the manuscript. CMH wrote the manuscript. CJM, YSY, HLT and CWH recruited patients to the study, and interpreted the clinical data. MYH and CJH are radiation oncologists who contributed to treat the patients. All authors read and approved the final manuscript.\n\nCompeting interests\nThe authors declare no competing interests.\n\nConsent for publication\nNot applicable.\n\nEthics approval and consent to participate\nThis study was approved by the Institutional Review Board in Kaohsiung Medical University Hospital [KMUHIRB-E(II)-20150195]. Eligible patients were given written informed consent.\n==== Refs\nReferences\n1. Jemal A Bray F Center MM Ferlay J Ward E Forman D Global cancer statistics CA Cancer J Clin 2011 61 2 69 90 10.3322/caac.20107 21296855 \n2. Ministry of Health and Welfare, the Executive Yuan, Republic of China. Health and Vital Statistics. [http://www.mohw.gov.tw/CHT/Ministry/]. Accessed 2013.\n3. Hohenberger W Weber K Matzel K Papadopoulos T Merkel S Standardized surgery for colonic cancer: complete mesocolic excision and central ligation--technical notes and outcome Colorectal Dis 2009 11 4 354 64 10.1111/j.1463-1318.2008.01735.x 19016817 \n4. Andre T Boni C Mounedji-Boudiaf L Navarro M Tabernero J Hickish T Oxaliplatin, fluorouracil, and leucovorin as adjuvant treatment for colon cancer N Engl J Med 2004 350 23 2343 51 10.1056/NEJMoa032709 15175436 \n5. Edge SB, Byrd DR, C. CC, Fritz AG, Greene F, Trotti A. AJCC Cancer Staging Manual 7th edition. 2010; Springer, New York, NY:143–64.\n6. Sauer R Becker H Hohenberger W Rodel C Wittekind C Fietkau R Preoperative versus postoperative chemoradiotherapy for rectal cancer N Engl J Med 2004 351 17 1731 40 10.1056/NEJMoa040694 15496622 \n7. Roh MS Colangelo LH O’Connell MJ Yothers G Deutsch M Allegra CJ Preoperative multimodality therapy improves disease-free survival in patients with carcinoma of the rectum: NSABP R-03 J Clin Oncol 2009 27 31 5124 30 10.1200/JCO.2009.22.0467 19770376 \n8. Deng Y Chi P Lan P Wang L Chen W Cui L Modified FOLFOX6 with or without radiation versus fluorouracil and leucovorin with radiation in neoadjuvant treatment of locally advanced rectal cancer: initial results of the Chinese FOWARC multicenter, open-label, randomized three-Arm phase III trial J Clin Oncol 2016 34 27 3300 7 10.1200/JCO.2016.66.6198 27480145 \n9. Willett CG Fung CY Kaufman DS Efird J Shellito PC Postoperative radiation therapy for high-risk colon carcinoma J Clin Oncol 1993 11 6 1112 7 10.1200/JCO.1993.11.6.1112 8501497 \n10. Willett CG Tepper JE Skates SJ Wood WC Orlow EC Duttenhaver JR Adjuvant postoperative radiation therapy for colonic carcinoma Ann Surg 1987 206 6 694 8 10.1097/00000658-198712000-00002 3689006 \n11. Martenson JA Jr Willett CG Sargent DJ Mailliard JA Donohue JH Gunderson LL Phase III study of adjuvant chemotherapy and radiation therapy compared with chemotherapy alone in the surgical adjuvant treatment of colon cancer: results of intergroup protocol 0130 J Clin Oncol 2004 22 16 3277 83 10.1200/JCO.2004.01.029 15249584 \n12. Mizukami H Yoshizawa Y Sasaya S Nemoto H Maezawa K Sanada Y A case of advanced colon cancer invading the rectum effectively treated with chemoradiation therapy before surgery Gan To Kagaku Ryoho 2007 34 6 953 6 17565265 \n13. Kuga Y Tanaka T Arita M Okanobu H Miwata T Yoshimi S A case of effective chemotherapy using S-1 and CPT-11 following chemoradiotherapy with UFT and Leucovorin for unresectable advanced sigmoid colon cancer Gan To Kagaku Ryoho 2010 37 3 531 4 20332698 \n14. Cukier M Smith AJ Milot L Chu W Chung H Fenech D Neoadjuvant chemoradiotherapy and multivisceral resection for primary locally advanced adherent colon cancer: a single institution experience Eur J Surg Oncol 2012 38 8 677 82 10.1016/j.ejso.2012.05.001 22632848 \n15. Taylor WE Donohue JH Gunderson LL Nelson H Nagorney DM Devine RM The Mayo Clinic experience with multimodality treatment of locally advanced or recurrent colon cancer Ann Surg Oncol 2002 9 2 177 85 10.1007/BF02557371 11888876 \n16. Huang CM Huang MY Tsai HL Huang CW Ma CJ Yeh YS An observational study of extending FOLFOX chemotherapy, lengthening the interval between radiotherapy and surgery, and enhancing pathological complete response rates in rectal cancer patients following preoperative chemoradiotherapy Therap Adv Gastroenterol 2016 9 5 702 12 10.1177/1756283X16656690 27582883 \n17. International Commission on Radiation Units and Measurements. Prescribing, recording and reporting photon beam therapy ICRU report 62. Bethesda, MD: International Commission on Radiation Units and Measurements; 1999, 2010.\n18. Mace AG Pai RK Stocchi L Kalady MF American Joint Committee on Cancer and College of American Pathologists regression grade: a new prognostic factor in rectal cancer Dis Colon Rectum 2015 58 1 32 44 10.1097/DCR.0000000000000266 25489692 \n19. Nagtegaal ID Quirke P What is the role for the circumferential margin in the modern treatment of rectal cancer? J Clin Oncol 2008 26 2 303 12 10.1200/JCO.2007.12.7027 18182672 \n20. Qiu B Ding PR Cai L Xiao WW Zeng ZF Chen G Outcomes of preoperative chemoradiotherapy followed by surgery in patients with unresectable locally advanced sigmoid colon cancer Chin J Cancer 2016 35 1 65 10.1186/s40880-016-0126-y 27389519 \n21. Chang GJ Rodriguez-Bigas MA Skibber JM Moyer VA Lymph node evaluation and survival after curative resection of colon cancer: systematic review J Natl Cancer Inst 2007 99 6 433 41 10.1093/jnci/djk092 17374833 \n22. Ceelen W Van Nieuwenhove Y Pattyn P Prognostic value of the lymph node ratio in stage III colorectal cancer: a systematic review Ann Surg Oncol 2010 17 11 2847 55 10.1245/s10434-010-1158-1 20559741 \n23. Rowe VL Frost DB Huang S Extended resection for locally advanced colorectal carcinoma Ann Surg Oncol 1997 4 2 131 6 10.1007/BF02303795 9084849 \n24. Valentini V Coco C Picciocchi A Morganti AG Trodella L Ciabattoni A Does downstaging predict improved outcome after preoperative chemoradiation for extraperitoneal locally advanced rectal cancer? A long-term analysis of 165 patients Int J Radiat Oncol Biol Phys 2002 53 3 664 74 10.1016/S0360-3016(02)02764-5 12062610 \n25. Martin ST Heneghan HM Winter DC Systematic review and meta-analysis of outcomes following pathological complete response to neoadjuvant chemoradiotherapy for rectal cancer Br J Surg 2012 99 7 918 28 10.1002/bjs.8702 22362002 \n26. Gerard JP Azria D Gourgou-Bourgade S Martel-Laffay I Hennequin C Etienne PL Comparison of two neoadjuvant chemoradiotherapy regimens for locally advanced rectal cancer: results of the phase III trial ACCORD 12/0405-Prodige 2 J Clin Oncol 2010 28 10 1638 44 10.1200/JCO.2009.25.8376 20194850 \n27. Aschele C Cionini L Lonardi S Pinto C Cordio S Rosati G Primary tumor response to preoperative chemoradiation with or without oxaliplatin in locally advanced rectal cancer: pathologic results of the STAR-01 randomized phase III trial J Clin Oncol 2011 29 20 2773 80 10.1200/JCO.2010.34.4911 21606427 \n28. O’Connell MJ Colangelo LH Beart RW Petrelli NJ Allegra CJ Sharif S Capecitabine and oxaliplatin in the preoperative multimodality treatment of rectal cancer: surgical end points from National Surgical Adjuvant Breast and Bowel Project trial R-04 J Clin Oncol 2014 32 18 1927 34 10.1200/JCO.2013.53.7753 24799484 \n29. Rodel C Graeven U Fietkau R Hohenberger W Hothorn T Arnold D Oxaliplatin added to fluorouracil-based preoperative chemoradiotherapy and postoperative chemotherapy of locally advanced rectal cancer (the German CAO/ARO/AIO-04 study): final results of the multicentre, open-label, randomised, phase 3 trial Lancet Oncol 2015 16 8 979 89 10.1016/S1470-2045(15)00159-X 26189067 \n30. Schmoll H, Haustermans K, Price T, Nordlinger B, Hofheinz R, Daisne J. Preoperative chemoradiotherapy and postoperative chemotherapy with capecitabine and oxaliplatin versus capecitabine alone in locally advanced rectal cancer: Disease-free survival results at interim analysis. Proc Am Soc Clin Oncol. 2014;32(3501a).\n31. Garcia-Aguilar J Chow OS Smith DD Marcet JE Cataldo PA Varma MG Effect of adding mFOLFOX6 after neoadjuvant chemoradiation in locally advanced rectal cancer: a multicentre, phase 2 trial Lancet Oncol 2015 16 8 957 66 10.1016/S1470-2045(15)00004-2 26187751 \n32. Foxtrot Collaborative G Feasibility of preoperative chemotherapy for locally advanced, operable colon cancer: the pilot phase of a randomised controlled trial Lancet Oncol. 2012 13 11 1152 60 10.1016/S1470-2045(12)70348-0 23017669 \n33. Jakobsen A Andersen F Fischer A Jensen LH Jorgensen JC Larsen O Neoadjuvant chemotherapy in locally advanced colon cancer. A phase II trial Acta Oncol 2015 54 10 1747 53 10.3109/0284186X.2015.1037007 25920359 \n34. Arredondo J, Baixauli J, Pastor C, Chopitea A, Sola JJ, Gonzalez I et al. Mid-term oncologic outcome of a novel approach for locally advanced colon cancer with neoadjuvant chemotherapy and surgery. Clin Transl Oncol. 2016. doi:10.1007/s12094-016-1539-4.\n35. Hari DM Leung AM Lee JH Sim MS Vuong B Chiu CG AJCC Cancer Staging Manual 7th edition criteria for colon cancer: do the complex modifications improve prognostic assessment? J Am Coll Surg 2013 217 2 181 90 10.1016/j.jamcollsurg.2013.04.018 23768788 \n36. Mohan HM Evans MD Larkin JO Beynon J Winter DC Multivisceral resection in colorectal cancer: a systematic review Ann Surg Oncol 2013 20 9 2929 36 10.1245/s10434-013-2967-9 23666095 \n37. Rodel C Liersch T Becker H Fietkau R Hohenberger W Hothorn T Preoperative chemoradiotherapy and postoperative chemotherapy with fluorouracil and oxaliplatin versus fluorouracil alone in locally advanced rectal cancer: initial results of the German CAO/ARO/AIO-04 randomised phase 3 trial Lancet Oncol 2012 13 7 679 87 10.1016/S1470-2045(12)70187-0 22627104 \n38. Arredondo J Gonzalez I Baixauli J Martinez P Rodriguez J Pastor C Tumor response assessment in locally advanced colon cancer after neoadjuvant chemotherapy J Gastrointest Oncol 2014 5 2 104 11 24772338 \n39. Croner RS Merkel S Papadopoulos T Schellerer V Hohenberger W Goehl J Multivisceral resection for colon carcinoma Dis Colon Rectum 2009 52 8 1381 6 10.1007/DCR.0b013e3181ab580b 19617748 \n40. Lehnert T Methner M Pollok A Schaible A Hinz U Herfarth C Multivisceral resection for locally advanced primary colon and rectal cancer: an analysis of prognostic factors in 201 patients Ann Surg 2002 235 2 217 25 10.1097/00000658-200202000-00009 11807361 \n41. Huang CM, Huang MY, Tsai HL, Huang CW, Ma CJ, Lin CH et al. A retrospective comparison of outcome and toxicity of preoperative image-guided intensity-modulated radiotherapy versus conventional pelvic radiotherapy for locally advanced rectal carcinoma. J Radiat Res. 2016. doi:10.1093/jrr/rrw098.\n\n",
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"mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols; D059248:Chemoradiotherapy; D017024:Chemotherapy, Adjuvant; D003082:Colectomy; D003110:Colonic Neoplasms; D005260:Female; D005472:Fluorouracil; D005500:Follow-Up Studies; D006801:Humans; D002955:Leucovorin; D008207:Lymphatic Metastasis; D008297:Male; D008875:Middle Aged; D020360:Neoadjuvant Therapy; D009364:Neoplasm Recurrence, Local; D009367:Neoplasm Staging; D009944:Organoplatinum Compounds; D011379:Prognosis; D012189:Retrospective Studies; D015996:Survival Rate",
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"title": "Neoadjuvant FOLFOX chemotherapy combined with radiotherapy followed by radical resection in patients with locally advanced colon cancer.",
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"abstract": "OBJECTIVE\nTo present clinical findings of a cluster of cases of inadvertent high-dose intracameral cefuroxime injection after uneventful phacoemulsification cataract surgery.\n\n\nMETHODS\nSix eyes of 6 patients (mean age 68.33 years, range 61-75, 4 male, 2 female) were operated on the same day by the same surgeon. At the end of surgery, 3 mg in 0.1 mL cefuroxime (30 mg/mL, Zinnat, GlaxoSmithKline) was erroneously injected into anterior chamber of 6 eyes. Incorrect dilution of cefuroxime was noticed at the end of operation day.\n\n\nRESULTS\nThe 6 patients were followed up very closely every day during the first week. No adverse reaction or inflammation was observed at postoperative examination. All patients achieved 20/20 or better vision at the end of the first week.\n\n\nCONCLUSIONS\nInadvertent intracameral (3 mg in 0.1 mL) cefuroxime injection did not cause any detectable adverse effect on ocular tissues.",
"affiliations": "Gozmer Eye Center, Denizli, Turkey. [email protected]",
"authors": "Sakarya|Yasar|Y|;Sakarya|Rabia|R|",
"chemical_list": "D000900:Anti-Bacterial Agents; D019999:Pharmaceutical Solutions; D002444:Cefuroxime",
"country": "United States",
"delete": false,
"doi": "10.1177/112067211002000232",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1120-6721",
"issue": "20(2)",
"journal": "European journal of ophthalmology",
"keywords": null,
"medline_ta": "Eur J Ophthalmol",
"mesh_terms": "D000368:Aged; D000867:Anterior Chamber; D000900:Anti-Bacterial Agents; D002444:Cefuroxime; D004305:Dose-Response Relationship, Drug; D009877:Endophthalmitis; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007267:Injections; D008297:Male; D008508:Medication Errors; D008875:Middle Aged; D018918:Phacoemulsification; D019999:Pharmaceutical Solutions; D013530:Surgical Wound Infection",
"nlm_unique_id": "9110772",
"other_id": null,
"pages": "460-1",
"pmc": null,
"pmid": "19882526",
"pubdate": "2010",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Cefuroxime dilution error.",
"title_normalized": "cefuroxime dilution error"
} | [
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{
"abstract": "Highly active antiretroviral therapy (HAART) has markedly decreased human immunodeficiency virus- (HIV-) related mortality and the incidence of opportunistic infections. The dramatic reduction in HIV-1 RNA and increase in CD4 lymphocyte count mean a recovery in immune function. This restoration in immune function may be associated with paradoxical deterioration in subclinical opportunistic infections in some patients, a condition called immune reconstitution inflammatory syndrome (IRIS). IRIS, a \"paradoxical\" inflammatory response to either previously treated or subclinical infections or noninfectious diseases, can manifest during the restoration phase of immunity hemophagocytic syndrome (HS) which is a very rare complication in patients with acquired immune deficiency syndrome (AIDS). We describe a case of hemophagocytic syndrome associated with IRIS in a patient with AIDS related Burkitt's leukemia/lymphoma (BL). IRIS was probably the cause of hemophagocytosis for our patient. Zoster infection may facilitate to IRIS. With the increasing number of people with HIV infection and the accompanying use of HAART, much more clinical manifestations of IRIS will be experienced especially in patients given high dose chemotherapy, just like in our case.",
"affiliations": "Department of Medical Oncology, Sisli Education and Research Hospital, Istanbul, Turkey.;Department of Clinical Microbiology and Infectious Disease, Istanbul School of Medicine, Turkey.;Department of Internal Medicine, Istanbul School of Medicine, Turkey.;Department of Medical Oncology, Sisli Education and Research Hospital, Istanbul, Turkey.;Department of Clinical Microbiology and Infectious Disease, Istanbul School of Medicine, Turkey.;Department of Hematology, Istanbul Bilim University, Turkey.",
"authors": "Kanıtez|Metin|M|;Kapmaz|Mahir|M|;Alpay|Nilufer|N|;Selcukbiricik|Fatih|F|;Cağatay|Atahan|A|;Diz-Küçükkaya|Reyhan|R|",
"chemical_list": null,
"country": "United States",
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"doi": "10.1155/2014/308081",
"fulltext": "\n==== Front\nCase Rep MedCase Rep MedCRIMCase Reports in Medicine1687-96271687-9635Hindawi Publishing Corporation 10.1155/2014/308081Case ReportHemophagocytic Syndrome Associated with Immune Reconstitution Inflammatory Syndrome in a Patient with AIDS Related Burkitt's Leukemia/Lymphoma Kanıtez Metin \n1\n*Kapmaz Mahir \n2\nAlpay Nilufer \n3\nSelcukbiricik Fatih \n1\nÇağatay Atahan \n2\nDiz-Küçükkaya Reyhan \n4\n1Department of Medical Oncology, Sisli Education and Research Hospital, Istanbul, Turkey2Department of Clinical Microbiology and Infectious Disease, Istanbul School of Medicine, Turkey3Department of Internal Medicine, Istanbul School of Medicine, Turkey4Department of Hematology, Istanbul Bilim University, Turkey*Metin Kanıtez: [email protected] Editor: Werner Rabitsch\n\n2014 27 5 2014 2014 3080817 2 2014 20 4 2014 Copyright © 2014 Metin Kanıtez et al.2014This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.Highly active antiretroviral therapy (HAART) has markedly decreased human immunodeficiency virus- (HIV-) related mortality and the incidence of opportunistic infections. The dramatic reduction in HIV-1 RNA and increase in CD4 lymphocyte count mean a recovery in immune function. This restoration in immune function may be associated with paradoxical deterioration in subclinical opportunistic infections in some patients, a condition called immune reconstitution inflammatory syndrome (IRIS). IRIS, a “paradoxical” inflammatory response to either previously treated or subclinical infections or noninfectious diseases, can manifest during the restoration phase of immunity hemophagocytic syndrome (HS) which is a very rare complication in patients with acquired immune deficiency syndrome (AIDS). We describe a case of hemophagocytic syndrome associated with IRIS in a patient with AIDS related Burkitt's leukemia/lymphoma (BL). IRIS was probably the cause of hemophagocytosis for our patient. Zoster infection may facilitate to IRIS. With the increasing number of people with HIV infection and the accompanying use of HAART, much more clinical manifestations of IRIS will be experienced especially in patients given high dose chemotherapy, just like in our case.\n==== Body\n1. Introduction\n\nHighly active antiretroviral therapy (HAART) has markedly decreased human immunodeficiency virus- (HIV-) related mortality and the incidence of opportunistic infections. The dramatic reduction in HIV-1 RNA and increase in CD4 lymphocyte count mean a recovery in immune function. This restoration in immune function may be associated with paradoxical deterioration in subclinical opportunistic infections in some patients, a condition called immune reconstitution inflammatory syndrome (IRIS) [1, 2]. IRIS may have very different clinical manifestations [1]. Hemophagocytic syndrome (HS) is a very rare complication in patients with acquired immune deficiency syndrome (AIDS), with a pathogenesis of unclear certainty [3]. Here, we describe a case of hemophagocytic syndrome associated with IRIS in a patient with AIDS related Burkitt's leukemia/lymphoma (BL).\n\n2. Case\nA 39-year-old woman had a diagnosis of BL with an Ann Arbor stage IVB in June 2008. She had thoracic and intra-abdominal lymphadenopathies with bone marrow involvement. HIV screening was positive with a CD4 lymphocyte count of 274 cells/mL and HIV-1 RNA of 124.000 copies/mL. The serology of Toxoplasma gondii, cytomegalovirus, herpesvirus, and hepatitis A, B, and C viruses was negative. Both hyper-CVAD (hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone) for BL and an antiretroviral therapy consisting of zidovudine-lamivudine with ritonavir-lopinavir were initiated.\n\nIn October 2008, a complete remission of the BL was shown by bone marrow biopsy and radiological findings, with an increasing count of CD4 lymphocytes to 412 cells/mL and HIV-1 RNA of 135 copies/mL. Then, ptosis developed on her right eye, with a facial palsy on her left. Cranial and orbital magnetic resonance images revealed a thickening of the third division (V3) of trigeminal nerve and a soft tissue development in the roof of left maxillary sinus (Figures 1(a) and 1(b)). The CSF analysis was normal with microbiological screening for Cryptococcus neoformans, cytomegalovirus (CMV), herpesvirus (HSV), and Mycobacterium found to be negative, and no malignant cell was observed. After two days, zosteriform lesions appeared on her right side reflecting V1 of trigeminal nerve. With a ten-day treatment of acyclovir, the lesions resolved. However, ptosis and facial palsy persisted with findings of painless ulcerative gingivitis, subfebrile fever, and hepatosplenomegaly. Blood and urine cultures were negative for bacteria, mycobacteria, and fungi. Laboratory tests showed pancytopenia (hemoglobin, 7 g/L; white blood cells, 1100 mL; platelets, 40.000 mL). Prothrombin and activated partial thromboplastin time were normal and lactate dehydrogenase was elevated (768 IU/L). The liver enzymes, vitamin B12, and folic acid were in normal range. The bone marrow aspiration revealed a hypocellularity with no malignant cells. Besides this, active hemophagocytosis with prominent phagocytosis of erythroid precursors was detected (Figure 2). Both Parvovirus IgM and Epstein Barr VCA IgM were negative. PCR for HSV types I and II and CMV were found to be negative. The repeated serology for Toxoplasma and Cryptococcus neoformans antigen were negative in serum. At this point, a diagnosis of IRIS was considered. The antiretroviral therapy was stopped. Although methyl prednisolone (1 g i.v. daily for three days) followed by intravenous immunoglobulin (1000 mg/kg daily for two days) was given, the patient died with a multiorgan failure during followup.\n\n3. Discussion\nIRIS, a “paradoxical” inflammatory response to either previously treated or subclinical infections or noninfectious diseases, can manifest during the restoration phase of immunity [4]. Its diagnosis is clinical and requires excluding alternative conditions. IRIS may give rise to a heterogeneous range of clinical presentations [1]. Otolaryngological [2, 5] and neurological manifestations [6, 7] are also reported. With this regard, the nonspecific soft tissue developments in maxillary sinus and facial palsy in our patient are thought to be associated with IRIS.\n\nBesides this, we diagnosed a hemophagocytic syndrome in our case, which may be an interesting manifestation of IRIS. In the literature, similarly, HS is reported as a probable presentation of IRIS [8]. HS is a rare disorder with a similar pathophysiology of IRIS and characterized by overproliferation of mature histiocytes, hemophagocytosis, and upswing of inflammatory cytokines [9]. The decrease in cytotoxicity of natural killer cells and cytotoxic T cells with upregulation of γ-interferon probably plays a role in the pathogenesis of HS, leading to an increase in macrophage activation and plentiful secretion of proinflammatory cytokines [4]. Infectious agents, mostly viruses of herpes family, usually are the triggers. Malignant lymphomas, especially in adults, may be associated with HS. An autopsy study of 56 patients with AIDS diagnosed an approximate 20% rate of hemophagocytosis [3]. Recent reports have suggested that HS may be a manifestation of acute HIV infection [10]. Because no evidence of Burkitt's lymphoma was found at the time of HS in our patient, it was excluded as a trigger. The herpes zoster infection, however, might be associated with IRIS and HS in this case. Although the chemotherapy given to the patient for the lymphoma was not thought to have a role with HS or IRIS, it might delay the possible symptoms of IRIS in such a way preventing the recovery of CD4 counts.\n\nThe guidelines for treatment of IRIS are not well defined. Nonsteroidal anti-inflammatory drugs and systemic corticosteroids may be used for complications secondary to the exaggerated inflammatory process in IRIS [11]. In severe cases, HAART may be helpful to be stopped until the inflammatory condition and/or the infection taken under control [1, 4]. The treatment options of HS are corticosteroids, immunoglobulins, etoposide, antithymocyte globulin, cyclosporine, and stem cell transplantation [9]. We preferred to stop antiretroviral therapy and initiated high dose prednisolone together with i.v. immunoglobulin, in a useless attempt for the patient at the end.\n\nIn conclusion, IRIS was probably the cause of hemophagocytosis for this patient. Zoster infection may facilitate IRIS. With the increasing number of people with HIV infection and the accompanying use of HAART, much more clinical manifestations of IRIS will be experienced especially in patients given high dose chemotherapy, just like in our case.\n\nConflict of Interests\nThe authors declare that there is no conflict of interests regarding the publication of this paper.\n\nFigure 1 The cranial and orbital sagittal T2-weighted magnetic resonance image revealing a thickening of the third division of trigeminal nerve (a) and a soft tissue development of one centimeter diameter in the roof of left maxillary sinus (b).\n\nFigure 2 The bone marrow aspiration revealing active hemophagocytosis with prominent mature histiocyte phagocytosis of red blood cells (May-Giemsa stain, ×100).\n==== Refs\n1 Dhasmana DJ Dheda K Ravn P Wilkinson RJ Meintjes G Immune reconstitution inflammatory syndrome in HIV-infected patients receiving antiretroviral therapy: pathogenesis, clinical manifestations and management Drugs 2008 68 2 191 208 2-s2.0-38149039310 18197725 \n2 Colebunders B Claes G Vlieghe E Demeester R Moerman F Colebunders R A frontal mucocele caused by an immune reconstitution inflammatory syndrome in a patient with HIV infection Rhinology 2008 46 3 243 245 2-s2.0-52949144499 18853879 \n3 Niedt GW Schinella RA Acquired immunodeficiency syndrome. Clinicopathologic study of 56 autopsies Archives of Pathology and Laboratory Medicine 1985 109 8 727 734 2-s2.0-0022411986 2990378 \n4 French MAH Antiretroviral therapy immune restoration disease in HIV-infected patients on HAART AIDS Reader 1999 9 8 548 562 2-s2.0-0032726530 11082733 \n5 Chan-Tack KM Chengappa KS Wolf JS Kao GF Reisler RB Immune reconstitution inflammatory syndrome presenting as sinusitis with inflammatory pseudotumor in an HIV-infected patient: a case report and review of the literature AIDS Patient Care and STDs 2006 20 12 823 828 2-s2.0-33846214381 17192147 \n6 Yeo JCL Trotter MI Wilson F Bilateral facial nerve palsy associated with HIV seroconversion illness Postgraduate Medical Journal 2008 84 992 328 329 2-s2.0-49049116320 18644926 \n7 Vendrely A Bienvenu B Gasnault J Thiebault JB Salmon D Gray F Fulminant inflammatory leukoencephalopathy associated with HAART-induced immune restoration in AIDS-related progressive multifocal leukoencephalopathy Acta Neuropathologica 2005 109 4 449 455 2-s2.0-18344386233 15739098 \n8 Huang DB Wu JJ Hamill RJ Reactive hemophagocytosis associated with the initiation of highly active antiretroviral therapy (HAART) in a patient with AIDS Scandinavian Journal of Infectious Diseases 2004 36 6-7 516 519 2-s2.0-4143084903 15307589 \n9 Janka GE Hemophagocytic syndromes Blood Reviews 2007 21 5 245 253 2-s2.0-34547691044 17590250 \n10 Sun H Chen M Fang C Hsieh S Hung C Chang S Hemophagocytic lymphohistiocytosis: an unusual initial presentation of acute HIV infection Journal of Acquired Immune Deficiency Syndromes 2004 37 4 1539 1540 2-s2.0-10044227130 15602134 \n11 Feller L Wood NH Lemmer J Herpes zoster infection as an immune reconstitution inflammatory syndrome in HIV-seropositive subjects: a review Oral Surgery, Oral Medicine, Oral Pathology, Oral Radiology and Endodontology 2007 104 4 455 460 2-s2.0-34648836769\n\n",
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"literaturereference": "KANJTEZ M, KAPMAZ M, ALPAY N, SELCUKBIRICIK F, ?ALATAY A, DIZ-K???KKAYA R. HEMOPHAGOCYTIC SYNDROME ASSOCIATED WITH IMMUNE RECONSTITUTION INFLAMMATORY SYNDROME IN A PATIENT WITH AIDS RELATED BURKITT^S LEUKEMIA/LYMPHOMA. CASE REPORTS IN MEDICINE. 2014;",
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"abstract": "BACKGROUND\nWilson disease (WD) is a hereditary disease inhibiting copper release from the liver. Multi-organ manifestations involve the liver, nervous system, kidneys, eyes, heart, and skin. Elastic fiber damage is a complication of the most frequently used medication in the treatment of WD D-penicillamine (D-PCA). These changes have very rarely been described in the oral cavity. The article describes oral complications associated with WD and its treatment by D-PCA.\n\n\nMETHODS\nClinical, radiographic, and microscopic evaluation was done on two WD female patients (aged 28 and 53), treated by D-PCA, with clinical and pathological evidence for oral drug-related complications.\n\n\nRESULTS\nThe lesions included multiple small red papules of the lips, gingival enlargement, early onset periodontitis, and repeated oral candidiasis. Biopsies of oral mucosa (gingiva, buccal) exhibited in one case granulomatous inflammation, and in both cases, thick irregular clumps of tortuous, red-staining abnormal elastic fibers. The red lip papules resemble elastosis perforans serpiginosa (EPS). Similar lesions have been described in the skin, but never before in association with oral or perioral tissue. In addition to the oral lesions, one of the patients developed general intolerance to the drug and was switched to trientine hydrochloride.\n\n\nCONCLUSIONS\nWD patients and others treated by D-PCA may develop oral and perioral complications, in some cases exhibiting features of damaged elastic fibers in the mucosa and periodontal apparatus. It is possible that this damage may be one of the factors responsible for poor periodontal health in WD patients. Recognition of the lesions can lead to replacement of the affecting therapeutic agent.",
"affiliations": "Department of Oral Medicine, Oral Pathology, Faculty of Dental Medicine, Carol Davila University, Bucharest, Romania.",
"authors": "Tovaru|Serban|S|;Parlatescu|Ioannina|I|;Dumitriu|Anca-Silvia|AS|;Bucur|Alexandru|A|;Kaplan|Ilana|I|",
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"medicinalproduct": "LACTULOSE."
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"activesubstancename": "URSODIOL"
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"medicinalproduct": "URSODEOXYCHOLIC ACID"
},
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"actiondrug": null,
"activesubstance": {
"activesubstancename": "SPIRONOLACTONE"
},
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"drugcharacterization": "2",
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"drugintervaldosagedefinition": "805",
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"medicinalproduct": "SPIRONOLACTONE."
}
],
"patientagegroup": null,
"patientonsetage": "32",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Gingival recession",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Osteitis",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Gingival hypertrophy",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Dental caries",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Periodontitis",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Alveolar bone resorption",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Gingival bleeding",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2005"
}
},
"primarysource": {
"literaturereference": "KAPLAN I, TOVARU S, PARLATESCU I, DUMITRIU A, BUCUR A. ORAL COMPLICATIONS ASSOCIATED WITH D-PENICILLAMINE TREATMENT FOR WILSON DISEASE: A CLINICOPATHOLOGIC REPORT. JOURNAL OF PERIODONTOLOGY. 2010 AUG?81(8):1231-1236.",
"literaturereference_normalized": "oral complications associated with d penicillamine treatment for wilson disease a clinicopathologic report",
"qualification": "1",
"reportercountry": "IL"
},
"primarysourcecountry": "IL",
"receiptdate": "20190212",
"receivedate": "20190212",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 15954449,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190417"
}
] |
{
"abstract": "BACKGROUND\nWith the increasing use of gemcitabine, more and more rare toxicities are encountered in practice. In general, gemcitabine may cause bone marrow suppression, mild cutaneous rash, and alopecia. We report a case of recurrent cutaneous toxicity during adjuvant chemotherapy with gemcitabine after complete resection of pancreatic adenocarcinoma.\n\n\nMETHODS\nThe patient developed recurrent toxic erythema on the skin of his lower extremities after each cycle of chemotherapy. Because of the misleading clinical features of the presentation, he was repeatedly treated with unnecessary antibiotics for \"cellulitis.\" A skin biopsy revealed possible early leukocytoclastic vasculitis and epidermal dysmaturation.\n\n\nCONCLUSIONS\nThe true mechanism of this phenomenon remains unclear. Our case suggests that vasculitis might play a role in the pathophysiology. More attention should be paid to atypical presentations, with correlation of clinical judgment and tissue biopsy. There is no effective prevention or treatment except discontinuation of the precipitating agent, and unnecessary antimicrobial treatment should be avoided if possible.",
"affiliations": "Department of Medical Oncology, Yale University School of Medicine, New Haven, Connecticut 06520, USA.",
"authors": "Li|Jia|J|;Ko|Christine J|CJ|;Saif|Muhammad Wasif|MW|",
"chemical_list": "D000964:Antimetabolites, Antineoplastic; D003841:Deoxycytidine; C056507:gemcitabine",
"country": "England",
"delete": false,
"doi": "10.1080/15569520903046942",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1556-9527",
"issue": "28(3)",
"journal": "Cutaneous and ocular toxicology",
"keywords": null,
"medline_ta": "Cutan Ocul Toxicol",
"mesh_terms": "D000964:Antimetabolites, Antineoplastic; D001706:Biopsy; D002481:Cellulitis; D003841:Deoxycytidine; D003937:Diagnosis, Differential; D004893:Erythema Nodosum; D006801:Humans; D008297:Male; D008875:Middle Aged; D010190:Pancreatic Neoplasms; D012008:Recurrence; D018366:Vasculitis, Leukocytoclastic, Cutaneous",
"nlm_unique_id": "101266892",
"other_id": null,
"pages": "144-8",
"pmc": null,
"pmid": "19527102",
"pubdate": "2009",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Recurrent cutaneous toxic erythema induced by gemcitabine in a patient with pancreatic cancer.",
"title_normalized": "recurrent cutaneous toxic erythema induced by gemcitabine in a patient with pancreatic cancer"
} | [
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"drugindication": "STAPHYLOCOCCAL INFECTION",
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"drugdosagetext": "1000 MG/M2, CYCLIC (3 WEEKS ON, 1 WEEK OFF)",
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"drugindication": "PANCREATIC CARCINOMA",
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"medicinalproduct": "DEXAMETHASONE."
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"medicinalproduct": "TRIMETHOPRIM."
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"activesubstancename": "FAMOTIDINE"
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"medicinalproduct": "FAMOTIDINE."
},
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"activesubstancename": "GEMCITABINE HYDROCHLORIDE"
},
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"medicinalproduct": "GEMCITABINE HYDROCHLORIDE."
},
{
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"activesubstancename": "DIPHENHYDRAMINE"
},
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"drugstartdateformat": "602",
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"medicinalproduct": "DIPHENHYDRAMINE."
}
],
"patientagegroup": null,
"patientonsetage": "59",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Toxic skin eruption",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": {
"narrativeincludeclinical": "CASE EVENT DATE: 2008"
}
},
"primarysource": {
"literaturereference": "LI, J.. RECURRENT CUTANEOUS TOXIC ERYTHEMA INDUCED BY GEMCITABINE IN A PATIENT WITH PANCREATIC CANCER.. CUTANEOUS AND OCULAR TOXICOLOGY. 2009?28(3):144-148",
"literaturereference_normalized": "recurrent cutaneous toxic erythema induced by gemcitabine in a patient with pancreatic cancer",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190621",
"receivedate": "20190621",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16463810,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
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"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190711"
}
] |
{
"abstract": "The mainstay of treatment for opioid use disorder are medications, methadone (a full opioid agonist), or buprenorphine (a partial opioid agonist), in conjunction with psychosocial interventions. Both treatments are effective but safety, efficacy, and patient preference can lead to a decision to change from one treatment to the other. Transfer from buprenorphine to methadone is not clinically challenging; however, changing from methadone to buprenorphine is more complex. Published reports describe varied approaches to manage this transfer to both minimize patient symptoms associated with withdrawal from methadone and reduce risk of precipitating withdrawal symptoms with introduction of the partial agonist buprenorphine [Lintzeris et al. J Addict Med. 2020; in press]. There is no single approach for methadone to buprenorphine that is superior to others and no approach that is suitable for all case presentations. This case conference describes three different approaches to achieve a successful methadone to buprenorphine transfer and provides commentary on how the case may be managed based on published transfer \"strategies.\"",
"affiliations": "NHS Lanarkshire, Motherwell, UK (DH); The Langton Centre, South East Sydney Local Health District, NSW Health, Surry Hills, New South Wales, Australia (VH, AD, NL); School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia (VH, AD); University Sydney, Division Addiction Medicine, Sydney, Australia (NL).",
"authors": "Hill|Duncan|D|;Hayes|Victoria|V|;Demirkol|Apo|A|;Lintzeris|Nicholas|N|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1097/ADM.0000000000000854",
"fulltext": "\n==== Front\nJ Addict Med\nJ Addict Med\nADM\nJournal of Addiction Medicine\n1932-0620\n1935-3227\nLippincott Williams & Wilkins Hagerstown, MD\n\n33870954\nJAM-D-20-00500\n10.1097/ADM.0000000000000854\n00010\nReviews\nClinical Case Conference: Strategies for Transferring From Methadone to Buprenorphine\nHill Duncan BSc (Hons), Pharmacy\nHayes Victoria MBBS, MPH, FAFPHM, FAChAM\nDemirkol Apo MD, MSc, MMed (Pain Mgt), PhD, FAFPHM, FAChAM\nLintzeris Nicholas BMedSci, MBBS, PhD, FAChAM\nNHS Lanarkshire, Motherwell, UK (DH); The Langton Centre, South East Sydney Local Health District, NSW Health, Surry Hills, New South Wales, Australia (VH, AD, NL); School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia (VH, AD); University Sydney, Division Addiction Medicine, Sydney, Australia (NL).\nSend correspondence to Nicholas Lintzeris, BMedSci, MBBS, PhD, FAChAM, Drug and Alcohol Services, South East Sydney Local Health District, Specialty of Addiction Medicine, University of Sydney, NSW Drug and Alcohol Clinical Research and Improvement Network, NSW Health, c/o The Langton Centre, 591 South Dowling Street, Surry Hills, New South Wales 2010, Australia. E-mail: [email protected].\nMar-Apr 2022\n15 4 2021\n16 2 152156\n11 11 2020\n01 3 2021\nCopyright © 2021 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Addiction Medicine.\n2021\nhttps://creativecommons.org/licenses/by-nc-nd/4.0/ This is an open access article distributed under the terms of the Creative Commons Attribution-Non Commercial-No Derivatives License 4.0 (CCBY-NC-ND), where it is permissible to download and share the work provided it is properly cited. The work cannot be changed in any way or used commercially without permission from the journal. http://creativecommons.org/licenses/by-nc-nd/4.0\n\nThe mainstay of treatment for opioid use disorder are medications, methadone (a full opioid agonist), or buprenorphine (a partial opioid agonist), in conjunction with psychosocial interventions. Both treatments are effective but safety, efficacy, and patient preference can lead to a decision to change from one treatment to the other. Transfer from buprenorphine to methadone is not clinically challenging; however, changing from methadone to buprenorphine is more complex. Published reports describe varied approaches to manage this transfer to both minimize patient symptoms associated with withdrawal from methadone and reduce risk of precipitating withdrawal symptoms with introduction of the partial agonist buprenorphine [Lintzeris et al. J Addict Med. 2020; in press]. There is no single approach for methadone to buprenorphine that is superior to others and no approach that is suitable for all case presentations. This case conference describes three different approaches to achieve a successful methadone to buprenorphine transfer and provides commentary on how the case may be managed based on published transfer “strategies.”\n\nKeywords\n\nbuprenorphine\nmethadone\nopioids\ntransfer\nOPEN-ACCESSTRUE\n==== Body\npmcThe mainstay of treatment for opioid use disorder (OUD) are medications, methadone (a full opioid agonist) or buprenorphine (a partial opioid agonist), in conjunction with psychosocial interventions. Both treatments are effective but safety, efficacy, and patient preference can lead to a decision to change from one treatment to the other. Transfer from buprenorphine to methadone is not clinically challenging; however, changing from methadone to buprenorphine is more complex. Published reports describe varied approaches to manage this transfer to both minimize patient symptoms associated with withdrawal from methadone and reduce risk of precipitating withdrawal symptoms with introduction of the partial agonist buprenorphine.1 There is no single approach for methadone to buprenorphine that is superior to others and no approach that is suitable for all case presentations. This case conference describes 3 different approaches to achieve a successful methadone to buprenorphine transfer and provides commentary on how the case may be managed based on published transfer “strategies.”\n\nCASE DESCRIPTION\n\nThroughout the case, buprenorphine refers to buprenorphine monotherapy sublingual tablet and the combination tablet or film (buprenorphine with naloxone).\n\nPresenting Complaint\n\nA 38-year-old man currently in methadone treatment for opioid dependence seeks to transfer to sublingual buprenorphine and seeks your advice.\n\nHistory of Presenting Complaint\n\nThe patient reports commencing heroin use at 21 while studying computer programming at university. Before commencing heroin use, he had a history of heavy alcohol and cannabis use but ceased these after commencing heroin use. The patient reports several brief OUD treatment episodes in his mid to late 20s including occasions of residential rehabilitation, buprenorphine and methadone treatment. Previous buprenorphine daily dose stabilised at 16 mg for 18 months, previous methadone treatment episodes daily dose 50 mg for 5 months, daily dose 120 mg for 16 months and 90 mg daily dose for 10 months.\n\nAged 29, the patient recommenced methadone treatment and was abstinent from nonprescribed opioids after 3 months of treatment with a prescribed methadone dose of 120 mg. During the following 12 months, the patient returned to work as a computer software programmer and did not use nonprescribed opioids. At this time, he requested to reduce his dose of methadone with a view to eventual cessation. His dose was reduced by 5 mg every 4 weeks initially; however, he found reducing the dose below 80 mg difficult to tolerate reporting that he experienced symptoms similar to normal withdrawal symptoms, including rhinorrhea, tearing, increased anxiety, sweating, increased agitation and restlessness, insomnia, diarrhea, and stomach cramps.\n\nThe patient continued methadone 80 mg for a further 2 years remaining abstinent from nonprescribed opioids during this time. The patient reports his 5-year-old son died in a motor vehicle accident at this time, which led to a period of grief and depression and triggered a relapse to heroin use. After several months of episodic heroin use, he increased his dose of methadone to 140 mg and was able to eventually cease his heroin use and resumed work.\n\nIn recent months, he has been gradually reducing his methadone dose at a rate of 5 mg every 4 weeks, and he is currently on 110 mg oral methadone. He reports no heroin or other opioid use for over 2 years (confirmed with opiate negative urine tests), and no use of alcohol, benzodiazepines, or stimulants in recent years.\n\nApart from a period of depression and grief after the death of his son, there seems to be no other mental health concerns, and he is not taking any medication. He is hepatitis C virus polymerase chain reaction positive, has normal liver function tests, and is considering antiviral treatment. He has a history of accidental overdose 5 years ago whilst using heroin.\n\nHe is separated from his wife and has no other children. He works as a computer software programmer for a small IT company, which he describes as enjoyable but at times stressful.\n\nHis main motivation to seek transfer to buprenorphine is that he is seeking to withdraw completely off opioid agonist treatment. He had previously found methadone withdrawal very difficult to cope with, especially at doses below 80 mg. In contrast, he describes coming off buprenorphine as somewhat easier, and would like to transfer to buprenorphine as soon as he can, with a view to coming off opioids altogether – ideally at some point in the next 6 months.\n\nPreparing the Patient for the Transfer\n\nThe patients’ motivation is key to the transition and the success of the change in treatment; reasons can vary but there is a need for a clear commitment and drive for the change from the patient. In this case, the patient is looking for abstinence from opioids eventually; he has struggled to achieve this with methadone treatment before and has found the process less challenging using buprenorphine treatment previously. The patient should be reminded of the potential differences in treatments and encouraged to relate his buprenorphine experiences back to you. In particular, the mental health issues after the patient's son's death might be worth checking as patients can report difficulty adjusting to perceived increased clarity of thinking after discontinuation of high doses of full opioid agonists.2,3 The patient may need additional support and wraparound services in case he starts to struggle with persistent negative thoughts unclouded by partial opioid agonist effects.2 Other factors to be discussed include the reason for the change to buprenorphine and assessing whether the patient is likely to do well on buprenorphine.\n\nKey considerations when transferring individuals from higher doses of methadone to sublingual buprenorphine are the risk of precipitating withdrawal on initiation of buprenorphine and the risk of destabilizing the patient regarding their substance use, or medical, psychiatric, or social conditions. To minimize the risk of these occurring, it is important to complete a comprehensive assessment of the current physical and mental health and substance use history focusing on the most recent drug use, thereby ensuring that the transfer process is not complicated by other substance use including benzodiazepines, pharmaceutical opioids, or other sedating agents.\n\nAs with any of the transition between treatments discussed below, it is necessary to discuss the process and options clearly, explaining the advantages and disadvantages and confirming the patient's expectations from this and for treatment after the transfer. Even in this case, where the patient has had both treatment options previously, it is important to remind the patient of the different effects he may experience due to the different treatments. Once the patient has consented and is well prepared for the admission, if undergoing an in-patient transfer, and the regulatory processes are completed as appropriate, the procedure can be initiated.\n\nCase Progression\n\nSeveral approaches have been described for management of transfer from methadone to buprenorphine, which were discussed with the patient. The following sections provide alternative scenarios for progression of this case, based on these different treatment approaches. For 2 methods being discussed, tapering and higher dose transfers, there is a requirement for the patient to present in a state of withdrawal. As part of the pretransition discussions for these methods, the importance of presenting in moderate withdrawal is key to the successful transfer, as well as awareness of the possibility of slight worsening of withdrawal symptoms as the patient's buprenorphine is rapidly titrated.\n\nTaper and Inpatient Transfer\n\nThis approach is in line with the NSW Clinical Guidelines for the Treatment of Opioid Dependence,4 which have been drawn from the Australian National Guidelines for Medically Assisted Treatment of Opioid Dependence.5 In Australia, the opioid agonist treatment for OUD is run through a permit system, which is regulated by the State Health Departments, and it is illegal to prescribe these medications in an outpatient setting without an authority.\n\nGiven the dose of methadone that this patient is prescribed, the most suitable setting in which to conduct the transfer would be an inpatient setting. As discussed, preparation of the patient is key to a successful transference, especially with regard to the risk of precipitated withdrawal and the need for the patient to be in moderate withdrawal before commencing sublingual buprenorphine. Often, it is necessary for the patient to miss a dose of methadone before presenting for admission to allow enough time for the patient to develop sufficient withdrawal before buprenorphine is initiated. The patient must be cognizant of each step of the process including what happens after discharge.\n\nThe patient's methadone dose is withheld the day before and on the day of his admission. On admission day, it is important to reassess the patient's recent substance use, as this may affect your management. Once admitted, the patient's withdrawal severity is assessed regularly, every 4 hours, using a validated assessment instrument such as the Clinical Opiate Withdrawal Scale (COWS).6 Once he is in moderate withdrawal, which correlates to a score of ≥13 on the COWS, and he is observed to have objective signs of withdrawal such as dilated pupils and tachycardia, a test dose of 2 mg of sublingual buprenorphine is given. The patient is observed for precipitated withdrawal and other adverse events and reassessed using the COWS after 1 hour. If there have been no adverse events, a further 6 mg of sublingual buprenorphine is given. Withdrawal severity assessment continues every 2 hours and supplemental doses of 2 to 8 mg are administered depending on the severity of the withdrawal until such a time as the majority of the opioid withdrawal symptoms have abated and the patient is not sedated. The maximum daily dose of sublingual buprenorphine in Australia is 32 mg.\n\nThe admission can be used opportunistically to address other health problems and complete investigations such as blood borne virus screening and organize referrals as appropriate.\n\nThe patient is discharged 24 hours after the first dose of buprenorphine to the care of their community prescriber and last dosing details are provided to ensure that the prescriber is able to write a prescription and that there is no disruption to treatment. It is best practice that the prescriber reviews the patient as soon as is practical after discharge, ideally within the first 4 days. The prescriber is then able to adjust the dose according to clinical need.\n\nTaper and Outpatient Transfer (2 Options – Slow Taper and High-Dose Transfer)\n\nNHS Lanarkshire, Scotland, provides 2 taper outpatient options, one of which is a slow taper at the rate of 5 to 10 mg per 4 weeks with the advantage of minimal withdrawal with transfer once 30 mg methadone dose is reached. However, this taper can take 1 to 2 years to achieve and may expose the patient to a longer period of suboptimal dosing for him, which is not considered as suitable given this patient's history.\n\nTherefore, an alternative method of a high-dose transfer (HDT) would be preferred because of the minimal time for the patient being on a low dose of methadone, thus reducing potential for a relapse. Rapid transition from doses of over 30 mg methadone to buprenorphine have been successfully conducted for a number of years now on an outpatient basis.7,8\n\nWith HDT, the main presenting risk is precipitated withdrawal, which can occur if the methadone has not been eliminated before transfer. The introduction of buprenorphine too early may cause this set of symptoms; however, this can be reduced through the counselling and advice to the patient and assessment of withdrawal symptoms before commencing treatment.\n\nThe patient continues with their usual dose of methadone daily until 36 to 48 hours before their clinic appointment. The patient is advised to stop his dose, which can be facilitated by accurate prescribing, ensuring the final dose prescribed is 2 days before the transition appointment. They need to be advised that they may feel uncomfortable due to withdrawals in this time frame, but they should refrain from using any illicit substances. A further explanation is that the service needs to see them at the clinic before starting the transition as they are; they need to be seen in withdrawal before commencing the process, as such symptoms should not be masked, as this may prevent the start of the transition. The service encourages 100% honesty with this because if they have used any opioids (particularly methadone), the transition can become unpleasant. It is important that they are made aware that on some occasions patients may experience withdrawal symptoms that worsen during the transition, which may be due to the final opioids being displaced from receptor sites by buprenorphine; this is normally transient and diminishes with additional buprenorphine doses.\n\nPatients are advised they will need to stay at the clinic for at least half a day (process takes several hours), whilst the buprenorphine dose is titrated quickly, but there is the need for observation between doses as well as evaluation of the patient and their symptoms. Doses are given every 45 to 60 minutes and increase to a maximum of 24 mg.7 The dose regimen is 2 mg, 2 mg, 4 mg, 8 mg, and 8 mg. Some patients may wish to stop at 16 mg; however, we would encourage a dose of 24 mg, which produces a high degree of opioid receptor saturation. Patients may wish to leave the clinic for a break, drink (nonalcoholic) or to smoke tobacco and if well they may be allowed to do this, but they should only be away for a short period of time. Patients are assessed and opioid withdrawal scales are completed (and agreed with patient) before each dose is given. Throughout, communication about the process and the expectations between the prescriber (or worker) and the patients are essential for a good outcome.\n\nMicrodosing Transfer (Bernese Method)\n\nA third option for the patient would be the use of microdosing. This is a relatively new development by NHS Lanarkshire and is based on experiences reported in the little published literature and anecdotal reports from other services with the UK.9–12\n\nThe principle underlying the process is to slowly but gradually introduce buprenorphine to the patients’ opioid agonist treatment, whilst they are on a full opioid agonist, titrating the dose up to a therapeutic dose before discontinuing their full opiate agonist. The dose of buprenorphine gradually increases and gently displaces the full opioid agonist from the receptor sites replacing this with buprenorphine, a partial opioid agonist, but with greater receptor affinity. The buprenorphine dose increases should be small initially and gradually increased to ensure there is not a rapid replacement of the full opioid agonist by the partial agonist, which could introduce withdrawal symptoms to the patient. The increases of buprenorphine should be made daily, with the methadone dose remaining the same as before the transfer started, until a therapeutic dose has been achieved of buprenorphine. At this stage, the methadone can be either reduced or stopped, whilst the final stages of the buprenorphine titration are completed. Once at a therapeutic dose of buprenorphine, ceasing the daily dose of methadone should cause no significant issues in relation to withdrawal symptoms due to the buprenorphine occupancy of opioid receptors.\n\nThe main advantage of the microdosing method is that the patient should only experience mild withdrawal symptoms at worst (if any) from any previous prescribed daily dose of methadone, although the negative is that the process takes a number of weeks to complete, but by the end, the patient should be on a stable daily dose of buprenorphine and no longer be on any methadone, providing a crossover in opioid agonist treatment.\n\nThe guidance developed locally for this method is to commence with sublingual 400 μg buprenorphine and gradually increase this dose every 24 hours initially by 400 μg, then as the dose has increased, increasing the dose increment at a greater rate (eg, 800 μg after dose reaches 3 mg, 1200 μg after dose reaches 8 mg, etc), whilst maintaining the methadone dose. Once the buprenorphine dose is over 12 mg, consideration to reducing the daily methadone dose can be made, up to 50%. Then as the buprenorphine increases further and the patient stabilizes on the dose, the methadone can be quickly reduced with few withdrawal symptoms expected, as the buprenorphine is occupying the majority of the receptor sites. The process can take 3 to 4 weeks to complete, but this is dependent on the individual patient and the rate of buprenorphine increase.\n\nOnce the process has started for the patient, it is necessary to work closely with them, with appointments more regularly than normal (a minimum of weekly appointments during the transition) to ensure the titration for buprenorphine is being tolerated and there are no signs of opioid toxicity. Appointments can be altered on an individual basis in response to the patient's progress or symptoms, thus altering the rate of increase of buprenorphine or reducing full opioid agonist doses as required.\n\nFor the patient in this scenario, this may be a good option as he has been treated with both methadone and buprenorphine previously but finds the reductions in methadone dose challenging and he struggles more with the withdrawal symptoms experienced. Additionally, looking beyond the transfer to buprenorphine, he reported that in the past he has found detoxing from buprenorphine is easier for him. The microdosing technique may provide a method of transitioning involving few if any withdrawal effects and, as such, appeal to the patient more than the other options of a slow and gradual reduction in methadone dose or the potential withdrawals (albeit for a brief period of time) experienced with the transition phase of an HDT. The process is then through the regular reviews tailored to his progress. However, one of the negatives for the process is the need for the regular contact and that the process can extend over a few weeks to complete.\n\nDISCUSSION\n\nThe ability to transition from methadone to buprenorphine medication has long been a challenge given the pharmacology of the 2 opioids. In some countries (eg, USA), methadone and buprenorphine are delivered in different treatment sectors, such that relatively few patients seek to make the transition. Elsewhere (eg, UK, Australia, and Europe), methadone and buprenorphine are routinely provided by the same service providers, and there seems to be greater experience in attempting transfers. Additionally, the treatment process and available resources in each country or state may differ (eg, access to inpatient facilities) and will be dependent on practices, facilities and product availabilities, but the review1 and this case study series are based on evidenced and peer reviewed articles and the clinical experience of the authors.\n\nIn 2020, 2 factors have highlighted the need for “smoother” transitions between the 2 medications. The introduction of depot buprenorphine medications13–15 in many countries, with once-a-week or once-a-month dosing greatly increases treatment convenience and satisfaction and is likely to result in many patients seeking to transition from methadone to depot products. The second factor has been the emergence of COVID-19, and the need to minimize direct contact of patients attending and congregating at services. The greater safety profile of buprenorphine compared to methadone makes it a medication better suited to large numbers of unsupervised doses. Again, the depot formulations have also been encouraged in many services to reduce COVID-19 risks.15,16\n\nHaving a range of potential options for the transition between methadone and buprenorphine is essential, and it is important to discuss these with each patient in advance to identify which method may be preferable for them, discussing the pros and cons of each and addressing any fears or concerns that they may have in relation to the process. By involving the patient in the choice of transition method, they will have more involvement in the process. In respect to the recent review,1 it can be seen that various options have been investigated, which all have advantages and disadvantages, therefore providing a number of possible options for patients dependent on their risks and preferences. Offering a range and getting the patient involved in these discussions may increase their engagement in the process and hopefully their success in transferring treatments. The review,1 however, does point out that there is still a limited evidence base for the transfer processes and unfortunately there is no clear strategy that one is better than the others. It is therefore important to note that while the available research does not support routine application of a single transfer strategy, it does support the narrative of positive outcomes described in these case vignettes. The review1 clearly indicates that most patients who initiate a transfer from methadone to buprenorphine do achieve a stable buprenorphine dose and successfully complete the transfer.\n\nIt is important to recognize that these results (based on the review1 and the above cases) are achieved in settings where patients are managed by experienced clinicians. In the absence of clear evidence, clinical experience and expert opinion are necessary to guide treatment. Available international clinical guidelines are derived from published clinical experience, therefore providing recommendations consistent with the available evidence. However, clinical guidelines should be seen as providing “guidance” rather than “protocols” for adherence. Although new approaches8,10–12 seems promising, further evidence of the safety and effectiveness of such approaches are required before they can be considered “routine” practice or occur outside of specialist sector services. This emphasizes the importance of clinicians and patients preparing in advance for the transfer exercising their judgment, based on the available evidence, as to which procedure is best suited for their particular transfer.\n\nConcluding Comment Regarding the Application of the Case Conference to Practice\n\nAs a final thought, through the process (irrespective of the transition method), it should be remembered that the patient is going to go through a challenging time as they transition from methadone to buprenorphine, which can allow other suppressed emotions to come to the surface and be a potential time for relapse, and as such the warning signs and dangers of using illicit substances should be clearly discussed and the provision of take home naloxone should be made to further encourage the patient's safety.\n\nDuncan Hill and Apo Demirkol have no conflicts of interest to disclose. Victoria Hayes has received money from Camurus and Viiv for providing education and training sessions. Nicholas Lintzeris has served on Advisory Boards for Mundipharma, Indivior, GW Pharmaceuticals and Camurus, and has received funding for conducting research from Camurus.\n==== Refs\nREFERENCES\n\n1. Lintzeris N Mankabady B Rojas-Fernandez C Amick H . Strategies for transfer from methadone to buprenorphine for treatment for opioid use disorders and associated outcomes: a systematic review. J Addict Med 2022; 16 :143–151.\n2. Bishop B Gilmour J Deering D . Readiness and recovery: transferring between methadone and buprenorphine/naloxone for the treatment of opioid use disorder. Int J Ment Health Nurs 2019; 28 (1) :226–236.30019812\n3. Hill D Gardner D Baldacchino A . Comparing cognitive function in patients receiving chronic methadone or buprenorphine for opioid dependence: a systematic review. Heroin Addict Relat Clin Probl 2018; 20 (5) :35–49.\n4. New South Wales Clinical Guidelines: Treatment of Opioid Dependence – 2018. Available at: https://www.health.nsw.gov.au/aod/Publications/nsw-clinical-guidelines-opioid.pdf. Accessed August 6, 2020.\n5. National Guidelines for Medically Assisted Treatment of Opioid Dependence 2014. Available at: https://www.health.gov.au/sites/default/files/national-guidelines-for-medication-assisted-treatment-of-opioid-dependence.pdf. Accessed August 6, 2020.\n6. Wesson DR Ling W . The Clinical Opiate Withdrawal Scale (COWS). J Psychoactive Drugs 2003; 35 (2) :253–259.12924748\n7. Hill D Conroy S . Case note review – transfer of patient to buprenorphine from daily doses of methadone greater than 30 mg. Heroin Addict Relat Clin Probl 2014; 16 (1) :55–64.\n8. Conroy S Hill D . Transfer to buprenorphine from daily doses of methadone greater than 30 mg – initial review of transfers. Heroin Addict Relat Clin Probl 2013; 15 (3) :19–28.\n9. Cassells N Hill DR Marr E . Stewart E. Microdosing case study series – transferring from methadone to oral buprenorphine. Heroin Addict Relat Clin Probl. 2020 Dec 4. [Epub ahead of print]. Available at: https://www.heroinaddictionrelatedclinicalproblems.org/harcp-archives-doi-articles.php.\n10. De Aquino JP Fairgrieve C Klaire S Garcia-Vassallo G . Rapid transition from methadone to buprenorphine utilizing a micro-dosing protocol in the outpatient veteran affairs setting. J Addict Med 2020; 14 (5) :e271–e273.32011408\n11. Haemmig R Kemter A Strasser J . Use of micro-doses for induction of buprenorphine treatment with overlapping full opioid agonist use: the Bernese method. Subst Abuse Rehabil 2016; 7 :99–105.27499655\n12. Terasaki D Smith C Calcaterra SL . Transitioning hospitalised patients with opioid use disorder from methadone to buprenorphine without a period of opioid abstinence using a micro-dosing protocol. Pharmacotherapy 2019; 39 (10) :1023–1029.31348544\n13. Ling W Nadipelli VR Solem CT . Patient-centered outcomes in participants of a buprenorphine monthly depot (BUP-XR) double-blind, placebo-controlled, multicenter phase 3 study. J Addict Med 2019; 13 :442–449.30844878\n14. Ling W Nadipelli VR Aldridge AP . Recovery from opioid use disorder (OUD) after monthly long-acting buprenorphine treatment: 12-month longitudinal outcomes from RECOVER, an observational study. J Addict Med 2020; 14 (5) :e233–e240.32187112\n15. Frost M Bailey GL Lintzeris N Strang J . Long-term safety of a weekly and monthly subcutaneous buprenorphine depot (CAM 2038) in the treatment of adult out-patients with opioid use disorder. Addiction 2019; 114 (8) :1416–1426.31013390\n16. Lintzeris N Hayes V Arunogiri S . Interim guidance for the delivery of medication assisted treatment of opioid dependence in response to COVID-19: a national response. Available at: https://www.racp.edu.au/docs/default-source/news-and-events/covid-19/interim-guidance-delivery-of-medication-assisted-treatment-of-opiod-dependence-covid-19.pdf?sfvrsn=e36eeb1a_4. Accessed August 6, 2020.\n\n",
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{
"abstract": "BACKGROUND\nCurrent treatment combinations for chronic hepatitis C virus infection still include pegylated interferon and ribavirin despite the new therapeutic options available. Interferon-based treatments are associated with a high incidence of adverse effects. Central nervous system events are among the most frequent adverse drug reactions and their influence on treatment adherence and effectiveness is controversial.\n\n\nOBJECTIVE\nThe aim of the study was to evaluate neuropsychiatric adverse effects of interferon-based treatment for chronic hepatitis C in standard multidisciplinary clinical practice. Risk factors for these adverse effects and their impact on adherence and sustained viral response were also evaluated. Setting Ambulatory care pharmacy in coordination with the liver unit and the infectious diseases unit at a 650-bed tertiary university hospital.\n\n\nMETHODS\nWe included all consecutive patients with chronic hepatitis C who completed treatment with pegylated interferon and ribavirin between 2005 and 2013. All patients underwent a multidisciplinary follow-up during treatment.\n\n\nMETHODS\nNeuropsychiatric adverse effects were evaluated in relation to severity, management and outcome. The presence of anxiety and depression was evaluated by means of specific tests.\n\n\nRESULTS\nA total of 717 treatments in 679 patients were included. During treatment, we detected 1679 neuropsychiatric adverse effects in 618 patients (86.2 %), generating 1737 clinical interventions. Fifty-seven (3.3 %) neuropsychiatric adverse effects were severe and 2 (0.1 %) were life-threatening (suicidal attempts). Most neuropsychiatric adverse effects (1555 events, 92.6 %) resolved without sequelae. Psychiatric medication was required in 289 patients (40.3 %). Sustained viral response was achieved in 400 cases (55.8 %) and was associated with adherence (OR = 1.942, 95 % CI = 1.235-3.052, p = 0.004). A multivariate analysis did not show any relationship between neuropsychiatric adverse effects and treatment adherence or sustained viral response. A psychiatric history was a strong risk factor for depression, anxiety and other psychiatric disorders during treatment.\n\n\nCONCLUSIONS\nNeuropsychiatric adverse effects during interferon-based treatments in patients with chronic hepatitis C were common but mostly mild or moderate. Early detection and accurate multidisciplinary management avoided treatment discontinuation, ensuring adherence and attaining sustained viral response. The identified risk factors could be used to determine patients eligible for interferon-free combinations, thus optimizing health system economics.",
"affiliations": "Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain. [email protected].;Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain.;Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain.;Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Gastroenterology Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Infectious Diseases Department, Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.;Pharmaceutical Care Research Group, School of Pharmacy, University of Granada, Granada, Spain.;Pharmacy Department, Hospital de la Santa Creu i Sant Pau, Sant Antoni Mª Claret, 167, 08025, Barcelona, Spain.",
"authors": "Masip|Montserrat|M|;Tuneu|Laura|L|;Pagès|Neus|N|;Torras|Xavier|X|;Gallego|Adolfo|A|;Guardiola|Josep Maria|JM|;Faus|María José|MJ|;Mangues|Maria Antònia|MA|",
"chemical_list": "D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a",
"country": "Netherlands",
"delete": false,
"doi": "10.1007/s11096-015-0177-1",
"fulltext": null,
"fulltext_license": null,
"issn_linking": null,
"issue": "37(6)",
"journal": "International journal of clinical pharmacy",
"keywords": "Depression; Detection; Hepatitis C treatment; Multidisciplinary management; Neuropsychiatric adverse effects; Pegylated interferon alpha; Prevalence; Ribavirin; Spain",
"medline_ta": "Int J Clin Pharm",
"mesh_terms": "D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents; D004359:Drug Therapy, Combination; D005260:Female; D006304:Health Status; D019698:Hepatitis C, Chronic; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D008297:Male; D055118:Medication Adherence; D001523:Mental Disorders; D008875:Middle Aged; D011092:Polyethylene Glycols; D015995:Prevalence; D012367:RNA, Viral; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin; D012307:Risk Factors; D012720:Severity of Illness Index; D012737:Sex Factors",
"nlm_unique_id": "101554912",
"other_id": null,
"pages": "1143-51",
"pmc": null,
"pmid": "26267215",
"pubdate": "2015-12",
"publication_types": "D016428:Journal Article",
"references": "25373120;19730115;15669887;18721241;3961039;22098185;25911336;18266996;18752386;24955454;24204676;7007235;17014581;22878466;24951901;25359924;23811030;12407599;17988237;12850660;25143025;22760009;24331294;17668880;15581735;16086622;21907062;23808990;18097297;7249508;23803249;12324553;25778747;19691667;10764032;11072960;23172780",
"title": "Prevalence and detection of neuropsychiatric adverse effects during hepatitis C treatment.",
"title_normalized": "prevalence and detection of neuropsychiatric adverse effects during hepatitis c treatment"
} | [
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"literaturereference": "MASIP M, TUNEU L, PAGES N, TORRAS X, GALLEGO A, GUARDIOLA J, FAUS M AND MANGUES M. PREVALENCE AND DETECTION OF NEUROPSYCHIATRIC ADVERSE EFFECTS DURING HEPATITIS C TREATMENT. INTERNATIONAL JOURNAL OF CLINICAL PHARMACY 2015 AUG 13?37 (6):1143-1151.",
"literaturereference_normalized": "prevalence and detection of neuropsychiatric adverse effects during hepatitis c treatment",
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{
"abstract": "Chronic thromboembolic pulmonary hypertension is a potentially curable form of pre-capillary pulmonary hypertension (PH) resulting from incomplete resolution of pulmonary thromboemboli. We describe an 11-year-old boy with homozygous sickle cell disease with an indwelling catheter found to have severe PH on routine screening echocardiography. The diagnosis was confirmed by CT, ventilation-perfusion scintigraphy, and right heart catheterization. The patient was medically managed until undergoing pulmonary thromboendarterectomy with resolution of his PH. This case highlights the need for pediatric providers to be aware of this underdiagnosed form of PH, particularly for patients at high risk.",
"affiliations": "Division of Pediatric Cardiology, Morgan Stanley Children's Hospital, New York, NY, United States.;Division of Pediatric Cardiology, Arnold Palmer Hospital for Children, Orlando, FL, United States.;Division of Cardiothoracic Surgery, Columbia University Medical Center, New York, NY, United States.;Division of Pediatric Cardiology, Morgan Stanley Children's Hospital, New York, NY, United States.",
"authors": "Spencer|Robert|R|;Valencia Villeda|Gerson|G|;Takeda|Koji|K|;Rosenzweig|Erika B|EB|",
"chemical_list": null,
"country": "Switzerland",
"delete": false,
"doi": "10.3389/fped.2020.00363",
"fulltext": "\n==== Front\nFront Pediatr\nFront Pediatr\nFront. Pediatr.\nFrontiers in Pediatrics\n2296-2360 Frontiers Media S.A. \n\n10.3389/fped.2020.00363\nPediatrics\nCase Report\nChronic Thromboembolic Pulmonary Hypertension in a Child With Sickle Cell Disease\nSpencer Robert 1* Valencia Villeda Gerson 2 Takeda Koji 3 Rosenzweig Erika B. 1 1Division of Pediatric Cardiology, Morgan Stanley Children's Hospital, New York, NY, United States\n2Division of Pediatric Cardiology, Arnold Palmer Hospital for Children, Orlando, FL, United States\n3Division of Cardiothoracic Surgery, Columbia University Medical Center, New York, NY, United States\nEdited by: Junjie Xiao, Shanghai University, China\n\nReviewed by: Jochen Grohmann, University of Freiburg, Germany; Muhammad Ali Mumtaz, Baylor College of Medicine, United States\n\n*Correspondence: Robert Spencer [email protected] article was submitted to Pediatric Cardiology, a section of the journal Frontiers in Pediatrics\n\n\n24 7 2020 \n2020 \n8 36327 4 2020 01 6 2020 Copyright © 2020 Spencer, Valencia Villeda, Takeda and Rosenzweig.2020Spencer, Valencia Villeda, Takeda and RosenzweigThis is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Chronic thromboembolic pulmonary hypertension is a potentially curable form of pre-capillary pulmonary hypertension (PH) resulting from incomplete resolution of pulmonary thromboemboli. We describe an 11-year-old boy with homozygous sickle cell disease with an indwelling catheter found to have severe PH on routine screening echocardiography. The diagnosis was confirmed by CT, ventilation-perfusion scintigraphy, and right heart catheterization. The patient was medically managed until undergoing pulmonary thromboendarterectomy with resolution of his PH. This case highlights the need for pediatric providers to be aware of this underdiagnosed form of PH, particularly for patients at high risk.\n\npediatric cardiologypulmonary hypertensionCTEPH—chronic thromboembolic pulmonary hypertensionsickle cell diseasehematology\n==== Body\nIntroduction\nChronic thromboembolic pulmonary hypertension (CTEPH) is a distinct form of pulmonary hypertension (PH) that results from unresolved acute pulmonary embolism. The disease is caused by mechanical obstruction of the pulmonary arteries by chronic, fibrotic organized thrombi (1, 2). It is rarely diagnosed in children and has an unknown incidence in the general population (3–5).\n\nEarly diagnosis and treatment are critical, particularly because patients will develop severe PH and right heart failure. When recognized in a timely manner, the disease is often curable by pulmonary thromboendarterectomy (PTE) (6–9). We report an 11-year-old boy with sickle cell disease and an indwelling venous catheter found to have elevated right ventricular (RV) systolic pressure on routine echocardiography. Further workup led to the diagnosis of CTEPH, and he was successfully treated with PTE.\n\nCase\nAn 11-year-old boy with hemoglobin SS sickle cell disease (SCD) was referred to our hospital for further treatment of CTEPH. He had a history of multiple pain crises, acute chest syndrome, and acute ischemic strokes at ages 3 and 7 years. His SCD was further complicated by moyamoya syndrome, for which he underwent encephalodurosynangiosis at age 7 years. His hypercoagulability workup had been negative for antithrombin deficiency, protein C deficiency, protein S deficiency, factor V Leiden, plasminogen deficiency, and anticardiolipin antibodies.\n\nApproximately 10 months before his referral, routine screening transthoracic echocardiogram (TTE) revealed a right atrial (RA) thrombus thought to be related to his Broviac central venous catheter, which had been used for exchange transfusions. He was started on enoxaparin and his Broviac catheter was replaced. TTEs over the ensuing months demonstrated persistent RA thrombus without change in size, with normal RV pressure and normal biventricular systolic function.\n\nSeven months later, the patient was electively admitted to the referring institution in anticipation of a bone marrow transplant (BMT), at which time routine TTE showed an elevated RV systolic pressure (58 mmHg plus the RA pressure), a change from his previous echocardiograms. CT scan of the chest at that time revealed multiple bilateral lower lobe and left upper lobe pulmonary emboli. Clinically, he reported mild dyspnea on exertion and exercise intolerance for several weeks. Medical management was started with bosentan and the patient's enoxaparin dose was increased.\n\nFollow-up TTE performed 3 months later showed severe PH, with RV systolic pressure of 90 mmHg plus the RA pressure and a corresponding blood pressure of 108/52 mmHg. This raised suspicion for CTEPH, which was supported by a ventilation-perfusion (VQ) scan showing multiple areas of wedge-shaped mismatched perfusion defects consistent with chronic bilateral thromboembolic disease and secondary PH consistent with CTEPH. The following day, right heart catheterization demonstrated pulmonary arterial pressure of 80/35 mmHg with a mean of 52 mmHg, pulmonary capillary wedge pressure of 14 mmHg, cardiac index of 5.7 L/min/m2, and pulmonary vascular resistance index of 6.6 WUm2. Pulmonary angiography revealed multiple areas of abrupt tapering of the pulmonary arteries, confirming the diagnosis. The patient was switched from bosentan to macitentan and riociguat, and he was referred to our center for PTE.\n\nAt admission, his blood pressure was 116/72 mmHg, heart rate was 114 beats per minute, respiratory rate was 18 breaths per minute, and oxygen saturation was 97% on room air. The result of the physical examination was unremarkable. Quantitative hemoglobin S was abnormal at 13.5%, and NT-ProBNP was elevated at 880.0 pg/mL (normal range, 10.0–242.0 pg/mL). The results of the remaining laboratory tests, including coagulation tests, were normal.\n\nHe successfully underwent bilateral PTE and removal of a calcified organized thrombus from the right atrium (Figure 1) without reported intraoperative complications. Post-operative transesophageal echocardiography demonstrated an estimated RV systolic pressure of 32 mmHg plus the RA pressure in the setting of a systolic blood pressure of 110 mmHg, with mildly decreased RV function. Central venous pressure was maintained under 8 mmHg with a furosemide infusion to avoid reperfusion injury. PH medications were discontinued at the time of surgery. Ten days after the procedure, the patient was completely asymptomatic with normal oxygen saturation and was discharged home on long-term warfarin. Four months later, he successfully underwent BMT, after which he had weekly TTEs to monitor for the development of PH (10). As of 6 months following surgery, the patient has remained clinically asymptomatic without echocardiographic evidence of RV hypertension based on tricuspid regurgitant jet and systolic septal position.\n\nFigure 1 Right atrial thrombus (center) surrounded by pulmonary thromboendarterectomy specimens.\n\nDiscussion\nTo our knowledge, successful PTE in a child with CTEPH and SCD has not been reported in the MEDLINE database to date. Our patient was noted to have unexplained PH on routine screening echocardiography in the setting of a chronic hypercoagulable state and recent RA thrombus associated with a central venous catheter, and his diagnosis was confirmed by lung VQ scan and right heart catheterization. While a recently published case report described a 12-year-old with CTEPH successfully treated with PTE, that patient had severe comorbidities including paraplegia, and he was found to have factor V Leiden and antiphospholipid antibodies during his hypercoagulable workup (11).\n\nCTEPH is a rare and life-threatening condition that can result in progressive right-sided heart failure and death. It occurs as a result of unresolved thrombi obstructing the pulmonary arteries. The following criteria are used to make the diagnosis after 3 months of anticoagulant therapy: (1) mean pulmonary artery pressure >25 mmHg with a pulmonary capillary wedge pressure ≤ 15 mmHg, and (2) at least one (segmental) perfusion defect detected by lung scan, CT angiography, or pulmonary angiography (1, 2, 12).\n\nDespite increasing awareness of it, the disease remains underdiagnosed. Studies suggest an incidence of 0.56–3.2% in adult pulmonary embolism survivors, while incidence in the pediatric population is unknown (3–5). Of note, risk factors for thromboembolism are identified in the majority of children with CTEPH, and approximately one third of patients have a positive family history of thromboembolism or a known hypercoagulable state. Children with lupus anticoagulant and anticardiolipin antibodies are at the highest risk of the disease (9). Other risk factors include splenectomy, infected ventriculo-atrial shunts, thyroid replacement therapy, history of malignancy, chronic inflammatory conditions, and indwelling catheters (13).\n\nOur patient did not have a history of an acute pulmonary embolism. Nevertheless, he had several risk factors for CTEPH. Specifically, he had a history of homozygous SCD, which is recognized as a chronic hypercoagulable state with an increased risk of thromboembolic events and PH (14–17). He also had an indwelling catheter for monthly exchange transfusions and history of catheter-related RA thrombus. Homozygous SCD additionally confers a significant risk of autosplenectomy, for which the patient did not undergo sonographic assessment at our institution (18).\n\nBecause there are no pathognomonic signs or symptoms for CTEPH, the diagnosis is often delayed or missed. Patients may present with exertional dyspnea, exercise intolerance, and non-specific abnormalities on physical examination. As the disease progresses, there is a high risk of developing right heart failure. While the natural history of acute pulmonary embolism is near-complete resolution of emboli within 3–6 months, the persistence of any signs or symptoms after this duration of antithrombotic therapy warrants further investigation.\n\nDiagnostic workup begins with chest radiography, pulmonary function studies, an ECG, and an echocardiogram. If CTEPH is suspected, a lung VQ scan should assess for subsegmental or larger unmatched perfusion defects. Given its high sensitivity, a normal lung VQ scan can effectively rule out the disease, while an abnormal test result prompts further evaluation with right heart catheterization, catheter-based pulmonary angiography, CT pulmonary angiography, or MRI (1, 19, 20).\n\nThe first step in management is anticoagulant therapy. Our patient was initially on subcutaneous low molecular weight heparin, and he was later transitioned to an oral anticoagulant. Once the diagnosis was established, he was also started on targeted PH therapy, including macitentan, an endothelin receptor antagonist, and riociguat, a soluble guanylate cyclase stimulator, while awaiting definitive surgery. Riociguat was chosen because it has been shown to improve exercise capacity and pulmonary vascular resistance in patients with CTEPH, and because it is safe and well-tolerated in patients with SCD (21, 22).\n\nPTE is the treatment of choice for operable patients, and its success has been demonstrated in children (9, 23). To be considered operable, a patient must have sufficient surgically accessible thromboembolic material without extensive distal disease (24). Patients with SCD may have additional risks of the PTE, given the need for prolonged cardiopulmonary bypass, deep hypothermia, and intervals of circulatory arrest, factors that increase the likelihood of sickling (25). Balloon pulmonary angioplasty is an emerging option for inoperable CTEPH or patients with recurrent or persistent PH after PTE; however, this approach is rarely used in children and long-term results are lacking (26). In our case, a multidisciplinary team including pulmonary hypertension, cardiology, hematology, critical care, and cardiothoracic surgery specialists reviewed the patient's clinical data and elected to proceed with surgery, which the patient underwent without complication. Given the success of this case, it is important to consider CTEPH in any children with unexplained PH, particularly when risk factors are present.\n\nConclusions\nWe describe a rare case of CTEPH in a child with SCD and an indwelling catheter who was found to have unexplained PH. CTEPH is a rare and life-threatening disease. Unlike other forms of PH, it is potentially curable with PTE. For this reason, early recognition and treatment are critical. Practitioners should consider this diagnosis in patients with unexplained PH, particularly in patients with risk factors, including but not limited to those with a hypercoagulable state, a history of thromboembolism, or an indwelling catheter.\n\nEthics Statement\nParental informed consent was obtained for the publication of this case report.\n\nAuthor Contributions\nRS was the consulting cardiology fellow for the patient. GV was the referring cardiologist who diagnosed the patient and he contributed references and revisions to the manuscript. KT performed the patient's thromboendarterectomy and he contributed revisions to the manuscript. ER was the precepting attending for RS and she contributed references and revisions to the manuscript. All authors approved the final version.\n\nConflict of Interest\nThe authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\n\nWe acknowledge the contributions of the many physicians, nurses, and other staff members who cared for this patient but are not named as authors. Additionally, we thank the family for consenting to the publication of this work so that others might learn from this case.\n\nAbbreviations\nBMTbone marrow transplant\n\nCTEPHchronic thromboembolic pulmonary hypertension\n\nRAright atrial\n\nRVright ventricular\n\nPHpulmonary hypertension\n\nPTEpulmonary thromboendarterectomy\n\nSCDsickle cell disease\n\nTTEtransthoracic echocardiogram\n\nVQventilation-perfusion.\n==== Refs\nReferences\n1. Mahmud E Madani MM Kim NH Poch D Ang L Behnamfar O . Chronic thromboembolic pulmonary hypertension\n. J Am Coll Cardiol. (2018 ) 71 :2468 –86\n. 10.1016/j.jacc.2018.04.009 29793636 \n2. Lang IM Pesavento R Bonderman D Yuan JX-J . Risk factors and basic mechanisms of chronic thromboembolic pulmonary hypertension: a current understanding\n. Eur Respir J. (2013 ) 41 :462 –8\n. 10.1183/09031936.00049312 22700839 \n3. Ende-Verhaar YM Cannegieter SC Vonk Noordegraaf A Delcroix M Pruszczyk P Mairuhu ATA . Incidence of chronic thromboembolic pulmonary hypertension after acute pulmonary embolism: a contemporary view of the published literature\n. Eur Respir J. (2017 ) 49 :1601792 . 10.1183/13993003.01792-2016 28232411 \n4. Pengo V Lensing AWA Prins MH Marchiori A Davidson BL Tiozzo F . Incidence of chronic thromboembolic pulmonary hypertension after pulmonary embolism\n. N Engl J Med. (2004 ) 350 :2257 –64\n. 10.1056/NEJMoa032274 15163775 \n5. Gall H Hoeper MM Richter MJ Cacheris W Hinzmann B Mayer E . An epidemiological analysis of the burden of chronic thromboembolic pulmonary hypertension in the USA, Europe and Japan\n. Eur Respir Rev. (2017 ) 26 :160121 . 10.1183/16000617.0121-2016 28356407 \n6. Madani MM Auger WR Pretorius V Sakakibara N Kerr KM Kim NH . Pulmonary endarterectomy: recent changes in a single institution's experience of more than 2,700 patients\n. Ann Thor Surg. (2012 ) 94 :97 –103\n. 10.1016/j.athoracsur.2012.04.004 22626752 \n7. Klepetko W Mayer E Sandoval J Trulock EP Vachiery J-L Dartevelle P . Interventional and surgical modalities of treatment for pulmonary arterial hypertension\n. J Am Coll Cardiol. (2004 ) 43 :S73 –80\n. 10.1016/j.jacc.2004.02.039 15194182 \n8. Ishida K Masuda M Tanabe N Matsumiya G Tatsumi K Nakajima N . Long-term outcome after pulmonary endarterectomy for chronic thromboembolic pulmonary hypertension\n. J Thor Cardiovasc Surg. (2012 ) 144 :321 –6\n. 10.1016/j.jtcvs.2011.09.004 21992851 \n9. Madani MM Wittine LM Auger WR Fedullo PF Kerr KM Kim NH . Chronic thromboembolic pulmonary hypertension in pediatric patients\n. J Thor Cardiovasc Surg. (2011 ) 141 :624 –30\n. 10.1016/j.jtcvs.2010.07.010 20800245 \n10. Levy M Moshous D Szezepanski I Galmiche L Castelle M Lesage F . Pulmonary hypertension after bone marrow transplantation in children\n. Eur Respir J. (2019 ) 54 :1900612 . 10.1183/13993003.00612-2019 31649064 \n11. Verbelen T Cools B Fejzic Z Van Den Eynde R Maleux G Delcroix M . Pulmonary endarterectomy in a 12-year-old boy with multiple comorbidities\n. Pulm Circ. (2019 ) 9 :204589401988624 . 10.1177/2045894019886249 32284848 \n12. Moser KM Auger WR Fedullo PF . Chronic major-vessel thromboembolic pulmonary hypertension\n. Circulation. (1990 ) 81 :1735 –43\n. 10.1161/01.CIR.81.6.1735 2188751 \n13. Jenkins D Mayer E Screaton N Madani M . State-of-the-art chronic thromboembolic pulmonary hypertension diagnosis and management\n. Eur Respir Rev. (2012 ) 21 :32 –9\n. 10.1183/09059180.00009211 22379172 \n14. Anthi A Machado RF Jison ML Taveira-DaSilva AM Rubin LJ Hunter L . Hemodynamic and functional assessment of patients with sickle cell disease and pulmonary hypertension\n. Am J Respir Crit Care Med. (2007 ) 175 :1272 –9\n. 10.1164/rccm.200610-1498OC 17379852 \n15. Gordeuk VR Castro OL Machado RF . Pathophysiology and treatment of pulmonary hypertension in sickle cell disease\n. Blood. (2016 ) 127 :820 –8\n. 10.1182/blood-2015-08-618561 26758918 \n16. Lim MY Ataga KI Key NS . Hemostatic abnormalities in sickle cell disease:\n\nCurr Opin Hematol . (2013 ). 20 :472 –7\n. 10.1097/MOH.0b013e328363442f 23817169 \n17. Parent F Lionnet F Habibi A Adnot S O'Callaghan DS Galacteros F . A hemodynamic study of pulmonary hypertension in sickle cell disease\n. N Engl J Med . (2011 ) 365 :44 –53\n. 10.1056/NEJMoa1005565 21732836 \n18. Jais X . Splenectomy and chronic thromboembolic pulmonary hypertension\n. Thorax. (2005 ) 60 :1031 –4\n. 10.1136/thx.2004.038083 16085731 \n19. Lang IM Madani M . Update on chronic thromboembolic pulmonary hypertension\n. Circulation. (2014 ) 130 :508 –18\n. 10.1161/CIRCULATIONAHA.114.009309 25092279 \n20. Lammers AE Apitz C Zartner P Hager A Dubowy K-O Hansmann G . Diagnostics, monitoring and outpatient care in children with suspected pulmonary hypertension/paediatric pulmonary hypertensive vascular disease. Expert consensus statement on the diagnosis treatment of paediatric pulmonary hypertension. The European Paediatric Pulmonary Vascular Disease Network, endorsed by ISHLT DGPK\n. Heart . (2016 ). 102 (Suppl. 2 ):ii1 –13\n. 10.1136/heartjnl-2015-307792 27053692 \n21. Ghofrani H-A D'Armini AM Grimminger F Hoeper MM Jansa P Kim NH . Riociguat for the treatment of chronic thromboembolic pulmonary hypertension\n. N Engl J Med. (2013 ) 369 :319 –29\n. 10.1056/NEJMoa1209657 23883377 \n22. Weir NA Conrey A Lewis D Mehari A . Riociguat use in sickle cell related chronic thromboembolic pulmonary hypertension: a case series\n. Pulm Circ. (2018 ) 8 :204589401879180 . 10.1177/2045894018791802 30033820 \n23. Kumbasar U Aypar E Karagöz T Demircin M Dogan R . Pulmonary thromboendarterectomy in pediatric patients: report of three cases\n. Turk J Pediatr. (2018 ) 60 :604 –7\n. 10.24953/turkjped.2018.05.023 30968628 \n24. Pepke-Zaba J Delcroix M Lang I Mayer E Jansa P Ambroz D . Chronic thromboembolic pulmonary hypertension (CTEPH): results from an international prospective registry\n. Circulation. (2011 ) 124 :1973 –81\n. 10.1161/CIRCULATIONAHA.110.015008 21969018 \n25. Yung GL Channick RN Fedullo PF Auger WR Kerr KM Jamieson SW . Successful pulmonary thromboendarterectomy in two patients with sickle cell disease\n. Am J Respir Crit Care Med. (1998 ) 157 :1690 –3\n. 10.1164/ajrccm.157.5.9710032 9603156 \n26. Lang I Meyer BC Ogo T Matsubara H Kurzyna M Ghofrani H-A . Balloon pulmonary angioplasty in chronic thromboembolic pulmonary hypertension\n. Eur Respir Rev. (2017 ) 26 :160119 . 10.1183/16000617.0119-2016 28356406\n\n",
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"abstract": "Buschke-Lowenstein tumor is a rare form of low-grade penile cancer. Its low prevalence amongst the population bars the establishment of a standardized treatment algorithm. We present a case of BLT that was managed with neoadjuvant chemotherapy followed by phallic sparing surgery.",
"affiliations": "St. George's, University of London, UK.;Marshall University, Joan C. Edwards School of Medicine, USA.;Marshall University, Joan C. Edwards School of Medicine, USA.",
"authors": "El Khoury|Anthony|A|;Jensen|James C|JC|;Pacioles|Tony|T|",
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"fulltext": "\n==== Front\nUrol Case RepUrol Case RepUrology Case Reports2214-4420Elsevier S2214-4420(19)30516-910.1016/j.eucr.2019.101111101111OncologyNeoadjuvant chemotherapy and penile conservation in the management of Buschke – Lowenstein tumor, a case report El Khoury Anthony [email protected]@gmail.comab∗Jensen James C. MDbcPacioles Tony MDbca St. George's, University of London, UKb Marshall University, Joan C. Edwards School of Medicine, USAc Edwards Comprehensive Cancer Center, USA∗ Corresponding author. St. George's, University of London, Marshall University, Joan C. Edwards School of Medicine, 607 22nd Street Apt. 1427, Huntington, WV, 25703, USA. [email protected]@gmail.com23 12 2019 3 2020 23 12 2019 29 1011116 12 2019 17 12 2019 20 12 2019 © 2019 Published by Elsevier Inc.2019This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).Buschke-Lowenstein tumor is a rare form of low-grade penile cancer. Its low prevalence amongst the population bars the establishment of a standardized treatment algorithm. We present a case of BLT that was managed with neoadjuvant chemotherapy followed by phallic sparing surgery.\n\nKeywords\nBuschke-Lowenstein tumorPenile cancerPenile surgeryNeoadjuvant chemotherapyQuality of life\n==== Body\nIntroduction\nBuschke-Lowenstein Tumor, also known as Giant Condyloma Acuminatum is a rare form of sexually transmitted disease that affecting the anogenital region. BLT is an aggressive locally invading tumor that grows in a wart-like fashion.1 This tumor is recognized as a form of ano-rectal cancer due to its heterogeneous but low grade, rapid local growth, and features that resemble squamous cell carcinoma.2 The disease is more prevalent in men, and risk factors include smoking, having an uncircumcised penis, first sexual experience at the of 16 or less.3Treatment of BLT varies based on size at presentation, local invasion, and patient preferences. In men, proposed treatments are local radiation therapy, topical chemotherapy with Imiquimod or 5-Fluorouracil, and lesion excision and radical penectomy. This strategy is consistent with the treatment strategy of carcinoma of the penis.4 Surgical resection, the preferred treatment modality. The rarity of the tumor prevents the establishment of a treatment algorithm.5 We present a case of BLT that was treated with neoadjuvant chemotherapy and multiple local excision with phallic preservation and skin grafting.\n\nCase report\n39-year-old white male with a history of tobacco smoking and polysubstance abuse presents to the clinic with a large lesion on the penis and scrotum, after being pulled over by a police officer who was suspicious of a large bulge in his pants. Physical examination shows a large cauliflower-like mass that is consistent with a BLT (Fig. 1). Treatment options were explained to the patient and an excisional biopsy was scheduled for pathological diagnosis. CT-KUB shows bilateral lymphadenopathy.Fig. 1 Tumor on initial physical examination displaying cauliflower-like growth.\n\nFig. 1\n\nBiopsy of the specimen was taken and found to be consistent with verrucous carcinoma of the penis. Surgical debulking vs primary chemotherapy was considered. Due to the complexity of the case, the patient was scheduled for neoadjuvant chemotherapy TIP (paclitaxel-ifosfamide-cisplatin) and surgical debulking. The mass was resected from the penis and the scrotum with roughly negative margins. Hemostasis was difficult to achieve due to the high vascularization of the tumor. A particularly challenging area was below the corona in the frenular area as the mass was tightly adherent to the urethra elevating the risk of urethral entry.\n\nPatient was brought back for secondary debridement of the distal left and right coronal margins, the peripheral margin, and the deep scrotal margin. The operation was carried to conserve the shaft and reconstruct the penis with an autografted flap (Fig. 2). Patient is currently s/p 4 cycles of TIP therapy and 3 separate procedures for excision of recurrent lesions. Pathology of recurrent lesions is consistent with condyloma acuminata is negative for high-grade verrucous carcinoma. Patient complained of the following side effects while receiving chemotherapy: weight loss, anorexia, nausea, arthralgias, and neuropathy of the lower extremities.Fig. 2 Patient status post chemical debulking, resection, and skin grafting. Recurrent condyloma acuminatum excised (circled area).\n\nFig. 2\n\nPatient reports painful erections and is under a pain management program.\n\nDiscussion\nManagement of BLT is not a straightforward process. BLT is characterized by it being a low-grade tumor. That, coupled with the sensitivity of the subject of male genitalia, makes the “obvious” choice of a radical penectomy not always suitable as a management plan as it highly impacts quality of life. Although the rarity of the tumor does not allow for a generalized management guideline and algorithm, the delicacy and high-risk of tumor resection with penile conservation is not prevalent practice. BLT is highly vascular and its erratic and rapid growth makes it difficult to manipulate intra-operatively and substantially increases surgical risks such as bleeding and urethral penetration.\n\nLike most patients, our patient wanted to fight for penile preservation. Their quality of life had been heavily impacted by the tumor especially since they had not experienced intimacy with their partners for years, due to their medical condition. Patient preferences are an important consideration when it comes to management plans and that principle is widely recognized amongst healthcare practitioners. It is therefore important to explore management plans that although impose a higher risk, would yield outcomes that are satisfactory to the patient and that would not contribute to a deterioration of the patient's quality of life.\n\nThe target of surgical resection is to resect a tumor with negative margins, in order to limit the possibilities of local invasion, recurrence, and distal spread. Neoadjuvant chemotherapy allowed us to achieve medical tumor shrinkage which lead to a safer debulking procedure. We therefore recommend neoadjuvant chemotherapy prior to tumor debulking when considering phallic-sparing surgery in the management of BLT. Consistent follow-up is required to ensure the absence of tumor recurrence.\n\nAuthor contributions\nDr. James C. Jensen: urologist.\n\nDr. Toni Pacioles: lead medical oncologist.\n\nMr. Anthony El Khoury: 4th year medical student, data gathering and manuscript development.\n\nFunding\nNo funding was allocated for the development of this care report.\n\nConsent\nThe patient has provided consent to the authors for the publication of this case report.\n\nDeclaration of competing interest\nThe authors have no conflicts of interest to declare.\n\nAppendix A Supplementary data\nThe following is the Supplementary data to this article:Multimedia component 1\nMultimedia component 1 \n\nAppendix A Supplementary data to this article can be found online at https://doi.org/10.1016/j.eucr.2019.101111.\n==== Refs\nReferences\n1 Talwar A. Puri N. Singh M. Giant condyloma acuminatum of Buschke and Löwenstein: successful surgical treatment Int J STD AIDS 21 6 2010 446 448 20606229 \n2 Chu Q.D. Vezeridis M.P. Libbey N.P. Giant condyloma acuminatum (Buschke-Lowenstein tumor) of the anorectal and perianal regions Dis Colon Rectum 37 950 1994 \n3 Venter F. Giant condylomata acuminata of Buschke-Lowenstein associated with paraneoplastic hypercalcemia J Investig. Med. High Impact Case Rep 2018 \n4 Fishman M.N. Clinical scenarios for neoadjuvant chemotherapy of squamous penile cancer that is clinically node positive Transl Androl Urol 6 5 2017 839 847 24 July 29184781 \n5 Nelson Montana Giant condyloma acuminatum (Buschke-Lowenstein tumor). Series of seven cases and review of the literature Rev Chil Radiol 20 2 2014 57 63\n\n",
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],
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},
{
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},
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] |
{
"abstract": "Use of non-vitamin K antagonist oral anticoagulants (NOACs), including dabigatran etexilate, rivaroxaban, apixaban, edoxaban or betrixaban provides a safe and convenient alternative to the traditional anticoagulation with vitamin K antagonists or heparin derivatives. Many patients receiving long-term seizure prophylaxis with antiepileptic drugs (AEDs) may require anticoagulation with NOACs. Providers caring for these patients need to be informed about potential interactions between AEDs and NOACs and the relevant clinical consequences. A systematic review of the existing literature was conducted to elucidate current knowledge on the clinically relevant interactions between AEDs and NOACs and highlight areas in which further research is needed. The systematic review protocol was developed using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidance. Ovid MEDLINE, Embase, The Cochrane Library and SciFinder were searched. Of the 630 non-duplicate items identified by the search, 13 met eligibility criteria. These 13 items included 8 case reports, 2 letters to the editor and 3 nonrandomized studies. The majority of pharmacokinetic interactions between NOACs and first generation AEDs occurred via the induction of the hepatic enzyme system and competition for the P-glycoprotein transporter and lead to decreased NOAC plasma levels and consequent thrombotic events. Only one article, a case report, was identified that focused on interactions between the second generation AED and a NOAC. At the present time, the limited evidence suggests that enzyme-inducing or inhibiting AEDs reduce the effectiveness of anticoagulation produced by several NOACs. This information may help providers anticipate possible interactions and guide therapy appropriately.",
"affiliations": "Department of Neurological Sciences, University of Nebraska Medical Center, 988435 Nebraska Medical Center, Omaha, NE, 68198-8435, USA. Electronic address: [email protected].;Department of Neurology, University of Kentucky, KY Clinic, J-401, Lexington, KY, 40536-0284, USA. Electronic address: [email protected].;McGoogan Library of Medicine, University of Nebraska Medical Center, 986705 Nebraska Medical Center, Omaha, NE, 68198-6705, USA. Electronic address: [email protected].;Department of Neurological Sciences, University of Nebraska Medical Center, 988435 Nebraska Medical Center, Omaha, NE, 68198-8435, USA. Electronic address: [email protected].;Department of Neurological Sciences, University of Nebraska Medical Center, 988435 Nebraska Medical Center, Omaha, NE, 68198-8435, USA. Electronic address: [email protected].",
"authors": "Taha|Mohamed|M|;Li|Wenyang|W|;Schmidt|Cynthia M|CM|;Gonzalez-Castellon|Marco|M|;Taraschenko|Olga|O|",
"chemical_list": "D000925:Anticoagulants; D000927:Anticonvulsants",
"country": "Netherlands",
"delete": false,
"doi": "10.1016/j.eplepsyres.2020.106304",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0920-1211",
"issue": "162()",
"journal": "Epilepsy research",
"keywords": "Anti-epileptic drugs; Non-vitamin K antagonist anticoagulants (NOAC); Novel anticoagulants; Seizures; Systematic review; oral anticoagulation",
"medline_ta": "Epilepsy Res",
"mesh_terms": "D000284:Administration, Oral; D000925:Anticoagulants; D000927:Anticonvulsants; D004347:Drug Interactions; D004827:Epilepsy; D006801:Humans",
"nlm_unique_id": "8703089",
"other_id": null,
"pages": "106304",
"pmc": null,
"pmid": "32155540",
"pubdate": "2020-05",
"publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't; D000078182:Systematic Review",
"references": null,
"title": "The interactions between anticonvulsants and non-vitamin K antagonist oral anticoagulant agents: A systematic review.",
"title_normalized": "the interactions between anticonvulsants and non vitamin k antagonist oral anticoagulant agents a systematic review"
} | [
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"literaturereference": "TAHA M, LI W, SCHMIDT CM, GONZALEZ-CASTELLON M, ET.AL. THE INTERACTIONS BETWEEN ANTICONVULSANTS AND NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANT AGENTS: A SYSTEMATIC REVIEW. EPILEPSY RESEARCH. 2020?162:106304",
"literaturereference_normalized": "the interactions between anticonvulsants and non vitamin k antagonist oral anticoagulant agents a systematic review",
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},
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{
"abstract": "A 45-year-old female who presented with loss of consciousness and a cold sweat was found to have a pancreatic tumor and multiple liver metastases. Laboratory studies showed marked hypoglycemia and inappropriately elevated serum insulin, C-peptide, and serum tumor markers. Fine needle aspiration revealed Grade 3 small-cell type primary pancreatic neuroendocrine carcinoma. Consequently, the diagnosis of malignant insulinoma was made. Transarterial embolization (TAE) for hepatic metastases resulted in the reduction of tumor volume and prompt resolution of hypoglycemic attacks, whereas diazoxide and systemic chemotherapy had been ineffective for controlling blood glucose levels, and octreotide was unavailable due to the allergic effect. This case report highlights the potential usefulness of TAE for malignant insulinomas in the management of hypoglycemia.",
"affiliations": "Department of Gastroenterology and Hepatology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8558, Japan.",
"authors": "Muro|Shinichiro|S|;Nasu|Junichiro|J|;Harada|Ryo|R|;Matsubara|Minoru|M|;Nakarai|Asuka|A|;Kanzaki|Hiromitsu|H|;Tsutsumi|Kouichiro|K|;Kato|Hironari|H|;Tanaka|Takehiro|T|;Fujiwara|Hiroyasu|H|;Uno|Masatoshi|M|;Okada|Hiroyuki|H|;Yamamoto|Kazuhide|K|",
"chemical_list": "D001786:Blood Glucose; D007328:Insulin",
"country": "Japan",
"delete": false,
"doi": "10.18926/AMO/52900",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0386-300X",
"issue": "68(5)",
"journal": "Acta medica Okayama",
"keywords": null,
"medline_ta": "Acta Med Okayama",
"mesh_terms": "D001786:Blood Glucose; D004358:Drug Therapy; D004621:Embolization, Therapeutic; D017809:Fatal Outcome; D005260:Female; D006499:Hepatic Artery; D006801:Humans; D007003:Hypoglycemia; D007328:Insulin; D007340:Insulinoma; D008113:Liver Neoplasms; D008875:Middle Aged; D018358:Neuroendocrine Tumors; D010190:Pancreatic Neoplasms; D016896:Treatment Outcome",
"nlm_unique_id": "0417611",
"other_id": null,
"pages": "303-6",
"pmc": null,
"pmid": "25338488",
"pubdate": "2014",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Prompt resolution of hypoglycemia by hepatic transarterial embolization for malignant insulinoma with multiple liver metastases.",
"title_normalized": "prompt resolution of hypoglycemia by hepatic transarterial embolization for malignant insulinoma with multiple liver metastases"
} | [
{
"companynumb": "PHHY2014JP165254",
"fulfillexpeditecriteria": "1",
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{
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"drugindication": "PANCREATIC CARCINOMA",
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"reaction": [
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"reactionmeddraversionpt": "20.0",
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},
{
"reactionmeddrapt": "Fungal infection",
"reactionmeddraversionpt": "20.0",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Metastases to liver",
"reactionmeddraversionpt": "20.0",
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},
{
"reactionmeddrapt": "Hypersensitivity",
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},
{
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}
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"literaturereference": "MURO S, NASU J, HARADA R, MATSUBARA M, NAKARAI A, KNAZAKI H ET. AL. PROMPT RESOLUTION OF HYPOGLYCEMIA BY HEPATIC TRANSARTERIAL EMBOLIZATION FOR MALIGNANT INSULINOMA WITH MULTIPLE LIVER METASTASES. ACTA MED. OKAYAMA. 2014;68(5):307-311",
"literaturereference_normalized": "prompt resolution of hypoglycemia by hepatic transarterial embolization for malignant insulinoma with multiple liver metastases",
"qualification": "3",
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},
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},
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"transmissiondate": "20170829"
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{
"abstract": "To evaluate the functional and anatomical results of patients with non-infectious intraocular inflammation (IOI) following intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection for the treatment of neovascular age-related macular degeneration (nAMD).\n\n\n\nThe medical records of patients receiving anti-VEGF treatment for nAMD between January 2015 and March 2019 were retrospectively analyzed. Preoperative and postoperative routine ophthalmological examinations, central macular thickness, duration of inflammation, and follow-up time of the patients with non-infectious IOI following anti-VEGF injection were recorded.\n\n\n\nNon-infectious IOI was determined in 13 eyes (11 eyes with aflibercept, 2 eyes with ranibizumab) of 1,966 patients who received a total of 12,652 anti-VEGF (4,796 aflibercept and 7,856 ranibizumab) injections. IOI was detected after a mean of 7 injections (2-12 injections). All eyes had both anterior chamber reaction (Tyndall +1/+3) and vitritis (grade 1-3). None of the patients had pain, hypopyon, or fibrin reaction. Visual acuity progressed to baseline levels within 28.3 days. Vitritis continued with a mean of 40 days. All patients recovered with topical steroid therapy. In 11 eyes, injection of the same anti-VEGF agent was continued. No recurrence of IOI was observed in any patients.\n\n\n\nNon-infectious IOI following intravitreal anti-VEGF injection typically occurs without pain, conjunctival injection, hypopyon, or fibrin and responds well to topical steroid therapy. Visual acuity returns to baseline levels within weeks according to the severity of inflammation.",
"affiliations": "Dokuz Eylül University Faculty of Medicine, Department of Ophthalmology, İzmir, Turkey.;Dokuz Eylül University Faculty of Medicine, Department of Ophthalmology, İzmir, Turkey.;Dokuz Eylül University Faculty of Medicine, Department of Ophthalmology, İzmir, Turkey.;Dokuz Eylül University Faculty of Medicine, Department of Ophthalmology, İzmir, Turkey.;Dokuz Eylül University Faculty of Medicine, Department of Ophthalmology, İzmir, Turkey.",
"authors": "Kaya|Mahmut|M|0000-0001-6255-3020;Öner|Ferit Hakan|FH|0000-0003-3310-8803;Akbulut Yağcı|Betül|B|0000-0002-0608-9195;Ataş|Ferdane|F|0000-0002-6743-1142;Öztürk|Taylan|T|0000-0001-6633-0553",
"chemical_list": null,
"country": "Turkey",
"delete": false,
"doi": "10.4274/tjo.galenos.2020.84042",
"fulltext": "\n==== Front\nTurk J Ophthalmol\nTurk J Ophthalmol\nTJO\nTurkish Journal of Ophthalmology\n2149-8695\n2149-8709\nGalenos Publishing\n\n33631912\n10.4274/tjo.galenos.2020.84042\n44757\nOriginal Article\nNon-infectious Intraocular Inflammation Following Intravitreal Anti-Vascular Endothelial Growth Factor Injection\nKaya Mahmut 1*https://orcid.org/0000-0001-6255-3020\n\nÖner Ferit Hakan 1https://orcid.org/0000-0003-3310-8803\n\nAkbulut Yağcı Betül 1https://orcid.org/0000-0002-0608-9195\n\nAtaş Ferdane 1https://orcid.org/0000-0002-6743-1142\n\nÖztürk Taylan 1https://orcid.org/0000-0001-6633-0553\n\n1 Dokuz Eylül University Faculty of Medicine, Department of Ophthalmology, İzmir, Turkey\n* Address for Correspondence: Dokuz Eylül University Faculty of Medicine, Department of Ophthalmology, İzmir, Turkey Phone: +90 505 525 22 16 E-mail:[email protected]\n1 2021\n25 2 2021\n51 1 3237\n11 4 2020\n16 7 2020\n© Copyright 2021 by Turkish Ophthalmological Association | Turkish Journal of Ophthalmology, published by Galenos Publishing House.\n2021\nThis is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.\nObjectives:\n\nTo evaluate the functional and anatomical results of patients with non-infectious intraocular inflammation (IOI) following intravitreal anti-vascular endothelial growth factor (anti-VEGF) injection for the treatment of neovascular age-related macular degeneration (nAMD).\n\nMaterials and Methods:\n\nThe medical records of patients receiving anti-VEGF treatment for nAMD between January 2015 and March 2019 were retrospectively analyzed. Preoperative and postoperative routine ophthalmological examinations, central macular thickness, duration of inflammation, and follow-up time of the patients with non-infectious IOI following anti-VEGF injection were recorded.\n\nResults:\n\nNon-infectious IOI was determined in 13 eyes (11 eyes with aflibercept, 2 eyes with ranibizumab) of 1,966 patients who received a total of 12,652 anti-VEGF (4,796 aflibercept and 7,856 ranibizumab) injections. IOI was detected after a mean of 7 injections (2-12 injections). All eyes had both anterior chamber reaction (Tyndall +1/+3) and vitritis (grade 1-3). None of the patients had pain, hypopyon, or fibrin reaction. Visual acuity progressed to baseline levels within 28.3 days. Vitritis continued with a mean of 40 days. All patients recovered with topical steroid therapy. In 11 eyes, injection of the same anti-VEGF agent was continued. No recurrence of IOI was observed in any patients.\n\nConclusion:\n\nNon-infectious IOI following intravitreal anti-VEGF injection typically occurs without pain, conjunctival injection, hypopyon, or fibrin and responds well to topical steroid therapy. Visual acuity returns to baseline levels within weeks according to the severity of inflammation.\n\nAnti-VEGF\nintraocular inflammation\ntopical steroid\nvitritis\n==== Body\nIntroduction\n\nNon-infectious intraocular inflammation (IOI) is an acute, sterile inflammation that is not associated with an infectious agent and resolves without intravitreal antibiotic therapy. It occurs as a rare complication of intravitreal pharmacological agents.1 As more intravitreal injections are performed, the number of such side effects is also increasing.1,2 Non-infectious IOI has been reported in response to all anti-vascular endothelial growth factor (anti-VEGF) drugs 1,3,4,5,6,7,8,9,10,11, triamcinolone 12,13, and ocriplasmin.14 It typically occurs within a few days after injection, manifesting with visual impairment and vitritis without conjunctival injection and substantial pain.3 The reported incidence ranges from 0.09% to 0.55%.1,8,9,10,11\n\nThe aim of this study was to evaluate the frequency, characteristics, treatment, and functional and anatomical outcomes of non-infectious IOI after intravitreal anti-VEGF injection in patients with wet age-related macular degeneration (AMD).\n\nMaterials and Methods\n\nThe medical records of 1966 patients who received intravitreal anti-VEGF (ranibizumab or aflibercept) injection for wet AMD in the retina unit of Dokuz Eylül University Department of Ophthalmology between January 2015 and March 2019 were retrospectively reviewed. The patients received a total of 12652 doses of anti-VEGF, and non-infectious IOI was detected in 13 eyes.\n\nThe study was conducted in accordance with the ethical standards stated in the Declaration of Helsinki after obtaining approval from the Dokuz Eylül University Ethics Committee. Patients aged 50 years and older who had wet AMD, were under ongoing anti-VEGF therapy and follow-up in our clinic, and were followed for at least 6 months were included in the study. Patients who did not receive the full anti-VEGF loading dose and those who had diabetes mellitus, uveitis, or history of ocular surgery in the last 6 months (cataract, glaucoma surgery) were excluded.\n\nAll anti-VEGF injections were performed under topical anesthesia with 0.5% proparacaine hydrochloride (Alcaine®, Alcon Laboratories Inc, Fort Worth, TX, USA) in the operating room under sterile conditions. Before the procedure, mydriasis was induced using 2.5% phenylephrine hydrochloride (Mydfrin®, Alcon Laboratories Inc, Fort Worth, TX, USA), 0.5% tropicamide (Tropamid®, Bilim Pharmaceuticals, Istanbul, Turkey), and 1% cyclopentolate hydrochloride (Sikloplejin®, Abdi İbrahim Pharmaceuticals, İstanbul, Turkey). Before injection, 5% povidone iodine was instilled in the lower fornix and left for at least 5 minutes. After cleaning the periocular skin and eyelids with 10% povidone iodine solution, a sterile eye drape was placed over the area and the eyelids were retracted using a blepharostat. Using a 30-gauge (G) needle, 0.05 ml of 0.5 mg ranibizumab or 2 mg aflibercept was administered in the superotemporal quadrant at a distance of 4.0 mm from the limbus in phakic eyes and 3.5 mm from the limbus in pseudophakic eyes. After administering the intravitreal injection, pressure was applied to the injection site with a sterile cotton-tip applicator while withdrawing the needle to prevent drug reflux and vitreous prolapse. Following injection, 5% povidone iodine was applied to the ocular surface. Patients were prescribed 0.3% ofloxacin (Exocin®, Allergan Pharmaceuticals Inc, Dublin, Ireland) eye drops and 1% fusidic acid (Fucithalmic®, Abdi İbrahim Pharmaceuticals, Istanbul, Turkey) viscous eye drops 6 times a day for 5 days. They were advised to present to our clinic immediately if they experienced vision loss, hyperemia, light sensitivity, or severe pain after the injection. Evaluations were performed at post-injection day 1, day 15, and day 30.\n\nFrom the records of patients who developed non-infectious IOI after intravitreal anti-VEGF injection, the following data were recorded in detail: best corrected visual acuity (BCVA) measured during the inflammation; presence of conjunctival hyperemia and cells, lens status, and presence of cells in the anterior vitreous on slit-lamp examination; and the presence of vitritis, optic disc and macula findings, peripheral retinal findings, and vascular changes observed in fundus examination. In addition, colored fundus photographs (Visucam 500®, Zeiss, Germany) and macular thicknesses measured from spectral domain-optical coherence tomography ([SD-OCT]; Spectralis OCT®, Heidelberg Engineering, Heidelberg, Germany) obtained during routine examination were recorded from the SD-OCT archive for all patients. After intravitreal anti-VEGF injection, color fundus photographs were obtained only for patients who developed choroidal neovascularization activation or complications/adverse effects. Non-infectious IOI was diagnosed according to the definition on the American Society of Retina Specialists website (https://www.asrs.org/) in the presence of blurred vision and only anterior chamber cells, vitreous cells, or mild fibrous opacity in the vitreous, in the absence of pain, hyperemia, severe vision loss, hypopyon, fibrin reaction, or retinitis focus. These eyes were treated with topical 1% prednisolone acetate (Pred Forte®, Allergan Inc, Dublin, Ireland) and follow-up was continued until complete clinical resolution was observed. Based on clinical severity, follow-up examinations were performed every other day for the first week. After the first week, follow-up intervals were extended according to the patient’s clinical presentation.\n\nStatistical Analysis\n\nAll patient data were recorded in the IBM SPSS Statistics (version 24.0, IBM Corp, Armonk, NY, USA) software package and statistical analyses were performed using paired t-test. The results are presented as mean ± standard deviation, and a p-value <0.05 was considered statistically significant.\n\nResults\n\nOf the 12652 anti-VEGF injections administered for wet AMD, 4796 were aflibercept and 7856 were ranibizumab. Non-infectious IOI was detected in a total of 13 eyes of 13 patients. Therefore, the incidence of non-infectious IOI per injection was 0.1% (13/12,652) and the incidence per patient was 0.66% (13/1,966). Nine (69.2%) of the 13 patients with IOI were male and 4 (30.8%) were female. The patients’ characteristics are summarized in Table 1. The median age was 73 (51-86) years. Nine eyes (69.2%) were pseudophakic. Non-infectious IOI occurred after ranibizumab in 2/7856 eyes (0.02%) and after aflibercept in 11/4796 eyes (0.2%). Median time to presentation to our clinic was 11 (4-21) days. None of the patients had IOI on postoperative day 1. Six patients (46.2%) presented to our clinic with complaints of blurred vision in the first 10 days after the procedure, while in the other 7 patients (53.8%) IOI was detected during routine follow-up examination at 2 weeks. When the patients’ symptoms were examined, we found that 13 patients (100%) had blurred vision, 5 patients (38.5%) had floaters, and 3 patients (23.1%) had photophobia. In wet AMD patients on ongoing anti-VEGF therapy, non-infectious IOI was detected after a median of 7 (2-12) injections.\n\nAccording to the patients’ medical records, it was determined that all patients had anterior chamber reaction (Tyndall +1 to +3) and vitritis (grade 1-3) (Figure 1A, B). Hypopyon and fibrin reactions were not observed in any of the eyes (Table 2). The median pre-injection visual acuity of the patients was 0.4 (0.1-0.7; ≤0.1 in 23.1% [3/13]; Snellen chart) and the median visual acuity with IOI was 0.2 (0.05-0.5; ≤0.1 in 30.8% [4/13]). After inflammation resolved, the median visual acuity was 0.5 (0.1-0.7; ≤0.1 in 7.7% [1/13]). We observed that BCVA was significantly reduced during IOI, then increased significantly compared to the inflammation period (p<0.0001). According to the patients’ SD-OCT archives, the median central macular thickness (CMT) before injection was 322 (226-398) µm. The median CMT was 276 (203-370) µm during inflammation and 235 (181-306) µm after the regression of inflammatory findings (Figure 1C, D). Changes in mean CMT due to IOI were not statistically significant compared to pre-injection (p=0.120).\n\nIn one patient, a vitreous sample had been obtained during follow-up due to grade 2 vitritis and a white opacity in the vitreous (Patient 2, Figure 2A, B, C). Upon detailed review of the patient’s records, we determined that the eye had been treated with intravitreal 1 mg/0.1 mL vancomycin, 2.25 mg/0.1 mL ceftazidime, and 0.4 mg/0.1 mL dexamethasone injections for presumed infectious endophthalmitis. However, no etiological agent was detected in vitreous culture or direct microscopic examination. For all other eyes, topical 1% prednisolone acetate (PredForte®) was given every hour for the first 2 days, every 2 hours for the next 3 days, then continued with tapering doses until IOI fully resolved (Figure 2D, E, F).\n\nPatient records indicated that both visual acuity and vitritis improved over time in all patients during follow-up after IOI. The median time to visual acuity recovery was 28 (17-42) days and the median time to vitritis resolution was 32 (20-75) days.\n\nFollowing functional and anatomical recovery after non-infectious IOI, treatment for wet AMD was continued with the same intravitreal agent in 11 eyes, with a median of 3 (1-12) additional injections. In the other 2 eyes, additional injections were not considered due to scar development. IOI did not recur in any of the eyes and no systemic adverse effects associated with anti-VEGF injection were reported.\n\nDiscussion\n\nNon-infectious IOI can develop after intravitreal injections of ocriplasmin, bevacizumab, ranibizumab, triamcinolone acetonide, and aflibercept.1,3,4,5,6,7,8,9,10,11,12,13,14 Its incidence after anti-VEGF injection varies between 0.09% and 0.37% in the literature.3,4,5 In the present study, it occurred after intravitreal anti-VEGF injection for wet AMD at a rate of 0.1% of all injections and 0.66% of all patients. The relationship between the indication for anti-VEGF administration and the incidence of IOI is not yet fully understood. In a series of 66 patients who developed IOI after aflibercept injections, Greenberg et al.1 reported that the indication for treatment was wet AMD in 74%, macular edema secondary to retinal vein occlusion in 13%, and diabetic macular edema in 10% of the patients.\n\nIn our study, the most common symptom at presentation was blurred vision and this symptom was present in all of the patients. The second most common symptom was floaters. The case series reported by Greenberg et al.1 is the largest on this subject and the most common symptoms were blurred vision and floaters, consistent with our case series. In our study, the mean time from anti-VEGF administration to presentation due to complaints of blurred vision and floaters was 11.7 days (4-21 days). This is a longer interval compared to previous studies in the literature, in which the mean time to admission was 2.6 to 5 days.7,8,9,10,11 We believe the longer time to admission in our patients may be due to the fact that most patients’ inflammation was mild to moderate in severity and therefore they waited for their scheduled follow-up on day 15. One of the patients presented on day 21, which was attributed to low initial visual acuity. However, there were also patients who developed severe inflammation and one-eyed patients who noticed blurred vision early and presented within the first 5 days. In patients with wet AMD who continue anti-VEGF therapy, slit-lamp examinations in addition to follow-up OCT are particularly important for the detection of such inflammation.\n\nStudies have reported the coexistence of anterior chamber reaction and vitritis in 60% to 74% of cases and the presence of severe inflammation (fibrin reaction, presence of hypopyon) in approximately 20%.1,8,9,10,11 In our study, all patients who developed non-infectious IOI had anterior chamber reaction and vitritis. Only 23% of our patients had +3 Tyndall and/or grade 3 vitritis, while the majority had mild to moderate IOI. None of our patients developed fibrin reaction and/or hypopyon.\n\nIn the present study, IOI was associated with a statistically significant decrease in visual acuity. Upon resolution of the inflammation, all patients showed a statistically significant increase in visual acuity. It was reported that patients with IOI may have functional loss in eyes with rapid symptom onset and severe initial inflammation.8,9,10 In this case series, as IOI was not severe in any of the eyes, inflammation resolved in 3 to 4 weeks of follow-up and visual acuity returned to the pre-inflammation level.\n\nThere are not many studies demonstrating a relationship between non-infectious IOI and activation of wet AMD.15 In our study, despite IOI there was a decrease in CMT compared to pre-injection values. However, only SD-OCT findings (subretinal and intraretinal fluid) were evaluated in terms of AMD activation in our case series. Prospective studies with large case series investigating the relationship between IOI development and activation of wet AMD lesions are needed.\n\nNon-infectious IOI can occur regardless of injection number.5 Some studies have reported that administration of aflibercept can induce sensitivity and increase the risk of immune reactions with subsequent injections.10 Other studies reported that a history of IOI associated with aflibercept injection did not increase the risk or severity of ocular inflammation with subsequent injections.3,11 In wet AMD patients who require ongoing treatment, even if IOI occurs it was reported to be unlikely to recur if treatment with the same anti-VEGF agent is continued after the inflammation resolves.1,7,8,9,10 Recurrence was not observed in any of the patients in our case series, despite receiving at least 3 anti-VEGF injections during a mean follow-up period of 1 year after IOI.\n\nThe mechanism by which non-infectious IOI develops after anti-VEGF injection is not fully understood. Many hypotheses have been proposed regarding the development of inflammation. The most likely hypothesis is that inflammation occurs as a result of an immune reaction caused by the molecular structure of the drug and patient-specific factors. The reported incidence of inflammation is higher after aflibercept than other anti-VEGF agents.1,3,8,9,10,11,16 This has been attributed to a proinflammatory interaction between the Fc component in the molecular structure of aflibercept and retinal Fc receptors and/or the fact that aflibercept is a fusion protein with a more viscous structure. We believe that the white opacity seen in the vitreous in one of our patients may be an immune complex formed via a similar mechanism. Other factors that increase the risk of inflammation include contamination of anti-VEGF agents with bacterial endotoxin,3,4,6 contamination of the syringes in injection kits with silicon particles,4 and inappropriate storage conditions of anti-VEGF agents (cold chain conditions).3,8\n\nThe most important consideration in cases with non-infectious IOI is the differential diagnosis from infectious endophthalmitis. Several important clinical findings in infectious endophthalmitis facilitate its differential diagnosis. According to the Endophthalmic Vitrectomy Study 17, the most important symptoms and findings in infectious endophthalmitis are intense pain, severe vision loss, conjunctival hyperemia, chemosis, fibrin reaction, hypotension, and dense vitreous opacities. The lack of severe visual loss, conjunctival hyperemia, fibrin reaction, hypotension, and dense vitreous opacities in our patients at admission were the main findings for the differential diagnosis of endophthalmitis. In only one of our patients, detection of a whitish opacity in the vitreous (Figure 1) raised suspicion of endophthalmitis and led to collection of a vitreous sample and intravitreal treatment. Examination of the sample revealed no infectious pathogens. During follow-up, the patient’s opacity disappeared within 10 days. The patient was followed up with topical 1% prednisolone acetate until the inflammation resolved.\n\nIn patients with non-infectious IOI, systemic and/or topical steroid therapy is recommended depending on the severity of the disease. In most cases, topical steroid therapy is sufficient. All patients in our series were treated with topical steroid therapy and their inflammation resolved. Systemic steroid therapy was not needed in any of our cases. The median time to functional recovery was 28 days and the median time to inflammation resolution was 32 days. No local or systemic adverse effects of topical steroid therapy were observed.\n\nStudy Limitations\n\nThe most important limitations of our study are that it was retrospective and included only wet AMD patients. Another limiting factor was the small number of cases.\n\nConclusion\n\nNon-infectious IOI following anti-VEGF therapy is a rare complication. The clinical course is mild in many patients. However, it is important to carefully differentiate the condition from infectious endophthalmitis. Patients should be followed very closely and those showing clinical deterioration should be presumed to have infectious endophthalmitis and treated accordingly. Non-infectious IOI responds well to topical steroid therapy. Functional recovery is usually seen in 3 to 4 weeks. After inflammation has completely resolved, treatment with the same anti-VEGF agent can be continued in patients with AMD reactivation.\n\nTable 1 Demographic characteristics and clinical findings of the patients\n\nTable 2 Features and recovery times of the patients’ intraocular inflammation\n\nFigure 1 Color fundus and Spectralis optical coherence tomography (OCT) imaging of Patient 1 during intraocular inflammation (A-D). Color fundus image at admission (A) and colored fundus image 1 month after admission (B). Spectralis OCT images before intraocular inflammation (C) and on day 7 of inflammation (D)\n\nFigure 2 Color fundus and Spectralis optical coherence tomography (OCT) imaging of intraocular inflammation in Patient 2 (A-F). Color fundus photographs at initial presentation (at onset of intraocular inflammation) (A) and at 1 month (B), 2 months (C), and 3 months (D) after presentation. Spectralis OCT images before development of intraocular inflammation (E) and on day 7 of inflammation (F)\n\nEthics\n\nEthics Committee Approval: Approval was obtained from the Non-interventional Research Ethics Committee of Dokuz Eylül University.\n\nInformed Consent: Consent was obtained from the patients.\n\nAuthor Contributions:\n\nSurgical and Medical Procedures: M.K., F.H.Ö., T.Ö., Concept: F.H.Ö., M.K., T.Ö., Design: M.K., F.H.Ö., T.Ö., Data Collection and Processing: M.K., F.H.Ö., B.A.Y., F.A., Analysis or Interpretation: M.K., F.H.Ö., Literature Search: M.K., F.H.Ö., B.A.Y., F.A., Writing: M.K., F.H.O., B.A.Y., F.A., T.O.\n\nConflict of Interest: The authors declare no conflicts of interest.\n\nFinancial Disclosure: The authors report receiving no financial support.\n==== Refs\nReferences\n\n1 Greenberg JP Belin P Butler J Feiler D Mueller C Tye A Friedlander SM Emerson GG Ferrone PJ Aflibercept Sterile Inflammation Research Group Aflibercept-related sterile intraocular inflammation outcomes Ophthalmology Retina 2019 3 753 759 31153850\n2 Topal T Kar T Yıldırım Y Sağdıç SK Büyükavşar C Kaya A Ayata A Sönmez M Ünal MH Evaluation of Aflibercept Treatment Responses in Eyes with Bevacizumab/Ranibizumab-resistant Wet Age-related Macular Degeneration Turk J Ophthalmol. 2017 47 133 137 28630787\n3 Agrawal S Joshi M Christoforidis JB Vitreous inflammation associated with intravitreal anti-VEGF pharmacotherapy Mediators Inflamm. 2013 2013 943409 24307762\n4 Ness T Feltgen N Agostini H Böhringer D Lubrich B Toxic vitreitis outbreak after intravitreal injection Retina 2010 30 332 338 20175274\n5 Daien V Nguyen V Essex RW Morlet N Barthelmes D Gillies MC Fight Retinal Blindness! Study Group Incidence and outcomes of infectious and noninfectious endophthalmitis after intravitreal injections for age-related macular degeneration Ophthalmology 2018 125 66 74 28801117\n6 Wang F Yu S Liu K Chen FE Song Z Zhang X Xu X Sun X Acute intraocular inflammation caused by endotoxin after intravitreal injection of counterfeit bevacizumab in Shanghai, China Ophthalmology 2013 120 355 361 23084126\n7 Williams PD Chong D Fuller T Callanan D Noninfectious vitritis after intravitreal injection of anti-VEFG agents: variations in rates and presentation by medication Retina 2016 36 909 913 27115856\n8 Goldberg RA Shah CP Wiegand TW Heier JS Noninfectious inflammation after intravitreal injection of aflibercept: clinical characteristics and visual outcomes Am J Ophthalmol 2014 158 733 737 24983791\n9 Hahn P Chung MM Flynn HW Jr Huang SS Kim JE Mahmoud TH Sadda SR Dugel PU Postmarketing analysis of aflibercept-related sterile intraocular inflammation JAMA Ophthalmol 2015 133 421 426 25590968\n10 Fine HF Roth DB Shah SP Haque T Wheatley HM Frequency and characteristics of intraocular inflammation after aflibercept injection Retina 2015 35 681 686 25394166\n11 Kim JY You YS Kwon OW Kim SH Sterile inflammation after intravitreal injection of aflibercept in a Korean population Korean J Ophthalmol 2015 29 325 330 26457038\n12 Roth DB Chieh J Spirn MJ Green SN Yarian DL Chaudhry NA Noninfectious endophthalmitis associated with intravitreal triamcinolone injection Arch Ophthalmol 2003 121 1279 1282 12963610\n13 Durmaz Engin C Ayhan Z Men S Yaman A Saatci AO Bilateral severe sterile inflammation with hypopyon after simultaneous intravitreal triamcinolone acetonide and aflibercept injection in a patient with bilateral marked rubeosis associated with ocular ischemic syndrome Case Rep Ophthalmol Med 2017 2017 5123963 28386497\n14 Han IC Scott AW Sterile endophthalmitis after intravitreal ocriplasmin injection: report of a single case Retin Cases Brief Rep 2015 9 242 244 25790316\n15 Sato T Takeuchi M Karasawa Y Enoki T Ito M Intraocular infammatory cytokines in patients with neovascular agerelated macular degeneration before and after initiation of intravitreal injection of anti-VEGF inhibitor Sci Rep 2018 8 1098 29348424\n16 Souied EH Dugel PU Ferreira A Hashmonay R Lu J Kelly SP Severe ocular inflammation following ranibizumab or aflibercept injections for age-related macular degeneration: a retrospective claims database analysis Ophthalmic Epidemiol 2016 23 71 79 26855278\n17 No authors listed Results of the Endophthalmitis Vitrectomy Study. A randomized trial of immediate vitrectomy and of intravenous antibiotics for the treatment of postoperative bacterial endophthalmitis. Endophthalmitis Vitrectomy Study Group Arch Ophthalmol. 1995 113 1479 1496 7487614\n\n",
"fulltext_license": "CC BY",
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{
"reactionmeddrapt": "Eye inflammation",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Vitritis",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Anterior chamber flare",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Vision blurred",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Vitreous opacities",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Visual acuity reduced",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KAYA M.? ONER F.H.? YAGCI B.A.? ATAS F.? OZTURK T.. NON?INFECTIOUS INTRAOCULAR INFLAMMATION FOLLOWING INTRAVITREAL ANTI?VASCULAR ENDOTHELIAL GROWTH FACTOR INJECTION. TURKISH JOURNAL OF OPHTHALMOLOGY. 2021?51(1):32?37",
"literaturereference_normalized": "non infectious intraocular inflammation following intravitreal anti vascular endothelial growth factor injection",
"qualification": "3",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20210528",
"receivedate": "20210512",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
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"sendertype": "2"
},
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"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
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}
] |
{
"abstract": "BACKGROUND\nRemoval of midline paraventricular gliomas is difficult because of their deep localization and invasive character, requiring biopsy for pathologic diagnosis. This study aimed to assess the pathologic findings and clinical course of midline paraventricular gliomas diagnosed using a neuroendoscope.\n\n\nMETHODS\nThis study was performed as a retrospective investigation using a neuroendoscope of 26 patients whose tumors were diagnosed as midline paraventricular gliomas. The main loci of the lesions were the thalamus (11 patients), tectum (6 patients), and other areas (9 patients). Of these 26 patients, 21 (81%) had accompanying obstructive hydrocephalus. Surgery was performed via the lateral ventricle using a flexible scope. For patients with obstructive hydrocephalus, we added endoscopic third ventriculostomy, septostomy, and/or plasty of the foramen of Monro. Pathologic diagnosis was determined according to hematoxylin-eosin staining and immunohistochemistry using anti-GFAP, anti-Ki-67, anti-H3-K27M, and anti-IDH1-R132H antibodies.\n\n\nRESULTS\nThe pathologic diagnoses were grade I (5 patients), grade II (3 patients), grade III (6 patients), and grade IV (4 patients) gliomas. Six patients were diagnosed as having high-grade glioma, which was difficult to distinguish between grade III and grade IV. Two patients were undiagnosable. H3-K27M was strongly positive in 8 of 15 patients with high-grade glioma. All patients with high-grade gliomas died or received best supportive care within 2 years after surgery.\n\n\nCONCLUSIONS\nNeuroendoscopic surgery is useful for midline paraventricular gliomas in terms of the treatment of obstructive hydrocephalus, as well as pathologic diagnosis and genetic analysis, which are required under the World Health Organization 2016 classification.",
"affiliations": "Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan. Electronic address: [email protected].;Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan.;Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan.;Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan.;Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan; Department of Quality and Safety in Healthcare, Tokyo Medical University, Tokyo, Japan.;Department of Neurosurgery, Tokyo Metropolitan Ohtsuka Hospital, Tokyo, Japan.;Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.;Department of Anatomic Pathology, Tokyo Medical University, Tokyo, Japan.;Department of Cancer Pathology, Hokkaido University Graduate School of Medicine, Sapporo, Japan.;Department of Neurosurgery, Tokyo Medical University, Tokyo, Japan.",
"authors": "Fukami|Shinjiro|S|;Nakajima|Nobuyuki|N|;Okada|Hirofumi|H|;Akimoto|Jiro|J|;Miki|Tamotsu|T|;Fukuhara|Hirokazu|H|;Shishido-Hara|Yukiko|Y|;Nagao|Toshitaka|T|;Tsuda|Masumi|M|;Kohno|Michihiro|M|",
"chemical_list": "D005904:Glial Fibrillary Acidic Protein; D019394:Ki-67 Antigen; D007521:Isocitrate Dehydrogenase; C543588:IDH1 protein, human",
"country": "United States",
"delete": false,
"doi": "10.1016/j.wneu.2018.02.185",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1878-8750",
"issue": "114()",
"journal": "World neurosurgery",
"keywords": "Glioma; Immunohistochemistry; Neuroendoscope; Paraventricular tumor; Pathology",
"medline_ta": "World Neurosurg",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms; D002648:Child; D005260:Female; D005904:Glial Fibrillary Acidic Protein; D005910:Glioma; D006801:Humans; D006849:Hydrocephalus; D007521:Isocitrate Dehydrogenase; D019394:Ki-67 Antigen; D008297:Male; D008875:Middle Aged; D020644:Midline Thalamic Nuclei; D044583:Neuroendoscopy; D012189:Retrospective Studies; D003336:Tectum Mesencephali; D014696:Ventriculostomy; D055815:Young Adult",
"nlm_unique_id": "101528275",
"other_id": null,
"pages": "e366-e377",
"pmc": null,
"pmid": "29530692",
"pubdate": "2018-06",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Pathologic Findings and Clinical Course of Midline Paraventricular Gliomas Diagnosed Using a Neuroendoscope.",
"title_normalized": "pathologic findings and clinical course of midline paraventricular gliomas diagnosed using a neuroendoscope"
} | [
{
"companynumb": "JP-009507513-1806JPN003983",
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},
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}
],
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{
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"reactionmeddraversionpt": "21.0",
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}
],
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},
"primarysource": {
"literaturereference": "FUKAMI S, NAKAJIMA N, OKADA H, AKIMOTO J, MIKI T, FUKUHARA H ET AL.. PATHOLOGIC FINDINGS AND CLINICAL COURSE OF MIDLINE PARAVENTRICULAR GLIOMAS DIAGNOSED USING A NEUROENDOSCOPE. WORLD NEUROSURGERY. 2018?114:E366-E377",
"literaturereference_normalized": "pathologic findings and clinical course of midline paraventricular gliomas diagnosed using a neuroendoscope",
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},
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},
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"transmissiondate": "20180711"
}
] |
{
"abstract": "Fibrolamellar hepatocellular carcinoma (fHCC) is a rare primary liver cancer that affects young adults with no prior liver disease. fHCC-associated hyperammonemic encephalopathy (HAE) is an uncommon and life-threatening complication. Hyperammonemia has been reported in both typical and fHCC as a result of intrahepatic shunting, side effect from immunotherapy or chemotherapy, or as a paraneoplastic phenomenon. We present a case of a 32-year-old woman with recurrent metastatic fHCC who developed HAE in the setting of steroid administration. Her hyperammonemia was exacerbated by steroid-induced protein catabolism. She was treated with ammonia scavenging medications, a low protein diet, and was placed on chronic ammonia scavenger therapy while undergoing chemotherapy. In this case report, we discuss the proposed mechanisms of HAE, and we review the literature regarding clinical presentation and treatment.",
"affiliations": "Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.;Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.;Department of Hematology, Mayo Clinic, Rochester, MN, USA.;Riley Hospital for Children, University of Indiana, Indianapolis, IN, USA.;Department of Clinical Genomics, Mayo Clinic, Rochester, MN, USA.;Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.;Department of Medical Oncology, Mayo Clinic, Rochester, MN, USA.",
"authors": "Cho|Janice|J|;Chen|Joy C Y|JCY|;Paludo|Jonas|J|;Conboy|Erin E|EE|;Lanpher|Brendan C|BC|;Alberts|Steven R|SR|;Halfdanarson|Thorvardur R|TR|",
"chemical_list": null,
"country": "China",
"delete": false,
"doi": "10.21037/jgo.2019.01.28",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "2078-6891",
"issue": "10(3)",
"journal": "Journal of gastrointestinal oncology",
"keywords": "Hyperammonemia; fibrolamellar hepatocellular carcinoma (fHCC); hyperammonemic encephalopathy (HAE); ornithine transcarbamylase (OTC) deficiency",
"medline_ta": "J Gastrointest Oncol",
"mesh_terms": null,
"nlm_unique_id": "101557751",
"other_id": null,
"pages": "582-588",
"pmc": null,
"pmid": "31183212",
"pubdate": "2019-06",
"publication_types": "D002363:Case Reports",
"references": "11148549;11677282;14999699;16602102;17098461;18414167;20010160;23000233;23089120;24711766;24731681;24997132;25891666;26975868;26990031;27508204;27807568;28076712;28270654;28304380;3306479",
"title": "Hyperammonemic encephalopathy in a patient with fibrolamellar hepatocellular carcinoma: case report and literature review.",
"title_normalized": "hyperammonemic encephalopathy in a patient with fibrolamellar hepatocellular carcinoma case report and literature review"
} | [
{
"companynumb": "US-SUN PHARMACEUTICAL INDUSTRIES LTD-2019R1-213476",
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},
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"medicinalproduct": "DEXAMETHASONE."
}
],
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"patientonsetage": "32",
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"reaction": [
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"reactionmeddrapt": "Hyperammonaemic encephalopathy",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Catabolic state",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Condition aggravated",
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"reactionoutcome": "6"
}
],
"summary": null
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"primarysource": {
"literaturereference": "CHO J, CHEN JCY, PALUDO J, CONBOY EE, LANPHER BC, ALBERTS SR, ET AL. HYPERAMMONEMIC ENCEPHALOPATHY IN A PATIENT WITH FIBROLAMELLAR HEPATOCELLULAR CARCINOMA: CASE REPORT AND LITERATURE REVIEW. J GASTROINTEST ONCOL. 2019?10(3):582-588",
"literaturereference_normalized": "hyperammonemic encephalopathy in a patient with fibrolamellar hepatocellular carcinoma case report and literature review",
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},
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"seriousnesshospitalization": null,
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"seriousnessother": 1,
"transmissiondate": "20191004"
},
{
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"drugdosagetext": "8 MG, 2X/DAY",
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"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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"drugstructuredosagenumb": "8",
"drugstructuredosageunit": "003",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "DEXAMETHASONE."
},
{
"actiondrug": "1",
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"drugadditional": null,
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"drugcharacterization": "1",
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"drugdosageform": null,
"drugdosagetext": "UNK, CYCLIC",
"drugenddate": null,
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"drugindication": "HEPATOCELLULAR CARCINOMA",
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}
],
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"reaction": [
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"reactionmeddrapt": "Autoimmune hepatitis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hyperammonaemic encephalopathy",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
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"literaturereference_normalized": "hyperammonemic encephalopathy in a patient with fibrolamellar hepatocellular carcinoma case report and literature review",
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},
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"seriousnesslifethreatening": 1,
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"transmissiondate": "20210114"
},
{
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"drugdosagetext": "16 MILLIGRAM DAILY; FOR THREE DAYS",
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"drugindication": "HEPATOCELLULAR CARCINOMA",
"drugintervaldosagedefinition": "804",
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"medicinalproduct": "DEXAMETHASONE."
},
{
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"drugindication": "HEPATOCELLULAR CARCINOMA",
"drugintervaldosagedefinition": null,
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}
],
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"patientsex": "2",
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"reaction": [
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"reactionoutcome": "2"
}
],
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},
"primarysource": {
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"literaturereference_normalized": "hyperammonemic encephalopathy in a patient with fibrolamellar hepatocellular carcinoma case report and literature review",
"qualification": "1",
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},
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{
"abstract": "In patients supported with extracorporeal membrane oxygenation, and who develop heparin-induced thrombocytopenia, there is no clear evidence to support changing to a non-heparin-coated extracorporeal membrane oxygenation circuit. Our goal was to evaluate clinical outcomes of patients who were continued on heparin-bonded circuits despite diagnosed heparin-induced thrombocytopenia.\n\n\n\nWe completed a single-center retrospective study of all patients who underwent extracorporeal membrane oxygenation support from July 2008 to July 2017 and were tested heparin-induced thrombocytopenia positive while on extracorporeal membrane oxygenation support. After diagnosis of heparin-induced thrombocytopenia, mean platelet count (k/µL) was measured on consecutive days for 14 days.\n\n\n\nOut of 455 patients, 14 (3.1%) had a diagnosis of heparin-induced thrombocytopenia by serotonin release assay and systemic heparin treatment was discontinued in every case. In total, 11 of the heparin-induced thrombocytopenia patients (78.6%) survived to discharge. The overall survival of all 455 extracorporeal membrane oxygenation patients was 54.1%. Platelets counts after discontinuation of systemic heparin in the heparin-induced thrombocytopenia patients increased from a mean of 59.8 k/µL at time of heparin-induced thrombocytopenia diagnosis to a mean of 280.2 k/µL at 14 days after discontinuation of heparin despite continuation of the heparin-bonded circuit. Platelet count increased in heparin-induced thrombocytopenia patients on extracorporeal membrane oxygenation support after discontinuation of systemic heparin even if maintained on the heparin-bonded circuit.\n\n\n\nDiscontinuation of systemic heparin but continuation of heparin-coated extracorporeal membrane oxygenation circuits appeared to be an appropriate response for our extracorporeal membrane oxygenation-supported patients who developed heparin-induced thrombocytopenia. Survival in this group was not significantly different to those patients on extracorporeal membrane oxygenation without heparin-induced thrombocytopenia. Larger studies should evaluate the safety of heparin-bonded extracorporeal membrane oxygenation systems in heparin-induced thrombocytopenia patients.",
"affiliations": "Heart and Vascular Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.;Bon Secours Richmond Health Systems, Richmond, VA, USA.;Heart and Vascular Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.;Heart and Vascular Institute, Penn State Health Milton S. Hershey Medical Center, Hershey, PA, USA.",
"authors": "Pabst|Dirk|D|0000-0003-0944-3273;Boone|Jacqueline B|JB|;Soleimani|Behzad|B|;Brehm|Christoph E|CE|",
"chemical_list": "D006493:Heparin",
"country": "England",
"delete": false,
"doi": "10.1177/0267659119842056",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0267-6591",
"issue": "34(7)",
"journal": "Perfusion",
"keywords": "ECMO; heparin-bonded circuit; heparin-induced thrombocytopenia; outcome",
"medline_ta": "Perfusion",
"mesh_terms": "D000328:Adult; D000368:Aged; D015199:Extracorporeal Membrane Oxygenation; D005260:Female; D006493:Heparin; D006801:Humans; D008297:Male; D008875:Middle Aged; D013921:Thrombocytopenia",
"nlm_unique_id": "8700166",
"other_id": null,
"pages": "584-589",
"pmc": null,
"pmid": "30977431",
"pubdate": "2019-10",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Heparin-induced thrombocytopenia in patients on extracorporeal membrane oxygenation and the role of a heparin-bonded circuit.",
"title_normalized": "heparin induced thrombocytopenia in patients on extracorporeal membrane oxygenation and the role of a heparin bonded circuit"
} | [
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}
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},
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"receiverorganization": "FDA",
"receivertype": "6"
},
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"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20200122"
},
{
"companynumb": "US-FRESENIUS KABI-FK201912733",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
"drugadditional": "3",
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"drugauthorizationnumb": "017029",
"drugbatchnumb": "UNKNOWN",
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"medicinalproduct": "HEPARIN (MANUFACTURER UNKNOWN)"
}
],
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"reaction": [
{
"reactionmeddrapt": "Sepsis",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Heparin-induced thrombocytopenia",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Multiple organ dysfunction syndrome",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "5"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "PABST D, BOONE J, SOLEIMANI B, BREHM C. HEPARIN-INDUCED THROMBOCYTOPENIA IN PATIENTS ON EXTRACORPOREAL MEMBRANE OXYGENATION AND THE ROLE OF A HEPARIN-BONDED CIRCUIT. PERFUSION. 2019 OCT?34(7):584-589.",
"literaturereference_normalized": "heparin induced thrombocytopenia in patients on extracorporeal membrane oxygenation and the role of a heparin bonded circuit",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20191118",
"receivedate": "20191118",
"receiver": {
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},
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"senderorganization": "FDA-Public Use",
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},
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}
] |
{
"abstract": "BACKGROUND\nIdarucizumab is used to reverse the effects of dabigatran. Information on the use of idarucizumab in the clinical setting remains very limited.\n\n\nOBJECTIVE\nThe objective of this study was to describe clinical experience with idarucizumab in a large medical teaching center in the USA.\n\n\nMETHODS\nPatients who received idarucizumab to reverse the effects of dabigatran between 1 January 2016 and 30 June 2018 were studied. In patients with major bleeding, the efficacy of idarucizumab was assessed using criteria of the International Society of Thrombosis and Hemostasis Scientific and Standardization Subcommittee. The course of treatment and clinical outcomes in patients who received idarucizumab for emergency surgery or procedures are described.\n\n\nRESULTS\nIn total, 13 patients received idarucizumab for atrial fibrillation during the study period. Their mean age was 77.5 ± 7.1 years, and 12 (92.3%) were men. Idarucizumab was used in 11 patients for major bleeding events and in two patients for emergency surgery or procedures. Intracranial hemorrhage (n = 6) and gastrointestinal bleed (n = 2) were the most common types of bleeding. Clinical hemostasis was achieved in 8 of 11 (72.7%) patients with major bleeding. One patient with acute kidney injury needed two doses of the reversal agent to achieve hemostasis. One patient underwent open heart surgery and developed postoperative hemorrhage despite receiving idarucizumab. None of the patients experienced thrombotic complications or side effects that could be attributed to idarucizumab.\n\n\nCONCLUSIONS\nReal-world experience in a US hospital with the use of idarucizumab in emergency situations requiring the reversal of the effects of dabigatran is described. Idarucizumab represents an exciting new antidote for dabigatran, but clinical efficacy and cost-effectiveness data remain lacking.",
"affiliations": "Department of Pharmacy Practice, Lebanese American University, Byblos, Lebanon. [email protected].",
"authors": "Sheikh-Taha|Marwan|M|",
"chemical_list": "D061067:Antibodies, Monoclonal, Humanized; D000931:Antidotes; D000991:Antithrombins; C000594745:idarucizumab; D000069604:Dabigatran",
"country": "New Zealand",
"delete": false,
"doi": "10.1007/s40256-018-0300-5",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1175-3277",
"issue": "19(1)",
"journal": "American journal of cardiovascular drugs : drugs, devices, and other interventions",
"keywords": null,
"medline_ta": "Am J Cardiovasc Drugs",
"mesh_terms": "D000368:Aged; D000369:Aged, 80 and over; D061067:Antibodies, Monoclonal, Humanized; D000931:Antidotes; D000991:Antithrombins; D001281:Atrial Fibrillation; D001777:Blood Coagulation; D000069604:Dabigatran; D005260:Female; D006470:Hemorrhage; D006487:Hemostasis; D006801:Humans; D020300:Intracranial Hemorrhages; D008297:Male; D008875:Middle Aged; D013927:Thrombosis; D016896:Treatment Outcome",
"nlm_unique_id": "100967755",
"other_id": null,
"pages": "59-64",
"pmc": null,
"pmid": "30203330",
"pubdate": "2019-02",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Idarucizumab for Reversal of Dabigatran: Single-Center Real-World Experience.",
"title_normalized": "idarucizumab for reversal of dabigatran single center real world experience"
} | [
{
"companynumb": "US-B.I. PHARMACEUTICALS,INC./RIDGEFIELD-2018-BI-046176",
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"actiondrug": "5",
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},
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"medicinalproduct": "PRADAXA"
}
],
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"reaction": [
{
"reactionmeddrapt": "Neurological decompensation",
"reactionmeddraversionpt": "21.0",
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},
{
"reactionmeddrapt": "Seizure",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Cardiac arrest",
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"reactionoutcome": "6"
}
],
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},
{
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},
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{
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],
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{
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},
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"reaction": [
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"reactionmeddrapt": "Haemorrhage",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "International normalised ratio increased",
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"reactionoutcome": "6"
}
],
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},
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},
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"occurcountry": "LB",
"patient": {
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{
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"activesubstance": {
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},
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"drugdosagetext": "150 MG",
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"drugindication": "ATRIAL FIBRILLATION",
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"medicinalproduct": "DABIGATRAN"
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{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "AMIODARONE"
},
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"medicinalproduct": "AMIODARONE"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "HEPARIN SODIUM"
},
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"drugauthorizationnumb": null,
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"drugdosageform": null,
"drugdosagetext": null,
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"drugindication": "ANTICOAGULANT THERAPY",
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"activesubstancename": "ASPIRIN"
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"drugstructuredosageunit": null,
"drugtreatmentduration": null,
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"medicinalproduct": "ASPIRIN /00002701/"
}
],
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"patientonsetage": "75",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Labelled drug-drug interaction medication error",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
},
{
"reactionmeddrapt": "Post procedural haemorrhage",
"reactionmeddraversionpt": "21.1",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "SHEIKH-TAHA M. IDARUCIZUMAB FOR REVERSAL OF DABIGATRAN: SINGLE-CENTER REAL-WORLD EXPERIENCE. AM-J-CARD-DRUGS 2018?:1-6.",
"literaturereference_normalized": "idarucizumab for reversal of dabigatran single center real world experience",
"qualification": "3",
"reportercountry": "LB"
},
"primarysourcecountry": "LB",
"receiptdate": "20181015",
"receivedate": "20181015",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15499843,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20190205"
},
{
"companynumb": "US-B.I. PHARMACEUTICALS,INC./RIDGEFIELD-2018-BI-046175",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ASPIRIN"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
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"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
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"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ASPIRIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "OMEGA-3 FATTY ACIDS"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
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"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
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"drugstartdate": null,
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"drugstructuredosageunit": null,
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"drugtreatmentdurationunit": null,
"medicinalproduct": "OMEGA 3"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DABIGATRAN ETEXILATE MESYLATE"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": "022512",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "ATRIAL FIBRILLATION",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": "2",
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "75",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PRADAXA"
}
],
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"patientonsetage": "80",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Drug interaction",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Acute kidney injury",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "SHEIKH?TAHA M. IDARUCIZUMAB FOR REVERSAL OF DABIGATRAN: SINGLE?CENTER REAL?WORLD EXPERIENCE. AMERICAN JOURNAL OF CARDIOVASCULAR DRUGS. 2018?.",
"literaturereference_normalized": "idarucizumab for reversal of dabigatran single center real world experience",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180919",
"receivedate": "20180919",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 15401103,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20181010"
}
] |
{
"abstract": "OBJECTIVE\nTo evaluate the efficacy of tenofovir in chronic hepatitis B (CHB) patients with adefovir resistance (ADF-R) and suboptimal response to adefovir (ADF-S).\n\n\nMETHODS\nNucleos(t)ide analogue (NA)-naïve patients and patients with previous adefovir failure receiving tenofovir therapy for at least 6 months were included in the study. Biochemical and virological tests were obtained at baseline and 3-month intervals in the first year and every 6 months thereafter. The primary outcome measure was complete virological response (CVR) (HBVDNA < 20 IU/ml). CVR rates were calculated by Kaplan-Meier analysis, and a multivariate Cox proportional hazard model was generated to find out factors independently associated with CVR.\n\n\nRESULTS\nA total of 165 patients (118 men, mean age 42 ± 12, 64 HBeAg(+) ) were included in the study. There were 105 patients in NA-naïve, 32 patients in ADF-S and 28 patients in ADF-R groups. All patients in the ADF-R group had multidrug resistance patterns. Mean duration of tenofovir treatment was 29 ± 14 months. CVR rates in NA-naïve, ADF-S and ADF-R groups were 65% vs. 75% vs. 58% at 12th month, 77% vs. 87% vs. 79% at 24th month and 83% vs. 94% vs. 79% at 36th month respectively. According to multivariate Cox regression model, HBeAg positivity (HR = 0.56, 95%CI 0.36-0.86, P = 0.008), high baseline HBVDNA level (HR = 0.64, 95%CI 0.55-0.74, P < 0.001) and ADF-R (HR = 0.47, 95%CI 0.28-0.81, P = 0.006) were independent predictors for CVR. Seven patients encountered mild renal dysfunction and were managed by dose adjustments.\n\n\nCONCLUSIONS\nCVR rates during the follow-up show that tenofovir has a decreased, yet still potent in vivo efficacy against multidrug-resistant strains of HBV.",
"affiliations": "Department of Gastroenterology, Koç University Hospital, Zeytinburnu, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Microbiology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Pathology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Microbiology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.;Department of Gastroenterohepatology, Istanbul Faculty of Medicine, Istanbul University, Capa, Istanbul, Turkey.",
"authors": "Baran|Bulent|B|;Soyer|Ozlem Mutluay|OM|;Ormeci|Asli Cifcibasi|AC|;Gokturk|Suut|S|;Evirgen|Sami|S|;Akyuz|Filiz|F|;Karaca|Cetin|C|;Demir|Kadir|K|;Besisik|Fatih|F|;Onel|Derya|D|;Gulluoglu|Mine|M|;Badur|Selim|S|;Kaymakoglu|Sabahattin|S|",
"chemical_list": "D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000068698:Tenofovir; D000410:Alanine Transaminase",
"country": "United States",
"delete": false,
"doi": "10.1111/liv.12831",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1478-3223",
"issue": "35(10)",
"journal": "Liver international : official journal of the International Association for the Study of the Liver",
"keywords": "adefovir failure; chronic hepatitis B; genotypic resistance; tenofovir disoproxil fumarate",
"medline_ta": "Liver Int",
"mesh_terms": "D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase; D000998:Antiviral Agents; D004279:DNA, Viral; D024882:Drug Resistance, Viral; D005260:Female; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus; D019694:Hepatitis B, Chronic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016016:Proportional Hazards Models; D000068698:Tenofovir; D016896:Treatment Outcome; D019562:Viral Load; D055815:Young Adult",
"nlm_unique_id": "101160857",
"other_id": null,
"pages": "2265-74",
"pmc": null,
"pmid": "25800974",
"pubdate": "2015-10",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Tenofovir disoproxil fumarate has a substantial efficacy against multidrug-resistant strains of hepatitis B virus.",
"title_normalized": "tenofovir disoproxil fumarate has a substantial efficacy against multidrug resistant strains of hepatitis b virus"
} | [
{
"companynumb": "TR-CIPLA LTD.-2015TR08132",
"fulfillexpeditecriteria": "1",
"occurcountry": "TR",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "TENOFOVIR DISOPROXIL FUMARATE"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "300 MG, QD",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHRONIC HEPATITIS B",
"drugintervaldosagedefinition": null,
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"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
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"drugstructuredosagenumb": "300",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "TENOFOVIR DISOPROXIL FUMARATE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LAMIVUDINE"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "CHRONIC HEPATITIS B",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LAMIVUDINE."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Hepatocellular carcinoma",
"reactionmeddraversionpt": "18.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "BULENT BARAN, OZLEM MUTLUAY SOYER, ASLI CIFCIBASI ORMECI, SUUT GOKTURK, SAMI EVIRGEN, SABAHATTIN KAYMAKOGLU ET AL. TENOFOVIR DISOPROXIL FUMARATE HAS A SUBSTANTIAL EFFICACY AGAINST MULTIDRUG-RESISTANT STRAINS OF HEPATITIS B VIRUS. LIVER INTERNATIONAL. 2015?2265 TO 2274",
"literaturereference_normalized": "tenofovir disoproxil fumarate has a substantial efficacy against multidrug resistant strains of hepatitis b virus",
"qualification": "1",
"reportercountry": "TR"
},
"primarysourcecountry": "TR",
"receiptdate": "20151029",
"receivedate": "20151029",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 11681667,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160304"
}
] |
{
"abstract": "BACKGROUND\nA 56-year-old man with a distant history of statin use presented with progressive isolated very proximal lower limb and truncal weakness. Electromyogram (EMG) showed isolated gluteal and lumbar paraspinal muscle involvement.\n\n\nMETHODS\nGluteus medius muscle biopsy was performed under general anesthesia.\n\n\nRESULTS\nThe biopsy showed a pauci-inflammatory necrotizing myopathy. Serum antibodies to 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR) were positive. He has since partially responded to corticosteroids and methotrexate.\n\n\nCONCLUSIONS\nAnti-HMGCR-associated necrotizing autoimmune myopathy (NAM) can present in a restricted form after cessation of a statin. Biopsy of a symptomatic but uncommonly studied muscle is worthwhile. Muscle Nerve 54: 150-152, 2016.",
"affiliations": "Department of Medicine, Whangarei Hospital, Private Bag 9742, Whangarei, 0112, New Zealand.;Department of Anatomical Pathology, Auckland, New Zealand.",
"authors": "McGrath|Nicole M|NM|;Turner|Clinton P|CP|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1002/mus.25130",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0148-639X",
"issue": "54(1)",
"journal": "Muscle & nerve",
"keywords": "anti-HMGCR immunology; autoimmune; myopathy; necrotizing; proximal weakness",
"medline_ta": "Muscle Nerve",
"mesh_terms": null,
"nlm_unique_id": "7803146",
"other_id": null,
"pages": "150-152",
"pmc": null,
"pmid": "27060972",
"pubdate": "2016-06",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "Isolated gluteal and paravertebral muscle weakness due to anti-3-hydroxy-3-methylglutaryl-coenzyme a reductase antibody-associated necrotizing autoimmune myopathy.",
"title_normalized": "isolated gluteal and paravertebral muscle weakness due to anti 3 hydroxy 3 methylglutaryl coenzyme a reductase antibody associated necrotizing autoimmune myopathy"
} | [
{
"companynumb": "NZ-APOTEX-2016AP009982",
"fulfillexpeditecriteria": "1",
"occurcountry": "NZ",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ATORVASTATIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "090548",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "TABLET",
"drugdosagetext": "40MG/DAY",
"drugenddate": "201301",
"drugenddateformat": "610",
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "40",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATORVASTATIN TABLETS"
}
],
"patientagegroup": null,
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Immune-mediated necrotising myopathy",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "MCGRATH NM, TURNER CP.. ISOLATED GLUTEAL AND PARAVERTEBRAL MUSCLE WEAKNESS DUE TO ANTI-3-HYDROXY-3-METHYLGLUTARYL-COENZYME A REDUCTASE ANTIBODY-ASSOCIATED NECROTIZING AUTOIMMUNE MYOPATHY.. MUSCLE-NERVE. 2016;54(1):150-152",
"literaturereference_normalized": "isolated gluteal and paravertebral muscle weakness due to anti 3 hydroxy 3 methylglutaryl coenzyme a reductase antibody associated necrotizing autoimmune myopathy",
"qualification": "1",
"reportercountry": "NZ"
},
"primarysourcecountry": "NZ",
"receiptdate": "20160729",
"receivedate": "20160729",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 12605559,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20161109"
},
{
"companynumb": "NZ-SUN PHARMACEUTICAL INDUSTRIES LTD-2016RR-122109",
"fulfillexpeditecriteria": "1",
"occurcountry": "NZ",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "ATORVASTATIN"
},
"drugadditional": "1",
"drugadministrationroute": "065",
"drugauthorizationnumb": "076477",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "40 MG, DAILY",
"drugenddate": "201301",
"drugenddateformat": "610",
"drugindication": "PRODUCT USED FOR UNKNOWN INDICATION",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "40",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ATORVASTATIN"
}
],
"patientagegroup": null,
"patientonsetage": "56",
"patientonsetageunit": "801",
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Immune-mediated necrotising myopathy",
"reactionmeddraversionpt": "19.1",
"reactionoutcome": "2"
}
],
"summary": null
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{
"abstract": "We report a female patient diagnosed of Gitelman disease who suffered from severe hypokalemia and hypomagnesemia during pregnancy. We discuss the therapeutic approach and materno-fetal outcome.",
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{
"abstract": "Cold agglutinin-mediated autoimmune haemolytic anaemia is associated with the development of autoantibodies that can agglutinate red blood cells at cold temperatures. While primary cold agglutinin disease is an idiopathic lymphoproliferative disorder, secondary cold agglutinin syndrome (CAS) complicates other diseases such as infections, autoimmune diseases and cancers, mostly low-grade lymphomas. Early recognition, treatment of CAS and treatment of its associated underlying diseases are crucial to a successful outcome. We report a case of CAS in a setting of diffuse large B cell lymphoma, in which the treatment course was complicated by worsened anaemia due to chemotherapy-induced myelosuppression. We reviewed previously reported cases and discussed diagnosis and treatment strategies, including novel complement inhibitors, as potential future therapy.",
"affiliations": "Division of Hematology and Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.;Department of Pathology, Indiana University School of Medicine, Indianapolis, Indiana, USA.;Division of Hematology and Oncology, Department of Medicine, Indiana University School of Medicine, Indianapolis, Indiana, USA.",
"authors": "Wongsaengsak|Sariya|S|;Czader|Magdalena|M|;Suvannasankha|Attaya|A|http://orcid.org/0000-0003-0757-1386",
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"issue": "2018()",
"journal": "BMJ case reports",
"keywords": "haematology (drugs and medicines); malignant and benign haematology; malignant disease and immunosuppression",
"medline_ta": "BMJ Case Rep",
"mesh_terms": "D000368:Aged; D000744:Anemia, Hemolytic, Autoimmune; D005260:Female; D006801:Humans; D016403:Lymphoma, Large B-Cell, Diffuse",
"nlm_unique_id": "101526291",
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"references": "17904258;25332595;18205841;8547087;16999726;18765795;12481390;8973098;28533306;219484;26696798;18365153;16585012;21887126;22330255;21385173;3088977;24695853;15193444;24143001;2239927;17577777;7377142;11205465;19372265;10771401;26521297;23757733",
"title": "Cold agglutinin-mediated autoimmune haemolytic anaemia associated with diffuse large B cell lymphoma.",
"title_normalized": "cold agglutinin mediated autoimmune haemolytic anaemia associated with diffuse large b cell lymphoma"
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{
"abstract": "Mechanical valve thrombosis is life-threatening complication especially in pregnant patients. The optimal anticoagulation regimen is still not certain as there are different fetal and maternal risks associated with anticoagulation. A 37-year-old woman with a history of rheumatic heart disease with a mechanical mitral valve replacement 13 years prior presented to the hospital with dyspnea on mild exertion associated with orthopnea for three days. She was nine weeks pregnant, she had been on warfarin prior to pregnancy, and was switched to low molecular weight heparin (LMWH) in her 6th week of pregnancy. Fluoroscopy showed that one leaflet of the mitral valve was nearly fixed, while the other leaflet had restricted motion at maximal opening. Transesophageal echocardiogram (TEE) showed a very large thrombus approximately 3-4 cm2 encompassing the entire mechanical valve with one immobile leaflet and limited mobility in other leaflet. In view of her clinical status (dyspnea with NYHA Class IV symptoms), the patient underwent uncomplicated bioprosthetic mitral valve replacement. However, the fetus did not survive. Mechanical heart valve (MHV) thrombosis is life-threatening complication in pregnancy. The optimal anticoagulation therapy in pregnancy is unclear. This case report brings into light that in spite of adequate anticoagulation, pregnant patients with mechanical heart valves are still at a high risk of developing valve thrombosis. It highlights the use of transthoracic and transesophageal echocardiogram along with fluoroscopy in diagnosing this and discusses the therapeutic options for this unique condition.",
"affiliations": "Internal Medicine, Westchester Medical Center, Valhalla, USA.;Internal Medicine, Westchester Medical Center, Valhalla, USA.;Cardiology, Westchester Medical Center, Valhalla, USA.",
"authors": "Gupta|Rahul|R|;Ranchal|Purva|P|;Harburger|Joseph|J|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.7759/cureus.5615",
"fulltext": "\n==== Front\nCureusCureus2168-8184Cureus2168-8184Cureus Palo Alto (CA) 10.7759/cureus.5615CardiologyObstetrics/GynecologyMechanical Valve Thrombosis in a Pregnant Patient: A Case of Therapeutic Failure Muacevic Alexander Adler John R Gupta Rahul 1Ranchal Purva 1Harburger Joseph 2\n1 \nInternal Medicine, Westchester Medical Center, Valhalla, USA \n2 \nCardiology, Westchester Medical Center, Valhalla, USA \nRahul Gupta [email protected] 9 2019 9 2019 11 9 e561512 8 2019 10 9 2019 Copyright © 2019, Gupta et al.2019Gupta et al.This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.This article is available from https://www.cureus.com/articles/21481-mechanical-valve-thrombosis-in-a-pregnant-patient-a-case-of-therapeutic-failureMechanical valve thrombosis is life-threatening complication especially in pregnant patients. The optimal anticoagulation regimen is still not certain as there are different fetal and maternal risks associated with anticoagulation.\n\nA 37-year-old woman with a history of rheumatic heart disease with a mechanical mitral valve replacement 13 years prior presented to the hospital with dyspnea on mild exertion associated with orthopnea for three days. She was nine weeks pregnant, she had been on warfarin prior to pregnancy, and was switched to low molecular weight heparin (LMWH) in her 6th week of pregnancy. Fluoroscopy showed that one leaflet of the mitral valve was nearly fixed, while the other leaflet had restricted motion at maximal opening. Transesophageal echocardiogram (TEE) showed a very large thrombus approximately 3-4 cm2 encompassing the entire mechanical valve with one immobile leaflet and limited mobility in other leaflet. In view of her clinical status (dyspnea with NYHA Class IV symptoms), the patient underwent uncomplicated bioprosthetic mitral valve replacement. However, the fetus did not survive.\n\nMechanical heart valve (MHV) thrombosis is life-threatening complication in pregnancy. The optimal anticoagulation therapy in pregnancy is unclear. This case report brings into light that in spite of adequate anticoagulation, pregnant patients with mechanical heart valves are still at a high risk of developing valve thrombosis. It highlights the use of transthoracic and transesophageal echocardiogram along with fluoroscopy in diagnosing this and discusses the therapeutic options for this unique condition.\n\nmechanical heart valvevalve thrombosispregnancyanticoagulationThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\nIntroduction\nMechanical valve thrombosis is a rare and potentially life-threatening complication, especially in patients with a pro-thrombotic state such as pregnancy [1]. Maintaining adequate anticoagulation is essential to reduce the risk of thromboembolic events. Due to different maternal and fetal risks associated with anticoagulation, along with absence of randomized prospective controlled trials, the optimal anticoagulation regimen in pregnant women remains uncertain [2, 3]. We present a case of mechanical mitral valve thrombosis in a pregnant female while on therapeutic anticoagulation.\n\nCase presentation\nA 37-year-old woman with a history of rheumatic heart disease with a mechanical mitral valve replacement 13 years prior presented to the hospital with dyspnea on mild exertion associated with orthopnea for three days. She was nine weeks pregnant, she had been on warfarin 5.5 mg/day prior to pregnancy with therapeutic international normalized ratio (INR) levels, and was switched to low molecular weight heparin (LMWH) in her 6th week of pregnancy. Her anti-Xa levels were found to be in the therapeutic range (1.2 IU/ml). Physical exam was pertinent for mild bibasilar rales, with no jugular venous distension or pedal edema. Laboratory findings were significant for hemoglobin of 7.1 mg/dl, troponin level of 0.06 ng/ml with brain natriuretic peptide 252 pg/ml. Chest X-ray showed mild pulmonary vascular congestion. Transthoracic echocardiogram (TTE) showed a normal left ventricle with ejection fraction of 70%, a dilated left atrium, and a bileaflet mechanical mitral valve, with mean transmitral diastolic gradient of 23 mm Hg at heart rate of 98, peak mitral diastolic velocity 266 cm/sec, mitral pressure half time 235 ms, and mitral valve velocity time integral/left ventricle outflow tract velocity time integral ratio of 4.8, with findings highly suspicious for mechanical mitral valve stenosis (Figure 1). Prior to her pregnancy, she had a normal mean gradient of 4 mm Hg at heart rate of 72 (Figure 2). Fluoroscopy showed that one leaflet of the mitral valve was nearly fixed, while the other leaflet had restricted motion at maximal opening (Video 1). Trans-esophageal echocardiogram (TEE) showed a very large thrombus approximately 3-4 cm2 encompassing the entire mechanical valve with one immobile leaflet and limited mobility in other leaflet (Videos 2-4, Figure 3). Intravenous infusion of unfractionated heparin (UFH) was immediately initiated to maintain an activated partial thromboplastin time (APTT) 1.5 to 2 times higher than the upper normal limit. In view of her clinical status (dyspnea with NYHA Class IV symptoms) urgent surgical consultation was requested.\n\nFigure 1 X-plane image of transesophageal echocardiography showing thrombus (Arrow) caked onto the mechanical mitral valve\nFigure 2 Transthoracic echocardiography doppler measurements showing increased mean pressure gradient across mechanical mitral valve\nVideo 1 Fluoroscopy showing fixed mechanical mitral valve leaflet with restricted mobility of the other leaflet during opening and closing of the valve\nVideo 2 Transesophageal echocardiography showing thrombus over the mechanical mitral valve\nVideo 3 Transesophageal echocardiography showing thrombus over the mechanical mitral valve\nVideo 4 Transesophageal echocardiography showing turbulent flow through the mechanical mitral valve due to the thrombus\nFigure 3 Transthoracic echocardiography doppler measurements showing normal mean pressure gradient across mechanical mitral valve prior to pregnancy\nAfter multidisciplinary evaluation and extensive discussions with the patient, a decision was made to perform a bioprosthetic mitral valve replacement. The patient had an uncomplicated bioprosthetic mitral valve replacement. However, the patient had missed abortion, most likely secondary to impact on placental perfusion secondary to down regulation of her blood volume and pressure, and her need for blood transfusion.\n\nDiscussion\nAnticoagulation in patients with mechanical heart valves (MHVs) during pregnancy is a challenging problem. The annual risk of a thrombotic event in patients not taking anticoagulation is approximately 4% while the risk in those on appropriate anticoagulation is 1% [4]. Oral vitamin K antagonists are the most effective anticoagulation regimen in patients with mechanical heart valves. However, vitamin K antagonists cross the placental barrier and can cause teratogenic effects, with reported incidence of teratogenicity between 0.6%-10% [5]. UFH and LMWH do not cross the placenta and do not have teratogenic effects. Current guidelines of the American College of Cardiology recommend continuing warfarin throughout the pregnancy if the dose is less than 5 mg/day [6, 7]. However, if the dose of warfarin exceeds 5 mg/day, strong consideration should be made to switch to UFH or LMWH to avoid teratogenicity. Dosing of UFH is done to maintain APTT 1.5-2 times control, while LMWH is dosed to maintain peak anti-Xa level measured four to six hours after administration of 1.0 IU/ml to 1.2 IU/ml.\n\nRisk factors for prosthetic valve thrombosis include patients with old or small mechanical mitral valve, previous thromboembolic complications, multiple mechanical heart valves or presence of atrial fibrillation or flutter. Most cases of mechanical heart valve thrombosis in pregnant patients treated with LMWH have been due to inadequate dosing, lack of monitoring, or subtherapeutic anti-Xa levels [8]. Our patient developed mechanical valve thrombosis despite adequate LMWH dosing and monitoring.\n\nTherapeutic options for mechanical valve thrombosis include medical therapy versus surgical replacement of the valve. Valve repair or replacement in pregnancy is indicated in pregnancy patients who remain symptomatic even after medical therapy [9]. Recently published guidelines (“2017 ESC/EACTS Guidelines for the management of valvular heart disease”) recommend surgical management for obstructive mechanical valve thromboses when there is no contraindication to surgery [10]. Our patient had NYHA class IV symptoms and large thrombotic burden warranting urgent surgical management. The increased mortality and morbidity associated with valve thrombosis in pregnant patients warrants extensive pre-pregnancy counseling and centralization of care, which could result in better outcomes in future.\n\nConclusions\nThrombotic complications of MHV mostly occur during the first trimester when anticoagulant regimens are switched from one regimen to another. The use of LMWH warrants monitoring and appropriate dose adjustments to maintain adequate anti-factor Xa levels to decrease the incidence of thromboembolic complications. In spite of that, there is still a risk of developing valve thrombosis as seen in our patient. The increased mortality and morbidity associated with mechanical valve thrombosis in pregnancy warrants extensive pre-pregnancy counseling and centralization of care.\n\nThe authors have declared that no competing interests exist.\n\nHuman Ethics\nConsent was obtained by all participants in this study\n==== Refs\nReferences\n1 The role of thrombophilia in pregnancy Thrombosis Battinelli E Marshall A Connors J 9 2013 2013 \n2 Valvular heart disease and pregnancy: part II: prosthetic valves J Am Coll Cardiol Elkayam U Bitar F 403 410 46 2005 16053950 \n3 Anticoagulation of pregnant women with mechanical heart valves Arch Intern Med Ginsberg JS Chan WS Bates SM Kaatz S 694 698 163 2003 12639202 \n4 Anticoagulant therapy in pregnant women with mechanical prosthetic heart valves: no easy option Thromb Res McLintock C 0 127 2011 \n5 ESC Guidelines on the management of cardiovascular diseases during pregnancy: the Task Force on the Management of Cardiovascular Diseases during Pregnancy of the European Society of Cardiology (ESC) Eur Heart J European Society of Gynecology (ESG) Association for European Paediatric Cardiology (AEPC) German Society for Gender Medicine (DGesGM) 3147 3197 32 2011 21873418 \n6 2014 AHA/ACC Guideline for the management of patients with valvular heart disease: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines Circulation Nishimura RA Otto CM Bonow RO 2440 2492 129 2014 24589852 \n7 Anticoagulation regimens during pregnancy in patients with mechanical heart valves: a systematic review and meta-analysis Can J Cardiol Xu Z Fan J Luo X 1248 32 2016 26927861 \n8 Low molecular weight heparin for the prophylaxis of thromboembolism in women with prosthetic mechanical heart valves during pregnancy Thromb Haemost Oran B Lee-Parritz A Ansell J 747 751 92 2004 15467905 \n9 Valvular heart disease and pregnancy: part I: native valves J Am Coll Cardiol Elkayam U Bitar F 223 230 46 2005 16022946 \n10 2017 ESC/EACTS Guidelines for the management of valvular heart disease Eur Heart J Baumgartner H Falk V Bax JJ 2739 2791 38 2017 28886619\n\n",
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"affiliations": "Department of Pharmacy, Tom Baker Cancer Center, Calgary, AB, Canada.;Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada.;Department of Pharmacy, Tom Baker Cancer Center, Calgary, AB, Canada.;Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada.;Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada.;Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada.;Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada.;Department of Medical Oncology and Hematology, Tom Baker Cancer Center, Calgary, AB, Canada.",
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{
"abstract": "OBJECTIVE\nAdministration of prothrombin complex concentrate (PCC) is recommended for vitamin K antagonist (VKA) reversal in patients with severe bleeding complications. However, there are only limited data available on its use for VKA reversal in patients with traumatic intracranial hemorrhage (ICH).\n\n\nMETHODS\nData from all anticoagulated patients referred to our hospital for treatment of traumatic ICH and who received PCC for anticoagulation reversal were retrospectively analysed with specific focus on bleeding and thromboembolic complications during the further in-hospital course.\n\n\nRESULTS\nA total of 142 patients were included in the present study. The median age was 78 years (Interquartile range [IQR]: 72-84) and the median Glasgow Coma Scale (GCS) score on admission was 12 (IQR: 7-14). Median International Normalized Ratio (INR) on admission was 2.5 [IQR: 2.0-3.3] and decreased to 1.2 [IQR: 1.1-1.3] following administration of a median dose of 2000 I.U. PCC [IQR: 1500-2625]. The in-hospital mortality rate was 13% and the median GCS of survivors at discharge was 14 [IQR: 12-15]. Thromboembolic events after PCC administration occurred in 4 patients (2.8%). The overall one-year mortality rate in this patient cohort was 49%.\n\n\nCONCLUSIONS\nPCC administration rapidly normalises INR and facilitates urgent neurosurgical procedures in anticoagulated patients with traumatic ICH.",
"affiliations": "Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany. Electronic address: [email protected].;Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.;Department of Neurology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.;Department of Neurology, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.;Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.;Department of Neurosurgery, Heidelberg University Hospital, Im Neuenheimer Feld 400, 69120 Heidelberg, Germany.",
"authors": "Beynon|Christopher|C|;Nofal|Mohammed|M|;Rizos|Timolaos|T|;Laible|Mona|M|;Sakowitz|Oliver W|OW|;Unterberg|Andreas W|AW|",
"chemical_list": "D000925:Anticoagulants; D001779:Blood Coagulation Factors; C025667:prothrombin complex concentrates",
"country": "Scotland",
"delete": false,
"doi": "10.1016/j.jocn.2020.07.006",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0967-5868",
"issue": "79()",
"journal": "Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia",
"keywords": "Coagulopathy; Emergency medicine; Hemostasis; Intracranial hemorrhage; Warfarin",
"medline_ta": "J Clin Neurosci",
"mesh_terms": "D000368:Aged; D000925:Anticoagulants; D001777:Blood Coagulation; D001779:Blood Coagulation Factors; D005260:Female; D015600:Glasgow Coma Scale; D006801:Humans; D020198:Intracranial Hemorrhage, Traumatic; D008875:Middle Aged; D016896:Treatment Outcome",
"nlm_unique_id": "9433352",
"other_id": null,
"pages": "197-202",
"pmc": null,
"pmid": "33070895",
"pubdate": "2020-09",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Prothrombin complex concentrate for vitamin K antagonist reversal in traumatic intracranial hemorrhage.",
"title_normalized": "prothrombin complex concentrate for vitamin k antagonist reversal in traumatic intracranial hemorrhage"
} | [
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"abstract": "BACKGROUND\nOmalizumab (Xolair) is a recombinant humanized monoclonal anti-IgE antibody with proven efficacy in patients with moderate-to-severe and severe persistent allergic (IgE-mediated) asthma.\n\n\nOBJECTIVE\nTo review clinical study data to assess the safety profile of omalizumab.\n\n\nMETHODS\nWe analysed the safety of omalizumab using data from completed clinical studies (up to 1 year) involving more than 7500 patients with asthma, rhinitis or related conditions and up to 4 years in one study of patients with severe allergic asthma, as well as post-marketing safety data. Analysis focuses on the risk of immune-system effects, hypersensitivity reactions, malignant neoplasia, parasitic infections and thrombocytopenia.\n\n\nRESULTS\nOmalizumab exhibited a good safety and tolerability profile that was maintained up to 4 years in one study. The incidence of anaphylaxis was 0.14% in omalizumab-treated patients and 0.07% in control patients. No omalizumab-treated patient developed measurable anti-omalizumab antibodies. Post-marketing, based on estimated exposure of 57,300 patients (June 2003-December 2006), the frequency of anaphylaxis attributed to omalizumab use was estimated to be at least 0.2% of patients. Current clinical trial data do not support an increased risk of malignant neoplasia or thrombocytopenia with omalizumab.\n\n\nCONCLUSIONS\nData indicate that the proven efficacy of add-on omalizumab in patients with moderate-to-severe or severe allergic asthma is accompanied by a favourable safety and tolerability profile.",
"affiliations": "Allergy Research Foundation, Los Angeles, CA 90025, USA. [email protected]",
"authors": "Corren|J|J|;Casale|T B|TB|;Lanier|B|B|;Buhl|R|R|;Holgate|S|S|;Jimenez|P|P|",
"chemical_list": "D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; C026408:anti-IgE antibodies; D000069444:Omalizumab",
"country": "England",
"delete": false,
"doi": "10.1111/j.1365-2222.2009.03214.x",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0954-7894",
"issue": "39(6)",
"journal": "Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology",
"keywords": null,
"medline_ta": "Clin Exp Allergy",
"mesh_terms": "D000707:Anaphylaxis; D018927:Anti-Asthmatic Agents; D000888:Antibodies, Anti-Idiotypic; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D001249:Asthma; D015267:Churg-Strauss Syndrome; D002986:Clinical Trials as Topic; D006801:Humans; D007239:Infections; D009369:Neoplasms; D000069444:Omalizumab; D013921:Thrombocytopenia",
"nlm_unique_id": "8906443",
"other_id": null,
"pages": "788-97",
"pmc": null,
"pmid": "19302249",
"pubdate": "2009-06",
"publication_types": "D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't; D016454:Review",
"references": null,
"title": "Safety and tolerability of omalizumab.",
"title_normalized": "safety and tolerability of omalizumab"
} | [
{
"companynumb": "US-ROCHE-2320836",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "OMALIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": "058",
"drugauthorizationnumb": "103976",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SYSTEMIC LUPUS ERYTHEMATOSUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "600",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OMALIZUMAB."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "LESS THAN 20 MG",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SYSTEMIC LUPUS ERYTHEMATOSUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
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"drugrecurrence": null,
"drugseparatedosagenumb": null,
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"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "PREDNISONE."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "METHYLPREDNISOLONE"
},
"drugadditional": "3",
"drugadministrationroute": "030",
"drugauthorizationnumb": null,
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "2",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SYSTEMIC LUPUS ERYTHEMATOSUS",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
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"drugrecurrence": null,
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"drugstartdateformat": null,
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"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "METHYLPREDNISOLONE."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "OMALIZUMAB"
},
"drugadditional": null,
"drugadministrationroute": "058",
"drugauthorizationnumb": "103976",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": "SOLUTION FOR INJECTION",
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": null,
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "300",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "OMALIZUMAB."
}
],
"patientagegroup": "5",
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Product use in unapproved indication",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Systemic lupus erythematosus",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Condition aggravated",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "HASNI S, GUPTA S, DAVIS M, PONCIO E, TEMESGEN-OYELAKIN Y, JOYAL E ET AL SAFETY AND TOLERABILITY OF OMALIZUMAB. A RANDOMIZED CLINICAL TRIAL OF HUMANIZED ANTI-LGE MONOCLONAL ANTIBODY IN SYSTEMIC LUPUS ERYTHEMATOSUS. ARTHRITIS AND RHEUMATOLOGY 2019?0 (0):1-6.",
"literaturereference_normalized": "safety and tolerability of omalizumab",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20190522",
"receivedate": "20190522",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 16340371,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20190711"
}
] |
{
"abstract": "Diurnal frequent urination is a common condition in elementary school children who are especially at risk for associated somatic and behavioral problems. Levetiracetam (LEV) is a broad-spectrum antiepileptic drug that has been used in both partial and generalized seizures and less commonly adverse effects including psychiatric and behavioral problems. Diurnal frequent urination is not a well-known adverse effect of LEV. Here, we reported 2 pediatric cases with epilepsy that developed diurnal frequent urination after LEV administration. Case 1 was a 6-year-old male patient who presented urinary frequency and urgency in the daytime since the third day after LEV was given as adjunctive therapy. Symptoms increased accompanied by the raised dosage of LEV. Laboratory tests and auxiliary examinations did not found evidence of organic disease. Diurnal frequent urination due to LEV was suspected, and then the drug was discontinued. As expected, his frequency of urination returned to normal levels. Another 13-year-old female patient got similar clinical manifestations after oral LEV monotherapy and the symptoms became aggravated while in stress state. Since the most common causes of frequent micturition had been ruled out, the patient was considered to be diagnosed with LEV-associated psychogenic frequent urination. The dosage of LEV was reduced to one-third, and the frequency of urination was reduced by 60%. Both patients got the Naranjo score of 6, which indicated that LEV was a \"probable\" cause of diurnal frequent urination. Although a definite causal link between LEV and diurnal urinary frequency in the 2 cases remains to be established, we argue that diurnal frequent urination associated with LEV deserves clinician's attention.",
"affiliations": "1Department of Pediatrics, Chinese PLA General Hospital, Beijing, China; and 2Center of Epilepsy, Beijing Institute for Brain Disorders, Beijing, China.",
"authors": "Ju|Jun|J|;Zou|Li-Ping|LP|;Shi|Xiu-Yu|XY|;Hu|Lin-Yan|LY|;Pang|Ling-Yu|LY|",
"chemical_list": "D000927:Anticonvulsants; D000077287:Levetiracetam; D010889:Piracetam",
"country": "United States",
"delete": false,
"doi": "10.1097/MJT.0000000000000201",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1075-2765",
"issue": "23(2)",
"journal": "American journal of therapeutics",
"keywords": null,
"medline_ta": "Am J Ther",
"mesh_terms": "D000293:Adolescent; D000927:Anticonvulsants; D002648:Child; D002940:Circadian Rhythm; D005260:Female; D006801:Humans; D000077287:Levetiracetam; D008297:Male; D010889:Piracetam; D014554:Urination",
"nlm_unique_id": "9441347",
"other_id": null,
"pages": "e624-7",
"pmc": null,
"pmid": "26938751",
"pubdate": "2016",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Levetiracetam: Probably Associated Diurnal Frequent Urination.",
"title_normalized": "levetiracetam probably associated diurnal frequent urination"
} | [
{
"companynumb": "CN-ORCHID HEALTHCARE-1051833",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "065",
"drugauthorizationnumb": "078526",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "SIMPLE PARTIAL SEIZURES",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": null,
"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
}
],
"patientagegroup": null,
"patientonsetage": "13",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": "50",
"reaction": [
{
"reactionmeddrapt": "Pollakiuria",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "JU J, ZOU LP, SHI XY, HU LY, PANG LY. LEVETIRACETAM: PROBABLY ASSOCIATED DIURNAL FREQUENT URINATION. AM J THER. 2016 MAR-APR; 23(2):E624-7.",
"literaturereference_normalized": "levetiracetam probably associated diurnal frequent urination",
"qualification": "1",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20160511",
"receivedate": "20160511",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 12353827,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": 1,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20160815"
},
{
"companynumb": "CN-LUPIN PHARMACEUTICALS INC.-2016-01734",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "078154",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "3000",
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"medicinalproduct": "LEVETIRACETAM."
},
{
"actiondrug": "1",
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"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "048",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "078154",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "250",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EPILEPSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
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"drugstructuredosageunit": null,
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
}
],
"patientagegroup": null,
"patientonsetage": "13",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pollakiuria",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "1"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "ZOU L, JU J, SHI X, HU L, PANG L. LEVETIRACETAM: PROBABLY ASSOCIATED DIURNAL FREQUENT URINATION. AMERICAN JOURNAL OF THERAPEUTICS. 2016;23:E624-E627.",
"literaturereference_normalized": "levetiracetam probably associated diurnal frequent urination",
"qualification": "1",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20160506",
"receivedate": "20160506",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "3",
"safetyreportid": 12340657,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160815"
},
{
"companynumb": "CN-ACCORD-038714",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": "2",
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "090843",
"drugbatchnumb": null,
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": "MONOTHERAPY",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "EPILEPSY",
"drugintervaldosagedefinition": null,
"drugintervaldosageunitnumb": null,
"drugrecurreadministration": null,
"drugrecurrence": null,
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
}
],
"patientagegroup": null,
"patientonsetage": "13",
"patientonsetageunit": "801",
"patientsex": "2",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Pollakiuria",
"reactionmeddraversionpt": "19.0",
"reactionoutcome": "2"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "JU J, ZOU LP, SHI XY, HU LY, PANG LY. LEVETIRACETAM: PROBABLY ASSOCIATED DIURNAL FREQUENT URINATION. AM J THER. 2016 MAR-APR? 23(2):E624-7.",
"literaturereference_normalized": "levetiracetam probably associated diurnal frequent urination",
"qualification": "3",
"reportercountry": "CN"
},
"primarysourcecountry": "CN",
"receiptdate": "20160317",
"receivedate": "20160317",
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},
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"sender": {
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"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20160526"
},
{
"companynumb": "CN-LUPIN PHARMACEUTICALS INC.-2016-01727",
"fulfillexpeditecriteria": "1",
"occurcountry": "CN",
"patient": {
"drug": [
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "078154",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
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"drugrecurrence": null,
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"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "25",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "078154",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
"drugdosagetext": null,
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"drugindication": "EPILEPSY",
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"drugrecurreadministration": null,
"drugrecurrence": null,
"drugseparatedosagenumb": null,
"drugstartdate": null,
"drugstartdateformat": null,
"drugstructuredosagenumb": "3.125",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
},
{
"actiondrug": "1",
"activesubstance": {
"activesubstancename": "LEVETIRACETAM"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": "078154",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
"drugcumulativedosageunit": null,
"drugdosageform": null,
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"drugenddate": null,
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"drugrecurrence": null,
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"drugstructuredosagenumb": "12.5",
"drugstructuredosageunit": "007",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "LEVETIRACETAM."
},
{
"actiondrug": null,
"activesubstance": {
"activesubstancename": "VALPROIC ACID"
},
"drugadditional": null,
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
"drugbatchnumb": null,
"drugcharacterization": "2",
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"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "VALPROIC ACID."
}
],
"patientagegroup": null,
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{
"abstract": "Nodular regenerative hyperplasia (NRH) is a well-described condition that leads to non-cirrhotic portal hypertension and is histologically characterised by a nodular transformation of the liver without fibrosis. It seems to be a consequence of obliterative portal venopathy of small hepatic veins. Its precise aetiology remains to be clearly determined. NRH was reported to occur in HIV-positive patients ten years ago. In this article, three consecutive clinical cases of HIV-related NRH were identified in a high volume reference centre of HIV positive patients and are presented. Clinical, diagnostic aspects and strategies for management of this under-diagnosed medical condition in the HIV population are also developed.",
"affiliations": null,
"authors": "Figueiredo|M|M|;Nkuize|M|M|;Mulkay|J P|JP|;De Wit|S|S|;Gomez|M|M|;Sersté|T|T|",
"chemical_list": null,
"country": "Belgium",
"delete": false,
"doi": null,
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"issn_linking": "1784-3227",
"issue": "80(1)",
"journal": "Acta gastro-enterologica Belgica",
"keywords": null,
"medline_ta": "Acta Gastroenterol Belg",
"mesh_terms": "D000368:Aged; D005260:Female; D006679:HIV Seropositivity; D006801:Humans; D006965:Hyperplasia; D008099:Liver; D008297:Male; D008875:Middle Aged; D012038:Regeneration",
"nlm_unique_id": "0414075",
"other_id": null,
"pages": "15-19",
"pmc": null,
"pmid": "29364092",
"pubdate": "2017",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": null,
"title": "Nodular Regenerative Hyperplasia in HIV-positive patients : a case series and review of the literature.",
"title_normalized": "nodular regenerative hyperplasia in hiv positive patients a case series and review of the literature"
} | [
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] |
{
"abstract": "Because of expanding indications and improvements in supportive care, the utilization of blood and marrow cell transplantation (BMT) to treat various conditions is increasing exponentially, and currently more than 60,000 BMTs are performed annually worldwide. By the year 2030, it is projected that the number of BMT survivors will increase 5-fold, potentially resulting in one half of a million survivors in the United States alone. As the majority of survivors now live beyond the first 2 years after BMT, they are prone to a unique set of complications and late effects. Until recently, BMT experts assumed responsibility for almost all of the care for these survivors, but now oncologists/hematologists, pediatricians, and internists are involved frequently in offering specialized care and preventive services to these survivors. To integrate and translate into clinical practice the unique BMT survivorship issues with current preventive guidelines, a team effort is required. This can be facilitated by a dedicated \"long-term-follow-up (LTFU)\" clinic that provides lifelong care for BMT survivors. In this review, we first illustrate with clinical vignettes the need for LTFU and then focus upon the following: (1) types of LTFU clinic models, (2) challenges and possible solutions to the establishment of LTFU clinic, and (3) vulnerable transition periods.",
"affiliations": "Division of Hematology, Mayo Clinic, Rochester, Minnesota. Electronic address: [email protected].;Department of Hematology Oncology, Fred Hutchinson Cancer Research Center, University of Washington, Seattle, Washington.;Division of Hematology/Oncology, Mayo Clinic, Phoenix, Arizona.;Diagnostic Hematology, University Hospital Basel, Basel, Switzerland.;Division of Hematology/Oncology, Vanderbilt University, Nashville, Tennessee.",
"authors": "Hashmi|Shahrukh|S|;Carpenter|Paul|P|;Khera|Nandita|N|;Tichelli|André|A|;Savani|Bipin N|BN|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1083-8791",
"issue": "21(2)",
"journal": "Biology of blood and marrow transplantation : journal of the American Society for Blood and Marrow Transplantation",
"keywords": "Blood and marrow transplantation; Late effects; Survivorship clinic",
"medline_ta": "Biol Blood Marrow Transplant",
"mesh_terms": "D000328:Adult; D000368:Aged; D016026:Bone Marrow Transplantation; D002386:Cataract; D002648:Child; D002908:Chronic Disease; D006086:Graft vs Host Disease; D006301:Health Services Needs and Demand; D019337:Hematologic Neoplasms; D018380:Hematopoietic Stem Cell Transplantation; D006782:Hospitals, Special; D006801:Humans; D007037:Hypothyroidism; D024821:Metabolic Syndrome; D018803:Models, Economic; D013313:Stress Disorders, Post-Traumatic; D017741:Survivors; D014481:United States; D000078329:Workforce",
"nlm_unique_id": "9600628",
"other_id": null,
"pages": "225-32",
"pmc": null,
"pmid": "24999225",
"pubdate": "2015-02",
"publication_types": "D016428:Journal Article; D016454:Review",
"references": null,
"title": "Lost in transition: the essential need for long-term follow-up clinic for blood and marrow transplantation survivors.",
"title_normalized": "lost in transition the essential need for long term follow up clinic for blood and marrow transplantation survivors"
} | [
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"abstract": "A case is reported in which a patient experienced somnambulistic episodes only after taking zolpidem tartrate for insomnia. Previous to the patient's use of zolpidem tartrate he had never experienced sleepwalking, and once the medication was discontinued the sleepwalking stopped. A search of the literature revealed only two other cases of zolpidem-induced sleepwalking, both involving individuals with a previous history of somnambulism in their youth.",
"affiliations": "Division of Mental Health, 82d Airborne, Fort Bragg, NC 28307-5000, USA.",
"authors": "Harazin|J|J|;Berigan|T R|TR|",
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"mesh_terms": "D006801:Humans; D006993:Hypnotics and Sedatives; D008297:Male; D008875:Middle Aged; D008889:Military Personnel; D017286:Polysomnography; D011725:Pyridines; D007319:Sleep Initiation and Maintenance Disorders; D013009:Somnambulism; D014481:United States; D014743:Videotape Recording; D000077334:Zolpidem",
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"title": "Zolpidem tartrate and somnambulism.",
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"literaturereference": "HARAZIN J, BERIGAN TR. ZOLPIDEM TARTRATE AND SOMNAMBULISM. MIL MED. 1999?164(9):669-70",
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"abstract": "Progressive multifocal leukoencephalopathy is a rare opportunistic infection of the brain by John Cunningham polyomavirus in immune-compromised patients. In cases where no overt option for immune reconstitution is available [e.g., in patients with primary immunodeficiency (PID)], the disease is lethal in the majority of patients. Immune checkpoint inhibition has been applied in recent years with mixed outcomes. We present four novel patients and the follow-up of a previously published patient suffering from progressive multifocal leukoencephalopathy (PML) due to PID and/or hematologic malignancy who were treated with the immune checkpoint inhibitor pembrolizumab. In two patients with PID, symptoms improved and stabilized. One patient died because of worsening PML another of intracranial hemorrhage which was unrelated to PML or its treatment with pembrolizumab. The fifth patient suffered from PID and died of a pre-existing immune dysregulation, possibly exacerbated by pembrolizumab. The long-term follow-up of the first patient provides support for therapeutic decisions during this therapy and is the longest published clinical course of a patient with checkpoint inhibition for PML. We conclude that pembrolizumab can control PML symptoms long term in a subgroup of patients with PID, in our cases for 21 and 36 months. However, therapy must be started early because symptoms are only partially reversible. In light of severe adverse events, application of pembrolizumab is only justified if the prognosis for the individual patient is very poor.",
"affiliations": "Department of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacherstr. 64, 79106, Freiburg, Germany.;Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany.;Department of Hematology and Oncology, University Medical Center, Freiburg, Germany.;Department of Neuroradiology, University Hospital Freiburg, Freiburg, Germany.;Department of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacherstr. 64, 79106, Freiburg, Germany.;Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany.;Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany.;Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany.;Department of Neurology, Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacherstr. 64, 79106, Freiburg, Germany. [email protected].",
"authors": "Volk|Timo|T|http://orcid.org/0000-0001-9388-042X;Warnatz|Klaus|K|;Marks|Reinhard|R|;Urbach|Horst|H|;Schluh|Gisela|G|;Strohmeier|Valentina|V|;Rojas-Restrepo|Jessica|J|;Grimbacher|Bodo|B|;Rauer|Sebastian|S|",
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"doi": "10.1007/s00415-021-10682-8",
"fulltext": "\n==== Front\nJ Neurol\nJ Neurol\nJournal of Neurology\n0340-5354\n1432-1459\nSpringer Berlin Heidelberg Berlin/Heidelberg\n\n34196768\n10682\n10.1007/s00415-021-10682-8\nOriginal Communication\nPembrolizumab for treatment of progressive multifocal leukoencephalopathy in primary immunodeficiency and/or hematologic malignancy: a case series of five patients\nhttp://orcid.org/0000-0001-9388-042X\nVolk Timo [email protected]\n\n1\nWarnatz Klaus 23\nMarks Reinhard 4\nUrbach Horst 5\nSchluh Gisela 1\nStrohmeier Valentina 236\nRojas-Restrepo Jessica 3678\nGrimbacher Bodo 378910\nRauer Sebastian [email protected]\n\n1\n1 grid.5963.9 Department of Neurology, Medical Center – University of Freiburg, Faculty of Medicine, University of Freiburg, Breisacherstr. 64, 79106 Freiburg, Germany\n2 grid.7708.8 0000 0000 9428 7911 Department of Rheumatology and Clinical Immunology, University Medical Center Freiburg, Freiburg, Germany\n3 grid.7708.8 0000 0000 9428 7911 Center for Chronic Immunodeficiency (CCI), University Medical Center Freiburg, Freiburg, Germany\n4 grid.7708.8 0000 0000 9428 7911 Department of Hematology and Oncology, University Medical Center, Freiburg, Germany\n5 grid.7708.8 0000 0000 9428 7911 Department of Neuroradiology, University Hospital Freiburg, Freiburg, Germany\n6 grid.5963.9 Faculty of Biology, University of Freiburg, Freiburg, Germany\n7 grid.5963.9 Institute for Immunodeficiency, University Medical Center, Medical Faculty, Albert-Ludwigs-University of Freiburg, Freiburg, Germany\n8 RESIST – Cluster of Excellence 2155 to Hanover Medical School, Satellite Center, Freiburg, Germany\n9 DZIF – German Center for Infection Research, Satellite Center Freiburg, Freiburg, Germany\n10 grid.5963.9 CIBSS – Centre for Integrative Biological Signalling Studies, Albert-Ludwigs University, Freiburg, Germany\n1 7 2021\n1 7 2021\n2022\n269 2 973981\n13 5 2021\n21 6 2021\n© The Author(s) 2021\nhttps://creativecommons.org/licenses/by/4.0/ Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.\nProgressive multifocal leukoencephalopathy is a rare opportunistic infection of the brain by John Cunningham polyomavirus in immune-compromised patients. In cases where no overt option for immune reconstitution is available [e.g., in patients with primary immunodeficiency (PID)], the disease is lethal in the majority of patients. Immune checkpoint inhibition has been applied in recent years with mixed outcomes. We present four novel patients and the follow-up of a previously published patient suffering from progressive multifocal leukoencephalopathy (PML) due to PID and/or hematologic malignancy who were treated with the immune checkpoint inhibitor pembrolizumab. In two patients with PID, symptoms improved and stabilized. One patient died because of worsening PML another of intracranial hemorrhage which was unrelated to PML or its treatment with pembrolizumab. The fifth patient suffered from PID and died of a pre-existing immune dysregulation, possibly exacerbated by pembrolizumab. The long-term follow-up of the first patient provides support for therapeutic decisions during this therapy and is the longest published clinical course of a patient with checkpoint inhibition for PML. We conclude that pembrolizumab can control PML symptoms long term in a subgroup of patients with PID, in our cases for 21 and 36 months. However, therapy must be started early because symptoms are only partially reversible. In light of severe adverse events, application of pembrolizumab is only justified if the prognosis for the individual patient is very poor.\n\nSupplementary Information\n\nThe online version contains supplementary material available at 10.1007/s00415-021-10682-8.\n\nKeywords\n\nPML\nPembrolizumab\nPID\nHematologic malignancy\nAutoimmunity\nhttp://dx.doi.org/10.13039/501100001659 Deutsche Forschungsgemeinschaft GR1617/14-1/iPAD; SFB1160/2_B5; RESIST–EXC 2155–Project ID 390874280; and CIBSS–EXC-2189–Project ID 390939984) SFB1160 TP A04 Warnatz Klaus Grimbacher Bodo http://dx.doi.org/10.13039/501100002347 Bundesministerium für Bildung und Forschung GAIN 01GM1910A Grimbacher Bodo Universitätsklinikum Freiburg (8975)Open Access funding enabled and organized by Projekt DEAL.\n\nissue-copyright-statement© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany 2022\n==== Body\npmcIntroduction\n\nProgressive multifocal leukoencephalopathy (PML) is a rare, life threatening, opportunistic infection of the central nervous system caused by the reactivation of John Cunningham polyomavirus (JCV) almost exclusively in immunocompromised patients. Treatment focusses on restoring immunity of the affected patients since no effective antiviral therapies for JCV are available. To this end, e.g. combined antiretroviral therapy is given in HIV-infected patients or immunosuppressive drugs such as natalizumab are withdrawn in e.g., MS patients. In contrast, PML in the context of hematologic malignancy or primary immunodeficiency (PID) is lethal in the majority of cases as there are no therapeutic options for immune reconstitution [1].\n\nThe checkpoint inhibitor pembrolizumab is a monoclonal antibody disrupting interactions of programmed cell death protein 1 (PD-1) on T cells and its ligands on antigen-presenting cells. By blocking this receptor involved in negative regulation of T-cell activation, they boost immune responses. Originally, checkpoint inhibitors were developed to foster the antitumor immune response and were able to significantly improve survival in patients with metastatic melanoma [2] and others. In line with this mechanism, an association between reduced T-cell function and high PD-1 expression has also been shown in chronic viral infections such as HIV [3, 4]. Moreover, blockade of PD-1 expression in monkeys with chronic simian immunodeficiency virus infection resulted in an increase in activated virus-specific T cells, a reduced viral load, and prolonged survival of the animals [5, 6], ultimately contributing to the establishment and maintenance of HIV-1 latency [7].\n\nLaboratory evidence of PD-1 upregulation on T cells in PML patients [8] led to the off-label use of checkpoint inhibitors in the therapy of PML patients where no other option was available to reinvigorate antiviral immunity. To our knowledge, 31 published patients with PML have so far been treated with either pembrolizumab or nivolumab. Treatment outcomes range from moderate improvement of symptoms with stabilization to death from disease progression [9–25]. To date, there are no clear prognostic factors to identify patients in whom checkpoint inhibition will be able to ameliorate PML [26].\n\nHere, we give an update on the clinical course of one previously published patient [21] and describe four additional unpublished patients treated with pembrolizumab for PML in the context of PID and/or hematologic malignancy.\n\nMethods\n\nPatients received pembrolizumab at a dose of 2 mg per kilogram body weight (unless otherwise stated) on a compassionate-use basis after informed consent was obtained. Data of patients presented in this report were retrospectively collected. For flow cytometric analyses of PD-1 expression, peripheral blood mononuclear cells were isolated from EDTA blood of patients and healthy controls by Ficoll density gradient centrifugation following Standard protocols. Staining for PD-1 was performed on freshly isolated PBMCs or whole blood. Staining was performed for 15 min at 4°. In case of whole blood staining, red blood cell lysis was performed, following staining, using OptiLyse B (Beckman Coulter). Data were acquired using an LSR Fortessa (BD Biosciences) or FACS CANTO II (BD Biosciences). Data were analyzed using FlowJo Software (Treestar). Cells were stained with antibodies against CD45RA (PE-Cy7, HI100), CD3 (APC-H7, SK7), CD 4 (FITC, RPA-T4, all above from BD Pharmingen, Heidelberg, Germany), CD8 (PerCP-Cy5.5, RPA-T8, Invitrogen, Carlsbad, USA), CD3 (PerCp-Cy5.5, SK7), CD4 (PE-Cy7, RPA-T4), CD8 (PE, SK1), CD45 (BV421, HI30), CD45RA (APC-Cy7, HI100) and PD-1 (APC, EH12.2H7, all above from Biolegend, San Diego, USA). Additional laboratory analysis and magnetic resonance imaging (MRI) were performed as part of standard clinical care.\n\nResults\n\nPatient 1: a 21-year-old male patient with the diagnosis of CD40-ligand deficiency (MIM #308,230) was referred to us with a diagnosis of PML after progressive visual impairment over the past two months. MRI showed bi-occipital lesions on FLAIR (fluid-attenuated inversion recovery) sequences and a lesion in the globus pallidus on the right. JCV-PCR from cerebrospinal fluid (CSF) was positive with 471 copies per milliliter. One week after the first dose of pembrolizumab, he developed a maculopapular rash, which dissolved without further specific treatment and was considered an immune‐related adverse event. After another week, the patient was in a stable clinical condition. MRI showed mild contrast enhancement (Fig. 1) as sign of possible immune reconstitution inflammatory syndrome (IRIS), the JCV-PCR was still positive (but < 500 copies/ml). Another 2 weeks later the patient developed short term memory impairment and mild disorientation. Contrast enhancement in MRI remained stable while FLAIR lesions showed progression. The patient received a second dose of pembrolizumab 5 weeks after the first one. Subsequently the disorientation and memory impairment abated, JCV-PCR was negative and MRI showed stable lesions with persistent contrast enhancement. A third dose of pembrolizumab was administered 8 weeks after the first infusion. In follow-up visits the patient reported minimal improvement of visual impairment but showed no signs of cognitive impairment. He was able to resume his studies. MRI showed constant FLAIR lesions without contrast enhancement and JCV-PCR remained negative at follow-up 15 months after the first dose of pembrolizumab. A graphical overview of the clinical course is given in Figure S1 in this article’s Online Repository.Fig. 1 Transiently contrast-enhancing lesion in Patient 1. A Two months before treatment, bi-occipital lesions with minimal contrast enhancemend on the right as well as a lesion in the globus pallidus are visible. B Lesions progress after treatment, a new lesion in the left frontal lobe, as well as bi-thalamic lesions are visible. Contrast enhancement is increased in the right occipital lesion. C Lesion in the thalamus is less intense, otherwise stable MRI. D + E Declining intensities of lesions, no contrast enhancement is detectable 15 months after initial treatment. Top row: FLAIR (Fluid-attenuated inversion recovery) MRI sequences, bottom row: MP RAGE (magnetization-prepared 180 degrees radio-frequency pulses and rapid gradient-echo sequences) MRI sequences post gadolinium application. m month, w week\n\nPatient 2: A 45-year-old woman presented with fluctuating hypesthesia of the left leg for a few weeks. The patient was on immunoglobulin replacement therapy for common variable immunodeficiency (CVID) with immune dysregulation including enteropathy, autoimmune cytopenia and interstitial lung disease. For enteropathy, she received budesonide. Rituximab had been administered 15 years before presentation for immune thrombocytopenia and hemolytic anemia. MRI showed a parietooccipital FLAIR lesion on the right hemisphere without contrast enhancement. A stereotactic biopsy was performed after extensive testing of CSF (including negative JCV-PCR). PML was diagnosed based on a strongly positive JCV-PCR from the biopsy and pembrolizumab was administered. Within days, symptoms progressed with mild hemiparesis on the right. MRI showed mild contrast enhancement as sign of IRIS. After a complete stabilization with only mild persistent hypesthesia and no signs of worsening enteropathy, the patient received a second dose of pembrolizumab after 3 weeks. Further treatment was withheld because of stabilization after the second dose and the potential reactivation of the pre-existing autoimmune condition. After intermittent diarrhea and leukopenia, a third dose was given 4 months after the first dose because of mild progression of FLAIR lesions on MRI without contrast enhancement concomitant with increase in PD-1 expression on T cells after an initial decrease (Fig. 2). Subsequently, the patient developed severe leukopenia requiring corticoid therapy and administration of granulocyte colony-stimulating factor and the diarrhea worsened. Additionally, there was laboratory evidence of autoimmune hepatitis. Because of newly developing cognitive deficits with neglect and progression of the parietooccipital FLAIR lesion and after discussion with the patient and relatives a fourth dose of pembrolizumab was administered with a reduced dose of 0.5 mg per kilogram body weight after leukopenia, diarrhea and hepatitis had abated over a period for approximately 1 week. PD-1 expression on T cells decreased again after the fourth dose but leukopenia reoccurred and she developed a pneumonia. In light of the clinical deterioration and the desperate situation the patient opted for palliative care and subsequently died from bleeding due to severe thrombocytopenia 6 months after the beginning of pembrolizumab treatment. A graphical overview of the clinical course is given in Figure S2 in this article’s Online Repository.Fig. 2 Patients show reduced expression of PD-1 on T cells after Pembrolizumab treatment. PD-1 expression is within normal range on CD4 + (A) and CD8 + (B) T cells in Patient 1 and 2 before treatment. Patient 3 and 4 show normal expression on CD8 + (B) and high normal expression on CD4 + T cells before treatment. All patients show a reduction of PD-1 expression after treatment. An increase is seen on T cells from Patient 2 four and five months after the first infusion during severe autoimmune adverse reactions. Cells from Patient 5 were analyzed only 16 and 18 months after commencement of therapy and show low to low normal expression of PD-1\n\nPatient 3: A 78-year-old man presented with slowly progressing hemianopia over a few weeks. He had received chemotherapy including rituximab for the treatment of a diffuse large B-cell lymphoma (DLBCL) 1 month prior to development of the symptom. MRI showed a large right occipital FLAIR lesion without contrast enhancement. JCV-PCR of CSF was positive (< 500 copies/ml). Pembrolizumab was administered. Three weeks later, the patient reported worsening vision of the left eye and a tumor of the iris was identified. Additionally, he showed several tumors of the arm and leg suspicious of enlarged lymph nodes. A biopsy of one lymph node showed a relapse of the lymphoma. The occipital FLAIR lesion had progressed without contrast enhancement. However, a left sided contrast-enhancing lesion had developed, suspicious of lymphoma. While being evaluated for further therapeutic options regarding the lymphoma, he developed a coma due to an extensive intracranial hemorrhage on the left hemisphere under full anticoagulation therapy for atrial fibrillation. He died a few days later under palliative care. A graphical overview of the clinical course is given in Figure S3 in this article’s Online Repository.\n\nPatient 4: A 45-year-old man presented with progressing dysarthria, impaired vision and attention deficit for 2 weeks. He suffered from a combined immunodeficiency due to a deleterious compound heterozygous mutation in DOCK8 (dedicator of cytokinesis 8, MIM # 243,700), symptomatic with recurrent tumors of the skin, two episodes of meningitis in childhood, and mild lymphopenia (including at presentation to our clinic). An MRI showed bi-occipital FLAIR lesions without contrast enhancement and after positive JCV-PCR in the CSF, the diagnosis of PML was made. Pembrolizumab was administered for the first time. Relatives described decreasing dysarthria after the first dose. After another 2 weeks the patient developed non-fluent aphasia, attention deficit, further deterioration of his vision and right-sided hemiparesis. JCV-PCR from the CSF rose to 10.000 copies/ml and FLAIR lesions progressed with contrast enhancement at the borders. A second dose of pembrolizumab was administered. After being discharged to a rehabilitation clinic with stable deficits, the patient developed abdominal pain without diarrhea. No clear etiology for this pain (including autoimmune enteropathy, pancreatitis or hepatitis) could be established, and the pain subsided after antibiotic treatment. Symptoms of PML had progressed to severe spastic hemiparesis, JCV-PCR from the CSF was again positive with 68.500 copies/ml and the MRI showed a progression of lesions to the thalamus. Since PML lesions progressed with only mild maculopapular rash as sign of an autoimmune adverse reaction a third dose of pembrolizumab was administered. One week later the patient had two generalized epileptic seizures and fell into a persistent coma. Palliative care was initiated and the patient died a few days later. A graphical overview of the clinical course is given in Figure S4 in this article’s Online Repository.\n\nPatient 5: A 49-year-old patient presented to us with aphasia, ataxia, apraxia and difficulties in memory. This patient’s initial clinical course has already been published [21]. In short, he was diagnosed with PML by positive JCV-PCR (1,150 copies/ml) in CSF and left-hemispheric FLAIR lesions on MRI. He had previously been diagnosed with CVID and had received Rituximab for DLBCL. Because of worsening of symptoms (mutism) and progressing lesions on MRI pembrolizumab was administered. The patient was subsequently able to speak again and JCV-PCR was negative except for 1 analysis when intervals of dosing were extended from 2 to 4 weeks. Contrast enhancement was detected on MRI after the 6th infusion compatible with IRIS, but the patient showed no corresponding symptoms. After the 8th infusion the patient had self-limiting diarrhea for a few days. Because of stable symptoms and MRI lesions dosing intervals were extended to monthly intervals after the 7th infusion. Before the 10th infusion, JCV-PCR was positive, therefore pembrolizumab was then given every 2 weeks and after negative PCR every 3 weeks. After the 24th infusion Transaminases were elevated and therefore pembrolizumab was halted. JCV-PCR was positive for 4 months (2 months after pembrolizumab was halted), but was negative again without further administration of pembrolizumab. Lymphopenia had abated without specific treatment. Thirty-nine months after onset of symptoms and 36 months after the first infusion, the patient is stable with severe aphasia, cognitive impairment and is dependent on care from his wife. However, during treatment he showed incremental improvement of aphasia and interaction (ability to utter needs with incomplete sentences and comprehension and execution of simple commands) and ataxia (ability to walk on his own and recently successful attempts to ride a bike with support). MRI shows progressive tissue atrophy without signs of active PML (Fig. 3). JCV-PCR remained negative. A graphical overview of the clinical course is given in Figure S5 in this article’s Online Repository.Fig. 3 Shrinking PML lesion during therapy and progressive atrophy in Patient 5. FLAIR images showing the largest lesion extension (A) after two months. B Shrinkage of the lesion four months later (B), previously published in [21]. (D) and (E) showing progressive tissue atrophy between 30 and 35 months after commencement of pembrolizumab. C is an overlay of A and B, (F) is an overlay of (D) and (E) with 50% transparency each. m indicating months after the first administration of pembrolizumab, over overlap\n\nDiscussion\n\nWithout efficient antiviral therapy, the mainstay of PML therapy is immune reconstitution. In conditions where reversal of immune suppression is not achieved mortality is high. This is demonstrated by a median survival of 2 months in a case series of patients with in hematologic malignancies and stem-cell transplantation [27]. Checkpoint inhibition has been applied so far in 11 cases with nivolumab therapy and 20 cases with pembrolizumab therapy (including our previous report) with varying results [9–25]. Here were report on a series of 4 novel patients with PML in the context of PID or hematologic malignancy treated with pembrolizumab and follow-up data on one previously reported patient [21].\n\nTwo patients in this cohort showed long-term stabilization judged by regression of MRI lesions and ultimately negative JCV-PCR from CSF. Symptoms improved moderately but patients still suffer from significant sequelae from PML. This is representative of other published patients with good clinical outcomes, in whom deficits were stable or showed moderate improvement [9, 10, 15, 23, 25]. Only one patient with frontal lobe syndrome due to PML showed complete independence in daily life after treatment with IL-2 and pembrolizumab [17]. The death of Patient 3 due to intracranial hemorrhage—most likely in a lesion of his recurrent lymphoma under anticoagulation therapy—rather demonstrates the aggressive disease causing the underlying immunodeficiency than failure of pembrolizumab. Death from other causes (mainly progressive cancer) is also reported in other PML patients treated with nivolumab or pembrolizumab [13, 17].\n\nIn Patient 4 disease progression could not be stopped, demonstrated by rising copy numbers of JCV-DNA in CSF and increasing lesions on MRI. Similar catastrophic clinical courses have been published previously, including a young patient who was diagnosed early after mild symptoms developed and had low copy numbers of JCV-DNA in CSF at diagnosis [10, 12, 18, 20, 22]. This challenges the concept that the disease can be controlled if treatment was commenced early and raises the question, if the underlying immunodeficiency itself is a prognostic factor. Medrano et al. hypothesize that the fatal outcome in all of their three patients was due to the cyclosporine given to prevent kidney transplant rejection [18]. However, a patient who responded to nivolumab also received cyclosporine one month prior to developing PML [23]. In our case the patient suffered from a combined immunodeficiency due to mutations in DOCK8 known for difficulties in the control of certain viral infections, so that even the blocking of PD1-mediated inhibition may have not been sufficient to overcome the T-cell deficiency which are also known to have a migratory defect in DOCK8-deficient patients, uncurable by checkpoint blockade.\n\nTherefore, a careful evaluation of the cellular immune status may be informative of the potential outcome. Severe and especially inborn lymphopenia or functional T-cell deficiency might dampen the therapeutic success of checkpoint inhibition. Along this line, two groups applied IL-2 before administration of pembrolizumab in three patients. One patient had a good outcome, the other two died of other diseases (lymphoma and pneumonia) [11, 17]. Patients with a desirable outcome in our report did not show lymphopenia before therapy (Patient 1) or showed rising lymphocyte counts during therapy (Patient 5). Regarding lymphocyte subsets, B-cell lymphopenia was most prominent in our cohort (Table 1) and in a recently published series of six cases [25]. However, B-cell counts did not serve as a prognostic marker exemplified by Patient 4 having normal B-cell counts and no response to therapy. T-cell subset analyses showed an expansion of activated memory T cells while naïve populations were reduced – often seen in patients with PID—and did not differ between patients with regard to their outcome (Table S1). Pawlitzki et al. propose analyzing lymphocyte subsets since they found higher frequencies of progenitor-exhausted T cells in a patient with good clinical response to pembrolizumab and higher frequencies of terminally exhausted T cells in a patient without response to pembrolizumab [20]. Progenitor and terminally exhausted T cells have not been analyzed in out cohort.Table 1 Patient characteristics, laboratory data and clinical course\n\nPatient Sex and age at presentation underlying condition\tCell counts before first dose [/µl]\tT-cell subsets before first dose†\tJCV PCR in CSF at diagnosis [copies/ml]\tJCV PCR in CSF during treatment\tStart of pembrolizumab after onset of PML symptoms\tIRIS\tPossible autoimmune adverse reactions\tOutcome\t\nPatient 1\n\nMale, 21 years CD40-ligand deficiency\n\n\tLeuko\n\nLympho\n\nCD3\n\nCD19\n\nCD4\n\nCD8\n\n\t6810\n\n3070 ↑\n\n2442 ↑\n\n479\n\n457\n\n1577↑\n\n\tExpansion of activated CD8 + T cells and\n\nearly and late CD8 + T cells\n\n\t471\tNegative after 2 infusions 8 weeks after first infusion\t10 weeks\tPossibly, CE after first infusion, confusion 4 weeks later\tMaculopapular rash\tStable, significant sequelae (cortical blindness)\t\nPatient 2\n\nFemale, 45 years CVID\n\n\tLeuko\n\nLympho\n\nCD3\n\nCD19\n\nCD4\n\nCD8\n\n\t4150\n\n200 ↓\n\n183 ↓\n\n0 ↓\n\n142 ↓\n\n37 ↓\n\n\tReduction of naive CD4 + T cells\n\nExpansion of memory CD8 + T cells\n\n\tNegative in CSF, PCR from brain biopsy positive\tNot applicable (negative in CSF at diagnosis)\tApprox. 3 months\tLikely, CE 4 days after first infusion, concomitant worsening of symptoms\tRecurrent diarrhea, severe pancytopenia\tDeath, possibly due to autoimmune complications (bleeding, severe thrombocytopenia), initially improved regarding PML symptoms\t\nPatient 3\n\nMale, 78 years DLBCL\n\n\tLeuko\n\nLympho\n\nCD3\n\nCD19\n\nCD4\n\nCD8\n\n\t7610\n\n864 ↓\n\n778\n\n0 ↓\n\n500\n\n265\n\n\tNot done\tPositive (< 500)\tNegative after 1 infusion 4 weeks after first infusion\t < 4 weeks (precise onset unknown)\tNo\tNone\tDeath, due to unrelated disease, stable regarding PML symptoms\t\nPatient 4\n\nMale, 45 years CID due to DOCK8 deficiency\n\n\tLeuko Lympho\n\nCD3\n\nCD19\n\nCD4\n\nCD8\n\n\t7580\n\n861 ↓\n\n555 ↓\n\n195\n\n261 ↓\n\n282\n\n\tReduction of naive CD4 + T cells and naive CD8 + T cells\t500\tRising to 68.500 after 2 infusions, 6 weeks after first infusion\t2 weeks\tNo, CE at borders of PML lesion concomitant with rising JCV in CSF suggestive of advancing PML\tmaculopapular rash\tDeath due to rapidly worsening PML\t\nPatient 5\n\nMale, 49 years\n\nCVID, DLBCL\n\n\tLeuko\n\nLympho\n\nCD3\n\nCD19\n\nCD4\n\nCD8\n\n\t5000\n\n234 ↓\n\n111 ↓\n\n0 ↓\n\n40 ↓\n\n62 ↓\n\n\tReduction of naive CD4 + and CD8 + T cells\n\nExpansion of activated T cells, antigen experienced CD4 + T cells and early CD8 + effector cells\n\n\t1150\tRising to 252.500 after first infusion\n\nNegative after 5 infusions\n\n9 weeks after first infusion\n\nSubsequently Transiently positive with low copy numbers§\n\n\t4 months\tUnlikely, CE 9 weeks after first infusion without corresponding symptoms\tTransient mild diarrhea, Transaminitis\tStable, initial improvement of attention and speech, severe sequelae\t\nJCV John Cunningham polyomavirus, CSF Cerebrospinal fluid, IRIS immune reconstitution inflammatory syndrome, CE contrast enhancement on MRI, CVID common variable immunodeficiency, Leuko Leukocytes, Lympho Lymphocytes, DLBCL diffuse large B-cell lymphoma, CID combined immunodeficiency\n\nBold numbers indicate values above (↑) or below (↓) reference values [30, 31]\n\n†Table depicting values of subsets and subset defining markers in Table S1 in this article’s Online Repository\n\nPD-1 expression on T cells from peripheral blood from our patients was within the range of healthy controls. Pembrolizumab administration abrogated PD-1 expression successfully on circulating T cells in all patients and therefore was not predictive for outcome or negativity of JCV-PCR (Fig. 2). Patient 1 showed an increase in PD-1 expression 14 months after the last infusion. JCV-PCR was negative 13 months after the last infusion, indicating that viral control is possible even after the effect of pembrolizumab wears off. In Patient 5 PD-1 expression was still decreased 4 months after the last infusion. JCV-PCR was transiently positive at that point. Patient 2 showed clinical and MRI progression of the disease after an initial response. While PML was progressing, PD-1 expression first increased and then decreased again. This indicates that a reduction in PD-1 expression might be prerequisite for viral control at beginning of therapy but does not strictly correlate with viral control or symptoms of PML.\n\nIn line with these findings, a clinical response to pembrolizumab was not correlated to PD-1 suppression in a cohort of eight patients published by Cortese et al. [10]. However, in vitro T-cell reactivity to JCV peptides was only detected in patients who also responded to therapy. This indicates that pembrolizumab might only be able to support a pre-existing immune response to JCV.\n\nAlthough pre-existing autoimmune diseases not necessarily exclude treatment with checkpoint inhibitors in patients with cancer, clinical experience regarding exacerbation of already established autoimmune conditions after application of checkpoint inhibitors is rare. Nevertheless, autoimmune phenomena (e.g., diarrhea, pneumonitis) as a result of checkpoint inhibition is frequently being observed in cancer patients. Autoimmune adverse reactions, such as myositis, rashes and worsening of a pre-existing digestive tract granulomatosis, have been reported in PML patients [14, 23, 25]. None of the previously published PML patients experienced autoimmune cytopenia after treatment with pembrolizumab or nivolumab, despite one of the patients suffered from autoimmune thrombocytopenia before development of PML [10, 16, 20, 24]. In contrast, Patient 2 showed marked exacerbation of pre-existing cytopenia with only transient response to granulocyte colony-stimulating factor and corticosteroid therapy and enteropathy, which was not prevented by increased budesonide prophylaxis. She developed a pneumonia during leukopenia and ultimately died from bleeding due to thrombocytopenia likely triggered by pembrolizumab after wishing for no further treatment. Given her significant initial improvement of symptoms caused by PML, our prophylactic options for secondary immune exacerbation must be improved and in the absence of suitable prophylaxis benefits of checkpoint inhibition must be strictly weighed against possible risks in patients with pre-existing autoimmune conditions and patients need to be plainly informed about the potential risk.\n\nIRIS after checkpoint inhibition has rarely been reported [13, 21, 22, 24]. Four of our five patients showed contrast enhancement on MRI after initiation of pembrolizumab, but only Patient 2 had concomitant worsening of symptoms. Paralleled to his clinical deterioration patient 4 showed marked contrast enhancement on the borders of the lesions on MRI also in line with progressing PML. In HIV-infected patients signs of IRIS have been proposed to indicate better prognosis [28, 29], results from our patients and previously published patients are ambiguous.\n\nGiven the short history of pembrolizumab therapy in PML, many therapeutic decisions have to be made without precedence. Observations from patients in this report including a unique 38-month follow-up add substantially to previously published data: (i) Patients with certain pre-existing T-cell deficiencies may not respond to pembrolizumab therapy for PML. (ii) The number of infusions required for disease control may vary between patients and (iii) patients with poorly controlled autoimmune disorders may not be able to receive the minimal effective dose of pembrolizumab due to severe life-threatening exacerbation of autoimmune adverse reactions. (iv) Fluctuating results from JCV-PCR may not necessitate reinstallation of pembrolizumab.\n\nConclusion\n\nFor a subset of patients with immunodeficiency due to PID and/or hematologic malignancy pembrolizumab treatment can stop disease progression while symptoms may improve only moderately. Further studies must carefully define subset of patients, in whom checkpoint inhibition is a valuable treatment option. Laboratory analyses of in vitro T-cell reactivity to JCV [10] or detection of progenitor-exhausted T cells are candidate surrogates for an immune state which can be enhanced by checkpoint inhibition. Pre-existing autoimmunity is a severe contraindication which requires a careful and consented decision if therapy is justified on an individual basis. Clinical courses of treated patients must be closely monitored and analyzed to reach optimal outcome.\n\nSupplementary Information\n\nBelow is the link to the electronic supplementary material.Supplementary file1 (PDF 930 KB)\n\nAuthor contributions\n\nTV analyzed and interpreted data and wrote the manuscript. KW, BG, and SR recruited patients, designed the research and edited the manuscript. RM, HU, VS, and JR-R analyzed and interpreted data.\n\nFunding\n\nOpen Access funding enabled and organized by Projekt DEAL. B.G. receives support by the Deutsche Forschungsgemeinschaft (GR1617/14-1/iPAD; SFB1160/2_B5; RESIST–EXC 2155–Project ID 390874280; and CIBSS–EXC-2189–Project ID 390939984) and the BMBF (GAIN 01GM1910A). He declares no conflict of interest wrt the content of this manuscript. V.S. is funded by the Deutsche Forschungsgemeinschaft (grant to K.W. SFB1160 TP A04). T.V., R.M., H.U., G.S., J.R.-R. and S.R. received no funding for this study.\n\nData availability\n\nNot applicable.\n\nCode availability\n\nNot applicable.\n\nDeclarations\n\nConflicts of interest\n\nDeclare no conflict of interest wrt the content of this manuscript.\n\nEthics approval\n\nNot applicable.\n\nConsent to participate\n\nAll patients received pembrolizumab on a compassionate-use basis after informed consent was obtained.\n\nConsent for publication\n\nAll patients, guardians or next of kin have gave written informed consent for publication.\n==== Refs\nReferences\n\n1. Cortese I Reich DS Nath A Progressive multifocal leukoencephalopathy and the spectrum of JC virus-related disease Nat Rev Neurol 2021 17 1 37 51 10.1038/s41582-020-00427-y 33219338\n2. Curry WT Lim M Immunomodulation: checkpoint blockade etc Neuro Oncol 2015 17 Suppl 7 vii26 vii31 10.1093/neuonc/nov174 26516223\n3. Grabmeier-Pfistershammer K Identification of PD-1 as a unique marker for failing immune reconstitution in HIV-1-infected patients on treatment J Acquir Immune Defic Syndr 2011 56 2 118 124 10.1097/QAI.0b013e3181fbab9f 20980914\n4. Zhang JY PD-1 up-regulation is correlated with HIV-specific memory CD8+ T-cell exhaustion in typical progressors but not in long-term nonprogressors Blood 2007 109 11 4671 4678 10.1182/blood-2006-09-044826 17272504\n5. Barber DL Restoring function in exhausted CD8 T cells during chronic viral infection Nature 2006 439 7077 682 687 10.1038/nature04444 16382236\n6. Velu V Enhancing SIV-specific immunity in vivo by PD-1 blockade Nature 2009 458 7235 206 210 10.1038/nature07662 19078956\n7. Evans VA Programmed cell death-1 contributes to the establishment and maintenance of HIV-1 latency AIDS 2018 32 11 1491 1497 10.1097/QAD.0000000000001849 29746296\n8. Tan CS Increased program cell death-1 expression on T lymphocytes of patients with progressive multifocal leukoencephalopathy J Acquir Immune Defic Syndr 2012 60 3 244 248 10.1097/QAI.0b013e31825a313c 22549384\n9. Audemard-Verger A Sustained response and rationale of programmed Cell Death-1-targeting for progressive multifocal leukoencephalopathy Open Forum Infect Dis 2019 6 10 ofz374 10.1093/ofid/ofz374 31660340\n10. Cortese I Pembrolizumab treatment for progressive multifocal leukoencephalopathy N Engl J Med 2019 380 17 1597 1605 10.1056/NEJMoa1815039 30969503\n11. Goereci Y Clearance of JC polyomavirus from cerebrospinal fluid following treatment with interleukin-2 and pembrolizumab in an individual with progressive multifocal leukoencephalopathy and no underlying immune deficiency syndrome Eur J Neurol 2020 27 11 2375 2377 10.1111/ene.14435 32644211\n12. Grassl N Nivolumab for treatment of progressive multifocal leukoencephalopathy in Sezary syndrome Eur J Neurol 2020 27 11 2373 2374 10.1111/ene.14433 32644207\n13. Hoang E Progressive multifocal leukoencephalopathy treated with nivolumab J Neurovirol 2019 25 2 284 287 10.1007/s13365-019-00738-x 30864100\n14. Holmes A Progressive multifocal leukoencephalopathy associated with a lymphoproliferative disorder treated with pembrolizumab J Neurovirol 2020 26 6 961 963 10.1007/s13365-020-00899-0 32910430\n15. Kapadia RK Ney D Stabilization of progressive multifocal leukoencephalopathy after pembrolizumab treatment Neurohospitalist 2020 10 3 238 239 10.1177/1941874420902872 32549952\n16. Kupper C Pembrolizumab for progressive multifocal leukoencephalopathy due to primary immunodeficiency Neurol Neuroimmunol Neuroinflamm 2019 6 6 e628 10.1212/NXI.0000000000000628 31597693\n17. Mahler C, et al. (2020) Sequential interleukin 2 and pembrolizumab use in progressive multifocal leukoencephalopathy. Neurol Neuroimmunol Neuroinflamm 7(4).\n18. Medrano C Effectiveness of immune checkpoint inhibitors in transplant recipients with progressive multifocal leukoencephalopathy Emerg Infect Dis 2019 25 11 2145 2147 10.3201/eid2511.190705 31625858\n19. Mozo Ruiz M Pembrolizumab treatment for progressive multifocal leukoencephalopathy in a patient with Human Immunodeficiency Virus infection Enferm Infecc Microbiol Clin 2020 38 8 396 397 10.1016/j.eimc.2019.12.008\n20. Pawlitzki M Ineffective treatment of PML with pembrolizumab: exhausted memory T-cell subsets as a clue? Neurol Neuroimmunol Neuroinflamm 2019 6 6 e627 10.1212/NXI.0000000000000627 31597692\n21. Rauer S Treatment of progressive multifocal leukoencephalopathy with pembrolizumab N Engl J Med 2019 380 17 1676 1677 10.1056/NEJMc1817193 30969507\n22. Stogbauer J Clinical and magnetic resonance imaging monitoring in progressive multifocal leukoencephalopathy treated with pembrolizumab: a case report Neurol Sci 2021 42 1 357 359 10.1007/s10072-020-04582-4 32700225\n23. Uzunov M Postallogeneic transplantation progressive multifocal leukoencephalopathy successfully treated by nivolumab Br J Haematol 2020 188 6 e82 e84 10.1111/bjh.16349 31797364\n24. Walter O Treatment of progressive multifocal leukoencephalopathy with nivolumab N Engl J Med 2019 380 17 1674 1676 10.1056/NEJMc1816198 30969500\n25. Roos-Weil D, et al. (2021) Immune checkpoint inhibitors for progressive multifocal leukoencephalopathy: a new gold standard? J Neurol.\n26. Du Pasquier RA Pembrolizumab as a treatment for PML? Waiting for Godot Neurol Neuroimmunol Neuroinflamm 2019 6 6 e629 10.1212/NXI.0000000000000629 31597694\n27. Adrianzen Herrera D Characteristics and outcomes of progressive multifocal leukoencephalopathy in hematologic malignancies and stem cell transplant - a case series Leuk Lymphoma 2019 60 2 395 401 10.1080/10428194.2018.1474523 29969336\n28. Berger JR Predictive factors for prolonged survival in acquired immunodeficiency syndrome-associated progressive multifocal leukoencephalopathy Ann Neurol 1998 44 3 341 349 10.1002/ana.410440309 9749600\n29. Sainz-de-la-Maza S Incidence and prognosis of immune reconstitution inflammatory syndrome in HIV-associated progressive multifocal leucoencephalopathy Eur J Neurol 2016 23 5 919 925 10.1111/ene.12963 26914970\n30. Hulstaert F Age-related changes in human blood lymphocyte. II. Subpopulations varying kinetics of percentage and absolute count measurements Clin Immunol Immunopathol 1994 70 2 152 158 10.1006/clin.1994.1023 7905366\n31. Schatorje EJ Age-matched reference values for B-lymphocyte subpopulations and CVID classifications in children Scand J Immunol 2011 74 5 502 510 10.1111/j.1365-3083.2011.02609.x 21815909\n\n",
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{
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{
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{
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}
] |
{
"abstract": "Tardive dyskinesia (TD), a condition characterized by involuntary movements, is found in patients taking antipsychotics or other agents that block dopamine receptors. Symptoms of TD are associated with reduced quality of life, psychosocial problems, and medication nonadherence. Few agents tested in the treatment of TD had sufficient data to support or refute their use, until recently. A review of new evidence was combined with the existing guideline to provide new treatment recommendations. This activity provides an overview of treatments for patients with TD, including valbenazine and deutetrabenazine, which both received FDA approval for the treatment of TD.",
"affiliations": "Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta University, Augusta, Georgia, USA.",
"authors": "McEvoy|Joseph P|JP|",
"chemical_list": "C000603978:valbenazine; D014633:Valine; C000609690:deutetrabenazine; D013747:Tetrabenazine",
"country": "United States",
"delete": false,
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"issn_linking": "0160-6689",
"issue": "81(1)",
"journal": "The Journal of clinical psychiatry",
"keywords": null,
"medline_ta": "J Clin Psychiatry",
"mesh_terms": "D006801:Humans; D055118:Medication Adherence; D017410:Practice Guidelines as Topic; D000071057:Tardive Dyskinesia; D013747:Tetrabenazine; D014633:Valine",
"nlm_unique_id": "7801243",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "31851437",
"pubdate": "2019-12-17",
"publication_types": "D016428:Journal Article; D016454:Review",
"references": null,
"title": "FDA-Approved Medications to Treat Tardive Dyskinesia.",
"title_normalized": "fda approved medications to treat tardive dyskinesia"
} | [
{
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}
],
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"literaturereference": "McEvoy JP. FDA-Approved Medications to Treat Tardive Dyskinesia. JOURNAL OF CLINICAL PSYCHIATRY. 2020;81(1):NIL_0141-7",
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{
"abstract": "Nivolumab is a checkpoint inhibiting immunotherapeutic agent prescribed for the treatment of resistant cancers. Many immune-related adverse effects including neurological effects have been described, but central nervous system (CNS) toxicities are rarely reported. We present a 59-year-old Caucasian woman with a history of treatment-resistant, progressive, laryngeal squamous cell carcinoma. She received nivolumab and presented with gradual weakness, confusion, and progressive dyspnea. Magnetic resonance imaging of the head showed multifocal cerebral demyelination, primarily involving the parietal lobe. The diagnosis of acute demyelinating encephalitis was made. She improved dramatically after stopping nivolumab and receiving treatment with high-dose intravenous steroid and immunoglobin therapy. We conclude, from this case and literature review, that immune checkpoint inhibitor treatment requires more investigation to determine if autoimmune encephalitis with demyelination can occur as a severe form of immune-related adverse events. CNS toxicity appears to be reversible with prompt cessation of immunotherapy followed by treatment with high doses of steroid with or without intravenous immunoglobulin therapy.",
"affiliations": "Department of Internal Medicine, Southern Illinois University, Springfield, IL.;Department of Internal Medicine, Southern Illinois University, Springfield, IL.;Department of Internal Medicine, Southern Illinois University, Springfield, IL.;Department of Internal Medicine, Southern Illinois University, Springfield, IL [email protected].",
"authors": "Zafar|Zubair|Z|;Vogler|Carrie|C|;Hudali|Tamer|T|;Bhattarai|Mukul|M|",
"chemical_list": "D000077594:Nivolumab",
"country": "United States",
"delete": false,
"doi": "10.3121/cmr.2019.1417",
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"issn_linking": "1539-4182",
"issue": "17(1-2)",
"journal": "Clinical medicine & research",
"keywords": "Anti PD-1; Checkpoint inhibitor; Demyelination; Nivolumab",
"medline_ta": "Clin Med Res",
"mesh_terms": "D002294:Carcinoma, Squamous Cell; D003711:Demyelinating Diseases; D004660:Encephalitis; D005260:Female; D006801:Humans; D007822:Laryngeal Neoplasms; D008875:Middle Aged; D000077594:Nivolumab",
"nlm_unique_id": "101175887",
"other_id": null,
"pages": "29-33",
"pmc": null,
"pmid": "31160476",
"pubdate": "2019-06",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "28626408;25399552;28068177;26419960;27271951;28280368;27893699;28915085;28064139;28228726;27380808;26906964;29320654;24980937",
"title": "Nivolumab-Associated Acute Demyelinating Encephalitis: A Case Report and Literature Review.",
"title_normalized": "nivolumab associated acute demyelinating encephalitis a case report and literature review"
} | [
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{
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{
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},
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},
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"medicinalproduct": "PACLITAXEL/PACLITAXEL LIPOSOME"
}
],
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"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Pneumonia",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "2"
},
{
"reactionmeddrapt": "Off label use",
"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
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},
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"literaturereference": "ZAFAR Z, VOGLER C, HUDALI T, BHATTARAI M. NIVOLUMAB-ASSOCIATED ACUTE DEMYELINATING ENCEPHALITIS: A CASE REPORT AND LITERATURE REVIEW. CLINICAL MEDICINE AND RESEARCH. 2019?17(1-2): 29-33. DOI:10.3121/CMR.2019.1417.",
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},
"primarysourcecountry": "US",
"receiptdate": "20190819",
"receivedate": "20190819",
"receiver": {
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"receivertype": "6"
},
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"sendertype": "2"
},
"serious": 1,
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"seriousnessother": 1,
"transmissiondate": "20191004"
}
] |
{
"abstract": "We present the case of a 2-year-old boy with a history of necrotizing enterocolitis (NEC) with ileostomy diagnosed with systemic juvenile idiopathic arthritis (sJIA) at 10 months of age controlled on anti-interleukin-1 (anti-IL-1) therapy (anakinra). At 17 months of age, ileostomy reversal and bowel re-anastomosis was scheduled with anakinra discontinued 3 days prior to the surgery and steroids initiated in its place. Ten days postoperatively, anakinra was re-started for signs of sJIA flare. Three months later, he developed persistent peripheral eosinophilia and subsequent anaphylactic reaction 6 months postoperatively. The patient safely tolerated an alternative anti-IL-1 agent (canakinumab). Anaphylaxis to anakinra has not been previously reported in the pediatric literature. This case highlights an important issue in a pediatric patient with sJIA: safety of an alternate anti-IL-1 agent, following development of allergy to one initial agent.",
"affiliations": "Department of Pediatric Rheumatology, Hospital for Special Surgery; New York-Presbyterian Hospital/Weill Cornell Medical College, 535 East 70th Street, New York, NY, 10021, USA. [email protected].;Department of Pediatric Rheumatology, Hospital for Special Surgery; New York-Presbyterian Hospital/Weill Cornell Medical College, 535 East 70th Street, New York, NY, 10021, USA.;Department of Pediatric Rheumatology, Hospital for Special Surgery; New York-Presbyterian Hospital/Weill Cornell Medical College, 535 East 70th Street, New York, NY, 10021, USA.;Department of Pediatric Rheumatology, Hospital for Special Surgery; New York-Presbyterian Hospital/Weill Cornell Medical College, 535 East 70th Street, New York, NY, 10021, USA.;Department of Pediatric Rheumatology, Hospital for Special Surgery; New York-Presbyterian Hospital/Weill Cornell Medical College, 535 East 70th Street, New York, NY, 10021, USA.",
"authors": "Aguiar|Cassyanne L|CL|;Pan|Nancy|N|;Adams|Alexa|A|;Barinstein|Laura|L|;Lehman|Thomas J|TJ|",
"chemical_list": "D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D013256:Steroids; C541220:canakinumab",
"country": "Germany",
"delete": false,
"doi": "10.1007/s10067-015-2889-y",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0770-3198",
"issue": "34(10)",
"journal": "Clinical rheumatology",
"keywords": "Anakinra; Anaphylaxis; Anti-interleukin-1; Canakinumab; Interleukin-1 receptor antagonist; Systemic juvenile idiopathic arthritis",
"medline_ta": "Clin Rheumatol",
"mesh_terms": "D000707:Anaphylaxis; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D018501:Antirheumatic Agents; D001171:Arthritis, Juvenile; D002675:Child, Preschool; D004802:Eosinophilia; D006801:Humans; D007081:Ileostomy; D053590:Interleukin 1 Receptor Antagonist Protein; D053583:Interleukin-1beta; D008297:Male; D013256:Steroids; D016896:Treatment Outcome",
"nlm_unique_id": "8211469",
"other_id": null,
"pages": "1821-4",
"pmc": null,
"pmid": "25697878",
"pubdate": "2015-10",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D016454:Review",
"references": "23378145;24092554;18625373;23252526;24192039;23754188;14760812;16086759;23252525;23519173;21280009;19417117;19213754",
"title": "Anaphylaxis to anakinra in a pediatric patient with systemic juvenile idiopathic arthritis successfully treated with canakinumab: a case-based review.",
"title_normalized": "anaphylaxis to anakinra in a pediatric patient with systemic juvenile idiopathic arthritis successfully treated with canakinumab a case based review"
} | [
{
"companynumb": "PHHY2015US022686",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DICLOFENAC"
},
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"drugdosagetext": "3 MG/KG, UNK",
"drugenddate": null,
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"abstract": "We present a case of Disseminated Herpes Zoster in a 73 year old man who had been taking Glatiramer acetate for 8 years as treatment for Multiple Sclerosis. He presented to the emergency room with complaints of a painful skin lesions on his buttocks and was found to have a generalized papulo-pustular rash. He was treated with IV Acyclovir and concurrent Piperacillin-Tazobactam plus Vancomycin for disseminated herpes zoster with a necrotic bacterial superinfection on his buttocks. Multiple Sclerosis is a chronic immune mediated disease of the CNS and is treated with immunomodulators and immunosuppressive medications. With more than 2 decades of Glatiramer acetate use, it is regarded as the safest immunomodulator without any associated reported infections. This is the first case of Disseminated Herpes Zoster associated with Glatiramer.",
"affiliations": "Department of Infectious Diseases, University of Florida-Jacksonville, United States.;Department of Infectious Diseases, University of Florida-Jacksonville, United States.;Department of Infectious Diseases, University of Florida-Jacksonville, United States.",
"authors": "Halasan|C|C|;Isache|C|C|;Sands|M|M|",
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"fulltext": "\n==== Front\nIDCases\nIDCases\nIDCases\n2214-2509 Elsevier \n\nS2214-2509(20)30181-5\n10.1016/j.idcr.2020.e00873\ne00873\nArticle\nA case of Disseminated Herpes Zoster in a patient with Multiple Sclerosis on Glatiramer acetate\nHalasan C. [email protected]⁎ Isache C. Sands M. Department of Infectious Diseases, University of Florida-Jacksonville, United States\n⁎ Corresponding author. [email protected]\n17 6 2020 \n2020 \n17 6 2020 \n21 e008738 6 2020 14 6 2020 © 2020 The Authors2020This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).We present a case of Disseminated Herpes Zoster in a 73 year old man who had been taking Glatiramer acetate for 8 years as treatment for Multiple Sclerosis. He presented to the emergency room with complaints of a painful skin lesions on his buttocks and was found to have a generalized papulo-pustular rash. He was treated with IV Acyclovir and concurrent Piperacillin-Tazobactam plus Vancomycin for disseminated herpes zoster with a necrotic bacterial superinfection on his buttocks.\n\nMultiple Sclerosis is a chronic immune mediated disease of the CNS and is treated with immunomodulators and immunosuppressive medications. With more than 2 decades of Glatiramer acetate use, it is regarded as the safest immunomodulator without any associated reported infections. This is the first case of Disseminated Herpes Zoster associated with Glatiramer.\n\nKeywords\nHerpes zosterDisseminated zosterShinglesGlatiramer acetateImmunomodulators\n==== Body\nIntroduction\nVaricella-zoster virus is a human alpha herpes virus known to cause Chicken pox (Varicella) on primary infection and Shingles (Zoster) upon reactivation. Varicella most commonly affects children, is typically a self-limited pruritic, vesicular eruption. Herpes Zoster characteristically presents with a prodrome of burning pain followed by outbreak of vesicles distributed unilaterally within a single or adjacent dermatomes.\n\nVaricella Zoster is caused by reactivation of VZV. Older adults and people with compromised or suppressed immune systems are more likely to be hospitalized. About 30 % of all people hospitalized with herpes zoster have compromised or suppressed immune systems. One study estimated that 96 deaths occur each year in which herpes zoster was the underlying cause (0.28 to 0.69 per 1 million population) [1].\n\nIt is hypothesized that the physiologic decline in varicella-zoster virus specific cell-mediated immunity among elderly and immunocompromised individuals helps trigger reactivation of the virus within the dorsal root ganglion [2]. Secondary complications of VZV infection include postherpetic neuralgia, bacterial superinfection progressing to cellulitis and visceral infection lead to increased morbidity and mortality. Disseminated cutaneous herpes zoster occurs almost exclusively in immunosuppressed patients [3].\n\nThis case is to make physicians aware that severe disseminated HZ infection can present atypically and that it can occur in individuals on Glatiramer acetate, a immunomodulator for Multiple Sclerosis. Clinicians should recognize atypical presentations of disseminated herpes zoster in order to initiate rapid treatment to decrease potential mortality and morbidity.\n\nCase presentation\nPatient is a 73 year old man with a past medical history of Multiple Sclerosis, Neurogenic Bladder andhypertension presented to the emergency department with a diffuse rash, fever and pain in his right buttocks. He reported that the skin lesions started on the buttocks as a “pimple” that was tender and eventually got worst with diffuse redness and drainage. Over the next several days he noted a vesicular rash all over his body. He also had subjective fevers and chills. He reported having had Chickenpox as a child.\n\nHe went to an urgent care facility and was told that he has cellulitis on his buttocks and was prescribed Clindamycin, but had no improvement in his buttock pain or lesions.\n\nThe patient had been on Glatiramer for 8 years for his MS. He was being managed by a Neurology specialist as an outpatient. He denied recent or prolonged use of steroids. He was never on other any other biologic medication.\n\nVital signs on initial presentation: Tmax: 101.5; Pulse Rate: 60, BP: 158/64 and RR: 16. Physical examination was significant for a diffuse papulo– vesicular rash with some pustules and crusting. The skin on the posterior-medial right thigh and right buttocks was erythematous with maculo-pustular lesions and tenderness on palpation. No oral lesions were noted. No rash was found on the hands or feet.\n\n\n\nThe pictures above are of the face and truck of the patient and show a mix of crusted and newly erupting erythematous rash. The picture below is the right medial thigh and buttocks with erythematous, necrotic tissue and a cluster of maculopapular crusted rash on the medial posterior are of the right thigh.\n\n\n\nLaboratory evaluation revealed a white count of 7.26 × 103/microL. He had negative blood cultures. A CT scan of the pelvis did not show any perirectal or ischiorectal abscess. A presumptive diagnosis of disseminated herpes zoster with superimposed cellulitis was made and he was begun on IV Acyclovir, Vancomycin and Piperacillin-Tazobactam. A VZV PCR from one of the pustular lesions was positive. Serum HIV RNA and RPR were negative.\n\nHe received a total of 2 weeks of antibacterials and IV Acyclovir with resolution of his lesions.\n\nDiscussion\nDisseminated herpes zoster when more than 2 contiguous dermatomes are affected, more than 20 vesicles are observed outside the initial dermatome, or involvement is systemic. DHZ is rare and most frequently occurs in immunocompromised host [4]. Multi-dermatomal zoster involves several adjacent dermatomes, while disseminated cutaneous herpes zoster (DCHZ) is defined as 20 or more vesicular lesions outside the primary and adjacent dermatomes. Generally, Disseminated Herpes Zoster remains limited to the skin, but extracutaneous or visceral disease can occur, with resultant pneumonia, encephalitis, meningitis, motor neuropathies and/or abdominal symptoms.\n\nMultiple Sclerosis (MS) is an immune-mediated illness. It is a chronic inflammatory disease of the central nervous system responsible for substantial morbidity and mortality. Historically, T cells have been considered the main drivers in the pathogenesis of MS. This has been supported by observations including the higher number of T cells than B cells in MS lesions. However, it is now understood that B cells play a pivotal role throughout the course of MS [5].\n\nBecause of the importance of humoral and cell mediated immunity in the pathophysiology of MS, nearly all therapies involve modulation of the immune system with immunosuppressive agents. Immunomodulators include Interferon and Glatiramer acetate. Immunosuppressive medications that have been approved by the FDA to treat MS include monoclonal antibodies (Natalizumab, Alemtizimab and Ocreluzumab), chemotherapeutic agent (Mitoxantrone) and Small molecule oral agents (Fingolimod, Dimethyl fumarate and Teriflunomide).\n\nAlmost all of these immunosuppressive medications have been associated with severe reactivation of latent infections. Reactivation of TB has been associated with Alemtuzumab, due to its production of prolonged profound lymphocytopenia and effects on both humoral and cell mediated immunity [6]. Teriflunomide which is a dihydroorotate dehydrogenase inhibitor impairs lymphocyte proliferation which can increase risk for TB reactivation. Ocrelizumab and Alemtuzumab have the highest risk of Hepatitis B reactivation. Progressive multifocal leukoencephalopathy is a particular concern for Natalizumab [7]. Alemtuzumab, Natalizumab and Fingolimod give a higher risk of herpes virus reactivation [6].\n\nBased on our review of literature, there have been no report of reactivation of latent infection or opportunistic infections reported with the use of Glatiramer Acetate.To our knowledge, this is the first case of Disseminated Herpes Zoster associated with Glatiramer Acetate. Since its release in 1996, it has not been associated with an increased risk of any specific infections.\n\nGlatiramer acetate is a mixture of random synthetic polypeptides composed of 4 amino acids (glutamate, lysine, alanine and tyrosine). It was initially developed at the Weizmann Institute in Israel as a chemical and immunologic analog of Myelin Basic Protein (MPB) to indice experimental autoimmune encephalomyelitis. Surprisingly, it was not encephalotigenicand did not induce encephalitis in animal models. Theoretically, it is thought to interfere with immune surveillance of infectious agents. It’s mechanism of action is its ability to skew the balance from proinflammatory to anti-inflammatory response [8]. During treatment there is a shift from T helper type 1 (Th1) to Th2 cells which is passes freely into the blood brain barrier. This shift leads to the increased production of anti-inflammatory cytokines: IL-4, IL-6, IL-10. Conversely, there is reduction of pro-inflammatory cytokines such as IL-12 [9]. Glatiramer acetate additionally promotes regulatory CD8+ cells and, via the conversion of conventional CD4+CD25+ T cells to regulatory CD4+CD25− T cells [10]. Glatiramer acetate also alters the profile of circulating B cells in patients with MS. It has been shown to reduce the total frequency of B cells (as a percentage of all lymphocytes), plasmablasts, and memory cells [11]\n\nBased on the clinical experience over more than 20 years, Glatiramer acetate is considered to be one of the safest MS therapies [7]. Its principal side effects include local injections reactions, allergic reactions, local lipoatrophy and regional lymphadenopathy [11].\n\nDisseminated HZ has potential life threatening complications. As such, an understanding of prevention and treatment modalities for VZV infection among immunocompromised patients is critical. Vaccination remains a potential strategy to reduce the incidence of Herpes Zoster in this patient population. Questions about chemoprophylaxis for patient who are taking Glatiramer acetate can't be answered at this time due to the rarity of case. Based on our case, closer monitoring of patients on Glatiramer and the recognition of potential opportunistic infections may be warranted.\n\nSource of funding\nNone.\n\nConsent\n'Written informed consent was obtained from the patient for publication of this case report and accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal on request\".\n\nAuthor contribution\nDr. Carol Halasan:researcher and writer (fellow)\n\nDr.Carmen lsache: edited\n\nDr.Michael Sands: researcher and writer and edited as well.\n\nDeclaration of Competing Interest\nNone.\n==== Refs\nReferences\n1 Shingles surveillance. https://www.cdc.gov/shingles/surveillance.html.\n2 Weinberg A. Levin M.J. VZV T cell-mediated immunity Abendroth A. Arvin A. Moffat J. Varicella-zoster virus. Current topics in microbiology and immunology vol 342 2010 Springer Berlin, Heidelberg \n3 McCrary Monica L. Severson Jessica Stephen K. Tyring, varicella zoster virus J Am Acad Dermatol 41 1 1999 10.1016/S0190-9622(99)70398-1 Pages 1-16,ISSN 0190-9622 \n4 Stratman E. Visceral zoster as the presenting feature of disseminated herpes zoster J Am Acad Dermatol 46 2002 771 774 doi:S0190962202710104 [pii] 12004322 \n5 Winkelmann A. Loebermann M. Reisinger E.C. Zettl U.K. MS treatment and infection Clin Exp Immunol 175 2014 425 438 10.1111/cei.12226 24134716 \n6 Epstein D.J. Dunn J. Deresinski S. Infectious complications of multiple sclerosis therapies: implications for screening, prophylaxis, and management Open Forum Infect Dis 5 8 2018 10.1093/ofid/ofy174 ofy174. Published 2018 Jul 16 \n7 Grebenciucova E. Pruitt A. Curr Neurol Neurosci Rep 17 2017 88 10.1007/s11910-017-0800-8 28940162 \n8 Duda P.W. Schmied M.C. Cook S.L. Krieger J.I. Hafler D.A. Glatiramer acetate (Copaxone) induces degenerate, Th2-polarized immune responses in patients with multiple sclerosis J Clin Invest 105 7 2000 967 976 10.1172/JCI8970 10749576 \n9 Ziemssen Tjalf Schrempf Wiebke Acetate Glatiramer Mechanisms of action in multiple sclerosis, International review of neurobiology Volume 79 2007 Academic Press 10.1016/S0074-7742(07)79024-4 Pages 537-570, ISSN 0074-7742, ISBN 9780123737366 \n10 Kuerten S. Jackson L.J. Kaye J. Vollmer T.L. Impact of glatiramer acetate on B cell-mediated pathogenesis of multiple sclerosis CNS Drugs 32 11 2018 1039 1051 10.1007/s40263-018-0567-8 30315499 \n11 Rommer P.S. Milo R. Han M.H. Immunological aspects of approved MS therapeutics Front Immunol 10 2019 1564 10.3389/fimmu.2019.01564 Published 2019 Jul 11 31354720\n\n",
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"keywords": "Disseminated zoster; Glatiramer acetate; Herpes zoster; Immunomodulators; Shingles",
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"title": "A case of Disseminated Herpes Zoster in a patient with Multiple Sclerosis on Glatiramer acetate.",
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"abstract": "The PROteKT study tested the hypothesis that rosuvastatin can inhibit aminoglycoside-induced nephrotoxicity in children with Cystic Fibrosis (CF). This open label, parallel group, randomised controlled trial recruited children and young people aged 6 to 18 years with CF at 13 paediatric CF treatment centres in the UK. Participants were randomised equally to either receive oral rosuvastatin (10 mg once daily) or no intervention (control) throughout clinically indicated treatment with intravenous tobramycin. The primary outcome was the difference between the groups in mean fold-change in urinary Kidney Injury Molecule-1 (KIM-1). Fifty (rosuvastatin n = 23, control n = 27) participants were recruited between May 2015 and January 2017. Primary outcome data was available for 88% (rosuvastatin n = 20, control n = 24). The estimated mean treatment difference in the geometric mean-fold change of normalised KIM-1 was 1.08 (95% CI 0.87-1.35, p = 0.48). In total there were 12 adverse reactions, all mild, reported by five participants randomised to rosuvastatin, and one serious adverse event in each group. Whilst no protective effect of rosuvastatin was seen, there was a lower than expected level of nephrotoxicity in the cohort. Therefore, we can neither confirm nor refute the hypothesis that rosuvastatin protects against aminoglycoside nephrotoxicity.",
"affiliations": "Department of Women's and Children's Health, University of Liverpool, Liverpool, Merseyside, United Kingdom. [email protected].;Clinical Trials Research Centre, University of Liverpool, a member of the Liverpool Health Partners, Liverpool, Merseyside, United Kingdom.;Clinical Trials Research Centre, University of Liverpool, a member of the Liverpool Health Partners, Liverpool, Merseyside, United Kingdom.;Institute of Translational Medicine, University of Liverpool, Liverpool, Merseyside, United Kingdom.;Institute of Translational Medicine, University of Liverpool, Liverpool, Merseyside, United Kingdom.;Department of Mathematics and Statistics, Lancaster University, Lancaster, United Kingdom.;Division of Child Health, Obstetrics & Gynaecology, University of Nottingham, Nottingham, United Kingdom.;University College London, Great Ormond Street Institute of Child Health, London, United Kingdom.;Department of Molecular and Clinical Pharmacology, and MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, Merseyside, United Kingdom.",
"authors": "McWilliam|Stephen J|SJ|http://orcid.org/0000-0002-0509-7425;Rosala-Hallas|Anna|A|;Jones|Ashley P|AP|;Shaw|Victoria|V|;Greenhalf|William|W|;Jaki|Thomas|T|;Smyth|Alan R|AR|;Smyth|Rosalind L|RL|;Pirmohamed|Munir|M|",
"chemical_list": "D000900:Anti-Bacterial Agents; C491143:HAVCR1 protein, human; D000072596:Hepatitis A Virus Cellular Receptor 1; D000068718:Rosuvastatin Calcium; D014031:Tobramycin",
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"doi": "10.1038/s41598-020-58790-1",
"fulltext": "\n==== Front\nSci RepSci RepScientific Reports2045-2322Nature Publishing Group UK London 5879010.1038/s41598-020-58790-1ArticleA randomised controlled trial of rosuvastatin for the prevention of aminoglycoside-induced kidney toxicity in children with cystic fibrosis http://orcid.org/0000-0002-0509-7425McWilliam Stephen J. [email protected] 1Rosala-Hallas Anna 2Jones Ashley P. 2Shaw Victoria 3Greenhalf William 3Jaki Thomas 4Smyth Alan R. 5Smyth Rosalind L. 6Pirmohamed Munir 71 0000 0004 1936 8470grid.10025.36Department of Women’s and Children’s Health, University of Liverpool, Liverpool, Merseyside United Kingdom 2 0000 0004 1936 8470grid.10025.36Clinical Trials Research Centre, University of Liverpool, a member of the Liverpool Health Partners, Liverpool, Merseyside United Kingdom 3 0000 0004 1936 8470grid.10025.36Institute of Translational Medicine, University of Liverpool, Liverpool, Merseyside United Kingdom 4 Department of Mathematics and Statistics, Lancaster University Lancaster, United Kingdom 5 0000 0004 1936 8868grid.4563.4Division of Child Health, Obstetrics & Gynaecology, University of Nottingham, Nottingham, United Kingdom 6 0000000121901201grid.83440.3bUniversity College London, Great Ormond Street Institute of Child Health, London, United Kingdom 7 0000 0004 1936 8470grid.10025.36Department of Molecular and Clinical Pharmacology, and MRC Centre for Drug Safety Science, University of Liverpool, Liverpool, Merseyside United Kingdom 4 2 2020 4 2 2020 2020 10 17968 9 2019 15 1 2020 © The Author(s) 2020Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.The PROteKT study tested the hypothesis that rosuvastatin can inhibit aminoglycoside-induced nephrotoxicity in children with Cystic Fibrosis (CF). This open label, parallel group, randomised controlled trial recruited children and young people aged 6 to 18 years with CF at 13 paediatric CF treatment centres in the UK. Participants were randomised equally to either receive oral rosuvastatin (10 mg once daily) or no intervention (control) throughout clinically indicated treatment with intravenous tobramycin. The primary outcome was the difference between the groups in mean fold-change in urinary Kidney Injury Molecule-1 (KIM-1). Fifty (rosuvastatin n = 23, control n = 27) participants were recruited between May 2015 and January 2017. Primary outcome data was available for 88% (rosuvastatin n = 20, control n = 24). The estimated mean treatment difference in the geometric mean-fold change of normalised KIM-1 was 1.08 (95% CI 0.87–1.35, p = 0.48). In total there were 12 adverse reactions, all mild, reported by five participants randomised to rosuvastatin, and one serious adverse event in each group. Whilst no protective effect of rosuvastatin was seen, there was a lower than expected level of nephrotoxicity in the cohort. Therefore, we can neither confirm nor refute the hypothesis that rosuvastatin protects against aminoglycoside nephrotoxicity.\n\nSubject terms\nPredictive markersToxin-induced nephropathyCystic fibrosisPaediatric researchAcute kidney injuryhttps://doi.org/10.13039/501100000272DH | National Institute for Health Research (NIHR)issue-copyright-statement© The Author(s) 2020\n==== Body\nIntroduction\nIn Cystic fibrosis (CF) the resistant pathogen Pseudomonas aeruginosa is commonly implicated in secondary bacterial lung infections and colonisation. Aminoglycoside antibiotics, usually combined with a beta-lactam, are frequently used to treat respiratory exacerbations in CF1, as they are effective against P. aeruginosa. Whilst this approach generally leads to improved patient outcomes, aminoglycoside use is also associated with an increased risk of nephrotoxicity.\n\nThe incidence of acute kidney injury (AKI) in children with CF is increased with current or recent exposure to aminoglycosides2–4, with rates of 20% reported using daily monitoring of serum creatinine5. The risk of AKI is higher with longer duration of aminoglycoside use and with recent previous aminoglycoside exposure6. In one cohort of adults with CF, between 31% and 42% had evidence of chronic renal impairment which was significantly associated with cumulative aminoglycoside exposure7. However, this has not been replicated in other cohorts8,9. Strategies such as therapeutic drug monitoring and extended-interval dosing10 are only partially effective in preventing aminoglycoside-induced nephrotoxicity. It is therefore important to develop further, more effective, strategies.\n\nAminoglycosides cause targeted toxicity to renal proximal tubule epithelial cells. Megalin, a multi-ligand receptor, facilitates the endocytosis and accumulation of aminoglycosides in these cells11. This pathway is activated by intermediates derived from mevalonate, which is formed from 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) via the enzyme HMG-CoA reductase12. We hypothesised that inhibiting HMG-CoA reductase with a statin would lead to a reduction in toxicity. Statins are inhibitors of megalin-mediated endocytosis in vitro13,14, and are therefore likely to reduce uptake of aminoglycosides in the proximal tubule. Indeed, in vivo studies of aminoglycoside-induced nephrotoxicity in rats have consistently demonstrated a protective effect of statins15–20.\n\nIn this paper, we describe the first clinical trial to evaluate the repurposing of a statin for the prevention of aminoglycoside-induced kidney toxicity. Rosuvastatin was chosen as it is hydrophilic, has minimal hepatic metabolism, and has some renal elimination of the parent drug21 (and therefore theoretically preferable in preventing megalin-mediated uptake rather than a hepatically metabolised statin). In addition, it is highly potent, and licensed for use in children. This trial was designed to test the hypothesis that rosuvastatin can inhibit aminoglycoside-induced nephrotoxicity in children with CF.\n\nResults\nStudy participants\nA total of 258 patients were assessed for eligibility across 13 CF centres in the UK (May 2015-January 2017); 208 were not randomised as they failed to meet the inclusion/exclusion criteria or did not provide consent. The planned sample size was met with twenty-three participants randomised to the intervention and 27 to the control (Fig. 1). Baseline characteristics are shown in Table 1. The two arms were well balanced and no clinical differences were deemed to be important.Figure 1 CONSORT Flow Diagram.\n\nTable 1 Characteristics of the participants at baseline.\n\nCharacteristic\tControl Group (n = 27)\tIntervention Group (n = 23)\t\nFemale sex – no. (%)\t19 (70)\t13 (57)\t\nAge - yr\t13.30 (2.65)\t12.09 (2.74)\t\nHeight – cm\t151.93 (16.07)\t148.43 (915.79)\t\nWeight - kg\t44.67 (15.58)\t40.63 (14.98)\t\nEthnic origin – no. (%)\t\n White\t27 (100)\t21 (91)\t\n Other White\t0 (0)\t1 (4)\t\n Mixed: White and Black African\t0 (0)\t1 (4)\t\nBlood Results\t\nSerum creatinine - µmol/L\t45.30 (10.56)\t43.57 (11.52)\t\neGFR - mL/min/1.73 m2\t139.90 (29.69)\t142.21 (27.02)\t\nAspartate transaminase - iu/L\t28.77 (11.09)a\t33.41 (17.69)a\t\nAlanine transaminase - iu/L\t25.48 (16.53)\t27.77 (17.09)\t\nHDL cholesterol - mmol/L\t1.06 (0.32)\t1.09 (0.40)\t\nLDL cholesterol - mmol/L\t1.47 (0.54)a\t1.25 (0.55)\t\nTotal cholesterol- mmol/L\t2.80 (0.67)\t2.75 (0.66)\t\nTriglycerides - mmol/L\t1.17 (0.77)\t1.00 (0.53)\t\nCreatine kinase - iu/L\t67.15 (33.13)\t83.83 (55.31)\t\nC Reactive Protein - mg/L\t10.46 (14.29)\t7.48 (8.41)\t\nSpirometry Results\t\nFEV in 1 second\t2.10 (1.30)\t1.86 (0.91)b\t\nFEV in 1 second (% predicted)\t74.05 (17.57)\t73.98 (19.59)b\t\nUrine Results\t\nKIM-1 (normalised to urinary creatinine) -ng/mgCr\t1.94 (2.45)c\t0.67 (0.45)c\t\nNGAL (normalised to urinary creatinine) - ng/mgCr\t61.08 (89.55)c\t22.46 (22.99)c\t\n*Plus-minus values are means ± SD aMeasurement missing for 1 participant. bMeasurement missing for 2 participants. cMeasurement missing for 3 participants.\n\n\n\nFive (22%) and four (15%) participants randomised to the intervention and control groups, respectively, discontinued tobramycin treatment early. Median duration of treatment was 14 days in both the intervention and control groups (Supplemental Table 1). Four participants in the intervention group discontinued tobramycin treatment due to a change in their condition and one due to line failure. One control group participant discontinued tobramycin treatment early due to a change in their condition, two were a clinical decision to cease and, in one case, no reason was given.\n\nAssessment of outcome measures\nIn terms of the primary outcome, the estimated geometric mean fold-change of normalised Kidney Injury Molecule-1 (KIM-1) was 1.85 and 2.00 in the control and intervention groups respectively (Table 2). The estimated mean treatment difference was 1.08 (95% CI: 0.87,1.35; p = 0.48). Four participants (intervention n = 1 and control n = 3) did not have baseline urine samples and were excluded from the primary analysis. Five sensitivity analyses confirmed the conclusion found in the primary analysis (Supplemental Table 2). The estimated mean treatment difference in the area under the curve (AUC) of normalised KIM-1 between the two treatment groups was 12.41 ng/mgCr (95% CI: −0.89,25.70; p = 0.07) (Supplemental Table 3). There were no statistically significant differences between the treatment groups and the treatment by time interactions were not significant for the secondary outcomes (Table 3). Mean profile plots for each outcome measure are included in Fig. 2.Table 2 Primary outcome: ANCOVA model results.\n\nPrimary outcome: log-transformed mean fold change from baseline to peak KIM-1 normalised to urinary creatinine\tNa\tEstimated geometric mean fold-change\tEstimated mean treatment differenceb\t95% CI\tP-value\t\nControl\t24\t1.85\t—\t—\t—\t\nRosuvastatin\t20\t2.00\t1.08\t0.87, 1.35\t0.48\t\na3 in the control and 1 in the intervention arm did not have baseline urine samples and were excluded; 2 in the intervention arm withdrew at baseline before commencing treatment and were excluded. bAdjusted for baseline normalised KIM-1.\n\nTable 3 Secondary outcomes: random intercept model results.\n\nSecondary Outcomes\tTreatment group\tN\tEstimated mean\tEstimated mean treatment difference\t95% CI\tP-value\t\nSerum creatinine (μmol/l)\tControl\t27\t47.61\t—\t—\t—\t\nRosuvastatin\t23\t44.66\t−2.95\t−9.61, 3.71\t0.38\t\neGFR (mls/min/1.73 m2)\tControl\t27\t142.01\t—\t—\t—\t\nRosuvastatin\t23\t140.59\t−1.43\t−16.64, 13.78\t0.85\t\nNGAL (ng/mgCr)\tControl\t27\t101.75\t—\t—\t—\t\nRosuvastatin\t21a\t47.04\t−54.71\t−102.25, −7.16\t0.02\t\nFEV in 1 second (L)\tControl\t27\t1.94\t—\t—\t—\t\nRosuvastatin\t21b\t1.93\t−0.01\t−0.50, 0.49\t0.98\t\nCRP (mg/L)\tControl\t27\t9\t—\t—\t—\t\nRosuvastatin\t23\t5.89\t−3.11\t−7.68, 1.46\t0.18\t\na2 participants withdrew at baseline prior to commencing treatment thus had no samples to contribute. b2 participants withdrew at baseline and had missing FEV1 samples at baseline.\n\nFigure 2 Mean profile plots. Mean profile plots for control and intervention (rosuvastatin) groups during tobramycin exposure for creatinine (A), KIM-1 normalised to urinary creatinine (B), Schwartz eGFR (C), and NGAL normalised to urinary creatinine (D).\n\n\n\nThe estimated geometric mean fold-change of normalised Neutrophil Gelatinase-Associated Lipocalin (NGAL) was 8.90 and 4.99 in the control and intervention groups respectively. The estimated mean treatment difference was 0.56 (95% CI: 0.27,1.15; p = 0.11) (Supplemental Table 4). The estimated mean treatment difference in the AUC of normalised NGAL between the two arms was 557.8 ng/mgCr (95% CI: 46.5,1069.2; p = 0.03) (Supplemental Table 3). The tobramycin and rosuvastatin data are reported in Supplemental Tables 5 and 6, respectively.\n\nAn analysis of serum creatinine data using the Kidney disease: Improving global outcomes (KDIGO) AKI criteria22 demonstrated that a total of four participants fulfilled the criteria for AKI during the trial: two patients in the control group both reached AKI stage 3, and two patients in the intervention group both reached AKI stage 1 (Supplemental Table 7).\n\nSafety and adverse events\nTwo participants randomised to the intervention group withdrew consent prior to receiving the intervention and were therefore not included in the safety analysis. Twelve adverse reactions were reported by 5 (25%) of the 21 participants in the intervention group (Table 4). All events were reported as mild in severity.Table 4 Adverse Reactions reported in the intervention group (n = 21).\n\nEvent\tNumber of participants (%)\tNumber of events\t\nMetabolism and nutrition disorders\t\nHypoglycaemia\t1 (4.76%)\t2\t\nInvestigations\t\nAlanine aminotransferase increased\t1 (4.76%)\t1\t\nAspartate aminotransferase increased\t1 (4.76%)\t1\t\nBlood cholesterol decreased\t1 (4.76%)\t1\t\nBlood creatine phosphokinase increased\t1 (4.76%)\t1\t\nBlood triglycerides decreased\t1 (4.76%)\t1\t\nBlood triglycerides increased\t1 (4.76%)\t1\t\nMusculoskeletal and connective tissue disorders\t\nBack pain\t1 (4.76%)\t1\t\nNervous system disorders\t\nHeadache\t1 (4.76%)\t1\t\nParaesthesia\t1 (4.76%)\t1\t\nParaesthesia oral\t1 (4.76%)\t1\t\n\n\nRecurrence of pulmonary exacerbation during follow-up, requiring hospitalisation, was the only serious adverse event in the control group, reported for one (4%) participant. Abnormal blood results requiring prolonged hospitalisation were reported as a serious adverse event for one (5%) participant in the intervention group but this was not considered to be related to the intervention.\n\nDiscussion\nThis is the first randomised controlled trial in man to assess whether rosuvastatin has a protective effect against tobramycin-induced nephrotoxicity. It was designed as an early phase trial using KIM-1 as a surrogate outcome measure. We found little evidence of a protective effect of rosuvastatin in this trial as determined by both primary and secondary outcomes, but this should be interpreted with caution as the control group only demonstrated a mean fold-change of KIM-1 of 1.85. The sample size calculation for this study was, however, based upon an expected mean fold-change in KIM-1 of 3.03 during exposure to tobramycin derived from an early analysis of samples in the URBAN CF study23. The trial was powered to detect a difference in fold-change between the groups of 2. The PROteKT and URBAN CF populations were similar, although PROteKT contained a greater proportion of female participants, and had higher mean age, height and weight (due to differences in the inclusion criteria for age). There were no differences in aminoglycoside prescribing practices between the two studies. We do not believe that the differences between the populations used in PROteKT and URBAN CF account for lower than expected levels of nephrotoxicity observed in our randomised controlled trial. Therefore, it is unclear whether this reflects lower than usual levels of toxicity in the PROteKT cohort, or higher than usual levels of toxicity in the cohort upon which the sample size calculation was based. This makes it difficult to definitively exclude the possibility of a protective effect of rosuvastatin. Indeed, some of our secondary outcome measures suggest a trend towards a protective effect. Importantly, the use of rosuvastatin was generally well tolerated.\n\nUrine KIM-1 is a cell membrane glycoprotein upregulated by proximal tubule epithelial cells in response to toxicity24. It was chosen as the primary outcome measure as it has previously shown potential for the identification of aminoglycoside-induced nephrotoxicity in preterm neonates25, and in children with CF23,26, as well as outperforming other biomarkers of aminoglycoside-induced nephrotoxicity in pre-clinical models27. In clinical practice, changes in serum creatinine meeting agreed criteria for AKI22 are more widely accepted for defining nephrotoxicity. However, changes in serum creatinine are a relatively late event in the process of nephrotoxicity, and for the purposes of a phase IIa trial, it was felt that KIM-1 was a good surrogate measure. Indeed, we identified no significant treatment effect upon serum creatinine in this study, consistent with our previous experience in the URBAN CF study23. The use of a change in serum creatinine as an outcome measure may be relevant to use in future trials, but given that this is estimated to occur in 14–20%5,6, a much larger sample size will be required.\n\nUrine NGAL is a 25 kDa protein expressed by kidney epithelial cells (as well as other tissues, including neutrophils)28. It is a sensitive predictor for AKI29, and has previously been shown to be elevated during aminoglycoside exposure in neonates25, and in children with CF23. Patients in the intervention group had a smaller estimated geometric mean fold-change of normalised NGAL (p = 0.11), and a significantly lower AUC of normalised NGAL. The difference in AUC between the groups must be interpreted in the light of a higher baseline urinary NGAL in the control compared to the intervention group (61.08 ng/mgCr and 22.46 ng/mgCr respectively). This may, in part, be explained by the higher proportion of females in the control versus intervention groups as females have been consistently shown to have higher baseline NGAL concentrations than males30. Whilst our results may be interpreted to suggest a protective effect of rosuvastatin, we feel that these should be interpreted cautiously.\n\nPublished studies in rat models of aminoglycoside-induced nephrotoxicity have consistently demonstrated a protective effect with a range of statins, including atorvastatin17–19, simvastatin15,16 and rosuvastatin20. We felt that rosuvastatin was the most promising candidate based upon its pharmacology. It is a hydrophilic statin, and has greater renal excretion than the more lipophilic atorvastatin and simvastatin. It causes more proteinuria than other statins, probably because it is secreted in the proximal tubules31 and inhibits megalin-mediated endocytosis. We considered whether we should have given the statin for a few days in advance of commencing the tobramycin in order to achieve steady-state concentrations. However, published pre-clinical studies demonstrated a protective effect of statins without the need for this15,17–20.\n\nThe recruitment of children with CF from thirteen different sites in the UK to participate in this trial ensures that differences in practice between centres should be accounted for in the randomisation. The trial was designed to cause the least disruption possible to standard daily care, and for the intervention to be minimally burdensome to patients (requiring only one additional medicine per day for 2 weeks). This was reflected in the good adherence to the randomised intervention, and by a low number of reported adverse reactions.\n\nIn conclusion, given the lower than expected level of nephrotoxicity seen in this study we feel that we can neither confirm nor refute the hypothesis that statins protect against aminoglycoside nephrotoxicity. Given the large amount of pre-clinical data which shows that statins can be protective15–20, we feel further studies in humans are warranted. These would need to be powered for a clinically acceptable primary outcome measure such as AKI (rise in creatinine). There are of course other interventions which have been attempted to reduce the risk of aminoglycoside nephrotoxicity, including extended-interval dosing and drug trough level monitoring10, and morning (versus evening) administration of the aminoglycoside32. All these interventions are not mutually exclusive, and it may be that combinations of interventions may be more successful in preventing renal injury when compared with individual interventions, and such a possibility should be investigated in an appropriately designed clinical trial in the future.\n\nMethods\nProtocol and trial population\nThis multi-centre, randomised, open-labelled, parallel group, phase IIa trial was registered in duplicate on both the EU Clinical Trials Register (EudraCT number 2014-002387-32, 27/06/2014) and the ISRCTN Registry (ISRCTN26104255, 05/09/2014). It received ethical approval from the National Research Ethics Service Committee North West – Greater Manchester Central, and was conducted in accordance with the Declaration of Helsinki. Participants were recruited at 13 paediatric CF treatment centres in the UK. Each parent or guardian gave written informed consent, and each child gave assent where appropriate.\n\nChildren and young people with CF, aged 6 to 18 years, who had a planned, clinically indicated (usually for a respiratory exacerbation of CF), course of treatment with IV tobramycin were eligible for randomisation. Key exclusion criteria included participants of Asian ancestry (specifically Japanese, Chinese, Filipino, Vietnamese and Korean subjects, as they have clinically significant increased systemic exposure to rosuvastatin33), previous adverse reaction to a statin, and existing treatment with a statin. Participants with renal disease, elevation of either transaminases and/or creatine kinase were also excluded. The full inclusion and exclusion criteria are described in the trial protocol (Appendix 1).\n\nThere were amendments to the eligibility criteria during the trial. The age inclusion criteria were changed from 10–18 to 6–18 years following a change in the licence for rosuvastatin34. A review of published pharmacokinetic data suggested that concomitant itraconazole35 or Asian-Indian ethnicity33 would result in clinically insignificant increases in rosuvastatin exposure and therefore these were removed from the exclusion criteria.\n\nRandomisation and trial procedures\nRandomisation was performed, by the Principal Investigator or delegated other at site, using a secure web-based system with random permuted blocks of 2 and 4 stratified by trial site. Randomisation lists were generated using Stata v9.0 by an independent statistician. Emergency back-up randomisation envelopes were available when there was a problem with this system. At enrolment eligible participants were randomised 1:1 to receive either rosuvastatin or no intervention.\n\nEach participant randomised to the intervention arm received a daily oral dose of 10 mg rosuvastatin (Crestor®; AstraZeneca UK Ltd) for the duration of a treatment course of IV tobramycin (usually 14 days). Tobramycin was the first choice aminoglycoside in CF for all centres, and dosing and monitoring of drug concentrations followed the British National Formulary36 (standard dosing is 10 mg/kg once daily) and local protocols. The first dose of rosuvastatin was given on the same calendar day and prior to the first dose of IV tobramycin. Subsequent daily doses of rosuvastatin were given prior to that day’s dose of tobramycin. Treatment with oral rosuvastatin continued for the duration of the course of IV tobramycin. If the tobramycin course was shorter than 14 days, rosuvastatin was discontinued after the final tobramycin dose. If the tobramycin course was longer than 14 days, rosuvastatin was continued until the final day of the tobramycin course. Participants randomised to the no intervention arm received usual care during their IV tobramycin treatment course. No placebo was provided.\n\nSample collection\nBaseline assessment before tobramycin therapy (T0) included collection of urine and blood samples for confirmation of eligibility criteria, and spirometry. During treatment with IV tobramycin urine samples were collected daily from each child. Participants had assessments on days T + 1, T + 8 and T + 13. These included adverse event assessment, a symptom-directed physical examination if required, and collection of blood and urine samples. Spirometry was performed at the T + 8 and T + 13 visits. A final follow-up visit, with collection of blood/urine samples and spirometry, was conducted 3–5 weeks following completion of tobramycin treatment.\n\nUrine samples were normally collected by clean catch into a sterile container. If the participant was an inpatient, the daily samples were sent directly to the local laboratory. If the participant received IV tobramycin at home, samples were stored in the home refrigerator in a sealed container until the next scheduled study visit. All samples were stored at fridge temperature (4 °C) for a total of one week (including time spent at the patient’s home) and then aliquoted and stored at −80 °C (or −20 °C for a maximum of 6 months) in the local laboratory. Stability of KIM-1 has previously been reported in urine stored at 4 °C for periods of one week37,38.\n\nWherever possible, study bloods were collected by venepuncture at the same time as any clinically indicated bloods in order to minimise the burden to the patient. A minimum of two 1.2 ml samples in Lithium/Heparin tubes, and one 1.2 ml sample in a serum tube were collected at each time point. Plasma and serum were extracted locally at each site, aliquoted and stored at −80 °C.\n\nBatched samples were couriered on dry ice to the Good Clinical Practice Laboratory (GCPLab) facility in Liverpool for subsequent storage and analysis (here samples were stored at −80 °C). All laboratory analyses were undertaken in a standardised manner, being blinded to allocation, time of sampling and clinical outcomes of patients.\n\nOutcome measures\nThe primary outcome was the difference in mean fold-change in urinary KIM-1 from baseline to ‘highest value’ concentration during exposure to tobramycin between the intervention and control arms.\n\nThe secondary outcome measures were the difference in serum creatinine, estimated glomerular filtration rate (eGFR) and urinary NGAL between the intervention and control arms during exposure to tobramycin. We assessed for pharmacokinetic interaction between rosuvastatin and tobramycin by comparing tobramycin concentrations between the rosuvastatin treated arm and the control arm. We assessed for pharmacodynamic interaction between rosuvastatin and tobramycin, by comparing change in percent of predicted Forced Expiratory Volume in 1 second (FEV1), between the rosuvastatin treated and control arms. This is a widely used indirect measure of aminoglycoside treatment outcome in children with CF39, and was measured locally during study visits. We also compared change in C-Reactive Protein (CRP), as a marker of inflammation/infection, between the two groups. Rosuvastatin concentrations were measured in the intervention arm participants to describe the pharmacokinetic profile of rosuvastatin, to assess compliance, and to relate rosuvastatin concentrations to change in urinary KIM-1.\n\nSafety\nAll the participants who received at least one dose of rosuvastatin were included in the safety analysis. Adverse reactions and serious adverse events were recorded from the point of informed consent and throughout the trial treatment period up until the final assessment (3–5 weeks after the participant had taken the final dose of rosuvastatin).\n\nLaboratory analyses\nUrinary KIM-1 and NGAL were measured using validated electrochemiluminescent assays (Meso Scale Discovery (MSD), US) as previously described23,30. Biomarker values were normalised to urinary creatinine which was determined spectrophotometically as previously described40. Serum creatinine, tobramycin concentrations and CRP were measured in the laboratory serving the local hospital site.\n\nRosuvastatin concentrations were measured centrally at the University of Liverpool. A high performance liquid chromatography mass spectrometric method for the estimation of rosuvastatin in plasma, was developed and validated using rosuvastatin-D6 as internal standard. Sample preparation was accomplished by protein precipitation. The samples were chromatographed on a C-18 Halo column using mobile phases consisting of 0.1% formic acid in water and 0.1% formic acid in acetonitrile. The method was validated over a concentration range of 0.5–100 ng/mL for rosuvastatin.\n\nStatistical analysis\nThe statistical analysis plan (Appendix 2) was written prior to any formal analysis. The trial was designed with a 92% power to detect a difference in fold-change in KIM-1 between the 2 groups at a 5% significance level (two sided). A standard deviation of 1.84 was derived from an early analysis of samples in the URBAN CF study23 from 10 participants receiving a single course of treatment with tobramycin. The same data was also inspected to assess that the assumption of normality is reasonable. Using these assumptions and utilizing a 2-sample t-test, a sample size of 20 in each arm would be sufficient. We planned to include 50 patients in order to compensate for 10% loss to follow up.\n\nThe principle of intention-to-treat was the main strategy of the analysis adopted for the primary outcome and all the secondary outcomes. These analyses were conducted on all randomised participants, in the group to which they were allocated, and for whom the outcome(s) of interest have been observed/measured.\n\nThe primary outcome was analysed using the method of analysis of covariance (ANCOVA). The outcome measure was the mean log-transformed fold-change of normalised KIM-1 (ng/mgCr) calculated by dividing the peak value, corresponding to the ‘highest value’ of normalised KIM-1 during exposure to tobramycin, by the baseline normalised KIM-1 value for each participant. The explanatory variables were treatment group and baseline normalised KIM-1 value. 95% confidence intervals will be reported and a p-value of <0.05 considered statistically significant. The secondary outcomes were analysed longitudinally using random intercept models with unstructured covariance matrices, including an interaction between treatment group and visit.\n\nIn an additional analysis of normalised NGAL (ng/mgCr), an ANCOVA model was used, as for KIM-1 above, comparing log-transformed mean fold-change from baseline to peak NGAL between the treatment groups, controlling for the baseline normalised NGAL. The model estimates were exponentiated to be interpretable on the normal scale.\n\nIn an additional descriptive analysis of serum creatinine data, change from baseline serum creatinine during tobramycin exposure was defined according to the KDIGO AKI criteria (Stage 1, increase ≥1.5 and <2 times from baseline; Stage 2, increase ≥2 and <3 times from baseline; Stage 3, increase ≥3 times from baseline)22.\n\nPre-specified sensitivity analyses tested impact of missing data; the statistical analysis plan includes full details of sensitivity analyses and analyses of secondary outcomes. Analyses were performed using SAS® version 9.4 (SAS Inc., USA).\n\nSupplementary information\n\nPROteKT Supplementary Material.\n\n \n\n\nPublisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.\n\nSupplementary information\nis available for this paper at 10.1038/s41598-020-58790-1.\n\nAcknowledgements\nThe study was funded by The JP Moulton Charitable Foundation. The funder had no role in design and conduct of the study or the analysis and interpretation of the results. The study was conducted with the support of the MRC Centre for Drug Safety Science, University of Liverpool. SJM is funded by a National Institute for Health Research (NIHR) Academic Clinical Lectureship for this research project. Both MP and RLS are NIHR Emeritus Senior Investigators. This publication presents independent research funded by the National Institute for Health Research (NIHR) and The JP Moulton Charitable Foundation. The views expressed are those of the authors and not necessarily those of the JP Moulton Charitable Foundation, the NHS, the NIHR or the Department of Health and Social Care. The PROTEKT Trial Management Group would like to acknowledge and thank all participating centres, the multi-disciplinary teams supporting the trial, and all children, young people and families who took part in this trial. Alder Hey Children’s Hospital: Dr. Kevin Southern, Naomi Rogers. Birmingham Children’s Hospital: Dr. Maya Desai, Rehana Bi, Helen Williamson. Bristol Royal Hospital for Children: Dr. Simon Langton-Hewer, Hope Lacy, Anja Keating, Lisa Tucker. Countess of Chester Hospital: Dr. Ravi Jayaram, Caroline Burchett. Great Ormond Street Hospital: Dr. Helen Spencer, Laura McCarthy, Sahra Shah. King’s College Hospital: Dr. Gary Ruiz, Hannah Fletcher, Eniola Nsirim. Norfolk and Norwich University Hospital: Dr. Caroline Kavanagh, Louisa Fear, Louise Coke. Nottingham Children’s Hospital: Prof Alan Smyth, Dr. Andrew Prayle, Lindsay Crate. Royal Alexandra Children’s Hospital, Brighton: Dr. Akshat Kapur, Catherine Olden, Sebastien Martin. Royal Devon & Exeter Hospital: Dr. Patrick Oades, Suzanne Wilkins. Sheffield Children’s Hospital: Dr. Sonal Kansra, Stuart Gormley. University Hospitals of Leicester NHS Trust: Dr. Erol Gaillard, Judy Maynard-Mills. University Hospitals of North Midlands NHS Trust: Dr. Francis Gilchrist, Rachel Pringle, Victoria Riches. The PROTEKT Trial Management Group would like to thank the help and support of the independent committees that had oversight of the trial. The Trial Steering Committee comprised: Professor Deborah Ashby, Professor Stuart Elborn and Dr. Malcolm Brodie; and the Independent Data and Safety Monitoring Committee: Professor Jane Davies, Dr. Edward Simmons and Dr James Wason.\n\nAuthor contributions\nS.J.M., A.R.-H., A.P.J., V.S., W.G., T.J., A.S., R.L.S. and M.P. wrote the manuscript. S.J.M., T.J., R.L.S. and M.P. designed the research. S.J.M., A.R.-H., A.P.J., V.S., W.G., A.S., R.L.S. and M.P. performed the research. S.J.M., A.R.-H. and A.P.J. analyzed the data.\n\nData availability\nData may be requested by submitting a written request to the corresponding author outlining the purposes for which the data would be used.\n\nCompeting interests\nThe authors declare no competing interests.\n==== Refs\nReferences\n1. Robinson CA Kuhn RJ Management of pulmonary disease in patients with cystic fibrosis J. Pharm. Pract. 2001 14 207 227 10.1106/4WVW-ACLD-EKV6-MBJJ \n2. Bertenshaw C Watson AR Lewis S Smyth A Survey of acute renal failure in patients with cystic fibrosis in the UK Thorax 2007 62 541 545 10.1136/thx.2006.067595 17234661 \n3. Saban JA Pizzi M Caldwell J Palijan A Zappitelli M Previous aminoglycoside use and acute kidney injury risk in non-critically ill children Pediatr. Nephrol. 2017 32 173 179 10.1007/s00467-016-3471-9 27718084 \n4. Smyth A Case-control study of acute renal failure in patients with cystic fibrosis in the UK Thorax 2008 63 532 535 10.1136/thx.2007.088757 18245146 \n5. Downes KJ Daily serum creatinine monitoring promotes earlier detection of acute kidney injury in children and adolescents with cystic fibrosis J. Cyst. Fibros. 2014 13 435 441 10.1016/j.jcf.2014.03.005 24718099 \n6. Downes KJ Risk factors for acute kidney injury during aminoglycoside therapy in patients with cystic fibrosis Pediatr. Nephrol. 2015 30 1879 1888 10.1007/s00467-015-3097-3 25912993 \n7. Al-Aloul M Renal impairment in cystic fibrosis patients due to repeated intravenous aminoglycoside use Pediatr. Pulmonol. 2005 39 15 20 10.1002/ppul.20138 15521084 \n8. Pedersen SS Jensen T Osterhammel D Osterhammel P Cumulative and acute toxicity of repeated high-dose tobramycin treatment in cystic fibrosis Antimicrob. Agents Chemother. 1987 31 594 599 10.1128/AAC.31.4.594 3606063 \n9. Stehling, F., Büscher, R., Grosse-Onnebrink, J., Hoyer, P. F. & Mellies, U. Glomerular and Tubular Renal Function after Repeated Once-Daily Tobramycin Courses in Cystic Fibrosis Patients. Pulm. Med. 2017 (2017).\n10. McWilliam SJ Antoine DJ Smyth RL Pirmohamed M Aminoglycoside-induced nephrotoxicity in children Pediatr. Nephrol. 2017 32 2015 2025 10.1007/s00467-016-3533-z 27848094 \n11. Schmitz C Megalin deficiency offers protection from renal aminoglycoside accumulation J. Biol. Chem. 2002 277 618 622 10.1074/jbc.M109959200 11700326 \n12. Khwaja A Connolly JO Hendry BM Prenylation inhibitors in renal disease Lancet 2000 355 741 744 10.1016/S0140-6736(99)08347-6 10703816 \n13. Sidaway JE Inhibitors of 3-hydroxy-3-methylglutaryl-CoA reductase reduce receptor-mediated endocytosis in opossum kidney cells J. Am. Soc. Nephrol. 2004 15 2258 2265 10.1097/01.ASN.0000138236.82706.EE 15339975 \n14. Verhulst A D’Haese PC De Broe ME Inhibitors of HMG-CoA reductase reduce receptor-mediated endocytosis in human kidney proximal tubular cells J. Am. Soc. Nephrol. 2004 15 2249 2257 10.1097/01.ASN.0000136778.32499.05 15339974 \n15. Chinnapa Reddy V Effect of simvastatin in gentamicin induced nephrotoxicity in albino rats Asian J. Pharm. Clin. Res. 2012 5 36 40 \n16. Jabbari M Rostami Z Jenabi A Bahrami A Mooraki A Simvastatin ameliorates gentamicin-induced renal injury in rats Saudi J. Kidney Dis. Transpl. 2011 22 1181 1186 22089778 \n17. Jaikumkao K Atorvastatin improves renal organic anion transporter 3 and renal function in gentamicin-induced nephrotoxicity in rats Exp. Physiol. 2016 101 743 753 10.1113/EP085571 27005971 \n18. Jaikumkao Krit Pongchaidecha Anchalee Thongnak La-ongdao Wanchai Keerati Arjinajarn Phatchawan Chatsudthipong Varanuj Chattipakorn Nipon Lungkaphin Anusorn Amelioration of Renal Inflammation, Endoplasmic Reticulum Stress and Apoptosis Underlies the Protective Effect of Low Dosage of Atorvastatin in Gentamicin-Induced Nephrotoxicity PLOS ONE 2016 11 10 e0164528 10.1371/journal.pone.0164528 27727327 \n19. Ozbek E Atorvastatin prevents gentamicin-induced renal damage in rats through the inhibition of p38-MAPK and NF-kB pathways Ren. Fail. 2009 31 382 392 10.1080/08860220902835863 19839839 \n20. Selim, A., khalaf, M. M., Gad, A. M. & Abd El-Raouf, O. M. Evaluation of the possible nephroprotective effects of vitamin E and rosuvastatin in amikacin-induced renal injury in rats. J. Biochem. Mol. Toxicol. 31 (2017).\n21. AstraZeneca UK Limited. Crestor 10 mg film-coated tablets - Summary of Product Characteristics. Available at, www.medicines.org.uk/emc/product/7559/smpc, (Accessed: 4th December 2019) (2019).\n22. Kellum JA Kidney disease: Improving global outcomes (KDIGO) acute kidney injury work group. KDIGO clinical practice guideline for acute kidney injury Kidney International Supplements 2012 2 1 138 10.1038/kisup.2012.1 \n23. McWilliam, S. J., Antoine, D. J., Jorgensen, A. L., Smyth, R. L. & Pirmohamed, M. Urinary Biomarkers of Aminoglycoside-Induced Nephrotoxicity in Cystic Fibrosis: Kidney Injury Molecule-1 and Neutrophil Gelatinase-Associated Lipocalin. Sci. Rep. 8 (2018).\n24. Zhang J Immunolocalization of Kim-1, RPA-1, and RPA-2 in Kidney of Gentamicin-, Mercury-, or Chromium-Treated Rats: Relationship to Renal Distributions of iNOS and Nitrotyrosine Toxicol. Pathol. 2008 36 397 409 10.1177/0192623308315832 18441258 \n25. McWilliam Stephen J. Antoine Daniel J. Sabbisetti Venkata Turner Mark A. Farragher Tracey Bonventre Joseph V. Park B. Kevin Smyth Rosalind L. Pirmohamed Munir Mechanism-Based Urinary Biomarkers to Identify the Potential for Aminoglycoside-Induced Nephrotoxicity in Premature Neonates: A Proof-of-Concept Study PLoS ONE 2012 7 8 e43809 10.1371/journal.pone.0043809 22937100 \n26. Lahiri T Guillet A Diehl S Ferguson M High-dose ibuprofen is not associated with increased biomarkers of kidney injury in patients with cystic fibrosis Pediatr. Pulmonol. 2014 49 148 153 10.1002/ppul.22795 23532925 \n27. Vaidya VS Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies Nat. Biotechnol. 2010 28 478 485 10.1038/nbt.1623 20458318 \n28. Kjeldsen L Johnsen AH Sengelov H Borregaard N Isolation and primary structure of NGAL, a novel protein associated with human neutrophil gelatinase J. Biol. Chem. 1993 268 10425 10432 7683678 \n29. Haase M Accuracy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) in Diagnosis and Prognosis in Acute Kidney Injury: A Systematic Review and Meta-analysis Am. J. Kidney Dis. 2009 54 1012 1024 10.1053/j.ajkd.2009.07.020 19850388 \n30. Mcwilliam SJ Reference intervals for urinary renal injury biomarkers KIM-1 and NGAL in healthy children Biomark. Med. 2014 8 1189 1197 10.2217/bmm.14.36 24661102 \n31. Agarwal R Statin induced proteinuria: Renal injury or renoprotection? J. Am. Soc. Nephrol. 2004 15 2502 2503 10.1097/01.ASN.0000143720.71748.79 15340001 \n32. Prayle AP The pharmacokinetics and toxicity of morning vs. evening tobramycin dosing for pulmonary exacerbations of cystic fibrosis: A randomised comparison J. Cyst. Fibros. 2016 15 510 517 10.1016/j.jcf.2015.07.012 26282839 \n33. Birmingham BK Rosuvastatin pharmacokinetics and pharmacogenetics in Caucasian and Asian subjects residing in the United States Eur. J. Clin. Pharmacol. 2015 71 329 340 10.1007/s00228-014-1800-0 25630984 \n34. Braamskamp MJAM Efficacy and safety of rosuvastatin therapy in children and adolescents with familial hypercholesterolemia: Results from the CHARON study J. Clin. Lipidol. 2015 9 741 750 10.1016/j.jacl.2015.07.011 26687694 \n35. Cooper KJ Effect of itraconazole on the pharmacokinetics of rosuvastatin Clin. Pharmacol. Ther. 2003 73 322 329 10.1016/S0009-9236(02)17633-8 12709722 \n36. Paediatric Formulary Committee. BNF for children. MeReC Extra Available at, www.medicinescomplete.com, (Accessed: 4th December 2019) (2005).\n37. Seo, M. S. et al. Effect of treatment on urinary kidney injury molecule-1 in IgA nephropathy. BMC Nephrol. 14 (2013).\n38. De Carvalho JAM Evaluation of the diagnostic characteristics of urinary kidney injury molecule 1 (uKIM-1) and uKIM-1/creatinine ratio in the assessment of incipient diabetic kidney disease Clin. Chem. Lab. Med. 2015 53 e51 e54 10.1515/cclm-2014-0655 25153602 \n39. Szczesniak R Heltshe SL Stanojevic S Mayer-Hamblett N Use of FEV1 in cystic fibrosis epidemiologic studies and clinical trials: A statistical perspective for the clinical researcher Journal of Cystic Fibrosis 2017 16 318 326 10.1016/j.jcf.2017.01.002 28117136 \n40. Waikar SS Sabbisetti VS Bonventre JV Normalization of urinary biomarkers to creatinine during changes in glomerular filtration rate Kidney Int. 2010 78 486 494 10.1038/ki.2010.165 20555318\n\n",
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{
"abstract": "We describe a rare case of recurrent Stenotrophomonas maltophilia bacteremia in a previously healthy 45-year-old man. The infection was caused by osteomyelitis at the site of an iliac crest bone graft harvest. A genetic analysis using enterobacterial repetitive intergenic consensus polymerase chain reaction (ERIC-PCR) revealed that the blood isolates and pathogens obtained from the surgical wound were identical. Initial treatment with levofloxacin and cefozopran was ineffective, but the patient's infection was successfully treated by long-term administration of latamoxef and trimethoprim-sulfamethoxazole. The present case suggests that attention should be given to the possibility of S. maltophilia infection in any situations.",
"affiliations": "Department of General Medicine, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Japan.",
"authors": "Hagiya|Hideharu|H|;Ogawa|Hiroko|H|;Ishida|Tomoharu|T|;Terasaka|Tomohiro|T|;Kimura|Kosuke|K|;Waseda|Koichi|K|;Hanayama|Yoshihisa|Y|;Horita|Masahiro|M|;Shimamura|Yasunori|Y|;Kondo|Eisei|E|;Otsuka|Fumio|F|",
"chemical_list": "D000890:Anti-Infective Agents; D004269:DNA, Bacterial; D015662:Trimethoprim, Sulfamethoxazole Drug Combination",
"country": "Japan",
"delete": false,
"doi": "10.2169/internalmedicine.53.1995",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0918-2918",
"issue": "53(15)",
"journal": "Internal medicine (Tokyo, Japan)",
"keywords": null,
"medline_ta": "Intern Med",
"mesh_terms": "D000890:Anti-Infective Agents; D016025:Bone Transplantation; D004269:DNA, Bacterial; D003937:Diagnosis, Differential; D005500:Follow-Up Studies; D016905:Gram-Negative Bacterial Infections; D006801:Humans; D007085:Ilium; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D012008:Recurrence; D020615:Stenotrophomonas maltophilia; D020858:Tissue and Organ Harvesting; D015662:Trimethoprim, Sulfamethoxazole Drug Combination",
"nlm_unique_id": "9204241",
"other_id": null,
"pages": "1693-8",
"pmc": null,
"pmid": "25088888",
"pubdate": "2014",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Recurrent Stenotrophomonas maltophilia bacteremia after iliac crest bone graft harvest.",
"title_normalized": "recurrent stenotrophomonas maltophilia bacteremia after iliac crest bone graft harvest"
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"abstract": "Drug-induced immune hemolytic anemia is an exceedingly rare adverse drug event. Thiazide diuretics, commonly used in the treatment of primary hypertension, have been associated with this complication. In this case report, we present a 77-year-old male who developed acute hemolytic anemia two days after starting hydrochlorothiazide in the treatment of high blood pressure.",
"affiliations": "Cardiology, Mount Sinai South Nassau, Oceanside, USA.;Internal Medicine, Coney Island Hospital, Brooklyn, USA.;Osteopathic Medicine, New York Institute of Technology, Old Westbury, USA.",
"authors": "Stevens-Cohen|Pilar|P|;Zaghi|Fardad|F|;Zhu|Lawrence|L|",
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"fulltext": "\n==== Front\nCureus\nCureus\n2168-8184\nCureus\n2168-8184\nCureus Palo Alto (CA)\n\n10.7759/cureus.17453\nCardiology\nInternal Medicine\nHematology\nA Rare Case of Hydrochlorothiazide-Induced Hemolytic Anemia\nMuacevic Alexander\nAdler John R\nStevens-Cohen Pilar 1\nZaghi Fardad 2\nZhu Lawrence 3\n1 Cardiology, Mount Sinai South Nassau, Oceanside, USA\n2 Internal Medicine, Coney Island Hospital, Brooklyn, USA\n3 Osteopathic Medicine, New York Institute of Technology, Old Westbury, USA\nLawrence Zhu [email protected]\n26 8 2021\n8 2021\n13 8 e1745325 8 2021\nCopyright © 2021, Stevens-Cohen et al.\n2021\nStevens-Cohen et al.\nhttps://creativecommons.org/licenses/by/3.0/ This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.\nThis article is available from https://www.cureus.com/articles/67814-a-rare-case-of-hydrochlorothiazide-induced-hemolytic-anemia\nDrug-induced immune hemolytic anemia is an exceedingly rare adverse drug event. Thiazide diuretics, commonly used in the treatment of primary hypertension, have been associated with this complication. In this case report, we present a 77-year-old male who developed acute hemolytic anemia two days after starting hydrochlorothiazide in the treatment of high blood pressure.\n\nimmune hemolytic anemia\ndrug-induced immune hemolytic anemia\nhydrochlorothiazide\nadverse drug event\nimmune-mediated hemolysis\nThe content published in Cureus is the result of clinical experience and/or research by independent individuals or organizations. Cureus is not responsible for the scientific accuracy or reliability of data or conclusions published herein. All content published within Cureus is intended only for educational, research and reference purposes. Additionally, articles published within Cureus should not be deemed a suitable substitute for the advice of a qualified health care professional. Do not disregard or avoid professional medical advice due to content published within Cureus.\n==== Body\npmcIntroduction\n\nDrug-induced hemolytic anemia is classified as an immune-mediated reaction. This type of hemolysis is mediated by the attachment of immune complexes to red blood cell (RBC) membranes. Although hydrochlorothiazide (HCTZ) induced hemolytic anemia is uncommon, a few cases of variable severity have been reported [1-3]. In this case report, we aim to present an acute drug-induced immune hemolytic anemia (DIIHA) after two days of HCTZ use.\n\nCase presentation\n\nA 77-year-old white male with a past medical history of coronary artery disease (CAD), hypertension, atrial fibrillation (AFib), and hyperlipidemia, and a past surgical history of coronary artery bypass graft (CABG) seven months prior, presented to the emergency department (ED) with severe malaise, chills, shortness of breath, jaundice, and dark urine. The patient's home medication consisted of lisinopril (20 mg), rosuvastatin (40 mg), aspirin (81 mg), and clopidogrel (75 mg). Two days prior, the patient was seen by his cardiologist and was prescribed HCTZ 12.5 mg. He took HCTZ for two days before developing these symptoms. The patient self-discontinued the medication at the onset of symptoms. The patient was seen by his primary care doctor one week prior to his ED admissions, during which the patient was asymptomatic.\n\nOn admission, patient’s complete blood count showed a white blood cell (WBC) count of 5.95 x 109/L (with 85.8% neutrophils), hemoglobin (Hgb) of 9.2 g/dL (normal range: 13.5-17.5 g/dL), hematocrit (Hct) of 27.4% (normal range: 41%-50%), reticulocyte count of 8.5% (normal range: 0.5%-2.5%) with a corrected reticulocyte count of 5.17%, platelet count of 134 x 103/µL (normal range: 150-450 x 103/µL), mean corpuscular volume (MCV) of 89.89 fL (normal range: 80-100 fL), and red cell distribution width (RDW) of 14.4% (normal range: 12.2%-16.1%). The patient had a blood urea nitrogen (BUN) of 44 mg/dL (normal range: 7-20 mg/dL) and creatinine (Cr) of 1.0 mg/dL (normal range: 0.7-1.2 mg/dL). His liver enzymes, aspartate aminotransferase (AST) and alanine aminotransferase (ALT), were 72 U/L (normal range: 5-40 U/L) and 20 U/L (normal range: 7-55 U/L), respectively. Total bilirubin was 14.4 mg/dL (normal range: 0-1.2 mg/dL); with the direct bilirubin at 2.10 mg/dL (normal range: 0.1-0.3 mg/dL) and indirect bilirubin at 12.3 mg/dL (normal range: 0.2-0.8 mg/dL). Alkaline phosphatase was 98 U/L (normal range: 20-140 U/L), lactate dehydrogenase (LDH) was 591 U/L (normal range: 140-280 U/L), haptoglobin was < 1 mg/dL (normal range: 40-200 mg/dL), iron was 197 mcg/dL (normal range: 60-170 mcg/dL), transferrin was 152 mg/dL (normal range: 204-360 mg/dL), transferrin saturation was 91% (normal range: 15%-50%), ferritin was 2256 ng/mL (normal range: 12-300 ng/mL), vitamin B12 was 491 pg/mL (normal range: 190-950 pg/mL), and folate 3.7 ng/mL (normal range: 2.7-17.0 ng/mL). However, according to his primary care, the patient had lab work done one week prior and all his results were unremarkable; his hemoglobin was 13.3 g/dL and total bilirubin was 0.7 mg/dL. In addition, a computed tomography (CT) scan of the abdomen was suggestive of a side-branch intraductal papillary mucinous neoplasm (IPMN) of the pancreas measuring < 10 mm, which was determined to have a low risk for malignancy and will require a repeat CT scan in one year. The patient’s Coombs test was negative. A peripheral blood smear was performed the following day, which showed bands and atypical lymphocytes, but otherwise normal WBC morphology, no nucleated RBCs, 0-2 schistocytes per high power field, normocytic RBCs, no bite cells, mild rouleaux formation, and no platelet clumping. Given the patient’s history, presentation, and lab results, he was admitted to inpatient medicine and a hematology-oncology consult was requested. Cardiology was also consulted given his history of AFib and CAD, and mildly elevated cardiac enzymes (troponin of 0.04 ng/mL).\n\nThe patient was started on Prednisone 1 mg/kg daily and two doses of intravenous immunoglobulin (IVIG). On day 3 , the patient’s Hgb dropped to 6.5 g/dL warranting two units of RBC suspension which raised his Hgb and Hct to 9.1 g/dL and 26.2%, respectively. His vitamin B12 level was normal, but folic acid was found to be low and ferritin level was high which prompted folic acid supplementation. During his stay, Hgb, Hct, RBC count, total bilirubin, direct bilirubin, indirect bilirubin, and LDH were monitored and their trends showed improvement as indicated in Figures 1-7. Upon discharge, the patient was doing well and was advised to avoid thiazide diuretics and sulfa drugs. His hypertension management now consisted of diet modification and metoprolol.\n\nFigure 1 Patient's hemoglobin trend.\n\nFigure 2 Patient's hematocrit trend.\n\nFigure 3 Patient's red blood cell (RBC) count trend.\n\nFigure 4 Patient's total bilirubin trend.\n\nFigure 5 Patient's direct bilirubin trend.\n\nFigure 6 Patient's indirect bilirubin trend.\n\nFigure 7 Patient's lactate dehydrogenase (LDH) trend.\n\nDiscussion\n\nDIIHA has been estimated to occur in one in a million patients per year [4]. Although exceedingly rare, DIIHA can be potentially fatal even without properly establishing a definitive diagnosis. Drug-induced hemolytic anemia is exhibited in a variety of conditions such as G6PD deficiency in which vulnerable erythrocytes are subjected to oxidative damage, drug-induced thrombotic microangiopathy, and immune-mediated hemolytic anemia (IHA). The first documented case was in 1953 to mephenytoin (Mesantoin®) [5], a hydantoin that was used as an anticonvulsant. Since then, more than 120 different drugs have been associated with DIIHA [6,7]. The largest series of cases of DIIHA was reported in the Berlin Case-Control Surveillance Study in which the development of IHA was associated with the use of beta-lactam antibiotics [8].\n\nThere are two types of DIIHA: drug-dependent and drug-independent. The serological differentiation between the antibodies found in each type is essential in determining management. Drug-dependent antibodies (DDABs) yield a positive direct antiglobulin test (DAT) with negative elution, thus making the DAT a keystone test in the diagnostic work-up of DIIHA. Still, many DDABs can behave like an auto-antibody via the indirect antiglobulin test methods (eg, positive serum or eluate reactivity) when the drug or drug-antibody complexes are still present in the blood. In-depth drug history is essential to any case of hemolysis [9]. In DIIHA, intravascular hemolysis occurs as a result of complement activation via the binding of the offending agent to the RBC membrane. The lysis of RBCs elevates LDH and bilirubin levels and results in anemia. In severe cases, organ failure may be observed [10].\n\nIn our case, there was high suspicion for DIIHA, despite a negative DAT test, because the patient developed anemia, malaise, shortness of breath, dark urine, and jaundice two days after starting HCTZ with the absence of these symptoms nine days prior. The patient's lab results also exhibited a continued fall in Hgb values despite the administration of RBC suspensions. In addition, the patient's hyperbilirubinemia, hemoglobinuria (cause of the dark urine), low haptoglobin levels, high ferritin levels, and anemia findings suggested intravascular hemolysis. Even though a positive DAT, also known as a Coombs test, is a keystone in diagnosing these types of hemolysis, a negative Coombs test does not rule out the diagnosis [11]. The direct Coombs test in the immune complex type of drug-induced hemolytic anemia is usually positive with anti-C3 antisera, but negative with anti IgG antisera. The indirect Coombs test is positive only if the drug and complement are added to the reaction mixture; under those circumstances, the RBCs have C3 on the surface, but no detectable IgG. Antibodies may also be detectable due to their ability to immunologically hemolyze the RBCs; this type of hemolysis may be enhanced by utilizing the RBCs of individuals with paroxysmal nocturnal hemoglobinuria. For many years, it was believed that the drug did not react with the RBCs and that the red cells were “innocent bystanders.” Research now suggests that the reaction is a typical hapten reaction in which the drug forms a loose complex with membrane glycoproteins [12]. Even if the DAT is negative, additional diagnostic tests are indicated based on the patient’s history and physical exam findings, which is evident in our case.\n\nIncidents of hemolytic anemia associated with the use of HCTZ have been documented in several instances. The first documented case was in 1976 in which Vila et al. [1] observed hemolytic episodes in a 67-year-old patient treated with a combination of methyldopa and HCTD for hypertension over a four-year period. They associated mild to moderate hemolytic anemia with the thiazide portion of the drug regimen. In 1980, Garratty et al. [2] documented a severe immune hemolytic anemia and acute renal failure in a 24-year old black patient who ingested 15-20 tablets of the same combination of drugs to commit suicide. They also determined that the hemolysis occurred via an immune-mediated mechanism against HCTZ. In both cases of intravascular hemolysis, antibodies were developed against HCTZ, but not against methyldopa. DIIHA, unlike other immune cytopenias, is poorly characterized and can go undiagnosed which can easily become fatal. Mortality in autoimmune hemolytic anemias is reported to be 11% [13,14]. The first recorded death associated with hemolytic anemia due to HCTZ use was reported in 1984 [3]. A 53-year-old black male expired 18 months after initiating methyldopa and HCTZ combination therapy. The patient had a positive direct and indirect Coombs test, a haptoglobin level at a low of 0.5 g/dL, and a high LDH. The actual cause of death was not established during the autopsy but was considered to be a fatal IHA associated with HCTZ use. It was not until 1986 that alternative diuretic therapies were offered to patients when Shirley et al. [15] characterized similar antibodies against diuretics such as HCTZ in serologic studies of a 53-year-old black female.\n\nEven though healthcare is improving drastically day by day and diagnostic tests are becoming more sensitive and specific, the diagnosis of DIIHA may be delayed by 1-3 weeks after initiation of a drug in non-severe cases. The anemia may be misattributed to other causes without an established diagnosis [16]. In 2016, an 80-year-old male patient with moderate anemia, a mild increase in LDH, and a positive Coombs test was not diagnosed until 20 days after using a combination of angiotensin receptor blockers and HCTZ to treat hypertension [17]. Therefore, practitioners should have a high clinical suspicion for DIIHA in patients with a significant medical history and clinical signs and symptoms of anemia after starting medications that are associated with DIIHA irrespective of Coomb's test results. Cessation of the offending agent in mild cases and corticosteroids in addition to supportive therapy in more severe cases are recommended. Our patient recovered after stopping the HCTZ, and steroid, IVIG, and supportive therapy were initiated. The patient was asked to avoid thiazide diuretics and sulfa drugs indefinitely.\n\nConclusions\n\nDIIHA is a rare adverse drug event, but, because of its variable presentation, a negative Coombs test does not rule out the diagnosis. Healthcare providers should maintain a high clinical suspicion in patients with a significant medical history and clinical signs and symptoms of anemia after starting medications that are known to be associated with DIIHA. Treatment involves stopping the offending agent and initiating supportive care. Steroids and IVIG may have some efficacy in treatment on a case-by-case basis.\n\nHuman Ethics\n\nThe authors have declared that no competing interests exist.\n\nConsent was obtained or waived by all participants in this study\n==== Refs\nReferences\n\n1 Thiazide-induced immune hemolytic anemia JAMA Vila JM Blum L Dosik H 1723 1724 236 1976 989521\n2 Acute immune intravascular hemolysis due to hydrochlorothiazide Am J Clin Pathol Garratty G Houston M Petz LD Webb M 73 78 76 1981 7258154\n3 Fatal intravascular immune hemolysis induced by hydrochlorothiazide Am J Clin Pathol Beck ML Cline JF Hardman JT Racela LS Davis JW 791 794 81 1984 6731360\n4 Drug-induced immune hemolytic anemia Clin Adv Hematol Oncol Garratty G 98 101 8 2010 https://pubmed.ncbi.nlm.nih.gov/20386530/ 20386530\n5 Hemolytic anemia secondary to mesantoin Ann Intern Med Snapper I Marks D Schwartz L Hollander L 619 623 39 1953 13080906\n6 Immune hemolytic anemia associated with drug therapy Blood Rev Garratty G 143 150 24 2010 20650555\n7 Drugs that have been shown to cause drug-induced immune hemolytic anemia or positive direct antiglobulin tests: some interesting findings since 2007 Immunohematology Garratty G Arndt PA 66 79 30 2014 https://pubmed.ncbi.nlm.nih.gov/25247621/ 25247621\n8 Drug induced immune haemolytic anaemia in the Berlin case-control surveillance study Br J Haematol Garbe E Andersohn F Bronder E 644 653 154 2011 21749359\n9 Pathology consultation on drug-induced hemolytic anemia Am J Clin Pathol Pierce A Nester T 7 12 136 2011 21685026\n10 Autoimmune hemolytic anemia Am J Hematol Gehrs BC Friedberg RC 258 271 69 2002 11921020\n11 One center's experience: the serology and drugs associated with drug-induced immune hemolytic anemia--a new paradigm Transfusion Johnson ST Fueger JT Gottschall JL 697 702 47 2007 17381629\n12 Antigenic determinants responsible for the reactions of drug-dependent antibodies with blood cells Br J Haematol Salama A Santoso S Mueller-Eckhardt C 535 539 78 1991 1716956\n13 Immune Hemolytic Anemias. 2nd ed Petz L Garratty G London Elsevier 2003 https://www.elsevier.com/books/immune-hemolytic-anemias/petz/978-0-443-08559-8\n14 Treatment of autoimmune hemolytic anemias Haematologica Zanella A Barcellini W 1547 1554 99 2014 25271314\n15 Characterization of antibody and selection of alternative drug therapy in hydrochlorothiazide-induced immune hemolytic anemia Transfusion Shirey RS Bartholomew J Bell W Pollack B Kickler TS Ness PM 70 72 28 1988 3341072\n16 Serology of antibodies to second- and third-generation cephalosporins associated with immune hemolytic anemia and/or positive direct antiglobulin tests Transfusion Arndt PA Leger RM Garratty G 1239 1246 39 1999 10604252\n17 Hemolytic anemia due to hydrochlorothiazide: a case report Int J Cardiovasc Acad Özlem S Ilgın K 111 113 3 2016\n\n",
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"keywords": "adverse drug event; drug-induced immune hemolytic anemia; hydrochlorothiazide; immune hemolytic anemia; immune-mediated hemolysis",
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"literaturereference": "Stevens-Cohen P, Zaghi F, Zhu L. A Rare Case of Hydrochlorothiazide-Induced Hemolytic Anemia. Cureus. 2021 Aug 26;13(8):e17453",
"literaturereference_normalized": "a rare case of hydrochlorothiazide induced hemolytic anemia",
"qualification": "3",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20211021",
"receivedate": "20211021",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19981690,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20220303"
}
] |
{
"abstract": "Granulicatella adiacens, which occurs as part of the oral microflora, is an uncommon cause of infection. However, it can cause serious bloodstream infections including infective endocarditis. Although oral bacteria, most commonly the Fusobacterium spp, can cause internal jugular vein (IJV) thrombophlebitis, there are no reported cases of IJV thrombosis caused by G. adiacens Here we report a patient with septic IJV thrombosis with G. adiacens bacteraemia. A middle-aged man presented to our hospital with fever and altered mental status. Blood cultures were positive for G. adiacens, and pan-scan CT with contrast showed left IJV thrombosis, pulmonary embolism and abscesses in the gluteal muscles. The patient was successfully treated with antibiotics. When confronted with G. adiacens bacteraemia in patients with poor oral hygiene, it is necessary to be cautious of the fact that this organism can cause IJV thrombophlebitis.",
"affiliations": "Department of General Internal Medicine, Kokuho Asahi Chuo Hospital, Asahi, Chiba, Japan [email protected].;Department of General Internal Medicine, Kokuho Asahi Chuo Hospital, Asahi, Chiba, Japan.",
"authors": "Kawai|Honami|H|;Shiojiri|Toshiaki|T|",
"chemical_list": "D000900:Anti-Bacterial Agents; D065427:Factor Xa Inhibitors; D011725:Pyridines; D013844:Thiazoles; C552171:edoxaban",
"country": "England",
"delete": false,
"doi": "10.1136/bcr-2020-238404",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1757-790X",
"issue": "14(1)",
"journal": "BMJ case reports",
"keywords": "infectious diseases; mouth",
"medline_ta": "BMJ Case Rep",
"mesh_terms": "D000038:Abscess; D000900:Anti-Bacterial Agents; D000071997:Blood Culture; D002081:Buttocks; D056568:Carnobacteriaceae; D004322:Drainage; D000081206:Duration of Therapy; D065427:Factor Xa Inhibitors; D016908:Gram-Positive Bacterial Infections; D006801:Humans; D007601:Jugular Veins; D008297:Male; D008875:Middle Aged; D011655:Pulmonary Embolism; D011725:Pyridines; D013844:Thiazoles; D013924:Thrombophlebitis; D014057:Tomography, X-Ray Computed",
"nlm_unique_id": "101526291",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "33472803",
"pubdate": "2021-01-20",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "31638919;17317605;24152679;25957375;22154996;24436600;23197986;31069174;22442291;25410567;22053963;12441902;31467742;24904685;17762792;19124638;15599753",
"title": "Internal jugular vein thrombosis associated with Granulicatella adiacens.",
"title_normalized": "internal jugular vein thrombosis associated with granulicatella adiacens"
} | [
{
"companynumb": "JP-SUN PHARMACEUTICAL INDUSTRIES LTD-2021R1-305666",
"fulfillexpeditecriteria": "1",
"occurcountry": "JP",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "LITHIUM"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "91027",
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"drugcharacterization": "1",
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"drugdosageform": null,
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"drugenddateformat": null,
"drugindication": "BIPOLAR DISORDER",
"drugintervaldosagedefinition": null,
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"medicinalproduct": "LITHIUM."
}
],
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"patientonsetage": "58",
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"patientweight": "54",
"reaction": [
{
"reactionmeddrapt": "Toxicity to various agents",
"reactionmeddraversionpt": "24.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KAWAI H, SHIOJIRI T. INTERNAL JUGULAR VEIN THROMBOSIS ASSOCIATED WITH GRANULICATELLA ADIACENS. BMJ CASE REP. 2021?14:E238404",
"literaturereference_normalized": "internal jugular vein thrombosis associated with granulicatella adiacens",
"qualification": "3",
"reportercountry": "JP"
},
"primarysourcecountry": "JP",
"receiptdate": "20210729",
"receivedate": "20210729",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "1",
"safetyreportid": 19623368,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
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},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
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"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20211014"
}
] |
{
"abstract": "Bevacizumab (avastin) and erlotinib (tarceva) had shown early clinical activity against head and neck cancer (HNC). We initiated a phase I trial of induction cisplatin, docetaxel, 5-fluorouracil and erlotinib (TPF-E) followed by cisplatin, bevacizumab and erlotinib (PA-E) with radiotherapy (XRT) for advanced HNC. The goal was to determine maximum tolerated erlotinib dose.\n\n\n\nEligible patients had stage IVA or higher HNC with good performance status, hematologic, and renal reserve. Two cycles of induction TPF-E were administered. XRT was administered with concurrent weekly cisplatin and bevacizumab every 2 weeks. Initial erlotinib dose was 50 mg daily from start of induction chemotherapy until radiotherapy completion. Erlotinib dose escalations to 100 and 150 mg were planned.\n\n\n\nThirteen patients with previously untreated locoregional disease (11 patients) or oligometastatic (2 patients) HNC were enrolled. Totally, 11 of 13 patients completed XRT as planned. Four of 8 patients in cohort 1 (erlotinib 50 mg), 3 of 4 patients in cohort 2 (100 mg), and 0 of 1 patients in cohort 3 (150 mg) completed the regimen. Two patients had significant gastrointestinal complications (bleeding and perforation), and 1 had dose-limiting diarrhea. Maximum tolerated dose was reached at 50 mg erlotinib. At median 23.4 months follow-up, 5 patients (38%) have no evidence of disease, and 2 (15%) have stable but measurable disease.\n\n\n\nErlotinib in combination with induction TPF followed by erlotinib, cisplatin, and bevacizumab with XRT is active but toxic. Gastrointestinal toxicities partly caused high rates of study withdrawal. All doses studied in this protocol caused unexpected toxicities and we do not recommend advancement to phase II.",
"affiliations": "Departments of Radiation Oncology.;Departments of Radiation Oncology.;Departments of Radiation Oncology.;Otolaryngology.;Otolaryngology.;Departments of Radiation Oncology.;Departments of Radiation Oncology.;Medical Oncology, Sidney Kimmel Medical College of Thomas, Jefferson University.",
"authors": "Ahn|Peter H|PH|;Machtay|Mitchell|M|;Anne|Pramila R|PR|;Cognetti|David|D|;Keane|William M|WM|;Wuthrick|Evan|E|;Dicker|Adam P|AP|;Axelrod|Rita S|RS|",
"chemical_list": "D000077143:Docetaxel; D000068258:Bevacizumab; D000069347:Erlotinib Hydrochloride; D002945:Cisplatin; D005472:Fluorouracil",
"country": "United States",
"delete": false,
"doi": "10.1097/COC.0000000000000317",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0277-3732",
"issue": "41(5)",
"journal": "American journal of clinical oncology",
"keywords": null,
"medline_ta": "Am J Clin Oncol",
"mesh_terms": "D000230:Adenocarcinoma; D000971:Antineoplastic Combined Chemotherapy Protocols; D000068258:Bevacizumab; D002294:Carcinoma, Squamous Cell; D059248:Chemoradiotherapy; D002945:Cisplatin; D000077143:Docetaxel; D000069347:Erlotinib Hydrochloride; D005260:Female; D005472:Fluorouracil; D005500:Follow-Up Studies; D006258:Head and Neck Neoplasms; D006801:Humans; D060828:Induction Chemotherapy; D008297:Male; D020714:Maximum Tolerated Dose; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate",
"nlm_unique_id": "8207754",
"other_id": null,
"pages": "441-446",
"pmc": null,
"pmid": "27391356",
"pubdate": "2018-05",
"publication_types": "D017426:Clinical Trial, Phase I; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Phase I Trial Using Induction Ciplatin, Docetaxel, 5-FU and Erlotinib Followed by Cisplatin, Bevacizumab and Erlotinib With Concurrent Radiotherapy for Advanced Head and Neck Cancer.",
"title_normalized": "phase i trial using induction ciplatin docetaxel 5 fu and erlotinib followed by cisplatin bevacizumab and erlotinib with concurrent radiotherapy for advanced head and neck cancer"
} | [
{
"companynumb": "US-MYLANLABS-2018M1038920",
"fulfillexpeditecriteria": "1",
"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ERLOTINIB"
},
"drugadditional": "3",
"drugadministrationroute": "048",
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"drugdosagetext": "100 MG, QD, RECEIVED ON DAY 1.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HEAD AND NECK CANCER",
"drugintervaldosagedefinition": "804",
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"drugrecurreadministration": "3",
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"drugstructuredosagenumb": "100",
"drugstructuredosageunit": "003",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "ERLOTINIB"
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FLUOROURACIL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
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"drugcumulativedosagenumb": null,
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"drugdosagetext": "750 MG/M2, QD, RECEIVED ON DAY 1 TO 4",
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"drugindication": "HEAD AND NECK CANCER",
"drugintervaldosagedefinition": "804",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUOROURACIL."
},
{
"actiondrug": "5",
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"activesubstancename": "CISPLATIN"
},
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"drugdosagetext": "75 MG/M2, QD, RECEIVED ON DAY 1.",
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"drugindication": "HEAD AND NECK CANCER",
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"medicinalproduct": "CISPLATIN."
},
{
"actiondrug": "5",
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"activesubstancename": "DOCETAXEL"
},
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"drugdosagetext": "75 MG/M2, QD, RECEIVED ON DAY 1",
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"drugindication": "HEAD AND NECK CANCER",
"drugintervaldosagedefinition": "804",
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"drugstructuredosagenumb": "75",
"drugstructuredosageunit": "009",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "DOCETAXEL."
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": "1",
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Fatigue",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Diverticulum",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Gastrointestinal perforation",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "AHN PH, MACHTAY M, ANNE PR, COGNETTI D, KEANE WM, WUTHRICK E, ET AL. PHASE I TRIAL USING INDUCTION CIPLATIN, DOCETAXEL, 5-FU AND ERLOTINIB FOLLOWED BY CISPLATIN, BEVACIZUMAB AND ERLOTINIB WITH CONCURRENT RADIOTHERAPY FOR ADVANCED HEAD AND NECK CANCER. AM-J-CLIN-ONCOL 2018?41(5):441-446.",
"literaturereference_normalized": "phase i trial using induction ciplatin docetaxel 5 fu and erlotinib followed by cisplatin bevacizumab and erlotinib with concurrent radiotherapy for advanced head and neck cancer",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20180611",
"receivedate": "20180611",
"receiver": {
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"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 14996144,
"safetyreportversion": 1,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180711"
},
{
"companynumb": "US-MYLANLABS-2018M1039059",
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"occurcountry": "US",
"patient": {
"drug": [
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "FLUOROURACIL"
},
"drugadditional": "3",
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"drugdosagetext": "750 MG/M2, QD, RECEIVED ON DAY 1 TO 4.",
"drugenddate": null,
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"drugindication": "HEAD AND NECK CANCER",
"drugintervaldosagedefinition": "804",
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"drugrecurrence": null,
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"medicinalproduct": "FLUOROURACIL."
},
{
"actiondrug": "5",
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},
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"drugdosagetext": "75 MG/M2, QD, RECEIVED ON DAY 1",
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"drugindication": "HEAD AND NECK CANCER",
"drugintervaldosagedefinition": "804",
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"drugstructuredosageunit": "009",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "CISPLATIN."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "DOCETAXEL"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": null,
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"drugcharacterization": "1",
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"drugdosagetext": "75 MG/M2, QD, RECEIVED ON DAY 1",
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"drugindication": "HEAD AND NECK CANCER",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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"drugstructuredosagenumb": "75",
"drugstructuredosageunit": "009",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "DOCETAXEL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "ERLOTINIB"
},
"drugadditional": "3",
"drugadministrationroute": "048",
"drugauthorizationnumb": null,
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"drugcharacterization": "1",
"drugcumulativedosagenumb": null,
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"drugdosageform": null,
"drugdosagetext": "150 MG, QD, RECEIVED ON DAY 1.",
"drugenddate": null,
"drugenddateformat": null,
"drugindication": "HEAD AND NECK CANCER",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
"drugrecurreadministration": "3",
"drugrecurrence": null,
"drugseparatedosagenumb": "1",
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"drugstartdateformat": null,
"drugstructuredosagenumb": "150",
"drugstructuredosageunit": "003",
"drugtreatmentduration": null,
"drugtreatmentdurationunit": null,
"medicinalproduct": "ERLOTINIB"
}
],
"patientagegroup": null,
"patientonsetage": null,
"patientonsetageunit": null,
"patientsex": null,
"patientweight": null,
"reaction": [
{
"reactionmeddrapt": "Acute kidney injury",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Diarrhoea",
"reactionmeddraversionpt": "21.0",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "AHN PH, MACHTAY M, ANNE PR, COGNETTI D, KEANE WM, WUTHRICK E, ET AL. PHASE I TRIAL USING INDUCTION CIPLATIN, DOCETAXEL, 5-FU AND ERLOTINIB FOLLOWED BY CISPLATIN, BEVACIZUMAB AND ERLOTINIB WITH CONCURRENT RADIOTHERAPY FOR ADVANCED HEAD AND NECK CANCER. AM-J-CLIN-ONCOL 2018?41(5):441-446.",
"literaturereference_normalized": "phase i trial using induction ciplatin docetaxel 5 fu and erlotinib followed by cisplatin bevacizumab and erlotinib with concurrent radiotherapy for advanced head and neck cancer",
"qualification": "1",
"reportercountry": "US"
},
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"receiptdate": "20180611",
"receivedate": "20180611",
"receiver": {
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},
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"safetyreportid": 14996168,
"safetyreportversion": 1,
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"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
"seriousnessdisabling": null,
"seriousnesshospitalization": 1,
"seriousnesslifethreatening": null,
"seriousnessother": 1,
"transmissiondate": "20180711"
},
{
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"fulfillexpeditecriteria": "1",
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"patient": {
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},
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},
{
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},
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"drugdosagetext": "RECEIVED ON DAYS 1 TO 4.",
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"drugstructuredosageunit": "009",
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"drugtreatmentdurationunit": null,
"medicinalproduct": "FLUOROURACIL."
},
{
"actiondrug": "5",
"activesubstance": {
"activesubstancename": "CISPLATIN"
},
"drugadditional": "3",
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"drugdosagetext": "RECEIVED ON DAY 1",
"drugenddate": null,
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"drugindication": "HEAD AND NECK CANCER",
"drugintervaldosagedefinition": "804",
"drugintervaldosageunitnumb": "1",
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{
"abstract": "We report here a case of CR of all target lesions in a patient with esophageal cancer with multiple metastases treated with systemic chemotherapy after nutritionalsupport. A 75-year-old man was referred to our hospital with a diagnosis of multiple- metastatic esophagealcancer in June 2014. He showed generalized weakness with poor dietary intake, and he was initially admitted for nutritional support by parenteral nutrition. Biopsy specimens revealed mixed squamous- and adenocarcinoma: MtLtUtAeG, 13 cm, type 2, cT3, IM1-St, cN3, cM1(liver, lungs, and stomach), cStage IV b esophagealcarcinoma. We had initiated 5-FU/CDDP/docetaxel(DCF)chemotherapy in July 2014. The target lesions exhibited PR after 2 courses of chemotherapy, and the primary esophageal lesion was markedly reduced, but was still present. The patient's renalfunction deteriorated after 8 courses of DCF, and the chemotherapy protocolwas changed to single-agent docetaxelonce every 3 weeks. The patient underwent 20 courses of the chemotherapy, and over a period of approximately 1 year from March 2015, CR of all target lesions was noted, with IR/SD of the primary tumor. The patient has survived and remained in good condition for 23 months following the initial diagnosis.",
"affiliations": "Dept. of Surgery, Fujisaki Hospital.",
"authors": "Fujisaki|Shigeru|S|;Takashina|Motoi|M|;Tomita|Ryouichi|R|;Sakurai|Kenichi|K|;Takayama|Tadatoshi|T|",
"chemical_list": "D000970:Antineoplastic Agents; D043823:Taxoids; D000077143:Docetaxel; D002945:Cisplatin; D005472:Fluorouracil",
"country": "Japan",
"delete": false,
"doi": null,
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0385-0684",
"issue": "43(12)",
"journal": "Gan to kagaku ryoho. Cancer & chemotherapy",
"keywords": null,
"medline_ta": "Gan To Kagaku Ryoho",
"mesh_terms": "D000230:Adenocarcinoma; D000368:Aged; D000970:Antineoplastic Agents; D000971:Antineoplastic Combined Chemotherapy Protocols; D002294:Carcinoma, Squamous Cell; D002945:Cisplatin; D000077143:Docetaxel; D004938:Esophageal Neoplasms; D005472:Fluorouracil; D006801:Humans; D008297:Male; D009362:Neoplasm Metastasis; D010288:Parenteral Nutrition; D043823:Taxoids",
"nlm_unique_id": "7810034",
"other_id": null,
"pages": "2000-2003",
"pmc": null,
"pmid": "28133202",
"pubdate": "2016-11",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "CR of All Target Lesions in a Patient with Metastatic Esophageal Cancer and Generalized Weakness Treated with Systemic Chemotherapy after Nutritional Support.",
"title_normalized": "cr of all target lesions in a patient with metastatic esophageal cancer and generalized weakness treated with systemic chemotherapy after nutritional support"
} | [
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}
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] |
{
"abstract": "BACKGROUND\nIntentional poisoning with warfarin is not the same as over-anticoagulation, for which guidelines exist. The coagulopathy resulting from a warfarin overdose is reversed with vitamin K1, the dose and timing of which is often guided by experience with the management of over-anticoagulation with warfarin therapy, rather than acute overdose.\n\n\nMETHODS\nWe report a case of a 50-year-old man who ingested an unknown amount of his warfarin, venlafaxine, and paracetamol. He presented with an international normalized ratio (INR) of 2.5, which steadily increased over 24 h to 7, despite receiving an initial 1 mg of vitamin K1. He was then treated with 5 mg vitamin K1, and once the INR returned to 4.5, 40 h post ingestion, he was discharged home. He was also treated with a full course of acetylcysteine for the paracetamol overdose. The following day his INR rebounded to 8.5 and he suffered a spontaneous epistaxis requiring readmission; he was treated with low titrated doses of vitamin K1. The warfarin concentration was 74.6 μg/mL 26 h post ingestion and decreased to 3.7 μg/mL over 72 h. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Our case highlights the risk of a rebound elevated INR even 3 days after acute warfarin overdose despite treatment with vitamin K1. Understanding the pharmacokinetics of vitamin K1 in comparison with warfarin, repeat INR testing, and continued treatment with oral vitamin K1 may help avoid complications of rebound coagulopathy in warfarin overdose.",
"affiliations": "Clinical Toxicology Research Group, University of Newcastle, Newcastle, New South Wales, Australia; Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.;Therapeutics Research Centre, University of Queensland, Brisbane, Australia; Pharmaceutical Chemistry Department, Faculty of Pharmacy, Helwan University, Ain Helwan, Cairo, Egypt.;Therapeutics Research Centre, University of Queensland, Brisbane, Australia.;Therapeutics Research Centre, University of Queensland, Brisbane, Australia; School of Pharmacy and Medical Sciences, University of South Australia, Adelaide, Australia.;Clinical Toxicology Research Group, University of Newcastle, Newcastle, New South Wales, Australia; Department of Clinical Toxicology and Pharmacology, Calvary Mater Newcastle, Newcastle, New South Wales, Australia.",
"authors": "Berling|Ingrid|I|;Mostafa|Ahmed|A|;Grice|Jeffrey E|JE|;Roberts|Michael S|MS|;Isbister|Geoffrey K|GK|",
"chemical_list": "D000925:Anticoagulants; D014812:Vitamin K; D000082:Acetaminophen; D014859:Warfarin; D000069470:Venlafaxine Hydrochloride; D000111:Acetylcysteine",
"country": "United States",
"delete": false,
"doi": "10.1016/j.jemermed.2016.05.068",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0736-4679",
"issue": "52(2)",
"journal": "The Journal of emergency medicine",
"keywords": "overdose; poisoning; vitamin K1; warfarin",
"medline_ta": "J Emerg Med",
"mesh_terms": "D000082:Acetaminophen; D000111:Acetylcysteine; D000437:Alcoholism; D000925:Anticoagulants; D003863:Depression; D062787:Drug Overdose; D004636:Emergency Service, Hospital; D006801:Humans; D019934:International Normalized Ratio; D008297:Male; D008875:Middle Aged; D013405:Suicide; D000069470:Venlafaxine Hydrochloride; D014812:Vitamin K; D014859:Warfarin",
"nlm_unique_id": "8412174",
"other_id": null,
"pages": "194-196",
"pmc": null,
"pmid": "27838137",
"pubdate": "2017-02",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Warfarin Poisoning with Delayed Rebound Toxicity.",
"title_normalized": "warfarin poisoning with delayed rebound toxicity"
} | [
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{
"abstract": "Patients who undergo kidney transplantation are at increased risk of cancer due to the long-term use of immunosuppressive treatment. Postrenal transplant cancers usually originate from recipient cells, but donor-related cancers have been rarely reported. We report the case of 49-year-old woman who developed multiple myeloma of donor origin 7 years after kidney transplantation. The donor was the mother of the recipient and also developed multiple myeloma 1 year after kidney donation. The diagnosis of multiple myeloma was based on IgG lambda monoclonal protein and the infiltration of plasma cells in bone marrow. The renal biopsy did not reveal plasmacytoma in the transplanted kidney. Epstein-Barr virus DNA load was negative in peripheral blood. The patient responded to lenalidomide and dexamethasone, and subsequently received autologous stem cell transplantation. Donor chimerism was detected in the recipient marrow by short tandem repeat analysis; however, studies of Ig gene rearrangement were inconclusive due to insufficient DNA quality. The chromosomal abnormalities in the two myelomas were different. This case suggests that donor cells with myeloma-initiating potential can be transferred to a recipient via a renal graft and can lead to the development of donor-derived multiple myeloma in the recipient under immunosuppression.",
"affiliations": "Division of Hematology, Jichi Medical University, Shimotuke, Japan.;Division of Hematology, Jichi Medical University, Shimotuke, Japan.;Division of Hematology, Jichi Medical University, Shimotuke, Japan.;Division of Renal Surgery and Transplantation, Jichi Medical University, Shimotuke, Japan.;Division of Renal Surgery and Transplantation, Jichi Medical University, Shimotuke, Japan.;Department of Pathology, Tokai University School of Medicine, Isehara, Japan.;Division of Renal Surgery and Transplantation, Jichi Medical University, Shimotuke, Japan.;Division of Hematology, Jichi Medical University, Shimotuke, Japan.",
"authors": "Fujiwara|Shin-Ichiro|SI|;Ikeda|Takashi|T|;Morita|Kaoru|K|;Shinzato|Takahiro|T|;Ishikawa|Nobuo|N|;Nakamura|Naoya|N|;Yagisawa|Takashi|T|;Kanda|Yoshinobu|Y|",
"chemical_list": "D007166:Immunosuppressive Agents",
"country": "United States",
"delete": false,
"doi": "10.1111/ajt.15373",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1600-6135",
"issue": "19(8)",
"journal": "American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons",
"keywords": "cancer/malignancy/neoplasia: hematogenous/leukemia/lymphoma; clinical research/practice; kidney transplantation/nephrology; kidney transplantation: living donor",
"medline_ta": "Am J Transplant",
"mesh_terms": "D000328:Adult; D046528:Chimerism; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents; D007676:Kidney Failure, Chronic; D016030:Kidney Transplantation; D009101:Multiple Myeloma; D009392:Nephrectomy; D011183:Postoperative Complications; D014019:Tissue Donors; D020858:Tissue and Organ Harvesting",
"nlm_unique_id": "100968638",
"other_id": null,
"pages": "2374-2377",
"pmc": null,
"pmid": "30916888",
"pubdate": "2019-08",
"publication_types": "D002363:Case Reports; D016428:Journal Article; D013485:Research Support, Non-U.S. Gov't",
"references": null,
"title": "Multiple myeloma derived from a kidney transplant donor who also developed myeloma after kidney donation.",
"title_normalized": "multiple myeloma derived from a kidney transplant donor who also developed myeloma after kidney donation"
} | [
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"reaction": [
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"reactionmeddraversionpt": "22.0",
"reactionoutcome": "6"
}
],
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},
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"reportercountry": "JP"
},
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] |
{
"abstract": "Priapism is a rare but severe urological emergency of erection of penis in the absence of physical and psychological sexual stimulation. Priapism is often idiopathic and is commonly associated with medications and underlying medical or traumatic causes. In this report, we present a case of a 70-year-old White Caucasian man who developed priapism after the administration of ondansetron, which is a selective serotonin type-3 (5-HT3) receptor antagonist. This case is unique, because, to date, there are only two presented cases in literature. The objective of this case report is to highlight the importance of recognising the possibility of priapism with ondansetron because this condition is not commonly seen in clinical practice to be associated with ondansetron and may go unrecognised. Also, potential pathophysiological mechanisms involved in the development of ondansetron-induced priapism are presented.",
"affiliations": "Department of Gastroenterology, Medical Faculty, Gulhane Military Medical Academy, Ankara, Turkey.;Department of Urology, Faculty of Medicine, Medical Park Bursa Hospital, Bahcesehir University, Bursa, Turkey.;Department of Urology, Istanbul Training and Research Hospital, Istanbul, Turkey.;Department of Urology, Faculty of Medicine, Medical Park Bursa Hospital, Kemerburgaz University, Bursa, Turkey.",
"authors": "Kilciler|G|G|;Kilciler|M|M|;Kadihasanoglu|M|M|;Atahan|O|O|",
"chemical_list": "D012702:Serotonin Antagonists; D017294:Ondansetron",
"country": "Germany",
"delete": false,
"doi": "10.1111/and.12686",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0303-4569",
"issue": "49(6)",
"journal": "Andrologia",
"keywords": "antagonist; nonischaemic; ondansetron; priapism; serotonin",
"medline_ta": "Andrologia",
"mesh_terms": "D000368:Aged; D006801:Humans; D008297:Male; D017294:Ondansetron; D011317:Priapism; D012702:Serotonin Antagonists",
"nlm_unique_id": "0423506",
"other_id": null,
"pages": null,
"pmc": null,
"pmid": "27709642",
"pubdate": "2017-08",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "Nonischaemic priapism associated with selective serotonin-3 receptor antagonist.",
"title_normalized": "nonischaemic priapism associated with selective serotonin 3 receptor antagonist"
} | [
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"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
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"reactionmeddraversionpt": "19.1",
"reactionoutcome": "6"
},
{
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"reactionoutcome": "1"
}
],
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},
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},
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},
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"literaturereference_normalized": "nonischaemic priapism associated with selective serotonin 3 receptor antagonist",
"qualification": "1",
"reportercountry": "TR"
},
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"receiptdate": "20171006",
"receivedate": "20161212",
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"transmissiondate": "20180320"
}
] |
{
"abstract": "α-methylacyl-CoA racemase (AMACR) deficiency is a rare disorder, affecting peroxisomal metabolism of pristanic acid, with ten published adult cases. We describe an AMACR deficiency case with a clinical presentation dominated by episodic hyperCKaemia, suggesting that myopathic features of AMACR should be considered.",
"affiliations": "Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.;John Walton Muscular Dystrophy Research Centre, Translational and Clinical Research Institute, Newcastle University and Newcastle Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK.;Copenhagen Neuromuscular Center, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark.",
"authors": "Krett|B|B|0000-0001-7612-7073;Straub|V|V|;Vissing|J|J|",
"chemical_list": "D019998:Racemases and Epimerases; C108352:alpha-methylacyl-CoA racemase; D003065:Coenzyme A",
"country": "England",
"delete": false,
"doi": "10.1111/ene.14588",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1351-5101",
"issue": "28(2)",
"journal": "European journal of neurology",
"keywords": "hyperCKaemia; muscular diseases; myopathy; rhabdomyolysis; α-methylacyl-CoA racemase (AMACR) deficiency",
"medline_ta": "Eur J Neurol",
"mesh_terms": "D000328:Adult; D003065:Coenzyme A; D006801:Humans; D008052:Lipid Metabolism, Inborn Errors; D019998:Racemases and Epimerases",
"nlm_unique_id": "9506311",
"other_id": null,
"pages": "729-731",
"pmc": null,
"pmid": "33047465",
"pubdate": "2021-02",
"publication_types": "D002363:Case Reports",
"references": null,
"title": "Episodic hyperCKaemia may be a feature of α-methylacyl-coenzyme A racemase deficiency.",
"title_normalized": "episodic hyperckaemia may be a feature of methylacyl coenzyme a racemase deficiency"
} | [
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"medicinalproduct": "FUROSEMIDE."
}
],
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"patientonsetage": "40",
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"reaction": [
{
"reactionmeddrapt": "Femur fracture",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Epilepsy",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Abnormal behaviour",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Rhabdomyolysis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Inborn error of lipid metabolism",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Confusional state",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Sepsis",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "5"
},
{
"reactionmeddrapt": "Depression",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Hypogonadism",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Tremor",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Blood creatine phosphokinase increased",
"reactionmeddraversionpt": "23.1",
"reactionoutcome": "6"
}
],
"summary": null
},
"primarysource": {
"literaturereference": "KRETT B., STRAUB V., VISSING J.. EPISODIC HYPERCKAEMIA MAY BE A FEATURE OF ??METHYLACYL?COENZYME A RACEMASE DEFICIENCY. EUROPEAN JOURNAL OF NEUROLOGY. 2021?28:729? 731",
"literaturereference_normalized": "episodic hyperckaemia may be a feature of methylacyl coenzyme a racemase deficiency",
"qualification": "1",
"reportercountry": "DK"
},
"primarysourcecountry": "DK",
"receiptdate": "20210212",
"receivedate": "20210212",
"receiver": {
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"receivertype": "6"
},
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"safetyreportversion": 1,
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"senderorganization": "FDA-Public Use",
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},
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] |
{
"abstract": "BACKGROUND\nMelanoma is an immune responsive malignancy and the need for immunosuppression for successful transplantation may lead to recurrent disease. The recommended waiting time is unknown with various groups recommending anywhere from no wait to 5 years.\n\n\nMETHODS\nIn this single-center, retrospective observational study all kidney transplant recipients' charts from 1991 to 2015 were reviewed for a diagnosis of melanoma before transplantation. The charts were reviewed for the clinical characteristics of melanoma pre transplantation, induction immunosuppression, maintenance immunosuppression, graft function, death, and recurrence of melanoma.\n\n\nRESULTS\nThirteen patients with a history of melanoma underwent kidney transplantation during this period. Recipients had been in remission for an average of 7.0 years (range, 10 months to 20 years, median 6 years). Approximately 61.5% received a living donor transplant, antithymocyte globulin was administered in 23.1% of recipients, and the remaining 76.9% received basiliximab. Melanoma recurred in 1 patient (7.7%). Maintenance immunosuppression varied, but only 2 patients remained on standard triple therapy with prednisone, calcineurin inhibitor, and antimetabolite therapy. Average follow-up time since transplant was 7.5 years, with 1 patient death 9 years post transplant from sepsis.\n\n\nCONCLUSIONS\nIn conclusion, with our center demonstrates safety of kidney transplantation in patients with a prior history of localized melanoma and shorter waiting time. In malignant melanoma stage 0 and 1, waiting the recommended 5 years from the time of remission to kidney transplantation should be reconsidered.",
"affiliations": "Department of Medicine, Division of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, California. Electronic address: [email protected].;Department of Medicine, Division of Nephrology, Kidney and Pancreas Transplant Research Center, David Geffen School of Medicine at UCLA, Los Angeles, California.;Department of Medicine, Division of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, California.;Department of Medicine, Division of Nephrology, David Geffen School of Medicine at UCLA, Los Angeles, California.",
"authors": "Qaqish|Shaker|S|;Datta|Nakul|N|;Bunnapradist|Suphamai|S|;Lum|Erik L|EL|",
"chemical_list": "D007166:Immunosuppressive Agents",
"country": "United States",
"delete": false,
"doi": "10.1016/j.transproceed.2020.04.1823",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0041-1345",
"issue": "52(10)",
"journal": "Transplantation proceedings",
"keywords": null,
"medline_ta": "Transplant Proc",
"mesh_terms": "D000328:Adult; D000368:Aged; D005260:Female; D006801:Humans; D016867:Immunocompromised Host; D007166:Immunosuppressive Agents; D007676:Kidney Failure, Chronic; D016030:Kidney Transplantation; D008297:Male; D008545:Melanoma; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local; D012189:Retrospective Studies; D012878:Skin Neoplasms",
"nlm_unique_id": "0243532",
"other_id": null,
"pages": "3033-3037",
"pmc": null,
"pmid": "32654800",
"pubdate": "2020-12",
"publication_types": "D016428:Journal Article; D064888:Observational Study",
"references": null,
"title": "Listing Malignant Melanoma Patients for Renal Transplantation.",
"title_normalized": "listing malignant melanoma patients for renal transplantation"
} | [
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"medicinalproduct": "PREDNISONE."
},
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"actiondrug": "5",
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},
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],
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{
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}
],
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}
},
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"literaturereference": "QAQISH S, DATTA N, BUNNAPRADIST S, LUM EL. LISTING MALIGNANT MELANOMA PATIENTS FOR RENAL TRANSPLANTATION. TRANSPLANT?PROC 2020?52(10):3033?3037.",
"literaturereference_normalized": "listing malignant melanoma patients for renal transplantation",
"qualification": "1",
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},
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},
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},
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"medicinalproduct": "SIROLIMUS."
},
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"activesubstance": {
"activesubstancename": "PREDNISONE"
},
"drugadditional": "3",
"drugadministrationroute": "065",
"drugauthorizationnumb": "080356",
"drugbatchnumb": null,
"drugcharacterization": "1",
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"drugindication": "IMMUNOSUPPRESSANT DRUG THERAPY",
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"medicinalproduct": "PREDNISONE."
}
],
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{
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"reactionmeddraversionpt": "24.0",
"reactionoutcome": "1"
}
],
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"narrativeincludeclinical": "CASE EVENT DATE: 2009"
}
},
"primarysource": {
"literaturereference": "QAQISH S, DATTA N, BUNNAPRADIST S, LUM EL. LISTING MALIGNANT MELANOMA PATIENTS FOR RENAL TRANSPLANTATION. TRANSPLANT?PROC 2020?52(10):3033?3037.",
"literaturereference_normalized": "listing malignant melanoma patients for renal transplantation",
"qualification": "1",
"reportercountry": "US"
},
"primarysourcecountry": "US",
"receiptdate": "20210712",
"receivedate": "20210321",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 19035990,
"safetyreportversion": 2,
"sender": {
"senderorganization": "FDA-Public Use",
"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": null,
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"seriousnessother": 1,
"transmissiondate": "20211014"
}
] |
{
"abstract": "BACKGROUND\nRadiation therapy in pediatric patients often requires anesthesia and poses environmental challenges. Monitoring must be done remotely to limit radiation exposure to the provider. Airway access can be limited by masks or frames. Care is often delivered in relatively inaccessible locations in the hospital. While individual institutions have reported their outcomes, this case series aims to review a multicenter registry of significant adverse events and make recommendations for improved care.\n\n\nMETHODS\nWake Up Safe: The Pediatric Quality Improvement Initiative maintains a multisite, voluntary registry of pediatric perianesthetic significant adverse events. This was queried for reports from radiation oncology from January 1, 2010 to May 10, 2018. The database contained 3,379 significant adverse events from approximately 3.3 million anesthetics. All 33 institutions submitted data on a standardized form to a central data repository (Axio Research, Seattle Washington). Prior to each significant adverse events case submission, three anesthesiologists who were not involved in the event analyzed the event using a standardized root cause analysis method to identify the causal or contributing factor(s).\n\n\nRESULTS\nSix significant adverse events were identified. In three, incorrect programming of a propofol infusion resulted in overdose. In case one, the 3-year-old female became hypotensive, requiring vasopressors and volume resuscitation. In the second, the 2-year-old female experienced airway obstruction and apnea requiring chin lift. In case three, the child suffered no consequences despite a noted overdose of propofol infusion. In case four, a 2-year-old female with recent respiratory infection suffered laryngospasm during an unmonitored transport to the recovery area. She developed profound oxygen desaturation with bradycardia treated with succinylcholine and chest compressions. In case five, a 6-year-old former premature child suffered laryngospasm at the conclusion of mask creation under general anesthesia with a laryngeal mask airway. The radiation mask delayed recognition of copious secretions. Finally, in case six, a 6-year-old undergoing stereotactic radiosurgery in a head halo suffered bronchospasm and unintended extubation during therapy which required multiple attempts at reintubation by multiple providers ultimately requiring cancellation of the treatment and transport to the intensive care unit.\n\n\nCONCLUSIONS\nThere were few radiation oncology significant adverse events, but analysis has led to the identification of several specific opportunities for improvement in pediatric anesthesia for radiation oncology.",
"affiliations": "Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan.;Department of Anesthesiology, University of Michigan, Ann Arbor, Michigan.;US Anesthesia Partners Colorado, Greenwood Village, Colorado.;Radiation Oncology, University of Michigan, Ann Arbor, Michigan.;Radiation Oncology, University of Michigan, Ann Arbor, Michigan.",
"authors": "Christensen|Robert E|RE|https://orcid.org/0000-0002-9838-6807;Nause-Osthoff|Rebecca C|RC|;Waldman|Jeffrey C|JC|;Spratt|Daniel E|DE|;Hearn|Jason W D|JWD|",
"chemical_list": "D006993:Hypnotics and Sedatives; D015742:Propofol",
"country": "France",
"delete": false,
"doi": "10.1111/pan.13567",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1155-5645",
"issue": "29(3)",
"journal": "Paediatric anaesthesia",
"keywords": "airway obstruction; anesthesia; child; medication errors; quality improvement; radiation oncology; retrospective studies",
"medline_ta": "Paediatr Anaesth",
"mesh_terms": "D000758:Anesthesia; D000762:Anesthesia Recovery Period; D000768:Anesthesia, General; D002648:Child; D002675:Child, Preschool; D006801:Humans; D006993:Hypnotics and Sedatives; D017214:Laryngeal Masks; D015742:Propofol; D058996:Quality Improvement; D018787:Radiation Oncology; D011878:Radiotherapy",
"nlm_unique_id": "9206575",
"other_id": null,
"pages": "265-270",
"pmc": null,
"pmid": "30580487",
"pubdate": "2019-03",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Adverse events in radiation oncology: A case series from wake up safe, the pediatric anesthesia quality improvement initiative.",
"title_normalized": "adverse events in radiation oncology a case series from wake up safe the pediatric anesthesia quality improvement initiative"
} | [
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"companynumb": "US-DRREDDYS-USA/USA/19/0106963",
"fulfillexpeditecriteria": "1",
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"patient": {
"drug": [
{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "PROPOFOL"
},
"drugadditional": null,
"drugadministrationroute": null,
"drugauthorizationnumb": "205067",
"drugbatchnumb": "UNKNOWN",
"drugcharacterization": "1",
"drugcumulativedosagenumb": "150",
"drugcumulativedosageunit": "003",
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{
"abstract": "Dabigatran is increasingly being used in clinical practice for the thromboprophylaxis in atrial fibrillation as a convenient therapy that needs no drug level monitoring. However, analysis of the data of the same clinical trial that led to the adoption of dabigatran in fixed-dosing regimens has indicated a small subgroup of patients that could be either over-treated, risking bleeding, or under-treated, risking embolism. Additional post-marketing data lends support to the favorable therapeutic profile of dabigatran but at the same time raises doubts about patient characteristics such as weight, age, renal function and their pharmacokinetic effects that, in some cases, could be serious enough to expose a minority of patients to risk. We will present a clinical case of a patient with an ischemic stroke while on dabigatran that was found with low dabigatran plasma levels and we will discuss the currently available data on the effects of inherent patient characteristics on dabigatran pharmacokinetics, the clinical impact of dabigatran plasma levels on safety and efficacy as well as the possibility of improving the risk-benefit profile of this agent by tailoring the dose for selected patient groups.",
"affiliations": "Stroke Unit, Department of Neurology, Brugmann University Hospital, Place Van Gehuchten 4, 1020 Bruxelles, Belgium.;First Department of Neurology, University of Athens, School of Medicine, 'Eginition' University Hospital, Athens, Greece.;Second Department of Cardiology, University of Athens, School of Medicine, 'Attikon' University Hospital, Athens, Greece.;Second Department of Neurology, University of Athens, School of Medicine, 'Attikon' University Hospital, Athens, Greece International Clinical Research Center, St. Anne's University Hospital in Brno, Czech Republic.",
"authors": "Safouris|Apostolos|A|;Triantafyllou|Nikos|N|;Parissis|John|J|;Tsivgoulis|Georgios|G|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1177/1756285615601360",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1756-2856",
"issue": "8(6)",
"journal": "Therapeutic advances in neurological disorders",
"keywords": "atrial fibrillation; dabigatran; dosing",
"medline_ta": "Ther Adv Neurol Disord",
"mesh_terms": null,
"nlm_unique_id": "101480242",
"other_id": null,
"pages": "245-54",
"pmc": null,
"pmid": "26600870",
"pubdate": "2015-11",
"publication_types": "D016428:Journal Article; D016454:Review",
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"title": "The case for dosing dabigatran: how tailoring dose to patient renal function, weight and age could improve the benefit-risk ratio.",
"title_normalized": "the case for dosing dabigatran how tailoring dose to patient renal function weight and age could improve the benefit risk ratio"
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"abstract": "We present the case of a 75-year-old man who had uneventful cataract surgery and administration of intracameral vancomycin for endophthalmitis prophylaxis, followed by the same procedure in the fellow eye 1 week later. The patient subsequently developed bilateral hemorrhagic occlusive retinal vasculitis, resulting in profound vision loss in both eyes. A second case of hemorrhagic occlusive retinal vasculitis previously reported from our institution is summarized. That case was characterized by a far milder course, with rapid resolution of vision loss. The 2 cases illustrate the broad range of toxicity potentially associated with intracameral vancomycin, suggest that bilateral administration results in a worse prognosis, and indicate that this disorder may be underrecognized due to the potential for a mild course. We recommend that intracameral vancomycin not be used for endophthalmitis prophylaxis.\n\n\n\nNone of the authors has a financial or proprietary interest in any material or method mentioned.",
"affiliations": "From the Department of Ophthalmology and Visual Sciences (Miller, Lenci, Russell), University of Iowa Hospitals and Clinics, Iowa City, Iowa, and the Retina Consultants of Central Illinois (Reddy), Peoria, Illinois, USA. Electronic address: [email protected].;From the Department of Ophthalmology and Visual Sciences (Miller, Lenci, Russell), University of Iowa Hospitals and Clinics, Iowa City, Iowa, and the Retina Consultants of Central Illinois (Reddy), Peoria, Illinois, USA.;From the Department of Ophthalmology and Visual Sciences (Miller, Lenci, Russell), University of Iowa Hospitals and Clinics, Iowa City, Iowa, and the Retina Consultants of Central Illinois (Reddy), Peoria, Illinois, USA.;From the Department of Ophthalmology and Visual Sciences (Miller, Lenci, Russell), University of Iowa Hospitals and Clinics, Iowa City, Iowa, and the Retina Consultants of Central Illinois (Reddy), Peoria, Illinois, USA.",
"authors": "Miller|Matthew A|MA|;Lenci|Lucas T|LT|;Reddy|Chittaranjan V|CV|;Russell|Stephen R|SR|",
"chemical_list": "D000900:Anti-Bacterial Agents; D014640:Vancomycin",
"country": "United States",
"delete": false,
"doi": "10.1016/j.jcrs.2016.09.013",
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"issue": "42(11)",
"journal": "Journal of cataract and refractive surgery",
"keywords": null,
"medline_ta": "J Cataract Refract Surg",
"mesh_terms": "D000368:Aged; D000867:Anterior Chamber; D000900:Anti-Bacterial Agents; D019072:Antibiotic Prophylaxis; D002386:Cataract; D002387:Cataract Extraction; D009877:Endophthalmitis; D015818:Eye Infections, Bacterial; D006801:Humans; D008297:Male; D011183:Postoperative Complications; D031300:Retinal Vasculitis; D014640:Vancomycin",
"nlm_unique_id": "8604171",
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"pages": "1676-1680",
"pmc": null,
"pmid": "27956296",
"pubdate": "2016-11",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Postoperative hemorrhagic occlusive retinal vasculitis associated with intracameral vancomycin prophylaxis during cataract surgery.",
"title_normalized": "postoperative hemorrhagic occlusive retinal vasculitis associated with intracameral vancomycin prophylaxis during cataract surgery"
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{
"abstract": "Treatment for severe systemic infections in heart transplantation is reduction in immunosuppression while treating the infection. An assay that measures adenosine triphosphate production in activated lymphocytes (ImmuKnow® ) objectively monitors cellular immunity of transplant recipients. In this study, we used ImmuKnow® to adjust immunosuppression in heart transplant recipients with severe systemic infections.\n\n\n\nHeart transplant recipients were followed with ImmuKnow® at the time of biopsy and diagnosis of systemic infection. Patients who developed an infection were monitored by ImmuKnow® assay with adjustments in immunosuppression based upon the results of the assay. Maintenance immunosuppression was reinstituted when the ImmuKnow® increased to >225 ng/mL of ATP.\n\n\n\nTwo or more ImmuKnow® assays were performed in 80 patients. Thirteen patients developed severe systemic infections. ImmuKnow® mean value at the time of diagnosis of infection was 109 ± 49.2 ng/mL. Reduction in immunosuppression and treatment of infection resulted in normalization of ImmuKnow® level, resolution of infection, and no episodes of rebound rejection.\n\n\n\nHeart transplant recipients with severe systemic infections presented with a decreased ImmuKnow® , suggesting over immunosuppression. ImmuKnow® can be used as an objective measurement in withdrawing immunosuppression in heart transplant recipients with severe systemic infections.",
"affiliations": "Tampa General Medical Group, Tampa, Florida.;Tampa General Medical Group, Tampa, Florida.;LifeLink Transplant Immunology Lab, Tampa, Florida.",
"authors": "Weston|Mark W|MW|0000-0002-1333-2130;Rinde-Hoffman|Debbie|D|;Lopez-Cepero|Mayra|M|",
"chemical_list": "D007166:Immunosuppressive Agents; D000255:Adenosine Triphosphate",
"country": "Denmark",
"delete": false,
"doi": "10.1111/ctr.13809",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0902-0063",
"issue": "34(3)",
"journal": "Clinical transplantation",
"keywords": "ImmuKnow; WBC count; heart transplantation; immunosuppression; severe systemic infection",
"medline_ta": "Clin Transplant",
"mesh_terms": "D000255:Adenosine Triphosphate; D015496:CD4-Positive T-Lymphocytes; D006084:Graft Rejection; D016027:Heart Transplantation; D006801:Humans; D007111:Immunity, Cellular; D007165:Immunosuppression Therapy; D007166:Immunosuppressive Agents; D012189:Retrospective Studies",
"nlm_unique_id": "8710240",
"other_id": null,
"pages": "e13809",
"pmc": null,
"pmid": "32003048",
"pubdate": "2020-03",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Monitoring cell-mediated immunity during immunosuppression reduction in heart transplant recipients with severe systemic infections.",
"title_normalized": "monitoring cell mediated immunity during immunosuppression reduction in heart transplant recipients with severe systemic infections"
} | [
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{
"reactionmeddrapt": "Gastritis",
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{
"reactionmeddrapt": "Hepatitis",
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},
{
"reactionmeddrapt": "Pneumonia",
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}
],
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},
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"receiptdate": "20200227",
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}
] |
{
"abstract": "Mirtazapine is a commonly used drug indicated for the treatment of severe depression. It works as a presynaptic α<sub>2</sub>-adrenoreceptor antagonist that increases central noradrenergic and serotonergic neurotransmission, and it is metabolized by the p450 cytochrome oxidase system. There is evidence within the literature to suggest a link between antidepressants and increased liver enzymes, although case reports demonstrating a link between mirtazapine specifically and steatosis are sparse. Here, we present a case of mirtazapine-induced steatosis in a 48-year-old office worker. She presented with painless jaundice of 2 days duration and generalized lethargy and peripheral edema present for 3 weeks beforehand. Extensive investigations were undertaken to identify the cause of her jaundice but no biochemical, blood-borne, or anatomical cause could be found. Mirtazapine was subsequently stopped, and her liver function, both clinically and biochemically, improved rapidly. She made a full recovery after discontinuation of her mirtazapine.
.",
"affiliations": null,
"authors": "Thomas|Elin|E|;Haboubi|Hasan|H|;Williams|Namor|N|;Lloyd|Aled|A|;Ch'ng|Chin Lye|CL|",
"chemical_list": "D058669:Adrenergic alpha-2 Receptor Antagonists; D000929:Antidepressive Agents, Tricyclic; D008803:Mianserin; D000078785:Mirtazapine",
"country": "Germany",
"delete": false,
"doi": "10.5414/CP202983",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0946-1965",
"issue": "55(7)",
"journal": "International journal of clinical pharmacology and therapeutics",
"keywords": null,
"medline_ta": "Int J Clin Pharmacol Ther",
"mesh_terms": "D058669:Adrenergic alpha-2 Receptor Antagonists; D000929:Antidepressive Agents, Tricyclic; D001706:Biopsy; D056486:Chemical and Drug Induced Liver Injury; D005234:Fatty Liver; D005260:Female; D006801:Humans; D007565:Jaundice; D008099:Liver; D008111:Liver Function Tests; D008803:Mianserin; D008875:Middle Aged; D000078785:Mirtazapine",
"nlm_unique_id": "9423309",
"other_id": null,
"pages": "630-632",
"pmc": null,
"pmid": "28427497",
"pubdate": "2017-07",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Mirtazapine-induced steatosis
.",
"title_normalized": "mirtazapine induced steatosis"
} | [
{
"companynumb": "IN-IMPAX LABORATORIES, INC-2018-IPXL-00321",
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"occurcountry": "IN",
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] |
{
"abstract": "Fatal road traffic crashes are often related to speeding, non-use of a seatbelt, and alcohol/drug-impaired driving. The aim of this study was to examine associations between driving under the influence of drugs and/or alcohol and driver-related risk factors that have been reported as significantly contributing causes of fatal road traffic crashes. The data were extracted from Norwegian road traffic crash registries and forensic toxicology databases. Drug/alcohol investigated car and van drivers and motorcycle riders fatally injured in road traffic crashes in Norway during 2005-2015 were included in this study (n = 772). Drug and alcohol concentrations corresponding to 0.5 g/kg alcohol in blood were used as the lower limits for categorising drivers/riders as impaired; 0.2 g/kg was the upper limit for being categorised as sober. Associations between driver-related risk factors and impairment from specific substance groups were calculated using multivariable logistic regression, adjusted for other substance groups, age, and sex, and were reported when the confidence intervals did not contain the value 1 or lower. Substances found in concentrations above the impairment limits were mainly alcohol (20%), medicinal drugs (10%: benzodiazepines, opioids, z-hypnotics), stimulants (5%: amphetamines, methylphenidate, and cocaine), and cannabis (4%: THC). The drug/alcohol-impaired drivers had compared to the sober drivers more often been speeding (68% versus 32%), not used a seatbelt (69% versus 30%), and been driving without a valid driver license (26% versus 1%). Logistic regression analysis showed that impairment from alcohol or stimulants (mainly amphetamines) was associated with all three risk factors, medicinal drugs with all except speeding, and impairment from cannabis (THC) with not having a valid driver license. Among motorcycle riders, drug/alcohol impairment was associated with not having a valid driver license and non-use of a helmet. At least one of the risk factors speeding, non-use of a seatbelt/helmet, and driving without a valid license were present among the vast majority of the drug/alcohol-impaired fatally injured drivers and riders, and also among more than half of the fatally injured sober drivers.",
"affiliations": "Oslo University Hospital, Department of Forensic Sciences, P.O. Box 4950 Nydalen, NO-0424 Oslo, Norway; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, P.O box 1171 Blindern, NO-0318 Oslo, Norway. Electronic address: [email protected].;Oslo University Hospital, Department of Forensic Sciences, P.O. Box 4950 Nydalen, NO-0424 Oslo, Norway; University of Oslo, Faculty of Medicine, Institute of Health and Society, Department of Nursing Science, P.O. Box 1130 Blindern, NO-0318 Oslo, Norway.;Oslo University Hospital, Department of Forensic Sciences, P.O. Box 4950 Nydalen, NO-0424 Oslo, Norway; University of Oslo, Faculty of Medicine, Institute of Clinical Medicine, P.O box 1171 Blindern, NO-0318 Oslo, Norway.;St. Olav University Hospital, Department of Clinical Pharmacology, NO-7006 Trondheim, Norway.;The Norwegian Public Roads Administration, Planning and Engineering Services Department, Traffic Technic and Analysis, P.O box 1010 Nordre Ål, NO-2605 Lillehammer, Norway; Swedish National Road and Transport Research Institute, Traffic Safety department, VTI, Olaus Magnus väg 35, SE-581 95 Linköping, Sweden.;Oslo University Hospital, Division of Emergencies and Critical Care, Department of Anesthesiology & Oslo University Hospital, Division of Emergencies and Critical Care, Department of Traumatology, P.O box 4956 Nydalen, NO-0424 Oslo, Norway.;Oslo University Hospital, Department of Forensic Sciences, P.O. Box 4950 Nydalen, NO-0424 Oslo, Norway.",
"authors": "Valen|Anja|A|;Bogstrand|Stig Tore|ST|;Vindenes|Vigdis|V|;Frost|Joachim|J|;Larsson|Magnus|M|;Holtan|Anders|A|;Gjerde|Hallvard|H|",
"chemical_list": null,
"country": "England",
"delete": false,
"doi": "10.1016/j.aap.2019.06.014",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0001-4575",
"issue": "131()",
"journal": "Accident; analysis and prevention",
"keywords": "Alcohol; Driving under the influence; Drugs; Forensic toxicology; Logistic model; Traffic accidents",
"medline_ta": "Accid Anal Prev",
"mesh_terms": "D000063:Accidents, Traffic; D000328:Adult; D016022:Case-Control Studies; D000066448:Driving Under the Influence; D005260:Female; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009049:Motorcycles; D009664:Norway; D012307:Risk Factors; D012309:Risk-Taking",
"nlm_unique_id": "1254476",
"other_id": null,
"pages": "191-199",
"pmc": null,
"pmid": "31306833",
"pubdate": "2019-10",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Driver-related risk factors of fatal road traffic crashes associated with alcohol or drug impairment.",
"title_normalized": "driver related risk factors of fatal road traffic crashes associated with alcohol or drug impairment"
} | [
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"companynumb": "NO-JNJFOC-20191102857",
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{
"actiondrug": "6",
"activesubstance": {
"activesubstancename": "METHYLPHENIDATE HYDROCHLORIDE"
},
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"reaction": [
{
"reactionmeddrapt": "Road traffic accident",
"reactionmeddraversionpt": "22.1",
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{
"reactionmeddrapt": "Disturbance in attention",
"reactionmeddraversionpt": "22.1",
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],
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},
"primarysource": {
"literaturereference": "BOGSTRAND S, VINDENES V, FROST J, LARSSON M, HOLTAN A, GJERDE H, VALEN A. DRIVER-RELATED RISK FACTORS OF FATAL ROAD TRAFFIC CRASHES ASSOCIATED WITH ALCOHOL OR DRUG IMPAIRMENT.. ACCIDENT ANALYSIS + PREVENTION. 2019?131:191-199.",
"literaturereference_normalized": "driver related risk factors of fatal road traffic crashes associated with alcohol or drug impairment",
"qualification": "3",
"reportercountry": "NO"
},
"primarysourcecountry": "NO",
"receiptdate": "20191111",
"receivedate": "20191111",
"receiver": {
"receiverorganization": "FDA",
"receivertype": "6"
},
"reporttype": "2",
"safetyreportid": 17016238,
"safetyreportversion": 1,
"sender": {
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"sendertype": "2"
},
"serious": 1,
"seriousnesscongenitalanomali": null,
"seriousnessdeath": 1,
"seriousnessdisabling": null,
"seriousnesshospitalization": null,
"seriousnesslifethreatening": null,
"seriousnessother": null,
"transmissiondate": "20200122"
}
] |
{
"abstract": "The use of a constant infusion of intravenous morphine sulfate in a patient with severe sickle cell crisis is described. After several days of poor control with intramuscular and intravenous narcotic injections, adequate analgesia was obtained with the infusion of morphine within two hours of initiation of therapy. No adverse effects were noted. With the advantages provided by an intravenous narcotic infusion, this protocol should be considered as a suitable alternative to conventional methods for providing pain control in patients in sickle cell crisis.",
"affiliations": null,
"authors": "Ives|T J|TJ|;Guerra|M F|MF|",
"chemical_list": "D009020:Morphine",
"country": "United States",
"delete": false,
"doi": "10.1177/1060028087021007-811",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0012-6578",
"issue": "21(7-8)",
"journal": "Drug intelligence & clinical pharmacy",
"keywords": null,
"medline_ta": "Drug Intell Clin Pharm",
"mesh_terms": "D000328:Adult; D000755:Anemia, Sickle Cell; D006801:Humans; D007262:Infusions, Intravenous; D008297:Male; D009020:Morphine; D010146:Pain",
"nlm_unique_id": "0212457",
"other_id": null,
"pages": "625-7",
"pmc": null,
"pmid": "3608811",
"pubdate": "1987",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Constant morphine infusion for severe sickle cell crisis pain.",
"title_normalized": "constant morphine infusion for severe sickle cell crisis pain"
} | [
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"activesubstancename": "MEPERIDINE HYDROCHLORIDE"
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"drugdosagetext": "UNK (ESCALATED TO 250?300 MG)",
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"abstract": "BACKGROUND Page kidney was described by Dr. Irving Page in animal kidneys in 1939 with renal failure and persistent arterial hypertension from \"cellophane perinephritis\". By 2009, about 100 cases of Page kidney had been reported. Bleeding complications after percutaneous kidney biopsy has, however, been well described. Moreover, the perioperative management of the recently introduced non-vitamin K antagonist anticoagulants (NOACs) remains uncertain due to inadequate evidence. Current guidelines to determine the appropriate duration of withholding NOACs before a surgical procedure, and when to restart NOACs safely after a procedure, however, cognizant of the implications of renal dysfunction, and levels of risk of the procedure are still unclear and sometimes conflicted. CASE REPORT We describe a case of Page kidney from an intrarenal hematoma complicating ultrasound-guided percutaneous right native kidney biopsy with acute kidney injury after withholding apixaban, a NOAC, for 3 days. Computed tomography evidence of continuing intrarenal bleeding from a renal pseudoaneurysm was treated with super-selective renal artery embolization; the case was further complicated by superimposed acute kidney injury from contrast-induced nephropathy. CONCLUSIONS We reviewed the vagaries of Page kidney with respect to the presence, or otherwise, of hypertension and how to explain worsening renal failure despite only unilateral involvement of a single kidney in a patient with 2 kidneys. Furthermore, we revisit the risks of contrast-induced nephropathy following iodinated contrast exposure. We explored the alternative management options for a post-biopsy renal pseudoaneurysm, that would avoid the use of iodinated contrast that could have potentially mitigated, if not fully prevented, the ensuing contrast-induced acute kidney injury.",
"affiliations": "Division of Nephrology, Department of Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA.;Division of Nephrology, Department of Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA.;Division of Nephrology, Department of Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA.;Division of Nephrology, Department of Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA.",
"authors": "Onuigbo|Macaulay A Chukwukadibia|MAC|;Sharma|Vivek|V|;Balogun|Omotola O|OO|;Ghimire|Allina|A|",
"chemical_list": "D003287:Contrast Media",
"country": "United States",
"delete": false,
"doi": "10.12659/AJCR.919701",
"fulltext": "\n==== Front\nAm J Case RepAm J Case RepamjcaserepThe American Journal of Case Reports1941-5923International Scientific Literature, Inc. 3196485810.12659/AJCR.919701919701ArticlesPost-Renal Biopsy Acute Kidney Injury and Page Kidney from Intra-Renal Hematoma Aggravated by Reversible Contrast-Induced Nephropathy Following Renal Arterial Embolization Chukwukadibia Onuigbo Macaulay A. ABCDEFSharma Vivek BCDEFBalogun Omotola O. DFGhimire Allina BCEFDivision of Nephrology, Department of Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, U.S.A.Authors’ Contribution:\n\nA Study Design\n\nB Data Collection\n\nC Statistical Analysis\n\nD Data Interpretation\n\nE Manuscript Preparation\n\nF Literature Search\n\nG Funds Collection\n\nConflict of interest: None declared\n\nCorresponding Author: Macaulay Amechi Chukwukadibia Onuigbo, e-mail: [email protected] 22 1 2020 21 e919701-1 e919701-5 27 8 2019 15 11 2019 © Am J Case Rep, 20202020This work is licensed under Creative Common Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0)Patient: Male, 73-year-old\n\nFinal Diagnosis: Page kidney from intra-renal hematoma aggravated by reversible contrast-induced nephropathy following renal arterial embolization\n\nSymptoms: Flank pain • nausea • vomiting\n\nMedication: Apixaban\n\nClinical Procedure: Kidney biopsy and subsequent renal arterial embolization\n\nSpecialty: Nephrology\n\nObjective:\nRare co-existance of disease or pathology\n\nBackground:\nPage kidney was described by Dr. Irving Page in animal kidneys in 1939 with renal failure and persistent arterial hypertension from “cellophane perinephritis”. By 2009, about 100 cases of Page kidney had been reported. Bleeding complications after percutaneous kidney biopsy has, however, been well described. Moreover, the perioperative management of the recently introduced non-vitamin K antagonist anticoagulants (NOACs) remains uncertain due to inadequate evidence.\n\nCurrent guidelines to determine the appropriate duration of withholding NOACs before a surgical procedure, and when to restart NOACs safely after a procedure, however, cognizant of the implications of renal dysfunction, and levels of risk of the procedure are still unclear and sometimes conflicted.\n\nCase Report:\nWe describe a case of Page kidney from an intrarenal hematoma complicating ultrasound-guided percutaneous right native kidney biopsy with acute kidney injury after withholding apixaban, a NOAC, for 3 days. Computed tomography evidence of continuing intrarenal bleeding from a renal pseudoaneurysm was treated with super-selective renal artery embolization; the case was further complicated by superimposed acute kidney injury from contrast-induced nephropathy.\n\nConclusions:\nWe reviewed the vagaries of Page kidney with respect to the presence, or otherwise, of hypertension and how to explain worsening renal failure despite only unilateral involvement of a single kidney in a patient with 2 kidneys. Furthermore, we revisit the risks of contrast-induced nephropathy following iodinated contrast exposure. We explored the alternative management options for a post-biopsy renal pseudoaneurysm, that would avoid the use of iodinated contrast that could have potentially mitigated, if not fully prevented, the ensuing contrast-induced acute kidney injury.\n\nMeSH Keywords:\nAcute Kidney InjuryContrast MediaHematomaPneumoradiography\n==== Body\nBackground\nPage kidney was described by Dr. Irving Page following his very elaborate experiments with animal kidneys in 1939 with the production of persistent arterial hypertension from “cellophane perinephritis” [1]. By 2009, about 100 cases of Page kidney had been reported [2]. Earlier on, most cases of Page kidney were related causatively to extrarenal compression following post-traumatic episodes from blunt abdominal trauma [2–4]. Nevertheless, more recent reports of Page kidney resulting from intrarenal pathology, such as cysts, tumors, and hematomas, have been described [2,5,6]. Bleeding complications after percutaneous kidney biopsy, albeit low, has been well described [7–12]. More recently, there has been an increasing use of super-selective renal artery embolization for the management of post-biopsy renal bleeding [13]. Furthermore, contrast-induced acute kidney injury complicating extrarenal coil embolization procedures has been reported [14]. We recently encountered a case of Page kidney with acute kidney injury resulting from a right lower pole hematoma complicating an ultrasound-guided right native kidney biopsy. Subsequently, on admission and following a super-selective right renal angiography procedure to stop the active intrarenal bleeding from a renal pseudoaneurysm, our patient developed reversible contrast-induced acute kidney injury. This raised the question of the most appropriate alternative management option for post-biopsy renal pseudoaneurysm that could have mitigated, if not fully prevented, the ensuing contrast-induced acute kidney injury.\n\nCase Report\nA 73-year-old white male was evaluated in our Emergency Department (ED) following a transfer from a peripheral medical center with 2 hours of excruciating, mostly non-radiating, acute onset right flank pain. There was no trauma. He reported some nausea with minimal vomiting up to 3 times but denied fever, chills, chest pain, dyspnea, abdominal pain, dysuria, hematuria, testicular pain, leg pain or tingling. He vaguely noted that since the kidney biopsy 26 days earlier, he had experienced mild discomfort in the same area. Tylenol, 1000 mg, was without effect. He had a history of hypertension, heart failure, and atrial fibrillation and had been taking apixaban 5 mg twice daily for about 2 years; he also had a history of Raynaud’s disease, previous laparoscopic cholecystectomy, tonsillectomy, vasectomy, and ablation for atrial fibrillation 2 years earlier. He had an uneventful ultrasound-guided right native kidney biopsy 26 days before presentation at our ED. His vital signs were stable: temperature was 35.7°C, pulse as 63 beats per minute, respiratory rate was 12 breathes per minute; blood pressure was 136/78 mm Hg, pulse oximetry was 100% on room air. Physical examination was unremarkable with the abdomen soft, not distended, non-tender, and was without costovertebral area tenderness. He was not dehydrated, appeared euvolemic, and was not orthostatic. Intravenous (IV) morphine sulfate was administered for pain control, together with some IV fluids. He also received 2106 units of prothrombin complex concentrate infused over 20 minutes.\n\nThe right kidney biopsy was carried out for increased baseline serum creatinine 3 years earlier, together with a new diagnosis of uveitis in the last year. Nonetheless, serum creatinine had been stable at about 1.30 mg/dL in the past 2 years before the kidney biopsy. Apixaban was withheld for 3 days before the right kidney biopsy. Protime international normalized ratio (INR) was 1.1 and partial thromboplastin time (PTT) was 13.2 seconds on the day of the kidney biopsy. Under ultra-sound guidance, a 17-gauge coaxial needle was advanced into the lower pole of the right kidney. Through the coaxial needle, multiple 18-gauge core biopsy samples were obtained. The coaxial needle was removed, and a sterile dressing was applied. The procedure was well tolerated and there were no immediate complications. Indeed, the post-biopsy renal ultrasound was normal. Apixaban was resumed 3 days after the kidney biopsy. The kidney biopsy demonstrated hypertensive nephrosclerosis, moderate interstitial fibrosis, and mild interstitial chronic inflammation; no further interventions were planned.\n\nUrinalysis was significant for trace ketones, 2+ blood, and 2+ protein. Serum creatinine was higher at 1.86 mg/dL; it was 1.31 mg/dL in May 2019, a month before the kidney biopsy (Figure 1). Serum electrolytes were normal. WBC was 12 000/mm3, platelet count 234 000/mm3, and hemoglobin 11.7 g/dL, just slightly lower than a level of 12.0 g/dL, 8 months earlier. Admission Protime INR was 1.3 (range 0.9–1.1) and PTT was 15.5 seconds (range 10.3–13.4 seconds).\n\nA computed tomography (CT) scan examination of the abdomen and pelvis, with and without contrast (100 cc), demonstrated a right lower pole intra-parenchymal renal hematoma measuring up to 5.9 cm together with evidence of active intrarenal bleeding (Figure 2). Our Interventional Radiology Department was consulted, and the patient quickly underwent a selective renal angiography with coil embolization of a ruptured pseudoaneurysm (Figure 3). The small bleeding pseudo-aneurysm in the lower pole of the right kidney was successfully embolized. The remainder of the right kidney perfusion remained patent although antegrade arterial perfusion was noted to be sluggish.\n\nThe patient received empiric antibiotics for leukocytosis and suspected pneumonia. Serum creatinine progressively increased, peaking at 3.60 mg/dL on hospital day 3. However, thereafter, serum creatinine started to improve and was 1.96 mg/dL on discharge, hospital day 9 (Figure 1). Additionally, within 24 hours of the coil embolization, the patient developed persistent frequent hiccups. Radiological evaluation with chest radiographs and a follow-up right abdominal upper quadrant ultrasound failed to reveal any new lesions including the absence of any sub-diaphragmatic abnormalities. He required combination oral metoclopramide 5 mg at 3 times per day, gabapentin 100 mg per day and baclofen 2.5 mg every 6 hours to control the hiccups. On discharge, the patient was feeling much better, with no flank pain and reduced frequency of the hiccups.\n\nDiscussion\nPage kidney from the intrarenal hematoma complicating the kidney biopsy would explain the initial increase in serum creatinine from 1.31 mg/dL to 1.86 mg/dL on admission [1,5] (Figure 1). The classic features of Page kidney include new-onset hypertension, in patients who are normotensive previously, with or without renal impairment [15–17].\n\nOur patient was clearly unusual since he had been a known hypertensive patient for many years and at the time of the index admission was on 3 antihypertensive agents: metoprolol 100 mg daily, spironolactone 25 mg daily, and torsemide 10 mg daily. Arguably, therefore, the continued administration of all 3 antihypertensive agents could have masked the appearance of new hypertension in the Emergency Department.\n\nMoreover, between 1999 and 2017, the patient had a baseline serum creatinine of about 0.7 gm/dL: eGFR (estimated glomerular filtration rate) was ∼85 mL/min/1.73 m2 BSA (body surface area). However, in 2017, for unknown reasons, the patient’s serum creatinine level had risen to about 1.3 mg/dL (eGFR ∼55–65 mL/min/1.73 m2 BSA). This loss of renal function and the simultaneous diagnosis by ophthalmologist of bilateral uveitis in 2018 had raised the possibility of the syndrome of tubulointerstitial nephritis with uveitis (TINU). From a practical perspective, we concluded that sometime in 2017, due to factors that remain unclear to us, he had lost significant renal functional reserve [18–22]. This necessarily placed the patient at a higher risk of either acute kidney injury or indeed chronic kidney disease progression [18–22]. These were the imperatives for the recommendation by our Nephrology Service Department to get a kidney biopsy.\n\nWhen the patient presented to the ED with the worsening right flank pain, his vomiting was minimal and consisted mostly of nausea. He was not dehydrated and had no evidence for hypovolemia or dehydration. Nevertheless, his serum creatinine level had increased from 1.3 mg/dL (eGFR=54 mL/min/1.73 m2 BSA) in May 2019 to 1.86 mg/dL (eGFR=35 mL/min/1.73 m2 BSA), 26 days after the kidney biopsy. This represented a 35% loss in kidney function since the biopsy. Thus, there was clearly significant acute kidney injury with a considerable loss of renal function as evident from a comparison of the eGFR changes (Figure 1).\n\nTypically, significant renal impairment in Page kidney has been described in patients with single functioning kidneys as exemplified by lone renal allografts [23,24]. On the other hand, renal insufficiency is not usually seen with unilateral kidney involvement with 2 kidneys because of normal per-fusion of the contralateral kidney which therefore maintains normal renal function [4]. Nevertheless, unilateral Page kidney in patients with 2 kidneys uncommonly can still present with worsening renal failure [15–17]. Indeed, in the Page kidney literature, there have been reports of acute kidney injury despite unilateral kidney involvement in a patient with 2 kidneys [15–17]. For example, McCune et al. described an increase in serum creatinine from 2.7 mg/dL to 3.8 mg/dL in a 32-year old white male with previous chronic kidney disease, 12 hours following a percutaneous ultrasound-guided right kidney biopsy [16]. The measured creatinine clearance had decreased from 0.85 mL/second (51 mL/minute) down to 0.58 mL/second (35 mL/minute). Radiologic imaging confirmed the presence of a large perinephric hematoma [16]. In another report, Wijeyesinghe et al. reported a rise in serum creatinine from 1.23 mg/dL to 1.80 mg/dL, 8 days following a left-sided percutaneous renal biopsy in a 29-year old white male with proteinuria, microscopic hematuria, and an active urinary sediment [15]. Ultrasound examination revealed a large left intrarenal and perirenal hematoma despite a normal appearing right kidney [15]. Furthermore, Babel et al. recounted their experience with an 89-year old hypertensive male with a long-standing history of chronic renal insufficiency who exhibited acute on chronic renal failure 3 weeks after a fall with serum creatinine rising from 1.14 mg/dL to 5.7 mg/dL on presentation to the hospital [17]. A non-contrast CT scan showed a large left subcapsular renal hematoma and a possibly atrophic right kidney [17]. One hypothesis to explain acute kidney injury with unilateral Page kidney in a patient with 2 kidneys is that with pre-existing chronic kidney disease, the impacted kidney was the dominant kidney and that the unaffected kidney was diseased from renovascular or other undiagnosed unilateral renal disease conditions [16,17].\n\nFrom the foregoing, we strongly argue that our patient did in fact have features on admission consistent with Page kidney. Without a doubt, he subsequently experienced superimposed contrast-induced nephropathy following the CT scan and Interventional Radiology Department interventions (Figures 1–3).\n\nThe subsequent acute rise in serum creatinine to peak at 3.60 mg/dL on hospital day 3 and then started to improve thereafter is consistent with contrast-induced nephropathy from double iodinated-contrast exposure from the CT scan and selective renal angiography on the day of admission [14]. Contrast-induced acute kidney injury after coil embolization for aneurysmal subarachnoid hemorrhage has been reported [14]. Of note, reports of contrast-induced kidney injury following super-selective renal embolization procedures is rare. Haochen et al. in 2019 described the successful treatment of 43 patients with bleeding complications following percutaneous renal biopsies with super-selective renal artery embolization and mean serum creatinine before and after the procedure had remained unchanged; one caveat was that in this study, all 31 patients with serum creatinine >300 umol/L underwent hemodialysis after the procedure [13]. Nevertheless, 1 out of 15 patients (7%), who underwent splenic arterial embolization in another report, developed contrast-induced nephropathy [25].\n\nAlthough our patient exhibited near return to admission serum creatinine levels on discharge at hospital day 9, the contrast-induced nephropathy may have contributed to the hic-cups as well as to the prolonged length of stay and therefore increased cost of hospitalization. Arguably, some alternative options for the management of the right renal pseudoaneurysm that could mitigated or totally avoid contrast-induced nephropathy call for mention here. Direct ultrasound-guided percutaneous embolization of renal pseudoaneurysm has been reported as an alternative to super-selective renal artery embolization with the touted benefits of the circumvention of contrast media exposure, mitigating the hazards of irradiation, and avoidance of the complications of angiographic catheterization [26]. The Egyptian report in 2009 posited that this method was recommended as a first-line treatment of actively bleeding renal pseudoaneurysms [26]. The successful use of ultra-low volumes of iodinated contrast during radiological examination has been achieved using iodinated contrast that was further diluted with normal saline [27]. Finally, in a 2014 report, Said et al. reported on the novel use of carbon dioxide arteriography during super-selective coil embolization of a renal artery pseudoaneurysm in an 82-year-old female with complicated past medical and surgical history including hypertension, diabetes mellitus, congestive heart failure, and a recent right heminephrectomy with poor renal function [28]. Pre-embolization serum creatinine was 1.85 mg/dL, whereas post-embolization serum creatinine was stable at 1.97 mg/dL and was even lower at 1.6 mg/dL, 6 months later [28].\n\nConclusions\nWe described the unusual presentation of Page kidney following an ultrasound-guided percutaneous native right kidney biopsy in a 73-year old male with 2 kidneys that still produced acute kidney injury despite the unilateral kidney insult. Following double contrast exposure from a contrast-enhanced CT scan and Interventional Radiology Department angioembolization to treat an actively bleeding intrarenal hematoma, our patient experienced further worsening of renal failure from contrast-induced nephropathy. In a bid to reduce the incidence of contrast nephropathy in such circumstances as we experienced with our patient, we posit that the study of alternative methods of renal imaging such as carbon dioxide arteriography, the use of dilute contrast medium and other non-contrast methodologies such as direct ultrasound-guided percutaneous embolization call for more intense study and analysis. The alternate therapeutic options to mitigate contrast nephropathy in this setting are revisited.\n\nThis work is dedicated to late Professor Wilson I. B. Onuigbo, former Professor of Pathology, at the University of Nigeria Teaching Hospital, Enugu, Nigeria. Professor Onuigbo taught the first author in medical school and worked with him in 1989 to describe the first published cases of multi-systemic vasculitis in Nigeria. The 3 cases were presented by the lead author to the West African College of Physicians in October 1989 as requirement for the dissertation for the award of the Fellowship of the West African College of Physicians in Nephrology.\n\nDepartment and Institution where work was done\n\nDepartment of Medicine, The Robert Larner, M.D. College of Medicine, University of Vermont, Burlington, VT, USA.\n\nConflict of interest\n\nNone.\n\nFigure 1. Serum creatinine trajectory before the native kidney biopsy and following recent hospital admission for selective renal arterial embolization.\n\nFigure 2. Computed tomography scan of the abdomen with contrast showing a right kidney lower pole hematoma measuring up to 5.9 cm with active bleeding before the coil embolization.\n\nFigure 3. Super-selective renal embolization of a right renal pseudoaneurysm.\n==== Refs\nReferences:\n1. Page IH The production of persistent arterial hypertension by cellophane perinephritis JAMA 1939 113 23 2046 48 \n2. Dopson SJ Jayakumar S Velez JC Page kidney as a rare cause of hyper-tension: Case report and review of the literature Am J Kidney Dis 2009 54 2 334 39 19167799 \n3. Smyth A Collins CS Thorsteinsdottir B Page kidney: Etiology, renal function outcomes and risk for future hypertension J Clin Hypertens (Greenwich) 2012 14 4 216 21 22458742 \n4. Kumar S Jayant K As S Page kidney secondary to large splenic artery aneurysm bleeding and its management by angioembolization Nephro Urol 2014 6 3 e17144 \n5. Zvavanjanja RC Ashton AS Page kidney secondary to subcapsular hematoma following percutaneous renal allograft biopsy Radiol Case Rep 2018 13 3 702 8 30046367 \n6. Wanic-Kossowska M Kobelski M Oko A Czekałski S Arterial hypertension due to perirenal and subcapsular hematoma induced by renal percutaneous biopsy Int Urol Nephrol 2005 37 1 141 43 16132777 \n7. Hocken AG Kille JN Late presenting, intrarenal haematoma as a complication of renal biopsy N Z Med J 1975 81 540 483 84 1057095 \n8. Russo D1 Iaccarino V Niola R Treatment of massive hemorrhage after renal biopsy with percutaneous arterial obliteration Nephron 1988 50 4 376 77 3237279 \n9. Eiro M Katoh T Watanabe T Risk factors for bleeding complications in percutaneous renal biopsy Clin Exp Nephrol 2005 9 1 40 45 15830272 \n10. Lees JS McQuarrie EP Mordi N Risk factors for bleeding complications after nephrologist-performed native renal biopsy Clin Kidney J 2017 10 4 573 77 28852497 \n11. Xu DM Chen M Zhou FD Zhao MH Risk factors for severe bleeding complications in percutaneous renal biopsy Am J Med Sci 2017 353 3 230 35 28262208 \n12. Bakdash K Schramm KM Annam A Complications of percutaneous renal biopsy Semin Intervent Radiol 2019 36 2 97 103 31123379 \n13. Haochen W Jian W Li S Superselective renal artery embolization for bleeding complications after percutaneous renal biopsy: A single-center experience J Int Med Res 2019 47 4 1649 59 30760109 \n14. Lee HG Kim WK Yeon JY Contrast-induced acute kidney injury after coil embolization for aneurysmal subarachnoid hemorrhage Yonsei Med J 2018 59 1 107 12 29214784 \n15. Wijeyesinghe EC Richardson RM Uldall PR Temporary loss of renal function: An unusual complication of perinephric hemorrhage after percutaneous renal biopsy Am J Kidney Dis 1987 10 4 314 17 3661552 \n16. McCune TR Stone WJ Breyer JA Page kidney: Case report and review of the literature Am J Kidney Dis 1991 18 5 593 99 1951341 \n17. Babel N Sakpal SV Chamberlain RS The Page kidney phenomenon secondary to a traumatic fall Eur J Emerg Med 2010 17 1 24 26 19543099 \n18. Graf H Stummvoll HK Luger A Prager R Effect of amino acid infusion on glomerular filtration rate N Engl J Med 1983 308 3 159 60 6401352 \n19. Bosch JP Saccaggi A Lauer A Renal functional reserve in humans. Effect of protein intake on glomerular filtration rate Am J Med 1983 75 6 943 50 6650549 \n20. Ronco C Rosner MH Acute kidney injury and residual renal function Crit Care 2012 16 4 144 22866976 \n21. Sharma A Mucino MJ Ronco C Renal functional reserve and renal recovery after acute kidney injury Nephron Clin Pract 2014 127 1–4 94 100 25343829 \n22. Ronco C Bellomo R Kellum J Understanding renal functional reserve Intensive Care Med 2017 6 43 6 917 920 10.1007/s00134-017-4691-6 Epub 2017 Feb 17. 28213622 \n23. Sampathkumar K Mukuntharajan T Rajiv A Anandan S Acute Page kidney phenomenon following renal allograft biopsy Kidney Int 2018 94 6 1241 30466571 \n24. Aida K Sasaki H Matsumura K Page kidney following a non-episode protocol renal allograft biopsy: A case report Transplant Proc 2018 50 10 3961 63 30577296 \n25. Ekeh AP McCarthy MC Woods RJ Haley E Complications arising from splenic embolization after blunt splenic trauma Am J Surg 2005 189 3 335 39 15792763 \n26. Sakr MA Desouki SE Hegab SE Direct percutaneous embolization of renal pseudoaneurysm J Endourol 2009 23 6 875 78 19473070 \n27. Garcarek J Kurcz J Guziński M Intraarterial CT angiography using ultra low volume of iodine contrast – own experiences Pol J Radiol 2015 80 344 49 26191113 \n28. Said MA McGuire BB Liu JS Novel use of carbon dioxide arteriography in renal artery pseudoaneurysm in patients with poor renal function BMJ Case Rep 2014 2014 pii: bcr2014206915\n\n",
"fulltext_license": "CC BY-NC-ND",
"issn_linking": "1941-5923",
"issue": "21()",
"journal": "The American journal of case reports",
"keywords": null,
"medline_ta": "Am J Case Rep",
"mesh_terms": "D058186:Acute Kidney Injury; D000368:Aged; D001706:Biopsy; D003287:Contrast Media; D004621:Embolization, Therapeutic; D006406:Hematoma; D006801:Humans; D008297:Male; D014057:Tomography, X-Ray Computed",
"nlm_unique_id": "101489566",
"other_id": null,
"pages": "e919701",
"pmc": null,
"pmid": "31964858",
"pubdate": "2020-01-22",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": "19473070;15792763;1057095;30046367;25343829;28262208;28852497;15830272;25498109;3237279;26191113;22458742;25032140;19543099;16132777;30466571;19167799;6401352;31123379;28213622;22866976;1951341;29214784;3661552;6650549;30577296;30760109",
"title": "Post-Renal Biopsy Acute Kidney Injury and Page Kidney from Intra-Renal Hematoma Aggravated by Reversible Contrast-Induced Nephropathy Following Renal Arterial Embolization.",
"title_normalized": "post renal biopsy acute kidney injury and page kidney from intra renal hematoma aggravated by reversible contrast induced nephropathy following renal arterial embolization"
} | [
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"companynumb": "US-BRISTOL-MYERS SQUIBB COMPANY-BMS-2020-011044",
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"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
},
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"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Renal haematoma",
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"reactionoutcome": "6"
},
{
"reactionmeddrapt": "Vascular pseudoaneurysm ruptured",
"reactionmeddraversionpt": "22.1",
"reactionoutcome": "6"
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"literaturereference": "ONUIGBO MAC, SHARMA V, BALOGUM OO, GHIMIRE A. POST-RENAL BIOPSY ACUTE KIDNEY INJURY AND PAGE KIDNEY FROM INTRA-RENAL HEMATOMA AGGRAVATED BY REVERSIBLE CONTRAST-INDUCED NEPHROPATHY FOLLOWING RENAL ARTERIAL EMBOLIZATION. THE AMERICAN JOURNAL OF CASE REPORTS. 2020?21:E919701",
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{
"abstract": "BACKGROUND\nRole of chemotherapy in patients who continue to have unresectable disease after pre-operative chemo-radiotherapy (CRT) remains largely unaddressed.\n\n\nMETHODS\nPatients with LA rectal cancer from January 2013 to June 2015 were evaluated. Post-CRT, patients, who were deemed unresectable, were considered for further interim chemotherapy (i-CT).\n\n\nRESULTS\nSeventy six patients (15%) with median age of 38.5 years received i-CT after CRT. About 61.8% patients receiving i-CT managed to undergo a definitive surgery and the extent of surgery was reduced in 48.7% patients. With the median follow up of 19 months, the estimated 2-year event free survival (EFS) of 48% and OS was 56%. The estimated 2-year OS was 81% in mucinous tumors whereas it was 44.4% in signet ring pathology (P=0.045). The 2-year OS of 86% for whom surgery was done vs. 38% (2-year OS) in whom surgery was not done (P=0.011). Survival was better in conservative surgery group vs. total pelvic exenteration (TPE) vs. no surgery (2-year OS: 84% vs. 59.1% vs. 38%; P=0.033). In the CAPE-OX group, 71.4% (14/23) underwent surgery whereas 75.9% (29/47) in the 5-FU plus irinotecan plus oxaliplatin (FOLFIRINOX) group with EFS (P=0.570) and OS (P=0.120). In conservative surgery group, OS was better in FOLFIRINOX (2-year OS: 95.7%) vs. capecitabine plus oxaliplatin (CAPOX) (2-year OS: 70%) (P=0.012).\n\n\nCONCLUSIONS\ni-CT can lead to improved resection rates, improved survivals and downstaging with acceptable toxicity. FOLFIRINOX appears to better over CAPOX, specifically in whom conservative surgery is feasible.",
"affiliations": "Department of Medical Oncology, TMH, Mumbai 400012, India.;Department of Radiation Oncology, TMH, Mumbai 400012, India.;Department of Medical Oncology, TMH, Mumbai 400012, India.;Department of Medical Oncology, TMH, Mumbai 400012, India.;Department of Medical Oncology, TMH, Mumbai 400012, India.;Department of Radiology, TMH, Mumbai 400012, India.;Department of Radiation Oncology, TMH, Mumbai 400012, India.;Department of Pathology, TMH, Mumbai 400012, India.;Department of Medical Gastroenterology, TMH, Mumbai 400012, India.;Department of Surgical Oncology, TMH, Mumbai 400012, India.;Department of Surgical Oncology, TMH, Mumbai 400012, India.",
"authors": "Ostwal|Vikas|V|;Engineer|Reena|R|;Ramaswamy|Anant|A|;Sahu|Arvind|A|;Zanwar|Saurabh|S|;Arya|Suprita|S|;Chopra|Supriya|S|;Bal|Munita|M|;Patil|Prachi|P|;Desouza|Ashwin|A|;Saklani|Avanish|A|",
"chemical_list": null,
"country": "China",
"delete": false,
"doi": "10.21037/jgo.2016.08.11",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "2078-6891",
"issue": "7(6)",
"journal": "Journal of gastrointestinal oncology",
"keywords": "5-FU plus irinotecan plus oxaliplatin (FOLFIRINOX); Locally advanced; downstaging; interim chemotherapy (i-CT); rectal adenocarcinoma; unresectable",
"medline_ta": "J Gastrointest Oncol",
"mesh_terms": null,
"nlm_unique_id": "101557751",
"other_id": null,
"pages": "958-967",
"pmc": null,
"pmid": "28078119",
"pubdate": "2016-12",
"publication_types": "D016428:Journal Article",
"references": "25220842;20106720;22529255;26187751;20605355;12190680;16971718;20472346;20888703;17470860;15609382;18389322;12130870;15496622;19211200;16446339;19934911;16009958;23524865",
"title": "Surgical outcomes of post chemoradiotherapy unresectable locally advanced rectal cancers improve with interim chemotherapy, is FOLFIRINOX better than CAPOX?",
"title_normalized": "surgical outcomes of post chemoradiotherapy unresectable locally advanced rectal cancers improve with interim chemotherapy is folfirinox better than capox"
} | [
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}
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}
],
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"literaturereference": "OSTWAL V,ENGINEER R,RAMASWAMY A,SAHU A,ZANWAR S,ARYA S. SURGICAL OUTCOMES OF POST CHEMORADIOTHERAPY UNRESECTABLE LOCALLY ADVANCED RECTAL CANCERS IMPROVE WITH INTERIM CHEMOTHERAPY, IS FOLFIRINOX BETTER THAN CAPOX. J-GASTROINTEST-ONCOL 2016;7(6):958-967.",
"literaturereference_normalized": "surgical outcomes of post chemoradiotherapy unresectable locally advanced rectal cancers improve with interim chemotherapy is folfirinox better than capox",
"qualification": "3",
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},
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] |
{
"abstract": "BACKGROUND\nInfections, particularly urinary tract infections, and cardiovascular accidents are the main causes of morbidity and mortality during the 1st year after kidney transplantation (KT). Bacteria and viruses, such as Escherichia coli, Enteroccoci, and Polyoma BK virus are common in the 1st 6 months, so they are controlled routinely. On the other hand, Clostridium perfringens infection is a rare life-threatening condition, associated with a high mortality rate especially in the transplant population, that is not controlled routinely.\n\n\nMETHODS\nA 50-year-old man with end-stage renal disease secondary to hypertension and focal segmental glomerulosclerosis underwent living-related KT. He recovered well and was discharged 11 days after KT. Two weeks after his discharge, he presented with severe abdominal pain, fever, and vomiting. Radiologic assessment showed pneumoperitoneum. Urgent exploratory laparotomy revealed significant amount of gas and no bowel perforation. However, right retroperitoneal gas collection was noted and drained. Blood culture was positive for C perfringens. Patient died after 48 hours, with signs of multiorgan failure.\n\n\nCONCLUSIONS\nClostridium perfringens sepsis is severe and usually lethal in the transplant population. Prevention is difficult because the origin of the infection is unclear. Keeping high suspicion in patients with sudden and unexplained septic shock and aggressive surgical and medical treatment are fundamental.",
"affiliations": "Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana. Electronic address: [email protected].;Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana.;Transplant Division, Department of Surgery, Indiana University School of Medicine, Indianapolis, Indiana.",
"authors": "Mihaylov|P|P|;Powelson|J A|JA|;Goggins|W C|WC|",
"chemical_list": null,
"country": "United States",
"delete": false,
"doi": "10.1016/j.transproceed.2016.03.030",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "0041-1345",
"issue": "48(9)",
"journal": "Transplantation proceedings",
"keywords": null,
"medline_ta": "Transplant Proc",
"mesh_terms": "D015746:Abdominal Pain; D003016:Clostridium perfringens; D004322:Drainage; D042241:Early Diagnosis; D017809:Fatal Outcome; D005738:Gas Gangrene; D006801:Humans; D007676:Kidney Failure, Chronic; D016030:Kidney Transplantation; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D012187:Retroperitoneal Space; D018805:Sepsis; D012772:Shock, Septic; D014552:Urinary Tract Infections",
"nlm_unique_id": "0243532",
"other_id": null,
"pages": "3112-3114",
"pmc": null,
"pmid": "27932159",
"pubdate": "2016-11",
"publication_types": "D002363:Case Reports; D016428:Journal Article",
"references": null,
"title": "Fulminant Clostridium perfringens Sepsis in Kidney Transplant: A Case Report.",
"title_normalized": "fulminant clostridium perfringens sepsis in kidney transplant a case report"
} | [
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},
{
"reactionmeddrapt": "Hypotension",
"reactionmeddraversionpt": "19.1",
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},
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{
"abstract": "BACKGROUND\nThis retrospective study was performed to assess the 3 year outcome of a unified protocol for childhood idiopathic nephrotic syndrome.\n\n\nMETHODS\nCyclosporine A (CsA) or CsA plus mycophenolate mofetil (MMF) were used in patients without remission on high-dose steroid therapy. CsA was maintained at an area under the whole blood concentration-time curve up to 4 h after dose (AUC0-4 ) of 1500 and 2000 ng·h/mL in steroid-dependent nephrotic syndrome (SDNS) and steroid-resistant nephrotic syndrome (SRNS), respectively. Ninety-one children were enrolled in the study (SDNS, n = 64; SRNS, n = 18). Patients were divided into minimal change (MC) and focal segmental glomerulosclerosis (FSGS) groups. Three year outcome was evaluated using clinical severity defined as degree of dependence on immunosuppressive therapy for maintenance of remission.\n\n\nRESULTS\nIn the SDNS group, the numbers of MC and no biopsy were 51 and 13, respectively. No patient had FSGS. Twelve SRNS patients had FSGS and six had MC. In SDNS, 15/64 patients (23%) received no medication. CsA was effective as steroid-sparing agent in 31/38 patients (82%). MMF was effective in all eight patients for whom CsA was unsuccessful. Remission rate in the SRNS group was 14/18 (78%; eight with CsA, and six with a combination of CsA + MMF). Five of the 14 SRNS remission patients received methylprednisolone pulse therapy. Four were resistant to therapy, and had impaired renal function. The clinical severity of MC and FSGS overlapped.\n\n\nCONCLUSIONS\nTreatment with CsA and combination of CsA plus MMF was useful for SDNS and for remission induction in SRNS.",
"affiliations": "Pediatric Nephrology Aichi Children's Health and Medical Center, Aichi, Japan.",
"authors": "Hibino|Satoshi|S|;Uemura|Osamu|O|;Nagai|Takuhito|T|;Yamakawa|Satoshi|S|;Iwata|Naoyuki|N|;Ito|Hidekazu|H|;Nakano|Masaru|M|;Tanaka|Kazuki|K|",
"chemical_list": "D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D009173:Mycophenolic Acid",
"country": "Australia",
"delete": false,
"doi": "10.1111/ped.12498",
"fulltext": null,
"fulltext_license": null,
"issn_linking": "1328-8067",
"issue": "57(1)",
"journal": "Pediatrics international : official journal of the Japan Pediatric Society",
"keywords": "childhood; cyclosporine A; mycophenolate mofetil; steroid-dependent nephrotic syndrome; steroid-resistant nephrotic syndrome",
"medline_ta": "Pediatr Int",
"mesh_terms": "D002675:Child, Preschool; D016572:Cyclosporine; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005938:Glucocorticoids; D006801:Humans; D007166:Immunosuppressive Agents; D008297:Male; D009173:Mycophenolic Acid; D009404:Nephrotic Syndrome; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome",
"nlm_unique_id": "100886002",
"other_id": null,
"pages": "85-91",
"pmc": null,
"pmid": "25225083",
"pubdate": "2015",
"publication_types": "D016428:Journal Article",
"references": null,
"title": "Three year outcome of childhood idiopathic nephrotic syndrome under a unified immunosuppressive protocol.",
"title_normalized": "three year outcome of childhood idiopathic nephrotic syndrome under a unified immunosuppressive protocol"
} | [
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