title: A multicentre prospective cohort study assessing the effectiveness of budesonide MMX® (Cortiment®MMX®) for active, mild-to-moderate ulcerative colitis.

text: Background Cortiment®MMX® (budesonide MMX®) is currently approved for the induction of remission in mild-to-moderate ulcerative colitis (UC) patients when 5-ASA treatment is not sufficient. Data in real-life settings are lacking. Methods This was a multicentre observational prospective cohort study conducted in Europe and Canada. Effectiveness, safety, and tolerability of Cortiment®MMX® in a real-life setting of patients treated for mild-to-moderate UC was investigated. Patients were prescribed Cortiment®MMX® in accordance with the Summary of the Product Characteristics (SmPC).The primary endpoint was the clinical benefit of Cortiment® MMX® in routine practice (improvement ≥ 3 points in the clinical sub-scores of the Ulcerative Colitis Disease Activity Index, UCDAI). Results Data from 326 patients with mild-to-moderate UC were analysed for the primary endpoint. Clinical benefit was achieved in 60.1% (196/326) of patients at the end of Cortiment®MMX® treatment. Clinical remission (UCDAI clinical sub-score ≤ 1), full symptoms resolution (rectal bleeding (RB) = 0 and stool frequency (SF) = 0) and symptoms resolution (RB = 0 + SF ≤ 1) at the end of the Cortiment®MMX® treatment were achieved in 51.8%, 45.1% and 63.2% of patients, respectively. The median time to symptoms resolution was 30 days (range 29.0-36.0 days). Fifty patients (14.3%) had to discontinue Cortiment®MMX® due to adverse events; 17.5% of patients (n = 61) reported at least one adverse event related to the study drug. Conclusions This was the first time that a large cohort study was conducted with Cortiment®MMX® in a real-life setting. It demonstrated that Cortiment®MMX® is effective, safe and well tolerated in about 60% of UC patients.


title: Pure transvaginal laparoscopic appendectomy.

text: BACKGROUND Natural orifice transluminal endoscopic surgery has been at the forefront of minimally invasive surgery. Benefits include no visible scars, less pain, and shorter recovery time. We describe a video of a 37-year-old female who underwent a pure transvaginal appendectomy (TVA) for acute appendicitis. This is 1 of 18 successfully performed TVAs at Yale-New Haven Hospital. Appropriate Institutional Review Board was obtained preoperatively. METHODS The patient was positioned in steep Trendelenburg and then a weighted speculum was introduced into the vagina allowing exposure of the posterior vaginal fornix. The cervix was grasped with a single-toothed tenaculum on the posterior cervical lip and the posterior vaginal fornix was visualized. Access to the peritoneum was achieved by electrocautery and then sharp dissection. A SILS™ port (Covidien, Mansfield, MA, USA) was introduced and pneumoperitoneum up to 15 mmHg was achieved. Two 5-mm trocars and one 12-mm trocar were used. A 5-mm 30° angled endoscope, a flexible reticulating endograsper, and straight standard instruments were used. The identified appendix was dissected and a stapler was used to divide the mesoappendix from the appendix. Following confirmation of good hemostasis and no spillage of bowel contents, the appendix was removed from the abdomen within a retrieval bag and the culdotomy was closed with a running absorbable suture. The patient tolerated the 27 min procedure well and was discharged home in good condition on postoperative day 1.


Cutting-edge progress in viral immunology.


title: A novel interaction between sympathetic overactivity and aberrant regulation of renin by miR-181a in BPH/2J genetically hypertensive mice.

text: Genetically hypertensive mice (BPH/2J) are hypertensive because of an exaggerated contribution of the sympathetic nervous system to blood pressure. We hypothesize that an additional contribution to elevated blood pressure is via sympathetically mediated activation of the intrarenal renin-angiotensin system. Our aim was to determine the contribution of the renin-angiotensin system and sympathetic nervous system to hypertension in BPH/2J mice. BPH/2J and normotensive BPN/3J mice were preimplanted with radiotelemetry devices to measure blood pressure. Depressor responses to ganglion blocker pentolinium (5 mg/kg i.p.) in mice pretreated with the angiotensin-converting enzyme inhibitor enalaprilat (1.5 mg/kg i.p.) revealed a 2-fold greater sympathetic contribution to blood pressure in BPH/2J mice during the active and inactive period. However, the depressor response to enalaprilat was 4-fold greater in BPH/2J compared with BPN/3J mice, but only during the active period (P=0.01). This was associated with 1.6-fold higher renal renin messenger RNA (mRNA; P=0.02) and 0.8-fold lower abundance of micro-RNA-181a (P=0.03), identified previously as regulating human renin mRNA. Renin mRNA levels correlated positively with depressor responses to pentolinium (r=0.99; P=0.001), and BPH/2J mice had greater renal sympathetic innervation density as identified by tyrosine hydroxylase staining of cortical tubules. Although there is a major sympathetic contribution to hypertension in BPH/2J mice, the renin-angiotensin system also contributes, doing so to a greater extent during the active period and less during the inactive period. This is the opposite of the normal renin-angiotensin system circadian pattern. We suggest that renal hyperinnervation and enhanced sympathetically induced renin synthesis mediated by lower micro-RNA-181a contributes to hypertension in BPH/2J mice.


title: Human serum amyloid P functions as a negative regulator of the innate and adaptive immune responses to DNA vaccines.

text: The utility of DNA vaccines has been limited by their failure to elicit sufficiently potent immune responses in many human applications, whereas DNA vaccinations in mice have been very successful. However, the underlying mechanisms remain unknown. We hypothesize that serum amyloid P component (SAP), which has a species-specific, DNA-binding ability, contributes to the differences between human and mice and then limits DNA vaccine's efficacy in vivo. In our study, DNA vaccine-induced adaptive immune responses were also significantly decreased in the human SAP (hSAP) transgenic mice. Using human promonocytic cell line THP-1-derived macrophages as a cell model, we found that cells incubated with a hSAP-DNA complex showed significant defects in innate immune activations, whereas mouse SAP had similar, albeit very weak, activities. hSAP also significantly inhibited the functions of two identified DNA sentinels, high-mobility group B protein 1 and antimicrobial peptide LL37, and redirected DNA update to FcRs leading to endocytosis and endosomal degradation. We also found that a chemical SAP inhibitor strongly recovered the suppressed innate immune responses to DNA in the presence of human serum and enhanced the immunogenicity of DNA vaccines in vivo. Our data indicated that SAP is a key negative regulator for innate immune responses to DNA and may be partly responsible for the insufficient immune responses after DNA vaccinations in humans. SAP suppression may be a novel strategy for improving efficacy of human DNA vaccines and requires further clinical investigations.


title: Evaluation of fibrin sealants for central nervous system sealing in the mongrel dog durotomy model.

text: BACKGROUND Watertight repair of the dura is imperative after neurosurgical procedures involving the brain or spinal cord because inadequately treated leakage of cerebrospinal fluid (CSF) from punctured dura can have serious consequences such as meningitis, arachnoiditis, or epidural abscess. OBJECTIVE To assess the efficacy of Evicel Fibrin Sealant (Human) to prevent CSF leakage using a 2.0-cm durotomy mongrel dog repair model and to compare the tissue response with Tisseel (a fibrin sealant) and Duraseal (a synthetic polyethylene glycol [PEG] hydrogel sealant). METHODS The canine durotomy repair model was used. This well-characterized model assesses the ability of sealants to achieve intraoperative watertight seals of the dura mater, as well as long-term safety and efficacy. This study included 27 mongrel dogs and had a 28-day duration. RESULTS The 3 sealants were 100% effective in preventing CSF leakage intraoperatively at 15 mm Hg. The 2 fibrin sealants were 100% effective in postoperative sealing; the PEG hydrogel was not. Microscopically, the tissue changes induced by Evicel at the durotomy site were similar in nature except for foamy macrophages seen only with the PEG hydrogel. The extent and severity of adhesions at 28 days were less with the fibrin sealants than with the PEG hydrogel. CONCLUSION Evicel, a fibrin sealant, was safe and effective in achieving and maintaining a watertight seal of the dura. The performance of the fibrin sealants was similar to that of the synthetic PEG hydrogel sealant with the exception of a Duraseal seal, which leaked.


title: Use of the Outreach Distal Access Catheter for microcatheter stabilization during intracranial arteriovenous malformation embolization.

text: The Outreach DAC is an intermediate-sized catheter designed for use with the Merci clot retriever in acute stroke. We investigated its utility as an adjunctive device during AVM pedicle embolization. In the authors' opinion, the DAC provided additional guide-catheter and microcatheter support, improved selective angiographic visualization of AVM angioarchitecture, aided microcatheter removal from its embedded position in the AVM Onyx cast, and enhanced local microcatheter control and safety, compared with embolization with the guide and microcatheter alone.


title: Laparoscopic versus open colectomy for patients with American Society of Anesthesiology (ASA) classifications 3 and 4: the minimally invasive approach is associated with significantly quicker recovery and reduced costs.

text: BACKGROUND Conceivably, the benefits of earlier recovery associated with a minimally invasive technique used in laparoscopic colectomy (LC) may be amplified for patients with comorbid disease. The dearth of evidence supporting the safety of laparoscopy for these patients led to a comparison of outcomes between LC and open colectomy (OC) for patients with American Society of Anesthesiology (ASA) classifications 3 and 4. METHODS Data for all ASA 3 and 4 patients who underwent elective LC were reviewed from a prospectively maintained laparoscopic database. The patients who underwent LC were matched with OC patients by age, gender, diagnosis, year, and type of surgery. Estimated blood loss, operation time, time to return of bowel function, length of hospital stay, readmission rate, and 30-day complication and mortality rates were compared using chi-square, Fisher's exact, and Wilcoxon tests as appropriate. A p value <0.05 was considered statistically significant. RESULTS In this study, 231 LCs were matched with 231 OCs. The median age of the patients was 68 years, and 234 (51%) of the patients were male. There were 44 (19%) conversions from LC to OC. More patients in the OC group had undergone previous major laparotomy (5 vs. 15%; p < 0.001). Estimated blood loss, return of bowel function, length of hospital stay, and total direct costs were decreased in the LC group. Wound infection was significantly greater with OC (p = 0.02). When patients with previous major laparotomy were excluded, the two groups had similar overall morbidity. The other benefits of LC, however, persisted. CONCLUSION The findings show that LC is a safe option for patients with a high ASA classification. The LC approach is associated with faster postoperative recovery, lower morbidity rates, and lower hospital costs than the OC approach.


title: Fast-track hip and knee arthroplasty: clinical and organizational aspects.

text: Fast-track hip and knee arthroplasty aims at giving the patients the best available treatment at all times, being a dynamic entity. Fast-track combines evidence-based, clinical features with organizational optimization including a revision of traditions resulting in a streamlined pathway from admission till discharge – and beyond. The goal is to reduce morbidity, mortality and functional convalescence with an earlier achievement of functional milestones including functional discharge criteria with subsequent reduced length of stay and high patient satisfaction. Outcomes are traditionally measured as length of stay; safety aspects in the form of morbidity/mortality; patient satisfaction; and – as a secondary parameter – economic savings. Optimization of the clinical aspects include focusing on analgesia; DVT-prophylaxis; mobilization; care principles including functional discharge criteria; patient-characteristics to predict outcome; and traditions which may be barriers in optimizing outcomes. Patients should be informed and motivated to be active participants and their expectations should be modulated in order to improve satisfaction. Also, organizational aspects need to be analyzed and optimized. New logistical approaches should be implemented; the ward ideally (re)structured to only admit arthroplasties; the staff educated to have a uniform approach; extensive preoperative information given including discharge criteria and intended length of stay. This thesis includes 9 papers on clinical and organizational aspects of fast-track hip and knee arthroplasty (I–IX). A detailed description of the fast-track set-up and its components is provided. Major results include identification of patient characteristics to predict length of stay and satisfaction with different aspects of the hospital stay (I); how to optimize analgesia by using a compression bandage in total knee arthroplasty (II); the clinical and organizational set-up facilitating or acting as barriers for early discharge (III); safety aspects following fast-track in the form of few readmissions in general (IV) and few thromboembolic complications in particular (V); feasibility studies showing excellent outcomes following fast-track bilateral simultaneous total knee arthroplasty (VI) and non-septic revision knee arthroplasty (VII); how acute pain relief in total hip arthroplasty is not enhanced by the use of local infiltration analgesia when multi-modal opioid-sparing analgesia is given (VIII); and a detailed description of which clinical and organizational factors detain patients in hospital following fast-track hip and knee arthroplasty (IX). Economic savings following fast-track hip and knee arthroplasty is also documented in studies, reviews, metaanalyses and Cochrane reviews – including the present fast-track (ANORAK). In conclusion, the published results (I–IX) provide substantial, important new knowledge on clinical and organizational aspects of fast-track hip and knee arthroplasty – with concomitant documented high degrees of safety (morbidity/mortality) and patient satisfaction. Future research strategies are multiple and include both research strategies as efforts to implement the fast-track methodology on a wider basis. Research areas include improvements in pain treatment, blood saving strategies, fluid plans, reduction of complications, avoidance of tourniquet and concomitant blood loss, improved early functional recovery and muscle strengthening. Also, improvements in information and motivation of the patients, preoperative identification of patients needing special attention and detailed economic studies of fast- track are warranted.


title: Conservative management of an unusual bilioduodenal fistula post laparoscopic Duodeno-Ileal Switch (SADI-S) case report.

text: INTRODUCTION Single anastomosis duodeno-ileal bypass with sleeve gastrectomy (SADI-S) is an advanced operation for morbid obesity. To our knowledge, no internal Biliodigestive Fistula has yet been reported as specific complication in the field of metabolic and bariatric Biliopancreatic diversion. CASE PRESENTATION In this case report, we detail the case of a 57-year-old man who underwent a Single Anastomosis Duodeno-Ileal Switch (SADI-S) bariatric procedure for morbid obesity. Upon admission 3 weeks after the SADI-S procedure acute sepsis caused by a delayed choledoco-duodenal Fistula was diagnosed. A conservative management of this rare complication was successful. DISCUSSION We highlight the differential diagnosis and optional treatment in such a rare complication, and how we succeeded in its conservative management, without any need for endoscopic nor surgical intervention. A review of the literature on different types of Internal Biliodigestive Fistulae and their appropriate management are reported and briefly discussed. CONCLUSION The aim of this case report is to highlight the existence of such a rare complication, and its successful multidisciplinary conservative medical management.


Anatomy and physiology of coronary blood flow.


title: Comparisons of surgical outcomes between transperitoneal and retroperitoneal approaches in robot-assisted laparoscopic partial nephrectomy for lateral renal tumors: a propensity score-matched comparative analysis.

text: OBJECTIVE To compare the surgical outcomes between the transperitoneal (TP) and retroperitoneal (RP) approaches in robot-assisted laparoscopic partial nephrectomy (RAPN) for lateral tumors. METHODS This study included patients who underwent RAPN for lateral renal tumors between 2013 and 2019. Lateral tumors were defined as X of A factors in the RENAL nephrometry score. In total, 290 and 48 patients with TP and RP, respectively, were included in the analysis. To minimize the effects of selection bias, the following variables were adjusted using 1:1 propensity score matching: age, sex, body mass index, American Society of Anesthesiologists score, preoperative estimated glomerular filtration rate, tumor size, and RENAL nephrometry score. RESULTS After matching, 48 patients were allocated to each group. The mean age was 55 years, and the mean preoperative estimated glomerular filtration rate (eGFR) was 68-69 mL/min/1.73 m2. The mean tumor size was 30-31 mm. The RP group had a shorter operative time (124 vs. 151 min, p = 0.0002), shorter console time (74 vs. 110 min, p < 0.0001), shorter warm ischemic time (14 vs. 17 min, p = 0.0343), lower estimated blood loss (EBL) (33 vs. 52 ml, p = 0.0002), and shorter postoperative length of hospital stay (PLOS) (3.3 vs. 4.0 days, p < 0.0001) than the TP group. The change in eGFR, incidence rate of perioperative complication, and positive surgical margin rate did not significantly differ between the two groups. CONCLUSION RP had better surgical outcomes, including shorter operative time, lower EBL, and shorter PLOS for lateral renal tumors, which may suggest that RP is the optimal approach for selected lateral renal tumors.


title: Emergence of Porcine epidemic diarrhea virus in the United States: clinical signs, lesions, and viral genomic sequences.

text: During the 10 days commencing April 29, 2013, the Iowa State University Veterinary Diagnostic Laboratory received the first 4 of many submissions from swine farms experiencing explosive epidemics of diarrhea and vomiting affecting all ages, with 90-95% mortality in suckling pigs. Histology revealed severe atrophy of villi in all segments of the small intestines with occasional villus-epithelial syncytial cells, but testing for rotaviruses and Transmissible gastroenteritis virus (Alphacoronavirus 1) were negative. Negative-staining electron microscopy of feces revealed coronavirus-like particles and a pan-coronavirus polymerase chain reaction (PCR) designed to amplify a conserved region of the polymerase gene for all members in the family Coronaviridae produced expected 251-bp amplicons. Subsequent sequencing and analysis revealed 99.6-100% identity among the PCR amplicons from the 4 farms and 97-99% identity to the corresponding portion of the polymerase gene of Porcine epidemic diarrhea virus (PEDV) strains, with the highest identity (99%) to strains from China in 2012. Findings were corroborated at National Veterinary Services Laboratories using 2 nested S-gene and 1 nested N-gene PCR tests where the sequenced amplicons also had the highest identity with 2012 China strains. Whole genome sequence for the virus from 2 farms in 2 different states using next-generation sequencing technique was compared to PEDV sequences available in GenBank. The 2013 U.S. PEDV had 96.6-99.5% identity with all known PEDV strains and the highest identity (>99.0%) to some of the 2011-2012 Chinese strains. The nearly simultaneous outbreaks of disease, and high degree of homology (99.6-100%) between the PEDV strains from the 4 unrelated farms, suggests a common source of virus.


title: The spread of awareness and its impact on epidemic outbreaks.

text: When a disease breaks out in a human population, changes in behavior in response to the outbreak can alter the progression of the infectious agent. In particular, people aware of a disease in their proximity can take measures to reduce their susceptibility. Even if no centralized information is provided about the presence of a disease, such awareness can arise through first-hand observation and word of mouth. To understand the effects this can have on the spread of a disease, we formulate and analyze a mathematical model for the spread of awareness in a host population, and then link this to an epidemiological model by having more informed hosts reduce their susceptibility. We find that, in a well-mixed population, this can result in a lower size of the outbreak, but does not affect the epidemic threshold. If, however, the behavioral response is treated as a local effect arising in the proximity of an outbreak, it can completely stop a disease from spreading, although only if the infection rate is below a threshold. We show that the impact of locally spreading awareness is amplified if the social network of potential infection events and the network over which individuals communicate overlap, especially so if the networks have a high level of clustering. These findings suggest that care needs to be taken both in the interpretation of disease parameters, as well as in the prediction of the fate of future outbreaks.


title: Integrating the selection of PHA storing biomass and nitrogen removal via nitrite in the main wastewater treatment line.

text: A novel scheme was developed for the treatment of municipal wastewater integrating nitritation/denitritation with the selection of polyhydroxyalkanoates (PHA) storing biomass under an aerobic/anoxic, feast/famine regime. The process took place in a sequencing batch reactor (SBR) and the subsequent PHA accumulation in a batch reactor. The carbon source added during the selection and accumulation steps consisted of fermentation liquid from the organic fraction of municipal solids waste (OFMSW FL) (Period I) and OFMSW and primary sludge fermentation liquid (Period II). Selection of PHA storing biomass was successful and denitritation was driven by internally stored PHA during the famine phase. Under optimum conditions of SBR operation ammonia removal was 93%, reaching a maximum nitrite removal of 98%. The treated effluent met the nitrogen limits, while PHA-storing biomass was successfully selected. The maximum accumulation of PHA was 10.6% (wt.) since the nutrients present in the carbon source promoted bacterial growth.


Single-incision laparoscopic hernioplasty with the assistance of the Radius Surgical System.


title: Repurposing of Kinase Inhibitors as Broad-Spectrum Antiviral Drugs.

text: The high cost of drug development and the narrow spectrum of coverage typically provided by direct-acting antivirals limit the scalability of this antiviral approach. This review summarizes progress and challenges in the repurposing of approved kinase inhibitors as host-targeted broad-spectrum antiviral therapies.


title: Quantitative margin assessment of radiofrequency ablation of a solitary colorectal hepatic metastasis using MIRADA RTx on CT scans: a feasibility study.

text: BACKGROUND Compared to surgery, radiofrequency ablation(RFA) for colorectal liver metastasis(CRLM) is associated with higher local recurrence(LR) rates. A wide margin (at least 5 mm) is generally recommended to prevent LR, but the optimal method to assess ablation margins is yet to be established. The aim of our study was to evaluate the feasibility and reproducibility of CT-CT co-registration, using MIRADA software, in order to assess ablation margins of patients with CRLM. METHODS In this retrospective study, pre- and post-ablation contrast-enhanced CT scans of 29 patients, treated with percutaneous RFA for a solitary CRLM, were co-registered. Co-registration was performed by two independent radiologist, based on venous structures in proximity to the tumor. Feasibility of CT-CT co-registration and inter-observer agreement for reproducibility and ablation margins was determined. Furthermore, the minimal ablation margin was compared with the occurrence of LR during follow-up. RESULTS Co-registration was considered feasible in 18 patients (61% male, 63.1(±10.9) year), with a perfect inter-observer agreement for completeness of ablation: κ = 1.0(p < 0.001). And substantial inter-observer agreement for measurement of the minimal margin (≤ 0 mm, 1-5 mm, ≥ 5 mm): κ = 0.723(p-value < 0.001). LR occurred in eight of nine(88.9%) incompletely ablated CRLM and in one of the nine completely ablated CRLM(11.1%). CONCLUSION Co-registration using MIRADA is reproducible and potentially a valuable tool in defining technical success. Feasibility of co-registration of pre- and post-ablation CT scans is suboptimal if scans are not acquired concordantly. Co-registration may potentially aid in the prediction of LR after percutaneous ablation.


title: Pipeline embolization device for the treatment of a traumatic intracranial aneurysm in a child.

text: INTRODUCTION Traumatic intracranial aneurysms in children are rare and may occur as the result of closed or penetrating head trauma. Their natural history seems to be more aggressive. Most traumatic aneurysms have complex shape, tending to have a large neck or even a fusiform morphology. CASE REPORT We present a case of a traumatic carotid artery aneurysm in a 9-year-old girl that was successfully treated with pipeline embolization device. DISCUSSION Due to its dissecting nature, wall friability and lack of a substantial neck can make surgical clipping and selective coiling difficult and risky. Although endovascular parent artery occlusion is the best approach in the acute phase, in some situations it is not possible or very risky. In such scenario the use of flow diverter devices would be an alternative approach. Additionally, we discuss the potential advantages and risks of flow diverter deployment inside a developing vessel.


Fecal testing for SARS-CoV-2 in patients undergoing elective lower gastrointestinal endoscopy.


title: The Arg719 residue at the C-terminal end of the stem region in hepatitis C virus JFH-1 E2 glycoprotein promotes viral infection.

text: Hepatitis C virus (HCV) envelope glycoprotein E2 is involved in virus assembly and initial entry into host cells. The tertiary organization of the E2 ectodomain is mainly composed of domains I-III, followed by the stem (ST) region and transmembrane (TM) domain. The ST region is critical for reorganizing the envelope glycoproteins during the membrane fusion process. While this region is relatively flexible, the physicochemical properties of its amino acid residues are conserved. Whether and how this physicochemical conservation is required for HCV infection is still unclear. The last residue of the E2 ST region evolved to be either an arginine or lysine among different HCV strains, suggesting that the residues confer different functions during HCV infection. To address this possibility, we constructed an R719K point mutant in the JFH-1 strain (genotype 2a) in the context of the cell-culture derived HCV (HCVcc) system. Compared with wild-type (wt) HCV, the R719K mutant exhibited decreased growth, and its extracellular and intracellular infectivity were also significantly decreased at 48 and 72 h post-electroporation. Correspondingly, less RNA and HCV core protein was observed in the supernatant for the R719K mutant, as well as less efficient RNA replication and protein expression. These findings indicate that the 719th residue of arginine on E2 is critical to promote HCV replication and infection. The data provide new clues for the biochemical function of E2, which is required for efficient HCV assembly and infection.


Impact of the COVID-19 Pandemic on the Urology Residency Match in Singapore.


title: Biochemistry, hormones and adipocytokines in prepubertal children born with IUGR evoke metabolic, hepatic and renal derangements.

text: Children born with IUGR develop features of the metabolic syndrome and exhibit deranged markers of hepatorenal physiology. Metabolic and hepatorenal biochemistry and the rs9939609 FTO polymorphism were investigated in prepubertal children born with IUGR. Ninety-eight prepubertal children (46 IUGR and 52 AGA), subdivided in <5 years and >5 years old groups were included. Anthropometry; creatinine, eGFR, urea, AST, ALT, triglycerides, uric acid, total cholesterol, HDL-c, LDL-c, glucose, C-peptide, insulin and glucagon z-scores; HOMA-IR; leptin and adiponectin concentrations; rs9939609 FTO polymorphism frequency were measured. In males, weight and ALT were higher and adiponectin was lower, in IUGR < 5 years; C-peptide, insulin and leptin were higher in IUGR > 5 years; C-peptide was higher in all IUGR, than the respective AGA. In females, creatinine and triglycerides were higher in IUGR < 5 years old; creatinine was higher and eGFR was lower in all IUGR, than the respective AGA. In males and females, creatinine was higher in all IUGR, than the respective AGA; C-peptide, insulin and HOMA-IR were lower, and AST was higher in IUGR < 5 than in IUGR > 5 years old. FTO rs9939609 frequency did not differ between IUGR and AGA. In conclusion prepubertal males born with IUGR increased weight, insulin and leptin and decreased adiponectin, as compared to males born AGA, emerge as early metabolic syndrome characteristics. The concentrations of these hormones do not differ between prepubertal males and females born with IUGR. Weight control, healthy nutrition and physical exercise should be recommended to these children. The deranged renal (particularly evident in females below the age of 5) and liver biochemistry in prepubertal children born with IUGR suggests that hepatorenal derangements might commence in utero. Regular checkup of biochemical and lipid profile is recommended for all children born with IUGR.


title: Liver Enzyme Elevation in Coronavirus Disease 2019: A Multicenter, Retrospective, Cross-Sectional Study

text: INTRODUCTION: Elevated liver enzyme levels are observed in patients with coronavirus disease 2019 (COVID-19); however, these features have not been characterized. METHODS: Hospitalized patients with COVID-19 in Zhejiang Province, China, from January 17 to February 12, 2020, were enrolled. Liver enzyme level elevation was defined as alanine aminotransferase level >35 U/L for men and 25 U/L for women at admission. Patients with normal alanine aminotransferase levels were included in the control group. Reverse transcription polymerase chain reaction was used to confirm severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, and patients symptomatic with SARS-CoV-2 infection were defined as patients with COVID-19. Epidemiological, demographic, clinical, laboratory, treatment, and outcome data were collected and compared. RESULTS: Of 788 patients with COVID-19, 222 (28.2%) patients had elevated liver enzyme levels (median [interquartile range {IQR}] age, 47.0 [35.0–55.0] years; 40.5% women). Being male, overweight, and smoking increased the risk of liver enzyme level elevation. The liver enzyme level elevation group had lesser pharyngalgia and more diarrhea than the control group. The median time from illness onset to admission was 3 days for liver enzyme level elevation groups (IQR, 2–6), whereas the median hospitalization time for 86 (38.7%) discharged patients was 13 days (IQR, 11–16). No differences in disease severity and clinical outcomes were noted between the groups. DISCUSSION: We found that 28.2% of patients with COVID-19 presented with elevated liver enzyme levels on admission, which could partially be related to SARS-CoV-2 infection. Male patients had a higher risk of liver enzyme level elevation. With early medical intervention, liver enzyme level elevation did not worsen the outcomes of patients with COVID-19.


Middle East respiratory syndrome coronavirus: epidemic potential or a storm in a teacup?


Cardiovascular pipeline decline quantified.


title: Single port sigmoidectomy in an experimental model with survival.

text: INTRODUCTION Single port laparoscopic access could reduce morbidity associated with additional trocar placement and, through the development of a hybrid intermediate, facilitate the clinical adoption of evolving techniques such as natural orifice transluminal endoscopic surgery. Advanced trocar technology, as much as adapted surgical technique, seems necessary to best facilitate this, however. METHODS A novel port (Airseal, Surgiquest) that uses vortex technology to create an air-curtain seal to maintain the pneumoperitoneum while facilitating the simultaneous passage of multiple working instruments was trialed. For this, 6 pigs (30 kg each) underwent sigmoid resection and reanastomosis using the port as the sole laparoscopic access for conventional instrumentation. All animals were thereafter survived for observation during a 2-week convalescence before undergoing repeat general anesthesia, sigmoidoscopy for anastomotic assessment, and forensic laparotomy for determination of intraperitoneal healing and complications. RESULTS The operation was technically feasible via a single port within a short time in every animal (mean duration 12.3 minutes). One anastomosis had to redone because of staple misfire but this too was accomplishable without additional port placement. All animals survived and convalesced normally without evincing clinical complication. At follow-up, all anastomoses were patent at sigmoidoscopy and only 1 animal had evidence of complicated anastomotic healing (the same animal that had needed anastomotic refashioning). CONCLUSIONS Single port colonic resection and reanastomosis is readily achievable in this animal model. As an operative approach, it may both advance in its own right as much as facilitate the evolution and clinical incorporation of other developmental access routes.


title: Endoscopic surgery for patients with syndromic craniosynostosis and the requirement for additional open surgery.

text: OBJECTIVE Recent reports have described early endoscopic suturectomy as a treatment option for patients with syndromic craniosynostosis, but such patients often require subsequent calvarial remodeling. The authors describe their experience with this patient population and seek to identify predictors of sufficiency of endoscopic surgery alone. METHODS The medical records of patients with syndromic craniosynostosis who underwent endoscopic repair were retrospectively reviewed. Demographic data, operative details, and follow-up data were collected. RESULTS A total of 6 patients with syndromic craniosynostosis underwent endoscopic surgery followed by helmet therapy during the study period. Of these, 3 patients were male. The involved syndromes included Crouzon, Pfeiffer, Jackson-Weiss, Muenke, Saethre-Chotzen, and craniosynostosis-3 (n = 1 each). The patients underwent endoscopic surgery at a median age of 2.1 months (range 0.9-4.1 months). The median estimated blood loss was 30 ml (range 20-100 ml), with 2 patients requiring a transfusion. The median length of stay in the hospital was 1.5 days (range 1-4 days), and the median follow-up was 29.0 months (range 16.8-81.7 months), with 1 patient (16.7%) requiring an open revision. Three patients (50%) were classified as Whitaker Category I at the last follow-up. The patients for whom additional open surgery was performed or recommended (Whitaker Category IV) were the oldest patients in the cohort, ranging from 2.6 to 4.1 months at the time of surgery. CONCLUSIONS This series demonstrates that endoscopic surgery can be sufficient to treat syndromic craniosynostosis without subsequent open calvarial remodeling over a median follow-up period of at least 2 years. The findings suggest that younger age at the time of endoscopic surgery may be an important factor in determining the sufficiency of this procedure. Even among patients who require subsequent open calvarial remodeling, early endoscopic surgery may allow for growth and development of the brain and skull while delaying the need for open remodeling until the patient is older and can better tolerate the procedure.


title: Global Health Security Demands a Strong International Health Regulations Treaty and Leadership From a Highly Resourced World Health Organization.

text: If the Ebola tragedy of West Africa has taught us anything, it should be that the 2005 International Health Regulations (IHR) Treaty, which gave unprecedented authority to the World Health Organization (WHO) to provide global public health security during public health emergencies of international concern, has fallen severely short of its original goal. After encouraging successes with the 2003 severe acute respiratory syndrome (SARS) pandemic, the intent of the legally binding Treaty to improve the capacity of all countries to detect, assess, notify, and respond to public health threats has shamefully lapsed. Despite the granting of 2-year extensions in 2012 to countries to meet core surveillance and response requirements, less than 20% of countries have complied. Today it is not realistic to expect that these gaps will be solved or narrowed in the foreseeable future by the IHR or the WHO alone under current provisions. The unfortunate failures that culminated in an inadequate response to the Ebola epidemic in West Africa are multifactorial, including funding, staffing, and poor leadership decisions, but all are reversible. A rush by the Global Health Security Agenda partners to fill critical gaps in administrative and operational areas has been crucial in the short term, but questions remain as to the real priorities of the G20 as time elapses and critical gaps in public health protections and infrastructure take precedence over the economic and security needs of the developed world. The response from the Global Outbreak Alert and Response Network and foreign medical teams to Ebola proved indispensable to global health security, but both deserve stronger strategic capacity support and institutional status under the WHO leadership granted by the IHR Treaty. Treaties are the most successful means the world has in preventing, preparing for, and controlling epidemics in an increasingly globalized world. Other options are not sustainable. Given the gravity of ongoing failed treaty management, the slow and incomplete process of reform, the magnitude and complexity of infectious disease outbreaks, and the rising severity of public health emergencies, a recommitment must be made to complete and restore the original mandates as a collaborative and coordinated global network responsibility, not one left to the actions of individual countries. The bottom line is that the global community can no longer tolerate an ineffectual and passive international response system. As such, this Treaty has the potential to become one of the most effective treaties for crisis response and risk reduction worldwide. Practitioners and health decision-makers worldwide must break their silence and advocate for a stronger Treaty and a return of WHO authority.


title: Differential susceptibility of different cell lines to swine-origin influenza A H1N1, seasonal human influenza A H1N1, and avian influenza A H5N1 viruses.

text: BACKGROUND The novel swine-origin influenza A H1N1 virus (S-OIV) causes the current pandemic. Its tissue tropism and replication in different cell lines are not well understood. OBJECTIVE Compare the growth characteristics of cell lines infected by S-OIV, seasonal influenza A H1N1 (sH1N1) and avian influenza A H5N1 (H5N1) viruses and the effect of temperature on viral replication. STUDY DESIGN Cytopathic effect (CPE), antigen expression by immunofluorescence (IF) and viral load profile by quantitative RT-PCR in 17 cell lines infected by S-OIV, sH1N1 and H5N1 were examined. Comparison of their replication efficiency in chick embryo was performed. The effect of temperature on viral replication in Madin-Darby canine kidney (MDCK) cells was determined by TCID(50) at 33 degrees C, 37 degrees C and 39 degrees C for 5 consecutive days. RESULTS S-OIV replicated in cell lines derived from different tissues or organs and host species with comparable viral load to sH1N1. Among 13 human cell lines tested, Caco-2 has the highest viral load for S-OIV. S-OIV showed a low viral load with no CPE or antigen expression in pig kidney cell PK-15, H5N1 demonstrated the most diverse cell tropism by CPE and antigen expression, and the highest viral replication efficiency in both cell lines and allantoic fluid. All three viruses demonstrated best growth at 37 degrees C in MDCK cells. CONCLUSION Cell line growth characteristics of S-OIV, sH1N1 and H5N1 appear to correlate clinically and pathologically with involved anatomical sites and severity. Low replication of S-OIV in PK-15 suggests that this virus is more adapted to human than swine.


title: Evolution of minimally invasive surgery for donor nephrectomy and outcomes.

text: BACKGROUND Laparoscopic donor nephrectomy was introduced into Australia in 1997 by this unit. However, some donors may be considered unsuitable, and few modifications to the existing technique can tailor this procedure for an individual donor. Recently, further changes including clustering of ports and single-port methods have been investigated. METHODS The laparoscopic method was offered to all but 3 donors from May 1997 to October 2009. Data were collected on all 289 donors who underwent laparoscopic procedures. RESULTS All but 5 donor procedures were completed laparoscopically, and in 4 of them conversion to open was necessary due to hemorrhage. The fifth was a planned conversion in our first right LDN. Delayed graft function was seen in 7 recipients and 5 required dialysis postoperatively. Two kidneys were lost due to arterial thrombosis, and 5 patients underwent segmental infarction with decreased renal function. Mean hospital stay was 2.35±1.67 days. There were no donor deaths or serious morbidity. CONCLUSIONS Although the benefits to the donor of the laparoscopic method are well recognized, our modifications will benefit those who may be precluded from this method.


title: Correction: Neuroprotection by Argon Ventilation after Perinatal Asphyxia: A Safety Study in Newborn Piglets.

text: [This corrects the article DOI: 10.1371/journal.pone.0113575.].


title: Dual-ports laparoscopy-assisted distal gastrectomy compared with conventional laparoscopy-assisted distal gastrectomy.

text: PURPOSE We performed laparoscopic gastrectomy using an umbilical port in addition with one other port (dual-ports laparoscopy-assisted distal gastrectomy, DP-LADG) since December 2009. We describe a retrospective study to evaluate the possibility of DP-LADG compared with conventional LADG (C-LADG). METHODS The indication for DP-LADG was preoperative clinical Stage IA gastric cancer. We compared 20 patients who underwent DP-LADG with 24 patients of clinical Stage IA patients who underwent C-LADG. RESULTS The mean operation time was significantly longer for DP-LADG (250.5 min) than for C-LADG (197.5 min); however, the mean operation time for the last 5 patients undergoing DP-LADG (209 ± 31.1 min) was almost the same as that for C-LADG. There were no significant differences between DP-LADG and C-LADG in terms of blood loss, number of lymph nodes dissected, rates of conversion to open surgery, postoperative complications, and length of postoperative hospital stay. CONCLUSIONS DP-LADG is technically feasible.


title: Effect of Phenylephrine and Ephedrine on Cerebral (Tissue) Oxygen Saturation During Carotid Endarterectomy (PEPPER): A Randomized Controlled Trial.

text: BACKGROUND Short-acting vasopressor agents like phenylephrine or ephedrine can be used during carotid endarterectomy (CEA) to achieve adequate blood pressure (BP) to prevent periprocedural stroke by preserving the cerebral perfusion. Previous studies in healthy subjects showed that these vasopressors also affected the frontal lobe cerebral tissue oxygenation (rSO2) with a decrease after administration of phenylephrine. This decrease is unwarranted in patients with jeopardized cerebral perfusion, like CEA patients. The study aimed to evaluate the impact of both phenylephrine and ephedrine on the rSO2 during CEA. METHODS In this double-blinded randomized controlled trial, 29 patients with symptomatic carotid artery stenosis underwent CEA under volatile general anesthesia in a tertiary referral medical center. Patients were preoperative allocated randomly (1:1) for receiving either phenylephrine (50 µg; n = 14) or ephedrine (5 mg; n = 15) in case intraoperative hypotension occurred, defined as a decreased mean arterial pressure (MAP) ≥ 20% compared to (awake) baseline. Intraoperative MAP was measured by an intra-arterial cannula placed in the radial artery. After administration, the MAP, cardiac output (CO), heart rate (HR), stroke volume, and rSO2 both ipsilateral and contralateral were measured. The timeframe for data analysis was 120 s before, until 600 s after administration. RESULTS Both phenylephrine (70 ± 9 to 101 ± 22 mmHg; p < 0.001; mean ± SD) and ephedrine (75 ± 11 mmHg to 122 ± 22 mmHg; p < 0.001) adequately restored MAP. After administration, HR did not change significantly over time, and CO increased 19% for both phenylephrine and ephedrine. rSO2 ipsilateral and contralateral did not change significantly after administration at 300 and 600 s for either phenylephrine or ephedrine (phenylephrine 73%, 73%, 73% and 73%, 73%, 74%; ephedrine 72%, 73%, 73% and 75%, 74%, 74%). CONCLUSIONS Within this randomized prospective study, MAP correction by either phenylephrine or ephedrine showed to be equally effective in maintaining rSO2 in patients who underwent CEA. Clinical Trial Registration ClincalTrials.gov, NCT01451294.


title: Morbidity, mortality, and weight loss outcomes after reoperative bariatric surgery in the USA.

text: BACKGROUND Obesity is successfully treated by bariatric operations, but some patients need reoperations. No large national studies are available to evaluate the safety and efficacy after reoperative bariatric surgery. METHODS Data from June 2007 through March 2012 from the Bariatric Outcomes Longitudinal Database were queried for safety and efficacy of reoperations and compared to those who had initial bariatric operations but did not undergo reoperations. Reoperations were subdivided into corrective operations and conversions. RESULTS Out of 449,753 bariatric operations, 28,720 (6.3%) underwent reoperations of which 19,970 (69.5%) were corrective and 8,750 (30.5%) were conversions. The conversion group compared to primary operations was older (47.63 ± 10.8 vs. 45.5 ± 11.8 years), had less males (13.5 vs. 21.3%), and had more African Americans (14.6 vs. 12%). Comparing primary operations to corrective and conversions operations, respectively, the following were observed: length of stay (1.78 ± 4.95 vs. 2.04 ± 6.44 and 2.86 ± 4.58 days), severe adverse events at 30 days (1.6 vs. 1.7 and 3.3%), severe adverse events at 1 year (2.15 vs. 1.9 and 3.61%), percent excess weight loss at 1 year (43.2 vs. 35.9 ± 92.4 and 39.3 ± 39.9%), 30-day mortality rate (0.1 vs. 0.12 and 0.21%), and 1-year mortality rate (0.17 vs. 0.24 and 0.31%). Comorbidities were resolved after both primary operations and reoperations. CONCLUSIONS Most bariatric surgery patients do not need reoperations. Among those who do, the complication rate is low and outcomes are clinically comparable to primary procedures.


title: Establishment of human clones producing neutralizing human monoclonal antibodies to the envelope E1/E2 protein of hepatitis C virus by EBV immortalization of immune CD22⁺ B cells.

text: We aimed to establish Human cell lines producing human monoclonal antibodies to the envelope E1/E2 protein of hepatitis C virus (HCV). Two protocols for EBV immortalization of CD22⁺ cells separated from HCV positive patients were used; 1) Immortalization with 100% EBV only, 2) immortalization by 30% EBV and CPG2006. Immortalization was checked microscopically and verified by screening the culture supernatant for antibody production using dot blot and ELISA analysis. ELISA plates were coated by HCV E1/E2 derived from cell lysate transfected by plasmid expressed HCV E1/E2. Also we tested the reactivity of human antibodies based on ELISA plates coating with one linear peptides derived from HCV E1 (a.a 315-319) and two peptides derived from HCV E2 (a.a 412-419) and (a.a 517-530). Neutralization activity was measured using H77C HCV retroviral pseudoparticles (HCVpp). Fifteen clones secreting human immunoglobulin G against HCV E1/E2 protein were isolated. Results of ELISA plates coated with HCV peptides showed that one antibody was binding to E2 peptide (a.a 517-530), and two antibodies binding to HCV E2 peptide (a.a 412-419). The three generated antibodies showed extremely neutralization activity against HCV pp. The three human antibodies were IgG3 and IgG2. These antibodies may be useful for passive immunotherapy of HCV infection.


title: Web-Based Multidomain Lifestyle Programs for Brain Health: Comprehensive Overview and Meta-Analysis.

text: BACKGROUND The number of people living with dementia is increasing worldwide, mainly because of aging of the population. To date, there is no pharmaceutical intervention to delay or treat cognitive decline or dementia. As an estimated one-third of dementia cases might be attributable to modifiable lifestyle factors (such as cognitive and physical activity), multidomain lifestyle interventions are a promising way to maintain or improve brain health. Offering programs online would enable large-scale implementation. An overview of multidomain Web-based lifestyle programs for brain health would facilitate comparison and improvement of such programs to develop effective and sustainable interventions. OBJECTIVE This study aimed to (1) provide a comprehensive overview of Web-based multidomain lifestyle programs aimed at optimizing brain health in healthy adult populations and (2) describe the programs and targeted lifestyle factors, availability, and evaluation of adherence and user experience. In addition, a meta-analysis was performed to evaluate the effectiveness of these programs. METHODS Electronic databases (PubMed, EMBASE, and PsycINFO) were searched for Web-based lifestyle programs that were included when the program (1) aimed to optimize brain health, (2) focused on multiple lifestyle factors, (3) was completely Web-based (website, Web application or mobile app), (4) consisted of multiple sessions, and (5) focused on a healthy adult population. Program characteristics (target population, duration, frequency, tailoring, platform, and availability) and results of program evaluations (effectiveness, user evaluations, and adherence) were extracted and compared. Studies using a controlled design were included in a random-effects meta-analysis on the effectiveness on brain health outcomes. Study quality was assessed using the physiotherapy evidence database (PEDro) scale. RESULTS The electronic searches yielded 44 documents describing 14 Web-based lifestyle programs; physical and cognitive activities were targeted in all programs. Four programs (4/14, 29%) were publicly available and free of charge, whereas others were restricted to research settings (5/14, 36%), available after payment (1/14, 7%), or not available at all (2/14, 14%). User evaluations were reported for 8 (57%) of the 14 programs. Reported dropout of the intervention groups ranged from 2% to 52%. Overall, 3 studies evaluated the effectiveness of a program using a controlled design and were included in the meta-analysis (moderate-to-high quality). Pooled results showed a significant small-to-medium effect of the Web-based multidomain lifestyle interventions on outcome measures for brain health (global cognition score, subjective cognitive score, and lifestyle risk score; standard mean difference=0.45; 95% CI 0.12-0.78), with a high degree heterogeneity across studies (I2=75%; P=.02). CONCLUSIONS In total, 14 Web-based multidomain lifestyle programs aimed at optimizing brain health were found. The programs showed heterogeneity in both characteristics and effectiveness evaluation. Despite this heterogeneity, this meta-analysis suggests that Web-based lifestyle programs can positively influence brain health outcomes and have the potential to contribute to the prevention of dementia.


title: CoViD-19 in Italy: homeless population needs protection.

text: Italy is one of the most affected countries by the new coronavirus (CoViD-19) pandemic. In the country, there are an estimated 49,000-52,000 homeless people. People experiencing homelessness are among the potentially most vulnerable groups to the CoViD-19. Despite this, in Italy there is a worrying delay in implementation of a national coordinated strategy to protect homeless people from the potentially devastating effects caused by CoViD-19. In order to contain the epidemic among the most vulnerable people, we propose a short operational agenda based on the field experience of the medical-humanitarian organization Medici per i Diritti Umani (Doctors for Human Rights, Italy - MEDU) as well as on the example of initiatives taken by other countries.


title: Prevalence of COVID-19-like symptoms among people living with HIV, and using antiretroviral therapy for prevention and treatment.

text: BACKGROUND COVID-19 has spread globally with remarkable speed, and currently, there is limited data available exploring any aspect of the intersection between HIV and SARS-CoV-2 co-infection. OBJECTIVE To estimate the prevalence of clinical symptoms associated with COVID-19 among people living with HIV (PLWH) in Tehran, Iran. DESIGN Cross-sectional study. METHODS A total of 200 PLWH were recruited through the positive club via sampling, and completed the symptom-based questionnaire for COVID-19, which was delivered by trained peers. RESULTS Of 200 participants, respiratory symptoms, including cough, sputum, and shortness of breath were the most prevalent among participants, but only one person developed symptoms collectively suggested COVID-19 and sought treatments. CONCLUSIONS It appears that existing infection with HIV or receiving ART might reduce the susceptibility to the infection with SARS-CoV-2 or decrease the severity of the infection acquired. Further research is needed to understand causal mechanisms.


title: Pyrexia in cats: Retrospective analysis of signalment, clinical investigations, diagnosis and influence of prior treatment in 106 referred cases.

text: OBJECTIVES The main aim of the study was to describe the features and diagnoses of a population of cats referred with pyrexia. Other aims were to report and evaluate the utility of clinical investigations performed, and describe any effect of treatment before referral on temperature at presentation and ability to make a diagnosis. METHODS Clinical records of cats with pyrexia (⩾39.2°C) documented at least twice were retrospectively reviewed. Cases were assigned to disease categories (infectious, inflammatory, immune-mediated, neoplastic, miscellaneous and no diagnosis [pyrexia of unknown origin, PUO]) based on diagnosis. The overall value of clinical investigations was assessed by classifying them as 'enabling', 'assisting' or 'no assistance' in achieving each diagnosis. The effect of treatment before referral was assessed for any association with temperature at presentation and ability to make a diagnosis (PUO vs other disease categories). RESULTS One hundred and six cases were identified. The most common cause of pyrexia was feline infectious peritonitis (22 cats, 20.8%) and the largest disease category was infectious (41/106, 38.7%). Inflammatory conditions were found in 19 (17.9%) cats, neoplasia in 13 (12.3%), miscellaneous causes in 11 (10.4%) and immune-mediated disease in six (5.7%). No diagnosis was reached in 16 (15.0%) cats, often despite extensive diagnostic investigations. Cytology and histopathology most often 'enabled' or 'assisted' in obtaining a diagnosis. Most cats (91, 85.8%) received treatment before referral, with antimicrobial treatment given to 87 (82.1%). Prior treatment before referral was not associated with temperature at presentation nor with success in establishing a diagnosis. CONCLUSIONS AND RELEVANCE This is the first study investigating causes of pyrexia in cats. Infectious diseases were most common and immune-mediated diseases were comparatively rare.


title: Management of acute kidney injury in COVID-19.

text: Acute kidney injury has been reported in as many as 29% of COVID-19 patients. Reported risk factors include elevated baseline serum creatinine, elevated blood urea nitrogen, acute kidney injury, proteinuria, and hematuria. Suspected causes include sepsis and acute tubular necrosis resulting from renal hypoperfusion, cytokine release syndrome, direct viral invasion, renal medullary hypoxia secondary to alveolar damage, rhabdomyolysis, and cardiorenal syndrome due to viral myocarditis.


title: 1H NMR derived metabolomic profile of neonatal asphyxia in umbilical cord serum: implications for hypoxic ischemic encephalopathy.

text: Neonatal hypoxic ischemic encephalopathy (HIE) is a severe consequence of perinatal asphyxia (PA) that can result in life-long neurological disability. Disease mechanisms, including the role and interaction of individual metabolic pathways, remain unclear. As hypoxia is an acute condition, aerobic energy metabolism is central to global metabolic pathways, and these metabolites are detectable using 1H NMR spectroscopy, we hypothesized that characterizing the NMR-derived umbilical cord serum metabolome would offer insight into the consequences of PA that lead to HIE. Fifty-nine at-risk infants were enrolled, together with 1:1 matched healthy controls, and stratified by disease severity (n=25, HIE; n=34, non-HIE PA). Eighteen of 37 reproducibly detectable metabolites were significantly altered between study groups. Acetone, 3-hydroxybutyrate, succinate, and glycerol were significantly differentially altered in severe HIE. Multivariate data analysis revealed a metabolite profile associated with both asphyxia and HIE. Multiple-linear regression modeling using 4 metabolites (3-hydroxybutyrate, glycerol, O-phosphocholine, and succinate) predicted HIE severity with an adjusted R2 of 0.4. Altered ketones suggest that systemic metabolism may play a critical role in preventing neurological injury, while altered succinate provides a possible explanation for hypoxia-inducible factor 1-α (HIF-1α) stabilization in HI injury.


title: The ketogenic diet as a treatment for traumatic brain injury: a scoping review.

text: Traumatic brain injury (TBI) is a leading cause of morbidity and mortality worldwide. The ketogenic diet (KD) has been identified as a potential therapy to enhance recovery after TBI. The purpose of this study is to complete a scoping review and synthesize the evidence regarding the KD and its therapeutic effects in TBI. The methodological framework of Arksey and O'Malley was employed. Databases searched include Medline, EMBASE, CCRCT, CINAHL and WebOfScience. Two reviewers independently screened titles, abstracts and full texts in a two-step screening protocol to determine inclusion. Abstracted data included study setting and therapeutic mechanism. The KD was demonstrated to reduce cerebral oedema, apoptosis, improve cerebral metabolism and behavioural outcomes in rodent TBIs. Additionally, the KD affected rodent TBIs in an age-dependent manner. Due to a lack of relevant outcome measures, the human trials did not establish much evidence with respect to the KD as a treatment for TBI; only its safety was established. The KD is an effective treatment for TBI recovery in rats and shows potential in humans. Future research should aim to better elucidate the KD's mechanisms of action in human TBIs and determine if the KD's effectiveness on clinical outcomes can be reproduced in humans.


title: Near-infrared spectroscopy for assessing microcirculation during laparoscopic gynaecological surgery under combined spinal-general anaesthesia or general anaesthesia alone: a randomised controlled trial.

text: While pneumoperitoneum causes negative macrohaemodynamic effects, much less is known about microcirculatory effects of different anaesthetic techniques and laparoscopy. Therefore, we aimed to explore microcirculatory effects of combined spinal-general anaesthesia and laparoscopy, as measured by near-infrared spectroscopy over forearm and calf muscles utilising a 3-min ischemic challenge. Patients (n = 102) undergoing elective laparoscopic gynaecological surgery were randomised to receive general anaesthesia alone or in combination with high-dose or low-dose spinal analgesia (levobupivacaine 7.5 mg or 3.75 mg, respectively, plus sufentanil 2.5 μg). Primary outcomes were near-infrared spectroscopy derived parameters before general anaesthesia induction, 5 min after tracheal intubation, and 15 min after pneumoperitoneum commencement. General anaesthesia resulted in impaired post-ischaemic recovery rate in the forearm (p < 0.001, within all groups), which improved during laparoscopy. For the calf, before general anaesthesia induction, high and low dose spinal analgesia significantly slowed the post-ischaemic recovery compared to control (34 ± 16% min-1 and 36 ± 13% min-1 vs. 52 ± 27% min-1, respectively; p = 0.002 and p = 0.006). General anaesthesia abolished differences between the groups (24 ± 14% min-1 and 25 ± 12% min-1 vs. 27 ± 18% min-1), while during laparoscopy high-dose spinal analgesia further reduced the post-ischaemic recovery compared to low-dose spinal and control groups (p = 0.023 and p = 0.040, respectively). During gynaecological laparoscopy patients show impaired calf but maintain forearm microcirculatory function, regardless of the anaesthetic technique. Reduction in post-ischaemic recovery with high-dose spinal analgesia is explained by its sympatholytic effects: number of perfused capillaries is increased, leading to a haemodynamically more favourable state. Blood pressure is positively correlated with the post-ischaemic recovery rate in vascular beds not affected by spinal analgesia.


title: A 3-Dimensional Biomimetic Platform to Interrogate the Safety of Autologous Fat Transfer in the Setting of Breast Cancer.

text: INTRODUCTION Obesity is a known risk factor for the development and prognosis of breast cancer. Adipocytes have been identified as a source of exogenous lipids in other cancer types and may similarly provide energy to fuel malignant survival and growth in breast cancer. This relationship is of particular relevance to plastic surgery, because many reconstructions after oncologic mastectomy achieve optimal aesthetics and durability using adjunctive autologous fat transfer (AFT). Despite the increasing ubiquity and promise of AFT, many unanswered questions remain, including safety in the setting of breast cancer. Clinical studies to examine this question are underway, but an in vitro system is critical to elucidate the complex interplay between the cells that normally reside at the surgical recipient site. To study these interactions and characterize possible lipid transfer between adipocytes to breast cancer cells, we designed a 3-dimensional in vitro model using primary patient-derived tissues. METHODS Breast adipose tissue was acquired from patients undergoing breast reduction surgery. The tissue was enzymatically digested and sorted to retrieve adipocytes and adipose stromal cells. Polydimethylsiloxane wells were filled with type I collagen-encapsulated adipocytes labeled with the fluorescent lipid dye boron dipyrromethene, as well as unlabeled adipose stromal cells. A monolayer of red fluorescently labeled MDA-MB-231 and MDA-MB-468 breast cancer cells was seeded on the surface of the construct. Lipid transfer at the interface between adipocytes and breast cancer cells was analyzed. RESULTS Confocal microscopy revealed a dense culture of native adipocytes containing fluorescent lipid droplets in the 3-dimensional collagen culture platform. RFP-positive breast cancer cells were found in close proximity to lipid-laden adipocytes. Lipid transfer from adipocytes to breast cancer cells was observed by the presence of boron dipyrromethene-positive lipid droplets within RFP-labeled breast cancer cells. CONCLUSION We have established a 3-dimensional model to study complex breast cancer-adipose tissue interactions. Direct transfer of fluorescently labeled lipids from adipocytes to breast cancer cells may indicate aberrant metabolism to fuel malignant growth and adaptive survival. Our novel platform can untangle the complex interplay within the breast cancer tumor microenvironment for high-throughput analysis and better elucidate the safety of AFT in postoncologic mastectomy.


Where Do the Children Play?


title: Collateral circulation prevents masticatory muscle impairment in rat middle cerebral artery occlusion model.

text: The rat suture middle cerebral artery occlusion (MCAO) is a frequently used animal model for investigating the mechanisms of ischemic brain injury. During suture MCAO, transection of the external carotid artery (ECA) potentially restrains blood flow and impairs masticatory muscle and other ECA-supported territories, consequently influencing post-operation animal survival. This study was aimed at investigating the effect of ECA transection on the hemodynamic alterations using a novel synchrotron radiation (SR) angiography technique and magnetic resonance imaging in live animals. Fifteen male adult Sprague-Dawley rats were used in this study. Animals underwent MCAO, in which the ECA was transected. SR angiography was performed before and after MCAO. Rats then underwent magnetic resonance imaging (MRI) to detect the tissue lesion both intra- and extra-cranially. Animals with SR angiography without other manipulations were used as control. High-resolution cerebrovascular morphology was analyzed using a novel technique of SR angiography. The masticatory muscle lesion was further examined by hematoxylin and eosin staining. MRI and histological results showed that there was no masticatory muscle lesion at 1, 7 and 28 days following MCAO with ECA transection. In normal condition, the ECA and its branch external maxillary artery were clearly detected. Following ECA transection, the external maxillary artery was still observed and the blood supply appeared from the anastomotic branch from the pterygopalatine artery. SR angiography further revealed the inter-relationship of hemisphere extra- and intra-cranial vasculature in the rat following MCAO. Transection of the ECA did not impair masticatory muscles in rat suture MCAO. Interrupted blood flow could be compensated by the collateral circulation from the pterygopalatine artery.


Covid-19: are we getting the communications right?


COVID-19 Interview: Dr. Belgin Eroğlu Kesim on Women in Science Advancing SARS-CoV-2 Tests-"One Health" and Changing the World for the Better.


title: Hepatectomy Combined with Diaphragmatic Resection for Hepatocellular Carcinoma with Diaphragmatic Involvement: A Propensity Score-Matched Analysis.

text: PURPOSE We evaluated the short- and long-term surgical outcomes of hepatectomy combined with diaphragmatic resection for hepatocellular carcinoma (HCC) with diaphragmatic involvement. METHODS We retrospectively reviewed the surgical outcomes of HCC patients with diaphragmatic resection (DR group) and HCC patients without diaphragmatic resection (non-DR group). We applied 1:1 propensity score matching (PSM) to these subjects. RESULTS The study included 46 patients in DR group and 828 patients in non-DR group. The DR group cases were pathologically more advanced, and both overall and relapse-free survival among the patients in this group with pathological diaphragmatic invasion were similar to cases with pathological diaphragmatic fibrous adhesion. There were 40 patients from each group subjected to PSM. In these matched cohorts, there was no statistically significant difference between the two groups regarding perioperative outcomes, overall survival, and relapse-free survival. Multivariate analyses of our matched HCC patients revealed that alpha-fetoprotein expression and tumor size were independent prognostic factors for overall survival and poor differentiation for relapse-free survival, whereas neither diaphragmatic invasion nor diaphragmatic resection were prognostic indicators. The most frequent site of recurrence in non-DR group was the liver, whereas the most frequent site of recurrence in DR group was the lung before and after PSM. CONCLUSIONS The short- and long-term surgical outcomes of DR HCC cases are equivalent to their non-DR counterparts under a matched clinicopathological background. Hepatectomy combined with DR is an acceptable treatment for HCC with either diaphragmatic fibrous adhesion or diaphragmatic invasion.


title: Pathophysiology of SARS-CoV-2 infection in patients with intracerebral hemorrhage.

text: Intracerebral hemorrhage (ICH) is associated with old age and underlying conditions such as hypertension and diabetes. ICH patients are vulnerable to SARS-CoV-2 infection and develop serious complications as a result of infection. The pathophysiology of ICH patients with SARS-CoV-2 infection includes viral invasion, dysfunction of the ACE2-Ang (1-7)-MasR and ACE-Ang II-AT1R axes, overactive immune response, cytokine storm, and excessive oxidative stress. These patients have high morbidity and mortality due to hyaline membrane formation, respiratory failure, neurologic deficits, and multiple organ failure.


title: Management of central nervous system demyelinating diseases during the coronavirus disease 2019 pandemic: a practical approach.

text: BACKGROUND The novel coronavirus disease 2019 (COVID-19) pandemic poses a potential threat to patients with autoimmune disorders, including multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). Such patients are usually treated with immunomodulatory or immunosuppressive agents, which may tamper with the organism's normal response to infections. Currently, no consensus has been reached on how to manage MS and NMOSD patients during the pandemic. OBJECTIVE To discuss strategies to manage those patients. METHODS We focus on how to 1) reduce COVID-19 infection risk, such as social distancing, telemedicine, and wider interval between laboratory testing/imaging; 2) manage relapses, such as avoiding treatment of mild relapse and using oral steroids; 3) manage disease-modifying therapies, such as preference for drugs associated with lower infection risk (interferons, glatiramer, teriflunomide, and natalizumab) and extended-interval dosing of natalizumab, when safe; 4) individualize the chosen MS induction-therapy (anti-CD20 monoclonal antibodies, alemtuzumab, and cladribine); 5) manage NMOSD preventive therapies, including initial therapy selection and current treatment maintenance; 6) manage MS/NMOSD patients infected with COVID-19. CONCLUSIONS In the future, real-world case series of MS/NMOSD patients infected with COVID-19 will help us define the best management strategies. For the time being, we rely on expert experience and guidance.


title: How to manage smoke evacuation and filter pneumoperitoneum during laparoscopy to minimize potential viral spread: different methods from SoMe.

text: Even if previous studies on HBV showed that hepatitis virus could be found in the intrabdominal gas, there is no evidence of SARS-CoV2 particles in the gas used during laparoscopy so far, but it is prudent to perform laparoscopy with safety strategies to avoid diffusion of potentially infected intrabdominal aerosol in the operating room.


title: Modified balloon assisted coil embolization for the treatment of intracranial and cervical arterial aneurysms using coaxial dual lumen balloon microcatheters: initial experience.

text: INTRODUCTION Traditional balloon assisted coil embolization techniques for intracranial aneurysms require a single lumen balloon to remodel the aneurysm neck and a separate microcatheter to place coils. Here we report utilization of a single coaxial dual balloon microcatheter to achieve both coil placement and neck remodeling in a series of intracranial and cervical arterial aneurysms. MATERIALS AND METHODS A series of five patients, including two with subarachnoid hemorrhage, presented to our institution with wide necked oblong aneurysms (8-30 mm maximum diameter). Coil embolization in four of these aneurysms was performed by advancing the tip of either a 4×10 mm Scepter C or a 4×11 mm Scepter XC balloon microcatheter (Microvention, Tustin, USA) into the aneurysm, inflating the balloon at the aneurysm neck, and placing the coils through the same microcatheter. In the fifth patient, who had a giant aneurysm at the top of the basilar artery, two Scepter XC balloon microcatheters were placed side by side and inflated simultaneously at the neck of the aneurysm; coil embolization was then successfully performed through both Scepter XC microcatheters. RESULTS Coil embolization was successfully performed with this technique in all five aneurysms. There was no instance of aneurysm rupture, thromboembolic complications, occlusion of branch vessels near the aneurysm neck, or prolapse of coil loops into the parent vessel. CONCLUSIONS Aneurysmal neck remodeling and coil embolization can both be achieved using a single coaxial dual lumen balloon microcatheter in selected oblong intracranial and cervical arterial aneurysms.


Time-limited vs unlimited physician certification--reply.


title: Prevention of Infectious Diseases due to Immunosuppression and Vaccinations in Asian Patients with Inflammatory Bowel Disease.

text: Background Inflammatory bowel disease (IBD) patients with immunocompromise have a high risk of developing complications related to viral infections. Western countries were the first to formulate vaccine guideline. Asian countries developed their national and international vaccine guidelines a little later in order to reduce the risk of mortality from viral infections. However, no studies to date have examined the differences in vaccinations that prevail among Asian countries. Summary This review summarizes the vaccination status and schedules in various Asian countries for immunocompromised IBD patients. Vaccination rates, regardless of the specific vaccine, were high in Japan, South Korea, and China and low in India and the Philippines. Vaccine schedules differed by country, and outbreaks of measles and rubella were seen due to low vaccination rates in Southeast Asia and South Asia. Live vaccines cannot be administered during immunosuppressive treatment. Infection with measles, mumps, and varicella during immunosuppressive therapy carries a high risk of mortality, and thus confirmation of immunization status is recommended as soon as IBD is diagnosed and, when possible, live vaccines should be administered before the initiation of immunosuppressive treatment. In patients seronegative for hepatitis B, administration of the hepatitis B vaccine is also recommended. Key Messages Physicians, while considering severity of outbreaks, should understand the differences in vaccination status that exist among the various Asian countries and regions.


Debate about funding comparative-effectiveness research.


title: Video-assisted thoracic surgery anatomical lobectomy for a primary lung tumor in a dog.

text: A female Bernese Mountain Dog was diagnosed with a right middle lung lobe mass. The dog was positioned in a left lateral recumbency and one-lung ventilation was used under general anesthesia. Video-assisted thoracic surgery anatomical lobectomy was performed with 4 cm small thoracotomy and two 6-mm ports. Pulmonary vessels and bronchus were dissected and isolated individually at the hilum of the right middle lung lobe. Pulmonary vessels were ligated and were coagulated and transected using a vessel sealing device. The bronchus was ligated and transected. The mass in the right middle lung lobe was removed with a clean margin and without complications. Video-assisted thoracic surgery anatomical lobectomy was used to successfully remove a primary lung tumor in a dog.


title: Effect of head rotation during surgery in the prone position on regional cerebral oxygen saturation: A prospective controlled study.

text: BACKGROUND Near-infrared spectroscopy (NIRS) has been used to study regional cerebral blood oxygen saturation (rScO2) in patients in the prone position. OBJECTIVES We aimed to test the hypothesis that head rotation more than 45° would affect the rScO2. DESIGN A prospective, controlled, single cohort study. SETTING University Hospital specialising in spinal surgery. PATIENTS Fifty-two patients undergoing spinal surgery in prone position were enrolled and 48 completed the study. INTERVENTIONS NIRS sensors were attached to each side of the forehead. Measurements were conducted during steady-state anaesthesia with the head in the neutral position, rotated left, rotated right and returned to the neutral position. Each series consisted of three measurements: resting on the head support, during head lift (to relieve pressure on the tissue at the sensors) and returned to rest on the head support. MAIN OUTCOME MEASURES The differences in rScO2 between the neutral and the turned head positions. RESULTS For both left and right sensors, the median differences in rScO2 between neutral and left or right positions were between 0 and -1 with the head up (P = 0.14 to 0.84). The median differences with the head down were between 3.8 and -0.8, with a significant difference for the left sensor when turned left (P < 0.01) and for the right sensor (P = 0.006) when turned right. Ten patients showed reductions of more than 10 in rScO2 in the rotated (and lifted) positions. When the head was lifted from the head support, the rScO2 was -0.5 to 3.75 units higher, but there was high variability between patients. CONCLUSION We recommend the neutral head position for prone patients.TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01760369.


title: Comparison of laparoscopic jejunostomy tube to percutaneous endoscopic gastrostomy tube with jejunal extension: long-term durability and nutritional outcomes.

text: INTRODUCTION Enteral access through the jejunum is indicated when patients cannot tolerate oral intake or gastric feeding. While multiple approaches for feeding jejunal access exist, few studies have compared the efficacy of these techniques. The purpose of this study was to investigate the long-term durability, re-intervention rates, and nutritional outcomes following percutaneous endoscopic gastrostomy tubes with jejunal extension tubes (PEG-JET) versus laparoscopic jejunostomy tubes (j-tubes). METHODS Retrospective chart review was performed on all patients who underwent PEG-JET or laparoscopic jejunostomy tube placement from January 2005 through December 2015 at our institution. Thirty-day and long-term outcomes were compared between the two groups. RESULTS A total of 105 patients underwent PEG-JET and 307 patients underwent laparoscopic j-tube placement during the defined study period. In terms of 30-day outcomes, patients who underwent PEG-JET placement were significantly more likely to experience a tube dislodgement event (p = 0.005) and undergo a re-intervention (p < 0.001). Patients who had a laparoscopic j-tube placed were significantly more likely to meet their enteral feeding goals (p = 0.002) and less likely to require nutritional supplementation with total parenteral nutrition (TPN) (p < 0.001). With regard to long-term outcomes, patients who underwent PEG-JET placement were significantly more likely to experience tube occlusion (p < 0.001) and require an endoscopic or surgical tube re-intervention (p < 0.001). Patients who underwent laparoscopic j-tube placement were significantly more likely to experience a tube site leak (p = 0.015) but were less likely to require nutritional supplementation with TPN (p = 0.001). CONCLUSION Laparoscopic jejunostomy tubes provide more durable long-term enteral access compared to PEG-JET. Consideration should be given to laparoscopic jejunostomy tube placement in eligible patients who cannot tolerate oral intake or gastric enteral feeding.


title: Single-pedicle hinge flap performed by shelter medicine team resolves chronic antebrachial wound in a cat.

text: CASE SUMMARY An approximately 3-year-old, male domestic longhair cat was presented to a mobile veterinary unit for routine neuter. Preoperative physical examination revealed an approximately 5 cm × 2 cm scab on the craniolateral portion of the left antebrachium. The cat was anesthetized for the neuter using an injectable anesthesia protocol. After castration, the wound area on the antebrachium was clipped, copiously lavaged and the wound edges were surgically debrided. Injectable antibiotics and analgesic management were instituted. The wound was conservatively managed using sugar bandaging and antibiotic dressings until the progression of healing plateaued. Procedures for closing the defect were explored, and it was decided that a single-pedicle hinge flap would be ideal. The procedure was performed on the mobile veterinary unit and managed postoperatively with pain control and biweekly bandage changes. After 3 weeks, the single-pedicle hinge flap was released to create a skin graft, which successfully filled the defect. RELEVANCE AND NOVEL INFORMATION Single-pedicle hinge flaps performed in feline patients have been minimally reported. This case report serves to provide detailed information on the surgical procedure and aftercare required for a successful outcome. Furthermore, this procedure was performed by a shelter medicine team in a mobile veterinary unit with no specialty equipment or instruments. This report documents an alternative procedure that may be used in a shelter environment for distal forelimb wounds rather than amputation or euthanasia.


title: Use of the iTClamp versus standard suturing techniques for securing chest tubes: A randomized controlled cadaver study.

text: Objectives Tube thoracostomy (TT) is a common yet potentially life-saving trauma procedure. After successful placement however, securing a TT through suturing is a skillset that requires practice, risking that the TT may become dislodged during prehospital transport. The purpose of this study was to examine if the iTClamp was a simpler technique with equivalent effectiveness for securing TTs. Materials and methods In a cadaver model, a 1.5 inch incision was utilized along the upper border of the rib below the 5th intercostal space at the anterior axillary line. TTs (sizes 28Fr, 32Fr, 36Fr and 40Fr) were inserted and secured with both suturing and iTClamp techniques according to the preset randomization. TT were then functionally tested for positive and negative pressure as well as the force required to remove the TT (pull test-up to 5 lbs). Time to secure the TT was also recorded. Results When sutured is placed by a trained surgeon, the sutures and iTClamp were functionally equivalent for holding a positive and negative pressure. Mean pull force for both sutures and iTClamp exceeded the 5 lb threshold; there was no significant difference between the groups. Securing the TT with the iTClamp was significantly faster (p < 0.0001) with the iTClamp having a mean application time of 37.0 ± 22.8 s and using a suture had a man application time of 96.3 ± 29.0 s. Conclusion The iTClamp was effective in securing TTs. The main benefit to the iTClamp is that minimal skill is required to adequately secure a TT to ensure that it does not become dislodged during transport to a trauma center.


title: Association between male sex and outcomes of Coronavirus Disease 2019 (Covid-19) - a Danish nationwide, register-based study.

text: BACKGROUND AND OBJECTIVES Male sex has been associated with severe Coronavirus disease 2019 (Covid-19) infection. We examined the association between male sex and severe Covid-19 infection and if an increased risk remains after adjustment for age and comorbidities. METHODS Nationwide register-based follow-up study of Covid-19 patients in Denmark until May 16, 2020. Average risk ratio comparing 30-day composite outcome of all-cause death, severe Covid-19 diagnosis or intensive care unit (ICU) admission for men versus women standardized to the age and comorbidity distribution of all patients were derived from multivariable Cox regression. Included covariates were age, hypertension, diagnoses including obesity, alcohol, sleep apnea, diabetes, chronic obstructive pulmonary disease, previous myocardial infarction (MI), ischemic heart disease (IHD), heart failure (HF), atrial fibrillation (AF), stroke, peripheral artery disease, cancer, liver-, rheumatic-, and chronic kidney disease (CKD). RESULTS Of 4,842 Covid-19 patients, 2,281 (47.1%) were men. Median age was 57 [25%-75% 43-73] for men versus 52 [38-71] for women (P<0.001); however, octogenarians had equal sex distribution. Alcohol diagnosis, diabetes, hypertension, sleep apnea, prior MI and IHD (all P<0.001) as well as AF, stroke and HF (all P=0.01) were more often seen in men, and so was CKD (P=0.03). Obesity diagnosis (P<0.001) were more often seen in women. Other comorbidity differences were insignificant (P>0.05). The fully adjusted average risk ratio was 1.63 [95% CI 1.44-1.84]. CONCLUSIONS Men with Covid-19 infection have >50% higher risk of all-cause death, severe Covid-19 infection, or ICU admission than women. The excess risk was not explained by age and comorbidities.


title: COVID-KOP: Integrating Emerging COVID-19 Data with the ROBOKOP Database.

text: In response to the COVID-19 pandemic, we established COVID-KOP, a new knowledgebase integrating the existing ROBOKOP biomedical knowledge graph with information from recent biomedical literature on COVID-19 annotated in the CORD-19 collection. COVID-KOP can be used effectively to test new hypotheses concerning repurposing of known drugs and clinical drug candidates against COVID-19. COVID-KOP is freely accessible at https://covidkop.renci.org/. For code and instructions for the original ROBOKOP, see: https://github.com/NCATS-Gamma/robokop.


title: Radiology of COVID-19 - Imaging the pulmonary damage.

text: A large part of the world is presently in the grip of the coronavirus disease (COVID-19) by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2 virus), declared a pandemic in March 2020. This document is a brief commentary of the imaging modalities used in the screening, diagnosis and management of COVID-19 pneumonia. Chest x-rays, especially portable, still form a part of majority of official guidelines, with reports of the suggestive radiologic features. The potential of CT scan and ultrasound is also realised, with earlier detection rate. Typical radiologic findings of bilateral, asymmetrical, crazy-paved ground glass opacification, consolidation, reverse halo sign, opacities, progressing to fibrosis are well described for both the X-ray and CT scan. Atypical findings include airway changes, pleural effusion, pulmonary nodules and acute pulmonary embolism. Absence of lymphadenopathy, pleural effusion and pneumothorax is notable. The role of portable lung ultrasound, reported to be useful in emergency, is yet to be established in the guidelines. Disinfection of the equipment is a major concern. Governmental guidelines still advocate X-ray despite professional societies increasingly recommending CT scan.


title: The use of self-gripping (Progrip™) mesh during laparoscopic total extraperitoneal (TEP) inguinal hernia repair: a prospective feasibility and long-term outcomes study.

text: BACKGROUND The use of self-gripping mesh during laparoscopic TEP inguinal hernia repairs may eliminate the need for any additional fixation, and thus reduce post-operative pain without the added concern for mesh migration. Long-term outcomes are not yet prospectively studied in a controlled fashion. METHODS Under IRB approval, from January 2011-April 2013, 91 hernias were repaired laparoscopically with self-gripping mesh without additional fixation. Patients were followed for at least 1 year. Demographics and intraoperative data (defect location, size, and mesh deployment time) are recorded. VAS is used in the recovery room (RR) to score pain, and the Carolinas Comfort Scale ™ (CCS), a validated 0-5 pain/quality of life (QoL) score where a mean score of >1.0 means symptomatic pain, is employed at 2 weeks and at 1 year. Morbidities, narcotic usage, days to full activity and return to work, and CCS scores are reported. RESULTS Sixty two patients, with 91 hernias repaired with self-gripping mesh, completed follow-up at a mean time period of 14.8 months. Seventeen hernias were direct defects (average size 3.0 cm). Mesh deployment time was 193.7 s. RR pain was 1.1/10 using a VAS. Total average oxycodone/acetaminophen (5 mg/325 mg) usage = 5.0 tablets, days to full activity was 1.6, and return to work was 4.2 days. Thirteen small asymptomatic seromas were palpated without any recurrences or groin tenderness, and all seromas resolved by the 6 month visit. Transient testis discomfort was reported in five patients. Urinary retention was 3.2%. Mean CCS™ scores at the first visit for groin pain laying, bending, sitting, walking, and step-climbing were 0.2, 0.5, 0.4, 0.3, and 0.3, respectively. At the first post op visit, 4.8% had symptomatic pain (CCS > 1). At 14.8 months, no patients reported symptomatic pain with CCS scores for all 62 patients averaging 0.02, (range 0-0.43). There are no recurrences thus far. CONCLUSIONS Self-gripping mesh can be safely used during laparoscopic TEP inguinal hernia repairs; our cohort had a rapid recovery, and at the 1-year follow-up visit, there were no recurrences and no patients reported any chronic pain as defined by a CCS™ > 1.


title: Catch me if you can: disappearing and reappearing posterior fossa dural arteriovenous malformation.

text: We report an unusual case of a dural arteriovenous fistula (dAVF) presenting as acute neck pain and quadripareis in a 55-year-old previously healthy man. Imaging was suspicious for cervicomedullary venous thrombosis and angiography failed to show evidence of arteriovenous malformation or dAVF. The patient was started on warfarin for a presumed cervicomedullary venous thrombosis and there was a significant clinical improvement. However, 3 weeks later, the symptoms recurred and repeat angiography revealed a dAVF fed by a posterior branch of the left middle meningeal artery draining into the posterior fossa vein. We postulated that warfarin caused recanalisation of the previously thrombosed venous pouch allowing for angiographic discovery and treatment of the dAVF. The dAVF was embolised with onyx resulting in the complete obliteration of the dAVF and symptomatic improvement. Although rare, some dAVF can be concealed or disappear on angiography due to thrombosis of the draining vein and warfarin can lead to recanalisation.


title: Laparoscopic Management of a Complex Adrenal Cyst.

text: Adrenal cysts are rare, and their clinical management remains controversial. We report a case involving an adrenal cyst with a complicated appearance on radiological studies. Unenhanced computed tomography revealed a unilocular, noncalcified, hypoattenuating mass with a thin wall in the left adrenal gland. The lesion gradually increased in size from 10 to 50 mm at two-year follow-up. On contrast-enhanced magnetic resonance imaging, a mural nodule with contrast enhancement was observed. The entire adrenal gland was excised en bloc via a lateral transperitoneal laparoscopic approach without violating the principles of surgical oncology. The pathological diagnosis was an adrenal pseudocyst. Laparoscopic adrenalectomy is a safe option for the treatment of complex adrenal cysts, while maintaining the benefits of minimal invasiveness.


title: Laparoscopic adrenalectomy for treatment of unilateral adrenocortical carcinomas: technique, complications, and results in seven dogs.

text: OBJECTIVE To investigate the feasibility of, and outcome after, laparoscopic adrenalectomy in dogs with unilateral adrenocortical carcinoma. STUDY DESIGN Case series. ANIMALS Dogs (n=7) with Cushing's syndrome caused by unilateral adrenocortical carcinoma. METHODS Laparoscopic adrenalectomy with the dog in lateral recumbency on the unaffected side. Three 5-mm portals (1 laparoscopic portal, 2 instrument portals) were placed in the paralumbar fossa. A fourth instrumental portal (5-12 mm) was placed above the kidney. After dissection and hemostatic control of the phrenicoabdominal vein, the adrenal gland was carefully dissected or when there was capsule fragility, necrotic content was partially aspirated. The remaining glandular tissue was removed through the 12-mm trocar site. RESULTS Dogs with unilateral adrenocortical carcinoma (3 right-sided, 4 left-sided) without invasion of the caudal vena cava were successfully operated by laparoscopic approach. There were no significant intraoperative complications; 2 dogs died within 48 hours of surgery because of respiratory complications. Five dogs were discharged 72 hours after surgery, and signs of hyperadrenocorticism disappeared thereafter (survival time ranged from 7 to 25 months). CONCLUSIONS Laparoscopic adrenalectomy is feasible in dogs with either right- or left-sided adrenocortical carcinoma not involving the caudal vena cava. CLINICAL RELEVANCE When performed by experienced surgeons, laparoscopic adrenalectomy offers a minimally invasive alternative to open laparotomy or retroperitoneal surgery for the treatment of unilateral adrenocortical carcinoma in dogs.


title: Isolation of CD4+ T cells from mouse lymph nodes using Miltenyi MACS purification.

text: Isolation of cells from the primary source is a necessary step in many more complex protocols. Miltenyi offers kits to isolate cells from several organisms including humans, non-human primates, rat and, as we describe here, mice. Magnetic bead-based cell separation allows for either positive selection (or cell depletion) as well as negative selection. Here, we demonstrate negative selection of untouched or na ve CD4+ helper T cells. Using this standard protocol we typically purify cells that are > or = 96% pure CD4+/CD3+. This protocol is used in conjunction with the protocol Dissection and 2-Photon Imaging of Peripheral Lymph Nodes in Mice published in issue 7 of JoVE, for purification of T cells and other cell types to adoptively transfer for imaging purposes. Although we did not demonstrate FACS analysis in this protocol video, it is highly recommended to check the overall purity of isolated cells using the appropriate antibodies via FACS. In addition, we demonstrate the non-sterile method of T cell isolation. If sterile cells are needed for your particular end-user application, be sure to do all of the demonstrated procedures in the tissue culture hood under standard sterile conditions. Thank you for watching and good luck with your own experiments!


Comprehensive endovascular treatment of multiple arterial emboli involving LIMA graft, distal aorta and upper and lower extremities in a patient with subacute cerebral hemorrhage.


title: Real-time transesophageal echocardiography facilitates antegrade balloon aortic valvuloplasty.

text: We report two cases of severe aortic stenosis (AS) where antegrade balloon aortic valvuloplasty (BAV) was performed under real-time transesophageal echocardiography (TEE) guidance. Real-time TEE can provide useful information for evaluating the aortic valve response to valvuloplasty during the procedure. It was led with the intentional wire-bias technique in order to compress the severely calcified leaflet, and consequently allowed the balloon to reach the largest possible size and achieve full expansion of the aortic annulus.


title: Putative suppressing effect of IgG Fc-conjugated haemagglutinin (HA) stalk of influenza virus H7N9 on the neutralizing immunogenicity of Fc-conjugated HA head: implication for rational design of HA-based influenza vaccines.

text: The emergence of influenza A H7N9 in infection has posed a great threat to public health globally. Poor immunogenicity of H7N9 haemagglutinin (HA) is a major obstacle to the development of an effective H7N9 vaccine. Here, we found that the vaccine containing the H7HA head conjugated with IgG Fc (Hd-Fc) induced strong neutralizing antibody responses and protection against H7N9 infection, whilst the Fc-conjugated H7HA stalk (St-Fc)-based vaccine could not induce neutralizing antibodies, although the St-Fc-immunized mice were partially protected. The vaccines containing the full-length extracellular domain of HA conjugated with Fc and the mixture of Hd-Fc plus St-Fc induced significantly lower neutralizing antibody and haemagglutination inhibition titres than the Hd-Fc-based vaccine. These results suggest that the St-Fc may have inhibitory effects on the neutralizing immunogenicity of Hd-Fc. Therefore, the neutralizing domain(s), such as the receptor-binding domain, in the HA head should be kept and the non-neutralizing domain(s) in the HA stalk with the ability to potentially suppress the neutralizing immunogenicity of HA head should be removed from Fc-conjugated HA-based influenza vaccines to increase the neutralizing antibody response.


Clinical and epidemiological characteristics of children with COVID-19.