title: Evaluation of unmet clinical needs in prophylaxis and treatment of venous thromboembolism in at-risk patient groups: pregnancy, elderly and obese patients.

text: Background Venous thromboembolism (VTE) accounts for an estimated 900,000 cases per year in the US alone and constitutes a considerable burden on healthcare systems across the globe. Objective To understand why the burden is so high, qualitative and quantitative research was carried out to gain insights from experts, guidelines and published studies on the unmet clinical needs and therapeutic strategies in VTE prevention and treatment in three populations identified as being at increased risk of VTE and in whom VTE prevention and treatment were regarded as suboptimal: pregnant women, the elderly and obese patients. Methodology A gap analysis methodology was created to highlight unmet needs in VTE management and to discover the patient populations considered most at risk. A questionnaire was devised to guide qualitative interviews with 44 thrombosis and haemostasis experts, and a review of the literature on VTE in the specific patient groups from 2015 to 2017 was completed. This was followed by a Think Tank meeting where the results from the research were discussed. Results This review highlights the insights gained and examines in detail the unmet needs with regard to VTE risk-assessment tools, biomarkers, patient stratification methods, and anticoagulant and dosing regimens in pregnant women, the elderly and obese patients. Conclusions Specifically, in pregnant women at high risk of VTE, low-molecular-weight heparin (LMWH) is the therapy of choice, but it remains unclear how to use anticoagulants when VTE risk is intermediate. In elderly patients, evaluation of the benefit of VTE prophylaxis against the bleeding risk is particularly important, and a head-to-head comparison of efficacy and safety of LMWH versus direct oral anticoagulants is needed. Finally, in obese patients, lack of guidance on anticoagulant dose adjustment to body weight has emerged as a major obstacle in effective prophylaxis and treatment of VTE.


This Spring Is Different.


title: Quantitative analysis of solid dosage forms of cefixime using Raman spectroscopy.

text: Quantification of antibiotics is of significant importance because of their use in the prevention and treatment of different diseases. Cefixime (CEF) is a cephalosporin antibiotic that is used against bacterial infections. In the present study, Raman spectroscopy has been applied for the identification and quantification of Raman spectral features of cefixime with different concentrations of Active Pharmaceutical Ingredient (API) and excipients in solid dosage forms. The changes in Raman spectral features of API and excipients in the solid dosage forms of cefixime were studied and Raman peaks were assigned based on the literature. Multivariate data analysis techniques including the Principal Component Analysis (PCA) and Partial Least Squares Regression analysis (PLSR) have been performed for the qualitative and quantitative analysis of solid dosage forms of cefixime. PCA was found helpful in differentiating all the Raman spectral data associated with the different solid dosage forms of cefixime. The coefficient of determination (R2), mean absolute error (MAE), and mean relative error (MRE) for the calibration data-set were 0.99, 0.72, and 0.01 respectively and for the validation data-set were 0.99, 3.15, and 0.02 respectively, that shows the performance of the model. The root mean square error of calibration (RMSEC) and root mean square error of prediction (RMSEP) were found to be 0.56 mg and 3.13 mg respectively.


title: Hydrofiber Dressing Saturated With Mafenide Acetate Extends the Duration of Antimicrobial Activity.

text: Mafenide acetate is used in some burn wounds for its ability to penetrate eschar but requires frequent uncomfortable dressing changes for its application. The authors hypothesize that hydrofiber dressings will hold mafenide acetate solution for an extended period of time and maintain antimicrobial activity longer than traditional gauze, thus possibly obviating the need for frequent dressing changes. Four experimental arms included: 1) hydrofiber, stored on a dry well plate as control, 2) gauze saturated with 2.5% mafenide acetate, stored on nonsterile porcine skin, 3) hydrofiber saturated with mafenide acetate, stored on dry well plate, and 4) hydrofiber saturated with mafenide acetate, stored on nonsterile porcine skin. At 0, 24, 48, and 72 hours, a 1-cm disk was cut from the dressing sheet of each study arm, placed on agar plates seeded with Staphylococcus aureus and Pseudomonas aeruginosa, and incubated for 24 hours, and the zone of inhibition was measured. A zone of 2 mm or greater was indicative of susceptibility. Each arm of the experiment was performed four times to demonstrate reproducibility. Plain hydrofiber (control) demonstrated no zone of inhibition at any time point, thereby possessing no antimicrobial activity alone. Gauze saturated with mafenide acetate did not reliably demonstrate antimicrobial activity beyond 0 hours. Hydrofiber saturated with mafenide acetate, whether stored on a dry well plate or nonsterile porcine skin, consistently possessed sustained antimicrobial activity as demonstrated by zones of inhibition greater than 2 mm to both S. aureus and P. aeruginosa. Mafenide acetate-soaked hydrofiber dressings stay moist and maintain antimicrobial activity against S. aureus and P. aeruginosa for at least 72 hours without repeated soaks.


SARS-CoV-2 infection in ambulatory and hospitalised Spanish children.


title: Surgical resection of ruptured fibrolamellar hepatocellular carcinoma.

text: Fibrolamellar hepatocellular carcinoma (FLH) is a rare primary tumor of the liver, which typically arises from noncirrhotic livers and affects patients below the age of 35. We report on a 29-year-old male patient who presented with a ruptured FLH and was treated with surgical resection. Options for treatment and review of the management are described.


title: Reversing the testing effect by feedback is a matter of performance criterion at practice.

text: Retrieval practice is generally considered to be one of the most effective long-term learning strategies and is presumed to be more favorable than repeated study. However, a few recent studies have demonstrated that repetitive feedback at final recall can reverse the long-term advantage of testing over restudy. The result that feedback at long-term tests can dramatically decrease the relative effectiveness of retrieval-based learning could be important for both theoretical and practical reasons. Considering that these earlier studies administered low retrieval success at retrieval practice, we investigated whether the effect of feedback on the testing effect is modulated by the level of retrieval success during practice. In three experiments the level of success at retrieval practice was manipulated by multiple pre-practice learning trials, and multiple tests with feedback were applied after a 1-week retention interval at final recall. Our results have demonstrated that a feedback-induced reversed testing effect was present only at low retrieval success during practice (Experiment 1), whereas with moderate (Experiment 2) and high retrieval success (Experiment 3) during practice a significant testing effect emerged and no reversed testing effect was found even after repeated cycles of feedback. These results point to the conclusion that the level of retrieval success was the key factor in reversing the testing effect in earlier studies. Application of high retrieval success during practice can produce long-lasting accessible memories even in learning settings applying multiple tests with feedback.


title: The impact of epidemic outbreak: the case of severe acute respiratory syndrome (SARS) and suicide among older adults in Hong Kong.

text: BACKGROUND Previous studies revealed that there was a significant increase in suicide deaths among those aged 65 and over in 2003. The peak coincided with the majority of SARS cases being reported in April 2003. AIMS In this paper we examine the mechanism of how the SARS outbreak resulted in a higher completed suicide rate especially among older adults in Hong Kong. METHODS We used Qualitative data analysis to uncover the association between the occurrence of SARS and older adult suicide. Furthermore, we used a qualitative study based on the Coroner Court reports to provide empirical evidence about the relationship between SARS and the excessive number of suicide deaths among the elderly. RESULTS SARS-related older adult suicide victims were more likely to be afraid of contracting the disease and had fears of disconnection. The suicide motives among SARS-related suicide deaths were more closely associated with stress over fears of being a burden to their families during the negative impact of the epidemic. Social disengagement, mental stress, and anxiety at the time of the SARS epidemic among a certain group of older adults resulted in an exceptionally high rate of suicide deaths. CONCLUSIONS We recommend that the mental and psychological well-being of the community, in particular older adults, be taken into careful account when developing epidemic control measures to combat the future outbreak of diseases in the community. In addition, it is important to alert family members to vulnerable individuals who are at potential risk because of their illnesses or anxieties.


title: Partial small bowel resection with sleeve gastrectomy increases adiponectin levels and improves glucose homeostasis in obese rodents with type 2 diabetes.

text: BACKGROUND The aim of this study was to examine the effect of small bowel resection with and without sleeve gastrectomy on glucose homeostasis in an obese rodent model of type 2 diabetes. METHODS Zucker diabetic fatty rats were randomized into three surgical groups: Sham, small bowel resection, and small bowel resection with sleeve gastrectomy (BRSG). Weight and fasting glucose levels were measured at randomization and monitored after surgery. Oral glucose tolerance testing was performed at baseline and 45 days after surgery to assess glucose homeostasis and peptide changes. RESULTS At baseline, all animals exhibited impaired glucose tolerance and showed no difference in weight or fasting (area under the curve) AUC(glucose). At sacrifice, Sham animals weighed more than BRSG animals (p = 0.047). At day 45, the Sham group experienced a significant increase in AUC(glucose) compared to baseline (p = 0.02), whereas there was no difference in AUC(glucose) in either surgical group at any time point: BR (p = 0.58) and BRSG (p = 0.56). Single-factor ANOVA showed a significant difference in AUC(glucose) of p = 0.004 between groups postoperatively: Sham (50,745 ± 11,170) versus BR (23,865 ± 432.6) (p = 0.01); Sham versus BRSG (28,710 ± 3188.8) (p = 0.02). There was no difference in plasma insulin, GLP-1, or adiponectin levels before surgery, although 45 days following surgery adiponectin levels where higher in the BRSG group (p = 0.004). CONCLUSIONS Partial small bowel resection improved glucose tolerance independent of weight. The combination of small bowel resection and sleeve gastrectomy leads to an increase in adiponectin levels, which may contribute to improved glucose homeostasis.


title: Establishing and managing a quarantine and isolation centre in COVID-19 pandemic.

text: The novel coronavirus disease (COVID-19) is a recent pandemic which has spread to over 200 countries of the world since its outbreak. As of 21st April, 2020, more than 2.3 million confirmed cases have been reported. The World Health Organization (WHO) has issued a strategic preparedness response plan for countries at risk. This is based on the knowledge of previous epidemics and experience shared by Chinese health authorities. There is special emphasis on strict 'quarantine and isolation' of suspected/diagnosed cases. Pakistan is a developing country with a weak healthcare system. Pakistan Armed Forces have always provided services to the countrymen during natural and man-made disasters. During this pandemic the largest rehabilitation institute in the country was converted into a 130-bed dedicated isolation and quarantine facility for the COVID-19 patients. We will share our experience of establishing and managing this quarantine and isolation facility and highlight the achievements and out-of-the-box solutions applicable for low resource countries like Pakistan.


title: Molecular epidemiology of influenza A virus infection in Cyprus in four consecutive seasons (2009 pandemic-2013).

text: The aim of this study was to investigate the epidemiology of influenza A virus infection in Cyprus from the 2009 pandemic until 2013. Pandemic influenza A(H1N1)2009 virus infections outnumbered infections with other respiratory viruses until the end of 2009. The pandemic virus was also the prevalent influenza strain during influenza season 2010-2011; however, it was completely replaced by H3N2 subtype in the next season. During the most recent influenza season, 2012-2013, the pandemic strain was once again the only influenza A virus circulating in Cyprus. Full-length neuraminidase gene sequencing revealed mutations that had previously been identified as permissive. No significant difference in the expression of the IFN-inducible genes OAS and IFIT1 were observed. The phylogenetic analysis of the neuraminidase gene sequences revealed a picture of continuous importation of influenza strains in the island of Cyprus with local circulation playing only a minor role in determining the prevalent strain of the next influenza season.


title: Murine coronavirus receptors are differentially expressed in the central nervous system and play virus strain-dependent roles in neuronal spread.

text: Coronavirus infection of the murine central nervous system (CNS) provides a model for studies of viral encephalitis and demyelinating disease. Mouse hepatitis virus (MHV) neurotropism varies by strain: MHV-A59 causes mild encephalomyelitis and demyelination, while the highly neurovirulent strain JHM.SD (MHV-4) causes fatal encephalitis with extensive neuronal spread of virus. In addition, while neurons are the predominant CNS cell type infected in vivo, the canonical receptor for MHV, the carcinoembryonic antigen family member CEACAM1a, has been demonstrated only on endothelial cells and microglia. In order to investigate whether CEACAM1a is also expressed in other cell types, ceacam1a mRNA expression was quantified in murine tissues and primary cells. As expected, among CNS cell types, microglia expressed the highest levels of ceacam1a, but lower levels were also detected in oligodendrocytes, astrocytes, and neurons. Given the low levels of neuronal expression of ceacam1a, primary neurons from wild-type and ceacam1a knockout mice were inoculated with MHV to determine the extent to which CEACAM1a-independent infection might contribute to CNS infection. While both A59 and JHM.SD infected small numbers of ceacam1a knockout neurons, only JHM.SD spread efficiently to adjacent cells in the absence of CEACAM1a. Quantification of mRNA for the ceacam1a-related genes ceacam2 and psg16 (bCEA), which encode proposed alternative MHV receptors, revealed low ceacam2 expression in microglia and oligodendrocytes and psg16 expression exclusively in neurons; however, only CEACAM2 mediated infection in human 293T cells. Therefore, neither CEACAM2 nor PSG16 is likely to be an MHV receptor on neurons, and the mechanism for CEACAM1a-independent neuronal spread of JHM.SD remains unknown.


title: 'Step-port' laparoscopic cystgastrostomy for the management of organized solid predominant post-acute fluid collections after severe acute pancreatitis.

text: BACKGROUND Post-acute pancreatic collections (PAPCs) may require intervention when persistent, large or symptomatic. An open cystgastrostomy is an effective treatment option particularly for larger, solid predominant collections. A laparoscopic cystgastrostomy (LCG) as initially described, could be technically challenging. This report describes the evolution of the operative technique and the results from LCG in a tertiary referral centre. METHODS Retrospective analysis of the unit's prospectively populated database was conducted. All patients who underwent a surgical cystgastrostomy (SCG) were identified. Patient demographics, outcome and complications were collected and analysed. RESULTS Forty-four patients underwent SCG: 8 open and 36 laparoscopic. Of the 36 LCG, 6 required open conversion, although with evolution of the technique all of the last 17 cases were completed laparoscopically. The median interquartile range (IQR) length of stay in patients completed laparoscopically was 6 (2-10) compared with 15.5 days (8-19) in those patients who were converted (P = 0.0351). The only peri-operative complication after a LCG was a self-limiting upper gastrointestinal bleed. With a median (IQR) follow-up of 891 days (527-1495) one patient required re-intervention for a residual collection with no recurrent collections identified. CONCLUSION LCG is a safe and effective procedure in patients with large, solid predominant PAPCs. With increased experience and technical expertise conversion rates can be lowered and outcome optimized.


EU health law and policy in and after the COVID-19 crisis.


Covid-19: Lack of capacity led to halting of community testing in March, admits deputy chief medical officer.


title: Teaching HIV-specific content for pre-licensure nursing and health professions students: a review and synthesis.

text: Persistent Human Immunodeficiency Virus (HIV) prevalence rates remain a challenge, particularly because health care providers (HCP) are not fully prepared to engage in HIV care. This hesitancy to engage creates access to care barriers for people living with HIV (PLWH). We conducted a systematic review to identify educational interventions focused on developing HIV competencies in higher education across health science disciplines. We searched databases for primary studies focused on interventions. Using PRISMA guidelines, we identified 20 articles from 19 distinct studies. While there was an overwhelming body of literature that assessed knowledge, skills, and attitudes in health sciences students on HIV and AIDS, the low number of intervention studies was notable. With the exception of two studies, PLWH were not included in the interventions. This finding stands in sharp contrast to the well-established Greater Involvement of People Living with HIV and/or AIDS (GIPA) and Meaningful Engagement of People Living with HIV and/or AIDS (MEPA) principles. The primary means of the educational intervention was focused on delivering lectures to address HIV and AIDS knowledge for HCP. There was a significant lack of focus on historical, cultural, policy and legal contexts of HIV and AIDS care; theoretical justifications for the interventions were absent. No study focused on the impact of an intervention on the care provided to PLWH by HCP after graduation. There is an urgent need to develop long-term sustainable and scalable interventions that address the consistently identified lack of knowledge and skills, and stigmatizing attitudes of HCP and students.


title: Cancer diagnostic rates during the 2020 'lockdown', due to COVID-19 pandemic, compared with the 2018-2019: an audit study from cellular pathology.

text: AIMS We performed an audit to evaluate the impact of the COVID-19 pandemic-related delay in the diagnosis of major cancers at a Pathology Unit of a Secondary Care Hospital Network in Italy. METHODS A comparison was made among the number of first cellular pathological diagnoses of malignancy made from the 11th to the 20th week of the years 2018-2020. RESULTS Cancer diagnoses fell in 2020 by 39% compared with the average number recorded in 2018 and 2019. Prostate cancer (75%) bladder cancer (66%) and colorectal cancer (CRC; 62%) had the greatest decrease. CRC was identified as carrying a potentially important diagnostic delay. CONCLUSIONS For CRC corrective procedures (continuing mass screening tests; patient triage by family physicians; diagnostic procedures alternative to colonoscopy; predictive evaluation on biopsy samples) were advised. Our simple audit model is widely applicable to avoid pandemic-related delay in clinical diagnosis of cancer.


title: Robotic-assisted colorectal surgery in the United States: a nationwide analysis of trends and outcomes.

text: BACKGROUND While robotic-assisted colorectal surgery (RACS) is becoming increasingly popular, data comparing its outcomes to other established techniques remain limited to small case series. Moreover, there are no large studies evaluating the trends of RACS at the national level. METHODS The Nationwide Inpatient Sample 2009-2010 was retrospectively reviewed for robotic-assisted and laparoscopic colorectal procedures performed for cancer, benign polyps, and diverticular disease. Trends in different settings, indications, and demographics were analyzed. Multivariate regression analysis was used to compare selected outcomes between RACS and conventional laparoscopic surgery (CLS). RESULTS An estimated 128,288 colorectal procedures were performed through minimally invasive techniques over the study period, and RACS was used in 2.78 % of cases. From 2009 to 2010, the use of robotics increased in all hospital settings but was still more common in large, urban, and teaching hospitals. Rectal cancer was the most common indication for RACS, with a tendency toward its selective use in male patients. On multivariate analysis, robotic surgery was associated with higher hospital charges in colonic ($11,601.39; 95 % CI 6,921.82-16,280.97) and rectal cases ($12,964.90; 95 % CI 6,534.79-19,395.01), and higher rates of postoperative bleeding in colonic cases (OR = 2.15; 95 % CI 1.27- 3.65). RACS was similar to CLS with respect to length of hospital stay, morbidity, anastomotic leak, and ileus. Conversion to open surgery was significantly lower in robotic colonic and rectal procedures (0.41; 95 % CI 0.25-0.67) and (0.10; 95 % CI 0.06-0.16), respectively. CONCLUSIONS The use of RACS is still limited in the United States. However, its use increased over the study period despite higher associated charges and no real advantages over laparoscopy in terms of outcome. The one advantage is lower conversion rates.


title: COVID-19: Perspectives From Nurses Across the Country.

text: The COVID-19 pandemic that is sweeping across the globe has impacted all health care professionals in multiple ways. This article surveyed a cross-section of the nursing profession from across the United States from the ANCC Practice Transition Accreditation Program® and ANCC Commission on Accreditation in Practice Transition Program. The article summarizes how they responded to the pandemic, addressed challenges, and learned valuable lessons. [J Contin Educ Nurs. 2020;51(7):304-308.].


[Discussion and suggestion on the classification of severe and critical coronavirus disease 2019 in Chinese experts' consensus on diagnosis and treatment of severe and critical coronavirus disease 2019].


title: A Municipality-Based Approach Using Commuting Census Data to Characterize the Vulnerability to Influenza-Like Epidemic: The COVID-19 Application in Italy.

text: In February 2020, Italy became the epicenter for COVID-19 in Europe, and at the beginning of March, the Italian Government put in place emergency measures to restrict population movement. Aim of our analysis is to provide a better understanding of the epidemiological context of COVID-19 in Italy, using commuting data at a high spatial resolution, characterizing the territory in terms of vulnerability. We used a Susceptible-Infectious stochastic model and we estimated a municipality-specific infection contact rate () to capture the susceptibility to the disease. We identified in Lombardy, Veneto and Emilia Romagna regions (52% of all Italian cases) significant clusters of high , due to the simultaneous presence of connections between municipalities and high population density. Local simulated spreading in regions, with different levels of infection observed, showed different disease geographical patterns due to different values and commuting systems. In addition, we produced a vulnerability map (in the Abruzzi region as an example) by simulating the epidemic considering each municipality as a seed. The result shows the highest vulnerability values in areas with commercial hubs, close to the highest populated cities and the most industrial area. Our results highlight how human mobility can affect the epidemic, identifying particular situations in which the health authorities can promptly intervene to control the disease spread.


title: Left Ventricular Compressions Improve Hemodynamics in a Swine Model of Out-of-Hospital Cardiac Arrest.

text: INTRODUCTION We hypothesized that chest compressions located directly over the left ventricle (LV) would improve hemodynamics, including coronary perfusion pressure (CPP), and return of spontaneous circulation (ROSC) in a swine model of cardiac arrest. METHODS Transthoracic echocardiography (echo) was used to mark the location of the aortic root and the center of the left ventricle on animals (n = 26) which were randomized to receive chest compressions in one of the two locations. After a period of ten minutes of ventricular fibrillation, basic life support (BLS) with mechanical cardiopulmonary resuscitation (CPR) was initiated and performed for ten minutes followed by advanced cardiac life support (ACLS) for an additional ten minutes. During BLS the area of maximal compression was verified using transesophageal echo. CPP and other hemodynamic variables were averaged every two minutes. RESULTS Mean CPP was not significantly higher in the LV group during all time intervals of resuscitation; mean CPP was significantly higher in the LV group during the 12-14 minute interval of BLS and during minutes 22-30 of ACLS (p < 0.05). Aortic systolic and diastolic pressures, right atrial systolic pressures, and end-tidal CO2 (ETCO2) were higher in the LV group during all time intervals of resuscitation (p < 0.05). Nine of the left ventricle group (69%) achieved ROSC and survived to 60 minutes compared to zero of the aortic root group (p < 0.001). CONCLUSIONS In our swine model of cardiac arrest, chest compressions over the left ventricle improved hemodynamics and resulted in a greater proportion of animals with ROSC and survival to 60 minutes.


[Epidemiology and Covid-19 in Italy. Accessing and sharing data to foster collaboration].


title: Clinical characteristics, diagnosis, and treatment of COVID-19: A case report.

text: BACKGROUND Since December 2019, many cases of pneumonia caused by novel coronavirus have been discovered in Wuhan, China, and such cases have spread nationwide quickly. At present, coronavirus disease 2019 (COVID-19) is a worldwide pandemic. What are the clinical features of this disease? What is the clinical diagnosis and how should such patients be treated? As a clinician, mastery of the clinical characteristics, basic diagnosis, and treatment methods of COVID-19 are required to provide help to patients. CASE SUMMARY A 42-year-old male patient with a cough lasting 6 d without obvious cause, as well as fever and fatigue for 1 d, was admitted to Hankou Hospital on January 22, 2020 and transferred to Huoshenshan Hospital on February 4. The main clinical symptoms were dry cough, fatigue, and fever. He was diagnosed with COVID-19. From the 4th d of admission, the patient's condition gradually worsened, with increased respiratory rate and body temperature. Peripheral blood lymphocytes decreased progressively. On the 8th d of admission, the patient's highest temperature was 40.7 °C, and oxygen saturation was 83% despite high-flow oxygen inhalation. Chest computed tomography results showed that the virus progressed rapidly. The number of lesions significantly increased with expanded scope and increased density. The distribution of lesions advanced from peripheral to central. In addition to nasal catheter oxygen inhalation and symptomatic support, antiviral drugs were used throughout the treatment. On January 22, oseltamivir phosphate capsules were given orally (75 mg, twice daily) for 6 d. On January 24, three tablets of lopinavir and ritonavir were added orally (twice daily). After 6 d, this was changed to 0.2 g (two tablets) arbidol, taken orally (three times daily) for 5 d. During the severe stage, methylprednisolone was given (40 mg) once every 12 h, immunoglobulin (20 g) was administered by intravenous drip infusion once daily, and thymosin (1.6 mg) was injected subcutaneously once daily combined with immunotherapy. On February 2, symptoms decreased, various indicators improved, and pulmonary inflammation was obviously reduced. Throat swabs on February 4 and 9 were negative for novel coronavirus nucleic acid. After 19 d in the hospital, the patient was successfully treated and discharged. CONCLUSION COVID-19 in young adults can be successfully treated with active treatment. We report a typical case of COVID-19, analyze its clinical characteristics, summarize its clinical diagnosis and treatment experience, and provide a reference for clinical colleagues.


title: Structural Basis for the Inhibition of Host Gene Expression by Porcine Epidemic Diarrhea Virus nsp1.

text: Porcine epidemic diarrhea virus (PEDV), an enteropathogenic Alphacoronavirus, has caused enormous economic losses in the pork industry. Nonstructural protein 1 (nsp1) is a characteristic feature of alpha- and betacoronaviruses, which exhibits both functional conservation and mechanistic diversity in inhibiting host gene expression and antiviral responses. However, the detailed structure and molecular mechanisms underlying the Alphacoronavirus nsp1 inhibition of host gene expression remain unclear. Here, we report the first full-length crystal structure of Alphacoronavirus nsp1 from PEDV. The structure displays a six-stranded β-barrel fold in the middle of two α-helices. The core structure of PEDV nsp1 shows high similarity to those of severe acute respiratory syndrome coronavirus (SARS-CoV) nsp1 and transmissible gastroenteritis virus (TGEV) nsp1, despite its low degree of sequence homology. Using ribopuromycylation and Renilla luciferase reporter assays, we showed that PEDV nsp1 can dramatically inhibit general host gene expression. Furthermore, three motifs (amino acids [aa] 67 to 71, 78 to 85, and 103 to 110) of PEDV nsp1 create a stable functional region for inhibiting protein synthesis, differing considerably from Betacoronavirus nsp1. These results elucidate the detailed structural basis through which PEDV nsp1 inhibits host gene expression, providing insight into the development of a new attenuated vaccine with nsp1 modifications.IMPORTANCE Porcine epidemic diarrhea virus (PEDV) has led to tremendous economic losses in the global swine industry. PEDV nsp1 plays a crucial role in inhibiting host gene expression, but its functional mechanism remains unclear. Here, we report the full-length structure of PEDV nsp1, the first among coronaviruses to be reported. The 1.25-Å resolution crystal structure of PEDV nsp1 shows high similarity to severe acute respiratory syndrome coronavirus (SARS-CoV) nsp113-128 and transmissible gastroenteritis virus (TGEV) nsp11-104, despite a lack of sequence homology. Structural and biochemical characterization demonstrated that PEDV nsp1 possesses a stable functional region for inhibition of host protein synthesis, which is formed by loops at residues 67 to 71, 78 to 85, and 103 to 110. The different functional regions in PEDV nsp1 and SARS-CoV nsp1 may explain their distinct mechanisms. Importantly, our structural data are conducive to understanding the mechanism of PEDV nsp1 inhibition of the expression of host genes and may aid in the development of a new attenuated vaccine.


title: Isolated pharmacomechanical thrombolysis plus primary stenting in a single procedure to treat acute thrombotic superior vena cava syndrome.

text: PURPOSE To report a combined procedure that opens the acutely thrombosed superior vena cava (SVC) to rapidly alleviate symptoms in seriously ill patients with SVC syndrome. CASE REPORTS Four patients aged 54 to 63 years old with underlying malignancies were referred for treatment of SVC syndrome. All received isolated pharmacomechanical thrombolysis (IPMT) with tissue plasminogen activator delivered in a Trellis Peripheral Infusion System that removed obstructive clot in minutes versus the 24 to 48 hours required for traditional catheter-directed thrombolysis. In each case, stents were inserted immediately following IPMT in a combined procedure lasting <1 hour. Patients exhibited near-immediate relief of debilitating symptoms; completion venography demonstrated patent vessels with excellent blood flow. CONCLUSION Combining IPMT with immediate stenting during the same session is an effective method for managing acute thrombotic SVC syndrome and limiting the exposure time and number of interventions performed on seriously ill patients.


title: Epidemiology and Determinants of Self-Injury Among High School Students in Iran: a Longitudinal Study.

text: Non-suicidal self-injury (NSSI) among adolescents is a major health concern globally. The epidemiology and determinant of NSSI have not been studied extensively in Iran. Thus, this longitudinal study sought to investigate the prevalence, incidence and contributing factors of NSSI among adolescents in Iran. This study was conducted at high school students aged 14-18 years old in the metropolitan city of Tabriz, located in north western Iran. Data were collected from 6229 10th-grade students at two time-points, with 12 months interval in October and November 2017 and 2018. A self-administered questionnaire was used to collect information on demographic, NSSI and cigarette and hookah smoking from the study participants. The results showed that lifetime prevalence of NSSI among students was 6.2% (95% confidence interval [CI]: 5.7 to 6.9) at the first assessment. Scratching and hair pulling were the most and least common methods of self-injury, respectively. Over the one year, 206 students (3.6% CI 95%: 3.1-4.1) reported the onset of NSSI. Tobacco smoking and previous year average grade were related to the incidence of NSSI. Although gender was significantly associated with the prevalence of NSSI, the relationship between gender and incidence of NSSI was not significant. Although the prevalence of NSSI was low among adolescents, the incidence rate was considerable. Further studies are required to understand the risk factors of NSSI in Iran.


title: Chester step test in patients with COPD: reliability and correlation with pulmonary function test results.

text: BACKGROUND The 5-stage Chester step test assesses aerobic capacity in healthy subjects. It has not been tested in patients with COPD. OBJECTIVE To determine the reliability of the Chester step test in patients with COPD and correlation with pulmonary function test and exercise test results. METHODS Thirty-two patients (mean ± SD FEV(1) 46 ± 15% of predicted) undertook 2 Chester step tests and two 6-min walk tests, on different days, in random order. A subgroup of 11 patients performed incremental cycle ergometry. RESULTS Thirty-one patients performed stage 1 of the Chester step test. Nineteen patients performed stage 2 of the Chester step test. The number of steps was highly reproducible: 66 ± 41 steps vs 68 ± 41 steps. There was no difference in heart rate or S(pO(2)) between the 2 Chester step tests at the peak of exercise or at the end of each stage. There was a significant correlation between number of steps and FEV(1) (r = 0.43, P = .02), and 6-min walk distance (r = 0.60, P = .001). Heart rate increased according to advanced stages of the Chester step test, up to 81 ± 13% of predicted. There was a significant correlation between number of steps and peak heart rate (r = 0.55, P = .001). In the 11 patients who performed the incremental cycling test there was a significant correlation between number of steps and peak work load (r = 0.69, P = .02). In the 6 patients in whom oxygen uptake could be estimated from the Chester step test, oxygen uptake was higher than that measured at the peak of the cycling test (30.8 ± 5.1 mL/kg/min vs 17.4 ± 4.5 mL/kg/min, respectively, P = .001). CONCLUSIONS Despite being highly reproducible, the Chester step test had a very short duration in patients with COPD. The number of steps incremented in each stage seems to be too large for these patients. An adaptation of the Chester step test should be considered for patients with COPD.


Diagnosis and Management of COVID-19 Disease.


title: Percutaneous Mesocaval Shunt Creation in a Patient with Chronic Portal and Superior Mesenteric Vein Thrombosis.

text: The creation of a transjugular intrahepatic portosystemic shunt (TIPS) is a critical procedure for the treatment of recurrent variceal bleeding and refractory ascites in the setting of portal hypertension. Chronic portal vein thrombosis remains a relative contraindication to conventional TIPS and options are limited in this scenario. Presented is a novel technique for management of refractory ascites in a patient with hepatitis C cirrhosis and chronic portal and superior mesenteric vein thrombosis secondary to schistosomiasis and lupus anticoagulant utilizing fluoroscopically guided percutaneous mesocaval shunt creation.


A Bayesian analysis of strategies to rule out COVID19 using reverse transcriptase-polymerase chain reaction (RT-PCR).


title: COVID and Coagulation: Bleeding and Thrombotic Manifestations of SARS-CoV2 Infection.

text: Patients with coronavirus disease 2019 (COVID-19) have elevated D-dimer levels. Early reports describe high venous thromboembolism (VTE) and disseminated intravascular coagulation (DIC) rates, but data are limited. This multicenter, retrospective study described the rate and severity of hemostatic and thrombotic complications of 400 hospital-admitted COVID-19 patients (144 critically ill) primarily receiving standard-dose prophylactic anticoagulation. Coagulation and inflammatory parameters were compared between patients with and without coagulation-associated complications. Multivariable logistic models examined the utility of these markers in predicting coagulation-associated complications, critical illness, and death. The radiographically-confirmed VTE rate was 4.8% (95% CI, 2.9-7.3%) and the overall thrombotic complication rate was 9.5% (6.8-12.8%). The overall and major bleeding rates were 4.8% (2.9-7.3%) and 2.3% (1.0-4.2%). In the critically ill, radiographically-confirmed VTE and major bleeding rates were 7.6% (3.9-13.3%) and 5.6% (2.4-10.7%). Elevated D-dimer at initial presentation was predictive of coagulation-associated complications during hospitalization [D-dimer >2,500 ng/mL, adjusted OR for thrombosis, 6.79 (2.39-19.30), adjusted OR for bleeding, 3.56 (1.01-12.66)], critical illness, and death. Additional markers at initial presentation predictive of thrombosis during hospitalization included platelet count >450×109/L [adjusted OR, 3.56 (1.27-9.97)], C-reactive protein (CRP) >100 mg/L [adjusted OR, 2.71 (1.26-5.86)], and erythrocyte sedimentation rate >40 mm/h [adjusted OR, 2.64 (1.07-6.51)]. ESR, CRP, fibrinogen, ferritin, and procalcitonin were higher in patients with thrombotic complications than those without. DIC, clinically-relevant thrombocytopenia, and reduced fibrinogen were rare and were associated with significant bleeding manifestations. Given the observed bleeding rates, randomized trials are needed to determine any potential benefit of intensified anticoagulant prophylaxis in COVID-19 patients.


title: Effect of methylprednisolone on acute kidney injury in patients undergoing cardiac surgery with a cardiopulmonary bypass pump: a randomized controlled trial.

text: BACKGROUND Perioperative corticosteroid use may reduce acute kidney injury. We sought to test whether methylprednisolone reduces the risk of acute kidney injury after cardiac surgery. METHODS We conducted a prespecified substudy of a randomized controlled trial involving patients undergoing cardiac surgery with cardiopulmonary bypass (2007-2014); patients were recruited from 79 centres in 18 countries. Eligibility criteria included a moderate-to-high risk of perioperative death based on a preoperative score of 6 or greater on the European System for Cardiac Operative Risk Evaluation I. Patients (n = 7286) were randomly assigned (1:1) to receive intravenous methylprednisolone (250 mg at anesthetic induction and 250 mg at initiation of cardiopulmonary bypass) or placebo. Patients, caregivers, data collectors and outcome adjudicators were unaware of the assigned intervention. The primary outcome was postoperative acute kidney injury, defined as an increase in the serum creatinine concentration (from the preoperative value) of 0.3 mg/dL or greater (≥ 26.5 μmol/L) or 50% or greater in the 14-day period after surgery, or use of dialysis within 30 days after surgery. RESULTS Acute kidney injury occurred in 1479/3647 patients (40.6%) in the methylprednisolone group and in 1426/3639 patients (39.2%) in the placebo group (adjusted relative risk 1.04, 95% confidence interval 0.96 to 1.11). Results were consistent across several definitions of acute kidney injury and in patients with preoperative chronic kidney disease. INTERPRETATION Intraoperative corticosteroid use did not reduce the risk of acute kidney injury in patients with a moderate-to-high risk of perioperative death who had cardiac surgery with cardiopulmonary bypass. Our results do not support the prophylactic use of steroids during cardiopulmonary bypass surgery. Trial registration: ClinicalTrials.gov, no. NCT00427388.


title: Coronavirus Disease 2019: Implications of Emerging Infections for Transplantation.

text: The recent identification of an outbreak of 2019- novel Coronavirus is currently evolving, and the impact on transplantation is unknown. However, it is imperative that we anticipate the potential impact on the transplant community in order to avert severe consequences of this infection on both the transplant community and contacts of transplant patients.


title: Persistence of human bocavirus DNA in immunocompromised children.

text: Human bocavirus is frequently detected in immunocompetent as well as in immunocompromised children. However, the course of infection in immunocompromised children is still poorly investigated. In the present study, we describe 4 cases of repeat human bocavirus detection in the presence of severe immunodeficiency. In the view of homologous viral sequences identified in serial samples, possible persistence and reactivation in these patients are discussed.


COVID-19: A message of hope from a young girl with severe cystic fibrosis.


title: Current status of robotic single-port colonic surgery.

text: INTRODUCTION The present paper reviews evidence and examines updates in single-port robotic surgery for colonic diseases reported in contemporary studies. MATERIALS AND METHODS A comprehensive online systematic search of PubMed databases was carried out in June 2015, identifying studies conducted on robotic single-port colectomy from 2008 to 2015. RESULTS The advantages and disadvantages of several available port-access systems, techniques for configuring robotic arms, and robotic surgical platforms, were presented. CONCLUSIONS Current studies show that single-port robotic colectomy is a safe and feasible procedure despite the lack of supporting evidence. Although significant advancements in the development and modification of single-access ports, configuration of robotic arms, and robotic surgical platforms have been achieved in the field of single-port robotic surgery for colonic disease, significant improvements to surgical platforms for single-port robotic surgery are needed. Copyright © 2016 John Wiley & Sons, Ltd.


title: Pandemic planning and response in academic pediatric emergency departments during the 2009 H1N1 influenza pandemic.

text: OBJECTIVES The terrorist attacks of September 11, 2001, initiated a shift toward a comprehensive, or "all-hazards," framework of emergency preparedness in the United States. Since then, the threat of H5N1 avian influenza, the severe acute respiratory syndrome epidemic, and the 2009 H1N1 influenza pandemic have underscored the importance of considering infectious events within such a framework. Pediatric emergency departments (EDs) were disproportionately burdened by the 2009 H1N1 influenza pandemic and therefore serve as a robust context for evaluation of pandemic preparedness. The objective of this study was to explore pediatric ED leaders' experiences with preparedness, response, and postincident actions related to the H1N1 pandemic to inform future pandemic and all-hazards planning and policy for EDs. METHODS The authors selected a qualitative design, well suited for exploring complex, multifaceted organizational processes such as planning for and responding to a pandemic and learning from institutional experiences. Purposeful sampling was used to recruit medical directors or their designated physician respondents from pediatric emergency medicine training institutions representing a range of geographic regions across the United States, hospital types, and annual ED volumes; snowball sampling identified additional information-rich respondents. Recruitment began in May 2011 and continued until thematic saturation was reached in January 2012 (n = 20). Data were collected through in-depth individual phone interviews that were recorded and professionally transcribed. Using a standard interview guide, respondents were asked open-ended questions about pandemic planning, response, and institutional learning related to the H1N1 pandemic. Data analysis was performed by a multidisciplinary team using a grounded theory approach to generate themes inductively from respondents' expressed perspectives. The constant comparative method was used to identify emerging themes. RESULTS Five common themes characterized respondents' experiences with pandemic planning and response: 1) national pandemic influenza preparedness guidance has not fully penetrated to the level of pediatric emergency physician (EP) leaders, leading to variable states of preparedness; 2) pediatric EDs that maintained strong relationships with local public health and other health care entities found those relationships to be beneficial to pandemic response; 3) pediatric EP leaders reported difficulty reconciling public health guidance with the reality of ED practice; 4) although many anticipated obstacles did not materialize, in some cases pediatric EP leaders experienced unexpected institutional challenges; and 5) pediatric EP leaders described varied experiences with organizational learning following the H1N1 pandemic experience. CONCLUSIONS Despite a decade of investment in hospital preparedness, gaps in pediatric ED pandemic preparedness remain. This work suggests that raising awareness of pandemic planning standards and promoting strategies to overcome barriers to their adoption could enhance ED and hospital preparedness. Helping hospitals better prepare for pandemic events may lead to strengthened all-hazards preparedness.


Presenting clinical features on darker skin: five minutes with . . . Malone Mukwende.


title: Endovascular treatment of lesions in the below-knee popliteal artery.

text: BACKGROUND Endovascular interventions are increasing; however, there are little data regarding outcomes of complex interventions involving the below-knee popliteal/P3 artery. This study evaluated the short-term and long-term results and predictors of success of below-knee popliteal artery endovascular interventions. METHODS This was a retrospective review of a prospectively maintained endovascular lower extremity database of all patients with below-knee popliteal interventions from 2004 to 2012. Patient demographics, angiographic findings, interventions, primary and secondary patency, limb loss, and mortality were recorded. Analysis was performed using Kaplan-Meier life-table and multivariate analysis, with P < .05 indicating significance. RESULTS There were 221 patients (56% male) with below-knee popliteal/P3 artery lesions. Mean age was 73 ± 11.2 years. Claudication was present in 22% and critical limb ischemia (CLI) in 78%. Mean lesion length was 10 ± 8.5 cm, with 45% having total occlusions. Treatment included percutaneous transluminal angioplasty (PTA) with or without a stent (47%), atherectomy (ATH) with or without PTA/stent (52%), and stenting with PTA and ATH (3%). Complications included embolization (0.4%), hematoma (2.7%), pseudoaneurysm (1.3%), and dissection (7%). Freedom from restenosis (peak systolic velocity ratio >2.4) was 65% at 1 year. Independent predictors of restenosis were CLI (hazard risk [HR], 4.4; 95% confidence interval [CI], 1.9-9.9) and stenting combined with PTA and ATH (HR, 2.7; 95% CI, 1.01-7.4). Primary assisted and secondary patencies were 95% and 85% at 1 year. ATH with PTA had lower short-term restenosis in diabetic patients compared with nondiabetic patients (95% vs 78% at 4 months). Limb loss was 18% at 4 years. Mortality was 24% at 4 years. Statin use was protective against primary restenosis (HR, 0.39; 95% CI, 0.23-0.67) and death (HR, 0.5; 95% CI, 0.28-1.0). CONCLUSIONS Endovascular intervention for lesions involving the below-knee popliteal artery is a safe and effective therapy for claudication and CLI. Diabetic patients benefit most from ATH with PTA. Statin use is protective against restenosis and mortality and should be the standard of care in patients undergoing peripheral endovascular interventions.


title: Murine hepatitis virus nonstructural protein 4 regulates virus-induced membrane modifications and replication complex function.

text: Positive-strand RNA viruses induce modifications of cytoplasmic membranes to form replication complexes. For coronaviruses, replicase nonstructural protein 4 (nsp4) has been proposed to function in the formation and organization of replication complexes. Murine hepatitis virus (MHV) nsp4 is glycosylated at residues Asn176 (N176) and N237 during plasmid expression of nsp4 in cells. To test if MHV nsp4 residues N176 and N237 are glycosylated during virus replication and to determine the effects of N176 and N237 on nsp4 function and MHV replication, alanine substitutions of nsp4 N176, N237, or both were engineered into the MHV-A59 genome. The N176A, N237A, and N176A/N237A mutant viruses were viable, and N176 and N237 were glycosylated during infection of wild-type (wt) and mutant viruses. The nsp4 glycosylation mutants exhibited impaired virus growth and RNA synthesis, with the N237A and N176A/N237A mutant viruses demonstrating more profound defects in virus growth and RNA synthesis. Electron microscopic analysis of ultrastructure from infected cells demonstrated that the nsp4 mutants had aberrant morphology of virus-induced double-membrane vesicles (DMVs) compared to those infected with wt virus. The degree of altered DMV morphology directly correlated with the extent of impairment in viral RNA synthesis and virus growth of the nsp4 mutant viruses. The results indicate that nsp4 plays a critical role in the organization and stability of DMVs. The results also support the conclusion that the structure of DMVs is essential for efficient RNA synthesis and optimal replication of coronaviruses.


title: Intermittent balloon occlusion to favor nidal penetration during embolization of arteriovenous malformations: a technique modification.

text: Endovascular embolization of brain arteriovenous malformations (AVMs) has improved with liquid occlusive agents, but flow-related and anatomic restrictions limit endovascular capabilities. AVM compartments supplied by leptomeningeal networks and feeding arteries too small and/or tortuous for safe catheterization are rarely penetrated by liquid occlusive agents. A case with both impediments prompted a novel solution. A balloon was inflated across the supply to a lenticulostriate feeder, thereby favoring penetration of the liquid occlusive agent, injected from a different feeding territory, back into the AVM compartment supplied by the temporarily occluded feeder. This technique may reduce the number of embolization stages in large high-flow AVMs and increase the likelihood of achieving complete occlusion. This technique is highly complex and requires meticulous monitoring of multiple events.


title: Art of performing dermoscopy during the times of coronavirus disease (COVID-19): Simple change in approach can save the day!

text: Dermatoscope is a convenient diagnostic tool used by dermatologists in the diagnosis of skin, hair and nail disorders. During dermoscopy, a dermatoscope comes in contact with the patient and hence can act as a potential source of nosocomial spread of infections.1 The uncertainty associated with the mode of spread of current coronavirus disease (COVID-19) has only lead to confusion and studies are underway to determine the role of zoonotic and environmental factors.2-4 There are reports of presence of severe acute respiratory syndrome coronavirus (SARS-CoV-2) on door handles, mobile phones and other surfaces.


Do us a favor.


title: Laparo-endoscopic combined approach for excision of gastrointestinal stromal tumour close to the oesophagogastric junction.

text: Tumours close to the oesophagogastric junction (OGJ) are difficult to excise due to high risk of complications. Laparoscopic and endoscopic combined surgery allows minimally invasive access while increasing tumour visualization. Computed tomography (CT) scanning of a 68-year-old female demonstrated a lesion suspicious of a gastrointestinal stromal tumour located 2 cm from the OGJ on the posterior gastric wall. Stapled excision was performed intragastrically and followed by endoscopic removal. Gastroscopy 7 months post-op and follow-up CT scan at 5 years demonstrated no recurrence of the primary tumour and no new disease. Laparoscopic and endoscopic combined approach is a safe and effective method of removing tumours close to the OGJ.


title: Preferential suppression of yellow head virus (YHV) envelope protein gp116 in shrimp that survive challenge with YHV.

text: The DNA sequence that encodes the first 406 amino acid residues at the N-terminus of yellow head virus (YHV) protein gp116, namely N/2 gp116deltaTM, and the DNA sequence that encodes the next 392 amino acid residues at the C-terminus of gp116 (without the transmembrane region), namely C/2 gp116deltaTM, were cloned into pGEX-6P-1 plasmid and expressed in E. coli. Both recombinant proteins were expressed, purified by SDS-PAGE and used to immunize mice. The mouse anti-recombinant N/2 gp116 and C/2 gp116 antisera bound specifically to both the recombinant proteins and to natural gp116 protein in YHV-infected haemolymph as shown by Western blotting and in tissues as shown by immunohistochemistry. Immunohistochemical localization of YHV using anti-gp116 antiserum or monoclonal antibodies specific to gp116 (V3-2B), gp64 (Y18) and p20 (Y19) revealed similar immunoreactivity patterns for all these reagents in muscle and mandibular tissue in shrimp showing gross signs of yellow head disease. However, in gill, hepatopancreas, lymphoid organ and thoracic ganglion tissues from experimental YHV-infected shrimp (Penaeus vannamei and Palaemon serrifer) that did not show signs of disease, immunoreactivity to gp116 was reduced or absent while that for gp64 and p20 remained intense. Thus, some shrimp species were able to selectively inhibit the synthesis of gp116 in a manner that was associated with absence of gross signs of disease.


title: Outcomes With the Use of the Retrograde Approach for Coronary Chronic Total Occlusion Interventions in a Contemporary Multicenter US Registry.

text: BACKGROUND We sought to examine the efficacy and safety of chronic total occlusion percutaneous coronary intervention using the retrograde approach. METHODS AND RESULTS We compared the outcomes of the retrograde versus antegrade-only approach to chronic total occlusion percutaneous coronary intervention among 1301 procedures performed at 11 experienced US centers between 2012 and 2015. The mean age was 65.5±10 years, and 84% of the patients were men with a high prevalence of diabetes mellitus (45%) and previous coronary artery bypass graft surgery (34%). Overall technical and procedural success rates were 90% and 89%, respectively, and in-hospital major adverse cardiovascular events occurred in 31 patients (2.4%). The retrograde approach was used in 539 cases (41%), either as the initial strategy (46%) or after a failed antegrade attempt (54%). When compared with antegrade-only cases, retrograde cases were significantly more complex, both clinically (previous coronary artery bypass graft surgery prevalence, 48% versus 24%; P<0.001) and angiographically (mean Japan-chronic total occlusion score, 3.1±1.0 versus 2.1±1.2; P<0.001) and had lower technical success (85% versus 94%; P<0.001) and higher major adverse cardiovascular events (4.3% versus 1.1%; P<0.001) rates. On multivariable analysis, the presence of suitable collaterals, no smoking, no previous coronary artery bypass graft surgery, and left anterior descending artery target vessel were independently associated with technical success using the retrograde approach. CONCLUSIONS The retrograde approach is commonly used in contemporary chronic total occlusion percutaneous coronary intervention, especially among more challenging lesions and patients. Although associated with lower success and higher major adverse cardiovascular event rates in comparison to antegrade-only crossing, retrograde percutaneous coronary intervention remains critical for achieving overall high success rates.


title: Exploring the role of regulation and the care of older people with depression living in long-term care? A systematic scoping review protocol.

text: INTRODUCTION This systematic scoping review will explore the role of regulation on the care of older people living with depression in long-term care. Depression presents a significant burden to older people living in long-term care. Regulation in the long-term care sector has increased, but there are still concerns about quality of care in the sector. METHODS AND ANALYSIS Using Arksey and O'Malley's scoping review methodology as a guide, our scoping review will search several databases: Embase; MEDLINE (using the OVID platform); Psych info; Ageline; and CINAHL, alongside the grey literature. An expert librarian has assisted the research team, using the Peer Review of Electronic Search Strategies, to assess the search strategy. The research team has formulated search strategies and two reviewers will independently screen studies for final study selection. We will summarise extracted data in tabular format; use a narrative format to describe their relevance; and finally, identify knowledge gaps and topics for future research. ETHICS AND DISSEMINATION This scoping review will outline the scope of the existing literature related to the influence of regulation on the care of older people living with depression in long-term care. The scoping review findings will be disseminated through publication in a peer-reviewed journal. The findings will be useful to policy-makers, managers and clinicians working in the long-term care sector.


COVID-19's impact on telehealth.


title: Impact of diabetes mellitus on acute outcomes of percutaneous coronary intervention in chronic total occlusions: insights from a US multicentre registry.

text: AIM To examine the impact of diabetes mellitus on procedural outcomes of patients who underwent percutaneous coronary intervention for chronic total occlusion. METHODS We assessed the impact of diabetes mellitus on the outcomes of percutaneous coronary intervention for chronic total occlusion among 1308 people who underwent such procedures at 11 US centres between 2012 and 2015. RESULTS The participants' mean ± sd age was 66 ± 10 years, 84% of the participants were men and 44.6% had diabetes. As compared with participants without diabetes, participants with diabetes were more likely to have undergone coronary artery bypass graft surgery (38 vs 31%; P = 0.006), and to have had previous heart failure (35 vs 22%; P = 0.0001) and peripheral arterial disease (19 vs 13%; P = 0.002). They also had a higher BMI (31 ± 6 kg/m2 vs 29 ± 6 kg/m2 ; P = 0.001), similar Japanese chronic total occlusion scores (2.6 ± 1.2 vs 2.5 ± 1.2; P = 0.82) and similar final successful crossing technique: antegrade wire escalation (46 vs 47%; P = 0.66), retrograde (30 vs 28%; P = 0.66) and antegrade dissection re-entry (24 vs 25%; P = 0.66). Technical (91 vs 90%; P = 0.80) and procedural (89 vs 89%; P = 0.93) success was similar in the two groups, as was the incidence of major adverse cardiac events (2.2 vs 2.5%; P = 0.61). CONCLUSIONS In a contemporary cohort of people undergoing percutaneous coronary intervention for chronic total occlusion, nearly one in two (45%) had diabetes mellitus. Procedural success and complication rates were similar in people with and without diabetes.


title: Posterior wall capture and femoral artery stenosis following use of StarClose closing device: diagnosis and therapy.

text: A case of femoral artery obstruction following application of a StarClose type arterial puncture closing device (APCD) is presented. Ultrasonographic and angiographic imaging of this complication was obtained. The posterior wall of the vessel was accidentally caught in the anchoring element of the nitinol clip. This complication was successfully resolved by endovascular treatment and the implantation of a stent.


title: Endoscopic ultrasound-guided inoculation of transmissible venereal tumor in the colon: A large animal model for colon neoplasia.

text: BACKGROUND To develop and evaluate the feasibility of emerging interventions, animal models with accurate anatomical environment are required. OBJECTIVES We aimed to establish a clinically relevant colorectal tumor model with canine transmissible venereal tumor (CTVT) utilizing endoscopic ultrasound (EUS) imaging guidance. DESIGN Survival study using a canine model. SETTING Endoscopic animal research laboratory at a tertiary cancer center. MATERIALS AND METHODS This study involved five canines. INTERVENTIONS A colorectal tumor model was established and evaluated in five canines under cyclosporine immune suppression. Under endoscopic imaging guidance, saline was injected into the submucosal layer forming a bleb. Subsequently, CTVT was inoculated into the bleb under EUS guidance. Endoscopy was the primary method of assessing tumor growth. Tumors developed in 60-130 days. Upon detection of lesions >1 cm, the animals were euthanized and the tumors were harvested for histopathological characterization. MAIN OUTCOME MEASUREMENTS Success rate of tumor growth. The presence or absence of vasculature inside tumors. RESULTS Colorectal tumor successfully developed in three out of the five animals (60%). Among the ones with tumor growth, average inoculated CTVT volume, incubation time, and tumor size was 1.8 cc, 65.7 days, and 2.0 cm, respectively. The two animals without tumor growth were observed for >100 days. In all the tumors, vascular structure was characterized with CD31 imunohistochemical stain. LIMITATIONS Small number of animals. CONCLUSION We succeeded in creating a new colorectal tumor canine model with CTVT utilizing EUS.


title: Evidence mapping based on systematic reviews of therapeutic interventions for gastrointestinal stromal tumors (GIST).

text: BACKGROUND Gastrointestinal Stromal Tumours (GISTs) are the most common mesenchymal tumours. Currently, different pharmacological and surgical options are used to treat localised and metastatic GISTs, although this research field is broad and the body of evidence is scattered and expanding. Our objectives are to identify, describe and organise the current available evidence for GIST through an evidence mapping approach. METHODS We followed the methodology of Global Evidence Mapping (GEM). We searched Pubmed, EMBASE, The Cochrane Library and Epistemonikos in order to identify systematic reviews (SRs) with or without meta-analyses published between 1990 and March 2016. Two authors assessed eligibility and extracted data. Methodological quality of the included systematic reviews was assessed using AMSTAR. We organised the results according to identified PICO questions and presented the evidence map in tables and a bubble plot. RESULTS A total of 17 SRs met eligibility criteria. These reviews included 66 individual studies, of which three quarters were either observational or uncontrolled clinical trials. Overall, the quality of the included SRs was moderate or high. In total, we extracted 14 PICO questions from them and the corresponding results mostly favoured the intervention arm. CONCLUSIONS The most common type of study used to evaluate therapeutic interventions in GIST sarcomas has been non-experimental studies. However, the majority of the interventions are reported as beneficial or probably beneficial by the respective authors of SRs. The evidence mapping is a useful and reliable methodology to identify and present the existing evidence about therapeutic interventions.


title: Screening of FDA-Approved Drugs for Treatment of Emerging Pathogens.

text: The current outbreaks of Middle East Respiratory Syndrome (MERS) and Ebolavirus (EboV) have revealed a gap in the development and availability of drugs to treat these infections. To date, there are no approved treatments for patients infected with MERS coronavirus (MERS-CoV), a virus that continues to infect new patients and that has now spread from the Middle East to Asia. Despite a downward trend in the number of new EboV cases in West Africa, new infections are still occurring, and many patients continue to suffer from this illness. People infected with MERS and Ebola viruses receive only supportive care in hopes of recovery. Investigation into repurposing drugs approved by the FDA is gaining interest. To identify better treatment strategies, several groups have used drug screens to repurpose FDA-approved drugs as inhibitors of MERS-CoV and EboV.


title: Outcomes Are Not Different between Patients with Intermediate and High DWI-ASPECTS after Stent-Retriever Embolectomy for Acute Anterior Circulation Stroke.

text: BACKGROUND AND PURPOSE Questions remain as to what benefits embolectomy provides to patients presented with considerable early ischemic changes on baseline imaging studies. This study aimed to investigate the impact of the Alberta Stroke Program Early CT Score applied to DWI on treatment outcomes in patients with acute stroke undergoing stent-retriever embolectomy. MATERIALS AND METHODS We retrospectively analyzed the clinical and DWI data from 171 patients with acute anterior circulation stroke who were treated with stent-retriever embolectomy within 6 hours of symptom onset. DWI-ASPECTS scores were analyzed with the full scale or were dichotomized (4-6 versus 7-10). Patients with DWI-ASPECTS ≤3 were excluded from the study. Associations between outcome and clinical and radiologic factors were determined with a multivariate logistic regression analysis. A good outcome was defined as a modified Rankin Scale score of 0-2 at 3 months. RESULTS The median DWI-ASPECTS was 7 (interquartile range, 6-8). The rates of good outcome, symptomatic hemorrhage, and mortality were not different between high DWI-ASPECTS (scores of 7-10) and intermediate DWI-ASPECTS (scores of 4-6) groups. In patients with an intermediate DWI-ASPECTS, good outcome was achieved in 46.5% (20/43) of patients with successful revascularization, whereas no patients without successful revascularization had a good outcome (P = .016). In multivariate logistic regression analysis, independent predictors of good outcome were age and successful revascularization. CONCLUSIONS Our study suggested that there were no differences in outcomes between patients with a high DWI-ASPECTS and those with an intermediate DWI-ASPECTS who underwent stent-retriever embolectomy for acute anterior circulation stroke. Thus, patients with an intermediate DWI-ASPECTS otherwise eligible for endovascular therapy may not be excluded from stent-retriever embolectomy or stroke trials.


title: Outcome Following Partial Unilateral Hysterectomy by Standing Flank Approach in Dairy Cattle.

text: OBJECTIVE To describe the clinical findings, surgical treatment, and long-term outcome of dairy cattle undergoing partial hysterectomy with or without unilateral ovariectomy. STUDY DESIGN Retrospective case series. ANIMALS Dairy cattle (n = 7). METHODS Medical records (June 2007-June 2014) of dairy cattle that had partial hysterectomy with or without ipsilateral ovariectomy were reviewed. Follow-up data were obtained by telephone interviews with owners and referring veterinarians between 6 months and 7 years following discharge. RESULTS Seven dairy cattle met the inclusion criteria. Diagnoses made intra- or postoperatively were ovarian abscess with multiorgan adhesions (4 cows), segmental aplasia of the uterus (2 cows), and uterine lymphosarcoma (1 cow). Partial hysterectomy with or without unilateral ovariectomy was performed without surgical complications by standing flank approach. All cows were successfully discharged from the hospital (short-term prognosis). Five cows became pregnant, and 4 delivered live calves and had a satisfactory productive life without long-term complications. CONCLUSION Partial hysterectomy by standing flank approach should be considered as a viable treatment option for unilateral ovarian or uterine problems in dairy cattle. Cattle undergoing partial hysterectomy with or without ipsilateral ovariectomy are capable of satisfactory reproduction and milk production after surgery with no short- or long-term complications.


title: A direct aspiration first pass technique for retrieval of a detached coil.

text: A 64-year-old man was referred to our hospital for treatment of a cerebral aneurysm that was incidentally found. The aneurysm was 7 mm in size and located on the left anterior communicating artery. Using a balloon assisted technique, we performed coil embolization. During the second coil insertion, the first coil was dislodged into the anterior communicating artery. We attempted coil retrieval using a snare, which was unsuccessful. We applied a direct aspiration first pass technique (ADAPT) and advanced a Penumbra 4MAX immediately proximal to the dislodged coil; the dislodged coil was then successfully retrieved. ADAPT is a simple procedure for retrieval of a detached coil, and it can be used as an alternative to the snare technique.


title: The impact of maternal prenatal and postnatal anxiety on children's emotional problems: a systematic review.

text: Maternal mental health problems during pregnancy and the postnatal period are a major public health issue. Despite evidence that symptoms of both depression and anxiety are common during pregnancy and the postpartum, the impact of maternal anxiety on the child has received relatively less attention than the impact of maternal depression. Furthermore, the evidence base for the direct impact of maternal anxiety during pregnancy and the postpartum on children's emotional outcomes lacks cohesion. The aim of this systematic review is to summarise the empirical evidence regarding the impact of maternal prenatal and postnatal anxiety on children's emotional outcomes. Overall, both maternal prenatal and postnatal anxiety have a small adverse effect on child emotional outcomes. However, the evidence appears stronger for the negative impact of prenatal anxiety. Several methodological weaknesses make conclusions problematic and replication of findings is required to improve the identification of at-risk parents and children with appropriate opportunities for intervention and prevention.


title: FIRST CASE OF CORONAVIRUS DISEASE 2019 IN CHILDHOOD LEUKEMIA IN CHINA.

text: We report the first case of coronavirus disease 2019 (COVID-19) comorbid with leukemia in a patient hospitalized in Beijing, China. The patient showed a prolonged manifestation of symptoms and a protracted diagnosis period of COVID-19. It is necessary to extend isolation time, increase the number of nucleic acid detections and conduct early symptomatic treatment for children with both COVID-19 and additional health problems.


title: Tinkering with translation: protein synthesis in virus-infected cells.

text: Viruses are obligate intracellular parasites, and their replication requires host cell functions. Although the size, composition, complexity, and functions encoded by their genomes are remarkably diverse, all viruses rely absolutely on the protein synthesis machinery of their host cells. Lacking their own translational apparatus, they must recruit cellular ribosomes in order to translate viral mRNAs and produce the protein products required for their replication. In addition, there are other constraints on viral protein production. Crucially, host innate defenses and stress responses capable of inactivating the translation machinery must be effectively neutralized. Furthermore, the limited coding capacity of the viral genome needs to be used optimally. These demands have resulted in complex interactions between virus and host that exploit ostensibly virus-specific mechanisms and, at the same time, illuminate the functioning of the cellular protein synthesis apparatus.


title: Detection of respiratory viruses among pilgrims in Saudi Arabia during the time of a declared influenza A(H1N1) pandemic.

text: BACKGROUND The objectives of this study were to determine whether pilgrim attendance at the Hajj was associated with an increased risk of acquiring influenza, and other respiratory viruses, and to evaluate the compliance of pilgrims with influenza vaccination and other recommended preventive measures. METHODS A cross-sectional survey was conducted among pilgrims as they arrived at the King Abdulaziz International Airport in Jeddah for the 2009 Hajj and as they departed from the same airport during the week after the Hajj. Nasopharyngeal and throat swabs were tested for 18 respiratory virus types and subtypes using the xTAG Respiratory Viral Panel FAST assay. RESULTS A total of 519 arriving pilgrims and 2,699 departing pilgrims were examined. Their mean age was 49 years and 58% were male. In all, 30% of pilgrims stated that they had received pandemic influenza A(H1N1) vaccine before leaving for the Hajj and 35% of arriving pilgrims reported wearing a face mask. Only 50% of arriving pilgrims were aware of preventive measures such as hand hygiene and wearing a mask. The prevalence of any respiratory-virus infection was 14.5% (12.5% among arriving pilgrims and 14.8% among departing pilgrims). The main viruses detected (both groups combined) were rhinovirus-enterovirus (N = 414, 12.9%), coronaviruses (N = 27, 0.8%), respiratory syncytial virus (N = 8, 0.2%), and influenza A virus (N = 8, 0.2%) including pandemic influenza A(H1N1) (N = 3, 0.1%). The prevalence of pandemic influenza A(H1N1) was 0.2% (N = 1) among arriving pilgrims and 0.1% (N = 2) among departing pilgrims. The prevalence of any respiratory virus infection was lower among those who said they received H1N1 vaccine compared to those who said they did not receive it (11.8% vs 15.6%, respectively, p = 0.009). CONCLUSION We found very low pandemic influenza A(H1N1) prevalence among arriving pilgrims and no evidence that amplification of transmission had occurred among departing pilgrims.


title: Single-layer versus double-layer closure of the vaginal cuff with barbed sutures in laparoscopic hysterectomy.

text: OBJECTIVES The utilization of barbed sutures in laparoscopic hysterectomy has become popular among gynecologic sur-geons. Our aim was to compare the outcomes of two different techniques for closing the vaginal cuff with barbed sutures in laparoscopic hysterectomies. MATERIAL AND METHODS A retrospective study was completed on 202 patients who underwent laparoscopic hysterectomy for benign diseases at Istanbul Kanuni Sultan Suleyman Training and Research Hospital from April 2014 through June 2016. In group 1 (n = 139), a single-layer continuous suturing method was used; each bite contained the pubocervical fascia and vaginal mucosa anteriorly, and vaginal mucosa and rectovaginal fascia posteriorly. In group 2 (n = 63), a double-layer continuous suturing method was used; only vaginal mucosa was included in the first layer, and a second layer incorporated the pubocervical and rectovaginal fascias. RESULTS Patient characteristics (age, body mass index, parity, previous abdominal surgery, smoking, comorbidity) were similar between the two groups. There were also no differences in total operation time, length of hospitalization, intraop-erative complications, and perioperative change in hemoglobin levels. There was no difference between the two groups in terms of vaginal cuff dehiscence, which was the primary outcome measure of the study. Secondary outcome measures (presence of granulation tissue, spotting, cuff cellulitis) were also similar between the two groups. CONCLUSIONS We observed no differences in outcomes between single- or double-layer vaginal closure techniques with barbed sutures.


title: Initial experience with the AXERA 2 Femoral Access System in neurovascular procedures.

text: INTRODUCTION Conventional cerebral angiography is a commonly performed procedure in medicine. Vascular closure devices have been developed as alternatives to manual compression at the arteriotomy site and prolonged bed rest. The risks of using these devices include arterial dissection, groin hematoma, and device failure. Herein, we describe our experience with the use of a novel device used for arterial access and closure, the AXERA 2 Access System. METHODS A total of 13 patients underwent vascular access and closure with the AXERA 2 Access System. RESULTS Arterial access using the AXERA 2 Access System was achieved in 11 of 13 patients. Amongst the patients with successful access, one patient experienced a groin hematoma requiring manual compression and two patients suffered occlusions of the common femoral artery due to dissections, with both patients requiring femoral artery thromboendarterectomies. CONCLUSIONS This small series highlights a heretofore underreported serious complication rate of the AXERA 2 Access System. Additional studies are warranted to provide further insight into risk factors for device failure and complication development.


title: Endovascular Thrombectomy for Acute Ischemic Stroke.

text: PURPOSE OF REVIEW To review the current evidence supporting the use of endovascular thrombectomy (EVT) for the treatment of acute ischemic stroke (AIS) due to anterior circulation large vessel occlusion (LVO). RECENT FINDINGS Recent advances in AIS management by EVT have led to significant reduction in morbidity and mortality in selected patients with LVO within the anterior circulation. Until recently, use of EVT was strictly based on time criteria, within 4.5 to 12 h of symptom onset with many patients presenting with "wake-up" stroke who were not considered for EVT. The positive results of the DAWN and DEFUSE-3 trials have shown benefit in extending the therapeutic window for EVT to 24 and 16 h, respectively, after last known normal (LKN) time in the setting of large ischemic penumbra. These trials represent a paradigm shift in contemporary treatment of AIS, changing from a purely time-based decision to treat to an individualized decision based on clinical and radiographic findings of salvageable tissue. Overall, acute stroke management has evolved considerably over the years from intravenous thrombolysis to include EVT, with paralleled improvements in patient selection and thrombectomy devices. Since the results of the DAWN and DEFUSE-3, EVT is now considered the standard of care in select patients with anterior circulation LVO up to 24 h from LKN time. Despite these developments, post-stroke disability remains pervasive and further studies are warranted in establishing the role of EVT in posterior circulation and distal vessel occlusions, with need for development of new and effective techniques for revascularization of small vessels.


title: Robotic valvuloplastic esophagogastrostomy using double flap technique following proximal gastrectomy: technical aspects and short-term outcomes.

text: BACKGROUND Valvuloplastic esophagogastrostomy by double flap technique (VEG-DFT) is a promising procedure to prevent reflux after proximal gastrectomy (PG), and is achieved by the burial of the abdominal esophagus into the gastric submucosa; however, laparoscopic VEG-DFT is technically demanding due to complicated suturing and ligation maneuvers. The present study was designed to determine the feasibility and safety of robotic VEG-DFT. METHODS After robotic PG, seromuscular flaps were extracorporeally created at the anterior wall of the remnant stomach through a small umbilical incision. Then, using a robot, the posterior wall of the esophagus was fixed to the cranial end of the mucosal window, and layer-to-layer sutures were placed between the anterior aspects of esophagus and the remnant stomach. Finally, the anastomosis was covered by seromuscular flaps. Short-term outcomes of 12 consecutive patients who underwent VEG-DFT between January 2014 and December 2015 were assessed. RESULTS Operations were successfully completed using robotic assistance in all patients. Median operative, surgeon console, and anastomosis times were 406 (324-613 min), 267 (214-483), and 104 (76-186) min, respectively, and median estimated blood loss was 31 (5-130) ml. The first six cases were required to reach a learning plateau. Both mortality and morbidity rates within 30 days after surgery were 0%. Postoperative hospital stay was 10 (9-30) days. No postoperative reflux esophagitis was observed, whereas anastomotic stenosis, which required endoscopic balloon dilation, developed in three patients (25%) in postoperative month 2. There was a significant association between the total number of stitches used for VEG-DFT and anastomotic stenosis (p < 0.001). CONCLUSIONS Robotic assistance may be useful for VEG-DFT with a short learning curve. Attention is required to prevent postoperative anastomotic stenosis possibly caused by an excessive number of stitches for esophagogastrostomy.


title: Parastomal hernia repair outcomes in relation to stoma site with diisocyanate cross-linked acellular porcine dermal collagen mesh.

text: PURPOSE Biologic meshes are increasingly used in parastomal hernia repair. This study evaluates the efficacy and safety of diisocyanate cross-linked acellular porcine dermal collagen mesh for parastomal hernia repair, with particular reference to the relationship of the stoma site to the rectus sheath. METHODS Hernias were repaired via a lateral approach, with onlay placement of the biologic mesh. A retrospective case note review and analysis of clinical outcomes was performed. The relationship of the stoma to the rectus sheath was determined by abdominal computed tomography (CT) and intraoperative findings. RESULTS Over a 16-month period, 27 consecutive patients, median age 72 years, underwent parastomal hernia repair utilising onlay biologic mesh to reinforce the external oblique aponeurosis. There were 20 paracolostomy and seven paraileostomy hernias. Eleven stomas passed through the rectus sheath and 16 were lateral to it. Recurrences occurred in 3 of 11 stomas within and 12 of 16 stomas lateral to the rectus sheath (P = 0.022). The median time to recurrence was 10.1 months. The median follow up of patients without recurrence was 16.6 months (range 0.2-39.3). There was one perioperative death. One patient developed a superficial post-operative abscess that was managed conservatively, but there were no complications related to the biologic mesh and no mesh required removal. CONCLUSIONS For parastomal hernias within the rectus sheath, diisocyanate cross-linked porcine dermal collagen mesh onlay repair gives good results and is safe to use. Repair of a parastomal hernia where the stoma is lateral to the rectus sheath has a significantly higher risk of recurrence and is not recommended.


Debrief: Joining the cult.


title: Everolimus Plus Endocrine Therapy for Postmenopausal Women With Estrogen Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer: A Clinical Trial.

text: Importance Cotargeting the mammalian target of rapamycin pathway and estrogen receptor may prevent or delay endocrine resistance in patients receiving first-line treatment for advanced breast cancer. Objective To investigate the combination of everolimus plus endocrine therapy in first-line and second-line treatment settings for postmenopausal women with estrogen receptor-positive, human epidermal growth receptor 2-negative advanced breast cancer. Design, Setting, and Participants In the multicenter, open-label, single-arm, phase 2 BOLERO-4 (Breast Cancer Trials of Oral Everolimus) clinical trial, 245 patients were screened for eligibility; 202 were enrolled between March 7, 2013, and December 17, 2014. A median follow-up of 29.5 months had been achieved by the data cutoff date (December 17, 2016). Interventions Patients received first-line treatment with everolimus, 10 mg/d, plus letrozole, 2.5 mg/d. Second-line treatment with everolimus, 10 mg/d, plus exemestane, 25 mg/d, was offered at the investigator's discretion upon initial disease progression. Main Outcomes and Measures The primary end point was investigator-assessed progression-free survival in the first-line setting per Response Evaluation Criteria in Solid Tumors, version 1.0. Safety was assessed in patients who received at least 1 dose of study medication and at least 1 postbaseline safety assessment. Results A total of 202 women treated in the first-line setting had a median age of 64.0 years (interquartile range, 58.0-70.0 years) with metastatic (194 [96.0%]) or locally advanced (8 [4.0%]) breast cancer. Median progression-free survival was 22.0 months (95% CI, 18.1-25.1 months) with everolimus and letrozole. Median overall survival was not reached; 24-month estimated overall survival rate was 78.7% (95% CI, 72.1%-83.9%). Fifty patients started second-line treatment; median progression-free survival was 3.7 months (95% CI, 1.9-7.4 months). No new safety signals were observed. In the first-line setting, the most common all-grade adverse event was stomatitis (139 [68.8%]); the most common grade 3 to 4 adverse event was anemia (21 [10.4%]). In the second-line setting, the most common adverse events were stomatitis and decreased weight (10 [20.0%] each); the most common grade 3 to 4 adverse event was hypertension (5 [10.0%]). There were 50 (24.8%) deaths overall during the study; 40 were due to study indication (breast cancer). Conclusions and Relevance The results of this trial add to the existing body of evidence suggesting that everolimus plus endocrine therapy is a good first-line treatment option for postmenopausal women with estrogen receptor-positive, human epidermal growth factor receptor 2-negative advanced breast cancer. Trial Registration clinicaltrials.gov Identifier: NCT01698918.


title: Contrast media use in the operating room.

text: Iodinated contrast media is frequently used in the OR, but often is not well understood by health care providers who are administering it. Although used for diagnosis rather than treatment, contrast media is classified as a drug by the FDA, and has indications, contraindications, adverse effects, drug interactions, disease interactions, and laboratory interference issues related to its use. Iodinated contrast media is classified according to osmolarity and ionicity, and these characteristics contribute to potential for adverse effects and choice of agent. Financial and safety concerns are factors to be considered when selecting an appropriate agent. Adverse effects can range from mild and self-limited to severe and life threatening; potentially the most serious of these are anaphylactoid reactions and contrast-induced acute renal failure. Knowledge of risk factors and preventive strategies is vital, as are issues related to substitution of gadolinium-based contrast, an off-label use. It is important for the perianesthesia nurse to become familiar with these commonly used imaging medications.


title: Effect of IV alteplase on the ischemic brain lesion at 24-48 hours after ischemic stroke.

text: OBJECTIVE To determine whether alteplase alters the development of ischemic lesions on brain imaging after stroke. METHODS The Third International Stroke Trial (IST-3) was a randomized controlled trial of IV alteplase for ischemic stroke. We assessed CT or brain MRI at baseline (pretreatment) and 24 to 48 hours posttreatment for acute lesion visibility, extent, and swelling, masked to all other data. We analyzed associations between treatment allocation, change in brain tissue appearances between baseline and follow-up imaging, and 6-month functional outcome in IST-3. We performed a meta-analysis of randomized trials of alteplase vs control with pre- and postrandomization imaging. RESULTS Of 3,035 patients recruited in IST-3, 2,916 had baseline and follow-up brain imaging. Progression in either lesion extent or swelling independently predicted poorer 6-month outcome (adjusted odds ratio [OR] = 0.92, 95% confidence interval [CI] 0.88-0.96, p < 0.001; OR = 0.73, 95% CI 0.66-0.79, p < 0.001, respectively). Patients allocated alteplase were less likely than controls to develop increased lesion visibility at follow-up (OR = 0.77, 95% CI 0.67-0.89, p < 0.001), but there was no evidence that alteplase reduced progression of lesion extent or swelling. In meta-analysis of 6 trials including IST-3 (n = 4,757), allocation to alteplase was associated with a reduction in ischemic lesion extent on follow-up imaging (OR = 0.85, 95% CI 0.76-0.95, p = 0.004). CONCLUSION Alteplase was associated with reduced short-term progression in lesion visibility. In meta-analysis, alteplase reduced lesion extent. These findings may indicate that alteplase improves functional outcome by reducing tissue damage. CLASSIFICATION OF EVIDENCE This study provides Class II evidence that IV alteplase impedes the progression of ischemic brain lesions on imaging after stroke.


The "Infodemic" of Journal Publication Associated with the Novel Coronavirus Disease.


title: Evolution and outcomes of sentinel lymph node mapping in vulvar cancer.

text: OBJECTIVES To characterize our institutional experience with sentinel lymph node (SLN) biopsy in patients with vulvar cancer. We describe the oncologic outcomes of these patients and the utilization of SLN detection techniques over time. METHODS A retrospective analysis of all patients who underwent inguinofemoral SLN biopsy as part of their treatment for vulvar cancer at Memorial Sloan Kettering Cancer Center from January 1, 2000 to April 1, 2019. Patients were included in this analysis if they underwent inguinofemoral SLN biopsy for vulvar cancer, irrespective of presenting factors such as histology, tumor size or laterality. An "at-risk groin" was defined as either the right or left groin for which SLN biopsy of inguinofemoral lymph nodes was performed. RESULTS A total of 160 patients were included in our analysis, representing 265 at-risk groins. 114 patients had squamous cell histology representing 195 at-risk groins. Of the 169 negative groins in patients with squamous cell carcinoma, the 2 year isolated groin recurrence rate was 1.2%. SLN detection rate, irrespective of modality, was 96.2%. Technetium-99 (TC-99) + blue dye detected SLNs in 91.8% of groins; TC-99 + indocyanine green detected SLNs in 100% of groins (p=0.157). Among the 110 groins that underwent mapping with TC-99 and blue dye, 4 patients had failed mapping with blue dye and mapped with TC-99 alone (3.6%). Among the 96 groins that underwent mapping with TC-99 and ICG, 14 patients failed to map with TC-99 and mapped with indocyanine green alone (14.6%). CONCLUSIONS SLN mapping in vulvar cancer is reliable and oncologically effective. The utilization of indocyanine green for mapping has increased over the past decade and is associated with high rates of SLN detection.


title: Differential Gene Expression in Coiled versus Flow-Diverter-Treated Aneurysms: RNA Sequencing Analysis in a Rabbit Aneurysm Model.

text: BACKGROUND AND PURPOSE The biologic mechanisms leading to aneurysm healing or rare complications such as delayed aneurysm ruptures after flow-diverter placement remain poorly understood. We used RNA sequencing following implantation of coils or flow diverters in elastase aneurysms in rabbits to identify genes and pathways of potential interest. MATERIALS AND METHODS Aneurysms were treated with coils (n = 5) or flow diverters (n = 4) or were left untreated for controls (n = 6). Messenger RNA was isolated from the aneurysms at 4 weeks following treatment. RNA samples were processed by using RNA-sequencing technology and were analyzed by using the Ingenuity Pathway Analysis tool. RESULTS With RNA sequencing for coiled versus untreated aneurysms, 464/9990 genes (4.6%) were differentially expressed (58 down-regulated, 406 up-regulated). When we compared flow-diverter versus untreated aneurysms, 177/10,041 (1.8%) genes were differentially expressed (8 down-regulated, 169 up-regulated). When we compared flow-diverter versus coiled aneurysms, 13/9982 (0.13%) genes were differentially expressed (8 down-regulated, 5 up-regulated). Keratin 8 was overexpressed in flow diverters versus coils. This molecule may potentially play a critical role in delayed ruptures due to plasmin production. We identified overregulation of apelin in flow diverters, supporting the preponderance of endothelialization, whereas we found overexpression of molecules implicated in wound healing (dectin 1 and hedgehog interacting protein) for coiled aneurysms. Furthermore, we identified metallopeptidases 1, 12, and 13 as overexpressed in coiled versus untreated aneurysms. CONCLUSIONS We observed different physiopathologic responses after endovascular treatment with various devices. Flow diverters promote endothelialization but express molecules that could potentially explain the rare delayed ruptures. Coils promote wound healing and express genes potentially implicated in the recurrence of coiled aneurysms.


title: Microscope transsphenoidal surgery.

text: BACKGROUND The transsphenoidal approach to the pituitary using the microscope has undergone continuous modification since its introduction by Hardy over 50 years ago. It is one of the most effective and safest of major neurosurgical procedures with excellent outcomes and low complication rates. METHODS Although being displaced by the endoscopic approach, it remains the 'gold standard' for a number of pituitary conditions such as Cushing's tumours, and for the majority of the remainder, has yet to be overtaken in outcome results by the endoscopic approach. CONCLUSION This description of the endonasal 'septal pushover' technique is from an author with experience in nearly 4,000 cases. The anatomy is described, and the step-by-step approach and tumour removal for micro- and pituitary macroadenomas are given. Complications and their avoidance are overviewed.


title: An Effective Case for Chyluria by Retroperitoneoscopic Lymphatic Disconnection.

text: BACKGROUND Chyluria is a rare disease in Japan. Lymphatic disconnection is the most effective treatment for patients with Chyluria, and laparoscopic approach is performed as a minimally invasive technique. CASE PRESENTATION We present a case of a 40-year-old man who referred to our hospital because of recurrence of chyluria. Chyluria had continued for 20 years, and the patient had received retrograde instillations of silver nitrate three times. The patient underwent retroperitoneoscopic nephrolympholysis, and the chyluria disappeared immediately. One year after surgery, chyluria has not recurred. CONCLUSION We treated a patient with chyluria by performing retroperitoneoscopic lymphatic disconnection and this procedure is less invasive and easy to perform.


ANNALS EXPRESS: Electrolyte Imbalances in Patients with Severe Coronavirus Disease 2019 (COVID-19).


title: Aspergillus fumigatus and pan-azole resistance: who should be concerned?

text: PURPOSE OF REVIEW Although clinical outcomes in the treatment of aspergillosis have markedly improved with the availability of newer triazoles, the development of resistance to these antifungals, especially in Aspergillus fumigatus, is a growing concern. The purpose of this review is to provide an update on azole resistance mechanisms and their epidemiology in A. fumigatus, the clinical implications of azole resistance, and to discuss future treatment options against azole-resistant aspergillosis. RECENT FINDINGS Resistance may develop through either patient or environmental azole exposure. Environmental exposure is the most prevalent means of resistance development, and these isolates can cause disease in various at-risk groups, which now include those with influenza, and potentially COVID-19. Although current treatment options are limited, newer therapies are in clinical development. These include agents with novel mechanisms of action which have in vitro and in vivo activity against azole-resistant A. fumigatus. SUMMARY Azole-resistant A. fumigatus is an emerging threat that hampers our ability to successfully treat patients with aspergillosis. Certain geographic regions and patient populations appear to be at increased risk for this pathogen. As new patient groups are increasingly recognized to be at increased risk for invasive aspergillosis, studies to define the epidemiology and management of azole-resistant A. fumigatus are critically needed. While treatment options are currently limited, new agents under clinical development may offer hope.