title: Perineal closure following extralevator abdominoperineal excision for cancer of the rectum.

text: AIM Extralevator abdominoperineal resection (ELAPE) may be complicated by perineal wound healing problems and herniation. We report a consecutive series of 38 such patients with selective use of a fasciocutaneous V-Y buttock advancement flap (BAF). METHOD Data were collected on a series of patients undergoing ELAPE for rectal malignancy between August 2011 and July 2017. Demographics, management and outcomes were recorded prospectively. Perineal wound problems were considered as 'major' if they required packing; otherwise, they were classed as 'minor'. RESULTS Thirty-eight patients [eight female and 30 male; median age 63 (range: 35-89) years] underwent ELAPE. Thirty-seven had an adenocarcinoma of the rectum and one had a malignant melanoma. The median tumour height (from the anal verge) was 30 (range: 0-80) mm. Sixteen patients had a BAF. The median length of stay was 10 (range: 6-25) days. Primary perineal healing occurred in 18 (47%) patients. Major wound breakdown occurred in three (10%) patients and minor wound breakdown in 17 (45%). Two of the 16 patients having a BAF had major wound breakdown: one wound took 9 weeks to heal completely and the other took 9 months. Of the 22 patients who did not have a BAF, one had a major wound breakdown which closed by 3 months. There were no perineal fistulae or chronic sinuses. There were two perineal herniae that were successfully repaired by perineal insertion of biological mesh (Permacol™; Covidien, Dublin, Ireland). CONCLUSIONS Selective use of a BAF for perineal closure can give good results in terms of healing and an acceptably low early perineal herniation rate.


title: Ultrasound Liver Map Technique for Laparoscopic Liver Resections.

text: BACKGROUND Laparoscopic liver resection (LLR) is reported as a safe procedure with potential advantages over open surgery albeit with inherent limitations, such as loss of haptic perception and spatial orientation. Ultrasound is considered the best tool to identify anatomic landmarks and the transection plane during liver surgery. The aim of this study was to analyse the outcomes of LLR performed with a standardized US guidance technique. METHODS We have standardized a 4-step technique for ultrasound-guided LLR: (1) compose a 3-D mind map by studying relationships among lesions and surrounding anatomic structures, (2) sketch the map on the liver surface, (3) check, and (4) correct the transection plane in real time. RESULTS Between 01/2006 and 12/2016, 190 consecutive patients treated with US-guided LLR were analysed. The indications for LLR included malignant tumours in 148 patients (81.8%). The procedures were classified according to a difficulty scale. There were 18 major hepatectomies (9.9%), 80 anatomic bi- and monosegmentectomies (44.2%), and 101 non-anatomic resections (55.8%). Redo resection was performed in 17 patients (9.4%), and multiple liver resections were performed in 25 patients (24.7%). Median intraoperative blood loss was 100 ± 154 mL. Overall and major morbidity rates were 14.9% and 1.6%, respectively. Mortality was nil. CONCLUSIONS Ultrasound liver map technique enables planning and real-time guidance during laparoscopic liver resections.


title: Travel health risk perceptions and preparations among travelers at Hong Kong International Airport.

text: Four levels of pre-travel health preparations were defined to allow the measurement of general travel health preparations by the traveling public. A cross-sectional survey of 770 travelers using Hong Kong International Airport was conducted. Important gaps were found in the self-preparation domain. Length of travel was the only factor associated with higher levels of health preparations after adjusting for potential confounders. Targeted health education should be considered to improve health risk perceptions among travelers in Hong Kong and other similar metropolitan cities that are critical hubs for commercial air transport.


title: Accelerated hemithoracic radiation followed by extrapleural pneumonectomy for malignant pleural mesothelioma.

text: OBJECTIVE To evaluate a new protocol of accelerated hemithoracic intensity-modulated radiation therapy (IMRT) followed by extrapleural pneumonectomy (EPP) for patients with resectable malignant pleural mesothelioma (MPM). METHODS A total of 25 Gy of radiation was delivered in 5 daily fractions over 1 week to the entire ipsilateral hemithorax with concomitant boost of 5 Gy to volumes at high risk based on computed tomography and positron emission tomography scan findings. EPP was performed at 6 ± 2 days after the end of radiation therapy. Adjuvant chemotherapy was offered to patients with ypN2 disease. RESULTS A total of 62 patients were included between November 2008 and October 2014. One patient died in the hospital 2 months after EPP, for an operative mortality of 1.6%, and 2 died after discharged from the hospital for an overall treatment-related mortality (grade 5 toxicity) of 4.8%. Twenty-four patients (39%) developed grade 3 to 5 (grade 3+) complications. On final pathology, 94% of the patients were stage III or IV, and 52% had ypN2 disease. The median survival for all patients as an intention-to-treat analysis was 36 months. The median overall survival and disease-free survival was 51 and 47 months, respectively, in epithelial subtypes, compared with 10 and 8 months in biphasic subtypes (P = .001). Ipsilateral chest recurrence occurred in 8 patients. CONCLUSIONS Accelerated hemithoracic IMRT followed by EPP has become our preferred approach for resectable MPM. The results have been encouraging in patients with epithelial subtype.


title: Evaluation of high-fidelity simulation as a training tool in transoral robotic surgery.

text: OBJECTIVES/HYPOTHESIS To develop and evaluate a high-fidelity training simulator for transoral robotic posterior hemiglossectomy. STUDY DESIGN Prospective observational study. METHODS We constructed a transoral robotic surgery (TORS) simulator using porcine tongue in a modified airway mannequin. Twenty-nine surgeons performed transoral robotic posterior hemiglossectomy on the simulator. The 20 resident subjects completed six trials each, and the five fellows and four attending surgeons completed two trials each. In addition to instrument vibrations, surgical video was recorded for each trial and was blindly rated using the Global Evaluative Assessment of Robotic Skill (GEARS), a validated instrument for assessing robotic surgical skill. RESULTS Attending surgeons were faster (P = .004) and demonstrated greater technical skill than fellows or residents (P < .001). Resident completion time generally decreased over the study, becoming significantly faster by the fifth trial (P = .02). A similar trend was seen in resident GEARS scores, which generally increased and were significantly improved by the fourth trial (P = .008). Instrument vibrations were not significantly different between subject groups. Finally, subjects highly rated the realism and training value of the TORS simulator (mean 4.4 and 4.7 out of 5, respectively). CONCLUSIONS The reported findings support using the described simulator as a training tool for TORS. Residents significantly improved in speed and technical skill over the course of six trials but did not achieve the performance levels of attending surgeons. These results demonstrate that high-fidelity simulation is a valuable tool for training novice surgeons in transoral robotic surgery. LEVEL OF EVIDENCE NA. Laryngoscope, 127:2790-2795, 2017.


title: SARS-CoV-2 Laboratory Testing in India's Pandemic Response: A Public Health Perspective.

text: Coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has resulted (at the time of writing) in over 3.3 million cases and 233,000 deaths globally and ~33,000 cases and ~1,100 deaths in India. The mainstay of the diagnosis is a reverse-transcription polymerase chain reaction assay to detect SARS-CoV-2 RNA. The accurate diagnosis is contingent on appropriate specimen choice, time of collection, and assay employed. In this commentary, we highlight the role of laboratory diagnostic tests used in the different stages of India's COVID-19 pandemic response.


title: Joint stability after canine cranial cruciate ligament graft reconstruction varies among femoral fixation sites.

text: OBJECTIVE To quantify stability in cranial cruciate ligament (CrCL) deficient canine stifles with hamstring grafts affixed at 3 femoral locations. STUDY DESIGN Canine stifle motion study using a multi-cohort, repeated measures design. SAMPLE POPULATION 27 canine cadaver stifles. METHODS Hamstring grafts (HG) were affixed at the gracilis-semitendinosus insertion and on the lateral femur (1) proximal trochlear ridge (TR), (2) craniodistal to fabella (F), or (3) condyle center (CC). Total, cranial, and caudal tibial translation and total, medial, and lateral angular displacement, with and without translational load, were quantified with the CrCL intact, transected, and reconstructed. Angular displacement was quantified from points on the distal femur and proximal tibia. Graft strain was calculated from tissue displacement measured at joint angles of 30°, 60°, 90°, and 120°. RESULTS Tibial translation was lowest in F constructs, which also achieved the least difference in tibial translation from intact stifles. Tibial translation was lower in intact stifles than in CrCL transected or reconstructed stifles. Less angular displacement of the proximal tibia was detected in the medial than in the lateral direction, and tibial displacement was lower in the cranial than the caudal direction. Angular displacement was lowest in the F treatment group. F constructs had the lowest graft strain at joint angles greater than 30°. CONCLUSIONS Femoral fixation of a canine hamstring graft craniodistal to the lateral fabella conferred the best joint stability and lowest graft strain in vitro. No fixation method restored joint stability of the intact CrCL.


title: The effects of environmental stressors on the mortality of the oldest old male population in Hong Kong, 1977-2006.

text: Although age-sex-specific mortality rates were decreasing over the years, such a trend was not observed for the male population aged 85 or above (the oldest old) in Hong Kong. Despite literature suggesting that environmental stressors were associated with higher mortality, the adverse effects of socioeconomic and political events were seldom included. Hence, this study explored the relationship between environmental stressors covering adverse weather conditions as well as key socioeconomic and political events and fluctuations in the oldest old mortality rates in Hong Kong during the period 1977 to 2006. The oldest old mortality rates in Hong Kong were observed to have a likelihood of being associated with these environmental stressors. Furthermore, men appeared to be more susceptible to these risk factors than did women. More care and attention should be given to the oldest old men, in particular, during periods of socioeconomic or political upheavals. A cohort study would be useful to study these stressors in greater detail.


title: Assessment of perioperative complications following primary bariatric surgery according to the Clavien-Dindo classification: comparison of sleeve gastrectomy and Roux-Y gastric bypass.

text: BACKGROUND Laparoscopic Roux-Y gastric bypass (LRYGBP) is the gold-standard procedure for the treatment of morbid obesity. It has been reported to be somewhat more efficient and durable than laparoscopic sleeve gastrectomy (LSG). However, it is considered more invasive and, therefore, more hazardous. There is a lack of unity in complication reporting following bariatric surgery. Thus, there is a possible misconception regarding the relative safety of the two major bariatric procedures performed worldwide. This may have contributed to a shift in practice with LSG gaining momentum "at the expense" of LRYGBP. The aim of this study was to evaluate the relative safety of primary LSG and LRYGBP according to the Clavien-Dindo complication grading system. METHODS A total of 2651 and 554 patients underwent primary LSG and LRYGBP, respectively at three high-volume centers. Thirty-day perioperative complications were recorded and graded. Length of hospital stays (LOS) and readmission rates were collected as well. RESULTS Complications occurred in 110 (3.7%) and 24 (4.3%) patients following LSG and LRYGBP, respectively (p = 0.9). No significant difference was found between the groups regarding overall and complication-grade-specific rates. Individual complication types were unevenly distributed, but not significantly so. Patients with complications were older than those without (47 and 43 years, respectively; p = 0.01). Gender was not a risk factor for complication. Median LOS and readmission rates were not significantly different. CONCLUSIONS LSG and LRYGBP are equally safe, at least in the perioperative period. Acknowledging and conveying this finding to surgeons and patients alike is important and might cause a pendulum shift in the distribution of bariatric procedures performed.


title: Cyclosporin A inhibits the replication of diverse coronaviruses.

text: Low micromolar, non-cytotoxic concentrations of cyclosporin A (CsA) strongly affected the replication of severe acute respiratory syndrome coronavirus (SARS-CoV), human coronavirus 229E and mouse hepatitis virus in cell culture, as was evident from the strong inhibition of GFP reporter gene expression and a reduction of up to 4 logs in progeny titres. Upon high-multiplicity infection, CsA treatment rendered SARS-CoV RNA and protein synthesis almost undetectable, suggesting an early block in replication. siRNA-mediated knockdown of the expression of the prominent CsA targets cyclophilin A and B did not affect SARS-CoV replication, suggesting either that these specific cyclophilin family members are dispensable or that the reduced expression levels suffice to support replication.


title: A Kinome-Wide Small Interfering RNA Screen Identifies Proviral and Antiviral Host Factors in Severe Acute Respiratory Syndrome Coronavirus Replication, Including Double-Stranded RNA-Activated Protein Kinase and Early Secretory Pathway Proteins.

text: UNLABELLED To identify host factors relevant for severe acute respiratory syndrome-coronavirus (SARS-CoV) replication, we performed a small interfering RNA (siRNA) library screen targeting the human kinome. Protein kinases are key regulators of many cellular functions, and the systematic knockdown of their expression should provide a broad perspective on factors and pathways promoting or antagonizing coronavirus replication. In addition to 40 proteins that promote SARS-CoV replication, our study identified 90 factors exhibiting an antiviral effect. Pathway analysis grouped subsets of these factors in specific cellular processes, including the innate immune response and the metabolism of complex lipids, which appear to play a role in SARS-CoV infection. Several factors were selected for in-depth validation in follow-up experiments. In cells depleted for the β2 subunit of the coatomer protein complex (COPB2), the strongest proviral hit, we observed reduced SARS-CoV protein expression and a >2-log reduction in virus yield. Knockdown of the COPB2-related proteins COPB1 and Golgi-specific brefeldin A-resistant guanine nucleotide exchange factor 1 (GBF1) also suggested that COPI-coated vesicles and/or the early secretory pathway are important for SARS-CoV replication. Depletion of the antiviral double-stranded RNA-activated protein kinase (PKR) enhanced virus replication in the primary screen, and validation experiments confirmed increased SARS-CoV protein expression and virus production upon PKR depletion. In addition, cyclin-dependent kinase 6 (CDK6) was identified as a novel antiviral host factor in SARS-CoV replication. The inventory of pro- and antiviral host factors and pathways described here substantiates and expands our understanding of SARS-CoV replication and may contribute to the identification of novel targets for antiviral therapy. IMPORTANCE Replication of all viruses, including SARS-CoV, depends on and is influenced by cellular pathways. Although substantial progress has been made in dissecting the coronavirus replicative cycle, our understanding of the host factors that stimulate (proviral factors) or restrict (antiviral factors) infection remains far from complete. To study the role of host proteins in SARS-CoV infection, we set out to systematically identify kinase-regulated processes that influence virus replication. Protein kinases are key regulators in signal transduction, controlling a wide variety of cellular processes, and many of them are targets of approved drugs and other compounds. Our screen identified a variety of hits and will form the basis for more detailed follow-up studies that should contribute to a better understanding of SARS-CoV replication and coronavirus-host interactions in general. The identified factors could be interesting targets for the development of host-directed antiviral therapy to treat infections with SARS-CoV or other pathogenic coronaviruses.


title: Impact of Dietary Interventions during Pregnancy on Maternal, Neonatal, and Child Outcomes in Low- and Middle-Income Countries.

text: Optimal nutrition plays a crucial role in pregnancy. Maternal malnutrition is a risk factor for maternal, fetal, and neonatal complications and is more prevalent in low and middle-income countries (LMICs). This review aims to study the effectiveness of antenatal macronutrient nutritional interventions on maternal, neonatal, and child outcomes. We searched the CENTRAL, PubMed, Embase, and other databases for randomized controlled trials and quasi-experimental designs on healthy pregnant women in LMICs. We also searched grey literature and reports from Google Scholar, Web of Science, and websites of different organizations. Title/abstract screening, full-text screening, and data extraction filtered 15 studies for inclusion. Balanced energy protein (BEP) supplementation (n = 8) studies showed a reduced incidence of perinatal mortality, stillbirths, low birth weight (LBW) infants, small for gestational age (SGA) babies and increased birth weight. Food distribution programs (FDPs) (n =5) witnessed reduced rates of SGA, stunting, wasting, and increased birth weight and birth length. Studies on intervention for obesity prevention (n = 2) showed reductions in birth weight. Other findings were statistically insignificant. Subgroup analyses were conducted to study the effectiveness of supplementation between regions, location, the timing of supplementation and nutritional status; however, there were a limited number of studies in each subgroup. Data from our review supports the antenatal supplementation of BEP and FDP for the prevention of adverse maternal, neonatal, and child outcomes that can be utilized for future policymaking. However, more research is required before recommending obesity prevention programs.


title: Update on Transanal NOTES for Rectal Cancer: Transitioning to Human Trials.

text: The feasibility of natural orifice translumenal endoscopic surgery (NOTES) resection for rectal cancer has been demonstrated in both survival swine and fresh human cadaveric models. In preparation for transitioning to human application, our group has performed transanal NOTES rectal resection in a large series of human cadavers. This experience both solidified the feasibility of resection and allowed optimization of technique prior to clinical application. Improvement in specimen length and operative time was demonstrated with increased experience and newer platforms. This extensive laboratory experience has paved the way for successful clinical translation resulting in an ongoing clinical trial. To date, based on published reports, 4 human subjects have undergone successful hybrid transanal NOTES resection of rectal cancer. While promising, instrument limitations continue to hinder a pure transanal approach. Careful patient selection and continued development of new endoscopic and flexible-tip instruments are imperative prior to pure NOTES clinical application.


Future delivery of health care: cybercare.


title: Spatial predisposition of dysplasia in Barrett's esophagus segments: a pooled analysis of the SURF and AIM dysplasia trials.

text: OBJECTIVES Surveillance endoscopy detects dysplasia within Barrett's esophagus (BE) and dictates treatment. Current biopsy regimens recommend uniformly spaced random biopsies. We assessed the distribution of dysplasia in BE to develop evidence-based biopsy regimens. METHODS We performed analysis of the distribution of dysplasia within BE using pretreatment biopsy data from two randomized controlled trials (RCTs) of radiofrequency ablation for dysplastic BE: the SURF (Surveillance vs. Radiofrequency Ablation) trial and the AIM Dysplasia (Ablation of Intestinal Metaplasia (AIM) Containing Dysplasia) trial. We used generalized linear models with generalized estimating equations (GEE) to estimate prevalence differences for dysplasia depending on the standardized location of biopsies. We performed Monte Carlo simulation of biopsy regimens to estimate their yield for any dysplasia within segments. RESULTS Dysplasia preferentially resides in the proximal-most half of the BE segment that is almost twice as likely to demonstrate dysplasia as the distal-most quartile. In pooled analysis, compared with the distal-most quarter, the prevalence difference in the proximal-most quarter was 22.6%, in the second proximal-most quarter 23.1%, and in the second distal-most quarter 15.3%. The best performing biopsy regimen in simulation studies acquired 8 biopsies in the most proximal cm of BE, 8 biopsies in the second cm, and 2 biopsies in each cm thereafter (q1cm: 8, 8, 2, 2…). A slightly simpler q2cm (every 2 cm) regimen (q2cm: 12, 12, 4…) was nearly as effective. CONCLUSIONS The post hoc analysis of two RCTs reveals a substantially increased prevalence of dysplasia proximally in BE segments. Our simulations suggest an altered biopsy regimen could increase sensitivity of biopsies in short-segment BE by >30%.


title: Intra-patient reproducibility of myocardial SPECT imaging with 201Tl.

text: BACKGROUND To define the physical and clinical reproducibility of (201)Tl myocardial perfusion SPECT (MPS), this study assesses the variation between two repeated rest (201)Tl MPS with repositioning only, with a two-hour time interval and with phantom measurements as a reference. METHODS Three anthropomorphic thorax phantoms were filled with (201)Tl. For each phantom five repeated (201)Tl MPS were obtained. In addition, in 20 patients repeated (201)Tl rest-MPS and in 26 patients early and delayed (201)Tl rest-MPS were performed. Quantitative analysis was done using MunichHeart. Statistical methods were used to calculate variability. Visual analysis was performed by 2 independent observers. RESULTS The average variation between repeated phantom MPS was 0.5% (95% confidence interval (CI): -0.4% to 1.4%). For patient scans this was -5.0% (95% CI: -2.5% to -7.5%) and between early and delayed (201)Tl MPS -15.5% (95% CI: -11.7% to -19.3%). Visual assessment revealed no clinical significant differences between rest (201)Tl and repeated or delayed (201)Tl MPS. CONCLUSIONS Repositioning in phantom (201)Tl MPS does not cause significant variation. Repeated (201)Tl MPS in patients shows 5.0% decrease of (201)Tl in 30 minutes, which increases to 15% during a two-hour time interval without quantitative or visual regional differences. This decrease indicates a time-related washout of (201)Tl, but does not change clinical diagnosis.


title: A network-based analysis of the 1861 Hagelloch measles data.

text: In this article, we demonstrate a statistical method for fitting the parameters of a sophisticated network and epidemic model to disease data. The pattern of contacts between hosts is described by a class of dyadic independence exponential-family random graph models (ERGMs), whereas the transmission process that runs over the network is modeled as a stochastic susceptible-exposed-infectious-removed (SEIR) epidemic. We fit these models to very detailed data from the 1861 measles outbreak in Hagelloch, Germany. The network models include parameters for all recorded host covariates including age, sex, household, and classroom membership and household location whereas the SEIR epidemic model has exponentially distributed transmission times with gamma-distributed latent and infective periods. This approach allows us to make meaningful statements about the structure of the population-separate from the transmission process-as well as to provide estimates of various biological quantities of interest, such as the effective reproductive number, R. Using reversible jump Markov chain Monte Carlo, we produce samples from the joint posterior distribution of all the parameters of this model-the network, transmission tree, network parameters, and SEIR parameters-and perform Bayesian model selection to find the best-fitting network model. We compare our results with those of previous analyses and show that the ERGM network model better fits the data than a Bernoulli network model previously used. We also provide a software package, written in R, that performs this type of analysis.


title: Sizing of patent ductus arteriosus in adults for transcatheter closure using the balloon pull-through technique.

text: OBJECTIVES To describe a novel balloon sizing technique used during adult transcatheter patent ductus arteriosus (PDA) closure. In addition, to determine the clinical and procedural outcomes in six patients who underwent PDA balloon sizing with subsequent deployment of a PDA occluder device. BACKGROUND Transcatheter PDA closure in adults has excellent safety and procedural outcomes. However, PDA sizing in adults can be challenging due to variable defect size, high flow state, or anatomical complexity. We describe a series of six cases where the balloon- pull through technique was successfully performed for PDA sizing prior to transcatheter closure. METHODS Consecutive adult patients undergoing adult PDA closure at our institution were studied retrospectively. A partially inflated sizing balloon was pulled through the defect from the aorta into the pulmonary artery and the balloon waist diameter was measured. Procedural success and clinical outcomes were obtained. RESULTS Six adult patients underwent successful balloon pull-through technique for PDA sizing during transcatheter PDA closure, since conventional angiography often gave suboptimal opacification of the defect. All PDAs were treated with closure devices based on balloon PDA sizing with complete closure and no complications. In three patients that underwent preprocedure computed tomography, the balloon size matched the CT derived measurements. CONCLUSION The balloon pull-through technique for PDA sizing is a safe and accurate sizing modality in adults undergoing transcatheter PDA closure.


title: Buying Time with COVID-19 Outbreak Response, Israel.

text: Israel's response during the containment phase of the COVID-19 outbreak in early 2020 led to a delay in sustained community transmission and effective mitigation. During February-April 2020, a total of 15,981 confirmed cases resulted in 223 deaths. A total of 179,003 persons reported electronically to self-quarantine and were entitled to paid sick leave.


title: Incidence, clearance, and disease progression of genital human papillomavirus infection in heterosexual men.

text: BACKGROUND In this analysis, we examine the incidence and clearance of external genital human papillomavirus (HPV) infection among heterosexual males aged 16-24 years. METHODS A total of 1732 males aged 16-24 years old in the placebo arm of a quadrivalent HPV vaccine trial were included in this analysis. Participants were enrolled from 18 countries in Africa, the Asia-Pacific region, Europe, Latin America, and North America. Subjects underwent anogenital examinations and sampling of the penis, scrotum, and perineal/perianal regions. RESULTS The incidence rate of any HPV DNA genotype 6, 11, 16, and/or 18 detection was 9.0 cases per 100 person-years. Rates of HPV DNA detection were highest in men from Africa. Median time to clearance of HPV genotypes 6, 11, 16, and 18 DNA was 6.1, 6.1, 7.7, and 6.2 months, respectively. Median time to clearance of persistently detected HPV 6, 11, 16, and 18 DNA was 6.7, 3.2, 9.2, and 4.7 months, respectively. CONCLUSION The study results suggest that the acquisition of HPV 6, 11, 16, and/or 18 in males is common and that many of these so-called infections are subsequently cleared, similar to findings for women. Nevertheless, given the high rate of HPV detection among young men, HPV vaccination of males may reduce infection in men and reduce the overall burden of HPV-associated disease in the community.


title: Bridging with reduced overlap: fixation and peritoneal grip can prevent slippage of DIS class A meshes.

text: PURPOSE Ventral hernia repair can be performed safely using meshes which are primarily stable upon dynamic intermittent straining (DIS) at recommended overlap. In specific clinical situations, e.g., at bony edges, bridging of the hernial orifice with reduced overlap might be necessary. To gain insight into the durability of various applications, two different meshes with the best tissue grip known so far were assessed. METHODS The model uses dynamic intermittent strain and comprises the repetition of submaximal impacts delivered via a hydraulically driven plastic containment. Pig tissue simulates a ventral hernia with a standardized 5 cm defect. Commercially available meshes classified as primarily stable at recommended overlap were used to bridge this defect at recommended and reduced overlap. RESULTS Using Parietex Progrip®, the peritoneum adds sufficient stability at least to a 2.5 cm overlap. Using Dynamesh Cicat®, four gluing spots with Glubran® are sufficient to stabilize a 3.75 cm overlap. A 2.5 cm overlap is stabilized with eight bonding spots Glubran® and 8 bonding spots combined with four sutures stabilize a 1.25 cm overlap. Here again, an intact peritoneum stabilizes the reconstruction significantly. CONCLUSIONS Based on a pig tissue model, a total of 23 different conditions were tested. A DIS class A mesh can be easily stabilized bridging a 5 cm hernial orifice with reduced overlap. Caution must be exerted to extend these results to other DIS classes and larger hernial orifices. Further DIS investigations can improve the durability of hernia repair.


title: Direct Oral Anticoagulants Versus Vitamin K Antagonists in Patients Undergoing Cardioversion for Atrial Fibrillation: a Systematic Review and Meta-analysis.

text: BACKGROUND Clinical guidelines recommend peri-cardioversion anticoagulation in patients with atrial fibrillation (AF). We performed a systematic review and meta-analysis to compare the safety and efficacy of direct oral anticoagulants (DOACs) versus vitamin K antagonists (VKAs) in patients with AF undergoing cardioversion. METHODS We searched CENTRAL, MEDLINE, and EMBASE for randomized controlled trials (RCTs) and observational studies comparing DOACs to VKAs in patients undergoing cardioversion for AF. We performed title, abstract, and full-text screening, data extraction, and risk of bias evaluation independently and in duplicate. We pooled data using a random effects model and evaluated the overall quality of evidence using Grading of Recommendations Assessment, Development and Evaluation. RESULTS We identified three eligible RCTs (n = 5203) and 21 observational studies (n = 11,855). The three RCTs and four observational studies were at low risk of bias. In RCTs (mean follow-up, 30 days), thromboembolic events occurred in 0.18% of patients receiving DOACs, as compared with 0.55% receiving VKAs (relative risk [RR] 0.40, 95% CI [0.13, 1.24], moderate quality). Major bleeding occurred in 0.42% of patients receiving DOACs as compared with 0.64% receiving VKAs (RR 0.62, 95% CI [0.28, 1.35], moderate quality), and death occurred in 0.28% of patients receiving DOACs as compared with 0.38% receiving VKAs (RR 0.70, 95% CI [0.23, 2.10], low quality). Confidence in the estimates of effect for observational studies was very low. CONCLUSION DOACs peri-cardioversion in patients with AF appears safe from both a bleeding and thromboembolic risk perspective. Available evidence supports the use of DOACs as standard of care peri-cardioversion in patients with AF.


title: Evidence-based occupational health and safety interventions: a comprehensive overview of reviews.

text: OBJECTIVES Occupational injuries and diseases are a huge public health problem and cause extensive suffering and loss of productivity. Nevertheless, many occupational health and safety (OHS) guidelines are still not based on the best available evidence. In the last decade, numerous systematic reviews on behavioural, relational and mixed interventions to reduce occupational injuries and diseases have been carried out, but a comprehensive synopsis is yet missing. The aim of this overview of reviews is to provide a comprehensive basis to inform evidence-based decision-making about interventions in the field of OHS. METHODS We conducted an overview of reviews. We searched MEDLINE (Ovid), the Cochrane Library (Wiley), epistemonikos.org and Scopus (Elsevier) for relevant systematic reviews published between January 2008 and June 2018. Two authors independently screened abstracts and full-text publications and determined the risk of bias of the included systematic reviews with the ROBIS (Risk of Bias in Systematic Reviews) tool. RESULTS We screened 2287 abstracts and 200 full-texts for eligibility. Finally, we included 25 systematic reviews with a low risk of bias for data synthesis and analysis. We identified systematic reviews on the prevention of occupational injuries, musculoskeletal, skin and lung diseases, occupational hearing impairment and interventions without specific target diseases. Several interventions led to consistently positive results on individual diseases; other interventions did not show any effects, or the studies are contradictory. We provide detailed results on all included interventions. DISCUSSION To our knowledge, this is the first comprehensive overview of behavioural, relational and mixed interventions and their effectiveness in preventing occupational injuries and diseases. It provides policymakers with an important basis for making evidence-based decisions on interventions in this field. PROSPERO REGISTRATION NUMBER CRD42018100341.


title: Arsenic-induced cell proliferation is associated with enhanced ROS generation, Erk signaling and CyclinA expression.

text: Arsenic is a well-established human carcinogen; however molecular mechanisms to arsenic-induced carcinogenesis are complex and elusive. The present study identifies a potential biomarker of arsenic exposure, and redefines arsenic-induced signaling in stimulation of cell proliferation. The effect of arsenic exposure on gene expression was evaluated in PBMC of arsenic-exposed individuals selected from a severely affected district of West Bengal, India. A novel, un-documented biomarker of arsenic exposure, CyclinA was identified by microarray analysis from the study. Non-transformed cell lines HaCat and Int407 when exposed to clinically achievable arsenic concentration showed significant increase of CyclinA substantiating the clinical data. An associated increase in S phase population of cells in cell cycle, indicative of enhanced proliferation was also noticed. On further investigation of the pathway to arsenic-induced proliferation, we observed that arsenic resulted: ROS generation; activated Erk signaling; stimulated AP-1 activity, including immediate early genes, c-Jun and c-Fos. N-Acetyl-l-cysteine, a ROS quencher, blocked the arsenic-induced effects. Our study underlines a previously undefined mechanism by which arsenic imparts its toxicity and results in uncontrolled cell proliferation.


Remote patient management of peritoneal dialysis during COVID-19 pandemic.


title: A systematic review and meta-analysis of supratotal versus gross total resection for glioblastoma.

text: PURPOSE Due to the infiltrative nature of glioblastoma (GBM) outside of the contrast-enhancing region on MRI, there is interest in exploring supratotal resections (SpTR) that extend beyond the contrast-enhancing portion of the tumor. However, there is currently no consensus on the potential survival benefit of SpTR in GBM compared to gross total resection (GTR). In this study, we compare the impact of SpTR versus GTR on overall survival (OS) of GBM patients. METHODS We performed a systematic review and meta-analysis of literature published on PubMed, Embase, The Cochrane Library, Web of Science, Scopus, and ClinicalTrials.gov, from inception to August 16, 2018, to identify articles comparing OS after SpTR versus GTR. RESULTS We identified 8902 unique citations, of which 11 articles met study inclusion criteria. 810 patients underwent SpTR out of a total of 2056 patients. 9 of 11 studies demonstrated improved outcomes with SpTR compared to GTR (median improvement in OS of 10.5 months), with no significant difference in postoperative complication rate. Overall study quality was variable, with ten studies presenting level IV evidence and one study presenting level IIIb evidence. Subgroup meta-analysis based on SpTR definition demonstrated a statistically significant 35% lower risk of mortality in patients who underwent anatomical SpTR compared to patients who underwent GTR (Hazard ratio = 0.65, 95% CI 0.47- 0.91, p = 0.003). CONCLUSION Our systematic review indicates SpTR may be associated with improved OS compared to GTR for GBM, especially with anatomical SpTR. However, this is limited by variable study design and significant clinical and methodological heterogeneity among studies. There is need for prospective clinical data to further guide parameters regarding the use of SpTR in GBM.


title: Posterior communicating and vertebral artery configuration and outcome in endovascular treatment of acute basilar artery occlusion.

text: BACKGROUND We aimed to evaluate if vertebrobasilar anatomic variations impact reperfusion and outcome in intra-arterial therapy (IAT) for basilar artery occlusion (BAO). METHODS Consecutive BAO patients with symptom onset <24 h treated with IAT were included. Vertebral artery (VA) V3 and posterior communicating artery (PCoA) diameters were measured (CT angiography or MR angiography). The presence of PCoA atresia, VA hypoplasia, VAs that end in the posterior inferior cerebellar artery (PICA), and extracranial VA occlusion was recorded. RESULTS 38 BAO patients were included. Mean age was 63±15 years; 52% were men. Baseline National Institutes of Health Stroke Scale score was 21±9, and mean/median time from symptom onset to IAT were 10/7 h. First generation thrombectomy devices were mostly used. Overall Treatment in Cerebral Ischemia 2b-3 reperfusion was 68.4%. Good outcome (modified Rankin Scale score ≤2) was observed in 17.8% and mortality in 64.3% of cases at 90 days. 55% of patients had an atretic PCoA while 47% had a hypoplastic VA. The mean sum of the bilateral PCoA and VA diameters were 2.3±1.2 and 5.2±5.2 mm, respectively. VAs that end in the PICA was noted in 23% of patients, and extracranial VA occlusion in 42%. BAO was proximal/mid/distal in 36%/29%/34%. Multivariate linear regression analysis indicated hypertensive disease (β=2.97; 95% CI 1.15 to 4.79; p<0.01) and reperfusion rate (β=-0.40; 95% CI -0.74 to -0.70; p=0.02) independently associated with outcome. Multivariate analysis for predictors of reperfusion failed to identify other associations. A trend for better reperfusion with stent retrievers was noted (β=1.82; 95% CI -0.24 to 3.88; p=0.08). CONCLUSIONS Reperfusion emerged as a predictor of good outcome in patients that underwent IAT for BAO. Angioarchitectural variations of the posterior circulation were not found to impact reperfusion or clinical outcome.


title: Effects of body tilt on multifrequency admittance tympanometry.

text: INTRODUCTION Hydrops and abnormalities of inner fluid pressure are involved in some otologic diseases such as Ménière's disease (MD). However, demonstrating abnormal perilymphatic or endolymphatic pressure is challenging. Multifrequency tympanometry studies in MD patients demonstrated an increase of the width of conductance tympanograms (outside an attack) compared with controls. To confirm that the increase in conductance width is caused by hyperpressure and not hypopressure in these patients tested outside an attack, we assessed the effect of changes in inner ear fluid pressure caused by body tilt on the results of multifrequency admittancemetry tympanograms. MATERIALS AND METHODS A multifrequency tympanometry including conductance (G) tympanogram at 2 kHz and resonance frequency measurements were performed in 20 volunteers (40 ears) free of otologic or neurologic disease. The measures were collected in three different positions: vertical, supine, and Trendelenburg positions. RESULTS Changes in inner ear fluid pressure caused by body tilt induced an increase in the width of G tympanograms. In the vertical position, the mean value was 141.7 ± 56.5 daPa; in the supine position, it increased to 158 ± 58.3 daPa; and increased even more in the Trendelenburg position (20 degrees), with a mean of 184 ± 69.6 daPa (p < 0.01). Resonance frequency also increased in the Trendelenburg position.We conclude that the increased width of G tympanograms in MD patients outside an attack may be caused by an increase in inner ear fluid pressure.


Use of Roeder knot with vicryl-reel ligature for laparoscopic appendicectomy: have we forgotten how to tie knots?


title: In-Play Cooling Interventions for Simulated Match-Play Tennis in Hot/Humid Conditions.

text: PURPOSE This study aimed to assess the efficacy of different in-play cooling strategies for mitigating heat strain during simulated tennis match-play activity in a hot/humid environment representing the most extreme conditions during the US Open (36°C, 50% relative humidity). METHODS On three occasions, nine males completed an intermittent treadmill protocol with an exercise intensity and activity profile simulating a four-set tennis match, with 90-s breaks between odd-numbered games and 120-s breaks between sets, according to International Tennis Federation rules. During breaks, 1) the currently used cooling strategy-an ice-filled damp towel around the neck and a cold-damp towel on the head and thighs (ICE); 2) wetting of arms, neck, face, and lower legs with a sponge in front of an electric fan (FANwet); or 3) no cooling (CON) were applied. Rectal (Tre) and mean skin (Tsk) temperature and HR were measured throughout. Thermal sensation and RPE were assessed during breaks. Trials were terminated upon reaching a Tre ≥ 39.5°C or volitional exhaustion. RESULTS Seven, five, and one participant completed FANwet, ICE, and CON, respectively. By end set 1, ΔTre was lower in FANwet (0.92°C ± 0.15°C) compared with CON (1.09°C ± 0.09°C, P = 0.01), and by end set 2, ΔTre was lower (P < 0.001) in FANwet (1.55°C ± 0.23°C) and ICE (1.59°C ± 0.17°C) compared with CON (1.99°C ± 0.19°C). Mean RPE (FANwet = 13.9 ± 2.2, ICE = 13.6 ± 1.8, CON = 16.6 ± 1.8), HR (FANwet = 163 ± 21, ICE 164 ± 22, CON = 175 ± 19 bpm), Tsk (FANwet = 36.56°C ± 0.69°C, ICE 36.12°C ± 0.44°C, CON = 37.21°C ± 0.42°C), and thermal sensation were lower in FANwet and ICE (P < 0.05) compared with CON by end set 2. CONCLUSIONS The currently recommended ICE strategy successfully mitigates thermal strain during simulated tennis match play in hot/humid conditions. The FANwet intervention is an equally effective alternative that may be more practical in limited resource settings.


title: Promoting Community Health Worker Leadership in Policy Development: Results from a Louisiana Workforce Study.

text: Community health workers (CHWs) are effective in improving public health, and many states are developing policy to support the workforce. In 2019, the Louisiana legislature created the CHW Workforce Study Committee (Committee) of at least half CHWs to study the workforce and provide the state with policy recommendations. The Committee followed national best practices in CHW engagement. A CHW and an academic team identified CHWs and employers statewide, administered a survey in partnership with a CHW professional association, and conducted in-depth interviews with CHWs and employers. Descriptive statistics were used to summarize survey data and applied thematic analysis was used to interpret interview transcripts. Sixty-five CHWs and 37 employers participated in the survey. Twenty-one CHWs and 15 employers completed interviews. Survey data indicated that Louisiana CHW roles and activities are consistent with national research. Interviews revealed a lack of knowledge about CHWs among key stakeholders, CHW workforce challenges including lack of community and professional resources, and differing ideas about the value of common workforce development practices such as standardized training and credentialing. Findings suggest a need for widespread education about CHWs and support for CHW participation in professional associations to address common workforce challenges. CHW co-leadership and partnering with a CHW professional association enabled successful study execution and full participation of CHWs in the formation of Committee recommendations. A subset of Committee members, made up of at least half CHWs, continues to meet to expand and support the workforce.


title: Validation of anatomical models to study aerosol deposition in human nasal cavities.

text: PURPOSE Intranasal deposition of aerosols is often studied using in vitro nasal cavity models. However, the relevance of these models to predict in vivo human deposition has not been validated. This study compared in vivo nasal aerosol deposition and in vitro deposition in a human plastinated head model (NC1) and its replica constructed from CT-scan (NC2). METHODS Two nebulizers (Atomisor Sonique® and Easynose®) were used to administer a 5.6 μm aerosol of (99m)Tc-DTPA to seven healthy volunteers and to the nasal models. Aerosol deposition was quantified by γ-scintigraphy in the nasal, upper nasal cavity and maxillary sinus (MS) regions. The distribution of aerosol deposition was determined along three nasal cavity axes (x, y and z). RESULTS There was no significant difference regarding aerosol deposition between the volunteers and NC1. Aerosol deposition was significantly lower in NC2 than in volunteers regarding nasal region (p < 0.05) but was similar for the upper nasal cavity and MS regions. Mean aerosol distribution for NC1 came within the standard deviation (SD) of in vivo distribution, whereas that of NC2 was outside the in vivo SD for x and y axes. CONCLUSIONS In conclusion, nasal models can be used to predict aerosol deposition produced by nebulizers, but their performance depends on their design.


The crucial role of molecular diagnostics.


title: [Suggestions on design of evidence-based traditional Chinese medicine clinical study for new public health emergencies].

text: 2019 novel coronavirus(2019-nCoV) has occurred for 2 months, and seriously affected the people's health in the world. Therefore, scientific prevention and control strategies and effective intervention measures are the only ways to solve the world problem. In the determination of intervention measures, not only the effectiveness evaluation, but also accessibility, treatment cost, inventory and production capacity and other relevant sociological issues shall be considered, especially in low and middle-income countries and regions. With the introduction of clinical epidemiological experiment design and evidence-based medicine evidence evaluation into the evaluation of curative effect of traditional Chinese medicine(TCM), TCM has officially entered the studies of syndrome regularity of new public health emergencies(such as SARS and influenza) clearly diagnosed by modern medicine for many years, as well as the development of relevant guidelines, consensus and paths. The results of curative effect show that TCM could significantly alleviate symptoms, control disease and tendency, reduce the occurrence of critical illness, and improve the clinical efficacy and the prognosis and quality of life of patients, which fully reflects the consciousness and self-confidence of traditional Chinese medicine workers. For the evidence-based evaluation of TCM intervention in new public health emergencies, the basic principles and general methods of clinical epidemiology and evidence-based medicine shall be followed to obtain high-quality evidence; besides, we shall also fully realize that clinical scientific study is carried out with the epidemic treatment as the primary task. The scientific hypothesis comes from the clinical problems unsolved. The scientific study conclusions aim to give feedbacks to clinical diagnosis and treatment regimens. The core elements of clinical trials are population(P), intervention(I), control(C), outcome(O), which are abbreviated as "PICO". The evaluation of intervention measures for new public health emergencies with traditional Chinese medicine shall have clear study objectives and a high quality, with a correct analysis method as the guarantee of real and reliable results. Then, the selection of patients, the de-finition of intervention measures and control measures, the development of end-point indicators, the clinical quality control under special epidemics, the data verification, and the data analysis methods to be adopted are all characteristics and key points that need special consideration. It is suggested that scientific experimental design, rigorous collection and scientific data analysis shall be conducted to reflect the therapeutic value of traditional Chinese medicine, so that the study results could be adopted and shared, and become the scientific evidence for China and even the global to republish the diagnosis and treatment regimens.


title: CUTANEOUS EPITHELIOTROPIC T-CELL LYMPHOMA WITH METASTASES IN A VIRGINIA OPOSSUM (DIDELPHIS VIRGINIANA).

text: A 2-yr-old, captive, intact female Virginia opossum ( Didelphis virginiana ) with a 7-mo history of ulcerative dermatitis and weight loss was euthanatized for progressive worsening of clinical signs. Initially the opossum was treated with several courses of antibiotics, both topically and systemically; systemic nonsteroidal anti-inflammatory medication; and, later, systemic glucocorticoids, with no improvement in clinical signs. Histopathologic samples of skin lesions taken 3 mo into the course of disease revealed no evidence of neoplasia; however, cytologic samples of a skin lesion taken 5 mo into the course of disease revealed mature lymphocytes, and were suggestive of cutaneous lymphoma. Postmortem histopathology revealed neoplastic cells consistent with lymphoma; these were found in the haired skin of the forearm, axilla, hind limb, face, and lateral body wall, as well as the liver, kidney, axillary lymph node, heart, and spleen. Multifocal neutrophilic and eosinophilic ulcerative and necrotizing dermatitis and folliculitis of the haired skin were also present. To the authors' knowledge, this is the first documented case of cutaneous lymphoma in a Virginia opossum and the first documented case with visceral metastases in a marsupial.


[Corrigendum to "New insights into the seriousness of acute myocardial injury during COVID-19" [G Ital Cardiol 2020;21(5):328-331]].


title: Publication Bias and Nonreporting Found in Majority of Systematic Reviews and Meta-analyses in Anesthesiology Journals.

text: BACKGROUND Systematic reviews and meta-analyses are used by clinicians to derive treatment guidelines and make resource allocation decisions in anesthesiology. One cause for concern with such reviews is the possibility that results from unpublished trials are not represented in the review findings or data synthesis. This problem, known as publication bias, results when studies reporting statistically nonsignificant findings are left unpublished and, therefore, not included in meta-analyses when estimating a pooled treatment effect. In turn, publication bias may lead to skewed results with overestimated effect sizes. The primary objective of this study is to determine the extent to which evaluations for publication bias are conducted by systematic reviewers in highly ranked anesthesiology journals and which practices reviewers use to mitigate publication bias. The secondary objective of this study is to conduct publication bias analyses on the meta-analyses that did not perform these assessments and examine the adjusted pooled effect estimates after accounting for publication bias. METHODS This study considered meta-analyses and systematic reviews from 5 peer-reviewed anesthesia journals from 2007 through 2015. A PubMed search was conducted, and full-text systematic reviews that fit inclusion criteria were downloaded and coded independently by 2 authors. Coding was then validated, and disagreements were settled by consensus. In total, 207 systematic reviews were included for analysis. In addition, publication bias evaluation was performed for 25 systematic reviews that did not do so originally. We used Egger regression, Duval and Tweedie trim and fill, and funnel plots for these analyses. RESULTS Fifty-five percent (n = 114) of the reviews discussed publication bias, and 43% (n = 89) of the reviews evaluated publication bias. Funnel plots and Egger regression were the most common methods for evaluating publication bias. Publication bias was reported in 34 reviews (16%). Thirty-six of the 45 (80.0%) publication bias analyses indicated the presence of publication bias by trim and fill analysis, whereas Egger regression indicated publication bias in 23 of 45 (51.1%) analyses. The mean absolute percent difference between adjusted and observed point estimates was 15.5%, the median was 6.2%, and the range was 0% to 85.5%. CONCLUSIONS Many of these reviews reported following published guidelines such as PRISMA or MOOSE, yet only half appropriately addressed publication bias in their reviews. Compared with previous research, our study found fewer reviews assessing publication bias and greater likelihood of publication bias among reviews not performing these evaluations.


title: Comparative analysis of perioperative outcomes of robotic versus open transversus abdominis release.

text: BACKGROUND Transversus abdominis release (TAR) has evolved as an effective approach to complex abdominal wall reconstructions. Although the role of robotics in hernia surgery is rapidly expanding, the benefits of a robotic approach for abdominal wall reconstruction have not been established well. We aimed to compare the impact of the application of robotics to the TAR procedure on the perioperative outcomes when compared to the open TAR repairs. METHODS Case-matched comparison of patients undergoing robotic TAR (R-TAR) at two specialized hernia centers to a matched historic cohort of open TAR (O-TAR) patients was performed. Outcome measures included patient demographics, operative details, postoperative complications, and length of hospitalization. RESULTS 38 consecutive patients undergoing R-TAR were compared to 76 matched O-TAR. Patient demographics were similar between the groups, but ASA III status was more prevalent in the O-TAR group. The average operative time was significantly longer in the R-TAR group (299 ± 95 vs.. 211 ± 63 min, p < 0.001) and blood loss was significantly lower for the R-TAR group (49 ± 60 vs. 139 ± 149 mL, p < 0.001). Wound morbidity was minimal in the R-TAR, but the rate of surgical site events and surgical site infection was not different between groups. Systemic complications were significantly less frequent in the R-TAR group (0 vs. 17.1%, p = 0.026). The length of hospitalization was significantly reduced in the R-TAR group (1.3 ± 1.3 vs. 6.0 ± 3.4 days, p < 0.001). CONCLUSIONS In our early experience, robotic TAR was associated with longer operative times. However, we found that the use of robotics was associated with decreased intraoperative blood loss, fewer systemic complications, shorter hospitalizations, and eliminated readmissions. While long-term outcomes and patient selection criteria for robotic TAR repair are under investigations, we advocate selective use of robotics for TAR reconstructions in patients undergoing AWR.


title: Noninvasive cardiac event monitoring to detect atrial fibrillation after ischemic stroke: a randomized, controlled trial.

text: BACKGROUND AND PURPOSE Atrial fibrillation (AF) elevates risk of recurrent stroke but is incompletely identified by standard investigation after stroke, though detection rates correlate with monitoring duration. We hypothesized that 7 days of noninvasive cardiac-event monitoring early after stroke would accelerate detection of AF and thus uptake of effective therapy. METHODS We performed a pragmatic randomized trial with objective outcome assessment among patients presenting in sinus rhythm with no AF history, within 7 days of ischemic stroke symptom onset. Patients were randomized to standard practice investigations (SP) to detect AF, or SP plus additional monitoring (SP-AM). AM comprised 7 days of noninvasive cardiac-event monitoring reported by an accredited cardiac electrocardiology laboratory. Primary outcome was detection of AF at 14 days. RESULTS One-hundred patients were enrolled from 2 centers. Within 14 days of stroke, sustained paroxysms of AF were detected in 18% of patients undergoing SP-AM versus 2% undergoing SP (P<0.05). Paroxysms of any-duration were detected in 44% of patients undergoing SP-AM versus 4% undergoing SP (P<0.001). These differences persisted at 90 days. Anticoagulant therapy was commenced within 14 days in 16% of SP-AM patients versus none randomized to SP (P<0.01). This difference persisted to 90 days (22% versus 6%; P<0.05). CONCLUSIONS Routine noninvasive cardiac-event monitoring after acute stroke enhances detection of paroxysmal AF and early anticoagulation. Extended monitoring should be offered to all eligible patients soon after acute stroke. Guidelines on investigation for AF in stroke patients could be strengthened. CLINICAL TRIAL REGISTRATION URL http://www.controlled-trials.com/isrctn/. Unique identifier: ISRCTN97412358.


title: National Public Health Institutes: contributing to the public good.

text: Donor and government funding for public health programs in low-resource countries - to increase immunizations or treat HIV/AIDS, for example - has risen dramatically. Rising less rapidly is the funding for public health functions that are not direct services or linked to programs for high-priority diseases and conditions. In many countries, these functions are housed in National Public Health Institutes (NPHIs). NPHIs are science-based agencies, usually within national governments, that include in their missions such public goods as assessing and monitoring the population's health and responding to outbreaks. Through a survey, we collected information from and about members of a new international organization for NPHIs. The responses illustrate the roles of NPHIs as purveyors of public goods. Data collected in the future on NPHI structures, practices, and challenges will be helpful to countries that are creating or restructuring NPHIs. The new knowledge will also help advocates for increasing budgetary support for the public goods functions of NPHIs.


title: Aplasia cutis congenita: clinical management of a rare congenital anomaly.

text: BACKGROUND Aplasia cutis congenita (ACC) is a rare congenital disorder characterized by absence of skin and adjacent tissue that usually affects the scalp, but any part of the body may be affected. Although ACC is more often superficial and small, it can be large and involve the underlying structures such as skull and dura, thus increasing the risk of hemorrhage, infection, and mortality. Controversy exists regarding nonsurgical versus surgical intervention for this condition. This study reviews indications and modalities for treatment of this rare congenital anomaly. RESULTS Management of this anomaly depends on size, location, and structures at risk. Small lesions with intact underlying structures and lesions affecting extremities are treated in a conservative fashion with dressings and ointments followed by delayed scar excision. Aplasia cutis congenita scar excision often requires complex tissue rearrangement, tissue expansion, or skin grafting. Larger ACC lesions or lesions with exposure of vital structures require early surgical intervention. Initially, exposed vital structures and bony ridges can be protected using conservative measures. Delayed definitive repair can then be performed using scalp flaps, split- and full-thickness skin grafts, cultured epithelial autografts, delayed split rib cranioplasty, tissue expansion, and composite cranioplasty. CONCLUSIONS Aplasia cutis congenita should be individually evaluated based on size, depth, location, and tissues involved. Using conservative and surgical modalities, one can achieve complete closure of the defect, thus avoiding risks of infection, hemorrhage, and further trauma.


title: Prevention of intraoperative awareness in a high-risk surgical population.

text: BACKGROUND Unintended intraoperative awareness, which occurs when general anesthesia is not achieved or maintained, affects up to 1% of patients at high risk for this complication. We tested the hypothesis that a protocol incorporating the electroencephalogram-derived bispectral index (BIS) is superior to a protocol incorporating standard monitoring of end-tidal anesthetic-agent concentration (ETAC) for the prevention of awareness. METHODS We conducted a prospective, randomized, evaluator-blinded trial at three medical centers. We randomly assigned 6041 patients at high risk for awareness to BIS-guided anesthesia (with an audible alert if the BIS value was <40 or >60, on a scale of 0 to 100, with 0 indicating the suppression of detectable brain electrical activity and 100 indicating the awake state) or ETAC-guided anesthesia (with an audible alert if the ETAC was <0.7 or >1.3 minimum alveolar concentration). In addition to audible alerts, the protocols included structured education and checklists. Superiority of the BIS protocol was assessed with the use of a one-sided Fisher's exact test. RESULTS A total of 7 of 2861 patients (0.24%) in the BIS group, as compared with 2 of 2852 (0.07%) in the ETAC group, who were interviewed postoperatively had definite intraoperative awareness (a difference of 0.17 percentage points; 95% confidence interval [CI], -0.03 to 0.38; P=0.98). Thus, the superiority of the BIS protocol was not demonstrated. A total of 19 cases of definite or possible intraoperative awareness (0.66%) occurred in the BIS group, as compared with 8 (0.28%) in the ETAC group (a difference of 0.38 percentage points; 95% CI, 0.03 to 0.74; P=0.99), with the superiority of the BIS protocol again not demonstrated. There was no difference between the groups with respect to the amount of anesthesia administered or the rate of major postoperative adverse outcomes. CONCLUSIONS The superiority of the BIS protocol was not established; contrary to expectations, fewer patients in the ETAC group than in the BIS group experienced awareness. (Funded by the Foundation for Anesthesia Education and Research and others; BAG-RECALL ClinicalTrials.gov number, NCT00682825.).


title: Five genetic polymorphisms of cytochrome P450 enzymes in the Czech non-Roma and Czech Roma population samples.

text: Objectives Cytochromes P450 play a role in human drugs metabolic pathways and their genes are among the most variable in humans. The aim of this study was to analyze genotype frequencies of five common polymorphisms of cytochromes P450 in Roma/Gypsy and Czech (non-Roma) population samples with Czech origin. Methods Roma/Gypsy (n=302) and Czech subjects (n=298) were genotyped for CYP1A2 (rs762551), CYP2A6 (rs4105144), CYP2B6 (rs3745274) and CYP2D6 (rs3892097; rs1065852) polymorphisms using PCR-RFLP or Taqman assay. Results We found significant allelic/genotype differences between ethnics in three genes. For rs3745274 polymorphism, there was increased frequency of T allele carriers in Roma in comparison with Czech population (53.1 vs. 43.7%; p=0.02). For rs4105144 (CYP2A6) there was higher frequency of T allele carriers in Roma in comparison with Czech population (68.7 vs. 49.8%; p<0.0001). For rs3892097 (CYP2D6) there was more carriers of the A allele between Roma in comparison with Czech population (39.2 vs. 38.2%; p=0.048). Genotype/allelic frequencies of CYP2D6 (rs1065852) and CYP1A2 (rs762551) variants did not significantly differ between the ethnics. Conclusions There were significant differences in allelic/genotype frequencies of some, but not all cytochromes P450 polymorphisms between the Czech Roma/Gypsies and Czech non-Roma subjects.


Angiotensin-converting enzyme inhibitors, angiotensin II type 1 receptor blockers and risk of COVID 19: information from Bartter's and Gitelman's syndromes patients.


DRC faces new Ebola outbreak, covid-19, and measles all at once.


title: Vesicular stomatitis virus as a novel cancer vaccine vector to prime antitumor immunity amenable to rapid boosting with adenovirus.

text: Vesicular stomatitis virus (VSV) has proven to be an effective vaccine vector for immunization against viral infection, but its potential to induce an immune response to a self-tumor antigen has not been investigated. We constructed a recombinant VSV expressing human dopachrome tautomerase (hDCT) and evaluated its immunogenicity in a murine melanoma model. Intranasal delivery of VSV-hDCT activated both CD4(+) and CD8(+) DCT-specific T-cell responses. The magnitude of these responses could be significantly increased by booster immunization with recombinant adenovirus (Ad)-hDCT, which led to enhanced efficacy against B16-F10 melanoma in both prophylactic and therapeutic settings. Notably, the interval of VSV/Ad heterologous vaccination could be shortened to as few as 4 days, making it a potential regimen to rapidly expand antigen-specific effector cells. Furthermore, VSV-hDCT could increase DCT-specific T-cell responses primed by Ad-hDCT, suggesting VSV is efficient for both priming and boosting of the immune response against a self-tumor antigen.


title: Non-enhanced magnetic resonance angiography can evaluate restenosis after carotid artery stenting with the Carotid Wallstent.

text: BACKGROUND Carotid artery stenting (CAS) requires follow-up imaging to assess in-stent restenosis (ISR). This study aimed to determine whether non-enhanced magnetic resonance angiography (NE-MRA) is useful for evaluating ISR. METHOD Between 2009 and 2013, we performed 118 consecutive CAS procedures using the Precise stent (n = 78) and the Carotid Wallstent (n = 40). We reviewed 1.5 T NE-MRA and examined visualization of the stent lumen and the degree of ISR if present. Other imaging modalities were used as references. RESULTS NE-MRA performed just after CAS was not able to visualize the stent lumen in all patients because of metal artifacts. In the Carotid Wallstent group, follow-up NE-MRA was available in 22 patients. The stent lumen was visible more than three months after CAS in all patients. Among them, >40 % ISR was observed by other modalities in eight lesions. The degree of restenosis measured by NE-MRA (y%) had a linear relationship with that measured by conventional angiography (x%) (y = 0.97x-0.4, r = 0.79, P = 0.021). In one case among 17 without ISR (6 %), NE-MRA showed false ISR. In the Precise stent group, NE-MRA did not visualize the stent lumen in the follow-up period. CONCLUSIONS NE-MRA can visualize the stent lumen in the Carotid Wallstent more than three months after CAS, but not in the Precise stent at follow-up. This delayed visualization might depend on endothelialization of the stent lumen. The degree of ISR measured by NE-MRA is comparable to that by conventional angiography. NE-MRA can evaluate ISR after CAS with the Carotid Wallstent (100 % sensitivity and 94 % specificity).


title: Ethnicity and Other Determinants of Quality of Functional Outcome in Acute Ischemic Stroke: The ENCHANTED Trial.

text: Background and Purpose- Patient-centered outcomes are important. We aimed to determine predictors of health-related quality of life (HRQoL) and develop utility-weighted modified Rankin Scale (mRS) scores in thrombolyzed acute ischemic stroke patients from both arms of ENCHANTED (Enhanced Control of Hypertension and Thrombolysis Stroke Study). Methods- ENCHANTED was an international quasi-factorial clinical trial of different doses of intravenous alteplase and intensities of blood pressure control in acute ischemic stroke patients, with outcomes on the 5-Dimensional European Quality of Life Scale and mRS assessed at 90 days post-randomization. Logistic regression models were used to identify baseline predictors of poor HRQoL (≤mean 5-Dimensional European Quality of Life Scale utility scores). Ordinary least squares regression derived utility-weighted mRS scores. Results- In 4016 acute ischemic stroke patients with complete 5-Dimensional European Quality of Life Scale and mRS data, independent predictors of poor HRQoL were older age (odds ratio, 1.19 [95% CI, 1.12-1.27], per 10-year increase), non-Asian ethnicity (1.91 [1.61-2.27]), greater stroke severity on the National Institutes of Health Stroke Scale (1.11 [1.09-1.12]), diabetes mellitus (1.41 [1.18-1.69]), premorbid disability (mRS score 1 versus 0; 1.62 [1.33-1.97]), large vessel atheromatous pathogenesis (1.32 [1.12-1.54]), and proxy respondent (2.35 [2.01-2.74]). Sensitivity analyses indicate the ethnicity influence on HRQoL was driven by the high proportion of Chinese (62.9% of Asian) participants with better HRQoL compared with non-Chinese or other Asian groups. Derived utility values across mRS scores 0 to 5 were 0.977, 0.885, 0.748, 0.576, 0.194, and -0.174, respectively. Correlations between mRS and 5-Dimensional European Quality of Life Scale scores were stronger in Asians. Conclusions- HRQoL is worse after thrombolyzed acute ischemic stroke in the elderly, non-Asians, with greater initial severity, diabetes mellitus, premorbid disability, due to large vessel atheroma, and proxy assessment. The broader significance of better HRQoL in Asians is tempered by Chinese participants dominating analyses. From utility-weighted mRS scores indicating the greatest steps in mRS scores are between 5 and 3, treatments to avoid major disability provide the greatest benefits for patients. Clinical Trial Registration- URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.


title: Viral kinetics and factors associated with rapid viral clearance during lopinavir/ritonavir-based combination therapy in non-severe COVID-19 patients.

text: OBJECTIVE Lopinavir/ritonavir has modest antiviral activity against severe acute respiratory syndrome coronavirus 2. The aim was to investigate the viral kinetics and factors associated with viral clearance during lopinavir/ritonavir-based combination treatment in non-severe patients. PATIENTS AND METHODS Sixty-four patients were retrospectively enrolled. Viral RNA was detected by real-time RT-PCR assay from sputum or throat swab samples at different time points. The patterns of viral kinetics were characterized, and factors associated with rapid viral clearance, which was defined as viral RNA undetectable within two weeks, were analyzed using multivariate logistic regression analyses. RESULTS All patients achieved viral RNA negativity and were discharged from the hospital. Furthermore, 48 (75%) and 16 (25%) patients achieved rapid and delayed viral clearance, respectively. The lymphocyte counts of rapid viral clearance patients (1.40 [1.20-1.80] × 109/L) were higher, when compared to delayed viral clearance patients (1.00 [0.70-1.47] × 109/L) (p=0.024). The multivariate logistic analysis revealed that high lymphocyte count (≥1.3×109/L) is an independent factor associated with rapid viral clearance (OR=7.62, 95% CI=1.15-50.34, p=0.035). CONCLUSIONS The viral shedding exhibited different patterns during treatment. Immune insufficiency is responsible for the delayed viral clearance, suggesting that an immunomodulator should be considered to promote viral clearance in patients with low lymphocyte counts.


Natural orifice transluminal endoscopic surgery.


title: Using common spatial distributions of atoms to relate functionally divergent influenza virus N10 and N11 protein structures to functionally characterized neuraminidase structures, toxin cell entry domains, and non-influenza virus cell entry domains.

text: The ability to identify the functional correlates of structural and sequence variation in proteins is a critical capability. We related structures of influenza A N10 and N11 proteins that have no established function to structures of proteins with known function by identifying spatially conserved atoms. We identified atoms with common distributed spatial occupancy in PDB structures of N10 protein, N11 protein, an influenza A neuraminidase, an influenza B neuraminidase, and a bacterial neuraminidase. By superposing these spatially conserved atoms, we aligned the structures and associated molecules. We report spatially and sequence invariant residues in the aligned structures. Spatially invariant residues in the N6 and influenza B neuraminidase active sites were found in previously unidentified spatially equivalent sites in the N10 and N11 proteins. We found the corresponding secondary and tertiary structures of the aligned proteins to be largely identical despite significant sequence divergence. We found structural precedent in known non-neuraminidase structures for residues exhibiting structural and sequence divergence in the aligned structures. In N10 protein, we identified staphylococcal enterotoxin I-like domains. In N11 protein, we identified hepatitis E E2S-like domains, SARS spike protein-like domains, and toxin components shared by alpha-bungarotoxin, staphylococcal enterotoxin I, anthrax lethal factor, clostridium botulinum neurotoxin, and clostridium tetanus toxin. The presence of active site components common to the N6, influenza B, and S. pneumoniae neuraminidases in the N10 and N11 proteins, combined with the absence of apparent neuraminidase function, suggests that the role of neuraminidases in H17N10 and H18N11 emerging influenza A viruses may have changed. The presentation of E2S-like, SARS spike protein-like, or toxin-like domains by the N10 and N11 proteins in these emerging viruses may indicate that H17N10 and H18N11 sialidase-facilitated cell entry has been supplemented or replaced by sialidase-independent receptor binding to an expanded cell population that may include neurons and T-cells.


title: Pandemics, Protocols, and the Plague of Athens: Insights from Thucydides.

text: When confronted by the novel ethical challenges posed by a pandemic, it is helpful to turn to history for guidance and direction. In this essay, the author revisits Thucydides's description of the Plague of Athens from The Peloponnesian War as he considers the New York State Task Force on Life and the Law's 2015 guidelines on ventilator allocation. Confronted by the exigencies of the Covid-19 surge that struck New York, he questions the task force's decision not to give any degree of preference to health care workers who might become ill. He posits that they are due a compensatory ethic and some deference given the risks they have assumed, often with inadequate protective gear. Reflecting on his ambivalence, he asks if his change of heart reflects the impact of experiential learning or the erosion of nomos-or governing norms-described by Thucydides when the plague struck Athens.


title: Management of patients with T1b esophageal adenocarcinoma: a retrospective cohort study on patient management and risk of metastatic disease.

text: BACKGROUND Esophagectomy for submucosal (T1b) esophageal adenocarcinoma (EAC) is performed in order to optimize patient outcomes given the risk of concurrent lymph node metastases (LNM). However, not seldom, comorbidity precludes these patients from surgery. Therefore, the aim of our study was to assess the course of follow-up after treatment in submucosal EAC patients undergoing surgery versus conservative therapy and to evaluate the incidence of metastatic disease. METHODS Between 2001 and 2012, all patients undergoing diagnostic endoscopic resection for EAC in two centers were reviewed. Only patients with histopathologically proven submucosal tumor invasion were included. Submucosal EACs were divided into tumors that were removed radically (R0) and irradically (R1). Subsequently, in the R0 group, EACs were classified as either low risk (LR; submucosal invasion <500 nm, G1-G2, no LVI) or high risk (HR; deep submucosal invasion >500 nm, G3-G4 and/or LVI). Metastatic disease was defined as LNM in surgical resection specimen and/or evidence of malignant disease during follow-up (FU). RESULTS Sixty-nine patients with a submucosal EAC were included [23 R1-resections and 46 R0-resection (14 R0-LR and 32 R0-HR)]. Twenty-six patients underwent surgical treatment (1 R0-LR, 12 R0-HR and 13 R1). None of the 14 R0-LR patients developed metastatic disease after a median FU of 60 months. In the R0-HR group and R1 group, metastatic disease was diagnosed in 16 and 30 % of patients, respectively. Surgical patients tended to have a better overall survival than non-surgical patients (p = 0.09). Tumor-related deaths, however, were 12 % in both groups. CONCLUSIONS In LR submucosal EAC, the risk of metastatic disease appears to be very low. In deep submucosal EAC (either R0- or R1-resection), the rate of metastatic disease is lower than reported in earlier surgical series. Given the reasonable disease-free survival and high background mortality, conservative management of these patients seems to be a valid alternative for surgery in selected cases.


title: Opposed regulation of type I IFN-induced STAT3 and ISGF3 transcriptional activities by histone deacetylases (HDACS) 1 and 2.

text: The antiviral and antiproliferative responses mediated by type I interferons (IFNs) depend on JAK/STAT signaling and ISGF3 (STAT1:STAT2:IRF9)-dependent transcription. In addition, type I IFNs stimulate STAT3 activation in many cell types, an event generally associated with cell cycle progression, survival, and proliferation. To gather more insight into this functionally contradictive phenomenon, we studied the regulation of STAT3 transcriptional activity upon type I IFN treatment. We show that IFNα2 stimulation strongly induces STAT3 phosphorylation, nuclear translocation, and promoter binding, yet the activation of transcription of a STAT3-dependent reporter and endogenous genes, such as SOCS3 and c-FOS, is impaired. Simultaneous treatment with IFNα2 and trichostatin A, as well as combined HDAC1/HDAC2 silencing, restores STAT3-dependent reporter gene and endogenous gene expression, strongly suggesting that HDAC1 and HDAC2 are directly involved in repressing IFNα2-activated STAT3. Of note, single silencing of only one of the two HDACs does not lead to enhanced STAT3 activity, supporting a functional redundancy between these two enzymes. In sharp contrast, HDAC1 and HDAC2 activities are required for ISGF3-dependent gene expression. We conclude that HDAC1 and HDAC2 differentially modulate STAT activity in response to IFNα2: while they are required for the induction of ISGF3-responsive genes, they impair the transcription of STAT3-dependent genes.


Pulmonary Artery Embolism in COVID-19 Despite Thrombosis Prophylaxis.


title: Influence of functionalized pyridine ligands on the radio/chemical behavior of [M(I)(CO)3](+) (M = Re and (99m)Tc) 2 + 1 complexes.

text: While a number of chelate strategies have been developed for the organometallic precursor fac-[M(I)(OH2)3(CO)3](+) (M = Re, (99m)Tc), a unique challenge has been to improve the overall function and performance of these complexes for in vivo and in vitro applications. Since its discovery, fac-[M(I)(OH2)3(CO)3](+) has served as an essential scaffold for the development of new targeted (99m)Tc based radiopharmaceuticals due to its labile aquo ligands. However, the lipophilic nature of the fac-[M(I)(CO)3](+) core can influence the in vivo pharmacokinetics and biodistribution of the complexes. In an effort to understand and improve this behavior, monosubstituted pyridine ligands were used to assess the impact of donor nitrogen basicity on binding strength and stability of fac-[M(I)(CO)3](+) in a 2 + 1 labeling strategy. A series of Re and (99m)Tc complexes were synthesized with picolinic acid as a bidentate ligand and 4-substituted pyridine ligands. These complexes were designed to probe the effect of pKa from the monodentate pyridine ligand both at the macro scale and radiochemical concentrations. Comparison of X-ray structural data and radiochemical solution experiments clearly indicate an increase in overall yield and stability as pyridine basicity increased.


title: Risk factors and determinants of carotid intima-media thickness in children: protocol for a systematic review and meta-analysis.

text: INTRODUCTION Carotid intima-media thickness (CIMT) is a surrogate marker of atherosclerosis that is measured in adults and children to better understand the natural history of cardiovascular disease (CVD). In adults, CIMT is predictive of myocardial infarction and stroke. In children and adolescents, CIMT is used to assess vascular changes in the presence of CVD risk factors (obesity, hypertension, smoking, etc) or clinical conditions associated with a high risk for premature CVD. However, there is no comprehensive overview, in a life-course epidemiology perspective, of the risk factors and determinants of CIMT in children. It is also important to evaluate between-study differences in CIMT measurement methods and take them into consideration when drawing conclusions. Our objective is to systematically review the evidence on the relationship between CIMT and prenatal and postnatal exposures or interventions in children, as well as documenting and discussing the CIMT measurement methods. METHODS AND ANALYSIS Systematic searches of the Medical Literature Analysis and Retrieval System Online (MEDLINE), Excerpta Medica (EMBASE)and Central Register of Controlled Trials (CENTRAL) databases will be conducted. The reference lists and other literatures sources will be browsed. Observational and experimental studies in children from birth up to 18 years will be included. Prenatal and postnatal exposures or interventions assessed in relationship with CIMT will be considered for inclusion. Examples might include gestational age, obesity, hypertension, tobacco exposure, specific at-risk conditions (chronic kidney disease, diabetes, etc) or statin treatment. The outcome will be CIMT assessed by ultrasonography. The setting, scanning and measurement methods for each included study will be described in detail. Results will be synthesised descriptively and, if appropriate, will be pooled across studies to perform meta-analyses. Separate meta-analyses for each exposure or intervention type will be conducted. ETHICS AND DISSEMINATION This systematic review will be published in a peer-reviewed journal. A report will be prepared for clinicians and other healthcare decision-makers. PROSPERO REGISTRATION NUMBER CRD42017075169.


title: Vessel perforation during stent retriever thrombectomy for acute ischemic stroke: technical details and clinical outcomes.

text: BACKGROUND Vessel perforation during stent retriever thrombectomy is a rare complication; typically only single instances have been reported. OBJECTIVE To report on a series of patients whose stent retriever thrombectomy was complicated by intraprocedural vessel perforation and discuss its potential mechanisms, rescue treatment strategies, and clinical significance. METHODS Cases with intraprocedural vessel perforation, where a stent retriever was used either as a primary treatment approach or as a part of a direct aspiration first pass technique (ADAPT), were included in the final analysis. Clinical data, procedural details, radiographic and clinical outcomes were collected from nine participating centers. RESULTS Intraprocedural vessel perforation during stent retriever thrombectomy occurred in 16 (1.0%) of 1599 cases. 63% of intraprocedural perforations occurred at distal locations. Endovascular rescue techniques (most commonly, intracranial balloon occlusion for tamponade) were attempted in 50% of cases. Procedure was aborted without any rescue attempts in 44% of cases. Mortality during hospitalization and at 3 months was 56% and 63%, respectively. 25% of patients achieved good functional outcome at 3 months after the procedure. CONCLUSIONS Intraprocedural perforations during stent retriever thrombectomy were rare, but when they occurred were associated with high mortality. Perforations most commonly occurred at distal occlusion sites and were often characterized by difficulty traversing the occlusion with a microcatheter or microwire, or while withdrawing the stent retriever. Nevertheless, 25% of patients had a favorable functional outcome, suggesting that in some patients with this complication good neurological recovery is achievable.


title: Knowledge synthesis of 100 million biomedical documents augments the deep expression profiling of coronavirus receptors.

text: The COVID-19 pandemic demands assimilation of all biomedical knowledge to decode mechanisms of pathogenesis. Despite the recent renaissance in neural networks, a platform for the real-time synthesis of the exponentially growing biomedical literature and deep omics insights is unavailable. Here, we present the nferX platform for dynamic inference from 45 quadrillion+ possible conceptual associations from unstructured text and triangulation with insights from Single Cell RNA-sequencing, bulk RNAseq and proteomics from diverse tissue types. A hypothesis-free profiling of ACE2 suggests tongue keratinocytes, olfactory epithelial cells, airway club cells and respiratory ciliated cells as potential reservoirs of the SARS-CoV-2 receptor. We find the gut as the putative hotspot of COVID-19, where a maturation correlated transcriptional signature is shared in small intestine enterocytes among coronavirus receptors(ACE2, DPP4, ANPEP). A holistic data science platform triangulating insights from structured and unstructured data holds potential for accelerating the generation of impactful biological insights and hypotheses.


title: Without its N-finger, the main protease of severe acute respiratory syndrome coronavirus can form a novel dimer through its C-terminal domain.

text: The main protease (M(pro)) of severe acute respiratory syndrome coronavirus (SARS-CoV) plays an essential role in the extensive proteolytic processing of the viral polyproteins (pp1a and pp1ab), and it is an important target for anti-SARS drug development. It was found that SARS-CoV M(pro) exists in solution as an equilibrium of both monomeric and dimeric forms, and the dimeric form is the enzymatically active form. However, the mechanism of SARS-CoV M(pro) dimerization, especially the roles of its N-terminal seven residues (N-finger) and its unique C-terminal domain in the dimerization, remain unclear. Here we report that the SARS-CoV M(pro) C-terminal domain alone (residues 187 to 306; M(pro)-C) is produced in Escherichia coli in both monomeric and dimeric forms, and no exchange could be observed between them at room temperature. The M(pro)-C dimer has a novel dimerization interface. Meanwhile, the N-finger deletion mutant of SARS-CoV M(pro) also exists as both a stable monomer and a stable dimer, and the dimer is formed through the same C-terminal-domain interaction as that in the M(pro)-C dimer. However, no C-terminal domain-mediated dimerization form can be detected for wild-type SARS-CoV M(pro). Our study results help to clarify previously published controversial claims about the role of the N-finger in SARS-CoV M(pro) dimerization. Apparently, without the N-finger, SARS-CoV M(pro) can no longer retain the active dimer structure; instead, it can form a new type of dimer which is inactive. Therefore, the N-finger of SARS-CoV M(pro) is not only critical for its dimerization but also essential for the enzyme to form the enzymatically active dimer.


title: Minimally Invasive Approach for Resection of Masseteric Vascular Malformations.

text: OBJECTIVE Vascular malformations (VMs) in the head and neck region often cause esthetic as well as functional problems for patients. Intramuscular VMs (IVM), such as those in the masseter, can cause severe facial asymmetry and typically are excised transcutaneously to facilitate wide exposure and safe dissection from the facial nerve. This requires extensive dissection, prolonged healing, and can lead to suboptimal facial scarring. METHODS We describe the technique of resecting large IVMs of the masseter muscle in 3 patients using an entirely intraoral approach with continuous nerve monitoring and without visible facial scarring or secondary deformity. Preoperative injection of sclerotherapy was performed to reduce intra-operative bleeding and optimize resection. RESULTS Successful excision was performed without complication in 3 patients to date. Total average operating room time was 120 minutes (range 95-145 minutes). Estimated blood loss was 213 mL (range 180-240 mL). The patients were discharged home either post-operative day (POD) 1 or 2, with 1 returning to work POD 4. Facial nerve function was normal postoperatively and no hematomas developed. Subjective masticatory function was equivalent to preoperative levels in all patients. CONCLUSIONS Intraoral excision of VMs of the masseter muscle can be safely performed without added risk or complication. Continuous facial nerve monitoring allows minimally invasive approaches to be considered with less risk of iatrogenic facial nerve injury. We purport that this is a safe and effective method with substantially better esthetic outcomes compared with traditional transcutaneous approaches.


title: Verbal communication for the ventilator-dependent patient requiring an inflated tracheotomy tube cuff: A prospective, multicenter study on the Blom tracheotomy tube with speech inner cannula.

text: BACKGROUND The purpose of this study was to present our findings on the impact of the Blom tracheotomy tube with speech inner cannula on voice production abilities and speech intelligibility scores of ventilator-dependent patients requiring a fully inflated tracheotomy tube cuff. METHODS Prospective single group case-series design permitted consecutive accrual of 23 adult inpatients from acute care and rehabilitation settings. Maximum ambient room noise, voice intensity, phonation duration of vowel /a/, and speech intelligibility scores were determined over 3 sessions. RESULTS All participants achieved audible voicing with the Blom tracheotomy tube. Voice intensity was significantly greater than ambient room noise by >10 dB SPL (p = .003). Speech intelligibility scores improved significantly from 80% to 85% (p = .03). Phonation duration averaged from 3.30 to 3.45 seconds. There were no significant changes in oxygen saturation (p > .05), and no significant complications occurred. CONCLUSION The Blom tracheotomy tube with speech inner cannula permitted individuals requiring mechanical ventilation with a fully inflated tracheotomy tube cuff to produce excellent speech intelligibility for verbal communication. © 2012 Wiley Periodicals, Inc. Head Neck, 2013.


title: Multiple applicator hepatic ablation with interstitial ultrasound devices: theoretical and experimental investigation.

text: PURPOSE To evaluate multiple applicator implant configurations of interstitial ultrasound devices for large volume ablation of liver tumors. METHODS A 3D bioacoustic-thermal model using the finite element method was implemented to assess multiple applicator implant configurations for thermal ablation with interstitial ultrasound energy. Interstitial applicators consist of linear arrays of up to four 10 mm-long tubular ultrasound transducers, each under separate and dynamic power control, enclosed within a water-cooled delivery catheter (2.4 mm OD). The authors considered parallel implants with two and three applicators (clustered configuration), spaced 2-3 cm apart, to simulate open surgical placement. In addition, the authors considered two applicator implants with applicators converging and diverging at angles of ∼20°, 30°, and 45° to simulate percutaneous placement. Heating experiments (10-15 min) were performed and compared against simulations employing the same experimental parameters. To estimate the performance of parallel, multiple applicator configurations in an in vivo setting, simulations were performed taking into account a range of blood perfusion levels (0, 5, 12, and 15 kg m(-3) s(-1)) that may occur in tumors of varying vascularity. The impact of tailoring the power supplied to individual transducer elements along the length of applicators is explored for applicators inserted in non-parallel (converging and diverging) configurations. Thermal dose (t(43) > 240 min) and temperature thresholds (T > 52 °C) were used to define the ablation zones, with dynamic changes to tissue acoustic and thermal properties incorporated within the model. RESULTS Experiments in ex vivo bovine liver yielded ablation zones ranging between 4.0-5.6 cm × 3.2-4.9 cm, in cross section. Ablation zone dimensions predicted by simulations with similar parameters to the experiments were in close agreement (within 5 mm). Simulations of in vivo heating showed that 15 min heating and interapplicator spacing less than 3 cm are required to obtain contiguous, complete ablation zones. The ability to create complete ablation zone profiles for nonparallel implants was illustrated by tailoring applied power levels along the length of applicators. CONCLUSIONS Parallel implants consisting of three interstitial ultrasound applicators in a triangular configuration yield complete ablation zones measuring up to 6.2 cm × 5.7 cm after 15 min heating. At larger interapplicator spacing, the level of blood perfusion in the tumor may yield indentations along the periphery of the ablation zone. Tailoring applied power along the length of the applicator can accommodate for nonparallel implants, without compromising safety.


title: Optimal Timing for Laparoscopic Cholecystectomy After Endoscopic Retrograde Cholangiopancreatography: A Systematic Review.

text: BACKGROUND AND AIMS Endoscopic retrograde cholangiopancreatography followed by laparoscopic cholecystectomy is often used as definitive treatment for common bile duct stones. The aim of this study was to investigate the optimal time interval between endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy. MATERIALS AND METHODS PubMed and Embase were searched for studies comparing different time delays between endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy. Observational studies and randomized controlled trials were included. Primary outcome was conversion rate from laparoscopic to open cholecystectomy and secondary outcomes were complications, mortality, operating time, and length of stay. RESULTS A total of 14 studies with a total of 1930 patients were included. The pooled estimate revealed an increase from a 4.2% conversion rate when laparoscopic cholecystectomy was performed within 24 h of endoscopic retrograde cholangiopancreatography to 7.6% for 24-72 h delay to 12.3% when performed within 2 weeks, to 12.3% for 2-6 weeks, and to a 14% conversion rate when operation was delayed more than 6 weeks. CONCLUSION According to this systematic review, it is preferable to perform cholecystectomy within 24 h of endoscopic retrograde cholangiopancreatography to reduce conversion rate. Early laparoscopic cholecystectomy does not increase mortality, perioperative complications, or length of stay and on the contrary it reduces the risk of reoccurrence and progression of disease in the delay between endoscopic retrograde cholangiopancreatography and laparoscopic cholecystectomy.


Countries test tactics in 'war' against COVID-19.


Should we rename low risk cancers?


title: Testing for coverage from personal protective equipment: Public Health England's guidance does not protect healthcare workers from droplet spray.

text: In order to reduce transmission of the SARS-CoV-2 virus, healthcare workers in the UK are advised to wear personal protective equipment (PPE). When undertaking aerosol-generating procedures, Public Health England recommends the use of gloves, gown, filtering mask and full-face visor or goggles . Despite this, uncertainty remains regarding the role of some items of PPE, such as hoods and visors .


title: Nephrometry score-guided off-clamp laparoscopic partial nephrectomy: patient selection and short-time functional results.

text: BACKGROUND Laparoscopic partial nephrectomy (LPN) is not a novel but a relatively technically challenging surgical procedure. Off-clamp LPN with zero ischemia can completely eliminate ischemic reperfusion injury to the kidney. The purpose of this study was to evaluate the safety and functional outcome of nephrometry score-guided off-clamp technique in LPN. METHODS A total of 44 patients underwent LPN between January 2015 and July 2015 for renal mass with radius, exophytic/endophytic, nearness to sinus, anterior/posterior location (RENAL) score 4 were enrolled. Twenty-two of them underwent off-clamp LPN with zero ischemia, and the other 22 received standard LPN with common renal artery clamp. Estimate blood loss (EBL), total operation time, resection time, renorrhaphy time, preoperative estimated glomerular filtration rate (eGFR), postoperative eGFR, eGFR change, and drainage after surgery were compared between these two groups using t test. RESULTS Patients' characteristics including gender, age, BMI, tumor size, and RENAL score were balanced between the two groups. Average EBL was more in the off-clamp group than in the on-clamp group (134.32 versus 70.23 ml, p = 0.001). Average eGFR change was less in the off-clamp group than in the on-clamp group (-1.56 versus -6.45, p < 0.001). Average drainage after surgery was 203.41 ml for the off-clamp group and 145.46 ml for the on-clamp group, p = 0.062. No urinary leakage and hematuria occurred in both groups. There were no statistical difference in total operation time, resection time, renorrhaphy time, preoperative eGFR, and postoperative eGFR between the two groups. CONCLUSIONS Off-clamp LPN is a safe and feasible approach to excise certain kidney tumors with RENAL score 4. This technique can better preserve kidney function without ischemic reperfusion injury.