title: COVID-19 in multiple sclerosis: The Dutch experience.

text: Here, we provide an extensive overview of all reported COVID-19 cases in multiple sclerosis (MS) patients in the Netherlands between 27 February and 9 June 2020, gathered by the Dutch MS Taskforce of the Netherlands Society of Neurology. A total of 86 MS patients were reported, 43 of whom tested positive for COVID-19. Of 43 patients who tested positive, 22 patients were hospitalized. Three intensive care unit (ICU) admissions and four deaths were reported. Our findings show no apparent difference in disease-modifying treatment (DMT) use and COVID-19 disease course in Dutch MS patients. In addition, a clear link between low lymphocyte count and severe disease was not observed.


title: The Diagnostic Utility of Synovial Fluid Markers in Periprosthetic Joint Infection: A Systematic Review and Meta-analysis.

text: INTRODUCTION This study is a systematic review of all reported synovial fluid markers for the diagnosis of periprosthetic joint infection and a meta-analysis of the most frequently reported markers to identify those of greatest diagnostic utility. METHODS A search of six databases was conducted to identify all studies evaluating the utility of synovial fluid markers in the diagnosis of periprosthetic joint infection. Two observers assessed methodologic quality and extracted data independently. A meta-analysis of the most frequently reported markers was performed. RESULTS Twenty-three studies were included in the meta-analysis. The most common markers (and their respective area under the curve) were interleukin-17 (0.974), leukocyte esterase (0.968), α-defensin (0.958), interleukin-6 (0.956), interleukin-1β (0.948), and C-reactive protein (0.927). Among these markers, α-defensin had the highest diagnostic odds ratio but did not achieve statistically significant superiority. CONCLUSION The most frequently studied synovial fluid markers for the diagnosis of periprosthetic joint infection are C-reactive protein, leukocyte esterase, interleukin-6, interleukin-1β, α-defensin, and interleukin-17, all of which have high diagnostic utility. LEVEL OF EVIDENCE Level II.


title: Ribavirin and interferon-α2b as primary and preventive treatment for Middle East respiratory syndrome coronavirus: a preliminary report of two cases.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly recognized transmissible viral infection with high virulence and case fatality rates for which there is no currently defined primary treatment or prophylaxis. Saudi Arabia has the largest reported number of cases so far. Like severe acute respiratory syndrome (SARS), MERS is caused by a coronavirus. Combination therapy with interferon-α2b and ribavirin has been used successfully as primary treatment and prophylaxis in SARS. Because of similarities between the two coronaviruses, treatment with ribavarin and interferon-α2b has been suggested as a potential therapy for MERS-CoV. Studies in animal models of MERS-CoV have shown the combination of ribavirin and interferon-α2b to be effective both as primary treatment and prophylaxis. In this report, we describe for the first time use of this combination as a primary treatment for a patient with MERS-CoV infection and as prophylaxis for his spouse and discuss its possible role.


title: How has COVID19 impacted on Learning Disability Nursing Services in Scotland?

text: The impact on acute NHS services and care homes has been well documented and at the forefront of media attention. Learning disability services have responded to the COVID19 pandemic however to date there has been limited consideration on how this is affecting individual lives. This has been considered and explored by one board area in Scotland.


title: Evolutionary origin of the immune system: a dialogue with Rod Langman.

text: The need of a specific defence mechanism against intracellular pathogens is proposed to have arisen very early in evolution, perhaps already in protozoa, e.g. amoebae. The phagocytic machinery of amoebae lends itself as a possible starting point for the evolution of such a mechanism. The hypothetical evolutionary pathway described here has been constructed to demonstrate the feasibility of developing a defence system against pathogens in the amoeba, which bears resemblances to contemporary cell-mediated immunity, and can thus be considered as its ancestor.


title: Evaluation of a minimally invasive cell sampling device coupled with assessment of trefoil factor 3 expression for diagnosing Barrett's esophagus: a multi-center case-control study.

text: BACKGROUND Barrett's esophagus (BE) is a commonly undiagnosed condition that predisposes to esophageal adenocarcinoma. Routine endoscopic screening for BE is not recommended because of the burden this would impose on the health care system. The objective of this study was to determine whether a novel approach using a minimally invasive cell sampling device, the Cytosponge, coupled with immunohistochemical staining for the biomarker Trefoil Factor 3 (TFF3), could be used to identify patients who warrant endoscopy to diagnose BE. METHODS AND FINDINGS A case-control study was performed across 11 UK hospitals between July 2011 and December 2013. In total, 1,110 individuals comprising 463 controls with dyspepsia and reflux symptoms and 647 BE cases swallowed a Cytosponge prior to endoscopy. The primary outcome measures were to evaluate the safety, acceptability, and accuracy of the Cytosponge-TFF3 test compared with endoscopy and biopsy. In all, 1,042 (93.9%) patients successfully swallowed the Cytosponge, and no serious adverse events were attributed to the device. The Cytosponge was rated favorably, using a visual analogue scale, compared with endoscopy (p < 0.001), and patients who were not sedated for endoscopy were more likely to rate the Cytosponge higher than endoscopy (Mann-Whitney test, p < 0.001). The overall sensitivity of the test was 79.9% (95% CI 76.4%-83.0%), increasing to 87.2% (95% CI 83.0%-90.6%) for patients with ≥3 cm of circumferential BE, known to confer a higher cancer risk. The sensitivity increased to 89.7% (95% CI 82.3%-94.8%) in 107 patients who swallowed the device twice during the study course. There was no loss of sensitivity in patients with dysplasia. The specificity for diagnosing BE was 92.4% (95% CI 89.5%-94.7%). The case-control design of the study means that the results are not generalizable to a primary care population. Another limitation is that the acceptability data were limited to a single measure. CONCLUSIONS The Cytosponge-TFF3 test is safe and acceptable, and has accuracy comparable to other screening tests. This test may be a simple and inexpensive approach to identify patients with reflux symptoms who warrant endoscopy to diagnose BE.


title: Transanal single-port laparoscopic total mesorectal excision in the treatment of rectal cancer.

text: Our objective was to report of our first experience with transanal total mesorectal excision (TME) of rectal cancer using single-port equipment, a pure natural orifice transluminal endoscopic surgery (NOTES) procedure, and to discuss the advantages and disadvantages of the technique. A patient with rectal cancer was selected according to preoperative evaluation criteria. Purse-string sutures were placed into the rectum distal to the tumor using the procedure of prolapse and hemorrhoids (PPH) anoscope. A full-thickness incision of the rectal wall was made circumferentially below the purse string and a three-channel cannula was inserted. The artificial orifice was insufflated. The entire mesorectum was dissected upward according to the principles of TME. Pneumoperitoneum was created by opening the rectouterine pouch. The sigmoid colon and its mesentery were dissected, and the inferior mesenteric vessels were ligated and divided. After dissection of a sufficient length of sigmoid colon, the PPH anoscope and the three-channel cannula were removed. The rectum and sigmoid colon were brought out through the anus. The tumor was resected. After removal of the specimens, a stapled end-to-end anastomosis was fashioned between the rectum and the sigmoid colon. Operative time was 300 min. The mesorectum was completely removed with negative distal and circumferential margin. The final pathological stage was pT3N1M0, with one positive lymph node (1/12). The patient recovered uneventfully after surgery. Pure-NOTES performed as transanal single-port laparoscopic TME for rectal cancer appears to be feasible and safe.


title: Delayed-Onset Chylous Ascites After a Living-Donor Liver Transplant: First Case Successfully Treated With Conservative Treatment?

text: Chylous ascites is a rare complication in liver transplant. Few cases have been reported to date. In most cases, chylous ascites is diagnosed within 1 month after surgery because of intraoperative injury of the hilar lymphatic system. Preoperative massive ascites and use of a LigaSure vessel sealing system for hilar dissection have been reported as risk factors. We report a case of chylous ascites after a living-donor liver transplant that was diagnosed after 6 months of uneventful follow-up. Sirolimus was added to cyclosporine early (2 wk after the operation) owing to poor renal function and it was found to be high (> 22 ng/mL) when the chylous ascites occurred. The patient was treated with total parenteral nutrition in combination with Sandostatin and rapid tapering of sirolimus after the failed initial conservative treatment. Residual abdominal fullness after meals and lymphedema of the legs disappeared 1 month after discontinuing sirolimus. This is the first case of delayed-onset chylous ascites after a liver transplant that was successfully treated conservatively.


title: Cerebral oxygen saturation during the first 72h after birth in infants diagnosed prenatally with congenital heart disease.

text: BACKGROUND Evidence suggests that hypoxic-ischemic brain injury in infants with congenital heart disease already occurs during early life. The aim of our study was, therefore, to assess the course of regional cerebral oxygen saturation (rcSO2) and fractional tissue oxygen extraction (FTOE) during the first 72h after birth in infants with prenatally diagnosed duct-dependent congenital heart disease. In addition, we identified clinical parameters that were associated with rcSO2. MATERIALS AND METHODS We included 56 infants with duct-dependent congenital heart disease. We measured arterial oxygen saturation (SpO2) and rcSO2 during the first 72h after birth. Simultaneously, we calculated FTOE. RESULTS We observed median rcSO2 values of approximately 60%, a decreasing FTOE from 0.34 on day 1 to 0.28 on day 3 and stable preductal SpO2 values around 90%. Several clinical variables were associated with rcSO2. In a multiple linear regression model only type of CHD and preductal SpO2 were significant predictors of rcSO2 during the first three days after birth. Infants with a duct-dependent pulmonary circulation had up to 12% lower rcSO2 values than infants with a duct-dependent systemic circulation. CONCLUSION We demonstrated that, during the first three days after birth, cerebral oxygen saturation is low in infants with duct-dependent congenital heart disease. Furthermore, this study provides preoperative reference values of rcSO2 and FTOE in infants with duct-dependent CHD.


title: How Medical Studies in Poland Prepare Future Healthcare Managers for Crises and Disasters: Results of a Pilot Study.

text: In the event of a crisis, rapid and effective assistance for victims is essential, and in many cases, medical assistance is required. To manage the situation efficiently, it is necessary to have a proactive management system in place that ensures professional assistance to victims and the safety of medical personnel. We evaluated the perceptions of students and graduates in public health studies at the Medical University of Lublin, Poland, concerning their preparation and management skills for crises such as the COVID-19 pandemic. This pilot study was conducted in March 2020; we employed an online survey with an anonymous questionnaire that was addressed to students and graduates with an educational focus in healthcare organization and management. The study involved 55 people, including 14 men and 41 women. Among the respondents, 41.8% currently worked in a healthcare facility and only 21.7% of them had participated in training related to preparation for emergencies and disasters in their current workplace. The respondents rated their workplaces' preparedness for the COVID-19 pandemic at four points. A significant number of respondents stated that if they had to manage a public health emergency, they would not be able to manage the situation correctly and not be able to predict its development. Managers of healthcare organizations should have the knowledge and skills to manage crises. It would be advisable for them to have been formally educated in public health or healthcare administration. In every healthcare facility, it is essential that training and practice of performing medical procedures in full personal protective equipment (PPE) be provided. Healthcare facilities must implement regular training combined with practical live scenario exercises to prepare for future crises.


title: Bioactive compounds from marine resources against novel corona virus (2019-nCoV): in silico study for corona viral drug.

text: Present research reports the molecular docking analysis of 2019-nCoV inhibition by antiviral compounds from marine natural resources. For this study, the structure of ligand (antiviral compound) and 2019-nCoV main protease (Mpro) was received from the databases of PubChem and Protein Data Bank (PDB), respectively. Molecular Docking was performed by Autodock version 4.2.6 software. Eight antiviral compounds identified showed inhibitory activities against novel 2019-nCoV protease. Of these compounds, Esculetin ethyl ester (-8.42 kcal/mol) from Marine Sponges Axinella cf. corrugata, has the strongest interaction with the protease enzyme of 2019-nCoV and it may be considered as an effective 2019-nCoV antiprotease drug.


title: Inferring influenza dynamics and control in households.

text: Household-based interventions are the mainstay of public health policy against epidemic respiratory pathogens when vaccination is not available. Although the efficacy of these interventions has traditionally been measured by their ability to reduce the proportion of household contacts who exhibit symptoms [household secondary attack rate (hSAR)], this metric is difficult to interpret and makes only partial use of data collected by modern field studies. Here, we use Bayesian transmission model inference to analyze jointly both symptom reporting and viral shedding data from a three-armed study of influenza interventions. The reduction in hazard of infection in the increased hand hygiene intervention arm was 37.0% [8.3%, 57.8%], whereas the equivalent reduction in the other intervention arm was 27.2% [-0.46%, 52.3%] (increased hand hygiene and face masks). By imputing the presence and timing of unobserved infection, we estimated that only 61.7% [43.1%, 76.9%] of infections met the case criteria and were thus detected by the study design. An assessment of interventions using inferred infections produced more intuitively consistent attack rates when households were stratified by the speed of intervention, compared with the crude hSAR. Compared with adults, children were 2.29 [1.66, 3.23] times as infectious and 3.36 [2.31, 4.82] times as susceptible. The mean generation time was 3.39 d [3.06, 3.70]. Laboratory confirmation of infections by RT-PCR was only able to detect 79.6% [76.5%, 83.0%] of symptomatic infections, even at the peak of shedding. Our results highlight the potential use of robust inference with well-designed mechanistic transmission models to improve the design of intervention studies.


title: Temporal Healing of Achilles Tendons After Injury in Rodents Depends on Surgical Treatment and Activity.

text: INTRODUCTION Achilles tendon ruptures affect 15 of 100,000 women and 55 of 100,000 men each year. Controversy continues to exist regarding optimal treatment and rehabilitation protocols. The objective of this study was to investigate the temporal effects of surgical repair and immobilization or activity on Achilles tendon healing and limb function after complete transection in rodents. METHODS Injured tendons were repaired (n = 64) or left nonrepaired (n = 64). The animals in both cohorts were further randomized into groups immobilized in plantar flexion for 1, 3, or 6 weeks that later resumed cage and treadmill activity for 5, 3, or 0 weeks, respectively (n = 36 for each regimen), which were euthanized at 6 weeks after injury, or into groups immobilized for 1 week and then euthanized (n = 20). RESULTS At 6 weeks after injury, the groups that had 1 week of immobilization and 5 weeks of activity had increased range of motion and decreased ankle joint toe stiffness compared with the groups that had 3 weeks of immobilization and 3 weeks of activity. The groups with 6 weeks of immobilization and no activity period had decreased tendon cross-sectional area but increased tendon echogenicity and collagen alignment. Surgical treatment dramatically decreased fatigue cycles to failure in repaired tendons from groups with 1 week of immobilization and 5 weeks of activity. Normalized comparisons between 1-week and 6-week postinjury data demonstrated that changes in tendon healing properties (area, alignment, and echogenicity) were maximized by 1 week of immobilization and 5 weeks of activity, compared with 6 weeks of immobilization and no activity period. DISCUSSION This study builds on an earlier study of Achilles tendon fatigue mechanics and functional outcomes during early healing by examining the temporal effects of different immobilization and/or activity regimens after initial postinjury immobilization. CONCLUSION This study demonstrates how the temporal postinjury healing response of rodent Achilles tendons depends on both surgical treatment and the timing of immobilization/activity timing. The different pattern of healing and qualities of repaired and nonrepaired tendons suggest that two very different healing processes may occur, depending on the chosen immobilization/activity regimen.


Finding the true prevalence of obstructive lung disease: two steps forward and one step back.


title: Randomized clinical trial of stapler versus clamp-crushing transection in elective liver resection.

text: BACKGROUND Various devices have been developed to facilitate liver transection and reduce blood loss in liver resections. None of these has proven superiority compared with the classical clamp-crushing technique. This randomized clinical trial compared the effectiveness and safety of stapler transection with that of clamp-crushing during open liver resection. METHODS Patients admitted for elective open liver resection between January 2010 and October 2011 were assigned randomly to stapler transection or the clamp-crushing technique. The primary endpoint was the total amount of intraoperative blood loss. Secondary endpoints included transection time, duration of operation, complication rates and resection margins. RESULTS A total of 130 patients were enrolled, 65 to clamp-crushing and 65 to stapler transection. There was no difference between groups in total intraoperative blood loss: median (i.q.r.) 1050 (525-1650) versus 925 (450-1425) ml respectively (P = 0·279). The difference in total intraoperative blood loss normalized to the transection surface area was not statistically significant (P = 0·092). Blood loss during parenchymal transection was significantly lower in the stapler transection group (P = 0·002), as were the parenchymal transection time (mean(s.d.) 30(21) versus 9(7) min for clamp-crushing and stapler transection groups respectively; P < 0·001) and total duration of operation (mean(s.d.) 221(86) versus 190(85) min; P = 0·047). There were no significant differences in postoperative morbidity (P = 0·863) or mortality (P = 0·684) between groups. CONCLUSION Stapler transection is a safe technique but does not reduce intraoperative blood loss in elective liver resection compared with the clamp-crushing technique. REGISTRATION NUMBER NCT01049607 (http://www.clinicaltrials.gov).


title: Laparoscopic Gastric Bypass with Fundectomy and Gastric Remnant Exploration (LRYGBfse): Results at 5-Year Follow-up.

text: BACKGROUND The laparoscopic Roux-en-Y gastric bypass (LRYGB) is the gold standard treatment for morbid obesity. After LRYGB, the endoscopic access to the gastric remnant and pancreaticobiliary system is challenging. The laparoscopic gastric bypass with fundectomy and exploration of the gastric remnant (LRYGBfse) was introduced in an attempt to overcome this limitation. The purpose of this study was to analyze the medium-term outcomes and safety of LRYGBfse. METHODS Observational prospective single-arm multicenter cohort study. Patients with BMI > 35 kg/m2 were included. Previous open abdominal surgery was an exclusion criterion. Postoperative 1, 2, 3, and 5-year weight loss, BMI decrease, and percentage of excess weight loss (%EWL) were recorded. Wilcoxon signed rank sum test was used for paired data. RESULTS Among 653 enrolled patients, 229 completed the 5-year follow-up. Preoperative median body weight (kg) and BMI (kg/m2) were 133.4 kg (interquartile range (IQR) = 12.0) and 48.2 kg/m2 (IQR = 10.1), respectively. Median 5-year body weight, BMI, and %EWL were 83.7 (IQR = 17.3), 31.2 (IQR = 7.7), and 74.8 (IQR = 23.4), respectively, all significantly improved compared to baseline (p = 0.002, p = 0.001, and p = 0.012, respectively). Comorbid improvement or resolution was observed in 88% of the patients. No major intraoperative complications were reported. Postoperative overall morbidity and mortality rates were 1 and 0%, respectively. Banding removal was necessary in one patient 62 months after the index operation. CONCLUSIONS The LRYGBfse seems safe and effective with durable results at 5-year follow-up. Endoscopic exploration of the gastric remnant is an additional valuable tool.


Tuberculosis vaccine trials.


title: H1N1 influenza vaccine compliance among hospital- and non-hospital-based healthcare personnel.

text: BACKGROUND The 2009 pandemic H1N1 influenza vaccine had lower uptake compared to seasonal influenza vaccine, and most studies examining uptake of H1N1 vaccine focused on hospital-based healthcare personnel (HCP). Determinants of H1N1 vaccine uptake among HCP in all work settings need to be identified so that interventions can be developed for use in encouraging uptake of future pandemic or emerging infectious disease vaccines. OBJECTIVE To identify factors influencing nonhospital HCP H1N1 influenza vaccine compliance. DESIGN AND SETTING An H1N1 influenza vaccine compliance questionnaire was administered to HCP working in myriad healthcare settings in March-June 2011. METHODS Surveys were used to assess H1N1 influenza vaccine compliance and examine factors that predicted H1N1 influenza vaccine uptake. RESULTS In all, 3,188 HCP completed the survey. Hospital-based HCP had higher compliance than did non-hospital-based personnel (Χ2 = 142.2, P < .001). In logistic regression stratified by hospital setting versus nonhospital setting, determinants of H1N1 vaccination among non-hospital-based HCP included extent to which H1N1 vaccination was mandated or encouraged, perceived importance of vaccination, access to no-cost vaccine provided on-site, no fear of vaccine side effects, and trust in public health officials when they say that the influenza vaccine is safe. Determinants of hospital-based HCP H1N1 vaccine compliance included having a mandatory vaccination policy, perceived importance of vaccination, no fear of vaccine side effects, free vaccine, perceived seriousness of H1N1 influenza, and trust in public health officials. CONCLUSIONS Non-hospital-based HCP versus hospital-based HCP reasons for H1N1 vaccine uptake differed. Targeted interventions are needed to increase compliance with pandemic-related vaccines.


title: A Yersinia pestis tat mutant is attenuated in bubonic and small-aerosol pneumonic challenge models of infection but not as attenuated by intranasal challenge.

text: Bacterial proteins destined for the Tat pathway are folded before crossing the inner membrane and are typically identified by an N-terminal signal peptide containing a twin arginine motif. Translocation by the Tat pathway is dependent on the products of genes which encode proteins possessing the binding site of the signal peptide and mediating the actual translocation event. In the fully virulent CO92 strain of Yersinia pestis, the tatA gene was deleted. The mutant was assayed for loss of virulence through various in vitro and in vivo assays. Deletion of the tatA gene resulted in several consequences for the mutant as compared to wild-type. Cell morphology of the mutant bacteria was altered and demonstrated a more elongated form. In addition, while cultures of the mutant strain were able to produce a biofilm, we observed a loss of adhesion of the mutant biofilm structure compared to the biofilm produced by the wild-type strain. Immuno-electron microscopy revealed a partial disruption of the F1 antigen on the surface of the mutant. The virulence of the ΔtatA mutant was assessed in various murine models of plague. The mutant was severely attenuated in the bubonic model with full virulence restored by complementation with the native gene. After small-particle aerosol challenge in a pneumonic model of infection, the mutant was also shown to be attenuated. In contrast, when mice were challenged intranasally with the mutant, very little difference in the LD50 was observed between wild-type and mutant strains. However, an increased time-to-death and delay in bacterial dissemination was observed in mice infected with the ΔtatA mutant as compared to the parent strain. Collectively, these findings demonstrate an essential role for the Tat pathway in the virulence of Y. pestis in bubonic and small-aerosol pneumonic infection but less important role for intranasal challenge.


title: The Future of Bioethics: It Shouldn't Take a Pandemic.

text: The Covid-19 pandemic has concentrated bioethics attention on the "lifeboat ethics" of rationing and fair allocation of scarce medical resources, such as testing, intensive care unit beds, and ventilators. This focus drives ethics resources away from persistent and systemic problems-in particular, the structural injustices that give rise to health disparities affecting disadvantaged communities of color. Bioethics, long allied with academic medicine and highly attentive to individual decision-making, has largely neglected its responsibility to address these difficult "upstream" issues. It is time to broaden our teaching, research, and practice to match the breadth of the field in order to help address these significant societal inequities and unmet health needs.


title: Laparoscopic pancreaticoduodenectomy in pancreatic cancer: Our initial experience.

text: Pancreas cancer is an important cause of mortality worldwide. It has no particular symptoms, and may cause different complaints according to tumor diameter and localization. Local invasion may develop in the short term and distant metastasis may occur in vascular structures in its neighborhood. That's why, resectability rates are low at the time of diagnosis with a negative effect on survival rates. Minimally invasive surgery is being increasingly implemented in pancreas lesions owing to the positive short-term oncologic results of the technique in many other procedures. Traditionally, conventional open surgery is performed in pancreatic head tumors. As laparoscopic resection of pancreatic head cancer has serious technical difficulties and requires advanced laparoscopic experience, minimal invasive attempts in this field have not yet reached sufficient acceptance worldwide. Besides the fact that laparoscopic pancreaticoduodenectomy may provide sufficient short-term oncologic results that are comparative with open surgery, it can be implemented in selected patients in centers with advanced laparoscopic resection capacity. In this case series, we aimed to present our experience of laparoscopic pancreaticoduodenectomy in pancreatic head cancer patients.


title: β-Blockers in sepsis: protocol for a systematic review and meta-analysis of randomised control trials.

text: INTRODUCTION Sepsis is a common and deadly complication of infection. As part of the host response, sympathetic stimulation can result in septic myocardial depression, and metabolic, haematological and immunological dysfunction. Administration of β-blockers may attenuate this pathophysiological response to infection, but the effects on clinical outcomes are unknown. The objective of this systematic review is to determine the efficacy and safety of β-blockers in adults with sepsis using data from randomised control trials. METHODS AND ANALYSIS We will identify randomised control trials comparing treatment with β-blockers, versus placebo or standard care in adults with sepsis. Data sources will include MEDLINE, EMBASE, CENTRAL, clinical trial registries and conference proceedings. Two reviewers will independently determine trial eligibility. For each included trial, we will conduct duplicate independent data extraction, risk of bias assessment and evaluation of the quality of the evidence using the GRADE approach. ETHICS AND DISSEMINATION Our systematic review will evaluate the effects of β-blockers in adults with sepsis, comprehensively summarising and appraising the available evidence from randomised control trials. The results of this systematic review will help clinicians treating patients with sepsis to understand the potential role of β-blockade, and inform future research on this topic. Our findings will be disseminated through conference presentation and publication in a peer-reviewed journal. TRIAL REGISTRATION NUMBER CRD42016036933.


title: Practical 'modular design' research of emergency drug supplies in hospitals.

text: Objectives To determine an effective framework for supplying emergency drugs under various scenarios using 'modular design' and information technology. Additionally, medicinal safety was improved by combining pharmacy monitoring with a safety alert system for medication. Methods Data from various emergency events and details of the disease related to the incident were analysed using Cluster, Delphi and Decision analyses. The optimal drug combination was determined and then divided into the different modules. We established the 'drug supply expedited system in emergencies' based on the above modules, and we organised emergency drills to verify the system's effectiveness and to improve efficiency. Pharmaceutical care services were performed by rehearsing the unexpected emergency incident and associated pharmaceutical care. Results We developed a drug supply framework for 'traffic accidents, poisoning first aid, natural disasters, epidemics and mass disturbances' and established an 'emergency drug supply expedited system'. We quickly equipped the drugs that were needed for the special emergency events, and we developed a 'green channel' between the emergency and drug supply centres. Medication safety was also important for the emergencies, and clinical pharmacists played a role in medicating the safety service personnel. The utility of our findings was demonstrated through several emergency drills. Conclusions In this study, we explored the optimal drug supply and pharmacy assistance models for emergency medicine. The clinical innovation of this study was that we provided a modular supply of medical supplies for traffic accidents. We also established a drug supply information system. This study provided effective reference values for emergency drug therapy.


title: ACR Appropriateness Criteria® acute respiratory illness in immunocompetent patients.

text: Acute respiratory illness is defined as one or more of the following: cough, sputum production, chest pain, or dyspnea (with or without fever). The workup of these patients depends on many factors, including clinical presentation and the suspected etiology. This study reviews the literature on the indications and usefulness of radiologic studies for the evaluation of acute respiratory illness in the immunocompetent patient. The following recommendations are the result of evidence-based consensus by the American College of Radiology Appropriateness Criteria Expert Panel on Thoracic Radiology. Chest radiographs are usually appropriate in (1) patients with positive physical examination or risk factors for pneumonia, (2) for the assessment of complicated pneumonia, or (3) in cases of emerging infections and biological warfare agents such as severe acute respiratory syndrome, H1N1, and anthrax. Computed tomography, although having a more limited role, is usually appropriate (1) in the assessment of complicated pneumonia and (2) in patients with suspected severe acute respiratory syndrome, H1N1, or anthrax and a normal radiograph.


title: Single-incision laparoscopic cholecystectomy using a modified dome-down approach with conventional laparoscopic instruments.

text: INTRODUCTION Single-incision laparoscopic cholecystectomy (SILC) may increase the risk of bile duct injury due to compromised operative exposure. Dome-down laparoscopic cholecystectomy provides the ability to evaluate the cystic duct circumferentially prior to its division, thus minimizing the risks of bile duct injury. This study assesses the feasibility and safety of SILC using a modified dome-down approach with all conventional laparoscopic instruments. METHODS Three low-profile 5-mm trocars are placed via a single transumbilical incision. The two working trocars are aimed laterally via the rectus to achieve adequate triangulation. An extralong 5-mm 30º laparoscope with an L-shaped light-cord adaptor is used to yield more external working space. Cephalic liver retraction is achieved with one transabdominal suture through the gallbladder fundus. Leaving the gallbladder fundus attached to the liver bed, a window is first created between the gallbladder body and the liver. The dissection is then carried down retrograde toward the porta hepatis. A 360º view of the gallbladder-cystic duct junction is achieved prior to transecting the cystic duct. The gallbladder is then freed by separation of the fundal attachments. The specimen is retrieved by enlarging the fascial incision. All fascial defects are then primarily closed. RESULTS Sixteen patients (mean age 31 years, mean BMI 26.3 kg/m(2)) were enrolled in this study. Thirteen had elective surgery for symptomatic cholelithiasis, and three had emergency surgery for acute cholecystitis. Mean operating time was 80.3 min, and blood loss was minimal. All patients were discharged within 24 h without complications. Follow-up at 1 month revealed a barely visible scar within the umbilicus. CONCLUSIONS SILC using a modified dome-down approach is technically feasible with all straight instruments, and it is safe because of good delineation of ductal anatomy. Adoption of this approach may minimize the risk of bile duct injury during early experience of SILC.


title: Effects of wearing lower leg compression sleeves on locomotion economy.

text: The purpose of this investigation was to assess the effect of compression sleeves on muscle activation cost during locomotion. Twenty-two recreationally active men (age: 25 ± 3 years) ran on a treadmill at four different speeds (ordered sequence of 2.8, 3.3, 2.2, and 3.9 m/s). The tests were performed without (control situation, CON) and while wearing specially designed lower leg compression sleeves (SL). Myoelectric activity of five lower leg muscles (tibialis anterior, fibularis longus, lateral and medial head of gastrocnemius, and soleus) was captured using Surface EMG. To assess muscle activation cost, the cumulative muscle activity per distance travelled (CMAPD) of the CON and SL situations was determined. Repeated measures analyses of variance were performed separately for each muscle. The analyses revealed a reduced lower leg muscle activation cost with respect to test situation for SL for all muscles (p < 0.05, ηp2 > 0.18). The respective significant reductions of CMAPD values during SL ranged between 4% and 16% and were largest at 2.8 m/s. The findings presented point towards an improved muscle activation cost while wearing lower leg compression sleeves during locomotion that have potential to postpone muscle fatigue.


title: A wearable chemical-electrophysiological hybrid biosensing system for real-time health and fitness monitoring.

text: Flexible, wearable sensing devices can yield important information about the underlying physiology of a human subject for applications in real-time health and fitness monitoring. Despite significant progress in the fabrication of flexible biosensors that naturally comply with the epidermis, most designs measure only a small number of physical or electrophysiological parameters, and neglect the rich chemical information available from biomarkers. Here, we introduce a skin-worn wearable hybrid sensing system that offers simultaneous real-time monitoring of a biochemical (lactate) and an electrophysiological signal (electrocardiogram), for more comprehensive fitness monitoring than from physical or electrophysiological sensors alone. The two sensing modalities, comprising a three-electrode amperometric lactate biosensor and a bipolar electrocardiogram sensor, are co-fabricated on a flexible substrate and mounted on the skin. Human experiments reveal that physiochemistry and electrophysiology can be measured simultaneously with negligible cross-talk, enabling a new class of hybrid sensing devices.


title: The experience of financial burden for patients with multimorbidity: A protocol for a systematic review of qualitative research.

text: Introduction: Multimorbidity is increasingly important due to its high disease burden, prevalence and related high healthcare utilisation. For patients, there is also a high financial burden due to direct and indirect costs arising from their multimorbidity. It is unclear how this financial burden affects patients. This study aims to synthesise qualitative evidence exploring the experience of financial burden from the perspective of patients with multimorbidity. Methods: The review will be reported using the ENTREQ guidelines. A systematic search of Lilacs, PubMed, CINAHL, EMBASE, PsycINFO, and Applied Social Sciences Index and Abstracts will be conducted using a predefined search strategy. A search of fourteen pre-specified websites will be conducted for grey literature. Forward and backward citation checking of included studies will be conducted also. Studies will be included if they contain primary qualitative research and reference the experience of financial burden from the perspective of adult (≥ 18 years) community dwelling patients with multimorbidity. Studies from any country and in any language will be included. Titles and abstracts of search results will be screened; if a study appears relevant, then full-texts will be screened for eligibility. Study characteristics of included articles will be extracted. Study quality will be evaluated using the critical appraisal skills programme (CASP) checklist for qualitative research. These three processes will be carried out by two reviewers independently. Thematic-synthesis will be used to analyse data. This will be carried out by one reviewer and cross-checked by a second reviewer. The GRADE CERQual approach will be used to assess the overall confidence in the evidence. Discussion: This review will identify evidence on the experiences of financial burden for patients with multimorbidity and forms part of a project to support consideration of financial burden for patients in the development of clinical guidelines in Ireland. PROSPERO registration number: CRD42019135284.


Get the facts first.


title: Dynamic respiratory endoscopic findings pre- and post laryngoplasty in Thoroughbred racehorses.

text: REASONS FOR PERFORMING STUDY To investigate laryngeal function in cases of recurrent laryngeal neuropathy pre- and post laryngoplasty (LP) using dynamic respiratory endoscopy (DRE). OBJECTIVES To compare the rima glottidis area during DRE pre- and post LP; document all forms of dynamic upper airway obstruction (DUAO) pre- and post LP and investigate the relationship between post operative abduction at rest and exercise. STUDY DESIGN Prospective case series. METHODS Thoroughbred racehorses with pre- and post LP DRE were included. Left-to-right arytenoid cartilage angle ratios and rima glottidis area ratios were used to quantify laryngeal function during rest and exercise, pre- and post LP. RESULTS In 35 horses, mean pre-LP ratios were greater during rest (left-to-right quotient angle ratio [LRQ] 0.76 ± 0.13; left-to-right arytenoid ratio [LRR] 0.72 ± 0.14; rima glottidis area ratio [RGA] 0.40 ± 0.10) than exercise (LRQ 0.39 ± 0.16, P < 0.001; LRR 0.38 ± 0.16, P < 0.001; RGA 0.15 ± 0.05, P < 0.001). Exercising ratios were larger post LP (LRQ 0.61 ± 0.13; LRR 0.60 ± 0.12; RGA 0.30 ± 0.08) than pre-LP (LRQ 0.39 ± 0.16, P < 0.001; LRR 0.38 ± 0.16, P < 0.001; RGA 0.15 ± 0.05, P < 0.001). A positive linear relationship was found between post LP resting and exercising ratios (R(2) = 0.48; P < 0.001) and post operative abduction grades (R(2) = 0.63; P < 0.001). Pre-LP all horses demonstrated left arytenoid cartilage collapse with bilateral vocal cord collapse and 37% had aryepiglottic fold collapse. Post LP 13 horses (37%) developed additional DUAOs and these horses had smaller RGAs (0.25 ± 0.08) than horses that did not develop DUAOs (0.32 ± 0.07, P = 0.01). CONCLUSIONS Multiple forms of DUAO occurred pre-LP and additional forms often developed post LP. Post LP the degree of arytenoid cartilage abduction at rest was useful to predict the degree of abduction during exercise.


title: Novel coronavirus disease pandemic and ophthalmologist's perspectives.

text: Ophthalmologists are among those healers facing a higher risk of acquiring novel coronavirus disease 2019, called COVID-19, during their professional duties since they have close physical contact with their patients. Some patients with COVID-19 may present with or may develop conjunctivitis during the course of the illness. The ocular secretions and tears have been identified to have positive results to COVID-19 tests and as such could be a source of spread. This review aims at providing the useful guidelines to ophthalmic professionals for their own safety, and safety of their patients based on the available current literature, and also based on personal experience and observations. Literature search was made on PubMed for COVID-19 in relation to ophthalmology in the limited period of the last quarter of 2019 and first quarter of 2020. Research also included access to current guidelines published by various ophthalmic societies. Accordingly, present and future ophthalmic practice patterns need to be modified.


title: Histologic evaluation of absorbable and non-absorbable barrier coated mesh secured to the peritoneum with fibrin sealant in a New Zealand white rabbit model.

text: PURPOSE The purpose of this study is to evaluate the histologic response to fibrin sealant (FS) as an alternative fixation method for laparoscopic ventral hernia repair. METHODS One non-absorbable barrier mesh (Composix™) and three absorbable barrier meshes (Sepramesh™, Proceed™, and Parietex™ Composite) were used for the study, with uncoated macroporous polypropylene mesh (ProLite Ultra™) as the control. Three methods of fixation were used: #0-polypropylene suture + FS (ARTISS™, Baxter Healthcare Corp.), FS alone (ARTISS™), or tacks alone (n = 10 for each group). Two pieces of mesh (of dimensions 4 × 4-cm) were secured intraperitoneally in 75 New Zealand white rabbits. After 8 weeks, hematoxylin and eosin (H&E)-stained specimens were evaluated for host tissue response. Statistical significance (P < 0.05) was determined using a one-way analysis of variance (ANOVA) with Fisher's least significant difference (LSD) post hoc test. RESULTS Composix™ with FS only showed significantly greater cellular infiltration than with suture + FS (P = 0.0007), Proceed™ with FS only had significantly greater neovascularization than with suture + FS (P = 0.0172), and ProLite Ultra™ with suture + FS had significantly greater neovascularization than with tacks only (P = 0.046). Differences due to mesh type showed that Composix™ exhibited less extensive cellular infiltration (P ≤ 0.0032), extracellular matrix (ECM) deposition, and neovascularization, and demonstrated less inflammatory cells and more fibroblasts compared to the other meshes (P < 0.05). CONCLUSIONS FS did not have a significant histologic effect compared to tacks when utilized for the fixation of mesh to the peritoneum of New Zealand White rabbits. However, the mesh type did have a significant histologic effect. The permanent barrier mesh (Composix™) was associated with less histologic incorporation than absorbable barrier and macroporous meshes, as evidenced by lower levels of cellular infiltration, ECM deposition, and neovascularization, independent of the fixation method used.


title: Immediate and follow-up results for 44 consecutive cases of small (<10 mm) internal carotid artery aneurysms treated with the pipeline embolization device.

text: BACKGROUND The pipeline embolization device (PED) provides effective, durable and safe endovascular reconstruction of large and giant intracranial aneurysms. However, 80% of all cerebral aneurysms found in the general population are less than 10 mm in size. Treatment of small aneurysms (<10 mm) with flow diverters may be advantageous over endosaccular modalities that carry risks of procedural rupture during aneurysm access or coil placement. METHODS We retrospectively reviewed a prospective, single-center aneurysm database to identify all patients with small (<10 mm) internal carotid artery (ICA) aneurysms who underwent endovascular treatment using the PED. Patient demographics, aneurysm characteristics, procedural details, complications, and technical and clinical outcomes were analyzed. RESULTS Forty-four cases were performed in 41 patients (age range 31-78 years). PED was successfully implanted in 42 cases. A single PED was used in 37/42 (88%) cases. Mean postprocedure hospital stay was 1.7 ± 0.3 days and 98% of patients were discharged home. Major complication occurred in one patient (2.3%), who died of early subarachnoid hemorrhage. Transient neurological deficit, delayed intracerebral hemorrhage (asymptomatic), and delayed groin infection occurred in one patient each. Follow-up rate was 91.8% (45 aneurysms in 35 patients) with a mean follow-up of 4.0 ± 1.9 months. By 6 months post-PED implantation, angiographic success (complete or near complete aneurysm occlusion) was observed in 80%. Mild (<50%), asymptomatic, nonflow limiting in-stent stenosis was observed in 5.4% (2/37 cases). All the 35 patients with follow-up remained at preprocedure neurological baseline. CONCLUSION Small (<10 mm) ICA aneurysm treatment with PED implantation is safe and carries a high rate of early angiographic success.


title: IL-10-dependent S100A8 gene induction in monocytes/macrophages by double-stranded RNA.

text: The S100 calcium-binding proteins S100A8 and S100A9 are elevated systemically in patients with viral infections. The S100A8-S100A9 complex facilitated viral replication in human CD4(+) T lymphocytes latently infected with HIV-1- and S100A8-induced HIV-1 transcriptional activity. Mechanisms inducing the S100 genes and the potential source of these proteins following viral activation are unknown. In this study, we show that S100A8 was induced in murine macrophages, and S100A8 and S100A9 in human monocytes and macrophages, by polyinosinic:polycytidylic acid, a dsRNA mimetic. Induction was at the transcriptional level and was IL-10 dependent. Similar to LPS-induced S100A8, induction by dsRNA was dependent on p38 and ERK MAPK. Protein kinase R (PKR) mediates antiviral defense and participates in MyD88-dependent/independent signaling triggered by TLR4 or TLR3. Like IL-10, S100 induction by polyinosinic:polycytidylic acid and by LPS was inhibited by the specific PKR inhibitor 2-aminopurine, indicating a novel IL-10, PKR-dependent pathway. Other mediators such as IFN-beta, which synergized with dsRNA, may also be involved. C/EBPbeta bound the defined promoter region in response to dsRNA. S100A8 was expressed in lungs of mice infected with influenza virus and was maximal at day 8 with strong immunoreactivity in epithelial cells lining the airways and in mononuclear cells and declined early in the recovery phase, implying down-regulation by mediator(s) up-regulated during resolution of the infection. IL-10 is implicated in viral persistence. Since S100A8/S100A9 levels are likely to be maintained in conditions where IL-10 is raised, these proteins may contribute to viral persistence in patients infected by some RNA viruses.


title: SARS-CoV regulates immune function-related gene expression in human monocytic cells.

text: Severe acute respiratory syndrome (SARS) is characterized by acute respiratory distress syndrome (ARDS) and pulmonary fibrosis, and monocytes/macrophages are the key players in the pathogenesis of SARS. In this study, we compared the transcriptional profiles of SARS coronavirus (SARS-CoV)-infected monocytic cells against that infected by coronavirus 229E (CoV-229E). Total RNA was extracted from infected DC-SIGN-transfected monocytes (THP-1-DC-SIGN) at 6 and 24 h after infection, and the gene expression was profiled in oligonucleotide-based microarrays. Analysis of immune-related gene expression profiles showed that at 24 h after SARS-CoV infection: (1) IFN-α/β-inducible and cathepsin/proteasome genes were downregulated; (2) hypoxia/hyperoxia-related genes were upregulated; and (3) TLR/TLR-signaling, cytokine/cytokine receptor-related, chemokine/chemokine receptor-related, lysosome-related, MHC/chaperon-related, and fibrosis-related genes were differentially regulated. These results elucidate that SARS-CoV infection regulates immune-related genes in monocytes/macrophages, which may be important to the pathogenesis of SARS.


title: Bipolar sealing increases mesenteric reach during bowel transection compared with stapled division: clinical evidence and laboratory support in a porcine model.

text: BACKGROUND The ideal technique for mesenteric division to create tension-free anastomoses has not been defined. For patients undergoing Roux-en-Y gastric bypass (RYGB), the mesenteric division technique was changed from stapler to bipolar sealing using LigaSure for cost reasons. This study aimed objectively to assess the impact of the mesenteric division method on mobilization length of the Roux limb in an animal model. Clinical complications related to Roux limb tension also were analyzed in the authors' population of RYGB patients. METHODS Bowel and mesenteric divisions were performed in a porcine model. Four pigs received six to eight mesenteric divisions each. Steady force was applied for 1 min. The distances between the divided limbs of bowel were compared. To assess the clinical impact with RYGB patients, anastomotic complications were analyzed before and after incorporation of bipolar sealing in the authors' practice. RESULTS In the porcine model, the length of mesenteric stretch averaged 93.7 mm with stapled division and 109 mm with bipolar sealing (p = 0.021). From a laparoscopic RYGB population, 160 patients with stapled division were included, all of whom were at least 1 year beyond their surgery. The study analyzed 792 patients with bipolar sealing for leak or bleeding and included 479 bipolar sealed patients more than 1 year beyond their surgery for analysis of their strictures. No difference in bleeding or leaks was found between these groups. The stricture rate was significantly different, with seven strictures after stapled division (4.37%) compared with one stricture after bipolar sealing (0.2%; p = 0.001). CONCLUSIONS Bipolar sealing for mesenteric division is superior to stapling for optimization of enteric limb length at constant tension in a laboratory model. Clinical evidence supports this hypothesis with patients undergoing RYGB surgery by a decrease in the complications that can arise from Roux limb tension.


title: Should nasogastric tube insertion during the COVID-19 pandemic be considered as an aerosol-generating procedure?

text: Nasogastric tubes are used frequently in surgical patients for bowel decompression, provision of enteral nutritional support and preventing aspiration of gastric contents. There is no conclusive research into the risk of COVID-19 transmission associated with nasogastric tube insertion, although evidence from the severe acute respiratory syndrome outbreak appears to suggest that there is no increased risk of transmission. However, close contact with a COVID-19 patient, especially those displaying respiratory symptoms, is likely to increase the risk of transmission. Nasogastric tube insertion requires increased time spent at a patient's bedside and can also cause pharyngeal irritation, resulting in coughing. In addition, the nasogastric tube can expose the healthcare worker to potentially infectious saliva. Therefore, there is a clear need for increased evidence regarding the risk of transmission associated with nasogastric tube insertion, to ensure that such risks can be mitigated.


title: Altered exhaled biomarker profiles in children during and after rhinovirus-induced wheeze.

text: Preschool rhinovirus-induced wheeze is associated with an increased risk of asthma. In adult asthma, exhaled volatile organic compounds (VOC) are associated with inflammatory activity. We therefore hypothesised that acute preschool wheeze is accompanied by a differential profile of exhaled VOC, which is maintained after resolution of symptoms in those children with rhinovirus-induced wheeze. We included 178 children (mean±sd age 22±9 months) from the EUROPA cohort comparing asymptomatic and wheezing children during respiratory symptoms and after recovery. Naso- and oropharyngeal swabs were tested for rhinovirus by quantitative PCR. Breath was collected via a spacer and analysed using an electronic nose. Between-group discrimination was assessed by constructing a 1000-fold cross-validated receiver operating characteristic curve. Analyses were stratified by rhinovirus presence/absence. Wheezing children demonstrated a different VOC profile when compared with asymptomatic children (p<0.001), regardless of the presence (area under the curve (AUC) 0.77, 95% CI 0.07) or absence (AUC 0.81, 95% CI 0.05) of rhinovirus. After symptomatic recovery, discriminative accuracy was maintained in children with rhinovirus-induced wheeze (AUC 0.84, 95% CI 0.06), whereas it dropped significantly in infants with non-rhinovirus-induced wheeze (AUC 0.67, 95% CI 0.06). Exhaled molecular profiles differ between preschool children with and without acute respiratory wheeze. This appears to be sustained in children with rhinovirus-induced wheeze after resolution of symptoms. Therefore, exhaled VOC may qualify as candidate biomarkers for early signs of asthma.


title: Defining a global research agenda for breast cancer.

text: In contrast to western high-income nations, the incidence and mortality from breast cancer are increasing in most low and middle-income countries worldwide. Current approaches to breast cancer control developed for populations of high-income societies should not be directly transferred without evaluation. A relevant research agenda includes population differences in tumor biology and metabolization of systemic therapies, cultural and psychosocial issues, and operations in healthcare systems. Highest priority should be given to assessments of clinical downstaging and basic systemic treatment effectiveness in low and middle-income populations. Partnerships of existing organizations in high-income nations with those in low and middle-income countries are currently the most feasible sources of research support.


title: Successful segmental thermal ablation of varicose saphenous veins in a patient with confirmed vascular Ehlers-Danlos syndrome.

text: We describe here the successful scheduled treatment of varicose veins by radiofrequency segmental thermal ablation in a 43-year-old patient with vascular Ehlers-Danlos syndrome. Her venous disease started at the age of 16 years, 1 year prior to her first major Ehlers-Danlos syndrome-related event which led to the diagnosis of her genetic condition. Surgical stripping was contra-indicated because of Ehlers-Danlos syndrome at the age of 18 years. More than 20 years later, her venous disease had become highly symptomatic despite daily compression and pain medication. Venous reassessment evidenced incompetent right and left great saphenous and left small saphenous veins, with increased diameters of both sapheno-femoral and sapheno-popliteal junctions. Radiofrequency endovenous ablation rather than surgery was considered because of its minimally invasive nature and because of standardized energy delivery.All intended-to-be-treated incompetent saphenous vein segments were occluded successfully, followed by an important improvement of clinical disease severity at day 30, persistent at 1 year post-treatment. Duplex ultrasound confirmed closure and fibrotic retraction of all treated venous segments at 1 year. This report shows that radiofrequency endovenous ablation may be a safe and effective therapy of varicose veins in patients with diagnosed vascular Ehlers-Danlos syndrome.


title: Anatomically based approach for endovascular treatment of vertebro-vertebral arteriovenous fistula.

text: Vertebro-vertebral arteriovenous fistula (VV-AVF) is a rare vascular disorder with an abnormal high-flow shunt between the extracranial vertebral artery (VA), its muscular or radicular branches and an adjacent vein. To date, there are no guidelines on the best treatment for VV-AVF. We present our experience of VV-AVF treatment with covered stents in three patients and detachable coils in two patients. One patient with fistula at the V3 segment had rapid fistula recurrence one week after covered stent treatment. The possible causes of failed treatment in this patient are discussed. The currently available treatment modalities for VV-AVF are also summarized after a literature review. At the end of this article, we propose a new concept of anatomically based approach for endovascular treatment of VV-AVF. Fistula in the V1-2 segments of vertebral artery could be treated safely and effectively by covered stent with the benefit of preserving VA patency. Embolization with variable embolizers should be considered first for fistula in the V3 segment because of the tortuous course and flexibility of the VA in this segment.


title: Lost and found: Coronary stent retrieval and review of literature.

text: A 61-year-old man with a history of percutaneous coronary intervention (PCI) of the mid right coronary artery (RCA) with a drug eluting stent (DES), presented with non-ST segment elevation myocardial infarction. Coronary angiography demonstrated complex disease of the distal RCA as well as in-stent stenosis of the previously placed mid RCA stent. The patient underwent bifurcation PCI of the distal RCA followed by attempted intervention with a DES on the mid RCA lesion. The stent could not cross the lesion and eventually became dissociated from its delivery system. The lost stent was successfully retrieved using two different snaring systems. The procedure was terminated without further attempts for stent delivery. The patient had an uneventful recovery and underwent successful PCI of the mid RCA lesion one month later.


Randomized clinical trial of fibrin sealant versus titanium tacks for mesh fixation in laparoscopic umbilical hernia repair (Br J Surg 2011; 98: 1537-1545).


title: Tapered-cuff Endotracheal Tube Does Not Prevent Early Postoperative Pneumonia Compared with Spherical-cuff Endotracheal Tube after Major Vascular Surgery: A Randomized Controlled Trial.

text: BACKGROUND Patients undergoing major vascular surgery often develop postoperative pneumonia that impacts their outcomes. Conflicting data exist concerning the potential benefit of tapered-shaped cuffs on tracheal sealing. The primary objective of this study was to assess the efficiency of a polyvinyl chloride tapered-cuff endotracheal tube at reducing the postoperative pneumonia rate after major vascular surgery. Secondary objectives were to determine its impact on microaspiration, ventilator-associated pneumonia rate, and inner cuff pressure. METHODS This prospective randomized controlled study included 109 patients who were randomly assigned to receive either spherical- (standard cuff) or taper-shaped (tapered cuff) endotracheal tubes inserted after anesthesia induction and then admitted to the intensive care unit after major vascular surgery. Cuff pressure was continuously recorded over 5 h. Pepsin and α-amylase concentrations in tracheal aspirates were quantified on postoperative days 1 and 2. The primary outcome was the early postoperative pneumonia frequency. RESULTS Comparing the tapered-cuff with standard-cuff group, respectively, postoperative pneumonia rates were comparable (42 vs. 44%, P = 0.87) and the percentage (interquartile range) of cuff-pressure time with overinflation was significantly higher (16.1% [1.5 to 50] vs. 0.6% [0 to 8.3], P = 0.01), with a 2.5-fold higher coefficient of variation (20.2 [10.6 to 29.4] vs. 7.6 [6.2 to 10.2], P < 0.001). Although microaspiration frequencies were high, they did not differ between groups. CONCLUSION For major vascular surgery patients, polyvinyl chloride tapered-cuff endotracheal tubes with intermittent cuff-pressure control did not lower the early postoperative pneumonia frequency and did not prevent microaspiration.


Twitter as a powerful tool for communication between pain physicians during COVID-19 pandemic.


title: Therapeutic potential of RNA interference: a new molecular approach to antiviral treatment for hepatitis C.

text: Hepatitis C virus (HCV) infection remains a major cause of chronic liver disease with an estimated 170 million carriers worldwide. Current treatments have significant side effects and have met with only partial success. Therefore, alternative antiviral drugs that efficiently block virus production are needed. During recent decades, RNA interference (RNAi) technology has not only become a powerful tool for functional genomics but also represents a new therapeutic approach for treating human diseases including viral infections. RNAi is a sequence-specific and post-transcriptional gene silencing process mediated by double-stranded RNA (dsRNA). As the HCV genome is a single-stranded RNA that functions as both a messenger RNA (mRNA) and replication template, it is an attractive target for the study of RNAi-based viral therapies. In this review, we will give a brief overview about the history and current status of RNAi and focus on its potential application as a therapeutic option for treatment for HCV infection.


title: Nonstructural proteins 7 and 8 of feline coronavirus form a 2:1 heterotrimer that exhibits primer-independent RNA polymerase activity.

text: Nonstructural proteins 7 and 8 of severe acute respiratory syndrome coronavirus (SARS-CoV) have previously been shown by X-ray crystallography to form an 8:8 hexadecamer. In addition, it has been demonstrated that N-terminally His(6)-tagged SARS-CoV Nsp8 is a primase able to synthesize RNA oligonucleotides with a length of up to 6 nucleotides. We present here the 2.6-Å crystal structure of the feline coronavirus (FCoV) Nsp7:Nsp8 complex, which is a 2:1 heterotrimer containing two copies of the α-helical Nsp7 with conformational differences between them, and one copy of Nsp8 that consists of an α/β domain and a long-α-helix domain. The same stoichiometry is found for the Nsp7:Nsp8 complex in solution, as demonstrated by chemical cross-linking, size exclusion chromatography, and small-angle X-ray scattering. Furthermore, we show that FCoV Nsp8, like its SARS-CoV counterpart, is able to synthesize short oligoribonucleotides of up to 6 nucleotides in length when carrying an N-terminal His(6) tag. Remarkably, the same protein harboring the sequence GPLG instead of the His(6) tag at its N terminus exhibits a substantially increased, primer-independent RNA polymerase activity. Upon addition of Nsp7, the RNA polymerase activity is further enhanced so that RNA up to template length (67 nucleotides) can be synthesized. Further, we show that the unprocessed intermediate polyprotein Nsp7-10 of human coronavirus (HCoV) 229E is also capable of synthesizing oligoribonucleotides up to a chain length of six. These results indicate that in case of FCoV as well as of HCoV 229E, the formation of a hexadecameric Nsp7:Nsp8 complex is not necessary for RNA polymerase activity. Further, the FCoV Nsp7:Nsp8 complex functions as a noncanonical RNA polymerase capable of synthesizing RNA of up to template length.


title: Advances in the causes and management of community acquired pneumonia in adults.

text: Community acquired pneumonia remains a common cause of morbidity and mortality. Usually, the causal organism is not identified and treatment remains empiric. Recent computed tomography and magnetic resonance imaging studies have challenged the accuracy of the clinical diagnosis of pneumonia, and epidemiologic studies are changing our perspective of what causes community acquired pneumonia, especially the role of viral pathogens and the frequent finding of multiple pathogens. The past decade has seen increasing overuse of empiric coverage of meticillin resistant Staphylococcus aureus and antibiotic resistant Gram negative pathogens owing to inappropriate application of guidelines for healthcare associated pneumonia. Optimal treatment remains a matter for debate, especially in very sick patients, including the role of combination antibiotic therapy and corticosteroids. Pneumonia care bundles are being defined to improve outcomes. Increased recognition of both acute and long term cardiac complications is shifting our concept of pneumonia from an acute lung disease to a multisystem problem with adverse chronic health consequences.


title: Delayed post-operative haemorrhage after carmustine wafer implantation: a case series from two UK centres.

text: OBJECT Significant haemorrhage following intracranial tumour resection may occur in 1-2% of cases and the majority occur within the first few hours post-operatively. Implantation of carmustine wafers has been associated with increased operative site complications in some series, but post-operative haematoma is not routinely reported. We analyzed the characteristics of post-operative haemorrhage after carmustine wafer insertion. METHODS We performed a retrospective audit of surgical site haematoma after tumour resection and insertion of carmustine wafers in two neurosurgical units in the UK (University Hospital of North Staffordshire, Stoke-on-Trent, March 2003 - July 2012; Wessex Neurological Centre, Southampton, October 2005 - January 2013). RESULTS During the specified time periods, carmustine wafers were inserted in 181 operations in 177 patients. We identified acute operative site haematomas after carmustine wafer insertion in 8 (4.4%) patients. All presented in a delayed fashion on or after Day 2 post-operatively. In contrast, acute operative site haematoma was present in 4/491 (0.81%) of patients who underwent resection without gliadel wafer insertion. CONCLUSIONS In contrast to the expected timing of bleeding following intracranial tumour resection, all carmustine wafer patients who experienced haemorrhage presented in a delayed fashion on or after Day 2 post-operatively. The causative factors for universally delayed post-operative haematoma after carmustine wafer insertion are unclear and further studies are required to characterize this phenomenon.


title: Tensile strength of a surgeon's or a square knot.

text: OBJECTIVE To test the integrity of surgeon's knots and flat square knots using 4 different suture materials. STUDY DESIGN Chromic catgut, polyglactin 910, silk, and polydioxanone sutures were tied in the 2 types of knot configurations. For all sutures, a 0-gauge United States Pharmacopeia suture was used. Knots were tied by a single investigator (J.B.). The suture was soaked in 0.9% sodium chloride for 60 s and subsequently transferred to a tensiometer where the tails were cut to 3-mm length. We compared the knots, measuring knot strength with a tensiometer until the sutures broke or untied. RESULTS A total of 119 throws were tied. We found no difference in mean tension at failure between a surgeon's knot (79.7 N) and a flat square knot (82.9 N). Using a chi(2) test, we did not find a statistically significant difference in the likelihood of knots coming untied between surgeon's knots (29%) and flat square knots (38%). CONCLUSIONS Under laboratory conditions, surgeon's knots and flat square knots did not differ in tension at failure or in likelihood of untying.


title: Outcomes After Flexor Tendon Repair Combined With the Application of Human Amniotic Membrane Allograft.

text: PURPOSE Clinically proven methods to prevent adhesion formation after flexor tendon repair have not yet been established. The aim of this pilot study was to assess the feasibility of amniotic membrane allograft as a mechanical barrier to decrease adhesion formation. METHODS Ten patients having flexor tendon injuries were planned to be recruited to the pilot study. The operative treatment consisted of tendon repair and fixation of amniotic membrane allograft around the repaired tendon. The primary outcome variable was the range of motion of the operated finger 6 months after the operation. Patients were monitored for infections and repair failures. RESULTS The study was terminated owing to unfavorable results after treatment of 5 patients. One patient had extensive stiffness and was subjected to tenolysis and joint release. Histopathological analysis of the tendon sheath revealed focal fibrosis. Another patient had a repair failure. The other 3 patients had fair to good results. CONCLUSIONS It seems improbable that the use of amniotic membrane allograft would yield clinically relevant improvement compared with the existing techniques. However, it remains unclear whether the unfavorable results are associated with technical factors, amniotic membrane allograft itself, or an irregular distribution of complications. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic V.


title: Fine antigenic variation within H5N1 influenza virus hemagglutinin's antigenic sites defined by yeast cell surface display.

text: Fifteen strains of mAb specific for HA of the A/Hong Kong/482/97 (H5N1) influenza virus were generated. The HA antigenic sites of the human A/Hong Kong/482/97 (H5N1) influenza virus were defined by using yeast cell surface-displaying system and anti-H5 HA mAb. Evolution analysis of H5 HA identified residues that exhibit diversifying selection in the antigenic sites and demonstrated surprising differences between residue variation of H5 HA and H3 HA. A conserved neutralizing epitope in the H5 HA protein recognized by mAb H5M9 was found using viruses isolated from 1997-2006. Seven single amino acid substitutions were introduced into the HA antigenic sites, respectively, and the alteration of antigenicity was assessed. The structure obtained by homology-modeling and molecular dynamic methods showed that a subtle substitution at residue 124 propagates throughout its nearby loop (152-159). We discuss how the structural changes caused by point mutation might explain the altered antigenicity of the HA protein. The results demonstrate the existence of immunodominant positions in the H5 HA protein, alteration of these residues might improve the immunogenicity of vaccine strains.


The Synergistic Effect of Social Media Use and Psychological Distress on Depression in China During the COVID-19 Epidemic.


title: A small-molecule oxocarbazate inhibitor of human cathepsin L blocks severe acute respiratory syndrome and ebola pseudotype virus infection into human embryonic kidney 293T cells.

text: A tetrahydroquinoline oxocarbazate (PubChem CID 23631927) was tested as an inhibitor of human cathepsin L (EC 3.4.22.15) and as an entry blocker of severe acute respiratory syndrome (SARS) coronavirus and Ebola pseudotype virus. In the cathepsin L inhibition assay, the oxocarbazate caused a time-dependent 17-fold drop in IC(50) from 6.9 nM (no preincubation) to 0.4 nM (4-h preincubation). Slowly reversible inhibition was demonstrated in a dilution assay. A transient kinetic analysis using a single-step competitive inhibition model provided rate constants of k(on) = 153,000 M(-1)s(-1) and k(off) = 4.40 x 10(-5) s(-1) (K(i) = 0.29 nM). The compound also displayed cathepsin L/B selectivity of >700-fold and was nontoxic to human aortic endothelial cells at 100 muM. The oxocarbazate and a related thiocarbazate (PubChem CID 16725315) were tested in a SARS coronavirus (CoV) and Ebola virus-pseudotype infection assay with the oxocarbazate but not the thiocarbazate, demonstrating activity in blocking both SARS-CoV (IC(50) = 273 +/- 49 nM) and Ebola virus (IC(50) = 193 +/- 39 nM) entry into human embryonic kidney 293T cells. To trace the intracellular action of the inhibitors with intracellular cathepsin L, the activity-based probe biotin-Lys-C5 alkyl linker-Tyr-Leu-epoxide (DCG-04) was used to label the active site of cysteine proteases in 293T lysates. The reduction in active cathepsin L in inhibitor-treated cells correlated well with the observed potency of inhibitors observed in the virus pseudotype infection assay. Overall, the oxocarbazate CID 23631927 was a subnanomolar, slow-binding, reversible inhibitor of human cathepsin L that blocked SARS-CoV and Ebola pseudotype virus entry in human cells.


title: Tracheal secretion management in the mechanically ventilated patient: comparison of standard assessment and an acoustic secretion detector.

text: BACKGROUND Standard indications for endotracheal suctioning are often based on clinical judgment on the deterioration of the patient's condition, and/or routine suctioning. TBA Care is a secretion detector that analyses airway sounds and indicates the need for suctioning. OBJECTIVE To determine the efficacy of TBA Care in detecting retained secretions, compared to standard indications. METHODS We conducted a prospective randomized trial with 72 general intensive care unit patients randomized at intubation into 2 groups, differing only in suctioning indications. The control group indications were at least 3 scheduled suctionings per day or were clinically driven. The secretion-detector group indications were device signal or clinically driven. At each suctioning session we recorded the indication for suctioning and the amount of secretions removed. Patients were followed until intensive care unit discharge or extubation. Diagnosis of ventilator-associated pneumonia was confirmed via microbiological analysis of suctioned secretions. RESULTS We analyzed 1,705 suctionings in the control group and 1,354 in the secretion-detector group. The secretion-detector group had fewer suctionings per day (3.9 ± 2.3 vs 4.8 ± 1.2, P = .002) and a lower rate of unnecessary suctionings (4% vs 12%, P < .001). In the secretion-detector group, 97% of the suctionings were performed following the signal from the TBA Care device. In the control group, clinical deterioration (65%) was the most frequent indication for suctioning. The incidence of ventilator-associated pneumonia was similar in the groups. CONCLUSIONS TBA Care seems to give valid and timely indications for suctioning, anticipating clinical deterioration due to secretion retention and reducing unnecessary suctionings. (ClinicalTrials.gov registration NCT00932776.).


title: Comparison Between Balloon-Assisted and Stent-Assisted Technique for Treatment of Unruptured Internal Carotid Artery Aneurysms.

text: PURPOSE To compare clinical and angiographic outcomes between balloon-assisted (BAC) and stent-assisted coiling for internal carotid artery unruptured aneurysms (ICA-UA). MATERIALS AND METHODS A total of 227 ICA-UA in 190 patients were treated with BAC (120 patients, 141 ICA-UA) or SAC (70 patients, 86 ICA-UA. We compared characteristics of patients and ICA-UA, and clinical and angiographic outcomes between groups. RESULTS Aneurysm size and neck diameter were greater for SAC than in BAC, but aneurysm volume and coil packing density were not different between groups. Immediate angiographic occlusion grade was better for BAC than for SAC. Periprocedural thromboembolic events were more frequent during SAC (11.6%) than BAC (2.4%) per aneurysm, but hemorrhagic events were the opposite (2.4% for BAC and none for SAC per aneurysm) (p < 0.05). At discharge, treatment-related morbi-mortality rates were 1.6% for BAC and 1.4% per patient for SAC. At clinical follow-up (BAC, 118 patients [98.3%] for a mean of 48.4 months; SAC, 69 patients [98.6%], for a mean of 37.4 months), 1 additional treatment-related infarction occurred during SAC, resulting in a modified Rankin scale score of 4. Thus, overall treatment-related morbi-mortality rates were 1.7% in BAC and 2.9% in SAC. At imaging follow-up (BAC, 135 aneurysms [95.7%] for 28.3 months; SAC, 81 aneurysms [94.1%] for 23.9 months), BAC and SAC showed stable or improved occlusion in 94.1% and 95.0%, minor recurrence in 4.4% and 2.5%, and major recurrence in 1.5% and 2.5%, respectively. CONCLUSION Both BAC and SAC were safe and effective techniques for ICA-UA. There were no differences in morbi-mortality and recurrence rates between groups.


title: Stroke Recovery in Rats after 24-Hour-Delayed Intramuscular Neurotrophin-3 Infusion.

text: OBJECTIVE Neurotrophin-3 (NT3) plays a key role in the development and function of locomotor circuits including descending serotonergic and corticospinal tract axons and afferents from muscle and skin. We have previously shown that gene therapy delivery of human NT3 into affected forelimb muscles improves sensorimotor recovery after stroke in adult and elderly rats. Here, to move toward the clinic, we tested the hypothesis that intramuscular infusion of NT3 protein could improve sensorimotor recovery after stroke. METHODS Rats received unilateral ischemic stroke in sensorimotor cortex. To simulate a clinically feasible time to treatment, 24 hours later rats were randomized to receive NT3 or vehicle by infusion into affected triceps brachii for 4 weeks using implanted catheters and minipumps. RESULTS Radiolabeled NT3 crossed from the bloodstream into the brain and spinal cord in rodents with or without strokes. NT3 increased the accuracy of forelimb placement during walking on a horizontal ladder and increased use of the affected arm for lateral support during rearing. NT3 also reversed sensory impairment of the affected wrist. Functional magnetic resonance imaging during stimulation of the affected wrist showed spontaneous recovery of peri-infarct blood oxygenation level-dependent signal that NT3 did not further enhance. Rather, NT3 induced neuroplasticity of the spared corticospinal and serotonergic pathways. INTERPRETATION Our results show that delayed, peripheral infusion of NT3 can improve sensorimotor function after ischemic stroke. Phase I and II clinical trials of NT3 (for constipation and neuropathy) have shown that peripheral high doses are safe and well tolerated, which paves the way for NT3 as a therapy for stroke. ANN NEUROL 2019;85:32-46.


title: What Is Performance? A Scoping Review of Performance Outcomes as Study Endpoints in Athletics.

text: PURPOSE This review set out to summarise, define, and provide future direction towards the use of performance outcome measures as endpoints in research performed at international benchmark events in athletics. METHODS Scoping review methodology was applied through a search of the PubMed and Sports Discus databases and a systematic article selection procedure. Articles that met the inclusion criteria underwent triage for further quantitative and qualitative analysis. A concept chart was generated to describe the methods by which performance had been measured and introduce descriptive labels for theoretical and practical application. RESULTS None of 2972 articles primarily identified from the database search met the triage standards for quantitative data extraction. Eleven articles were included in a qualitative analysis. The analysis identified the common methods by which performance has been measured, reported and analysed. The resulting concept chart collates labels from the qualitative analysis (categories, themes, and constructs) with sports practice labels (performance metrics, framework, and analysis). CONCLUSIONS The state of knowledge concerning methods to employ performance metrics as endpoints in studies performed at major competitions in athletics has been summarised. Constructing a methodology that combines the performance metric variables (continuous and ordinal) that are currently utilised as endpoints remains a challenge.


title: Chronic biloma after right hepatectomy for stage IV hepatoblastoma managed with Roux-en-Y biliary cystenterostomy.

text: We report the complex case of a 12-month-old girl with stage IV hepatoblastoma accompanied by thrombosis and cavernous transformation of the portal vein. After neoadjuvant chemotherapy, she underwent right hepatectomy, which was complicated by iatrogenic injury of her left hepatic duct, and subsequently developed a postoperative biloma and chronic biliocutaneous fistula. Concomitant with multiple percutaneous interventions to manage the biloma nonoperatively while the child completed her adjuvant chemotherapy, she progressed to develop chronic malnutrition, jaundice, and failure to thrive. Once therapy was completed and the child was deemed free of disease, she underwent exploratory laparotomy with Roux-en-Y biliary cystenterostomy for definitive management, resulting in resolution of her biliary fistula, jaundice, and marked improvement in her nutritional status. Roux-en-Y biliary cystenterostomy is a unique and efficacious management option in the highly selected patient population with chronic biliary leak refractory to minimally invasive management.


title: Randomized clinical trial of laparoscopic hernia repair comparing titanium-coated lightweight mesh and medium-weight composite mesh.

text: BACKGROUND The use of lightweight meshes in incisional hernia repair could have beneficial effects on quality of life. This study aimed to compare a new titanium-coated lightweight mesh with a standard composite mesh after laparoscopic incisional hernia repair. METHODS A randomized controlled single-center clinical trial was designed using the basic principle of one unit, one surgeon, one technique (midline incisional hernia with a laparoscopic approach), and two meshes: a lightweight titanium-coated mesh (group 1) and a medium-weight collagen-polyester composite mesh (group 2) used in 102 patients. The primary end points were pain and recurrence. The secondary end points were morbidity and patient outcomes (analgesic consumption, return to everyday activities). RESULTS The postoperative complication rates were similar for the two meshes. Pain was significantly less common in group 1 than in group 2 at 1 month (P = 0.029) but was similar for the two groups at 6 months and 1 year. There was a significant difference between the two groups in the average use of analgesics: 6.1 days in group 1 versus 1.6 days in group 2 (P < 0.001). The lightweight group returned to everyday activities after 6.9 days versus 9.7 days for the composite group (P < 0.001). The rate of recurrence did not differ between the two groups at the 2-year follow-up evaluation. CONCLUSIONS The light titanium-covered polypropylene mesh was associated with less postoperative pain in the short term, lower analgesic consumption, and a quicker return to everyday activities than the Parietex composite medium-weight mesh. The recurrence rates at 2 years showed no difference between the two groups.


title: Molecular dynamics simulations of DPPC/CTAB monolayers at the air/water interface.

text: An atomistic-level understanding of cationic lipid monolayers is essential for development of gene delivery agents based on cationic micelle-like structures. We employ molecular dynamics (MD) simulations for a detailed atomistic study of lipid monolayers composed of both pure zwitterionic dipalmitoylphosphatidylcholine (DPPC) and a mixture of DPPC and cationic cetyltrimethylammonium bromide (CTAB) at the air/water interface. We aim to investigate how the composition of the DPPC/CTAB monolayers affects their structural and electrostatic properties in the liquid-expanded phase. By varying the molar fraction of CTAB, we found the cationic CTAB lipids have significant condensing effect on the DPPC/CTAB monolayers, i.e., at the same surface tension or surface pressure, monolayers with higher CTAB molar fraction have smaller area per lipid. The DPPC/CTAB monolayers are also able to achieve negative surface tension without introducing buckling into the monolayer structure. We also found the condensing effect is caused by the interplay between the cationic CTAB headgroups and the zwitterionic phosphatidylcholine (PC) headgroups which has electrostatic origin. With CTAB in its vicinity, the P-N vector of PC headgroups reorients from being parallel to the monolayer plane to a more vertical orientation. Moreover, detailed analysis of the structural properties of the monolayers, such as the density profile analysis, hydrogen bonding analysis, chain order parameter calculations, and radial distribution function calculations were also performed for better understanding of cationic DPPC/CTAB monolayers.


Recommendations of management in SARS-CoV-2 infection of the Polish Association of Epidemiologists and Infectiologists.


title: Stent-assisted coiling of paraclinoid aneurysms: risks and effectiveness.

text: BACKGROUND Stent assistance for treatment of wide-based aneurysms is becoming rapidly accepted. METHODS Cases of aneurysms arising in the paraclinoid location of the internal carotid artery treated with intracranial stents and/or bare platinum coils were analyzed retrospectively from our prospectively collected database. We identified 70 aneurysms treated with stent assistance (including one stenting-alone case) and 24 aneurysms treated with coiling alone. Stenting-assisted coiling was achieved either as a one-time treatment or as a two-step maneuver with the stent placed several weeks before coiling, or stent-assisted coiling was used as a second maneuver in aneurysms that recanalized after previous coiling. RESULTS In aneurysms treated with stent assistance, 60% had ≥95% occlusion at treatment completion, a result comparing favorably with the 54.2% rate of ≥95% occlusion associated with coiling alone. At last follow-up, 60 aneurysms treated with stent assistance had a 66.7% incidence of ≥95% occlusion, with no in-stent stenosis; 75% of patients treated with coiling alone had ≥95% aneurysm occlusion. Thrombus occurred during stent deployment in two patients, one with and one without neurologic sequelae; stent displacement occurred in one patient without neurologic sequelae. At last follow-up, 57 of 62 patients (91.9%) treated with stent-assisted coiling experienced excellent/good outcomes (modified Rankin scale score ≤2). These results compared favorably with those for the coiling-alone group in which 23 of 24 (95.8%) had good outcomes. CONCLUSION Stent-assisted coiling of paraclinoid aneurysms did not add significantly to morbidity; overall effectiveness was comparable to that of bare coiling of paraclinoid aneurysms. These results require confirmation by a prospective controlled trial.


title: Vasculitis: determinants of disease patterns.

text: The vasculitides are a large group of heterogeneous diseases for which it has been assumed that pathogenesis is largely autoimmune. As clinicians, we distinguish one form of vasculitis from another on the basis of observed patterns of organ injury, the size of the vessels affected and histopathological findings. The terms 'small-vessel', 'medium-vessel' and 'large-vessel' vasculitis are useful clinical descriptors, but fail to inform us about why vessels of a certain calibre are favoured by one disease and not another. Classification based on vessel size also fails to consider that vessels of a specific calibre are not equally prone to injury. Distinct vulnerabilities undoubtedly relate to the fact that same-size vessels in different tissues may not be identical conduits. In fact, vessels become specialized, from the earliest stages of embryonic development, to suit the needs of different anatomical locations. Vessels of the same calibre in different locations and organs are as different as the organ parenchymal cells through which they travel. The dialogue between developing vessels and the tissues they perfuse is designed to meet special local needs. Added to the story of vascular diversity and vulnerability are changes that occur during growth, development and ageing. An improved understanding of the unique territorial vulnerabilities of vessels could form the basis of new hypotheses for the aetiopathogenesis of the vasculitides. This Review considers how certain antigens, including infectious agents, might become disease-relevant and how vascular diversity could influence disease phenotypes and the spectrum of vascular inflammatory diseases.


title: Involvement of proteases in porcine reproductive and respiratory syndrome virus uncoating upon internalization in primary macrophages.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) replicates in differentiated macrophages. In macrophages, heparan sulphate glycosaminoglycans mediate the initial PRRSV attachment and the receptor sialoadhesin mediates both PRRSV attachment and internalization into endosomes. Upon a pH drop, PRRSV is uncoated and its genome is released from the endosomes into the cytoplasm, which allows virus replication. However, expression of heparan sulphate and sialoadhesin in non-susceptible cells only allows virus internalization, but no virus uncoating and infection, indicating that other factors are involved. In the present study, it is shown that treatment of macrophages with serum (mainly the alpha-globulin fraction) inhibited PRRSV infection without affecting attachment and internalization. Because alpha-globulins contain several protease inhibitors, macrophages were treated with different protease inhibitors to investigate the involvement of proteases in PRRSV uncoating. Treatment of macrophages with broadly active inhibitors of serine or aspartic proteases, but not cysteine- or metallo-proteases, inhibited PRRSV uncoating and infection. Further investigation using specific inhibitors indicated that the aspartic protease cathepsin E is involved during PRRSV uncoating, but did not allow identification of the serine protease involved. The involvement of cathepsin E during PRRSV uncoating was confirmed by partial co-localization of internalized PRRSV with cathepsin E. Furthermore, cathepsin E expression increased with macrophage cultivation, which was positively correlated with an increased susceptibility to PRRSV infection. Together, these data show that, in macrophages, both the aspartic protease cathepsin E and an unidentified trypsin-like serine protease are involved in uncoating of internalized PRRSV and subsequent infection.


title: Comorbid diabetes results in immune dysregulation and enhanced disease severity following MERS-CoV infection.

text: Middle East respiratory syndrome coronavirus (MERS-CoV) emerged in 2012 in the Kingdom of Saudi Arabia and has caused over 2400 cases and more than 800 deaths. Epidemiological studies identified diabetes as the primary comorbidity associated with severe and/or lethal MERS-CoV infection. Understanding how diabetes affects MERS is important due to the global burden of diabetes and pandemic potential of MERS-CoV. We used a model in which mice were made susceptible to MERS-CoV by expressing human DPP4 and type 2 diabetes was induced by administering a high fat diet. Upon infection with MERS-CoV, diabetic mice had a prolonged phase of severe disease and delayed recovery which was independent of virus titers. Histological analysis revealed that diabetic mice had delayed inflammation which was then prolonged through 21 dpi. Diabetic mice had fewer inflammatory monocyte/macrophages and CD4+ T cells which correlated with lower levels of Ccl2 and Cxcl10 expression. Diabetic mice also had lower levels of Tnfa, Il6, Il12b, and Arg1 expression and higher levels of Il17a expression. These data suggest that the increased disease severity observed in individuals with MERS and comorbid type 2 diabetes is likely due to a dysregulated immune response which results in more severe and prolonged lung pathology.


title: Remote video auditing in the endoscopy unit for evaluation of duodenoscope reprocessing in a tertiary care center.

text: BACKGROUND : A significant proportion of duodenoscope-transmitted infections have resulted from errors related to reprocessing. Remote video auditing (RVA) is a tool that can monitor reprocessing compliance but it has not been previously evaluated in a tertiary care setting. The aims of this study were to evaluate: 1) RVA feasibility in a tertiary care setting (defined as the ability to audit every step of duodenoscope reprocessing without delaying the next procedure due to unavailability of duodenoscopes); and 2) the use of RVA as a compliance monitoring tool. METHODS : This was a prospective study at a tertiary care center. A video camera with offsite monitoring was installed in March 2018. Auditors delivered a compliance score after each procedure. The duodenoscope was not used until it passed the audit. Feasibility and compliance data were collected from April 2018 to August 2019 after a 1-month run-in phase. Both per-step compliance and overall 100 % compliance rates were measured. RESULTS : Of 743 duodenoscope reprocessing procedures, 32 666 individual steps were audited and 99.9 % of the steps were fully viewable. The mean time per audit was 38.3 minutes, the mean duodenoscope turnover time was 76.1 minutes, and there were no delays to the next procedure due to unavailability of duodenoscopes. The per-step compliance rate was 99.5 % but the overall 100 % compliance rate was 90.3 %. CONCLUSIONS : The use of RVA in duodenoscope reprocessing was feasible and promoted sustained high-level compliance in a tertiary care center.


title: Mouse dipeptidyl peptidase 4 is not a functional receptor for Middle East respiratory syndrome coronavirus infection.

text: Human dipeptidyl peptidase 4 (hDPP4) was recently identified as the receptor for Middle East respiratory syndrome coronavirus (MERS-CoV) infection, suggesting that other mammalian DPP4 orthologs may also support infection. We demonstrate that mouse DPP4 cannot support MERS-CoV infection. However, employing mouse DPP4 as a scaffold, we identified two critical amino acids (A288L and T330R) that regulate species specificity in the mouse. This knowledge can support the rational design of a mouse-adapted MERS-CoV for rapid assessment of therapeutics.


title: Crystal structure of the receptor-binding domain from newly emerged Middle East respiratory syndrome coronavirus.

text: The newly emerged Middle East respiratory syndrome coronavirus (MERS-CoV) has infected at least 77 people, with a fatality rate of more than 50%. Alarmingly, the virus demonstrates the capability of human-to-human transmission, raising the possibility of global spread and endangering world health and economy. Here we have identified the receptor-binding domain (RBD) from the MERS-CoV spike protein and determined its crystal structure. This study also presents a structural comparison of MERS-CoV RBD with other coronavirus RBDs, successfully positioning MERS-CoV on the landscape of coronavirus evolution and providing insights into receptor binding by MERS-CoV. Furthermore, we found that MERS-CoV RBD functions as an effective entry inhibitor of MERS-CoV. The identified MERS-CoV RBD may also serve as a potential candidate for MERS-CoV subunit vaccines. Overall, this study enhances our understanding of the evolution of coronavirus RBDs, provides insights into receptor recognition by MERS-CoV, and may help control the transmission of MERS-CoV in humans.


title: Arthroscopic ligamentum teres reconstruction using semitendinosus tendon: surgical technique and an unusual outcome.

text: Although the exact biomechanical function of the ligamentum teres (LT) remains unclear, an important role in hip stability has been suggested. In some patients, perhaps because of their specific anatomy or physical activity, it seems to have a major function as a hip stabilizer. Therefore, after a complete LT tear, this group of patients may have persistent hip pain and mechanical symptoms probably related to microinstability and subtle subluxation. We present the case of a female patient with a complete LT tear. This had been treated by debridement and anterior capsule tightening, followed by prolonged rehabilitation. However, she had persistent symptoms. An LT reconstruction with a novel surgical technique was performed. The LT was reconstructed with double-stranded semitendinosus graft. The acetabular end was fixed with 2 anchors, and the femoral end was passed into a bone tunnel and fixed with an interference screw. After surgery, the patient's modified Harris Hip Score and Non-Arthritic Hip Score improved from 53 and 73 to 100 and 95, respectively, at 12 months of follow-up. At repeat arthroscopy 15 months after surgery, it was observed that the graft had resorbed, although the 2 Ticron stitches (Covidien, Mansfield, MA) remained firmly attached and were still acting as a small synthetic ligament.