title: Advanced head and neck surgery training during the COVID-19 pandemic.

text: BACKGROUND The COVID-19 pandemic has significantly impacted medical training. Here we assess its effect on head and neck surgical education. METHODS Surveys were sent to current accredited program directors and trainees to assess the impact of COVID-19 on the fellow's experience and employment search. Current fellows' operative logs were compared with those of the 2018 to 2019 graduates. RESULTS Despite reduction in operative volume, 82% of current American Head and Neck Society fellows have reached the number of major surgical operations to support certification. When surveyed, 86% of program directors deemed their fellow ready to enter practice. The majority of fellows felt prepared to practice ablative (96%), and microvascular surgery (73%), and 57% have secured employment to follow graduation. Five (10%) had a pending job position put on hold due to the pandemic. CONCLUSIONS Despite the impact of the COVID-19 pandemic, current accredited trainees remain well-positioned to obtain proficiency and enter the work-force.


title: Local Government Efforts to Mitigate the Novel Coronavirus Pandemic among Older Adults.

text: As the coronavirus crisis spreads swiftly through the population, it takes a particularly heavy toll on minority individuals and older adults, with older minority adults at especially high risk. Given the shockingly high rates of infections and deaths in nursing homes, staying in the community appears to be a good option for older adults in this crisis, but in order for some older adults to do so much assistance is required. This situation draws attention to the need for benevolent intervention on the part of the state should older adults become ill or lose their sources of income and support during the crisis. This essay provides a brief overview of public support and the financial and health benefits for older individuals who remain in the community during the pandemic. It reports the case example of Austin, Texas, a city with a rapidly aging and diverse population of almost a million residents, to ask how we can assess the success of municipalities in responding to the changing needs of older adults in the community due to COVID-19. It concludes with a discussion of what governmental and non-governmental leadership can accomplish in situations such as that brought about by the current crisis.


docid: ctzucvdw

title: Innovative programs in telemedicine. European Institute of Telesurgery (EITS)/WeBSurg.


title: Safety and advantages of combined resection and microwave ablation in patients with bilobar hepatic malignancies.

text: BACKGROUND The multimodality approach has significantly improved outcomes for hepatic malignancies. Microwave ablation is often used in isolation or succession, and seldom in combination with resection. Potential benefits and pitfalls from combined resection and ablation therapy in patients with complex and extensive bilobar hepatic disease have not been well defined. METHODS A review of the University of Louisville prospective Hepato-Pancreatico-Biliary Patients database was performed with multi-focal bilobar disease that underwent microwave ablation with resection or microwave only included. RESULTS One hundred and eight were treated with microwave only (MWA, n = 108) or combined resection and ablation (CRA, n = 84) and were compared with similar disease-burden patients undergoing resection only (n = 84). The groups were comparable except that the MWA group was older (p = .02) and with higher co-morbidities (diabetes, hepatitis). The resection group had larger tumours (4 vs. 3.2 and 3 cm) but the CRA group had more numerous lesions (4 vs. 3 and 2, p = .002). Short-term outcomes including morbidity (47.6% vs. 43%, p = .0715) were similar between the CRA and resection only groups. Longer operative time (164 vs. 126 min, p = .003) and need for blood transfusion (p = .001) were independent predictors of complications. Survival analyses for colorectal metastasis patients (n = 158) demonstrated better overall survival (OS) (43.9 vs. 37.6 and 30.5 months, p = .035), disease-free survival (DFS) (38 vs. 26.6 and 16.9 months, p = .028) and local recurrence-free survival (LRFS) (55.4 vs. 17 and 22.9 months, p < .001) with resection only. CONCLUSION The use of microwave ablation in addition to surgical resection did not significantly increase the morbidities or short-term outcomes. In combination with systemic and other local forms of therapy, combined resection and ablation is a safe and effective procedure.


title: Establishing the learning curve of transanal minimally invasive surgery for local excision of rectal neoplasms.

text: INTRODUCTION Transanal minimally invasive surgery (TAMIS) is an endoscopic operating platform for local excision of rectal neoplasms. However, it may be technically demanding, and its learning curve has yet to be adequately defined. The objective of this study was to determine the number of TAMIS procedures for the local excision of rectal neoplasm required to reach proficiency. METHODS AND PROCEDURES All TAMIS cases performed from 07/2009 to 12/2016 at a single high-volume tertiary care institution for local excision of benign and malignant rectal neoplasia were identified from a prospective database. A cumulative summation (CUSUM) analysis was performed to determine the number of cases required to reach proficiency. The main proficiency outcome was rate of margin positivity (R1 resection). The acceptable and unacceptable R1 rates were defined as the R1 rate of transanal endoscopic microsurgery (TEM-10%) and traditional transanal excision (TAE-26%), which was obtained from previously published meta-analyses. Comparisons of patient, tumor, and operative characteristics before and after TAMIS proficiency were performed. RESULTS A total of 254 TAMIS procedures were included in this study. The overall R1 resection rate was 7%. The indication for TAMIS was malignancy in 57%. CUSUM analysis reported that TAMIS reached an acceptable R1 rate between 14 and 24 cases. Moving average plots also showed that the mean operative times stabilized by proficiency gain. The mean lesion size was larger after proficiency gain (3.0 cm (SD 1.5) vs. 2.3 cm (SD 1.3), p = 0.008). All other patient, tumor, and operative characteristics were similar before and after proficiency gain. CONCLUSIONS TAMIS for local excision of rectal neoplasms is a complex procedure that requires a minimum of 14-24 cases to reach an acceptable R1 resection rate and lower operative duration.


title: Selection and Use of Respiratory Protection by Healthcare Workers to Protect from Infectious Diseases in Hospital Settings.

text: OBJECTIVES Infection control policies and guidelines recommend using facemasks and respirators to protect healthcare workers (HCWs) from respiratory infections. Common types of respirators used in healthcare settings are filtering facepiece respirators (FFRs) and powered air-purifying respirators (PAPRs). Aims of this study were to examine the current attitudes and practices of HCWs regarding the selection and use of respiratory protection and determine the acceptability of a novel PAPR. METHODS In-depth interviews were undertaken with 20 HCWs from a large tertiary hospital in Sydney, Australia. Participants were fit tested with a lightweight tight-fitting half-facepiece PAPR (CleanSpace2™ Power Unit, PAF-0034, by CleanSpace Technology®) using the TSI™ Portacount quantitative fit test method. RESULTS Interview results showed that HCWs had a limited role in the selection and use of facemasks and respirators and had been using the devices provided by the hospital. The majority of subjects had no knowledge of hospital policy for the use of facemasks and respirators, had not been trained on the use of respirators, and had not been fit tested previously. Compliance with the use of facemasks and respirators was perceived as being low and facemasks and respirators were typically used only for short periods of time.All 20 participants were successfully fit tested to the CleanSpace2™ PAPR (overall geometric mean fit factor-6768). According to the exit surveys, CleanSpace2™ PAPRs were easy to don (14/20) and doff (15/20) and comfortable to wear (14/20). Most participants believed that PAPRs provide higher protection, comfort and reusability over N95 FFR and can be used during pandemics and other high-risk situations. CONCLUSIONS HCWs should be aware of infection control policies and training should be provided on the correct use of respiratory protective devices. PAPRs can be used in hospital settings to protect HCWs from certain highly infectious and emerging pathogens, however, HCWs require adequate training on storage, use, and cleaning of PAPRs.


title: Factors affecting the adoption of telemedicine during COVID-19.

text: Novel coronavirus disease (COVID-19) has put restriction of travel, and social distancing has become a new normal. This outbreak of the pandemic has made telemedicine more relevant than ever. The objective of this study is to identify the factors affecting the rate of adoption of telemedicine and effect of the COVID-19 on these factors. The research develops five hypotheses to test the influence of a disease outbreak on the rate of telemedicine adoption. The method used for the study is the Wilcoxon signed-rank test, and the sampling method used for the study is purposive sampling. The respondents were taken from a multispecialty clinic in North India and the sample size for the study is 43. The study concludes that patients are seeing more value in the use of telemedicine during COVID-19. They are more willing to experiment with telemedicine and are not intimidated by the technology related to telemedicine.


title: Phosphorylation of the type II transmembrane serine protease, TMPRSS13, in hepatocyte growth factor activator inhibitor-1 and -2-mediated cell-surface localization.

text: TMPRSS13 is a member of the type II transmembrane serine protease (TTSP) family. Although various TTSPs have been characterized in detail biochemically and functionally, the basic properties of TMPRSS13 remain unclear. Here, we investigate the activation, inhibition, post-translational modification, and localization of TMPRSS13. We show that TMPRSS13 is a glycosylated, active protease and that its own proteolytic activity mediates zymogen cleavage. Full-length, active TMPRSS13 exhibits impaired cell-surface expression in the absence of the cognate Kunitz-type serine protease inhibitors, hepatocyte growth factor activator inhibitor (HAI)-1 or HAI-2. Concomitant presence of TMPRSS13 with either HAI-1 or -2 mediates phosphorylation of residues in the intracellular domain of the protease, and it coincides with efficient transport of the protease to the cell surface and its subsequent shedding. Cell-surface labeling experiments indicate that the dominant form of TMPRSS13 on the cell surface is phosphorylated, whereas intracellular TMPRSS13 is predominantly non-phosphorylated. These data provide novel insight into the cellular properties of TMPRSS13 and highlight phosphorylation of TMPRSS13 as a novel post-translational modification of this TTSP family member and potentially other members of this family of proteases.


title: [Investigation of a cluster epidemic of COVID-19 in Ningbo].

text: Objective: To investigate a cluster epidemic of COVID-19 after a mass gathering activity in Ningbo of Zhejiang province and analyze the transmission chain and status of infection cases of different generations. Methods: The tracking of all the close contacts of the first COVID-19 case and epidemiological investigation were conducted on January 29, 2020 after a cluster epidemic of COVID-19 related with a Buddhism rally on January 19 (the 1.19 rally) in Ningbo occurred. The swabs of nose/throat of the cases and close contacts were collected and tested for nucleic acids by real-time fluorescence quantitative RT-PCR. Results: From January 26 to February 20, 2020, a total of 67 COVID-19 cases and 15 asymptomatic infection cases related with the 1.19 rally were reported in Ningbo. The initial case was the infection source who infected 29 second generation cases and 4 asymptomatic infection cases, in whom 23 second generation cases and 3 asymptomatic infection cases once took bus with the initial case, the attack rate was 33.82% (23/68) and the infection rate was 38.24% (26/68). The risks of suffering from COVID-19 and being infected were 28.91 times and 26.01 times higher in rally participants taking bus with initial case compared with those taking no bus with initial case. In this epidemic, 37 third+ generation cases and 11 related asymptomatic infection cases occurred, the attack rate was 2.88% (37/1 283) and the infection rate was 4.76% (48/1 008). The main transmission routes included vehicle sharing and family transmission. Conclusion: It was a cluster epidemic of COVID-19 caused by a super spreader in a massive rally. The epidemic has been under effective control.


title: Lipopolysaccharide-induced inflammation of bronchi and emphysematous changes of pulmonary parenchyma in miniature pigs (Sus scrofa domestica).

text: Lipopolysaccharide (LPS) is widely used to induce chronic obstructive pulmonary disease (COPD) in animal models. Rodents are most commonly used to model COPD, but their substantial anatomic and physiological differences from humans present a challenge in the research of COPD pathogenesis. The authors induced COPD in miniature pigs by intratracheal administration of LPS solution. They carried out bronchoalveolar lavage (BAL) and collected the fluid for analyses of white blood cells, cytokines and proteases and obtained lung tissues for histological assessment. Intratracheal administration of LPS caused bronchitis, obstruction of distal bronchi and damage of pulmonary alveoli, as well as increases in white blood cell counts and expression levels of cytokines and proteases. These results are consistent with the presentation of COPD in humans, making LPS administration in miniature pigs a valuable animal model for the research of pathogenesis and treatment of COPD.


Femoral arterial access and closure.


Urgent call for greater multilateralism and coordination of covid-19 trials.


title: Cloaca and hydrocolpos: laparoscopic-, cystoscopic- and colposcopic-assisted vaginostomy tube placement.

text: Hydrocolpos presenting at birth in a neonate with a cloacal malformation may lead to massive distension, with compression of adjacent structures. At times, the hydrocolpos requires urgent drainage. Additionally, these neonates need a divided colostomy to divert their fecal stream and prevent genitourinary contamination. We present a novel approach by which these two procedures can be performed as a single operation guided by a combination of cystoscopy, colposcopy, and laparoscopy. This provides a minimally invasive technique with excellent outcome and potentially superior visualization of the necessary intra-abdominal structures.


title: Capsule endoscopy findings for the diagnosis of Crohn's disease: a nationwide case-control study.

text: BACKGROUND Capsule endoscopy can be used to identify the early stage of small bowel Crohn's disease (CD). We evaluated significant small bowel capsule endoscopy (SBCE) findings that can lead to early diagnosis of CD. METHODS We retrospectively accumulated clinical and SBCE data of 108 patients (63 with and 45 without CD). Types of small bowel mucosal injuries, including erosion, ulceration, and cobblestone appearance, and the alignment of diminutive lesions were compared between patients with and without CD. Inter- and intra-observer agreement in the determination of lesions was assessed in 25 pairs of SBCE from the two groups. RESULTS Under SBCE, cobblestone appearance (33% vs. 2%, p < 0.0001), longitudinal ulcers (78% vs. 20%, p < 0.0001), and irregular ulcers (84% vs. 60%, p < 0.01) were more frequently found in patients with CD. Linear erosion (90% vs. 38%, p < 0.0001) and irregular erosion (89% vs. 64%, p < 0.005) were also more frequent in patients with CD. Furthermore, circumferential (75% vs. 9%, p < 0.0001) and longitudinal (56% vs. 7%, p < 0.0001) alignment of diminutive lesions, mainly observed in the 1st tertile of the small bowel, was more frequent in patients with CD. Good intra-observer agreement was found for ulcers, cobblestone appearance, and lesion alignment. However, inter-observer agreement of SBCE findings differed among observers. CONCLUSIONS Circumferential or longitudinal alignment of diminutive lesions, especially in the upper small bowel, may be a diagnostic clue for CD under SBCE, while inter-observer variations should be cautiously considered when using SBCE.


title: Meeting report of the 14th Japan-Korea joint symposium on cancer and aging research: current status of translational research and approaches to precision medicine.

text: PURPOSE The 14th Japan-Korea joint symposium on cancer and aging research was held at an auditorium of Saga University, Japan, May 31-Jun 2, 2018. Participants presented 31 oral and 21 poster presentations, two lectures at a luncheon seminar, plus special lectures from two Korean Emeritus Professors and founders of our joint symposia. The essential parts of the lectures are reviewed here. RESULTS This Symposium was called Japan-Korea, because the host country comes first. Our symposia are organized every 18 months and the program includes keynote and plenary lectures, and oral and poster presentations. (1) Subjects related to cancer development at this symposium were: prostate cancer progression, molecules activating GSK3β, suppressing the activation of cancer stem cells, profiling human B cell receptor repertoires, and hereditary gastrointestinal cancer syndrome. (2) Subjects related to treatment were: G-quadruplex ligands for glioma stem cells, tankyrase inhibitor for colorectal cancer, and eradication of ATL. (3) Cancer prevention subjects were: physical adsorption of EGCG to cell membrane, inhibition of immune evasion of cancer cells with EGCG, and prevention with antidiabetic agents. (4) Aging subjects were life span extension with Toll-like receptor 5 vaccine and reversal of senescence with inhibitors of ATM and ROCK. (5) The results of epidemiology focused on aldehyde dehyrogenase-2 and alcohol consumption. CONCLUSION The 14th symposium demonstrated the cutting-edge of presentations with discussion of numerous ideas by the participants.


title: A bioinspired mucoadhesive restores lubrication of degraded cartilage through reestablishment of lamina splendens.

text: Adsorbed lubricious films composed of biomacromolecules are natively present at all articulating interfaces in the human body where they provide ultralow friction and maintain normal physiological function. Biolubrication gets impaired due to diseases such as osteoarthritis, in which cartilage damage results from alterations in synovial fluid and lamina splendens composition. Osteoarthritis is treated with hyaluronic acid (HA) orally or via intra-articular injection, but due to the poor adsorption of HA on the cartilage surface in the absence of adhesive molecules, pain relief is temporary. Here, we describe how natural lubrication on degraded cartilage surface can be restored with the help of a bioinspired mucoadhesive biopolymer chitosan catechol (Chi-C). Quartz crystal microbalance was used to mimic the formation of lamina splendens in vitro, known as synovial fluid conditioning films (SyCF), and colloidal probe atomic force microscopy was used to measure their nanoscale frictional properties. Clear evidence of glycoprotein (PRG4) recruitment by Chi-C increased the softness of SyCF, which also improved nanoscale lubrication in vitro, decreasing the friction coefficient from 0.06 to 0.03. At the macroscale, cartilage damage induced by Chondroitinase ABC increased the coefficient of friction (COF) from 0.07 ± 0.04 (healthy tissue) to 0.15 ± 0.03 (after tissue damage) in the presence of synovial fluid after sliding for 50 min. After Chi-C treatment of damaged cartilage, the COF fell to 0.06 ± 0.03, which is comparable to healthy cartilage. Chi-C did not adversely affect the metabolic activity of human chondrocytes. This study provides new key insight into the potential for restoring biolubrication through the use of muco-adhesive molecules.


title: Potential Utility of Multiplex Amplification Respiratory Viral Panel Testing in the Management of Acute Respiratory Infection in Children: A Retrospective Analysis.

text: BACKGROUND Multiplex real-time polymerase chain reaction respiratory viral panel (RVP) testing offers enhanced test performance characteristics compared with older testing methods. However, the impact of RVP testing on physician antimicrobial prescription practices remains unclear. Our objective was to assess the potential relationship of RVP testing to physician treatment practices for children hospitalized with acute respiratory illness (ARI). METHODS We performed a retrospective chart review of children hospitalized for ARI during peak prevalence of respiratory viral infections in 2009-2011. Demographics, diagnostic testing, antimicrobial use, and clinical outcomes were abstracted from the electronic medical record. Antimicrobial use was compared with RVP testing data. RESULTS A total of 1727 patients met inclusion criteria. Of these patients, 254 (14.7%) children who were hospitalized for ARI received oseltamivir and 856 (49.6%) children received antibiotics. More children who received oseltamivir were positive for influenza by RVP (76.9% vs 18.0%; P < .0001). Children who underwent RVP testing received antibiotics more often than those who were not tested (53.7% vs 46.0%; P = .001), but children with a positive RVP test result received antibiotics less often (51.6% vs 67.0%; P = .003). A total of 5.8% of children who were positive for a viral pathogen by RVP had antibiotics discontinued. Antibiotics were started in fewer children when RVP results were positive (10.9% vs 100.0%; P < .0001). CONCLUSIONS Respiratory viral panel testing was associated with more appropriate oseltamivir use in children hospitalized with ARI. Physicians started antibiotics more often in children with a negative RVP test result and occasionally discontinued antibiotics in children diagnosed with a viral pathogen. These results suggest that RVP testing may enhance physician decision-making when prescribing antimicrobials in children hospitalized with ARI.


title: Evaluation of the suitability of 19 pharmacogenomics biomarkers for individualized metformin therapy for type 2 diabetes patients.

text: Objectives Type 2 Diabetes mellitus is a progressive metabolic disease characterized by relative insulin insufficiency and insulin resistance resulting in hyperglycemia. Despite the widespread use of metformin, there is considerable variation in treatment response; with approximately one-third of patients failing to achieve adequate glycemic control. Studies have reported the involvement of single nucleotide polymorphisms and their interactions in genetic pathways i.e., pharmacodynamics and pharmacokinetics. This study aims to investigate the association between 19 pharmacogenetics biomarkers and response to metformin treatment. Methods MassARRAY panels were designed and optimized by Inqaba Biotechnical Industries, to genotype 19 biomarkers for 140 type 2 diabetic outpatients. Results The CT genotype of the rs12752688 polymorphism was significantly associated with increased response to metformin therapy after correction (OR=0.33, 95% CI [0.16-0.68], p-value=0.006). An association was also found between the GA genotype of SLC47A2 rs12943590 and a decreased response to metformin therapy after correction (OR=2.29, 95% CI [1.01-5.21], p-value=0.01). Conclusions This is the first study investigating the association between genetic variants and responsiveness to medication for diabetic patients from the indigenous Nguni population in South Africa. It is suggested that rs12752688 and rs12943590 be included in pharmacogenomics profiling systems to individualize metformin therapy for diabetic patients from African populations.


title: Introduction of laparoscopic gastrectomy for gastric cancer in a Western tertiary referral centre: A prospective cost analysis during the learning curve.

text: AIM To evaluate the costs of the introduction of a laparoscopic surgery program for gastric cancer in a Western community training hospital and tertiary referral centre for gastric cancer surgery. METHODS All patients who underwent surgery for gastric cancer with curative intent in 2013 and 2014 were prospectively included. Primary outcomes were costs regarding surgery and hospital stay. RESULTS Laparoscopic gastrectomy was used in 52 patients [mean age 68 years (± 9, range 50 to 87)] and open gastrectomy was used in 25 patients [mean age 70 years (± 10, range 46 to 85)]. Mean costs (in euro's) of surgical instrumentation were significantly higher for laparoscopic surgery: 2270 ± 670 vs 1181 ± 680 in the open approach (P < 0.001). Costs of theatre use were higher in the laparoscopic group: mean 3819 ± 865 vs 2545 ± 1268 in the open surgery (P < 0.001). Total costs of hospitalization (i.e., costs of surgery and admission) were not different between laparoscopic and open surgery, 8187 ± 4864 and 7673 ± 8064 respectively (P = 0.729). Mean length of hospital stay was 9 ± 12 d in the laparoscopic group vs 14 ± 14 d in the open group (P = 0.044). CONCLUSION The introduction of laparoscopic gastrectomy for gastric cancer coincided with higher costs for theatre use and surgical instrumentation compared to the open technique. Total costs were not significantly different due to shorter length of stay and less intensive care unit (ICU) admissions and shorter ICU stay in the laparoscopic group.


title: Targeted In Situ Biosynthetic Transcriptional Activation in Native Surface-Level Human Articular Chondrocytes during Lesion Stabilization.

text: OBJECTIVE Safe articular cartilage lesion stabilization is an important early surgical intervention advance toward mitigating articular cartilage disease burden. While short-term chondrocyte viability and chondrosupportive matrix modification have been demonstrated within tissue contiguous to targeted removal of damaged articular cartilage, longer term tissue responses require evaluation to further clarify treatment efficacy. The purpose of this study was to examine surface chondrocyte responses within contiguous tissue after lesion stabilization. METHODS Nonablation radiofrequency lesion stabilization of human cartilage explants obtained during knee replacement was performed for surface fibrillation. Time-dependent chondrocyte viability, nuclear morphology and cell distribution, and temporal response kinetics of matrix and chaperone gene transcription indicative of differentiated chondrocyte function were evaluated in samples at intervals to 96 hours after treatment. RESULTS Subadjacent surface articular cartilage chondrocytes demonstrated continued viability for 96 hours after treatment, a lack of increased nuclear fragmentation or condensation, persistent nucleic acid production during incubation reflecting cellular assembly behavior, and transcriptional up-regulation of matrix and chaperone genes indicative of retained biosynthetic differentiated cell function. CONCLUSIONS The results of this study provide further evidence of treatment efficacy and suggest the possibility to manipulate or induce cellular function, thereby recruiting local chondrocytes to aid lesion recovery. Early surgical intervention may be viewed as a tissue rescue, allowing articular cartilage to continue displaying biological responses appropriate to its function rather than converting to a tissue ultimately governed by the degenerative material property responses of matrix failure. Early intervention may positively impact the late changes and reduce disease burden of damaged articular cartilage.


Issues to be considered when planning sero-epidemiological studies in regions with a low incidence of SARS-CoV-2.


title: [Pathological changes of fatal coronavirus disease 2019 (COVID-19) in the lungs: report of 10 cases by postmortem needle autopsy].

text: Objectives: To observe the pulmonary changes with coronavirus disease 2019 (COVID-19) in postmortem needle specimens, to detect the presence of 2019 novel coronavirus(2019-nCoV) in the lung tissues, and to analyze the clinicopathological characteristics. Methods: For 10 decedents with 2019-nCoV infection in Wuhan, bilateral lungs underwent ultrasound-guided percutaneous multi-point puncture autopsy, and pulmonary pathological changes were described in routine hematoxylin-eosin staining (HE) slides. Electron microscopy was also performed. The reverse transcription polymerase chain reaction (RT-PCR) was employed to detect 2019-nCoV nucleic acid in lung tissue, and the pathological characteristics were demonstrated in combination with clinical data analysis. Results: Of the 10 deaths associated with COVID-19, 7 were male and 3 were female. The average age was 70 (39-87) years. Medical record showed that 7 patients had underlying diseases. The average course of disease was 30 (16-36) days. Nine cases showed fibrinous and suppurative exudation in the alveolar cavity accompanied by the formation of hyaline membrane, and fibroblastic proliferation of alveolar septum. Type Ⅱ alveolar epithelial cells showed reactive hyperplasia and desquamation. Many macrophages accumulated in the alveolar cavity. Capillary hyaline thrombus and intravascular mixed thrombus were noted. In some cases, acute bronchiolitis with mucous membrane exfoliation, accumulation of bronchiolar secretions, and bronchiolar epithelial metaplasia occurred. In the cohort, a large number of bacteria (cocci) were detected in 1 case and a large number of fungi (yeast type) were detected in 1 case. Nine cases were positive for the nucleic acids of 2019-nCoV while one case remained negative by RT-PCR. Coronavirus particles were detected in the cytoplasm of type Ⅱ alveolar epithelium. Conclusions: The pulmonary pathological changes of fatal COVID-19 are diffuse alveolar damage (DAD), mainly in the acute exudative stage and the organic proliferative stage. There are fibrinous exudate aggregation in alveolar cavity with hyaline membrane formation, fibroblastic proliferation in alveolar septum, and alveolar epithelial cell injuries with reactive hyperplasia and desquamation of type Ⅱ alveolar epithelial cells. A large amount of neutrophils and monocytes infiltration is present in most cases and bacteria and fungi are detected in some cases, suggesting a serious bacterial or fungal infection secondary to the DAD.


title: The effect of foot orthoses and insoles on running economy and performance in distance runners: A systematic review and meta-analysis.

text: Foot orthoses and insoles are prescribed to runners, however their impact on running economy and performance is uncertain. The aim of this systematic review and meta-analysis was to determine the effect of foot orthoses and insoles on running economy and performance in distance runners. Seven electronic databases were searched from inception until June 2018. Eligible studies investigated the effect of foot orthoses or insoles on running economy (using indirect calorimetry) or running performance. Standardised mean differences (SMDs) were computed and meta-analyses were conducted using random effects models. Methodological quality was assessed using the Quality Index. Nine studies met the criteria and were included: five studies investigated the effect of foot orthoses on running economy and four investigated insoles. Foot orthoses were associated with small negative effects on running economy compared to no orthoses (SMD 0.42 [95% CI 0.17,0.72] p = 0.007). Shock absorbing insoles were also associated with negative effects on running economy, but an imprecise estimate (SMD 0.26 [95% CI -0.33,0.84] p = 0.83). Quality Index scores ranged from 4 to 15 out of 17. Foot orthoses and shock absorbing insoles may adversely affect running economy in distance runners. Future research should consider their potential effects on running performance.


title: Comparison of the Luminex xTAG RVP Fast assay and the Idaho Technology FilmArray RP assay for detection of respiratory viruses in pediatric patients at a cancer hospital.

text: Respiratory viruses are increasingly recognized as serious causes of morbidity and mortality in immunocompromised patients. The rapid and sensitive detection of respiratory viruses is essential for the early diagnosis and administration of appropriate antiviral therapy, as well as for the effective implementation of infection control measures. We compared the performance of two commercial assays, xTAG RVP Fast (Luminex Diagnostics, Toronto, Canada) and FilmArray RVP (FA RVP; Idaho Technology, Salt Lake City, UT), in pediatric patients at Memorial Sloan-Kettering Cancer Center. These assays detect the following viruses: respiratory syncytial virus; influenza A and B viruses; parainfluenza viruses 1, 2, 3, and 4; human metapneumovirus; adenovirus; enterovirus-rhinovirus; coronaviruses NL63, HKU1, 229E, and OC43; and bocavirus. We tested a total of 358 respiratory specimens from 173 pediatric patients previously tested by direct fluorescence assay (DFA) and viral culture. The overall detection rate (number of positive specimens/total specimens) for viruses tested by all methods was 24% for DFA/culture, 45% for xTAG RVP Fast, and 51% for FA RVP. The agreement between the two multiplex assays was 84.5%, and the difference in detection rate was statistically significant (P < 0.0001). Overall, the FA RVP assay was more sensitive than the xTAG RVP Fast assay and had a turnaround time of approximately 1 h. The sensitivity, simplicity, and random-access platform make FA RVP an excellent choice for laboratory on-demand service with low to medium volume.


docid: pbqocrrk

title: θ-Defensins: cyclic peptides with endless potential.

text: θ-Defensins, the only cyclic peptides of animal origin, have been isolated from the leukocytes of rhesus macaques and baboons. Their biogenesis is unusual because each peptide is an 18-residue chimera formed by the head-to-tail splicing of nonapeptides derived from two separate precursors. θ-Defensins have multiple arginines and a ladder-like tridisulfide array spanning their two antiparallel β-strands. Human θ-defensin genes contain a premature stop codon that prevents effective translation of the needed precursors; consequently, these peptides are not present in human leukocytes. Synthetic θ-defensins with sequences that correspond to those encoded within the human pseudogenes are called retrocyclins. Retrocyclin-1 inhibits the cellular entry of HIV-1, HSV, and influenza A virus. The rhesus θ-defensin RTD-1 protects mice from an experimental severe acute respiratory syndrome coronavirus infection, and retrocyclin-1 protects mice from infection by Bacillus anthracis spores. The small size, unique structure, and multiple host defense activities of θ-defensins make them intriguing potential therapeutic agents.


title: Molecular Detection of Avian Infectious Bronchitis Viruses in Live Bird Markets, Gilan Province.

text: Coronaviruses (AvCoV) which include infectious bronchitis virus (IBV) and other bird coronaviruses belong to the genus gammacoronavirus, subfamily Coronavirinae. One of the most prominent representatives of gammacoronavirus genus is infectious bronchitis virus (IBV) which is a highly contagious viral pathogen of chickens causing considerable economic losses to the poultry industry. IBVs mostly affect the respiratory, urinary, and reproductive tracts leading to a substantial drop in production. Backyard poultry in the villages usually share their food and water with free flight birds which puts them at serious risk of disease transmission. Furthermore, the poor hygienic measurements which are often used in backyard flocks make them a potential reservoir for diseases that can be transferred to commercial poultry flocks. Live bird markets (LBMs) which receive live poultry to be resold or slaughtered and sold onsite play a significant role in spreading infectious diseases among the different bird species. In the present study, a number of 354 cloacal swab samples were collected from different bird species from LBMs of Gilan province. Subsequently, after RNA extraction, reverse transcription-polymerase chain reaction (RT-PCR) technique was carried out using specific primers of S1 gene to detect coronavirus infectious bronchitis virus. Two samples from backyard chickens were reported to be positive to coronavirus which were named Iran/Backyardchicken 96/2017 and Iran/Backyardchicken 94/2017. The results of the phylogenetic analysis demonstrated that these two isolates are placed in QX and IS-1494 strains, respectively. On a final note, the obtained results highlighted the role of live birds offered in LBMs in the epidemiology of IBV and the transmission of the virus to the industrial flock.


title: Outcome impact of hemodynamic and depth of anesthesia monitoring during major cancer surgery: a before-after study.

text: Hemodynamic and depth of anesthesia (DOA) monitoring are used in many high-risk surgical patients without well-defined indications and objectives. We implemented monitoring guidelines to rationalize hemodynamic and anesthesia management during major cancer surgery. In early 2014, we developed guidelines with specific targets (Mean arterial pressure > 65 mmHg, stroke volume variation < 12%, cardiac index > 2.5 l min-1 m-2, central venous oxygen saturation > 70%, 40 < bispectral index < 60) for open abdominal cancer surgeries > 2 h. Pre-, intra-, and post-operative data were collected from our electronic medical record database and compared before (March-August 2013) and after (March-August 2014) guideline implementation. A total of 596 patients were studied, 313 before (Before group) and 283 after (After group) guideline implementation. The two groups were comparable for age, ASA score, physiological P-POSSUM score, and surgery duration, but the operative P-POSSUM score was higher in the after group (20 vs. 18, p = 0.009). The use of cardiac output, central venous oxygen saturation and DOA monitoring increased from 40 to 61%, 20 to 29%, and 60 to 88%, respectively (all p-values < 0.05). Intraoperative fluid volumes decreased (16.0 vs. 14.5 ml kg-1 h-1, p = 0.002), whereas the use of inotropes increased (6 vs. 11%, p = 0.022). Postoperative delirium (16 vs. 8%, p = 0.005), urinary tract infections (6 vs. 2%, p = 0.012) and median hospital length of stay (9.6 vs. 8.8 days, p = 0.032) decreased. In patients undergoing major open abdominal surgery for cancer, despite an increase in surgical risk, the implementation of guidelines with predefined targets for hemodynamic and DOA monitoring was associated with a significant improvement in postoperative outcome.


title: The response of a standardized fluid challenge during cardiac surgery on cerebral oxygen saturation measured with near-infrared spectroscopy.

text: Near infrared spectroscopy (NIRS) has been used to evaluate regional cerebral tissue oxygen saturation (ScO2) during the last decades. Perioperative management algorithms advocate to maintain ScO2, by maintaining or increasing cardiac output (CO), e.g. with fluid infusion. We hypothesized that ScO2 would increase in responders to a standardized fluid challenge (FC) and that the relative changes in CO and ScO2 would correlate. This study is a retrospective substudy of the FLuid Responsiveness Prediction Using Extra Systoles (FLEX) trial. In the FLEX trial, patients were administered two standardized FCs (5 mL/kg ideal body weight each) during cardiac surgery. NIRS monitoring was used during the intraoperative period and CO was monitored continuously. Patients were considered responders if stroke volume increased more than 10% following FC. Datasets from 29 non-responders and 27 responders to FC were available for analysis. Relative changes of ScO2 did not change significantly in non-responders (mean difference - 0.3% ± 2.3%, p = 0.534) or in fluid responders (mean difference 1.6% ± 4.6%, p = 0.088). Relative changes in CO and ScO2 correlated significantly, p = 0.027. Increasing CO by fluid did not change cerebral oxygenation. Despite this, relative changes in CO correlated to relative changes in ScO2. However, the clinical impact of the present observations is unclear, and the results must be interpreted with caution.Trial registration: http://ClinicalTrial.gov identifier for main study (FLuid Responsiveness Prediction Using Extra Systoles-FLEX): NCT03002129.


title: Percutaneous Radiofrequency Ablation Versus Robotic-Assisted Partial Nephrectomy for the Treatment of Small Renal Cell Carcinoma.

text: INTRODUCTION The authors compared the oncologic outcomes of radiofrequency ablation (RFA) with robotic-assisted partial nephrectomy (RPN) for the treatment of T1 stage renal cell carcinoma (RCC). MATERIALS AND METHODS This was a retrospective data analysis of a high-volume single tertiary centre. Patients were treated with RFA or RPN following multidisciplinary decision making. Only histologically proven RCCs were included. Baseline demographics were collected, and PADUA scores of tumour features were calculated to standardize baseline anatomy. Peri-operative complications, kidney function and oncological outcomes were compared. RESULTS Sixty-three cases were included in each group. Baseline renal function was poorer in RFA, and 16/63 RFA patients had tumours in single kidneys compared to 1/63 RPN cases (p < 0.001). Length of stay was shorter in RFA (1 vs. 3 days, p < 0.0001). Post-procedure renal function decline at 30 days was significantly less in RFA [(-0.8) ± 9.6 vs. (-16.1) ± 19.5 mls/min/1.73 m2; p < 0.0001]. More minor complications were recorded in RPN (10/63 vs. 4/63, p = 0.15), but local recurrence was numerically higher in RFA (6/63 vs. 1/63, p = 0.11). Disease-free survival (DFS) was not significantly different (adjusted HR = 0.6, 95 % Cl 0.1-3.7; p = 0.60). Increasing tumour size was an independent predictor of local recurrence (adjusted HR = 1.7; 95 % Cl 1.1-2.6 per cm; p = 0.02). CONCLUSIONS Both RPN and RFA offer very good oncological outcomes for the treatment of T1 RCC with low peri-operative morbidity and similar oncologic outcomes. RFA demonstrated fewer peri-operative complications and better preservation of renal function, whereas RPN had an insignificantly lower local recurrence rate. RFA should be offered alongside RPN for selected cases.


title: Evaluation of the Superior Labial Musculomucosal Flap in Dogs: An Angiographic Study and Case Report.

text: OBJECTIVE The aim of this study was to evaluate the angiosome of the superior and inferior labial arteries within the superior and inferior labia and to describe superior and inferior labial musculomucosal axial pattern flaps that can be used for intra-oral wound reconstruction. This study also presents the clinical use of a superior labial musculomucosal flap in a dog. MATERIALS AND METHODS The common carotid arteries of six canine cadavers were injected with barium sulphate. The skin of the face and labial mucosa was removed and radiographed to study the vascular supply of the superior and inferior labia. RESULTS The angiograms in all dogs demonstrated that the superior and inferior labial arteries were located within the musculomucosal layer of the labia. At the junction of the rostral and caudal half of the upper lip, extensive choke anastomoses joined the angiosome of the infra-orbital artery. The inferior labial artery perfused the caudal half of the lower labium and had extensive choke anastomoses with the middle and rostral mental arteries. CLINICAL SIGNIFICANCE The musculomucosal flaps of the superior and inferior labia contain a rich arterial blood supply, which suggests that these flaps may survive in live dogs. The superior labial musculomucosal flap was successfully used to reconstruct a large cleft palate in a single clinical case.


Advances in laparoscopic spay techniques for dogs: the past, present and future.


title: Wild-type and innate immune-deficient mice are not susceptible to the Middle East respiratory syndrome coronavirus.

text: The Middle East respiratory syndrome coronavirus (MERS-CoV) is a newly emerging highly pathogenic virus causing almost 50 % lethality in infected individuals. The development of a small-animal model is critical for the understanding of this virus and to aid in development of countermeasures against MERS-CoV. We found that BALB/c, 129/SvEv and 129/SvEv STAT1 knockout mice are not permissive to MERS-CoV infection. The lack of infection may be due to the low level of mRNA and protein for the MERS-CoV receptor, dipeptidyl peptidase 4 (DPP4), in the lungs of mice. The low level of DPP4 in the lungs likely contributes to the lack of viral replication in these mouse models and suggests that a transgenic mouse model expressing DPP4 to higher levels is necessary to create a mouse model for MERS-CoV.


Organ donation during the financial crisis in Greece.


Family Member Visits to Critically Ill Patients During COVID-19: A New Pathway (Telemed J E Health 2020. [Epub ahead of print]; DOI: 10.1089/tmj.2020.29040.rb).


docid: jinwkhnp

title: A Case Report of Chyloretroperitoneum Post Living-Donor Transplantation.

text: Chyloretroperitoneum is a rare complication of urological surgery. Here we report a case of chyloretroperitoneum that occurred in a 28-year-old man post living-donor transplantation. Twenty-nine days post transplantation, perirenal fluid collection and hydronephrosis were detected and percutaneous drainage was performed. The fluid was chylous and revealed a very high triglyceride concentration (1,197 mg/dL). Total parenteral nutrition and administration of octreotide were performed, but the leakage did not improve. On the contrary, the drainage fluid gradually increased to 1,600 mL/day, and a laparoscopic fenestration was performed owing to a concern about the adverse effects of massive lymph loss. Ascites temporarily appeared but disappeared 3 months post fenestration. To our knowledge, this is the first case report of pelvic chyloretroperitoneum post living-donor transplantation. Furthermore, if chyloretroperitoneum treatment using diet control or octreotide is ineffective, laparoscopic fenestration can be considered as a treatment option.


title: A Multigene Test Could Cost-Effectively Help Extend Life Expectancy for Women at Risk of Hereditary Breast Cancer.

text: BACKGROUND The National Comprehensive Cancer Network recommends that women who carry gene variants that confer substantial risk for breast cancer consider risk-reduction strategies, that is, enhanced surveillance (breast magnetic resonance imaging and mammography) or prophylactic surgery. Pathogenic variants can be detected in women with a family history of breast or ovarian cancer syndromes by multigene panel testing. OBJECTIVES To investigate whether using a seven-gene test to identify women who should consider risk-reduction strategies could cost-effectively increase life expectancy. METHODS We estimated effectiveness and lifetime costs from a payer perspective for two strategies in two hypothetical cohorts of women (40-year-old and 50-year-old cohorts) who meet the National Comprehensive Cancer Network-defined family history criteria for multigene testing. The two strategies were the usual test strategy for variants in BRCA1 and BRCA2 and the seven-gene test strategy for variants in BRCA1, BRCA2, TP53, PTEN, CDH1, STK11, and PALB2. Women found to have a pathogenic variant were assumed to undergo either prophylactic surgery or enhanced surveillance. RESULTS The incremental cost-effectiveness ratio for the seven-gene test strategy compared with the BRCA1/2 test strategy was $42,067 per life-year gained or $69,920 per quality-adjusted life-year gained for the 50-year-old cohort and $23,734 per life-year gained or $48,328 per quality-adjusted life-year gained for the 40-year-old cohort. In probabilistic sensitivity analysis, the seven-gene test strategy cost less than $100,000 per life-year gained in 95.7% of the trials for the 50-year-old cohort. CONCLUSIONS Testing seven breast cancer-associated genes, followed by risk-reduction management, could cost-effectively improve life expectancy for women at risk of hereditary breast cancer.


title: Frequency of Abnormalities Detected by Point-of-Care Lung Ultrasound in Symptomatic COVID-19 Patients: Systematic Review and Meta-Analysis.

text: The COVID-19 pandemic has resulted in significant morbidity, mortality, and strained healthcare systems worldwide. Thus, a search for modalities that can expedite and improve the diagnosis and management of this entity is underway. Recent data suggested the utility of lung ultrasound (LUS) in the diagnosis of COVID-19 by detecting an interstitial pattern (B-pattern). Hence, we aimed to pool the proportion of various reported lung abnormalities detected by LUS in symptomatic COVID-19 patients. We conducted a systematic review (PubMed, MEDLINE, and EMBASE until April 25, 2020) and a proportion meta-analysis. We included seven studies examining the role of LUS in 122 COVID-19 patients. The pooled proportion (PP) of B-pattern detected by lung ultrasound (US) was 0.97 (95% CI: 0.94-1.00 I 2 0%, Q 4.6). The PP of finding pleural line abnormalities was 0.70 (95% CI: 0.13-1.00 I 2 96%, Q 103.9), of pleural thickening was 0.54 (95% 0.11-0.95 I 2 93%, Q 61.1), of subpleural or pulmonary consolidation was 0.39 (95% CI: 0.21-0.58 I 2 72%, Q 17.8), and of pleural effusion was 0.14 (95% CI: 0.00-0.37 I 2 93%, Q 27.3). Our meta-analysis revealed that almost all SARS-CoV-2-infected patients have abnormal lung US. The most common abnormality is interstitial involvement depicted as B-pattern. The finding from our review highlights the potential role of this modality in the triage, diagnosis, and follow-up of COVID-19 patients. A sizable diagnostic accuracy study comparing LUS, computed tomography scan, and COVID-19-specific tests is warranted to further test this finding and to delineate the diagnostic and prognostic yield of each of these modalities.


title: Perioperative Complications of Hysterectomy After a Previous Cesarean Section: A Systematic Review and Meta-Analysis.

text: Background With increasing rates of cesarean sections (CS), the number of hysterectomies performed among women with a previous CS is on the rise. Objective To provide the association between the odds of complications following a hysterectomy performed later in life and a previous CS. Search strategy A comprehensive search was performed using major electronic databases, ie, MEDLINE, Scopus, ISI Web of Science, from their inception to April 2019. Selection criteria Analytical studies, irrespective of language or publication status, were included. Data collection and analysis Outcomes were extracted in duplicate. The methodological quality of the included studies was independently evaluated by two review authors. A three-level meta-analysis was applied for outcomes with dependent effect sizes. Main results Twenty-six studies were included involving 54,815 women. The odds of the following complications were increased in women with a previous CS: urinary tract injury (pooled unadjusted odds ratio (OR)=3.15, 95% CI=2.01-4.94, 15 studies, 33,902 women, and pooled adjusted OR=2.21, 95% CI=1.46-3.34, 3 studies, 31,038 women), gastrointestinal tract injury (pooled unadjusted OR=1.73, 95% CI=1.19-2.53; 7 studies, 30,050, and pooled adjusted OR=1.83, 95% CI=1.11-3.03, 1 study, 25,354 women), postoperative infections (pooled unadjusted OR=1.44, 95% CI=1.22-1.71, 6 studies, 37,832 women), wound complications (pooled unadjusted OR=2.24, 95% CI=1.94-2.57, 9 studies, 37,559 women), reoperation (pooled unadjusted OR=1.46, 95% CI=1.19-1.78, 2 studies, 9,899 women), and blood transfusion (pooled unadjusted OR=1.35, 95% CI=1.03-1.76, 7 studies, 13,430 women). Conclusion Previous CS increases risks of various complications following hysterectomy. This information reminds the gynecologists to be aware of the associations between previous CS and potential complications among women undergoing hysterectomy. Prospero registration number CRD42018085061.


title: Endovascular Thrombus Removal for Acute Iliofemoral Deep Vein Thrombosis.

text: BACKGROUND The ATTRACT trial (Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis) previously reported that pharmacomechanical catheter-directed thrombolysis (PCDT) did not prevent postthrombotic syndrome (PTS) in patients with acute proximal deep vein thrombosis. In the current analysis, we examine the effect of PCDT in ATTRACT patients with iliofemoral deep vein thrombosis. METHODS Within a large multicenter randomized trial, 391 patients with acute deep vein thrombosis involving the iliac or common femoral veins were randomized to PCDT with anticoagulation versus anticoagulation alone (No-PCDT) and were followed for 24 months to compare short-term and long-term outcomes. RESULTS Between 6 and 24 months, there was no difference in the occurrence of PTS (Villalta scale ≥5 or ulcer: 49% PCDT versus 51% No-PCDT; risk ratio, 0.95; 95% CI, 0.78-1.15; P=0.59). PCDT led to reduced PTS severity as shown by lower mean Villalta and Venous Clinical Severity Scores ( P<0.01 for comparisons at 6, 12, 18, and 24 months), and fewer patients with moderate-or-severe PTS (Villalta scale ≥10 or ulcer: 18% versus 28%; risk ratio, 0.65; 95% CI, 0.45-0.94; P=0.021) or severe PTS (Villalta scale ≥15 or ulcer: 8.7% versus 15%; risk ratio, 0.57; 95% CI, 0.32-1.01; P=0.048; and Venous Clinical Severity Score ≥8: 6.6% versus 14%; risk ratio, 0.46; 95% CI, 0.24-0.87; P=0.013). From baseline, PCDT led to greater reduction in leg pain and swelling ( P<0.01 for comparisons at 10 and 30 days) and greater improvement in venous disease-specific quality of life (Venous Insufficiency Epidemiological and Economic Study Quality of Life unit difference 5.6 through 24 months, P=0.029), but no difference in generic quality of life ( P>0.2 for comparisons of SF-36 mental and physical component summary scores through 24 months). In patients having PCDT versus No-PCDT, major bleeding within 10 days occurred in 1.5% versus 0.5% ( P=0.32), and recurrent venous thromboembolism over 24 months was observed in 13% versus 9.2% ( P=0.21). CONCLUSIONS In patients with acute iliofemoral deep vein thrombosis, PCDT did not influence the occurrence of PTS or recurrent venous thromboembolism. However, PCDT significantly reduced early leg symptoms and, over 24 months, reduced PTS severity scores, reduced the proportion of patients who developed moderate-or-severe PTS, and resulted in greater improvement in venous disease-specific quality of life. CLINICAL TRIAL REGISTRATION URL: https://www.clinicaltrials.gov . Unique identifier: NCT00790335.


title: Initiation Factor 3 is Dispensable For Mitochondrial Translation in Cultured Human Cells.

text: The initiation of protein synthesis in bacteria is ruled by three canonical factors: IF1, IF2, and IF3. This system persists in human mitochondria; however, it functions in a rather different way due to specialization and adaptation to the organellar micro-environment. We focused on human mitochondrial IF3, which was earlier studied in vitro, but no knock-out cellular models have been published up to date. In this work, we generated human HeLa cell lines deficient in the MTIF3 gene and analyzed their mitochondrial function. Despite the lack of IF3mt in these cells, they preserved functional mitochondria capable of oxygen consumption and protein synthesis; however, the translation of ATP6 mRNA was selectively decreased which compromised the assembly of ATP synthase. Together with the analogous results obtained earlier for baker's yeast mitochondrial IF3, our findings point to a functional divergence of mitochondrial initiation factors from their bacterial ancestors.


Should the Benefit of Adjuvant Chemotherapy in Colon Cancer Be Re-Evaluated?


title: The people behind the papers - Wael Noor El-Nachef and Marianne Bronner.

text: The enteric nervous system (ENS) derives from the neural crest and innervates the gastrointestinal system, in which it is essential for gut function throughout life. A new paper in Development uses zebrafish to investigate the poorly understood process of post-embryonic ENS neurogenesis, in both development and injury contexts. To find out more, we met the paper's two authors, Wael Noor El-Nachef, Assistant Clinical Professor of Medicine at UCLA, and Marianne Bronner, Albert Billings Ruddock Professor of Biology and Biological Engineering at Caltech.


title: GnRH Agonist Trigger and LH Activity Luteal Phase Support versus hCG Trigger and Conventional Luteal Phase Support in Fresh Embryo Transfer IVF/ICSI Cycles-A Systematic PRISMA Review and Meta-analysis.

text: INTRODUCTION The use of GnRH agonist (GnRHa) for final oocyte maturation trigger in oocyte donation and elective frozen embryo transfer cycles is well established due to lower ovarian hyperstimulation syndrome (OHSS) rates as compared to hCG trigger. A recent Cochrane meta-analysis concluded that GnRHa trigger was associated with reduced live birth rates (LBRs) in fresh autologous IVF cycles compared to hCG trigger. However, the evidence is not unequivocal, and recent trials have found encouraging reproductive outcomes among couples undergoing GnRHa trigger and individualized luteal LH activity support. Thus, the aim was to compare GnRHa trigger followed by luteal LH activity support with hCG trigger in IVF patients undergoing fresh embryo transfer. MATERIAL AND METHODS We conducted a systematic review and meta-analysis of randomized trials published until December 14, 2016. The population was infertile patients submitted to IVF/ICSI cycles with GnRH antagonist cotreatment who underwent fresh embryo transfer. The intervention was GnRHa trigger followed by LH activity luteal phase support (LPS). The comparator was hCG trigger followed by a standard LPS. The critical outcome measures were LBR and OHSS rate. The secondary outcome measures were number of oocytes retrieved, clinical and ongoing pregnancy rates, and miscarriage rates. RESULTS A total of five studies met the selection criteria comprising a total of 859 patients. The LBR was not significantly different between the GnRHa and hCG trigger groups (OR 0.84, 95% CI 0.62, 1.14). OHSS was reported in a total of 4/413 cases in the GnRHa group compared to 7/413 in the hCG group (OR 0.48, 95% CI 0.15, 1.60). We observed a slight, but non-significant increase in miscarriage rate in the GnRHa triggered group compared to the hCG group (OR 1.85; 95% CI 0.97, 3.54). CONCLUSION GnRHa trigger with LH activity LPS resulted in comparable LBRs compared to hCG trigger. The most recent trials reported LBRs close to unity indicating that individualization of the LH activity LPS improved the luteal phase deficiency reported in the first GnRHa trigger studies. However, LPS optimization is needed to further limit OHSS in the subgroup of normoresponder patients (<14 follicles ≥ 11 mm). PROSPERO REGISTRATION NUMBER CRD42016051091.


Endovascular therapy for large vessel occlusion stroke: an update on the most recent clinical trials.


title: Comparison of five bacteriophages as models for viral aerosol studies.

text: Bacteriophages are perceived to be good models for the study of airborne viruses because they are safe to use, some of them display structural features similar to those of human and animal viruses, and they are relatively easy to produce in large quantities. Yet, only a few studies have investigated them as models. It has previously been demonstrated that aerosolization, environmental conditions, and sampling conditions affect viral infectivity, but viral infectivity is virus dependent. Thus, several virus models are likely needed to study their general behavior in aerosols. The aim of this study was to compare the effects of aerosolization and sampling on the infectivity of five tail-less bacteriophages and two pathogenic viruses: MS2 (a single-stranded RNA [ssRNA] phage of the Leviviridae family), Φ6 (a segmented double-stranded RNA [dsRNA] phage of the Cystoviridae family), ΦX174 (a single-stranded DNA [ssDNA] phage of the Microviridae family), PM2 (a double-stranded DNA [dsDNA] phage of the Corticoviridae family), PR772 (a dsDNA phage of the Tectiviridae family), human influenza A virus H1N1 (an ssRNA virus of the Orthomyxoviridae family), and the poultry virus Newcastle disease virus (NDV; an ssRNA virus of the Paramyxoviridae family). Three nebulizers and two nebulization salt buffers (with or without organic fluid) were tested, as were two aerosol sampling devices, a liquid cyclone (SKC BioSampler) and a dry cyclone (National Institute for Occupational Safety and Health two-stage cyclone bioaerosol sampler). The presence of viruses in collected air samples was detected by culture and quantitative PCR (qPCR). Our results showed that these selected five phages behave differently when aerosolized and sampled. RNA phage MS2 and ssDNA phage ΦX174 were the most resistant to aerosolization and sampling. The presence of organic fluid in the nebulization buffer protected phages PR772 and Φ6 throughout the aerosolization and sampling with dry cyclones. In this experimental setup, the behavior of the influenza virus resembled that of phages PR772 and Φ6, while the behavior of NDV was closer to that of phages MS2 and ΦX174. These results provide critical information for the selection of appropriate phage models to mimic the behavior of specific human and animal viruses in aerosols.


title: A Simplified Approach to Extravascular Lung Water Assessment Using Point-of-Care Ultrasound in Patients with End-Stage Chronic Renal Failure Undergoing Hemodialysis.

text: BACKGROUND Fluid overload leading to pulmonary congestion is an important issue in patients undergoing hemodialysis. This study aimed to determine if a simplified method of extravascular lung water assessment using ultrasound provided clinically relevant information. METHODS This prospective study recruited 47 patients from a single hemodialysis center. Pulmonary ultrasound was performed before and after 2 hemodialysis sessions in 28 regions on the thorax. The B-line score was defined as the percentage regions where B-lines were present. RESULTS When B-lines were detected before hemodialysis, a significant relationship was found between fluid removal and the change in B-line score. Patients with a B-line score of ≥21.4% (4th quartile) after the second hemodialysis session were more likely to be hospitalized for pulmonary edema or acute coronary syndrome. CONCLUSIONS A simplified pulmonary assessment using ultrasound provides relevant information about pulmonary congestion in hemodialysis patients and identifies patients at risk of hospitalization for heart-related problems.


title: Does type of immunosupression influence the course of Covid-19 infection?

text: Coronavirus disease 19 (Covid-19) is a new emerging virus responsible for pandemic and death. High blood pressure, diabetes, obesity have been described as poor prognosis factors. Few data have been reported in patient with immunocompromised status (solid tumor, hematological malignancy, rheumatoid conditions or organ transplant). We evaluated the characteristics of patients, including the outcome, with immunodepression hospitalized in Besancon University hospital (East of France). We wanted to identify if a type of immunosupression influences the course of Covid-19. In a cohort of 80 patients with immunosupression (42 solid tumors, 20 hematological malignancy and 18 non neoplastic immunosupression), poor outcomes (Intensive care unit hospitalization and or deaths) was frequent (38%) and tended to be more frequent in patients with hematological malignancy.


title: Markers of Borna disease virus infection in cats with staggering disease.

text: Borna disease virus (BDV) is a RNA-virus causing neurological disorders in a wide range of mammals. In cats, BDV infection may cause staggering disease. Presently, staggering disease is a tentative clinical diagnosis, only confirmed at necropsy. In this study, cats with staggering disease were investigated to study markers of BDV infection aiming for improvement of current diagnostics. Nineteen cats fulfilled the inclusion criteria based on neurological signs and pathological findings. In 17/19 cats, BDV infection markers (BDV-specific antibodies and/or BDV-RNA) were found, and antibodies in serum (13/16, 81%) were the most common marker. BDV-RNA was found in 11/19 cats (58%). In a reference population without neurological signs, 4/25 cats were seropositive (16%). The clinical history and neurological signs in combination with presence of BDV infection markers, where serology and rRT-PCR on blood can be helpful tools, improve the diagnostic accuracy in the living cat.


title: Sniffing out the evidence; It's now time for public health bodies recognize the link between COVID-19 and smell and taste disturbance.

text: Since the outbreak of the pandemic, anecdotal observations have been accumulating rapidly that sudden anosmia and dysgeusia are peculiar symptoms associated with the COVID-19 infection. Prof C. Hopkins, as President of British Rhinological Society, published a letter describing "the loss of sense of smell as a marker of COVID-19 infection" and proposed that adults presenting with anosmia but no other symptoms should self-isolate for seven days. The Hopkins team published the first case report and case series as well as other evidence that isolated sudden onset anosmia (ISOA), should be considered highly suspicious for SARS-CoV-2(1). Subsequently, a larger series of 2428 patients presenting with new onset anosmia during the COVID-19 pandemic has been reported, of whom 16% report loss of sense of smell as an isolated symptom. Only 51% reported the recognized symptoms of cough or fever. A major limitation of this series however, was a lack of access to testing to confirm the COVID-19 status of the patients(2); in the 80 who had been tested 74% were positive. In the same way, the American Academy of Otolaryngology-head and neck surgery (AA0-HNS) proposed "that anosmia could be added to the list of screening tools for possible COVID-19 infection. More, they warrant serious consideration for self-isolation and testing those patients".


title: Stent-assisted coiling versus balloon remodeling of wide-neck aneurysms: comparison of angiographic outcomes.

text: BACKGROUND AND PURPOSE Stent-assisted coiling and balloon-assisted coiling are 2 well-established techniques for treatment of wide-neck intracranial aneurysms. A direct comparative analysis of angiographic outcomes with the 2 techniques has not been available. We compare the angiographic outcomes of wide-neck aneurysms treated with stent-assisted coiling versus balloon-assisted coiling. MATERIALS AND METHODS A retrospective review was conducted on 101 consecutive patients treated at our institution, 69 with stent-assisted coiling and 32 with balloon-assisted coiling. Two multivariate logistic regression analyses were performed to determine predictors of aneurysm obliteration and predictors of progressive aneurysm thrombosis at follow-up. RESULTS The 2 groups were comparable with respect to all baseline characteristics with the exception of a higher proportion of ruptured aneurysms in the balloon-assisted coiling group (65.6%) than in the stent-assisted coiling group (11.5%, P < .001). Procedural complications did not differ between the stent-assisted coiling group (6%) and the balloon-assisted coiling group (9%, P = .5). The rates of complete aneurysm occlusion (Raymond score 1) at the most recent follow-up were significantly higher for the stent-assisted coiling group (75.4%) compared with the balloon-assisted coiling group (50%, P = .01). Progressive occlusion of incompletely coiled aneurysms was noted in 76.6% of aneurysms in the stent-assisted coiling group versus 42.8% in the balloon-assisted coiling group (P = .02). Retreatment rates were significantly lower with stent-assisted coiling (4.3%) versus balloon-assisted coiling (15.6%, P = .05). In multivariate analysis, stented aneurysms independently predicted both complete aneurysm obliteration and progression of occlusion. CONCLUSIONS Stent-assisted coiling may yield lower rates of retreatment and higher rates of aneurysm obliteration and progression of occlusion at follow-up than balloon-assisted coiling with a similar morbidity rate.


title: Plastic freezer bags: a cost-effective method to protect extraction sites in laparoscopic colorectal procedures?

text: PURPOSE To review surgical-site infection (SSI) and retrieval-site tumor recurrence rates in laparoscopic colorectal procedures when using a plastic freezer bag as a wound protector. METHODS Laparoscopic colorectal procedures where a plastic freezer bag used as a wound protector at the extraction site were reviewed between 1991 and 2008 from a prospectively collected database. χ test was used to compare SSI and tumor recurrence rates between groups. Costing data were obtained from the operating room supplies department. RESULTS A total of 936 cases with 51 (5.45%) surgical-site infections were identified. SSI rates did not differ when comparing groups based on demographic factors, diagnosis, or location of procedure. Retrieval-site tumor recurrence rate was 0.21% (1/474). Cost of plastic freezer bags including sterilization ranged from $0.25 to $3. CONCLUSIONS Plastic freezer bags as wound protectors in laparoscopic colorectal procedures are cost effective and have SSI and retrieval-site tumor recurrence rates that compare favorably to published data.


title: A pre-immediate-early role for tegument ICP0 in the proteasome-dependent entry of herpes simplex virus.

text: Herpes simplex virus (HSV) entry requires host cell 26S proteasomal degradation activity at a postpenetration step. When expressed in the infected cell, the HSV immediate-early protein ICP0 has E3 ubiquitin ligase activity and interacts with the proteasome. The cell is first exposed to ICP0 during viral entry, since ICP0 is a component of the inner tegument layer of the virion. The function of tegument ICP0 is unknown. Deletion of ICP0 or mutations in the N-terminal RING finger domain of ICP0 results in the absence of ICP0 from the tegument. We show here that these mutations negatively influenced the targeting of incoming capsids to the nucleus. Inhibitors of the chymotrypsin-like activity of the proteasome the blocked entry of virions containing tegument ICP0, including ICP0 mutants that are defective in USP7 binding. However, ICP0-deficient virions were not blocked by proteasomal inhibitors and entered cells via a proteasome-independent mechanism. ICP0 appeared to play a postpenetration role in cells that supported either endocytosis or nonendosomal entry pathways for HSV. The results suggest that ICP0 mutant virions are defective upstream of viral gene expression at a pre-immediate-early step in infection. We propose that proteasome-mediated degradation of a virion or host protein is regulated by ICP0 to allow efficient delivery of entering HSV capsids to the nuclear periphery.


title: A Systematic Review of Risk Factors for Sleep Disruption in Critically Ill Adults.

text: OBJECTIVES Numerous risk factors for sleep disruption in critically ill adults have been described. We performed a systematic review of all risk factors associated with sleep disruption in the ICU setting. DATA SOURCES PubMed, EMBASE, CINAHL, Web of Science, Cochrane Central Register for Controlled Trials, and Cochrane Database of Systematic Reviews. STUDY SELECTION English-language studies of any design published between 1990 and April 2018 that evaluated sleep in greater than or equal to 10 critically ill adults (> 18 yr old) and investigated greater than or equal to 1 potential risk factor for sleep disruption during ICU stay. We assessed study quality using Newcastle-Ottawa Scale or Cochrane Risk of Bias tool. DATA EXTRACTION We abstracted all data independently and in duplicate. Potential ICU sleep disruption risk factors were categorized into three categories based on how data were reported: 1) patient-reported reasons for sleep disruption, 2) patient-reported ratings of potential factors affecting sleep quality, and 3) studies reporting a statistical or temporal association between potential risk factors and disrupted sleep. DATA SYNTHESIS Of 5,148 citations, we included 62 studies. Pain, discomfort, anxiety/fear, noise, light, and ICU care-related activities are the most common and widely studied patient-reported factors causing sleep disruption. Patients rated noise and light as the most sleep-disruptive factors. Higher number of comorbidities, poor home sleep quality, home sleep aid use, and delirium were factors associated with sleep disruption identified in available studies. CONCLUSIONS This systematic review summarizes all premorbid, illness-related, and ICU-related factors associated with sleep disruption in the ICU. These findings will inform sleep promotion efforts in the ICU and guide further research in this field.


title: Neurophysiologic effects of repeated exposure to antidepressant medication: are brain functional changes during antidepressant administration influenced by learning processes?

text: Major Depressive Disorder (MDD) is a lifelong and recurrent illness, such that many individuals require multiple courses of antidepressant medication treatment. While some patients respond completely to each course of treatment, many do not, and with each unsuccessful antidepressant trial the likelihood that a patient will respond decreases. This raises the possibility that neurophysiologic response in subsequent antidepressant treatment may be influenced by learning processes including sensitization, habituation, and/or classical conditioning. Classical conditioning would entail the association of cues such as pill-taking (conditioned stimuli; CS) with the effects of active medication (unconditioned stimulus; US), such that later presentation of the CS alone would come to elicit a conditioned response (CR). Such effects could be revealed by blinded administration of placebo following a period of treatment with active medication. Habituation effects (tolerance), or sensitization effects (increased response), which require only repeated exposure to a stimulus, might be evidenced after repeated courses of antidepressant treatment. Knowledge of how learning processes impact neurophysiologic response to successive courses of antidepressant treatment would have relevance for clinical populations. Specific hypotheses, however, may be tested in healthy non-clinical samples to avoid potential confounding factors related to severity or chronicity of illness. Learning theories would suggest two hypotheses: (1) neurophysiologic response to placebo will differ between subjects who were previously treated with antidepressant treatment as compared to placebo (classical conditioning hypothesis); and (2) neurophysiologic response to an initial course of antidepressant treatment will differ from response to a repeated course of antidepressant treatment. Pilot data addressed these hypotheses in healthy never-depressed women who had previously received four weeks of venlafaxine IR, 150 mg (antidepressant-experienced subjects; n=2) or matching placebo (antidepressant-naive subjects; n=4) under double-blind conditions. Six-and-a-half years later, we treated these six women with placebo for one week, followed by four weeks of double-blind treatment with venlafaxine IR, 150 mg. Brain functional changes over the course of treatment were assessed using quantitative electroencephalography (qEEG) to compare prefrontal neurophysiologic responses between subjects who had, versus had not, previously been exposed to venlafaxine. Antidepressant-experienced versus antidepressant-naive subjects showed greater decreases in prefrontal cordance (PFC) during venlafaxine administration (sensitization hypothesis) but did not show significantly different PFC changes during treatment with placebo in this small pilot sample (classical conditioning hypothesis). Data suggest that brief treatment with antidepressant medication may have an enduring impact on neurophysiologic responses to a subsequent course of antidepressant treatment. Hypotheses should be tested in larger samples.


title: Effects of intranasal xylometazoline, alone or in combination with ipratropium, in patients with common cold.

text: BACKGROUND Common cold is one of the most prevalent conditions that family doctors encounter. One of the first symptoms to occur is nasal congestion, which can have a negative impact on daily life and prompts many patients to seek treatment for relief. Xylometazoline nasal spray (Otrivin*) is a topical decongestant that has been used successfully for many years and is generally recognized as an effective and safe therapy. However, most studies have investigated its clinical efficacy in healthy patients and few have included patients with common cold. SCOPE To review the published clinical efficacy and safety of xylometazoline alone and in combination in the management of nasal congestion in patients with common cold. Literature searches of PubMed and the Cochrane Library were conducted to obtain published open or blinded, randomized, placebo- or active-controlled studies on the use of xylometazoline hydrochloride for the symptomatic relief of nasal congestion in patients with common cold. Searches included papers published in English only, up to September 2009. FINDINGS Despite the small number of studies identified in common cold (n = 4), as per search criteria defined, intranasal xylometazoline quickly and effectively relieved nasal congestion. When used alone, xylometazoline had a clinically relevant decongestant effect that was significantly superior for up to 10 hours compared with placebo. The superior decongestant effect with xylometazoline led to high patient satisfaction with treatment. When used in combination with ipratropium bromide, nasal congestion and rhinorrhoea were treated simultaneously, leading to significantly higher patient general impression scores compared with either agent used alone. Xylometazoline was well tolerated, with generally mild to moderate nasal-related side effects (e.g. epistaxis in 3.4% of patients, and blood-tinged mucus in 10-26% of patients) that were easily resolved; the most frequently reported non-nasal AEs were headache (3.4%) and period pain (10.3%); no cases of sedation were reported. As expected, no rhinitis medicamentosa or rebound congestion was noted with short-term use (<10 days). No clinically important differences in ciliary motility and mucociliary clearance were observed. Xylometazoline does not result in sympathomimetic systemic side effects seen with oral decongestants (e.g. pseudoephedrine, phenylephrine). CONCLUSIONS The few studies available in common cold suggest that intranasal xylometazoline provides fast and effective relief of nasal congestion and is well tolerated. When xylometazoline is used in combination with ipratropium, patients with common cold experience the additive benefit of nasal congestion and rhinorrhoea being treated simultaneously.


title: Successful extirpation of thoracic pleural lipoma by single-port thoracoscopic surgery.

text: Video-assisted thorascopic surgery (VATS) is a common technique for thoracic operations. Surgery with access via a single port has gradually become popular. We herein report the unusual case of a 53-year-old Japanese male patient whose chest X-rays revealed an abnormal shadow, which continued to increase in size. The tumor was excised by single-port access surgery. The resected tumor was a pedunculated pleural mass, yellowish in color, and pathological diagnosis confirmed a lipoma. We describe the first known successful treatment by single-port VATS.


Selenium supplementation can relieve the clinical complications of COVID-19 and other similar viral infections.


What can countries learn from Hong Kong's response to the COVID-19 pandemic?


docid: dtnhlwzr

title: Rationale and Design of the Hamburg City Health Study.

text: The Hamburg City Health Study (HCHS) is a large, prospective, long-term, population-based cohort study and a unique research platform and network to obtain substantial knowledge about several important risk and prognostic factors in major chronic diseases. A random sample of 45,000 participants between 45 and 74 years of age from the general population of Hamburg, Germany, are taking part in an extensive baseline assessment at one dedicated study center. Participants undergo 13 validated and 5 novel examinations primarily targeting major organ system function and structures including extensive imaging examinations. The protocol includes validate self-reports via questionnaires regarding lifestyle and environmental conditions, dietary habits, physical condition and activity, sexual dysfunction, professional life, psychosocial context and burden, quality of life, digital media use, occupational, medical and family history as well as healthcare utilization. The assessment is completed by genomic and proteomic characterization. Beyond the identification of classical risk factors for major chronic diseases and survivorship, the core intention is to gather valid prevalence and incidence, and to develop complex models predicting health outcomes based on a multitude of examination data, imaging, biomarker, psychosocial and behavioral assessments. Participants at risk for coronary artery disease, atrial fibrillation, heart failure, stroke and dementia are invited for a visit to conduct an additional MRI examination of either heart or brain. Endpoint assessment of the overall sample will be completed through repeated follow-up examinations and surveys as well as related individual routine data from involved health and pension insurances. The study is targeting the complex relationship between biologic and psychosocial risk and resilience factors, chronic disease, health care use, survivorship and health as well as favorable and bad prognosis within a unique, large-scale long-term assessment with the perspective of further examinations after 6 years in a representative European metropolitan population.


docid: fhjnerun

title: Postoperative radiotherapy for pathologic N2 non-small-cell lung cancer treated with adjuvant chemotherapy: a review of the National Cancer Data Base.

text: PURPOSE To investigate the impact of modern postoperative radiotherapy (PORT) on overall survival (OS) for patients with N2 non-small-cell lung cancer (NSCLC) treated nationally with surgery and adjuvant chemotherapy. PATIENTS AND METHODS Patients with pathologic N2 NSCLC who underwent complete resection and adjuvant chemotherapy from 2006 to 2010 were identified from the National Cancer Data Base and stratified by use of PORT (≥ 45 Gy). A total of 4,483 patients were identified (PORT, n = 1,850; no PORT, n = 2,633). The impact of patient and treatment variables on OS was explored using Cox regression. RESULTS Median follow-up time was 22 months. On univariable analysis, improved OS correlated with younger age, treatment at an academic facility, female sex, urban population, higher income, lower Charlson comorbidity score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT. On multivariable analysis, improved OS remained independently predicted by younger age, female sex, urban population, lower Charlson score, smaller tumor size, multiagent chemotherapy, resection with at least a lobectomy, and PORT (hazard ratio, 0.886; 95% CI, 0.798 to 0.988). Use of PORT was associated with an increase in median and 5-year OS compared with no PORT (median OS, 45.2 v 40.7 months, respectively; 5-year OS, 39.3% [95% CI, 35.4% to 43.5%] v 34.8% [95% CI, 31.6% to 38.3%], respectively; P = .014). CONCLUSION For patients with N2 NSCLC after complete resection and adjuvant chemotherapy, modern PORT seems to confer an additional OS advantage beyond that achieved with adjuvant chemotherapy alone.


title: Prediction of clinical outcomes in individuals with chronic low back pain: a protocol for a systematic review with meta-analysis.

text: BACKGROUND Low back pain (LBP) is one of the most prevalent and recurrent conditions in the general population, with personal, professional, social and economic impact. However, there is a lack of consistent evidence about chronic low back pain (CLBP) prognosis, especially highlighting predictors that influence CLBP outcome. Existing systematic reviews are scarce, outdated and incomplete. The primary aim of this systematic review is to identify multivariable models and/or predictors associated with clinical outcomes in subjects with CLBP (namely pain intensity, disability, return to work, psychological well-being and quality of life). METHODS We will systematically search Ovid MEDLINE (PubMed), Scopus and Web of Science databases for longitudinal studies, published until June 2017, including adults with CLBP (defined as persistent pain with ≥ 3 months duration), which studied the association between multivariable models and/or predictors with at least one of the selected clinical outcomes after ≥ 3 months of follow-up. Articles' screening and selection will be conducted by two reviewers, blindly and independently. Disagreements will be resolved by a third reviewer. Models' discriminative ability will be assessed using C-statistic. The link between multivariable models and predictors with the clinical outcome will be analysed through association measures. Qualitative and quantitative synthesis of the available evidence will be performed. Meta-analysis will be conducted to aggregate each type of measure. In the absence or in the presence of only slight to moderate of heterogeneity, we will use the fixed or random effects model, respectively. In case of moderate to severe heterogeneity, an attempt to explain variability in detail will be made through subgroups and sensitivity analyses. Subgroup analysis will be conducted according to clinical outcome, follow-up duration (≤ 6 months versus > 6 months) and type of context (pain management clinics versus other therapeutic settings). DISCUSSION We consider that it is urgent to highlight the available evidence about CLBP prognosis. This systematic review will help identify multivariable models and individual predictors that may enhance pain management success. One potential limitation will be the difficulty of aggregating quantitative measures from several prognostic models and predictors, with different clinical outcomes. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017079233.


title: New Verapamil Analogs Inhibit Intracellular Mycobacteria without Affecting the Functions of Mycobacterium-Specific T Cells.

text: There is a growing interest in repurposing mycobacterial efflux pump inhibitors, such as verapamil, for tuberculosis (TB) treatment. To aid in the design of better analogs, we studied the effects of verapamil on macrophages and Mycobacterium tuberculosis-specific T cells. Macrophage activation was evaluated by measuring levels of nitric oxide, tumor necrosis factor alpha (TNF-α), interleukin-1 beta (IL-1β), and gamma interferon (IFN-γ). Since verapamil is a known autophagy inducer, the roles of autophagy induction in the antimycobacterial activities of verapamil and norverapamil were studied using bone marrow-derived macrophages from ATG5(flox/flox) (control) and ATG5(flox/flox) Lyz-Cre mice. Our results showed that despite the well-recognized effects of verapamil on calcium channels and autophagy, its action on intracellular M. tuberculosis does not involve macrophage activation or autophagy induction. Next, the effects of verapamil and norverapamil on M. tuberculosis-specific T cells were assessed using flow cytometry following the stimulation of peripheral blood mononuclear cells from TB-skin-test-positive donors with M. tuberculosis whole-cell lysate for 7 days in the presence or absence of drugs. We found that verapamil and norverapamil inhibit the expansion of M. tuberculosis-specific T cells. Additionally, three new verapamil analogs were found to inhibit intracellular Mycobacterium bovis BCG, and one of the three analogs (KSV21) inhibited intracellular M. tuberculosis replication at concentrations that did not inhibit M. tuberculosis-specific T cell expansion. KSV21 also inhibited mycobacterial efflux pumps to the same degree as verapamil. More interestingly, the new analog enhances the inhibitory activities of isoniazid and rifampin on intracellular M. tuberculosis. In conclusion, KSV21 is a promising verapamil analog on which to base structure-activity relationship studies aimed at identifying more effective analogs.


title: Emergency laparoscopic treatment of acute incarcerated incisional hernia.

text: BACKGROUND The emergency treatment of incisional hernias can be accomplished by a laparoscopic approach in order to avoid the common complications following open techniques. METHODS From January 2001 to September 2007, we performed 48 emergency laparoscopic treatments of incarcerated hernias. RESULTS In our hospital, 320 patients with incisional hernia and 65 patients with primary abdominal wall hernia were treated laparoscopically. Forty-eight patients (30 females and 18 males) underwent emergency surgery. The mean operative time was 62 min (range 45–80 min). The average length of hospital stay was 4 days (range 3–6 days). We had eight post-surgical seromas, all of which were treated successfully by needle aspiration. We saw no mesh sepsis and no metabolic or surgical complications. We had no recurrence nor the need for a second operation. Mortality was nil. CONCLUSIONS The results of this series prove the feasibility of emergency laparoscopic surgery in incarcerated incisional hernias using new-generation meshes.


title: The value of corneoscleral rim cultures in keratoplasty: a systematic review and cost-effectiveness analysis.

text: PURPOSE This study evaluated the performance of donor corneoscleral rim cultures for predicting infection after corneal transplantation, and determines if there is a correlation between positive corneoscleral rim cultures and postkeratoplasty infection. DESIGN AND DATA SOURCES This was a systematic review, prognostic accuracy analysis, and cost-effectiveness analysis. Databases searched were: Medline (Ovid), Embase (Ovid), CINAHL, Cochrane Library, Web of Science, and BioSis Previews. Grey literature was also explored. MATERIALS AND METHODS A systematic review was conducted to locate published and unpublished studies. All studies examining corneal button contamination and its association with endophthalmitis and keratitis posttransplantation were included. Extracted data were used to calculate sensitivity, specificity, positive predictive value, and negative predictive value. Cost data from the London Laboratory Services Group in London, ON were used to calculate the cost-effectiveness of culturing donor rim cultures. RESULTS Of 7,870 grafts, 954 had a positive rim culture (12.1%), with 12 patients going on to develop keratitis or endophthalmitis (1.3%). The prevalence of keratitis and endophthalmitis in this study was 0.15%, and the positive predictive value 1.5%. Of the 12 infections, nine were fungal and three bacterial. The estimated cost of a positive and negative test result was CAD$45.99 and $14.15, respectively. The cost to run all 7,870 tests was estimated to be $141,735.86, with an incremental cost-effectiveness ratio of $40,215.70. CONCLUSION There was a significant divergence between bacterial and fungal rim-culture results. Bacterial cultures predicted clinical infection poorly, did not change management, and were expensive. Fungal cultures predicted clinical infection in over 10% of patients, had the potential to change management, and were 40% less expensive than full rim culturing (bacterial and fungal tests). Fungal rim cultures may be considered in areas where fungal infection rates are high.


title: Transcription factor Sox11b is involved in spinal cord regeneration in adult zebrafish.

text: Adult zebrafish have the ability to recover from spinal cord injury and exhibit re-growth of descending axons from the brainstem to the spinal cord. We performed gene expression analysis using microarray to find damage-induced genes after spinal cord injury, and found that Sox11b mRNA is up-regulated at 11 days after injury. However, the functional relevance of Sox11b for regeneration is not known. Here, we report that the up-regulation of Sox11b mRNA after spinal cord injury is mainly localized in ependymal cells lining the central canal and in newly differentiating neuronal precursors or immature neurons. Using an in vivo morpholino-based gene knockout approach, we demonstrate that Sox11b is essential for locomotor recovery after spinal cord injury. In the injured spinal cord, expression of the neural stem cell associated gene Nestin, and the proneural gene Ascl1a (Mash1a), which are involved in the self-renewal and cell fate specification of endogenous neural stem cells, respectively, is regulated by Sox11b. Our data indicate that Sox11b promotes neuronal determination of endogenous stem cells and regenerative neurogenesis following spinal cord injury in the adult zebrafish. Enhancing Sox11b expression to promote proliferation and neurogenic determination of endogenous neural stem cells after injury may be a promising strategy in restorative therapy after spinal cord injury in mammals.


title: Order of Treatment Matters in Ischemic Stroke: Mechanical Thrombectomy First, Then Carotid Artery Stenting for Tandem Lesions of the Anterior Circulation.

text: BACKGROUND One endovascular treatment option of acute ischemic stroke due to tandem occlusion (TO) comprises intracranial thrombectomy and acute extracranial carotid artery stenting (CAS). In this setting, the order of treatment may impact the clinical outcome in this stroke subtype. METHODS Retrospective analysis was performed on data prospectively collected in 4 international stroke centers between 2013 and 2017. One hundred sixty-five patients with anterior TO were treated by endovascular therapy. Clinical and procedural data were evaluated. Favorable clinical outcome was defined as modified Rankin Scale (mRS) ≤2 at 90 days. Propensity score matching was performed for different treatment strategies. RESULTS Patients' mean age was 65 ± 11 years and 118 were male (69%). The median admission National Institutes of Health Stroke Scale was 15 (interquartile range 8). In 59% of the patients (n = 101), the antegrade strategy (first stenting, then thrombectomy) was -performed, in 41% (n = 70) retrograde treatment (first thrombectomy, then stenting). Successful reperfusion (mTICI ≥2b) was achieved in 128 patients (75%). Fifty-nine patients (39%) showed a favorable clinical outcome after 90 days. After propensity score matching, data of 100 patients could be analyzed. Analysis revealed that the retrograde strategy yielded a significantly higher rate of successful reperfusion compared to the antegrade strategy (92 vs. 56%; p < 0.001). The rate of favorable clinical outcome after 90 days (mRS ≤2) was consistently higher (44 vs. 30%; p < 0.05) in the retrograde strategy group. CONCLUSION Mechanical thrombectomy prior to acute CAS in TO is a predictive factor for favorable clinical outcome at 90 days.


Epidemic Insurance.


title: Neonatal brain oxygenation during thoracoscopic correction of esophageal atresia.

text: BACKGROUND Little is known about the effects of carbon dioxide (CO2) insufflation on cerebral oxygenation during thoracoscopy in neonates. Near-infrared spectroscopy can measure perioperative brain oxygenation [regional cerebral oxygen saturation (rScO2)]. AIMS To evaluate the effects of CO2 insufflation on rScO2 during thoracoscopic esophageal atresia (EA) repair. METHODS This is an observational study during thoracoscopic EA repair with 5 mmHg CO2 insufflation pressure. Mean arterial blood pressure (MABP), arterial oxygen saturation (SaO2), partial pressure of arterial carbon dioxide (paCO2), pH, and rScO2 were monitored in 15 neonates at seven time points: baseline (T0), after anesthesia induction (T1), after CO2-insufflation (T2), before CO2-exsufflation (T3), and postoperatively at 6 (T4), 12 (T5), and 24 h (T6). RESULTS MABP remained stable. SaO2 decreased from T0 to T2 [97 ± 3-90 ± 6 % (p < 0.01)]. PaCO2 increased from T0 to T2 [41 ± 6-54 ± 15 mmHg (p < 0.01)]. pH decreased from T0 to T2 [7.33 ± 0.04-7.25 ± 0.11 (p < 0.05)]. All parameters recovered during the surgical course. Mean rScO2 was significantly higher at T1 compared to T2 [77 ± 10-73 ± 7 % (p < 0.05)]. Mean rScO2 levels never dropped below a safety threshold of 55 %. CONCLUSION The impact of neonatal thoracoscopic repair of EA with insufflation of CO2 at 5 mmHg was studied. Intrathoracic CO2 insufflation caused a reversible decrease in SaO2 and pH and an increase in paCO2. The rScO2 was higher at anesthesia induction but remained stable and within normal limits during and after the CO2 pneumothorax, which suggest no hampering of cerebral oxygenation by the thoracoscopic intervention. Future studies will focus on the long-term effects of this surgery on the developing brain.


title: Using Genome Sequence to Enable the Design of Medicines and Chemical Probes.

text: Rapid progress in genome sequencing technology has put us firmly into a postgenomic era. A key challenge in biomedical research is harnessing genome sequence to fulfill the promise of personalized medicine. This Review describes how genome sequencing has enabled the identification of disease-causing biomolecules and how these data have been converted into chemical probes of function, preclinical lead modalities, and ultimately U.S. Food and Drug Administration (FDA)-approved drugs. In particular, we focus on the use of oligonucleotide-based modalities to target disease-causing RNAs; small molecules that target DNA, RNA, or protein; the rational repurposing of known therapeutic modalities; and the advantages of pharmacogenetics. Lastly, we discuss the remaining challenges and opportunities in the direct utilization of genome sequence to enable design of medicines.