Covid-19: protecting patients in hospital for neurorehabilitation and their therapists.


title: Prognostic value of cerebral tissue oxygen saturation during neonatal extracorporeal membrane oxygenation.

text: OBJECTIVES Extracorporeal membrane oxygenation support is indicated in severe and refractory respiratory or circulatory failures. Neurological complications are typically represented by acute ischemic or hemorrhagic lesions, which induce higher morbidity and mortality. The primary goal of this study was to assess the prognostic value of cerebral tissue oxygen saturation (StcO2) on mortality in neonates and young infants treated with ECMO. A secondary objective was to evaluate the association between StcO2 and the occurrence of cerebral lesions. STUDY DESIGN This was a prospective study in infants < 3 months of age admitted to a pediatric intensive care unit and requiring ECMO support. MEASUREMENTS The assessment of cerebral perfusion was made by continuous StcO2 monitoring using near-infrared spectroscopy (NIRS) sensors placed on the two temporo-parietal regions. Neurological lesions were identified by MRI or transfontanellar echography. RESULTS Thirty-four infants <3 months of age were included in the study over a period of 18 months. The ECMO duration was 10±7 days. The survival rate was 50% (17/34 patients), and the proportion of brain injuries was 20% (7/34 patients). The mean StcO2 during ECMO in the non-survivors was reduced in both hemispheres (p = 0.0008 right, p = 0.03 left) compared to the survivors. StcO2 was also reduced in deceased or brain-injured patients compared to the survivors without brain injury (p = 0.002). CONCLUSION StcO2 appears to be a strong prognostic factor of survival and of the presence of cerebral lesions in young infants during ECMO.


title: Neutralizing Complement C5a Protects Mice with Pneumococcal Pulmonary Sepsis.

text: BACKGROUND Community-acquired pneumonia and associated sepsis cause high mortality despite antibiotic treatment. Uncontrolled inflammatory host responses contribute to the unfavorable outcome by driving lung and extrapulmonary organ failure. The complement fragment C5a holds significant proinflammatory functions and is associated with tissue damage in various inflammatory conditions. The authors hypothesized that C5a concentrations are increased in pneumonia and C5a neutralization promotes barrier stabilization in the lung and is protective in pneumococcal pulmonary sepsis. METHODS The authors investigated regulation of C5a in pneumonia in a prospective patient cohort and in experimental pneumonia. Two complementary models of murine pneumococcal pneumonia were applied. Female mice were treated with NOX-D19, a C5a-neutralizing L-RNA-aptamer. Lung, liver, and kidney injury and the inflammatory response were assessed by measuring pulmonary permeability (primary outcome), pulmonary and blood leukocytes, cytokine concentrations in lung and blood, and bacterial load in lung, spleen, and blood, and performing histologic analyses of tissue damage, apoptosis, and fibrin deposition (n = 5 to 13). RESULTS In hospitalized patients with pneumonia (n = 395), higher serum C5a concentrations were observed compared to healthy subjects (n = 24; 6.3 nmol/l [3.9 to 10.0] vs. 4.5 nmol/l [3.8 to 6.6], median [25 to 75% interquartile range]; difference: 1.4 [95% CI, 0.1 to 2.9]; P = 0.029). Neutralization of C5a in mice resulted in lower pulmonary permeability in pneumococcal pneumonia (1.38 ± 0.89 vs. 3.29 ± 2.34, mean ± SD; difference: 1.90 [95% CI, 0.15 to 3.66]; P = 0.035; n = 10 or 11) or combined severe pneumonia and mechanical ventilation (2.56 ± 1.17 vs. 7.31 ± 5.22; difference: 4.76 [95% CI, 1.22 to 8.30]; P = 0.011; n = 9 or 10). Further, C5a neutralization led to lower blood granulocyte colony-stimulating factor concentrations and protected against sepsis-associated liver injury. CONCLUSIONS Systemic C5a is elevated in pneumonia patients. Neutralizing C5a protected against lung and liver injury in pneumococcal pneumonia in mice. Early neutralization of C5a might be a promising adjunctive treatment strategy to improve outcome in community-acquired pneumonia. : WHAT WE ALREADY KNOW ABOUT THIS TOPIC: Pneumonia, sepsis, and immune dysregulation cause morbidity and mortalityC5a is a component of the complement system and a proinflammatory mediator that modulates the innate immune response in critical illnessDisruption of the C5a receptor axis with antibodies or antagonists was previously protective in various animal sepsis models WHAT THIS ARTICLE TELLS US THAT IS NEW: In hospitalized patients with community-acquired pneumonia, serum C5a concentrations were 1.4-fold higher compared to healthy subjectsIn two mouse models of pneumonia and sepsis, NOX-D19, a C5a-neutralizing L-RNA aptamer, caused lower pulmonary hyperpermeability and sepsis-related acute liver injury.


title: Pandemic influenza planning: addressing the needs of children.

text: Children represent one quarter of the US population. Because of its enormous size and special needs, it is critically important to address this population group in pandemic influenza planning. Here we describe the ways in which children are vulnerable in a pandemic, provide an overview of existing plans, summarize the resources available, and, given our experience with influenza A(H1N1), outline the evolving lessons we have learned with respect to planning for a severe influenza pandemic. We focus on a number of issues affecting children-vaccinations, medication availability, hospital capacity, and mental health concerns-and emphasize strategies that will protect children from exposure to the influenza virus, including infection control practices and activities in schools and child care programs.


title: Robot-assisted thoracoscopic resection of intralobar sequestration.

text: In this paper, we report the first case of a robot-assisted thoracoscopic resection of intralobar sequestration. By virtue of greater dexterity and three-dimensional visualization, the da Vinci robot enables a safer, more precise dissection of sequestered tissue in the face of chronic inflammatory adhesions than conventional video-assisted thoracoscopic surgery does. Thus, in expert hands, such robotic technology is likely to result in less bleeding complications and less conversions to open surgery in cases of sequestration.


title: Evolution of glycolipid profile after sleeve gastrectomy vs. Roux-en-Y gastric bypass: results of a prospective randomized clinical trial.

text: BACKGROUND This study aims to report glycolipid changes after sleeve gastrectomy (SG) or Roux-en-Y gastric bypass (RYGB) in the setting of a prospective randomized clinical trial. METHODS One hundred patients were randomly assigned to RYGB (n = 45) and SG (n = 55). Fasting glucose, insulin, glycated hemoglobin (HbA1c%), triglycerides, and serum cholesterol (total, HDL, and LDL) were evaluated at inclusion and after 1, 3, 6, and 12 months. The index for homeostasis model assessment of insulin resistance (HOMA-IR) and β cell function (HOMA-B) were assessed. RESULTS Mean postoperative 1-, 3-, 6-, and 12-month excess weight loss was 25.39, 43.47, 63.75, and 80.38 % after RYGB and 25.25, 51.32, 64.67, and 82.97 % after SG, respectively. Mean fasting glucose and fasting serum insulin were similarly and statistically significantly reduced in both RYGB and SG. Mean HOMA-IR improved in both groups, particularly in case of high preoperative values, and mean HOMA-B improved at 1 year after RYGB. HbA1c% dropped from 5.66 % (SD = 0.61) to 5.57 % (SD = 0.32) after RYGB and from 5.64 % (SD = 0.43) to 5.44 % (SD = 0.43) after SG. Total cholesterol was significantly higher at 1 month (p = 0.04), 3 months (p = 0.03), and 1 year (p = 0.005) after SG as compared to RYGB. LDL cholesterol decreased significantly after RYGB at 1 month (p = 0.03), 3 months (p = 0.0001), and 1 year (p = 0.0004) as compared to SG. HDL cholesterol was increased at 1 year in the RYGB group but not in the SG group. Triglycerides decreased similarly in both groups. CONCLUSIONS Short-term glycemic control was comparable after SG and RYGB. An improved lipid profile was noted after RYGB in patients with abnormal preoperative values.


title: Automated contour tracking and trajectory classification of pelvic organs on dynamic MRI.

text: A method is presented to automatically track and segment pelvic organs on dynamic magnetic resonance imaging (MRI) followed by multiple-object trajectory classification to improve understanding of pelvic organ prolapse (POP). POP is a major health problem in women where pelvic floor organs fall from their normal position and bulge into the vagina. Dynamic MRI is presently used to analyze the organs' movements, providing complementary support for clinical examination. However, there is currently no automated or quantitative approach to measure the movement of the pelvic organs and their correlation with the severity of prolapse. In the proposed method, organs are first tracked and segmented using particle filters and [Formula: see text]-means clustering with prior information. Then, the trajectories of the pelvic organs are modeled using a coupled switched hidden Markov model to classify the severity of POP. Results demonstrate that the presented method can automatically track and segment pelvic organs with a Dice similarity index above 78% and Hausdorff distance of [Formula: see text] for 94 tested cases while demonstrating correlation between organ movement and POP. This work aims to enable automatic tracking and analysis of multiple deformable structures from images to improve understanding of medical disorders.


title: Angiotensin-converting enzyme 2, a SARS-CoV-2 receptor, is upregulated by interleukin-6 via STAT3 signaling in synovial tissues.

text: The severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has spread explosively worldwide and resulted in a pandemic of a new respiratory disease called coronavirus disease 2019 (COVID-19) in 2020. Symptoms of COVID-19 include fever, malaise, cough, and in severe cases, pneumonia and acute respiratory distress syndrome (1,2).


title: Favipiravir: pharmacokinetics and concerns about clinical trials for 2019-nCoV infection.

text: An outbreak of 2019-nCoV infection in China has spread across the world. No specific antiviral drugs have been approved for the treatment of COVID-2019. In addition to the recommended antiviral drugs such as interferon-ɑ, lopinavir/ritonavir, ribavirin, and chloroquine phosphate, some clinical trials focusing on virus RNA dependent RNA polymerase (RdRp) inhibitors have been registered and initiated. Favipiravir, a purine nucleic acid analog and potent RdRp inhibitor approved for use in influenza, is also considered in several clinical trials. Herein, we summarized the pharmacokinetic characteristics of favipiravir and possible drug-drug interactions from the view of drug metabolism. We hope this will be helpful for the design of clinical trials for favipiravir in COVID-2019, as data regarding in vitro virus inhibition and efficacy in preclinical animal studies are still not available.


Is thromboprophylaxis with high-dose enoxaparin really necessary for COVID-19 patients? A new "prudent" randomised clinical trial.


title: Systematic drug repositioning for a wide range of diseases with integrative analyses of phenotypic and molecular data.

text: Drug repositioning, or the application of known drugs to new indications, is a challenging issue in pharmaceutical science. In this study, we developed a new computational method to predict unknown drug indications for systematic drug repositioning in a framework of supervised network inference. We defined a descriptor for each drug-disease pair based on the phenotypic features of drugs (e.g., medicinal effects and side effects) and various molecular features of diseases (e.g., disease-causing genes, diagnostic markers, disease-related pathways, and environmental factors) and constructed a statistical model to predict new drug-disease associations for a wide range of diseases in the International Classification of Diseases. Our results show that the proposed method outperforms previous methods in terms of accuracy and applicability, and its performance does not depend on drug chemical structure similarity. Finally, we performed a comprehensive prediction of a drug-disease association network consisting of 2349 drugs and 858 diseases and described biologically meaningful examples of newly predicted drug indications for several types of cancers and nonhereditary diseases.


title: Middle East respiratory syndrome coronavirus (MERS-CoV) in dromedary camels in Nigeria, 2015.

text: Evidence of current and past Middle East respiratory syndrome coronavirus (MERS-CoV) infection in dromedary camels slaughtered at an abattoir in Kano, Nigeria in January 2015, was sought by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and serology. MERS-CoV RNA was detected in 14 (11%) of 132 nasal swabs and antibody in 126 (96%) of 131 serum samples. Phylogenetic analyses demonstrate that the viruses in Nigeria are genetically distinct from those reported in the Arabian peninsula.


title: Antihistamines for the common cold.

text: BACKGROUND The common cold is an upper respiratory tract infection, most commonly caused by a rhinovirus. It affects people of all age groups and although in most cases it is self limiting, the common cold still causes significant morbidity. Antihistamines are commonly offered over the counter to relieve symptoms for patients affected by the common cold, however there is not much evidence of their efficacy. OBJECTIVES To assess the effects of antihistamines on the common cold. SEARCH METHODS We searched CENTRAL (2015, Issue 6), MEDLINE (1948 to July week 4, 2015), EMBASE (2010 to August 2015), CINAHL (1981 to August 2015), LILACS (1982 to August 2015) and Biosis Previews (1985 to August 2015). SELECTION CRITERIA We selected randomised controlled trials (RCTs) using antihistamines as monotherapy for the common cold. We excluded any studies with combination therapy or using antihistamines in patients with an allergic component in their illness. DATA COLLECTION AND ANALYSIS Two authors independently assessed trial quality and extracted data. We collected adverse effects information from the included trials. MAIN RESULTS We included 18 RCTs, which were reported in 17 publications (one publication reports on two trials) with 4342 participants (of which 212 were children) suffering from the common cold, both naturally occurring and experimentally induced. The interventions consisted of an antihistamine as monotherapy compared with placebo. In adults there was a short-term beneficial effect of antihistamines on severity of overall symptoms: on day one or two of treatment 45% had a beneficial effect with antihistamines versus 38% with placebo (odds ratio (OR) 0.74, 95% confidence interval (CI) 0.60 to 0.92). However, there was no difference between antihistamines and placebo in the mid term (three to four days) to long term (six to 10 days). When evaluating individual symptoms such as nasal congestion, rhinorrhoea and sneezing, there was some beneficial effect of the sedating antihistamines compared to placebo (e.g. rhinorrhoea on day three: mean difference (MD) -0.23, 95% CI -0.39 to -0.06 on a four- or five-point severity scale; sneezing on day three: MD -0.35, 95% CI -0.49 to -0.20 on a four-point severity scale), but this effect is clinically non-significant. Adverse events such as sedation were more commonly reported with sedating antihistamines although the differences were not statistically significant. Only two trials included children and the results were conflicting. The majority of the trials had a low risk of bias although some lacked sufficient trial quality information. AUTHORS' CONCLUSIONS Antihistamines have a limited short-term (days one and two of treatment) beneficial effect on severity of overall symptoms but not in the mid to long term. There is no clinically significant effect on nasal obstruction, rhinorrhoea or sneezing. Although side effects are more common with sedating antihistamines, the difference is not statistically significant. There is no evidence of effectiveness of antihistamines in children.


title: Infarct growth despite full reperfusion in endovascular therapy for acute ischemic stroke.

text: AIM To explore the predictors of infarct core expansion despite full reperfusion after intra-arterial therapy (IAT). METHODS We retrospectively reviewed 604 consecutive patients who underwent IAT for anterior circulation large vessel occlusion acute ischemic stroke in two tertiary centers (2008-2013/2010-2013). Sixty patients selected by MRI or CT perfusion presenting within <24 h of onset with modified Thrombolysis In Cerebral Infarction (mTICI) grade 3 or 2c reperfusion were included. Significant infarct growth (SIG) was defined as infarct expansion >11.6 mL. RESULTS Mean age was 67.0±13.7 years, 56% were men. Mean National Institute of Health Stroke Scale (NIHSS) score was 16.2±6.1, time from onset to puncture was 6.8±3.1 h, and procedure length was 1.3±0.6 h. MRI was used for baseline core analysis in 43% of patients. Mean baseline infarct volume was 17.1±19.1 mL, absolute infarct growth was 30.6±74.5 mL, and final infarct volume was 47.7±77.7 mL. Overall, 35% of patients had SIG. Three of 21 patients (14%) treated with stent-retrievers had SIG compared with 14 of 39 (36%) with first-generation devices. Eight of 21 patients (38%) with intravenous tissue plasminogen activator (IV t-PA) had infarct growth compared with 25/39 (64%) without. 23% of patients with SIG had a modified Rankin Scale score ≤2 at 3 months compared with 48% of those without SIG. Multivariate logistic regression indicated that race affected infarct growth. Use of IV t-PA (p=0.03) and stent-retrievers (p=0.03) were independently and inversely correlated with SIG. CONCLUSIONS Despite full reperfusion, infarct growth is relatively frequent and may explain poor clinical outcomes in this setting. Ethnicity was found to influence SIG. Use of IV t-PA and stent-retrievers were associated with less infarct core expansion.


title: Renal function and cardiac adrenergic impairment in patients affected by heart failure.

text: Although in heart failure (HF) there is a strict correlation between heart and kidney, no data are available on the potential relationship in HF between renal dysfunction (RD) and the impaired sympathetic innervation. Aim of the present study was to assess the relationship between RD and cardiac sympathetic innervation in HF patients with reduced ejection fraction. Two hundred and sixty-three patients with mild-to-severe HF underwent iodine-123 meta-iodobenzylguanidine myocardial scintigraphy to assess sympathetic innervation, evaluating early and late heart-to-mediastinum (H/M) ratios and washout rate. In all patients, glomerular filtration rate (eGFR) by Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was assessed. A direct association was found between EPI-eGFR and late H/M (r = .215; P < .001). Dividing the population into moderate-to-severe eGFR reduction and normal-to-mildly reduced eGFR (cutoff ≤ 60 mL·min-1·1.73 m-2), a statistically significant reduction of late H/M value was found in patients with RD compared to patients with preserved eGFR (P = .030). By multivariable linear regression analysis, eGFR resulted in the prediction of impaired late H/M in patients with RD (P = .005). Patients with RD and HF show more impaired cardiac sympathetic activity than HF patients with preserved renal function, and reduced eGFR is a predictor of reduced late H/M.


title: New operative strategy for refractory microcystic lymphangioma.

text: The optimal management of microcystic lymphatic malformations (LMs) in children has not been established. We describe how we used the Ligasure™ Vessel Sealing System (LVSS) to achieve partial resection of refractory microcystic LMs in a 1-year-old boy. The child was admitted in respiratory distress caused by infection and swelling of cervical LMs. The LMs had been diagnosed prenatally, but had not decreased in size despite three treatments with OK-432 sclerotherapy. We performed direct dissection of the microcystic LMs using the LVSS with minimal intraoperative blood loss or lymphatic leakage. The LMs were resected as completely as possible without damage to the jugular vein or major nerves. His postoperative course was uneventful. Histological examination revealed complete sealing of the lymphovascular channels with obliterated lumens. Resection using the LVSS is effective and easy to perform for partial resection of microcystic LMs. We recommend the combination of initial OK-432 injection therapy and subsequent partial resection using the LVSS for refractory microcystic LMs.


title: Successful management of severe unilateral re-expansion pulmonary edema after mitral valve repair with mini-thoracotomy using extracorporeal membrane oxygenation.

text: A 60-year-old man received mitral valve repair via right mini-thoracotomy, which was followed by unilateral re-expansion pulmonary edema on the right side and severe hemoptysis just after the surgery. Despite differential lung ventilation with unilateral high positive end expiratory pressure was initiated for the affected right lung, respiratory function did not improved and hemodynamics was collapsed in the next day. Veno-venous extracorporeal membrane oxygenation was initiated by cannulation of the right jugular and the left femoral vein. After pulmonary function recovered gradually, veno-venous extracorporeal membrane oxygenation was terminated on the fifth postoperative day. He was discharged in ambulatory condition on postoperative day 52.


Covid-19: undocumented migrants are probably at greatest risk.


title: Prophylactic Mesh Placement During Formation of an End-colostomy Reduces the Rate of Parastomal Hernia: Short-term Results of the Dutch PREVENT-trial.

text: OBJECTIVE The aim of this study was to investigate the incidence of parastomal hernias (PSHs) after end-colostomy formation using a polypropylene mesh in a randomized controlled trial versus conventional colostomy formation. BACKGROUND A PSH is the most frequent complication after stoma formation. Symptoms may range from mild abdominal pain to life-threatening obstruction and strangulation. The treatment of a PSH is notoriously difficult and recurrences up to 20% have been reported despite the use of mesh. This has moved surgical focus toward prevention. METHODS Augmentation of the abdominal wall with a retro-muscular lightweight polypropylene mesh was compared with the traditional formation of a colostomy. In total, 150 patients (1:1 ratio) were included. The incidence of a PSH, morbidity, mortality, quality of life, and cost-effectiveness was measured after 1 year of follow-up. RESULTS There was no difference between groups regarding demographics and predisposing factors for PSH. Three out of 67 patients (4.5%) in the mesh group and 16 out of 66 patients (24.2%) in the nonmesh group developed a PSH (P = 0.0011). No statistically significant difference was found in infections, concomitant hernias, SF-36 questionnaire, Von Korff pain score, and cost-effectiveness between both study groups. CONCLUSION Prophylactic augmentation of the abdominal wall with a retromuscular lightweight polypropylene mesh at the ostomy site significantly reduces the incidence of PSH without a significant difference in morbidity, mortality, quality of life, or cost-effectiveness.


Coronavirus misinformation needs researchers to respond.


title: Rapid development of broadly influenza neutralizing antibodies through redundant mutations.

text: The neutralizing antibody response to influenza virus is dominated by antibodies that bind to the globular head of haemagglutinin, which undergoes a continuous antigenic drift, necessitating the re-formulation of influenza vaccines on an annual basis. Recently, several laboratories have described a new class of rare influenza-neutralizing antibodies that target a conserved site in the haemagglutinin stem. Most of these antibodies use the heavy-chain variable region VH1-69 gene, and structural data demonstrate that they bind to the haemagglutinin stem through conserved heavy-chain complementarity determining region (HCDR) residues. However, the VH1-69 antibodies are highly mutated and are produced by some but not all individuals, suggesting that several somatic mutations may be required for their development. To address this, here we characterize 197 anti-stem antibodies from a single donor, reconstruct the developmental pathways of several VH1-69 clones and identify two key elements that are required for the initial development of most VH1-69 antibodies: a polymorphic germline-encoded phenylalanine at position 54 and a conserved tyrosine at position 98 in HCDR3. Strikingly, in most cases a single proline to alanine mutation at position 52a in HCDR2 is sufficient to confer high affinity binding to the selecting H1 antigen, consistent with rapid affinity maturation. Surprisingly, additional favourable mutations continue to accumulate, increasing the breadth of reactivity and making both the initial mutations and phenylalanine at position 54 functionally redundant. These results define VH1-69 allele polymorphism, rearrangement of the VDJ gene segments and single somatic mutations as the three requirements for generating broadly neutralizing VH1-69 antibodies and reveal an unexpected redundancy in the affinity maturation process.


title: Long-term patterns and predictors of pain following laparoscopic inguinal hernia repair: a patient-centered analysis.

text: BACKGROUND Laparoscopic inguinal hernia repair has been shown to offer patients the benefit of less postoperative pain as compared to traditional open techniques. However, the risk of experiencing significant postoperative pain may affect patient's decision making. We aimed to elucidate potential patterns of pain and the predictors of such, up to 2 years postoperatively, using both generic and specific quality of life tools. METHODS Patients undergoing laparoscopic totally extra-peritoneal inguinal hernia repair were identified from a prospectively maintained database. Short form-36, Surgical Outcomes Measurement System (SOMS) and Carolinas Comfort Scale (CCS) surveys were administered pre- and postoperatively at 3 weeks, 6 months, 1 and 2 years. Patients with concomitant procedures were excluded. Significant pain was considered mild but bothersome or worse on either specific tool (SOMS scores ≥3/4, CCS scores ≥2). Predictors of significant pain were determined by logistic regression. RESULTS From 2009 to 2015, 482 patients enrolled in our database underwent elective TEP repair of 626 hernias and completed an assessment tool. Mean age was 57 (±15) years, with 93 % male. Reported pain on all three tools improved significantly from baseline over time (p < 0.01). Significant pain on either specific tool, related or unrelated to surgery, was reported by 52 % of respondents (158/301) preoperatively, and postoperatively by 50 % at 3 weeks (111/220), 21 % at 6 months (15/70), 13 % at 1 year (14/108), and 25 % at 2 years (30/121). Significant pain at 6 months-2 years correlated more significantly with general health status than surgical factors. CONCLUSIONS Significant pain can be as high as 50 % at 3 weeks on surgery-specific quality of life measures, but with significant improvement by 6 months which is maintained through 2 years. Poor quality of life and general health were the main predictors of pain after 6 months.


title: European surveillance for pantropic canine coronavirus.

text: Highly virulent pantropic canine coronavirus (CCoV) strains belonging to subtype IIa were recently identified in dogs. To assess the distribution of such strains in Europe, tissue samples were collected from 354 dogs that had died after displaying systemic disease in France (n = 92), Hungary (n = 75), Italy (n = 69), Greece (n = 87), The Netherlands (n = 27), Belgium (n = 4), and Bulgaria (n = 1). A total of 124 animals tested positive for CCoV, with 33 of them displaying the virus in extraintestinal tissues. Twenty-four CCoV strains (19.35% of the CCoV-positive dogs) detected in internal organs were characterized as subtype IIa and consequently assumed to be pantropic CCoVs. Sequence and phylogenetic analyses of the 5' end of the spike protein gene showed that pantropic CCoV strains are closely related to each other, with the exception of two divergent French viruses that clustered with enteric strains.


title: Fundamental Use of Surgical Energy (FUSE): An Essential Educational Program for Operating Room Safety.

text: Operating room (OR) safety has become a major concern in patient safety since the 1990s. Improvement of team communication and behavior is a popular target for safety programming at the institutional level. Despite these efforts, essential safety gaps remain in the OR and procedure rooms. A prime example is the use of energy-based devices in ORs and procedural areas. The lack of fundamental understanding of energy device function, design, and application contributes to avoidable injury and harm at a rate of approximately 1 to 2 per 1000 patients in the US. Hundreds of OR fires occur each year in the US, some causing severe injury and even death. Most of these fires are associated with the use of energy-based surgical devices.In response to this safety issue, the Society of American Gastrointestinal and Endoscopic Surgeons (SAGES) developed the Fundamental Use of Surgical Energy (FUSE) program. This program includes a standardized curriculum targeted to surgeons, other physicians, and allied health care professionals and a psychometrically designed and validated certification test. A successful FUSE certification documents acquisition of the basic knowledge needed to safely use energy-based devices in the OR. By design FUSE fills a void in the curriculum and competency assessment for surgeons and other procedural specialists in the use of energy-based devices in patients.


title: Broad receptor engagement of an emerging global coronavirus may potentiate its diverse cross-species transmissibility.

text: Porcine deltacoronavirus (PDCoV), identified in 2012, is a common enteropathogen of swine with worldwide distribution. The source and evolutionary history of this virus is, however, unknown. PDCoV belongs to the Deltacoronavirus genus that comprises predominantly avian CoV. Phylogenetic analysis suggests that PDCoV originated relatively recently from a host-switching event between birds and mammals. Insight into receptor engagement by PDCoV may shed light into such an exceptional phenomenon. Here we report that PDCoV employs host aminopeptidase N (APN) as an entry receptor and interacts with APN via domain B of its spike (S) protein. Infection of porcine cells with PDCoV was drastically reduced by APN knockout and rescued after reconstitution of APN expression. In addition, we observed that PDCoV efficiently infects cells of unusual broad species range, including human and chicken. Accordingly, PDCoV S was found to target the phylogenetically conserved catalytic domain of APN. Moreover, transient expression of porcine, feline, human, and chicken APN renders cells susceptible to PDCoV infection. Binding of PDCoV to an interspecies conserved site on APN may facilitate direct transmission of PDCoV to nonreservoir species, including humans, potentially reflecting the mechanism that enabled a virus, ancestral to PDCoV, to breach the species barrier between birds and mammals. The APN cell surface protein is also used by several members of the Alphacoronavirus genus. Hence, our data constitute the second identification of CoVs from different genera that use the same receptor, implying that CoV receptor selection is subjected to specific restrictions that are still poorly understood.


title: A single-cell atlas of the peripheral immune response in patients with severe COVID-19.

text: There is an urgent need to better understand the pathophysiology of Coronavirus disease 2019 (COVID-19), the global pandemic caused by SARS-CoV-2, which has infected more than three million people worldwide1. Approximately 20% of patients with COVID-19 develop severe disease and 5% of patients require intensive care2. Severe disease has been associated with changes in peripheral immune activity, including increased levels of pro-inflammatory cytokines3,4 that may be produced by a subset of inflammatory monocytes5,6, lymphopenia7,8 and T cell exhaustion9,10. To elucidate pathways in peripheral immune cells that might lead to immunopathology or protective immunity in severe COVID-19, we applied single-cell RNA sequencing (scRNA-seq) to profile peripheral blood mononuclear cells (PBMCs) from seven patients hospitalized for COVID-19, four of whom had acute respiratory distress syndrome, and six healthy controls. We identify reconfiguration of peripheral immune cell phenotype in COVID-19, including a heterogeneous interferon-stimulated gene signature, HLA class II downregulation and a developing neutrophil population that appears closely related to plasmablasts appearing in patients with acute respiratory failure requiring mechanical ventilation. Importantly, we found that peripheral monocytes and lymphocytes do not express substantial amounts of pro-inflammatory cytokines. Collectively, we provide a cell atlas of the peripheral immune response to severe COVID-19.


title: Video-assisted thoracoscopic transdiaphragmatic liver resection for hepatocellular carcinoma.

text: Because of technical complexity, concern for vascular control, and uncertainty in regard to oncologic outcome, the application of minimally invasive techniques to liver surgery has been slower than in most other abdominal procedures. This is despite well-known advantages with respect to postoperative pain, length of hospitalization, and recovery time. Although laparoscopic liver surgery has recently become more common, the majority of laparoscopic liver resections comprise anterolateral wedge resections and left lateral sectorectomies. Laparoscopic resections of the posterosuperior segments are more difficult and few reports are available in the literature. Compared to laparoscopy, gaining access to tumors in the dome of the liver may be more easily obtained via thoracoscopy, thereby preserving the benefits of minimally invasive surgery. This technical report describes two cases of hepatocellular carcinoma in segments VII and VIII resected via a video-assisted thoracoscopic transdiaphragmatic approach.


title: Rift Valley Fever Outbreak in Livestock, Mozambique, 2014.

text: In early 2014, abortions and death of ruminants were reported on farms in Maputo and Gaza Provinces, Mozambique. Serologic analysis and quantitative and conventional reverse transcription PCR confirmed the presence of Rift Valley fever virus. The viruses belonged to lineage C, which is prevalent among Rift Valley fever viruses in southern Africa.


title: Treatment of Moyamoya Disease and Unruptured Intracranial Aneurysm in Floating-Harbor Syndrome.

text: BACKGROUND This is the first report of the successful treatment of moyamoya disease and an unruptured intracranial aneurysm in a patient with Floating-Harbor syndrome. CASE DESCRIPTION A 35-year-old, phenotypically syndromic woman presented with signs and symptoms consistent with ischemic stroke. Magnetic resonance imaging and catheter angiography confirmed diagnosis of moyamoya and a 6-mm basilar apex artery aneurysm (BAA). She underwent right-sided craniotomy for direct and indirect revascularization by means of superficial temporal artery-middle cerebral artery bypass and encephalo-duro-arterio-synangiosis. Three months later, she underwent stent-assisted coiling of the BAA. At 9 months, the patient remains without her preoperative neurological deficits. Interval catheter angiography confirms revascularization of her right hemisphere and obliteration of her BAA. CONCLUSIONS We present the first case of diagnosis and treatment of moyamoya disease and BAA in a patient with Floating-Harbor syndrome. Due to a paucity of literature on this rare disorder, there has not been an associated link between Floating-Harbor syndrome and cerebrovascular disease. Our report and literature review suggest that these patients may be prone to cerebrovascular disorders and should be followed closely with neurovascular imaging.


Covid-19: Leading statistician welcomes UK government's move to improve testing data.


title: The Barrel vascular reconstruction device for endovascular coiling of wide-necked intracranial aneurysms: a multicenter, prospective, post-marketing study.

text: BACKGROUND AND PURPOSE The Barrel vascular reconstruction device (Barrel VRD) is a novel stent with design features that allow endovascular coiling of wide-necked bifurcation aneurysms while preserving adjacent branches, without necessitating dual stent implantation. This study aimed to assess the safety and effectiveness of the Barrel VRD at 12-month follow-up. MATERIALS AND METHODS The Barrel VRD trial is a prospective, multicenter, observational post-marketing registry evaluating the use of the Barrel VRD for treatment of wide-necked bifurcation aneurysms. The primary effectiveness endpoint was successful aneurysm treatment measured by digital subtraction angiography with a Raymond-Roy occlusion grade of 1 or 2 in the absence of retreatment, parent artery stenosis (>50%), or target aneurysm rupture at 12 months. The primary safety endpoint was the absence of neurological death or major stroke at 12 months. RESULTS Twenty patients were enrolled from December 2013 to December 2014. The device was implanted in 19 patients with 19 aneurysms (8 middle cerebral artery, 4 anterior communicating artery, 1 internal carotid artery terminus, 4 basilar artery aneurysms; mean dome height 5.7±1.91 mm; mean neck length 4.8±1.35 mm, mean dome-to-neck ratio 1.6±2.0). Coiling was performed in all cases. The primary effectiveness endpoint was achieved in 78.9% of subjects (15/19; 12 complete occlusions, 3 neck remnants), and the primary safety endpoint was 5.3% (1/19). CONCLUSIONS This prospective study demonstrates that the Barrel VRD device resulted in ~80% occlusion rates and ~5% rates of neurological complications at 1 year after endovascular treatment of wide-necked bifurcation intracranial aneurysms. REGISTERED CLINICAL TRIAL: NCT02125097;Results.


title: Porcine Reproductive and Respiratory Syndrome Virus Infection Induces both eIF2α Phosphorylation-Dependent and -Independent Host Translation Shutoff.

text: Porcine reproductive and respiratory syndrome virus (PRRSV) is an Arterivirus that has caused tremendous economic losses in the global swine industry since it was discovered in the late 1980s. Inducing host translation shutoff is a strategy used by many viruses to optimize their replication and spread. Here, we demonstrate that PRRSV infection causes host translation suppression, which is strongly dependent on viral replication. By screening PRRSV-encoded nonstructural proteins (nsps), we found that nsp2 participates in the induction of host translation shutoff and that its transmembrane (TM) domain is required for this process. nsp2-induced translation suppression is independent of protein degradation pathways and the phosphorylation of eukaryotic initiation factor 2α (eIF2α). However, the overexpression of nsp2 or its TM domain significantly attenuated the mammalian target of rapamycin (mTOR) signaling pathway, an alternative pathway for modulating host gene expression. PRRSV infection also attenuated the mTOR signaling pathway, and PRRSV-induced host translation shutoff could be partly reversed when the attenuated mTOR phosphorylation was reactivated by an activator of the mTOR pathway. PRRSV infection still negatively regulated the host translation when the effects of eIF2α phosphorylation were completely reversed. Taken together, our results demonstrate that PRRSV infection induces host translation shutoff and that nsp2 is associated with this process. Both eIF2α phosphorylation and the attenuation of the mTOR signaling pathway contribute to PRRSV-induced host translation arrest.IMPORTANCE Viruses are obligate parasites, and the production of progeny viruses relies strictly on the host translation machinery. Therefore, the efficient modulation of host mRNA translation benefits viral replication, spread, and evolution. In this study, we provide evidence that porcine reproductive and respiratory syndrome virus (PRRSV) infection induces host translation shutoff and that the viral nonstructural protein nsp2 is associated with this process. Many viruses induce host translation shutoff by phosphorylating eukaryotic initiation factor 2α (eIF2α). However, PRRSV nsp2 does not induce eIF2α phosphorylation but attenuates the mTOR signaling pathway, another pathway regulating the host cell translational machinery. We also found that PRRSV-induced host translation shutoff was partly reversed by eliminating the effects of eIF2α phosphorylation or reactivating the mTOR pathway, indicating that PRRSV infection induces both eIF2α phosphorylation-dependent and -independent host translation shutoff.


Combatting the Myth of Neuropathology.


title: Intra-arterial Contrasted Cone-beam Computed Tomography Assessment of Vessels Distal from Occluded Site in Acute Ischemic Stroke with Major Vessel Occlusion.

text: Characterization of vessels distal from occluded site is important when considering endovascular revascularization therapy (EVT) for acute ischemic stroke. The goal of this study was to assess the clinical value of intra-arterial contrasted high-resolution cone-beam computed tomography from the ascending aorta (Ao-CBCT) for visualization of the vessels distal from occluded site. Acute ischemic stroke patients with large vessel occlusion who were to undergo EVT were evaluated. In EVT, digital subtraction angiography (DSA) and Ao-CBCT were performed with local anesthesia. Ao-CBCT images were acquired in a 20-second rotational scan. Contrast medium was injected (1 mL/s for a total of 30 seconds using a 4-Fr catheter and an imaging delay of 10 seconds) from the ascending aorta. We assessed the image quality of Ao-CBCT and compared the visualization of the vessels distal from occluded site among magnetic resonance angiography (MRA), DSA and Ao-CBCT. We analyzed 14 patients (mean age, 66 years; three female patients). Stroke subtypes were cardiogenic (n = 6), atherothrombotic (n = 5) and others/unknown (n = 3). Occluded sites were middle cerebral artery (MCA) M1 (n = 8), MCA M2 (n = 2), internal carotid artery (ICA) (n = 2), MCA M4 (n = 1) and basilar artery (BA) (n = 1). All obtained Ao-CBCT images successfully characterized the vessels distal from occluded site, and 11 images (79%) were excellent. In all cases, Ao-CBCT images could depict distal vessels with more detail when compared with MRA and DSA. Ao-CBCT is an efficient method to obtain detailed information regarding vessels distal from occluded site when compared with conventional examination methods.


docid: rvqyrkgl

title: Practical approaches to pedagogically rich online tutorials in health professions education.

text: Health professions education in tertiary, industrial and other contexts often entails face-to-face small group learning through tutorials. The current novel coronavirus, COVID-19, has reduced face-to-face contact, and this has challenged how health professionals and clinical students can access training, accreditation and development. Online and other remote mechanisms are available to tutors and course designers; however, they might not feel comfortable with such affordances, in light of expectations to so rapidly change familiar teaching and delivery styles. This may result in the loss of interaction and disruption of peer learning, which are hallmarks of the small group tutorial. Collaborative learning is essential to develop and refine an emerging sense of belonging to a professional community through formal studies, and interactive learning is a requirement for some registered health professions to satisfy ongoing professional accreditation. Online media has been used to promote social learning in regional, rural and remote communities for some time. Strategies for learning activity design and tutor training are proposed to equip course designers and educators to support health professions education remotely, through the synchronous, online small group. This may herald a new era of increased access to training and professional development for non-urban learners, beyond COVID-19.


Can angiotensin receptor-blocking drugs perhaps be harmful in the COVID-19 pandemic?


docid: bdlfscyb

title: The relationship between minute ventilation and end tidal CO2 in intubated and spontaneously breathing patients undergoing procedural sedation.

text: BACKGROUND Monitoring respiratory status using end tidal CO2 (EtCO2), which reliably reflects arterial PaCO2 in intubated patients under general anesthesia, has often proven both inaccurate and inadequate when monitoring non-intubated and spontaneously breathing patients. This is particularly important in patients undergoing procedural sedation (e.g., endoscopy, colonoscopy). This can be undertaken in the operating theater, but is also often delivered outside the operating room by non-anesthesia providers. In this study we evaluated the ability for conventional EtCO2 monitoring to reflect changes in ventilation in non-intubated surgical patients undergoing monitored anesthesia care and compared and contrasted these findings to both intubated patients under general anesthesia and spontaneously breathing volunteers. METHODS Minute Ventilation (MV), tidal volume (TV), and respiratory rate (RR) were continuously collected from an impedance-based Respiratory Volume Monitor (RVM) simultaneously with capnography data in 160 patients from three patient groups: non-intubated surgical patients managed using spinal anesthesia and Procedural Sedation (n = 58); intubated surgical patients under General Anesthesia (n = 54); and spontaneously breathing Awake Volunteers (n = 48). EtCO2 instrument sensitivity was calculated for each patient as the slope of a Deming regression between corresponding measurements of EtCO2 and MV and expressed as angle from the x-axis (θ). All data are presented as mean ± SD unless otherwise indicated. RESULTS While, as expected, EtCO2 and MV measurements were negatively correlated in most patients, we found gross systematic differences across the three cohorts. In the General Anesthesia patients, small changes in MV resulted in large changes in EtCO2 (high sensitivity, θ = -83.6 ± 9.9°). In contrast, in the Awake Volunteers patients, large changes in MV resulted in insignificant changes in EtCO2 (low sensitivity, θ = -24.7 ± 19.7°, p < 0.0001 vs General Anesthesia). In the Procedural Sedation patients, EtCO2 sensitivity showed a bimodal distribution, with an approximately even split between patients showing high EtCO2 instrument sensitivity, similar to those under General Anesthesia, and patients with low EtCO2 instrument sensitivity, similar to the Awake Volunteers. CONCLUSIONS When monitoring non-intubated patients undergoing procedural sedation, EtCO2 often provides inadequate instrument sensitivity when detecting changes in ventilation. This suggests that augmenting standard patient care with EtCO2 monitoring is a less than optimal solution for detecting changes in respiratory status in non-intubated patients. Instead, adding direct monitoring of MV with an RVM may be preferable for continuous assessment of adequacy of ventilation in non-intubated patients.


title: Early chest tube removal after video-assisted thoracic surgery lobectomy with serous fluid production up to 500 ml/day.

text: OBJECTIVES In fast-track pulmonary resections, we removed chest tubes after video-assisted thoracic surgery (VATS) lobectomy with serous fluid production up to 500 ml/day. Subsequently, we evaluated the frequency of recurrent pleural effusions requiring reintervention. METHODS Data from 622 consecutive patients undergoing VATS lobectomy from January 2009 to December 2011 were registered prospectively in an institutional database. Data included age, gender, lobe(s) resected, bleeding and duration of surgery. Follow-up was 30 days from discharge. All complications requiring pleurocentesis or reinsertion of a chest tube, and all readmissions were registered. Twenty-three patients were excluded due to missing data, in-hospital mortality and loss to follow-up, leaving 599 for final analysis. Our primary outcome was the number of patients requiring reintervention due to recurrent pleural effusion. Secondary outcomes included time of chest tube removal and time to discharge. The incidence of recurrent pleural effusions requiring reintervention was compared between three groups according to the postoperative day (POD) of chest tube removal (Day 0-1, 2-3 and ≥4, respectively) using Fisher's exact test. RESULTS Pleural effusion after chest tube removal required reintervention in 17 patients (2.8%). Of these, 7 needed readmission. Median time from surgery to chest tube removal was 2 days, and median time from surgery to discharge was 4 days. No statistically significant association was found between the incidence of reinterventions due to recurrent pleural effusion and the POD of chest tube removal (P=0.50). The median time from chest tube removal to discharge was 1 day in all groups. Of the patients who needed reintervention, none had complications regarding this, except one who developed pneumothorax after pleurocentesis. CONCLUSIONS Our findings suggest that chest tube removal after VATS lobectomy is safe despite volumes of serous fluid production up to 500 ml/day. The proportion of patients who developed pleural effusion necessitating reintervention was low (2.8%), and a complication of the reintervention was seen in only 1 patient.


title: Single-center comparative study of laparoscopic versus open colorectal surgery: a 2-year experience.

text: AIM To examine the change in practice from open to laparoscopic practice in our local trust, a national training colorectal unit. METHODS Retrospective comprehensive review of clinical case notes of all colorectal resections between October 2007 and October 2009. Patients were identified through clinical coding and data were analyzed using SPSS. RESULTS Comparison of 113 open versus 103 laparoscopic colorectal surgeries for various indications and short-term outcomes was made. There was an expected overall increase in the laparoscopic colorectal resections. The mean age was 73 years for open and 68 years for laparoscopic surgeries. There was no significant difference between the 2 groups with respect to age, sex, and the American Society of Anaesthesiologists. Of the 103 patients who were initially treated with laparoscopy-assisted colectomy, 12 (11.7%) were shifted to open procedures. Perioperative recovery was faster in the laparoscopic-surgery group than in the open-colectomy group, as reflected by a shorter hospital stay (median, 8 vs. 13 d). The overall complication rate was significantly less in the laparoscopy-assisted colectomy group than in the open-colectomy group (33% vs. 46%, P=0.05). CONCLUSIONS Our local hospital practices support the many benefits of laparoscopic colorectal surgery. Substantial improvements in rates of hospital stay and wound infection were noted, hence shifting our practice safely in a district general hospital.


title: Neurologic applications of whole-brain volumetric multidetector computed tomography.

text: The introduction of computed tomography (CT) scanning in the 1970s revolutionized the way clinicians could diagnose and treat stroke. Subsequent advances in CT technology significantly reduced radiation dose, reduced metallic artifact, and achieved speeds that enable dynamic functional studies. The recent addition of whole-brain volumetric CT perfusion technology has given clinicians a powerful tool to assess parenchymal perfusion parameters as well as visualize dynamic changes in blood vessel flow throughout the brain during a single cardiac cycle. This article reviews clinical applications of volumetric multimodal CT that helped to guide and manage care.


title: Actinobacillus pleuropneumoniae culture supernatant antiviral effect against porcine reproductive and respiratory syndrome virus occurs prior to the viral genome replication and transcription through actin depolymerization.

text: PURPOSE Recently, the strong antiviral activity of an Actinobacillus pleuropneumoniae (App) culture supernatant against porcine reproductive and respiratory syndrome virus (PRRSV) was discovered. Following this finding, the objective of the present study was to understand how the App culture supernatant inhibits PRRSV replication in its natural targeted host cells, i.e. porcine alveolar macrophages (PAMs). METHODOLOGY Several assays were conducted with App culture supernatant-treated PRRSV-infected cell lines, such as PAM, St-Jude porcine lung and MARC-145 cells. RT-qPCR assays were used to determine the expression levels of type I and II IFN mRNAs, viral genomic (gRNA) and sub-genomic RNAs (sgRNAs). Proteomic, Western blot and immunofluorescence assays were conducted to determine the involvement of actin filaments in the App culture supernatant antiviral effect.Results/Key findings. Type I and II IFN mRNA expressions were not upregulated by the App culture supernatant. Time courses of gRNA and sgRNA expression levels demonstrated that the App culture supernatant inhibits PRRSV infection before the first viral transcription cycle. Western blot experiments confirmed an increase in the expression of cofilin (actin cytoskeleton dynamics regulator) and immunofluorescence also demonstrated a significant decrease of actin filaments in App culture supernatant-treated PRRSV-infected PAM cells. App culture supernatant antiviral activity was also demonstrated against other PRRSV strains of genotypes I and II. CONCLUSION App culture supernatant antiviral effect against PRRSV takes place early during PRRSV infection. Results suggest that App culture supernatant antiviral effect may take place via the activation of cofilin, which induces actin depolymerization and subsequently, probably affects PRRSV endocytosis. Other experiments are needed to fully validate this latest hypothesis.


title: Beta-blocker therapy and impact on outcome after aneurysmal subarachnoid hemorrhage: a cohort study.

text: OBJECTIVE Cerebral vasospasm (cVSP) is a frequent complication of aneurysmal subarachnoid hemorrhage (aSAH), with a significant impact on outcome. Beta blockers (BBs) may blunt the sympathetic effect and catecholamine surge associated with ruptured cerebral aneurysms and prevent cardiac dysfunction. The purpose of this study was to investigate the association between preadmission BB therapy and cVSP, cardiac dysfunction, and in-hospital mortality following aSAH. METHODS This was a retrospective cohort study of patients with aSAH who were treated at a tertiary high-volume neurovascular referral center. The exposure was defined as any preadmission BB therapy. The primary outcome was cVSP assessed by serial transcranial Doppler with any mean flow velocity ≥ 120 cm/sec and/or need for endovascular intervention for medically refractory cVSP. Secondary outcomes were cardiac dysfunction (defined as cardiac troponin-I elevation > 0.05 μg/L, low left ventricular ejection fraction [LVEF] < 40%, or LV wall motion abnormalities [LVWMA]) and in-hospital mortality. RESULTS The cohort consisted of 210 patients treated between February 2009 and September 2010 (55% were women), with a mean age of 53.4 ± 13 years and median Hunt and Hess Grade III (interquartile range III-IV). Only 13% (27/210) of patients were exposed to preadmission BB therapy. Compared with these patients, a higher percentage of patients not exposed to preadmission BBs had transcranial Doppler-mean flow velocity ≥ 120 cm/sec (59% vs 22%; p = 0.003). In multivariate analyses, lower Hunt and Hess grade (OR 3.9; p < 0.001) and preadmission BBs (OR 4.5; p = 0.002) were negatively associated with cVSP. In multivariate analysis, LVWMA (OR 2.7; p = 0.002) and low LVEF (OR 1.1; p = 0.05) were independent predictors of in-hospital mortality. Low LVEF (OR 3.9; p = 0.05) independently predicted medically refractory cVSP. The in-hospital mortality rate was higher in patients with LVWMA (47.4% vs 14.8%; p < 0.001). CONCLUSIONS The study data suggest that preadmission therapy with BBs is associated with lower incidence of cVSP after aSAH. LV dysfunction was associated with higher medically refractory cVSP and in-hospital mortality. BB therapy may be considered after aSAH as a cardioprotective and cVSP preventive therapy.


title: Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor.

text: NL63 coronavirus (NL63-CoV), a prevalent human respiratory virus, is the only group I coronavirus known to use angiotensin-converting enzyme 2 (ACE2) as its receptor. Incidentally, ACE2 is also used by group II SARS coronavirus (SARS-CoV). We investigated how different groups of coronaviruses recognize the same receptor, whereas homologous group I coronaviruses recognize different receptors. We determined the crystal structure of NL63-CoV spike protein receptor-binding domain (RBD) complexed with human ACE2. NL63-CoV RBD has a novel beta-sandwich core structure consisting of 2 layers of beta-sheets, presenting 3 discontinuous receptor-binding motifs (RBMs) to bind ACE2. NL63-CoV and SARS-CoV have no structural homology in RBD cores or RBMs; yet the 2 viruses recognize common ACE2 regions, largely because of a "virus-binding hotspot" on ACE2. Among group I coronaviruses, RBD cores are conserved but RBMs are variable, explaining how these viruses recognize different receptors. These results provide a structural basis for understanding viral evolution and virus-receptor interactions.


title: Advantages of Laparoscopic Radiofrequency Ablation Over Percutaneous Radiofrequency Ablation in Hepatocellular Carcinoma.

text: BACKGROUND Inoperable hepatocellular carcinoma (HCC) can be treated with laparoscopic radiofrequency ablation (LRFA), which is generally a more accurate and accessible procedure than percutaneous RFA (PRFA). However, few studies have compared survival outcomes between LRFA and PRFA in patients with HCC. AIMS This study aimed to compare the efficacy of LRFA and PRFA for HCC treatment. METHODS Patients who underwent PRFA or LRFA as an initial treatment modality between April 2005 and April 2016 were enrolled in this study. The overall and recurrence-free survival rates were examined for each patient. Additionally, propensity score matching was performed for both groups. RESULTS The baseline characteristics of patients in the PRFA and LRFA groups showed several minor differences. Multivariate analysis showed that the RFA method was not a critical determinant of recurrence-free or overall survival (p = 0.069 and p = 0.406). Among patients who underwent RFA as the initial treatment modality, there was no significant effect between either RFA procedures on survival. After propensity score matching, univariate analysis showed a significant difference in overall survival between PRFA and LRFA (p = 0.031). Multivariate analysis showed that LRFA is a strong factor that contributed to an improved overall survival in HCC patients (hazard ratio 0.108, p = 0.040). Furthermore, our data showed that LRFA was able to limit multiple intrahepatic recurrences, as well as prevent marginal recurrence. CONCLUSIONS LRFA appears to be superior to PRFA in terms of survival. LRFA may help reduce mortality in HCC patients.


title: Using effective hand hygiene practice to prevent and control infection.

text: Decontamination using hand hygiene remains one of the most important and effective methods for reducing healthcare-associated infections and cross-infection between patients. In 1860, Florence Nightingale wrote that nurses should wash their hands frequently throughout the day, demonstrating an early awareness of the effectiveness of this simple procedure. The COVID-19 pandemic has demonstrated that effectively applied hand hygiene is a vital intervention that can be used to prevent the spread of disease. This article details the correct procedure required for effective hand hygiene and emphasises the need for nurses to keep up to date with evidence-based guidelines. The article also outlines the differences between hand decontamination using alcohol-based hand gels and soap and water, and the complex factors that can interfere with effective hand hygiene compliance.


title: Laparoscopic single site adrenalectomy using a conventional laparoscope and instrumentation.

text: BACKGROUND AND OBJECTIVES We present a case of Laparoendoscopic Single Site Surgery (LESS) left adrenalectomy performed with a conventional laparoscope and instruments. METHODS A 45-year-old male was diagnosed with hyperaldosteronism. Computed tomography detected a left adrenal nodule. Bilateral adrenal vein sampling was consistent with a left-sided source for hyperaldosteronism. RESULTS Total operative time for LESS left adrenalectomy was 120 minutes. The surgery was performed with conventional instruments, a standard 5-mm laparoscope, and a SILS port, with no additional incisions or trocars needed. No complications occurred, and the patient reported an uneventful recovery. CONCLUSIONS LESS adrenalectomy is a feasible procedure. Although articulating instruments and laparoscopes may offer advantages, LESS adrenalectomy can be done without these.


title: Natural products for the management of the hepatitis C virus: a biochemical review.

text: Chronic hepatitis C virus (HCV) infection is a significant public health problem, with a worldwide prevalence of approximately 170 million. Current therapy for HCV infection includes the prolonged administration of a combination of ribavirin and PEGylated interferon-α, for over a decade. This regimen is expensive and often associated with a poor antiviral response and unwanted side effects. A highly effective combination treatment is likely required for the future management of HCV infections and entry inhibitors could play an important role. Currently, no entry inhibitor has been licensed for the prophylactic treatment of hepatitis C. Therefore, additional agents that combat HCV infection are urgently needed and must be developed. Many phytochemical constituents have been identified that display considerable inhibition of HCV at some stage of the life cycle. This review will summarise the current state of knowledge on natural products and their possible activities in the context of HCV infection.


title: Predictors of Outcome and Hemorrhage in Patients Undergoing Endovascular Therapy with Solitaire Stent for Acute Ischemic Stroke.

text: BACKGROUND Endovascular mechanical thrombectomy is emerging as a promising therapeutic approach for acute ischemic stroke and show some advantages. However, the data of predicting clinical outcome after thrombectomy with Solitaire retriever were limited. We attempt to identify prognostic factors of clinical outcome in patients with acute ischemic stroke undergoing thrombectomy with Solitaire retriever. METHODS We conducted a retrospective analysis of consecutive acute ischemic strokes cases treated between December 2010 and December2013 where the Solitaire stent retriever was used for acute ischemic stroke. We assessed the effect of selected demographic characteristics, clinical factors on poor outcome at 3 months (modified Rankin score 3-6), mortality at 3 months, and hemorrhage within 24 h (symptomatic and asymptomatic). Clinical, imaging and logistic variables were analyzed. A multivariate logistic regression analysis was used to identify variables influencing clinical outcome, based on discharge NIHSS score change and mRS at 3 months. RESULTS Eighty nine consecutive patients with acute ischemic stroke underwent mechanical thrombectomy. Multivariate analysis revealed that admission NIHSS score, Serum glucose and endovascular procedure duration were independently associated with clinical outcome. Sex, NIHSS score at admission, diabetes and time of operation were associated with sICH in 1 day. NIHSS score ≥20 (OR 9.38; 95% CI 2.41-36.50), onset to reperfusion >5 hours (OR 5.23; 95% CI1.34,20.41) and symptomatic intracranial hemorrhage (OR 10.19; 95% CI1.80,57.83) were potential predictive factors of mortality at 3 months. CONCLUSION Multiple pre- and intra-procedural factors can be used to predict clinical outcome, symptomatic intracranial hemorrhage and mortality in acute ischemic stroke patients undergoing endovascular therapy. This knowledge is helpful for patients selection for endovascular mechanical thrombectomy.


title: A multidisciplinary approach to the minimally invasive pulmonary vein isolation for treatment of atrial fibrillation.

text: Bilateral pulmonary vein isolation along with amputation of the left atrial appendage has become a well-recognized technique for the management of atrial fibrillation. We describe our multidisciplinary approach to minimally invasive bilateral pulmonary vein isolation, left atrial appendage resection, and ablation of autonomic ganglia.


title: Age-dependent effects in the transmission and control of COVID-19 epidemics.

text: The COVID-19 pandemic has shown a markedly low proportion of cases among children1-4. Age disparities in observed cases could be explained by children having lower susceptibility to infection, lower propensity to show clinical symptoms or both. We evaluate these possibilities by fitting an age-structured mathematical model to epidemic data from China, Italy, Japan, Singapore, Canada and South Korea. We estimate that susceptibility to infection in individuals under 20 years of age is approximately half that of adults aged over 20 years, and that clinical symptoms manifest in 21% (95% credible interval: 12-31%) of infections in 10- to 19-year-olds, rising to 69% (57-82%) of infections in people aged over 70 years. Accordingly, we find that interventions aimed at children might have a relatively small impact on reducing SARS-CoV-2 transmission, particularly if the transmissibility of subclinical infections is low. Our age-specific clinical fraction and susceptibility estimates have implications for the expected global burden of COVID-19, as a result of demographic differences across settings. In countries with younger population structures-such as many low-income countries-the expected per capita incidence of clinical cases would be lower than in countries with older population structures, although it is likely that comorbidities in low-income countries will also influence disease severity. Without effective control measures, regions with relatively older populations could see disproportionally more cases of COVID-19, particularly in the later stages of an unmitigated epidemic.


More than 100 countries still not using global outbreak surveillance regulations.


title: A Quarter Century of Emerging Infectious Diseases - Where Have We Been and Where Are We Going?

text: A quarter century ago the landmark report from the U. S. National Academies of Sciences, Engineering, and Medicine entitled "Emerging Infections, Microbial Threats to Health in the United States" was released. This classic study captured the societal changes then underway in our rapidly growing world: The growth of the world's population and changing human behavior; the advances and globalization of technology and industry; the changes in economic development and land use; the dramatic increase in speed and frequency of international travel and commerce; the adaptation of microbes and the appearance of never before seen pathogens; and the breakdown of traditional public health measures. This societal evolution has only increased and the growing frequency of outbreaks foretold in the report has come to pass. Each new disaster has precipitated changes and adaptations in our global response to infectious diseases designed to reduce risks and avoid future outbreaks. We discuss these past events and how each led to change in an effort to mitigate future threats. We also look to the future to consider what challenges might lay ahead. CONCLUSION Major outbreaks over the past quarter century validated the concept of emerging infectious diseases and led to improvements in global policies and national public health programs; however, there will likely always be new diseases and the threat of reemergence of diseases once thought controlled leading to a constant need for vigilance in public health preparedness.


What is a pandemic?


title: Potential relevance of pre-operative quality of life questionnaires to identify candidates for surgical treatment of genital prolapse: a pilot study.

text: BACKGROUND To evaluate prolapse-related symptoms, quality of life and sexuality of patients with validated questionnaires before and after surgery for genital prolapse and assess relevance of such an evaluation to select women for surgery. METHODS From November 2009 to April 2010, 16 patients operated on for genital prolapse of grade greater than or equal to 2 (POP-Q classification) were evaluated prospectively by three questionnaires of quality of life Pelvic Floor Distress Inventory (PFDI-20), Pelvic Floor Impact Questionnaire (PFIQ-7) and Pelvic Organ Prolaps/Urinary Incontinence Sexual Questionnaire (PISQ-12). Data were collected the day before surgery and 6 weeks postoperatively. RESULTS Eleven patients had laparoscopic surgery and five vaginal surgery. There was a significant decrease in pelvic heaviness, vaginal discomfort and urinary symptoms after surgery. The score of symptoms of prolapse, the PFDI-20 score was 98.5 preoperatively and 31.8 postoperatively (p < 0.0001). The score for quality of life, the PFIQ-7 score was 54.5 preoperatively and 7.4 postoperatively (p = 0.001). The score of sexuality, the PISQ-12 score was 35.3 preoperatively and 37.5 postoperatively (p = 0.1). Two of the 3 patients with a PFIQ 7 under or equal to 20 were not improved while all the women with a preoperative PFIQ-7 over 20 were improved after surgery. CONCLUSIONS This study suggests that surgery improves quality of life of patients with genital prolapse. Quality of life questionnaires could help select good candidates for surgery. Further studies are required to determine threshold to standardize indications of surgery.


Emergence of Coronavirus (COVID-19) outbreak: Anthropological and social science perspectives.


title: Haematological and biochemical reference intervals in adult Maine Coon cat blood donors.

text: OBJECTIVES The objectives of this study were to derive Maine Coon haematological and biochemical reference intervals (RIs) from adult healthy blood donors, to validate (or reject) the use of published RIs for the general feline population in this breed, and to evaluate the effects of age, sex and weight on the haematological and biochemical results. METHODS Haematological and biochemical data were retrieved retrospectively from a database of 81 healthy adult Maine Coon cat blood donors and were analysed to generate normal RIs. RIs were determined and compared with established non-breed-specific feline RIs according to the Clinical and Laboratory Standards Institute guidelines and the American Society of Veterinary Clinical Pathology guidelines using Reference Value-Advisor (version 2.1) software. RESULTS The age of the cats ranged from 1-8 years (mean 4.4 years), 42 were female and 39 were male, and weights ranged from 4.9-8.5 kg (mean 6.7 kg). New Maine Coon RIs were proposed for red blood cell count, mean corpuscular volume, mean corpuscular haemoglobin concentration, reticulocyte count and percentage. Haematocrit was higher in male cats (mean HCT 42.9% vs 41% in females; P = 0.001) and in heavier cats (P = 0.003; slope 1.0, regression equation HCT = 35.1 + 1.0 × weight). New biochemical RIs were proposed for urea, aspartate aminotransferase, γ-glutamyl transpeptidase (GGT), alkaline phosphatase, total protein and albumin in Maine Coons. Females had higher GGT (median GGT value in females 4.0 vs 3.0 in males; P = 0.011) and albumin values (mean albumin value 3.3 in females vs 3.1 in males; P = 0.013). CONCLUSIONS AND RELEVANCE Currently published RIs for some haematological and biochemical parameters are not appropriate for use in adult Maine Coon cats. A breed-specific variation could be a plausible explanation for the new haematological and serum biochemical analytes proposed in this study. Breed-specific RIs for Maine Coon cats will help prevent misinterpretation of laboratory results in diagnosis and in the selection of ideal blood donors.


Health of the Hajj.


title: The papain-like protease of porcine epidemic diarrhea virus negatively regulates type I interferon pathway by acting as a viral deubiquitinase.

text: Porcine epidemic diarrhea virus (PEDV) is the cause of an economically important swine disease. Previous studies suggested that PEDV does not elicit a robust IFN response, but the mechanism(s) used to evade or block this innate immune response was not known. In this study, we found that PEDV infection blocked synthetic dsRNA-induced IFN-β production by interfering with the activation of interferon regulatory factor 3 (IRF3). We identified PEDV replicase encoded papain-like protease 2 (PLP2) as an IFN antagonist that depends on catalytic activity for its function. We show that levels of ubiquitinated proteins are reduced during PEDV infection and that PEDV PLP2 has deubiquitinase (DUB) activity that recognizes and processes both K-48 and K-63 linked polyubiquitin chains. Furthermore, we found that PEDV PLP2 strongly inhibits RIG-I- and STING-activated IFN expression and that PEDV PLP2 can be co-immunoprecipitated with and deubiquitinates RIG-I and STING, the key components of the signalling pathway for IFN expression. These results show that PEDV infection suppresses production of IFN-β and provides evidence indicating that the PEDV papain-like protease 2 acts as a viral DUB to interfere with the RIG-I- and STING-mediated signalling pathway.


title: The cytolytic molecules Fas ligand and TRAIL are required for murine thymic graft-versus-host disease.

text: Thymic graft-versus-host disease (tGVHD) can contribute to profound T cell deficiency and repertoire restriction after allogeneic BM transplantation (allo-BMT). However, the cellular mechanisms of tGVHD and interactions between donor alloreactive T cells and thymic tissues remain poorly defined. Using clinically relevant murine allo-BMT models, we show here that even minimal numbers of donor alloreactive T cells, which caused mild nonlethal systemic graft-versus-host disease, were sufficient to damage the thymus, delay T lineage reconstitution, and compromise donor peripheral T cell function. Furthermore, to mediate tGVHD, donor alloreactive T cells required trafficking molecules, including CCR9, L selectin, P selectin glycoprotein ligand-1, the integrin subunits alphaE and beta7, CCR2, and CXCR3, and costimulatory/inhibitory molecules, including Ox40 and carcinoembryonic antigen-associated cell adhesion molecule 1. We found that radiation in BMT conditioning regimens upregulated expression of the death receptors Fas and death receptor 5 (DR5) on thymic stromal cells (especially epithelium), while decreasing expression of the antiapoptotic regulator cellular caspase-8-like inhibitory protein. Donor alloreactive T cells used the cognate proteins FasL and TNF-related apoptosis-inducing ligand (TRAIL) (but not TNF or perforin) to mediate tGVHD, thereby damaging thymic stromal cells, cytoarchitecture, and function. Strategies that interfere with Fas/FasL and TRAIL/DR5 interactions may therefore represent a means to attenuate tGVHD and improve T cell reconstitution in allo-BMT recipients.


title: The Ribavirin Pregnancy Registry: Findings after 5 years of enrollment, 2003-2009.

text: INTRODUCTION Ribavirin, with interferons or pegylated interferons, is used to treat chronic hepatitis C. Ribavirin is contraindicated in pregnancy (FDA Pregnancy Category X) and in men whose partners may become pregnant. In 2003, the Ribavirin Pregnancy Registry was established to monitor pregnancy exposures to ribavirin and to evaluate the potential human teratogenicity of prenatal exposure. METHODS This voluntary registry enrolls pregnant women who have been exposed to ribavirin during pregnancy or during the six months prior to conception either directly, by taking ribavirin, or indirectly through sexual contact with a man taking ribavirin. Women are followed until delivery; live born infants are followed for one year. The Registry aims to enroll 131 live births following direct (maternal) exposure to ribavirin and 131 live births following indirect (male) exposures. RESULTS After more than five years of operation, the Registry has enrolled 49 live births with direct exposure and 69 live births following indirect exposure. Six outcomes with birth defects have been reported. All were among live born infants: torticollis (2), hypospadias (1), polydactyly and a neonatal tooth (1), glucose-6-phosphate dehydrogenase deficiency (1), ventricular septal defect and cyst of 4th ventricle of the brain (1). Three received direct exposures ([6.1% (95% CI: 1.2, 16.9)], three were exposed indirectly [4.3% (95% CI: 0.9, 12.2)]. CONCLUSIONS Although current enrollment is far short of the required sample size, preliminary findings have not detected a signal indicating human teratogenicity for ribavirin. However, findings must be interpreted with caution concerning direct or indirect prenatal ribavirin exposures.


title: A high normal ankle-brachial index is associated with biopsy-proven severe renal small artery intimal thickening and impaired renal function in chronic kidney disease.

text: A significant relationship has been established between central hemodynamics and renal microvascular damage. We hypothesized that the increase in the ankle-brachial index (ABI) with age is due to increased arterial stiffness and wave reflection and is thus associated with the pathogenesis of the renal small artery in patients with chronic kidney disease (CKD). We recruited 122 patients with CKD (stages 1-5) who underwent renal biopsy and ABI measurements between 2010 and 2013. Renal small artery intimal thickening (SA-IT) severity was assessed by semiquantitative grading. The median age was 47 years, with a range of 15-86 years (47% women). The median estimated glomerular filtration rate (eGFR) was 62 mL/min/1.73 m2. Compared with patients with the lowest 1-3 SA-IT index quartile, those with the highest quartile of the SA-IT index were older in age had higher mean arterial pressure, ABI, brachial-ankle pulse wave velocity, and lower eGFR. ABI was positively associated with SA-IT severity and inversely associated with eGFR. Multivariate logistic regression analyses showed that ABI was significantly associated with the highest quartile of the SA-IT index (odds ratio per SD increase in ABI, 1.83; 95% confidence interval, 1.08-3.26) and low eGFR (<60 mL/min/1.73 m2) (odds ratio per SD increase in ABI, 1.74; 95% confidence interval, 1.03-3.03). In conclusion, a high normal ABI was associated with severe renal small artery intimal thickening and low eGFR in patients with CKD.


title: Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment.

text: The high mortality associated with the novel Middle East respiratory syndrome coronavirus (MERS-CoV) has raised questions about the possible role of a cytokine storm in its pathogenesis. Although recent studies showed that MERS-CoV infection is associated with an attenuated IFN response, no induction of inflammatory cytokines was demonstrated during the early phase of infection. To study both early and late cytokine responses associated with MERS-CoV infection, we measured the mRNA levels of eight cytokine genes [TNF-α, IL-1β, IL-6, IL-8, IFN-β, monocyte chemotactic protein-1, transforming growth factor-β and IFN-γ-induced protein (IP)-10] in cell lysates of polarized airway epithelial Calu-3 cells infected with MERS-CoV or severe acute respiratory syndrome (SARS)-CoV up to 30 h post-infection. Among the eight cytokine genes, IL-1β, IL-6 and IL-8 induced by MERS-CoV were markedly higher than those induced by SARS-CoV at 30 h, whilst TNF-α, IFN-β and IP-10 induced by SARS-CoV were markedly higher than those induced by MERS-CoV at 24 and 30 h in infected Calu-3 cells. The activation of IL-8 and attenuated IFN-β response by MERS-CoV were also confirmed by protein measurements in the culture supernatant when compared with SARS-CoV and Sendai virus. To further confirm the attenuated antiviral response, cytokine response was compared with human HCoV-229E in embryonal lung fibroblast HFL cells, which also revealed higher IFN-β and IP-10 levels induced by HCoV-229E than MERS-CoV at 24 and 30 h. Whilst our data supported recent findings that MERS-CoV elicits attenuated innate immunity, this represents the first report to demonstrate delayed proinflammatory cytokine induction by MERS-CoV. Our results provide insights into the pathogenesis and treatment of MERS-CoV infections.


title: CD4 T cells promote CD8 T cell immunity at the priming and effector site during viral encephalitis.

text: CD4 T cell activation during peripheral infections not only is essential in inducing protective CD8 T cell memory but also promotes CD8 T cell function and survival. However, the contributions of CD4 T cell help to antiviral CD8 T cell immunity during central nervous system (CNS) infection are not well established. Encephalitis induced by the sublethal coronavirus JHMV was used to identify when CD4 T cells regulate CD8 T cell responses following CNS infection. Peripheral expansion of virus-specific CD8 T cells was impaired when CD4 T cells were ablated prior to infection but not at 4 days postinfection. Delayed CD4 T cell depletion abrogated CD4 T cell recruitment to the CNS but only slightly diminished CD8 T cell recruitment. Nevertheless, the absence of CNS CD4 T cells was associated with reduced gamma interferon (IFN-γ) and granzyme B expression by infiltrating CD8 T cells, increased CD8 T cell apoptosis, and impaired control of infectious virus. CD4 T cell depletion subsequent to CD4 T cell CNS migration restored CD8 T cell activity and virus control. Analysis of γc-dependent cytokine expression indicated interleukin-21 (IL-21) as a primary candidate optimizing CD8 T cell activity within the CNS. These results demonstrate that CD4 T cells play critical roles in both enhancing peripheral activation of CD8 T cells and prolonging their antiviral function within the CNS. The data highlight the necessity for temporally and spatially distinct CD4 T cell helper functions in sustaining CD8 T cell activity during CNS infection.


title: Successful introduction of laparoendoscopic single-site donor nephrectomy after experience with laparoscopic single-site plus-one trocar donor nephrectomy.

text: PURPOSE To assess the feasibility, safety, and efficacy of the laparoendoscopic single-site (LESS) donor nephrectomy (LESSDN) procedure after experience with the LESS-plus-one-trocar donor nephrectomy (LEPODN) procedure. PATIENTS AND METHODS From 2009 to 2014, 126 left laparoscopic donor nephrectomies (LDNs) were performed, including 59 Standard (Std)-LDN, 30 LEPODN, and 37 LESSDN. In the LEPODN procedure, a 5-mm trocar was added as a right-hand working trocar to the LESSDN procedure. A GelPOINT(®) platform was applied on a pararectal single incision in both LEPODN and LESSDN procedures. After performing the LEPODN procedure several times, each surgeon performed the LESSDN procedure. RESULTS Std-LDN, LEPODN, and LESSDN procedures were performed by 10, 10, and 7 surgeons, respectively. The mean operative time, estimated blood loss, warm ischemia time, time to ambulation, and length of postoperative hospital stay were the shortest for the LESSDN procedure (P<0.012, P=0.007, P<0.001, P=0.027, and P=0.001, respectively). No significant difference in the complication rate, delayed graft function rate, and mean 7-day post-transplant serum creatinine levels was observed among the three procedures. Individual results of the operative time and estimated blood loss for the LESSDN procedure were not significantly inferior to those of Std-LDN and LEPODN procedures for each surgeon. CONCLUSIONS The LESSDN procedure can be introduced safely and effectively without compromising the operative time, complication rate, and graft function after experience with the LEPODN procedure among multiple surgeons. The LEPODN procedure may be an effective bridge from standard multiport LDN to LESSDN.


title: Gastric bypass vs sleeve gastrectomy for type 2 diabetes mellitus: a randomized controlled trial.

text: OBJECTIVES To determine the efficacies of 2 weight-reducing operations on diabetic control and the role of duodenum exclusion. DESIGN Double-blind randomized controlled trial. SETTING Department of Surgery of the Min-Sheng General Hospital, National Taiwan University. PATIENTS We studied 60 moderately obese patients (body mass index >25 and <35) aged >30 to <60 years who had poorly controlled type 2 diabetes mellitus (T2DM) (hemoglobin A(1c) [HbA(1c)] >7.5%) after conventional treatment (>6 months) from September 1, 2007, through June 30, 2008. Patients and observers were masked during the follow-up, which ended in 2009, 1 year after final enrollment. INTERVENTIONS Gastric bypass with duodenum exclusion (n = 30) vs sleeve gastrectomy without duodenum exclusion (n = 30). MAIN OUTCOME MEASURES The primary outcome was remission of T2DM (fasting glucose <126 mg/dL and HbA(1c) <6.5% without glycemic therapy). Secondary measures included weight and metabolic syndrome. Analysis was by intention to treat. RESULTS Of the 60 patients enrolled, all completed the 12-month follow-up. Remission of T2DM was achieved by 28 (93%) in the gastric bypass group and 14 (47%) in the sleeve gastrectomy group (P = .02). Participants assigned to gastric bypass had lost more weight, achieved a lower waist circumference, and had lower glucose, HbA(1c), and blood lipid levels than the sleeve gastrectomy group. No serious complications occurred in either group. CONCLUSIONS Participants randomized to gastric bypass were more likely to achieve remission of T2DM. Duodenum exclusion plays a role in T2DM treatment and should be assessed. Trial Registration clinicaltrials.gov Identifier: NCT00540462 (http://www.clinicaltrials.gov).


title: Effect of individualized PEEP titration guided by intratidal compliance profile analysis on regional ventilation assessed by electrical impedance tomography - a randomized controlled trial.

text: BACKGROUND The application of positive end-expiratory pressure (PEEP) may reduce dynamic strain during mechanical ventilation. Although numerous approaches for PEEP titration have been proposed, there is no accepted strategy for titrating optimal PEEP. By analyzing intratidal compliance profiles, PEEP may be individually titrated for patients. METHODS After obtaining informed consent, 60 consecutive patients undergoing general anesthesia were randomly allocated to mechanical ventilation with PEEP 5 cmH2O (control group) or PEEP individually titrated, guided by an analysis of the intratidal compliance profile (intervention group). The primary endpoint was the frequency of each nonlinear intratidal compliance (CRS) profile of the respiratory system (horizontal, increasing, decreasing, and mixed). The secondary endpoints measured were respiratory mechanics, hemodynamic variables, and regional ventilation, which was assessed via electrical impedance tomography. RESULTS The frequencies of the CRS profiles were comparable between the groups. Besides PEEP [control: 5.0 (0.0), intervention: 5.8 (1.1) cmH2O, p < 0.001], the respiratory and hemodynamic variables were comparable between the two groups. The compliance profile analysis showed no significant differences between the two groups. The loss of ventral and dorsal regional ventilation was higher in the control [ventral: 41.0 (16.3)%; dorsal: 25.9 (13.8)%] than in the intervention group [ventral: 29.3 (17.6)%; dorsal: 16.4 (12.7)%; p (ventral) = 0.039, p (dorsal) = 0.028]. CONCLUSIONS Unfavorable compliance profiles indicating tidal derecruitment were found less often than in earlier studies. Individualized PEEP titration resulted in slightly higher PEEP. A slight global increase in aeration associated with this was indicated by regional gain and loss analysis. Differences in dorsal to ventral ventilation distribution were not found. TRIAL REGISTRATION This clinical trial was registered at the German Register for Clinical Trials (DRKS00008924) on August 10, 2015.


title: Current strategies and future perspectives for intraperitoneal adhesion prevention.

text: INTRODUCTION The formation of peritoneal adhesions still is a relevant clinical problem after abdominal surgery. Until today, the most important clinical strategies for adhesion prevention are accurate surgical technique and the physical separation of traumatized serosal areas. Despite a variety of barriers which are available in clinical use, the optimal material has not yet been found. DISCUSSION Mesothelial cells play a crucial physiological role in friction less gliding of the serosa and the maintenance of anantiadhesive surface. The formation of postoperative adhesions results from a cascade of events and is regulated by various cellular and humoral factors. Therefore, optimization or functionalization of barrier materials by developments interacting with this cascade on a structural or pharmacological level could give an innovative input for future strategies in peritoneal adhesion prevention. For this purpose, the proper understanding of the formal pathogenesis of adhesion formation is essential. Based on the physiology of the serosa and the pathophysiology of adhesion formation, the available barriers in current clinical practice as well as new innovations are discussed in the present review.


title: Cardiopulmonary resuscitation in COVID-19 patients.

text: COVID-19 is extremely transmissible. Cardiopulmonary resuscitation (CPR) is associated with multiple aerosol-generating procedures including chest compression, positive pressure ventilation, and airway manipulation. Healthcare providers who perform CPR are at high risk of contracting COVID-19. CPR in patients with suspected or proven COVID-19 must be performed without compromising the safety of healthcare providers. An overview of special considerations.


title: Improved health and survival of FIV-infected cats is associated with the presence of autoantibodies to the primary receptor, CD134.

text: We analyzed antibody responses in sera from feline immunodeficiency virus (FIV)-infected and uninfected cats. A strong antiviral response to the viral surface glycoprotein (SU) was noted in both natural and experimental infections. In addition, 143 of 226 FIV-infected animals (63%) also expressed antibodies to the primary binding receptor, CD134, whereas cats infected with other feline RNA viruses, including calicivirus, coronavirus, herpesvirus, and feline leukemia virus, did not. Both affinity-purified anti-CD134 and anti-SU antibodies blocked FIV infection ex vivo. FACS analyses revealed that the anti-CD134 antibodies bound to a cryptic epitope on the receptor that was only exposed when SU bound to CD134. Anti-CD134 binding caused displacement of SU from the surface of the cell and inhibition of infection. The presence of antibodies to CD134 correlated with lower virus loads and a better overall health status in FIV(+) cats, whereas anti-SU antibodies were present independent of health status. The findings are consistent with a role for antireceptor antibodies in protection from virus spread and disease progression.


A meeting framework for inclusive and sustainable science.


title: Tocilizumab for treatment of mechanically ventilated patients with COVID-19.

text: BACKGROUND Severe COVID-19 can manifest in rapid decompensation and respiratory failure with elevated inflammatory markers, consistent with cytokine release syndrome for which IL-6 blockade is approved treatment. METHODS We assessed effectiveness and safety of IL-6 blockade with tocilizumab in a single-center cohort of patients with COVID-19 requiring mechanical ventilation. The primary endpoint was survival probability post-intubation; secondary analyses included an ordinal illness severity scale integrating superinfections. Outcomes in patients who received tocilizumab compared to tocilizumab-untreated controls were evaluated using multivariable Cox regression with propensity score inverse probability weighting (IPTW). RESULTS 154 patients were included, of whom 78 received tocilizumab and 76 did not. Median follow-up was 47 days (range 28-67). Baseline characteristics were similar between groups, although tocilizumab-treated patients were younger (mean 55 vs. 60 years), less likely to have chronic pulmonary disease (10% vs. 28%), and had lower D-dimer values at time of intubation (median 2.4 vs. 6.5 mg/dL). In IPTW-adjusted models, tocilizumab was associated with a 45% reduction in hazard of death [hazard ratio 0.55 (95% CI 0.33, 0.90)] and improved status on the ordinal outcome scale [odds ratio per 1-level increase: 0.58 (0.36, 0.94)]. Though tocilizumab was associated with an increased proportion of patients with superinfections (54% vs. 26%; p<0.001), there was no difference in 28-day case fatality rate among tocilizumab-treated patients with versus without superinfection [22% vs. 15%; p=0.42]. Staphylococcus aureus accounted for ~50% of bacterial pneumonia. CONCLUSIONS In this cohort of mechanically ventilated COVID-19 patients, tocilizumab was associated with lower mortality despite higher superinfection occurrence.


title: Evidence and evidence gaps in the treatment of Eustachian tube dysfunction and otitis media.

text: Evidence-based medicine is an approach to medical treatment intended to optimize patient-oriented decision-making on the basis of empirically proven effectiveness. For this purpose, a classification system has been established to categorize studies - and hence therapy options - in respect of associated evidence according to defined criteria. The Eustachian tube connects the nasopharynx with the middle ear cavity. Its key function is to ensure middle ear ventilation. Compromised ventilation results in inflammatory middle ear disorders. Numerous evidence-based therapy options are available for the treatment of impaired middle ear ventilation and otitis media, the main therapeutic approach being antibiotic treatment. More recent procedures such as balloon dilation of the Eustachian tube have also shown initial success but must undergo further evaluation with regard to evidence. There is, as yet, no evidence for some of the other long-established procedures. Owing to the multitude of variables, the classification of evidence levels for various treatment approaches calls for highly diversified assessment. Numerous evidence-based studies are therefore necessary in order to evaluate the evidence pertaining to existing and future therapy solutions for impaired middle ear ventilation and otitis media. If this need is addressed, a wealth of implications can be expected for therapeutic approaches in the years to come.


title: Endovascular stent-based revascularization of malignant superior vena cava syndrome with concomitant implantation of a port device using a dual venous approach.

text: PURPOSE The aim of this paper is to evaluate the safety and efficacy of endovascular revascularization of malignant superior vena cava syndrome (SVCS) and simultaneous implantation of a totally implantable venous access port (TIVAP) using a dual venous approach. MATERIALS AND METHODS Retrospectively, 31 patients (mean age 67 ± 8 years) with malignant CVO who had undergone revascularization by implantation of a self-expanding stent into the superior vena cava (SVC) (Sinus XL®, OptiMed, Germany; n = 11 [Group1] and Protégé ™ EverFlex, Covidien, Ireland; n = 20 [Group 2]) via a transfemoral access were identified. Simultaneously, percutaneous access via a subclavian vein was used to (a) probe the lesion from above, (b) facilitate a through-and-through maneuver, and (c) implant a TIVAP. Primary endpoints with regard to the SVC syndrome were technical (residual stenosis < 30%) and clinical (relief of symptoms) success; with regard to TIVAP implantation technical success was defined as positioning of the functional catheter within the SVC. Secondary endpoints were complications as well as stent and TIVAP patency. RESULTS Technical and clinical success rate were 100% for revascularization of the SVS and 100% for implantation of the TIVAP. One access site hematoma (minor complication, day 2) and one port-catheter-associated sepsis (major complication, day 18) were identified. Mean catheter days were 313 ± 370 days. Mean imaging follow-up was 184 ± 172 days. Estimated patency rates at 3, 6, and 12 months were 100% in Group 1 and 84, 84, and 56% in Group 2 (p = 0.338). CONCLUSION Stent-based revascularization of malignant SVCS with concomitant implantation of a port device using a dual venous approach appears to be safe and effective.