title: Protective and pathologic roles of the immune response to mouse hepatitis virus type 1: implications for severe acute respiratory syndrome.

text: Intranasal mouse hepatitis virus type 1 (MHV-1) infection of mice induces lung pathology similar to that observed in severe acute respiratory syndrome (SARS) patients. However, the severity of MHV-1-induced pulmonary disease varies among mouse strains, and it has been suggested that differences in the host immune response might account for this variation. It has also been suggested that immunopathology may represent an important clinical feature of SARS. Little is known about the host immune response to MHV-1 and how it might contribute to some of the pathological changes detected in infected mice. In this study we show that an intact type I interferon system and the adaptive immune responses are required for controlling MHV-1 replication and preventing morbidity and mortality in resistant C57BL/6J mice after infection. The NK cell response also helps minimize the severity of illness following MHV-1 infection of C57BL/6J mice. In A/J and C3H/HeJ mice, which are highly susceptible to MHV-1-induced disease, we demonstrate that both CD4 and CD8 T cells contribute to morbidity during primary infection, and memory responses can enhance morbidity and mortality during subsequent reexposure to MHV-1. However, morbidity in A/J and C3H/HeJ mice can be minimized by treating them with immune serum prior to MHV-1 infection. Overall, our findings highlight the role of the host immune response in contributing to the pathogenesis of coronavirus-induced respiratory disease.


title: Presence of non-hypervascular hypointense nodules on Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid-enhanced magnetic resonance imaging in patients with hepatocellular carcinoma.

text: BACKGROUND AND AIMS Gadolinium-ethoxybenzyl-diethylenetriamine pentaacetic acid (Gd-EOB-DTPA)-enhanced magnetic resonance imaging (MRI) performed before curative therapy for hepatocellular carcinoma (HCC) can distinguish between intrahepatic distant recurrence and hypervascularization. This study aimed to retrospectively evaluate the presence of non-hypervascular hypointense nodules on hepatobiliary phase images from Gd-EOB-DTPA-enhanced MRI as a risk factor of the intrahepatic distant recurrence of early stage HCC following radiofrequency ablation (RFA). METHODS A total of 132 patients who underwent preprocedural Gd-EOB-DTPA-enhanced MRI followed by initial RFA were retrospectively analyzed. Post-RFA intrahepatic distant recurrence, which excluded the hypervascularization of non-hypervascular hypointense nodules detected by preprocedural Gd-EOB-DTPA-enhanced MRI, was evaluated according to the presence of non-hypervascular hypointense nodules on preprocedural Gd-EOB-DTPA-enhanced MRI. RESULTS Intrahepatic distant recurrence rates following RFA were higher in patients with non-hypervascular hypointense nodules (1-year: 22.5%, 2-year: 52.1%, 5-year: 89.1%) compared with in patients without non-hypervascular hypointense nodules (1-year: 7.0%, 2-year: 28.8%, 5-year: 48.7%). The presence of non-hypervascular hypointense nodules was associated with markedly increased cumulative recurrence rates of both identical and different subsegment intrahepatic distant recurrence, being an independent risk factor for post-RFA identical and different subsegment intrahepatic distant recurrence (identical: HR = 2.365, P = 0.027; different: HR = 3.276, P < 0.001). CONCLUSION The presence of non-hypervascular hypointense nodules on hepatobiliary phase images from Gd-EOB-DTPA-enhanced MRI obtained prior to RFA is an important predictive factor of intrahepatic distant recurrence following RFA of HCC.


title: Glyco-analytical multispecific proteolysis (Glyco-AMP): a simple method for detailed and quantitative Glycoproteomic characterization.

text: Despite recent advances, site-specific profiling of protein glycosylation remains a significant analytical challenge for conventional proteomic methodology. To alleviate the issue, we propose glyco-analytical multispecific proteolysis (Glyco-AMP) as a strategy for glycoproteomic characterization. Glyco-AMP consists of rapid, in-solution digestion of an analyte glycoprotein (or glycoprotein mixture) by a multispecific protease (or protease cocktail). Resulting glycopeptides are chromatographically separated by isomer-specific porous graphitized carbon nano-LC, quantified by high-resolution MS, and structurally elucidated by MS/MS. To demonstrate the consistency and customizability of Glyco-AMP methodology, the glyco-analytical performances of multispecific proteases subtilisin, pronase, and proteinase K were characterized in terms of quantitative accuracy, sensitivity, and digestion kinetics. Glyco-AMP was shown be effective on glycoprotein mixtures as well as glycoproteins with multiple glycosylation sites, providing detailed, quantitative, site- and structure-specific information about protein glycosylation.


title: Predictors of adverse outcome in patients hospitalised for exacerbation of chronic obstructive pulmonary disease.

text: BACKGROUND It is crucial to identify risk factors for poor evolution of patients admitted to hospital with chronic obstructive pulmonary disease (COPD) in order to provide adequate intensive therapy and closer follow-up. OBJECTIVES To identify predictors of adverse outcomes in patients hospitalised for exacerbation of COPD. METHODS A prospective, observational study was conducted in patients admitted for exacerbation of COPD. Demographic and clinical parameters were evaluated, including different multidimensional prognostic scores. Adverse outcomes included the following: death during hospitalisation or 1-month follow-up, intensive care unit admission, invasive or non-invasive mechanical ventilation, prolonged hospitalisation (>11 days) and COPD-related emergency visit or readmission within 1 month after discharge. Univariate and multivariate analysis were performed. RESULTS Of 155 patients included, an adverse outcome occurred in 69 (45%). Patients with an adverse outcome had lower forced expiratory volume in 1 s (p = 0.004) and more frequent exacerbations (p = 0.011), more frequently used oxygen at home (p = 0.042) and presented with lower pH (p < 0.001), lower ratio of arterial oxygen pressure to the fraction of inspired oxygen (p = 0.006), higher arterial carbon dioxide pressure (p < 0.001) and a worse score on several prognostic indices at admission. Independent predictors of adverse outcome were exacerbation of COPD in the previous year [odds ratio 3.9, 95% confidence interval (CI) 1.6-9.9; p = 0.004], hypercapnia (odds ratio 9.4, 95% CI 3.7-23.6; p < 0.001) and hypoxaemia (odds ratio 4.3, 95% CI 1.5-12.6; p = 0.008). In the presence of all three characteristics, the probability of an adverse outcome was 95%, while hypercapnia was the strongest prognostic factor with a risk of 54%. CONCLUSIONS Patients with previous exacerbation of COPD, hypercapnia and hypoxaemia had the highest risk of an unfavourable evolution. The calculation of prognostic indices did not provide additional discriminative power.


title: Erythropoiesis-stimulating Agents in Critically Ill Trauma Patients: A Systematic Review and Meta-analysis.

text: OBJECTIVE To perform a meta-analysis of all relevant randomized controlled trials assessing the effect of erythropoiesis-stimulating agents (ESAs) in critically ill trauma patients. BACKGROUND ESAs have effects beyond erythropoiesis. The administration of the ESA epoetin alfa to critically ill trauma patients has been associated with a reduction in mortality. METHODS We performed a systematic review and meta-analysis with trial sequential analysis. We searched Medline, Medline in Process, and other nonindexed citations, EMBASE, and the Cochrane Database from inception until September 9, 2015, for randomized controlled trials comparing ESAs to placebo (or no ESA). RESULTS We identified 9 eligible studies that randomly assigned 2607 critically ill patients after trauma to an ESA or placebo (or no ESA). Compared with placebo (or no ESA), ESA therapy was associated with a substantial reduction in mortality [risk ratio (RR) 0.63, 95% confidence interval (CI) 0.49-0.79, P = 0.0001, I = 0%). In patients with traumatic brain injury, ESA therapy did not increase the number of patients surviving with moderate disability or good recovery (RR 1.00, 95% CI 0.88-1.15, P = 0.95, I = 0%). With the dosing regimens employed in the included studies, ESA therapy did not increase the risk of lower limb proximal deep venous thrombosis (RR 0.97, 95% CI 0.72-1.29, P = 0.78, I = 0%). CONCLUSIONS The administration of ESAs to critically ill trauma patients is associated with a significant improvement in mortality without an increase in the rate of lower limb proximal deep venous thrombosis. Given the worldwide public health significance of these findings research to validate or refute them is required.


Are Flow Diverting Stents a Treatment Option in Acutely Ruptured Complex A1-A2 Junction Aneurysms?


title: Clinical performance of a rapid influenza test and comparison of nasal versus throat swabs to detect 2009 pandemic influenza A (H1N1) infection in Thai children.

text: We identified febrile pediatric outpatients seeking care for influenza like illness in Bangkok. Two nasal and 1 throat swab were tested using the QuickVue A+B rapid influenza kit and reverse transcription-polymerase chain reaction. Among 142 pandemic influenza A (H1N1)-positive patients, the QuickVue test identified 89 positive tests for a sensitivity of 62.7% (95% confidence interval [CI]: 54.7-70.6). Specificity was 99.2% (95% CI: 98-100). In the 0 to 2 years age group, sensitivity was 76.7% (95% CI: 61.5-91.8). Throat and nasal swabs are equally useful diagnostic specimens for reverse transcription-polymerase chain reaction diagnosis.


title: Risk factors for fecal carriage of drug-resistant Escherichia coli: a systematic review and meta-analysis.

text: BACKGROUND Antimicrobial resistance is a serious public health problem. Fecal carriage of drug-resistant bacteria has been suggested as an important source of antimicrobial resistant genes (ARGs). We aimed to identify risk factors associated with fecal carriage of drug-resistant commensal Escherichia coli among healthy adult population. METHODS We conducted a systematic review and meta-analysis following the PRISMA guideline. We identified observational studies published from 2014 to 2019 through PubMed, Embase, and Web of Science. Studies were eligible if they investigated and reported risk factors and accompanying measure of associations for fecal carriage of drug-resistant E. coli for healthy population aged 18-65. Data on risk factors assessed in three or more studies were extracted. RESULTS Fifteen of 395 studies involving 11480 healthy individuals were included. The pooled prevalence of drug-resistant Enterobacteriaceae was 14% (95% confidence interval [CI] 8-23%). Antimicrobial use within the 12 months prior to stool culture (odds ratio [OR] 1.84 [95%CI 1.35-2.51]), diarrhea symptoms (OR 1.56 [95%CI 1.09-2.25]), travel to India (OR 4.15 [95%CI 2.54-6.78]), and vegetarian diet (OR 1.60 [95%CI 1.00(1.0043)-2.56(2.5587)]) were associated with increased risk of fecal carriage of drug-resistant E. coli. Among travellers, antimicrobial use (OR 2.81 [95%CI 1.47-5.36]), diarrhea symptoms (OR 1.65 [95%CI 1.02-2.68]), travel to India (OR 3.80 [95%CI 2.23-6.47]), and vegetarian diet (OR 1.92 [95%CI 1.13-3.26]) were associated with increased risk. Among general adult population, antimicrobial use (OR 1.51 [95%CI 1.17-1.94]), diarrhea symptoms (OR 1.53 [95%CI 1.27-1.84]), and travel to Southeast Asia (OR 1.67 [95%CI 1.02-2.73]) were associated with the increased risk of drug-resistant E. coli carriage. CONCLUSIONS The findings indicate that dietary habit as well as past antimicrobial use and travel to high-risk country are associated with the risk of fecal carriage of drug-resistant commensal E. coli.


Bariatric Surgery vs Lifestyle Intervention for Type 2 Diabetes Mellitus.


title: Melatonin-triggered post-transcriptional and post-translational modifications of ADAMTS1 coordinately retard tumorigenesis and metastasis of renal cell carcinoma.

text: A disintegrin and metalloprotease with thrombospondin motifs (ADAMTS) family are widely implicated in tissue remodeling events manifested in cancer development. ADAMTS1, the most fully characterized ADAMTS, plays conflicting roles in different cancer types; however, the role of ADAMTS1 in renal cell carcinoma (RCC) remains unclear. Herein, we found that ADAMTS1 is highly expressed in RCC tissues compared to normal renal tissues, and its expression was correlated with an advanced stage and a poor prognosis of RCC patients. In vitro, we observed higher expression of ADAMTS1 in metastatic (m)RCC cells compared to primary cells, and manipulation of ADAMTS1 expression affected cell invasion and clonogenicity. Results from protease array showed that ADAMTS1 is modulated by melatonin through mechanisms independent of the MT1 receptor in mRCC cells, and overexpression of ADAMTS1 relieved the invasion/clonogenicity and growth/metastasis inhibition imposed by melatonin treatment in vitro and in an orthotopic xenograft model. The human microRNA (miR) OneArray showed that miR-181d and miR-let-7f were induced by melatonin and respectively targeted the 3'-UTR and non-3'UTR of ADAMTS1 to suppress its expression and mRCC invasive ability. Clinically, RCC patients with high levels of miR-181d or miR-let-7f and a low level of ADAMTS1 had the most favorable prognoses. In addition, ubiquitin/proteasome-mediated degradation of ADAMTS1 can also be triggered by melatonin. Together, our study indicates that ADAMTS1 may be a useful biomarker for predicting RCC progression. The novel convergence between melatonin and ADAMTS1 post-transcriptional and post-translational regulation provides new insights into the role of melatonin-induced molecular regulation in suppressing RCC progression.


title: Combined use of directional atherectomy and drug-coated balloon for the endovascular treatment of common femoral artery disease: immediate and one-year outcomes.

text: AIMS Surgical endarterectomy is the therapy of choice for atherosclerotic common femoral artery (CFA) obstruction. Recently, some large single-centre series have shown encouraging results for the percutaneous treatment of CFA obstructions. The purpose of this study was to evaluate the safety, feasibility, and one-year efficacy of the endovascular treatment of CFA obstructions with combined use of directional atherectomy (DA) and a paclitaxel-coated balloon (DCB). METHODS AND RESULTS Between January 2012 and July 2014, 30 consecutive patients with severely calcified obstructions of the common femoral artery were treated in our centre using DA followed by DCB dilatation. Provisional stenting was allowed in the case of a suboptimal result. Twenty cases (66%) were isolated CFA interventions, whereas five (17%) and five (17%) also involved inflow and outflow vessels, respectively. Chronic total CFA occlusions (CTO) were recanalised in six cases (20%). Procedural success was achieved in all cases; stenting was needed in three cases (10%). At one year, restenosis and target lesion revascularisation were observed in two of 30 (6.6%) and one of 30 (3.3%) patients, respectively. The secondary patency rate was 96.7%. CONCLUSIONS This single-centre prospective study suggests that the combined use of DA and DCB is a safe and effective alternative to surgery, a treatment option for common femoral artery lesions and provides encouraging results in this setting.


title: The polysialic acid-specific O-acetyltransferase OatC from Neisseria meningitidis serogroup C evolved apart from other bacterial sialate O-acetyltransferases.

text: Neisseria meningitidis serogroup C is a major cause of bacterial meningitis and septicaemia. This human pathogen is protected by a capsule composed of alpha2,9-linked polysialic acid that represents an important virulence factor. In the majority of strains, the capsular polysaccharide is modified by O-acetylation at C-7 or C-8 of the sialic acid residues. The gene encoding the capsule modifying O-acetyltransferase is part of the capsule gene complex and shares no sequence similarities with other proteins. Here, we describe the purification and biochemical characterization of recombinant OatC. The enzyme was found as a homodimer, with the first 34 amino acids forming an efficient oligomerization domain that worked even in a different protein context. Using acetyl-CoA as donor substrate, OatC transferred acetyl groups exclusively onto polysialic acid joined by alpha2,9-linkages and did not act on free or CMP-activated sialic acid. Motif scanning revealed a nucleophile elbow motif (GXS286XGG), which is a hallmark of alpha/beta-hydrolase fold enzymes. In a comprehensive site-directed mutagenesis study, we identified a catalytic triad composed of Ser-286, Asp-376, and His-399. Consistent with a double-displacement mechanism common to alpha/beta-hydrolase fold enzymes, a covalent acetylenzyme intermediate was found. Together with secondary structure prediction highlighting an alpha/beta-hydrolase fold topology, our data provide strong evidence that OatC belongs to the alpha/beta-hydrolase fold family. This clearly distinguishes OatC from all other bacterial sialate O-acetyltransferases known so far because these are members of the hexapeptide repeat family, a class of acyltransferases that adopt a left-handed beta-helix fold and assemble into catalytic trimers.


Coronavirus and the race to distribute reliable diagnostics.


The coronavirus pandemic: can we handle such epidemics better?


Covid-19: Mental health services must be boosted to deal with "tsunami" of cases after lockdown.


title: Long-term outcomes after prophylactic use of onlay mesh in midline laparotomy.

text: BACKGROUND The prevalence of incisional hernias (IHs) is still high after midline laparotomy (ML). There is an increasing body of evidence that prophylactic mesh placement (PMP) can be safe and efficient in the short-term outcomes, but there still are some concerns about the potential long-term complications of these meshes. This study describes our long-term PMP experience. METHODS Observational and prospective study including all patients undergoing the use of prophylactic onlay large-pore polypropylene meshes for the closure of ML since 2008 to 2014. Outcome measures included demographics, perioperative details, wound complications, recurrences, reoperations and chronic complications. RESULTS A cohort of 172 patients was analysed: 75% elective surgery, 25% emergency cases. Mean age was 68 years with mean body mass index (BMI) of 28.6 kg/m2. Wound classification: 6.4% clean; 85% clean-contaminated; 1.2% contaminated and 8.1% dirty. Follow-up of patients was up to 8 years (mean: 5 ± 1.6). Two meshes were removed due to chronic infection in first six postoperative months. Of the 13 patients (9.02%) who developed IH, 5 of them have been reoperated for IH repair without any difficulty related to previous mesh. During follow-up, 8 patients have been reoperated for other reasons and the integrity of abdominal wall was also checked. After the comparative study, higher BMI and emergency surgery were still risk factors for IH despite PMP. CONCLUSIONS In our setting, the use of polypropylene prophylactic meshes in MLs is safe, efficient and durable.


title: Anticoagulant treatment is associated with decreased mortality in severe coronavirus disease 2019 patients with coagulopathy.

text: BACKGROUND A relatively high mortality of severe coronavirus disease 2019 (COVID-19) is worrying, the application of heparin in COVID-19 has been recommended by some expert consensus due to the risk of disseminated intravascular coagulation and venous thromboembolism. However, its efficacy remains to be validated. METHODS Coagulation results, medications and outcomes of consecutive patients being classified as severe COVID-19 in Tongji hospital were retrospectively analysed. The 28-day mortality between heparin users and nonusers were compared, also in different risk of coagulopaphy which was stratified by the sepsis-induced coagulopathy (SIC) score or D-dimer result. RESULTS There were 449 patients with severe COVID-19 enrolled into the study, 99 of them received heparin (mainly with low molecular weight heparin, LMWH) for 7 days or longer. The D-dimer, prothrombin time and age were positively, and platelet count was negatively, correlated with 28-day mortality in multivariate analysis. No difference on 28-day mortality was found between heparin users and nonusers (30.3% vs 29.7%, P=0.910). But the 28-day mortality of heparin users were lower than nonusers In patients with SIC score ≥4 (40.0% vs 64.2%, P=0.029), or D-dimer > 6 fold of upper limit of normal (32.8% vs 52.4%, P=0.017). CONCLUSIONS Anticoagulant therapy mainly with LMWH appears to be associated with better prognosis in severe COVID-19 patients meeting SIC criteria or with markedly elevated D-dimer.


Prevalent low-grade dysplasia: the strongest predictor of malignant progression in Barrett's columnar-lined oesophagus.


title: Transanal endoscopic microsurgery for giant circumferential rectal adenomas.

text: AIM Transanal endoscopic microsurgery (TEM) was originally invented by Buess et al. (Chirurg, 1984, 55, 677-80) for the treatment of infraperitoneal rectal adenomas. Its indications have progressively expanded to include larger and more advanced lesions. The aim of the study was to report the results of TEM used for the treatment of circumferential rectal lesions. METHOD We retrospectively reviewed the medical records of 17 consecutive patients [median age 69 (32-89) years; nine men] who underwent TEM for a circumferential rectal lesion in our department between September 2010 and January 2015. RESULTS The median distance from the anal verge was 4 (3-11) cm, the median longitudinal extent was 7 (3-10) cm and the median surface area was 75 (40-255) cm(2) . An end-to-end anastomosis without proximal bowel mobilization was completed endoscopically in all cases. The median operating time was 120 (40-240) min. Persistent, endoscopically uncontrollable endoluminal bleeding in one patient was successfully treated with a second TEM procedure. One patient underwent preoperative radiotherapy for adenocarcinoma detected at the preoperative assessment. Surgical histology showed a pT3 cancer in one patient who refused further surgery, a pT2 cancer in two who subsequently underwent abdominoperineal resection, a pT1 cancer in four and a ypT0 in one patient. All are at present free of disease. No patients developed faecal incontinence or urinary or sexual dysfunction. Four patients required endoscopic balloon dilatation for stenosis. CONCLUSION Transanal endoscopic microsurgery is a feasible and safe technique for large circumferential lesions with a satisfactory outcome. Preoperative staging may be inaccurate.


title: A recombinant rabies vaccine expressing the trimeric form of the glycoprotein confers enhanced immunogenicity and protection in outbred mice.

text: Rabies is a disease characterized by an invariably lethal encephalitis of viral origin that can be controlled by preventive vaccination programs of wildlife, domestic animals and humans in areas with a high risk of exposure. Currently available vaccines are expensive, cumbersome to produce and require intensive immunization and booster schemes to induce and maintain protective immunity. In the present study, we describe the development of candidate recombinant subunit rabies vaccines based on the glycoprotein G of the prototype rabies virus (RABV-G) expressed either as a monomer (RABV-mG) or in its native trimeric configuration (RABV-tG), with or without Matrix-M™ adjuvant. Immunogenicity and protective efficacy of the respective candidate vaccines were tested in outbred NIH Swiss albino mice. The RABV-tG candidate vaccine proved to be superior to the RABV-mG vaccine candidate both in terms of immunogenicity and efficacy. The relatively poor immunogenicity of the RABV-mG vaccine candidate was greatly improved by the addition of the adjuvant. A single, low dose of RABV-tG in combination with Matrix-M™ induced high levels of high avidity neutralizing antibodies and protected all mice against challenge with a lethal dose of RABV. Consequently RABV-tG used in combination with Matrix-M™ is a promising vaccine candidate that overcomes the limitations of currently used vaccines.


title: Coil-Protected Technique for Liquid Embolization in Neurovascular Malformations.

text: OBJECTIVE To evaluate the safety and efficacy of the coil-protected technique for liquid embolization in neurovascular malformations. MATERIALS AND METHODS Twenty-two patients who underwent coil-protected liquid embolization for symptomatic cranial (n = 13) and spinal (n = 9) arteriovenous fistula (AVF) or arteriovenous malformations (AVMs) were identified. A total of 36 target feeder vessels were embolized with N-butyl cyanoacrylate and/or Onyx (Medtronic). This technique was used to promote delivery of a sufficient amount of liquid embolic agent into the target shunt or nidus in cases where tortuous feeding arteries preclude a microcatheter wedging techniqu and/or to prevent reflux of the liquid embolic agent in cases with a short safety margin. The procedure was considered technically successful if the target lesion was sufficiently filled with liquid embolic agent without unintentional reflux. Angiographic and clinical outcomes were retrospectively evaluated. RESULTS Technical success was achieved for all 36 target feeders. Post-embolization angiographies revealed complete occlusion in 16 patients and near-complete and partial occlusion in three patients each. There were no treatment-related complications. Of the six patients who showed near-complete or partial occlusion, five received additional treatments: two received stereotactic radiosurgery for cerebral AVM, two underwent surgical removal of cerebral AVM, and one underwent additional embolization by direct puncture for a mandibular AVM. Finally, all patients showed complete (n = 19) or near-complete (n = 3) occlusion of the target AVF or AVM on follow-up angiographies. The presenting neurological symptoms improved completely in 15 patients (68.2%) and partially in seven patients (31.8%). CONCLUSION The coil-protected technique is a safe and effective method for liquid embolization, especially in patients with various neurovascular shunts or malformations who could not be successfully treated with conventional techniques.


title: Tissue healing during degradation of a long-lasting bioresorbable gamma-ray-sterilised poly(lactic acid) mesh in the rat: a 12-month study.

text: AIM The purpose was to evaluate soft-tissue healing after poly(lactic acid) (PLA(94)) mesh implantation in a rat model. METHODS Full-thickness abdominal wall defects were created in 108 Wistar rats, and reconstructed with 83 PLA(94) and 25 lightweight polypropylene (PPL) meshes. The meshes were previously gamma-ray sterilised with 25, 75 or 125 kGy to accelerate PLA(94) degradation. RESULTS The inflammatory response in PLA(94) was significantly less pronounced and collagen organisation significantly better than in PPL. The higher the level of gamma-radiation, the higher the incidence of abdominal wall herniation (22.2, 31.3 and 52.6% with 25, 75 and 125 kGy, respectively). No herniation occurred in the PPL group. Tensile strength was dramatically reduced after gamma-ray-sterilised PLA(94) mesh implantation. CONCLUSION The gamma-ray-sterilised PLA(94) mesh was poor in preventing abdominal wall hernia recurrences in a rat model.


title: Three trocar laparoscopic Roux-en-y gastric bypass: a novel technique en route to the single-incision laparoscopic approach.

text: BACKGROUND Laparoscopic Roux-en-Y gastric bypass is the gold standard bariatric procedure. Typically, the procedure necessitates five to seven small skin incisions for trocar placement. The senior author (AA Saber) has developed a three-trocar approach for laparoscopic Roux-en-Y gastric bypass. METHODS Sixteen patients underwent triple-incision laparoscopic Roux-en-Y gastric bypass between May 2009 and August 2009. The same surgeon performed all surgical interventions. The umbilicus was the main point of entry for all patients and the same operative technique and perioperative protocol were used in all patients. RESULTS A total of sixteen triple-incision laparoscopic Roux-en-Y gastric bypasses were performed. The procedures were successfully performed in all patients. Mean operating time was 145.4 min. None of the patients required conversion to an open procedure. There were no mortalities or post-operative technical complications noted during the immediate post-operative period. CONCLUSION Three trocar laparoscopic Roux-en-Y gastric bypass is safe, technically feasible and reproducible. This technique may be considered a "precursor" to single-incision laparoscopic Roux-en-Y gastric bypass.


title: COVID-19 and gastroenterology: clinical insights and recommendations for gastroenterology care providers.

text: While the COVID-19 pandemic evolves, we are beginning to understand the role the gastrointestinal tract plays in the disease and the impact of the infection on the care of patients with gastrointestinal (GI) and liver diseases. We review the data and understanding around the virus related to the digestive tract, impact of the pandemic on delivery of GI services and daily gastroenterology clinical practice, and the effects on patients with pre-existing GI diseases.


title: Liver tumor ablation: percutaneous and open approaches.

text: The global incidence of liver cancer is greater than a million cases a year. Surgical resection where applicable is still the standard of care for these patients. Various liver-directed regional therapies have been developed in an effort to treat the vast majority of unresectable liver tumors. This article reviews the principles behind various ablation therapies currently available for malignant liver tumors and their outcomes.


title: Cone-beam computed tomography as an adjunct to performance of percutaneous cementoplasty of the acetabulum.

text: Acetabuloplasty is a valuable palliative adjunct for the treatment of patients with painful metastatic disease to the pelvis in selected cases. We report the case of a 45-year-old woman with morbid obesity and with breast carcinoma who was technically difficult to treat under fluoroscopic guidance due to very poor visualization secondary to her body habitus. It was possible to perform radiofrequency ablation and acetabuloplasty with the use of cone-beam computed tomography for guidance.


title: Treatment of NASH with Gastric Bypass.

text: PURPOSE OF REVIEW Nonalcoholic steatohepatitis (NASH) is a spectrum of nonalcoholic fatty liver disease (NAFLD). It is defined as the presence of fatty liver along with inflammation and hepatocyte injury. To date, weight loss achieved via lifestyle intervention remains the mainstay of NASH treatment. However, given the known benefit of weight loss on NASH and the known effect of bariatric surgery on weight loss, several studies have explored the potential role of bariatric surgery on the treatment of NASH. RECENT FINDINGS This review article summarizes the evidence on the effect of Roux-en-Y gastric bypass (RYGB), a common bariatric surgery, on NASH therapy. Specifically, studies show that RYGB is associated with an improvement of all NASH histologic features at 1 year. Compared to adjustable gastric band, RYGB appears to be superior at treating NASH. Randomized controlled trials and long-term studies are underway to better clarify the role of these procedures specifically for NASH therapy.


title: In vivo white light and contrast-enhanced vital-dye fluorescence imaging of Barrett's-related neoplasia in a single-endoscopic insertion.

text: A modular video endoscope is developed to enable both white light imaging (WLI) and vital-dye fluorescence imaging (VFI) in a single-endoscopic insertion for the early detection of cancer in Barrett’s esophagus (BE). We demonstrate that VFI can be achieved in conjunction with white light endoscopy, where appropriate white balance is used to correct for the presence of the emission filter. In VFI mode, a contrast enhancement feature is implemented in real time to further highlight glandular patterns in BE and related malignancies without introducing artifacts. In a pilot study, we demonstrate accurate correlation of images in two widefield modalities, with representative images showing the disruption and effacement of glandular architecture associated with cancer development in BE. VFI images of these alterations exhibit enhanced contrast when compared to WLI. Results suggest that the usefulness of VFI in the detection of BE-related neoplasia should be further evaluated in future in vivo studies.


Understanding H7N9 avian flu.


title: Endovascular treatment of ruptured paraclinoid aneurysms: results, complications, and follow-up.

text: BACKGROUND AND PURPOSE Paraclinoid aneurysms are an uncommon cause of aneurysmal SAH, and their treatment is challenging. To assess the effectiveness and safety of endovascular treatment of ruptured paraclinoid aneurysms, we performed a retrospective analysis of 33 patients. MATERIALS AND METHODS Clinical and radiologic information on 33 patients undergoing endovascular therapy between 1999 and 2010 was retrospectively reviewed. Angiographic results were evaluated with the modified Raymond grading system, whereas clinical outcomes were evaluated with the mRS scale. RESULTS Seventeen (52%) aneurysms were classified as clinoid segment aneurysms, and 16 (48%), as ophthalmic segment aneurysms. Twenty-six (79%) aneurysms were small, 6 (18%) were large, 1 was (3%) giant, and 39% were wide-neck. Coiling was done with balloon assistance in 36% of cases and stent-assistance in 6%. Technical complications occurred in 1 patient, contributing to death. Early clinical complications causing permanent disability occurred in 3% of cases. One patient (3%) had fatal rebleeding 18 days after treatment. Overall, procedure-related morbidity and mortality were, respectively, 3% and 6%. Complete occlusion of the aneurysm was achieved in 36% of patients after initial treatment and in 65% during follow-up (average, 29.3 months). Seven patients had recurrences requiring retreatment (30%). Clinical outcome (average, 32.9 months) was good in 75% of patients and poor in 25%. No delayed complications related to treatment and/or the aneurysm occurred. CONCLUSIONS Ruptured paraclinoid aneurysms are challenging lesions from an endovascular and surgical point of view. Despite the high rate of recurrences, good clinical results and protection against rebleeding can be achieved with current endovascular techniques.


title: Meta-analysis of bioabsorbable staple line reinforcement and risk of fistula following pancreatic resection.

text: BACKGROUND Stapled pancreatic transection is widely used although pancreatic fistula remains a common post-surgical complication. METHODS We performed a meta-analysis of existing data regarding pancreatic fistula following stapled pancreatic transection, comparing bare metal staples to reinforced staple loads. RESULTS We identified ten manuscripts between 2007 and 2009 reporting outcomes following stapled division of the pancreas (five retrospective reviews, five prospective case series). A total of 483 stapled pancreatic resections are included in this meta-analysis. Of these, 234(48 %) were reinforced (REINF) and 249 (52 %) were bare staples (STPL). Out of 483 cases, there were a total of 100 documented pancreatic leaks (21 %). Sixty-one leaks were reported out of 249 STPL divisions (24 %), while 39 leaks were reported following REINF division (17 %). The overall relative risk of developing a pancreatic fistula following distal pancreatectomy was not significantly different comparing STPL to REINF when all studies were combined (RR 1.00, 95% CI 0.65-1.53). We further evaluated the data stratifying by study design (prospective or retrospective) and found that prospective studies reported a significantly higher risk of pancreatic fistula with STPL compared to REINF technique (RR 14.45, 95 % CI 3.15-66.21). CONCLUSION Reinforced staples may be a preferred method of pancreatic stump closure following distal pancreatectomy.


title: Olfactory Dysfunction: A Highly Prevalent Symptom of COVID-19 With Public Health Significance.

text: OBJECTIVE Coronavirus disease 2019 (COVID-19) is a global pandemic affecting millions of individuals, killing hundreds of thousands. Although typically described with characteristic symptoms of fever, cough, and shortness of breath, greater understanding of COVID-19 has revealed myriad clinical manifestations. Olfactory dysfunction (OD)-hyposmia and anosmia-has recently been recognized as an important symptom of COVID-19 and increasingly gained traction as a public health tool for identifying COVID-19 patients, in particular otherwise asymptomatic carriers who, unawares, may be major drivers of disease spread. The objective of this study is to review the scientific evidence about anosmia in COVID-19. DATA SOURCES PubMed, Google Scholar, and Web of Science. REVIEW METHODS Comprehensive literature search of primary studies pertinent to the objectives of this review using the chosen data sources. CONCLUSIONS Current evidence shows that OD is highly prevalent in COVID-19, with up to 80% of patients reporting subjective OD and objective olfactory testing potentially showing even higher prevalence. OD is frequently accompanied by taste dysfunction. Up to 25% of COVID-19 patients may experience sudden-onset OD as the first symptom. A large proportion of COVID-19 OD cases may resolve over the period of a few weeks. IMPLICATIONS FOR PRACTICE Sudden anosmia should be considered a symptom of COVID-19. Assessing for sudden-onset anosmia may increase sensitivity of COVID-19 screening strategies, in particular for identifying patients at the earliest stages of disease. Since many cases of OD due to COVID-19 may resolve in the short term, conservative management, including observation, is reasonable, while advanced imaging is unnecessary.


title: Antidiabetic efficacy of obesity surgery in Germany: a quality assurance nationwide survey.

text: BACKGROUND Obesity and diabetes usually co-exist. Obesity surgery seems to offer solutions for both. The objective of this study was to show the effect of obesity surgery on the diabetic profile. METHODS Data on obesity surgery in Germany (2005-2011) were collected from the Institute of Quality Assurance at the research university. Follow-up of the diabetic profile at 1, 2, and up to 6 years after surgery was done. RESULTS Among 17,670 patients, 5,506 (31.2%) were diabetics. Follow-up was accomplished in 87.4%, 82.5%, and 68.9% of eligible patients at 1, 2, and up to 6 years, respectively, after surgery. Of the study participants, 38.2% were insulin-treated (IT) patients and 61.8% were noninsulin-treated patients (NIT). Of the patients' procedures, 2878 (52.3%) Roux-en-Y gastric bypasses (RYGB), 1711 (31.1%) sleeve gastrectomies (SG), 679 (12.3%) laparoscopic adjustable gastric bands (LAGB), 165 (3%) biliopancreatic diversions with duodenal switch (BPD/DS), and 68 (1.3%) biliopancreatic diversions (BPD) were performed. Female gender percentage and mean body mass index (BMI) were significantly higher in the RYGB and LAGB groups. Mean age was significantly higher in BPD/DS group. At 1 year, remission/improvement (RI) percentage was 83.5%, 82.5%, 67.8%, 93.4%, and 84.8% after RYGB, SG, LAGB, BPD, and BPD/DS, respectively. At 2 years, RI% was 84.9%, 79.5%, 67.7%, 94.5%, and 90.9% after RYGB, SG, LAGB, BPD, and BPD/DS, respectively. At late follow-up, RI% was 83.2%, 59.5%, 58.9%, 100%, and 86.4% after RYGB, SG, LAGB, BPD, and BPD/DS, respectively. IT patients showed insignificantly higher RI% than NIT patients at all follow-up points. Malabsorptive procedures (RYGB, BPD, and BPD/DS) showed a significantly higher RI% than restrictive procedures (LAGB and SG) at late follow-up. CONCLUSION Obesity surgery has promising antidiabetic efficacy, especially in IT patients. Malabsorptive procedures show higher, gradually descending, but durable antidiabetic efficacy.


title: Performance Assessment of SARS-CoV-2 PCR Assays Developed by WHO Referral Laboratories.

text: A reliable diagnostic assay is crucial to early detect new COVID-19 cases and limit severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) transmission. Since the onset of the COVID-19 pandemic, the World Health Organization has published several diagnostic molecular approaches developed by referral laboratories, including Charité (Germany), HKU (Hong Kong), China CDC (China), US CDC (United States), and Institut Pasteur, Paris (France). We aimed to compare the sensitivity and specificity of these different RT-PCR assays using SARS-CoV-2 cell culture supernatants and clinical respiratory samples. Overall, the different RT-PCR assays performed well for SARS-CoV-2 detection and were all specific except the N Charité (Germany), and N2 US CDC (United States) assays. RdRp Institut Pasteur (IP2, IP4), N China CDC, and N1 US CDC were found to be the most sensitive assays. The data presented herein are of prime importance to facilitate the equipment choice of diagnostic laboratories, as well as for the development of marketed tests.


title: The impact of dual viral infection in infants admitted to a pediatric intensive care unit associated with severe bronchiolitis.

text: INTRODUCTION Bronchiolitis is a major cause of morbidity and mortality in early childhood worldwide. The presence of more than one pathogen may influence the natural history of acute bronchiolitis in infants. OBJECTIVE To investigate the relevance of dual viral infection in infants with severe bronchiolitis hospitalized in a short-term unit compared with those in a pediatric intensive care unit (PICU). STUDY DESIGN One hundred eighty infants <1 year old hospitalized with bronchiolitis in a short-term unit (n = 92) or admitted to the PICU (n = 88) during 2 consecutive winter seasons 2003/2004 and 2004/2005 were evaluated. Molecular biology and standard methods were used to diagnose human respiratory viruses in nasal/throat swabs and nasal aspirates. Clinical data related to host factors and viral prevalence were compared among infants requiring or not PICU support. RESULTS A viral agent was identified in 96.1% of infants with bronchiolitis. Respiratory syncytial virus (70.6% and 73.6%, respectively in the short-term unit and PICU) and rhinovirus (18.5% and 25.3%, respectively in the short-term unit and PICU) were the main detected respiratory viruses in infants hospitalized in both units. No significant difference in viral prevalence was observed between the populations studied. From multivariate analysis, infants with coinfections were 2.7 times (95% CI: 1.2-6.2) more at risk for PICU admission than those with a single infection. Respiratory syncytial virus and rhinovirus were the viruses most frequently identified in mixed infections in infants hospitalized with bronchiolitis. CONCLUSIONS Dual viral infection is a relevant risk factor for the admission of infants with severe bronchiolitis to the PICU.


title: Single-pill amlodipine/atorvastatin helps patients of diverse ethnicity attain recommended goals for blood pressure and lipids (the Gemini-AALA study).

text: The Gemini-AALA (Australia, Asia, Latin America, Africa/Middle East) study evaluated the efficacy and safety of single-pill amlodipine/atorvastatin (Caduet) for the treatment of patients of diverse ethnicity with concomitant hypertension and dyslipidaemia. This was a 14-week, open-label study including patients from 27 countries across the Middle East, Asia-Pacific, Africa and Latin America. Eight dosage strengths of single-pill amlodipine/atorvastatin (5/10, 10/10, 5/20, 10/20, 5/40, 10/40, 5/80 and 10/80 mg) were titrated to improve blood pressure and lipid control. Blood pressure and lipid goals were determined according to the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) and National Cholesterol Education Program Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (NCEP ATP III) guidelines, respectively (blood pressure, <140/90 or <130/80 mm Hg; low-density lipoprotein cholesterol (LDL-C), <4.1 to <2.6 mmol l(-1) (<160 to <100 mgdl(-1))). Overall, 1649 patients received study medication. Most patients (91.4%) had >or=1 cardiovascular risk factor (as defined by NCEP ATP III guidelines) in addition to hypertension/dyslipidaemia, and 61.7% had coronary heart disease/risk equivalent. At baseline, mean blood pressure was 146.6/88.3 mm Hg and LDL-C was 3.4 mmol l(-1) (130.2 mgdl(-1)). At week 14, 55.2% of patients reached both blood pressure and lipid goals, 61.3% reached blood pressure goal and 87.1% reached lipid goal (34.0% were at lipid goal at baseline). Mean blood pressure reduction was 20.2/11.4 mm Hg. For patients who were lipid-lowering drug naive at baseline, mean reduction in LDL-C was 41.0%. Treatment-related adverse events led to the discontinuation of 3.6% of patients. Single-pill amlodipine/atorvastatin therapy was well tolerated and effective for the reduction of blood pressure and lipids to recommended goals in patients from diverse ethnic backgrounds.


title: Comparison of single-incision plus one additional port laparoscopy-assisted anterior resection with conventional laparoscopy-assisted anterior resection for rectal cancer.

text: BACKGROUND Reduced-port laparoscopic surgery is the latest innovation in minimally invasive surgery. We performed single-incision plus one additional port laparoscopy-assisted anterior resection (SILS + 1-AR) starting in August 2010. This study aimed at evaluating the feasibility of SILS + 1-AR and comparing it with that of conventional laparoscopy-assisted anterior resection (C-AR). METHODS Patients with preoperative clinical stage 0 to stage III rectal cancer were included. Demographic, intraoperative, and pathological examination data, as well as short-term outcome data, of 20 patients who underwent SILS + 1-AR were retrospectively compared with that of 20 patients who underwent C-AR. Invasiveness of the two procedures was also evaluated through a vital signs diary and hematological examination on postoperative days (POD) 1, 3, and 7. RESULTS Operating time, mean estimated blood loss, the number of lymph nodes dissected, the number of lymph node metastases, and the mean distal resection margin length were not significantly different. However, postoperative neutrophil counts in the SILS + 1-AR group were lower than those in the C-AR group (P = 0.085). A significant difference in body temperature was observed in the SILS + 1-AR group on POD 1 (P = 0.028). No significant differences were observed in perioperative and overall morbidity between the two groups. Conversion to open surgery was required in 2 (10 %) of the 20 patients in the SILS + 1-AR group. The mean postoperative length of stay and recurrence rates were similar in the two groups. CONCLUSION SILS + 1-AR for rectal cancer is similar to C-AR in safety, feasibility, and provision of oncological radicality.


title: Virus-like particles in vaccine development.

text: Virus-like particles (VLPs) are multiprotein structures that mimic the organization and conformation of authentic native viruses but lack the viral genome, potentially yielding safer and cheaper vaccine candidates. A handful of prophylactic VLP-based vaccines is currently commercialized worldwide: GlaxoSmithKline's Engerix (hepatitis B virus) and Cervarix (human papillomavirus), and Merck and Co., Inc.'s Recombivax HB (hepatitis B virus) and Gardasil (human papillomavirus) are some examples. Other VLP-based vaccine candidates are in clinical trials or undergoing preclinical evaluation, such as, influenza virus, parvovirus, Norwalk and various chimeric VLPs. Many others are still restricted to small-scale fundamental research, despite their success in preclinical tests. This article focuses on the essential role of VLP technology in new-generation vaccines against prevalent and emergent diseases. The implications of large-scale VLP production are discussed in the context of process control, monitorization and optimization. The main up- and down-stream technical challenges are identified and discussed accordingly. Successful VLP-based vaccine blockbusters are briefly presented concomitantly with the latest results from clinical trials and the recent developments in chimeric VLP-based technology for either therapeutic or prophylactic vaccination.


U.S. academic research funding stays healthy despite pandemic.


title: Targets for antiviral therapy of hepatitis C.

text: Presently, interferon- (IFN-) containing treatment regimens are the standard of care for patients with hepatitis C virus (HCV) infections. Although this therapy eliminates the virus in a substantial proportion of patients, it has numerous side effects and contraindications. Recent approval of telaprevir and boceprevir, targeting the protease residing in nonstructural protein 3 (NS3) of the HCV genome, increased therapy success when given in combination with pegylated IFN and ribavirin, but side effects are more frequent and the management of treatment is complex. This situation will change soon with the introduction of new highly potent direct-acting antivirals. They target, in addition to the NS3 protease, NS5A, which is required for RNA replication and virion assembly and the NS5B RNA-dependent RNA polymerase. Moreover, host-cell factors such as cyclophilin A or microRNA-122, essential for HCV replication, have been pursued as therapeutic targets. In this review, the authors briefly summarize the main features of viral and cellular factors involved in HCV replication that are utilized as therapy targets for chronic hepatitis C.


title: Federal actions to support and strengthen local efforts to combat COVID-19: Primary Health Care (PHC) in the driver's seat.

text: The Ministry of Health, through the Primary Health Care Secretariat and in partnership with the Secretariat of Health Surveillance, built and implemented Primary Health Care (PHC) strategies within the scope of support to local managers and in partnership with the National Health Secretaries Council (CONASS) and the National Municipal Health Secretariats Council (CONASEMS) to combat COVID-19. These actions have PHC as the main responsible for several areas and physical, human, and financial resources, as well as allow boosting national progress towards the use of information and communication technologies and new partnerships for conducting research.


title: Collectrin and ACE2 in renal and intestinal amino acid transport.

text: Neutral amino acid transporters of the SLC6 family are expressed at the apical membrane of kidney and/or small intestine, where they (re-)absorb amino acids into the body. In this review we present the results concerning the dependence of their apical expression with their association to partner proteins. We will in particular focus on the situation of B0AT1 and B0AT3, that associate with members of the renin-angiotensin system (RAS), namely Tmem27 and angiotensin-converting enzyme 2 (ACE2), in a tissue specific manner. The role of this association in relation to the formation of a functional unit related to Na+ or amino acid transport will be assessed. We will conclude with some remarks concerning the relevance of this association to Hartnup disorder, where some mutations have been shown to differentially interact with the partner proteins.


Retrieval of a chronically implanted leadless pacemaker within an isolated heart using direct visualization.


Middle East respiratory syndrome coronavirus infection not found in camels in Japan.


How neuroscience labs can limit their environmental impact.


Love in the time of coronavirus.


title: Effect of minimized perfusion circuit on brain injury markers carnosinase and brain-type fatty binding protein in coronary artery bypass grafting patients.

text: A minimized perfusion circuit (MPC) has proven to be superior to the conventional circulatory perfusion bypass (CCPB) as it reduces the blood-material interaction and hemodilution. Until now not much is known about impact these different perfusion systems have on the brain. The objective of this study is to determine carnosinase and brain-type fatty binding protein (BFABP) activity as novel specific biomarkers for ischemic brain tissue damage and how their activity differs during and after MPC and CCPB as well as to compare the inflammatory response of both perfusion systems. In a prospective pilot study, 28 patients undergoing coronary artery bypass grafting were randomly divided into an MPC group (n = 14) and a CCPB group (n = 14). Blood samples were taken before, during, and after operation until the fifth postoperative day. The brain biomarker carnosinase was determined by measuring the rate of histidine production from the substrate homocarnosine, whereas BFABP and interleukin-6 were determined by enzyme-linked immunosorbent assay (ELISA). C-reactive protein (CRP) and endothelin-1 were determined by enzyme immunoassay. The mean serum carnosinase activity was significantly higher in MPC (0.57 ± 0.34 nM histidine/mL/min) as compared with the CCPB group (0.36 ± 0.13 nM histidine/mL/min) at the end of operation (P = 0.02). The BFABP did not show any difference between the two groups in the immediate postoperative period until the second postoperative day. From that time point onward, it showed a steep increase in the CCPB group (581.3 ± 157.11 pg/mL) as compared with the concentrations in the MPC group (384.6 ± 39 pg/mL) (P = 0.04). The inflammation markers interleukin-6 and CRP showed a similar pattern in both groups without significant difference. In contrast, the leukocyte count on operation day and endothelin-1 on the first postoperative day were significantly higher in the CCPB group (P = 0.01, P = 0.03, respectively). MPC showed a significant higher and stable serum carnosinase activity during extracorporeal circulation as compared with the CCPB due to less hemodilution and a better preserved oxygen capacity. As a consequence, the antioxidant stress during MPC is limited as compared with CCPB, which means less brain tissue damage reflected by a lower BFABP release. Except endothelin-1 and leukocyte count, the inflammatory response of the MPC and CCPB was equal.


docid: vdsrdxrn

title: Rapid expansion of CD8+ T cells in wild-type and type I interferon receptor-deficient mice correlates with protection after low-dose emergency immunization with modified vaccinia virus Ankara.

text: UNLABELLED Immunization with modified vaccinia virus Ankara (MVA) can rapidly protect mice against lethal ectromelia virus (ECTV) infection, serving as an experimental model for severe systemic infections. Importantly, this early protective capacity of MVA vaccination completely depends on virus-specific cytotoxic CD8(+) T cell responses. We used MVA vaccination in the mousepox challenge model using ECTV infection to investigate the previously unknown factors required to elicit rapid protective T cell immunity in normal C57BL/6 mice and in mice lacking the interferon alpha/beta receptor (IFNAR(-/-)). We found a minimal dose of 10(5) PFU of MVA vaccine fully sufficient to allow robust protection against lethal mousepox, as assessed by the absence of disease symptoms and failure to detect ECTV in organs from vaccinated animals. Moreover, MVA immunization at low dosage also protected IFNAR(-/-) mice, indicating efficient activation of cellular immunity even in the absence of type I interferon signaling. When monitoring for virus-specific CD8(+) T cell responses in mice vaccinated with the minimal protective dose of MVA, we found significantly enhanced levels of antigen-specific T cells in animals that were MVA vaccinated and ECTV challenged compared to mice that were only vaccinated. The initial priming of naive CD8(+) T cells by MVA immunization appears to be highly efficient and, even at low doses, mediates a rapid in vivo burst of pathogen-specific T cells upon challenge. Our findings define striking requirements for protective emergency immunization against severe systemic infections with orthopoxviruses. IMPORTANCE We demonstrate that single-shot low-dose immunizations with vaccinia virus MVA can rapidly induce T cell-mediated protective immunity against lethal orthopoxvirus infections. Our data provide new evidence for an efficient protective capacity of vaccination with replication-deficient MVA. These data are of important practical relevance for public health, as the effectiveness of a safety-tested, next-generation smallpox vaccine based on MVA is still debated. Furthermore, producing sufficient amounts of vaccine is expected to be a major challenge should an outbreak occur. Moreover, prevention of other infections may require rapidly protective immunization; hence, MVA could be an extremely useful vaccine for delivering heterologous T cell antigens, particularly for infectious diseases that fit a scenario of emergency vaccination.


docid: pkqvemny

title: International Health Regulations (2005): public health event communications in the Western Pacific Region.


title: The therapeutic potential of deubiquitinating enzyme inhibitors.

text: Proteases play a key role in various pathological processes and several protease inhibitors are already available for treatment. DUBs (deubiquitinating enzymes) constitute one of the largest classes of human proteases and are key effectors of the ubiquitin-proteasome system. This pathway regulating cellular protein turnover has been implicated in the pathogenesis of many human diseases, including neurodegenerative disorders, viral diseases and cancer. The therapeutic efficacy of the proteasome inhibitor Velcade (bortezomib) for treating multiple myeloma and mantle cell lymphoma establishes this system as a valid target for cancer treatment. A promising alternative to targeting the proteasome itself would be to target the upstream, ubiquitin conjugation/deconjugation system, to generate more specific, less toxic anticancer agents. Advances in small molecule-based inhibitors specifically targeting DUBs are presented in this review.


title: Antibiotic Prophylaxis With Trimethoprim/Sulfamethoxazole Instead of Cloxacillin/Cefotaxime Increases Inguinal Surgical Site Infection Rate After Lower Extremity Revascularization.

text: Due to the consistently high proportion of surgical site infections (SSI) after vascular surgery, a change of prophylactic antibiotic therapy from cloxacillin/cefotaxime to trimethoprim/sulfamethoxazole (TMP-SMX) was conducted in 2016. The study included consecutive patients undergoing lower extremity revascularization due to acute or chronic lower extremity arterial disease. The antibiotic regime was changed in between the two sampling periods (2014 -2016 versus 2016 -2017). The diagnosis of SSI was based on clinical examination and microbiological results, and severity was classified according to the Szilagyi classification. One hundred and twenty-two patients in the cloxacillin/cefotaxime and 67 patients in the TMP-SMX group were included. The SSI rates were 32.0% and 40.3%, respectively (p=0.25). The proportion of women were higher in the TMP-SMX group (32.8% versus 47.8%, respectively, p=0.043). No other differences between the two groups were found regarding patient, vascular surgery procedure characteristics or severity of SSI. Groin infection rate was higher in the TMP-SMX group (15.4% versus 30.5%, respectively, p=0.022). When adjusting for gender, groin infection was more common in the TMP-SMX group (Odds Ratio 2.5, 95% CI 1.1 -5.4). The groin SSI rate was higher after elective surgery in the TMP-SMX group (13.0% versus 27.8%, respectively, p=0.027), and also after adjusting for gender (Odds Ratio 2.6, 95% CI 1.1 -6.2). The change in antibiotic prophylaxis from Cloxacillin/Cefotaxime to TMP-SMX was associated with an increased rate of inguinal SSI in patients undergoing lower extremity revascularization, despite a possible Hawthorne effect.


title: Ergonomic design and evaluation of the handle for an endoscopic dissector.

text: The purpose of this study was to design an endoscopic dissector handle and objectively assess its usability. The handles were designed with increased contact area between the fingers and thumb and the eye rings, and the eye rings were modified to have a more perpendicular insertion angle to the finger midline. Four different handle models were compared, including a conventional product. Subjects performed dissection, exclusion, grasping, precision manipulation and precision handling tasks. Electromyography and subjective evaluations were measured. Compared to conventional handles, the designated handle reduced the muscle load in the extensor and flexor muscles of the forearm and increased subjective stability. The activity of the first dorsal interosseous muscle was sometimes influenced by the shape of the other parts. The ergonomically designed endoscopic dissector handle used in this study achieved high usability. Medical instrument designs based on ergonomic concepts should be assessed with objective indices. Practitioner Summary: The endoscopic dissector handles were designed with increased contact area and more suitable insertion angle between the fingers and thumb and the eye rings. Compared to conventional handles, the designated handle reduced the muscle load in the extensor and flexor muscles of the forearm and increased subjective stability.


title: Pathogenesis of Hendra and Nipah virus infection in humans.

text: Hendra virus (HeV) and Nipah virus (NiV) are emerging zoonotic viruses that cause severe and often lethal respiratory illness and encephalitis in humans. Henipaviruses can infect a wide range of species and human-to-human transmission has been observed for NiV. While the exact route of transmission in humans is not known, experimental infection in different animal species suggests that infection can be efficiently initiated after respiratory challenge. The limited data on histopathological changes in fatal human cases of HeV and NiV suggest that endothelial cells are an important target during the terminal stage of infection; however, it is unknown where these viruses initially establish infection and how the virus disseminates from the respiratory tract to the central nervous system and other organs. Here we review the current concepts in henipavirus pathogenesis in humans.


title: Controversies in single-port laparoscopic surgery.

text: Single-port laparoscopic surgery (SPLS) is a rapidly involving minimally invasive surgical technique. SPLS has been applied to a variety of surgical procedures, including appendectomy, cholecystectomy, colectomy, and bariatric surgery. The true advantage of SPLS over conventional laparoscopic surgery has been always a topic of debate. Here, we discuss few controversies related to SPLS, starting from nomenclature, access techniques, true technical challenges, port-site hernia, and ideal patient for SPLS.


title: A beginner's guide to digital health for ambulatory care clinicians.

text: Digital health technology is already playing a larger role in how healthcare consumers receive information about health concerns and how patients manage wellness and disease. The influence of mobile apps, wireless medical devices and other tools for patient monitoring will soon be felt in almost every physician practice. In an environment where regulatory standards are still in flux, some of these technologies are validated and reliable, others are not. We present the first in a series of systematic guidelines to assist physicians in navigating digital health technologies that they will encounter in the office setting.


title: Covid-19: A view from New York.

text: I live in New York City, identified as the epicenter of the Covid-19 pandemic. My view differs from that of many of the millions living in this large metropolitan area who are poor. I am not rich, but I am privileged: I have a retirement income for which I have saved all my working life and I have no debts. I am isolated in my apartment having food delivered. But what if I require hospitalization, from Covid-19 or another medical condition? New York State has guidelines for allocation of scarce ventilators in times of scarcity. The guidelines reject advanced age as a criterion for triage because it discriminates against the elderly. Other proposals contend that priority should be given to those who have not yet ;lived a full life. Allocation guidelines set a priority on saving the most lives, but hard choices remain within that broadly defined goal. Key words: Covid-19 pandemic, New York epicenter, resource allocation, age-based selection, shortage of ventilators, triage committee.


docid: bccboqfy

title: The importance and timing of optic canal exploration and decompression during endoscopic endonasal resection of tuberculum sella and planum sphenoidale meningiomas.

text: BACKGROUND Suprasellar meningiomas often invade the optic canals (OCs). The feasibility of removing these tumors through a minimal-access endonasal route has been demonstrated, but the importance, safety, and timing of OC exploration and decompression are not well described. OBJECTIVE To create a simple decision-tree algorithm for OC exploration and decompression in the endonasal endoscopic surgery for planum sphenoidale and tuberculum sella meningiomas. METHODS We identified a consecutive series of 8 planum sphenoidale and tuberculum sella meningiomas resected endonasally. "Late" OC exploration and decompression was performed in 4 of 8 patients. The extent of resection, visual outcome, and complications were recorded. RESULTS Five patients had OC invasion on magnetic resonance imaging. Endoscopic inspection did not reveal additional OC invasion. The OC was opened bilaterally in 2 patients and unilaterally in 2 patients. Gross total resection was achieved in 6 of 7 patients in whom it was the goal. Vision improved in 3 patients (3 of 3 OCs opened) and was stable in 4 (1 of 4 OCs opened). In 1 patient, the bitemporal hemianopsia improved, but there was unilateral deterioration (no OC invasion) because the tumor was extremely adherent to 1 optic nerve. After an average follow-up of 20.9 months, all patients had an Glasgow Outcome Scale score of 5, and there were no cerebrospinal fluid leaks. CONCLUSION Exploration and decompression of the OC are feasible, safe, and important to optimize visual outcome and to minimize recurrence in planum sphenoidale and tuberculum sella meningiomas resected endonasally. It may not be important to open the canal early during surgery because tumor debulking can be performed without manipulating the optic nerves. Early decompression, however, is technically feasible.


Post the Pandemic: How will COVID-19 Transform Diabetic Foot Disease Management?


title: Phenylephrine increases near-infrared spectroscopy determined muscle oxygenation during head-up tilt in men.

text: Phenylephrine is an α-adrenergic agent and yet seems to increase near-infrared spectroscopy determined muscle oxygenation (SmO2) that reflects the ratio between oxygenated (O2Hb) and deoxygenated (Hb) haemoglobin/myoglobin. We examined whether the increase in SmO2 by phenylephrine reflects veno-constriction and to secure filling of the veins, subjects were exposed to head-up tilt (HUT). Phenylephrine (0.2 mg) was administered to 10 healthy males (24 years (22-27; median with interquartile range)) during 40° HUT with SmO2, O2Hb and Hb determined for the biceps brachii and vastus lateralis muscles. Changes in red cell volume within the thorax and thigh were evaluated by electrical admittance and brachial vein diameter determined by ultrasound. HUT accumulated blood in arms and legs as indicated by reduced thoracic and conversely enhanced thigh electrical admittance. Both over the arm and leg, HUT reduced SmO2 as a consequence of reduced O2Hb and increased Hb (p < .05). After 5 min HUT, phenylephrine increased MAP and total peripheral resistance, and both arm and thigh SmO2 increased due to a decrease in Hb and an increase in O2Hb. The results confirm that SmO2 decreases during HUT and demonstrate venous filling in the limbs. Furthermore, vasoconstriction during HUT is indicated by a decrease in O2Hb. Conversely, phenylephrine increased SmO2 likely illustrating increased muscle blood flow and venoconstriction as O2Hb increased while Hb was reduced.


title: Receptor recognition mechanisms of coronaviruses: a decade of structural studies.

text: Receptor recognition by viruses is the first and essential step of viral infections of host cells. It is an important determinant of viral host range and cross-species infection and a primary target for antiviral intervention. Coronaviruses recognize a variety of host receptors, infect many hosts, and are health threats to humans and animals. The receptor-binding S1 subunit of coronavirus spike proteins contains two distinctive domains, the N-terminal domain (S1-NTD) and the C-terminal domain (S1-CTD), both of which can function as receptor-binding domains (RBDs). S1-NTDs and S1-CTDs from three major coronavirus genera recognize at least four protein receptors and three sugar receptors and demonstrate a complex receptor recognition pattern. For example, highly similar coronavirus S1-CTDs within the same genus can recognize different receptors, whereas very different coronavirus S1-CTDs from different genera can recognize the same receptor. Moreover, coronavirus S1-NTDs can recognize either protein or sugar receptors. Structural studies in the past decade have elucidated many of the puzzles associated with coronavirus-receptor interactions. This article reviews the latest knowledge on the receptor recognition mechanisms of coronaviruses and discusses how coronaviruses have evolved their complex receptor recognition pattern. It also summarizes important principles that govern receptor recognition by viruses in general.


title: The temperature change in an endotracheal tube during high frequency ventilation using an artificial neonatal lung model with Babylog® 8000 plus.

text: OBJECTIVE There is little available data on airway humidity during high-frequency ventilation (HFV). The purpose of this study is to evaluate the temperature drop in an endotracheal tube (ETT) during HFV. METHODS We examined the airway temperature in a neonatal HFV system using Babylog® 8000 plus. We measured the temperature change of inspired gases in the ETT under various oscillatory frequencies and oscillatory volumes with a fixed base flow. The temperatures in the ETT during HFV were compared with the temperatures during conventional intermittent positive pressure ventilation (IPPV). RESULTS As the oscillatory frequency was increased and the oscillatory volume (VThf) decreased, the difference in temperature between the Y piece and the inlet of an artificial lung in the ETT (ETT outside of body) increased. However, as the oscillatory frequency increased, there was no difference in the ETT temperature under constant oscillatory volume. In contrast, as the oscillatory volume was decreased, the difference in temperature in the ETT was greater under constant oscillatory frequency. Moreover, the temperature drop in the ETT with HFV was lower than that in the IPPV temperature with a similar respiratory volume. CONCLUSIONS The temperature change in the ETT was not dependent on the oscillatory frequency when the oscillatory volume was fixed; however, the temperature was dependent on the oscillatory volume when the oscillatory frequency was fixed.


Acute maculopapular eruption in Covid-19 patient: a case report.


title: A totally thoracoscopic approach for pulmonary anatomic segmentectomies.

text: Reported experience with video-assisted anatomic pulmonary segmentectomy is still limited. Over a 28-month period, totally thoracoscopic (TT) anatomic segmentectomies, i.e. using only endoscopic instrumentation and video-display without utility incision, were attempted on 50 patients (25 males and 25 females), aged 18-81 years (mean: 57 years). The indication was a clinical N0 non-small cell lung carcinoma in 25 cases, a solitary metastasis in nine cases and a benign lesion in 16 cases. The following segmentectomies were performed: right apicosuperior (9) right superior (6), right basilar (7), lingula sparing left upper lobectomy (7), left apicosuperior (4), lingula (4), left superior (6) and left basilar (7). It was associated with a radical lymphadenectomy in 20 cases. There was one conversion to thoracotomy. The mean operative time was 188±54 min, the mean intraoperative blood loss was 91±82 ml (range: 0-450 ml). There were four minor postoperative complications (11.7%). The median postoperative stay was 5.6±2.4 days. Out of the 25 patients operated on for a cN0 lung carcinoma, two were finally upstaged to N2. TT anatomic pulmonary segmentectomies are feasible and safe.


title: Engineered autologous cartilage tissue for nasal reconstruction after tumour resection: an observational first-in-human trial.

text: BACKGROUND Autologous native cartilage from the nasal septum, ear, or rib is the standard material for surgical reconstruction of the nasal alar lobule after two-layer excision of non-melanoma skin cancer. We assessed whether engineered autologous cartilage grafts allow safe and functional alar lobule restoration. METHODS In a first-in-human trial, we recruited five patients at the University Hospital Basel (Basel, Switzerland). To be eligible, patients had to be aged at least 18 years and have a two-layer defect (≥50% size of alar subunit) after excision of non-melanoma skin cancer on the alar lobule. Chondrocytes (isolated from a 6 mm cartilage biopsy sample from the nasal septum harvested under local anaesthesia during collection of tumour biopsy sample) were expanded, seeded, and cultured with autologous serum onto collagen type I and type III membranes in the course of 4 weeks. The resulting engineered cartilage grafts (25 mm × 25 mm × 2 mm) were shaped intra-operatively and implanted after tumour excision under paramedian forehead or nasolabial flaps, as in standard reconstruction with native cartilage. During flap refinement after 6 months, we took biopsy samples of repair tissues and histologically analysed them. The primary outcomes were safety and feasibility of the procedure, assessed 12 months after reconstruction. At least 1 year after implantation, when reconstruction is typically stabilised, we assessed patient satisfaction and functional outcomes (alar cutaneous sensibility, structural stability, and respiratory flow rate). FINDINGS Between Dec 13, 2010, and Feb 6, 2012, we enrolled two women and three men aged 76-88 years. All engineered grafts contained a mixed hyaline and fibrous cartilage matrix. 6 months after implantation, reconstructed tissues displayed fibromuscular fatty structures typical of the alar lobule. After 1 year, all patients were satisfied with the aesthetic and functional outcomes and no adverse events had been recorded. Cutaneous sensibility and structural stability of the reconstructed area were clinically satisfactory, with adequate respiratory function. INTERPRETATION Autologous nasal cartilage tissues can be engineered and clinically used for functional restoration of alar lobules. Engineered cartilage should now be assessed for other challenging facial reconstructions. FUNDING Foundation of the Department of Surgery, University Hospital Basel; and Krebsliga beider Basel.


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title: Cancer Labs Pivot to Battle COVID-19.

text: As cancer researchers shutter their labs to comply with COVID-19-related work restrictions, some are turning their attention, resources, and technical know-how to the challenge of tackling the deadly coronavirus.


Psychosis in Patients in COVID-19-Related Quarantine: A Case Series.


title: Individual indicators of appropriate hypnotic level during propofol anesthesia: highest alpha power and effect-site concentrations of propofol at loss of response.

text: BACKGROUND Electroencephalogram (EEG) waveforms vary widely among individuals, this decreases the usefulness of BIS™ monitors for assessing the effects of propofol. Practically, anesthesia is only seen as too deep when evidence of burst-suppression is seen. We designed an experiment to help towards better assessment of individual anesthetic needs. First, to mark the Ce (effect-site concentration) of propofol at loss of response to calling name and gently shaking shoulders (LOR), we defined Ce-LOR. To mark the transient power increase in the alpha range (9-14 Hz), common to all patients, when propofol concentration gradually increases, we defined Ce-alpha as the highest recorded alpha power for Ce. We also defined Ce-OBS as the Ce of propofol at initial observation of burst-suppression. Then we tried to predict Ce-LOR and Ce-alpha from Ce-OBS, vice versa, and considered the significance of these parameters. METHODS We enrolled 26 female patients (age 33-65) who were undergoing scheduled mastectomy. During anesthesia, we recorded all raw EEG packets as well as EEG-derived parameters on a computer from BIS-XP™ monitor. Propofol was infused using a TCI pump. Target concentration was adjusted so that Ce of propofol was gradually increased. RESULTS We obtained the following regression equation; Ce-alpha or Ce-OBS = Ce-LOR × 0.87 + 1.06 + dummy × 0.83 (for Ce-alpha dummy = 0, and for Ce-OBS = 1; adjusted r = 0.90, p < 2.2e-16) by ANCOVA. At Ce-alpha, BIS was 50.2 ± 7.7. CONCLUSION Ce-alpha and Ce-OBS could be estimated from Ce-LOR. Based on Ce-LOR it is possible to manage the hypnotic level of individual patients.


title: Analysis of standard multiport versus single-site access for laparoscopic skills training.

text: BACKGROUND Single-site-access (SSA) laparoscopy is more challenging to perform than multiport (MP) laparoscopy. This study examined the effect of MP versus SSA skills training on laparoscopic performance using surgically naive medical students. METHODS For the study, 40 medical students at the end of their first year were randomized into two groups. Both groups were trained in four basic laparoscopic drills (peg, rope, bean drop, pattern cutting) using a standard MP setup (group 1) and an SSA approach (group 2). The time and number of repetitions required to attain proficiency were recorded. Each group then crossed over to the alternate approach and repeated the sequence. Data are presented as mean ± standard deviation, and statistical analysis was performed using the two-tailed, unpaired t test. RESULTS The total times required to attain proficiency for the SSA and MP approaches were not significantly different between the MP-trained group (234.0 ± 114.9 min) and the SSA-trained group (216.4 ± 106.5 min) (p = 0.67). The MP-trained group required less time to reach proficiency on the standard MP setup than the group using the SSA approach (119.1 ± 69.7 vs. 178.0 ± 93.4 min; p = 0.058) and significantly fewer repetitions (77.6 ± 42.6 vs. 118.8 ± 54.3; p = 0.027). The SSA-trained group required significantly less time to reach proficiency on the MP setup than the standard MP-trained group (38.4 ± 29.4 vs. 119.1 ± 69.7 min; p = 0.0013) and needed only a mean of 26.9 repetitions. When the standard MP trainees crossed over to the SSA setup, they required significantly less time to reach proficiency with the SSA approach than the SSA-trained group (114.8 ± 50.5 vs. 178.0 ± 93.4 min; p = 0.026) but required more repetitions than with the MP approach (86.2 ± 35.2 vs. 77.6 ± 42.6; nonsignificant difference). CONCLUSIONS Laparoscopic SSA skills training results in longer times and more repetitions to achieve proficiency than MP training, but the skills acquired transfer well to the MP approach.


title: DC-SIGN, DC-SIGNR and LSECtin: C-type lectins for infection.

text: The C-type lectins DC-SIGN, DC-SIGNR and LSECtin are encoded by the lectin gene cluster on chromosome 19p13.3 and perform cell-adhesion and pathogen recognition functions on dendritic cells, liver cells and lymph node sinusoidal endothelial cells. DC-SIGN and DC-SIGNR share similar overall gene and protein molecule structures, and they exhibit high affinity for high-mannose carbohydrates. LSECtin, a Ca2+-dependent C-type lectin, interacts with mannose, NAcGlc and fucose. These lectins allow pathogen recognition (e.g., viruses, bacteria and allergens) and cell adhesion for dendritic and endothelial cells in different tissues, which may enhance the infection and facilitate the spread of those pathogens. A better understanding of these lectins may yield information about how pathogens are captured by particular cells and how they spread in different tissues. These studies would provide more detail about the physiopathological mechanisms of viral and bacterial infections and may also lead to new strategies to treat or prevent infections.


title: Revealing oxidative damage to enzymes of carbohydrate metabolism in yeast: An integration of 2D DIGE, quantitative proteomics, and bioinformatics.

text: Clinical usage of lidocaine, a pro-oxidant has been linked with severe, mostly neurological complications. The mechanism(s) causing these complications is independent of the blockade of voltage-gated sodium channels. The budding yeast Saccharomyces cerevisiae lacks voltage-gated sodium channels, thus provides an ideal system to investigate lidocaine-induced protein and pathway alterations. Whole-proteome alterations leading to these complications have not been identified. To address this, S. cerevisiae was grown to stationary phase and exposed to an LC50 dose of lidocaine. The differential proteomes of lidocaine treatment and control were resolved 6 h post exposure using 2D DIGE. Amine reactive dyes and carbonyl reactive dyes were used to assess protein abundance and protein oxidation, respectively. Quantitative analysis of these dyes (⩾ 1.5-fold alteration, p ⩽ 0.05) revealed a total of 33 proteoforms identified by MS differing in abundance and/or oxidation upon lidocaine exposure. Network analysis showed enrichment of apoptotic proteins and cell wall maintenance proteins, while the abundance of proteins central to carbohydrate metabolism, such as triosephosphate isomerase and glyceraldehyde-3-phosphate dehydrogenase, and redox proteins superoxide dismutase and peroxiredoxin were significantly decreased. Enzymes of carbohydrate metabolism, such as phosphoglycerate kinase and enolase, the TCA cycle enzyme aconitase, and multiple ATP synthase subunits were found to be oxidatively modified. Also, the activity of aconitase was found to be decreased. Overall, these data suggest that toxic doses of lidocaine induce significant disruption of glycolytic pathways, energy production, and redox balance, potentially leading to cell malfunction and death.


title: Assessment of Dual-Antiplatelet Regimen for Pipeline Embolization Device Placement: A Survey of Major Academic Neurovascular Centers in the United States.

text: INTRODUCTION Flow diversion with the Pipeline Embolization Device (PED) currently is adopted for treatment of a variety of intracranial aneurysms. The elevated risk of thromboembolic complications associated with the device necessitates the need for administration of antiplatelet agents. We sought to assess current dual-antiplatelet therapy practices patterns and their associated costs after PED placement. MATERIALS AND METHODS An online questionnaire that assessed dual-antiplatelet regimens after flow diversion for treatment of intracranial aneurysms was developed and disseminated to 80 neurosurgeons at major academic cerebrovascular centers. Pricing information from 2 of the largest prescription payers in Massachusetts was used to calculate the monthly cost of these agents. RESULTS Twenty-six responses (32.5%) were received. All respondents (100%) affirmed using clopidogrel and aspirin dual-antiplatelet therapy as a first-line regimen. Twenty-three (88.5%) routinely use platelet function testing. Eleven respondents (42.3%) each identified that they administer aspirin/ticagrelor and aspirin/prasugrel to clopidogrel hypo- or nonresponders. For uninsured patients, prasugrel was found to have the highest cumulative monthly cost ($471), followed by ticagrelor ($396), clopidogrel ($149), and ticlopidine ($110). CONCLUSIONS Significant heterogeneity in dual-antiplatelet regimens after PED placement and associated costs exists at major academic neurovascular centers. The most commonly used first-line dual-antiplatelet regimen consists of aspirin and clopidogrel. Two major alternate protocols involving ticagrelor and prasugrel are administered to clopidogrel hyporesponders. The optimal dual-antiplatelet regimen for patients with cerebrovascular conditions has not been established, given limited prospective data within the neurointerventional literature.


title: Intracorporeal robot-assisted radical cystectomy, together with an enhanced recovery programme, improves postoperative outcomes by aggregating marginal gains.

text: OBJECTIVE To assess the cumulative effect of an enhanced recovery after surgery (ERAS) pathway and minimally invasive robot-assisted radical cystectomy with intracorporeal urinary diversion (iRARC) in comparison with open radical cystectomy (ORC) on length of hospital stay (LOS) and peri-operative outcomes. MATERIALS AND METHODS Between February 2009 and October 2017, 304 radical cystectomy cases were performed at a single institution (ORC, n = 54; robot-assisted radical cystectomy [RARC], n = 250). Data were prospectively collected. We identified 45 consecutive ORC cases performed without ERAS before the commencement of the RARC programme (Cohort A), 50 consecutive iRARC cases performed without ERAS (Cohort B) and 40 iRARC cases with ERAS (Cohort C). The primary outcome measure was LOS, while secondary outcome measures included peri-operative 90-day complications and readmission rate. Complications were accessed using the Clavien-Dindo system. RESULTS Patients in all cohorts were evenly matched with regard to age, sex, body mass index, neoadjuvant treatment, tumour stage, lymph node yield, previous pelvic radiotherapy and surgery, peri-operative anaemia, as well as physiological state. Patients who underwent iRARC with ERAS had a significantly higher American Society of Anesthesiologists score (III-IV) and were more likely to receive neobladder reconstruction. The median (interquartile range) LOS was shorter in the iRARC with ERAS group (7 [6-10]) days than in the iRARC without ERAS group (11 [8-15]) days and the ORC group (17 [14-21] days). In a propensity score-matched cohort of patients who underwent iRARC, patients who followed the ERAS pathway had significantly lower 90-day readmission rates. Additionally, implementing ERAS in an iRARC cohort resulted in a significantly lower 90-day all (P < 0.001) and gastrointestinal-related complications (P = 0.001). The ERAS pathway and younger patients were independently associated with an LOS of ≤10 days on multinomial logistic regression. CONCLUSION A comprehensive ERAS programme can significantly reduce LOS in patients undergoing iRARC without increasing 90-day readmission rates. An ERAS programme can augment the benefits of iRARC in improving peri-operative outcomes. In studies comparing ORC and RARC, the presence or absence of an ERAS programme will be a confounding factor and only level 1 evidence can be interpreted reliably.


title: Pathology and Pathogenesis of SARS-CoV-2 Associated with Fatal Coronavirus Disease, United States.

text: An ongoing pandemic of coronavirus disease (COVID-19) is caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Characterization of the histopathology and cellular localization of SARS-CoV-2 in the tissues of patients with fatal COVID-19 is critical to further understand its pathogenesis and transmission and for public health prevention measures. We report clinicopathologic, immunohistochemical, and electron microscopic findings in tissues from 8 fatal laboratory-confirmed cases of SARS-CoV-2 infection in the United States. All cases except 1 were in residents of long-term care facilities. In these patients, SARS-CoV-2 infected epithelium of the upper and lower airways with diffuse alveolar damage as the predominant pulmonary pathology. SARS-CoV-2 was detectable by immunohistochemistry and electron microscopy in conducting airways, pneumocytes, alveolar macrophages, and a hilar lymph node but was not identified in other extrapulmonary tissues. Respiratory viral co-infections were identified in 3 cases; 3 cases had evidence of bacterial co-infection.


title: A comparison of single-port laparoscopic cholecystectomy and an alternative technique without a suspension suture.

text: OBJECTIVE Many surgeons face difficulties during single-incision laparoscopic cholecystectomy (SILC) surgery and are forced to use an additional port. We compared the results of a technique that we developed with SILC. MATERIAL AND METHODS Fifty-four patients who were diagnosed with chronic cholelithiasis were prospectively randomized and divided into two groups. An additional 5-mm port (MCAP: with an additional port using a multi-channel device through the umbilicus) was placed in the subxiphoid area instead of a transabdominal suspension suture in one group of patients. The other group was operated on with the SILC technique. The demographic and surgical data of the patients were compared. RESULTS The MCAP technique shortened the surgery duration by more than half (MCAP: 35.0±12.3, SILC: 79.1±27.7 min) (p<0.05). No difference was found between the two methods in terms of estimated blood loss, length of hospitalization, postoperative day 1 and 7 visual analog scale scores, need for analgesia in the postoperative period, and rate of changing to another technique due to inadequacy of the surgical technique. CONCLUSION MCAP is as safe as SILC for cholecystectomy and is easier for the surgeon to perform.


title: Single-incision laparoscopic appendectomy: prospective case series at a single centre in Singapore.

text: PURPOSE Laparoscopic appendectomy is widely accepted as a standard of care for acute appendicitis. Aim of our study is to assess the safety and feasibility of single-incision laparoscopic appendectomy (SILA) in our hospital setting. METHODS From March to August 2010, 30 patients (21 male, 9 female) with mean age 30.4 years (range, 17 to 64 y) with clinical diagnosis of acute appendicitis underwent SILA. RESULTS The procedure was successful in 28 of 30 patients. Mean operative time was 80.4 minutes (range, 31 to 136 min). There was no mortality or major postoperative complication. The median hospital stay was 1.9 days (range, 1 to 5 d). The mean visual analogue scale score at the time of discharge was 2.2 (range, 1 to 4). CONCLUSIONS In our early experience, SILA is safe and feasible, with acceptable operative time, short learning curve, and good cosmetic result.


title: Effects of gastric bypass surgery in patients with type 2 diabetes and only mild obesity.

text: OBJECTIVE Roux-en-Y gastric bypass (RYGB) ameliorates type 2 diabetes in severely obese patients through mechanisms beyond just weight loss, and it may benefit less obese diabetic patients. We determined the long-term impact of RYGB on patients with diabetes and only class I obesity. RESEARCH DESIGN AND METHODS Sixty-six consecutively selected diabetic patients with BMI 30-35 kg/m(2) underwent RYGB in a tertiary-care hospital and were prospectively studied for up to 6 years (median 5 years [range 1-6]), with 100% follow-up. Main outcome measures were safety and the percentage of patients experiencing diabetes remission (HbA(1c) <6.5% without diabetes medication). RESULTS Participants had severe, longstanding diabetes, with disease duration 12.5 ± 7.4 years and HbA(1c) 9.7 ± 1.5%, despite insulin and/or oral diabetes medication usage in everyone. For up to 6 years following RYGB, durable diabetes remission occurred in 88% of cases, with glycemic improvement in 11%. Mean HbA(1c) fell from 9.7 ± 1.5 to 5.9 ± 0.1% (P < 0.001), despite diabetes medication cessation in the majority. Weight loss failed to correlate with several measures of improved glucose homeostasis, consistent with weight-independent antidiabetes mechanisms of RYGB. C-peptide responses to glucose increased substantially, suggesting improved β-cell function. There was no mortality, major surgical morbidity, or excessive weight loss. Hypertension and dyslipidemia also improved, yielding 50-84% reductions in predicted 10-year cardiovascular disease risks of fatal and nonfatal coronary heart disease and stroke. CONCLUSIONS This is the largest, longest-term study examining RYGB for diabetic patients without severe obesity. RYGB safely and effectively ameliorated diabetes and associated comorbidities, reducing cardiovascular risk, in patients with a BMI of only 30-35 kg/m(2).


title: Stent dislodgement induced by a vasodilator used for severe coronary artery spasm caused by Kounis syndrome.

text: Coronary stent dislodgement is a rare but critical complication of percutaneous coronary intervention. It can potentially result in serious consequences, such as stent embolization and emergent coronary artery bypass graft surgery. Here, we describe the successful retrieval of an extracoronary dislodged stent, where dislodgement was induced by a vasodilator used for severe coronary artery spasm caused by Kounis syndrome.


title: Oxygen saturation histogram monitoring to reduce death or retinopathy of prematurity: a quality improvement initiative.

text: OBJECTIVES Maintaining preterm infants within a goal oxygen saturation range challenges care providers. Through periodic assessment of saturation trends on infants' bedside histogram reports, our initiative aimed to (1) increase time spent at goal saturations and (2) reduce death or severe retinopathy of prematurity. STUDY DESIGN The initiative integrated histogram monitoring into provider, respiratory, and nursing care. Achieved oxygen saturations, chart audits, and bedside histogram monitoring flowsheets provided process measures with the outcome measure of death or severe retinopathy of prematurity. RESULTS In infants <29 weeks' gestation (n = 518), the rate of death or severe retinopathy of prematurity prior to hospital discharge decreased from 32.1% to 18.0%. Time at goal saturations (90-95%) increased from 48.7% to 57.6%. CONCLUSION In infants born at <29 weeks' gestation, periodic, multidisciplinary oxygen saturation histogram monitoring improved time at goal saturations and was associated with a reduction in death or severe retinopathy of prematurity.


COVID-19 infection in a patient with FMF: does colchicine have a protective effect?


title: Decreased Pseudomonas aeruginosa biofilm formation on nanomodified endotracheal tubes: a dynamic lung model.

text: Ventilator-associated pneumonia (VAP) is a serious complication of mechanical ventilation that has been shown to be associated with increased mortality rates and medical costs in the pediatric intensive care unit. Currently, there is no cost-effective solution to the problems posed by VAP. Endotracheal tubes (ETTs) that are resistant to bacterial colonization and that inhibit biofilm formation could provide a novel solution to the problems posed by VAP. The objective of this in vitro study was to evaluate differences in the growth of Pseudomonas aeruginosa on unmodified polyvinyl chloride (PVC) ETTs and on ETTs etched with a fungal lipase, Rhizopus arrhizus, to create nanoscale surface features. These differences were evaluated using an in vitro model of the pediatric airway to simulate a ventilated patient in the pediatric intensive care unit. Each experiment was run for 24 hours and was supported by computational models of the ETT. Dynamic conditions within the ETT had an impact on the location of bacterial growth within the tube. These conditions also quantitatively affected bacterial growth especially within the areas of tube curvature. Most importantly, experiments in the in vitro model revealed a 2.7 log reduction in the number (colony forming units/mL) of P. aeruginosa on the nanoroughened ETTs compared to the untreated PVC ETTs after 24 hours. This reduction in total colony forming units/mL along the x-axis of the tube was similar to previous studies completed for Staphylococcus aureus. Thus, this dynamic study showed that lipase etching can create surface features of nanoscale roughness on PVC ETTs that decrease bacterial attachment of P. aeruginosa without the use of antibiotics and may provide clinicians with an effective and inexpensive tool to combat VAP.


title: Blood cell counts and lymphocyte subsets of patients admitted during the COVID-19 pandemic: a prospective cohort study.

text: Aberrant blood cell counts, most prominently lymphopenia, have been identified as markers of the degree of severity of coronavirus disease 2019 (COVID-19) (Terpos et al, 2020; Yang et al, 2020; Wan et al, 2020; Wang et al, 2020; Zhao et al, 2020). However, most of these studies lack comparison to a COVID-19 negative, contemporary control group. Additionally, the longitudinal composition and dynamics of lymphocyte subsets in COVID-19 patients are insufficiently characterized.


Immunoglobulins or convalescent plasma to tackle COVID-19: buying time to save lives - current situation and perspectives.