title: Prompt closure versus gradual weaning of extraventricular drainage for hydrocephalus in adult patients with aneurysmal subarachnoid haemorrhage: a systematic review protocol with meta-analysis and trial sequential analysis.

text: INTRODUCTION In Neuro Intensive Care Units (NICU) and neurosurgical units, patients with an external ventricular drain (EVD) due to hydrocephalus following aneurysmal subarachnoid haemorrhage (SAH) are commonly seen. Cessation of the EVD involves the dilemma of either closing the EVD directly, or gradually weaning it before removal. Development of increased intracranial pressure (ICP) and acute hydrocephalus with subsequent need of a permanent shunt has been associated with prompt closure of theEVD, whereas increased risk of infection with possible spreading to the brain and subsequent patient fatality is suspected in connection to a longer treatment as seen in gradual weaning. Sparse data exist on the recommendation of cessation strategy and patients are currently being treated on the basis of personal experience and expert opinion. The objective of this systematic review is to assess the available evidence from clinical trials on the effects of prompt closure versus gradual weaning of EVD treatment for hydrocephalus in adult patients with SAH. METHODS AND ANALYSIS We will search for randomised clinical trials in major international databases. Two authors will independently screen and select references for inclusion, extract data and assess the methodological quality of the included randomised clinical trials using the Cochrane risk of bias tool. Any disagreement will be resolved by consensus. We will analyse the extracted data using Review Manager and trial sequential analysis. To assess the quality of the evidence, we will create a 'Summary of Findings' table containing our primary and secondary outcomes using the GRADE assessment. ETHICS AND DISSEMINATION Results will be published widely according to the interest of the society. No possible impact, harm or ethical concerns are expected doing this protocol. TRIAL REGISTRATION NUMBER PROSPERO CRD42018108801.


title: The impact of an integrated heart failure service in a medium-sized district general hospital.

text: OBJECTIVES Assessing the impact of a new integrated heart failure service (IHFS) in a medium-sized district general hospital (DGH) on heart failure (HF) mortality, readmission rates, and provision of HF care. METHODS A retrospective, observational study encompassing all patients admitted with a diagnosis of HF over two 12-month periods before (2012/2013), and after (2015/2016) IHFS establishment. RESULTS Total admissions for HF increased by 40% (385 vs 540), with a greater number admitted to the cardiology ward (231 vs 121). After IHFS implementation, patients were more likely to see a cardiologist (35.1% vs 43.7%, p=0.009), undergo echocardiography (70.1% vs 81.5%, p<0.001), be initiated on all three disease modifying HF medications (angiotensin-converting enzyme inhibitors (ACEi), angiotensin II receptor blockers (ARB) and mineralocorticoid receptor antagonists (MRA)) in the heart failure with reduced ejection fraction (HFrEF) group (42% vs 99%, p<0.001) and receive specialist HF input (81.6% vs 85.4%, p=0.2). Both 30-day post-discharge mortality and HF related readmissions were significantly lower in patients with heart failure with preserved ejection fraction (HFpEF) (8.9% vs 3.1%, p=0.032, 58% reduction, p=0.043 respectively) with no-significant reductions in all other HF groups. In-patient mortality was similar. Length of stay in Cardiology wards increased from 8.4 to 12.7 days (p<0.001). CONCLUSION Establishment of an IHFS within a DGH with limited resources and only a modest service re-design has resulted in significantly improved provision of specialist in-patient care, use of HFrEF medications, early heart failure nurse follow-up, and is associated with a reduction in early mortality, particularly in the HFpEF cohort, and HF related readmissions.


title: The diagnostic efficacy of natural orifice transluminal endoscopic surgery: is there a role in the intensive care unit?

text: BACKGROUND Evaluation of a potential source for abdominal sepsis in a critically ill patient can be challenging. With flexible endoscopy readily available in this setting, we sought to evaluate the diagnostic efficacy of a transgastric natural orifice transluminal endoscopic surgery (NOTES) peritoneoscopy vs. laparoscopic exploration in the identification of intra-abdominal pathology in a porcine model. METHODS In this acute study, 15 pigs were randomized to demonstrate 0 to 4 pathologic lesions: small bowel ischemia (SBI), small bowel perforation (SBP), colon perforation (CP), and gangrenous cholecystitis (GC). Two blinded surgical endoscopists were allowed 60 min to perform NOTES or laparoscopy (LAP) to correctly identify or exclude each lesion. A prototype endoscope (R-scope, Olympus, Inc), which enables independent instrument mobility, was used in the NOTES arm. RESULTS When considering all lesions, LAP was more sensitive diagnostically than NOTES (77.4% vs. 61.3%) overall. LAP also displayed a slightly higher NPV compared with NOTES (79.4% vs. 70.7%). However, NOTES was 100% specific with 100% positive predictive value (PPV) compared with 93.1% and 92.3% with LAP, respectively. Individually, NOTES was found most sensitive with CP identification (87.5%) and least sensitive with SBP (37.5%). The sensitivity of NOTES for SBI and GC was 62.5% and 57.1%, respectively. CONCLUSIONS The utilization of NOTES as a diagnostic tool may have an important role in the critically ill patient when operative intervention is highly morbid. Although it may be overall inferior diagnostically compared with laparoscopy, a positive identification was highly specific with a strong predictive value. Further investigation addressing an improved small bowel evaluation technique would be beneficial. A human trial of NOTES in the ICU utilizing the current technology would still initially mandate laparoscopic or open surgical confirmation and treatment.


title: A Case of Laparoscopic Resection for Carcinoma of the Gastric Remnant following Proximal Gastrectomy Reconstructed with Jejunal Interposition.

text: A 72-year-old Japanese man had a history of proximal gastrectomy for early gastric cancer located in the upper third of the stomach in 2007. Our usual treatment strategy for early gastric cancer in the upper third of the stomach in 2007 was open proximal gastrectomy reconstructing by jejunal interposition with a 10 cm single loop. Upper gastrointestinal fiberscopy for annual follow-up revealed a type 0-IIc-shaped tumor with ulcer scar, 4.0 cm in size, located in the gastric remnant near the jejunogastrostomy. A clinical diagnosis of cancer of the gastric remnant, clinical T1b(SM)N0M0, Stage IA, following the proximal gastrectomy was made and a laparoscopic approach was selected because of the cancer's early stage. Remnant total gastrectomy with D1 plus lymphadenectomy was carried out with five ports by a pneumoperitoneal method. Complete resection of the reconstructed jejunum was undergone along with the jejunal mesentery. Reconstruction by the Roux-en-Y method via the antecolic route was selected. Total operative time was 395 min and blood loss was 40 mL. Our patient was the first successful case of resection for carcinoma of the gastric remnant following proximal gastrectomy reconstructed with jejunal interposition in a laparoscopic approach.


title: COVID-19 and animals: What do we know?

text: Coronaviruses, which were generally considered harmless to humans before 2003, have appeared again with a pandemic threatening the world since December 2019 after the epidemics of SARS and MERS. It is known that transmission from person to person is the most important way to spread. However, due to the widespread host diversity, a detailed examination of the role of animals in this pandemic is essential to effectively fight against the outbreak. Although coronavirus infections in pets are known to be predominantly related to the gastrointestinal tract, it has been observed that there are human-to-animal transmissions in this outbreak and some animals have similar symptoms to humans. Although animal-to-animal transmission has been shown to be possible, there is no evidence of animal-to-human transmission.


docid: pshirnuz

title: Intraoperative Tumor Perforation is Associated with Decreased 5-Year Survival in Colon Cancer: A Nationwide Database Study.

text: BACKGROUND It is a widely held belief that intraoperative tumor perforation in colon cancer impairs survival and causes local recurrence, although the prognostic importance remains unclear. AIM The aim of this study was to assess the effect of unintended intraoperative tumor perforation on postoperative mortality and long-term survival. MATERIAL AND METHODS This national cohort study was based on data from a prospectively maintained nationwide colorectal cancer database. We included 16,517 colon cancer patients who were resected with curative intent from 2001 to 2012. RESULTS Intraoperative tumor perforation produced a significantly impaired 5-year survival of 40% compared to 64% in non-perforated colon cancer. Intraoperative tumor perforation was an independent risk factor for death, hazard ratio 1.63 (95% confidence interval: 1.4-1.94), with a significantly increased 90-day postoperative mortality of 17% compared to 7% in non-perforated tumors, p < 0.001. We showed that tumor fixation, emergency operations, and laparotomies were associated with an increased risk of intraoperative tumor perforation. CONCLUSION This nationwide study demonstrates that intraoperative tumor perforation in colon cancer is associated with statistically significant reduced long-term survival and increased postoperative mortality.


title: Modified intracorporeal gastroduodenostomy in totally laparoscopic distal gastrectomy for gastric cancer: early experience.

text: PURPOSE This study presents findings on the clinical usefulness of an overlap method that is another modification for the currently well-known intracorporeal gastroduodenostomy in totally laparoscopic distal gastrectomy (TLDG). METHODS We studied 42 patients diagnosed with gastric cancer who underwent TLDG between December 2011 and March 2013. Endoscopic linear staplers were used for intracorporeal anastomosis and patients were observed with endoscopic tracking six months after surgery. We retrospectively reviewed the outcome of the operation, the clinical pathological results, and the endoscopy results. RESULTS The mean duration of the operation for 42 patients was 228.3 ± 42.5 minutes and the mean time to complete the anastomosis was 12.18 ± 2.3 minutes. There were no mortalities and no cases of open conversion. Following the operation, 37 patients had stage IA, 5 in stage IB, and 3 in stage II gastric cancer. Abscesses were seen in 3 patients and 5 cases of stasis during the postoperative period. Duodenoscopy 6 months after the operation showed 11 cases of gastric stasis, 28 cases of bile reflux, and 1 new case of erosive gastritis. We did not observe contraction in any of the patients. CONCLUSION The overlap method for intracorporeal gastroduodenostomy, using an endoscopic linear stapler, can be considered a feasible and safe technique for the treatment of stomach cancer. However, a long-term comparative study is required to sufficiently evaluate our findings.


title: Comparative analysis of processing methods in fat grafting.

text: BACKGROUND Centrifugation is a popular processing method, with an unclear mechanism of action. Hypotheses include fat concentration, reduced inflammatory response by removal of blood, and concentration of adipose-derived stem cells. The authors performed multiple experiments to determine the role of centrifugation and compared it with a different processing method (mesh/gauze technique). METHODS Lipoaspirate components were quantified after centrifugation at increasing speed to determine concentration efficacy. For comparison, the authors quantified the concentration efficacy of mesh/gauze. They also compared the number of adipose-derived stem cells isolated by either method. To determine the effects of each component, they compared fat alone to fat mixed with various spinoff components in a mouse model. They also compared centrifugation to mesh/gauze. RESULTS The adipocyte fraction remains constant above 5000 g, whereas 1200 g results in 91 percent concentrated fat. Mesh/gauze also results in 90 percent concentrated fat. The number of adipose-derived stem cells in 1 g of fat was 1603 ± 2020 and 1857 ± 1832 in the centrifuge and mesh/gauze groups, respectively (p = 0.86). Five "add-back" groups were created: fat plus oil, fat plus surgical tumescence, fat plus fresh tumescence, fat plus cell pellets and fresh tumescence, and fat plus cell pellets. The fat-only group had better retention than the groups mixed with tumescence, regardless of whether it was surgical, fresh, or had cell pellets. Oil did not affect grafts. Centrifugation at 1200 g was equivalent to mesh/gauze (0.73 ± 0.12 g and 0.72 ± 0.13 g, respectively). CONCLUSIONS Centrifugation improves graft retention by concentration of the adipocyte fraction. The concentration efficacy of mesh/gauze is equivalent to centrifugation at 1200 g, with equivalent in vivo outcomes.


title: Neuroprotective effect of apolipoprotein D against human coronavirus OC43-induced encephalitis in mice.

text: Apolipoprotein D (apoD) is a lipocalin upregulated in the nervous system after injury or pathologies such as Alzheimer's disease, Parkinson's disease, and multiple sclerosis. We previously demonstrated that apoD protects against neuropathology by controlling the level of peroxidated lipids. Here, we further investigated the biological function of apoD in a mouse model of acute encephalitis. Our results show that apoD transcript and protein are upregulated during acute encephalitis induced by the human coronavirus OC43 (HCoV-OC43) infection. The apoD upregulation coincides with glial activation, and its expression returns to normal levels when the virus is cleared, concomitantly to a resolved glial reactivity. In addition, the overexpression of human apoD in the neurons of Thy-1/ApoD transgenic mice results in a threefold increase of the number of mice surviving to HCoV-OC43 infection. This increased survival rate is correlated with an upregulated glial activation associated with a limited innate immune response (cytokines, chemokines) and T-cell infiltration into infected brains. Moreover, the protection seems to be associated with a restricted phospholipase A2 activity. These data reveal a role for apoD in the regulation of inflammation and suggest that it protects from HCoV-OC43-induced encephalitis, most likely through the phospholipase A2 signaling pathways.


title: Lomboaortic Lymphadenectomy in Gynecological Oncology: Laparotomy, Laparoscopy or Robot-Assisted Laparoscopy?

text: BACKGROUND The outcomes of paraaortic lymphadenectomy were compared for the treatment of gynecological malignancies to identify the most appropriate surgical approach. METHODS Our retrospective, multicentric study included 1304 patients who underwent paraaortic lymphadenectomy for gynecological malignancies. The patients were categorized into the following five groups based on treatment type: transperitoneal laparoscopy (group A, n = 198), extraperitoneal laparoscopy (group B, n = 681), robot-assisted transperitoneal laparoscopy (group C, n = 135), robot-assisted extraperitoneal laparoscopy (group D, n = 44), and laparotomy (group E, n = 246). RESULTS The prevalence of cancer types differed according to the surgical approach: there were more ovarian cancers in group E and more cervical cancers in groups B and D (p < 0.001). Estimated blood loss was higher in group E (844.2 mL) than in groups treated with minimally invasive interventions (115.8-141.5 mL, p < 0.005). For infrarenal dissection, fewer nodes were removed in group C compared with the other approaches (16 vs. 21 nodes, respectively, p < 0.05). The average operative time ranged from 169 min for group A to 247 min for group E (p < 0.001). Length of hospital stay was 14 days for group E versus 3.5 days for minimally invasive procedures (p < 0.05). The early postoperative grade 3 and superior Dindo-Clavien complications occurred in 9-10% of the patients in groups B-D, 15% of the patients in group E, and only 3% and 4% for groups A and C, respectively. The most common complication was lymphocele. CONCLUSIONS Laparotomy increases preoperative and postoperative morbidity. The robot-assisted transperitoneal approach demonstrated a poorer lymph node yield than laparotomy and extraperitoneal approaches.


title: Design Strategies and Applications of Biomaterials and Devices for Hernia Repair.

text: Hernia repair is one of the most commonly performed surgical procedures worldwide, with a multi-billion dollar global market. Implant design remains a critical challenge for the successful repair and prevention of recurrent hernias, and despite significant progress, there is no ideal mesh for every surgery. This review summarizes the evolution of prostheses design toward successful hernia repair beginning with a description of the anatomy of the disease and the classifications of hernias. Next, the major milestones in implant design are discussed. Commonly encountered complications and strategies to minimize these adverse effects are described, followed by a thorough description of the implant characteristics necessary for successful repair. Finally, available implants are categorized and their advantages and limitations elucidated, including non-absorbable and absorbable (synthetic and biologically derived) prostheses, composite prostheses, and coated prostheses. This review not only summarizes the state of the art in hernia repair, but also suggests future research directions toward improved hernia repair utilizing novel materials and fabrication methods.


title: In the rivers: Multiple adaptive radiations of cyprinid fishes (Labeobarbus) in Ethiopian Highlands.

text: Multiple repeated patterns of adaptive radiation were revealed in cyprinid fish inhabiting the compact geographic region of the Ethiopian Highlands. We found four independently evolved radiations in the evolutionary hexaploid (2n = 150) Labeobarbus lineage based on matrilineal relationships of >800 individuals. Each radiation displayed similar patterns of mouth phenotype diversification, and included ecomorphs/species of the generalized, lipped, scraping (one or two), and large-mouthed (one to three) types. All radiations were detected in geographically isolated rivers, and originated from different ancestral populations. This is the first documented case in which numerous parallel radiations of fishes occurred-via different ways-in a riverine environment. Some radiations are very recent and monophyletic, while others are older and include ecomorphs that originated in separate mini flocks and later combined into one. The diversification bursts among Ethiopian Labeobarbus were detected in the mid-upper reaches of rivers (1050-1550 m above sea level), which likely offer ecological opportunities that include diverse habitats yet poor fauna (i.e. lower competition and relaxed selection). This promising example of parallel evolution of adaptive radiation warrants further investigation.


title: Negative Susceptibility Vessel Sign and Underlying Intracranial Atherosclerotic Stenosis in Acute Middle Cerebral Artery Occlusion.

text: BACKGROUND AND PURPOSE The role of MR imaging in predicting underlying intracranial atherosclerotic stenosis before endovascular stroke therapy has not been studied. Our aim was to determine the diagnostic value of the negative susceptibility vessel sign on T2*-weighted gradient-echo MR imaging for predicting underlying intracranial atherosclerotic stenosis in patients with acute MCA occlusion. MATERIALS AND METHODS Ninety-one consecutive patients with acute stroke because of MCA occlusion underwent gradient-echo MR imaging and MRA before endovascular therapy. The negative susceptibility vessel sign was defined as an absence of a hypointense signal change within the occluded MCA on gradient-echo imaging. Underlying intracranial atherosclerotic stenosis was determined by conventional angiography. The sensitivity, specificity, predictive values, and accuracy of the negative susceptibility vessel sign for predicting the presence of underlying intracranial atherosclerotic stenosis were assessed. RESULTS The negative susceptibility vessel sign was identified in 42 (46.1%) of 91 patients, and 18 (19.8%) patients had an underlying intracranial atherosclerotic stenosis responsible for acute ischemic symptoms. The negative susceptibility vessel sign was more frequently observed in patients with intracranial atherosclerotic stenosis than in those without it (100% versus 32.9%, P < .001). In the prediction of an underlying intracranial atherosclerotic stenosis, the negative susceptibility vessel sign had 100% sensitivity, 67.1% specificity, 42.9% positive predictive value, 100% negative predictive value, and an accuracy of 73.6%. CONCLUSIONS The negative susceptibility vessel sign on gradient-echo MR imaging is a sensitive marker with a high negative predictive value for the presence of an underlying intracranial atherosclerotic stenosis in patients with acute ischemic stroke because of MCA occlusions. The susceptibility vessel sign can be used in decision-making when performing subsequent endovascular revascularization therapy in patients with acute MCA occlusions.


title: Transplantation of donor grafts with defined ratio of conventional and regulatory T cells in HLA-matched recipients.

text: BACKGROUNDIn preclinical murine and early clinical studies of hematopoietic cell transplantation, engineering of donor grafts with defined ratios of CD4+CD25+FoxP3+ Tregs to conventional T cells (Tcons) results in the prevention of graft-versus-host disease and improved immune reconstitution. The use of highly purified primary graft Tregs for direct cell infusion has potential advantages over impure immunomagnetic selection or culture expansion, but has not been tested clinically. We performed a phase I study of the timed addition of CD34-selected hematopoietic stem cells and Tregs, followed by Tcons for the treatment of patients with high-risk hematological malignancies.METHODSWe present interim evaluation of a single-center open phase I/II study of administration of human leukocyte-matched Tregs and CD34-selected hematopoietic cells, followed by infusion of an equal ratio of Tcons in adult patients undergoing myeloablative hematopoietic stem cell transplantation (HCT) for high-risk or active hematological malignancies. Tregs were purified by immunomagnetic selection and high-speed cell sorting.RESULTSHere we report results for the first 12 patients who received Tregs of between 91% and 96% purity. Greater than grade II GVHD was noted in 2 patients in the first cohort of 5 patients, who received cryopreserved Tregs, but neither acute nor chronic GVHD was noted in the second cohort of 7 patients, who received fresh Tregs and single-agent GVHD prophylaxis. Patients in the second cohort appeared to have normal immune reconstitution compared with patients who underwent transplantation and did not develop GVHD.CONCLUSIONOur study shows that the use of highly purified fresh Tregs is clinically feasible and supports continued investigation of the strategy.TRIAL REGISTRATIONClinicalTrials.gov NCT01660607.FUNDINGNIH NHBLI R01 HL114591 and K08HL119590.


title: Glucosamine conjugates bearing N,N,O-donors: potential imaging agents utilizing the [M(CO)3]+ core (M = Re, Tc).

text: The design rationale, synthesis and radiolabeling evaluation of four glucosamine conjugated ligands for the [(99m)Tc(CO)(3)](+) core is described. The capability to bind the tricarbonyl core is initially demonstrated using the cold surrogate [Re(CO)(3)](+). The four compounds are competent chelates in binding [(99m)Tc(CO)(3)](+) as labeling studies show, with yields ranging from 79 to 96% and the resulting complexes showing stability in the presence of competing chelates for 24 h at 37 degrees C. The rhenium complexes were tested for hexokinase-catalysed phosphorylation, and the technetium complexes were tested for GLUT-1 mediated cell uptake--they showed a small amount of uptake but it was not glucose dependent, suggesting that it was not via the GLUT-1 transporters.


title: Transcranial Direct Current Stimulation in ADHD: A Systematic Review of Efficacy, Safety, and Protocol-induced Electrical Field Modeling Results.

text: Transcranial direct current stimulation (tDCS) is a promising method for altering cortical excitability with clinical implications. It has been increasingly used in neurodevelopmental disorders, especially attention-deficit hyperactivity disorder (ADHD), but its efficacy (based on effect size calculations), safety, and stimulation parameters have not been systematically examined. In this systematic review, we aimed to (1) explore the effectiveness of tDCS on the clinical symptoms and neuropsychological deficits of ADHD patients, (2) evaluate the safety of tDCS application, especially in children with ADHD, (3) model the electrical field intensity in the target regions based on the commonly-applied and effective versus less-effective protocols, and (4) discuss and propose advanced tDCS parameters. Using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses approach, a literature search identified 14 empirical experiments investigating tDCS effects in ADHD. Partial improving effects of tDCS on cognitive deficits (response inhibition, working memory, attention, and cognitive flexibility) or clinical symptoms (e.g., impulsivity and inattention) are reported in 10 studies. No serious adverse effects are reported in 747 sessions of tDCS. The left and right dorsolateral prefrontal cortex are the regions most often targeted, and anodal tDCS the protocol most often applied. An intensity of 2 mA induced stronger electrical fields than 1 mA in adults with ADHD and was associated with significant behavioral changes. In ADHD children, however, the electrical field induced by 1 mA, which is likely larger than the electrical field induced by 1 mA in adults due to the smaller head size of children, was sufficient to result in significant behavioral change. Overall, tDCS seems to be a promising method for improving ADHD deficits. However, the clinical utility of tDCS in ADHD cannot yet be concluded and requires further systematic investigation in larger sample sizes. Cortical regions involved in ADHD pathophysiology, stimulation parameters (e.g. intensity, duration, polarity, and electrode size), and types of symptom/deficit are potential determinants of tDCS efficacy in ADHD. Developmental aspects of tDCS in childhood ADHD should be considered as well.


title: Long-acting muscarinic antagonists (LAMA) added to inhaled corticosteroids (ICS) versus higher dose ICS for adults with asthma.

text: BACKGROUND Long-acting muscarinic antagonists (LAMA), a class of drugs with proven effectiveness in chronic obstructive pulmonary disease (COPD), are being considered as an add-on option for adults with asthma whose condition is uncontrolled on inhaled corticosteroids (ICS). It is important to assess the safety and efficacy of LAMA add-on as an alternative to the prolonged use of higher doses of ICS, which are known to cause undesirable side effects in some people. OBJECTIVES To compare the effects of adding a LAMA to any dose of ICS versus increasing the dose of ICS, for uncontrolled asthma in adults. SEARCH METHODS We searched the Cochrane Airways Group Specialised Register (CAGR) from its inception in 1995 to April 2015, imposing no restriction on language of publication. We also handsearched trial registries, reference lists of primary studies and existing reviews, as well as manufacturers' websites. SELECTION CRITERIA We looked for parallel or cross-over randomised controlled trials lasting at least 12 weeks, in which adults whose asthma was not well controlled on ICS alone were randomised to treatment with LAMA add-on to ICS or with an increased dose of ICS. Trials were excluded if patients were taking long-acting beta2-agonists during the study period. DATA COLLECTION AND ANALYSIS Two review authors independently screened the searches and extracted data from studies meeting all the inclusion criteria. We used Covidence to manage duplicate screening, data extraction and risk of bias judgements, and to form a consensus where discrepancies arose. We used standard methods expected by The Cochrane Collaboration.The pre-specified primary outcomes were exacerbations requiring a course of oral corticosteroids (OCS), effects on quality of life and serious adverse events. MAIN RESULTS One cross-over randomised controlled trial met the inclusion criteria. The trial was performed in 210 patients with moderate to severe asthma and compared the use of the LAMA tiotropium bromide with double dose beclomethasone (an ICS) using a cross-over design and 14-week treatment periods.Compared with people taking a double dose of ICS, fewer people taking a LAMA add-on had an exacerbation requiring treatment with OCS (odds ratio (OR) 0.57, 95% confidence interval (CI) 0.22 to 1.43) or an exacerbation resulting in emergency department admission (OR 0.49, 95% CI 0.09 to 2.77), but the confidence intervals for both outcomes did not exclude the possibility that double dose ICS was more effective. Serious adverse events and exacerbations requiring hospitalisation occurred in similarly low numbers of people taking each treatment, but confidence intervals were too wide to suggest that the two treatment options were equivalent.Asthma-related quality of life was similar in both treatment groups (mean difference (MD) in change from baseline 0.10, 95% CI - 0.07 to 0.27). Those taking LAMA add-on scored slightly better on a scale measuring asthma control than those increasing their ICS dose (MD in change from baseline - 0.18, 95% CI - 0.34 to - 0.02), although the difference was clinically small. Evidence was deemed low quality for both quality of life and asthma control.There was moderate-quality evidence that participants' trough forced expiratory volume in one second (FEV1) was 100 mL better when taking LAMA add-on than with increased ICS dose (MD in change from baseline 0.10, 95% CI 0.03 to 0.17). AUTHORS' CONCLUSIONS Only one randomised trial was found, comparing tiotropium add-on to increased dose beclomethasone. Differences between the treatments were too small or imprecise to understand whether adding a LAMA to ICS is safer or more effective than increasing the dose of ICS, and there is a possibility of carry-over effects due to the study's cross-over design. LAMA add-on may lead to more improvement in lung function (FEV1) than an increased dose of ICS.The results of this review, alongside pending results from related reviews assessing the use of LAMA against other treatments, will help to define the role of these drugs in asthma management, and this review should be updated as results from future trials emerge. Studies assessing the role of LAMA add-on should be longer and include a double-ICS treatment arm so that the results can be interpreted in the context of the guideline-recommended treatment options that are available to physicians.


What is the potential function of microRNAs as biomarkers and therapeutic targets in COVID-19?


title: Laparoscopic Spigelian Hernia Repair: A Series of 40 Patients.

text: Spigelian hernias are a rare abdominal wall hernia. The aim of this study was to assess the efficacy and outcomes of patients who underwent a laparoscopic spigelian hernia repair. A retrospective study was performed reviewing all patients who had a laparoscopic spigelian hernia repair. We assessed the success of the procedure including conversion rates, postoperative morbidities, and recurrence rates. Forty patents had a laparoscopic repair. Two thirds (n=25) had an intraperitoneal repair. There was no conversion to open repair. Four patients had postoperative morbidities. At 6-month follow-up all patients were pain free, with 1 recurrence. There is considerable evidence supporting the opinion that laparoscopic repair offers excellent outcomes. This report is the largest series to date, and we advocate that this approach should become the standard of care.


title: Factors affected by surgical technique when treating total colonic aganglionosis: laparoscopy-assisted versus open surgery.

text: INTRODUCTION We compared laparoscopy-assisted Duhamel (Lap-D) with open surgery (Duhamel or Soave = D/S) for treating total colonic aganglionosis (TCA) in children to establish what factors may affect outcome. METHODS Fourteen TCA cases treated between 1990 and 2010 were reviewed. Open D/S (O-D/S) through a vertical midline abdominal incision was routine from 1990 to 2005, whereupon Lap-D became routine. Lap-D involves laparoscopic colon resection, ileostomy take-down, and ileum pull-through through an additional Pfannenstiel incision. We compared pre-operative nutrition, operating time, intraoperative blood loss, duration until oral challenge, postoperative analgesic usage, incidence of enterocolitis, early complications that arose within 30 days of surgery, and late complications, and wound cosmesis 1 year postoperatively (Grade-1: unacceptable, Grade-2: passable, Grade-3: excellent). RESULTS Six had O-D/S (2D, 4S) and eight had Lap-D. Differences in patient demographics, mean ages/weights at surgery, average length of the aganglionic segment from the terminal ileum, operating time, and time taken for oral challenge were all not significant, full feeding took longer in O-D/S (6.7 vs. 5.9 days). Preoperative central vein intravenous hyperalimentation was required for one case in O-D/S and two cases in Lap-D. These three required hospitalization for at least 30 days postoperatively and parenteral nutrition after discharge. Although there were no intraoperative complications in either group, there was one case of transient ileus in O-D/S that resolved conservatively. Cosmesis was significantly better in Lap-D (O-D/S = 1.2; Lap-D = 2.1; p < 0.05). CONCLUSIONS Cosmesis was the only factor that was significantly different between Lap-D and O-D/S; all other factors were similar.


title: Integrity of the early secretory pathway promotes, but is not required for, severe acute respiratory syndrome coronavirus RNA synthesis and virus-induced remodeling of endoplasmic reticulum membranes.

text: To accommodate its RNA synthesis in the infected cell, severe acute respiratory syndrome coronavirus (SARS-CoV) induces a cytoplasmic reticulovesicular network (RVN) that is derived from endoplasmic reticulum (ER) membranes. We set out to investigate how the early secretory pathway interacts with the RVN and the viral replication/transcription complex (RTC) that is anchored to it. When the secretory pathway was disrupted by brefeldin A (BFA) treatment at the start of infection, RVN formation and viral RTC activity were not blocked and continued up to 11 h postinfection, although RNA synthesis was reduced by ca. 80%. In vitro RTC assays, using membrane fractions from infected cells, demonstrated that BFA does not directly interfere with the activity of the viral RNA-synthesizing enzymes. Confocal microscopy studies showed that early secretory pathway components are not associated with SARS-CoV-induced replication sites, although our studies revealed that infection induces a remarkable redistribution of the translocon subunit Sec61alpha. Ultrastructural studies, including electron tomography, revealed that the formation of the RVN and all its previously documented features can occur in the presence of BFA, despite differences in the volume and morphology of the network. We therefore conclude that early secretory pathway proteins do not play a direct role in RVN morphogenesis or the functionality of the SARS-CoV RTC. The BFA-induced disruption of ER integrity and functionality probably affects the overall quality of the membrane scaffold that is needed to support the viral RTC and/or the availability of specific host factors, which in turn compromises viral RNA synthesis.


The Evolving Role of Computed Tomographic Angiography for Lower Gastrointestinal Hemorrhage.


title: Neutrophils are essential for induction of vaccine-like effects by antiviral monoclonal antibody immunotherapies.

text: Using a mouse retroviral model, we have shown that mAb-based immunotherapy can induce life-long endogenous protective immunity (vaccine-like effects). This observation has potentially important consequences for treating life-threatening human viral infections. Here, we investigated the role of neutrophils in this effect. Neutrophils are innate immunity effector cells with well-established microbe-killing activities that are rapidly mobilized upon infection. They are also emerging as orchestrators of innate and adaptive immunities. However, their immunomodulatory activity during antiviral mAb immunotherapies has never been studied. Our data reveal that neutrophils have an essential role in immunotherapy-induced immune protection of infected mice. Unexpectedly, neutrophils have a limited effect in controlling viral propagation upon passive immunotherapy administration, which is mostly mediated by NK cells. Instead, neutrophils operate as essential inducers of a potent host humoral antiviral response. Thus, neutrophils play an unexpected key role in protective immunity induction by antiviral mAbs. Our work opens approaches to improve antiviral immunotherapies, as it suggests that preserving neutrophil functions and counts might be required for achieving mAb-induced protective immunity.


title: Target-dependent B7-H1 regulation contributes to clearance of central nervous system infection and dampens morbidity.

text: The neurotropic coronavirus JHM strain of mouse hepatitis virus persists in oligodendroglia despite the presence of virus-specific CD8 T cells. Expression of programmed death 1 (PD-1) and B7-H1 were studied during acute and persistent infection to examine whether this negative regulatory mechanism contributes to CNS viral persistence. The majority of CNS-infiltrating CD8 T cells expressed PD-1, with the highest levels on virus-specific CD8 T cells. Moreover, despite control of infectious virus, CD8 T cells within the CNS of persistently infected mice maintained high PD-1 expression. Analysis of virus-susceptible target cells in vivo revealed that B7-H1 expression was regulated in a cell type-dependent manner. Oligodendroglia and microglia up-regulated B7-H1 following infection; however, although B7-H1 expression on oligodendroglia was prominent and sustained, it was significantly reduced and transient on microglia. Infection of mice deficient in the IFN-gamma or IFN-alpha/beta receptor demonstrated that B7-H1 expression on oligodendroglia is predominantly regulated by IFN-gamma. Ab blockade of B7-H1 on oligodendroglia in vitro enhanced IFN-gamma secretion by virus-specific CD8 T cells. More efficient virus control within the CNS of B7-H1-deficient mice confirmed inhibition of CD8 T cell function in vivo. Nevertheless, the absence of B7-H1 significantly increased morbidity without altering demyelination. These data are the first to demonstrate glia cell type-dependent B7-H1 regulation in vivo, resulting in adverse effects on antiviral CD8 T cell function. However, the beneficial role of PD-1:B7-H1 interactions in limiting morbidity highlights the need to evaluate tissue-specific intervention strategies.


title: Rapid hemostasis in a sheep model using particles that propel thrombin and tranexamic acid.

text: OBJECTIVES/HYPOTHESIS Bleeding during endoscopic sinus surgery and open surgeries can easily obstruct the surgeons' field of view and increase morbidity and risk of intraoperative complications. Intraoperative bleeding could potentially be addressed by a hemostatic agent that safely disperses itself through the escaping blood. We tested the safety and efficacy of a self-propelling formulation of thrombin and tranexamic acid (SPTT) in stopping bleeding in a paranasal sinus injury and in an open surgical carotid injury sheep model. STUDY DESIGN Interventional animal study. METHODS SPTT was tested in the sinonasal space following endoscopic injury to the inferior turbinate of six sheep, and to the common carotid artery following open surgical injury in eight sheep. In the nasal cavity, bleeding time and local inflammation were measured and compared to plain gauze. Following carotid arteriotomy, successful hemostasis and markers of thrombosis and coagulopathy were compared to Floseal. RESULTS SPTT significantly decreased bleeding times in the sinonasal space compared to plain gauze (mean difference = 3.8 minutes, P = .002). All of the carotid bleeds (100%) were successfully controlled with SPTT after 10 minutes of application under pressure, compared to 25% with Floseal. No adverse events were noted, and there was no evidence of thromboembolism. CONCLUSIONS SPTT significantly reduced bleeding time in a sheep model of surgical sinus bleeding and successfully stopped bleeding following catastrophic carotid artery injury, with no adverse events observed. LEVEL OF EVIDENCE NA Laryngoscope, 127:787-793, 2017.


Clinical Rounds.


title: Managing New-Onset Type 1 Diabetes During the COVID-19 Pandemic: Challenges and Opportunities.

text: Background: The current COVID-19 pandemic provides an incentive to expand considerably the use of telemedicine for high-risk patients with diabetes, and especially for the management of type 1 diabetes (T1D). Telemedicine and digital medicine also offer critically important approaches to improve access, efficacy, efficiency, and cost-effectiveness of medical care for people with diabetes. Methods: Two case reports are presented where telemedicine was used effectively and safely after day 1 in person patient education. These aspects of the management of new-onset T1D patients (adult and pediatric) included ongoing diabetes education of the patient and family digitally. The patients used continuous glucose monitoring with commercially available analysis software (Dexcom Clarity and Glooko) to generate ambulatory glucose profiles and interpretive summary reports. The adult subject used multiple daily insulin injections; the pediatric patient used an insulin pump. The subjects were managed using a combination of e-mail, Internet via Zoom, and telephone calls. Results: These two cases show the feasibility and effectiveness of use of telemedicine in applications in which we had not used it previously: new-onset diabetes education and insulin dosage management. Conclusions: The present case reports illustrate how telemedicine can be used safely and effectively for new-onset T1D training and education for both pediatric and adult patients and their families. The COVID-19 pandemic has acutely stimulated the expansion of the use of telemedicine and digital medicine. We conclude that telemedicine is an effective approach for the management of patients with new-onset T1D.


title: Does radiofrequency ablation (RFA) epiphysiodesis affect adjacent joint cartilage?

text: PURPOSE To test the hypothesis that epiphysiodesis made with radiofrequency ablation (RFA) is a safe procedure that disrupts the growth plate without damaging the adjacent joint articular cartilage. METHODS RFA epiphysiodesis was done during 8 min in vivo in 40 growing pig tibia physis. In addition, three tibiae were ablated for 16 min and three more for 24 min. As a burned cartilage reference, six tibiae were ablated on the joint articular cartilage for 8 min. After the procedure, the animals were terminated and the tibiae were harvested. Magnetic resonance imaging (MRI) was done ex vivo to evaluate the joint articular cartilage in all samples. We used T1-weighted, T2-weighted, and water content sequences under a 1.5 T magnetic field. RESULTS On the burned articular cartilage, intensity changes were observed at MRI. We found no evidence of articular cartilage damage on the 40 8-min RFA procedures. The tibiae ablated for 16 min and 24 min showed intact joint cartilage. CONCLUSIONS Epiphysiodesis using RFA is safe for the adjacent articular cartilage. This study shows that RFA can be done safely in the growing physis of pigs, even with triple duration procedures.


title: Gastric Band Surgery Leads to Improved Insulin Secretion in Overweight People with Type 2 Diabetes.

text: BACKGROUND We aimed to determine the effects of laparoscopic adjustable gastric band (LAGB) on beta-cell function in overweight people with type 2 diabetes and to assess the relationship between baseline beta-cell function and glycemic outcomes. METHODS We studied 44 overweight but not obese people with type 2 diabetes who participated in a randomized trial whose primary outcome was the rate of diabetes remission after 2 years of multidisciplinary diabetes care (MDC group) or multidisciplinary care combined with LAGB. Dynamic beta-cell function was assessed by intravenous glucose challenge, and basal beta-cell function (HOMA-B) and insulin sensitivity (HOMA-S) were determined using the homeostatic model. RESULTS Twelve LAGB participants and two MDC participants were in diabetes remission at 2 years. HOMA-S and the C-peptide response to intravenous glucose increased significantly in LAGB but not in MDC participants. The insulin response to glucose did not change in LAGB participants, whereas their fasting C-peptide/insulin ratio increased. Baseline measures of beta-cell function correlated with diabetes remission but not with reduction in HbA1c following LAGB. CONCLUSIONS In overweight people with diabetes, LAGB improves endogenous beta-cell function after 2 years. Baseline beta-cell function correlated with diabetes remission, but not with HbA1c change following LAGB.


title: Oropharyngeal pH Testing Does Not Predict Response to Proton Pump Inhibitor Therapy in Patients with Laryngeal Symptoms.

text: OBJECTIVES Predicting response to proton pump inhibitor (PPI) therapy in patients with laryngeal symptoms is challenging. The Restech Dx-pH probe is a transnasal catheter that measures oropharyngeal pH. In this study, we aimed to investigate the prognostic potential of oropharyngeal pH monitoring to predict responsiveness to PPI therapy in patients with laryngeal symptoms. METHODS We conducted a physician-blinded prospective cohort study at a single academic institution between January 2013 and October 2014. Adult patients with Reflux Symptom Index scores (RSI) ≥13 off PPI therapy were recruited. Patients underwent video laryngoscopy and 24-h oropharyngeal pH monitoring, followed by an 8- to 12-week trial of omeprazole 40 mg daily. Prior to and following PPI therapy, patients completed various symptom questionnaires. The primary outcome was the association between PPI response and oropharyngeal pH metrics. PPI response was separated into three subgroups based on the post-treatment RSI score and % RSI response: non-response=RSI ≥13; partial response=post-treatment RSI <13 and change in RSI <50%; and complete response=post-treatment RSI <13 and change in RSI ≥50%. The primary analysis utilized a multinomial logistic regression controlling for the pre-treatment RSI score. A secondary analysis assessed the relationship between the change in RSI (post-pre) and oropharyngeal pH metrics via ordinary least square regression. RESULTS Thirty-four patients completed the study and were included in final analysis. Symptom response to PPI therapy was as follows: 50% no response, 15% partial response, and 35% complete response. Non-responders had a higher pre-treatment RSI (P<0.01). There were no significant differences in oropharyngeal acid exposure (below pH of 4.0, 5.0, 5.5, 6.0, and RYAN scores) between responder types. The secondary analysis noted a trend between lower PPI response and a greater total percent time below pH of 5.0 (P=0.03), upright percent time below pH of 5.0 (P=0.07), and RYAN supine (corrected; P=0.03), as well as an association between PPI response and greater decreases in the Anxiety Sensitivity Inventory (P<0.01), Brief Symptom Inventory-18 (P<0.01), and Negative Affect Scale (P<0.01). CONCLUSIONS Oropharyngeal pH testing did not predict laryngeal symptom response to PPI therapy. Contrary to hypothesis, our study signaled that the degree of oropharyngeal acid exposure is inversely related to PPI response. In addition, reduction in negative affect and psychological distress parallels PPI response.


title: Oncohematological diseases in the Vale do Paraíba, State of São Paulo: demographic aspects, prevalences and incidences.

text: BACKGROUND Based on the necessity of detailed information that supports effective strategies to improve cancer outcomes in the different regions of Brazil, the aims of this study were to report demographic aspects and to calculate the prevalence and incidence rates of oncohematological diseases in the region of Vale do Paraíba. METHODS This is a multicentric prospective study carried out from October 2009 to March 2010. A total of 500 over 19-year-old patients were enrolled. Data such as type of healthcare insurance, gender, age, ethnic classification, place of residence, schooling, income, body mass index, new cases and the period between the first symptoms and a definite diagnosis were collected. The prevalence and incidence rates were calculated according to an estimated number of 1,319,800 inhabitants. RESULTS The prevalence and incidence rates per 100,000 inhabitants in the period of six months were, respectively: acute myeloid leukemia 1.5 and 0.7; acute lymphoblastic leukemia 0.5 and 0.1; chronic lymphocytic leukemia 2.4 and 0.4; chronic myeloid leukemia 6.2 and 0.8; Hodgkin's lymphoma 2.9 and 0.9; non-Hodgkin lymphoma 9.8 and 4.3; multiple myeloma 5.7 and 0.7; myelodysplastic syndromes 2.1 and 0.2 and myeloproliferative syndromes 5.1 and 0.3. CONCLUSION Giving the paucity of data in this field of investigation, our data may be useful for comparisons with those of other regions of Brazil and will assist in the implementation of treatment programs of oncohematological diseases in this region.


title: Influence of hang time and location on bacterial contamination of intravenous bags in a veterinary emergency and critical care setting.

text: OBJECTIVE To assess the rate of bacterial contamination of fluid and ports in intravenous bags in a veterinary emergency room (ER) and intensive care unit (ICU). DESIGN Experimental model. SETTING Ninety intravenous fluid bags of lactated balanced-electrolytes solution (1 L) hung in a university hospital. INTERVENTIONS Bags were hung in 2 different locations in the ER (sink and bins) and one location in the ICU (sink) for 11 days. Bags were punctured 3 times daily with a sterile needle to simulate clinical use. Injection ports were swabbed and 50 mL of fluid were collected in duplicates on days 0, 2, 4, 7, and 10. Aerobic bacterial cultures were performed on the fluid and injection port. Contamination was defined as bacterial growth of a similar phenotype across 2 consecutive times. Increase in the fluid contamination rate from day 0 was tested using an exact binomial test. Port contamination rate between locations was tested using Fisher's exact test. MAIN RESULTS Combined bacterial growth on injection ports reached a mean (95% confidence interval) of 8.1 (0.005-16.2) cfu/port on day 10. The combined port contamination was 3.3%, 11.1%, 17.8%, and 31.1% on days 0, 2, 4, and 7, respectively. Port contamination was similar between ER and ICU. However, port contamination was higher in the sink versus the bins area (38.3% vs 16.7%, P = 0.032). No fluid bag was contaminated at days 0 and 2. The contamination rate of fluid bag was 1.1% and 4.4% on days 4 and 7, respectively. All bags with contaminated fluid were in the ER (6.7%, 95% exact binomial confidence interval 1.9-16.2%). CONCLUSIONS Injection port contamination reached 31.1% on day 7. Contamination was more likely when the bags were hung next to a sink. In our model of bag puncture, fluid contamination occurred between days 2 and 4.


title: Surgical complications after peritoneal dialysis catheter implantation depend on children's weight.

text: BACKGROUND Surgical complications are estimated to be as high as 30%-40% during the first 8 weeks after implantation of peritoneal dialysis (PD) catheters. METHODS 70 PD catheters which were implanted by transplant surgeons in 61 children (median age 3.3years, range 0.01-15.5years, 31 boys and 30 girls) in 2009-2014 were retrospectively reviewed. The incidence of complications and revisions during the first 6months after implantation was analyzed depending on children's weight and diagnosis. RESULTS 17 out of 70 catheters needed a surgical revision within 6months after implantation (24.3%). Peritonitis was the most common complication affecting 18.6% of peritoneal dialysis catheters followed by obstruction and dislocation, which it occurred in 9 (12.9%) and 7 (10%) catheters, respectively. Leakage (n=5) only occurred in children with a weight of less than 10kg. The total proportion of complications was higher in children with less than 10kg of weight (P<0.001). CONCLUSION PD is safe in children with acute renal failure and older children with chronic renal failure; however children with a weight of less than 10kg are more likely to develop complications.


title: Telemedicine Algorithm for the Management of Dizzy Patients.

text: As a result of the COVID-19 pandemic, telemedicine has been thrust to the forefront of health care. Despite its inherent limitations, telemedicine offers many advantages to both patient and physician as an alternative to in-person evaluation of select patients. In the near term, telemedicine allows nonpandemic care to proceed while observing appropriate public health concerns to minimize the spread of pandemic pathogens. Thus, it behooves practitioners to use telemedicine consultations for common otolaryngology complaints. Assessment of the dizzy patient is well-suited to an algorithmic approach that can be adapted to a telemedicine setting. As best practices for telemedicine have yet to be defined, we present herein a practical approach to the history and limited physical examination of the dizzy patient in the telemedicine setting for the general otolaryngologist. Indeed, once the acute crisis has abated, we suspect that this approach will continue to be an effective way to manage dizzy patients.


title: Antagonism of RNase L Is Required for Murine Coronavirus Replication in Kupffer Cells and Liver Sinusoidal Endothelial Cells but Not in Hepatocytes.

text: Mouse hepatitis virus strain A59 infection of mice is a useful tool for studying virus-host interaction during hepatitis development. The NS2H126R mutant is attenuated in liver replication due to loss of phosphodiesterase activity, which the wild-type (WT) virus uses to block the 2',5'-oligoadenylate synthetase (OAS)-RNase L (RNase L) antiviral pathway. The activation of RNase L by NS2H126R is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We tested the hypothesis that the resident liver macrophages, Kupffer cells (KC), represent the cell type most likely to restrict NS2H126R and prevent hepatitis. As found previously, A59 and NS2H126R replicate similarly in hepatocytes and neither activates RNase L, as assessed by an rRNA degradation assay. In contrast, in KC, A59 exhibited a 100-fold-higher titer than NS2H126R and NS2H126R induced rRNA degradation. Interestingly, in liver sinusoidal endothelial cells (LSEC), the cells that form a barrier between blood and liver parenchymal cells, NS2H126R activates RNase L, which limits viral replication. Similar growth kinetics were observed for the two viruses in KC and LSEC from RNase L-/- mice, demonstrating that both use RNase L to limit NS2H126R replication. Depletion of KC by gadolinium(III) chloride or of LSEC by cyclophosphamide partially restores liver replication of NS2H126R, leading to hepatitis. Thus, during mouse hepatitis virus (MHV) infection, hepatitis, which damages the parenchyma, is prevented by RNase L activity in both KC and LSEC but not in hepatocytes. This may be explained by the undetectable levels of RNase L as well as by the OASs expressed in hepatocytes. IMPORTANCE Mouse hepatitis virus infection of mice provides a useful tool for studying virus-host interactions during hepatitis development. The NS2H126R mutant is attenuated in liver replication due to loss of phosphodiesterase activity, by which the wild-type virus blocks the potent OAS-RNase L antiviral pathway. RNase L activation by NS2H126R is cell type dependent and correlates with high basal expression levels of OAS, as found in myeloid cells. We showed that the hepatocytes that comprise the liver parenchyma do not activate RNase L when infected with NS2H126R or restrict replication. However, both Kupffer cells (KC) (i.e., the liver-resident macrophages) and the liver sinusoidal endothelial cells (LSEC) which line the sinusoids activate RNase L in response to NS2H126R These data suggest that KC and LSEC prevent viral spread into the parenchyma, preventing hepatitis. Furthermore, hepatocytes express undetectable levels of OASs and RNase L, which likely explains the lack of RNase L activation during NS2H126R infection.


title: Embedded Bio-Mimetic System for Functional Electrical Stimulation Controlled by Event-Driven sEMG.

text: The analysis of the surface ElectroMyoGraphic (sEMG) signal for controlling the Functional Electrical Stimulation (FES) therapy is being widely accepted as an active rehabilitation technique for the restoration of neuro-muscular disorders. Portability and real-time functionalities are major concerns, and, among others, two correlated challenges are the development of an embedded system and the implementation of lightweight signal processing approaches. In this respect, the event-driven nature of the Average Threshold Crossing (ATC) technique, considering its high correlation with the muscle force and the sparsity of its representation, could be an optimal solution. In this paper we present an embedded ATC-FES control system equipped with a multi-platform software featuring an easy-to-use Graphical User Interface (GUI). The system has been first characterized and validated by analyzing CPU and memory usage in different operating conditions, as well as measuring the system latency (fulfilling the real-time requirements with a 140 ms FES definition process). We also confirmed system effectiveness, testing it on 11 healthy subjects: The similarity between the voluntary movement and the stimulate one has been evaluated, computing the cross-correlation coefficient between the angular signals acquired during the limbs motion. We obtained high correlation values of 0.87 ± 0.07 and 0.93 ± 0.02 for the elbow flexion and knee extension exercises, respectively, proving good stimulation application in real therapy-scenarios.


The Spectrum of Neurologic Disease in the Severe Acute Respiratory Syndrome Coronavirus 2 Pandemic Infection: Neurologists Move to the Frontlines.


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title: Single-incision versus 3-port laparoscopic cholecystectomy in symptomatic gallstones: A prospective randomized study.

text: BACKGROUND Laparoscopic cholecystectomy is the standard treatment for symptomatic gallbladder disease. Single-incision laparoscopic surgery was developed with the aim of decreasing the invasiveness of conventional laparoscopy. The aim of this study was to compare the clinical outcome of single-incision laparoscopic cholecystectomy with 3-port laparoscopic cholecystectomy. METHODS From February 2014 to September 2016, 187 patients with symptomatic cholecystolithiasis were randomized to a single-incision laparoscopic cholecystectomy group (89 patients) or a 3-port laparoscopic cholecystectomy group (98 patients). The primary outcomes were a postoperative pain score (at 6 hours and 1 day) and patients of complications, while the secondary outcomes were operative time, estimated blood loss, opioid requirements, duration of hospital stay, and patient satisfaction with aesthetic effects. RESULTS When comparing 3-port laparoscopic cholecystectomy and single-incision laparoscopic cholecystectomy, there were differences in the (mean ± standard deviation) operative time (58.9 ± 18.6 minutes vs 45.2 ± 11.8 minutes; P < .001), success rate (93% vs 99%; P < .01), conversion rate (7% vs 1%; P < .001), and aesthetic score (7.9 ± 1.6 vs 6.7 ± 1.4; P = .008). There were no statistically significant differences in estimated blood loss, postoperative pain, opioid requirement, complications, and hospital stay between both groups. CONCLUSION Single-incision laparoscopic cholecystectomy is a safe and feasible procedure in selected patients. The main advantage is the superior aesthetic results, while the main disadvantage is a greater operative time with some technical difficulties.


title: Safety and Feasibility of Linear Stapling Device with Bioabsorbable Polyglycolic Acid Sheet for Duodenal Closure in Gastric Cancer Surgery: A Multi-institutional Phase II Study.

text: BACKGROUND Duodenal stump fistula (DSF) after gastrectomy is of low frequency but a critical complication in gastric cancer surgery. Manual oversewing for reinforcement of the duodenal stump is not applicable when free longitudinal margin is short and has technical difficulties in laparoscopic surgery. This trial evaluated the safety and feasibility of using a linear stapler with bioabsorbable polyglycolic acid (PGA) sheet for duodenal stump closure and reinforcement in gastric cancer surgery. METHODS This multi-institutional, prospective phase II trial included gastric cancer patients who were scheduled to undergo distal or total gastrectomy with R-Y reconstruction. In all cases, duodenum was transected using a linear stapler with PGA sheet. The primary endpoint was the incidence of postoperative DSF. Sample size was set at 100 patients considering an expected value of 3% and threshold value of 8% with one-sided testing at a 10% significance level. RESULTS Between June 2014 and June 2015, a total of 100 patients were registered in this trial. Postoperative DSF was observed in two cases (2.0%, 90% CI 0.4-6.2%) which was developed on postoperative days 13 and 20. Intraoperative bleeding at the duodenal stump staple line was observed in one case but was easily controlled without additional suturing. Postoperative bleeding was not observed in any of the cases. CONCLUSION This study suggested that the use of PGA sheet as a reinforcement material for closure of the duodenal stump during gastrectomy for gastric cancer is both safe and feasible. Trial registration number UMIN 000014398.


title: PARASITOLOGY AND SEROLOGY OF FREE-RANGING COYOTES (CANIS LATRANS) IN NORTH CAROLINA, USA.

text: Coyotes (Canis latrans) have expanded recently into the eastern US and can serve as a source of pathogens to domestic dogs (Canis lupus familiaris), livestock, and humans. We examined free-ranging coyotes from central North Carolina, US, for selected parasites and prevalence of antibodies against viral and bacterial agents. We detected ticks on most (81%) coyotes, with Amblyomma americanum detected on 83% of those with ticks. Fifteen (47%) coyotes were positive for heartworms (Dirofilaria immitis), with a greater detection rate in adults (75%) than juveniles (22%). Serology revealed antibodies against canine adenovirus (71%), canine coronavirus (32%), canine distemper virus (17%), canine parvovirus (96%), and Leptospira spp. (7%). We did not detect antibodies against Brucella abortus/suis or Brucella canis. Our results showed that coyotes harbor many common pathogens that present health risks to humans and domestic animals and suggest that continued monitoring of the coyote's role in pathogen transmission is warranted.


title: Mechanical Thrombectomy with Solitaire Stent Retrieval for Acute Cardioembolic Stroke.

text: Objective Few studies have reported the outcome of mechanical thrombectomy with Solitaire stent retrival (MTSR) in subtypes of acute ischemic stroke. The purpose of this study was to evaluate the efficacy and result of MTSR in acute cardioembolic stroke. Methods Twenty consecutive patients with acute cardioembolic stroke were treated by MTSR. The angiographic outcome was assessed by thrombolysis in cerebral infarction (TICI) grade. TICI grade 2a, 2b, or 3 with a measurable thrombus that was retrieved was considered as a success when MTSR was performed in the site of primary vessel occlusion, and TICI grade 2b or 3 was considered as a success when final result was reported. Clinical and radiological results were compared between two groups divided on the basis of final results of MTSR. Persistent thrombus compression sign on angiogram was defined as a stenotic, tapered arterial lumen whenever temporary stenting was performed. The clinical outcomes were assessed by the modified Rankin Scale (mRS) at 3 months. Results The failure rate of MTSR was 20% (4/20) and other modalities, such as permanent stenting, were needed. Final successful recanalization (TICI grade 2b or 3) was 80% when other treatments were included. The rate of good outcome (mRS≤2) was 35% at the 3-month follow-up. Failure of MTSR was significantly correlated with persistent thrombus compression sign (p=0.001). Conclusion Some cases of cardioembolic stroke are resistant to MTSR and may need other treatment modalities. Careful interpretation of angiogram may be helpful to the decision.


title: Cohort profile: Thrombolysis in Ischemic Stroke Patients (TRISP): a multicentre research collaboration.

text: PURPOSE The ThRombolysis in Ischemic Stroke Patients (TRISP) collaboration aims to address clinically relevant questions about safety and outcomes of intravenous thrombolysis (IVT) and endovascular thrombectomy. The findings can provide observational information on treatment of patients derived from everyday clinical practice. PARTICIPANTS TRISP is an open, investigator-driven collaborative research initiative of European stroke centres with expertise in treatment with revascularisation therapies and maintenance of hospital-based registries. All participating centres made a commitment to prospectively collect data on consecutive patients with stroke treated with IVT using standardised definitions of variables and outcomes, to assure accuracy and completeness of the data and to adapt their local databases to answer novel research questions. FINDINGS TO DATE Currently, TRISP comprises 18 centres and registers >10 000 IVT-treated patients. Prior TRISP projects provided evidence on the safety and functional outcome in relevant subgroups of patients who were excluded, under-represented or not specifically addressed in randomised controlled trials (ie, pre-existing disability, cervical artery dissections, stroke mimics, prior statin use), demonstrated deficits in organisation of acute stroke care (ie, IVT during non-working hours, effects of onset-to-door time on onset-to-needle time), evaluated the association between laboratory findings on outcome after IVT and served to develop risk estimation tools for prediction of haemorrhagic complications and functional outcome after IVT. FUTURE PLANS Further TRISP projects to increase knowledge of the effect and safety of revascularisation therapies in acute stroke are ongoing. TRISP welcomes participation and project proposals of further centres fulfilling the outlined requirements. In the future, TRISP will be extended to include patients undergoing endovascular thrombectomy.


title: Advances in the management of coronary chronic total occlusions.

text: Chronic total occlusions (CTOs) have been called "the last frontier" of percutaneous coronary intervention (PCI) due to traditionally low success rates and high risk for restenosis and re-occlusion. Recent advances in equipment and crossing techniques have significantly increased CTO PCI success rates while maintaining low risk of complications. Specifically, the retrograde approach and controlled antegrade dissection and re-entry in conjunction with advanced guidewires and microcatheters have significantly improved procedural success rates. Moreover, the introduction of the "hybrid" approach has created a unified framework for operators to approach CTOs in a systematic and efficient fashion. Finally, drug-eluting stents, especially second generation, have improved long-term patency after CTO PCI.


title: The importance of tracheostomy progression in the intensive care unit.

text: A plan to progress a tracheostomy toward decannulation should be initiated unless the tracheostomy has been placed for irreversible conditions. In most cases, tracheostomy progression can begin once a patient is free from ventilator dependence. Progression often begins with cuff deflation, which frequently results in the patient's ability to phonate. A systematic approach to tracheostomy progression involves assessing (1) hemodynamic stability, (2) whether the patient has been free from ventilator support for at least 24 hours, (3) swallowing, cough strength, and aspiration risk, (4) management of secretions, and (5) toleration of cuff deflation, followed by (6) changing to a cuffless tube, (7) capping trials, (8) functional decannulation trials, (9) measuring cough strength, and (10) decannulation. Critical care nurses can facilitate the process and avoid unnecessary delays and complications.


title: Depth of anesthesia monitoring: a survey of attitudes and usage patterns among Australian anesthesiologists.

text: BACKGROUND Utility of depth of anesthesia (DoA) monitors is contentious as evidence appears ambiguous regarding their clinical effectiveness and exact role. We conducted a survey of Australian anesthesiologists to determine their attitudes toward, and how and why they use, DoA monitors. METHODS A random sample of 963 anesthesiologists was invited to participate in an anonymous online survey. RESULTS The overall response rate was 30% (289 respondents). Twenty-nine percent (95% confidence interval, 24%-34%) of respondents thought DoA monitoring was indicated in all cases under relaxant general anesthesia. During total IV anesthesia with muscle relaxants, 74% of respondents (69%-79%) opined that DoA monitoring should be mandatory. DoA usage was never used by 5% of respondents (3%-8%), used in less than one-third of cases by 66% (61%-72%), and in more than one-third of cases by 29% (24%-35%). Belief in the usefulness of DoA monitoring for prevention of awareness was strongly associated with higher usage (P < 0.0001, Pearson correlation 0.32). Anesthesiologists were more influenced by higher DoA numbers than lower ones. In comparison with end-tidal anesthetic concentration monitoring, 30% (25%-35%) of respondents felt that DoA monitoring was more effective for prevention of intraoperative awareness. Thirty percent (25%-36%) of respondents reported having a previous case of awareness. CONCLUSIONS The relatively frequent use of DoA monitoring contrasts with patterns in the UK, suggesting greater acceptance by Australian anesthesiologists. "Awareness prevention" rather than "recovery enhancement" appears to be the primary driver in DoA monitoring use in Australia. Highly variable usage patterns of DoA monitoring in the context of the current body of evidence suggest the need for greater education on the appropriate use of these monitors.


title: Robotic-assisted laparoscopic stage II restorative proctectomy for toxic ulcerative colitis.

text: BACKGROUND There is a paucity of literature reporting minimally invasive proctectomy for ulcerative colitis (UC). We report a novel application of a robotic system to perform restorative proctectomy in patients with toxic UC. METHODS Retrospective review, case series report. RESULTS Robotic-assisted laparoscopic proctectomy with ileal J-pouch anal anastomosis was performed in three patients with toxic UC. All patients previously underwent urgent laparoscopic total abdominal colectomy. One female and two male patients were aged 39, 24 and 43, respectively. The procedures were performed safely with minimal complications. The robotic proctectomy operative time was reduced from 134 to 106 min. None of the patients have experienced fecal incontinence, nocturnal seepage or sexual dysfunction. CONCLUSIONS This is a case series report of a robotic-assisted laparoscopic proctectomy with restorative ileal J-pouch in patients with toxic UC. This technique has been previously described for use in patients with medically refractory UC and neoplasia associated with chronic UC. This series exemplifies an ideal application of a robotic system with improved visibility, rotation and ergonomics.


Development and efficacy of a 1-d thoracic ultrasound training course.


title: Deciphering the Association Between Psoriasis and Obesity: Current Evidence and Treatment Considerations.

text: PURPOSE OF REVIEW Obesity and psoriasis represent chronic inflammatory states that are interconnected in a vicious cycle, sharing also a degree of synergy. In this review, we aim to decipher the various lines of evidence supporting the bidirectional association between psoriasis and obesity highlighting their pathophysiologic connections as well as we attempt to strategize a therapeutic holistic approach for obese psoriatic patients. RECENT FINDINGS Recent meta-analyses have shown that (1) genetically higher BMI increased the odds of psoriasis occurrence; (2) obesity is associated with higher incidence and prevalence of psoriasis as well as psoriasis severity; (3) obesity is associated with lower efficacy to anti-TNF agents and may predict biologic treatment discontinuation; and (4) weight loss through diet and physical exercise may improve pre-existing psoriasis and prevent from de novo psoriasis. Methotrexate, acitretin, and cyclosporine could worsen hypertension, liver steatosis, and dyslipidemia. Since infliximab and ustekinumab are weight adjusted, they may be ideal drugs to treat obese psoriatic patients. IL-17 inhibitors are very effective independently from body weight; however, they tend to present better clearance rates in normal weight patients. There is a paucity on weight data regarding the efficacious IL-23 inhibitors. Apremilast may induce weight loss as an adverse effect presenting also some beneficial metabolic actions. Finally, simvastatin and some antidiabetic drugs could decrease psoriasis severity. More mechanistic, observational studies and well-conducted RCTs are necessary to decipher the enigmatic link between psoriasis and obesity, and to provide evidence-based specific guidelines for the screening and management of obese psoriatic patients.


title: Comparison of thermal coagulation profiles for bipolar forceps with different cooling mechanisms in a porcine model of spinal surgery.

text: BACKGROUND Coagulation accomplished using bipolar forceps is common in neurosurgery. Control of thermal spread from the forceps tips into surrounding neural tissues is a persistent concern, as neural tissues are especially vulnerable to heat injury. The purpose of our investigation was to compare the efficacy of cooling mechanisms for four different bipolar forceps and to understand thermal spread when coagulating vessels on the spinal cord. METHODS Immediately following euthanasia, the dura mater of an ex vivo porcine model was opened to expose vessels on the spinal cord for coagulation. Temperature profiles were measured at generator power of 25 W and at fixed 5-second activation times. The bipolar forceps used in this study included regular stainless steel, titanium, heat-pipe embedded, and SILVERGlide forceps. Temperature was measured by micro-thermistor at the midpoint between the bipolar tips, and 1 and 2 mm away from the midpoint along the centerline. Statistical analysis was performed to evaluate temperature differences. RESULTS Temperature profiles indicated that heat-pipe embedded forceps create the least amount of temperature increase and the highest normalized temperature decreasing slope after activation. The decreasing slope of SILVERGlide forceps is slightly higher than that of regular stainless steel forceps. CONCLUSIONS Bipolar forceps incorporating either heat-pipe embedded technology or SILVERGlide coating can effectively limit excessive thermal spread, thus decreasing potential injury to adjacent tissues when compared with standard stainless steel and titanium bipolar forceps. Of the two, heat-pipe embedded technology appeared safest, having better cooling efficiency at higher temperature.


title: Intermittent catheterization with hydrophilic catheters as a treatment of chronic neurogenic urinary retention.

text: AIMS Neurogenic bladder can be effectively managed with intermittent catheterization (IC) to improve or restore continence, but there is no consensus on which type of catheter is preferred. Hydrophilic catheters were developed to reduce urethral friction, thereby minimizing trauma and sticking, and making them more acceptable to the patient, and easier and safer to use. The objective of this article was to review the literature on the benefits of hydrophilic catheters in patients with neurogenic bladder. METHODS A large body of experimental and observational evidence, including randomized controlled trials, was identified using PubMed. RESULTS Compared with plastic catheters that have been manually lubricated with gel, hydrophilic catheters reduce urinary tract infection and microhematuria. Hydrophilic catheters are also associated with high levels of patient satisfaction because they are comfortable to use. CONCLUSIONS There is a wealth of evidence, including randomized controlled trials, to support the benefits of hydrophilic catheters in terms of safety and quality of life, especially in men with spinal cord injury. More data are required for spina bifida, multiple sclerosis, and in women. Further research is warranted, especially large-scale and long-term robust comparisons of different types of catheter, and in well-defined and stratified populations.


title: Correlation between capnography and arterial carbon dioxide before, during, and after severe chest injury in swine.

text: The relationship between end-tidal carbon dioxide (EtCO(2)) and arterial carbon dioxide (PaCO(2))-if better defined-could facilitate the difficult task of ventilation in prehospital trauma patients. We aimed to study the PaCO(2)-EtCO(2) relationship before, during, and after chest trauma, hemorrhage, and resuscitation in swine. Twenty-four swine were intubated, anesthetized, and monitored in an animal intensive care unit during three phases: phase 1 (day 1, healthy animals); phase 2 (day 2, injury), which consisted of blunt chest trauma, hemorrhage, and resuscitation; and phase 3 (day 2, after injury). "Respiratory maneuvers" (changes in respiratory rate and tidal volume [TV], intended to vary the PaCO(2) over a range of 25 to 85 mmHg, were performed during phases 1 and 3. End-tidal CO(2) and PaCO(2) were recorded after each respiratory maneuver and analyzed using linear regression. During phase 1, PaCO(2) and EtCO(2) were strongly correlated (r(2) = 0.97, P < 0.01). During phase 2, animals developed decreased oxygenation (PaO(2):FiO(2) [fraction of inspired oxygen] ratio <200) and hypotension (mean arterial pressure, 20-50 mmHg); the PaCO(2)-EtCO(2) relationship deteriorated (r(2) = 0.25, P < 0.0001). During phase 3, oxygenation, hemodynamics, and the PaCO(2)-EtCO(2) relationship recovered (r(2) = 0.92, P < 0.01). End-tidal CO(2) closely correlates to PaCO(2) in healthy animals and after injury/resuscitation across a wide range of respiratory rates and tidal volumes. Once oxygenation and hemodynamics are restored, EtCO(2) can be used to predict PaCO(2) following chest trauma/hemorrhage and should be considered for patient monitoring. This work demonstrated that EtCO(2) alone can reliably be used to estimate PaCO(2) in uninjured subjects and in those subjects who have been resuscitated from severe injury. Immediately after blunt chest injury, the correlation between EtCO(2) and PaCO(2) is temporarily unstable. Under these circumstances (with abnormal oxygenation and/or hemodynamics), greater caution and other monitoring tools may be required.


title: Alterations in melatonin and 5-HT signalling in the colonic mucosa of mice with dextran-sodium sulfate-induced colitis.

text: BACKGROUND AND PURPOSE Inflammatory bowel disease (IBD) is characterized by pain, bleeding, cramping and altered gastrointestinal (GI) function. Changes in mucosal 5-HT (serotonin) signalling occur in animal models of colitis and in humans suffering from IBD. Melatonin is co-released with 5-HT from the mucosa and has a wide variety of actions in the GI tract. Here, we examined how melatonin signalling is affected by colitis and determined how this relates to 5-HT signalling. EXPERIMENTAL APPROACH Using electroanalytical approaches, we investigated how 5-HT release, reuptake and availability as well as melatonin availability are altered in dextran sodium sulfate (DSS)-induced colitis in mice. Studies were conducted to explore if melatonin treatment during active colitis could reduce the severity of colitis. KEY RESULTS We observed an increase in 5-HT and a decrease in melatonin availability in DSS-induced colitis. A significant reduction in 5-HT reuptake was observed in DSS-induced colitis animals. A reduction in the content of 5-HT was observed, but no difference in tryptophan levels were observed. A reduction in deoxycholic acid-stimulated 5-HT availability and a significant reduction in mechanically-stimulated 5-HT and melatonin availability were observed in DSS-induced colitis. Orally or rectally administered melatonin once colitis was established did not significantly suppress inflammation. CONCLUSION AND IMPLICATIONS Our data suggest that DSS-induced colitis results in a reduction in melatonin availability and an increase in 5-HT availability, due to a reduction/loss of tryptophan hydroxylase 1 enzyme, 5-HT content and 5-HT transporters. Mechanosensory release was more susceptible to inflammation when compared with chemosensory release.


title: Novel strategy for laparoscopic treatment of pT2 gallbladder carcinoma.

text: BACKGROUND This study evaluated our new strategy for treating suspected T2 gallbladder carcinoma (GBC) using a laparoscopic approach. METHODS We examined 19 patients with suspected T2 GBC who were treated laparoscopically (LS group) between December 2007 and December 2013; these patients were compared with 14 patients who underwent open surgery (OS group). Laparoscopic staging was initially performed to exclude factors making the patients ineligible for curative resection. Intraoperative pathological examination of the surgical margin of the cystic duct was performed prior to laparoscopic gallbladder bed resection, and pathological examination was again performed to confirm the presence of carcinoma and the depth of tumor invasion. Surgery was completed when the pathological findings indicated that the patient was cancer free. Lymph node dissection was performed according to the depth of tumor invasion. RESULTS None of the patients required conversion to laparotomy. For three patients with benign lesions, only gallbladder bed resection was required. Additional regional lymph node dissection was performed in 16 patients in the LS group. The mean operative time (309 vs. 324 min, p = 0.755) and mean number of dissected lymph nodes (12.6 vs. 10.2, p = 0.361) were not significantly different between the LS and OS groups. The intraoperative blood loss was significantly lower (104 vs. 584 mL, p = 0.002) and the postoperative hospital stay was significantly shorter (9.1 vs. 21.6 days, p = 0.002) for LS patients than for those in the OS group. In the LS group, one patient developed postoperative pneumonia, but all patients survived without recurrence after a mean follow-up of 37 months. CONCLUSION Our strategy for suspected T2 gallbladder GBC is safe and useful, avoids unnecessary procedures, and is associated with similar oncologic outcomes as the open method.


Preparing for COVID-19's aftermath: simple steps to address social determinants of health.


Covid-19: Italy confirms 11 deaths as cases spread from north.


title: Robotic-assisted left renal vein transposition as a novel surgical technique for the treatment of renal nutcracker syndrome.

text: Renal nutcracker syndrome is an anatomic anomaly characterized by the compression of the left renal vein between the superior mesenteric artery and the aorta or between the aorta and the vertebral body. Diagnosis is often challenging. Common presenting symptoms include hematuria, abdominal pain, and pelvic congestion. Several open and endovascular techniques have been described to treat this syndrome. We report a novel surgical technique with robotic-assisted left renal vein transposition to treat a 19-year-old woman with renal nutcracker syndrome. Robotic vascular surgery can be a safe and effective therapy for this condition.


title: Time course of expiratory propofol after bolus injection as measured by ion molecule reaction mass spectrometry.

text: Propofol in exhaled breath can be detected and monitored in real time by ion molecule reaction mass spectrometry (IMR-MS). In addition, propofol concentration in exhaled breath is tightly correlated with propofol concentration in plasma. Therefore, real-time monitoring of expiratory propofol could be useful for titrating intravenous anesthesia, but only if concentration changes in plasma can be determined in exhaled breath without significant delay. To evaluate the utility of IMR-MS during non-steady-state conditions, we measured the time course of both expiratory propofol concentration and the processed electroencephalography (EEG) as a surrogate outcome for propofol effect after an IV bolus induction of propofol. Twenty-one patients scheduled for routine surgery were observed after a bolus of 2.5 mg kg(-1) propofol for induction of anesthesia. Expiratory propofol was measured using IMR-MS and the cerebral propofol effect was estimated using the bispectral index (BIS). Primary endpoints were time to detection of expiratory propofol and time to onset of propofol's effect on BIS, and the secondary endpoint was time to peak effect (highest expiratory propofol or lowest BIS). Expiratory propofol and changes in BIS were first detected at 43 ± 21 and 49 ± 11 s after bolus injection, respectively (P = 0.29). Peak propofol concentrations (9.2 ± 2.4 parts-per-billion) and lowest BIS values (23 ± 4) were reached after 208 ± 57 and 219 ± 62 s, respectively (P = 0.57). Expiratory propofol concentrations measured by IMR-MS have similar times to detection and peak concentrations compared with propofol effect as measured by the processed EEG (BIS). This suggests that expiratory propofol concentrations may be useful for titrating intravenous anesthesia.


title: Real-time intravascular photoacoustic-ultrasound imaging of lipid-laden plaque in human coronary artery at 16 frames per second.

text: Intravascular photoacoustic-ultrasound (IVPA-US) imaging is an emerging hybrid modality for the detection of lipid-laden plaques, as it provides simultaneous morphological and lipid-specific chemical information of an artery wall. Real-time imaging and display at video-rate speed are critical for clinical utility of the IVPA-US imaging technology. Here, we demonstrate a portable IVPA-US system capable of imaging at up to 25 frames per second in real-time display mode. This unprecedented imaging speed was achieved by concurrent innovations in excitation laser source, rotary joint assembly, 1 mm IVPA-US catheter size, differentiated A-line strategy, and real-time image processing and display algorithms. Spatial resolution, chemical specificity, and capability for imaging highly dynamic objects were evaluated by phantoms to characterize system performance. An imaging speed of 16 frames per second was determined to be adequate to suppress motion artifacts from cardiac pulsation for in vivo applications. The translational capability of this system for the detection of lipid-laden plaques was validated by ex vivo imaging of an atherosclerotic human coronary artery at 16 frames per second, which showed strong correlation to gold-standard histopathology. Thus, this high-speed IVPA-US imaging system presents significant advances in the translational intravascular and other endoscopic applications.


title: Acute environmental hypoxia induces LC3 lipidation in a genotype-dependent manner.

text: Hypoxia-induced muscle wasting is a phenomenon often described with prolonged stays at high altitude, which has been attributed to altered protein metabolism. We hypothesized that acute normobaric hypoxia would induce a negative net protein balance by repressing anabolic and activating proteolytic signaling pathways at rest and postexercise and that those changes could be partially genetically determined. Eleven monozygotic twins participated in an experimental trial in normoxia and hypoxia (10.7% O2). Muscle biopsy samples were obtained before and after a 20-min moderate cycling exercise. In hypoxia at rest, autophagic flux was increased, as indicated by an increased microtubule-associated protein 1 light chain 3 type II/I (LC3-II/I) ratio (+25%) and LC3-II expression (+60%) and decreased p62/SQSTM1 expression (-25%; P<0.05), whereas exercise reversed those changes to a level similar to that with normoxia except for p62/SQSTM1, which was further decreased (P<0.05). Hypoxia also increased Bnip3 (+34%) and MAFbx (+18%) mRNA levels as well as REDD1 expression (+439%) and AMP-activated protein kinase phosphorylation (+22%; P<0.05). Among the molecular responses to hypoxia and/or exercise, high monozygotic similarity was found for REDD1, LC3-II, and LC3-II/I (P<0.05). Our results indicate that environmental hypoxia modulates protein metabolism at rest and after moderate exercise by primarily increasing markers of protein breakdown and, more specifically, markers of the autophagy-lysosomal system, with a modest genetic contribution.


title: Analysis of hemodynamics and aneurysm occlusion after flow-diverting treatment in rabbit models.

text: BACKGROUND AND PURPOSE Predicting the outcome of flow diversion treatment of cerebral aneurysms remains challenging. Our aim was to investigate the relationship between hemodynamic conditions created immediately after flow diversion and subsequent occlusion of experimental aneurysms in rabbits. MATERIALS AND METHODS The hemodynamic environment before and after flow-diversion treatment of elastase-induced aneurysms in 20 rabbits was modeled by using image-based computational fluid dynamics. Local aneurysm occlusion was quantified by using a voxelization technique on 3D images acquired 8 weeks after treatment. Global and local voxel-by-voxel hemodynamic variables were used to statistically compare aneurysm regions that later thrombosed to regions that remained patent. RESULTS Six aneurysms remained patent at 8 weeks, while 14 were completely or nearly completely occluded. Patent aneurysms had statistically larger neck sizes (P = .0015) and smaller mean transit times (P = .02). The velocity, vorticity, and shear rate were approximately 2.8 times (P < .0001) larger in patent regions-that is, they had larger "flow activity" than regions that progressed to occlusion. Statistical models based on local hemodynamic variables were capable of predicting local occlusion with good precision (84% accuracy), especially away from the neck (92%-94%). Predictions near the neck were poorer (73% accuracy). CONCLUSIONS These results suggests that the dominant healing mechanism of occlusion within the aneurysm dome is related to slow-flow-induced thrombosis, while near the neck, other processes could be at play simultaneously.


docid: ubyplrlf

title: Infection with human coronavirus NL63 enhances streptococcal adherence to epithelial cells.

text: Understanding the mechanisms of augmented bacterial pathogenicity in post-viral infections is the first step in the development of an effective therapy. This study assessed the effect of human coronavirus NL63 (HCoV-NL63) on the adherence of bacterial pathogens associated with respiratory tract illnesses. It was shown that HCoV-NL63 infection resulted in an increased adherence of Streptococcus pneumoniae to virus-infected cell lines and fully differentiated primary human airway epithelium cultures. The enhanced binding of bacteria correlated with an increased expression level of the platelet-activating factor receptor (PAF-R), but detailed evaluation of the bacterium-PAF-R interaction revealed a limited relevance of this process.


title: Gravity predominates over ventilatory pattern in the prevention of ventilator-associated pneumonia.

text: OBJECTIVE In the semirecumbent position, gravity-dependent dissemination of pathogens has been implicated in the pathogenesis of ventilator-associated pneumonia. We compared the preventive effects of a ventilatory strategy, aimed at decreasing pulmonary aspiration and enhancing mucus clearance versus the Trendelenburg position. DESIGN Prospective randomized animal study. SETTING Animal research facility, University of Barcelona, Spain. SUBJECTS Twenty-four Large White-Landrace pigs. INTERVENTIONS Pigs were intubated and on mechanical ventilation for 72 hours. Following surgical preparation, pigs were randomized to be positioned: 1) in semirecumbent/prone position, ventilated with a duty cycle (TITTOT) of 0.33 and without positive end-expiratory pressure (control); 2) as in the control group, positive end-expiratory pressure of 5 cm H2O and TITTOT to achieve a mean expiratory-inspiratory flow bias of 10 L/min (treatment); 3) in Trendelenburg/prone position and ventilated as in the control group (Trendelenburg). Following randomization, Pseudomonas aeruginosa was instilled into the oropharynx. MEASUREMENTS AND MAIN RESULTS Mucus clearance rate was measured through fluoroscopic tracking of tracheal markers. Microspheres were instilled into the subglottic trachea to assess pulmonary aspiration. Ventilator-associated pneumonia was confirmed by histological/microbiological studies. The mean expiratory-inspiratory flow in the treatment, control, and Trendelenburg groups were 10.7 ± 1.7, 1.8 ± 3.7 and 4.3 ± 2.8 L/min, respectively (p < 0.001). Mucus clearance rate was 11.3 ± 9.9 mm/min in the Trendelenburg group versus 0.1 ± 1.0 in the control and 0.2 ± 1.0 in the treatment groups (p = 0.002). In the control group, we recovered 1.35% ± 1.24% of the instilled microspheres per gram of tracheal secretions, whereas 0.22% ± 0.25% and 0.97% ± 1.44% were recovered in the treatment and Trendelenburg groups, respectively (p = 0.031). Ventilator-associated pneumonia developed in 66.67%, 85.71%, and 0% of the animals in the control, treatment, and Trendelenburg groups (p < 0.001). CONCLUSIONS The Trendelenburg position predominates over expiratory flow bias and positive end-expiratory pressure in the prevention of gravity-dependent translocation of oropharyngeal pathogens and development of ventilator-associated pneumonia. These findings further substantiate the primary role of gravity in the pathogenesis of ventilator-associated pneumonia.


title: Pulmonary function testing precautions in a time of COVID-19.

text: During the COVID-19 pandemic, Cleveland Clinic has put in place several pulmonary function testing precautions to reduce the risk of infection. Precautions include efforts to perform only essential testing, wear personal protective equipment, reduce exposure to aerosolized particles, manage virtually by phone conference, conserve scare medications, clean equipment as recommended, consolidate testing, and defer testing.


title: Preoperative testing for radial forearm free flaps to reduce donor site morbidity.

text: OBJECTIVE To compare the clinical Allen test, preoperative Doppler ultrasonography, and intraoperative surgical Allen test with postoperative clinical findings in reconstruction of complex head and neck defects using radial forearm free flaps. DESIGN, SETTING, AND PATIENTS Retrospective review of 143 consecutive patients who underwent radial forearm free flap reconstruction from January 1, 1992, through December 31, 2006, at Vanderbilt University Medical Center. RESULTS Flap survival rate was 96.4%. No patients experienced digital necrosis or other findings of acute ischemia. Two patients (1.9%) who had normal results of clinical and surgical Allen tests developed hand contracture and palmar nodule formation. Surgical Allen test findings were normal in all patients who underwent reconstruction. Eighty-two arms had documentation of clinical Allen testing and Doppler ultrasonography in the patients' medical records. Agreement between these measures was 92.7%. The clinical Allen test result was 100% sensitive and 75% specific in predicting an abnormal Doppler ultrasonographic finding. CONCLUSIONS The clinical Allen test is an appropriate preoperative evaluation before radial forearm free flap reconstruction. The addition of Doppler ultrasonography should be limited to patients with abnormal clinical Allen test results. The surgical Allen test provides reassurance but does not preclude the possibility of ischemic hand complications.


docid: wrkzrqee

title: Galectins and Immune Responses-Just How Do They Do Those Things They Do?

text: Galectins are a family of mammalian carbohydrate-binding proteins expressed by many cell types. Galectins can function intracellularly and can also be secreted to bind to cell surface glycoconjugate counterreceptors. Some galectins are made by immune cells, whereas other galectins are secreted by different cell types, such as endothelial or epithelial cells, and bind to immune cells to regulate immune responses. Galectin binding to a single glycan ligand is a low-affinity interaction, but the multivalency of galectins and the glycan ligands presented on cell surface glycoproteins results in high-avidity binding that can reversibly scaffold or cluster these glycoproteins. Galectin binding to a specific glycoprotein counterreceptor is regulated in part by the repertoire of glycosyltransferase enzymes (which make the glycan ligands) expressed by that cell, and the effect of galectin binding results from clustering or retention of specific glycoprotein counterreceptors bearing these specific ligands.