title: Identification of multiple novel viruses, including a parvovirus and a hepevirus, in feces of red foxes.

text: Red foxes (Vulpes vulpes) are the most widespread members of the order of Carnivora. Since they often live in (peri)urban areas, they are a potential reservoir of viruses that transmit from wildlife to humans or domestic animals. Here we evaluated the fecal viral microbiome of 13 red foxes by random PCR in combination with next-generation sequencing. Various novel viruses, including a parvovirus, bocavirus, adeno-associated virus, hepevirus, astroviruses, and picobirnaviruses, were identified.


docid: ziunowky

title: Post-operative outcomes after cleft palate repair in syndromic and non-syndromic children: a systematic review protocol.

text: BACKGROUND There is a lack of high-level evidence on the surgical management of cleft palate. An appreciation of the differences in the complication rates between different surgical techniques and timing of repair is essential in optimizing cleft palate management. METHOD A comprehensive electronic database search will be conducted on the complication rates associated with cleft palate repair using MEDLINE, EMBASE, and the Cochrane Central Register of Controlled Trials. Two independent reviewers with expertise in cleft pathology will screen all appropriate titles, abstracts, and full-text publications prior to deciding whether each meet the predetermined inclusion criteria. The study findings will be tabulated and summarized. The primary outcomes will be the rate of palatal fistula, the incidence and severity of velopharyngeal insufficiency, and the rate of maxillary hypoplasia with different techniques and also the timing of the repair. A meta-analysis will be conducted using a random effects model. DISCUSSION The evidence behind the optimal surgical approach to cleft palate repair is minimal, with no gold standard technique identified to date for a certain type of cleft palate. It is essential to appreciate how the complication rates differ between each surgical technique and each time point of repair, in order to optimize the management of these patients. A more critical evaluation of the outcomes of different cleft palate repair methods may also provide insight into more effective surgical approaches for different types of cleft palates.


title: An exploratory analysis of U.S. FDA Class I medical device recalls: 2014-2018.

text: Medical device manufacturing and distribution is globalised; consequently, medical device failures pose serious but preventable global public health hazard. Moreover, a clear understanding of recalls will help firms improve their operations. This study examines 871 U.S. FDA Class I (i.e. most serious) medical device recalls, highlights the shortcomings of the recall reporting system and proposes recommendations for improvement. Top three recall reasons are: "packaging" (47.4%), "component" issues (14%) and "design" (13.3%). About 40% of recall events have mischaracterised or ambiguous "FDA Determined Cause". Ninety-four firms are related to the recalls and the majority (78%) of the recall events emanate from U.S.-headquartered firms. Thirty-four firms (36%) have been acquired or are a subsidiary of another. Results also yield recommendations for improvement. The cause classification scheme needs revision and there might be a case for more than one classification scheme. Specifically, the "device design" cause designation is conflated with "component quality" issues. "Other", "unknown" and "under investigation" designations should be replaced with real cause determinations. The effectiveness of "Good Manufacturing Practices (GMP)" and the impact of mergers and acquisitions (M&A) on device quality should be examined. Devising a "recall severity measure" and improving and standardising the recalls database are other important issues. Results and recommendations may hold lessons for other jurisdictions as well.


title: CXCL10-CXCR3 enhances the development of neutrophil-mediated fulminant lung injury of viral and nonviral origin.

text: RATIONALE Patients who developed acute respiratory distress syndrome (ARDS) after infection with severe respiratory viruses (e.g., severe acute respiratory syndrome-coronavirus, H5N1 avian influenza virus), exhibited unusually high levels of CXCL10, which belongs to the non-ELR (glutamic-leucine-arginine) CXC chemokine superfamily. CXCL10 may not be a bystander to the severe virus infection but may directly contribute to the pathogenesis of neutrophil-mediated, excessive pulmonary inflammation. OBJECTIVES We investigated the contribution of CXCL10 and its receptor CXCR3 axis to the pathogenesis of ARDS with nonviral and viral origins. METHODS We induced nonviral ARDS by acid aspiration and viral ARDS by intratracheal influenza virus infection in wild-type mice and mice deficient in CXCL10, CXCR3, IFNAR1 (IFN-α/β receptor 1), or TIR domain-containing adaptor inducing IFN-β (TRIF). MEASUREMENTS AND MAIN RESULTS We found that the mice lacking CXCL10 or CXCR3 demonstrated improved severity and survival of nonviral and viral ARDS, whereas mice that lack IFNAR1 did not control the severity of ARDS in vivo. The increased levels of CXCL10 in lungs with ARDS originate to a large extent from infiltrated pulmonary neutrophils, which express a unique CXCR3 receptor via TRIF. CXCL10-CXCR3 acts in an autocrine fashion on the oxidative burst and chemotaxis in the inflamed neutrophils, leading to fulminant pulmonary inflammation. CONCLUSIONS CXCL10-CXCR3 signaling appears to be a critical factor for the exacerbation of the pathology of ARDS. Thus, the CXCL10-CXCR3 axis could represent a prime therapeutic target in the treatment of the acute phase of ARDS of nonviral and viral origins.


title: Curative reconstruction of a cerebral aneurysm by flow diversion with the Pipeline embolisation device in a patient with Loeys-Dietz syndrome.

text: Loeys-Dietz syndrome is a recently described connective tissue disorder with a natural history of extreme vessel tortuosity and aggressive arterial aneurysm formation and rupture. This is the case of a 23-year-old woman with a large, dysplastic cavernous aneurysm who had successful endovascular treatment by flow diversion with the Pipeline embolisation device. Ten-month follow-up demonstrated complete aneurysm occlusion and curative reconstruction of the parent vessel without evidence of vessel injury or dissection. Endovascular treatment with flow-diverting devices is a valid treatment option and can be performed safely and effectively in this complex patient population.


Outcomes of the ninth international conference on pediatric mechanical circulatory support systems and pediatric cardiopulmonary perfusion.


title: Endovascular treatment of acute portal vein thrombosis using ultrasound-accelerated catheter-directed thrombolysis.

text: We report a case of extensive acute portal vein thrombosis (PVT) presenting with severe diffuse abdominal pain and impending small bowel infarction. The patient was successfully treated with ultrasound-accelerated catheter-directed thrombolysis (EKOS endowave system; Covidien, Mansfield, Massachusetts), which resulted in prompt recanalization of his portal vein (PV) and its tributaries. The patient eventually had ischemic stricture that necessitated bowel resection. However, we believe that our technique was successful in rapidly restoring the patency of the PV and its tributaries, and therefore, avoiding a life-threatening complication of more extensive bowel infarction. To our knowledge, the use of ultrasound-accelerated thrombolysis in treatment of PVT has not been previously described in the literature.


title: Observer variability in a phase II trial - assessing consistency in RECIST application.

text: OBJECTIVE To assess the consistency of Response Evaluation Criteria in Solid Tumours (RECIST) application in a phase II trial. MATERIAL AND METHODS Patients with metastatic non-resectable colorectal cancer treated with a combination of an antibody and a chemotherapeutic drug, were included. Computed tomography (CT) scans (thorax, abdomen and pelvis) were performed at baseline and after every fourth treatment cycle. RECIST was intended for response evaluation. The scans were consecutively read by a heterogeneous group of radiologists as a part of daily work and hereafter retrospectively reviewed by a dedicated experienced radiologist. Agreement on best overall response (BOR) between readers and reviewer was quantified using κ-coefficients and the discrepancy rate was correlated with the number of different readers per patient using a χ(2)-test. RESULTS One hundred patients with 396 CT scans were included. Discrepancies between the readers and the reviewer were found in 47 patients. The majority of discrepancies concerned the application of RECIST. With the review, BOR changed in 17 patients, although, only in six patients the change was potentially treatment altering. Overall, the κ-coefficient of agreement between readers and reviewer was 0.71 (good). However, in the subgroup of responding patients the κ-coefficient was 0.21 (fair). The number of patients with discrepancies was significantly higher with three or more different readers per patient than with less (p =0.0003). CONCLUSION RECIST was not consistently applied and the majority of the reader discrepancies were RECIST related. Post review, 17 patients changed BOR; six patients in a potentially treatment altering manner. Additionally, we found that the part of patients with discrepancies increased significantly with more than three different readers per patient. The findings support a peer-review approach where a few dedicated radiologists perform double blinded readings of all the on-going cancer trial patients' CT scans.


What's happening in covid-19 ICUs? An intensive care doctor answers some common questions.


title: Evaluation of local tumor residue after percutaneous radiofrequency ablation therapy for hepatocellular carcinoma.

text: BACKGROUND/AIMS This study's purpose was to compare the efficacy of CO2-enhanced ultrasonography (US) with that of Sonazoid-enhanced US and conventional US in detecting local tumor residue after percutaneous radiofrequency (RF) ablation therapy for hepatocellular carcinoma. MATERIALS AND METHODS Between February 2009 and March 2010, 141 lesions of 121 hepatocellular carcinoma patients were treated by percutaneous RF ablation, and 22 tumor residues were detected in 22 patients by contrast-enhanced computed tomography. These 22 patients were examined by conventional US, Sonazoid-enhanced US (0.5 mL/body of Sonazoid, intravenous administration), and CO2-enhanced US (10 mL of CO2, hepatic arterial administration). RESULTS Tumor residue was confirmed by CO2-enhanced US in all the 22 patients (sensitivity: 100%) in 19 of the 22 patients by Sonazoid-enhanced US (sensitivity: 86%; 3 lesions that were not detected by this modality were located deeper than the sonographic depth (p=0.0109)), and in 17 of the 22 patients by conventional US (sensitivity: 77%; 5 lesions that were not detected by this modality were smaller in terms of the sonographic tumor size (p=0.0278)). CONCLUSION Although CO2-enhanced US requires angiography, it was superior to both Sonazoid-enhanced US and conventional US for detecting tumor residues, particularly deep-seated ones, after percutaneous RF ablation.


docid: vkvgpysj

title: Evaluation of SSYA10-001 as a replication inhibitor of severe acute respiratory syndrome, mouse hepatitis, and Middle East respiratory syndrome coronaviruses.

text: We have previously shown that SSYA10-001 blocks severe acute respiratory syndrome coronavirus (SARS-CoV) replication by inhibiting SARS-CoV helicase (nsp13). Here, we show that SSYA10-001 also inhibits replication of two other coronaviruses, mouse hepatitis virus (MHV) and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). A putative binding pocket for SSYA10-001 was identified and shown to be similar in SARS-CoV, MERS-CoV, and MHV helicases. These studies show that it is possible to target multiple coronaviruses through broad-spectrum inhibitors.


title: COVID-19 meets Cystic Fibrosis: for better or worse?

text: Cystic fibrosis (CF) is one of the most common autosomal recessive life-limiting conditions affecting Caucasians. The resulting defect in the cystic fibrosis transmembrane conductance regulator protein (CFTR) results in defective chloride and bicarbonate secretion, as well as dysregulation of epithelial sodium channels (ENaC). These changes bring about defective mucociliary clearance, reduced airway surface liquid and an exaggerated proinflammatory response driven, in part, by infection. In this short article we explore the overlap in the pathophysiology of CF and COVID-19 infection and discuss how understanding the interaction between both diseases may shed light on future treatments.


Viral Load Kinetics of MERS Coronavirus Infection.


title: Recommendations for a standardized avian coronavirus (AvCoV) nomenclature: outcome from discussions within the framework of the European Union COST Action FA1207: "towards control of avian coronaviruses: strategies for vaccination, diagnosis and surveillance".

text: Viruses within the Coronaviridae family show variations within their genome sequences, especially within the major structural protein the Spike (S) glycoprotein gene. Therefore, many different antigenic forms, serotypes or variant strains of avian coronaviruses (AvCoV) exist worldwide. Only a few of them, the so called protectotypes, cross protect against different serotypes. New serotypes arise by recombination or spontaneous mutations. From time to time, antigenic virus variants appear, which differ significantly from known serotypes. The result of this variability is an inconsistent nomenclature and classification of virus strains. Furthermore, there are currently no standard classification methods defined. Within the framework of the COST Action FA1207 "Towards control of avian coronaviruses: strategies for diagnosis, surveillance and vaccination" (working groups "Molecular virology" and "Epidemiology"), we aimed at defining and developing a unified and internationally standardized nomenclature and classification of AvCoVs. We recommend the use of "CoV Genus/AvCov/host/country/specimen id/year" to refer to AvCoV strains.


title: Multiparametric MRI and CT models of infarct core and favorable penumbral imaging patterns in acute ischemic stroke.

text: BACKGROUND AND PURPOSE Objective imaging methods to identify optimal candidates for late recanalization therapies are needed. The study goals were (1) to develop magnetic resonance imaging (MRI) and computed tomography (CT) multiparametric, voxel-based predictive models of infarct core and penumbra in acute ischemic stroke patients, and (2) to develop patient-level imaging criteria for favorable penumbral pattern based on good clinical outcome in response to successful recanalization. METHODS An analysis of imaging and clinical data was performed on 2 cohorts of patients (one screened with CT, the other with MRI) who underwent successful treatment for large vessel, anterior circulation stroke. Subjects were divided 2:1 into derivation and validation cohorts. Pretreatment imaging parameters independently predicting final tissue infarct and final clinical outcome were identified. RESULTS The MRI and CT models were developed and validated from 34 and 32 patients, using 943 320 and 1 236 917 voxels, respectively. The derivation MRI and 2-branch CT models had an overall accuracy of 74% and 80%, respectively, and were independently validated with an accuracy of 71% and 79%, respectively. The imaging criteria of (1) predicted infarct core ≤90 mL and (2) ratio of predicted infarct tissue within the at-risk region ≤70% identified patients as having a favorable penumbral pattern with 78% to 100% accuracy. CONCLUSIONS Multiparametric voxel-based MRI and CT models were developed to predict the extent of infarct core and overall penumbral pattern status in patients with acute ischemic stroke who may be candidates for late recanalization therapies. These models provide an alternative approach to mismatch in predicting ultimate tissue fate.


title: Innominate Artery Stenosis Presenting With Migratory Digital Ischemia.

text: BACKGROUND Atherosclerotic lesions of the supra-aortic trunk vessels, including the innominate artery, subclavian artery, or the common carotid artery, tend to present either as low-flow state distal to the lesion or as embolic events. The risk of embolic cerebrovascular event complicates the management of this condition via a pure endovascular approach. A combined operative-endovascular intervention may be a valuable approach in order to reduce the risk of intraoperative stroke and prevent future embolic events. CASE PRESENTATION An 84-year-old female presented at the emergency department (ED) with a 4-month history of migratory digital cyanotic lesions across various fingers on her right hand. The lesion eventually progressed into dry gangrene on her right middle finger. Selective angiography of the aortic arch vessels demonstrated significant atherosclerotic plaque burden throughout her supra-aortic vessels and a segmental stenosis at the proximal innominate artery. A right carotid cut down was performed to allow clamping of the carotid artery so as to minimize the risk of intraoperative stroke from plaque manipulation. Retrograde balloon angioplasty was performed, and stent was placed across the stenotic segment. The patient tolerated the procedure well and had an uneventful postoperative course. She was discharged on postoperative day 3. At 2-week follow-up, she has had no progression of her digital ischemia nor other focal cranial nerve deficits. CONCLUSION Migratory digital ischemia is a rare presentation of atherosclerotic disease of the supra-aortic vessels. It represents a challenging situation for endovascular intervention due to concern about plaque dislodgment during the procedure. A retrograde balloon-stent angioplasty following distal carotid control with an open approach may be safe and effective in selected patients.


docid: wkszgsft

title: Conditioning With Sevoflurane in Liver Transplantation: Results of a Multicenter Randomized Controlled Trial.

text: BACKGROUND During times of organ scarcity and extended use of liver grafts, protective strategies in transplantation are gaining importance. We demonstrated in the past that volatile anesthetics such as sevoflurane attenuate ischemia-reperfusion injury during liver resection. In this randomized study, we examined if volatile anesthetics have an effect on acute graft injury and clinical outcomes after liver transplantation. METHODS Cadaveric liver transplant recipients were enrolled from January 2009 to September 2012 at 3 University Centers (Zurich/Sao Paulo/Ghent). Recipients were randomly assigned to propofol (control group) or sevoflurane anesthesia. Postoperative peak of aspartate transaminase was defined as primary endpoint, secondary endpoints were early allograft dysfunction, in-hospital complications, intensive care unit, and hospital stay. RESULTS Ninety-eight recipients were randomized to propofol (n = 48) or sevoflurane (n = 50). Median peak aspartate transaminase after transplantation was 925 (interquartile range, 512-3274) in the propofol and 1097 (interquartile range, 540-2633) in the sevoflurane group. In the propofol arm, 11 patients (23%) experienced early allograft dysfunction, 7 (14%) in the sevoflurane one (odds ratio, 0.64 (0.20 to 2.02, P = 0.45). There were 4 mortalities (8.3%) in the propofol and 2 (4.0%) in the sevoflurane group. Overall and major complication rates were not different. An effect on clinical outcomes was observed favoring the sevoflurane group (less severe complications), but without significance. CONCLUSIONS This first multicenter trial comparing propofol with sevoflurane anesthesia in liver transplantation shows no difference in biochemical markers of acute organ injury and clinical outcomes between the 2 regimens. Sevoflurane has no significant added beneficial effect on ischemia-reperfusion injury compared to propofol.


title: Recommendations for Trauma and Emergency General Surgery Practice During COVID-19 Pandemic.

text: COVID-19 is a new disease, based on currently available limited information, older adults and people of any age who have severe underlying medical conditions may be at higher risk for severe illness from COVID-19. People of all age groups are also at risk. Healthcare providers have always been the professionals most exposed to the risk of contracting to any kind of infection due to the nature of their profession. Elective interventions have been postponed to give care of patients with COVID-19. However, some interventions cannot be delayed, such as trauma surgery, acute abdomen, and emergency endoscopies. To maintain the sustainability of the healthcare system, the protection of healthcare providers should be the top priority. On the other hand, patients, who need emergency healthcare, should also be provided with appropriate treatment. Healthcare professionals should choose a treatment method appropriately in the circumstances to protect themselves and their patients as much as possible. This paper aims to summarize how a surgeon may act appropriately when an intervention is inevitable during the COVID-19 pandemic.


title: Best practices in cancer nanotechnology: perspective from NCI nanotechnology alliance.

text: Historically, treatment of patients with cancer using chemotherapeutic agents has been associated with debilitating and systemic toxicities, poor bioavailability, and unfavorable pharmacokinetics. Nanotechnology-based drug delivery systems, on the other hand, can specifically target cancer cells while avoiding their healthy neighbors, avoid rapid clearance from the body, and be administered without toxic solvents. They hold immense potential in addressing all of these issues, which has hampered further development of chemotherapeutics. Furthermore, such drug delivery systems will lead to cancer therapeutic modalities that are not only less toxic to the patient but also significantly more efficacious. In addition to established therapeutic modes of action, nanomaterials are opening up entirely new modalities of cancer therapy, such as photodynamic and hyperthermia treatments. Furthermore, nanoparticle carriers are also capable of addressing several drug delivery problems that could not be effectively solved in the past and include overcoming formulation issues, multidrug-resistance phenomenon, and penetrating cellular barriers that may limit device accessibility to intended targets, such as the blood-brain barrier. The challenges in optimizing design of nanoparticles tailored to specific tumor indications still remain; however, it is clear that nanoscale devices carry a significant promise toward new ways of diagnosing and treating cancer. This review focuses on future prospects of using nanotechnology in cancer applications and discusses practices and methodologies used in the development and translation of nanotechnology-based therapeutics.


title: Effects of pelvic organ prolapse repair on urinary symptoms: a comparative study between the laparoscopic and vaginal approach.

text: OBJECTIVE To compare changes in urinary symptoms before and after pelvic organ prolapse (POP) surgery, using either laparoscopic sacrocolpopexy (LSC) or transvaginal porcine dermis hammock placement with sacrospinous ligament suspension (VS). MATERIALS AND METHODS Data were prospectively collected from all women undergoing POP surgery between May 2001 and October 2009. Pre- and postoperative urinary symptoms, Urinary Distress Inventory (UDI), and Urinary Impact Questionnaires (UIQ) scores were compared within and between groups. A generalized linear model was used for multivariate analysis. RESULTS Out of the 151 patients included, 87 patients underwent LSC, and 64 VS. Overall, after a median follow-up of 32.4 months, POP surgery improved urinary frequency (P = 0.006), voiding difficulty (P = 0.001), stress urinary incontinence (SUI) (P = 0.001), but not urgency (P = 0.29). VS was more effective in treating SUI (P < 0.001 vs. 0.52) while LSC more effective on voiding difficulty (P = 0.01 vs. 0.08). Postoperative de novo symptoms were observed in 35.8% of patients with no difference between the groups (P = 0.06). UDI (P = 0.04) and UIQ (P = 0.01) scores were significantly lower after surgery. However, LSC significantly improved UDI (P = 0.03) with no effect on UIQ (P = 0.29) scores while VS significantly improved both scores (P = 0.02 and 0.001, respectively). Upon multivariate analysis, only the improvement in the impact of urinary symptoms on daily living was independently associated to VS (OR = 5.45 [95% confidence interval 2.20-13.44], P = 0.01). CONCLUSION Most preoperative urinary symptoms decreased after POP surgery with equivalent proportion of de novo symptoms after vaginal and laparoscopic approaches.


title: Direct Mechanical Intervention Versus Bridging Therapy in Stroke Patients Eligible for Intravenous Thrombolysis: A Pooled Analysis of 2 Registries.

text: BACKGROUND AND PURPOSE Randomized controlled trials have shown that mechanical thrombectomy (MT) plus best medical treatment improves outcome in stroke patients with large-vessel occlusion in the anterior circulation. Whether direct MT is equally effective as bridging thrombolysis (intravenous thrombolysis plus MT) in intravenous thrombolysis eligible patients remains unclear. METHODS We compared clinical and radiological outcomes at 3 months in 249 bridging patients with 111 patients receiving direct MT for large-vessel occlusion anterior circulation stroke from 2 prospective registries (study period Essen: June 2012 to August 2013, Bern February 2009 to August 2014). We matched all patients from the direct MT group who would have qualified for intravenous thrombolysis with controls from the bridging group, using multivariate and propensity score methods. Subgroup analyses for internal carotid artery occlusions were performed. RESULTS Baseline characteristics did not differ between the direct MT group and bridging cohort, except for higher rates of coronary heart disease (P=0.029) and shorter intervals from onset to endovascular therapy (P<0.001) in the MT group. Functional outcome, mortality, and intracerebral hemorrhage did not differ, neither in univariate nor after multivariate and propensity score matching. However, in patients with internal carotid artery occlusion, mortality in the direct cohort was significantly lower. CONCLUSIONS In this matched-pair analysis, there was no difference in outcome in patients with large-vessel occlusion anterior circulation stroke treated with direct MT compared with those treated with bridging thrombolysis; however, mortality in patients with internal carotid artery occlusion treated with direct MT was significantly lower than after bridging thrombolysis. Randomized trials comparing direct MT with bridging therapy are needed.


The COVID-19 Pandemic: A "Tech"-tonic Shift Toward Virtual Diabetes Care.


docid: lkpeoiyp

title: Acute effect on ambulatory blood pressure from aerobic exercise: a randomised cross-over study among female cleaners.

text: PURPOSE High occupational physical activity (OPA) is shown to increase the risk for elevated blood pressure, cardiovascular diseases and mortality. Conversely, aerobic exercise acutely lowers the blood pressure up to 25 h post exercise. However, it is unknown if this beneficial effect also apply for workers exposed to high levels of OPA. Cleaners constitute a relevant occupational group for this investigation because of a high prevalence of OPA and cardiovascular disease. Accordingly, the objective was to investigate the acute effects on ambulatory blood pressure from a single aerobic exercise session among female cleaners. METHODS Twenty-two female cleaners were randomised to a cross-over study with a reference and an aerobic exercise session. Differences in 24-h, work hours, leisure time, and sleep ambulatory blood pressure (ABP) were evaluated using repeated measure 2 × 2 mixed-models. RESULTS After the aerobic exercise session, the 24-h systolic ambulatory blood pressure was significantly lowered by 2.4 mmHg (p < 0.01) compared to the reference session. The 24-h diastolic ABP was unaltered. During work hours, a lowered systolic ABP of 2.2 mmHg (p = 0.02) and a higher diastolic ABP of 1.5 mmHg (p = 0.03) were found after the aerobic exercise session. During leisure time, the systolic ABP was lowered by 1.7 mmHg (p = 0.04) and the diastolic ABP was unaltered. During sleep, the systolic and diastolic ABP was unaltered. CONCLUSION A single aerobic exercise session lowered 24-h systolic ABP of 2.4 mmHg. Thus, an aerobic exercise session seems to be beneficial for lowering the risk of hypertension among cleaners.


Fully endoscopic removal of migrated mesh after laparoscopic fundoplication eroded into the gastroesophageal junction: a case report (with video).


title: G-quadruplex oligonucleotide AS1411 as a cancer-targeting agent: Uses and mechanisms.

text: BACKGROUND AS1411 is a 26-mer G-rich DNA oligonucleotide that forms a variety of G-quadruplex structures. It was identified based on its cancer-selective antiproliferative activity and subsequently determined to be an aptamer to nucleolin, a multifunctional protein that preferentially binds quadruplex nucleic acids and which is present at high levels on the surface of cancer cells. AS1411 has exceptionally efficient cellular internalization compared to non-quadruplex DNA sequences. SCOPE OF REVIEW Recent developments related to AS1411 will be examined, with a focus on its use for targeted delivery of therapeutic and imaging agents. MAJOR CONCLUSIONS Numerous research groups have used AS1411 as a targeting agent to deliver nanoparticles, oligonucleotides, and small molecules into cancer cells. Studies in animal models have demonstrated that AS1411-linked materials can accumulate selectively in tumors following systemic administration. The mechanism underlying the cancer-targeting ability of AS1411 is not completely understood, but recent studies suggest a model that involves: (1) initial uptake by macropinocytosis, a form of endocytosis prevalent in cancer cells; (2) stimulation of macropinocytosis by a nucleolin-dependent mechanism resulting in further uptake; and (3) disruption of nucleolin-mediated trafficking and efflux leading to cargoes becoming trapped inside cancer cells. SIGNIFICANCE Human trials have indicated that AS1411 is safe and can induce durable remissions in a few patients, but new strategies are needed to maximize its clinical impact. A better understanding of the mechanisms by which AS1411 targets and kills cancer cells may hasten the development of promising technologies using AS1411-linked nanoparticles or conjugates for cancer-targeted therapy and imaging. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio.


Impact of COVID-19 on loss and grief: a personal lens.


docid: ztdhgxno

title: The Impact of COVID-19 on the Health-Care Workforce: From Heroes to Zeroes?


Transgastric endoscopic vacuum therapy with a new open-pore film drainage device in a case of infective pancreatic necrosis.


title: Safety of Opioids in Osteoarthritis: Outcomes of a Systematic Review and Meta-Analysis.

text: OBJECTIVE We aimed to assess the safety of opioids in the management of osteoarthritis (OA) in a systematic review and meta-analysis of randomized, placebo-controlled trials. METHODS A comprehensive literature search was undertaken in the MEDLINE, Cochrane Central Register of Controlled Trials (Ovid CENTRAL), and Scopus electronic databases. Randomized, double-blind, placebo-controlled, parallel-group trials that assessed adverse events (AEs) with opioids in patients with OA were eligible for inclusion. Two authors appraised titles, abstracts and full-text papers for suitability and then assessed the studies for random sequence generation, allocation concealment, blinding of participants and personnel, blinding of outcome assessment, incomplete outcome data and selective outcomes reporting. The primary outcomes of interest were gastrointestinal (GI) disorders, cardiac disorders, vascular disorders, nervous system disorders, skin and subcutaneous tissue disorders, renal and urinary disorders, respiratory, thoracic and mediastinal disorders, as well as overall severe and serious AEs and drug-related AEs. Secondary outcomes were withdrawals due to AEs (i.e. the number of participants who stopped the treatment due to an AE) and total number of AEs (i.e. the number of patients who experienced any AE at least once). RESULTS Database searches identified 2189 records, from which, after exclusions, 17 papers were included in the meta-analysis. More disorders of the lower GI tract (constipation, fecaloma) were reported with both immediate-release (IR) and extended-release (ER) formulations of opioids versus placebo: IR opioids (relative risk [RR] 5.20, 95% confidence interval [CI] 3.42-7.89); ER opioids (RR 4.22, 95% CI 3.44-5.17). The risk of upper GI AEs increased fourfold with ER opioids compared with placebo (RR 4.03, 95% CI 0.87-18.62), and the risk of nausea, vomiting or loss of appetite increased four- to fivefold with both formulations: IR opioids (RR 3.39, 95% CI 2.22-5.18); ER opioids (RR 4.03, 95% CI 3.37-4.83). An increased risk of dermatologic AEs (rash and pruritis; IR opioids: RR 3.60, 95% CI 1.74-7.43; ER opioids: RR 7.87, 95% CI 5.20-11.89) and central nervous system disorders (dizziness, headache, fatigue, somnolence, insomnia; IR opioids: RR 2.76, 95% CI 1.90-4.02; ER opioids: RR 2.76, 95% CI 2.19-3.47) was found with all opioid formulations versus placebo. CONCLUSIONS Our results confirm that there are considerable safety and tolerability issues surrounding the use of opioids in OA, and support the recommendation of international and national guidelines to use opioids in OA after other analgesic options, and for short time periods.


title: SARS-CoV-2 infection in patients with autoimmune rheumatic diseases in northeast Italy: A cross-sectional study on 916 patients.

text: BACKGROUND Whether patients with autoimmune rheumatic diseases (ARD) have a higher risk for SARS-CoV-2 infection (COVID-19) and how SARS-CoV-2 pandemic impacts on adherence to therapy has not been fully elucidated. We assessed the rate and clinical presentation of COVID-19, and adherence to therapy in a large cohort of patients with ARD followed-up in a tertiary University-Hospital in Northeast Italy. METHODS Between April 9th and April 25th, 2020, after SARS-CoV-2 infection peak, a telephone survey investigating the impact of COVID-19 on patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc), rheumatoid arthritis (RA), ANCA-associated vasculitis (AAV), and idiopathic inflammatory myopathies (IIM) was administered. Demographics, disease activity status, therapy, occupational exposure, and adherence to social distancing advise were also collected. RESULTS 916 patients (397 SLE, 182 AAV, 176 SSc, 111 RA, 50 IIM) completed the survey. 148 patients developed at least one symptom compatible with COVID-19 (cough 96, sore throat 64, fever 64, arthromyalgias 59, diarrhea 26, conjunctivitis 18, ageusia/hyposmia, 18). Among the 916 patients, 65 (7.1%) underwent SARS-CoV-2 nasopharyngeal swab (18 symptomatic and 47 asymptomatic), 2 (0.21%) tested positive, a proportion similar to that observed in the general population of the Veneto region. No deaths occurred. 31 patients (3.4%) withdrew ≥1 medication, mainly immunosuppressants or biologics. Adoption of social distancing was observed by 860 patients (93.9%), including 335 (36.6%) who adopted it before official lockdown. CONCLUSIONS COVID-19 incidence seems to be similar in our cohort compared to the general population. Adherence to therapy and to social distancing advise was high.


title: On being a neurologist in Italy at the time of the COVID-19 outbreak.

text: Italy is facing its fifth week of crisis due to the COVID-19 outbreak, with affected patients and deaths near to 70.000 and 6000 respectively [1], numbers that are increasing every day. Whether government imposition of quarantines, travel bans and lockdown throughout the country will have effect in the next weeks in limiting the spreading of this disease has still to be seen. Meanwhile, a great spirit of sacrifice is required to health care personnel and authorities have to manage resource allocation to rapidly increase the number of intensive care beds to assist COVID-19 patients [2]. Although operating rooms and a number of wards have been turned into dedicated intensive units, beds and resources are hardly sufficient to satisfy the needs of so many simultaneously critically ill patients [3,4]. Notably, among infected people about 10% are health workers and their number is increasing, also due to the scarcity of efficacious protective measures.


title: The DERIVO Embolization Device in the Treatment of Intracranial Aneurysms: Short- and Midterm Results.

text: OBJECTIVE The DERIVO embolization device (DED) is a new nitinol flow diverter stent manufactured for the treatment of intracranial aneurysms. In this study, we evaluated the safety and efficacy of the DED in the treatment of intracranial aneurysms and present the short- and midterm results. METHODS We treated 34 aneurysms using 26 devices in 24 patients with wide-necked, mostly medium-sized, and fusiform aneurysms. Fourteen of the patients included in the study were women and the other 10 were men. Headache was the most frequent symptom. Although 31 (91.2%) aneurysms were in the anterior circulation, 3 (8.8%) were in the posterior. Intracranial stent medication was accomplished in all patients. All patients were evaluated 1 day later for any ischemic lesion with diffusion-weighted imaging. The first and second follow-up angiograms were planned to be performed after 3 and 9 months. RESULTS In all patients, the treatment was successful. No hemorrhagic complication was seen on computed tomography scan performed immediately after the procedure. All patients were discharged without any neurologic deficit. Although 20 (71.4%) of 28 aneurysms in 20 patients were totally closed on the 3-month follow-up angiogram, 14 (77.8%) of 18 aneurysms in 9 patients were totally closed on the 9-month follow-up. General morbidity was 8.4%, and mortality was 4.3%. CONCLUSIONS The DED seems effective and safe in the treatment of different kinds of intracranial aneurysms.


title: Suppression of innate immune pathology by regulatory T cells during Influenza A virus infection of immunodeficient mice.

text: The viral infection of higher vertebrates elicits potent innate and adaptive host immunity. However, an excessive or inappropriate immune response also may lead to host pathology that often is more severe than the direct effects of viral replication. Therefore, several mechanisms exist that regulate the magnitude and class of the immune response. Here, we have examined the potential involvement of regulatory T (Treg) cells in limiting pathology induced by influenza A virus (IAV) infection. Using lymphocyte-deficient mice as hosts, we showed that Treg cell reconstitution resulted in a significant delay in weight loss and prolonged survival following infection. The adoptively transferred Treg cells did not affect the high rate of IAV replication in the lungs of lymphocyte-deficient hosts, and therefore their disease-ameliorating effect was mediated through the suppression of innate immune pathology. Mechanistically, Treg cells reduced the accumulation and altered the distribution of monocytes/macrophages in the lungs of IAV-infected hosts. This reduction in lung monocytosis was associated with a specific delay in monocyte chemotactic protein-2 (MCP-2) induction in the infected lungs. Nevertheless, Treg cells failed to prevent the eventual development of severe disease in lymphocyte-deficient hosts, which likely was caused by the ongoing IAV replication. Indeed, using T-cell-deficient mice, which mounted a T-cell-independent B cell response to IAV, we further showed that the combination of virus-neutralizing antibodies and transferred Treg cells led to the complete prevention of clinical disease following IAV infection. Taken together, these results suggested that innate immune pathology and virus-induced pathology are the two main contributors to pathogenesis during IAV infection.


Laboratory abnormalities in children with novel coronavirus disease 2019.


Covid-19: state governors assert control over US response as Trump struggles for a role.


title: The Impact of Indocyanine-Green Fluorescence Angiography on Intraoperative Decision-Making and Postoperative Outcome in Free Flap Surgery.

text: BACKGROUND Reliable perfusion of the distal portions of free flaps is decisive for the reconstructive success. Indocyanine green near-infrared video angiography (ICG-NIR-VA) has been adopted for objective assessment of free flap tissue perfusion but is thus far not used on a routine basis. Therefore, we investigated its intraoperative impact on decision-making and postoperative outcome. METHODS From January 2017 to June 2019, 88 consecutive adipo- or fasciocutaneus free flaps were performed in conjunction with intraoperative ICG-NIR-VA. Free flap tissue perfusion was first assessed clinically and then compared with ICG-NIR-VA findings. Based on the results, the decision for intraoperative trimming of critically perfused flap zones was made. The way of decision-making, flap success, and failure rates as well as intra- and postoperative complication rates were analyzed. RESULTS The overall free flap success rate was 92.0%. Partial flap necrosis occurred in five cases (5.7%) and total flap necrosis in two cases (2.3%). ICG-NIR-VA aided decision-making and flap design in 34 cases (38.6%) and led to complication-free postoperative courses. When ICG-NIR-VA was relied on (82 out of 88 flaps; 93.2%), there was no unpredicted postoperative tissue necrosis (overestimation). When ICG-NIR-VA was not relied on (6 out of 88 flaps; 6.8%), there were five cases of postoperative partial flap necrosis and one case of uneventful healing (underestimation). The sensitivity of ICG-NIR-VA was 100% (95% confidence interval [CI]: 64.6-100) and the specificity was 98.8% (95% CI: 93.3-100) with a positive predictive value of 87.5% (95% CI: 52.9-99.4) and a negative predictive value of 100% (95% CI: 95.4-100). CONCLUSION Intraoperative ICG-NIR-VA objectified free flap perfusion and thus refined surgical decision-making on flap design in all cases. It could always predict tissue necrosis and subjectively improved outcomes in free flap surgery at our institution. Furthermore, it could be easily implemented in intraoperative routine, only adding minimal additional operative time.


History of science. Public Science 2.0--back to the future.


title: Neurally adjusted ventilatory assist and lung transplant in a child: A case report.

text: OBJECTIVE To report the successful application of neurally adjusted ventilatory assist to a child with cystic fibrosis who underwent single-lung transplantation. DESIGN Case report. SETTING Pediatric cardiac intensive care unit. PATIENT A 15-yr-old male with cystic fibrosis was admitted to our pediatric cardiac intensive care unit after single-lung transplantation. The child had previously received two bowel resections at the age of 1 yr, right pneumonectomy at the age of 3 yrs, and endoscopic percutaneus gastrostomy at the age of 10 yrs. After transplant, the child failed several attempts of weaning off mechanical ventilation with pressure-support ventilation, due to infection, pneumothorax, and ventilator asynchrony that caused gastric distension and numerous episodes of nausea and vomiting. INTERVENTION Use of neurally adjusted ventilatory assist to avoid patient-ventilator dyssynchrony and consequent gastric distension. CONCLUSIONS The utilization of neurally adjusted ventilatory assist allowed to limit the risk of overassistance and prevent patient-ventilator asynchrony and to successfully wean the child off mechanical ventilation after single-lung transplant.


title: Effects of manual rib cage compressions on expiratory flow and mucus clearance during mechanical ventilation.

text: OBJECTIVES We investigated the effects of two different types of manual rib cage compression on expiratory flow and mucus clearance during prolonged mechanical ventilation in pigs. DESIGN Prospective randomized animal study. SETTING Animal research facility, University of Barcelona, Spain. SUBJECTS Nine healthy pigs. MEASUREMENT AND MAIN RESULTS Pigs were tracheally intubated, sedated, paralyzed, and mechanically ventilated. The animals were prone on a surgical bed in the anti-Trendelenburg position. The experiments were carried out at approximately 60 and 80 hrs from the beginning of mechanical ventilation. Two types of manual rib cage compressions were tested: Hard and brief rib cage compressions synchronized with early expiratory phase (hard manual rib cage compression) and soft and gradual rib cage compressions applied during the late expiratory phase (soft manual rib cage compression). The interventions were randomly applied for 15min with a 15-min interval between treatments. Respiratory flow and mucus movement were assessed during the interventions. Respiratory mechanics and hemodynamics were assessed prior to and after the interventions. Peak expiratory flow increased to 60.1±7.1L/min in comparison to 51.2±4.6L/min without treatment (p < 0.0015) and 48.7±4.3L/min with soft manual rib cage compression (p = 0.0002). Similarly, mean expiratory flow increased to 28.4±5.2L/min during hard manual rib cage compression vs. 15.9±2.2 and 16.6±2.8L/min without treatment and soft manual rib cage compression, respectively (p = 0.0006). During hard manual rib cage compression, mucus moved toward the glottis (1.01 ± 2.37mm/min); conversely, mucus moved toward the lungs during no treatment and soft manual rib cage compression, -0.28 ± 0.61 and -0.15±0.95mm/min, respectively (p = 0.0283). Soft manual rib cage compression slightly worsened static lung elastance and cardiac output (p = 0.0391). CONCLUSIONS Hard manual rib cage compression improved mucus clearance in animals positioned in the anti-Trendelenburg position. The technique appeared to be safe. Conversely, soft manual rib cage compression was not effective and potentially unsafe. These findings corroborate the predominant role of peak expiratory flow on mucus clearance.


title: Evaluation of Burkholderia mallei ΔtonB Δhcp1 (CLH001) as a live attenuated vaccine in murine models of glanders and melioidosis.

text: BACKGROUND Glanders caused by Burkholderia mallei is a re-emerging zoonotic disease affecting solipeds and humans. Furthermore, B. mallei is genetically related to B. pseudomallei, which is the causative agent of melioidosis. Both facultative intracellular bacteria are classified as tier 1 select biothreat agents. Our previous study with a B. mallei ΔtonB Δhcp1 (CLH001) live-attenuated vaccine demonstrated that it is attenuated, safe and protective against B. mallei wild-type strains in the susceptible BALB/c mouse model. METHODOLOGY/PRINCIPAL FINDING In our current work, we evaluated the protective efficacy of CLH001 against glanders and melioidosis in the more disease-resistant C57BL/6 mouse strain. The humoral as well as cellular immune responses were also examined. We found that CLH001-immunized mice showed 100% survival against intranasal and aerosol challenge with B. mallei ATCC 23344. Moreover, this vaccine also afforded significant cross-protection against B. pseudomallei K96243, with low level bacterial burden detected in organs. Immunization with a prime and boost regimen of CLH001 induced significantly greater levels of total and subclasses of IgG, and generated antigen-specific splenocyte production of IFN-γ and IL-17A. Interestingly, protection induced by CLH001 is primarily dependent on humoral immunity, while CD4+ and CD8+ T cells played a less critical protective role. CONCLUSIONS/SIGNIFICANCE Our data indicate that CLH001 serves as an effective live attenuated vaccine to prevent glanders and melioidosis. The quantity and quality of antibody responses as well as improving cell-mediated immune responses following vaccination need to be further investigated prior to advancement to preclinical studies.


title: Long-term quality of life after peroral endoscopic myotomy remains compromised in patients with achalasia type III.

text: Background and study aims Peroral endoscopic myotomy (POEM) is an excellent endoscopic treatment for achalasia. Clinical and manometric parameters are used for evaluation and follow-up. However, clinical success does not guarantee high quality of life (QoL) scores, generating doubts about their direct relationship. We aimed to evaluate QoL scores before and after POEM at medium and long term, to evaluate differences between achalasia subtypes and find which factors related to low QoL scores. Patients and methods Achalasia-confirmed patients undergoing POEM between February 2012 and November 2016. and completing at least 1 year of follow-up, were included. Assessment before and at 1, 6, 12, 24, 36 and 48 months after POEM employed manometry, barium series, Eckardt score, and the AE-18 health-related QoL scale. Demographic, clinical, and procedure characteristics were documented, with comparisons between subgroups. Multiple logistic regression analysis was done. Results 65 of 88 patients were included (38 women, 27 men; median age 47 years, interquartile range [IQR] 20 - 81), and 50 (76.9 %) completed 4 years of follow-up. Eckardt score improved (median, preprocedure 10 vs. post-procedure 2; P = 0.002) and this persisted. There was initial improvement in median integrated relaxation pressure (IRP) (29.4 mmHg [16 - 55] vs. 10.3 mmHg [3 - 18]; P = 0.000) and median QoL scores (40 vs. 68 at 1 month; P = 0.002); however IRP increased and QoL scores decreased. Men with confirmed type III achalasia had low QoL scores. Conclusions All patients had significant clinical improvement after POEM, with medium- to long-term persistence. Though quality of life and IRP initially improved, they deteriorated in the long term. Male sex and type III achalasia seem to be associated with low QoL scores.


title: Comparison of VividTrac®, Airtraq®, King Vision®, Macintosh Laryngoscope and a Custom-Made Videolaryngoscope for difficult and normal airways in mannequins by novices.

text: BACKGROUND Direct laryngoscopy remains the gold standard for endotracheal intubation and is preferred by experienced operators. However, an increasing number of reports currently support videolaryngoscopy, particularly for novice users. The widespread use of videolaryngoscopy may be limited due to financial limitations, especially in low-income countries. Therefore, affordable single-use scopes are now becoming increasingly popular. We sought to compare these new scopes with direct laryngoscopes and the previously tested videolaryngoscopes in mannequins by novices. METHODS Fifty medical students were recruited to serve as novice users. Following brief, standardized training, students were asked to execute endotracheal intubation with each of the devices, including the Airtraq®, a custom-made videolaryngoscope, the King Vision®, the Macintosh laryngoscope and the VividTrac®, on an airway trainer (Laerdal Airway Management Trainer®) in normal and difficult airway scenarios. We evaluated the time to and the proportion of successful intubation, the best view of the glottis, esophageal intubation, dental trauma and user satisfaction. RESULTS We observed no differences in esophageal intubation. However, intubation-related times, the view of the glottis and operator satisfaction were significantly better throughout the study with the commercial videolaryngoscopes. In comparison, the custom-made videolaryngoscope performance proved to be similar to that of the Macintosh laryngoscope. The VividTrac® performance was similar (P > 0.05) or significantly better than that of the King Vision® in both scenarios. CONCLUSIONS Based upon our results, the Airtraq®, King Vision® and VividTrac® were superior to the Macintosh laryngscope in both normal and difficult airway scencarios for novice users. In particular, our study is the first to report that the VividTrac® shows promise for further clinical evaluation.


title: Uro-oncology in times of COVID-19: The available evidence and recommendations in the Indian scenario.

text: The Corona Virus Disease-2019 (COVID-19), one of the most devastating pandemics ever, has left thousands of cancer patients to their fate. The future course of this pandemic is still an enigma, but health care services are expected to resume soon in a phased manner. This might be a long drawn process and we need to have policies in place, to be able to fight both, the SARS-CoV-2 virus and cancer, simultaneously, and emerge triumphant. An extensive literature search for impact of delay in management of various urological malignancies was carried out. Expert opinions were sought wherever there was paucity of evidence, in order to reach a consensus and come up with recommendations for directing uro-oncology services in the times of COVID-19. The panel recommends deferring treatment of patients with renal cell carcinoma by 3 to 6 months, except for those with ongoing hematuria and/or inferior vena cava thrombus, which warrant immediate surgery. Metastatic renal cell cancers should be started on targeted therapy. Low grade non-muscle invasive bladder cancers can be kept on active surveillance while high risk non-muscle invasive bladder cancers and muscle invasive bladder cancers should be treated within 3 months. Neoadjuvant chemotherapy should be avoided. Management of low and intermediate risk prostate cancer can be deferred for 3 to 6months while high risk prostate cancer patients can be initiated on neoadjuvant androgen deprivation therapy. Patients with testicular tumors should undergo high inguinal orchiectomy and be treated according to stage without delay, with stage I patients being offered surveillance. Penile cancers should undergo penectomy, while clinically negative groins can be kept on surveillance. Neoadjuvant chemotherapy should be avoided and adjuvant therapy should be deferred. We need to tailor our treatment strategies to the prevailing present conditions, so as to fight and defeat both, the SARS-CoV-2 virus and cancer. Protection of health care workers, judicious use of available resources, and a rational and balanced outlook towards different malignancies is the need of the hour.


title: Endoscopic Mucosal Healing Predicts Favorable Clinical Outcomes in Inflammatory Bowel Disease: A Meta-analysis.

text: BACKGROUND Mucosal healing (MH) in inflammatory bowel disease has been associated with improved long-term clinical outcomes. Uncertainty remains as to the magnitude of this effect and to how this association changes with time and degree of healing. METHODS PubMed, EMBASE, and Web of Science searches identified 1570 citations. Screening of abstracts identified 155 articles for full-text review, of which 19 met inclusion criteria. For 3 outcomes of interest (surgeries, hospitalizations, remission), weighted random-effects meta-analysis was performed. RESULTS In pooled analysis, MH predicted fewer major abdominal surgeries (relative risk [RR], 0.34; 95% confidence interval [CI], 0.26-0.46), increased remission (RR, 1.84; 95% CI, 1.43-2.36), and fewer hospitalizations (RR, 0.58; 95% CI, 0.42-0.78). Complete MH and partial MH both showed significantly higher rates of favorable outcomes. Separate analyses for Crohn's disease and ulcerative colitis showed identical patterns for surgeries and remission. When subjects with no healing were excluded, and complete versus partial healing was compared, rates of surgery were not significantly different (RR, 0.82; 95% CI, 0.46-1.44). However, complete healing was superior in predicting corticosteroid-free remission (RR, 1.71; 95% CI, 1.24-2.34). Meta-regression found that the predictive power of this complete versus partial healing distinction was strongly associated with the duration of follow-up after endoscopy. CONCLUSIONS MH is a strong predictor of fewer surgeries, long-term clinical remission, and fewer hospitalizations. Complete healing is not significantly more favorable than partial healing for predicting surgeries or hospitalizations, but it did predict higher rates of clinical remission. This benefit of complete MH over partial healing increases with follow-up time.


title: High incidence but low burden of coronaviruses and preferential associations between respiratory viruses.

text: Respiratory viruses are the leading cause of acute infections in humans. However, the burden of certain respiratory viruses, such as coronaviruses, and the relevance of viral coinfections remain unclear. In this study, we investigated the distribution and seasonal occurrences of respiratory viruses detected by multiplex molecular assay in 6,014 samples from 2008 to 2011 in a French hospital. We assessed the detection frequencies of 14 respiratory viruses and their clinical impact in immunosuppressed and nonimmunosuppressed patients. Furthermore, we explored the preferential association patterns between respiratory viruses in multiple infections. Our results indicated that human rhinovirus/enterovirus (HRV/EV) and coronavirus (HCoV) were frequently detected in respiratory samples (48.81% and 11.74% of infected samples, respectively), and the detection frequencies of these viruses were further increased in immunosuppressed patients. The most common subtypes of HCoV were HCoV-229E (33.80%) and HCoV-HKU1 (32.39%). A sharp increase in the detection frequencies of HCoV-229E and HCoV-HKU1 over several months suggested that these subtypes were epidemic in our population. In immunosuppressed patients, HCoV contributed to upper respiratory tract infections (52%). Evidence did not support lower respiratory tract infections exclusive to a unique HCoV infection. In multiply infected individuals, determined in 6.3% of samples, HRV/EV and HCoV were detected in 33.29% and 22.90% of samples, respectively. Interestingly, nearly 50% of HCoV infections were detected in association with another virus. Since the distributions of respiratory viruses in multiply infected patients were subject to preferential association patterns between viruses, we propose complex interactions between different respiratory viruses and host factors.


title: Laparoscopic transvesical removal of erosive mesh after transobturator tape procedure.

text: We have experienced two cases of intravesical transobturator tape (TOT) tape successfully removed by laparoscopic transvesical procedure. Patient 1 was a 67-year-old woman complaining of irritative symptoms of the urinary bladder. In another hospital she had undergone anterior corporrhaphy and a TOT procedure to treat a cystocele and stress urinary incontinence (SUI) 17 months before the initial consultation. A cystoscopy revealed tape extrusion and adherent calculi at the 4 to 5 O'clock position of the bladder neck. After filling the bladder with carbon dioxide, three 5-mm ports were placed in lower abdomen directly into the bladder. The tape extruding from the bladder muscle layer was completely excised, and extirpated with the adherent calculi. The bladder mucosa and muscle layer were continuously sutured using 4-0 Vicryl (Ethicon Inc., Somerville, NJ, USA). The port entry sites were closed under direct vision using 4-0 Vicryl. SUI recurred 15 months later and a second TOT surgery was performed. Neither SUI nor mesh extrusion have been observed during the 18 months following the second TOT. Patient 2 was a 74-year-old woman. She consulted our hospital for the removal of an intravesically extruded tape and adherent calculi. She had undergone a vaginal hysterectomy and TOT surgery for uterine prolapse and SUI at another hospital 3 years before her visit. A cystoscopy revealed tape extrusion and adherent calculi on the right bladder wall. We performed an endoscopic transvesical extirpation of the intravesical foreign bodies in a same manner described below. There has been no recurrent SUI or mesh erosion during the 18-month follow up.


Flow diverting stents for cerebral aneurysm treatment: time to replace coiling?


title: Repeated percutaneous radiofrequency ablation for hepatocellular carcinoma in patients with cirrhosis: assessment of safety based on liver function and portal hypertension parameters.

text: PURPOSE To evaluate changes in liver function and portal hypertension parameters after repeated percutaneous radiofrequency (RF) ablation for hepatocellular carcinoma (HCC) in patients with cirrhosis. MATERIALS AND METHODS This study included 24 patients (male-to-female ratio, 15:9; mean age, 59.4 y) with early-stage HCC (mean tumor size, 1.91 cm) and cirrhosis who underwent three consecutive treatments with RF ablation between April 1999 and August 2011. Serial changes of liver function and portal hypertension parameters after repeated RF ablation were compared with baseline values using a mixed model and Wilcoxon signed rank test. RESULTS The interval between the first and second RF ablation measurements and between the second and third RF ablation measurements was 26.1 months ± 18.3 (range, 3.8-65.8 mo) and 16.6 months ± 9.8 (range, 4.7-35.4 mo), respectively. Total bilirubin level was significantly increased between the first RF ablation and 6 months after the third RF ablation (0.75 g/dL ± 0.37 to 1.06 g/dL ± 0.68, P = .001), but all values were within the normal range. No other liver function parameter showed a significant change (P > .05 for all). Portal hypertension parameters did not show significant changes between the first RF ablation and 6 months after the third RF ablation (P > .05). CONCLUSIONS Repeated RF ablation for controlling recurrent HCC did not seem to affect liver function and portal hypertension in patients.


title: Do exposures to aerosols pose a risk to dental professionals?

text: Background Dental care professionals are exposed to aerosols from the oral cavity of patients containing several pathogenic microorganisms. Bioaerosols generated during dental treatment are a potential hazard to dental staff, and there have been growing concerns about their role in transmission of various airborne infections and about reducing the risk of contamination. Aims To investigate qualitatively and quantitatively the bacterial and fungal aerosols before and during clinical sessions in two dental offices compared with controls. Methods An extra-oral evacuator system was used to measure bacterial and fungal aerosols. Macroscopic and microscopic analysis of bacterial species and fungal strains was performed and strains of bacteria and fungi were identified based on their metabolic properties using biochemical tests. Results Thirty-three bioaerosol samples were obtained. Quantitative and qualitative evaluation showed that during treatment, there is a significant increase in airborne concentration of bacteria and fungi. The microflora included mainly gram-positive organisms (Staphylococcus epidermidis and Micrococcus spp.), gram-positive rod-shaped bacteria and those creating endospores as well as non-porous bacteria and mould fungi (Cladosporium and Penicillium). Conclusions Exposure to the microorganisms identified is not a significant occupational hazard for dental care professionals; however, evidence-based prevention measures are recommended.


title: Simplified synchronous disconnection of pulmonary arteries and veins for right upper lobectomy.

text: BACKGROUND Video-assisted thoracoscopic lobectomy with lymphadenectomy is considered one of the most effective treatments for early non-small cell lung cancer. We developed a novel approach for lobectomy in patients with right upper lung cancer through simplified synchronous disconnection of pulmonary arteries and veins. This study aimed to evaluate the feasibility, efficacy, safety, and cost-effectiveness of this minimally invasive technique in managing right upper lobectomy. PATIENTS AND METHODS From March 2016 to September 2017, 62 patients with right upper lung cancer underwent lobectomy via simplified synchronous disconnection of pulmonary arteriovenous by video-assisted thoracoscopic surgery. All patients were followed up for 6-12 months after the procedure through clinic visits or telephone/e-mail interviews. RESULTS Of the 62 patients (mean age, 57.2 ± 8.7 years), 28 were men (45.2%) and 34 (54.8%) were women. All procedures were successfully performed by thoracoscopy, with a mean operating time of 66.2 ± 9.0 min. The mean blood loss was 40.3 ± 19.5 mL. Only 1 (1.61%) patient required blood transfusion. The mean number of endoscopic linear stapling devices used was 2.6 ± 0.7. The mean number of lymph nodes harvested was 16.0 ± 1.6. Postoperative pneumonia was encountered in 4 (6.45%) patients. There was no postoperative mortality. The mean length of hospital stay was 5.3 ± 1.3 days. Six-month follow-up revealed an excellent clinical result and degree of satisfaction. CONCLUSIONS Simplified synchronous disconnection of pulmonary arteries and veins is a feasible, economical, safe, and effective therapeutic procedure for right upper lung carcinoma. This novel procedure shows promise as a viable surgical approach for right upper lobectomy.


title: Peptide receptor radionuclide therapy with 177Lu-DOTATATE for patients with somatostatin receptor-expressing neuroendocrine tumors: the first US phase 2 experience.

text: OBJECTIVE Peptide receptor radionuclide therapy with radiolabeled somatostatin analogs is a novel method of treatment in patients with metastatic neuroendocrine tumors (NETs). For the first time in the United States, we present preliminary results of the treatment with Lutetium (177)(Lu) DOTATATE in patients with progressive NETs. METHODS Thirty-seven patients with grade 1 and grade 2 disseminated and progressive gastroenteropancreatic NET were enrolled in a nonrandomized, phase 2 clinical trial. Repeated cycles of 200 mCi (7.4 GBq; ±10%) were administered up to the cumulative dose of 800 mCi (29.6 GBq; ±10%). RESULTS Among 32 evaluable patients, partial response and minimal response to treatment were seen in 28% and 3%, respectively, and stable disease was seen in 41% of patients. A total of 28% had progressive disease. A response to treatment was significantly associated with lower burden of disease in the liver. No significant acute or delayed hematologic or kidney toxicity was observed. An impressive improvement of performance status and quality of life were seen after Lu-DOTATATE therapy. CONCLUSIONS Treatment with multiple cycles of (177)Lu-DOTATATE peptide receptor radionuclide therapy is well tolerated. This treatment results in control of the disease in most patients, whereas systemic toxicities are limited and reversible. Quality of life is also improved.


title: Genomics and zoonotic infections: Middle East respiratory syndrome.

text: The emergence of Middle East respiratory syndrome (MERS) and the discovery of MERS coronavirus (MERS-CoV) in 2012 suggests that another SARS-like epidemic is occurring. Unlike the severe acute respiratory syndrome (SARS) epidemic, which rapidly disappeared in less than one year, MERS has persisted for over three years. More than 1,600 cases of MERS have been reported worldwide, and the disease carries a worryingly high fatality rate of >30%. A total of 182 MERS-CoV genomes have been sequenced, including 94 from humans and 88 from dromedary camels. The 182 genomes all share >99% identity, indicating minimal variation among MERS-CoV genomes. MERS-CoV is a lineage C Betacoronavirus (ßCoV). MERS-CoV genomes can be roughly divided into two clades: clade A, which contains only a few strains, and clade B, to which most strains belong. In contrast to ORF1ab and structural proteins, the putative proteins encoded by ORF3, ORF4a, ORF4b, ORF5 and ORF8b in the MERS-CoV genome do not share homology with any known host or virus protein, other than those of its closely related lineage C ßCoVs. Human and dromedary viral genomes have intermingled, indicating that multiple camel-to-human transmission events have occurred. The multiple origins of MERS-CoV suggest that the virus has been resident in dromedaries for many years. This is consistent with the detection of anti-MERS-CoV antibodies in dromedary camels as early as the 1980s.


title: Gastric bypass promotes more lipid mobilization than a similar weight loss induced by low-calorie diet.

text: Background. Recently, we found large reductions in visceral and subcutaneous fat one month after gastric bypass (GBP), without any change in liver fat content. Purpose. Firstly to characterize weight loss-induced lipid mobilization after one month with preoperative low-calorie diet (LCD) and a subsequent month following GBP, and secondly, to discuss the observations with reference to our previous published findings after GBP intervention alone. Methods. 15 morbidly obese women were studied prior to LCD, at GBP, and one month after GBP. Effects on metabolism were measured by magnetic resonance techniques and blood tests. Results. Body weight was similarly reduced after both months (mean: -8.0 kg, n = 13). Relative body fat changes were smaller after LCD than after GBP (-7.1 ± 3.6% versus -10 ± 3.2%, P = .029, n = 13). Liver fat fell during the LCD month (-41%, P = .001, n = 13) but was unaltered one month after GBP (+12%). Conclusion. Gastric bypass seems to cause a greater lipid mobilization than a comparable LCD-induced weight loss. One may speculate that GBP-altered gastrointestinal signalling sensitizes adipose tissue to lipolysis, promoting the changes observed.


title: Single-incision laparoscopic cholecystectomy: the first 100 outpatients.

text: BACKGROUND Single-incision laparoscopic surgery (SILS) is a well-described technique for many general surgical procedures. The SILS techniques applied to cholecystectomy vary, and reporting has been sparse. Because most cholecystectomies are outpatient procedures performed by busy, practicing general surgeons, the authors report their initial experience adopting this technique. METHODS From March, 2008 to January, 2009, SILS was performed for 100 consecutive outpatients needing cholecystectomy. All the patients underwent a single-incision, multiport laparoscopic (SIMPL) technique using existing instrumentation. The patients were followed postoperatively for at least 6 months. RESULTS Of the 100 patients, 98 underwent SIMPL cholecystectomy and 2 required conversion to the standard laparoscopic technique because of bleeding from the cystic artery. No major postoperative complications occurred, including infections and hernias. CONCLUSIONS The findings show SIMPL cholecystectomy to be safe in the outpatient setting. It is an excellent alternative to traditional three- or four-port cholecystectomy for the ideal candidate with a lower body mass index (BMI), early disease, and no previous abdominal surgery. The authors' initial outpatient experience shows that it can be performed using existing instrumentation without increasing costs by a reproducible technique that can be adopted by any practicing general surgeon.


Epidemiology of pertussis in Marrakech and contribution of molecular diagnosis.


title: Association of body temperature with obesity. The CoLaus study.

text: BACKGROUND AND AIMS There is conflicting evidence regarding the association between body temperature and obesity. We aimed to assess the associations between body temperature and several adiposity and metabolic markers according to gender and menopausal status in a large population-based sample. METHODS The data collected between 2009 and 2012 from 4224 participants (mean age 57.3 ± 10.4 years, 2225 women) of the CoLaus study (Lausanne, Switzerland). Body temperature was measured at the tympanic membrane. RESULTS Mean body temperature was 36.1 ± 0.4, 36.4 ± 0.4 and 36.3 ± 0.4 °C in men, premenopausal, and postmenopausal women, respectively (p < 0.001). In men and postmenopausal women, body temperature was positively and significantly (p < 0.05) associated with body mass index (Spearman correlation coefficients 0.157 and 0.083, respectively), waist (r = 0.163 and r = 0.104), waist to hip ratio (r = 0.187 and r = 0.132), body area (r = 0.094 and r = 0.085), resting heart rate (r = 0.227 and r = 182), glucose (r = 0.104 and r = 0.088) and insulin (r = 0.148 and r = 0.117). Except for body area and BMI in postmenopausal women, all associations remained significant after multivariable adjustment. In premenopausal women, body temperature was positively associated with resting heart rate (r = 0.140) and insulin (r = 0.170), and no significant associations were found after multivariable adjustment. CONCLUSION Body temperature is strongly associated with obesity markers in men and postmenopausal women. The absence of association in premenopausal women might be due to the influence of the menstrual cycle.


title: Sequential regimen of clofarabine, cytosine arabinoside and reduced-intensity conditioned transplantation for primary refractory acute myeloid leukemia.

text: The prognosis of patients with acute myeloid leukemia in whom primary treatment fails remains very poor. In order to improve such patients' outcome, we conducted a phase 2, prospective, multicenter trial to test the feasibility of a new sequential regimen, combining a short course of intensive chemotherapy and a reduced intensity-conditioning regimen, before allogeneic stem-cell transplantation. Twenty-four patients (median age, 47 years) with acute myeloid leukemia in primary treatment failure were included. Cytogenetic risk was poor in 15 patients (62%) and intermediate in nine (38%). The sequential regimen consisted of clofarabine (30 mg/m2/day) and cytosine arabinoside (1 g/m2/day) for 5 days, followed, after a 3-day rest, by reduced-intensity conditioning and allogeneic stem-cell transplantation combining cyclophosphamide (60 mg/kg), intravenous busulfan (3.2 mg/kg/day) for 2 days and anti-thymocyte globulin (2.5 mg/kg/day) for 2 days. Patients in complete remission at day +120 received prophylactic donor lymphocyte infusion. Eighteen patients (75%) achieved complete remission. With a median follow-up of 24.6 months, the Kaplan-Meier estimate of overall survival was 54% (95% CI: 33-71) at 1 year and 38% (95% CI: 18-46) at 2 years. The Kaplan-Meier estimate of leukemia-free survival was 46% (95% CI: 26-64) at 1 year and 29% (95% CI: 13-48) at 2 years. The cumulative incidence of non-relapse mortality was 8% (95% CI: 1-24) at 1 year and 12% (95% CI: 3-19) at 2 years. Results from this phase 2 prospective multicenter trial endorsed the safety and efficacy of a clofarabine-based sequential reduced-toxicity conditioning regimen, which warrants further investigation. This study was registered at www.clinicaltrials.gov, identifier number: NCT01188174.


title: Efficacy and safety of the novel electrosurgical vessel sealing and cutting instrument BiCision®.

text: BACKGROUND The use of energy-based tissue-sealing and cutting instruments is becoming more and more popular in visceral, urological, and gynecological surgery. For their safe and efficacious use in clinical practice, such instruments have to reliably seal vessels with a minimal sealing failure rate, cause minimal thermal damage to adjacent tissue, and have good cutting qualities. METHODS The efficacy and safety of the novel energy-based instrument for dissection, hemostasis and cutting (BiCision(®), ERBE) was compared to a commercially available device (EnSeal(®), Ethicon Endo-Surgery). We investigated vessel-sealing reliability (success rate), sealing quality and sealing time, lateral thermal damage cutting quality, tissue sticking to the instrument, burst pressure and delayed complications in an acute and chronic pig model after splenectomy, small bowel resection, nephrectomy, salpingo-oophorectomy, and sealing of peripheral vessels. RESULTS For all parameters investigated, BiCision(®) was at least equivalent to EnSeal(®). BiCision(®) was even superior to EnSeal(®) with respect to the burst pressure in arteries (p = 0.044) and veins (p = 0.023) and the cut quality in all locations (arteries, p = 0.0009; veins, p = 0.043). The course of the 7-day chronic study was uneventful except for one animal that developed an intestinal obstruction. None of the animals showed any signs of postoperative bleeding. On second-look laparotomy at day 7, macroscopic inspection of the sealed tissue and vessels did not show any signs of complications or evidence that bleeding had occurred. Histologically, the integrity of vessel wall fusion, thermal alterations, and inflammatory reactions were comparable, confirming substantial equivalence. CONCLUSION We demonstrated that the efficacy and quality of vessel sealing with BiCision(®) is at least equivalent to those of EnSeal(®) for vessel diameters up to 7 mm. Since EnSeal(®) has already been shown to be safe in clinical practice, BiCision(®) should be as reliable as EnSeal(®) under clinical conditions.


Going virtual.


title: Implementation of Bubble CPAP in a Rural Ugandan Neonatal ICU.

text: BACKGROUND Respiratory distress is a leading cause of neonatal death in low-income and middle-income countries. CPAP is a simple and effective respiratory support modality used to support neonates with respiratory failure and can be used in low-income and middle-income countries. The goal of this study was to describe implementation of the Silverman-Andersen respiratory severity score (RSS) and bubble CPAP in a rural Ugandan neonatal NICU. We sought to determine whether physicians and nurses in a low-income/middle-income setting would assign similar RSS in neonates after an initial training period and over time. METHODS We describe the process of training NICU staff to use the RSS to assist in decision making regarding initiation, titration, and termination of bubble CPAP for neonates with respiratory distress. Characteristics of all neonates with respiratory failure treated with bubble CPAP in a rural Ugandan NICU from January to June 2012 are provided. RESULTS Nineteen NICU staff members (4 doctors and 15 nurses) received RSS training. After this, the Spearman correlation coefficient for respiratory severity scoring between doctor and nurse was 0.73. Twenty-one infants, all < 3 d of age, were treated with CPAP, with 17 infants starting on the day of birth. The majority of infants (16/21, 76%) were preterm, 10 (48%) were <1,500 g (birthweight), and 13 (62%) were outborn. The most common diagnoses were respiratory distress syndrome (16/21, 76%) and birth asphyxia (5/21, 24%). The average RSS was 7.4 ± 1.3 before starting CPAP, 5.2 ± 2.3 after 2-4 h of CPAP, 4.9 ± 2.7 after 12-24 h of CPAP, and 3.5 ± 1.9 before CPAP was discontinued. Duration of treatment with CPAP averaged 79 ± 43 h. Approximately half (11/21, 52%) of infants treated with CPAP survived to discharge. CONCLUSIONS Implementing bubble CPAP in a low-income/middle-income setting is feasible. The RSS may be a simple and useful tool for monitoring a neonate's respiratory status and for guiding CPAP management.


Exposed: cells' sugary secrets.


title: Spectrum of Imaging Findings on Chest Radiographs, US, CT, and MRI Images in Multisystem Inflammatory Syndrome in Children (MIS-C) Associated with COVID-19.

text: This case series examines the spectrum of imaging findings on chest radiographs, US, CT, and MRI images in 35 children admitted to a tertiary pediatric hospital in April-May 2020 with a post COVID-19 inflammatory condition known as multisystem inflammatory syndrome in children (MIS-C). The constellation of findings includes airway inflammation and rapid development of pulmonary edema on thoracic imaging, coronary artery aneurysms, and extensive right iliac fossa inflammatory changes on abdominal imaging. Awareness of this emerging condition and the expected multi-organ imaging findings will aid radiologists in the assessment of these complex cases.


HLA studies in the context of coronavirus outbreaks.


title: Longitudinal assessment of T cell inhibitory receptors in liver transplant recipients and their association with posttransplant infections.

text: Current immunosuppression regimens in organ transplantation primarily inhibit T cells. However, T cells are also critical in protective immunity, especially in immune-compromised patients. In this study, we examined the association of T cell dysfunction, as marked by expression of T cell exhaustion molecules, and posttransplant infections in a cohort of liver transplant patients. We focused on Programmed Death 1 (PD-1) and T cell Ig- and mucin-domain molecule 3 (Tim-3), which are potent co-inhibitory receptors, and their persistent expression often leads to T cell dysfunction and compromised protective immunity. We found that patients with the highest expression of PD-1 +Tim-3+ T cells in the memory compartment before transplantation had increased incidence of infections after liver transplantation, especially within the first 90 days. Longitudinal analysis in the first year showed a strong association between variability of PD-1 and Tim-3 expression by T cells and infectious episodes in transplant patients. Furthermore, T cells that expressed PD-1 and Tim-3 had a significantly reduced capacity in producing interferon (IFN)-γ in vitro, and this reduced IFN-γ production could be partially reversed by blocking PD-1 and Tim-3. Interestingly, the percentage of Foxp3+ regulatory T cells in liver transplant patients was stable in the study period. We concluded that the functional status of T cells before and after liver transplantation, as shown by PD-1 and Tim-3 expression, may be valuable in prognosis and management of posttransplant infections.


docid: qtamwrun

title: Covid-19 and inflammatory bowel disease: questions on incidence, severity, and impact of treatment?


title: A social-cognitive model of pandemic influenza H1N1 risk perception and recommended behaviors in Italy.

text: The outbreak of the pandemic influenza H1N1 2009 (swine flu) between March and April 2009 challenged the health services around the world. Indeed, misconceptions and worries have led the public to refuse to comply with precautionary measures. Moreover, there have been limited efforts to develop models incorporating cognitive, social-contextual, and affective factors as predictors of compliance with recommended behaviors. The aim of this study was to apply a social-cognitive model of risk perception and individual response to pandemic influenza H1N1 in a representative sample of Italian population. A sample of 1,010 Italians of at least 18 years of age took part in a telephone survey. The survey included measures of perceived preparedness of institutions, family members and friends' levels of worry, exposure to media campaigns (social-contextual factors), perceived coping efficacy, likelihood of infection, perceived seriousness, personal impact, and severity of illness (cognitive evaluations), affective response and compliance with recommended behaviors. Results demonstrated that affective response fully mediated the relationship between cognitive evaluations and social-contextual factors (with the exception of exposure to media campaigns) and compliance with recommended behaviors. Perceived coping efficacy and preparedness of institutions were not related to compliance with recommended behaviors.


title: Porcine reproductive and respiratory syndrome virus modifies innate immunity and alters disease outcome in pigs subsequently infected with porcine respiratory coronavirus: implications for respiratory viral co-infections.

text: The innate immune response is critical for host defence against respiratory coronaviruses (CoVs). This study demonstrated that an ongoing respiratory virus infection compromises innate immune responses and affects the pathogenesis of a respiratory CoV co-infection. An innate immunosuppressive respiratory virus infection was established by infecting weaned pigs with porcine reproductive and respiratory syndrome virus (PRRSV); 10 days later, the pigs were exposed to porcine respiratory coronavirus (PRCV). The PRRSV/PRCV dual-infected pigs had reduced weight gains, a higher incidence of fever and more severe pneumonia compared with either single infection. Significant suppression of innate immune responses [reduced alpha interferon (IFN-alpha) levels in the lungs and reduced blood natural killer cell cytotoxicity] by the ongoing PRRSV infection was observed in dual-infected pigs, which coincided with exacerbated pneumonia during early PRCV infection. The subsequent PRCV infection led to enhanced PRRSV replication in the lungs and a trend towards increased serum T-helper type 1 (Th1) (IFN-gamma) but decreased Th2 [interleukin (IL)-4] responses, further exacerbating PRRSV pneumonia. Following PRCV infection, more severe PRRSV-related pulmonary alveolar macrophage (PAM) apoptosis occurred, as determined by an in situ terminal deoxynucleotidyl transferase-mediated dUTP nick end labelling assay, suggesting increased PRRSV replication in PAMs. Collectively, these observations suggest interactive effects between PRCV and PRRSV via early innate (IFN-alpha) and later adaptive Th1 (IFN-gamma) and Th2 (IL-4) immune responses. These findings imply that an existing immunomodulating respiratory viral co-infection may be a contributing factor to more severe pneumonia in respiratory CoV disease. This study provides new insights into host-pathogen interactions related to co-infection by CoVs and other respiratory viruses.


title: Single incision laparoscopic surgery for acute appendicitis: feasibility in pediatric patients.

text: Background. Laparoscopic appendicectomy is accepted by many as the gold standard approach for the treatment of acute appendicitis. The use of Single Incision Laparoscopic Surgery (SILS) has the potential of further reducing postoperative port site complications as well as improving cosmesis and patient satisfaction. Method. In this paper we report our experience and assess the feasibility of SILS appendicectomy in the pediatric setting. Results. Five pediatric patients with uncomplicated appendicitis underwent SILS appendicectomy. There were no significant intraoperative or postoperative complications. All patients were discharged within 24 hours. Conclusions. The use of Single Incision Laparoscopic Surgery appears to be a feasible and safe technique for the treatment of uncomplicated appendicitis in the pediatric setting. Further studies are warranted to fully investigate the potential advantages of this new technique.


Emerging challenges and opportunities in medical microbiology.


title: Is 2020 the year when primatologists should cancel fieldwork? A reply.

text: The aim of this article is to explore the impact of coronavirus disease (COVID-19) pandemic on primate-related conservation work. The withdrawal of primatologists and conservation staff from field research can lead to a number of detrimental effects not just on conservation but also on local communities in low- and middle-income countries. Inequalities in access to health and financial insecurities may be drivers for the illegal wildlife trade and the lack of tourism and research activity may allow poachers to work with greater ease. The paper also looks at how conservation organizations and research bodies should modify their field protocols by developing robust occupational health policies that will not only make field work safer but also support local staff as they are likely to face the greatest threats to their physical health, psychological health, and economic loss from COVID-19. By adopting a One Health approach that considers the complex interactions between human and primate health, researchers will be able to find new ways of working not only to protect primates but understand how they adapt to the COVID-19 pandemic.


title: Structural features of fusogenic model transmembrane domains that differentially regulate inner and outer leaflet mixing in membrane fusion.

text: The transmembrane domains of fusion proteins are known to be important for their fusogenic activity. In an effort to systematically investigate the structure/function relationships of transmembrane domains we had previously designed LV-peptides that mimic natural fusion protein TMDs in their ability to drive fusion after incorporation into liposomal membranes. Here, we investigate the impact of different structural features of LV-peptide TMDs on inner and outer leaflet mixing. We find that fusion driven by the helical peptides involves a hemifusion intermediate as previously seen for natural fusion proteins. Helix backbone dynamics enhances fusion by selectively promoting outer leaflet mixing. Furthermore, the hydrophobic length of the peptides as well as covalent attachment of long acyl chains affects outer and inner leaflet mixing to different extents. Different structural features of transmembrane domains thus appear to differentially influence the rearrangements of lipids in fusion initiation and the hemifusion-to-fusion transition. The relevance of these findings in respect to the function of natural fusion proteins is discussed.


title: Outcome of laparoscopic modified Duhamel procedure with Z-shaped anastomosis for Hirschsprung's disease.

text: BACKGROUND Several laparoscopic Duhamel-type procedures for Hirschsprung's disease (HD) have been reported, but laparoscopic, Z-shaped, colorectal, side-to-side anastomosis has not been described. Z-shaped anastomosis has been used as the treatment of choice for HD at our clinic for a long time. A laparoscopic approach was adopted to perform this Z-shaped anastomosis in 2001. We describe herein our experiences with laparoscopic Z-shaped anastomosis and evaluate the clinical outcomes. METHODS Between 2001 and 2010, 26 children with rectosigmoid HD underwent a laparoscopic modified Duhamel procedure comprising Z-shaped anastomosis. Mean age at operation was 17.2 months. Mean weight was 8.7 kg. No children had a colostomy. Seven children had trisomy 21 and one had Klinefelter syndrome. Laparoscopic modified Duhamel procedure was performed using three 5-mm trocars. Intra- and postoperative complications and functional outcomes were evaluated. Patients with trisomy 21 were excluded from the functional evaluation. RESULTS The operation was completed laparoscopically for 25 of the 26 patients, with only one patient requiring conversion to an open procedure because of injury to the ureter. Mean operating time was 296 min. In one case, a minor leak was observed. No infections or related complications were observed. Mean follow-up period was 50.4 months. Sudden death secondary to rotaviral enterocolitis occurred 8 months postoperatively in one case. Twenty-one of the 25 patients (84%) showed episodes of constipation during the early follow-up period, and one child required late myectomy due to sphincter achalasia. As the child grew older, the need for medication was diminished. Of the 14 patients over 4 years old, excluding those patients with trisomy 21, all achieved normal defecation without incontinence. CONCLUSIONS Our series revealed that all patients over 4 years old who underwent laparoscopic Z-shaped colorectal anastomosis achieved normal defecation without fecal incontinence. Laparoscopic Z-shaped colorectal anastomosis for HD appears feasible and safe to perform with good results.


Evolving strategies to prevent implant-associated infections.


COVID-19 in Patients with Kidney Disease.


docid: iaykbiza

title: Technique of robotic assisted minimally invasive esophagectomy (RAMIE).

text: Minimally invasive esophagectomy (MIE) has gained popularity over the last two decades as an oncologically sound alternative to open esophagectomy. Robotic assisted minimally invasive esophagectomy (RAMIE) has been developed at few highly-specialized centers, and overall experience with this technique remains limited. Herein, we describe our overall approach to this operation and specific technical issues.


title: Noninvasive assessment of peripheral microcirculation by near-infrared spectroscopy: a comparative study in healthy smoking and nonsmoking volunteers.

text: Smokers are exposed to early endothelial dysfunction. This microcirculatory damage can be demonstrated by near-infrared spectroscopy (NIRS). The aim of this study was to compare microvascular reactivity by NIRS during a dynamic vascular occlusion test in healthy smokers and nonsmokers volunteers. Twenty healthy volunteers (10 men, 10 women), aged from 22 to 38 years old, were included after approval of the local Ethics Committee and divided into two groups: smokers (n = 10) and nonsmokers (n = 10). Tissue oxygen saturation (StO2) was measured at the level of each individual's calves during an ischemia and reperfusion test. In addition, during the ischemia phase, the slope of decline in StO2 was determined. Therefore, for each group, we were able to deduce the speed of desaturation (ΔStO2/ischemia time). The same was applied for resaturation rates during the reperfusion phase (ΔStO2/reperfusion time). StO2 values were comparable at all experimental steps between smokers and nonsmokers. During the vascular occlusion test, rates of desaturation were the same between smokers and nonsmokers [respectively 3.7%·min(-1) (range 2.5-12.6) and 3.7%·min(-1) (range 1.8-15.1); p = 0.50]. It was the same for the rate of resaturation [smokers 30.4%·min(-1) (range 14.2-51.6) and nonsmokers 30.5%·min(-1) (range 18.6-44.5); p = 0.82]. NIRS study of microvascular reactivity during a dynamic vascular occlusion test did not reveal any difference between smokers and nonsmokers. Therefore, NIRS could not be sensitive enough to highlight endothelial dysfunction in healthy subjects exposed to tobacco smoke.


title: New insights in equine steroidogenesis: an in-depth look at steroid signaling in the placenta.

text: Steroid production varies widely among species, with these differences becoming more pronounced during pregnancy. As a result, each species has its own distinct pattern of steroids, steroidogenic enzymes, receptors, and transporters to support its individual physiological requirements. Although the circulating steroid profile is well characterized during equine pregnancy, there is much yet to be explored regarding the factors that support steroidogenesis and steroid signaling. To obtain a holistic view of steroid-related transcripts, we sequenced chorioallantois (45 days, 4 months, 6 months, 10 months, 11 months, and post-partum) and endometrium (4 months, 6 months, 10 months, 11 months, and diestrus) throughout gestation, then looked in-depth at transcripts related to steroid synthesis, conjugation, transportation, and signaling. Key findings include: 1) differential expression of HSD17B isoforms among tissues (HSD17B1 high in the chorioallantois, while HSD17B2 is the dominant form in the endometrium) 2) a novel isoform with homology to SULT1A1 is the predominant sulfotransferase transcript in the chorioallantois; and 3) nuclear estrogen (ESR1, ESR2) and progesterone (PGR) expression is minimal to nonexistant in the chorioallantois and pregnant endometrium. Additionally, several hypotheses have been formed, including the possibility that the 45-day chorioallantois is able to synthesize steroids de novo from acetate and that horses utilize glucuronidation to clear estrogens from the endometrium during estrous, but not during pregnancy. In summary, these findings represent an in-depth look at equine steroid-related transcripts through gestation, providing novel hypotheses and future directions for equine endocrine research.


title: A case-matched comparison of single-incision versus multiport laparoscopic right colectomy for colon cancer.

text: PURPOSE To minimize the parietal trauma associated with multiple surgical access sites, single-incision laparoscopic surgery for colectomy has been emerging with the improvements in instrumentation and surgical techniques. The purpose of this study was to compare the clinicopathological outcomes between single-incision laparoscopic right colectomy (SILC) and multiport laparoscopic right colectomy (MLC) for right colon cancer. METHODS Thirty-five consecutive patients undergoing SILC from a prospective single-institution database were case matched according to demographic data to an equivalent number of patients who underwent MLC. RESULTS The SILC patients had decreased scores for maximal pain assessed by a visual analog scale on postoperative days 1 and 3, and used fewer postoperative systemic narcotics. The median length of the hospital stay for the SILC patients was significantly shorter compared with the MLC patients. The postoperative morbidity rates were similar between the groups. The oncological findings were not significantly different between the groups. CONCLUSION SILC is a feasible and safe alternative to conventional MLC for patients with right colon cancer.


Pandemic corona virus issue - how do we respond?