title: Chitosan-Sodium Tetradecyl Sulfate Hydrogel: Characterization and Preclinical Evaluation of a Novel Sclerosing Embolizing Agent for the Treatment of Endoleaks.

text: PURPOSE To compare the efficacy of an embolization agent with sclerosing properties (made of chitosan and sodium tetradecyl sulfate, CH-STS) with a similar embolization agent but without sclerosing properties (made of chitosan, CH) in treating endoleaks in a canine endovascular aneurysm repair model. METHODS Two chitosan-based radiopaque hydrogels were prepared, one with STS and one without STS. Their rheological, injectability, and embolizing properties were assessed in vitro; afterwards, their efficacy in occluding endoleaks was compared in a canine bilateral aneurysm model reproducing type I endoleaks (n = 9 each). The primary endpoint was endoleak persistence at 3 or 6 months, assessed on a CT scan and macroscopic examination. Secondary endpoints were the occurrence of stent-graft (SG) thrombosis, the evolution of the aneurysm mean diameter, as well as aneurysm healing and inflammation scores in pathology examinations. RESULTS In vitro experiments showed that both products gelled rapidly and presented initial storage moduli greater than 800 Pa, which increased with time. Both gels were compatible with microcatheter injection and occlude flow up to physiological pressure in vitro. In a type I endoleak model, the injection of CH-STS sclerosing gel tended to reduce the risk of occurrence of endoleaks, compared to CH non-sclerosing agent (2/9 vs. 6/9, p = 0.069). No case of SG thrombosis was observed. Moderate inflammation was found around both gels, with a comparable intensity score in both CH and CH-STS groups (2.6 ± 0.9 and 2.7 ± 0.9, respectively; p = 0.789). CONCLUSIONS Flow occlusion combined with chemical endothelial denudation appears promising for the treatment of endoleaks. LEVEL OF EVIDENCE N/A.


COVID-19 National Pakistan Guidelines: Radiological Society of Pakistan (RSP) Recommendations Regarding Utilisation of Chest Imaging.


Covid-19: England plan to ease lockdown is "confusing" and "risky," say doctors.


title: Electrochemical magnetoimmunosensing approach for the sensitive detection of H9N2 avian influenza virus particles.

text: A novel electrochemical magnetoimmunosensor for fast and ultrasensitive detection of H9N2 avian influenza virus particles (H9N2 AIV) was designed based on the combination of high-efficiency immunomagnetic separation, enzyme catalytic amplification, and the biotin-streptavidin system. The reusable, homemade magneto Au electrode (M-AuE) was designed and used for the direct sensing. Immunocomplex-coated magnetic beads (IMBs) were easily accumulated on the surface of the M-AuE to obtain the catalytically reduced electrochemical signal of H2 O2 after the immunoreaction. The transducer was regenerated through a simple washing procedure, which made it possible to detect all the samples on a single electrode with higher reproducibility. The magnetic-bead-based electrochemical immunosensor showed better analytical performance than the planar-electrode-based immunosensor with the same sandwich construction. Amounts as low as 10 pg mL(-1) H9N2 AIV could be detected even in samples of chicken dung. This electrochemical magnetoimmunosensor not only provides a simple platform for the detection of the virus with high sensitivity, selectivity, and reproducibility but also shows great potential in the early diagnosis of diseases.


Reinforcing Cardiology Training During a Pandemic: An Open Letter to Our Leaders.


title: Preclinical studies of a modified vaccinia virus Ankara-based HIV candidate vaccine: antigen presentation and antiviral effect.

text: Poxvirus-based human immunodeficiency virus (HIV) vaccine candidates are currently under evaluation in preclinical and clinical trials. Modified vaccinia virus Ankara (MVA) vectors have excellent safety and immunogenicity records, but their behavior in human cell cultures remains only partly characterized. We studied here various virological and immunological aspects of the interactions of MVA-HIV, a vaccine candidate developed by the French National Agency for AIDS Research (ANRS), with primary human cells. We report that MVA-HIV infects and drives Gag expression in primary macrophages, dendritic cells (DCs), and epithelial and muscle cells. MVA-HIV-infected DCs matured, efficiently presented Gag, Pol, and Nef antigens, and activated HIV-specific cytotoxic T lymphocytes (CTLs). As expected with this type of vector, infection was cytopathic and led to DC apoptosis. Coculture of MVA-HIV-infected epithelial cells or myotubes with DCs promoted efficient Gag antigen major histocompatibility complex class I (MHC-I) cross-presentation without inducing direct infection and death of DCs. Antigen-presenting cells (APCs) infected with MVA-HIV also activated HIV-specific CD4(+) T cells. Moreover, exposure of DCs to MVA-HIV or to MVA-HIV-infected myotubes induced type I interferon (IFN) production and inhibited subsequent HIV replication and transfer to lymphocytes. Altogether, these results show that MVA-HIV promotes efficient MHC-I and MHC-II presentation of HIV antigens by APCs without facilitating HIV replication. Deciphering the immune responses to MVA in culture experiments will help in the design of innovative vaccine strategies.


title: Single Incision Versus Conventional Laparoscopic Sleeve Gastrectomy for Morbid Obesity: A Meta-Analysis.

text: INTRODUCTION The purpose of this study was to review the existing evidence on obese patients treated with single-incision laparoscopic sleeve gastrectomy (SILSG) or conventional laparoscopic sleeve gastrectomy (LSG), to compare the perioperative parameters and outcomes of the two bariatric procedures. MATERIALS AND METHODS A systematic literature search was performed in PubMed, Scopus, and Cochrane library, in accordance with the PRISMA guidelines. Seventeen articles met the inclusion criteria and incorporated 3843 patients. RESULTS This study reveals comparable mean operative time, length of hospital stay, and complications between the two approaches. The SILSG approach was associated with enhanced cosmetic results, but increased incisional hernia rate. CONCLUSIONS These outcomes should be treated with caution given the small number of included comparative studies. Well-designed, randomized controlled studies, comparing LSG to SILSG, are necessary to assess further their clinical outcomes.


title: New challenges in viral hepatitis.

text: Over the past few decades there has been remarkable progress in viral hepatitis. Beginning with discovery of the viral agents, we now have reliable methods to diagnose and monitor all hepatitis virus infections, as well significant advances in treatment and prevention. Nonetheless, important challenges remain. This supplement to Gut looks forward to the next generation of challenges in the field of viral hepatitis, and this introductory article highlights several key issues.


Covid-19: South Korea relaxes social distancing after the number of new cases drops below 10 a day.


The Untold Toll - The Pandemic's Effects on Patients without Covid-19.


title: Staple Line Reinforcement with Stitch in Laparoscopic Sleeve Gastrectomies. Is It Useful or Harmful?

text: BACKGROUND Reinforcement of the staple line in laparoscopic sleeve gastrectomy (LSG) is a practice that leads to less morbidity, but equivocal results have been reported in the literature. MATERIALS AND METHODS This is a prospective randomized study comparing two groups of patients who underwent LSG. In one group LSG was performed with a running absorbable suture placement at the staple line. In the other group the running suture was not placed. General data of the patients, as well as intraoperative and postoperative data, were gathered and statistically analyzed. RESULTS Overall, 146 patients were subjected to LSG. In 84 patients a running suture was placed, and in 62 patients no suture was placed. No significant differences were found between the two groups in demographic data. No significant differences were found also in the intraoperative data, such as number of trocars, number and type of cartridges, drain placement, and operative time (45±21 versus 40±20 minutes, respectively; P<.05). Intraoperative complications were significantly more in the group with the suture placement (33.3% versus 16.1%, respectively; P<.05). Hematomas developed intraoperatively in more patients after the placement of the running suture (9.5% versus 0.0%, respectively; P<.05). Postoperatively, there was no significant difference in morbidity between the two groups (8.3% versus 9.7%, respectively; P>.05). CONCLUSIONS After this randomized study, final conclusions about the efficacy of this running suture to the staple line cannot be made. To the contrary, problems seem to exist after such reinforcement of the staple line, such as hematomas. Dealing with possible leaks and hemorrhage of the staple line is also problematic after placement of the running suture.


Words of wisdom. Re: laparoscopic versus open nephroureterectomy: perioperative and oncologic outcomes from a randomised prospective study.


title: Majority of symptoms in esophageal reflux PPI non-responders are not related to reflux.

text: BACKGROUND Genesis of persistent gastro-esophageal reflux symptoms despite proton pump inhibitor (PPI) therapy is not fully understood. We aimed at determining reflux patterns on 24-h pH-impedance monitoring performed on PPI and correlating impedance patterns and symptom occurrence in PPI non-responders. METHODS Seventy-eight PPI non-responder patients underwent 24-h pH-impedance monitoring on PPI. Reflux impedance characterization included gastric and supragastric belches and proximal extent of reflux. Symptoms were considered associated with reflux if occurring within 5 min after a reflux event. Patients were classified into three groups: persistent acid reflux (acid esophageal exposure [AET] >5% of time), reflux sensitivity (AET <5%, symptom index [SI] ≥50%), and functional symptoms (AET <5%, SI <50%). Dominant impedance pattern was determined for each patient. KEY RESULTS Seven patients (9%) had persistent acid reflux, 28 (36%) reflux sensitivity, and 43 (55%) functional symptoms. A total of 4296 reflux events were identified (median per patient 45 [range 4-221]). Although liquid reflux was the most common pattern in all groups, patients with reflux sensitivity and functional symptoms had much more variability in their pattern profile with a large proportion being associated with gastric and supragastric belching. Only 417 reflux events (9.7%) were associated with symptoms. Reflux with a supragastric component and proximal extent were more likely to be associated with symptoms. CONCLUSIONS & INFERENCES The impedance reflux profile in PPI non-responders was heterogeneous and the majority of reflux events were not associated with symptoms. Thus, the treatment of PPI non-responders should focus on mechanisms beyond reflux, such as visceral hypersensitivity and hypervigilance.


Telepsychiatry as a public health imperative: Slowing COVID-19.


title: Comparison of vessel sealing systems with conventional.

text: BACKGROUND Haemorrhoids are cushions of submucosal vascular tissue located in the anal canal starting just distal to the dentate line. Haemorrhoidal disease is a common anorectal disorder which has symptoms of bleeding, prolapse, pain, thrombosis, mucus discharge, and pruritus. Haemorrhoidectomy is one of most frequently performed anorectal operation worldwide. OBJECTIVES The aim of this study was to compare the effectiveness of the LigaSure tissue sealing device, Harmonic Scalpel and conventional MM open haemorrhoidectomy. MATERIALS AND METHODS Sixty-nine patients with newly diagnosed symptomatic grade three or grade four haemorrhoidal disease, from July 2011 to December 2011 were recruited for the study. Patients were prospectively randomized to LigaSure, Harmonic Scalpel and conventional haemorrhoidectomy. Patients were evaluated on the basis of the mean operative time, postoperative pain, day of discharge, early and late complications. RESULTS Each group has twenty-three patients. Ten (14.5 %) were female and fifty-nine (85.5 %) were male. Mean age were 44.5 ± 10.8 for LigaSure group, 39.5±14.4 for Harmonic Scalpel group and 39.8 ± 13.6 for conventional haemorrhoidectomy group. Mean operative time was 12.6 ± 2.9 for LigaSure group, 12.6 ± 2.5 for Harmonic Scalpel group and 22.3 ± 4.5 for conventional haemorrhoidectomy group. Postoperative pain and required analgesic dose were significantly lower for conventional haemorrhoidectomy. Wound healing was also more rapid in conventional haemorrhoidectomy than both LigaSure and Harmonic Scalpel. CONCLUSIONS Lateral heat dissipation of energy based cautery such as Harmonel Scalpel and LigaSure is considerably high when compared with conventional methods. More thermal damage which is generated on tissue seems to be the reason for increased degree of postoperative pain and delay in wound healing.


title: Percutaneous left atrial appendage occlusion: the Munich consensus document on definitions, endpoints, and data collection requirements for clinical studies.

text: The increasing interest in left atrial appendage occlusion (LAAO) for ischaemic stroke prevention in atrial fibrillation (AF) fuels the need for more clinical data on the safety and effectiveness of this therapy. Besides an assessment of the effectiveness of the therapy in specific patients groups, comparisons with pharmacological stroke prophylaxis, surgical approaches, and other device-based therapies are warranted. This paper documents the consensus reached among clinical experts in relevant disciplines from Europe and North America, European cardiology professional societies, and representatives from the medical device industry regarding definitions for parameters and endpoints to be assessed in clinical studies. Adherence to these definitions is proposed in order to achieve a consistent approach across clinical studies on LAAO among the involved stakeholders and various clinical disciplines and thereby facilitate continued evaluation of therapeutic strategies available.


title: Clinical features of gastric emptying after distal gastrectomy.

text: Purpose Gastric emptying may influence the quality of life of patients who undergo distal gastrectomy. Little is known, however, about gastric emptying after distal gastrectomy. The aim of our study was to investigate gastric emptying patterns after distal gastrectomy. Methods This gastric-emptying study investigated patients who underwent distal gastrectomy in the 6 months or more before May 2008 to July 2013 at Chungbuk National University Hospital with a study sample of 205 patients. We analyzed patterns of gastric emptying. Results Delayed gastric emptying was found in 109 of the 205 patients (53.2%). Food stasis was more frequent in a group with delayed gastric emptying. In multivariate analysis, risk factors for gastroparesis were laparoscopic operation (hazard ratio [HR], 2.731; P = 0.008) and duration of less than 24 months after distal gastrectomy (HR, 2.795; P = 0.001). Delayed gastric emptying tended to decrease with duration of the postoperative period. Conclusion Delayed gastric emptying is common in distal gastrectomy, and is related to laparoscopic operation and duration of the postoperative period. Food stasis was more frequent in a group with delayed gastric emptying.


title: Utility of Non-Invasive Monitoring of Cardiac Output and Cerebral Oximetry during Pain Management of Children with Sickle Cell Disease in the Pediatric Emergency Department.

text: Pain crisis in children with sickle cell disease (SCD) is typically managed with intravenous fluids and parenteral opioids in the pediatric emergency department. Electrical cardiometry (EC) can be utilized to measure cardiac output (CO) and cardiac index (CI) non-invasively. Near-infrared spectroscopy (NIRS) measuring cerebral (rCO₂) and splanchnic regional (rSO₂) mixed venous oxygenation non-invasively has been utilized for monitoring children with SCD. We studied the value and correlation of NIRS and EC in monitoring hemodynamic status in children with SCD during pain crisis. We monitored EC and NIRS continuously for 2 h after presentation and during management. Forty-five children participated in the study. CO (D = 1.72), CI (D = 1.31), rSO₂ (D = 11.6), and rCO₂ (D = 9.3), all increased over time. CO max and CI max were achieved 1 h after starting resuscitation. rCO₂ max attainment was quicker than rSO₂, as monitored by NIRS. CI max correlated with rCO₂ max (r = -0.350) and rSO₂ max (r = -0.359). In adjustment models, initial CI significantly impacted initial rCO₂ (p = 0.045) and rCO₂ max (p = 0.043), while initial CO impacted rCO₂ max (p = 0.030). Cardiac output monitoring and NIRS monitoring for cerebral and splanchnic oxygenation were feasible and improved the monitoring of therapeutic interventions for children with SCD during pain crisis.


title: Long-term outcomes with first- vs. second-generation drug-eluting stents in saphenous vein graft lesions.

text: BACKGROUND As compared with bare metal stents, first-generation drug-eluting stents (DES) improved post-procedural outcomes in aortocoronary saphenous vein graft (SVG) lesions, but there is limited information on outcomes after use of second-generation DES in SVGs. METHODS We compared the outcomes of patients who received first- (n = 81) with those who received second-generation (n = 166) DES in SVG lesions at our institution between 2006 and 2013. Major adverse cardiac events (MACE) were defined as the composite of all-cause death, myocardial infarction, and target vessel revascularization. RESULTS Mean age was 66.0 ± 8.1 years and 97.6% of the patients were men. Mean SVG age was 11.1 ± 0.4 years. First-generation DES were sirolimus-eluting (n = 17) and paclitaxel-eluting (n = 64) stents. Second-generation DES were everolimus-eluting (n = 115) and zotarolimus-eluting (n = 51) stents. Median follow-up was 41 months. At 2-years post-procedure, patients with first- and second-generation DES had similar rates of death (20.91% vs. 20.27%, P = 0.916), target lesion revascularization (16.39% vs. 20.00%, P = 0.572), target vessel revascularization (20.97% vs. 23.16%, P = 0.747), myocardial infarction (26.15% vs. 23.00%, P = 0.644), and MACE (43.5% vs. 40.87%, P = 0.707), respectively. CONCLUSIONS Outcomes with first- and second-generation DES in SVGs are similar. Novel stent designs are needed to further improve the clinical outcomes in this challenging patient and lesion subgroup. © 2015 Wiley Periodicals, Inc.


title: The "trust" heuristic: arguments from authority in public health.

text: The work of public health depends on a relationship of trust between health workers and members of the public. This relationship is one in which the public must trust the advice of health experts, even if that advice is not always readily understood or judged to be agreeable. However, it will be argued in this article that the pact of trust between public health workers and members of the public has been steadily eroded over many years. The reasons for this erosion are examined as are attempts to characterize the concept of trust in empirical studies. The discussion then considers how a so-called informal fallacy, known as the "argument from authority," might contribute to attempts to understand the trust relationship between the public and health experts. Specifically, this argument enables the lay person to bridge gaps in knowledge and arrive at judgements about public health problems by attending to certain logical and epistemic features of expertise. The extent to which lay people are able to discern these features is considered by examining the results of a study of public health reasoning in 879 members of the public.


How long will social distancing take to work? Experts weigh in on Canada's COVID-19 response.


title: Structural and inhibitor studies of norovirus 3C-like proteases.

text: Noroviruses have a single-stranded, positive sense 7-8kb RNA genome, which encodes a polyprotein precursor processed by a virus-encoded 3C-like cysteine protease (3CLpro) to generate mature non-structural proteins. Because processing of the polyprotein is essential for virus replication, norovirus 3CLpro has been targeted for the discovery of anti-norovirus small molecule therapeutics. Thus, we performed functional, structural and inhibition studies of norovirus 3CLpro with fluorescence resonance energy transfer (FRET) assay, X-ray crystallography, and NMR spectroscopy with a synthetic protease inhibitor. Three 3CLpro from Norwalk virus (NV, genogroup I), MD145 (genogroup II) and murine norovirus-1 (MNV-1, genogroup V) were optimized for a FRET assay, and compared for the inhibitory activities of a synthetic protease inhibitor (GC376). The apo 3D structures of NV 3CLpro determined with X-ray crystallography and NMR spectroscopy were further analyzed. In addition, the binding mode of NV 3CLpro-GC376 was compared with X-ray crystallography and NMR spectroscopy. The results of this report provide insight into the interaction of NV 3CLpro with substrate/inhibitor for better understanding of the enzyme and antiviral drug development.


title: Diagnosis by endoscopy and advanced imaging.

text: Evaluation of patients with Barrett's oesophagus (BO) using dye-based chromoendoscopy, optical chromoendoscopy, autofluorescence imaging, or confocal laser endomicroscopy does not significantly increase the number of patients with a diagnosis of early neoplasia compared with high-definition white light endoscopy (HD-WLE) with random biopsy analysis. These newer imaging techniques are not more effective in standard surveillance of patients with BO because the prevalence of early neoplasia is low and HD-WLE with random biopsy analysis detects most cases of neoplasia. The evaluation and treatment of patients with BO and early-stage neoplasia should be centralized in tertiary referral centers, where procedures are performed under optimal conditions, by expert endoscopists. Lesions that require resection are almost always detected by HD-WLE, although advanced imaging techniques can detect additional flat lesions. However, these are of limited clinical significance because they are effectively eradicated by ablation therapy. No endoscopic imaging technique can reliably assess submucosal or lymphangio-invasion. Endoscopic resection of early-stage neoplasia in patients with BO is important for staging and management. Optical chromoendoscopy can also be used to evaluate lesions before endoscopic resection and in follow-up after successful ablation therapy.


title: How Will COViD-19 Affect Long-Term Care?

text: The decision of the Centers for Medicare & Medicaid Services to suspend routine surveys in favor of focused inspections targeted at infection control is the first signal that long-term care will be at the epicenter of federal oversight.


title: Association of Clonal Hematopoiesis of Indeterminate Potential With Inflammatory Gene Expression in Patients With Severe Degenerative Aortic Valve Stenosis or Chronic Postischemic Heart Failure.

text: Importance Cytokine release syndrome is a complication of coronavirus disease 2019. Clinically, advanced age and cardiovascular comorbidities are the most important risk factors. Objective To determine whether clonal hematopoiesis of indeterminate potential (CHIP), an age-associated condition with excess cardiovascular risk defined as the presence of an expanded, mutated somatic blood cell clone in persons without other hematological abnormalities, may be associated with an inflammatory gene expression sensitizing monocytes to aggravated immune responses. Design, Setting, and Participants This hypothesis-generating diagnostic study examined a cohort of patients with severe degenerative aortic valve stenosis or chronic postinfarction heart failure, as well as age-matched healthy control participants. Single-cell RNA sequencing and analyses of circulating peripheral monocytes was done between 2017 and 2019 to assess the transcriptome of circulating monocytes. Exposures Severe degenerative aortic valve stenosis or chronic postinfarction heart failure. Main Outcomes and Measures CHIP-driver sequence variations in monocytes with a proinflammatory signature of genes involved in cytokine release syndrome. Results The study included 8 patients with severe degenerative aortic valve stenosis, 6 with chronic postinfarction heart failure, and 3 healthy control participants. Their mean age was 75.7 (range, 54-89) years, and 6 were women. Mean CHIP-driver gene variant allele frequency was 4.2% (range, 2.5%-6.9%) for DNMT3A and 14.3% (range, 2.6%-37.4%) for TET2. Participants with DNMT3A or TET2 CHIP-driver sequence variations displayed increased expression of interleukin 1β (no CHIP-driver sequence variations, 1.6217 normalized Unique Molecular Identifiers [nUMI]; DNMT3A, 5.3956 nUMI; P < .001; TET2, 10.8216 nUMI; P < .001), the interleukin 6 receptor (no CHIP-driver sequence variations, 0.5386 nUMI; DNMT3A, 0.9162 nUMI; P < .001;TET2, 0.5738 nUMI; P < .001), as well as the NLRP3 inflammasome complex (no CHIP-driver sequence variations, 0.4797 nUMI; DNMT3A, 0.9961 nUMI; P < .001; TET2, 1.2189 nUMI; P < .001), plus upregulation of CD163 (no CHIP-driver sequence variations, 0.5239 nUMI; DNMT3A, 1.4722 nUMI; P < .001; TET2, 1.0684 nUMI; P < .001), a cellular receptor capable of mediating infection, macrophage activation syndrome, and other genes involved in cytokine response syndrome. Gene ontology term analyses of regulated genes revealed that the most significantly upregulated genes encode for leukocyte-activation and interleukin-signaling pathways in monocytes of individuals with DNMT3A (myeloid leukocyte activation: log[Q value], -50.1986; log P value, -54.5177; regulation of cytokine production: log[Q value], -21.0264; log P value, -24.1993; signaling by interleukins: log[Q value], -18.0710: log P value, -21.1597) or TET2 CHIP-driver sequence variations (immune response: log[Q value], -36.3673; log P value, -40.6864; regulation of cytokine production: log[Q value], -13.1733; log P value, -16.3463; signaling by interleukins: log[Q value], -12.6547: log P value, -15.7977). Conclusions and Relevance Monocytes of individuals who carry CHIP-driver sequence variations and have cardiovascular disease appear to be primed for excessive inflammatory responses. Further studies are warranted to address potential adverse outcomes of coronavirus disease 2019 in patients with CHIP-driver sequence variations.


title: Mechanisms of Diabetes Improvement Following Bariatric/Metabolic Surgery.

text: More than 20 years ago, Pories et al. published a seminal article, "Who Would Have Thought It? An Operation Proves to Be the Most Effective Therapy for Adult-Onset Diabetes Mellitus." This was based on their observation that bariatric surgery rapidly normalized blood glucose levels in obese people with type 2 diabetes mellitus (T2DM), and 10 years later, almost 90% remained diabetes free. Pories et al. suggested that caloric restriction played a key role and that the relative contributions of proximal intestinal nutrient exclusion, rapid distal gut nutrient delivery, and the role of gut hormones required further investigation. These findings of T2DM improvement/remission after bariatric surgery have been widely replicated, together with the observation that bariatric surgery prevents or delays incident T2DM. Over the ensuing two decades, important glucoregulatory roles of the gastrointestinal (GI) tract have been firmly established. However, the physiological and molecular mechanisms underlying the beneficial glycemic effects of bariatric surgery remain incompletely understood. In addition to the mechanisms proposed by Pories et al., changes in bile acid metabolism, GI tract nutrient sensing and glucose utilization, incretins, possible anti-incretin(s), and the intestinal microbiome are implicated. These changes, acting through peripheral and/or central pathways, lead to reduced hepatic glucose production, increased tissue glucose uptake, improved insulin sensitivity, and enhanced β-cell function. A constellation of factors, rather than a single overarching mechanism, likely mediate postoperative glycemic improvement, with the contributing factors varying according to the surgical procedure. Thus, different bariatric/metabolic procedures provide us with experimental tools to probe GI tract physiology. Embracing this approach through the application of detailed phenotyping, genomics, metabolomics, and gut microbiome studies will enhance our understanding of metabolic regulation and help identify novel therapeutic targets.


title: Perceptions of food and eating among Chinese patients with cancer: findings of an ethnographic study.

text: This article explores the ways that participants in a Chinese cancer support group talk about food, diet, and eating. An ethnographic research design was used, including participant observation at a Chinese cancer support group over an 8-month period and key informant interviews with 7 members of the group. Food, eating, and diet were a recurrent focus of discussion at support group meetings throughout the fieldwork period. The ways in which support group participants talked about food centered on 3 distinct but interconnected themes: the prevalence of eating issues as an adverse effect of cancer and its treatment, the importance of eating ability, and questions and concerns connected with the differing and often contradictory cultural models of diet that they were exposed to. Culturally specific understandings of the relationship between food and health informed Chinese patients' experience of eating issues during cancer treatments and their ongoing concern with food and nutrition after the completion of treatment. Health professionals need to pay more attention to the meanings and attributes of food and eating beyond their physiological properties, and further research needs to be conducted with other immigrant populations with culturally distinct understandings of food.


title: Surface mechanomyography and electromyography provide non-invasive indices of inspiratory muscle force and activation in healthy subjects.

text: The current gold standard assessment of human inspiratory muscle function involves using invasive measures of transdiaphragmatic pressure (Pdi) or crural diaphragm electromyography (oesEMGdi). Mechanomyography is a non-invasive measure of muscle vibration associated with muscle contraction. Surface electromyogram and mechanomyogram, recorded transcutaneously using sensors placed over the lower intercostal spaces (sEMGlic and sMMGlic respectively), have been proposed to provide non-invasive indices of inspiratory muscle activation, but have not been directly compared to gold standard Pdi and oesEMGdi measures during voluntary respiratory manoeuvres. To validate the non-invasive techniques, the relationships between Pdi and sMMGlic, and between oesEMGdi and sEMGlic were measured simultaneously in 12 healthy subjects during an incremental inspiratory threshold loading protocol. Myographic signals were analysed using fixed sample entropy (fSampEn), which is less influenced by cardiac artefacts than conventional root mean square. Strong correlations were observed between: mean Pdi and mean fSampEn |sMMGlic| (left, 0.76; right, 0.81), the time-integrals of the Pdi and fSampEn |sMMGlic| (left, 0.78; right, 0.83), and mean fSampEn oesEMGdi and mean fSampEn sEMGlic (left, 0.84; right, 0.83). These findings suggest that sMMGlic and sEMGlic could provide useful non-invasive alternatives to Pdi and oesEMGdi for the assessment of inspiratory muscle function in health and disease.


title: Modeling infectious disease dynamics in the complex landscape of global health.

text: Despite some notable successes in the control of infectious diseases, transmissible pathogens still pose an enormous threat to human and animal health. The ecological and evolutionary dynamics of infections play out on a wide range of interconnected temporal, organizational, and spatial scales, which span hours to months, cells to ecosystems, and local to global spread. Moreover, some pathogens are directly transmitted between individuals of a single species, whereas others circulate among multiple hosts, need arthropod vectors, or can survive in environmental reservoirs. Many factors, including increasing antimicrobial resistance, increased human connectivity and changeable human behavior, elevate prevention and control from matters of national policy to international challenge. In the face of this complexity, mathematical models offer valuable tools for synthesizing information to understand epidemiological patterns, and for developing quantitative evidence for decision-making in global health.


Emergency Department-Based Palliative Care during COVID.


Helen Salisbury: Testing times for GPs.


title: A new method for inframammary fold recreation using a barbed suture.

text: BACKGROUND There are inherent limitations with previously reported inframammary fold (IMF) recreation methods. The IMF is firmly fixed to the chest wall, but not physiologically, and it is difficult to determine the correct IMF position in the supine position and in the absence of an implant. METHODS With our new IMF reconstruction method (i.e., drawstring method), the IMF is recreated by drawing a barbed suture, penetrating the dermis, along the IMF. The barbed suture is fixed to the costal cartilage at the medial IMF, and the head is drawn and cut externally at the lateral IMF. The IMF level and depth can be finely adjusted by the tension, in a seated position after implant insertion. Furthermore, the approach can be from a small incision, and a smooth IMF curve is reconstructed. RESULTS Our drawstring method was performed in 102 patients who underwent reconstruction using a breast implant (n = 95) or flap (n = 7). The mean patient age was 52.0 years (range 33-77 years) and the follow-up period was 12 months (range 3-18 months). Suture or implant infection or exposure did not occur. Suture slack occurred in ten patients with implant-based reconstruction; their IMF became shallow. Insufficient skin expansion (P < 0.005) and strong traction of the barbed suture from the caudal side (P < 0.05) were related to IMF slack. The total revision rate was 2.9 %. CONCLUSIONS With sufficient skin expansion, the drawstring method using a barbed suture enables smooth and symmetrical IMF reconstruction. LEVEL OF EVIDENCE IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .


title: Chest CT evaluation of 11 persistent asymptomatic patients with SARS-CoV-2 infection.

text: Eleven asymptomatic carriers who received nasal or throat swab test for SARS-CoV-2 after close contacts with patients who developed symptomatic 2019 coronavirus disease (COVID-19) were enrolled in this study. The chest CT images of enrolled patients were analyzed qualitatively and quantitatively. There were 3 (27.3%) patients had normal first chest CT, two of which were under age of 15 years. Lesions in 2 (18.2%) patients involved one lobe with unifocal presence. Subpleural lesions were seen in 7 (63.6%) patients. Ground glass opacity (GGO) was the most common sign observed in 7 (63.6%) patients. Crazy-paving pattern and consolidation were detected in 2 (18.2%) and 4 (36.4%) cases, respectively. Based on deep learning quantitative analysis, volume of intrapulmonary lesions on first CT scans was 85.73±84.46 cm3. In patients with positive findings on CT images, average interval days between positive real-time reverse transcriptase polymerase chain reaction assay and peak volume on CT images were 5.1±3.1 days. In conclusion, typical CT findings can be detected in over 70% of asymptomatic SARS-CoV-2 carriers. It mainly starts as GGO along subpleural regions and bronchi, and absorbs in nearly 5 days.


title: Sleeve Gastrectomy Postoperative Hemorrhage is Linked to Type-2 Diabetes and Not to Surgical Technique.

text: BACKGROUND The degree, prevalence, and risk factors linked to sleeve gastrectomy (SG) postoperative hemorrhage (POH) have not been fully defined. METHODS An analysis was conducted on a prospectively collected database of 394 consecutive primary SGs performed in a single practice from January 2014 to December 2015. END POINTS (1) acute POH, defined by red blood cell (RBC) transfusion and/or re-exploration; (2) subclinical POH, defined by postoperative hemoglobin drop (HgbD) >one standard deviation above mean. Variables tested included three surgical techniques: normal stapling (n = 137), "tight" stapling, (n = 142) and oversewing, (n = 115); age; gender; body mass index (BMI); co-morbidities; and elevated postoperative systolic blood pressure. RESULTS Acute POH occurred in 11/394 patients (2.8%) and subclinical POH (HgbD > 2.2 g/dL) was detected in 27/312 (7.7%) of patients with available HgbD data. Acute POH patients had a mean HgbD of 5.43 ± 1.40 g/dl (p < 0.001) reflecting approximately 38.6% ± 10.0% of total blood volume. No difference in prevalence of POH was observed for the different surgical techniques. Compared with non-bleeders (n = 312), acute and subclinical POH patients (n = 38) had 52.6 vs. 27.2% prevalence type-2 diabetes (T2D) and 60.5 vs. 40.1% prevalence of dyslipidemia and higher mean preoperative hemoglobin 14.3 ± 11 vs.13.5 ± 1.2 (p < 0.05 for all). On regression analysis, only T2D (OR 2.6; 95% CI 1.2-5.6) and higher level of preoperative hemoglobin (OR 1.7; 95% CI 1.3-2.4) were independent risk factors for POH. CONCLUSION In this study, acute and subclinical POH were primarily linked to T2D and not to surgical techniques. Special consideration is recommended for patients with T2D undergoing SG.


title: Small Hepatocellular Carcinoma: Radiofrequency Ablation versus Nonanatomic Resection--Propensity Score Analyses of Long-term Outcomes.

text: PURPOSE To compare radiofrequency (RF) ablation with nonanatomic resection (NAR) as first-line treatment in patients with a single Barcelona Clinic Liver Cancer (BCLC) stage 0 or A hepatocellular carcinoma (HCC) and to evaluate the long-term outcomes of both therapies. MATERIALS AND METHODS This retrospective study was approved by the institutional review board. The requirement for informed consent was waived. Data were reviewed from 580 patients with HCCs measuring 3 cm or smaller (BCLC stage 0 or A) who underwent ultrasonographically (US) guided percutaneous RF ablation (n = 438) or NAR (n = 142) as a first-line treatment. Local tumor progression, intrahepatic distant recurrence, disease-free survival, and overall survival rates were analyzed by using propensity score matching to compare therapeutic efficacy. In addition, major complications and length of postoperative hospital stay were compared. RESULTS Before propensity score matching (n = 580), the 5-year cumulative rates of local tumor progression for RF ablation and NAR (20.9% vs 12.7%, respectively; P = .093) and overall survival rates (85.5% vs 90.9%, respectively; P = .194) were comparable, while the 5-year cumulative intrahepatic distant recurrence rates (62.7% vs 36.6%, respectively; P < .001) and disease-free survival rates (31.7% vs 61.1%, respectively; P < .001) in the NAR group were significantly better than those in the RF ablation group. After matching (n = 198), there were no significant differences in therapeutic outcomes between the RF ablation and NAR groups, including 5-year cumulative intrahepatic distant recurrence (47.0% vs 40.2%, respectively; P = .240) and disease-free survival rates (48.9% vs 54.4%, respectively; P = .201). RF ablation was superior to NAR for major complication rates and length of postoperative hospital stay (P < .001). CONCLUSION In patients with one BCLC stage 0 or A (≤ 3 cm) HCC who received RF ablation or NAR as first-line treatment, there were no significant differences in long-term therapeutic outcomes; however, RF ablation was associated with fewer major complications and a shorter hospital stay after treatment.


title: Human polyclonal immunoglobulin G from transchromosomic bovines inhibits MERS-CoV in vivo.

text: As of 13 November 2015, 1618 laboratory-confirmed human cases of Middle East respiratory syndrome coronavirus (MERS-CoV) infection, including 579 deaths, had been reported to the World Health Organization. No specific preventive or therapeutic agent of proven value against MERS-CoV is currently available. Public Health England and the International Severe Acute Respiratory and Emerging Infection Consortium identified passive immunotherapy with neutralizing antibodies as a treatment approach that warrants priority study. Two experimental MERS-CoV vaccines were used to vaccinate two groups of transchromosomic (Tc) bovines that were genetically modified to produce large quantities of fully human polyclonal immunoglobulin G (IgG) antibodies. Vaccination with a clade A γ-irradiated whole killed virion vaccine (Jordan strain) or a clade B spike protein nanoparticle vaccine (Al-Hasa strain) resulted in Tc bovine sera with high enzyme-linked immunosorbent assay (ELISA) and neutralizing antibody titers in vitro. Two purified Tc bovine human IgG immunoglobulins (Tc hIgG), SAB-300 (produced after Jordan strain vaccination) and SAB-301 (produced after Al-Hasa strain vaccination), also had high ELISA and neutralizing antibody titers without antibody-dependent enhancement in vitro. SAB-301 was selected for in vivo and preclinical studies. Administration of single doses of SAB-301 12 hours before or 24 and 48 hours after MERS-CoV infection (Erasmus Medical Center 2012 strain) of Ad5-hDPP4 receptor-transduced mice rapidly resulted in viral lung titers near or below the limit of detection. Tc bovines, combined with the ability to quickly produce Tc hIgG and develop in vitro assays and animal model(s), potentially offer a platform to rapidly produce a therapeutic to prevent and/or treat MERS-CoV infection and/or other emerging infectious diseases.


title: A low incidence of perineal hernia when using a biological mesh after extralevator abdominoperineal excision with or without pelvic exenteration or distal sacral resection in locally advanced rectal cancer patients.

text: BACKGROUND Extralevator abdominoperineal excision (ELAPE), abdominoperineal excision (APE) or pelvic exenteration (PE) with or without sacral resection (SR) for locally advanced rectal cancer leaves a significant defect in the pelvic floor. At first, this defect was closed primarily. To prevent perineal hernias, the use of a biological mesh to restore the pelvic floor has been increasing. The aim of this study, was to evaluate the outcome of the use of a biological mesh after ELAPE, APE or PE with/without SR. METHODS A retrospective study was conducted on patients who had ELAPE, APE or PE with/without SR with a biological mesh (Permacol™) for pelvic reconstruction in rectal cancer in our center between January 2012 and April 2015. The endpoints were the incidence of perineal herniation and wound healing complications. RESULTS Data of 35 consecutive patients [22 men, 13 women; mean age 62 years (range 31-77 years)] were reviewed. Median follow-up was 24 months (range 0.4-64 months). Perineal hernia was reported in 3 patients (8.6%), and was asymptomatic in 2 of them. The perineal wound healed within 3 months in 37.1% (n = 13), within 6 months in 51.4% (n = 18) and within 1 year in 62.9% (n = 22). In 17.1% (n = 6), the wound healed after 1 year. It was not possible to confirm perineal wound healing in the remaining 7 patients (20.0%) due to death or loss to follow-up. Wound dehiscence was reported in 18 patients (51.4%), 9 of whom needed vacuum-assisted closure therapy, surgical closure or a flap reconstruction. CONCLUSIONS Closure of the perineal wound after (EL)APE with a biological mesh is associated with a low incidence of perineal hernia. Wound healing complications in this high-risk group of patients are comparable to those reported in the literature.


title: Renal Denervation Therapy for Drug-Resistant Hypertension: Does It Still Work?

text: OPINION STATEMENT Hypertension is a global public health problem affecting one-fourth of the world's population. A subset of these patients with resistant hypertension presents a particular management problem and suffers a marked increase in cardiovascular risk. Treatment options have been limited, but the past decade has witnessed the emergence of catheter-based renal denervation to interrupt the sympathetic nervous system, long considered to play an important role in the development and maintenance of hypertension. Phase 1 and 2 studies reported remarkable reductions in blood pressure and sparked an excessive exuberance that ground to a halt with negative results of the SYMPLICITY HTN-3 pivotal trial. The subsequent and sober reappraisal has shed light on potential failure modes. Armed with appropriately cautious optimism, the field has resumed its move forward to realize the potential for therapeutic application in hypertension and other conditions characterized by sympathetic overactivity. This article summarizes the rich experimental data, early surgical experience, and available clinical trial results for catheter platforms. It concludes with discussion of knowledge gaps, lessons learned, and future directions.


title: Ophthalmology Practice During the Coronavirus Disease 2019 Pandemic: The University of Pittsburgh Experience in Promoting Clinic Safety and Embracing Video Visits.

text: The coronavirus disease 2019 pandemic has led to widespread change as public health strategies for containment have emphasized social distancing and remaining at home. These policies have led to downscaled clinic volumes, cancellation of elective procedures, enhanced personal protective strategies in the clinic, and adoption of telemedicine encounters. We describe the evidence-based practical approach taken in our ophthalmology department to continue delivering eye care during the pandemic by rescheduling visits, enhancing clinic safety, and adopting virtual video encounters.


Covid-19: the precarious position of Spain's nursing homes.


Covid-19: Admit ethnic minority pregnant women to hospital earlier, says NHS England.


title: Nonabsorbable versus absorbable sutures in large, hang-back medial rectus muscle recessions.

text: PURPOSE To investigate the value of nonabsorbable sutures in reducing the incidence of consecutive exotropia after large, "hang-back" medial rectus recessions. METHODS The medical records of patients who underwent medial rectus recession of ≥6.5 mm in individuals ≤2 years of age, or ≥7.0 mm in those >2 years were retrospectively reviewed. Patients were divided into two groups based on suture material used: absorbable, polyglactin 910 sutures (44 patients); nonabsorbable, polyester sutures (50 patients). Preoperative measurements, ductions, strabismus surgery, and postoperative results were analyzed. Inadequate anchoring of the medial rectus muscle was suspected when consecutive exotropia developed 4-7 weeks after surgery after initial satisfactory alignment and was confirmed if during reoperation the medial rectus muscle appeared recessed >2 mm beyond the originally intended recession. RESULTS Consecutive exotropia due to inadequate anchoring of the medial rectus muscle occurred in 11 of 66 muscles (17%) in the absorbable suture group. The muscle was found 6-10 mm posterior to the intended recession. Limited duction in the field of action of the involved medial rectus muscle occurred in 9 of the 11 muscles (82%). None of the eyes with nonabsorbable sutures showed inadequate anchoring. The incidence of consecutive exotropia was higher in the absorbable suture group (30%) than in the nonabsorbable suture group (6%) (P < 0.005). CONCLUSIONS Using nonabsorbable suture for large, hang-back medial rectus recessions greatly reduces the incidence of consecutive exotropia that can occur when absorbable suture dissolves.


Renin-angiotensin-aldosterone system inhibitors and COVID-19.


title: Predictive Factors for Good Outcome and Mortality After Stent-Retriever Thrombectomy in Patients With Acute Anterior Circulation Stroke.

text: BACKGROUND AND PURPOSE Predictive factors associated with stent-retriever thrombectomy for patients with acute anterior circulation stroke remain to be elucidated. This study aimed to investigate clinical and procedural factors predictive of good outcome and mortality after stent-retriever thrombectomy in a large cohort of patients with acute anterior circulation stroke. METHODS We analyzed clinical and procedural data in 335 patients with acute anterior circulation stroke treated with stent-retriever thrombectomy. A good outcome was defined as a modified Rankin Scale score of 0 to 2 at 3 months. The associations between clinical, imaging, and procedural factors and good outcome and mortality, respectively, were evaluated using logistic regression analysis. RESULTS Using multivariate analysis, age (odds ratio [OR], 0.965; 95% confidence interval [CI], 0.944-0.986; P=0.001), successful revascularization (OR, 4.658; 95% CI, 2.240-9.689; P<0.001), parenchymal hemorrhage (OR, 0.150; 95% CI, 0.049-0.460; P=0.001), and baseline NIHSS score (OR, 0.908; 95% CI, 0.855-0.965; P=0.002) were independent predictors of good outcome. Independent predictors of mortality were age (OR, 1.043; 95% CI, 1.002-1.086; P=0.041), successful revascularization (OR, 0.171; 95% CI, 0.079-0.370; P<0.001), parenchymal hemorrhage (OR, 2.961; 95% CI, 1.059-8.276; P=0.038), and a history of previous stroke/TIA (OR, 3.124; 95% CI, 1.340-7.281; P=0.008). CONCLUSIONS Age, revascularization status, and parenchymal hemorrhage are independent predictors of both good outcome and mortality after stent retriever thrombectomy for acute anterior circulation stroke. In addition, NIHSS score on admission is independently associated with good outcome, whereas a history of previous stroke is independently associated with mortality.


title: Rehospitalization to primary versus different facilities following abdominal aortic aneurysm repair.

text: OBJECTIVE Reducing readmissions represents a unique opportunity to improve care and reduce health care costs and is the focus of major payers. A large number of surgical patients are readmitted to hospitals other than where the primary surgery was performed, resulting in clinical decisions that do not incorporate the primary surgeon and potentially alter outcomes. This study characterizes readmission to primary vs different hospitals after abdominal aortic aneurysm (AAA) repair and examines the implications with regard to mortality and cost. METHODS Patients who underwent open or endovascular aneurysm repair for AAA were identified from the Centers for Medicare and Medicaid Services Chronic Conditions Warehouse, a random 5% national sample of Medicare beneficiaries from 2005 to 2009. Outcomes for patients who underwent AAA repair and were readmitted within 30 days of initial discharge were compared based on readmission location (primary vs different hospital). RESULTS A total of 885 patients underwent AAA repair and were readmitted within 30 days. Of these, 626 (70.7%) returned to the primary facility, and 259 (29.3%) returned to a different facility. Greater distance from patient residence to the primary hospital was the strongest predictor of readmission to a different facility. Patients living 50 to 100 miles from the primary hospital were more likely to be readmitted to a different hospital compared with patients living <10 miles away (odds ratio, 8.50; P < .001). Patients with diagnoses directly related to the surgery (eg, wound infection) were more likely to be readmitted to the primary hospital, whereas medical diagnoses (eg, pneumonia and congestive heart failure) were more likely to be treated at a different hospital. There was no statistically significant difference in mortality between patients readmitted to a different or the primary hospital. Median total 30-day payments were significantly lower at different vs primary hospitals (primary, $11,978 vs different, $11,168; P = .04). CONCLUSIONS Readmission to a different facility after AAA repair is common and occurs more frequently than for the overall Medicare population. Patients travelling a greater distance for AAA repair are more likely to return to different vs the primary hospital when further care is required. For AAA repair, quality healthcare may be achieved at marginally lower cost and with greater patient convenience for selected readmissions at hospitals other than where the initial procedure was performed.


title: Re-Tubularization of Highly-Ischemic Anti-Mesenteric Border (ReHAB): A Novel Bowel Preservation Technique in Complex Gastroschisis.

text: Complex gastroschisis with bowel necrosis poses an operative challenge. Surgeons must weigh the decision between resection versus preservation of ischemic bowel. As one of the leading causes of short bowel syndrome, aggressive resection in complicated gastroschisis subjects children to prolonged dependence on parenteral nutrition and its attendant complications. Herein, we describe a novel technique aimed towards bowel preservation in complex gastroschisis patients with severe bowel ischemia with the ultimate goal for enteral autonomy.


title: Anticipating the perceived risk of nanotechnologies.

text: Understanding emerging trends in public perceptions of nanomaterials is critically important for those who regulate risks. A number of surveys have explored public perceptions of their risks and benefits. In this paper we meta-analyse these surveys to assess the extent to which the following four hypotheses derived from previous studies of new technologies might be said to be valid for nanotechnologies: risk aversion will prevail over benefit appreciation; an increase in knowledge will not result in reduced aversion to risks; judgements will be malleable and subject to persuasion given risk-centric information; and contextual, psychometric and attitudinal predictors of perceived risk from prior studies can help anticipate future perceptions of nanotechnologies. We find that half the public has at least some familiarity with nanotechnology, and those who perceive greater benefits outnumber those who perceive greater risks by 3 to 1. However, a large minority of those surveyed (44%) is unsure, suggesting that risk judgements are highly malleable. Nanotechnology risk perceptions also appear to contradict some long-standing findings. In particular, unfamiliarity with nanotechnology is, contrary to expectations, not strongly associated with risk aversion and reduced 'knowledge deficits' are correlated with positive perceptions in this early and controversy-free period. Psychometric variables, trust and affect continue to drive risk perceptions in this new context, although the influence of both trust and affect is mediated, even reversed, by demographic and cultural variables. Given the potential malleability of perceptions, novel methods for understanding future public responses to nanotechnologies will need to be developed.


title: MIS in the management of colon and rectal cancer: consensus meeting of the Colorectal Cancer Association of Canada.

text: A consensus conference on the role of minimally invasive surgery (MIS) in the management of colon and rectal cancer was convened by the Colorectal Cancer Association of Canada in Toronto on April 18, 2012. This is a report of the consensus of an invited group of Canadian experts in MIS and surgery of the colon and rectum that addresses the role this technology should play in treatment and also considers advocacy and resources.


title: Comparison of short-term outcomes in laparoscopic vs open hepatectomy.

text: IMPORTANCE Despite the increasing role of laparoscopy in partial hepatic resection, its short-term benefit compared with traditional open surgery remains unclear. OBJECTIVE To compare short-term (30-day) outcomes between laparoscopic (LH) and open (OH) partial hepatectomies. DESIGN, SETTING, AND PARTICIPANTS Retrospective matched case-control study from April 1, 2004, to March 31, 2013, in a tertiary hepatobiliary referral center. Patients who underwent partial hepatic resection (OH or LH) for benign or malignant disease were matched first by extent of resection, then by pathological diagnosis, and finally by age and sex to the extent possible. EXPOSURE Partial hepatectomy for liver disease. MAIN OUTCOMES AND MEASURES Thirty-day morbidity and mortality rates. RESULTS After the matching process, we included 104 patients (52 undergoing LH and 52 undergoing OH) in the study. Patients were evenly matched with respect to age, sex, extent of resection, and diagnosis. Cirrhosis was present in 17 patients (33%) in each group. We found no difference in positive margin status (1 patient [2%] for LH vs 2 patients [4%] for OH; P > .99). Although the estimated blood loss differed significantly between groups (237 mL for LH vs 387 mL for OH; P = .049), we found no difference in the rate of perioperative blood transfusion (1 patient [2%] for LH vs 5 [10%] for OH; P = .20). Operative time (219 minutes for LH vs 198 minutes for OH; P = .16), hospital length of stay (5 days for LH vs 6 days for OH; P = .13), and readmission rate (4 patients [8%] for LH vs 5 [10%] for OH; P = .70) were similar in both groups. The rates of major complications (4 patients [8%] for LH vs 4 patients [8%] for OH; P = 10), overall 30-day morbidity (22 patients [42%] for LH vs 19 [37%] for OH; P = .70), and 30-day mortality (1 patient [2%] for LH vs 2 [4%] for OH; P > .99) were not significantly different. CONCLUSIONS AND RELEVANCE Patients who undergo LH have similar short-term outcomes when compared with those who undergo OH. Laparoscopic hepatectomy was associated with lower intraoperative blood loss, although the clinical significance of this finding is uncertain given the lack of difference in perioperative transfusion or morbidity rates. In addition, we found no difference in margin status between the 2 groups. Future studies are needed to define which patients derive benefit from LH and to determine oncologic equivalence to OH.


title: Use of routine interventions in labour and birth in Canadian hospitals: comparing results of the 1993 and 2007 Canadian hospital maternity policies and practices surveys.

text: OBJECTIVES To compare policies and practices of routine interventions in labour and birth in Canadian hospitals in 1993 and 2007 and to describe trends regarding adherence to evidence-based guidelines. METHODS We used data from surveys of Canadian hospitals in 1993 and 2007 on routine maternity care practices and policies, including interventions in labour and birth. RESULTS The response rate of hospitals in 1993 was 91% (523/572), and in 2007 it was 92% (323/353). In 1993, 65% of hospitals (335/516) had a policy that all women should have initial electronic fetal heart rate monitoring, and in 2007, 74% (235/319) had such a policy. In 1993, 55% of hospitals (284/516) used epidural anaesthesia as one of the methods for pain control, and in 2007, 87% of hospitals (278/318) did so. In 1993, 37% of hospitals (193/521) had a "no enema/suppository" policy on admission, and in 2007, 88% (282/322) did. In 1993, 87% of hospitals (450/516) had a policy encouraging the presence of both the woman's partner and other labour support people in the room during the course of labour; in 2007, 80% (259/323) did. In 1993, hospitals estimated that 62% of primiparous women and 44% of multiparous women had an episiotomy in their units. In 2007, the episiotomy rate, irrespective of parity, was 17%. In 1993, 20% of hospitals (98/498) had a policy specifying the length of the second stage of labour, and in 2007, 33% (101/307) had such a policy. CONCLUSION Positive and negative trends in adherence to best practices were seen in policies and practices of routine interventions during labour and birth in Canadian hospitals between 1993 and 2007.


title: Venous pseudoaneurysm of the great saphenous vein stump as late complication of flush saphenofemoral ligation and stripping.

text: Guidelines now recommend endovenous thermal ablation over open treatment of saphenous incompetence, but flush saphenofemoral ligation and stripping remain relevant when appropriately applied and expertly executed. Complications are rare but could be severe, needing further surgical correction. We report a unique case of a late venous pseudoaneurysm of the great saphenous vein stump after flush saphenofemoral ligation and stripping, successfully treated with surgical sac excision. We highlight the importance of continuous follow-up for patients previously submitted to open venous surgery.


title: Loss of smell or taste as the only symptom of COVID-19.

text: BACKGROUND Olfactory and taste disorders (OTDs) have recently been reported among patients with COVID-19, and it has been hypothesised that oral and nasal tissues may contain host cells of SARS-CoV-2. We report on two cases (spouses) with SARS-CoV-2 infection with self-reported OTDs, but otherwise no typical respiratory symptoms of COVID-19. CASE PRESENTATION A man in his nineties (index patient) had respiratory symptoms and dysgeusia, and was diagnosed with COVID-19. His daughter-in-law and son had no respiratory COVID-19 symptoms. However, they experienced complete loss of smell and taste, respectively, 7 and 10 days after their first close contact with the index patient. Both tested positive for SARS-CoV-2 RNA. INTERPRETATION Our case histories support recent reports hypothesising that anosmia and ageusia may be the only symptoms of SARS-CoV-2 infection, and that SARS-CoV-2 may infect oral and nasal tissues. Together, these findings may inform future research, diagnosis, prevention and treatment of COVID-19.


title: Guest Editorial: An Update on Stroke Intervention.

text: Endovascular treatment for acute ischemic stroke has changed remarkably over the past decade. Beginning with IA thrombolytic administration, endovascular strategies have evolved to include aspiration, self-expanding intracranial stents, and now retrievable stents. With the recent publication of 5 randomized, controlled studies (MR CLEAN, EXTEND-IA, ESCAPE, SWIFT PRIME, and REVASCAT), mechanical thrombectomy, when used in combination with IV tPA, has demonstrated a significant radiographic and clinical benefit over traditional strategies with IV tPA alone. These results have placed endovascular therapy at the forefront of stroke treatment, redefining the standard of care.


title: How defensive medicine is defined and understood in European medical literature: protocol for a systematic review.

text: INTRODUCTION The term defensive medicine, referring to actions motivated primarily by litigious concerns, originates from the USA and has been used in medical research literature since the late 1960s. Differences in medical legal systems between the US and most European countries with no tort legislation raise the question whether the US definition of defensive medicine holds true in Europe. AIM To present the protocol of a systematic review investigating variations in definitions and understandings of the term 'defensive medicine' in European research articles. METHODS AND ANALYSIS In concordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, a systematic review of all medical research literature that investigate defensive medicine will be performed by two independent reviewers. The databases PubMed, Embase and Cochrane will be systematically searched on the basis of predetermined criteria. Data from all included European studies will systematically be extracted including the studies' definitions and understandings of defensive medicine, especially the motives for doing medical actions that the study regards as 'defensive'. ETHICS AND DISSEMINATION No ethics clearance is required as no primary data will be collected. The results of the systematic review will be published in a peer-reviewed, international journal. PROSPERO REGISTRATION NUMBER This review has been submitted to International Prospective Register of Systematic Reviews (PROSPERO) and is awaiting registration.


Racial Health Disparities and Covid-19 - Caution and Context.


title: Passive immunization: Paradoxical and traditional method for new pandemic challenge COVID-19.

text: World has been suffering from pandemic caused by mysterious Coronavirus. The novel member of Coronaviridae causing COVID-19 disease is named as SARS-Cov-2. Its first case was reported in China by the end of 2019, but its exponential spread has wrapped entire globe, suspended and is penalizing mankind. A retrospective meta-analysis study showed that outbreaks of Middle East Respiratory Syndrome (MERS) and SARS-Cov-1 (Coronaviridae), influenza infection H1N1 and West-African Ebola caused lower mortality than this new pandemic COVID-19. Virus has appeared as a new human pathogen so to counter COVID-19 no specific vaccine, monoclonal antibodies have been manufactured till day. The outbreak of novel Coronavirus is treated with antimicrobial drugs but they have their own mild side effects. But the drastic spread of COVID-19 compels us also to use other ways to counter pandemic. Thus, passive immunization can be opted to hold back this mysterious virus. Passive immunization has been in use since early 20th century and showed its effectiveness against all previous infectious outbreaks including MERS and SARS-Cov-1 members of Coronaviridae. The review argues that convalescent plasma is an explicit option for containment of COVID-19 disease.


title: Comparison of different ADM materials in breast surgery.

text: This is a brief review of the history of the role of acellular dermal matrices in breast reconstruction surgery, with a summary of several currently available products, including a table of comparisons. Key features, including biologic tissue source, surgical preparation, sterility, polarity, contraindications, shelf life, and cost, are examined. A paucity of data exists to directly compare AlloDerm®, DermaMatrix®, Strattice™, Permacol™, DermACELL, FlexHD®, SurgiMend®, and ALLOMAX™ for breast reconstruction; most studies relate to hernia repair. An ideal acellular dermal matrix product is still unavailable but the information provided in this review should facilitate a breast surgeons decision-making process.


title: Public Health Policy and Experience of the 2009 H1N1 Influenza Pandemic in Pune, India.

text: BACKGROUND Prior experience and the persisting threat of influenza pandemic indicate the need for global and local preparedness and public health response capacity. The pandemic of 2009 highlighted the importance of such planning and the value of prior efforts at all levels. Our review of the public health response to this pandemic in Pune, India, considers the challenges of integrating global and national strategies in local programmes and lessons learned for influenza pandemic preparedness. METHODS Global, national and local pandemic preparedness and response plans have been reviewed. In-depth interviews were undertaken with district health policy-makers and administrators who coordinated the pandemic response in Pune. RESULTS In the absence of a comprehensive district-level pandemic preparedness plan, the response had to be improvised. Media reporting of the influenza pandemic and inaccurate information that was reported at times contributed to anxiety in the general public and to widespread fear and panic. Additional challenges included inadequate public health services and reluctance of private healthcare providers to treat people with flu-like symptoms. Policy-makers developed a response strategy that they referred to as the Pune plan, which relied on powers sanctioned by the Epidemic Act of 1897 and resources made available by the union health ministry, state health department and a government diagnostic laboratory in Pune. CONCLUSION The World Health Organization's (WHO's) global strategy for pandemic control focuses on national planning, but state-level and local experience in a large nation like India shows how national planning may be adapted and implemented. The priority of local experience and requirements does not negate the need for higher level planning. It does, however, indicate the importance of local adaptability as an essential feature of the planning process. Experience and the implicit Pune plan that emerged are relevant for pandemic preparedness and other public health emergencies.


title: Impact of Mycoplasma hyopneumoniae and Lawsonia intracellularis on the performance of pigs divergently selected for feed efficiency.

text: Feed efficiency (FE) is a valuable trait, yet how genetic selection for enhanced FE affects other processes such as response to disease is unknown. Disease from endemic respiratory and enteric pathogens such as Mycoplasma hyopneumoniae (Mh) and Lawsonia intracellularis (LI) are common in swine production. Therefore, the aim of this study was to examine if pigs selected for high vs. low FE based on residual feed intake (RFI) respond differently to a dual respiratory and enteric challenge. Pigs selected for low RFI (LRFI, high FE) are considered more FE compared to their high RFI (HRFI, low FE) selected counterparts. Using a 2 × 2 factorial design, 25 littermate pairs from the HRFI and 25 littermate pairs from the LRFI line (barrows, 50 ± 7 kg BW) were selected, with one pig from each pair assigned to individual pens in either the challenge or the nonchallenge (control) rooms (n = 25 barrows/line/challenge). On days post inoculation (dpi) 0, the challenged pigs were inoculated with LI and Mh (MhLI). Feed intake, BW, fecal swabs, and serum samples were collected and recorded weekly for 42 d. On dpi -2 and 47, 14 littermate pairs (n = 7 barrows/line/challenge) were utilized for initial and final body composition scans using dual-energy X-ray absorptiometry to calculate longitudinal whole body tissue accretion rates for lean, protein, fat, and bone mineral content. Serum antibody levels and fecal shedding of LI were used to confirm infection. Control pigs remained negative by all measures during the 6-wk trial and MhLI inoculated pigs were confirmed positive via serological antibody responses by dpi 14 for LI and Mh. There were no interactions between RFI line and challenge status for any overall performance parameter (P > 0.05). The 6-wk MhLI challenge resulted in a 17% reduction in ADG, a 12% reduction in ADFI, and a 7% reduction in G:F vs. Controls (P < 0.05). In addition, compared to the Control pigs, MhLI challenge reduced lean, protein, and lipid accretion rates by 16% (P < 0.05). Genetic selection for high FE resulted in decreased ADFI and increased G:F (P < 0.01), but did not impact ADG or tissue accretion vs. low FE pigs. Collectively, these results demonstrate that a dual enteric and respiratory pathogen challenge reduced ADG, ADFI, G:F, and tissue accretion in growing pigs. Further, there was no evidence that selection for enhanced FE based on RFI index affects response to disease.


Uniportal video-assisted thoracoscopy surgery in lung cancer: largest experience.


title: We're Not All in This Together: On COVID-19, Intersectionality, and Structural Inequality.

text: We are not all in this together. My 32-year history with the HIV/AIDS epidemic in the United States-initially as an HIV/AIDS policy analyst and now as an HIV-prevention researcher-has provided the dubitable opportunity to witness how adroitly deadly viruses spotlight fissures of structural inequality. In the late 1980s, "changing face" was the term often used to describe the epidemic's transition from one that affected predominantly White and class-privileged gay and bisexual men to one that exacted a disproportionate toll on people at the most marginalized demographic intersections: Black and Latinx gay and bisexual men, cisgender and transgender women, injection drug users, and poor people. (Am J Public Health. Published online ahead of print May 28, 2020: e1-e2. doi:10.2105/AJPH.2020.305766).


title: International expert consensus statement: Percutaneous transluminal renal denervation for the treatment of resistant hypertension.

text: Catheter-based radiofrequency ablation technology to disrupt both efferent and afferent renal nerves has recently been introduced to clinical medicine after the demonstration of significant systolic and diastolic blood pressure reductions. Clinical trial data available thus far have been obtained primarily in patients with resistant hypertension, defined as standardized systolic clinic blood pressure ≥ 160 mm Hg (or ≥ 150 mm Hg in patients with type 2 diabetes) despite appropriate pharmacologic treatment with at least 3 antihypertensive drugs, including a diuretic agent. Accordingly, these criteria and blood pressure thresholds should be borne in mind when selecting patients for renal nerve ablation. Secondary forms of hypertension and pseudoresistance, such as nonadherence to medication, intolerance of medication, and white coat hypertension, should have been ruled out, and 24-h ambulatory blood pressure monitoring is mandatory in this context. Because there are theoretical concerns with regard to renal safety, selected patients should have preserved renal function, with an estimated glomerular filtration rate ≥ 45 ml/min/1.73 m(2). Optimal periprocedural management of volume status and medication regimens at specialized and experienced centers equipped with adequate infrastructure to cope with potential procedural complications will minimize potential patient risks. Long-term safety and efficacy data are limited to 3 years of follow-up in small patient cohorts, so efforts to monitor treated patients are crucial to define the long-term performance of the procedure. Although renal nerve ablation could have beneficial effects in other conditions characterized by elevated renal sympathetic nerve activity, its potential use for such indications should currently be limited to formal research studies of its safety and efficacy.


title: Simplifying alternating peptide synthesis by protease-catalyzed dipeptide oligomerization.

text: A unique route to perfectly alternating oligopeptides is described. First, AG-OEt was prepared by standard chemical coupling. Then, AG-OEt was converted by papain-catalysis in 30 s to (AG)(x) (80%-yield, x = 9.4 ± 0.3). Extension of this strategy to other alternating peptide compositions as well as the importance of selecting a protease and reaction conditions that avoid competing transamidation and hydrolysis reactions is discussed.


title: In Vitro comparison of 213Bi- and 177Lu-radiation for peptide receptor radionuclide therapy.

text: BACKGROUND Absorbed doses for α-emitters are different from those for β-emitters, as the high linear energy transfer (LET) nature of α-particles results in a very dense energy deposition over a relatively short path length near the point of emission. This highly localized and therefore high energy deposition can lead to enhanced cell-killing effects at absorbed doses that are non-lethal in low-LET type of exposure. Affinities of DOTA-DPhe1-Tyr3-octreotate (DOTATATE), 115In-DOTATATE, 175Lu-DOTATATE and 209Bi-DOTATATE were determined in the K562-SST2 cell line. Two other cell lines were used for radiation response assessment; BON and CA20948, with a low and high expression of somatostatin receptors, respectively. Cellular uptake kinetics of 111In-DOTATATE were determined in CA20948 cells. CA20948 and BON were irradiated with 137Cs, 177Lu-DTPA, 177Lu-DOTATATE, 213Bi-DTPA and 213Bi-DOTATATE. Absorbed doses were calculated using the MIRDcell dosimetry method for the specific binding and a Monte Carlo model of a cylindrical 6-well plate geometry for the exposure by the radioactive incubation medium. Absorbed doses were compared to conventional irradiation of cells with 137Cs and the relative biological effect (RBE) at 10% survival was calculated. RESULTS IC50 of (labelled) DOTATATE was in the nM range. Absorbed doses up to 7 Gy were obtained by 5.2 MBq 213Bi-DOTATATE, in majority the dose was caused by α-particle radiation. Cellular internalization determined with 111In-DOTATATE showed a linear relation with incubation time. Cell survival after exposure of 213Bi-DTPA and 213Bi-DOTATATE to BON or CA20948 cells showed a linear-exponential relation with the absorbed dose, confirming the high LET character of 213Bi. The survival of CA20948 after exposure to 177Lu-DOTATATE and the reference 137Cs irradiation showed the typical curvature of the linear-quadratic model. 10% Cell survival of CA20948 was reached at 3 Gy with 213Bi-DOTATATE, a factor 6 lower than the 18 Gy found for 177Lu-DOTATATE and also below the 5 Gy after 137Cs external exposure. CONCLUSION 213Bi-DTPA and 213Bi-DOTATATE lead to a factor 6 advantage in cell killing compared to 177Lu-DOTATATE. The RBE at 10% survival by 213Bi-ligand compared to 137Cs was 2.0 whereas the RBE for 177Lu-DOTATATE was 0.3 in the CA20948 in vitro model.


Religious discrimination is hindering the covid-19 response.


title: Clinical evaluation of a pre-tied ligating loop for liver biopsy and liver lobectomy.

text: OBJECTIVES The aim of this prospective case series was to evaluate the suitability of a pre-tied ligating loop for liver biopsy or partial or complete liver lobectomy via midline coeliotomy for diagnosis or treatment of hepatic disease. METHODS Nine client-owned animals (six dogs and three cats) in which liver biopsy or partial or complete liver lobectomy was performed using a 2-0 Polysorb™ pre-tied ligating loop (SurgiTie™; Covidien) via midline coeliotomy were included. The fit of the loop, space for incision and presence and character of bleeding from the incised surface were assessed. Pre- and postoperative haematocrit and peri-operative complications were noted. Dimensions, histopathology and mineral analysis of acquired specimens were reviewed. RESULTS The pre-tied ligating loop was successfully employed for liver biopsy and resection of torsed liver lobes and neoplastic tissue. Dirty margins were obtained in one case in which complete resection of neoplastic tissue was the primary goal. Few perioperative complications were noted, the most common being generalised oozing from the cut surface in four cases, effectively controlled with local haemostasis. CLINICAL SIGNIFICANCE The pre-tied ligating loop is a versatile and safe method for liver biopsy or lobectomy. As with other surgical techniques, alternative methods of haemostasis should always be available.


Epidemiology of COVID-19 in Brazil: using a mathematical model to estimate the outbreak peak and temporal evolution.


title: Evaluation of the Learning Curve of Hand-Assisted Laparoscopic Donor Nephrectomy.

text: BACKGROUND In this study, we analyzed the learning curve of hand-assisted laparoscopic donor nephrectomy (HALDN). MATERIAL AND METHODS The first 198 consecutive donors (110 cases by expert surgeon and 88 cases by newbie surgeon) operated on using HALDN were included in this study. The primary outcome measures were warm ischemic time (WIT), total operation time and estimated blood loss (EBL). The secondary outcome measures included length of hospital stay (LOS), graft outcome, and surgery-related complications. We used the cumulative sum (CUSUM) method to generate learning curves. RESULTS Except for WIT, all operative and convalescence parameters of donors and graft outcomes were similar for the 2 groups, including the total operation time (174.13 minutes vs. 171.75 minutes, P=0.140), EBL (108.27 cc vs. 116.82 cc, P=0.494), LOS (4.80 days vs. 4.92 days, P=0.144), and overall rates of intraoperative and postoperative complications (P>0.05). A significant difference was observed in WIT between the 2 groups (140.59 sec vs. 106.85 sec, P=0.027). Upon visual assessment of the CUSUM plots, a downward inflexion point for decreasing WIT was observed in 4 cases, total operation time in 12 cases, and EBL in 15 cases. CONCLUSIONS HALDN has a relatively short learning curve and similar results may be expected from newbie urologists who are trained in minimally invasive surgery fellowship.


title: Radiofrequency ablation combined with transarterial chemoembolization for subcapsular hepatocellular carcinoma: a prospective cohort study.

text: OBJECTIVE This study evaluated the safety and efficacy of using radiofrequency ablation combined with transarterial chemoembolization to treat hepatocellular carcinoma in a subcapsular location, given the increased risk of complications when using radiofrequency ablation alone. MATERIALS AND METHODS From January 2000 to December 2011, 1213 patients with unresectable hepatocellular carcinoma (up to three nodules) were screened. Of these, 132 patients with 132 subcapsular nodules (mean size, 3.0 cm; range, 1.2-5.0 cm) were enrolled in the study. After transarterial chemoembolization, percutaneous radiofrequency ablation was performed under ultrasound or C-arm cone-beam computed tomography guidance, on the same day or within 3 days. Local recurrence and survival curves were obtained using the Kaplan-Meier method. RESULTS Technical success of treatment was achieved in 130 patients (98.5%). Major complications, including pleural effusion, secondary peritonitis, and liver abscess, occurred in 3 patients (2.3%); the incidence of complications was associated with the number of needle insertions (1-2 vs. 3-4, P=0.039, Fisher's exact test). No patients developed permanent sequelae, tumor seeding, or tumor bleeding. The 3-year local recurrence rate was 9.7%. Local recurrence was associated with the pretreatment serum des-gamma-carboxy prothrombin level (≤200 mAU/mL vs. >200 mAU/mL, P=0.019, log-rank test). The 3-, 5-, and 7-year overall survival rates in treatment-naïve cases (n=82) were 79.3%, 60.6%, and 50.9%, respectively. CONCLUSION Combination therapy using radiofrequency ablation and transarterial chemoembolization was a safe and useful therapeutic option for patients with subcapsular hepatocellular carcinoma.


Human Rights and Covid-19 pandemic.


title: Initiation of hepatitis C virus infection requires the dynamic microtubule network: role of the viral nucleocapsid protein.

text: Early events leading to the establishment of hepatitis C virus (HCV) infection are not completely understood. We show that intact and dynamic microtubules play a key role in the initiation of productive HCV infection. Microtubules were required for virus entry into cells, as evidenced using virus pseudotypes presenting HCV envelope proteins on their surface. Studies carried out using the recent infectious HCV model revealed that microtubules also play an essential role in early, postfusion steps of the virus cycle. Moreover, low concentrations of vinblastin and nocodazol, microtubule-affecting drugs, and paclitaxel, which stabilizes microtubules, inhibited infection, suggesting that microtubule dynamic instability and/or treadmilling mechanisms are involved in HCV internalization and early transport. By protein chip and direct core-dependent pull-down assays, followed by mass spectrometry, we identified beta- and alpha-tubulin as cellular partners of the HCV core protein. Surface plasmon resonance analyses confirmed that core directly binds to tubulin with high affinity via amino acids 2-117. The interaction of core with tubulin in vitro promoted its polymerization and enhanced the formation of microtubules. Immune electron microscopy showed that HCV core associates, at least temporarily, with microtubules polymerized in its presence. Studies by confocal microscopy showed a juxtaposition of core with microtubules in HCV-infected cells. In summary, we report that intact and dynamic microtubules are required for virus entry into cells and for early postfusion steps of infection. HCV may exploit a direct interaction of core with tubulin, enhancing microtubule polymerization, to establish efficient infection and promote virus transport and/or assembly in infected cells.


title: Efficacy and safety of bilastine 20 mg compared with cetirizine 10 mg and placebo in the treatment of perennial allergic rhinitis.

text: OBJECTIVE Bilastine is a non-sedating second-generation H(1) antihistamine with proven efficacy and safety in the treatment of patients with seasonal allergic rhinitis and urticaria. The objective of this study was to demonstrate the efficacy and safety of bilastine in patients with perennial allergic rhinitis (PAR). METHODS In a multicenter, randomized, placebo-controlled, double-blind, parallel-group study, patients with symptomatic PAR (n = 650) from Argentina, Europe, and South Africa received bilastine 20 mg, cetirizine 10 mg, or placebo once daily for 4 weeks. The primary efficacy outcome was the mean area under the curve (AUC) of reflective total 6-symptom scores (rT6SS) from baseline visit to day 28 (D28). Secondary outcome measures included mean AUC of instantaneous total 6-symptom scores (iT6SS), and mean AUCs of reflective and instantaneous total 4-nasal symptom scores (T4NSS) and total 2-ocular symptom scores (T2OSS) from baseline to D28. An open-label extension phase evaluated the safety of bilastine 20 mg administered to patients (n = 513) for one year. RESULTS In the overall population no significant differences in efficacy outcomes were found between active treatments and placebo. On account of the high placebo response in South Africa, a post-hoc analysis was conducted. This analysis demonstrated that statistically significant differences existed between active treatments and placebo in the mean AUC of rT6SS (p < 0.05) and T4NSS (p < 0.02), respectively, from baseline to D28 visit for the intent-to-treat population in patients from Europe and Argentina, whereas the difference was not statistically significant in South Africa. Whether this is related to differences in the demographic or clinical characteristics of South African patients (they had PAR for longer and reported more severe symptoms) and/or the disease management process compared with their European and Argentinean counterparts warrants further investigation. CONCLUSIONS A post-hoc analysis indicated that bilastine and cetirizine were similarly effective and more effective than placebo during a 4-week treatment period in patients with PAR. In addition, bilastine was shown to be safe and well-tolerated over a 1-year treatment period. CLINICAL TRIAL REGISTRY NUMBER NCT01127620.


title: So Many Roads: the Multifaceted Regulation of Autophagy Induction.

text: Autophagy is an evolutionary conserved, degradative process from single-cell eukaryotes, such as Saccharomyces cerevisiae, to higher mammals, such as humans. The regulation of autophagy has been elucidated through the combined study of yeast, Caenorhabditis elegans, mice, Drosophila melanogaster, and humans. MTOR, the major negative regulator of autophagy, and activating nutrient kinases, such as 5'-AMP-activated protein kinase (AMPK), interact with the autophagy regulatory complex: ULK1/2, RB1CC1, ATG13, and ATG101. The ULK1/2 complex induces autophagy by phosphorylating downstream autophagy complexes, such as the BECN1 PIK3 signaling complex that leads to the creation of LC3+ autophagosomes. We highlight in this review various reports of autophagy induction that are independent of these regulators. We discuss reports of MTOR-independent, AMPK-independent, ULK1/2-independent, and BECN1-PIK3C3-independent autophagy. We illustrate that autophagy induction and the components required vary by the nature of the induction signal and type of cell and do not always require canonical members of the autophagy signaling pathway. We illustrate that rather than thinking of autophagy as a linear pathway, it is better to think of autophagy induction as an interconnecting web of key regulators, many of which can induce autophagy through different requirements depending on the type and length of induction signals.


title: Cast saw noise does not reach occupational hazard levels.

text: BACKGROUND The purpose of our study was to measure the sound level generated by selected commercially available cast saws. These levels were then compared with the level of everyday sounds and to accepted intensities by Safety Administrations to see whether the mandatory use of hearing protection should be recommended to prevent noise-induced hearing loss. METHODS We assessed the sound levels generated by the Quiet Cast Removal System (QCR; OrthoPediatrics Corp., Warsaw, IN), Stryker 986 Cast Vac (Stryker Corp.), and the Stryker 840 Cast Cutter (Stryker Corp.). The sound generated by these saws was measured with a sound level meter at the source and at 6, 12, and 36 inches. The sound level from each device was assessed both while operating alone and while cutting casts for a total of 3 repetitions at each of the distances tested and analyzed statistically. RESULTS The maximal mean sound intensity of the Stryker 986 and Stryker 840 saws was 90.7 and 88.6 dBA at 36 inches, respectively while cutting a cast, whereas the QCR System produced 50.1 dBA at this distance. At 6 inches, the mean sound intensity was 99.4, 96.4, and 64.5 dBA for the Stryker 840, 986, and QCR, respectively. Statistically significant differences in sound intensity between Stryker and QCR saws were noted under all testing scenarios (P<0.0001). CONCLUSIONS None of the cast saws produced intensities exceeding recommended standards for a single exposure or intensities reaching occupational hazard levels. The QCR saw was significantly quieter than both the Stryker 840 and 986 under all scenarios. The need for a recommendation of mandatory usage of hearing protection for patients and office personal could not be demonstrated. CLINICAL RELEVANCE Cast saw noise is common in orthopaedic clinics. Our study demonstrates sound levels from commercially available saws do not reach occupational hazards but are sufficiently high that practical methods to reduce intensity may be warranted.


title: Evolutionary dynamics of bovine coronaviruses: natural selection pattern of the spike gene implies adaptive evolution of the strains.

text: Coronaviruses demonstrate great potential for interspecies transmission, including zoonotic outbreaks. Although bovine coronavirus (BCoV) strains are frequently circulating in cattle farms worldwide, causing both enteric and respiratory disease, little is known about their genomic evolution. We sequenced and analysed the full-length spike (S) protein gene of 33 BCoV strains from dairy and feedlot farms collected during outbreaks that occurred from 2002 to 2010 in Sweden and Denmark. Amino acid identities were >97 % for the BCoV strains analysed in this work. These strains formed a clade together with Italian BCoV strains and were highly similar to human enteric coronavirus HECV-4408/US/94. A high similarity was observed between BCoV, canine respiratory coronavirus (CRCoV) and human coronavirus OC43 (HCoV-OC43). Molecular clock analysis of the S gene sequences estimated BCoV and CRCoV diverged from a common ancestor in 1951, while the time of divergence from a common ancestor of BCoV and HCoV-OC43 was estimated to be 1899. BCoV strains showed the lowest similarity to equine coronavirus, placing the date of divergence at the end of the eighteenth century. Two strongly positive selection sites were detected along the receptor-binding subunit of the S protein gene: spanning amino acid residues 109-131 and 495-527. By contrast, the fusion subunit was observed to be under negative selection. The selection pattern along the S glycoprotein implies adaptive evolution of BCoVs, suggesting a successful mechanism for BCoV to continuously circulate among cattle and other ruminants without disappearance.


title: Cerebral microembolization during atrial fibrillation ablation: comparison of different single-shot ablation techniques.

text: BACKGROUND Clinically silent cerebral ischemia (SCI) detected by diffusion-weighted MRI has been reported in 5-40% of patients undergoing pulmonary vein isolation (PVI). Although initial reports suggested a high rate of SCI with phased radiofrequency (RF) ablation on use of the pulmonary vein ablation catheter (PVAC), the incidence was subsequently markedly reduced in consequence of procedural modifications in recent studies. We analyzed cerebral microembolization as assessed with transcranial Doppler during phased RF ablation and with two other single-shot AF ablation technologies: the cryoballoon (CB) and the nMARQ™ multipolar irrigated RF ablation system. METHODS AND RESULTS A total of 89 patients (mean age: 57, SD: 12years; 62 males) with paroxysmal or persistent AF underwent PVI. Phased RF was used according to the initial protocol in 7 patients (PVAC Group I), with procedural modifications and a newer (14.4) version of the RF generator in 37 patients (PVAC Group II) and with the most recent (version 15.1) generator in 18 patients (PVAC Group III). Ablation was performed with the CB in 13 and with the nMARQ system in 14 patients. The number of microemboli (mean+(SD)) detected in the middle cerebral arteries was 2703 (918) in PVAC Group I, 1087 (542) in PVAC Group II, 719 (469) in PVAC Group III, 1057 (784) with CB and 2166 (1047) with nMARQ (p<0.01). CONCLUSION Significant decreases in MES counts were observed thanks to the procedural modifications and newer RF generator with phased RF. High MES counts comparable to those with the initial phased RF resulted from the use of nMARQ.


title: Misconceptions About Negative Pressure Rooms and Their Impact Aboard USNS Comfort in New York City.

text: The outbreak of novel coronavirus disease 2019 (COVID-19) has had a momentous impact on the field of otolaryngology due to the high number of aerosol-generating procedures involving the upper aerodigestive tract. These procedures bear significant risk to the provider and clinical environment due to the possibility of viral aerosolization. While significant attention has been appropriately paid to personal protective equipment during this pandemic, an understanding of industrial hygiene is also necessary for the safe delivery of health care to mitigate the risk of exposure to other patients and health care workers. We provide a review of air ventilation practices and their role in reducing pathogen spread. In addition, we share our experiences with effectively treating COVID-19-positive patients aboard the USNS Comfort through proper environment control measures.


title: A transgenic Marc-145 cell line of piggyBac transposon-derived targeting shRNA interference against porcine reproductive and respiratory syndrome virus.

text: Porcine reproductive and respiratory syndrome (PRRS) is now considered to be one of the most important diseases in countries with intensive swine industries. The two major membrane-associated proteins of porcine reproductive and respiratory syndrome virus (PRRSV), GP5 and M (encoded by ORF5 and ORF6 genes, respectively), are associated as disulfide-linked heterodimers (GP5/M) in the virus particle. In this study, we designed 5 of the small hairpin RNAs (shRNAs) targeting the GP5 and M gene of PRRSV respectively, and investigated their inhibition to the production of PRRSV. The highest activity displayed in shRNAs of the ORF6e sequence (nts 261-279), which the inhibition rate reached was 99.09%. The result suggests that RNAi technology might serve as a potential molecular strategy for PRRSV therapy. Furthermore, the transgenic Marc-145 cell line of piggyBac transposon-derived targeting shRNA interference against PRRS virus was established. It presented stable inhibition to the replication and amplification of PRRS. The work implied that shRNAs targeting the GP5 and M gene of PRRSV may be used as potential RNA vaccines in vivo, and supplied the screening methods of transformed pig embryonic fibroblast which are prerequisite for the disease-resistant transgenic pigs to PRRS.


Adapting a Comfort Care Order Set in a Large Health System during the COVID-19 Pandemic.


title: Totally endoscopic magnetic enteral bypass by external guided rendez-vous technique.

text: OBJECTIVE This study aimed to assess the feasibility of a totally endoscopic enteral bypass using a self-orienting, dual ring, magnetic anastomosis system (MAGNAMOSIS) guided by a magnetic tracking system (3D METRIS). MATERIALS AND METHODS In an anesthetized pig, 2 endoscopes were advanced, one each into the stomach and the colon. Both endoscopes were equipped with a MAGNAMOSIS ring secured with an endoscopic snare and a 3D METRIS within one working channel. The whole procedure was followed laparoscopically. The tracking system guided tips of endoscopes to a "rendez-vous" location between the colon and stomach. RESULTS MAGNAMOSIS magnets automatically joined in the correct configuration when guided to within 2 cm of each other. At necropsy, magnetic rings were secure without entrapment of excess bowel or mesentery. CONCLUSION An endoscopic enteral bypass with magnetic anastomosis and magnetic tracking device was feasible. More accurate tracking and advanced techniques could enable endoscopic bypasses at multiple sites in the gastrointestinal tract.


title: Delayed Carotid Pseudoaneurysms from Iatrogenic Clival Meningeal Branches Avulsion: Recognition and Proposed Management.

text: BACKGROUND Carotid injury during anterior skull base approaches is promptly recognizable and mandates immediate treatment; likewise, development of pseudoaneurysms after such injuries is anticipated and managed. METHODS We report here on the delayed development of a pseudoaneurysm as the result of avulsion of clival meningeal arteries that manifests as unalarming intraoperative bleeding. RESULTS AND CONCLUSIONS The bleeding is brisk and arterial but easily controlled. Immediate postoperative angiography is negative, necessitating repeated angiography to depict the delayed formation. It is best treated by endovascular means that maintains patency of the carotid artery, calling for the development of a suitable device that obliterates the opening of the pseudoaneurysm while maintaining carotid flow that is deployable in the tortuous carotid artery.


Stellar Quake.