title: Delayed antibiotic prescribing for respiratory tract infections: protocol of an individual patient data meta-analysis.

text: INTRODUCTION Delayed prescribing can be a useful strategy to reduce antibiotic prescribing, but it is not clear for whom delayed prescribing might be effective. This protocol outlines an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) and observational cohort studies to explore the overall effect of delayed prescribing and identify key patient characteristics that are associated with efficacy of delayed prescribing. METHODS AND ANALYSIS A systematic search of the databases Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL Plus and Web of Science was conducted to identify relevant studies from inception to October 2017. Outcomes of interest include duration of illness, severity of illness, complication, reconsultation and patient satisfaction. Study authors of eligible papers will be contacted and invited to contribute raw IPD data. IPD data will be checked against published data, harmonised and aggregated to create one large IPD database. Multilevel regression will be performed to explore interaction effects between treatment allocation and patient characteristics. The economic evaluation will be conducted based on IPD from the combined trial and observational studies to estimate the differences in costs and effectiveness for delayed prescribing compared with normal practice. A decision model will be developed to assess potential savings and cost-effectiveness in terms of reduced antibiotic usage of delayed prescribing and quality-adjusted life years. ETHICS AND DISSEMINATION Ethical approval was obtained from the University of Southampton Faculty of Medicine Research Ethics Committee (Reference number: 30068). Findings of this study will be published in peer-reviewed academic journals as well as General Practice trade journals and will be presented at national and international conferences. The results will have important public health implications, shaping the way in which antibiotics are prescribed in the future and to whom delayed prescriptions are issued. PROSPERO REGISTRATION NUMBER CRD42018079400.


title: Superparamagnetic nanoparticle capture of prions for amplification.

text: Prion diseases are associated with the presence of PrP(Sc), a disease-associated misfolded conformer of the prion protein. We report that superparamagnetic nanoparticles bind PrP(Sc) molecules efficiently and specifically, permitting magnetic separation of prions from a sample mixture. Captured PrP(Sc) molecules retain the activity to seed protein misfolding cyclic amplification (PMCA) reactions, enabling the rapid concentration of dilute prions to improve detection. Furthermore, superparamagnetic nanoparticles clear contaminated solutions of PrP(Sc). Our findings suggest that coupling magnetic nanoparticle capture with PMCA could accelerate and improve prion detection. Magnetic nanoparticles may also be useful for developing a nontoxic prion decontamination method for biologically derived products.


title: Transglanular repair of impending penile prosthetic cylinder extrusion.

text: INTRODUCTION Penile prosthetic devices are highly satisfactory in the management of erectile dysfunction but carry a number of risks including the potential for erosion. In some cases, impending extrusion can be identified and managed before frank erosion occurs. AIMS To report our results using a transglanular approach for management of impending distal erosion of penile prosthetic devices. METHODS Patients who presented with impending erosion of penile prosthetics were identified by retrospective chart review. Patients who were managed with a transglanular surgical approach constitute the study group. MAIN OUTCOME MEASURES Clinical data were culled from the charts. Identified patients were contacted and were asked a battery of questions regarding their subjective assessment of the treatment's efficacy. RESULTS Six men were identified. Mean age at time of surgery was 56 years. Four men had had implants placed within the past 2 years and two had implants that had been in place for greater than 12 years. Mean operative time was 25 minutes. Four patients were successfully managed with a single repair procedure. Two men required repeat revision surgery. Of men that were available for additional postoperative contact, three of four reported satisfaction with the procedure. CONCLUSIONS The transglanular approach for repair of impending distal erosion of penile prosthetics is a quick and minimally morbid procedure that produces satisfactory results in the majority of patients. Further refinements of technique will likely lead to greater overall improvement in outcomes.


title: Flexor tendon injuries in the child.

text: This review aims to highlight the differences in the management of flexor tendon injuries between children and adults. These include differences in epidemiology, anatomy, classification, diagnosis, incisions and skin closure, the size of the flexor tendons, technical aspects of zones I and II repairs, core suture purchase length, rehabilitation, results, and complications of primary flexor tendon repair. Finally, one- versus two-stage flexor tendon reconstruction in children is reviewed.


title: Coil Embolization for Ruptured Basilar Tip Aneurysm After Mechanical Thrombectomy for Acute Basilar Artery Occlusion.

text: BACKGROUND There is no published report of ruptured cerebral aneurysm accompanied by target vessel occlusion. We present a case of ruptured basilar tip aneurysm with concomitant basilar artery (BA) occlusion. CASE DESCRIPTION A 53-year-old man presented to our emergency room with the acute onset of disturbance. Plain head computed tomography showed diffuse subarachnoid hemorrhage. Computed tomography angiography and digital subtraction angiography showed a BA tip aneurysm with BA trunk occlusion. Endovascular treatment with mechanical thrombectomy using a stent retriever and coil embolization was performed. Clinical and radiologic results were good. The patient was discharged 30 days after onset (modified Rankin Scale score = 1). CONCLUSIONS We were able to recanalize the BA trunk and perform coil embolization of the ruptured BA tip aneurysm. Our case is the first published report of a ruptured aneurysm with target large-vessel occlusion. Awareness of the issues raised in this case is required to determine the best treatment strategy, and preoperative consideration allows neurointerventionalists to avoid unpleasant surprises in the angiography suite.


title: Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel.

text: Current infectious disease molecular tests are largely pathogen specific, requiring test selection based on the patient's symptoms. For many syndromes caused by a large number of viral, bacterial, or fungal pathogens, such as respiratory tract infections, this necessitates large panels of tests and has limited yield. In contrast, next-generation sequencing-based metagenomics can be used for unbiased detection of any expected or unexpected pathogen. However, barriers for its diagnostic implementation include incomplete understanding of analytical performance and complexity of sequence data analysis. We compared detection of known respiratory virus-positive (n= 42) and unselected (n= 67) pediatric nasopharyngeal swabs using an RNA sequencing (RNA-seq)-based metagenomics approach and Taxonomer, an ultrarapid, interactive, web-based metagenomics data analysis tool, with an FDA-cleared respiratory virus panel (RVP; GenMark eSensor). Untargeted metagenomics detected 86% of known respiratory virus infections, and additional PCR testing confirmed RVP results for only 2 (33%) of the discordant samples. In unselected samples, untargeted metagenomics had excellent agreement with the RVP (93%). In addition, untargeted metagenomics detected an additional 12 viruses that were either not targeted by the RVP or missed due to highly divergent genome sequences. Normalized viral read counts for untargeted metagenomics correlated with viral burden determined by quantitative PCR and showed high intrarun and interrun reproducibility. Partial or full-length viral genome sequences were generated in 86% of RNA-seq-positive samples, allowing assessment of antiviral resistance, strain-level typing, and phylogenetic relatedness. Overall, untargeted metagenomics had high agreement with a sensitive RVP, detected viruses not targeted by the RVP, and yielded epidemiologically and clinically valuable sequence information.


COVID-19 and district and community nursing.


title: Evaluation of the Renal Arteries of 2,144 Living Kidney Donors Using Computed Tomography Angiography and Comparison with Intraoperative Findings.

text: OBJECTIVES A carefully chosen and suitably prepared kidney donor is essential in living-donor kidney transplantation. Computed tomography angiography (CTA) is an effective imaging method for evaluating the renovascular morphology of donor candidates. The aim of this study was to evaluate renal artery variations in kidney donors using CTA and compare the findings with the number of arteries detected during laparoscopic donor nephrectomy. MATERIALS AND METHODS The study included 2,144 living donors who underwent pretransplant renovascular assessment using CTA and laparoscopic donor nephrectomy in our center between August 2012 and October 2018. The number of renal arteries to the donor kidney detected on CTA was compared with the number of arteries discovered intraoperatively. RESULTS The mean age of the 2,144 living kidney donors included in the study was 47.19 ± 13.3 (18-87) years. According to CTA findings, 81.1% (n = 1,738) had a single renal artery, 17.2% (n = 369) had double renal arteries, 1.6% (n = 35) had triple renal arteries, and 0.1% (n = 2) had quadruple renal arteries. The same number of renal arteries were detected by CTA and in laparoscopic donor nephrectomy in 97.9% (n = 2,099) of the donors. In the other 2.1% (n = 45), fewer renal arteries were detected intraoperatively compared to their CTA findings. None of the donors included in the study had a greater number of renal arteries discovered during nephrectomy than by CTA. CONCLUSION CTA is a highly accurate method for the evaluation of renovascular variations in donor candidates for living-donor kidney transplantation. However, it must be kept in mind that double or multiple renal artery variations may be detected on CTA in 18.9% of donor candidates.


title: Chikungunya virus emergence is constrained in Asia by lineage-specific adaptive landscapes.

text: Adaptation of RNA viruses to a new host or vector species often results in emergence of new viral lineages. However, lineage-specific restrictions on the adaptive processes remain largely unexplored. Recently, a Chikungunya virus (CHIKV) lineage of African origin emerged to cause major epidemics of severe, persistent, debilitating arthralgia in Africa and Asia. Surprisingly, this new lineage is actively replacing endemic strains in Southeast Asia that have been circulating there for 60 y. This replacement process is associated with adaptation of the invasive CHIKV strains to an atypical vector, the Aedes albopictus mosquito that is ubiquitously distributed in the region. Here we demonstrate that lineage-specific epistatic interactions between substitutions at amino acid positions 226 and 98 of the E1 envelope glycoprotein, the latter of which likely resulted from a founder effect, have for 60 y restricted the ability of endemic Asian CHIKV strains to adapt to this new vector. This adaptive constraint appears to be allowing invasion of the unoccupied vector niche by Ae. albopictus-adapted African strains. These results underscore how different adaptive landscapes occupied by closely related viral genotypes can profoundly affect the outcome of viral evolution and disease emergence.


title: The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours.

text: OBJECTIVE The aim of this study was to assess the diagnostic efficiency of (99m)Tc-EDDA/HYNIC-Octreotate in comparison with (111)Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. METHODS Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both (99m)Tc- EDDA/HYNIC-octreotate and (111)In-pentetrotide. Images were evaluated both visually and semiquantitatively. RESULTS On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by (99m)Tc- EDDA/HYNICOctreotate were higher than the number of lesions detected by (111)In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT (99m)Tc- EDDA/HYNIC-Octreotate scans. CONCLUSION The results of this study suggested that, (99m)Tc- EDDA/HYNIC-Octreotate may be a better alternative to (111)In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. CONFLICT OF INTEREST None declared.


Mental Health of Communities during the COVID-19 Pandemic.


title: Identification of a coronavirus transcription enhancer.

text: Coronavirus (CoV) transcription includes a discontinuous mechanism during the synthesis of sub-genome-length minus-strand RNAs leading to a collection of mRNAs in which the 5' terminal leader sequence is fused to contiguous genome sequences. It has been previously shown that transcription-regulating sequences (TRSs) preceding each gene regulate transcription. Base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) in the nascent RNA is a determinant factor during CoV transcription. In fact, in transmissible gastroenteritis CoV, a good correlation has been observed between subgenomic mRNA (sg mRNA) levels and the free energy (DeltaG) of TRS-L and cTRS-B duplex formation. The only exception was sg mRNA N, the most abundant sg mRNA during viral infection in spite of its minimum DeltaG associated with duplex formation. We postulated that additional factors should regulate transcription of sg mRNA N. In this report, we have described a novel transcription regulation mechanism operating in CoV by which a 9-nucleotide (nt) sequence located 449 nt upstream of the N gene TRS core sequence (CS-N) interacts with a complementary sequence just upstream of CS-N, specifically increasing the accumulation of sg mRNA N. Alteration of this complementarity in mutant replicon genomes showed a correlation between the predicted stability of the base pairing between 9-nt sequences and the accumulation of sg mRNA N. This interaction is exclusively conserved in group 1a CoVs, the only CoV subgroup in which the N gene is not the most 3' gene in the viral genome. This is the first time that a long-distance RNA-RNA interaction regulating transcriptional activity specifically enhancing the transcription of one gene has been described to occur in CoVs.


title: Embolization of cerebral arteriovenous malformations with silk suture particles prior to stereotactic radiosurgery.

text: We aimed to determine the long term durability of silk suture and polyvinyl alcohol (PVA) particle embolization (SPE) of arteriovenous malformations (AVM), and to evaluate the outcomes following multimodality management of AVM with combined SPE and stereotactic radiosurgery (SRS). A general supposition among neurointerventionalists is that embolization of cerebral AVM with silk sutures and PVA particles does not yield a durable occlusion. We performed a retrospective review of all AVM patients treated at our institution with combined SPE and SRS. After extracting the baseline, embolization and SRS data for each patient, the durability of SPE was determined by evaluating the postembolization recanalization between the last procedural angiogram and the most recent neuroimaging. Four AVM patients who underwent a total of nine SPE procedures through 21 arterial pedicles were included for the analyses. The nidus volumes were 5.8-75 cm(3) and the Spetzler-Martin grades were II and V in one patient and III in two patients. The median degree of devascularization per procedure was <25%. There were no procedural complications, with all patients maintaining functional independence after embolization (modified Rankin scale score 0-2). After a median follow-up duration of 27 months (range: 23-36), there were no patients with recanalization. SRS (marginal dose 13-18 Gy) resulted in 40 to >95% volume reduction. Following SRS, one patient remained asymptomatic, two patients improved, and one patient deteriorated due to a latency period AVM hemorrhage. In conclusion, SPE can safely provide durable AVM devascularization, therefore, appropriately selected nidi can be effectively treated with combined SPE and SRS.


docid: qrragpie

title: Vascular perforation by enterprise stent during stent-assisted coil embolization for intracranial aneurysm.


docid: yoyofprr

title: Coronavirus Host Range Expansion and Middle East Respiratory Syndrome Coronavirus Emergence: Biochemical Mechanisms and Evolutionary Perspectives.

text: Coronaviruses have frequently expanded their host range in recent history, with two events resulting in severe disease outbreaks in human populations. Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2003 in Southeast Asia and rapidly spread around the world before it was controlled by public health intervention strategies. The 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak represents another prime example of virus emergence from a zoonotic reservoir. Here, we review the current knowledge of coronavirus cross-species transmission, with particular focus on MERS-CoV. MERS-CoV is still circulating in the human population, and the mechanisms governing its cross-species transmission have been only partially elucidated, highlighting a need for further investigation. We discuss biochemical determinants mediating MERS-CoV host cell permissivity, including virus spike interactions with the MERS-CoV cell surface receptor dipeptidyl peptidase 4 (DPP4), and evolutionary mechanisms that may facilitate host range expansion, including recombination, mutator alleles, and mutational robustness. Understanding these mechanisms can help us better recognize the threat of emergence for currently circulating zoonotic strains.


Chinese Officials Investigate Cause of Pneumonia Outbreak in Wuhan.


Chronic wounds?


Correction to Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles.


title: Contraception and reproductive planning during the COVID-19 pandemic.

text: INTRODUCTION The coronavirus disease (COVID-19) is a global health emergency. Major disruption to healthcare services during the current COVID 19 pandemic will last even after its peak. Sexual and reproductive health (SRH), specially contraception, needs to be understood as an essential service. AREAS COVERED This paper is a narrative review. Data from PubMed/MEDLINE, Scopus, and websites of scientific societies were screened during the months of April and May 2020. It addresses the main aspects related to contraception during the COVID-19 pandemic, with special emphasis on family planning services, extended use of long-acting reversible contraceptive (LARC) methods, drug interactions and thromboembolism risk. We also specified some issues focused on the Brazilian reality. EXPERT OPINION Ensuring proper contraception use in the COVID-19 time is very important. We encourage women, healthcare providers, policy makers, and the society to consider SRH services as priority.


title: Epidemiology of outpatient and inpatient eye injury in Taiwan: 2000, 2005, 2010, and 2015.

text: PURPOSE To estimate the incidence rate of eye injuries (EI) requiring inpatient and outpatient treatment in Taiwan and compare the epidemiologic characteristics of EI (age, sex, treatment setting, seasonality, occupation, external cause, diagnosis, and surgery) in the years 2000, 2005, 2010, and 2015. METHODS We analyzed four random samples of 1,000,000 beneficiaries each from 2000, 2005, 2010, and 2015 of the Taiwan National Health Insurance Program. The direct age-standardized rate, with 95% confidence interval (CI), was used to compare EI rates for the four calendar years. The chi-square test and chi-square test for trend were used to compare data for the four calendar years. RESULTS Annual EI incidence rates were between 2.57% in 2000 and 3.28% in 2015. The age-standardized rates were 2.73% (95% CI, 2.70%-2.76%) in 2000, 3.37% (95% CI, 3.33%-3.41%) in 2005, 3.31% (95% CI, 3.28%-3.35%) in 2010, and 3.02% (95% CI, 2.99%-3.06%) in 2015. Manual workers had the highest EI incidence rate, followed by non-manual workers and civil servants. The proportion of EI requiring inpatient treatment declined from 1.34% in 2000 to 0.63% in 2015 (P <0.0001). Analysis of seasonality showed a consistent decrease in February in the four sampling years; however, this decrease in EI was only seen in outpatients, not in EI requiring hospitalization. The proportion of outpatients requiring surgery significantly decreased, from 2.53% in 2000 to 1.2% in 2015 (P<0.0001). However, the proportion of inpatients requiring surgery for EI as the principal diagnosis increased from 69.32% in 2000 to 83.02% in 2015 (P = 0.29), and the proportion of inpatients requiring surgery for EI as a secondary diagnosis increased from 54.86% in 2000 to 71.6% in 2015 (P = 0.0019). Among inpatients with EI, the most common cause of EI was a traffic accident (44.79%, especially motorcycles), followed by falls (9.75%) and homicide (6.05%). CONCLUSION In Taiwan, the annual EI incidence rate slightly increased from 2000 to 2005 and then decreased through 2015. The proportion of EI patients requiring hospitalization decreased from 1.34% in 2000 to 0.63% in 2015, but the percentage of inpatients requiring surgery increased. Traffic accidents (especially those involving motorcyclists) remained the predominant external cause of EI requiring hospitalization during the study period.


title: Validated computed cleansing score for video capsule endoscopy.

text: BACKGROUND AND AIM Diagnostic yield of video capsule endoscopy may be hampered by intestinal content or air bubbles. A major limitation in video capsule-related study is the lack of a validated objective score for bowel preparation quality. We aimed to design and validate a computed small bowel preparation score for research and clinical use. METHODS Two experienced physicians reached a consensus regarding bowel preparation quality based on known criteria used in previous studies and their confidence of an accurate medical interpretation of the procedure. A computed algorithm based on the pixels in the color bar was created and validated. Concordance between the gastroenterologists' agreement (gold standard) and the computed analysis was assessed. RESULTS Of 85 videos studied, 44 (52%), 13 (15%) and 28 (33%) had adequate, borderline and inadequate bowel preparation, respectively, according to the gastroenterologists' agreement. Computer analysis restricted to adequate and inadequate cases yielded accurate classification of bowel preparation in 65/72 cases (90% agreement, sensitivity 95%, specificity 82%, total accuracy 90%, Kappa 0.79). When adding the borderline definition, the computer analysis correctly classified 71/85 of the cases, yielding an overall agreement of 84% (Kappa 0.72). Minute-by-minute analysis of 10 cases also yielded an agreement of 91.4%. CONCLUSION The present study introduces a user-friendly computer analysis-based small bowel preparation score, which demonstrated excellent concordance with the physician's assessment. This score holds promise as a standardization tool in research and clinical practice of video capsule endoscopy. Further validation is warranted.


title: Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses.IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection.


title: A multicenter single-arm Phase II clinical trial of second-line FOLFIRI plus panitumumab after first-line treatment with FOLFOX plus panitumumab for initial RAS wild-type colorectal cancer with evaluation of circulating tumor DNA: A protocol study.

text: The efficacy and safety of the continuous use of panitumumab in first- and second-line treatments for colorectal cancer (CRC) have yet to be determined. Liquid biopsy of circulating tumor DNA is capable of assessing the gene mutation status at several time-points, and could predict the efficacy of ongoing panitumumab treatment. To address these two points, a multicenter single-arm Phase II clinical trial will be conducted by evaluating the effect of FOLFIRI with panitumumab as second-line chemotherapy in patients with CRC, after failure or intolerance of first-line treatment with FOLFOX with panitumumab. The primary endpoint is the 6-month progression-free survival rate. Gene mutation status using circulating tumor DNA will be assessed at multiple time-points during the study period as one of the secondary endpoints. The observed 6-month PFS rate will be compared with the threshold 6-month PFS rate of 35% with a one-sided significance level of 10% using the binomial exact test. The target number of cases in this study is 55 patients. The study protocol was approved by the Institutional Review Board of the Epidemiological and Clinical Research Information Network (17-0601-1) and will be conducted after approval by the Institutional Review Board of each participating institute. This study is registered in UMIN (UMIN000026817, March 31, 2017). The results of the present study will be presented at related international congresses, and will be disseminated in peer-reviewed journals.


title: Clamp-crushing versus stapler hepatectomy for transection of the parenchyma in elective hepatic resection (CRUNSH)--a randomized controlled trial (NCT01049607).

text: BACKGROUND Hepatic resection is still associated with significant morbidity. Although the period of parenchymal transection presents a crucial step during the operation, uncertainty persists regarding the optimal technique of transection. It was the aim of the present randomized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique. METHODS/DESIGN The CRUNSH Trial is a prospective randomized controlled single-center trial with a two-group parallel design. Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General-, Visceral- and Transplantation Surgery, University of Heidelberg are enrolled into the trial and randomized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy, respectively. The primary endpoint is total intraoperative blood loss. A set of general and surgical variables are documented as secondary endpoints. Patients and outcome-assessors are blinded for the treatment intervention. DISCUSSION The CRUNSH Trial is the first randomized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection. TRIAL REGISTRATION ClinicalTrials.gov: NCT01049607.


title: Impact of COVID-19 pandemic on people living with visual disability.

text: People living with visual disabilities/impairment are more likely vulnerable to get contracted from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV 2) than people without visual impairment. This means more than 253 million people globally will be at higher risk of affecting by the COVID-19. The current pandemic, followed by a nationwide emergency lockdown to slow the unprecedented spread of the virus, will have a serious impact on people living with visual disabilities and even endangers their lives in the long run. Many restrictive and control measures, including the adoption of new behavioural changes (for example, social distance during outdoor movement, limiting touch or tactile contact) recommended by the government will pose immense challenges to individuals with a visual loss. This serious impact, including challenges in healthcare access, can be minimized through inclusive service approaches, involving persons with visual disabilities, caregivers, family members, and healthcare providers, along with the community to a large extent, and finally, support to improve the overall outcomes. The government, along with profit or non-profit private sectors, should consider initiating such inclusive approaches while planning responses to the pandemic. Indeed, the present COVID-19 pandemic provides an opportunity for health care planners and decision-makers of various organizations across India for a reformation of disabilities care. Impacts due to the pandemic and lockdown can be reduced substantially if planning and policy are in place before any emergency happened in the future.


Tens of thousands of scientists are redeploying to fight coronavirus.


title: Community-acquired pneumonia.

text: PURPOSE OF REVIEW Community-acquired pneumonia (CAP) is a major cause of morbidity, mortality and expenditure of resources. When followed, guidelines for CAP management have been demonstrated to improve clinical outcomes; however, several issues are still open. This review summarizes the recent advances in this field and the priority needs for future research. RECENT FINDINGS Recently identified clinical and biochemical tools promise to improve the assessment of CAP severity; however, definition of the most accurate and feasible rule(s) for clinical practice is now necessary. Some empirical antimicrobial regimens are still being debated, such as the need for atypical pathogen coverage in home-treated and nonsevere hospitalized patients and the inclusion of respiratory fluoroquinolones among first-choice molecules. New drugs such as tigecycline and cethromycin appear promising. Pharmacokinetically enhanced amoxicillin/clavulanate is highly effective, even for treating CAP caused by multiple-drug-resistant Streptococcus pneumoniae. Other aspects recently clarified include the inappropriateness of rigid time-to-first-antibiotic-dose rules, the advantages of shorter antibiotic treatments for nonsevere patients and the need of special clinical attention for acute myocardial infarction among patients with severe CAP or clinical failure. SUMMARY Recent developments have significantly contributed to refine the management of CAP patients. However, various hot topics remain undefined as yet and urgently require ad-hoc research in order to optimize the outcomes and the costs of this highly social-impacting disease.


Critically ill patients with influenza A(H1N1)pdm09 virus infection in 2014.


title: Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients.

text: INTRODUCTION Previous studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients. METHODS This was a prospective, non-randomized study at a 16-bed, medical-surgical intensive care unit of a university hospital. We included 12 severe hyperdynamic septic shock patients (norepinephrine requirements > 0.3 μg/kg/min and cardiac index > 3.0 L/min/m2) who underwent a 12-hour HVHF as a rescue therapy according to a predefined algorithm. Sublingual microcirculation (Microscan for NTSC, Microvision Medical), systemic hemodynamics and perfusion parameters were assessed at baseline, at 12 hours of HVHF, and 6 hours after stopping HVHF. RESULTS Microcirculatory flow index increased after 12 hours of HVHF and this increase persisted 6 hours after stopping HVHF. A similar trend was observed for the proportion of perfused microvessels. The increase in microcirculatory blood flow was inversely correlated with baseline levels. There was no significant change in microvascular density or heterogeneity during or after HVHF. Mean arterial pressure and systemic vascular resistance increased while lactate levels decreased after the 12-hour HVHF. CONCLUSIONS The use of HVHF as a rescue therapy in patients with severe hyperdynamic septic shock does not deteriorate sublingual microcirculatory blood flow despite the increase in systemic vascular resistance.


title: Structure of replicating SARS-CoV-2 polymerase.

text: The coronavirus SARS-CoV-2 uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes1-3. Here we present the cryo-electron microscopic structure of the SARS-CoV-2 RdRp in active form, mimicking the replicating enzyme. The structure comprises the viral proteins nsp12, nsp8, and nsp7, and over two turns of RNA template-product duplex. The active site cleft of nsp12 binds the first turn of RNA and mediates RdRp activity with conserved residues. Two copies of nsp8 bind to opposite sides of the cleft and position the second turn of RNA. Long helical extensions in nsp8 protrude along exiting RNA, forming positively charged 'sliding poles'. These sliding poles can account for the known processivity of the RdRp that is required for replicating the long coronavirus genome3. Our results enable a detailed analysis of the inhibitory mechanisms that underlie the antiviral activity of substances such as remdesivir, a drug for the treatment of coronavirus disease 2019 (COVID-19)4.


title: Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial.

text: BACKGROUND Drug-eluting balloons (DEB) may reduce infrapopliteal restenosis and reintervention rates versus percutaneous transluminal angioplasty (PTA) and improve wound healing/limb preservation. OBJECTIVES The goal of this clinical trial was to assess the efficacy and safety of IN.PACT Amphirion drug-eluting balloons (IA-DEB) compared to PTA for infrapopliteal arterial revascularization in patients with critical limb ischemia (CLI). METHODS Within a prospective, multicenter, randomized, controlled trial with independent clinical event adjudication and angiographic and wound core laboratories 358 CLI patients were randomized 2:1 to IA-DEB or PTA. The 2 coprimary efficacy endpoints through 12 months were clinically driven target lesion revascularization (CD-TLR) and late lumen loss (LLL). The primary safety endpoint through 6 months was a composite of all-cause mortality, major amputation, and CD-TLR. RESULTS Clinical characteristics were similar between the 2 groups. Significant baseline differences between the IA-DEB and PTA arms included mean lesion length (10.2 cm vs. 12.9 cm; p = 0.002), impaired inflow (40.7% vs. 28.8%; p = 0.035), and previous target limb revascularization (32.2% vs. 21.8%; p = 0.047). Primary efficacy results of IA-DEB versus PTA were CD-TLR of 9.2% versus 13.1% (p = 0.291) and LLL of 0.61 ± 0.78 mm versus 0.62 ± 0.78 mm (p = 0.950). Primary safety endpoints were 17.7% versus 15.8% (p = 0.021) and met the noninferiority hypothesis. A safety signal driven by major amputations through 12 months was observed in the IA-DEB arm versus the PTA arm (8.8% vs. 3.6%; p = 0.080). CONCLUSIONS In patients with CLI, IA-DEB had comparable efficacy to PTA. While primary safety was met, there was a trend towards an increased major amputation rate through 12 months compared to PTA. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733).


Covid-19: Don't apply advance care plans to groups of people, doctors' leaders warn.


docid: pxracwsk

title: Traumatic lumbar hernia repair: a laparoscopic technique for mesh fixation with an iliac crest suture anchor.

text: Traumatic lumbar hernia (TLH) is a rare presentation. Traditionally, these have been repaired via an open approach. Recurrence can be a problem due to the often limited tissue available for mesh fixation at the inferior aspect of the hernia defect. We report the successful use of bone suture anchors placed in the iliac crest during transperitoneal laparoscopy for mesh fixation to repair a recurrent TLH. This technique may be particularly useful after previous failed attempts at open TLH repair.


docid: crjmhsxc

title: Assessing the Effect of Preoperative Nutrition on Upper Body Function in Elderly Patients Undergoing Elective Abdominal Surgery.

text: BACKGROUND Malnutrition among elderly surgical patients has been associated with poor postoperative outcomes and reduced functional status. Although previous studies have shown that nutrition contributes to patient outcomes, its long-term impact on functional status requires better characterization. This study examines the effect of nutrition on postoperative upper body function over time in elderly patients undergoing elective surgery. METHODS This is a 2-year prospective study of elderly patients (≥70 years) undergoing elective abdominal surgery. Preoperative nutrition status was determined with the Subjective Global Assessment (SGA). The primary outcome was handgrip strength (HGS) at 1, 4, 12, and 24 weeks postsurgery. Repeated measures analysis was used to determine whether SGA status affects the trajectory of postoperative HGS. RESULTS The cohort included 144 patients with a mean age of 77.8 ± 5.0 years and a mean body mass index of 27.7 ± 5.1 kg/m2 . The median (interquartile range) Charlson Comorbidity Index was 3 (2-6). Participants were categorized as well-nourished (86%) and mildly to moderately malnourished (14%), with mean preoperative HGS of 25.8 ± 9.2 kg and 19.6 ± 7.0 kg, respectively. At 24 weeks, 64% of well-nourished patients had recovered to baseline HGS, compared with 44% of mildly to moderately malnourished patients. Controlling for relevant covariates, SGA did not significantly affect the trajectory of postoperative HGS. CONCLUSION While HGS values over the 24 weeks were consistently higher in the well-nourished SGA group than the mildly to moderately malnourished SGA group, no difference in the trajectories of HGS was detected between the groups.


WU polyomavirus infection in children, Germany.


title: Leukotriene B4-type I interferon axis regulates macrophage-mediated disease tolerance to influenza infection.

text: Host defence against influenza A virus (IAV) infection depends not only on host resistance to eliminate the virus, but also disease tolerance to limit lung tissue damage and maintain pulmonary function. Fatal IAV infections are frequently the result of a maladaptive immune response that compromises disease tolerance rather than host resistance to infection. Here, we show that the leukotriene B4 (LTB4)-type I interferon (IFN) axis promotes a distinct mechanism of disease tolerance to pulmonary IAV infection. We demonstrate that mice genetically deficient in LTB4 signalling (Blt1R-/-) are more susceptible to IAV infection compared to control mice, despite similar pulmonary viral loads. The increased susceptibility of Blt1R-/- mice is associated with an accumulation of inflammatory monocyte-derived macrophages (IMMs) causing increased lung immunopathology. We mechanistically define that LTB4 signalling via the BLT1 receptor enhances the activation of the type I IFN-α/β receptor (IFNAR)/ and signal transducer and activator of transcription 1 (STAT1), which leads to IFN-α production by interstitial macrophages to suppresse in situ IMM proliferation. Importantly, the delivery of a single dose of LTB4 at the peak viral load reduces IMM proliferation, controls tissue damage and increases survival without affecting host resistance to IAV. These results reveal an unexpected anti-inflammatory role of LTB4 in disease tolerance to IAV infection.


Gadolinium Deposition in the Brain: Do We Know Enough to Change Practice?


docid: xzkqcgpb

title: Predicting Discharge to Institutional Long-Term Care After Stroke: A Systematic Review and Metaanalysis.

text: BACKGROUND/OBJECTIVES Stroke is a leading cause of disability worldwide, and a significant proportion of stroke survivors require long-term institutional care. Understanding who cannot be discharged home is important for health and social care planning. Our aim was to establish predictive factors for discharge to institutional care after hospitalization for stroke. DESIGN We registered and conducted a systematic review and meta-analysis (PROSPERO: CRD42015023497) of observational studies. We searched MEDLINE, EMBASE, and CINAHL Plus to February 2017. Quantitative synthesis was performed where data allowed. SETTING Acute and rehabilitation hospitals. PARTICIPANTS Adults hospitalized for stroke who were newly admitted directly to long-term institutional care at the time of hospital discharge. MEASUREMENTS Factors associated with new institutionalization. RESULTS From 10,420 records, we included 18 studies (n = 32,139 participants). The studies were heterogeneous and conducted in Europe, North America, and East Asia. Eight studies were at high risk of selection bias. The proportion of those surviving to discharge who were newly discharged to long-term care varied from 7% to 39% (median 17%, interquartile range 12%), and the model of care received in the long-term care setting was not defined. Older age and greater stroke severity had a consistently positive association with the need for long-term care admission. Individuals who had a severe stroke were 26 times as likely to be admitted to long-term care than those who had a minor stroke. Individuals aged 65 and older had a risk of stroke that was three times as great as that of younger individuals. Potentially modifiable factors were rarely examined. CONCLUSION Age and stroke severity are important predictors of institutional long-term care admission directly from the hospital after an acute stroke. Potentially modifiable factors should be the target of future research. Stroke outcome studies should report discharge destination, defining the model of care provided in the long-term care setting.


title: Venous thromboembolism risk in ischemic stroke patients receiving extended-duration enoxaparin prophylaxis: results from the EXCLAIM study.

text: BACKGROUND AND PURPOSE The optimal duration of venous thromboembolism prophylaxis in acute stroke patients is unknown. This subanalysis of the Extended Prophylaxis for Venous ThromboEmbolism in Acutely Ill Medical Patients With Prolonged Immobilization (EXCLAIM) study investigated extended-duration thromboprophylaxis with enoxaparin, compared with placebo following standard-duration enoxaparin, in ischemic stroke patients. METHODS Acutely ill medical patients with recently reduced mobility received open-label enoxaparin 40 mg for 10±4 days, and they were then randomized to double-blind enoxaparin 40 mg daily or placebo for further 28±4 days. Venous thromboembolism incidence (symptomatic/asymptomatic deep-vein thrombosis, symptomatic/fatal pulmonary embolism) up to day 28 after randomization and major bleeding rates up to 48 h after the last dose of study treatment were reported. RESULTS In total, 389 of 5963 (6.5%) randomized patients had ischemic stroke: 198 received extended-duration prophylaxis and 191 placebo. Extended-duration prophylaxis reduced venous thromboembolism incidence versus placebo (2.4% versus 8.0%; absolute risk difference, -5.6%; 95% CI, -10.5% to -0.7%), but it was associated with an increase in major bleeding (1.5% versus 0% in enoxaparin and placebo groups; absolute risk difference, +1.5%; 95% CI, -0.2% to 3.2%). CONCLUSIONS Extended-duration thromboprophylaxis with enoxaparin was associated with reduced venous thromboembolism risk and increased major bleeding in the subgroup of patients with ischemic stroke in the EXCLAIM study.


title: Outcomes of bariatric surgery in patients with body mass index <35 kg/m2.

text: BACKGROUND Patients who are categorized with class I obesity have a body mass index (BMI) of 30-34.99 kg/m(2). This population of patients has a predisposition to diabetes, hypertension, and dyslipidemia. The aim of the present study was to investigate the improvements of these co-morbidities in a class I obese population that had undergone a bariatric procedure. METHODS After internal review board approval and with adherence to the Health Insurance Portability and Accountability Act guidelines, a retrospective review was performed of a prospectively maintained database of 42 class I obese patients who underwent a bariatric procedure at our institution during a 10-year period, from February 2000 to May 2010. The fasting glucose level, glycosylated hemoglobin level, lipid profile, initial weight, and BMI were measured in the preoperative and postoperative periods. RESULTS Our patient population consisted of 30 women and 12 men, with a preoperative mean BMI of 33.9 kg/m(2). Laparoscopic sleeve gastrectomy was performed in 24 patients (57%), laparoscopic Roux-en-Y gastric bypass in 8 (19%), and laparoscopic adjustable gastric banding in 10 (24%). Of these 42 patients, 25 (60%) had type 2 diabetes, 1 patient was glucose intolerant, 27 (64%) had arterial hypertension, 25 (60%) had dyslipidemia, 17 (40%) had sleep apnea, and 8 (19%) had osteoarthritis. The postoperative findings included a mean BMI of 26.5 kg/m(2) and a mean weight loss of 41.4 lb. Of the 25 diabetic patients, 5 (20%) gained remission and 12 (48%) improvement of their diabetic status. The single patient with glucose intolerance showed improvement. Of the 27 patients with arterial hypertension, 9 (33%) showed remission and 13 (52%) improvement. Dyslipidemia resolved in 5 patients (20%) and improved in 13 (52%). Obstructive sleep apnea resolved in 10 (59%) and improvement was seen in 1 patient (6%). Finally, osteoarthritis resolved in 1 patient (12%) and improved in 5 (63%). CONCLUSION Bariatric surgery can significantly improve or resolve co-morbid metabolic conditions in patients with class I obesity.


title: Chronic work stress and exhaustion is associated with higher allostastic load in female school teachers.

text: Epidemiological studies have shown that chronic work stress or unfavourable psychosocial work conditions are prospectively associated with different adverse health outcomes. The aim of the present cross-sectional study was to investigate the relationship between work-related chronic stress as well as exhaustion and a cumulative measure of physiological wear-and-tear called allostastic load (AL). AL could be a possible biological pathway for how chronic work stress and exhaustion lead to health impairments in the long run. As the teaching profession has been proposed to be a potentially high stressful occupation, chronic work stress (effort-reward-imbalance) and exhaustion were assessed in 104 female school teachers. AL was first analyzed according to McEwen's classical model comprised of ten parameters including cortisol, epinephrine and norepinephrine, dehydroepiandrosterone-sulphate (DHEA-S), waist/hip-ratio (WHR), glycosylated haemoglobin (HbA1c), high-density lipoprotein (HDL), total cholesterol/HDL-ratio, and systolic and diastolic blood pressure. Additionally it was extended to include tumor-necrosis-factor-alpha (TNF-alpha), C-reactive protein (CRP), fibrinogen, D-dimer, percent-body-fat, triglycerides, and glucose levels. A substantial proportion of our sample was highly exhausted whereas relatively few teachers showed high effort-reward-imbalance. AL scores were significantly higher in women high on effort-reward-imbalance or suffering from exhaustion. Although all teachers had been in a good health status, chronic work stress as well as exhaustion appears to be associated with changes in a multi-system summary indicator of physiological risk.


docid: wshmclbz

title: Con: renal denervation for all resistant hypertensive patients: the Emperor's new clothes.


title: Binge drinking in young people: protocol for a systematic review of neuropsychological, neurophysiological and neuroimaging studies.

text: INTRODUCTION Binge drinking is the most common pattern of alcohol use among young people in Western countries. Adolescence and young adulthood is a vulnerable developmental period and binge drinking during this time has a higher potential for neurotoxicity and interference with ongoing neural and cognitive development. The purpose of this systematic review will be to assess and integrate evidence of the impact of binge drinking on cognition, brain structure and function in youth aged 10-24 years. Cross-sectional studies will synthesise the aberrations associated with binge drinking, while longitudinal studies will distinguish the cognitive and neural antecedents from the cognitive and neural effects that are a consequence of binge drinking. METHODS AND ANALYSIS A total of five peer-reviewed databases (PubMed, EMBASE, Medline, PsychINFO, ProQuest) will be systematically searched and the search period will include all studies published prior to 1 April 2018. The search terms will be a combination of MeSH keywords that are based on previous relevant reviews. Study selection will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and study quality will be assessed using The Grades of Recommendation, Assessment, Development and Evaluation approach. All studies will be screened against eligibility criteria designed to synthesise studies that examined a young binge drinking sample and used neuropsychological, neurophysiological or neuroimaging assessment techniques. Studies will be excluded if participants were significantly involved in other substances or if they had been clinically diagnosed with an alcohol use disorder, or any psychiatric, neurological or pharmacological condition. If available data permits, a meta-analysis will be conducted. ETHICS AND DISSEMINATION Formal ethics approval is not required as primary data will not be collected. The results will be disseminated through a peer-reviewed publication, conference presentations and social media. TRIAL REGISTRATION NUMBER International Prospective Register for Systematic Reviews (PROSPERO) number: CRD42018086856.


title: Poly(ADP-ribose) Polymerase Inhibition in Acute Lung Injury: A Re-emerging Concept.

text: Poly(ADP-ribose) polymerase 1 (PARP1), the major isoform of a family of ADP-ribosylating enzymes, has been implicated in the regulation of various biological processes including DNA repair, gene transcription and cell death. The concept that PARP1 becomes activated in acute lung injury (ALI), and pharmacological inhibition or genetic deletion of this enzyme can provide therapeutic benefits has emerged over 20 years ago. The current article provides an overview of the cellular mechanisms involved in the pathogenetic roles of PARP1 in ALI, and overviews the preclinical data supporting the efficacy of PARP inhibitors. In recent years, several ultrapotent PARP inhibitors have been approved for clinical use (for the therapy of various oncological diseases): these newly-approved PARP inhibitors were recently reported to show efficacy in animal models of ALI. These observations offer the possibility of therapeutic repurposing of these inhibitors for patients with ALI. The current article lays out a potential roadmap for such repurposing efforts. In addition, the article also overviews the scientific basis of potentially applying PARP inhibitors for the experimental therapy of viral ALI, such as COVID-19-associated ARDS.


title: Endovascular Therapy Proven for Stroke – Finally!

text: Cardiologists often remark that the field of ischaemic stroke follows in the footsteps of cardiology, just one to two decades later. In the case of endovascular reperfusion therapies this certainly seems to have been the case but there are now multiple positive randomised trials establishing the benefit of mechanical thrombectomy over and above standard care, which included intravenous alteplase in most cases. We will outline the new evidence, contrast the recent trials with the earlier negative studies and discuss some important differences between acute myocardial infarction and ischaemic stroke and the techniques required to treat them.


title: Investigation of Visual System Involvement in Spinocerebellar Ataxia Type 14.

text: Spinocerebellar ataxia type 14 (SCA-PRKCG, formerly SCA14) is a rare, slowly progressive disorder caused by conventional mutations in protein kinase Cγ (PKCγ). The disease usually manifests with ataxia, but previous reports suggested PRKCG variants in retinal pathology. To systematically investigate for the first time visual function and retinal morphology in patients with SCA-PRKCG. Seventeen patients with PRKCG variants and 17 healthy controls were prospectively recruited, of which 12 genetically confirmed SCA-PRKCG patients and 14 matched controls were analyzed. We enquired a structured history for visual symptoms. Vision-related quality of life was obtained with the National Eye Institute Visual Function Questionnaire (NEI-VFQ) including the Neuro-Ophthalmic Supplement (NOS). Participants underwent testing of visual acuity, contrast sensitivity, visual fields, and retinal morphology with optical coherence tomography (OCT). Measurements of the SCA-PRKCG group were analyzed for their association with clinical parameters (ataxia rating and disease duration). SCA-PRKCG patients rate their vision-related quality of life in NEI-VFQ significantly worse than controls. Furthermore, binocular visual acuity and contrast sensitivity were worse in SCA-PRKCG patients compared with controls. Despite this, none of the OCT measurements differed between groups. NEI-VFQ and NOS composite scores were related to ataxia severity. Additionally, we describe one patient with a genetic variant of uncertain significance in the catalytic domain of PKCγ who, unlike all confirmed SCA-PRKCG, presented with a clinically silent epitheliopathy. SCA-PRKCG patients had reduced binocular vision and vision-related quality of life. Since no structural retinal damage was found, the pathomechanism of these findings remains unclear.


title: Hydrogel Tethering Enhances Interdomain Stabilization of Single-Chain Antibodies.

text: Here, we identify the importance of molecular crowding agents in the functional stabilization of scFv antibodies. Antibodies were tethered through an engineered calmodulin (CaM)-binding peptide into a stimulus-responsive hydrogel composed of poly(ethylene glycol) (PEG)-functionalized CaM. Macromolecular crowding is modulated by transient heating, which decreases effective pore sizes. Using a fluorescent ligand bound to the scFv, frequency-domain fluorescence spectroscopy was used to assess the structural coupling between the VH and the VL domains and relationships with functional stabilization. There is minimal structural coupling between the VH and the VL domains in solution, as is apparent from the substantial rotational mobility for the bound ligand, that is suggestive of an independent mobility for the VH and the VL domains. In comparison, the hydrogel matrix acts to structurally couple the VH and the VL domains, resulting in a reduction in rotational mobility and a retention of ligand binding in the presence of 8.0 M urea. Under these same conditions, ligand binding is disrupted for scFv antibodies in solution. Increases in the stabilization of scFv antibodies in hydrogels is not simply the result of molecular crowding because decreases in pore size act to destabilize ligand binding. Rather, our results suggest that the functional stabilization of the scFv antibody within the PEG hydrogel matrix includes important factors involving protein solvation that stabilize interdomain interactions between the VH and the VL domains necessary for ligand binding.


Show evidence that apps for COVID-19 contact-tracing are secure and effective.


title: SARS-CoV-2 and myocardial injury: Few answers, many questions.

text: Patients with COVID-19 and acute cardiac injury as measured by an elevated high-sensitivity troponin I or troponin T upon admission or during hospitalization have a mortality rate of over 50% in initial reports. The mechanism of SARS-CoV-2 and associated myocardial injury, whether SARS-CoV-2 patients with myocardial injury are a distinct population, and possible treatment options for myocardial injury associated with SARS-CoV-2 are unknown.


docid: zubwliwj

title: Reply to LTE: COVID-19 and pulmonary embolism: diagnostic imaging trends.


title: Dexmedetomidine vs midazolam or propofol for sedation during prolonged mechanical ventilation: two randomized controlled trials.

text: CONTEXT Long-term sedation with midazolam or propofol in intensive care units (ICUs) has serious adverse effects. Dexmedetomidine, an α(2)-agonist available for ICU sedation, may reduce the duration of mechanical ventilation and enhance patient comfort. OBJECTIVE To determine the efficacy of dexmedetomidine vs midazolam or propofol (preferred usual care) in maintaining sedation; reducing duration of mechanical ventilation; and improving patients' interaction with nursing care. DESIGN, SETTING, AND PATIENTS Two phase 3 multicenter, randomized, double-blind trials carried out from 2007 to 2010. The MIDEX trial compared midazolam with dexmedetomidine in ICUs of 44 centers in 9 European countries; the PRODEX trial compared propofol with dexmedetomidine in 31 centers in 6 European countries and 2 centers in Russia. Included were adult ICU patients receiving mechanical ventilation who needed light to moderate sedation for more than 24 hours (midazolam, n = 251, vs dexmedetomidine, n = 249; propofol, n = 247, vs dexmedetomidine, n = 251). INTERVENTIONS Sedation with dexmedetomidine, midazolam, or propofol; daily sedation stops; and spontaneous breathing trials. MAIN OUTCOME MEASURES For each trial, we tested whether dexmedetomidine was noninferior to control with respect to proportion of time at target sedation level (measured by Richmond Agitation-Sedation Scale) and superior to control with respect to duration of mechanical ventilation. Secondary end points were patients' ability to communicate pain (measured using a visual analogue scale [VAS]) and length of ICU stay. Time at target sedation was analyzed in per-protocol population (midazolam, n = 233, vs dexmedetomidine, n = 227; propofol, n = 214, vs dexmedetomidine, n = 223). RESULTS Dexmedetomidine/midazolam ratio in time at target sedation was 1.07 (95% CI, 0.97-1.18) and dexmedetomidine/propofol, 1.00 (95% CI, 0.92-1.08). Median duration of mechanical ventilation appeared shorter with dexmedetomidine (123 hours [IQR, 67-337]) vs midazolam (164 hours [IQR, 92-380]; P = .03) but not with dexmedetomidine (97 hours [IQR, 45-257]) vs propofol (118 hours [IQR, 48-327]; P = .24). Patients' interaction (measured using VAS) was improved with dexmedetomidine (estimated score difference vs midazolam, 19.7 [95% CI, 15.2-24.2]; P < .001; and vs propofol, 11.2 [95% CI, 6.4-15.9]; P < .001). Length of ICU and hospital stay and mortality were similar. Dexmedetomidine vs midazolam patients had more hypotension (51/247 [20.6%] vs 29/250 [11.6%]; P = .007) and bradycardia (35/247 [14.2%] vs 13/250 [5.2%]; P < .001). CONCLUSIONS Among ICU patients receiving prolonged mechanical ventilation, dexmedetomidine was not inferior to midazolam and propofol in maintaining light to moderate sedation. Dexmedetomidine reduced duration of mechanical ventilation compared with midazolam and improved patients' ability to communicate pain compared with midazolam and propofol. More adverse effects were associated with dexmedetomidine. TRIAL REGISTRATION clinicaltrials.gov Identifiers: NCT00481312, NCT00479661.


title: Prevalence and risk factors for cats testing positive for feline immunodeficiency virus and feline leukaemia virus infection in cats entering an animal shelter in New Zealand.

text: AIMS To estimate the prevalence of cats testing positive for antibodies to feline immunodeficiency virus (FIV) and feline leukaemia virus (FeLV) antigens in domestic cats entering a New Zealand animal shelter, based on a commercial point-of-care ELISA, to identify risk factors associated with cats testing positive, and to compare the results obtained from the ELISA with those obtained using PCR-based testing. METHOD A cross-sectional study was performed on 388 cats entering the Royal New Zealand Society for the Prevention of Cruelty to Animals animal shelter in Auckland, New Zealand between 7 February 2014 and 30 May 2014. Whole blood samples were collected from each cat and tested for FIV antibody and FeLV antigen using a commercial point-of-care ELISA. Information on the signalment and health status of the cat at the time of entry was also recorded. Blood and saliva samples from a subset of cats were tested for FIV and FeLV proviral DNA using a real-time PCR assay. RESULTS Of the 388 cats in the study sample, 146 (37.6%) had been relinquished by owners, 237 (62.4%) were strays, and 5 (1.3%) were of unknown origin. Overall, 53/388 (13.7%) cats tested positive for FIV antibodies and 4/388 (1.0%) were positive for FeLV antigen. Stray cats had a higher FIV seroprevalence than relinquished cats (42/237 (17.8%) vs. 11/146 (7.5%); p=0.008). Of 53 cats that were FIV-seropositive, 51 (96%) tested positive for FIV proviral DNA using PCR testing of blood. Of these 51 cats, 28 (55%) were positive by PCR testing of saliva. Of the four cats that were FeLV antigen-positive by ELISA, two (50%) were positive for FeLV proviral DNA by PCR testing of blood. The odds of a cat being seropositive for FIV were greater for intact compared to desexed cats (OR=3.3; 95% CI=1.6-7.4) and for male compared to female cats (OR=6.5; 95% CI=3.2-14.0). CONCLUSIONS AND CLINICAL RELEVANCE The seroprevalence for FIV was 14% among cats entering an animal shelter in Auckland, whereas the prevalence of FeLV antigen-positive cats was only 1%. These findings suggest differences in the transmission dynamics of each virus in free-roaming cat populations in New Zealand. Our study also highlights the potential role of desexing cats in reducing transmission of FIV. However, further data from first-opinion veterinary practices are required to confirm that these findings may be generalised to the wider domestic cat population in New Zealand.


title: The Peru Approach against the COVID-19 Infodemic: Insights and Strategies.

text: The COVID-19 epidemic has spawned an "infodemic," with excessive and unfounded information that hinders an appropriate public health response. This perspective describes a selection of COVID-19 fake news that originated in Peru and the government's response to this information. Unlike other countries, Peru was relatively successful in controlling the infodemic possibly because of the implementation of prison sentences for persons who created and shared fake news. We believe that similar actions by other countries in collaboration with social media companies may offer a solution to the infodemic problem.


title: COVID-19 Incidentally Detected on PET/CT During Work-up for Locally Advanced Head and Neck Cancer.

text: AIM To describe the incidental detection of COVID-19 disease on positron-emission tomography/computed tomography (PET/CT) in a patient with cancer despite initial negative swab by polymerase chain reaction (PCR). CASE REPORT Clinical and radiographic data were obtained from the electronic medical record. Nasopharyngeal swabs were obtained and evaluated for COVID-19 by the Food and Drug Administration-approved reverse transcription-PCR assays. On radiographic examination, PET/CT was consistent with COVID-19-related pneumonia not seen on prior imaging. Initial nasopharyngeal swab 2 days after PET/CT imaging was negative for COVID-19. Subsequent repeat swab 10 days later was positive for COVID-19, while the patient was febrile on screening assessment. The patient remained COVID-19-positive until 1 month after abnormal PET/CT imaging. CONCLUSION PET/CT can be sensitive for early COVID-19 detection, even in the setting of a negative confirmatory PCR test. This highlights the importance of continued patient surveillance and use of appropriate personal protective equipment to minimize COVID-19 transmission.


title: Comparative study between biologic porcine dermal meshes: risk factors of postoperative morbidity and recurrence.

text: OBJECTIVE Different types of biologic mesh have been introduced as an alternative to synthetic mesh for use in repairing contaminated ventral hernias because of their biocompatible nature. The aim of this study was to compare the clinical outcomes of patients who underwent complex ventral hernia repairs with either non cross-linked or cross-linked porcine dermal meshes. METHOD This was retrospective analysis from a prospectively maintained database from January 2010 to May 2013. Patients undergoing open incisional hernia repair with a biologic mesh in the presence of a clean-contaminated, contaminated or dirty wound were reviewed. RESULTS There were 39 patients who underwent single-staged abdominal wall reconstruction for a contaminated ventral hernia with a biologic mesh. In 15 cases, non cross-linked mesh was used (Strattice, n=8; Protexa, n=1; XenMatrix, n=6); a cross-linked mesh was used in the remaining 24 cases (Permacol n=21; CollaMend n=3). The median follow-up was 11.9 ± 10.6 months. The overall morbidity was 71.8% (n=28), with 15.4% (n=6) for grade I, 23.1% (n=9) for grade II, 23.1% (n=9) for grade III (n=3 grade IIIA, n=6 grade IIIB), 7.7% (n=3) for grade IV and 2.6% (n=1) for grade V. In the cross-linked group, there were six complications directly linked to the biologic mesh, compared with three in the non-cross-linked group. Overall wound morbidity was 41.0% (n=16). There were 13 hernia recurrences (33.3%), and recurrence rate was not significantly different for both groups. CONCLUSION Despite the high rate of wound morbidity associated with the single-staged reconstruction of contaminated fields, it can be safely performed with biologic mesh reinforcement. Recurrence rate was not significantly different between cross-linked and non cross-linked porcine meshes.


docid: mbtunaef

title: Ethics in the Covid-19 emergency: Examining rationing decisions.

text: Early last month, the Italian Society of Anaesthesia was forced to publish the above guideline (1) for the country's hospitals. Besides the rising cases of infection, the doctors realised that patients required up to 15-20 days of intensive care as the disease progressed (2). In the face of medical resource scarcities, the guideline established that everyone could not be saved from the coronavirus. And a massive death toll ensued.


title: Randomized comparison of self-fixating and sutured mesh in open inguinal hernia repair.

text: BACKGROUND Chronic groin pain after mesh repair of inguinal hernia has been attributed to the presence of sutures. METHODS This randomized clinical trial compared inguinal hernia repair using a self-fixating composite mesh or a sutured lightweight mesh, with pain at 1 year as primary outcome. Patients completed a self-evaluation questionnaire at 2 weeks and were examined after 1 year. RESULTS Some 198 patients received self-fixating mesh and 196 sutured mesh. There were no differences between the groups in mean pain scores measured on a visual analogue scale during 2 weeks of immediate convalescence or at 1 year. Chronic pain and discomfort was experienced by 36.3 per cent of patients in the self-fixating and 34.1 per cent in the sutured mesh group (P = 0.658), affecting the everyday life of 1.1 and 2.8 per cent respectively (P = 0.448). CONCLUSION Open inguinal hernia repair with a composite self-fixating mesh resulted in similar pain in the early postoperative convalescence period and at 1 year as repair with a sutured lightweight mesh.


title: Sensitive and rapid detection of infectious pancreatic necrosis virus by reverse transcription loop mediated isothermal amplification.

text: A new molecular diagnostic assay was developed for rapid and sensitive diagnosis of infectious pancreatic necrosis virus (IPNV) by using a one step, one tube reverse transcription loop-mediated isothermal amplification (RT-LAMP). A set of six LAMP primers was designed to amplify the target RNA by incubation with Bst DNA polymerase plus reverse transcriptase and the reaction was optimised at 65 degrees C for 60 min. Three different methods for detection of the amplified product by naked eye gave identical results to gel electrophoresis, which was run for confirmation. Negative results obtained with RNA from four other fish viruses confirmed the specificity of the test. The IPNV-RT-LAMP assay demonstrated superior analytical sensitivity compared to conventional RT-PCR conducted according to published methods (1:10(12) dilution of RNA extracted from an IPNV-infected cell culture supernatant vs. 1:10(6) for the conventional RT-PCR). The feasibility of the RT-LAMP assay for detection of IPNV RNA in clinical specimen was authenticated using kidney tissue samples from experimentally IPNV-infected Atlantic salmon (Salmo salar) post-smolts. The results suggest that the RT-LAMP is a rapid and highly sensitive diagnostic assay for IPNV which lends itself well to use in aquaculture health management and disease control.


title: Non-Vitamin K Oral Anticoagulants in Stroke Patients: Practical Issues.

text: Non-vitamin-K oral anticoagulants (NOACs) represent a major advance in the prevention of stroke in patients with atrial fibrillation (AF), offering a similar, if not superior, efficacy and safety profile and several practical advantages over oral vitamin K antagonists (VKAs). The rapid onset of action of the NOACs, their relatively short half-live, and the availability of specific reversal agents may be advantageous when managing acute ischemic strokes, and in the post-stroke, post-transient ischemic attack, and post-intracranial hemorrhage settings. In this review article, we offer practical guidance on the use of NOACs in these settings, focusing on managing the acute event and on initiating or resuming anticoagulation for secondary prevention. We also assess the use of NOACs to prevent stroke and bleeding in patients with AF who have chronic kidney disease, are elderly, or cognitively impaired, and we offer guidance on optimizing the use of NOACs and VKAs in these patient groups in the absence of evidence-based guidelines.


title: Intravenous lacosamide in clinical practice-Results from an independent registry.

text: PURPOSE This non-interventional study was conducted to evaluate the efficacy and tolerability of intravenous lacosamide (LCM-iv) under routine conditions in daily clinical practice as a prospective registry. METHODS Patients with any type of seizure or epilepsy syndrome were recruited in 16 neurological and neuropediatric centers in Germany if the treating physician decided to administer LCM-iv for any reason. Observation time per patient was 10 days with daily documentation of LCM-iv administration, type and frequency of seizures, currently used drugs and doses, and adverse events. Treatment efficacy, tolerability, and handling of LCM-iv were assessed using a five-step scale. RESULTS In 119 patients treating physicians classified epilepsies as focal in 66.1% and generalized in 17.4% (16.5% unclassifiable). Most common etiologies of seizures were tumors (36.1%) and cerebrovascular diseases (21.8%). Reasons for LCM-iv treatment included preparation for surgery (25.2%), convulsive (24.4%) and non-convulsive (18.5%) status epilepticus (SE), series of seizures (16.0%), gastrointestinal causes (5.9%), and acute seizures (4.2%). The median dose of LCM-iv was 300mg per day. In 45 of 64 patients (70.3%) with SE or series of seizures, epileptic activity ceased during observation time. Five patients showed abnormalities in ECG prior to the infusion and one patient afterwards, but during infusion no abnormalities were reported. Treating physicians rated efficacy and tolerability as very good or good in 77.6% and 93.1% of patients, respectively. CONCLUSIONS This large and independent multicenter registry on the use of LCM-iv in clinical practice demonstrates that LCM-iv is well-tolerated and highly efficacious when given in emergency situations, including patients experiencing SE. It is advisable to perform an electrocardiogram prior to LCM-iv administration.


title: Implicit as compared with explicit safety procedures: the experiences of Israeli nurses.

text: Approaches to nurses' safety in health care organizations, including modifying individual behavior through enforced compliance with safety rules and mandatory participation in safety training, have been of only modest benefit in reducing injuries. Apparently, what matters is not the existence of guidelines, but their implementation. The aim of the present study was to explore nurses' implicit safety theories concerning when to comply with safety rules. Using a multimethod approach, including semistructured interviews (perceptions), observations (real-time behavior), and documentary evidence from 15 nursing units (90 nurses), we found that nurses developed implicit rules for when and how to protect themselves. These included: (a) continue providing care for the patient even at the price of protecting yourself, (b) do not disturb other nurses' work, (c) it cannot happen to me!, (d) be aware of recently occurring accidents, and (e) protect yourself when significant others are present. These implicit rules seemed to be reinforced by personal, social, and contextual factors at the unit, limiting the likelihood that the decision makers (nurses) would discover their fallacy.


title: Hope as a Generative Force: Lifting Our Gaze to the Future.

text: Pandemics are by nature "out of the blue." Their unpredictable nature and impact can leave nurses and support systems reeling. Nurses are physically and emotionally exhausted but also may be isolated from the physical and emotional support of families and other loved ones. As leaders concurrently manage the logistical and resource challenges of the COVID-19 epidemic, it is essential for leaders to also lift their gaze to the future. Leaders can be a force multiplier for supporting resilience in their teams. [J Contin Educ Nurs. 2020;51(5):203-204].


title: Influencing factors for port-site hernias after single-incision laparoscopy.

text: PURPOSE Single-incision laparoscopic surgery (SILS) has been demonstrated to be a feasible alternative to multiport laparoscopy, but concerns over port-site incisional hernias have not been well addressed. A retrospective study was performed to determine the rate of port-site hernias as well as influencing risk factors for developing this complication. METHODS A review of all consecutive patients who underwent SILS over 4 years was conducted using electronic medical records in a multi-specialty integrated healthcare system. Statistical evaluation included descriptive analysis of demographics in addition to bivariate and multivariate analyses of potential risk factors, which were age, gender, BMI, procedure, existing insertion-site hernia, wound infection, tobacco use, steroid use, and diabetes. RESULTS 787 patients who underwent SILS without conversion to open were reviewed. There were 454 cholecystectomies, 189 appendectomies, 72 colectomies, 21 fundoplications, 15 transabdominal inguinal herniorrhaphies, and 36 other surgeries. Cases included 532 (67.6 %) women, and among all patients mean age was 44.65 (±19.05) years and mean BMI of 28.04 (±6). Of these, 50 (6.35 %) patients were documented as developing port-site incisional hernias by a health care provider or by incidental imaging. Of the risk factors analyzed, insertion-site hernia, age, and BMI were significant. Multivariate analysis indicated that both preexisting hernia and BMI were significant risk factors (p value = 0.00212; p value = 0.0307). Morbidly obese patients had the highest incidence of incisional hernias at 18.18 % (p value = 0.02). CONCLUSIONS When selecting patients for SILS, surgeons should consider the presence of an umbilical hernia, increased age and obesity as risk factors for developing a port-site hernia.


title: High fidelity virtual stenting (HiFiVS) for intracranial aneurysm flow diversion: in vitro and in silico.

text: A flow diverter (FD) is a flexible, densely braided stent-mesh device placed endoluminally across an intracranial aneurysm to induce its thrombotic occlusion. FD treatment planning using computational virtual stenting and flow simulation requires accurate representation of the expanded FD geometry. We have recently developed a high fidelity virtual stenting (HiFiVS) technique based on finite element analysis to simulate detailed FD deployment processes in patient-specific aneurysms (Ma et al. J. Biomech. 45:2256-2263,(2012)). This study tests if HiFiVS simulation can recapitulate real-life FD implantation. We deployed two identical FDs (Pipeline Embolization Device) into phantoms of a wide-necked segmental aneurysm using a clinical push-pull technique with different delivery wire advancements. We then simulated these deployment processes using HiFiVS and compared results against experimental recording. Stepwise comparison shows that the simulations precisely reproduced the FD deployment processes recorded in vitro. The local metal coverage rate and pore density quantifications demonstrated that simulations reproduced detailed FD mesh geometry. These results provide validation of the HiFiVS technique, highlighting its unique capability of accurately representing stent intervention in silico.


title: Views of cancer patients regarding cardiopulmonary resuscitation in Greece.

text: Cardiopulmonary resuscitation (CPR) in patients with cancer is an ethical issue of worldwide interest. A questionnaire-based study was carried out in a Greek oncology hospital aiming to explore the attitude of Greek cancer patients towards CPR. Overall, 200 patients (94 male, 106 female) of a mean age of 62.8 years took part in the study. Only 42 (21%) patients indicated that they knew what CPR really involves and only 20 (10%) patients thought that CPR has serious side effects, while the mean estimated in-hospital CPR survival rate to hospital discharge was 56.6% (minimum = 2%, maximum = 99%, standard deviation [SD] = 25.16) and 42.1% (minimum = 0%, maximum = 90%, SD = 24.56%) in case of unselected and cancer patients respectively. Despite their poor knowledge, 177 (88.5%) patients were willing to undergo CPR in case of an in-hospital arrest, 127 (63.5%) thought that they had the right to choose their CPR status and 141 (70.5%) believed that they should be asked about it when they enter the hospital. Most patients (36%) wanted their CPR status to be decided by themselves, their family and their doctor jointly. These findings indicate that specific measures should be applied to clinical practice in order to best manage this ethical issue, and consequently, improve cancer care.


title: Ecological Approaches to Studying Zoonoses.

text: Concern over emerging infectious diseases (EIDs) and a better understanding of their causes has resulted in increasing recognition of the linkages among human, animal, and ecosystem health. It is now well recognized that human activities can promote the emergence of infectious diseases through the large-scale modification of natural environments and inadvertent vectoring (e.g., international trade and travel). These perturbations can alter the ecological and evolutionary relationships among humans, wildlife, and the pathogens that move between them, resulting in disease emergence. In recent years, the rise in zoonotic EIDs has not only increased our awareness of the need for cross-sectoral collaborations, but has also highlighted the disconnect between current ecological theory and biological reality. As the One Health movement continues to gain steam, further integration of ecological approaches into the One Health framework will be required. We discuss the importance of ecological methods and theory to the study of zoonotic diseases by (i) discussing key ecological concepts and approaches, (ii) reviewing methods of studying wildlife diseases and their potential applications for zoonoses, and (iii) identifying future directions in the One Health movement.


Coronavirus Disease 2019 (COVID-19) and Pregnancy: Responding to a Rapidly Evolving Situation.


title: The emerging role of lung ultrasound in COVID-19 pneumonia.

text: In the last decades lung ultrasound (LUS) has become of crucial importance in the evaluation and monitoring of a widely range of pulmonary diseases. One of the major benefits which favours this examination, is that this is a non-invasive, low-cost and radiation-free imaging modality which allows repeated imaging. LUS plays an important role in a wide range of pathologies, including cardiogenic oedema, acute respiratory distress syndrome and fibrosis. Specific LUS findings have proved useful and predictive of acute respiratory distress syndrome which is of particular relevance in the suspicion and monitoring of patients with lung disease. Furthermore, several studies have confirmed the role of LUS in the screening of interstitial lung diseases in connective tissue diseases. Given these data, LUS will likely play an important role in the management of COVID-19 patients from identification of specific abnormalities corresponding to definite pneumonia phases and CT scans findings. In addition, LUS could allow reduction in the exposure of health-care workers to potential infection. Herein, we provide a summary on emerging role of lung ultrasound in COVID-19 pneumonia.


One disease, different features: COVID-19 laboratory and radiological findings in three Italian patients.


title: Incorporation of paramagnetic, fluorescent and PET/SPECT contrast agents into liposomes for multimodal imaging.

text: A series of metal-chelating lipid conjugates has been designed and synthesized. Each member of the series bears a 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) macrocycle attached to the lipid head group, using short n-ethylene glycol (n-EG) spacers of varying length. Liposomes incorporating these lipids, chelated to Gd(3+), (64)Cu(2+), or (111)In(3+), and also incorporating fluorescent lipids, have been prepared, and their application in optical, magnetic resonance (MR) and single-photon emission tomography (SPECT) imaging of cellular uptake and distribution investigated in vitro and in vivo. We have shown that these multimodal liposomes can be used as functional MR contrast agents as well as radionuclide tracers for SPECT, and that they can be optimized for each application. When shielded liposomes were formulated incorporating 50% of a lipid with a short n-EG spacer, to give nanoparticles with a shallow but even coverage of n-EG, they showed good cellular internalization in a range of tumour cells, compared to the limited cellular uptake of conventional shielded liposomes formulated with 7% 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[carboxy(polyethyleneglycol)(2000)] (DSPE-PEG2000). Moreover, by matching the depth of n-EG coverage to the length of the n-EG spacers of the DOTA lipids, we have shown that similar distributions and blood half lives to DSPE-PEG2000-stabilized liposomes can be achieved. The ability to tune the imaging properties and distribution of these liposomes allows for the future development of a flexible tri-modal imaging agent.


title: A Glimpse into the Future.

text: The novel coronavirus will forever change the world in ways we have yet to realize. What will our lives look like when the crisis abates? Will we still shake hands? Will my Italian relatives still kiss me on both cheeks (or just give air kisses)? When this is over there may be fewer elderly, more guns, less movie theaters and greater paranoia in America… but perhaps more generosity and kindness as well. Most of what will change after the pandemic is beyond my ability to guess. However, I see more clearly the changes that will come to Emergency Medicine once the Hot Zone has cooled. Let's pull back the curtain of time and glimpse into the future for our specialty after the Time of COVID….


title: Generalized myoclonus in COVID-19.

text: OBJECTIVE To report 3 patients infected with severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) who developed generalized myoclonus. METHODS Patient data were obtained from medical records from the University Hospital "12 de Octubre," Madrid, Spain. RESULTS Three patients (2 men, and one woman, aged 63-88) presented with mild hypersomnia and generalized myoclonus following the onset of the so-called "inflammatory" phase of coronavirus disease 2019 (COVID-19). All of them had presented previously with anosmia. Myoclonus had a stereotypical pattern, being both positive and negative, generalized, with a predominant involvement of nasopharyngeal, facial, and upper limbs areas. These jerky movements occurred spontaneously and were extremely sensitive to multisensory stimuli (auditive and tactile) or voluntary movement, with an exaggerated startle response. Other causes of myoclonus were ruled-out, and none of them had undergone respiratory arrest or significant prolonged hypoxia. All of them improved, at least partially, with immunotherapy. CONCLUSIONS Our 3 cases highlight the occurrence of myoclonus during the COVID-19 pandemic as a postinfectious/immune-mediated disorder. However, we cannot rule out that SARS-CoV-2 may spread transneuronally to first- and second-order structures connected with the olfactory bulb. Further investigation is required to clarify the full clinical spectrum of neurologic symptoms and its optimal treatment.


title: Gene classification using codon usage and support vector machines.

text: A novel approach for gene classification, which adopts codon usage bias as input feature vector for classification by support vector machines (SVM) is proposed. The DNA sequence is first converted to a 59-dimensional feature vector where each element corresponds to the relative synonymous usage frequency of a codon. As the input to the classifier is independent of sequence length and variance, our approach is useful when the sequences to be classified are of different lengths, a condition that homology-based methods tend to fail. The method is demonstrated by using 1,841 Human Leukocyte Antigen (HLA) sequences which are classified into two major classes: HLA-I and HLA-II; each major class is further subdivided into sub-groups of HLA-I and HLA-II molecules. Using codon usage frequencies, binary SVM achieved accuracy rate of 99.3% for HLA major class classification and multi-class SVM achieved accuracy rates of 99.73% and 98.38% for sub-class classification of HLA-I and HLA-II molecules, respectively. The results show that gene classification based on codon usage bias is consistent with the molecular structures and biological functions of HLA molecules.


COVID-19 will change MS care forever - Commentary.


title: Physical interventions to interrupt or reduce the spread of respiratory viruses.

text: BACKGROUND Viral epidemics or pandemics of acute respiratory infections like influenza or severe acute respiratory syndrome pose a world-wide threat. Antiviral drugs and vaccinations may be insufficient to prevent catastrophe. OBJECTIVES To systematically review the effectiveness of physical interventions to interrupt or reduce the spread of respiratory viruses. SEARCH STRATEGY We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, issue 2); MEDLINE (1966 to May 2009); OLDMEDLINE (1950 to 1965); EMBASE (1990 to May 2009); and CINAHL (1982 to May 2009). SELECTION CRITERIA We scanned 2958 titles, excluded 2790 and retrieved the full papers of 168 trials, to include 59 papers of 60 studies. We included any physical interventions (isolation, quarantine, social distancing, barriers, personal protection and hygiene) to prevent transmission of respiratory viruses. We included the following study designs: randomised controlled trials (RCTs), cohorts, case controls, cross-over, before-after, and time series studies. DATA COLLECTION AND ANALYSIS We used a standardised form to assess trial eligibility. RCTs were assessed by: randomisation method; allocation generation; concealment; blinding; and follow up. Non-RCTs were assessed for the presence of potential confounders, and classified into low, medium, and high risks of bias. MAIN RESULTS The risk of bias for the four RCTs, and most cluster RCTs, was high. The observational studies were of mixed quality. Only case-control data were sufficiently homogeneous to allow meta-analysis.The highest quality cluster RCTs suggest respiratory virus spread can be prevented by hygienic measures, such as handwashing, especially around younger children. Additional benefit from reduced transmission from children to other household members is broadly supported in results of other study designs, where the potential for confounding is greater. Six case-control studies suggested that implementing barriers to transmission, isolation, and hygienic measures are effective at containing respiratory virus epidemics. We found limited evidence that N95 respirators were superior to simple surgical masks, but were more expensive, uncomfortable, and caused skin irritation. The incremental effect of adding virucidals or antiseptics to normal handwashing to decrease respiratory disease remains uncertain. Global measures, such as screening at entry ports, were not properly evaluated. There was limited evidence that social distancing was effective especially if related to the risk of exposure. AUTHORS' CONCLUSIONS Many simple and probably low-cost interventions would be useful for reducing the transmission of epidemic respiratory viruses. Routine long-term implementation of some of the measures assessed might be difficult without the threat of a looming epidemic.


title: Risk factors for vaginal mesh erosion after sacrocolpopexy in Korean women.

text: OBJECTIVE Although sacrocolpopexy (SCP) can provide durable apical support, the use of mesh may give rise to various complications, including vaginal mesh erosion. The aim of this study was to identify the risk factors for vaginal mesh erosion after SCP in Korean women. METHODS This retrospective cohort study included 363 women who underwent SCP with type 1 polypropylene mesh. They were evaluated at 1, 4, and 12 months after surgery and then annually thereafter with respect to anatomy and complications. Univariate and multivariate analyses using the Cox proportional hazard model were performed to identify the risk factors for mesh erosion. RESULTS During the median 2-year follow-up period, vaginal mesh erosion was found in 29 women (8.0%). Among them, 19 (65.5%) required surgical correction. Estrogenic status was the only independent risk factor for mesh erosion. The risk for mesh erosion was 4.5 times higher in premenopausal women than in menopausal women not on estrogen replacement therapy (ERT) (95% confidence intervals [CI] 1.9-10.9, p<0.01). Menopausal women on ERT also had an increased risk, with a statistically marginal significance (hazard ratio 2.5, 95% CI 0.9-6.6; p = 0.07). CONCLUSIONS Premenopausal or menopausal women on ERT are at high risk for mesh erosion after SCP with type 1 polypropylene mesh, and two-thirds of mesh erosion cases require reoperation. This information should be incorporated into patient counseling and treatment decisions.


title: The increased cost of ventral hernia recurrence: a cost analysis.

text: PURPOSE Over 300,000 ventral hernia repairs (VHRs) are performed each year in the US. We sought to assess the economic burden related to ventral hernia recurrences with a focused comparison of those with the initial open versus laparoscopic surgery. METHODS The Premier Alliance database from 2009 to 2014 was utilized to obtain patient demographics and comorbid indices, including the Charlson comorbidity index (CCI). Total hospital cost and resource expenses during index laparoscopic and open VHRs and subsequent recurrent repairs were also obtained. The sample was separated into laparoscopic and open repair groups from the initial operation. Adjusted and propensity score matched cost outcome data were then compared amongst groups. RESULTS One thousand and seventy-seven patients were used for the analysis with a recurrence rate of 3.78 %. For the combined sample, costs were significantly higher during recurrent hernia repair hospitalization ($21,726 versus $19,484, p < 0.0001). However, for index laparoscopic repairs, both the adjusted total hospital cost and department level costs were similar during the index and the recurrent visit. The costs and resource utilization did not go up due to recurrence, even though these patients had greater severity during the recurrent visit (CCI score 0.92 versus 1.06; p = 0.0092). Using a matched sample, the total hospital recurrence cost was higher for the initial open group compared to laparoscopic group ($14,520 versus $12,649; p = 0.0454). CONCLUSIONS Based on our analysis, need for recurrent VHR adds substantially to total hospital costs and resource utilization. Following initial laparoscopic repair, however, the total cost of recurrent repair is not significantly increased, as it is following initial open repair. When comparing the initial laparoscopic repair versus open, the cost of recurrence was higher for the prior open repair group.


Protocol for the development of a rapid advice guideline for prevention, management and care of children with 2019 novel coronavirus infection.


title: COVID-19 and your rheumatology patients.

text: The COVID-19 pandemic has caused a sense of unease in the rheumatology community about the risk to patients with immune-mediated diseases, given their predisposition to infection due to underlying disease states and immunosuppressive therapies. Thus far, there have been few cases of COVID-19 reported in patients with immune-mediated diseases and there have been no formal guidelines released on the management of patients with immune-mediated diseases in the setting of COVID-19. Results of clinical trials and data from the Global Rheumatology Alliance registry are eagerly awaited to gain further insight into the impact of this novel infection on our vulnerable patient population.


docid: eczdjsux

title: Treatment for right colon polyps not removable using standard colonoscopy: combined laparoscopic-colonoscopic approach.

text: BACKGROUND For complex right colon polyps, not removable using colonoscopy, right colon resection is considered the optimal treatment. Combined endoscopic-laparoscopic surgery, using both laparoscopy and CO2 colonoscopy, has been introduced as a new approach for these complex colon polyps with intent to avoid bowel resection. OBJECTIVE This study aimed to evaluate the safety and outcomes of combined endoscopic-laparoscopic surgery used for treatment of complex right colon polyps. DESIGN This is a retrospective study of patients undergoing combined endoscopic-laparoscopic surgery for treatment of benign right colon polyps from 2003 to 2008. SETTINGS This is a single-institution study. PATIENTS Twenty-three patients with complex right colon polyps were included. MAIN OUTCOME MEASURES The main outcome measures included the length of hospital stay, postoperative complications, and polyp recurrence. RESULTS Of 23 patients, 20 (87%) patients had their polyp removed successfully by combined endoscopic-laparoscopic surgery and 3 (13%) needed laparoscopic resection, after laparoendoscopic evaluation. The median length of hospital stay was 2 days (range, 1-5), and there were no postoperative complications. Median follow-up time was 12 months. Three patients had recurrent polyps, and the recurrence-free interval at 36 months was 55.7% (95% CI = 8.6%, 87.0%). All recurrences were benign polyps and were removed by colonoscopic snaring. CONCLUSIONS Combined endoscopic-laparoscopic surgery can be safely offered to selected patients with benign right colon polyps that can not be removed by colonoscopy. This combined approach may provide a viable alternative to right colon resection for complex benign colon lesions and warrants future investigation.