title: Case report: central venous catheterization via internal jugular vein with associated formation of perioperative venous thrombosis during surgery in the prone position.

text: An unusual case of central venous catheter (CVC)-related thrombosis during supine surgery in the prone position is presented. A 76-year-old woman was scheduled for elective surgery to repair a broken lumbar instrument. A single-lumen CVC was inserted via the right internal jugular vein. Surgery was performed in the prone position, with the patient's face directed downward in the standard median position (i.e., no rotation), but with slight forward flexion at the neck. After the surgery, the external jugular vein was dilated, and a postoperative X-ray revealed an infiltrative shadow in the right thoracic cavity. Because cervical echography showed dilated cervical veins with a "moyamoya-type" echo, possibly indicating a thrombus, contrast-enhanced computed tomography was performed, revealing a venous thrombus in the right internal jugular vein. An internal jugular venous-velocity measurement suggested that her slightly flexed neck position and her prone position during surgery may have kinked the internal jugular vein, causing engorgement with venous blood. The presence of the internal jugular venous catheter may have created thrombogenic conditions. A patient's position during surgery can reduce deep venous-flow velocity, and venous blood may stagnate, contributing greatly to thrombogenicity. We should consider a patient's position during surgery as a risk factor for thrombus formation, and a careful preoperative evaluation should be made as to which route should be chosen for CVC.


Temporoparietal fascia flap "sandwich" technique for repair of near-total traumatic auricle avulsion.


title: Household epidemics: modelling effects of early stage vaccination.

text: A Markovian susceptible --> infectious --> removed (SIR) epidemic model is considered in a community partitioned into households. A vaccination strategy, which is implemented during the early stages of the disease following the detection of infected individuals is proposed. In this strategy, the detection occurs while an individual is infectious and other susceptible household members are vaccinated without further delay. Expressions are derived for the influence on the reproduction numbers of this vaccination strategy for equal and unequal household sizes. We fit previously estimated parameters from influenza and use household distributions for Sweden and Tanzania census data. The results show that the reproduction number is much higher in Tanzania (6 compared with 2) due to larger households, and that infected individuals have to be detected (and household members vaccinated) after on average 5 days in Sweden and after 3.3 days in Tanzania, a much smaller difference.


title: Association between eczema and major cardiovascular outcomes in population-based studies: a systematic review protocol.

text: INTRODUCTION Chronic inflammatory diseases such as eczema (also known as atopic dermatitis) have been inconsistently linked to cardiovascular disease and stroke in both mechanistic and epidemiological studies. There is a need to review the existing epidemiological data examining the association between eczema and major cardiovascular outcomes, including angina, myocardial infarction, coronary revascularisation, heart failure, cardiac arrhythmias, stroke and cardiovascular death, in order to improve our understanding of the comorbidities of eczema. METHODS AND ANALYSIS We will systematically review population-based studies, including cohort, case-control and cross-sectional studies, reporting on the association between eczema and cardiovascular outcomes. We will search Medline, Embase and Global Health, from their date of inception to April 2017, using a comprehensive search strategy formulated with the help of a librarian. Two reviewers will independently screen titles and abstracts in duplicate, followed by independent data extraction and quality assessment. We will group studies by the cardiovascular outcome under study and synthesise them narratively. If sufficient numbers of homogeneous studies are returned, we will perform meta-analyses to obtain pooled effect estimates. Preferred Reporting Items for Systematic Review and Meta-Analysis will be used to inform the reporting of this study. TRIAL REGISTRATION NUMBER CRD42017060359.


COVID19 and Breastfeeding: Not That Simple.


Nature Biotechnology's academic spinouts of 2019.


title: JNK and p38 mitogen-activated protein kinase pathways contribute to porcine circovirus type 2 infection.

text: Infection with a wide variety of viruses often perturbs host cell signaling pathways including the Jun NH(2)-terminal kinase/stress-activated kinase (JNK/SAPK) and the p38 mitogen-activated protein kinase (p38/MAPK), which are important components of cellular signal transduction pathways. The present study demonstrated for the first time that porcine circovirus type 2 (PCV2), which is the primary causative agent of an emerging swine disease, postweaning multisystemic wasting syndrome, can activate JNK1/2 and p38 MAPK pathways in PCV2-infected PK15 cells. However, PCV2 at an early stage of infection, as well as UV-irradiated PCV2, failed to activate these two MAPK families, which demonstrated that PCV2 replication was necessary for their activation. We further found that PCV2 activated the phosphorylation of JNK1/2 and p38 MAPK downstream targets c-Jun and ATF-2 with virus replication in the cultured cells. The roles of these kinases in PCV2 infection were further evaluated using specific inhibitors: the JNK inhibitor 1 for JNK1/2 and SB202190 for p38. Inhibition of JNK1/2 and p38 kinases by these specific inhibitors did result in significant reduction of PCV2 viral mRNA transcription and protein synthesis, viral progeny release, and blockage of PCV2-induced apoptotic caspase-3 activation in the infected cells. Taken together, these data suggest that JNK/SAPK and p38 MAPK pathways play important roles in the PCV2 replication and contribute to virus-mediated changes in host cells.


Respiratory Mechanics of COVID-19 vs. Non-COVID-19 Associated Acute Respiratory Distress Syndrome.


title: Hand-held medical robots.

text: Medical robots have evolved from autonomous systems to tele-operated platforms and mechanically-grounded, cooperatively-controlled robots. Whilst these approaches have seen both commercial and clinical success, uptake of these robots remains moderate because of their high cost, large physical footprint and long setup times. More recently, researchers have moved toward developing hand-held robots that are completely ungrounded and manipulated by surgeons in free space, in a similar manner to how conventional instruments are handled. These devices provide specific functions that assist the surgeon in accomplishing tasks that are otherwise challenging with manual manipulation. Hand-held robots have the advantages of being compact and easily integrated into the normal surgical workflow since there is typically little or no setup time. Hand-held devices can also have a significantly reduced cost to healthcare providers as they do not necessitate the complex, multi degree-of-freedom linkages that grounded robots require. However, the development of such devices is faced with many technical challenges, including miniaturization, cost and sterility, control stability, inertial and gravity compensation and robust instrument tracking. This review presents the emerging technical trends in hand-held medical robots and future development opportunities for promoting their wider clinical uptake.


Reply to: "HCV RNA kinetics on-treatment do not predict sustained virologic response in HCV genotype 3 patients receiving sofosbuvir and ribavirin".


title: QT interval and antidepressant use: a cross sectional study of electronic health records.

text: OBJECTIVE To quantify the impact of citalopram and other selective serotonin reuptake inhibitors on corrected QT interval (QTc), a marker of risk for ventricular arrhythmia, in a large and diverse clinical population. DESIGN A cross sectional study using electrocardiographic, prescribing, and clinical data from electronic health records to explore the relation between antidepressant dose and QTc. Methadone, an opioid known to prolong QT, was included to demonstrate assay sensitivity. SETTING A large New England healthcare system comprising two academic medical centres and outpatient clinics. PARTICIPANTS 38,397 adult patients with an electrocardiogram recorded after prescription of antidepressant or methadone between February 1990 and August 2011. MAIN OUTCOME MEASURES Relation between antidepressant dose and QTc interval in linear regression, adjusting for potential clinical and demographic confounding variables. For a subset of patients, change in QTc after drug dose was also examined. RESULTS Dose-response association with QTc prolongation was identified for citalopram (adjusted beta 0.10 (SE 0.04), P<0.01), escitalopram (adjusted beta 0.58 (0.15), P<0.001), and amitriptyline (adjusted beta 0.11 (0.03), P<0.001), but not for other antidepressants examined. An association with QTc shortening was identified for bupropion (adjusted beta 0.02 (0.01) P<0.05). Within-subject paired observations supported the QTc prolonging effect of citalopram (10 mg to 20 mg, mean QTc increase 7.8 (SE 3.6) ms, adjusted P<0.05; and 20 mg to 40 mg, mean QTc increase 10.3 (4.0) ms, adjusted P<0.01). CONCLUSIONS This study confirmed a modest prolongation of QT interval with citalopram, and identified additional antidepressants with similar observed risk. Pharmacovigilance studies using electronic health record data may be a useful method of identifying potential risk associated with treatments.


COVID-19 and emergency planning.


Training and Fit Testing of Health Care Personnel for Reusable Elastomeric Half-Mask Respirators Compared With Disposable N95 Respirators.


title: Hospital-acquired infection in public hospital buildings in the Philippines: Is the type of ventilation increasing the risk?

text: INTRODUCTION Hospital-acquired infections (HAIs) are associated with increased morbidity and mortality, especially in developing countries. However, limited information is available about the risk of HAIs in naturally ventilated wards (NVWs) and mechanically ventilated intensive care units (MVICUs) of public hospitals in the Philippines. We aimed to assess the association between HAIs and type of ventilation in an urban tertiary care hospital in the Philippines. METHODOLOGY A cross-sectional point-prevalence survey of infections was done in NVWs and MVICUs of a tertiary care hospital in December 2013. Multivariate analyses were done to examine the associations between HAIs and type of ventilation and other risk factors. RESULTS Of the 224 patients surveyed, 63 (28%) patients had 69 HAIs. Pneumonia was the most common HAI (35%). Wards near areas with high vehicular activity had more respiratory HAI cases. Being immunocompromised is a risk factor for HAI for pediatric and adult patients. Among pediatric patients, staying in MVICUs had a lower risk for HAIs (adjusted odds ratio [AOR]: 0.33; 95% confidence interval [CI]: 0.10-1.08) compared to staying in NVWs. For adult patients, a higher risk for HAIs (AOR: 2.41; 95% CI: 0.29-18.20) was observed in MVICUs compared to NVWs. CONCLUSIONS Type of ventilation is not a risk factor for HAIs. Patients who are immunocompromised may be at a higher risk for HAI. Indoor air pollution, proximity to congested main thoroughfare, and increased human foot traffic may contribute to the susceptibility of patients to HAIs. Hospital layout should be considered in infection control.


title: Genome-wide codon usage profiling of ocular infective Chlamydia trachomatis serovars and drug target identification.

text: Chlamydia trachomatis (C.t) is a Gram-negative obligate intracellular bacteria and is a major causative of infectious blindness and sexually transmitted diseases. Among the varied serovars of this organism, A, B and C are reported as prominent ocular pathogens. Genomic studies of these strains shall aid in deciphering potential drug targets and genomic influence on pathogenesis. Hence, in this study we performed deep statistical profiling of codon usage in these serovars. The overall base composition analysis reveals that these serovars are over biased to AU than GC. Similarly, relative synonymous codon usage also showed preference towards A/U ending codons. Parity Rule 2 analysis inferred unequal distribution of AT and GC, indicative of other unknown factors acting along with mutational pressure to influence codon usage bias (CUB). Moreover, absolute quantification of CUB also revealed lower bias across these serovars. The effect of natural selection on CUB was also confirmed by neutrality plot, reinforcing natural selection under mutational pressure turned to be a pivotal role in shaping the CUB in the strains studied. Correspondence analysis (COA) clarified that, C.t C/TW-3 to show a unique trend in codon usage variation. Host influence analysis on shaping the codon usage pattern also inferred some speculative relativity. In a nutshell, our finding suggests that mutational pressure is the dominating factor in shaping CUB in the strains studied, followed by natural selection. We also propose potential drug targets based on cumulative analysis of strand bias, CUB and human non-homologue screening.


The Covid-19 Pandemic and the Incidence of Acute Myocardial Infarction.


title: NMR metabolomics of human blood and urine in disease research.

text: This paper reviews the main applications of NMR metabolomics of blood and urine in disease research, over the last 5 years. The broad range of disease types addressed attests the increasing interest within the academic and medical communities to explore the recognised potential of metabolomics to (1) provide insight into underlying disease pathogenesis and (2) unveil new metabolic markers for disease diagnosis and follow up. Importantly, most recent studies reveal an increasing awareness of possible limitations and pitfalls of the metabolomics approach, together with efforts for improved study design and statistical validation, which are crucial requisites for the sound development of NMR metabolomics and its progress into the clinical setting.


title: Compliant neurovascular balloon catheters may not be compatible with liquid embolic materials: intraprocedural rupture of the protecting balloon during tumor embolization using n-butyl cyanoacrylate and lipiodol mixture.

text: BACKGROUND Simultaneous use of balloon catheters with embolic materials can cause unwanted rupture of the balloon occlusion catheters, which might cause a serious problem. Therefore, knowledge of the compatibility of occlusion balloon catheters with liquid embolic materials is important in various interventional procedures. OBJECTIVE To determine the compatibility of occlusion balloon catheters with commonly used embolic materials in vitro. METHODS We used three types of occlusion balloon catheters (Scepter C, Microvention, Tustin, California, USA; Hyperform, Covidien, Irvine, California, USA; and Ascent, Codman Neurovascular, Raynham, Massachusetts, USA) to test their tolerances to Lipiodol, n-butyl cyanoacrylate (NBCA; Histoacryl; B Braun, Melsungen, Germany), and dimethyl sulfoxide (DMSO) with Onyx. The balloon was inflated just as it is in an endovascular procedure, then put on a Petri dish to observe its morphological change after one drop of liquid embolic material was added using a 1 mL syringe. The presence of rupture and the time to rupture were evaluated by constant video monitoring. Additionally, we observed morphological changes of the balloon catheter surface after contact with embolic materials with a scanning electron microscope. RESULTS Lipiodol or a 33% NBCA-Lipiodol mixture dropping onto the three types of balloon catheter resulted in ruptures of all three. All three types of balloon catheter were tolerant to NBCA and to DMSO followed by Onyx. CONCLUSIONS Glue embolization should not be performed with all three kinds of balloon catheter on the market, but DMSO and Onyx are compatible with those balloon catheters.


title: Initial multicenter technical experience with the Apollo device for minimally invasive intracerebral hematoma evacuation.

text: BACKGROUND No conventional surgical intervention has been shown to improve outcomes for patients with spontaneous intracerebral hemorrhage (ICH) compared with medical management. OBJECTIVE We report the initial multicenter experience with a novel technique for the minimally invasive evacuation of ICH using the Penumbra Apollo system (Penumbra Inc, Alameda, California). METHODS Institutional databases were queried to perform a retrospective analysis of all patients who underwent ICH evacuation with the Apollo system from May 2014 to September 2014 at 4 centers (Medical University of South Carolina, Stony Brook University, University of California at San Diego, and Semmes-Murphy Clinic). Cases were performed either in the neurointerventional suite, operating room, or in a hybrid operating room/angiography suite. RESULTS Twenty-nine patients (15 female; mean age, 62 ± 12.6 years) underwent the minimally invasive evacuation of ICH. Six of these parenchymal hemorrhages had an additional intraventricular hemorrhage component. The mean volume of ICH was 45.4 ± 30.8 mL, which decreased to 21.8 ± 23.6 mL after evacuation (mean, 54.1 ± 39.1% reduction; P < .001). Two complications directly attributed to the evacuation attempt were encountered (6.9%). The mortality rate was 13.8% (n = 4). CONCLUSION Minimally invasive evacuation of ICH and intraventricular hemorrhage can be achieved with the Apollo system. Future work will be required to determine which subset of patients are most likely to benefit from this promising technology.


title: Right ventricular outflow tract prestenting with AndraStent XXL before percutaneous pulmonary valve implantation.

text: BACKGROUND The indications for percutaneous pulmonary valve implantation (PPVI) have been extended to include large dysfunctional right ventricular outflow tracts (RVOTs). Prestenting of the RVOT is commonly performed before PPVI in order to ensure a stable landing zone. The AndraStent XXL (AndraMed GmbH, Reutlingen, Germany), a cobalt-chromium stent with semi-open cell design, has unique mechanical properties in this indication but is no longer available in France. AIMS To assess the efficiency of AndraStent XXL before PPVI. METHODS In this retrospective multicentre cohort study, 86 AndraStents XXL were implanted in 77 patients in 6 centres. RESULTS PPVI was indicated mainly for pulmonary regurgitation (75.3%) in native or patched RVOT (88.3%). The stents were manually mounted on balloon catheters and delivered through sheaths using a conventional femoral approach. PPVI was performed successfully in 97.4% of patients after successful prestenting, generally during the same procedure (77.9%). There were no deaths associated with stent implantation, and four patients experienced five complications, mainly stent embolization, including one requiring surgery. Neither stent fracture nor dysfunction were observed in any patient during a mean follow-up of 19.2±8.7months. Stent analysis showed an excellent maximal stent expansion (97.1%) regardless of balloon size. A 22.3%±3.4 stent shortening with a 30mm balloon was observed. CONCLUSIONS Implantation of large cobalt-chromium AndraStent XXL stents is efficient for prestenting before PPVI.


Gradual orbital contraction after facial bipartition: correction of wide no. 0 to 14 craniofacial cleft.


title: Impact of metal and plastic stents on endoscopic ultrasound-guided aspiration cytology and core histology of head of pancreas masses.

text: BACKGROUND Stents are frequently placed in patients with biliary obstruction due to a mass in the head of the pancreas. The impact of plastic or self-expandable metal stents (SEMSs) on endoscopic ultrasound (EUS)-guided tissue sampling is unclear. This study aimed to assess, using strict pathological criteria, whether stents impair fine-needle aspiration (FNA) or fine-needle biopsy (FNB). METHODS All patients with a solid mass in the head of the pancreas who underwent EUS-guided tissue sampling between 2010 and 2016 at our unit were included. Factors with possible impact on diagnostic performance were analyzed using logistic regression. Analysis was performed using both strict (malignant only) and less strict (suspicious for malignancy) cutoffs. RESULTS Of 631 individuals undergoing 698 procedures, 535 (84.8 %) had a final diagnosis of malignancy, 141 had SEMS, 149 had plastic stents, and 341 had no stent. Using strict criteria, SEMS were associated with an increased occurrence of incorrect diagnosis of EUS tissue sampling, with an odds ratio (OR) of 1.96 (95 % confidence interval [CI] 1.24 - 3.10). Increasing tumor size (OR 0.72, 95 %CI 0.59 - 0.87), increasing number of passes (OR 0.84, 95 %CI 0.72 - 0.99), and fork-tip biopsy needle (OR 0.52, 95 %CI 0.31 - 0.86) were independently associated with a decrease in incorrect diagnosis. Repeat tissue sampling was more common with SEMSs (10.2 %) than with plastic stents (2.9 %) or no stents (4.5 %) (P < 0.02). CONCLUSION SEMS use had a negative impact on tissue diagnosis in pancreatic head masses, whereas use of a fork-tip biopsy needle and increasing number of passes were independently associated with improved accuracy.


title: Evaluation of polymorphisms in inflammatory mediator and cellular adhesion genes as risk factors for feline infectious peritonitis.

text: OBJECTIVES Feline infectious peritonitis (FIP) is a high mortality infectious disease. Single nucleotide polymorphisms (SNPs) in the genes encoding interferon gamma (IFNG), tumour necrosis factor alpha (TNFA) and dendritic cell-specific intercellular adhesion molecule-grabbing non-integrin (DC-SIGN; CD209) have been associated with increased and decreased risk of developing FIP. This study was designed to determine whether these associations were present in a UK population of pedigree cats using samples from cats euthanased with a confirmed diagnosis (FIP, n = 22; non-FIP, n = 10) or clinically healthy cats over 11 years of age (n = 3). METHODS DNA was extracted from tissue (n = 32) or blood (n = 3) and PCR performed for regions of IFNG, TNFA and CD209. PCR amplicons were sequenced, each SNP genotype was determined, and genotype/allele frequency for each SNP and FIP status were compared. RESULTS No significant association was found between the genotype and FIP status for any SNP analysed. There was a trend for the heterozygous CT genotype at both IFNG g.401 and IFNG g.408 to be associated with FIP (P = 0.13), but this genotype was also found in a substantial proportion of non-FIP cats. There was also a trend for the heterozygous CT genotype at IFNG g.428 to be associated with FIP (P = 0.06), although most cats with FIP had the CC genotype at this locus. No associations were found between any allele at TNFA g.-421, CD209 g.1900, CD209 g.2276, CD209 g.2392 and CD209 g.2713 and FIP. CONCLUSIONS AND RELEVANCE The use of the IFNG, TNFA and CD209 SNPs described to predict the risk of FIP cannot currently be recommended.


title: A simulator study of tube exchange with three different designs of double-lumen tubes.

text: BACKGROUND We sought to determine whether the design of 3 different double-lumen endobronchial tubes (DLT) (Rusch, Mallinckrodt, Fuji) has an effect on the ease of placement over an airway exchange catheter (AEC) using a video laryngoscope. METHODS A convenience sample of 17 anesthesia residents and fellows with at least 3 years of anesthesia training was recruited from teaching hospitals in Toronto for a randomized crossover trial. Each participant passed each DLT over an AEC in an airway simulator, visualized and video recorded via a video laryngoscope (GlideScope). The order of exchange was randomized by blindly pulling the name of the manufacturer of a DLT from a box. The primary outcome was time to intubate, defined as time from the bronchial lumen entering the GlideScope view to the bronchial lumen passing the vocal cords. Also recorded were participants' subjective rating of the ease of use and failure rate, defined as an attempt >150-second duration. RESULTS Time to intubate was faster with the Fuji-Phycon DLT (median 2 seconds) compared with both the Rusch (median 27 seconds, P = 0.0144) and Mallinckrodt (median 21 seconds, P = 0.0117). On a scale of 1 to 10, with 10 being very easy to use and 1 being very difficult, the Fuji-Phycon was judged to be easier to use (median 10 seconds) compared with the Rusch (median 3, P = 0.0186) and the Mallinckrodt (median 4 seconds, P = 0.0123). The Rusch was associated with significantly more failures than the other DLTs, P = 0.002. CONCLUSIONS The Fuji-Phycon DLT was easier to pass over an AEC in this simulator trial and warrants consideration in patients with difficult airways who require 1-lung ventilation.


title: Endogenous hepadnaviruses, bornaviruses and circoviruses in snakes.

text: We report the discovery of endogenous viral elements (EVEs) from Hepadnaviridae, Bornaviridae and Circoviridae in the speckled rattlesnake, Crotalus mitchellii, the first viperid snake for which a draft whole genome sequence assembly is available. Analysis of the draft assembly reveals genome fragments from the three virus families were inserted into the genome of this snake over the past 50 Myr. Cross-species PCR screening of orthologous loci and computational scanning of the python and king cobra genomes reveals that circoviruses integrated most recently (within the last approx. 10 Myr), whereas bornaviruses and hepadnaviruses integrated at least approximately 13 and approximately 50 Ma, respectively. This is, to our knowledge, the first report of circo-, borna- and hepadnaviruses in snakes and the first characterization of non-retroviral EVEs in non-avian reptiles. Our study provides a window into the historical dynamics of viruses in these host lineages and shows that their evolution involved multiple host-switches between mammals and reptiles.


title: Comparative study of lung sealants in a porcine ex vivo model.

text: BACKGROUND Lung sealants are often used to prevent alveolar air leaks after lung resection surgery. Some sealants have shown to be effective in clinical studies, but extensive comparative evaluation has not yet been conducted. We aimed to evaluate different sealant burst pressures in an ex vivo model mimicking air leakage after lung resection. METHODS Fifty-four porcine lungs comprised the study material. Six different sealants were evaluated: Bioglue (V-Tech, Roskilde, Denmark), TachoSil (Nycomed, Roskilde, Denmark), Tisseel (Baxter, Allerød, Denmark), Evicel (OMRIX biopharmaceuticals S.A, Rhode-St-Genèse, Belgium), TissuePatchDural (Vingmed, Roskilde, Denmark), and Pleuraseal (Covidien, Copenhagen, Denmark). After creating a standardized pleural defect, each lung was randomized into 1 of the 6 treatment groups (n= 9). Each lung was ventilated with incremental airway pressure. Air leakage was assessed after each increment. If leakage occurred, the burst pressure was recorded. RESULTS The Evicel fibrin sealant and Tisseel fibrin sealant exhibited significantly lower burst pressures compared with the Bioglue, TachoSil, and Pleuraseal (p < 0.05). Bioglue had the highest median burst pressure (55 cm H(2)O) followed by TachoSil (35 cm H(2)O), PleuraSeal (35 cm H(2)O), TissuePatchDural (25 cm H(2)O), Evicel (15 cm H(2)O), and Tisseel (15 cm H(2)O). CONCLUSIONS This model has shown to be feasible in determining and comparing the burst pressures of different lung sealants. Further studies are needed to determine responses in living tissue and burst pressure over time in vivo.


title: Extensive gene remodeling in the viral world: new evidence for nongradual evolution in the mobilome network.

text: Complex nongradual evolutionary processes such as gene remodeling are difficult to model, to visualize, and to investigate systematically. Despite these challenges, the creation of composite (or mosaic) genes by combination of genetic segments from unrelated gene families was established as an important adaptive phenomena in eukaryotic genomes. In contrast, almost no general studies have been conducted to quantify composite genes in viruses. Although viral genome mosaicism has been well-described, the extent of gene mosaicism and its rules of emergence remain largely unexplored. Applying methods from graph theory to inclusive similarity networks, and using data from more than 3,000 complete viral genomes, we provide the first demonstration that composite genes in viruses are 1) functionally biased, 2) involved in key aspects of the arm race between cells and viruses, and 3) can be classified into two distinct types of composite genes in all viral classes. Beyond the quantification of the widespread recombination of genes among different viruses of the same class, we also report a striking sharing of genetic information between viruses of different classes and with different nucleic acid types. This latter discovery provides novel evidence for the existence of a large and complex mobilome network, which appears partly bound by the sharing of genetic information and by the formation of composite genes between mobile entities with different genetic material. Considering that there are around 10E31 viruses on the planet, gene remodeling appears as a hugely significant way of generating and moving novel sequences between different kinds of organisms on Earth.


title: Detection of infectious influenza virus in cough aerosols generated in a simulated patient examination room.

text: BACKGROUND The potential for aerosol transmission of infectious influenza virus (ie, in healthcare facilities) is controversial. We constructed a simulated patient examination room that contained coughing and breathing manikins to determine whether coughed influenza was infectious and assessed the effectiveness of an N95 respirator and surgical mask in blocking transmission. METHODS National Institute for Occupational Safety and Health aerosol samplers collected size-fractionated aerosols for 60 minutes at the mouth of the breathing manikin, beside the mouth, and at 3 other locations in the room. Total recovered virus was quantitated by quantitative polymerase chain reaction and infectivity was determined by the viral plaque assay and an enhanced infectivity assay. RESULTS Infectious influenza was recovered in all aerosol fractions (5.0% in >4 μm aerodynamic diameter, 75.5% in 1-4 μm, and 19.5% in <1 μm; n = 5). Tightly sealing a mask to the face blocked entry of 94.5% of total virus and 94.8% of infectious virus (n = 3). A tightly sealed respirator blocked 99.8% of total virus and 99.6% of infectious virus (n = 3). A poorly fitted respirator blocked 64.5% of total virus and 66.5% of infectious virus (n = 3). A mask documented to be loosely fitting by a PortaCount fit tester, to simulate how masks are worn by healthcare workers, blocked entry of 68.5% of total virus and 56.6% of infectious virus (n = 2). CONCLUSIONS These results support a role for aerosol transmission and represent the first reported laboratory study of the efficacy of masks and respirators in blocking inhalation of influenza in aerosols. The results indicate that a poorly fitted respirator performs no better than a loosely fitting mask.


title: Distress screening and supportive care referrals used by telephone-based health services: a systematic review.

text: PURPOSE People affected by chronic diseases such as cancer report high levels of distress and a need for psychosocial support. It is unclear whether telephone-based services for people affected by chronic disease are a practical setting for implementing distress screening, referral protocols and rescreening to direct supportive care where it is needed. This systematic review aimed to describe the published literature regarding distress screening and supportive care referral practices in telephone-based services for people affected by chronic diseases such as cancer. METHODS A systematic literature search of MEDLINE, Embase, PsycInfo, CINAHL, Cochrane and Scopus was conducted in February 2018. Included quantitative studies involved: patients or caregivers affected by chronic diseases including cancer and describe a health service assessing psychosocial needs or distress via telephone. Extracted data included the type of cancer or other chronic disease, sample size, screening tool, referral or rescreening protocols, and type of health service. RESULTS The search identified 3989 potential articles with additional searches returning 30 studies (n = 4019); fourteen were eligible for full-text review. Of the 14 studies, 13 included cancer patients. Studies were across multiple settings and identified nine distress screening tools in use. CONCLUSION The reviewed studies indicate that validated distress-screening tools are being used via telephone to identify distress, particularly in relation to cancer. Screening-driven supportive care referrals are also taking place in telephone-based services. However, not all services use an established referral protocol. Ongoing rescreening of callers' distress is also limited despite it being an important recommendation from psycho-oncology guidelines.


title: Journal of Clinical Monitoring and Computing 2015 end of year summary: tissue oxygenation and microcirculation.

text: Last year we started this series of end of year summaries of papers published in the 2014 issues of the Journal Of Clinical Monitoring And Computing with a review on near infrared spectroscopy (Scheeren et al. in J Clin Monit Comput 29(2):217-220, 2015). This year we will broaden the scope and include papers published in the field of tissue oxygenation and microcirculation, or a combination of both entities. We present some promising new technologies that might enable a deeper insight into the (patho)physiology of certain diseases such as sepsis, but also in healthy volunteers. These may help researchers and clinicians to evaluate both tissue oxygenation and microcirculation beyond macro-hemodynamic measurements usually available at the bedside.


title: Systematic review of community participation interventions to improve maternal health outcomes in rural South Asia.

text: BACKGROUND This is a systematic review on the effectiveness of community interventions in improving maternal health care outcomes in South Asia. METHODS We searched electronic databases to June 2017. Randomised or cluster randomised studies in communities within rural/remote areas of Nepal, Bangladesh, India and Pakistan were included. Data were analysed as risk ratios (RR) or odds ratios (OR), and effects were adjusted for clustering. Meta-analyses were performed using random-effects and evidence quality was assessed. RESULTS Eleven randomised trials were included from 5440 citations. Meta-analysis of all community interventions combined compared with control showed a small improvement in the number of women attending at least one antenatal care visit (RR 1.19, 95% CI 1.06 to 1.33). Two community mobilisation sub groups: home care using both male and female mobilisers, and education by community mobilisers, improved the number of women attending at least one antenatal visit. There was no difference in the number of women attending at least one antenatal visit for any other subgroup. There was no difference in the number of women attending 3 or more antenatal visits for all community interventions combined, or any community subgroup. Likewise, there was no difference in attendance at birth between all community interventions combined and control. Health care facility births were modestly increased in women's education groups (adjusted RR (1.15, 95% CI 1.11 to 1.20; 2 studies)). Risk of maternal deaths after 2 years (RR 0.63, 95% CI 0.24 to 1.64; 5 studies), and 3 years (RR 1.11, 95% CI 0.52 to 2.36; 2 studies), were no different between women's education groups and control. Community level mobilisation rather than health care messages at district level improved the numbers of women giving birth at health care facilities (RR1.09 (95%CI 1.06 to 1.13; 1 study)). Maternal health care knowledge scores improved in two community-based interventions, one involving education of male community members. CONCLUSION Women's education interventions may improve the number of women seeking birth at a health care facility, but the evidence is of low quality. No impact on maternal mortality was observed Future research should explore the effectiveness of including male mobilisers. TRIAL REGISTRATION This systematic review is registered with PROSPERO CRD42016033201 .


Phage therapy for severe infections tested in the first multicentre trial.


title: WHO International Health Regulations (IHR) vs COVID-19 Uncertainty.

text: One of WHO primary function is to control and monitor internationally the spread of infectious diseases of the common killers. After SARS-COV, the International Health Regulations (IHR) was adopted in 2005 by all 194 member states to set up national preparedness for an efficient "early alert and response system". COVID-19 is a novel virus with an unpredictable course and many uncertainties about its biological, clinical and epidemiological characteristics. COVID-19 is a game changer and calls for a revision of IHR as well as a more biological, clinical and community-cantered preparedness strategy.


title: Genomic characterization of severe acute respiratory syndrome-related coronavirus in European bats and classification of coronaviruses based on partial RNA-dependent RNA polymerase gene sequences.

text: Bats may host emerging viruses, including coronaviruses (CoV). We conducted an evaluation of CoV in rhinolophid and vespertilionid bat species common in Europe. Rhinolophids carried severe acute respiratory syndrome (SARS)-related CoV at high frequencies and concentrations (26% of animals are positive; up to 2.4×10(8) copies per gram of feces), as well as two Alphacoronavirus clades, one novel and one related to the HKU2 clade. All three clades present in Miniopterus bats in China (HKU7, HKU8, and 1A related) were also present in European Miniopterus bats. An additional novel Alphacoronavirus clade (bat CoV [BtCoV]/BNM98-30) was detected in Nyctalus leisleri. A CoV grouping criterion was developed by comparing amino acid identities across an 816-bp fragment of the RNA-dependent RNA polymerases (RdRp) of all accepted mammalian CoV species (RdRp-based grouping units [RGU]). Criteria for defining separate RGU in mammalian CoV were a >4.8% amino acid distance for alphacoronaviruses and a >6.3% distance for betacoronaviruses. All the above-mentioned novel clades represented independent RGU. Strict associations between CoV RGU and host bat genera were confirmed for six independent RGU represented simultaneously in China and Europe. A SARS-related virus (BtCoV/BM48-31/Bulgaria/2008) from a Rhinolophus blasii (Rhi bla) bat was fully sequenced. It is predicted that proteins 3b and 6 were highly divergent from those proteins in all known SARS-related CoV. Open reading frame 8 (ORF8) was surprisingly absent. Surface expression of spike and staining with sera of SARS survivors suggested low antigenic overlap with SARS CoV. However, the receptor binding domain of SARS CoV showed higher similarity with that of BtCoV/BM48-31/Bulgaria/2008 than with that of any Chinese bat-borne CoV. Critical spike domains 472 and 487 were identical and similar, respectively. This study underlines the importance of assessments of the zoonotic potential of widely distributed bat-borne CoV.


title: Suppression of anti-drug antibodies to infliximab or adalimumab with the addition of an immunomodulator in patients with inflammatory bowel disease.

text: BACKGROUND Loss of response to anti-tumour necrosis factor (TNF) therapy in patients with inflammatory bowel disease (IBD) is often caused by anti-drug antibody formation with neutralisation of drug effect. Addition of an immunomodulator has been suggested to reduce immunogenicity, leading to regained response. AIM To investigate whether addition of an immunomodulator to anti-TNF monotherapy could lead to anti-drug antibody suppression and regained clinical response in IBD patients. METHODS We retrospectively collected measurements of infliximab or adalimumab serum concentrations and anti-drug antibodies to identify anti-drug positive patients with loss response who were given an immunomodulator. RESULTS Anti-drug antibodies against infliximab and adalimumab were detected in 98/376 (26%) and in 61/226 (27%) patients, respectively. Immunomodulators were given to 17/159 patients. Clinical response was recaptured in 6/10 patients receiving a thiopurine and in all (7/7) patients receiving methotrexate. In 7/8 patients on infliximab, serum concentrations increased (median 2.84 μg/mL; IQR: 1.19-4.98) and in 6/9 patients on adalimumab (median 3.10 μg/mL; IQR: 1.45-4.45). This was accompanied by a decrease in anti-drug antibodies to undetectable levels (median 11 months for both anti-TNF agents). In 23 patients, no immunomodulator was added but anti-TNF interval was shortened (17/23) or dosage was increased (6/23), which resulted in a clinical response in 10/17 and 2/6 patients, respectively. CONCLUSION In 77% of IBD patients with loss of response due to immunogenicity, addition of immunomodulator resulted in undetectable anti-drug antibody levels, increased serum drug concentrations and regained clinical response. This strategy should be considered in this patient population before switching to other agents.


title: Extra corporeal membrane oxygenation in the critical trauma patient.

text: PURPOSE OF REVIEW The purpose of this review is to describe recent evidence regarding the use of extracorporeal membrane oxygenation (ECMO) as salvage therapy for severe cardiac or respiratory failure in patients with trauma. The characteristics of this cohort of patients, including the risk of bleeding and the need for systemic anticoagulation, are generally considered as relative contraindications to ECMO treatment. However, recent evidence suggests that the use of ECMO should be taken in consideration even in this group of patients. RECENT FINDINGS The recent findings suggest that venous-venous ECMO can be feasible in the treatment of refractory respiratory failure and severe acute respiratory distress syndrome trauma-related. The improvement of ECMO techniques including the introduction of centrifugal pumps and heparin-coated circuits are progressively reducing the amount of heparin required; moreover, the application of heparin-free ECMO showed good outcomes and minimal complications. Venous-arterial ECMO has emerged as a salvage intervention in patients with cardiogenic shock and after cardiac arrest. Venous-arterial ECMO provides circulatory support allowing time for other treatments to promote recovery in presence of acute cardiopulmonary failure. Only poor-quality evidence is available, for venous-arterial ECMO in trauma patients. SUMMARY ECMO can be considered as a safe rescue therapy even in trauma patients, including neurological injury, chest trauma as well as burns. However, evidence is still poor; further studies are warranted focusing on trauma patients undergoing ECMO, to better clarify the effect on survival, the type and dose of anticoagulation to use, as well as the utility of dedicated multidisciplinary trauma-ECMO units.


title: Retrospective Analysis of Radiological Recurrence Patterns in Glioblastoma, Their Prognostic Value And Association to Postoperative Infarct Volume.

text: Recent studies suggested that postoperative hypoxia might trigger invasive tumor growth, resulting in diffuse/multifocal recurrence patterns. Aim of this study was to analyze distinct recurrence patterns and their association to postoperative infarct volume and outcome. 526 consecutive glioblastoma patients were analyzed, of which 129 met our inclusion criteria: initial tumor diagnosis, surgery, postoperative diffusion-weighted imaging and tumor recurrence during follow-up. Distinct patterns of contrast-enhancement at initial diagnosis and at first tumor recurrence (multifocal growth/progression, contact to dura/ventricle, ependymal spread, local/distant recurrence) were recorded by two blinded neuroradiologists. The association of radiological patterns to survival and postoperative infarct volume was analyzed by uni-/multivariate survival analyses and binary logistic regression analysis. With increasing postoperative infarct volume, patients were significantly more likely to develop multifocal recurrence, recurrence with contact to ventricle and contact to dura. Patients with multifocal recurrence (Hazard Ratio (HR) 1.99, P = 0.010) had significantly shorter OS, patients with recurrent tumor with contact to ventricle (HR 1.85, P = 0.036), ependymal spread (HR 2.97, P = 0.004) and distant recurrence (HR 1.75, P = 0.019) significantly shorter post-progression survival in multivariate analyses including well-established prognostic factors like age, Karnofsky Performance Score (KPS), therapy, extent of resection and patterns of primary tumors. Postoperative infarct volume might initiate hypoxia-mediated aggressive tumor growth resulting in multifocal and diffuse recurrence patterns and impaired survival.


title: Proceedings from Duke resistant hypertension think tank.

text: To identify patients at increased risk for cardiovascular outcomes, apparent treatment resistant hypertension (aTRH) is defined as having a blood pressure (BP) above goal despite the use of ≥3 antihypertensive therapies of different classes at maximally tolerated doses, ideally including a diuretic. In light of growing scientific interest in the treatment of this group, a multistakeholder think tank was convened to discuss the current state of knowledge, improve the care of these patients, and identify appropriate study populations for future observational and randomized trials in the field. Although recent epidemiologic studies in selected populations estimate that the prevalence of aTRH is 10% to 15% of hypertensive patients, further large-scale observational studies will be needed to better elucidate risk factors. To spur the development of therapies for aTRH, the development of an "aTRH" label for pharmacologic and device therapies with a developmental pathway including treatment added to the use of existing therapies is favored. Although demonstration of adequate BP lowering should be sufficient to gain Food and Drug Administration approval for therapies targeting aTRH, assessment of improvement in quality of life and cardiovascular outcomes is also desirable and considered in Centers for Medicare and Medicaid Services coverage decisions. Device trials under the aTRH label will need uniform and consistent processes for defining appropriate patient populations as well as postapproval registries assessing both long-term safety and duration of responses. Finally, patients with aTRH are likely to benefit from evaluation by a hypertension team to assure proper patient identification, diagnostic work-up, and therapeutic management before consideration of advanced or novel therapies to lower BP.


title: Changes in depressive symptoms and social functioning in the sequenced treatment alternatives to relieve depression study.

text: Major depressive disorder (MDD) profoundly affects social functioning, including the ability to enjoy social activities with peers, friends, and family members. We sought to compare changes in social functioning and depressive symptoms in the first level of the Sequenced Treatment Alternatives to Relieve Depression (STAR*D) study. Adult outpatients (N = 2876) with diagnoses of MDD were treated using flexible doses of citalopram for up to 14 weeks. We compared the change over the course of treatment in the social activities item of the Work and Social Adjustment Scale to the change in individual items of the Quick Inventory of Depressive Symptoms-Self-Rated (QIDS-SR). Improvement in social functioning was modestly positively correlated with improvement in sad mood, concentration/decision making, involvement, and energy/fatigability. Only 16% to 22% of the variance in the change in social functioning was accounted for by these symptoms, and only 32% was accounted for by the total QIDS-SR score. In this large real-world sample of outpatients treated using citalopram, changes in depressive symptoms do not entirely explain improvements in social functioning.


title: Prevalence and Determinants of Chronic Post-Traumatic Stress Disorder After Floods.

text: OBJECTIVE To explore the prevalence and determinants of chronic post-traumatic stress disorder (PTSD) among flood victims. METHODS A cross-sectional survey was carried out in 2014 among individuals who had experienced the 1998 floods and had been diagnosed with PTSD in 1999 in Hunan, China. Cluster sampling was used to select subjects from the areas that had been surveyed in 1999. PTSD was diagnosed according to DSM-IV criteria, social support was measured according to a Social Support Rating Scale, coping style was measured according to a Simplified Coping Style Questionnaire, and personality was measured by use of the revised Eysenck Personality Questionnaire Short Scale for Chinese. Data were collected through face-to-face interviews by use of a structured questionnaire. Multivariate logistic regression analysis was used to reveal the determinants of chronic PTSD. RESULTS A total of 123 subjects were interviewed, 17 of whom (14.4%) were diagnosed with chronic PTSD. Chronic PTSD was significantly associated with disaster stressors (odds ratio [OR]: 1.74; 95% confidence interval [CI]: 1.22-2.47), nervousness (OR: 1.09; 95% CI: 1.01-1.17), and social support (OR: 0.85; 95 CI%: 0.74-0.98). CONCLUSIONS Chronic PTSD in flood victims is significantly associated with disaster stressors, nervousness, and social support. These factors may play important roles in identifying persons at high risk of chronic PTSD.


Healthcare information for all.


title: Evidence-based treatment of chronic leg ulcers.

text: BACKGROUND Chronic leg ulcers are defined as those that show no tendency to heal after 3 months of appropriate treatment or are still not fully healed at 12 months. In this article, we present an approach to the challenging problem of chronic leg ulcers that is based on the principles of evidence-based medicine, i.e., the explicit use of the best available scientific evidence as a guide to treatment. METHODS Selective review of the relevant literature, including current guidelines and meta-analyses, concerning diagnostic and therapeutic strategies for chronic leg ulcers. RESULTS The main types of causally directed treatment are: vein surgery to eliminate pathological reflux, interventions to improve the circulation in arterial occlusive disease, and treatment of underlying diseases, such as diabetes mellitus. CONCLUSION Physicians providing modern evidence-based management of chronic leg ulcers should make use of their own clinical experience in combination with the best current scientific evidence. It seems clear that the many available treatment options should be evaluated critically in an interdisciplinary setting. In particular, causally directed treatment must be provided in addition to symptomatic, stage-based local wound treatment.


title: Health professional-delivered obesity prevention interventions during the first 1,000 days: A systematic review of external validity reporting.

text: Background: Childhood obesity prevention interventions delivered by health professionals during the first 1,000 days show some evidence of effectiveness, particularly in relation to behavioural outcomes. External validity refers to how generalisable interventions are to populations or settings beyond those in the original study. The degree to which external validity elements are reported in such studies is unclear however. This systematic review aimed to determine the extent to which childhood obesity interventions delivered by health professionals during the first 1,000 days report on elements that can be used to inform generalizability across settings and populations. Methods: Eligible studies meeting study inclusion and exclusion criteria were identified through a systematic review of 11 databases and three trial registers. An assessment tool based on the RE-AIM (Reach, Effectiveness, Adoption, Implementation, Maintenance) framework was used to assess the external validity of included studies. It comprised five dimensions: reach and representativeness of individuals, reach and representativeness of settings, implementation and adaptation, outcomes for decision making maintenance and/or institutionalisation. Two authors independently assessed the external validity of 20% of included studies; discrepancies were resolved, and then one author completed assessments of the remaining studies. Results: In total, 39 trials involving 46 interventions published between 1999 and 2019 were identified. The majority of studies were randomized controlled trials (n=24). Reporting varied within and between dimensions. External validity elements that were poorly described included: representativeness of individuals and settings, treatment receipt, intervention mechanisms and moderators, cost effectiveness, and intervention sustainability and acceptability. Conclusions: Our review suggests that more emphasis is needed on research designs that consider generalisability, and the reporting of external validity elements in early life childhood obesity prevention interventions. Important gaps in external validity reporting were identified that could facilitate decisions around the translation and scale-up of interventions from research to practice. Registration: PROSPERO CRD42016050793 03/11/16.


title: Perforated sigmoid diverticulitis in a lumbar hernia after iliac crest bone graft--a case report.

text: BACKGROUND The combination of perforated diverticulitis in a lumbar hernia constitutes an extremely rare condition. CASE PRESENTATION We report a case of a 66 year old Caucasian woman presenting with perforated sigmoid diverticulitis localized in a lumbar hernia following iliac crest bone graft performed 18 years ago. Emergency treatment consisted of laparoscopic peritoneal lavage. Elective sigmoid resection was scheduled four months later. At the same time a laparoscopic hernia repair with a biologic mesh graft was performed. CONCLUSION This case shows a very seldom clinical presentation of lumbar hernia. Secondary colonic resection and concurrent hernia repair with a biologic implant have proven useful in treating this rare condition.


title: Factors associated with people's behavior in social isolation during the COVID-19 pandemic.

text: This paper presents the results of an opinion poll conducted in Brazil on the perception of social isolation during the COVID-19 pandemic. The questionnaire was prepared on Google Forms, disseminated through social networks, with questions about the socioeconomic profile and factors associated with isolation. A non-probabilistic sample was obtained with 16,440 respondents. Data were analyzed using the Stata 13 software. Social interaction was the most affected aspect among people with higher education and income (45.8%), and financial problems caused a more significant impact (35%) among people with low income and education. Those who practice some physical activity showed lower levels of stress 13%, as well as greater normality in sleep 50.3%. People who reported living in worse habitability conditions reported willingness to remain isolated for less time, 73.9%. Among non-isolated people (10.7% of the total sample), 75.8% believe that social isolation will reduce the number of victims of COVID-19. We conclude, based on this sample, that the perception about social isolation as a pandemic mitigation action varies by income, education, age, and gender. However, most believe that it is the most appropriate control measure and are willing to wait as long as necessary to contribute to the fight against COVID-19.


Of Mosquito Nets and Condoms: The Zika Virus Challenge.


title: Multimodal image-guided surgery of HER2-positive breast cancer using [111In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast tumor model.

text: BACKGROUND Combining modalities using dual-labeled antibodies may allow preoperative and intraoperative tumor localization and could be used in image-guided surgery to improve complete tumor resection. Trastuzumab is a monoclonal antibody against the human epidermal growth factor-2 (HER2) receptor and dual-labeled trastuzumab with both a fluorophore (IRDye800CW) and a radioactive label (111In) can be used for multimodal imaging of HER2-positive breast cancer. The aim of this study was to demonstrate the feasibility of HER2-targeted multimodal imaging using [111In]In-DTPA-trastuzumab-IRDye800CW in an orthotopic breast cancer model. METHODS Trastuzumab was conjugated with p-isothiocyanatobenzyl (ITC)-diethylenetriaminepentaacetic acid (DTPA) and IRDye800CW-NHS ester and subsequently labeled with 111In. In a dose escalation study, the biodistribution of 10, 30, and 100 μg [111In]In-DTPA-trastuzumab-IRDye800CW was determined 48 h after injection in BALB/c nude mice with orthotopic high HER2-expressing tumors. Also, a biodistribution study was performed in a low HER2-expressing breast cancer model. In addition, multimodal image-guided surgery was performed in each group. Autoradiography, fluorescence microscopy, and immunohistochemically stained slices of the tumors were compared for co-localization of tumor tissue, HER2 expression, fluorescence, and radiosignal. RESULTS Based on the biodistribution data, a 30 μg dose of dual-labeled trastuzumab (tumor-to-blood ratio 13 ± 2) was chosen for all subsequent studies. [111In]In-DTPA-trastuzumab-IRDye800CW specifically accumulated in orthotopic HER2-positive BT474 tumors (101 ± 7 %IA/g), whereas uptake in orthotopic low HER2-expressing MCF7 tumor was significantly lower (1.2 ± 0.2 %IA/g, p = 0.007). BT474 tumors could clearly be visualized with both micro-SPECT/CT, fluorescence imaging and subsequently, image-guided resection was performed. Immunohistochemical analyses of BT474 tumors demonstrated correspondence in fluorescence, radiosignal, and high HER2 expression. CONCLUSIONS Dual-labeled trastuzumab showed specific accumulation in orthotopic HER2-positive BT474 breast tumors with micro-SPECT/CT and fluorescence imaging and enabled image-guided tumor resection. In the clinical setting, [111In]In-DTPA-trastuzumab-IRDye800CW could be valuable for preoperative detection of (metastatic) tumors by SPECT/CT imaging, and intraoperative localization by using a gamma probe and fluorescence image-guided surgery to improve radical resection of tumor tissue in patients with HER2-positive tumors.


title: Usefulness of a flexible port for natural orifice transluminal endoscopic surgery by the transrectal and transvaginal routes.

text: We developed a flexible port for NOTES which allows the use of conventional forceps for laparoscope-assisted surgery without change. The port is not affected by the location of the through hole in the gastrointestinal tract or vagina which elicits a problem in conventional NOTES, and its length can be adjusted during surgery by cutting the port itself. The port is made of polymer resin with a low friction coefficient. Furthermore, the port walls have a square wave structure which contributes to (1) the prevention of devices, for example, endoscope, from getting stuck at the time of insertion and retrieval, (2) the prevention of port slippage in the surgical opening for port insertion, (3) the prevention of unexpected port removal, (4) the prevention of port bore deformation, and (5) the improvement of port flexibility in the longitudinal direction. We validated the insertion and retrieval capacities of commercially available forceps for laparoscope-assisted surgery and power devices. Furthermore, we used the flexible port to conduct cholecystectomy and partial gastrectomy. We could confirm that the selection of the flexible port diameter according to the device type allowed the smooth insertion and retrieval of the device and that the port produced no air leakage. We affirmed that it is possible to conduct surgery by the cross or parallel method similarly to single port surgery. We considered that the flexible port has a potential of becoming a revolutionary port in NOTES.


title: Moving stroke rehabilitation evidence into practice: a systematic review of randomized controlled trials.

text: OBJECTIVE The aim of this study was to investigate the effectiveness of interventions aimed at moving research evidence into stroke rehabilitation practice through changing the practice of clinicians. DATA SOURCES EMBASE, CINAHL, Cochrane and MEDLINE databases were searched from 1980 to April 2019. International trial registries and reference lists of included studies completed our search. REVIEW METHODS Randomized controlled trials that involved interventions aiming to change the practice of clinicians working in stroke rehabilitation were included. Bias was evaluated using RevMan to generate a risk of bias table. Evidence quality was evaluated using GRADE criteria. RESULTS A total of 16 trials were included (250 sites, 14,689 patients), evaluating a range of interventions including facilitation, audit and feedback, education and reminders. Of which, 11 studies included multicomponent interventions (using a combination of interventions). Four used educational interventions alone, and one used electronic reminders. Risk of bias was generally low. Overall, the GRADE criteria indicated that this body of literature was of low quality. This review found higher efficacy of trials which targeted fewer outcomes. Subgroup analysis indicated moderate-level GRADE evidence (103 sites, 10,877 patients) that trials which included both site facilitation and tailoring for local factors were effective in changing clinical practice. The effect size of these varied (odds ratio: 1.63-4.9). Education interventions alone were not effective. CONCLUSION A large range of interventions are used to facilitate clinical practice change. Education is commonly used, but in isolation is not effective. Multicomponent interventions including facilitation and tailoring to local settings can change clinical practice and are more effective when targeting fewer changes.


title: Fluorescence lifetime imaging reveals regulation of presynaptic Ca2+ by glutamate uptake and mGluRs, but not somatic voltage in cortical neurons.

text: Brain function relies on vesicular release of neurotransmitters at chemical synapses. The release probability depends on action potential-evoked presynaptic Ca2+ entry, but also on the resting Ca2+ level. Whether these basic aspects of presynaptic calcium homeostasis show any consistent trend along the axonal path, and how they are controlled by local network activity, remains poorly understood. Here, we take advantage of the recently advanced FLIM-based method to monitor presynaptic Ca2+ with nanomolar sensitivity. We find that, in cortical pyramidal neurons, action potential- evoked calcium entry (range 10-300 nM), but not the resting Ca2+ level (range 10-100 nM), tends to increase with higher order of axonal branches. Blocking astroglial glutamate uptake reduces evoked Ca2+ entry but has little effect on resting Ca2+ whereas both appear boosted by the constitutive activation of group 1/2 metabotropic glutamate receptors. We find no consistent effect of transient somatic depolarisation or hyperpolarisation on presynaptic Ca2+ entry or its basal level. The results unveil some key aspects of presynaptic machinery in cortical circuits, shedding light on basic principles of synaptic connectivity in the brain.


title: The Coronavirus Pandemic: What Does the Evidence Show?

text: Coronavirus disease 2019 (COVID-19) is a newly emerged disease that has become a global public health concern as it rapidly spread around the world. The etiologic agent responsible for this disease has been named as severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) by the International Committee on Taxonomy of Viruses as it shows similar genomic features to that of SARS-CoV which caused a pandemic in 2002. This disease first appeared in Hubei province of China and it follows human-to-human transmission but the path this virus took to set up human infection remains a mystery. By 17 April 2020, globally there have been 2,074,529 confirmed cases with 139,378 deaths because of COVID-19. SARS-CoV-2 shows several similarities with SARS?CoV, and Middle East Respiratory Syndrome Coronavirus (MERS-CoV) with its clinical presentations. This can vary from asymptomatic infection to severe disease and mortality. Real-time reverse-transcription polymerase chain reaction (rRT-PCR) screening is considered as the standard laboratory test for the diagnosis of COVID-19. There is no proven antiviral agent against SARS-CoV-2 so the treatment for COVID-19 is symptomatic, aiming for the management of the symptoms and prevention of the complications. The outbreak of COVID-19 has led to the implementation of extraordinary public health measures throughout the world. Numerous antiviral compounds used to treat other infections are being clinically researched to find possible treatment. Similarly, the traditional public health outbreak response strategy of isolation, quarantine, social distancing and community containment has been implemented in multiple countries and has played an important role in the prevention of new outbreaks. This review aims to enhance our understanding of COVID 19. Keywords: Coronavirus disease 2019; COVID-19; SARS-CoV-2; novel coronavirus 2019; severe acute respiratory syndrome-2.


Experience With a Simulator-Based Angiography Course for Neurosurgical Residents: Beyond a Pilot Program.


Patients with systemic lupus erythematosus using hydroxychloroquine or chloroquine develop severe COVID-19 at similar frequency as patients not on antimalarials: need to explore antithrombotic benefits for COVID-19 coagulopathy. Response to: 'Clinical course of COVID-19 in patients with systemic lupus erythematosus under long-term treatment with hydroxychloroquine' by Carbillon et al.


title: Robotic and laparoscopic pancreaticoduodenectomy: a hybrid approach.

text: OBJECTIVES Minimally invasive surgery is beneficial for complex operations; robotics may improve performance in these procedures; however, robotic pancreaticoduodenectomy (PD) has been plagued by long operative times. We describe a small series (n = 5) of patients who underwent a hybrid PD for treatment of obstructive jaundice and pancreatic mass. METHODS After diagnostic laparoscopy, the gallbladder was retracted cephalad and the porta hepatis was dissected. The lesser sac was opened to expose the superior mesenteric vein below the pancreas. Once the vein was cleared, the bile duct, stomach, pancreas, and jejunum were transected. After the uncinate process was cleared, the specimen was removed. The da Vinci S Surgical Robotic System was docked to perform a mucosa-to-mucosa pancreaticojejunostomy and an end-to-side choledochojejunostomy. A stapled gastrojejunostomy and drain placement completed the operation. RESULTS Five patients underwent hybrid PD between May 2006 and June 2007. All patients had a history of pancreatitis and presented with obstructive jaundice and a pancreatic mass. The operations were completed with 5 ports. The mean operative time was 7 hours. The mean hospital stay was 9.6 days. At 6 months after the operation, all patients were disease-free. CONCLUSIONS Complex procedures such as PD can be accomplished with minimally invasive surgical techniques using robotic instrumentation.


title: The identification and treatment of mental health and substance misuse problems in sexual assault services: A systematic review.

text: BACKGROUND Specialist sexual assault services, which collect forensic evidence and offer holistic healthcare to people following sexual assault, have been established internationally. In England, these services are called sexual assault referral centres (SARCs). Mental health and substance misuse problems are common among SARC attendees, but little is known about how SARCs should address these needs. This review aims to seek and synthesise evidence regarding approaches to identification and support for mental health and substance misuse problems in SARCs and corresponding services internationally; empirical evidence regarding effective service models; and stakeholders' views and policy recommendations about optimal SARC practice. METHODS A systematic review was undertaken. PsycINFO, MEDLINE, IBSS and CINAHL were searched from 1975 to August 2018. A web-based search up to December 2018 was also conducted to identify government and expert guidelines on SARCs. Quality assessment and narrative synthesis were conducted. RESULTS We included 107 papers. We found that identification based on clinical judgement, supportive counselling and referral to other services without active follow-up were the most common approaches. Evaluations of interventions for post-rape psychopathology in attendees of sexual assault services provided mixed evidence of moderate quality. Very little evidence was found regarding interventions or support for substance misuse. Stakeholders emphasised the importance of accessibility, flexibility, continuity of care, in-house psychological support, staff trained in mental health as well as specialist support for LGBT groups and people with learning difficulties. Guidelines suggested that SARCs should assess for mental health and substance misuse and provide in-house emotional support, but the extent and nature of support were not clarified. Both stakeholders and guidelines recommended close partnership between sexual assault services and local counselling services. CONCLUSIONS This review suggests that there is big variation in the mental health and substance misuse provision both across and within different sexual assault service models. We found no robust evidence about how sexual assault services can achieve good mental health and substance misuse outcomes for service users. Clearer guidance for service planners and commissioners, informed by robust evidence about optimal service organisations and pathways, is required. PROSPERO registration number: CRD42018119706.


title: Sniffing out Covid-19.

text: Georgina Mills reports on how dogs are being trained to detect coronavirus.


title: First fully laparoscopic donor hepatectomy for pediatric liver transplantation using the indocyanine green near-infrared fluorescence imaging in the Middle East: a case report.

text: Living donor liver transplantation (LDLT) is a well-established treatment modality for several pediatric end-stage liver diseases owning excellent long-term results. Left lateral sectionectomy (LLS) through an open approach is a well-standardized procedure. This technique has been modified for a fully laparoscopic approach and gaining more and more interest worldwide. We report herein the first fully laparoscopic LLS for pediatric LDLT in the Middle East with the use of indocyanine green dye and near-infrared fluorescence imaging to identify the biliary ducts intraoperatively. The recipient was a 2-year-old girl affected by glycogen storage disease type IV. The mother, aged 21 years, was her donor. The surgical technique, key-points of this procedure, and outcome are hereby discussed.


Small animal disease surveillance 2019: respiratory disease, antibiotic prescription and canine infectious respiratory disease complex.


title: Plasmacytoid dendritic cells: recent progress and open questions.

text: Plasmacytoid dendritic cells (pDCs) are specialized in rapid and massive secretion of type I interferon (IFN-α/β) in response to foreign nucleic acids. Combined with their antigen presentation capacity, this powerful functionality enables pDCs to orchestrate innate and adaptive immune responses. pDCs combine features of both lymphocytes and classical dendritic cells and display unique molecular adaptations to nucleic acid sensing and IFN production. In the decade since the identification of the pDC as a distinct immune cell type, our understanding of its molecular underpinnings and role in immunity has progressed rapidly. Here we review select aspects of pDC biology including cell fate establishment and plasticity, specific molecular mechanisms of pDC function, and the role of pDCs in T cell responses, antiviral immunity, and autoimmune diseases. Important unresolved questions remain in these areas, promising exciting times in pDC research for years to come.


title: High-flow oxygen therapy for treatment of acute migraine: A randomized crossover trial.

text: Background Impaired oxygen utilization and cerebrovascular dysfunction are implicated in migraine. High-flow oxygen is effective in cluster headache and has shown promise in animal models of migraine, but has not been adequately studied in patients with migraine. Methods In this randomized, crossover-design, placebo-controlled trial, adult migraineurs self-administered high-flow oxygen or medical air at 10-15 l/min via face mask in blinded fashion starting soon after symptom onset for 30 minutes, for a total of four migraine attacks. Participants recorded the severity of headache, nausea, and visual symptoms on visual analog scales periodically up to 60 minutes. Results We enrolled 22 individuals (mean age 36 years, 20 women) who self-treated 64 migraine attacks (33 oxygen, 31 air). The pre-specified primary endpoint (mean decrease in pain score from baseline to 30 minutes) was 1.38 ± 1.42 in oxygen-treated and 1.22 ± 1.61 in air-treated attacks ( p = 0.674). Oxygen therapy resulted in relief (severity score 0-1) of pain (24% versus 6%, p = 0.05), nausea (42% versus 23%, p = 0.08) and visual symptoms (36% versus 7%, p = 0.004) at 60 minutes. Exploratory analysis showed that in moderately severe attacks (baseline pain score <6), pain relief was achieved in six of 13 (46%) oxygen versus one of 15 (7%) air ( p = 0.02). Gas therapy was used per protocol in 91% of attacks. There were no significant adverse events. Conclusion High-flow oxygen may be a feasible and safe strategy to treat acute migraine. Further studies are required to determine if this relatively inexpensive, widely available treatment can be used as an adjunct or alternative migraine therapy.


title: Some aspects of the airborne transmission of infection.

text: The relationship between the human body and the dissemination of potentially pathogenic particles and droplets is described. Airborne transmission of infection in operating theatres and a burns unit and the part played by the human microclimate and its interaction with ventilating air flows is discussed. The mechanisms by which different garment assemblies used for surgery can enhance particle dispersion are illustrated and the way that floor cleaning can increase the concentration of airborne organisms is described. The development of the successful use of ultra-clean air systems in orthopaedic implant surgery is reviewed. Relationships between contact and airborne transmission of disease are explored and ways by which containment strategies and metrics used in pharmaceutical and electronics manufacturing can be applied to the design and monitoring of healthcare areas is discussed. It is suggested that currently available techniques involving architectural, ventilation and operational aspects of healthcare provision, when properly applied, can markedly improve treatment outcomes that may otherwise be compromised by hospital-acquired infections involving both bacteria and viruses.


Severe acute respiratory syndrome coronavirus 2 infection, angiotensin-converting enzyme 2 and treatment with angiotensin-converting enzyme inhibitors or angiotensin II type 1 receptor blockers.


title: Epidemiology and pathogenesis of otitis media: construction of a phenotype landscape.

text: Otitis media (OM) represents a complex set of clinically defined disease phenotypes. Epidemiological and pathological data suggest that inflammation of the middle ear occurs on a continuum of disease. Here I review epidemiological data and apply mathematical modelling to better define the interrelation of OM phenotypes, including the relationship of upper respiratory tract infection to acute OM (AOM), of AOM to OM with effusion, and of recurrent OM to chronicity of effusion. I use these mathematical models to represent OM graphically as a 'landscape of disease'. This novel nosology may enable clinicians and researchers to better conceptualise middle ear inflammation in its various forms, although the limits of its application are also discussed.


title: To notify or not to notify: decision aid for policy makers on whether to make an infectious disease mandatorily notifiable.

text: Mandatory notification can be a useful tool to support infectious disease prevention and control. Guidelines are needed to help policymakers decide whether mandatory notification of an infectious disease is appropriate. We developed a decision aid, based on a range of criteria previously used in the Netherlands or in other regions to help decide whether to make a disease notifiable. Criteria were categorised as being effective, feasible and necessary with regard to the relevance of mandatory notification. Expert panels piloted the decision aid. Here we illustrate its use for three diseases (Vibrio vulnificus infection, chronic Q fever and dengue fever) for which mandatory notification was requested. For dengue fever, the expert panel advised mandatory notification; for V. vulnificus infection and chronic Q fever, the expert panel concluded that mandatory notification was not (yet) justified. Use of the decision aid led to a structured, transparent decision making process and a thorough assessment of the advantages and disadvantages of mandatory notification of these diseases. It also helped identify knowledge gaps that required further research before a decision could be made. We therefore recommend use of this aid for public health policy making.


title: Low- Versus Standard-Dose Alteplase in Patients on Prior Antiplatelet Therapy: The ENCHANTED Trial (Enhanced Control of Hypertension and Thrombolysis Stroke Study).

text: BACKGROUND AND PURPOSE Many patients receiving thrombolysis for acute ischemic stroke are on prior antiplatelet therapy (APT), which may increase symptomatic intracerebral hemorrhage risk. In a prespecified subgroup analysis, we report comparative effects of different doses of intravenous alteplase according to prior APT use among participants of the international multicenter ENCHANTED study (Enhanced Control of Hypertension and Thrombolysis Stroke Study). METHODS Among 3285 alteplase-treated patients (mean age, 66.6 years; 38% women) randomly assigned to low-dose (0.6 mg/kg) or standard-dose (0.9 mg/kg) intravenous alteplase within 4.5 hours of symptom onset, 752 (22.9%) reported prior APT use. Primary outcome at 90 days was the combined end point of death or disability (modified Rankin Scale [mRS] scores, 2-6). Other outcomes included mRS scores 3 to 6, ordinal mRS shift, and symptomatic intracerebral hemorrhage by various standard criteria. RESULTS There were no significant differences in outcome between patients with and without prior APT after adjustment for baseline characteristics and management factors during the first week; defined by mRS scores 2 to 6 (adjusted odds ratio [OR], 1.01; 95% confidence interval [CI], 0.81-1.26; P=0.953), 3 to 6 (OR, 0.95; 95% CI, 0.75-1.20; P=0.662), or ordinal mRS shift (OR, 1.03; 95% CI, 0.87-1.21; P=0.770). Alteplase-treated patients on prior APT had higher symptomatic intracerebral hemorrhage (OR, 1.82; 95% CI, 1.00-3.30; P=0.051) according to the safe implementation of thrombolysis in stroke-monitoring study definition. Although not significant (P-trend, 0.053), low-dose alteplase tended to have better outcomes than standard-dose alteplase in those on prior APT compared with those not using APT (mRS scores of 2-6; OR, 0.84; 95% CI, 0.62-1.12 versus OR, 1.16; 95% CI, 0.99-1.36). CONCLUSIONS Low-dose alteplase may improve outcomes in thrombolysis-treated acute ischemic stroke patients on prior APT, but this requires further evaluation in a randomized controlled trial. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT01422616.


Pernicious anaemia: self-administration of hydroxocobalamin in the covid-19 crisis.


title: Host Innate Immunity against Hepatitis E Virus and Viral Evasion Mechanisms.

text: Hepatitis E virus (HEV) infections cause epidemic or sporadic acute hepatitis, which are mostly self-limiting. However, viral infection in immunocompromised patients and pregnant women may result in serious consequences, such as chronic hepatitis and liver damage, mortality of the latter of which reaches up to 20-30%. Type I interferon (IFN)-induced antiviral immunity is known to be the first-line defense against virus infection. Upon HEV infection in the cell, the virus genome is recognized by pathogen recognition receptors, leading to rapid activation of intracellular signaling cascades. Expression of type I IFN triggers induction of a barrage of IFN-stimulated genes, helping the cells cope with viral infection. Interestingly, some of the HEV-encoded genes seem to be involved in disrupting signaling cascades for antiviral immune responses, and thus crippling cytokine/chemokine production. Antagonistic mechanisms of type I IFN responses by HEV have only recently begun to emerge, and in this review, we summarize known HEV evasion strategies and compare them with those of other hepatitis viruses.


title: Robotic longitudinal pancreaticojejunostomy for chronic pancreatitis: Comparison of clinical outcomes and cost to the open approach.

text: BACKGROUND This study compares clinical and cost outcomes of robot-assisted laparoscopic (RAL) and open longitudinal pancreaticojejunostomy (LPJ) for chronic pancreatitis. METHODS Clinical and cost data were retrospectively compared between open and RAL LPJ performed at a single center from 2008-2015. RESULTS Twenty-six patients underwent LPJ: 19 open and 7 RAL. Two robot-assisted cases converted to open were included in the open group for analysis. Patients undergoing RAL LPJ had less intraoperative blood loss, a shorter surgical length of stay, and lower medication costs. Operation supply cost was higher in the RAL group. No difference in hospitalization cost was found. CONCLUSIONS Versus the open approach, RAL LPJ performed for chronic pancreatitis shortens hospitalization and reduces medication costs; hospitalization costs are equivalent. A higher operative cost for RAL LPJ is mitigated by a shorter hospitalization. Decreased morbidity and healthcare resource economy support use of the robotic approach for LPJ when appropriate.


title: Contrast-enhanced time-resolved MRA for follow-up of intracranial aneurysms treated with the pipeline embolization device.

text: BACKGROUND AND PURPOSE Endovascular reconstruction and flow diversion by using the Pipeline Embolization Device is an effective treatment for complex cerebral aneurysms. Accurate noninvasive alternatives to DSA for follow-up after Pipeline Embolization Device treatment are desirable. This study evaluated the accuracy of contrast-enhanced time-resolved MRA for this purpose, hypothesizing that contrast-enhanced time-resolved MRA will be comparable with DSA and superior to 3D-TOF MRA. MATERIALS AND METHODS During a 24-month period, 37 Pipeline Embolization Device-treated intracranial aneurysms in 26 patients underwent initial follow-up by using 3D-TOF MRA, contrast-enhanced time-resolved MRA, and DSA. MRA was performed on a 1.5T unit by using 3D-TOF and time-resolved imaging of contrast kinetics. All patients underwent DSA a median of 0 days (range, 0-68) after MRA. Studies were evaluated for aneurysm occlusion, quality of visualization of the reconstructed artery, and measurable luminal diameter of the Pipeline Embolization Device, with DSA used as the reference standard. RESULTS The sensitivity, specificity, and positive and negative predictive values of contrast-enhanced time-resolved MRA relative to DSA for posttreatment aneurysm occlusion were 96%, 85%, 92%, and 92%. Contrast-enhanced time-resolved MRA demonstrated superior quality of visualization (P = .0001) and a higher measurable luminal diameter (P = .0001) of the reconstructed artery compared with 3D-TOF MRA but no significant difference compared with DSA. Contrast-enhanced time-resolved MRA underestimated the luminal diameter of the reconstructed artery by 0.965 ± 0.497 mm (27% ± 13%) relative to DSA. CONCLUSIONS Contrast-enhanced time-resolved MRA is a reliable noninvasive method for monitoring intracranial aneurysms following flow diversion and vessel reconstruction by using the Pipeline Embolization Device.


title: The overlap method is a safe and feasible for esophagojejunostomy after laparoscopic-assisted total gastrectomy.

text: BACKGROUND Laparoscopic procedures are increasingly being applied to gastric cancer surgery, including total gastrectomy for tumors located in the upper gastric body. Even for expert surgeons, esophagojejunostomy after laparoscopy-assisted total gastrectomy (LATG) can be technically challenging. We perform the overlap method of esophagojejunostomy after LATG for gastric cancer. However, technical questions remain. Is the overlap method safer and more useful than other anastomosis techniques, such as methods using a circular stapler? In addition, while we perform this overlap reconstruction after LATG in a deep and narrow operative field, can the overlap method be performed safely regardless of body habitus? This study aimed to evaluate these issues retrospectively and to review the literature. METHODS From October 2005 to August 2013, we performed LATG with lymph-node dissection and Roux-en-Y reconstruction using the overlap method in 77 patients with gastric cancer. This study examined pre-, intra- and postoperative data. RESULTS Mean operation time, time to perform anastomosis, and estimated blood loss were 391.4 min, 36.3 min, and 146.9 ml, respectively. There were no deaths, and morbidity rate was 13%, including one patient (1%) who developed anastomotic stenosis. Mean postoperative hospitalization was 13.4 days. Surgical outcomes did not differ significantly by body mass index. CONCLUSIONS First, the overlap method for esophagojejunostomy after LATG is safe and useful. Second, this method can be performed irrespective of the body type of the patient. In particular, in a deep and narrow operative field, the overlap method is more versatile than other anastomosis methods. We believe that the overlap method can become a standard reconstruction technique for esophagojejunostomy after LATG.


title: The United States StuDy for EvalUating EndovasculaR TreAtments of Lesions in the Superficial Femoral Artery and Proximal Popliteal By usIng the Protégé EverfLex NitInol STent SYstem II (DURABILITY II).

text: OBJECTIVE Angioplasty and stenting are options for revascularization of symptomatic femoral popliteal disease. Although angioplasty alone is effective in short lesions, longer lesions are often treated with stents. Multiple overlapping stents are expensive and may be associated with stent fracture. This trial evaluated the safety and efficacy of a single self-expanding stent up to 20 cm in length in patients with atherosclerotic disease of the superficial femoral artery (SFA) and proximal popliteal artery. METHODS Patients with lesions >4 cm and <18 cm were enrolled in this nonrandomized, prospective, multicenter trial that evaluated the Protégé EverFlex Self-Expanding Peripheral Stent System (Covidien, Plymouth, Minn). The study's primary end points were the 30-day major adverse event rate and duplex ultrasound-assessed patency at 1 year. These were compared with published performance goals. A preplanned analysis was conducted for the primary effectiveness end points at 1 year. Follow-up, including history, ankle-brachial index, patient-reported outcomes, duplex ultrasound assessment, and radiographs, is planned through 3 years. There was core laboratory review of angiograms, ultrasound scans, and plain radiographs. A subgroup of patients was studied with graded treadmill testing. RESULTS The study enrolled 287 patients (66% male; mean age, 68 years) with stenotic, restenotic, or occluded lesions of the SFA at 44 investigational sites in the United States and Europe. Systemic comorbidities included hypertension (88%), hyperlipidemia (86%), diabetes (43%), and prior SFA intervention (41%). The mean lesion length measured by the core laboratory was 89 mm. The mean normal-to-normal lesion length measured by sites was 110 mm. A total of 303 stents were implanted, and 95% of patients received a single stent. No major adverse events occurred at 30 days. At 1 year, primary outcome of duplex ultrasound stent patency was 67.7% in evaluable patients, and among 1-year secondary outcomes, the mean ankle-brachial index increased by 0.25. Walking Improvement Questionnaire scores improved in pain by 33.7, distance by 37.1, speed by 18.6, and stair climbing by 24.7. The Kaplan-Meier estimate of primary patency was 77.2%, primary assisted patency was 86.9%, and secondary patency was 87.3%. Rutherford clinical category improved in 83.5% of patients. Stent fracture rate was 0.4%. Matched absolute claudication distance was 412 feet greater and was not statistically different in this subgroup of 29 individuals. CONCLUSIONS The results of DURABILITY II (StuDy for EvalUating EndovasculaR TreAtments of Lesions in the Superficial Femoral Artery and Proximal Popliteal By usIng the Protégé EverfLex NitInol Stent SYstem II) suggest that a new single stent strategy is safe and effective for the treatment of long lesions of the SFA and proximal popliteal arteries at 1 year.


title: Normothermic Ex Vivo Kidney Perfusion Reduces Warm Ischemic Injury of Porcine Kidney Grafts Retrieved After Circulatory Death.

text: BACKGROUND Cold storage is poorly tolerated by kidney grafts retrieved after donation after circulatory death. It has been determined that normothermic ex vivo kidney perfusion (NEVKP) preservation decreases injury by minimizing cold ischemic storage. The impact of NEVKP on warm ischemic injury is unknown. METHODS We compared pig kidneys retrieved after 30 minutes warm ischemia and immediate transplantation (no-preservation) with grafts that were exposed to 30 minutes of warm ischemia plus 8-hour NEVKP or plus 8-hour static cold storage (SCS). RESULTS After transplantation, the NEVKP group demonstrated lower daily serum creatinine levels indicating better early graft function compared with no-preservation (P = 0.02) or SCS group (P < 0.001). In addition, NEVKP preserved grafts had a significantly lower grade of tubular injury and interstitial inflammation 30 minutes after reperfusion compared to grafts without any storage (injury score, NEVKP 1-2 vs no-preservation, 2-2, P = 0.029; inflammation score, NEVKP, 0-0.5 vs no-preservation, 1-2; P = 0.002), although it did not reach significance level when compared to the SCS group (injury score, 1-2, P = 0.071; inflammation score, 1-1; P = 0.071). Regeneration was assessed 30 minutes after reperfusion by Ki-67 staining. The NEVKP group demonstrated significantly higher number of Ki-67-positive cells: 9.2 ± 3.7 when compared with SCS group (3.9 ± 1.0, P = 0.015) and no-preservation group (4.2 ± 0.7, P = 0.04). CONCLUSIONS In this porcine model of donation after circulatory death kidney transplantation NEVKP reduced kidney injury and improved graft function when compared with no-preservation. The results suggest that NEVKP does not cause additional damage to grafts during the preservation period, but may reverse the negative effects of warm ischemic insult itself and promotes regeneration.


title: Forensic Psychiatry and Covid-19: Accelerating Transformation in Forensic Psychiatry.

text: Swift medically led scientifically informed responses to the Covid-19 epidemic nationally have been demonstrably superior to other, non-scientific approaches. In forensic psychiatry and across all psychiatric services, urgent and clinically led responses have underlined redundancies and confusions in the governance of mental health services and a vacuum in policy makers. For the future, a greater emphasis on services for patients with schizophrenia and other severe, enduring mental disorders must aim at reducing standardised mortality ratios, managing risk of violence and improving hard outcomes such as symptomatic remission, functional recovery and forensic recovery of autonomy. This will require more use of information technology at service level and at national level where Scandinavian-style population based data linkage research must now become legally sanctioned and necessary. A national research and development centre for medical excellence in forensic psychiatry is urgently required and is complimentary to and different from quality management.


title: 2020 Reflections from a Mid-Career Academic Psychologist: Select Tips for Prospective Graduate Psychology Students.

text: This paper provides some personal and academic reflections from a mid-career academic psychologist. In doing so, several select tips and suggestions are offered to prospective graduate psychology students, in particular. This paper strikes to encourage such students to seriously and thoughtfully consider why they wish to attend graduate school and some of the realistic possible negative consequences of doing so. Several select additional suggestions are noted for those students who ultimately decide to attend graduate school with a particular emphasis on the value and importance of forging a productive and collegial relationship with one's graduate mentor. Keywords: graduate school; mid-career; academia; psychology; mentorship.


title: Contact tracing the first Middle East respiratory syndrome case in the Philippines, February 2015.

text: BACKGROUND Middle East respiratory syndrome (MERS) is an illness caused by a coronavirus in which infected persons develop severe acute respiratory illness. A person can be infected through close contacts. This is an outbreak investigation report of the first confirmed MERS case in the Philippines and the subsequent contact tracing activities. METHODS Review of patient records and interviews with health-care personnel were done. Patient and close contacts were tested for MERS-coronavirus (CoV) by real time-polymerase chain reaction. Close contacts were identified and categorized. All traced contacts were monitored daily for appearance of illness for 14 days starting from the date of last known exposure to the confirmed case. A standard log sheet was used for symptom monitoring. RESULTS The case was a 31-year-old female who was a health-care worker in Saudi Arabia. She had mild acute respiratory illness five days before travelling to the Philippines. On 1 February, she travelled with her husband to the Philippines while she had a fever. On 2 February, she attended a health facility in the Philippines. On 8 February, respiratory samples were tested for MERS-CoV and yielded positive results. A total of 449 close contacts were identified, and 297 (66%) were traced. Of those traced, 15 developed respiratory symptoms. All of them tested negative for MERS. DISCUSSION In this outbreak investigation, the participation of health-care personnel in conducting vigorous contact tracing may have reduced the risk of transmission. However, being overly cautious to include more contacts for the outbreak response should be further reconsidered.


title: Outcomes of patients with continuous flow left ventricular assist device undergoing emergency endovascular treatment for atraumatic bleeding.

text: INTRODUCTION Severe spontaneous bleeding is a significant complication in patients with continuous flow left ventricular assist devices; there is little evidence on endovascular treatment to support its use. MATERIALS AND METHODS We observed seven patients (five men, two women, age 43-67 years) with continuous flow left ventricular assist devices on antiaggregant/coagulant therapy, admitted to our hospital for uncorrectable symptomatic anemia; CT-angiography and diagnostic angiography confirmed the presence of atraumatic arterious bleeding from the gastrointestinal tract (six patients), from the intercostal artery and from the bronchial tree (one patient). RESULTS All patients where successfully treated via an endovascular approach with superselective embolization of the involved arterial branches with coils and particles. CONCLUSION Spontaneous atraumatic bleeding is a frequent complication in patients with continuous flow left ventricular assist devices; endovascular treatment represents a promising alternative to the surgical approach as it is less invasive, easily repeatable and associated to a reduced procedural risk.