title: Isolated colonic neurofibroma, a rare tumor: A case report and review of literature.

text: BACKGROUND Neurofibromas are tumors comprised of peripheral nerve sheath and connective tissue components. They can occur sporadically or as part of familial syndromes such as neurofibromatosis type 1. Isolated colonic neurofibroma without systemic manifestations is a rarely reported clinical entity. Here we present a case of a 51 years old male with an isolated colonic neurofibroma seen on a screening colonoscopy. CASE SUMMARY Fifty-one years old male who was otherwise healthy without a significant family history of cancer underwent a screening colonoscopy and was found have a 2.3 cm × 1.4 cm lesion in the colon. Tissue biopsy revealed a spindle cell tumor. Magnetic resonance imaging of the pelvis was negative for adenopathy. He underwent an endoscopic ultrasound that showed an ill-defined avascular lesion of mixed echogenicity measuring 2.8 cm × 15.2 cm in the submucosa with no communication with muscularis mucosa or propria. Immunohistochemistry staining of the tumor was strongly positive for S100, with rare penetrating axons deep within the tumor. Tumor cells were negative for c-kit and desmin and had low Ki-67 index. These findings were consistent with a solitary colonic submucosal neurofibroma. A detailed history and physical examination did not reveal any evidence of extraintestinal neurofibromatosis. He underwent transanal surgical resection of the tumor. The patient tolerated the procedure well without any complications. CONCLUSION While neurofibromas have been well described in literature, an isolated colonic neurofibroma is a rare pathological entity. Malignant transformation of neurofibromas has been reported in patients with neurofibromatosis syndromes. We report a case of isolated colonic neurofibroma and highlight the importance of resection due to the increased risk of tumorigenesis.


title: Burden, risk factors and outcomes of hyperemesis gravidarum in low-income and middle-income countries (LMICs): systematic review and meta-analysis protocol.

text: INTRODUCTION Hyperemesis gravidarum (HG) is a pregnancy condition characterised by excessive nausea and vomiting resulting in dehydration, weight loss and serious adverse pregnancy outcomes including termination of pregnancies. Even though evidence in low-income and middle-income countries (LMICs) is limited, the prevalence of HG in pregnancy ranges from 0.3% to 10.8%. With this systematic review and meta-analysis, we aim to determine the prevalence/burden, risk factors, and maternal and perinatal outcomes of HG in LMICs. METHODS PubMed, CINAHL, EMBASE, EBSCO, Ovid maternity and infant care databases, Cochrane Database of Systematic Reviews, Web of Science and SCOPUS databases will be searched. Reference lists of selected articles will be assessed in order to identify other potential studies of interest. Observational studies and (non) randomised controlled trials conducted from January 2000 to September 2018 in LMIC will be included. A weighted inverse-variance meta-analysis using fixed-effects and random-effects model will be done to generate a pooled estimate. Funnel plot and Egger's regression statistical test will be applied to check publication bias. Heterogeneity among studies will be checked using Τ2 to determine dispersion. Moreover, meta-regression analysis will be performed to investigate the source of heterogeneity. STATA V.14 will be used to analyse the data. ETHICS AND DISSEMINATION Formal ethical approval and patient consent are not required; as primary data collection will not be employed. The result will be published in a peer-reviewed scientific journal and will be presented at scientific conferences and public press. PROSPERO REGISTRATION NUMBER CRD42018096284.


title: Skin as a marker of general feline health: Cutaneous manifestations of infectious disease.

text: Practical relevance: Infectious disease in feline patients often presents a diagnostic challenge. This article reviews the most relevant viral, bacterial and protozoal diseases and their cutaneous manifestations. Many of the diseases discussed have overlapping presentations or may mimic more common noninfectious disease processes. The purpose of the article is to reinforce knowledge of common and uncommon infectious diseases, help practitioners identify possible infectious dermatoses, create a comprehensive and prioritized differential list, and provide guidance for the diagnosis of these diseases. A working knowledge of these clinical syndromes is important if what is thought to be a case of a common disease does not respond to conventional management. AUDIENCE This review is aimed at veterinarians who treat cats and especially those with an interest in feline dermatology. Tables are included to allow the reader to formulate a concise list of differential diagnoses for clinically similar presentations. The diagnostic approach to a case of ulcerative facial dermatitis is reviewed in a Case Notes quiz. Evidence base: This article includes up-to-date information regarding dermatologic manifestations of less commonly encountered feline cutaneous infectious diseases. Information has been drawn from the published, peer-reviewed literature and the most recent textbook chapters with a particular aim of describing and differentiating clinical lesions and the diagnostic approach to cutaneous disease, especially in unusual cases.


title: Intranasal treatment with poly(I•C) protects aged mice from lethal respiratory virus infections.

text: In the 2002-2003 severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic, no patients under 24 years of age died, while mortality was greater than 50% in those over 65 years. Greater than 90% of all deaths from influenza A virus (IAV) occur in the elderly (>65 years of age). To address this age-related susceptibility to SARS-CoV and IAV, we infected C57BL/6 (B6) mice with mouse-adapted SARS-CoV (MA15) or IAV (PR8), both of which cause severe disease in aged mice. Intranasal pretreatment of aged mice with poly(I·C) (a TLR3 agonist) and, to a lesser extent, CpG, R848, or lipopolysaccharide (TLR9, TLR7/8, or TLR4 agonists), provided a high level of protection [90% to 100% survival rate after poly(I·C) treatment] against lethal MA15 or IAV challenge and reduced pathological changes and virus loads in the lungs at early times after infection. Poly(I·C) pretreatment upregulated beta interferon (IFN-β), IFN-γ, IL-1β, and tumor necrosis factor (TNF) gene expression in the lungs. Intranasal pretreatment with IFN-β or IFN-γ but not IL-1β or TNF also protected aged mice, consistent with the notion that poly(I·C) pretreatment functioned, at least in part, by inducing IFN-β and IFN-γ. We also identified a potential cellular target for poly(I·C) by showing that treatment inhibited virus replication in primary human airway epithelial cells. These results suggest that intranasal poly(I·C) should be evaluated as a prophylactic agent in aged individuals at high risk for contracting SARS-CoV or IAV infections.


title: Physically active lessons in schools and their impact on physical activity, educational, health and cognition outcomes: a systematic review and meta-analysis.

text: OBJECTIVE This review provides the first meta-analysis of the impact of physically active lessons on lesson-time and overall physical activity (PA), as well as health, cognition and educational outcomes. DESIGN Systematic review and meta-analysis of controlled studies. Six meta-analyses pooled effects on lesson-time PA, overall PA, in-class educational and overall educational outcomes, cognition and health outcomes. Meta-analyses were conducted using the metafor package in R. Risk of bias was assessed using the Cochrane tool for risk of bias. DATA SOURCES PubMed, Embase, PsycINFO, ERIC and Web of Science, grey literature and reference lists were searched in December 2017 and April 2019. STUDIES ELIGIBILITY CRITERIA Physically active lessons compared with a control group in a randomised or non-randomised design, within single component interventions in general school populations. RESULTS 42 studies (39 in preschool or elementary school settings, 27 randomised controlled trials) were eligible to be included in the systematic review and 37 of them were included across the six meta-analyses (n=12 663). Physically active lessons were found to produce large, significant increases in lesson-time PA (d=2.33; 95% CI 1.42 to 3.25: k=16) and small, increases on overall PA (d=0.32; 95% CI 0.18 to 0.46: k=8), large, improvement in lesson-time educational outcomes (d=0.81; 95% CI 0.47 to 1.14: k=7) and a small improvement in overall educational outcomes (d=0.36; 95% CI 0.09 to 0.63: k=25). No effects were seen on cognitive (k=3) or health outcomes (k=3). 25/42 studies had high risk of bias in at least two domains. CONCLUSION In elementary and preschool settings, when physically active lessons were added into the curriculum they had positive impact on both physical activity and educational outcomes. These findings support policy initiatives encouraging the incorporation of physically active lessons into teaching in elementary and preschool setting. TRIAL REGISTRATION NUMBER CRD42017076933.


Re-infection by COVID-19: a real threat for the future management of pandemia?


title: Optimizing Mask Ventilation: Literature Review and Development of a Conceptual Framework.

text: Mask ventilation is lifesaving, especially in cases of difficult intubation. Many publications have offered distinct techniques for optimizing mask ventilation. This article reviews currently available difficult mask ventilation literature and theory. We divide difficult mask ventilation into 3 broad categories based on etiology: inadequate mask seal, increased airway resistance, and decreased respiratory compliance. Published strategies for overcoming difficulty are presented and organized by etiology.


title: Diagnostic Value of Serial Measurement of C-Reactive Protein in the Detection of a Surgical Complication after Laparoscopic Bowel Resection for Endometriosis.

text: AIMS The study aimed to assess the diagnostic value of serial monitoring of biochemical inflammatory markers (C-reactive protein (CRP) and white blood cell (WBC) count) in the postoperative diagnosis of anastomotic leakage or ureteral injury after bowel resection for deep infiltrating endometriosis. METHODS This is a review of prospectively collected data from 217 patients who underwent laparoscopic bowel resection for endometriosis from January 2009 to April 2015. Patients with an anastomotic leakage or ureteral injury were identified and classified. RESULTS The frequency of anastomotic leakage requiring reoperation was 8.3%. The frequency of ureteral injury was 4.6%. Median time to diagnosis was 6 days for anastomotic leakage and 8 days for ureteral injury. The daily mean values of serum CRP were significantly higher in patients with a surgical complication starting at the second postoperative day (POD 2, p = 0.004). WBC was significantly higher (p < 0.05) on POD 2 and 3 in patients with a surgical complication. A decrease in CRP from POD 1 to 3 predicted an uncomplicated course in 92.1% of the cases. CONCLUSION A decrease in CRP from POD 1 to 3 was an indicator of uncomplicated subsequent postoperative course. The test is recommended when early discharge after rectal resection for deep infiltrating endometriosis is considered.


title: Comparing LigasureTM Exact dissector with other energy devices in total thyroidectomy: a pilot study.

text: Background Hemostasis is fundamental in thyroid surgery. The aim of this randomized active comparator-controlled study was to compare the effectiveness of LigasureTM Exact to previously existing sealing devices in patients undergoing thyroidectomy. Methods A total of 180 patients were randomly allocated into 4 groups according to the hemostatic device used: Focus Harmonic Scalpel® (FHS), LigasureTM Small Jaw (LSJ), Thunderbeat® (TB), and LigasureTM Exact (LE). We recorded epidemiologic and biochemical data, operative difficulty, postoperative vocal alteration and pain, complications, operating time, grams of gland excised per minute, and hospitalization. Results Differences (P<0.001) were observed concerning duration of surgery, operative difficulty and quantity of gland removed per minute. Concerning duration of surgery it is shorter for LE followed by TB and then by both FHS and LSJ. Concerning the quantity of thyroid removed per minute LE leads, followed by FHS and TB. The least amount of gland removed per minute is by LSJ. Finally, operative difficulty was less for LE, while it was equal for all other three devices. Conclusions Energy devices are now frequently used in thyroidectomy. Comparing these devices seems to qualify them as equal concerning post-operative complications, hemostasis, and acute inflammatory reaction. However, LigasureTM Exact Dissector seems to have better results concerning duration of surgery, quantity of thyroid tissue removed per minute and intraoperative difficulty.


title: Pre-clinical study protocol: Blood transfusion in endotoxaemic shock.

text: The Surviving Sepsis Campaign (SCC) and the American College of Critical Care Medicine (ACCM) guidelines recommend blood transfusion in sepsis when the haemoglobin concentration drops below 7.0 g/dL and 10.0 g/dL respectively, while the World Health Organisation (WHO) guideline recommends transfusion in septic shock 'if intravenous (IV) fluids do not maintain adequate circulation', as a supportive measure of last resort. Volume expansion using crystalloid and colloid fluid boluses for haemodynamic resuscitation in severe illness/sepsis, has been associated with adverse outcomes in recent literature. However, the volume expansion effect(s) following blood transfusion for haemodynamic circulatory support, in severe illness remain unclear with most previous studies having focused on evaluating effects of either different RBC storage durations (short versus long duration) or haemoglobin thresholds (low versus high threshold) pre-transfusion. •We describe the protocol for a pre-clinical randomised controlled trial designed to examine haemodynamic effect(s) of early volume expansion using packed RBCs (PRBCs) transfusion (before any crystalloids or colloids) in a validated ovine-model of hyperdynamic endotoxaemic shock.•Additional exploration of mechanisms underlying any physiological, haemodynamic, haematological, immunologic and tissue specific-effects of blood transfusion will be undertaken including comparison of effects of short (≤5 days) versus long (≥30 days) storage duration of PRBCs prior to transfusion.


title: Cloning and identification of porcine programmed death 1.

text: Programmed death 1 (PD-1) is a member of the immunoglobulin (Ig) superfamily, which is expressed on activated T cells, B cells and monocytes. Many researches have demonstrated that a high level of PD-1 expression is closely related to persistent infection and immune evasion in some human infections. In order to study the relationship between PD-1 expression and persistent infections caused by some porcine viruses, we first cloned the porcine PD-1 from porcine PBMCs based on the blast result in the EST database using the human PD-1 sequence. Sequence analysis showed that the cloned PD-1 molecule shares 63 and 54% amino acid sequence identity with human and murine PD-1, respectively. Its molecular structure is also similar to that of human and murine PD-1, containing an IgV-like domain in the extracellular region and two immune regulatory motifs in its cytoplasmic tail. The in vitro T cell proliferation assay showed that the cloned PD-1 could inhibit porcine T cell proliferation by 71% and secretion of IFN-gamma and IL-2 by 64 and 53%, respectively. These data suggest that porcine PD-1 negatively regulates the porcine immune response in a similar manner to that of its counterpart in the human and mouse immune system.


title: Bedside ultrasound to detect central venous catheter misplacement and associated iatrogenic complications: a systematic review and meta-analysis.

text: BACKGROUND Insertion of a central venous catheter (CVC) is common practice in critical care medicine. Complications arising from CVC placement are mostly due to a pneumothorax or malposition. Correct position is currently confirmed by chest x-ray, while ultrasonography might be a more suitable option. We performed a meta-analysis of the available studies with the primary aim of synthesizing information regarding detection of CVC-related complications and misplacement using ultrasound (US). METHODS This is a systematic review and meta-analysis registered at PROSPERO (CRD42016050698). PubMed, EMBASE, the Cochrane Database of Systematic Reviews, and the Cochrane Central Register of Controlled Trials were searched. Articles which reported the diagnostic accuracy of US in detecting the position of CVCs and the mechanical complications associated with insertion were included. Primary outcomes were specificity and sensitivity of US. Secondary outcomes included prevalence of malposition and pneumothorax, feasibility of US examination, and time to perform and interpret both US and chest x-ray. A qualitative assessment was performed using the QUADAS-2 tool. RESULTS We included 25 studies with a total of 2548 patients and 2602 CVC placements. Analysis yielded a pooled specificity of 98.9 (95% confidence interval (CI): 97.8-99.5) and sensitivity of 68.2 (95% CI: 54.4-79.4). US examination was feasible in 96.8% of the cases. The prevalence of CVC malposition and pneumothorax was 6.8% and 1.1%, respectively. The mean time for US performance was 2.83 min (95% CI: 2.77-2.89 min) min, while chest x-ray performance took 34.7 min (95% CI: 32.6-36.7 min). US was feasible in 97%. Further analyses were performed by defining subgroups based on the different utilized US protocols and on intra-atrial and extra-atrial misplacement. Vascular US combined with transthoracic echocardiography was most accurate. CONCLUSIONS US is an accurate and feasible diagnostic modality to detect CVC malposition and iatrogenic pneumothorax. Advantages of US over chest x-ray are that it can be performed faster and does not subject patients to radiation. Vascular US combined with transthoracic echocardiography is advised. However, the results need to be interpreted with caution since included studies were often underpowered and had methodological limitations. A large multicenter study investigating optimal US protocol, among other things, is needed.


title: Optimization of conditions for secretion of dengue virus type 2 envelope domain III using Pichia pastoris.

text: We have developed a recombinant clone of the methylotrophic yeast Pichia pastoris capable of secreting dengue virus type 2 envelope domain III (sEDIII-2). We explored various induction parameters including media composition, temperature, pH, and methanol concentration, to optimize conditions for sEDIII-2 expression in shake flask culture. Induction at 20°C in the presence of 2% (v/v) methanol in a medium buffered to pH 5.8 resulted in highest secretion of sEDIII-2. This yield could be further enhanced up to 70% by repeated induction of the same initial biomass. Using a fed-batch cultivation strategy, we observed that shake-flask yields can be scaled up ∼8-fold in a bioreactor. We obtained ∼94% purity with >70% recovery after purification. This study, which demonstrates for the first time the feasibility of secreting envelope domain III using the P. pastoris host, will be relevant to sub-unit approaches to dengue vaccine development.


title: Real-time monitoring of human blood-brain barrier disruption.

text: Chemotherapy aided by opening of the blood-brain barrier with intra-arterial infusion of hyperosmolar mannitol improves the outcome in primary central nervous system lymphoma. Proper opening of the blood-brain barrier is crucial for the treatment, yet there are no means available for its real-time monitoring. The intact blood-brain barrier maintains a mV-level electrical potential difference between blood and brain tissue, giving rise to a measurable electrical signal at the scalp. Therefore, we used direct-current electroencephalography (DC-EEG) to characterize the spatiotemporal behavior of scalp-recorded slow electrical signals during blood-brain barrier opening. Nine anesthetized patients receiving chemotherapy were monitored continuously during 47 blood-brain barrier openings induced by carotid or vertebral artery mannitol infusion. Left or right carotid artery mannitol infusion generated a strongly lateralized DC-EEG response that began with a 2 min negative shift of up to 2000 μV followed by a positive shift lasting up to 20 min above the infused carotid artery territory, whereas contralateral responses were of opposite polarity. Vertebral artery mannitol infusion gave rise to a minimally lateralized and more uniformly distributed slow negative response with a posterior-frontal gradient. Simultaneously performed near-infrared spectroscopy detected a multiphasic response beginning with mannitol-bolus induced dilution of blood and ending in a prolonged increase in the oxy/deoxyhemoglobin ratio. The pronounced DC-EEG shifts are readily accounted for by opening and sealing of the blood-brain barrier. These data show that DC-EEG is a promising real-time monitoring tool for blood-brain barrier disruption augmented drug delivery.


title: Behavioral Correlates of Muscular Fitness in Children and Adolescents: A Systematic Review.

text: BACKGROUND Muscular fitness (MF) is considered a powerful marker of health, but the extent to which common health behaviors are associated with MF during childhood and adolescence is currently unclear. OBJECTIVE We conducted a systematic review of studies investigating associations between MF (i.e., strength/power, local muscular endurance) and physical activity, sedentary behaviors, and sleep in children and adolescents. METHODS A systematic search of six electronic databases was performed on 8 March, 2017. Search results were screened for relevance and studies conducted with children and adolescents (3-18 years) that explored associations between MF and physical activity, sedentary behavior, or sleep were considered eligible. Data were extracted and checked by a second author. The proportion of studies reporting a statistically significant association between each MF component and behavioral variables was calculated, and additional coding was conducted to account for risk of bias. RESULTS There was consistent evidence for a positive association between MF and physical activity. For both MF components, there was support for objectively measured physical activity, particularly for activity of vigorous intensity. Sports participation was also consistently linked with both MF components, whereas the association with active transport was inconsistent. For both MF components, associations with sedentary behaviors were inconsistent irrespective of measurement method, and the association between MF and sleep was considered uncertain. CONCLUSIONS The available evidence supports a link between MF and physical activity, particularly for vigorous intensity activity and organized sports participation. Conversely, there is limited support for an association with sedentary behaviors, and more research exploring MF and sleep is required.


title: Fear of COVID-19 scale: Psychometric characteristics, reliability and validity in the Israeli population.

text: Mental health clinicians worldwide have been expressing concerns regarding the broad psychological effects of the COVID-19 pandemic. Nonetheless, only a few studies have thus far evaluated the degree of fear of COVID-19, partially due to the lack of validated measures. In this study we evaluated the psychometric properties of the Hebrew version of the Fear of COVID-19 scale (FCV-19S), recently developed to assess different aspects of the fear of the pandemic, in a normative population of participants in Israel. Participants (n = 639) were asked to complete the FCV-19S scale, as well as to report anxiety, depression, and stress levels using validated scales. The results a unidimensional factor structure of the FCV-19S which explained 53.71% of the variance. When forcing a two-factor structure model, the analysis revealed two factors pertaining to emotional fear reactions and symptomatic expressions of fear. Gender, sociodemographic status, chronic illness, being in an at-risk group, and having a family member dying of COVID-19 were positively associated with fear of COVID-19. The measure was associated with anxiety, stress and depression. These results suggest that the FCV-19S has good psychometric properties, and can be utilized in studies assessing the effects of the pandemic on the population's mental health.


Cosmetic surgeries amidst pandemic area of COVID-19: suggested protocol.


title: The Past, Present and Future of Endovascular Aneurysm Treatment.

text: The technology available for the endovascular treatment of intracranial aneurysms is rapidly evolving. Both current and future devices are described. This includes, among others, UNO for parent vessel occlusion, the Medina device for saccular filling, the Comaneci device for remodeling, pCONus for assisted coil occlusion, and WEB and pCANvas for intrasaccular flow disruption. Perspectives of further development such as surface coating for increased radioopacity and decreased thrombogenicity are explained.


title: Generation of Xeno-Free, cGMP-Compliant Patient-Specific iPSCs from Skin Biopsy.

text: This unit describes protocols for the generation of clinical-grade patient-specific induced pluripotent stem cell (iPSC)-derived retinal cells from patients with inherited retinal degenerative blindness. Specifically, we describe how, using xeno-free reagents in an ISO class 5 environment, one can isolate and culture dermal fibroblasts, generate iPSCs, and derive autologous retinal cells via 3-D differentiation. The universal methods described herein for the isolation of dermal fibroblasts and generation of iPSCs can be employed regardless of disease, tissue, or cell type of interest. © 2017 by John Wiley & Sons, Inc.


title: A microwave-assisted diastereoselective multicomponent reaction to access dibenzo[c,e]azepinones: synthesis and biological evaluation.

text: An unprecedented microwave-assisted multicomponent strategy has been elaborated for the fast, efficient, and diastereoselective generation of the dibenzo[c,e]azepinone scaffold. The generated compounds were evaluated for their bioactivity.


Appearance deceives: unusual pneumothorax: traumatic phrenic nerve paralysis.


title: Detection of 11 common viral and bacterial pathogens causing community-acquired pneumonia or sepsis in asymptomatic patients by using a multiplex reverse transcription-PCR assay with manual (enzyme hybridization) or automated (electronic microarray) detection.

text: Community-acquired pneumonia (CAP) and sepsis are important causes of morbidity and mortality. We describe the development of two molecular assays for the detection of 11 common viral and bacterial agents of CAP and sepsis: influenza virus A, influenza virus B, respiratory syncytial virus A (RSV A), RSV B, Mycoplasma pneumoniae, Chlamydophila pneumoniae, Legionella pneumophila, Legionella micdadei, Bordetella pertussis, Staphylococcus aureus, and Streptococcus pneumoniae. Further, we report the prevalence of carriage of these pathogens in respiratory, skin, and serum specimens from 243 asymptomatic children and adults. The detection of pathogens was done using both a manual enzyme hybridization assay and an automated electronic microarray following reverse transcription and PCR amplification. The analytical sensitivities ranged between 0.01 and 100 50% tissue culture infective doses, cells, or CFU per ml for both detection methods. Analytical specificity testing demonstrated no significant cross-reactivity among 19 other common respiratory organisms. One hundred spiked "surrogate" clinical specimens were all correctly identified with 100% specificity (95% confidence interval, 100%). Overall, 28 (21.7%) of 129 nasopharyngeal specimens, 11 of 100 skin specimens, and 2 of 100 serum specimens from asymptomatic subjects tested positive for one or more pathogens, with S. pneumoniae and S. aureus giving 89% of the positive results. Our data suggest that asymptomatic carriage makes the use of molecular assays problematic for the detection of S. pneumoniae or S. aureus in upper respiratory tract secretions; however, the specimens tested showed virtually no carriage of the other nine viral and bacterial pathogens, and the detection of these pathogens should not be a significant diagnostic problem. In addition, slightly less sensitive molecular assays may have better correlation with clinical disease in the case of CAP.


title: GENETIC RELATEDNESS OF EPIZOOTIC HEMORRHAGIC DISEASE VIRUS SEROTYPE 2 FROM 2012 OUTBREAK IN THE USA.

text: During summer and early fall of 2012, the US experienced the largest outbreak of hemorrhagic disease (HD) on record; deer (both Odocoileus virginianus and Odocoileus hemionus) in 35 states were affected, including many northern states where HD typically does not occur. Epizootic hemorrhagic disease virus (EHDV) was the predominant virus isolated, with serotype 2 (EHDV-2) representing 66% (135/205) of all isolated viruses. Viruses within the EHDV serogroup are genetically similar, but we hypothesized that subtle genetic distinctions between viruses would exist across the geographic range of the outbreak if multiple EHDV-2 strains were responsible. We examined viral relatedness and molecular epidemiology of the outbreak by sequencing the mammalian binding protein (VP2) gene and the insect vector binding protein (VP7) gene of 34 EHDV-2 isolates from 2012 across 21 states. Nucleotide sequences of VP2 had 99.0% pairwise identity; VP7 nucleotide sequences had 99.1% pairwise identity. Very few changes were observed in either protein at the amino acid level. Despite the high genetic similarity between isolates, subtle nucleotide differences existed. Both VP2 and VP7 gene sequences separated into two distinct clades based on patterns of single-nucleotide polymorphisms after phylogenetic analysis. The clades were divided geographically into eastern and western clades, although those divisions were not identical between VP2 and VP7. There was also an association between percent sequence identity and geographic distance between isolates. We concluded that multiple EHDV-2 strains contributed to this outbreak.


Risky Business: lessons from covid-19.


title: Human pathogenic bacteria, fungi, and viruses in Drosophila: disease modeling, lessons, and shortcomings.

text: Drosophila has been the invertebrate model organism of choice for the study of innate immune responses during the past few decades. Many Drosophila-microbe interaction studies have helped to define innate immunity pathways, and significant effort has been made lately to decipher mechanisms of microbial pathogenesis. Here we catalog 68 bacterial, fungal, and viral species studied in flies, 43 of which are relevant to human health. We discuss studies of human pathogens in flies revealing not only the elicitation and avoidance of immune response but also mechanisms of tolerance, host tissue homeostasis, regeneration, and predisposition to cancer. Prominent among those is the emerging pattern of intestinal regeneration as a defense response induced by pathogenic and innocuous bacteria. Immunopathology mechanisms and many microbial virulence factors have been elucidated, but their relevance to human health conventionally necessitates validation in mammalian models of infection.


title: Systematic Review and Meta-Analysis on the Value of Chest CT in the Diagnosis of Coronavirus Disease (COVID-19): Sol Scientiae, Illustra Nos.

text: OBJECTIVE. The purpose of this article is to systematically review and meta-analyze the diagnostic accuracy of chest CT in detecting coronavirus disease (COVID-19). MATERIALS AND METHODS. MEDLINE was systematically searched for publications on the diagnostic performance of chest CT in detecting COVID-19. Methodologic quality was assessed using the Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2) tool. Meta-analysis was performed using a bivariate random-effects model. RESULTS. Six studies were included, comprising 1431 patients. All six studies included patients at high risk of COVID-19, and five studies explicitly reported that they included only symptomatic patients. Mean prevalence of COVID-19 was 47.9% (range, 27.6-85.4%). High or potential risk of bias was present throughout all QUADAS-2 domains in all six studies. Sensitivity ranged from 92.9% to 97.0%, and specificity ranged from 25.0% to 71.9%, with pooled estimates of 94.6% (95% CI, 91.9-96.4%) and 46.0% (95% CI, 31.9-60.7%), respectively. The included studies were statistically homogeneous in their estimates of sensitivity (p = 0.578) and statistically heterogeneous in their estimates of specificity (p < 0.001). CONCLUSION. Diagnostic accuracy studies on chest CT in COVID-19 suffer from methodologic quality issues. Chest CT appears to have a relatively high sensitivity in symptomatic patients at high risk of COVID-19, but it cannot exclude COVID-19. Specificity is poor. These data, along with other local factors such as COVID-19 prevalence, available real-time reverse transcriptase-polymerase chain reaction tests, staff, hospital, and CT scanning capacity, can be useful to healthcare professionals and policy makers to decide on the utility of chest CT for COVID-19 detection in the hospital setting.


title: High Prevalence of Middle East Respiratory Coronavirus in Young Dromedary Camels in Jordan.

text: Prevalence of Middle East respiratory syndrome coronavirus (MERS-CoV) was determined in 45 dromedary camels from two geographically separated herds in Jordan. Virus shedding was only detected in swabs obtained from the respiratory tract and primarily observed in camels younger than 3 years. MERS-CoV seroprevalence increased with age of camels. Bovine and sheep sera were seronegative. Phylogenetic analysis of partial S2 clustered the Jordanian MERS-CoV strains with contemporary MERS-CoV strains associated with nosocomial outbreaks.


title: Technique and Patient Selection Criteria of Right Anterior Mini-Thoracotomy for Minimal Access Aortic Valve Replacement.

text: Aortic valve stenosis has become the most prevalent valvular heart disease in developed countries, and is due to the aging of these populations. The incidence of the pathology increases with growing age after 65 years. Conventional surgical aortic valve replacement through median sternotomy has been the gold standard of patient care for symptomatic aortic valve stenosis. However, as the risk profile of patients worsens, other therapeutic strategies have been introduced in an attempt to maintain the excellent results obtained by the established surgical treatment. One of these approaches is represented by transcatheter aortic valve implantation. Although the outcomes of high-risk patients undergoing treatment for symptomatic aortic valve stenosis have improved with transcatheter aortic valve replacement, many patients with this condition remain candidates for surgical aortic valve replacement. In order to reduce the surgical trauma in patients who are candidates for surgical aortic valve replacement, minimally invasive approaches have garnered interest during the past decade. Since the introduction of right anterior thoracotomy for aortic valve replacement in 1993, right anterior mini-thoracotomy and upper hemi-sternotomy have become the predominant incisional approaches among cardiac surgeons performing minimal access aortic valve replacement. Beside the location of the incision, the arterial cannulation site represents the second major landmark of minimal access techniques for aortic valve replacement. The two most frequently used arterial cannulation sites include central aortic and peripheral femoral approaches. With the purpose of reducing surgical trauma in these patients, we have opted for a right anterior mini-thoracotomy approach with a central aortic cannulation site. This protocol describes in detail a technique for minimally invasive aortic valve replacement and provides recommendations for patient selection criteria, including cardiac computer tomography measurements. The indications and limitations of this technique, as well as its alternatives, are discussed.


title: Heat shock protein 70 enhances mucosal immunity against human norovirus when coexpressed from a vesicular stomatitis virus vector.

text: UNLABELLED Human norovirus (NoV) accounts for 95% of nonbacterial gastroenteritis worldwide. Currently, there is no vaccine available to combat human NoV as it is not cultivable and lacks a small-animal model. Recently, we demonstrated that recombinant vesicular stomatitis virus (rVSV) expressing human NoV capsid protein (rVSV-VP1) induced strong immunities in mice (Y. Ma and J. Li, J. Virol. 85:2942-2952, 2011). To further improve the safety and efficacy of the vaccine candidate, heat shock protein 70 (HSP70) was inserted into the rVSV-VP1 backbone vector. A second construct was generated in which the firefly luciferase (Luc) gene was inserted in place of HSP70 as a control for the double insertion. The resultant recombinant viruses (rVSV-HSP70-VP1 and rVSV-Luc-VP1) were significantly more attenuated in cell culture and viral spread in mice than rVSV-VP1. At the inoculation dose of 1.0 × 10(6) PFU, rVSV-HSP70-VP1 triggered significantly higher vaginal IgA than rVSV-VP1 and significantly higher fecal and vaginal IgA responses than rVSV-Luc-VP1, although serum IgG and T cell responses were similar. At the inoculation dose of 5.0 × 10(6) PFU, rVSV-HSP70-VP1 stimulated significantly higher T cell, fecal, and vaginal IgA responses than rVSV-VP1. Fecal and vaginal IgA responses were also significantly increased when combined vaccination of rVSV-VP1 and rVSV-HSP70 was used. Collectively, these data indicate that (i) insertion of an additional gene (HSP70 or Luc) into the rVSV-VP1 backbone further attenuates the VSV-based vaccine in vitro and in vivo, thus improving the safety of the vaccine candidate, and (ii) HSP70 enhances the human NoV-specific mucosal and T cell immunities triggered by a VSV-based human NoV vaccine. IMPORTANCE Human norovirus (NoV) is responsible for more than 95% of acute nonbacterial gastroenteritis worldwide. Currently, there is no vaccine for this virus. Development of a live attenuated vaccine for human NoV has not been possible because it is uncultivable. Thus, a live vector-based vaccine may provide an alternative vaccine strategy. In this study, we developed a vesicular stomatitis virus (VSV)-based human NoV vaccine candidate. We constructed rVSV-HSP70-VP1, coexpressing heat shock protein (HSP70) and capsid (VP1) genes of human NoV, and rVSV-Luc-VP1, coexpressing firefly luciferase (Luc) and VP1 genes. We found that VSVs with a double gene insertion were significantly more attenuated than VSV with a single VP1 insertion (rVSV-VP1). Furthermore, we found that coexpression or coadministration of HSP70 from VSV vector significantly enhanced human NoV-specific mucosal immunity. Collectively, we developed an improved live vectored vaccine candidate for human NoV which will be useful for future clinical studies.


title: Integrative Physiological Aspects of Brain RAS in Hypertension.

text: PURPOSE OF REVIEW The renin-angiotensin system (RAS) plays an important role in modulating cardiovascular function and fluid homeostasis. While the systemic actions of the RAS are widely accepted, the role of the RAS in the brain, its regulation of cardiovascular function, and sympathetic outflow remain controversial. In this report, we discuss the current understanding of central RAS on blood pressure (BP) regulation, in light of recent literature and new experimental techniques. RECENT FINDINGS Studies using neuronal or glial-specifc mouse models have allowed for greater understanding into the site-specific expression and role centrally expressed RAS proteins have on BP regulation. While all components of the RAS have been identified in cardiovascular regulatory regions of the brain, their actions may be site specific. In a number of animal models of hypertension, reduction in Ang II-mediated signaling, or upregulation of the central ACE2/Ang 1-7 pathway, has been shown to reduce BP, via a reduction in sympathetic signaling and increase parasympathetic tone, respectively. Emerging evidence also suggests that, in part, the female protective phenotype against hypertension may be due to inceased ACE2 activity within cardiovascular regulatory regions of the brain, potentially mediated by estrogen. Increasing evidence suggests the importance of a central renin-angiotensin pathway, although its localization and the mechanisms involved in its expression and regulation still need to be clarified and more precisely defined. All reported studies/experiments with human or animal subjects performed by the authors have been previously published and complied with all applicable ethical standards (including the Helsinki declaration and its amendments, institutional/national research committee standards, and international/national/institutional guidelines).


title: What to do about fibrin rich 'tough clots'? Comparing the Solitaire stent retriever with a novel geometric clot extractor in an in vitro stroke model.

text: BACKGROUND Despite advances in revascularization tools for large vessel occlusion presenting as acute ischemic stroke, a significant subset of clots remain recalcitrant to current strategies. We assessed the effectiveness of a novel thrombectomy device that was specifically designed to retrieve resistant fibrin rich clots, the geometric clot extractor (GCE; Neuravi, Galway, Ireland), in an in vitro cerebrovascular occlusion stroke model. METHODS After introducing fibrin rich clot analogues into the middle cerebral artery of the model, we compared the rates of recanalization between GCE and Solitaire flow restoration stent retriever (SR; Medtronic, Minneapolis, Minnesota, USA; control group) cases. A maximum of three passes of each device was allowed. If the SR failed to recanalize the vessel after three passes, one pass of the GCE was allowed (rescue cases). RESULTS In a total of 26 thrombectomy cases (13 GCE, 13 SR), successful recanalization (Thrombolysis in Cerebral Infarction score of 2b or 3) was achieved 100% of the time in the GCE cases with an average of 2.13 passes per case. This rate was significantly higher compared with the Solitaire recanalization rate (7.7%, P<0.0001) with an average of three passes per case. After SR failure (in 92% of cases), successful one pass GCE rescue recanalization was achieved 66% of the time (P<0.005). CONCLUSION Application of the GCE in this experimental stroke model to retrieve typically recalcitrant fibrin rich clots resulted in higher successful recanalization rates than the SR.


title: COVID-19: Hygiene and Public Health to the front.

text: Public Health professionals and academics have been on the frontline of Italian history during the COVID-19 response like they never did before. Ancient professors of Hygiene such as Celli, Pagliani, Sclavo, Petragnani, Seppilli and Giovanardi flanked politicians in other critical moments. They helped them to manage healthcare reforms, earthquakes response, Seveso Dioxin disaster, cholera and poliomielitis epidemics and other health threats. The ongoing COVID-19 epidemic has highlighted the paramount importance of the practical application of basic concepts of public health, which were considered so far became obsolete, such as personal hygiene, quarantine, individual protective devices or basic epidemiological measures. Hygiene and Public Health used to have a targeted audience in professionals and lecturers. Nowadays, these topics are critical and of concern of a much larger audience. Public Health women and men are now asked to act in task forces, media broadcasts, webinars and consulting activities. In phase 2 of this epidemic - which is about to begin when this volume is to be published - the role of Public Health professionals could become even more relevant. However, this unexpected season must be managed with seriousness and intelligence, capitalizing it also for the future. If our Post-Graduate Schools of Public Health ("Igiene e Medicina Preventiva"), our scientific associations, our academic lecturers and our officers do not prove to be up to the situation, a dull future for the discipline might very well be. On the contrary, if as we all hope, we will be able to ride the wave of a dramatic health crisis, transforming it into a relevant scientific and professional opportunity, then we will be able to build on the post-COVID-19 a cutting-edge, a more attractive, relevant and modern discipline. This Supplement of Acta Biomedica, planned before the onset of the epidemic emergency in Italy, but already successful in presenting two papers on COVID-19, is further proof of how current and lively our discipline is.


title: Alginate encapsulation as long-term immune protection of allogeneic pancreatic islet cells transplanted into the omental bursa of macaques.

text: The transplantation of pancreatic islet cells could restore glycaemic control in patients with type-I diabetes. Microspheres for islet encapsulation have enabled long-term glycaemic control in diabetic rodent models; yet human patients transplanted with equivalent microsphere formulations have experienced only transient islet-graft function, owing to a vigorous foreign-body reaction (FBR), to pericapsular fibrotic overgrowth (PFO) and, in upright bipedal species, to the sedimentation of the microspheres within the peritoneal cavity. Here, we report the results of the testing, in non-human primate (NHP) models, of seven alginate formulations that were efficacious in rodents, including three that led to transient islet-graft function in clinical trials. Although one month post-implantation all formulations elicited significant FBR and PFO, three chemically modified, immune-modulating alginate formulations elicited reduced FBR. In conjunction with a minimally invasive transplantation technique into the bursa omentalis of NHPs, the most promising chemically modified alginate derivative (Z1-Y15) protected viable and glucose-responsive allogeneic islets for 4 months without the need for immunosuppression. Chemically modified alginate formulations may enable the long-term transplantation of islets for the correction of insulin deficiency.


Covid-19: are face masks a good long term strategy?


title: Hyperglycemia management in the critically ill patient with COVID-19.

text: Hyperglycemia is common in critically ill patients and is associated with worse outcomes in those admitted to an intensive care unit. Glucose control helps prevent and control infections and their complications. For critically ill patients with COVID-19, management of hyperglycemia must consider caregiver protection and the frequency of monitoring glucose based on patient safety and the use of personal protective equipment. If steroids are used in the management plan, be aware of steroid-induced hyperglycemia. An endocrinology consult may be beneficial to help manage drip rate and frequency of glucose checks.


title: The efficacy of hepatic 90Y resin radioembolization for metastatic neuroendocrine tumors: a meta-analysis.

text: UNLABELLED (90)Y resin radioembolization is an emerging treatment in patients with liver-dominant metastatic neuroendocrine tumors (mNETs), despite the absence of level I data. The aim of this study was to evaluate the efficacy of this modality in a meta-analysis of the published literature. METHODS A comprehensive review protocol screened all reports in the literature. Strict selection criteria were applied to ensure consistency among the selected studies: human subjects, complete response data with time interval, resin microspheres, more than 5 patients, not a duplicate cohort, English language, and separate and complete data for resin-based (90)Y treatment of mNET if the study included multiple tumor and microsphere types. Selected studies were critically appraised on 50 study criteria, in accordance with the research reporting standards for radioembolization. Response data (Response Evaluation Criteria in Solid Tumors) were extracted and analyzed using both fixed and random-effects meta-analyses. RESULTS One hundred fifty-six studies were screened; 12 were selected, totaling 435 procedures for response assessment. Funnel plots showed no evidence of publication bias (P = 0.841). Critical appraisal revealed a median of 75% of desired criteria included in selected studies. Very high between-study heterogeneity ruled out a fixed-effects model. The random-effects weighted average objective response rate (complete and partial responses, CR and PR, respectively) was 50% (95% confidence interval, 38%-62%), and weighted average disease control rate (CR, PR, and stable disease) was 86% (95% confidence interval, 78%-92%). The percentage of patients with pancreatic mNET was marginally associated with poorer response (P = 0.030), accounting for approximately 23% of the heterogeneity among studies. The percentage of CR and PR correlated with median survival (R = 0.85; P = 0.008). CONCLUSION This meta-analysis confirms radioembolization to be an effective treatment option for patients with hepatic mNET. The pooled data demonstrated a high response rate and improved survival for patients responding to therapy.


title: Nasolaryngeal Distances in the Adult Population and an Evaluation of Commercially Available Nasotracheal Tubes.

text: BACKGROUND Preformed nasal endotracheal tubes (NETs) come with a predefined insertion depth due to their curved design. While size indication refers to internal diameter, there is a considerable variability in the corresponding lengths and proportions of same-sized tubes of different manufacturers which is probably based on the lack of data of nasolaryngeal distances (NLDs) in the adult population. Choosing the best-fitting NET is therefore difficult and carries the risk of endobronchial intubation or, on the contrary, cuff inflation at the vocal cord level. The aim of this study was to develop a prediction model for NLD and a selection guide to choose the appropriate NET based on a radiographic description of NLD in comparison to the measurements of available NETs of several manufacturers. METHODS After institutional ethics board review, 388 computed tomography (CT) scan images of head, neck, and upper thorax in a heterogeneous adult cohort were included. Mean distances from the nares to the lower border of the thyroid cartilage were measured. NETs from different manufacturers were measured and compared to the NLD derived from the radiographic analysis. The patients' sex, body height, and weight were considered as possible covariates in quantile regression models for predicting the NLD. RESULTS Data from 200 patients were analyzed. NLD was associated with sex, body height, and weight. A simple quantile regression model using the body height as the only covariate sufficed to achieve accurate predictions of NLD. Validation on independent test data showed that 92.8% of the NLD predictions were closer than ±20 mm to the observed NLD values. Measurements of equal-sized NETs varied considerably in outer diameter, proportion, the nasopharyngeal part, and guide marks. Length differences of the bend-to-cuff distance, containing the anatomically NLD, ranged between 218 and 270 mm at same sizes. CONCLUSIONS A reliable prediction of NLD can be obtained simply by body height, using the formula NLD (mm) = -13.2 + 1.1 × body height (cm). As manufacturers' tube lengths vary substantially, additional information about the bend-to-cuff distance as corresponding tube section would allow for more accurate tube selection.


Response to COVID-19 in Taiwan: Big Data Analytics, New Technology, and Proactive Testing.


title: A SARS-CoV-2 Coronavirus Nucleocapsid Antigen-Detecting Half-Strip Lateral Flow Assay Towards the Development of Point of Care Tests Using Commercially Available Reagents.

text: The SARS-CoV-2 pandemic has created an unprecedented need for rapid diagnostic testing to enable the efficient treatment and mitigation of COVID-19. The primary diagnostic tool currently employed is reverse transcription polymerase chain reaction (RT-PCR), which can have good sensitivity and excellent specificity. Unfortunately, implementation costs and logistical problems with reagents during the global SARS-CoV-2 pandemic have hindered its universal on demand adoption. Lateral flow assays (LFAs) represent a class of diagnostic that, if sufficiently clinically sensitive, may fill many of the gaps in the current RT-PCR testing regime, especially in low- and middle-income countries (LMICs). To date, many serology LFAs have been developed, though none meet the performance requirements necessary for diagnostic use cases, primarily due to the relatively long delay between infection and seroconversion. However, based on previously reported results from SARS-CoV-1, antigen-based SARS-CoV-2 assays may have significantly better clinical sensitivity than serology assays. To date, only a very small number of antigen-detecting LFAs have been developed. Development of a half-strip LFA is a useful first step in the development of any LFA format. In this paper we present a half-strip LFA using commercially available antibodies for the detection of SARS-CoV-2. We have tested this LFA in buffer and measured an LOD of 0.65 ng/ mL (95% CI of 0.53 to 0.77 ng/mL) ng/mL with recombinant antigen using an optical reader with sensitivity equivalent to a visual read. Further development, including evaluating the appropriate sample matrix, will be required for this assay approach to be made useful in a point of care setting, though this half-strip LFA may serve as a useful starting point for others developing similar tests.


title: Allergic contact dermatitis associated with Biosyn suture in a patient with gastroesophageal junction cancer.

text: A PUBMED literature review revealed no reports of allergic contact dermatitis to Biosyn(™) suture material. We present the first case of such an allergic reaction. The case emphasizes the need to remember that suture material can occasionally elicit an allergic dermatitis which may increase the complications and morbidity associated with any surgical procedure.


title: Ontogeny of a surgical technique: Robotic kidney transplantation with regional hypothermia.

text: INTRODUCTION Innovation is a hallmark of surgical practice. It is generally accepted that a new procedure will undergo technical changes during its evolution; however, quantitative accounts of the process are limited. METHODS Multiple groups, including our own, have recently described a minimally-invasive approach to conventional kidney transplantation (KT) operation. Unique to our experience is a structured development of the technique within the confines of a safe surgical innovation framework - the IDEAL framework (idea, development, exploration, assessment, long-term monitoring; stages 0-4). We here provide a first-hand narrative of the progress of robotic KT operation from preclinical trial to clinical application. RESULTS Overall, 54 patients underwent robotic KT with regional hypothermia successfully. Major technical changes including selection of optimal patient position (flank vs. lithotomy), robotic instrumentation, vascular occlusion method (bulldog vs. tourniquet) and suture material (prolene vs. GoreTex) occurred early during the procedure development (IDEAL stage 0, preclinical). Minor technical changes such as utilization of the aortic punch for arteriotomy (case 3), use of barbed suture during ureteroneocystostomy (case 6) and extraperitonealization of the graft kidney (case 6) that increased the efficiency and safety of the procedure continued throughout procedure development (IDEAL stages 1-2, clinical stages). CONCLUSIONS We demonstrate that a surgical technique evolves continually; although, the majority of technical alterations occur early in the life-cycle of the procedure. Development of a new technique within the confines a structured surgical innovation framework allows for evidence based progression of the technique and may minimize the risk of harm to the patient.


title: Dihydrocelastrol inhibits multiple myeloma cell proliferation and promotes apoptosis through ERK1/2 and IL-6/STAT3 pathways in vitro and in vivo.

text: Multiple myeloma (MM) is the second most frequent malignant hematological disease. Dihydrocelastrol (DHCE) is synthesized by hydrogenated celastrol, a treterpene isolated from Chinese medicinal plant Tripterygium regelii. In this study, we first reported the anti-tumor activity of DHCE on MM cells. We found that DHCE could inhibit cell proliferation and promote apoptosis through caspase-dependent way in vitro. In addition, DHCE could inactivate the expression of interleukin (IL)-6 and downregulate the phosphorylation of extracellular regulated protein kinases (ERK1/2) and the signal transducer and activator of transcription 3 (STAT3) in MM. It also retained its activity against MM cell lines in the presence of IL-6. Furthermore, treatment of MM cells with DHCE resulted in an accumulation of cells in G0/G1 phase of the cell cycle. Notably, DHCE reduced the expression of cyclin D1 and cyclin-dependent kinases 4 and 6 in MM cell lines. Additionally, its efficacy toward the MM cell lines could be enhanced in combination with the histone deacetylase inhibitor panobinostat (LBH589), which implied the possibility of the combination treatment of DHCE and LBH589 as a potential therapeutic strategy in MM. In addition, treatment of NCI-H929 tumor-bearing nude mice with DHCE (10 mg/kg/d, i.p., 1-14 days) resulted in 73% inhibition of the tumor growth in vivo. Taken together, the results of our present study indicated that DHCE could inhibit cellular proliferation and induce cell apoptosis in myeloma cells mediated through different mechanisms, possibly through inhibiting the IL-6/STAT3 and ERK1/2 pathways. And it may provide a new therapeutic option for MM patients.


title: Application of TaqMan low-density arrays for simultaneous detection of multiple respiratory pathogens.

text: The large and growing number of viral and bacterial pathogens responsible for respiratory infections poses a challenge for laboratories seeking to provide rapid and comprehensive pathogen identification. We evaluated a novel application of the TaqMan low-density array (TLDA) cards for real-time PCR detection of 21 respiratory-pathogen targets. The performance of the TLDA was compared to that of individual real-time PCR (IRTP) assays with the same primers and probes using (i) nucleic acids extracted from the 21 pathogen strains and 66 closely related viruses and bacteria and (ii) 292 clinical respiratory specimens. With spiked samples, TLDA cards were about 10-fold less sensitive than IRTP assays. By using 292 clinical specimens to generate 2,238 paired individual assays, the TLDA card exhibited 89% sensitivity (95% confidence interval [CI], 86 to 92%; range per target, 47 to 100%) and 98% specificity (95% CI, 97 to 99%; range per target, 85 to 100%) overall compared to IRTP assays as the gold standard with a threshold cycle (C(T)) cutoff of 43. The TLDA card approach offers promise for rapid and simultaneous identification of multiple respiratory pathogens for outbreak investigations and disease surveillance.


title: Hendra virus fusion protein transmembrane domain contributes to pre-fusion protein stability.

text: Enveloped viruses utilize fusion (F) proteins studding the surface of the virus to facilitate membrane fusion with a target cell membrane. Fusion of the viral envelope with a cellular membrane is required for release of viral genomic material, so the virus can ultimately reproduce and spread. To drive fusion, the F protein undergoes an irreversible conformational change, transitioning from a metastable pre-fusion conformation to a more thermodynamically stable post-fusion structure. Understanding the elements that control stability of the pre-fusion state and triggering to the post-fusion conformation is important for understanding F protein function. Mutations in F protein transmembrane (TM) domains implicated the TM domain in the fusion process, but the structural and molecular details in fusion remain unclear. Previously, analytical ultracentrifugation was utilized to demonstrate that isolated TM domains of Hendra virus F protein associate in a monomer-trimer equilibrium (Smith, E. C., Smith, S. E., Carter, J. R., Webb, S. R., Gibson, K. M., Hellman, L. M., Fried, M. G., and Dutch, R. E. (2013) J. Biol. Chem. 288, 35726-35735). To determine factors driving this association, 140 paramyxovirus F protein TM domain sequences were analyzed. A heptad repeat of β-branched residues was found, and analysis of the Hendra virus F TM domain revealed a heptad repeat leucine-isoleucine zipper motif (LIZ). Replacement of the LIZ with alanine resulted in dramatically reduced TM-TM association. Mutation of the LIZ in the whole protein resulted in decreased protein stability, including pre-fusion conformation stability. Together, our data suggest that the heptad repeat LIZ contributed to TM-TM association and is important for F protein function and pre-fusion stability.


title: Development of a dynamic model for ventral hernia mesh repair.

text: INTRODUCTION The adequate way of mesh fixation in laparoscopic ventral hernia repair is still subject to debate. So far, simulation has only been carried out in a static way, thereby omitting dynamic effects of coughing or vomiting. We developed a dynamic model of the anterior abdominal wall. MATERIALS AND METHODS An aluminium cylinder was equipped with a pressure controlled, fluid-filled plastic bag, simulating the abdominal viscera. A computer-controlled system allowed the control of influx and efflux, thus creating pressure peaks of up to 200 mmHg to simulate coughing and 290 mmHg to simulate vomiting. We tested fixation with tacks (Absorbatack, Covidien Deutschland, Neustadt a. D., Germany). The model was controlled for the friction coefficient of the tissue against the mesh and the physiologic elasticity of the abdominal wall surrogate. RESULTS The model was able to create pressure peaks equivalent to physiologic coughs or vomiting. Physiologic elasticity was thereby maintained. We could show that the friction coefficient is crucial to achieve a physiologic situation. The meshes showed a tendency to dislocate with an increasing number of coughs (Fig. 4). Nevertheless, when applied in a plain manner, the meshes withstood more cough cycles than when applied with a bulge as in laparoscopic surgery. CONCLUSIONS The dynamic movement of the abdominal wall, the friction between tissue and mesh and the way of mesh application are crucial factors that have to be controlled for in simulation of ventral abdominal hernia closure. We could demonstrate that patient specific factors such as the frequency of coughing as well as the application technique influence the long term stability of the mesh.


title: EVALUATION OF CHEMICAL IMMOBILIZATION IN CAPTIVE BLACK BEARS ( URSUS AMERICANUS) RECEIVING A COMBINATION OF NALBUPHINE, MEDETOMIDINE, AND AZAPERONE.

text: To assess potential seasonal differences in responses to immobilization, we sedated eight orphaned yearling black bears ( Ursus americanus) being held for rehabilitation at a wildlife facility in Colorado, US, using a premixed combination of nalbuphine (40 mg/mL), azaperone (10 mg/mL), and medetomidine (10 mg/mL; NalMed-A) in October (autumn) prior to hibernation and again after emergence in May (spring) prior to their release. We dosed all bears at 1 mL NalMed-A per estimated 45 kg body mass (1 mL NalMed-A/45 kg), delivered by intramuscular injection using a pole syringe, to facilitate routine examination and ear tagging. Arterial blood gases were measured to assess oxygenation and acid-base status of bears both pre and post oxygen supplementation. The mean (SE) dose calculated post hoc was 0.9 (0.04) mg nalbuphine/kg, 0.2 (0.01) mg azaperone/kg, and 0.2 (0.01) mg medetomidine/kg. The mean induction time was 8 (1) min for six of the bears in October and 6 (1) min for eight bears in May. The NalMed-A combination provided good sedation in captive yearling black bears in autumn and spring and was effectively antagonized with a combination of naltrexone and atipamezole. Mild hypoxemia (PaO2: 53.5-54.4 mmHg) was the most significant side effect and was corrected (PaO2: 68.4-150.1 mmHg) with supplemental oxygen administered at 2-5 L/min for 5 min (point of sampling).


title: Acute ischaemic stroke outcomes following mechanical thrombectomy in the elderly versus their younger counterpart: a retrospective cohort study.

text: OBJECTIVES Many physicians debate the efficacy of mechanical thrombectomy for ischaemic stroke, but most agree that to establish potential benefit, patient selection must be examined further. People >80 years are a growing population of patients with ischaemic stroke but are largely excluded from clinical trials. The benefit of thrombectomy for them may be greatly reduced due to diminishing neuroplasticity and a larger number of medical comorbidities. To address this knowledge gap, we examined clinical and economic outcomes after mechanical thrombectomy in the ischaemic stroke population from the Nationwide Inpatient Sample. Our null hypotheses were that elderly patients (>80 years) would have a similar rate of inpatient mortality in comparison to their younger counterparts and incur a similar economic expense. DESIGN Retrospective cohort study. SETTING A 20% stratified sample of US community hospitals within the Nationwide Inpatient Sample. PARTICIPANTS All patients from 2008 to 2010 with a primary diagnosis of ischaemic stroke that received mechanical thrombectomy were included. PRIMARY AND SECONDARY OUTCOME MEASURES The primary outcome was inpatient mortality. Secondary outcomes included hospital charges and length of stay. RESULTS Less than 1% of all ischaemic stroke cases (9300) were treated with mechanical thrombectomy. Of these, 18% involved patients over 80 years of age. The odds of inpatient mortality in elderly patients treated with mechanical thrombectomy were approximately twice that of their younger counterparts (OR1.993, p < 0.001). The elderly experienced no significant difference in hospital charges (p=0.105) and length of stay (p=0.498). CONCLUSIONS The odds of inpatient mortality after mechanical thrombectomy in patients over 80 years of age were twice that of their younger counterparts. This is consistent with the overall worse prognosis seen in the natural history of this age group. Studies to better identify patients that would benefit from endovascular mechanical thrombectomy may improve outcomes and reduce the gap currently observed in age stratifications.


title: Identifying the probable timing and setting of respiratory virus infections.

text: OBJECTIVE Show how detailed incubation period estimates can be used to identify and investigate potential healthcare-associated infections and dangerous diseases. METHODS We used the incubation period of 9 respiratory viruses to derive decision rules for distinguishing between community- and hospital-acquired infection. We developed a method, implemented in a simple spreadsheet, that can be used to investigate the exposure history of an individual patient and more specifically to identify the probable time and location of infection. Illustrative examples are used to explain and evaluate this technique. RESULTS If the risks of hospital and community infection are equal, 95% of patients who develop symptoms of adenovirus infection within 5 days of hospital admission will have been infected in the community, as will 95% of patients who develop symptoms within 3 days for human-coronavirus infection, 2.5 days for severe acute respiratory syndrome, 1 day for influenza A, 0.5 day for influenza B, 12 days for measles, 2 days for parainfluenza, 4 days for respiratory syncytial virus infection, and 1.5 days for rhinovirus infection. Sources of infection suggested by analysis of the symptom onset times of individual patients are consistent with those from detailed investigations. CONCLUSIONS This work shows how a detailed understanding of the incubation period can be an effective tool for identifying the source of infection, ultimately ensuring patient safety.


title: Percutaneous Coronary Intervention of Saphenous Vein Graft.

text: BACKGROUND Percutaneous coronary intervention (PCI) of saphenous vein grafts (SVGs) has historically been associated with a high risk of adverse ischemic events, but there is a paucity of contemporary data on the second-generation drug-eluting stent use within SVG, and the relative importance of high platelet reactivity (HPR) in SVG PCI versus native lesion PCI is unknown. We studied ischemic and bleeding events after SVG PCI and their association with HPR. METHODS AND RESULTS Subjects in the prospective, multicenter ADAPT-DES study (Assessment of Dual Antiplatelet Therapy With Drug-Eluting Stents) were stratified according to whether they had PCI of an SVG or a non-SVG lesion. Two-year outcomes were compared between groups using univariate and multivariable Cox proportional hazards models. HPR was defined as on-clopidogrel P2Y12 platelet reaction units >208 as measured by the VerifyNow assay; major adverse cardiac events were defined as the composite of cardiac death, myocardial infarction, or stent thrombosis. Among 8582 subjects in ADAPT-DES, 405 (4.7%) had SVG PCI. SVG PCI was independently associated with a higher 2-year risk of major adverse cardiac events (adjusted hazard ratio, 2.34; 95% confidence interval, 1.69-3.23; P<0.0001), ischemia-driven target vessel revascularization (adjusted hazard ratio, 1.82; 95% confidence interval, 1.37-2.42; P<0.0001), and stent thrombosis (adjusted hazard ratio, 2.26; 95% confidence interval, 1.42-3.59; P=0.0006), but not of bleeding (adjusted hazard ratio, 0.99; 95% confidence interval, 0.68-1.46; P=0.97). There was no statistical interaction between HPR and SVG PCI in regard to major adverse cardiac events (adjusted Pinteraction=0.99). CONCLUSIONS SVG PCI is associated with a considerably higher risk of 2-year adverse ischemic events, with HPR conferring similar risk in SVG and non-SVG PCI. More potent and longer antiplatelet therapy may be beneficial for patients undergoing SVG PCI. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00638794.


Existing Drugs Might Treat COVID-19.


title: The association between severe COVID-19 and low platelet count: evidence from 31 observational studies involving 7613 participants.

text: A novel coronavirus disease 2019 (COVID-19) broke out at 2019 and had caused a pandemic around the world. This disease was found resulting from the infection of 2019 novel coronavirus (2019-nCoV) (Zhu, et al 2020). The severity of COVID-19 disease has a wide range and varies from asymptomatic to critical severe, clinical researches reported that 10-15% of the patients were in the severe situation and required a great deal of attention of treatment and nursing (WHO-China-Joint-Mission 2020).


Blood transfusion during haemodialysis improves systemic tissue oxygenation: A case report.


title: The effect of Adacolumn® on ulcerative colitis with COVID-19.

text: Crespo et al. comment on the influence of immunomodulators and biological drugs on ulcerative colitis and SARS-CoV-2 infection. Granulo-monocytoapheresis is a treatment used in ulcerative colitis outbreaks, whose mechanism of action is to selectively retain activated granulocytes and monocytes, in order to reduce the inflammatory process.


title: Comparison of serum neutralization and enzyme-linked immunosorbent assay on sera from porcine epidemic diarrhea virus vaccinated pigs.

text: BACKGROUND Porcine epidemic diarrhea virus (PEDV) is an economically important pathogen of swine. OBJECTIVE Serum neutralization (SN) and enzyme-linked immunosorbent assay (ELISA) test results as well as the utility of spike proteins S1, S2, and S3 and entire nucleocapsid protein were compared. ANIMALS AND METHODS Serum samples from 400 pigs vaccinated against PEDV strain SM98P were collected from 78 farms in Korea. SN test and ELISA were performed to confirm the presence of antibodies. For prokaryotic expression of partial fragments of spike protein the size and location of S1, S2, and S3, and full nucleocapsid protein, polymerase chain reaction was performed using specific primers. RESULTS Comparison of these results demonstrated that there was a correlation between the SN and ELISA results. Sera with higher neutralizing activity also had higher IgG titer. The antibody profiling data presented the correlation of neutralizing activity with the level of spike protein antibody. In particular, the S3 region may have an important role in neutralizing activity. CONCLUSIONS We confirmed that the carboxy-terminal region that includes the endodomain of the S protein induced stronger neutralizing activity than the region that includes the ectodomain. CLINICAL RELEVANCE The region of the S protein may have a stronger neutralizing KPEDV-9 epitope and could be useful for the evaluation of future PEDV vaccine efficacy.


title: The rise of adverse childhood experiences during the COVID-19 pandemic.

text: Adverse childhood experiences, which is defined by different forms of abuse, neglect, and household dysfunction occurring before the age of 18 years, is a major public health problem in the United States that has the potential to worsen in the current COVID-19 pandemic. Moreover, the challenge is even greater for children and youth from low-income communities and communities of color. Thus, there is a greater need for investments in youth-serving systems within and beyond health care and public health to effectively address adverse childhood experiences and prevent its short- and long-term negative health and social sequelae well beyond the current public health crisis. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


Harnessing behavioural science in public health campaigns to maintain 'social distancing' in response to the COVID-19 pandemic: key principles.


title: Impact of COVID-19 on Brazilian medical residencies in obstetrics and gynecology.

text: Brazil has become the epicenter for COVID-19 cases worldwide, after the United States, with more than 500 000 cases and almost 30 000 deaths as of June 1, 2020.[1] This pandemic has resulted in the need to modify all hospitals to be adapted for receiving patients with severe cases of COVID-19. In many institutions, postgraduate residents have experienced an interruption of their ordinary activities. Brazil is a vast country, with many structural inequalities and a postgraduate medical residency program sponsored within the public health system.


title: Analysis of Clinical Predictors of Resolution of Sleep Disturbance Related to Frequent Nighttime Heartburn and Acid Regurgitation Symptoms in Individuals Taking Esomeprazole 20 mg or Placebo.

text: BACKGROUND AND OBJECTIVE Sleep disturbances related to reflux symptoms have a significant impact on the daily lives of affected individuals. These analyses identified clinical factors related to resolution of reflux-related sleep disturbance in subjects treated with esomeprazole 20 mg for 14 days. METHODS Data from the first 14 days of 2 similar randomized, double-blind studies were pooled for subjects experiencing frequent heartburn and related sleep disturbances receiving esomeprazole 20 mg (n = 357) or placebo (n = 346). A stepwise logistic regression analysis was performed with pooled and individual study data to evaluate relationships between clinical factors [treatment (esomeprazole vs. placebo), run-in sleep disturbance frequency, occurrence (yes/no) of 24-h, daytime, and nighttime heartburn (yes: ≥1 episode in 14-day treatment period)] and complete sleep disturbance resolution (no disturbances for 7 consecutive days). RESULTS Absence of daytime (p = 0.0018) or nighttime (p < 0.0001) heartburn during treatment was a significant predictor of complete sleep disturbance resolution at 14 days for the total population, while higher run-in sleep disturbance frequency (p < 0.0001) was associated with a lower likelihood of resolution. Esomeprazole treatment was an independent significant predictor of improvement across all endpoints (p < 0.0001). A significant treatment by run-in sleep disturbance interaction was observed for complete resolution (p = 0.0231), indicating greater therapeutic benefit with esomeprazole in subgroups with higher run-in symptom frequency. CONCLUSIONS Lower run-in sleep disturbance frequency, no occurrence of daytime or nighttime heartburn during therapy, and esomeprazole treatment predicted complete reflux-related sleep disturbance resolution. The magnitude of therapeutic benefit for esomeprazole 20 mg over placebo increased with increasing baseline sleep disturbance.


title: Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity.

text: Influenza A and B viruses are a global threat to human health and increasing resistance to the existing antiviral drugs necessitates new concepts to expand the therapeutic options. Glycopeptide derivatives have emerged as a promising new class of antiviral agents. To avoid potential antibiotic resistance, these antiviral glycopeptides are preferably devoid of antibiotic activity. We prepared six vancomycin aglycone hexapeptide derivatives with the aim of obtaining compounds having anti-influenza virus but no antibacterial activity. Two of them exerted strong and selective inhibition of influenza A and B virus replication, while antibacterial activity was successfully eliminated by removing the critical N-terminal moiety. In addition, these two molecules offered protection against several other viruses, such as herpes simplex virus, yellow fever virus, Zika virus, and human coronavirus, classifying these glycopeptides as broad antiviral molecules with a favorable therapeutic index.


title: Allergenic immunotherapy and seasonal changes in nitric oxide concentration in exhaled air in seasonal rhinitis patients.

text: BACKGROUND Concentration of nitric oxide in exhaled air (FeNO) was revealed to decrease as a result of immunotherapy. However, individuals who are exposed to environmental allergens are characterized by elevated values of FeNO. The aim of this study was to analyze the effects of subcutaneous immunotherapy (SCIT) on the dynamics of FeNO determined during consecutive pollination seasons. METHODS This study, performed between 2005 and 2008, included 41 patients with confirmed sensitivity to grass pollens and predominating symptoms of seasonal allergic rhinitis, randomly assigned to desensitization by preseasonal or maintenance SCIT. FeNO was measured prior to and during each pollen season (November-January and May-July, respectively). The results were conferred to data on grass pollination intensity in 2006-2008 (air concentration of grass pollen grains, seasonal number of days when air concentration of grass pollen reached at least 50 grains per 1 m(3)). RESULTS Median content of FeNO in exhaled air was significantly higher in 2007 compared to 2006 and 2008 pollen seasons. During 2007 and 2008 pollen seasons, significant increase in FeNO was observed compared to the respective preseasonal values. Median number of days with air concentration of grass pollen ≥ 50 grains per 1 m(3) of air during 4 weeks preceding seasonal FeNO measurement was significantly higher in 2007, corresponding to higher FeNO value recorded during this pollen season. However, no significant correlation was observed between seasonal number of days with ≥ 50 grass pollen grains per 1 m(3) of air and FeNO in exhaled air (r=0.09, p=0.362). CONCLUSIONS Most seasonal allergic rhinitis patients show physiological levels of FeNO prior to the pollen seasons and a marked increase in this parameter, probably proportional to pollination intensity, is observed within the seasons. ISRCTN Registry: ISRCTN86562422.


title: Iterative Reconstruction Improves Both Objective and Subjective Image Quality in Acute Stroke CTP.

text: PURPOSE Computed tomography perfusion (CTP) imaging in acute ischemic stroke (AIS) suffers from measurement errors due to image noise. The purpose of this study was to investigate if iterative reconstruction (IR) algorithms can be used to improve the diagnostic value of standard-dose CTP in AIS. METHODS Twenty-three patients with AIS underwent CTP with standardized protocol and dose. Raw data were reconstructed with filtered back projection (FBP) and IR with intensity levels 3, 4, 5. Image quality was objectively (quantitative perfusion values, signal-to-noise ratio (SNR), contrast-to-noise ratio (CNR)) and subjectively (overall image quality) assessed. Ischemic core and perfusion mismatch were visually rated. Discriminative power for tissue outcome prediction was determined by the area under the receiver operating characteristic curve (AUC) resulting from the overlap between follow-up infarct lesions and stepwise thresholded CTP maps. RESULTS With increasing levels of IR, objective image quality (SNR and CNR in white matter and gray matter, elimination of error voxels) and subjective image quality improved. Using IR, mean transit time (MTT) was higher in ischemic lesions, while there was no significant change of cerebral blood volume (CBV) and cerebral blood flow (CBF). Visual assessments of perfusion mismatch changed in 4 patients, while the ischemic core remained constant in all cases. Discriminative power for infarct prediction as represented by AUC was not significantly changed in CBV, but increased in CBF and MTT (mean (95% CI)): 0.72 (0.67-0.76) vs. 0.74 (0.70-0.78) and 0.65 (0.62-0.67) vs 0.67 (0.64-0.70). CONCLUSION In acute stroke patients, IR improves objective and subjective image quality when applied to standard-dose CTP. This adds to the overall confidence of CTP in acute stroke triage.


title: Tocilizumab and Remdesivir in a Pregnant Patient With Coronavirus Disease 2019 (COVID-19).

text: BACKGROUND There are limited data regarding treatment options for pregnant women with severe coronavirus disease 2019 (COVID-19). CASE A 35-year-old primigravid patient at 22 weeks of gestation presented with 7 days of fever, cough, anosmia, and dyspnea. Nasopharyngeal swab was positive for the novel coronavirus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and a chest X-ray demonstrated bilateral patchy infiltrates. Laboratory evaluation was notable for marked elevation of interleukin-6 and C-reactive protein concentrations. On hospital day 3, owing to increased dyspnea and oxygen requirement, the patient was treated with tocilizumab followed by 5 days of remdesivir. She responded well, recovered to room air, and was discharged home after a 9-day hospitalization. CONCLUSION Tocilizumab and remdesivir may be effective for treatment of severe COVID-19 in pregnancy, but additional data are needed to guide risk-benefit considerations.


title: Identification of the same polyomavirus species in different African horseshoe bat species is indicative of short-range host-switching events.

text: Polyomaviruses (PyVs) are considered to be highly host-specific in different mammalian species, with no well-supported evidence for host-switching events. We examined the species diversity and host specificity of PyVs in horseshoe bats (Rhinolophus spp.), a broadly distributed and highly speciose mammalian genus. We annotated six PyV genomes, comprising four new PyV species, based on pairwise identity within the large T antigen (LTAg) coding region. Phylogenetic comparisons revealed two instances of highly related PyV species, one in each of the Alphapolyomavirus and Betapolyomavirus genera, present in different horseshoe bat host species (Rhinolophus blasii and R. simulator), suggestive of short-range host-switching events. The two pairs of Rhinolophus PyVs in different horseshoe bat host species were 99.9 and 88.8 % identical with each other over their respective LTAg coding sequences and thus constitute the same virus species. To corroborate the species identification of the bat hosts, we analysed mitochondrial cytb and a large nuclear intron dataset derived from six independent and neutrally evolving loci for bat taxa of interest. Bayesian estimates of the ages of the most recent common ancestors suggested that the near-identical and more distantly related PyV species diverged approximately 9.1E4 (5E3-2.8E5) and 9.9E6 (4E6-18E6) years before the present, respectively, in contrast to the divergence times of the bat host species: 12.4E6 (10.4E6-15.4E6). Our findings provide evidence that short-range host-switching of PyVs is possible in horseshoe bats, suggesting that PyV transmission between closely related mammalian species can occur.


title: Widespread 3'-end uridylation in eukaryotic RNA viruses.

text: RNA 3' uridylation occurs pervasively in eukaryotes, but is poorly characterized in viruses. In this study, we demonstrate that a broad array of RNA viruses, including mycoviruses, plant viruses and animal viruses, possess a novel population of RNA species bearing nontemplated oligo(U) or (U)-rich tails, suggesting widespread 3' uridylation in eukaryotic viruses. Given the biological relevance of 3' uridylation to eukaryotic RNA degradation, we propose a conserved but as-yet-unknown mechanism in virus-host interaction.


title: Lost needle: a dilemma in robotic-assisted laparoscopic surgery.

text: A case is presented where a needle was lost in the assistant's port during a robotic-assisted radical prostatectomy. This complication generated a unique dilemma: whether or not to disengage the robot and search for the needle or to continue with the operation and look for the needle at the end of the operation.


title: Comparison of mortality risk in patients with cirrhosis and COVID-19 compared with patients with cirrhosis alone and COVID-19 alone: multicentre matched cohort.

text: OBJECTIVE Comorbid conditions are associated with poor prognosis in COVID-19. Registry data show that patients with cirrhosis may be at high risk. However, outcome comparisons among patients with cirrhosis+COVID-19 versus patients with COVID-19 alone and cirrhosis alone are lacking. The aim of this study was to perform these comparisons. DESIGN A multicentre study of inpatients with cirrhosis+COVID-19 compared with age/gender-matched patients with COVID-19 alone and cirrhosis alone was performed. COVID-19 and cirrhosis characteristics, development of organ failures and acute-on-chronic liver failure (ACLF) and mortality (inpatient death+hospice) were compared. RESULTS 37 patients with cirrhosis+COVID-19 were matched with 108 patients with COVID-19 and 127 patients with cirrhosis from seven sites. Race/ethnicity were similar. Patients with cirrhosis+COVID-19 had higher mortality compared with patients with COVID-19 (30% vs 13%, p=0.03) but not between patients with cirrhosis+COVID-19 and patients with cirrhosis (30% vs 20%, p=0.16). Patients with cirrhosis+COVID-19 versus patients with COVID-19 alone had equivalent respiratory symptoms, chest findings and rates of intensive care unit transfer and ventilation. However, patients with cirrhosis+COVID-19 had worse Charlson Comorbidity Index (CCI 6.5±3.1 vs 3.3±2.5, p<0.001), lower presenting GI symptoms and higher lactate. Patients with cirrhosis alone had higher cirrhosis-related complications, maximum model for end-stage liver disease (MELD) score and lower BiPAP/ventilation requirement compared with patients with cirrhosis+COVID-19, but CCI and ACLF rates were similar. In the entire group, CCI (OR 1.23, 95% CI 1.11 to 1.37, p<0.0001) was the only variable predictive of mortality on multivariable regression. CONCLUSIONS In this multicentre North American contemporaneously enrolled study, age/gender-matched patients with cirrhosis+COVID-19 had similar mortality compared with patients with cirrhosis alone but higher than patients with COVID-19 alone. CCI was the only independent mortality predictor in the entire matched cohort.


title: Pharmacotherapy for lower respiratory tract infections.

text: INTRODUCTION Bacterial infections play an important role as etiological agents in acute exacerbations of chronic obstructive pulmonary disease (AECOPD), and exacerbations of non-cystic fibrosis (CF) bronchiectasis. In acute bronchitis and asthma exacerbations their role is less well defined than with patients with COPD. The clinical features, causative pathogens and therapies of common acute respiratory tract infections are detailed in this review. AREAS COVERED This article covers medical literature published in any language from 2000 to 2014, on 'lower respiratory tract infections', identified using PubMed, MEDLINE and ClinicalTrial.gov. The search terms used were 'COPD exacerbations', 'bronchiectasis', 'macrolides' and 'inhaled antibiotics'. EXPERT OPINION Given that almost half of AECOPD are caused by bacteria, administration of antibacterial agents is recommended for patients with severe exacerbations or severe underlying COPD. Chronic prophylactic use of macrolides seems to be of benefit, particularly in patients with bronchiectasis and chronic mucous hypersecretion. In an effort to manage chronic airway infection non-CF bronchiectasis due to drug-resistant pathogens, aerosolized antibiotics may be of value, and the data from recent studies are examined to demonstrate the potential value of this therapy, which is often used as an adjunctive measure to systemic antimicrobial therapy.


title: [The epidemiological characteristics of an outbreak of 2019 novel coronavirus diseases (COVID-19) in China].

text: Objective: An outbreak of 2019 novel coronavirus diseases (COVID-19) in Wuhan, China has spread quickly nationwide. Here, we report results of a descriptive, exploratory analysis of all cases diagnosed as of February 11, 2020. Methods: All COVID-19 cases reported through February 11, 2020 were extracted from China's Infectious Disease Information System. Analyses included: 1) summary of patient characteristics; 2) examination of age distributions and sex ratios; 3) calculation of case fatality and mortality rates; 4) geo-temporal analysis of viral spread; 5) epidemiological curve construction; and 6) subgroup analysis. Results: A total of 72 314 patient records-44 672 (61.8%) confirmed cases, 16 186 (22.4%) suspected cases, 10567 (14.6%) clinical diagnosed cases (Hubei only), and 889 asymptomatic cases (1.2%)-contributed data for the analysis. Among confirmed cases, most were aged 30-79 years (86.6%), diagnosed in Hubei (74.7%), and considered mild (80.9%). A total of 1 023 deaths occurred among confirmed cases for an overall case-fatality rate of 2.3%. The COVID-19 spread outward from Hubei sometime after December 2019 and by February 11, 2020, 1 386 counties across all 31 provinces were affected. The epidemic curve of onset of symptoms peaked in January 23-26, then began to decline leading up to February 11. A total of 1 716 health workers have become infected and 5 have died (0.3%). Conclusions: The COVID-19 epidemic has spread very quickly. It only took 30 days to expand from Hubei to the rest of Mainland China. With many people returning from a long holiday, China needs to prepare for the possible rebound of the epidemic.


title: Safe abortion amid the COVID-19 pandemic: The case of Italy.

text: An estimated 56 million induced abortions occur globally every year, of which 54.9% are unsafe.[1] This is a major public health issue, especially where access to legal abortion is highly restricted, resulting in an estimated 7.9% of maternal deaths annually due to unsafe abortion.


title: Making the most of the first prenatal visit: The challenge of expanding prenatal genetic testing options and limited clinical encounter time.

text: OBJECTIVE Advances in prenatal genetics place additional challenges as patients must receive information about a growing array of screening and testing options. This raises concerns about how to achieve a shared decision-making process that prepares patients to make an informed decision about their choices about prenatal genetic screening and testing options, calling for a reconsideration of how healthcare providers approach the first prenatal visit. METHODS We conducted interviews with 40 pregnant women to identify components of decision-making regarding prenatal genetic screens and tests at this visit. Analysis was approached using grounded theory. RESULTS Participants brought distinct notions of risk to the visit, including skewed perceptions of baseline risk for a fetal genetic condition and the implications of screening and testing. Participants were very concerned about financial considerations associated with these options, ranking out-of-pocket costs on par with medical considerations. Participants noted diverging priorities at the first visit from those of their healthcare provider, leading to barriers to shared decision-making regarding screening and testing during this visit. CONCLUSION Research is needed to determine how to restructure the initiation of prenatal care in a way that best positions patients to make informed decisions about prenatal genetic screens and tests. This article is protected by copyright. All rights reserved.


title: Management of acute bacterial skin and skin structure infections with a focus on patients at high risk of treatment failure.

text: Over the last 25 years, the terminology of skin and soft tissue infections, as well as their classification for optimal management of patients, has changed. The so-called and recently introduced term 'acute bacterial skin and skin structure infections' (ABSSSIs), a cluster of fairly common types of infection, including abscesses, cellulitis, and wound infections, require an immediate effective antibacterial treatment as part of a timely and cautious management. The extreme level of resistance globally to many antibiotic drugs in the prevalent causative pathogens, the presence of risk factors of treatment failure, and the high epidemic of comorbidities (e.g. diabetes and obesity) make the appropriate selection of the antibiotic for physicians highly challenging. The selection of antibiotics is primarily empirical for ABSSSI patients which subsequently can be adjusted based on culture results, although rarely available in outpatient management. There is substantial evidence suggesting that inappropriate antibiotic treatment is given to approximately 20-25% of patients, potentially prolonging their hospital stay and increasing the risk of morbidity and mortality. The current review paper discusses the concerns related to the management of ABSSSI and the patient types who are most vulnerable to poor outcomes. It also highlights the key management time-points that treating physicians and surgeons must be aware of in order to achieve clinical success and to discharge patients from the hospital as early as possible.


title: Sequence identity between the genomes of humans and viruses.

text: OBJECTIVE People exposed to viruses usually do not develop diseases. Viruses cause diseases; however, most of the pathologic effects of these diseases are not caused directly by the viruses but by the side effects of the immune response. It is possible that sequence identity may exist between viruses and humans and may be biologically relevant to the infection of virus. The aim of this study was to find out whether sequence identity exists between viruses and humans. METHODS BLAST searches of virus genome sequences against human genome were performed using the resources of the National Center for Biotechnology Information (NCBI). RESULTS All the viruses that were compared to humans contain different numbers of short identical regions to the human genome. Each identical region was 20-30 nt and some were found at multiple sites within the human genome. CONCLUSION A new role of the virus in the relationship between viruses and humans was taken into account. We assume that viruses have brought their sequence into the human genome in the long past history of human-virus interaction. In the process, viruses play roles as carriers to transfer external sequence information into the human genome.