title: Global surge in measles and major international survey reinforce the need for greater awareness and uptake of all vaccinations.

text: Infectious diseases have posed significant challenges for the worldwide medical community since records began. COVID-19, which originated in China, has provided yet another timely reminder of how vulnerable we can be, despite considerable medical advances. But another worrying trend has been emerging in recent years and that is the resurgence of deaths from infectious disease that can be prevented by effective vaccination programmes. The global increase in measles is a classic example.


title: Interobserver agreement after pipeline embolization device implantation.

text: BACKGROUND AND PURPOSE Although flow diversion devices are popular in treatment of aneurysms, angiographic assessment with these devices has rarely been verified by interobserver variability study. The purpose of this study was to determine the interobserver agreement of a 3-point grading system for assessing the angiographic outcome after flow diversion therapy of intracranial, saccular aneurysms and to determine factors affecting such agreement. MATERIALS AND METHODS After approval by the institutional review board, 5 independent readers assessed pretreatment and follow-up digital subtraction angiograms from 96 patients treated with the Pipeline embolization device by using a 3-point grading system (complete, near-complete, and incomplete occlusion). "Minor discrepancy" was defined as a difference between any 2 readers of 1 grade, that is, complete vs near-complete or near-complete vs incomplete. "Major discrepancy" was defined as a difference between any 2 readers in which 1 reader noted complete occlusion and the other reader noted incomplete occlusion. We performed statistical analysis for the interobserver agreement by using the intraclass correlation coefficient. Subgroup analyses for discrepancy rate and ICC were performed for previously coiled aneurysms. RESULTS The interobserver agreement was excellent (ICC, 0.76; 95% CI, 0.69-0.92). Among 96 cases, there was absolute agreement in 74 (77%), of which 67 had unanimous consensus of "complete" occlusion, 2 "near-complete" occlusion, and 5 "incomplete" occlusion. Discordance between any 2 readers was noted in 22 cases (23%), of which 7 (7.3%) revealed a major discrepancy. Subgroup analysis showed that minor discrepancies were more common among patients previously treated with coils vs those not previously treated with coils (37.5% vs 11.2%; P < .05). CONCLUSIONS The observer agreement regarding occlusion after PED therapy is excellent. Only a minority of cases demonstrated discrepancy considered as major in this study.


title: Evaluation of a monoclonal antibody-based rapid immunochromatographic test for direct detection of rabies virus in the brain of humans and animals.

text: Rabies diagnosis uses a direct fluorescent antibody test (FAT) that is difficult, costly, and time-consuming, and requires trained personnel. We developed a rapid immunochromatographic test (RICT) for the diagnosis of rabies. The efficacy of the RICT was compared with that of the FAT. Brain samples were collected from humans, dogs, cats, and other animals in Sri Lanka (n = 248), Bhutan (n = 27), and Thailand (n = 228). The sensitivity (0.74-0.95), specificity (0.98-1.0), positive predictive value (0.98-1.0), negative predictive value (0.75-0.97), accuracy (0.91-0.98), and kappa measure of agreement (0.79-0.93) were all satisfactory for animal samples and samples preserved in 50% glycerol saline solution. Because the RICT showed high sensitivity but low specificity with human brain samples, it is unsuitable for confirming rabies in humans. No amino acid substitutions were found in the antibody attachment sites of the nucleoprotein gene with FAT-positive, RICT-negative samples. The RICT is reliable, user friendly, rapid, robust, and can be used in laboratories with a modest infrastructure.


title: Effects of ventilator settings, nebulizer and exhalation port position on albuterol delivery during non-invasive ventilation: an in-vitro study.

text: BACKGROUND Few studies have investigated the factors affecting aerosol delivery during non-invasive ventilation (NIV). Our aim was to investigate, using a bench-top model, the effect of different ventilator settings and positions of the exhalation port and nebulizer on the amount of albuterol delivered to a lung simulator. METHODS A lung model simulating spontaneous breathing was connected to a single-limb NIV ventilator, set in bi-level positive airway pressure (BIPAP) with inspiratory/expiratory pressures of 10/5, 15/10, 15/5, and 20/10 cmH2O, or continuous positive airway pressure (CPAP) of 5 and 10 cmH2O. Three delivery circuits were tested: a vented mask with the nebulizer directly connected to the mask, and an unvented mask with a leak port placed before and after the nebulizer. Albuterol was collected on a filter placed after the mask and then the delivered amount was measured with infrared spectrophotometry. RESULTS Albuterol delivery during NIV varied between 6.7 ± 0.4% to 37.0 ± 4.3% of the nominal dose. The amount delivered in CPAP and BIPAP modes was similar (22.1 ± 10.1 vs. 24.0 ± 10.0%, p = 0.070). CPAP level did not affect delivery (p = 0.056); in BIPAP with 15/5 cmH2O pressure the delivery was higher compared to 10/5 cmH2O (p = 0.033) and 20/10 cmH2O (p = 0.014). Leak port position had a major effect on delivery in both CPAP and BIPAP, the best performances were obtained with the unvented mask, and the nebulizer placed between the leak port and the mask (p < 0.001). CONCLUSIONS In this model, albuterol delivery was marginally affected by ventilatory settings in NIV, while position of the leak port had a major effect. Nebulizers should be placed between an unvented mask and the leak port in order to maximize aerosol delivery.


docid: zucngyys

title: Clinical epidemiology and outcomes of community acquired infection and sepsis among hospitalized patients in a resource limited setting in Northeast Thailand: A prospective observational study (Ubon-sepsis).

text: Infection and sepsis are leading causes of death worldwide but the epidemiology and outcomes are not well understood in resource-limited settings. We conducted a four-year prospective observational study from March 2013 to February 2017 to examine the clinical epidemiology and outcomes of adults admitted with community-acquired infection in a resource-limited tertiary-care hospital in Ubon Ratchathani province, Northeast Thailand. Hospitalized patients with infection and accompanying systemic manifestations of infection within 24 hours of admission were enrolled. Subjects were classified as having sepsis if they had a modified sequential organ failure assessment (SOFA) score ≥2 at enrollment. This study was registered with ClinicalTrials.gov, number NCT02217592. A total of 4,989 patients were analyzed. Of the cohort, 2,659 (53%) were male and the median age was 57 years (range 18-101). Of these, 1,173 (24%) patients presented primarily to the study hospital, 3,524 (71%) were transferred from 25 district hospitals or 8 smaller hospitals in the province, and 292 (6%) were transferred from one of 30 hospitals in other provinces. Three thousand seven hundred and sixteen (74%) patients were classified as having sepsis. Patients with sepsis had an older age distribution and a greater prevalence of comorbidities compared to patients without sepsis. Twenty eight-day mortality was 21% (765/3,716) in sepsis and 4% (54/1,273) in non-sepsis patients (p<0.001). After adjusting for gender, age, and comorbidities, sepsis on admission (adjusted hazard ratio [HR] 3.30; 95% confidence interval [CI] 2.48-4.41, p<0.001), blood culture positive for pathogenic organisms (adjusted HR 2.21; 95% CI 1.89-2.58, p<0.001) and transfer from other hospitals (adjusted HR 2.18; 95% CI 1.69-2.81, p<0.001) were independently associated with mortality. In conclusion, mortality of community-acquired sepsis in Northeast Thailand is considerable and transferred patients with infection are at increased risk of death. To reduce mortality of sepsis in this and other resource-limited setting, facilitating rapid detection of sepsis in all levels of healthcare facilities, establishing guidelines for transfer of sepsis patients, and initiating sepsis care prior to and during transfer may be beneficial.


title: Cholesterol effectively blocks entry of flavivirus.

text: Japanese encephalitis virus (JEV) and dengue virus serotype 2 (DEN-2) are enveloped flaviviruses that enter cells through receptor-mediated endocytosis and low pH-triggered membrane fusion and then replicate in intracellular membrane structures. Lipid rafts, cholesterol-enriched lipid-ordered membrane domains, are platforms for a variety of cellular functions. In this study, we found that disruption of lipid raft formation by cholesterol depletion with methyl-beta-cyclodextrin or cholesterol chelation with filipin III reduces JEV and DEN-2 infection, mainly at the intracellular replication steps and, to a lesser extent, at viral entry. Using a membrane flotation assay, we found that several flaviviral nonstructural proteins are associated with detergent-resistant membrane structures, indicating that the replication complex of JEV and DEN-2 localizes to the membranes that possess the lipid raft property. Interestingly, we also found that addition of cholesterol readily blocks flaviviral infection, a result that contrasts with previous reports of other viruses, such as Sindbis virus, whose infectivity is enhanced by cholesterol. Cholesterol mainly affected the early step of the flavivirus life cycle, because the presence of cholesterol during viral adsorption greatly blocked JEV and DEN-2 infectivity. Flavirial entry, probably at fusion and RNA uncoating steps, was hindered by cholesterol. Our results thus suggest a stringent requirement for membrane components, especially with respect to the amount of cholesterol, in various steps of the flavivirus life cycle.


title: Metformin Treatment Was Associated with Decreased Mortality in COVID-19 Patients with Diabetes in a Retrospective Analysis.

text: Metformin was proposed to be a candidate for host-directed therapy for COVID-19. However, its efficacy remains to be validated. In this study, we compared the outcome of metformin users and nonusers in hospitalized COVID-19 patients with diabetes. Hospitalized diabetic patients with confirmed COVID-19 in the Tongji Hospital of Wuhan, China, from January 27, 2020 to March 24, 2020, were grouped into metformin and no-metformin groups according to the diabetic medications used. The demographics, characteristics, laboratory parameters, treatments, and clinical outcome in these patients were retrospectively assessed. A total of 283 patients (104 in the metformin and 179 in the no-metformin group) were included in this study. There were no significant differences between the two groups in gender, age, underlying diseases, clinical severity, and oxygen-support category at admission. The fasting blood glucose level of the metformin group was higher than that of the no-metformin group at admission and was under effective control in both groups after admission. Other laboratory parameters at admission and treatments after admission were not different between the two groups. The length of hospital stay did not differ between the two groups (21.0 days for metformin versus 19.5 days for no metformin, P = 0.74). However, in-hospital mortality was significantly lower in the metformin group (3/104 (2.9%) versus 22/179 (12.3%), P = 0.01). Antidiabetic treatment with metformin was associated with decreased mortality compared with diabetics not receiving metformin. This retrospective analysis suggests that metformin may offer benefits in patients with COVID-19 and that further study is indicated.


title: Structural Equation Modeling of Social Networks: Specification, Estimation, and Application.

text: Psychologists are interested in whether friends and couples share similar personalities or not. However, no statistical models are readily available to test the association between personalities and social relations in the literature. In this study, we develop a statistical model for analyzing social network data with the latent personality traits as covariates. Because the model contains a measurement model for the latent traits and a structural model for the relationship between the network and latent traits, we discuss it under the general framework of structural equation modeling (SEM). In our model, the structural relation between the latent variable(s) and the outcome variable is no longer linear or generalized linear. To obtain model parameter estimates, we propose to use a two-stage maximum likelihood (ML) procedure. This modeling framework is evaluated through a simulation study under representative conditions that would be found in social network data. Its usefulness is then demonstrated through an empirical application to a college friendship network.


title: Trigeminal postherpetic neuralgia responsive to treatment with capsaicin 8 % topical patch: a case report.

text: Postherpetic neuralgia has been variably defined but is generally understood to be pain that persists for longer than a few months after an attack of herpes zoster. Pain persists for years in approximately 10 % of those afflicted with acute herpes zoster. The likelihood of postherpetic neuralgia increases with older age, severity of the zoster, trigeminal location, and other factors. Postherpetic neuralgia is a neuropathic pain and treatment usually involves sequential trials of topical and systemic drugs; a variety of other therapies may be considered in refractory cases. A new topical capsaicin 8 % patch has been approved for this indication based on the positive studies in patients with non-trigeminal postherpetic neuralgia. Experience with the use of the capsaicin 8 % patch for trigeminal distribution neuralgia is lacking. We report a case of trigeminal postherpetic neuralgia which was safely and effectively treated with capsaicin 8 % patch.


docid: kudggfhq

title: JNK1 and ERK1/2 modulate lymphocyte homeostasis via BIM and DRP1 upon AICD induction.

text: The Activation-Induced Cell Death (AICD) is a stimulation-dependent form of apoptosis used by the organism to shutdown T-cell response once the source of inflammation has been eliminated, while allowing the generation of immune memory. AICD is thought to progress through the activation of the extrinsic Fas/FasL pathway of cell death, leading to cytochrome-C release through caspase-8 and Bid activation. We recently described that, early upon AICD induction, mitochondria undergo structural alterations, which are required to promote cytochrome-C release and execute cell death. Here, we found that such alterations do not depend on the Fas/FasL pathway, which is instead only lately activated to amplify the cell death cascade. Instead, such alterations are primarily dependent on the MAPK proteins JNK1 and ERK1/2, which, in turn, regulate the activity of the pro-fission protein Drp1 and the pro-apoptotic factor Bim. The latter regulates cristae disassembly and cooperate with Drp1 to mediate the Mitochondrial Outer Membrane Permeabilization (MOMP), leading to cytochrome-C release. Interestingly, we found that Bim is also downregulated in T-cell Acute Lymphoblastic Leukemia (T-ALL) cells, this alteration favouring their escape from AICD-mediated control.


title: Efficacy of Instant Hand Sanitizers against Foodborne Pathogens Compared with Hand Washing with Soap and Water in Food Preparation Settings: A Systematic Review.

text: Hands can be a vector for transmitting pathogenic microorganisms to foodstuffs and drinks, and to the mouths of susceptible hosts. Hand washing is the primary barrier to prevent transmission of enteric pathogens via cross-contamination from infected persons. Conventional hand washing involves the use of water, soap, and friction to remove dirt and microorganisms. The availability of hand sanitizing products for use when water and soap are unavailable has increased in recent years. The aim of this systematic review was to collate scientific information on the efficacy of hand sanitizers compared with washing hands with soap and water for the removal of foodborne pathogens from the hands of food handlers. An extensive literature search was carried out using three electronic databases: Web of Science, Scopus, and PubMed. Twenty-eight scientific publications were ultimately included in the review. Analysis of this literature revealed various limitations in the scientific information owing to the absence of a standardized protocol for evaluating the efficacy of hand products and variation in experimental conditions. However, despite conflicting results, scientific evidence seems to support the historical skepticism about the use of waterless hand sanitizers in food preparation settings. Water and soap appear to be more effective than waterless products for removal of soil and microorganisms from hands. Alcohol-based products achieve rapid and effective inactivation of various bacteria, but their efficacy is generally lower against nonenveloped viruses. The presence of food debris significantly affects the microbial inactivation rate of hand sanitizers.


title: Equid herpesvirus type 1 activates platelets.

text: Equid herpesvirus type 1 (EHV-1) causes outbreaks of abortion and neurological disease in horses. One of the main causes of these clinical syndromes is thrombosis in placental and spinal cord vessels, however the mechanism for thrombus formation is unknown. Platelets form part of the thrombus and amplify and propagate thrombin generation. Here, we tested the hypothesis that EHV-1 activates platelets. We found that two EHV-1 strains, RacL11 and Ab4 at 0.5 or higher plaque forming unit/cell, activate platelets within 10 minutes, causing α-granule secretion (surface P-selectin expression) and platelet microvesiculation (increased small events double positive for CD41 and Annexin V). Microvesiculation was more pronounced with the RacL11 strain. Virus-induced P-selectin expression required plasma and 1.0 mM exogenous calcium. P-selectin expression was abolished and microvesiculation was significantly reduced in factor VII- or X-deficient human plasma. Both P-selectin expression and microvesiculation were re-established in factor VII-deficient human plasma with added purified human factor VIIa (1 nM). A glycoprotein C-deficient mutant of the Ab4 strain activated platelets as effectively as non-mutated Ab4. P-selectin expression was abolished and microvesiculation was significantly reduced by preincubation of virus with a goat polyclonal anti-rabbit tissue factor antibody. Infectious virus could be retrieved from washed EHV-1-exposed platelets, suggesting a direct platelet-virus interaction. Our results indicate that EHV-1 activates equine platelets and that α-granule secretion is a consequence of virus-associated tissue factor triggering factor X activation and thrombin generation. Microvesiculation was only partly tissue factor and thrombin-dependent, suggesting the virus causes microvesiculation through other mechanisms, potentially through direct binding. These findings suggest that EHV-1-induced platelet activation could contribute to the thrombosis that occurs in clinically infected horses and provides a new mechanism by which viruses activate hemostasis.


title: U.S. medical countermeasure development since 2001: a long way yet to go.

text: The U.S. government has taken significant steps toward developing and acquiring vaccines, drugs, and other medical countermeasures (MCMs) to protect and treat the population after a biological attack. In contrast to 2001, there is now a procedure for the Department of Health and Human Services (HHS) to develop, license, and stockpile MCMs for civilian use. Another major accomplishment is smallpox preparedness: There is now an adequate supply of vaccine for every person in the U.S., and there is an alternative vaccine meant for immunocompromised people and those with close contact with them. In spite of these and other accomplishments, the U.S. government MCM effort has been criticized by federal advisory committees, National Academy of Sciences reports, a congressional commission, and outside analysts who state that the efforts lack central leadership and accountability and that the pace of progress has been slow. A clear operational strategy for using MCMs, which would guide their development and acquisition, is also lacking. In this article, we review key areas of progress made since 2001 to develop and acquire MCMs, and we summarize what we judge to be the most critical and often mentioned areas where improvements are needed.


docid: asliteau

title: Racial and Socioeconomic Disparities in Hysterectomy Route for Benign Conditions.

text: BACKGROUND The aim of this paper was to explore disparities associated with the route of hysterectomy in the University of Pittsburgh Medical Center (UPMC) health system and to evaluate whether the hysterectomy clinical pathway implementation impacted disparities in the utilization of minimally invasive hysterectomy (MIH). METHODS We performed a retrospective medical record review of all the patients who have undergone hysterectomy for benign indications at UPMC-affiliated hospitals between fiscal years (FY) 2012 and 2014. RESULTS A total number of 6373 hysterectomy patient cases were included in this study: 88.7% (5653) were European American (EA), 11.02% (702) were African American (AA), and the remaining 0.28% (18) were of other ethnicities. We found that non-EA, women aged 45-60, traditional Medicaid, and traditional Medicare enrollees were more likely to have a total abdominal hysterectomy (TAH). Residence in higher median income zip code (> $61,000) was associated with 60% lower odds of undergoing TAH. Both FY 2013 and 2014 were associated with significantly lower odds of TAH. Logistic regression results from the model for non-EA patients for FY 2012 and FY 2014 demonstrated that FY and zip code income group were not significant predictors of surgery type in this subgroup. Pathway implementation did not reduce racial disparity in MIH utilization. CONCLUSION This study demonstrated that there is a significant disparity in MIH utilization, where non-EA and Medicaid/Medicare recipients had higher odds of undergoing TAH. Further research is needed to investigate how care standardization may alleviate healthcare disparities.


title: Involvement of gadolinium chelates in the mechanism of nephrogenic systemic fibrosis: an update.

text: Nephrogenic systemic fibrosis (NSF) is a highly debilitating scleroderma-like disease occurring exclusively in patients with severe or end-stage renal failure. Since the recognition of a link between gadolinium chelates (GCs) used as contrast agents for MR imaging and NSF by two independent European teams in 2006, numerous studies have described the clinical issues and investigated the mechanism of this disease. So far the most commonly reported hypothesis is based on the in vivo dechelation of GCs. The physicochemical properties of GCs, especially their thermodynamic and kinetic stabilities, are described in the present article. High kinetic stability provided by the macrocyclic structure, combined with high thermodynamic stability, minimizes the amount of free gadolinium released in the body. The current hypotheses regarding the pathophysiologic mechanism are critically discussed.


title: Duodenal Rupture after Blunt Abdominal Trauma by Bicycle Handlebar: Case Report and Literature Review.

text: Blunt abdominal trauma is most frequent in the pediatric population. Duodenal lesions after abdominal trauma in children are infrequent and tend to be secondary to traffic accidents. It is up to five times more frequent in males, with an average age between 16 and 30 years. Bicycle accidents continue to lead to morbidity and mortality in children, representing between 5% and 14% of total blunt abdominal injuries. The diagnosis of duodenal injuries after trauma is difficult and requires a high index of clinical suspicion. We present the case of a 17-year-old patient seen in the emergency room after falling off his bicycle and presented a blunt trauma in the epigastric region. On physical examination, there was a swelling in the upper right abdominal quadrant and epigastrium with tenderness on deep palpation. He presented with hematemesis without hemodynamic repercussion. A contrast abdominal computed tomography was performed and he was diagnosed with third-part duodenal rupture. A resection of the perforated third-part duodenal rupture was performed, and the transit was reconstructed using a Roux-Y duodenojejunostomy. The postoperative period was uneventful and the patient was discharged after 16 days of stay. Duodenal injury is very rare, produced by high-energy trauma. They rarely present as single lesions as other visceral lesions are usually associated. The early diagnosis is important to reduce the morbidity and mortality.


title: COVID19 in South Asians/Asian Indians: Heterogeneity of Data and Implications for Pathophysiology and Research.

text: Despite a large population and limited health infrastructure, the incidence and mortality of Coronavirus Disease 2019 (COVID-19) has been lower in South Asia than many regions. The underlying reasons and mechanisms for this relative protection are not established. However both genetic and environmental factors might play a role. Polymorphisms in ACE2 gene, ACE gene and in genes for some of the host cell proteases could affect the viral entry and replication. There is some evidence that HLA polymorphisms and several pathways involved in immune and inflammatory response could contribute to ethnic variation. Cross immunity because of past exposure to viral infections as well as malaria is likely to protect from the severe manifestations of disease. Role of BCG vaccination in trained innate immunity is recognised and could be a protective factor against COVID-19. There is limited evidence of the possibility of a less virulent viral strain circulating in South Asia. There is evidence from different parts of the world that temperature and humidity can influence viral survival as well as the host immune response. Finally implementation of early containment measures by some South Asian countries has also contributed to a less disease burden.


title: Human T-cells directed to seasonal influenza A virus cross-react with 2009 pandemic influenza A (H1N1) and swine-origin triple-reassortant H3N2 influenza viruses.

text: Virus-specific CD8(+) T-cells contribute to protective immunity against influenza A virus (IAV) infections. As the majority of these cells are directed to conserved viral proteins, they may afford protection against IAVs of various subtypes. The present study assessed the cross-reactivity of human CD8(+) T-lymphocytes, induced by infection with seasonal A (H1N1) or A (H3N2) influenza virus, with 2009 pandemic influenza A (H1N1) virus [A(H1N1)pdm09] and swine-origin triple-reassortant A (H3N2) [A(H3N2)v] viruses that are currently causing an increasing number of human cases in the USA. It was demonstrated that CD8(+) T-cells induced after seasonal IAV infections exerted lytic activity and produced gamma interferon upon in vitro restimulation with A(H1N1)pdm09 and A(H3N2)v influenza A viruses. Furthermore, CD8(+) T-cells directed to A(H1N1)pdm09 virus displayed a high degree of cross-reactivity with A(H3N2)v viruses. It was concluded that cross-reacting T-cells had the potential to afford protective immunity against A(H1N1)pdm09 viruses during the pandemic and offer some degree of protection against infection with A(H3N2)v viruses.


title: Systematic review of the design, implementation and effectiveness of mass media and nutrition education interventions for infant and young child feeding.

text: OBJECTIVE To systematically review the design, implementation and effectiveness of mass media and nutrition education interventions for improving infant and young child feeding (IYCF) practices and related psychosocial factors. DESIGN A search of PubMed, Embase and PsycINFO databases, a Google search, and a consultation with experts in the field of IYCF performed in July 2016. SETTING Low- and middle-income countries, as defined by the World Bank Group. SUBJECTS Eligible studies: included a mass media component (with or without nutrition education); conducted a pre-post evaluation (with or without a control group); assessed IYCF knowledge, attitudes, beliefs and/or practices; and were published in English between 2000 and present. RESULTS Eighteen unique studies were identified that examined the effect of mass media (types included: television; print; voice and/or SMS (text) messages; radio; megaphones/loudspeakers; videos; social media; songs/dramas) and nutrition education interventions on IYCF practices within thirteen countries. Of these, fifteen studies reported improvements in breast- and/or complementary feeding practices, using indicators recommended by the WHO, and six studies reported improvements in related psychosocial factors. However, little detail was provided on the use of formative research, a formal behaviour change theory and behaviour change techniques. Few studies reported both dose delivered and participants' exposure to the intervention. CONCLUSIONS Despite evidence of effectiveness, few common elements in the design of interventions were identified. Future research should consistently report these details to open the 'black box' of IYCF interventions, identify effective design components and ensure replicability.


title: Detection and significance of serum protein markers of small-cell lung cancer.

text: Currently, no satisfactory biomarkers are available to screen for small-cell lung cancer (SCLC). We applied a surface-enhanced laser desorption/ionization time-of-flight mass spectrometry (SELDI-TOF MS) ProteinChip system to detect 150 serum samples (including 54 SCLC patients, 24 non-small cell lung cancer [NSCLC] patients, 32 pneumonia patients, and 40 healthy individuals). The spectra data were analyzed by support vector machine (SVM) and potential biomarkers were chosen for the system training and used to construct diagnostic model. Pattern 1, constructed of four protein peaks with mass/charge (m/z) of 4,293 Da, 4,612 Da, 6,455 Da, and 7,582 Da, separated SCLC patients from the healthy individuals with a sensitivity of 88.9% and a specificity of 85.7%. This pattern performed significantly better than the current marker, neuron-specific enolase (NSE) (P<0.05). Pattern 2, constructed of protein peaks with mass/charge (m/z) of 2,764 Da and 1,7368 Da, separated SCLC from pneumonia with a sensitivity of 88.9% and a specificity of 91.7%. Pattern 3, constructed of another three protein peaks with m/z of 3,912 Da, 7,562 Da, and 13,777 Da, separated SCLC from NSCLC. The sensitivity and specificity were 83.3% and 75.0%, respectively. These results suggested that SELDI-TOF MS combined with support vector machine yields significantly higher sensitivity and specificity for the detection of serum protein of SCLC.


Fever in a traveler returning from Ethiopia.


title: Fistula-in-ano: when to cut, tie, plug, or sew.

text: INTRODUCTION Management of fistula-in-ano requires understanding of both perianal and rectal anatomy, as well as the surgical approaches available to ensure the highest possible postoperative continence and wound healing. Further, high rates of recurrence with medical management commonly bring these patients under the care of the colorectal surgeon after variable periods of failed conservative management. Novel techniques provide surgeons with tools to treat increasingly complex fistulas with a focus on maintaining sphincteric functionality and limiting recurrence. METHOD This manuscript presents our practice, including perioperative decision making regarding surgical approach, in managing patients with fistula-in-ano. CONCLUSION Familiarity with these techniques prepares the general surgeon and colorectal surgeon to improve wound healing and functional outcomes in these patients, especially with complex disease involving the external and internal anal sphincters.


title: Status of endoscopes and instruments used during NOTES.

text: Natural orifice translumenal endoscopic surgery (NOTES) requires an intentional perforation of a hollow lumen to pass an endoscope into an otherwise inaccessible body cavity with diagnostic or therapeutic intent. The limitations of current flexible instruments for this purpose are outlined, including the unsuitability for NOTES of current flexible needle knives, guidewires, balloons, overtubes, grasping forceps, and scissors. The development of novel suturing instruments, trocars, articulating instruments, flexible bipolar forceps, flexible clips, magnetic devices, and staplers as well as the advent of manual mechanical manipulators for flexible accessories is outlined. New instrument solutions for endosurgery are described, such as articulating flexible accessories for gastroscopes, novel "platforms" that can be rigidized, and unconventional scope arrangements. Debatably, the greatest current benefit of NOTES is that it may lead to further development of better instrumentation for endosurgery.


title: Predicting transient particle transport in enclosed environments with the combined computational fluid dynamics and Markov chain method.

text: To quickly obtain information about airborne infectious disease transmission in enclosed environments is critical in reducing the infection risk to the occupants. This study developed a combined computational fluid dynamics (CFD) and Markov chain method for quickly predicting transient particle transport in enclosed environments. The method first calculated a transition probability matrix using CFD simulations. Next, the Markov chain technique was applied to calculate the transient particle concentration distributions. This investigation used three cases, particle transport in an isothermal clean room, an office with an underfloor air distribution system, and the first-class cabin of an MD-82 airliner, to validate the combined CFD and Markov chain method. The general trends of the particle concentrations vs. time predicted by the Markov chain method agreed with the CFD simulations for these cases. The proposed Markov chain method can provide faster-than-real-time information about particle transport in enclosed environments. Furthermore, for a fixed airflow field, when the source location is changed, the Markov chain method can be used to avoid recalculation of the particle transport equation and thus reduce computing costs.


title: Health economic evaluations of sepsis interventions in critically ill adult patients: a systematic review.

text: Background Sepsis is a global health priority. Interventions to reduce the burden of sepsis need to be both effective and cost-effective. We performed a systematic review of the literature on health economic evaluations of sepsis treatments in critically ill adult patients and summarised the evidence for cost-effectiveness. Methods We systematically searched MEDLINE, Embase, and the Cochrane Library using thesaurus (e.g. MeSH) and free-text terms related to sepsis and economic evaluations. We included all articles that reported, in any language, an economic evaluation of an intervention for the management of sepsis in critically ill adult patients. Data extracted included study details, intervention details, economic evaluation methodology, and outcomes. Included studies were appraised for reporting quality using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. Results We identified 50 records representing 46 economic evaluations for a variety of interventions including antibiotics (n = 5), fluid therapy (n = 2), early goal-directed therapy and other resuscitation protocols (n = 8), immunoglobulins (n = 2), and interventions no longer in clinical use such as monoclonal antibodies (n = 7) and drotrecogin alfa (n = 13). Twelve (26%) evaluations were of excellent reporting quality. Incremental cost-effectiveness ratios (ICERs) ranged from dominant (lower costs and higher effectiveness) for early goal-directed therapy, albumin, and a multifaceted sepsis education program to dominated (higher costs and lower effectiveness) for polymerase chain reaction assays (LightCycler SeptiFast testing MGRADE®, SepsiTest™, and IRIDICA BAC BSI assay). ICERs varied widely across evaluations, particularly in subgroup analyses. Conclusions There is wide variation in the cost-effectiveness of sepsis interventions. There remain important gaps in the literature, with no economic evaluations identified for several interventions routinely used in sepsis. Given the high economic and social burden of sepsis, high-quality economic evaluations are needed to increase our understanding of the cost-effectiveness of these interventions in routine clinical practice and to inform decision makers. Trial registration PROSPERO CRD42018095980.


title: Single versus multimodality training basic laparoscopic skills.

text: INTRODUCTION Even though literature provides compelling evidence of the value of simulators for training of basic laparoscopic skills, the best way to incorporate them into a surgical curriculum is unclear. This study compares the training outcome of single modality training with multimodality training of basic laparoscopic skills. METHODS Thirty-six medical students without laparoscopic experience performed six training sessions of 45 min each, one per day, in which four different basic tasks were trained. Participants in the single-modality group (S) (n = 18) practiced solely on a virtual reality (VR) simulator. Participants in the multimodality group (M) (n = 18) practiced on the same VR simulator (2x), a box trainer (2x), and an augmented reality simulator (2x). All participants performed a pre-test and post-test on the VR simulator (the four basic tasks + one additional basic task). Halfway through the training protocol, both groups performed a salpingectomy on the VR simulator as interim test. RESULTS Both groups improved their performance significantly (Wilcoxon signed-rank, P < 0.05). The performances of group S and group M in the additional basic task and the salpingectomy did not differ significantly (Mann-Whitney U test, P > 0.05). Group S performed the four basic tasks in the post-test on the VR faster than group M (P ≤ 0.05), which can be explained by the fact that they were much more familiar with these tasks. CONCLUSIONS Training of basic laparoscopic tasks on single or multiple modalities does not result in different training outcome. Both training methods seem appropriate for the attainment of basic laparoscopic skills in future curricula.


title: Is VLSM a valid tool for determining the functional anatomy of the brain? Usefulness of additional Bayesian network analysis.

text: OBJECTIVES The ability of voxel-based lesion-symptom mapping (VLSM) to define the functional anatomy of the human brain has not been fully assessed. With a view to assessing VLSM's validity, the present study analyzed the technique's ability to determine the known clinical-anatomic correlates of hemiparesis in stroke patients. DESIGN Lesions (damaged in at least 5 patients) associated with transformed limb motor score (after adjustment on lesion volume) at 6 months were examined in 272 patients using VLSM. The value of additional multivariable linear, logistic and Bayesian analyses was examined. RESULTS We first checked that motor hemiparesis was fully accounted for by corticospinal tract (CST) lesions (sensitivity = 100%; p = 0.0001). Conventional VLSM analysis flagged up 2 regions corresponding to the CST, but also 8 regions located outside the CST. All 10 brain regions achieving statistical significance in the VLSM analysis were submitted to 3 additional analyses. The backward linear regression analysis selected 5 regions, one only corresponding to the CST (R2: 0.03, p = 0.0008). The logistic regression analysis selected correctly the CST (OR: 2.39, 95%CI: 1.44-3.96; 0.001). The Bayesian network analysis selected regions including the CST (in 92% of 3000 bootstrap replications) and identified the source of multicollinearity. These lesions evaluated by structural equation modeling resulted in an excellent fit (p-value = 0.228, chi/df = 1.19, RMSEA = 0.032, CFI = 0.999). Analyses of confusion factors showed that conventional VLSM analyses were strongly influenced by lesion frequency (R2 = 0.377; p = 0.0001) and multicollinearity. CONCLUSIONS Conventional VLSM analyses are sensitive but weakened by a type I error due to the combined effects of multicollinearity and lesion frequency. We demonstrate that the addition of a Bayesian network analysis, and to a lesser extent of logistic regression, controlled for this type I error and constituted a reliable means of defining the functional anatomy of the motor system in stroke patients.


Respiratory health and disease in Europe: the new European Lung White Book.


title: Complications of bronchial stapling in thoracic surgery.

text: OBJECTIVE The use of staplers for thoracic surgery has been widely accepted and regarded as a safe procedure. However, complications of stapling are occasionally experienced. The aim of this retrospective study was to analyze complications of bronchial stapling. METHODS A retrospective multi-institutional review was conducted by the Central Japan Lung Cancer Surgery Study Group, comprising 29 institutions. All instances of bronchial stapling in thoracic surgery were reviewed during the research period. RESULTS Bronchial stapling was performed 2,030 times, using 36 kinds of staplers. The total number of complications related to stapling was 36 (1.8 %); 31 events occurred intraoperatively and five events occurred postoperatively. The intraoperative complications were air leakage (N = 20) and stapling failure (N = 11), which were caused by stapler-tissue thickness mismatch (N = 17), stapler defect (N = 3), tissue fragility (N = 2), and unknown reasons (N = 9). In all 31 cases, intraoperative complications were recovered intraoperatively with additional suturing, and no further complications were observed postoperatively. The postoperative complications were bronchopleural fistula (BPF) (N = 4) and bleeding from the chest wall (intercostal artery) (N = 1). The rate of BPF was 0.2 % (4 of 2,030). Two of four BPFs induced critical conditions. Postoperative bleeding was caused by the use of Duet TRS(TM). Both total complications and BPF occurred more frequently in the main bronchus than in the lobar or segmental bronchus. No relationship was seen between the incidence of complications and cartridge colors in lobar bronchial stapling. The compression types of staplers were associated with the incidence of complication. CONCLUSIONS Intraoperative and postoperative complications of bronchial stapling were studied. Generally, bronchial stapling in recent thoracic surgery was safe, but rare postoperative complications may induce critical conditions. Knowledge of potential complications and causes of bronchial stapling may decrease the incidence of stapling complications.


title: Structure-activity relationship study of the tumour-targeting peptide A20FMDV2 via modification of Lys16, Leu13, and N- and/or C-terminal functionality.

text: The 20-residue linear peptide A20FMDV2 has been shown to exhibit high selectivity and affinity for the tumour-related αvβ6 integrin and has potential as a vector for therapeutic drugs. However, it exhibits poor half-life in plasma in part due to its high susceptibility to serum proteases. In this study fourteen A20FMDV2 analogues incorporating non-proteinogenic substitutes of the native Lys16 and Leu13 residues and six A20FMDV2 analogues containing modified N- and C-termini were synthesised to increase the half-life and activity of A20FMDV2. The analogues incorporating modified terminal motifs of A20FMDV2 were found to strongly bind to the αvβ6 integrin and were subsequently functionalized with the diethylenetriaminepentaacetic acid chelating agent to facilitate coupling with radioactive indium-111 for human plasma stability and in vivo biodistribution studies. A20FMDV2 peptide variants incorporating an N-terminal d-Asn and C-terminal d-Thr exhibited improved relative activity in vitro and were less susceptible to plasma degradation.


title: Clampless laparoendoscopic single-site partial nephrectomy for renal cancer with low PADUA score: technique and surgical outcomes.

text: UNLABELLED WHAT'S KNOWN ON THE SUBJECT? AND WHAT DOES THE STUDY ADD?: Laparoendoscopic single-site (LESS) surgery has proved to be immediately applicable in the clinical field, being safe and feasible in the hands of experienced laparoscopic surgeons in well-selected patients. All extirpative and reconstructive urological procedures have been described in the literature, but LESS partial nephrectomy (PN) is one of the most complex procedures and few studies have been published on this subject. The study describes a clampless technique for LESS PN, by reducing the blood pressure and increasing the intra-abdominal pressure of the pneumoperitoneum to 20 mmHg, timed to precisely coincide with excision of the tumour. This technique was found to be safe and feasible in the treatment of low-risk T1a RCC. OBJECTIVE To describe the technique and report the surgical outcomes of clampless laparoendoscopic single-site (LESS) partial nephrectomy (PN) in the treatment of renal cell carcinoma (RCC) with low PADUA score. PATIENTS AND METHODS Clampless LESS PN was performed in 14 patients with cT1a renal tumours. Indications to perform a clampless LESS PN were low-risk, laterally based renal tumours, located away from the renal hilum, with a PADUA score ≤7. Demographic data and peri-operative and postoperative variables were recorded and analysed. Kidney function was evaluated by measuring serum creatinine concentration and estimated glomerular filtration rate (eGFR) pre- and postoperatively and at 6-month follow-up. RESULTS The median operating time was 120 min and warm ischaemia time was zero in all cases. Only one early complication (Clavien grade 1) was recorded: one patient developed a flank haematoma which it was possible to treat by conservative therapy. Serum creatinine and modification of diet renal disease eGFR were not found to be significantly different pre- and postoperatively and at 6-month follow-up. Definitive pathological results showed 12 pT1a RCCs and two pT1a-chromophobe RCCs. All tumours were removed with negative surgical margins. All patients were satisfied with the cosmetic results. At a median (range) follow-up period of 12 (8-15) months, all patients were alive without evidence of tumour recurrence or port-site metastasis. CONCLUSION Clampless LESS PN is a safe and feasible surgical procedure in the treatment of low-risk T1a RCC, with excellent cosmetic results.


title: Structure of coronavirus hemagglutinin-esterase offers insight into corona and influenza virus evolution.

text: The hemagglutinin-esterases (HEs) are a family of viral envelope glycoproteins that mediate reversible attachment to O-acetylated sialic acids by acting both as lectins and as receptor-destroying enzymes (RDEs). Related HEs occur in influenza C, toro-, and coronaviruses, apparently as a result of relatively recent lateral gene transfer events. Here, we report the crystal structure of a coronavirus (CoV) HE in complex with its receptor. We show that CoV HE arose from an influenza C-like HE fusion protein (HEF). In the process, HE was transformed from a trimer into a dimer, whereas remnants of the fusion domain were adapted to establish novel monomer-monomer contacts. Whereas the structural design of the RDE-acetylesterase domain remained unaltered, the HE receptor-binding domain underwent remodeling to such extent that the ligand is now bound in opposite orientation. This is surprising, because the architecture of the HEF site was preserved in influenza A HA over a much larger evolutionary distance, a switch in receptor specificity and extensive antigenic variation notwithstanding. Apparently, HA and HEF are under more stringent selective constraints than HE, limiting their exploration of alternative binding-site topologies. We attribute the plasticity of the CoV HE receptor-binding site to evolutionary flexibility conferred by functional redundancy between HE and its companion spike protein S. Our findings offer unique insights into the structural and functional consequences of independent protein evolution after interviral gene exchange and open potential avenues to broad-spectrum antiviral drug design.


title: Implementing wildlife disease surveillance in the Netherlands, a One Health approach.

text: The surveillance of (emerging) wildlife diseases can provide important, objective evidence of the circulation of pathogens of interest for veterinary and/or public health. The involvement of multiple research institutions in wildlife disease surveillance can ensure the best use of existing knowledge and expertise, but can also complicate or add challenges to the integration of wildlife disease surveillance components into a national programme. Documenting the existing efforts in a country's surveillance of wildlife diseases, including the institutes in which it takes place, provides a basis for policy-makers and authorities to identify gaps and priorities in their current surveillance programmes. This paper describes the wildlife disease surveillance activities taking place in the Netherlands. The authors recommend that, in addition to funding these current activities, surveillance resources should be allocated with the flexibility to allow for additional targeted surveillance, to detect and adequately respond to newly introduced or emerging pathogens. Similar structured overviews of wildlife disease surveillance in other countries would be very useful to facilitate international collaboration.


title: Avian coronaviruses.

text: Coronaviruses (CoVs) mainly cause enteric and / or respiratory signs. Mammalian CoVs including COVID-19 (now officially named SARS-CoV-2) belong to either the Alphacoronavirus or Betacoronavirus genera. In birds the majority of the known CoVs belong to the Gammacoronavirus genus, whilst a small number are classified as Deltacoronaviruses. Gammacoronaviruses continue to be reported in an increasing number of avian species, generally by detection of viral RNA. Apart from infectious bronchitis virus in chickens, the only avian species in which CoV has been definitively associated with disease are the turkey, pheasant and guinea fowl. Whilst there is strong evidence for recombination between gammacoronaviruses of different avian species, and between betacoronaviruses in different mammals, evidence of recombination between coronaviruses of different genera is lacking. Furthermore, recombination of an apha or betacoronavirus with a gammacoronavirus is extremely unlikely. For recombination to happen, the 2 viruses would need to be present in the same cell of the same animal at the same time; a highly unlikely scenario as they cannot replicate in the same host!


title: Influence of Molecular Design on the Targeting Properties of ABD-Fused Mono- and Bi-Valent Anti-HER3 Affibody Therapeutic Constructs.

text: Overexpression of human epidermal growth factor receptor type 3 (HER3) is associated with tumour cell resistance to HER-targeted therapies. Monoclonal antibodies (mAbs) targeting HER3 are currently being investigated for treatment of various types of cancers. Cumulative evidence suggests that affibody molecules may be appropriate alternatives to mAbs. We previously reported a fusion construct (3A3) containing two HER3-targeting affibody molecules flanking an engineered albumin-binding domain (ABD035) included for the extension of half-life in circulation. The 3A3 fusion protein (19.7 kDa) was shown to delay tumour growth in mice bearing HER3-expressing xenografts and was equipotent to the mAb seribantumab. Here, we have designed and explored a series of novel formats of anti-HER3 affibody molecules fused to the ABD in different orientations. All constructs inhibited heregulin-induced phosphorylation in HER3-expressing BxPC-3 and DU-145 cell lines. Biodistribution studies demonstrated extended the half-life of all ABD-fused constructs, although at different levels. The capacity of our ABD-fused proteins to accumulate in HER3-expressing tumours was demonstrated in nude mice bearing BxPC-3 xenografts. Formats where the ABD was located on the C-terminus of affibody binding domains (3A, 33A, and 3A3) provided the best tumour targeting properties in vivo. Further development of these promising candidates for treatment of HER3-overexpressing tumours is therefore justified.


Universal Testing-Based Response to COVID-19 Outbreak by a Long-Term Care and Post-Acute Care Facility.


World leaders in covid-19 control.


title: Securitization of infectious diseases in Vietnam: the cases of HIV and avian influenza.

text: The frequent and swift emergence of new and devastating infectious diseases has brought renewed attention to health as an issue of international importance. Some states and regional organizations, including in Asia, have begun to regard infectious disease as a national and international security issue. This article seeks to examine the Vietnamese government's response to the epidemics of avian influenza and Human immunodeficiency virus. Both diseases have been recognized at different times as threats to international security and both are serious infectious disease problems in Vietnam. Yet, the character of the central government's response to these two epidemics has been starkly different. How and why this disparity in policy approaches occurs depends largely on the epidemiological, economic and political context in which they occur. Although epidemiological factors are frequently explored when discussing disease as a security issue, seldom are the political, social and economic characteristics of the state invoked. These dimensions, and their interaction with the epidemiology of the disease, are central to understanding which diseases are ultimately treated by states as security issues. In particular, the role of economic security as a powerful motivator for resistance to control measures and the role that local implementation of policies can have in disrupting the effect of central government policy are explored. In exploring both the outcomes of securitization, and its facilitating conditions, I suggest some preliminary observations on the potential costs and benefits of securitizing infectious disease and its utility as a mechanism for protecting health in Asia.


Silent casualty of COVID-19: Training and education.


docid: yuonsshf

title: As We Went to Press: The United States Responds to COVID-19.

text: Ventilators, masks, and tests are in short supply.


title: A prospective, multi-centre US clinical trial to determine accuracy of FebriDx point-of-care testing for acute upper respiratory infections with and without a confirmed fever.

text: BACKGROUND FebriDx is a 10-minute disposable point-of-care test designed to identify clinically significant systemic host immune responses and aid in the differentiation of bacterial and viral respiratory infection by simultaneously detecting C-reactive protein (CRP) and myxovirus resistance protein A (MxA) from a fingerstick blood sample. FebriDx diagnostic accuracy was evaluated in the emergency room and urgent care setting. METHODS A prospective, multicentre, observational cohort study of acute upper respiratory tract infections (URIs), with and without a confirmed fever at the time of enrolment, was performed to evaluate the diagnostic accuracy of FebriDx to identify clinically significant bacterial infection with host response and acute pathogenic viral infection. The reference method consisted of an algorithm with physician override that included bacterial cell culture, respiratory PCR panels for viral and atypical pathogens, procalcitonin, and white blood cell count. RESULTS Among 220 patients enrolled, 100% reported fever 100.5°F within the last 72 hours while 55% had a measured hyperthermia (T > 100.4) at the time of enrolment. FebriDx demonstrated a sensitivity of 95% (95% CI: 77-100%), specificity of 94% (88-98%), PPV of 76% (59-87%), and a NPV of 99% (93-100%). CONCLUSION FebriDx may identify clinically significant bacterial URI's and supports outpatient antibiotic decisions. Key messages FebriDx is an outpatient POC test designed to identify a clinically significant systemic host immune response and aid in the differentiation of viral and bacterial infection through rapid measurement of MxA and CRP from a fingerstick blood sample. FebriDx test was determined to be an accurate test, with a 85% sensitivity, 93% specificity and 97% NPV to rule out bacterial infection for any patient presenting with symptoms and reported fever within the prior 3 days, and when confirming fever (hyperthermia) at the time of testing, the test was even more sensitive (95%) and specific (94%) with a 99% NPV. FebriDx may support antibiotic stewardship by rapidly identifying clinically significant bacterial URIs.


title: Laparoscopic transperitoneal left adrenalectomy and wandering spleen risk.

text: BACKGROUND AND OBJECTIVES Laparoscopic transperitoneal left adrenalectomy (LTLA) has become the standard treatment for adrenal masses<6 cm. LTLA involves the dissection of splenic suspensory ligaments, which replicates their congenital absence or weakening, present in cases of wandering spleen (WS). WS is a rare condition in which the spleen migrates from the left upper quadrant to a more caudal location in the abdomen. A unique case of WS after LTLA was described by Corcione et al. In this prospective study, we investigated the possibility of WS as a consequence of LTLA. METHODS Twenty-four patients, 8 men and 16 women, who underwent LTLA with the dissection of splenoparietal and splenorenal ligaments were selected. RESULTS Clinical and ultrasonographic follow-up showed no evidence of postoperative WS. CONCLUSIONS In the literature, WS is not commonly reported as a postoperative complication of LTLA. In effect, especially in the case of small adrenal masses, the spleen's repositioning in its seat is autonomous. However, the alarming possibility of WS should not be ignored, especially in the case of extensive dissection of the left colic flexure. It would be useful for other authors to signal this complication, so that different approaches and consequent results may be compared.


title: Adolescent cohorts assessing growth, cardiovascular and cognitive outcomes in low and middle-income countries.

text: INTRODUCTION Life-course studies are needed to explore how exposures during adolescence, particularly puberty, contribute to later cardiovascular risk and cognitive health in low and middle-income countries (LMIC), where 90% of the world's young people live. The extent of any existing cohorts investigating these outcomes in LMIC has not previously been described. METHODS We performed a systematic literature review to identify population cohort studies of adolescents in LMIC that assessed anthropometry and any of cardiovascular risk (blood pressure, physical activity, plasma glucose/lipid profile and substance misuse), puberty (age at menarche, Tanner staging, or other form of pubertal staging) or cognitive outcomes. Studies that recruited participants on the basis of a pre-existing condition or involved less than 500 young people were excluded. FINDINGS 1829 studies were identified, and 24 cohorts fulfilled inclusion criteria based in Asia (10), Africa (6) and South / Central America (8). 14 (58%) of cohorts identified were based in one of four countries; India, Brazil, Vietnam or Ethiopia. Only 2 cohorts included a comprehensive cardiovascular assessment, tanner pubertal staging, and cognitive outcomes. CONCLUSION Improved utilisation of existing datasets and additional cohort studies of adolescents in LMIC that collect contemporaneous measures of growth, cognition, cardiovascular risk and pubertal development are needed to better understand how this period of the life course influences future non-communicable disease morbidity and cognitive outcomes.


title: Total inverse transgastric resection with transoral specimen removal.

text: BACKGROUND Laparoscopic local excision is accepted for gastrointestinal stromal tumors (GIST) and benign lesions of the stomach. Yet, tumors at the gastroesophageal junction, on the posterior wall, or in the distal antrum are difficult to approach. Such tumors often must be exposed via gastrotomy or using a rendezvous maneuver. Our method of total intragastric laparoscopic resection using 'pneumogastrum', rigid laparoscope, and conventional laparoscopic instruments is described in an intuitive video. METHODS Two cases of total inverse transgastric resection involved resection of a submucosal GIST, one at the front wall of the cardia and the other on the posterior wall of the antrum. The third case required excision of a large prepyloric cystic lesion leading to a gastric outlet stenosis. After insertion of three trocars under laparoscopic control, a further trocar was introduced into the stomach and 'pneumogastrum' was established. Two additional 5-mm trocars were intragastrally placed. Intragastric endoscopy with a rigid optic provided an excellent view. The tumor was exposed resected with a linear stapler. The specimen was inserted into an Endo Pouch™ which was sutured to an orally inserted gastric tube. The Endo Pouch™ was gently pulled transorally. After removal of the intragastric trocars, the entrance points were laparoscopically closed. RESULTS From the first and second cases, we retrieved GIST tumors. In the third case, we retrieved a gastritis cystica profunda. Postoperative course was uneventful. CONCLUSIONS Gastric GIST should be resected laparoscopically if negative margins are safely achieved regardless of its size. Tumors at the frontwall and exophytic backwall GIST are addressed by laparoscopic wedge resection. Tumors at the gastrojejunal junction, in the prepyloric region, and fundus as well as submucous GIST of the gastric backwall are best approached by intragastric laparoscopic resection. Transoral specimen retrieval is an interesting option in smaller tumors.


title: Censored Regression Modeling To Predict Virus Inactivation in Wastewaters.

text: Among the many uncertainties presented by poorly studied pathogens is possible transmission via human fecal material or wastewaters. Such worries were a documented concern during the 2013 Ebola outbreak in West Africa. Using published experimental data on virus inactivation rates in wastewater and similar matrices, we extracted data to construct a model predicting the T90 (1 × log10 inactivation measured in seconds) of a virus. Extracted data were as follows: RNA or DNA genome, enveloped or not, primary transmission pathway, temperature, pH, light levels, and matrix. From the primary details, we further determined matrix level of contamination, genus, and taxonomic family. Prior to model construction, three records were separated for verification. A censored normal regression model provided the best fit model, which predicted T90 from DNA or RNA structure, enveloped status, whether primary transmission pathway was fecal-oral, temperature, and whether contamination was low, medium, or high. Model residuals and predicted values were evaluated against observed values. Mean values of model predictions were compared to independent data and considering 95% confidence ranges (which could be quite large). A relatively simple model can predict virus inactivation rates from virus and matrix attributes, providing valuable input when formulating risk management strategies for little studied pathogens.


docid: urswrdlv

title: Factors in B cell competition and immunodominance.

text: The majority of all vaccines work by inducing protective antibody responses. The mechanisms by which the B cells responsible for producing protective antibodies are elicited to respond are not well understood. Interclonal B cell competition to complex antigens, particularly in germinal centers, has emerged as an important hurdle in designing effective vaccines. This review will focus on recent advances in understanding the roles of B cell precursor frequency, B cell receptor affinity for antigen, antigen avidity, and other factors that can substantially alter the outcomes of B cell responses to complex antigens. Understanding the interdependence of these fundamental factors that affect B cell responses can inform current vaccine design efforts for pathogens with complex proteins as candidate immunogens such as HIV, influenza, and coronaviruses.


title: A functional proteogenomic analysis of endometrioid and clear cell carcinomas using reverse phase protein array and mutation analysis: protein expression is histotype-specific and loss of ARID1A/BAF250a is associated with AKT phosphorylation.

text: BACKGROUND Ovarian cancer is now recognized as a number of distinct diseases primarily defined by histological subtype. Both clear cell ovarian carcinomas (CCC) and ovarian endometrioid carcinomas (EC) may arise from endometriosis and frequently harbor mutations in the ARID1A tumor suppressor gene. We studied the influence of histological subtype on protein expression with reverse phase protein array (RPPA) and assessed proteomic changes associated with ARID1A mutation/BAF250a expression in EC and CCC. METHODS Immunohistochemistry (IHC) for BAF250a expression was performed on 127 chemotherapy-naive ovarian carcinomas (33 CCC, 29 EC, and 65 high-grade serous ovarian carcinomas (HGSC)). Whole tumor lysates were prepared from frozen banked tumor samples and profiled by RPPA using 116 antibodies. ARID1A mutations were identified by exome sequencing, and PIK3CA mutations were characterized by MALDI-TOF mass spectrometry. SAM (Significance Analysis of Microarrays) was performed to determine differential protein expression by histological subtype and ARID1A mutation status. Multivariate logistic regression was used to assess the impact of ARID1A mutation status/BAF250a expression on AKT phosphorylation (pAKT). PIK3CA mutation type and PTEN expression were included in the model. BAF250a knockdown was performed in 3 clear cell lines using siRNA to ARID1A. RESULTS Marked differences in protein expression were observed that are driven by histotype. Compared to HGSC, SAM identified over 50 proteins that are differentially expressed in CCC and EC. These included PI3K/AKT pathway proteins, those regulating the cell cycle, apoptosis, transcription, and other signaling pathways including steroid hormone signaling. Multivariate models showed that tumors with loss of BAF250a expression showed significantly higher levels of AKT-Thr308 and AKT-Ser473 phosphorylation (p < 0.05). In 31 CCC cases, pAKT was similarly significantly increased in tumors with BAF250a loss on IHC. Knockdown of BAF250a by siRNA in three CCC cell lines wild type for ARID1A showed no increase in either pAKT-Thr308 or pAKT-S473 suggesting that pAKT in tumor tissues is indirectly regulated by BAF250a expression. CONCLUSIONS Proteomic assessment of CCC and EC demonstrates remarkable differences in protein expression that are dependent on histotype, thereby further characterizing these cancers. AKT phosphorylation is associated with ARID1A/BAF250a deficient tumors, however in ovarian cancers the mechanism remains to be elucidated.


European universities dismal at reporting results of clinical trials.


Case-Fatality Rate and Characteristics of Patients Dying in Relation to COVID-19 in Italy.


title: Gastroscopic surveillance with targeted biopsies compared with random biopsies in CDH1 mutation carriers.

text: BACKGROUND : The International Gastric Cancer Linkage Consortium (IGCLC) consensus guideline advises prophylactic gastrectomy in early adulthood to prevent gastric cancer development in CDH1 germline mutation carriers; psychosocial reasons may postpone gastrectomy. We analyzed the yield of signet-ring cell carcinoma (SRCC) during surveillance gastroscopy in CDH1 mutation carriers. METHODS : A retrospective analysis on surveillance gastroscopies in CDH1 mutation carriers was performed. The yield of SRCC in both targeted and random biopsies was studied. Endoscopic (biopsy) results were compared with the histopathologic outcomes in gastrectomy specimens. RESULTS : 42 CDH1 mutation carriers (18 men; mean age 43, range 20-82 years) underwent 96 surveillance gastroscopies. SRCC lesions were identified on surveillance gastroscopy in 21 patients (50 %), by either targeted biopsies only (n = 11), random biopsies only (n = 3), or both random and targeted biopsies (n = 7). SRCC was detected in 41 /377 targeted biopsies (11 %), whereas random biopsies revealed SRCC in 14/1563 biopsies (0.9 %). At least one SRCC lesion was found in 26 of 30 gastrectomy specimens. In 18 of these 26 specimens (69 %), SRCC had been identified by endoscopic biopsies. Missed lesions were all small superficial SRCC foci, mainly in the body of the stomach. CONCLUSION : In our cohort of CDH1 mutation carriers, SRCC lesions were identified by an extensive endoscopic surveillance protocol in 69 % of SRCC-positive patients who underwent a gastric resection. The low number of SRCC detected through random sampling demands a critical reappraisal of random biopsy sampling in the IGCLC guideline.


Cells edited with CRISPR prove safe in humans.


Pandemic influenza viruses--hoping for the road not taken.


title: A Human Long Non-Coding RNA ALT1 Controls the Cell Cycle of Vascular Endothelial Cells Via ACE2 and Cyclin D1 Pathway.

text: BACKGROUND/AIMS ALT1 is a novel long non-coding RNA derived from the alternatively spliced transcript of the deleted in lymphocytic leukemia 2 (DLEU2). To date, ALT1 biological roles in human vascular endothelial cells have not been reported. METHODS ALT1 was knocked down by siRNAs. Cell proliferation was analyzed by cck-8. The existence and sequence of human ALT1 were identified by 3' rapid amplification of cDNA ends. The interaction between lncRNA and proteins was analyzed by RNA-Protein pull down assay, RNA immunoprecipitation, and mass spectrometry analysis. RESULTS ALT1 was expressed in human umbilical vein endothelial cells (HUVECs). The expression of ALT1 was significantly downregulated in contact-inhibited HUVECs and in hypoxia-induced, growth-arrested HUVECs. Knocking down of ALT1 inhibited the proliferation of HUVECs by G0/G1 cell cycle arrest. We observed that angiotensin converting enzyme Ⅱ(ACE2) was a direct target gene of ALT1. Knocking-down of ALT1 or its target gene ACE2 could efficiently decrease the expression of cyclin D1 via the enhanced ubiquitination and degradation, in which HIF-1α and protein von Hippel-Lindau (pVHL) might be involved. CONCLUSION The results suggested the human long non-coding RNA ALT1 is a novel regulator for cell cycle of HUVECs via ACE2 and cyclin D1 pathway.


title: Screening of an FDA-approved compound library identifies four small-molecule inhibitors of Middle East respiratory syndrome coronavirus replication in cell culture.

text: Coronaviruses can cause respiratory and enteric disease in a wide variety of human and animal hosts. The 2003 outbreak of severe acute respiratory syndrome (SARS) first demonstrated the potentially lethal consequences of zoonotic coronavirus infections in humans. In 2012, a similar previously unknown coronavirus emerged, Middle East respiratory syndrome coronavirus (MERS-CoV), thus far causing over 650 laboratory-confirmed infections, with an unexplained steep rise in the number of cases being recorded over recent months. The human MERS fatality rate of ∼ 30% is alarmingly high, even though many deaths were associated with underlying medical conditions. Registered therapeutics for the treatment of coronavirus infections are not available. Moreover, the pace of drug development and registration for human use is generally incompatible with strategies to combat emerging infectious diseases. Therefore, we have screened a library of 348 FDA-approved drugs for anti-MERS-CoV activity in cell culture. If such compounds proved sufficiently potent, their efficacy might be directly assessed in MERS patients. We identified four compounds (chloroquine, chlorpromazine, loperamide, and lopinavir) inhibiting MERS-CoV replication in the low-micromolar range (50% effective concentrations [EC(50)s], 3 to 8 μM). Moreover, these compounds also inhibit the replication of SARS coronavirus and human coronavirus 229E. Although their protective activity (alone or in combination) remains to be assessed in animal models, our findings may offer a starting point for treatment of patients infected with zoonotic coronaviruses like MERS-CoV. Although they may not necessarily reduce viral replication to very low levels, a moderate viral load reduction may create a window during which to mount a protective immune response.


title: Trach tubes designed to maximize safety may increase risk to ventilated patients.

text: Dual-cannulae tracheostomy tubes with low-pressure cuffs, such as the Shiley LPC, are widely regarded as inherently safer than single lumen tubes with low-volume cuffs. For the patient who undergoes tracheostomy for failure to wean from mechanical ventilation, however, the insertion of a tube that occupies a large amount of space within the trachea can delay subsequent efforts to liberate him from the ventilator. With an aim to promote more timely rehabilitation of ventilated patients, London Ontario's University Hospital has been inserting the Bivona TTS, a single lumen tube with an elastic cuff, during tracheostomy. This allows caregivers to better exploit the benefits of a functional upper airway early during the weaning process, which may reduce complications associated with prolonged mechanical ventilation. We urge clinical studies to determine how the choice of initial tracheostomy tube can affect rehabilitation strategies and important patient outcomes.


title: Multifaceted Pharmacist-led Interventions in the Hospital Setting: A Systematic Review.

text: Clinical pharmacy services often comprise complex interventions. In this MiniReview, we conducted a systematic review aiming to evaluate the impact of multifaceted pharmacist-led interventions in a hospital setting. We searched MEDLINE, Embase, Cochrane Library and CINAHL for peer-reviewed articles published from 2006 to 1 March 2018. Controlled trials concerning hospitalized patients in any setting receiving patient-related multifaceted pharmacist-led interventions were considered. All types of outcome were accepted. Inclusion and data extraction were performed. Study characteristics were collected, and risk of bias assessment was conducted utilizing the Cochrane Risk of Bias tools. All stages were conducted by at least two independent reviewers. The review was registered in PROSPERO (CRD42017075808). A total of 11,896 publications were identified, and 28 publications were included. Of these, 17 were conducted in Europe. Six of the included publications were multi-centre studies, and 16 were randomized trials. Usual care was the comparator. Significant results on quality of medication use were reported as positive in eleven studies (n = 18; 61%) and negative in one (n = 18, 6%). Hospital visits were reduced significantly in seven studies (n = 16; 44%). Four studies (n = 12; 33%) reported a positive significant effect on either length of stay or time to revisit, and one study reported a negative effect (n = 12; 6%). All studies investigating mortality (n = 6), patient-reported outcome (n = 7) and cost-effectiveness (n = 1) showed no significant results. This MiniReview indicates that multifaceted pharmacist-led interventions in a hospital setting may improve the quality of medication use and reduce hospital visits and length of stay, while no effect was seen on mortality, patient-reported outcome and cost-effectiveness.


Calling all coronavirus researchers: keep sharing, stay open.


title: Prevention and treatment of viral diarrhea in pediatrics.

text: Diarrhea is the second largest cause of mortality worldwide in children from the perinatal period to the age of 5 years. Rotavirus has been the most commonly identified viral cause of diarrhea in children. Norovirus is now recognized as the second most common viral pathogen. Adenovirus, astrovirus and sapovirus are the other major viral causes of pediatric gastroenteritis. Strategies for prevention include basic hygiene, optimization of nutrition and, ultimately, vaccination. Two new vaccines have recently been licensed for the prevention of rotavirus, the monovalent human rotavirus vaccine (Rotarix) and the pentavalent bovine-human reassortant vaccine (RotaTeq). These vaccines have already dramatically decreased the morbidity associated with rotavirus in countries where they are widely used. Efforts to develop a norovirus vaccine face substantial hurdles. Treatment of the viral pathogens is primarily limited to symptomatic measures.


title: Bispectral index detects intraoperative cerebral ischaemia during balloon assisted cerebral aneurysm coiling.

text: Bispectral index (BIS) is a monitoring modality designed and used for monitoring depth of anaesthesia. We wish to report a case where BIS monitoring may have alerted us to a potential adverse neurological event during angiographic coiling of a cerebral aneurysm.


Covid-19 Crisis Triage - Optimizing Health Outcomes and Disability Rights.


title: Nephrectomy via ventral median celiotomy in equids.

text: OBJECTIVE To report technique for, and outcome after, nephrectomy through a ventral median celiotomy in equids. STUDY DESIGN Case series. ANIMALS Equids with unilateral renal disease (n = 6), aged 2 months to 18 years, weighing 90-434 kg. METHODS A ventral median celiotomy was used to access the left or right kidney. To facilitate surgical exposure, the small intestine was reflected towards the diaphragm using laparotomy sponges and the ascending colon was exteriorized and in some cases evacuated. The peritoneum over the affected kidney was incised and blunt dissection used to free the kidney from the retroperitoneal fat, then the renal artery, vein, and ureter were isolated and ligated. Abdominal lavage with sterile saline solution was performed before abdominal closure. RESULTS Four horses, 1 donkey, and 1 mule had unilateral nephrectomy to treat verminous nephritis (1), idiopathic hematuria (1), and ectopic ureter (4). A ventral median approach provided adequate access to the kidney in all 6 cases. Two horses had postoperative complications (peritonitis, chylous abdominal effusion) that resolved with medical therapy. No complications attributable to nephrectomy were reported by the owners upon follow-up 1-8 years after surgery. CONCLUSIONS A ventral median approach for nephrectomy can be used for unilateral nephrectomy in equids weighing up to 434 kg.


title: Cardiovascular system and COVID-19: perspectives from a developing country.

text: A novel coronavirus, SARS-CoV-2, thought to have originated from bats causes COVID-19 infection which was first reported from Wuhan, China in December 2019. This virus has a high infectivity rate and has impacted a significant chunk of the population worldwide. The spectrum of disease ranges from mild to severe with respiratory system being the most commonly affected. Cardiovascular system often gets involved in later stages of the disease with acute cardiac injury, heart failure and arrhythmias being the common complications. In addition, the presence of cardiovascular co-morbidities such as hypertension, coronary artery disease in these patients are often associated with poor prognosis. It is still not clear regarding the exact mechanism explaining cardiovascular system involvement in COVID-19. Multiple theories have been put forward however, more robust studies are required to fully elucidate the "heart and virus" link. The disease has already made its presence felt on the global stage and its impact in the developing countries is going to be profound. These nations not only have a poorly developed healthcare system but there is also a huge burden of cardiovascular diseases. As a result, COVID-19 would adversely impact the already overburdened healthcare network leading to impaired cardiovascular care delivery especially for acute coronary syndrome and heart failure patients.


Recent advances in laparoscopic live donor nephrectomy.


title: Benefits of Cardiac Resynchronization Therapy in an Asynchronous Heart Failure Model Induced by Left Bundle Branch Ablation and Rapid Pacing.

text: It is now well recognized that heart failure (HF) patients with left bundle branch block (LBBB) derive substantial clinical benefits from cardiac resynchronization therapy (CRT), and LBBB has become one of the important predictors for CRT response. The conventional tachypacing-induced HF model has several major limitations, including absence of stable LBBB and rapid reversal of left ventricular (LV) dysfunction after cessation of pacing. Hence, it is essential to establish an optimal model of chronic HF with isolated LBBB for studying CRT benefits. In the present study, a canine model of asynchronous HF induced by left bundle branch (LBB) ablation and 4 weeks of rapid right ventricular (RV) pacing is established. The RV and right atrial (RA) pacing electrodes via the jugular vein approach, together with an epicardial LV pacing electrode, were implanted for CRT performance. Presented here are the detailed protocols of radiofrequency (RF) catheter ablation, pacing leads implantation, and rapid pacing strategy. Intracardiac and surface electrograms during operation were also provided for a better understanding of LBB ablation. Two-dimensional speckle tracking imaging and aortic velocity time integral (aVTI) were acquired to validate the chronic stable HF model with LV asynchrony and CRT benefits. By coordinating ventricular activation and contraction, CRT uniformed the LV mechanical work and restored LV pump function, which was followed by reversal of LV dilation. Moreover, the histopathological study revealed a significant restoration of cardiomyocyte diameter and collagen volume fraction (CVF) after CRT performance, indicating a histologic and cellular reverse remodeling elicited by CRT. In this report, we described a feasible and valid method to develop a chronic asynchronous HF model, which was suitable for studying structural and biologic reverse remodeling following CRT.


title: Biochanin-A elicits relaxation in coronary artery of goat through different mechanisms.

text: Flavonoids have shown beneficial effects in various disease conditions as reported by various previous studies. Biochanin-A is a flavonoid present in various plants in nature. Present investigation was done to assess the vasorelaxant potential of biochanin-A on isolated coronary artery of goat and its possible mechanism of action. Vascular reactivity experiments were done on circumflex coronary artery of goats using the tension experiments. Goat coronary arterial rings were relaxed with biochanin-A in concentration (0.1-100 μM)-dependent manner. Endothelium had no effect on biochanin-A-induced relaxation. Maximum relaxation induced by biochanin-A was 116.54 ± 12.21% in endothelium-intact artery and it was not significantly different with maximal relaxation (108.22 ± 1.88%) of endothelium-denuded vessel. L-NAME (100 μM) did not show any effect on biochanin-A-induced relaxation. TEA (BKCa channel blocker), and BaCl2 (KIR blocker) had no effect on biochanin-A-induced relaxation. However, biochanin-A-induced maximal relaxation (71.72 ± 4.50%) was reduced significantly (P < .001) in the presence of 4-aminopyridine (KV channel blocker, 3 mM) in comparison with control (114.07 ± 4.33%). Glibenclaminde (KATP channel blocker), H89 (PKA inhibitor), ICI182780 (estrogen receptor antagonist) showed partial attenuation in the biochanin-A-induced relaxation. ODQ (sGC blocker) and HC067047 (TRPV4 channel blocker) had no effect on biochanin-A-induced relaxation. In K+-depolarized endothelium-denuded arterial rings, biochanin-A (30 μM) significantly (P < .05; P < .001) decreased CaCl2-induced contractions (0.02 ± 0.01 g vs. control 0.73 ± 0.30 g). Biochanin-A did not influence the fasudil (rho kinase inhibitor) and SNP (NO-donor)-induced relaxation in this vessel. Biochanin-A showed relaxation in goat coronary artery in endothelium-independent pathways and showed the partial involvement of KATP, protein kinase A and estrogen receptors and full involvement of Cav1.2 channels.


title: Association of Cardiac Injury With Mortality in Hospitalized Patients With COVID-19 in Wuhan, China.

text: Importance Coronavirus disease 2019 (COVID-19) has resulted in considerable morbidity and mortality worldwide since December 2019. However, information on cardiac injury in patients affected by COVID-19 is limited. Objective To explore the association between cardiac injury and mortality in patients with COVID-19. Design, Setting, and Participants This cohort study was conducted from January 20, 2020, to February 10, 2020, in a single center at Renmin Hospital of Wuhan University, Wuhan, China; the final date of follow-up was February 15, 2020. All consecutive inpatients with laboratory-confirmed COVID-19 were included in this study. Main Outcomes and Measures Clinical laboratory, radiological, and treatment data were collected and analyzed. Outcomes of patients with and without cardiac injury were compared. The association between cardiac injury and mortality was analyzed. Results A total of 416 hospitalized patients with COVID-19 were included in the final analysis; the median age was 64 years (range, 21-95 years), and 211 (50.7%) were female. Common symptoms included fever (334 patients [80.3%]), cough (144 [34.6%]), and shortness of breath (117 [28.1%]). A total of 82 patients (19.7%) had cardiac injury, and compared with patients without cardiac injury, these patients were older (median [range] age, 74 [34-95] vs 60 [21-90] years; P < .001); had more comorbidities (eg, hypertension in 49 of 82 [59.8%] vs 78 of 334 [23.4%]; P < .001); had higher leukocyte counts (median [interquartile range (IQR)], 9400 [6900-13 800] vs 5500 [4200-7400] cells/μL) and levels of C-reactive protein (median [IQR], 10.2 [6.4-17.0] vs 3.7 [1.0-7.3] mg/dL), procalcitonin (median [IQR], 0.27 [0.10-1.22] vs 0.06 [0.03-0.10] ng/mL), creatinine kinase-myocardial band (median [IQR], 3.2 [1.8-6.2] vs 0.9 [0.6-1.3] ng/mL), myohemoglobin (median [IQR], 128 [68-305] vs 39 [27-65] μg/L), high-sensitivity troponin I (median [IQR], 0.19 [0.08-1.12] vs <0.006 [<0.006-0.009] μg/L), N-terminal pro-B-type natriuretic peptide (median [IQR], 1689 [698-3327] vs 139 [51-335] pg/mL), aspartate aminotransferase (median [IQR], 40 [27-60] vs 29 [21-40] U/L), and creatinine (median [IQR], 1.15 [0.72-1.92] vs 0.64 [0.54-0.78] mg/dL); and had a higher proportion of multiple mottling and ground-glass opacity in radiographic findings (53 of 82 patients [64.6%] vs 15 of 334 patients [4.5%]). Greater proportions of patients with cardiac injury required noninvasive mechanical ventilation (38 of 82 [46.3%] vs 13 of 334 [3.9%]; P < .001) or invasive mechanical ventilation (18 of 82 [22.0%] vs 14 of 334 [4.2%]; P < .001) than those without cardiac injury. Complications were more common in patients with cardiac injury than those without cardiac injury and included acute respiratory distress syndrome (48 of 82 [58.5%] vs 49 of 334 [14.7%]; P < .001), acute kidney injury (7 of 82 [8.5%] vs 1 of 334 [0.3%]; P < .001), electrolyte disturbances (13 of 82 [15.9%] vs 17 of 334 [5.1%]; P = .003), hypoproteinemia (11 of 82 [13.4%] vs 16 of 334 [4.8%]; P = .01), and coagulation disorders (6 of 82 [7.3%] vs 6 of 334 [1.8%]; P = .02). Patients with cardiac injury had higher mortality than those without cardiac injury (42 of 82 [51.2%] vs 15 of 334 [4.5%]; P < .001). In a Cox regression model, patients with vs those without cardiac injury were at a higher risk of death, both during the time from symptom onset (hazard ratio, 4.26 [95% CI, 1.92-9.49]) and from admission to end point (hazard ratio, 3.41 [95% CI, 1.62-7.16]). Conclusions and Relevance Cardiac injury is a common condition among hospitalized patients with COVID-19 in Wuhan, China, and it is associated with higher risk of in-hospital mortality.


title: Impact of Anesthetic Management on Safety and Outcomes Following Mechanical Thrombectomy for Ischemic Stroke in SWIFT PRIME Cohort.

text: Background and purpose: The optimal anesthetic management of acute ischemic stroke patients during mechanical thrombectomy (MT) remains controversial. In this post-hoc analysis, we investigated the impact of anesthesia type on clinical outcomes in patients included in SWIFT PRIME trial. Methods: Ninety-seven patients treated with MT were included. Patients treated in centers with general anesthesia (GA) policy (n = 32) were compared with those treated in centers with conscious sedation (CS) policy (n = 65). Primary outcomes studied included times to treatment initiation (TTI), rates of successful recanalization (TICI 2b/3), and functional independence (mRS 0-2 at 90 days). Secondary outcomes were adverse events, lowest systolic and diastolic blood pressures (LSBP and LDBP) during MT. Univariate analysis and multivariate regression logistic modeling were conducted. Results: The GA-policy and CS-policy groups presented comparable TTI (94 ± 36 min vs. 102 ± 48 min; p = 0.44), rates of TICI 2b/3 recanalization (22/32 [68.8%] vs. 51/65 [78.5%]; p = 0.32). CS-policy was associated to higher rate of functional independence than GA-policy, but the difference was not significant (43/65 [66.2%] vs. 16/32 [50.0%]; p = 0.18). GA-policy patients had a higher rate of postoperative pneumonia (11/32 [34.4%] vs. 8/65 [12.3%]; p = 0.02) and lower LSBP (110 [30,160] mmHg vs. 119 [77,170] mmHg; p = 0.03) and LDBP (55 (15,75) mmHg vs. 67 [40,121]; p < 0.001). When corrected for differences in baseline characteristics, GA-policy was associated with lower rate of functional independence (OR 0.32; p = 0.05). A 10-point increase in perprocedural LDBP was associated with an increased likelihood of favorable outcome (OR 1.51; p = 0.01). Conclusions: GA-policy for MT presented comparable TTI and rates of successful revascularization to CS-policy. However, GA-policy was associated with lower rates of functional independence and with higher incidence of perprocedural hypotension and postoperative pneumonia. Clinical Trial Registration: URL-http://www.clinicaltrials.gov. Unique identifier: NCT01657461.


title: Effectiveness and adequacy of blinding in the moderation of pain outcomes: Systematic review and meta-analyses of dry needling trials.

text: Background Blinding is critical to clinical trials because it allows for separation of specific intervention effects from bias, by equalising all factors between groups except for the proposed mechanism of action. Absent or inadequate blinding in clinical trials has consistently been shown in large meta-analyses to result in overestimation of intervention effects. Blinding in dry needling trials, particularly blinding of participants and therapists, is a practical challenge; therefore, specific effects of dry needling have yet to be determined. Despite this, dry needling is widely used by health practitioners internationally for the treatment of pain. This review presents the first empirical account of the influence of blinding on intervention effect estimates in dry needling trials. The aim of this systematic review was to determine whether participant beliefs about group allocation relative to actual allocation (blinding effectiveness), and/or adequacy of blinding procedures, moderated pain outcomes in dry needling trials. Methods Twelve databases (MEDLINE, EMBASE, AMED, Scopus, CINAHL, PEDro, The Cochrane Library, Trove, ProQuest, trial registries) were searched from inception to February 2016. Trials that compared active dry needling with a sham that simulated dry needling were included. Two independent reviewers performed screening, data extraction, and critical appraisal. Available blinding effectiveness data were converted to a blinding index, a quantitative measurement of blinding, and meta-regression was used to investigate the influence of the blinding index on pain. Adequacy of blinding procedures was based on critical appraisal, and subgroup meta-analyses were used to investigate the influence of blinding adequacy on pain. Meta-analytical techniques used inverse-variance random-effects models. Results The search identified 4,894 individual publications with 24 eligible for inclusion in the quantitative syntheses. In 19 trials risk of methodological bias was high or unclear. Five trials were adequately blinded, and blinding was assessed and sufficiently reported to compute the blinding index in 10 trials. There was no evidence of a moderating effect of blinding index on pain. For short-term and long-term pain assessments pooled effects for inadequately blinded trials were statistically significant in favour of active dry needling, whereas there was no evidence of a difference between active and sham groups for adequately blinded trials. Discussion The small number and size of included trials meant there was insufficient evidence to conclusively determine if a moderating effect of blinding effectiveness or adequacy existed. However, with the caveats of small sample size, generally unclear risk of bias, statistical heterogeneity, potential publication bias, and the limitations of subgroup analyses, the available evidence suggests that inadequate blinding procedures could lead to exaggerated intervention effects in dry needling trials.


title: Percutaneous embolization of a postnephrectomy arteriovenous fistula with intervening pseudoaneurysm using the Amplatzer vascular plug 2.

text: Although renal arteriovenous fistula (AVF) is an uncommon condition, it may lead to high cardiac output heart failure and renal insufficiency. Recently, percutaneous transcatheter embolization has replaced traditional surgery as the first line of treatment. We report a case of a 68-year-old male who presented with a renal AVF and was treated by percutaneous transcatheter embolization using the Amplatzer Vascular Plug 2 (AVP 2; St Jude Medical, Plymouth, Minnesota) through an arterial access. To our knowledge, the use of AVP 2 device in the treatment of renal AVF as a single embolotherapy device through the transarterial route has not been previously reported in the literature. Our technique demonstrates the feasibility and safety of AVP 2 device in the treatment of renal AVF.


title: Characterization of human coronavirus OC43 and human coronavirus NL63 infections among hospitalized children <5 years of age.

text: BACKGROUND Multiplex molecular assays now make it possible for clinical laboratories to detect human coronaviruses (HCoVs). We investigated the clinical characteristics of HCoV-OC43 and HCoV-NL63 in patients <5 years of age during a recent coronavirus season. METHODS Respiratory viruses were detected using a multiplex molecular assay at St. Louis Children`s Hospital starting in November 2012. We analyzed demographic and clinical data from all patients <5 years of age with solo detection of HCoV-OC43 (n = 52) and HCoV-NL63 (n = 44) and for comparison, samples of children with respiratory syncytial virus, parainfluenza virus and picornaviruses. RESULTS During the study period, HCoV-OC43 (4%) was the 5th and HCoV-NL63 the 8th (2%) most common respiratory virus. Coinfections were detected in 35% and 38% of children with HCoV-OC43 and HCoV-NL63, respectively. Croup was more common with HCoV-NL63 (30%) than with HCoV-OC43 (2%). Lower respiratory tract infection occurred in 33% of children with HCoV-OC43 and 25% of children with HCoV-NL63. Severe illness was less common in HCoV-NL63, HCoV-OC43 and parainfluenza virus (14%, each) compared with respiratory syncytial virus (30%) and picornaviruses (26%; P = 0.055 for HCoVs combined compared with the other respiratory viruses) and occurred mainly in those with underlying medical conditions. CONCLUSIONS Infections caused by HCoV-OC43 and HCoV-NL63 are common and include some with lower respiratory tract involvement and severe disease, especially in children with underlying medical conditions. Overall, a substantial burden of disease associated with both HCoV-OC43 and HCoV-NL63 was observed for hospitalized children <5 years of age.