title: Frontal electroencephalogram variables are associated with the outcome and stage of hepatic encephalopathy in acute liver failure.

text: Acute liver failure (ALF) and hepatic encephalopathy (HE) can lead to an elevated intracranial pressure (ICP) and death within days. The impaired liver function increases the risks of invasive ICP monitoring, whereas noninvasive methods remain inadequate. The purpose of our study was to explore reliable noninvasive methods of neuromonitoring for patients with ALF in the intensive care unit (ICU) setting; more specifically, we wanted to track changes in HE and predict the outcomes of ALF patients treated with albumin dialysis. The study included 20 patients with severe ALF at admission who had been referred to the ICU of the liver transplantation (LT) center for albumin dialysis treatment and evaluation for transplantation. Data were collected from all study patients in the form of continuous frontal electroencephalography (EEG) recordings and transcranial Doppler (TCD) measurements of cerebral blood flow. Among the studied EEG variables, the 50% spectral edge frequency decreased and the delta power increased as the HE stage increased. Both variables were predictive of the stage of HE [prediction probability (PK) of 50% spectral edge frequency = 0.23, standard error (SE) = 0.03; PK of delta power = 0.76, SE = 0.03]. The total wavelet subband entropy, a novel variable that we used for tracking abnormal EEG activity, predicted the outcome of ALF patients treated with albumin dialysis (PK = 0.88, SE = 0.09). With a threshold value of 1.6, the TCD pulsatility index had an odds ratio of 1.1 (95% confidence interval = 0.1-9.3) for a poor outcome (LT or death). In conclusion, EEG variables are useful for the monitoring of HE and can be used to predict outcomes of ALF. TCD measurements do not predict patient outcomes.


title: Effects of Noisy Galvanic Vestibular Stimulation During a Bimanual Tracking Robotic Task.

text: Background Noisy galvanic vestibular stimulation (nGVS) has been shown to improve motor performance in people with and without disabilities. Previous investigations on the use of nGVS to improve upper-limb motor performance have focused on unimanual fine motor movements, nevertheless, bimanual gross movements are also essential for conducting activities of daily living and can be affected as a result of cerebral dysfunction. Consequently, in this study we investigated the effects of nGVS on bimanual gross motor performance. Methods Twelve healthy participants completed a visuomotor task in which they performed bimanual upper-limb movements using two robots. During the task, participants tracked a target that oscillated following a sinusoidal amplitude-modulated trajectory. In half of the trials, participants received subthreshold nGVS, in the other half, they received sham stimulation. Primary outcome measure: percent improvement in root mean square error (RMSE) between the target's and cursors' trajectories. Secondary outcome measures: percent improvement in lag between the cursors and target; and percent improvement in RMSE between the cursors' trajectories. A post-test questionnaire was administered to evaluate the experience of participants. Results Tracking error was not affected by nGVS: left -2.6(5.5)%, p = 0.128; right -0.9(6.2)%, p = 0.639; nor was bimanual coordination -1.5(9.6)%, p = 0.590. When comparing if one hand was affected more than the other, we did not find a statistically significant difference (-1.7(3.3)%, p = 0.098). Similar results were found for the lag. Questionnaire results indicated that the robotic devices did not limit participants' movements, did not make participants feel unsafe, nor were they difficult to control. Furthermore, participants did not feel unsafe with the nGVS device, nor did they report any discomfort due to nGVS. Conclusion Results suggest that nGVS applied to people without disabilities do not affect bimanual gross motor performance. However, as this was the first study to investigate such effects, stimulation parameters were based on previous unimanual fine motor studies. Future studies should investigate optimal stimulation parameters for improving upper-limb gross motor performance. Overall, participants felt safe using the robotic devices and receiving the noisy electrical stimulation. As such, a similar setup could potentially be employed for subsequent studies investigating the relation between upper-limb performance and nGVS.


Hydrogel sutureless facial nerve repair: pilot clinical investigation.


title: Speech pathology management of non-progressive dysarthria: a systematic review of the literature.

text: PURPOSE The purpose of this study is to conduct a systematic review of interventions for the treatment of non-progressive dysarthria in adults. MATERIALS AND METHODS Five electronic databases (PubMed, Embase, CINAHL, PSYCINFO, Cochrane Collaboration) were searched for all studies that described and evaluated treatment used for non-progressive dysarthria in adults. Studies were included if (1) participants were adults (18+ years) with a confirmed diagnosis of non-progressive dysarthria, (2) participants received intervention with pre-post outcome data, and (3) the article was published between 2006 and 2017 (including early online publications). Data extracted included the number of participants; etiology; dysarthria type and severity; age; gender; presence of a control group; intervention tasks, frequency and duration; outcome measures; and conclusions. Data extraction was completed by a member of the research team independently and crosschecked by another team member. RESULTS Of the 6728 articles identified, 21 met the inclusion criteria. The predominant study design was a case study or case series. The methodological quality of the studies varied. Typically, the interventions included impairment-based and activity level tasks targeting conversation. Approximately half of the interventions adhered to a treatment manual. CONCLUSIONS The evidence base to guide treatment for non-progressive dysarthria is increasing, with interventions showing promise in results, participant numbers, and positive participant feedback. Implications for rehabilitation The evidence base to guide treatment for non-progressive dysarthria is increasing, but remains limited. The majority of evidence is of moderate methodological quality. The emergence of new research indicates that health professionals need to be continuously aware and critically appraise new literature in the area.


title: Potential impact of SARS-CoV-2 infection on the thymus.

text: Understanding the pathogenesis of certain viral agents is essential for developing new treatments and obtaining a clinical cure. With the onset of the new coronavirus (SARS-CoV-2) pandemic in the beginning of 2020, a rush to conduct studies and develop drugs has led to the publication of articles that seek to address knowledge gaps and contribute to the global scientific research community. There are still no reports on the infectivity or repercussions of SARS-CoV-2 infection on the central lymphoid organ, the thymus, neither on thymocytes or thymic epithelial cells. In this brief review, we present a hypothesis about lymphopenia observed in SARS patients and the probable pathological changes that the thymus may undergo due to this new virus. Key words: Thymus, coronavirus, lymphopenia.


title: Risk Factors for Portal Vein System Thrombosis After Laparoscopic Splenectomy in Cirrhotic Patients with Hypersplenism.

text: BACKGROUND Portal vein system thrombosis (PVST) is a frequent and potentially life-threatening complication after laparoscopic splenectomy (LS) in cirrhotic patients with hypersplenism. The mechanisms and risk factors of PVST are poorly understood. This study investigated risk factors for PVST following LS in cirrhotic patients with hypersplenism. MATERIALS AND METHODS A total of 56 consecutive cirrhotic patients with hypersplenism who underwent successful LS between 2013 and 2014 were included in this retrospective study. Based on the absence or presence of postoperative PVST on postoperative day (POD) 7, the patients were divided into non-PVST and PVST groups. Demographic and preoperative factors were analyzed. RESULTS PVST increased in size in 24 (42.9%) of 56 patients after LS on POD 7. Logistic multivariate regression showed that a portal vein diameter >13 mm (relative risk 35.796, 95% confidence interval 4.534-282.614, and P = .001) and age >50 years (relative risk 20.127, 95% confidence interval 3.598-112.578, and P = .001) were significant independent risk factors for PVST. The incidence of PVST after LS in the portal vein diameter >13 mm group was significantly higher than that in the portal vein diameter ≤13 mm group (P = .001). Similarly, the incidence of PVST after LS in the age >50 years group was significantly higher than that in the age ≤50 years group (P = .001). CONCLUSION A portal vein diameter >13 mm and age >50 years are independent risk factors for PVST after LS in cirrhotic patients with hypersplenism due to portal hypertension.


Governance lessons from COVID-19.


title: Transcranial focused ultrasound stimulation of human primary visual cortex.

text: Transcranial focused ultrasound (FUS) is making progress as a new non-invasive mode of regional brain stimulation. Current evidence of FUS-mediated neurostimulation for humans has been limited to the observation of subjective sensory manifestations and electrophysiological responses, thus warranting the identification of stimulated brain regions. Here, we report FUS sonication of the primary visual cortex (V1) in humans, resulting in elicited activation not only from the sonicated brain area, but also from the network of regions involved in visual and higher-order cognitive processes (as revealed by simultaneous acquisition of blood-oxygenation-level-dependent functional magnetic resonance imaging). Accompanying phosphene perception was also reported. The electroencephalo graphic (EEG) responses showed distinct peaks associated with the stimulation. None of the participants showed any adverse effects from the sonication based on neuroimaging and neurological examinations. Retrospective numerical simulation of the acoustic profile showed the presence of individual variability in terms of the location and intensity of the acoustic focus. With exquisite spatial selectivity and capability for depth penetration, FUS may confer a unique utility in providing non-invasive stimulation of region-specific brain circuits for neuroscientific and therapeutic applications.


title: Can a pressure-limited V-A shunt for obstructive uropathy really protect the kidney?

text: BACKGROUND In our fetal lamb model of lower urinary tract obstruction, a valved shunt preserves bladder function. This study investigates the effects on renal histology. METHODS We created obstructive uropathy (OU) in 60-day gestation fetal lambs, ligating the urethra and urachus, and delivering them at term (130-145days). We compared renal histology in 4 groups: group A-OU without shunt, group B-low-pressure shunt (15-54mmH2O), group C-high-pressure shunt (95-150mmH2O). Shunts were inserted 3weeks post-obstruction. Group D were normal controls. RESULTS We delivered 32 fetuses from 23 ewes: 13 fetuses in group A (9 survived), 6 fetuses in group B (5 survived), 7 fetuses in group C (5 survived), and 6 fetuses in group D. Histologically, we found renal tubular distention, vacuolated degeneration of tubular epithelial cells in 7 lambs, and cyst formation in 4 lambs in group A. There was renal tubular distention in two lambs, and cyst formation in one lamb in both groups B and C, with vacuolated degeneration of tubular epithelial cells observed in all but 1 lamb in each group. CONCLUSIONS V-A shunting prevents multicystic dysplastic kidney (MCDK). Some lambs have renal tubular distention and vacuolated degeneration of renal tubular epithelial cells.


title: Approach to Acute Cardiovascular Complications in COVID-19 Infection.

text: The novel coronavirus disease 2019, otherwise known as COVID-19, is a global pandemic with primary respiratory manifestations in those who are symptomatic. It has spread to more than 187 countries with a rapidly growing number of affected patients. Underlying cardiovascular disease is associated with more severe manifestations of COVID-19 and higher rates of mortality. COVID-19 can have both primary (arrhythmias, myocardial infarction, myocarditis) and secondary (myocardial injury/biomarker elevation, heart failure) cardiac involvement. In severe cases, profound circulatory failure can result. This review discusses the presentation and management of patients with severe cardiac complications of COVID-19 disease, with an emphasis on a "Heart-Lung" team approach in patient management. Furthermore, it focuses on the use of and indications for acute mechanical circulatory support in cardiogenic and/or mixed shock.


title: Educational pamphlets for improving uptake of cancer screening: a systematic review.

text: INTRODUCTION The effectiveness of cancer screening programmes is highly dependent on screening uptake. Many interventions have been tested to increase screening uptake. AIM The goal of this study was to evaluate the effectiveness of cancer screening pamphlets as a standalone intervention. The outcome of interest was uptake of cancer screening tests. METHODS A systematic review was performed on the effectiveness of pamphlets compared to usual care without pamphlets. We searched five databases for research papers in English from 2000 up to May 2019. Randomised controlled trials were included. This research group independently selected studies, extracted data, assessed risk of bias and then compared the information as a group. RESULTS A total of nine trials involving 4912 participants met our inclusion criteria, of which five were about colorectal cancer screening, three were about prostate cancer screening and one was about lung cancer screening. Five of the nine trials showed that pamphlets alone increased uptake significantly, while the remaining four trials did not show significant effects. DISCUSSION There is some evidence that pamphlets increase uptake for cancer screenings, especially for colorectal cancer. Due to the small number of studies in this area, generalisability could be limited.


title: Dexamethasone, light anaesthesia, and tight glucose control (DeLiT) randomized controlled trial.

text: BACKGROUND The inflammatory response to surgical tissue injury is associated with perioperative morbidity and mortality. We tested the primary hypotheses that major perioperative morbidity is reduced by three potential anti-inflammatory interventions: (i) low-dose dexamethasone, (ii) intensive intraoperative glucose control, and (iii) lighter anaesthesia. METHODS We enrolled patients having major non-cardiac surgery who were ≥40 yr old and had an ASA physical status ≤IV. In a three-way factorial design, patients were randomized to perioperative i.v. dexamethasone (a total of 14 mg tapered over 3 days) vs placebo, intensive vs conventional glucose control 80-110 vs 180-200 mg dl(-1), and lighter vs deeper anaesthesia (bispectral index target of 55 vs 35). The primary outcome was a collapsed composite of 15 major complications and 30 day mortality. Plasma high-sensitivity (hs) C-reactive protein (CRP) concentration was measured before operation and on the first and second postoperative days. RESULTS The overall incidence of the primary outcome was about 20%. The trial was stopped after the second interim analysis with 381 patients, at which all three interventions crossed the futility boundary for the primary outcome. No three-way (P=0.70) or two-way (all P>0.52) interactions among the interventions were found. There was a significantly smaller increase in hsCRP in patients given dexamethasone than placebo [maximum 108 (64) vs 155 (69) mg litre(-1), P<0.001], but none of the other two interventions differentially influenced the hsCRP response to surgery. CONCLUSIONS Among our three interventions, dexamethasone alone reduced inflammation. However, no intervention reduced the risk of major morbidity or 1 yr mortality. TRIAL REGISTRATION IDENTIFIER: NCT00433251 at www.clinicaltrials.gov.


title: Stability of siRNA polyplexes from poly(ethylenimine) and poly(ethylenimine)-g-poly(ethylene glycol) under in vivo conditions: effects on pharmacokinetics and biodistribution measured by Fluorescence Fluctuation Spectroscopy and Single Photon Emission Computed Tomography (SPECT) imaging.

text: In search of optimizing siRNA delivery systems for systemic application, one critical parameter remains their stability in blood circulation. In this study, we have traced pharmacokinetics and biodistribution of each component of siRNA polyplexes formed with polyethylenimine 25 kDa (PEI) or PEGylated PEIs by in vivo real-time gamma camera recording, SPECT imaging, and scintillation counting of blood samples and dissected organs. In vivo behavior of siRNA and polymers were compared and interpreted in the context of in vivo stability of the polyplexes which had been measured by fluorescence fluctuation spectroscopy (FFS). Both pharmacokinetics and biodistribution of polymer-complexed siRNA were dominated by the polymer. PEGylated polymers and their siRNA polyplexes showed significantly less uptake into liver (13.6-19.7% ID of PEGylated polymer and 9.5-10.2% ID of siRNA) and spleen compared to PEI 25 kDa (liver deposition: 36.2% ID of polymer and 14.6% ID of siRNA). With non-invasive imaging methods we were able to predict both kinetics and deposition in living animals allowing the investigation of organ distribution in real time and at different time points. FFS measurements proved stability of the applied polyplexes under in vivo conditions which explained the different behavior of complexed from free siRNA. Despite their stability in circulation, we observed that polyplexes dissociated upon liver passage. Therefore, siRNA/(PEG-)PEI delivery systems are not suitable for systemic administration, but instead may be useful when the first-pass effect is circumvented, which is the case in local application.


title: Classifying atopic dermatitis: protocol for a systematic review of subtypes (phenotypes) and associated characteristics.

text: INTRODUCTION Atopic dermatitis is a complex disease with differing clinical presentations. Many attempts have been made to identify uniform subtypes, or phenotypes, of atopic dermatitis in order to identify different aetiologies, improve diagnosis, estimate more accurate clinical prognoses, inform treatment andmanagement or predict treatment efficacy andeffectiveness. However, no consensus yet exists on exactly what defines these phenotypes or how many there are and whether they are genuine or statistical artefacts. This review aims to identify previously reported phenotypes of atopic dermatitis, the features used to define them and any characteristics or clinical outcomes significantly associated with them. METHODS AND ANALYSIS We will search Ovid Embase, Ovid MEDLINE and Web of Science from inception to the latest available date at the time of the search for studies attempting to classify atopic dermatitis in humans using any cross-sectional or longitudinal epidemiological or interventional design. Primary outcomes are atopic dermatitis phenotypes, features used to define them and characteristics associated with them in subsequent analyses. A secondary outcome is the methodological approach used to derive them. Two reviewers will independently screen titles and abstracts for inclusion, extract data and assess study quality. We will present the results of this review descriptively and with frequencies where possible. ETHICS AND DISSEMINATION Ethical approval is not required for this study as it is a systematic review. We will report results from this systematic review in a peer-reviewed journal. The main value of this study will be to inform further research. PROSPERO REGISTRATION NUMBER CRD42018087500.


title: Thoracoscopic lobectomy for congenital cystic lung diseases in neonates and small infants.

text: BACKGROUND There are still few reports on thoracoscopic lobectomy in neonates. The rate of prenatally diagnosed congenital cystic lung diseases is increasing, and such diseases appear to be a good indication for thoracoscopic lobectomy. METHODS We performed a prospective trial of thoracoscopic lobectomy for all congenital cystic lung diseases in children. Complete thoracoscopic lobectomy was performed by employing carbon dioxide insufflation without single lung ventilation. The results were analyzed, comparing patients with pre- and postnatal diagnoses. RESULTS Seven patients were prenatally diagnosed with congenital pulmonary airway malformations (CPAM) between January 2008 and August 2009, and all but one underwent surgery during the neonatal period (prenatal group). Nine patients underwent surgery after infection subsided due to lesions (7 CPAM, 2 intrapulmonary sequestration) postnatally identified by infection presence (median 2 years; range 15 days to 14 years) (postnatal group). The prenatal group showed a significantly lower rate of adhesions, shorter operation time, and smaller volume of blood loss. There were two conversions in the postnatal group. There were two postoperative complications (persistent air leak and phrenic nerve paralysis) in the prenatal group. The esthetic results were good. CONCLUSIONS Thoracoscopic lobectomy for congenital cystic lung diseases in neonates was practicable, with good esthetic results. Dissection was easier with significantly less blood loss in patients without adhesions, even in neonates. However, this procedure necessitated highly skilled endoscopic maneuvers within a small working space.


DNACPR notices: campaigner for patients' right to be consulted says government has misunderstood her demands.


title: The Prebiotic Provenance of Semi-Aqueous Solvents.

text: The numerous and varied roles of phosphorylated organic molecules in biochemistry suggest they may have been important to the origin of life. The prominence of phosphorylated molecules presents a conundrum given that phosphorylation is a thermodynamically unfavorable, endergonic process in water, and most natural sources of phosphate are poorly soluble. We recently demonstrated that a semi-aqueous solvent consisting of urea, ammonium formate, and water (UAFW) supports the dissolution of phosphate and the phosphorylation of nucleosides. However, the prebiotic feasibility and robustness of the UAFW system are unclear. Here, we study the UAFW system as a medium in which phosphate minerals are potentially solubilized. Specifically, we conduct a series of chemical experiments alongside thermodynamic models that simulate the formation of ammonium formate from the hydrolysis of hydrogen cyanide, and demonstrate the stability of formamide in such solvents (as an aqueous mixture). The dissolution of hydroxylapatite requires a liquid medium, and we investigate whether a UAFW system is solid or liquid over varied conditions, finding that this characteristic is controlled by the molar ratios of the three components. For liquid UAFW mixtures, we also find the solubility of phosphate is higher when the quantity of ammonium formate is greater than urea. We suggest the urea within the system can lower the activity of water, help create a stable and persistent solution, and may act as a condensing agent/catalyst to improve nucleoside phosphorylation yields.


Authors' response to the letter by Dr. Eisa-Beygi.


title: Preventive effect of diverting stoma on anastomotic leakage after laparoscopic low anterior resection with double stapling technique reconstruction applied based on risk stratification.

text: INTRODUCTION During laparoscopic low anterior resection with double stapling technique reconstruction, it is necessary to securely implement rectal transection and anastomosis to prevent anastomotic leakage (AL). However, risk factors and preventive measures for AL are not known sufficiently. Therefore, this study aimed to elucidate risk factors associated with AL and to clarify strategies to prevent it. METHODS We analyzed a total of 296 cases with rectal cancer who had undergone laparoscopic low anterior resection with double stapling technique reconstruction at the National Cancer Center Hospital East. The relationship between AL and patient, tumor, and treatment characteristics were retrospectively investigated. RESULTS There were 186 male and 110 female patients with a median age of 62. Overall, AL occurred in 24 cases (8.1%). Being a man, having an anal verge distance ≤7 cm, and undergoing neoadjuvant chemotherapy were associated with an elevated risk for AL (P = 0.0005, 0.0034, and 0.0222, respectively). Neither an anal drainage tube nor diverting stoma creation correlated with incidence of AL. Multivariate analysis demonstrated that being a man (odds ratio = 18.0; 95% confidence interval: 2.4-138) and having an anal verge distance ≤7 cm (odds ratio = 3.8; 95% confidence interval: 1.5-9.4) were significant risk factors. These two factors were present in 61 cases, including 14 who developed AL (23.0%). In this high-risk group, diverting stoma creation significantly reduced the occurrence of AL (P = 0.0363), but an anal drainage tube had no effect on incidence of AL (P = 0.3399). CONCLUSION We identified the high-risk population for AL after laparoscopic low anterior resection with double stapling technique reconstruction based on two factors. This will enable surgeons to appropriately recommend diverting stoma creation.


title: Perceived HIV-Associated Stigma among HIV-Seropositive Men: Psychometric Study of HIV Stigma Scale.

text: OBJECTIVES To assess the internal consistency and factor structure of the abridged Spanish version of the Berger HIV Stigma Scale (HSS-21), to provide evidence for its convergent and discriminant validity, and to describe perceived stigma in an urban population from northeast Mexico. METHODS Seventy-five HIV-positive men who have sex with men (MSM) were recruited. Participants answered the Spanish versions of three Likert-type scales: HSS-21, Robsenberg's self-esteem scale, and the abbreviated version of the Zung's Depression Scale. RESULTS HSS-21 showed high reliability and validity; its factor structure included four components: concern with public attitudes; negative self-image; disclosure concerns; and enacted stigma. The level of stigma was high in 27 out of 75 (36%) participants; nevertheless, the score found in the component related to disclosure concerns indicated high level of stigma in 68% of participants. The score of HSS-21 was positively correlated with the score of depression and negatively correlated with the score of self-esteem. CONCLUSION Results demonstrated high reliability for the HSS-21; correlations with other scales supported its validity. This scale demonstrated to be a practical tool for assessing stigma among Mexican HIV-positive MSM. High level of stigma was found only in the factor related to disclosure concerns. POLICY IMPLICATIONS Identifying HIV-associated stigma through a short, reliable, and validated instrument will allow the development of interventions that cope and manage stigma in HIV-positive MSM. HSS-21 distinguishes between different dimensions of stigma and will contribute to a better understanding of this phenomenon.


title: Radionuclide treatment of painful bone metastases in patients with breast cancer: a systematic review.

text: Bone-seeking radionuclides, such as Sr-89, Sm-153, and Re-186, have been shown to have an effect on pain from bone metastasis in prostate cancer. The effect on bone pain in other cancer types, including breast cancer, remains unclear. The purpose of the study was to perform a systematic review of the use of radioisotopes for pain relief in metastatic breast cancer. A literature search was performed in PubMed, EMBASE, and Web of Science (1970 to September 2009) for clinical studies with a primary outcome of pain, performance status, or quality of life. Eligibility criteria were the following: (1) the trial must include at least 10 breast cancer patients with painful bone metastasis, (2) the radionuclide has been approved by regulatory authorities in Europe or the United States and is commercially available (Sr-89, Sm-153, and Re-186), (3) the dose of radionuclides must be clinically effective, (4) the primary endpoint must be pain, performance status or quality of life, and (5) separate reporting of efficacy should be available for breast cancer patients provided the trial included patients with various types of cancer. The literature search identified 189 individual studies of which 19 trials fulfilled the eligibility criteria. There were three randomized controlled trials of which two trials compared two different radionuclides, and one trial compared two doses of Sm-153. In addition, there were 16 uncontrolled trials. Reporting of trial research methodology in the randomized as well as the uncontrolled trials was low (median Jadad score of 1, range 1-2). Key trial details, such as patient recruitment, description of prior palliative therapies, baseline characteristics, follow up, and reporting of outcome was insufficient in a large proportion of the trials. According to Center of Evidence-based Medicine criteria, there is level 4 documentation for the effect of radionuclides in painful bone metastasis in breast cancer. It has been concluded that there is limited clinical evidence supporting the clinical effect of radionuclides in relieving pain from bone metastasis in breast cancer. Large, randomized controlled trials are needed to establish the utility of bone-seeking radionuclides in the palliative care of breast cancer patients.


title: TANK-binding kinase 1 as a novel therapeutic target for viral diseases.

text: INTRODUCTION TANK-binding kinase 1 (TBK1) is vital for the induction of antiviral innate immune responses. Both RNA and DNA viral infection induces TBK1 activation, triggers phosphorylation of interferon regulatory factor (IRF) 3 and subsequent expression of type I interferons (IFNs; IFN-α/β). Type I IFNs can induce the expression of numerous antiviral genes called interferon-stimulated genes (ISGs) to build a remarkable antiviral state and limit viral replication. Thus, optimal TBK1 activity is crucial for IRF3-induced type I IFNs expression and ISGs-mediated viral elimination. Areas covered: This review provides an overview of the diverse roles of TBK1 in antiviral innate immune responses, the regulatory mechanisms of TBK1 activity and the implication in antiviral development. Expert opinion: TBK1 is a key kinase against antiviral infection via inducing type I IFNs expression. Multiple types of post-translational modifications of TBK1 tightly regulate TBK1 activity and subsequent TBK1-dependent antiviral responses. The identified regulators of TBK1 unveil regulatory mechanisms of host antiviral innate immunity and immuno-escape mechanism of virus provide strategies to control viral diseases by modulating TBK1 activity.


title: Safety and Acceptability of Esophageal Cytosponge Cell Collection Device in a Pooled Analysis of Data From Individual Patients.

text: BACKGROUND & AIMS Diagnosis and surveillance of Barrett's esophagus (BE) and eosinophilic esophagitis (EoE) have become emerging public health issues. Cytosponge is a novel, minimally invasive esophageal cell collection device. We aimed to assess the data on safety and acceptability of this device. METHODS We performed a patient-level review of 5 prospective trials assessing Cytosponge performance in patients with reflux disease, BE and EoE in primary and secondary care. Acceptability of Cytosponge and subsequent endoscopy were recorded with visual analogue scale (VAS), wherein 0 and 10 denoted lowest and highest acceptability. Median VAS scores were compared using a Mann-Whitney test. The number of attempts, failures in swallowing the device and occurrence of adverse events were analyzed. Risk factors for failure in swallowing were analyzed using a multivariate regression model. RESULTS In total, 2672 Cytosponge procedures were performed, in 2418 individuals from 2008 through 2017. There were 2 adverse events related to the device: a minor pharyngeal bleed and a case of detachment (<1:2000). The median acceptability score for the Cytosponge was 6.0 (interquartile range [IQR], 5.0-8.0), which was higher than the score for endoscopy without sedation (median 5.0; IQR, 3.0-7.0; P < .001) and lower than the score for endoscopy with sedation (median 8.0; IQR, 5.0-9.0; P < .001). Nearly all patients (91.1%) successfully swallowed the Cytosponge, most on the first attempt (90.1%). Failure to swallow the device was more likely to occur in secondary care (odds ratio, 5.13; 95% CI, 1.48-17.79; P < .01). CONCLUSIONS The Cytosponge test is a safe procedure with good acceptability ratings in a variety of health care settings.


Extended US travel ban harms global science.


title: Identification of the functional domain of the porcine epidemic diarrhoea virus receptor.

text: Porcine aminopeptidase N (pAPN) is a functional receptor for porcine epidemic diarrhoea virus (PEDV). Although PEDV is known to use the pAPN as the major receptor for cell entry, the crucial domain of the pAPN that interacts with the PEDV is still unknown. In the present study, in order to determine the crucial domain of the pAPN, the extracellular domain of pAPN was divided into three subdomains named SPA, SPB and SPC, based on its secondary structure. Recombinant plasmid pcDNA3.1 expressing SPA, SPB and SPC was constructed and introduced into Madin-Darby canine kidney (MDCK) cells by transfection. Following the detection of PEDV infection in transfected MDCK cells after PEDV challenge, we clearly demonstrated that the SPC subdomain plays a key role in cell entry of PEDV and its expression permits PEDV growth in transfected MDCK cells, while virus propagation can be inhibited by anti-SPC serum, indicating that the SPC subdomain appears to be a crucial functional domain in contributing to efficient PEDV infection.


title: Comparative analysis of the effect of glycyrrhizin diammonium and lithium chloride on infectious bronchitis virus infection in vitro.

text: The effects of glycyrrhizin diammonium (GD) and lithium chloride (LiCl) on cell infection by avian infectious bronchitis virus (IBV) were investigated using cytopathic effect observation, plaque-reduction assay and reverse transcriptase-polymerase chain reaction. The anti-viral effect of GD and LiCl on virus, on virus-infected cells or on cells pre-treated by both drugs was analysed, respectively. Our results showed that GD had a direct antiviral activity, leading to complete inhibition of cell infection. The cell infection was not alleviated by either pre-treatment of cells with GD or addition of the drug post infection, confirming that the inhibitory effect of GD, unlike LiCl, on IBV is a viral factor, rather than a cellular factor. The inhibitory effect of both drugs was confirmed by infecting primary chicken embryo kidney cells. In addition, apoptosis of infected cells was positively related with cytopathic effect and could be inhibited by effective drug treatment. Our data indicate that GD and LiCl have potential to prevent IBV infection in vitro through different antiviral mechanisms. The data are helpful for using antivirals efficiently.


title: Onsite telemedicine strategy for coronavirus (COVID-19) screening to limit exposure in ED.

text: Coronavirus (severe acute respiratory syndrome coronavirus 2) outbreak is a public health emergency and a global pandemic. During the present coronavirus disease (COVID-19) crisis, telemedicine has been recommended to screen suspected patients to limit risk of exposure and maximise medical staff protection. We constructed the protective physical barrier with telemedicine technology to limit COVID-19 exposure in ED. Our hospital is an urban community hospital with annual ED volume of approximately 50 000 patients. We equipped our patient exam room with intercom and iPad for telecommunication. Based on our telemedicine screening protocol, physician can conduct a visual physical examination on stable patients via intercom or videoconference. Telemedicine was initially used to overcome the physical barrier between patients and physicians. However, our protocol is designed to create a protective physical barrier to protect healthcare workers and enhance efficiency in ED. The implementation can be a promising protocol in making ED care more cost-effective and efficient during the COVID-19 pandemic and beyond.


Covid-19: Deaths in Mexico triple since reopening began in June.


title: Hyperinvasive approach to out-of hospital cardiac arrest using mechanical chest compression device, prehospital intraarrest cooling, extracorporeal life support and early invasive assessment compared to standard of care. A randomized parallel groups comparative study proposal. "Prague OHCA study".

text: BACKGROUND Out of hospital cardiac arrest (OHCA) has a poor outcome. Recent non-randomized studies of ECLS (extracorporeal life support) in OHCA suggested further prospective multicenter studies to define population that would benefit from ECLS. We aim to perform a prospective randomized study comparing prehospital intraarrest hypothermia combined with mechanical chest compression device, intrahospital ECLS and early invasive investigation and treatment in all patients with OHCA of presumed cardiac origin compared to a standard of care. METHODS This paper describes methodology and design of the proposed trial. Patients with witnessed OHCA without ROSC (return of spontaneous circulation) after a minimum of 5 minutes of ACLS (advanced cardiac life support) by emergency medical service (EMS) team and after performance of all initial procedures (defibrillation, airway management, intravenous access establishment) will be randomized to standard vs. hyperinvasive arm. In hyperinvasive arm, mechanical compression device together with intranasal evaporative cooling will be instituted and patients will be transferred directly to cardiac center under ongoing CPR (cardiopulmonary resuscitation). After admission, ECLS inclusion/exclusion criteria will be evaluated and if achieved, veno-arterial ECLS will be started. Invasive investigation and standard post resuscitation care will follow. Patients in standard arm will be managed on scene. When ROSC achieved, they will be transferred to cardiac center and further treated as per recent guidelines. PRIMARY OUTCOME 6 months survival with good neurological outcome (Cerebral Performance Category 1-2). Secondary outcomes will include 30 day neurological and cardiac recovery. DISCUSSION Authors introduce and offer a protocol of a proposed randomized study comparing a combined "hyperinvasive approach" to a standard of care in refractory OHCA. The protocol is opened for sharing by other cardiac centers with available ECLS and cathlab teams trained to admit patients with refractory cardiac arrest under ongoing CPR. A prove of concept study will be started soon. The aim of the authors is to establish a net of centers for a multicenter trial initiation in future. ETHICS AND REGISTRATION: The protocol has been approved by an Institutional Review Board, will be supported by a research grant from Internal Grant Agency of the Ministry of Health, Czech Republic NT 13225-4/2012 and has been registered under ClinicalTrials.gov identifier: NCT01511666.


title: Pandemic influenza and pediatric intensive care.

text: OBJECTIVE To assess the adequacy of preparedness planning for an influenza pandemic by modeling the pediatric surge capacity of healthcare facility and pediatric intensive care unit (PICU) requirements over time. Governments and Public Health authorities have planned preparedness activities and training for a flu pandemic. PICU facilities will be the limiting factor in healthcare provision for children but detailed analyses for needs and demands in PICU care have not been published. DESIGN Based on the Center for Disease Control and Prevention and World Health Organization estimates and published models of the expected evolution of pandemic flu, we modeled the pediatric surge capacity of healthcare facility and PICU requirements over time. Various scenarios with different assumptions were explored. We compared these demands with estimates of maximal PICU capacity factoring in healthcare worker absenteeism as well as reported and more realistic estimates derived from semistructured telephone interviews with key stakeholders in ICUs in the study area. SETTING All hospitals and intensive care facilities in the Northern Region in The Netherlands with near 1.7 million inhabitants, of whom approximately 25% is <18 yrs. MEASUREMENTS AND MAIN RESULTS Using well-established modeling techniques, evidence-based medicine, and incorporating estimates from the Centers for Disease Control and Prevention and World Health Organization, we show that PICU capacity may suffice during an influenza pandemic. Even during the peak of the pandemic, most children requiring PICU admission may be served, even those who have nonflu-related conditions, provided that robust indications and decision rules are maintained, both for admission, as well as continuation (or discontinuation) of life support. CONCLUSIONS We recommend that a model, with assumptions that can be adapted with new information obtained during early stages of the pandemic that is evolving, be an integral part of a preparedness plan for a pandemic influenza with new human transmissible agent like influenza A virus.


title: Effects of pain and prescription opioid use on outcomes in a collaborative care intervention for anxiety.

text: OBJECTIVE To determine the effects of pain and opioid pain medication use on clinical and functional outcomes in 1004 primary care patients with an anxiety disorder randomized to receive the Coordinated Anxiety Learning and Management (CALM) collaborative care intervention (cognitive-behavioral therapy and/or medication) versus usual care. METHODS A total of 1004 patients with panic disorder, generalized anxiety disorder, social anxiety disorder, or posttraumatic stress disorder were randomized to CALM or usual care. Outcomes at 6, 12, and 18 months were compared in patients with and without moderate pain interference (for the entire anxiety disorder group and then just those with comorbid major depression) and in patients taking and not taking opioid medication (entire group, just those with comorbid major depression, and just those with moderate pain interference). RESULTS Patients with pain interference and patients taking opioid pain medication were more anxious [Brief Symptom Inventory anxiety subscale] and disabled (Sheehan Disability) at baseline, improved over time at similar rates, but at 18 months had lower response and remission rates. There was no moderating effect on the intervention. In patients with comorbid major depression, patients using opioid medications showed a trend for less disability improvement over time, and in patients with pain, patients using opioids showed less sustained anxiety response at 18 months. CONCLUSIONS Anxious patients with pain benefit as much as those without pain from cognitive-behavioral therapy and medication treatment. Among patients with pain, however, there is some evidence of a reduced anxiety treatment response in those taking opioid medication, which should be further studied.


title: Testing for inherited thrombophilias in arterial stroke: can it cause more harm than good?

text: BACKGROUND AND PURPOSE Despite a paucity of evidence supporting a true association of ischemic stroke and the inherited thrombophilias, it is common practice for many neurologists to order these tests as part of the work-up of ischemic stroke, especially in young patients. Treatment with oral anticoagulation is often used in patients with positive results for the inherited thrombophilias. METHODS We reviewed the literature focusing on case-control studies of the 5 most commonly inherited disorders of coagulation: protein C deficiency, protein S deficiency, antithrombin deficiency, and the factor V Leiden and prothrombin gene mutations in patients with stroke. We also analyzed the available data on stroke patients with inherited thrombophilia and patent foramen ovale. RESULTS Multiple case-control studies have not convincingly shown an association of the inherited thrombophilias with ischemic stroke, even in young patients and patients with patent foramen ovale. CONCLUSIONS If there is an association between the inherited thrombophilias and arterial stroke, then it is a weak one, likely enhanced by other prothrombotic risk factors. The consequences of ordering these tests and attributing causality to an arterial event can result in significant costs to the health care system and pose a potential risk to patients, because this may lead to inappropriate use of long-term oral anticoagulants, exposing patients to harm without a clearly defined benefit.


title: Factors affecting the quality of life after total knee arthroplasties: a prospective study.

text: BACKGROUND The purpose of the study is to evaluate the self-reported outcomes in the first year after primary total knee arthroplasty (TKA), and to determine factors influencing the quality of life (QoL) 6 weeks, 3, 6, and 12 months after TKA. METHODS A cohort of patients with knee osteoarthritis undergoing primary TKA at two hospitals (a regional university hospital and a capital's metropolitan hospital) was prospectively followed for 12 months. Patients were assessed preoperatively and at 4 postoperative time-points, with the use of self-reported measurements for pain, physical function and depression with the following evaluation tools: Western Ontario and McMaster Osteoarthritis Index [WOMAC], Knee Society Scoring system [KSS], Centre for Epidemiological Studies Depression Scale, [CES-D10] and visual analog scale [VAS] for pain). General linear modelling for repeated measures was used to evaluate the effect of each independent variable including clinical and sociodemographic data. Differences between groups at different time points were tested by the independent samples t-test. RESULTS Of the 224 eligible patients, 204 (162 females, mean age 69.2) were included in the analysis. Response rate at one year was 90%. At 6 weeks after surgery, despite improvement in pain and alleviation of the depressive mood, the physical function remained less satisfactory. Females presented lower scores in terms of quality of life, both preoperatively and 6 weeks after TKA. Significant improvement was already experienced at 3 months postoperatively. According to WOMAC, KSS, CES-D10 and pain VAS scores the Qol was significantly improved 12 months after TKA (P < 0.001). CES-D10 score was positively correlated with WOMAC and pain VAS scores at all the time points assessed (P < 0.001). Age, body mass index (BMI), place of residence, level of education and social support were not significant predictors of QoL after TKA. CONCLUSIONS Patients experienced great improvement in their QoL after TKA in spite of a less satisfactory physical function in the first 6 weeks after surgery, with noticeable differences in the QoL among genders in the same time period. After that period all patients experienced significant improvement for all the measured parameters, until the third postoperative month with smaller changes thereafter.


title: Older Age Predicts Worse Function 1 Year After an Acute Achilles Tendon Rupture: A Prognostic Multicenter Study on 391 Patients.

text: Background There is limited evidence regarding the patient-related factors that influence treatment outcomes after an acute Achilles tendon rupture. Purpose/Hypothesis The purpose of this study was to determine the predictors of functional and patient-reported outcomes 1 year after an acute Achilles tendon rupture using a multicenter cohort and to determine patient characteristics for reporting within the top and bottom 10% of the Achilles tendon Total Rupture Score (ATRS) and heel-rise height outcomes. The hypothesis was that older age, greater body mass index (BMI), and female sex would lead to inferior outcomes. Study Design Cohort study; Level of evidence, 2. Methods Patients were selected by combining 5 randomized controlled trials from 2 different centers in Sweden. Functional outcomes were assessed using validated heel-rise tests (height, number of repetitions, total work, and concentric power) for muscular endurance and strength, and the relationship between injured and uninjured legs was calculated as the limb symmetry index (LSI). Patient-reported outcomes were measured using the ATRS. All outcomes were collected at the 1-year follow-up. Independent predictors included were patient sex, smoking, BMI, age, and surgical versus nonsurgical treatment. Results Of the 391 included patients, 307 (79%) were treated surgically. The LSI of heel-rise height at the 1-year follow-up decreased by approximately 4% for every 10-year increment in age (beta, -3.94 [95% CI, -6.19 to -1.69]; P = .0006). In addition, every 10-year increment in age resulted in a 1.79-fold increase in the odds of being in the lowest 10% of the LSI of heel-rise height. Moreover, a nonsignificant superior LSI of heel-rise height was found in patients treated surgically compared with nonsurgical treatment (beta, -4.49 [95% CI, -9.14 to 0.16]; P = .058). No significant predictor was related to the ATRS. Smoking, patient sex, and BMI did not significantly affect the 1-year results for the LSI of the heel-rise tests. Conclusion Older age at the time of injury negatively affected heel-rise height 1 year after an Achilles tendon rupture. Irrespective of age, a nonsignificant relationship toward the superior recovery of heel-rise height was seen in patients treated surgically. None of the factors studied affected patient-reported outcomes.


title: Laparoendoscopic single-site surgery versus conventional laparoscopy for hysterectomy: a systematic review and meta-analysis.

text: PURPOSE To assess the safety and effectiveness of LESS compared to conventional hysterectomy. METHODS The systematic review and meta-analysis was performed according to the MOOSE guideline, and quality of evidence was assessed using GRADE. Different databases were searched up to 4th of August 2016. Randomized controlled trials and cohort studies comparing LESS to the conventional laparoscopic hysterectomy were considered for inclusion. RESULTS Of the 668 unique articles, 23 were found relevant. We investigated safety by analyzing the complication rate and found no significant differences between both groups [OR 0.94 (0.61, 1.44), I 2 = 19%]. We assessed effectiveness by analyzing conversion risk, postoperative pain, and patient satisfaction. For conversion rates to laparotomy, no differences were identified [OR 1.60 (0.40, 6.38), I 2 = 45%]. In 3.5% of the cases in the LESS group, an additional port was needed during LESS. For postoperative pain scores and patient satisfaction, some of the included studies reported favorable results for LESS, but the clinical relevance was non-significant. Concerning secondary outcomes, only a difference in operative time was found in favor of the conventional group [MD 11.3 min (5.45-17.17), I 2 = 89%]. The quality of evidence for our primary outcomes was low or very low due to the study designs and lack of power for the specified outcomes. Therefore, caution is urged when interpreting the results. CONCLUSION The single-port technique for benign hysterectomy is feasible, safe, and equally effective compared to the conventional technique. No clinically relevant advantages were identified, and as no data on cost effectiveness are available, there are currently not enough valid arguments to broadly implement LESS for hysterectomy.


title: Right minithoracotomy versus conventional median sternotomy for patients undergoing mitral valve surgery and Cox-maze IV ablation with entirely bipolar radiofrequency clamp.

text: Cox-maze IV ablation by bipolar radiofrequency clamp was considered to be only performed through median sternotomy (MS), but impossible through right minithoracotomy (RM). Now, we developed a novel technique of performing Cox-maze IV ablation entirely by bipolar clamp through RM. To compare the outcomes of RM or MS for patients undergoing mitral valve surgery and concomitant Cox-maze IV ablation with entirely bipolar clamp. All 152 patients underwent mitral valve surgery and concomitant Cox-maze IV ablation with bipolar clamp through RM (n = 69) or MS (n = 83) were analyzed for outcome differences. The etiology of mitral valve disease was rheumatic (n = 97) and degenerative (n = 55). All patients had long-standing persistent atrial fibrillation (AF). Diameter of left atrium ranged from 42 to 60 mm. All patients successfully underwent Cox-maze IV ablation by bipolar clamp. RM group had longer cardiopulmonary bypass time (130.3 ± 17.7 vs 115.3 ± 14.4 min; P < 0.001) and aortic cross-clamp time (91.8 ± 12.7 vs 74.6 ± 9.3 min; P < 0.001). But mechanical ventilation time (14.2 ± 6.6 vs 21.3 ± 9.0 h; P < 0.001) and hospital length of stay (9.3 ± 2.6 vs 11.7 ± 3.0 days; P < 0.001) were shorter in RM group. At discharge, the maintenance of normal sinus rhythm (NSR) was 94.2% in RM group and 95.1% in MS group (P = 1.000). Cumulative maintenance of NSR at 2 years postoperatively was 85.1 ± 5.8% in RM group and 88.6 ± 3.6% in MS group (P = 0.767). RM can achieve similar therapeutic effect to MS for patients undergoing mitral valve surgery and concomitant Cox-maze IV ablation with entirely bipolar clamp. In addition, patients through RM had faster recovery.


title: Effects of Toll-like receptor signals in T-cell neoplasms.

text: T-cell neoplasms have poor prognosis and few effective therapeutic options. Therefore, identification of factors in T-cell leukemia/lymphoma that are associated with cancer progression may represent novel therapeutic targets. Recent studies have highlighted a previously unappreciated role for the expression of Toll-like receptors (TLRs) on T cells and their effects on cell survival and proliferation. TLRs can bind exogenous molecules derived from pathogens as well as endogenous self-ligands released from damaged cells. Recent reports demonstrate that TLR engagement on primary mouse or human T cells enhances proliferation and/or cell survival. The mechanisms by which TLR stimulation on T cells influences these parameters and the different T-cell subsets that are affected by TLR stimulation are currently under investigation. Furthermore, neither the biological importance of stimulating TLRs on neoplastic T cells nor the prevalence of TLR expression in T-cell malignancies have yet to be characterized. Based on published reports and compelling preliminary data, we propose that the activation of the TLR-MyD88 signaling pathway in neoplastic T cells contributes to disease progression by reducing cell death and enhancing cell division. In this article, we present both theoretical arguments and experimental data in support of this hypothesis.


title: Uniportal thoracoscopic resection of intralobar and extralobar pulmonary sequestration.

text: Pulmonary sequestration (PS) is a rare congenital malformation of the respiratory tract. Two main variants are described, the intralobar and the extralobar PS. Clinical manifestations vary from accidental findings to life threatening complications. Surgical resection is the definitive and indicated treatment of PS. The operation could be performed through an open thoracotomy or video-assisted thoracic surgery approach. We report the management of two patients with diagnosis of extralobar PS in the first case and intralobar PS in the second case. Both patients underwent uniportal video-assisted thoracic surgery resection of PS with success. In our experience, we confirm that uniportal video-assisted thoracic surgery is a safe and feasible approach for extralobar and intralobar PS.


title: Minimally invasive central pancreatectomy and pancreatogastrostomy: current surgical technique and outcomes.

text: Recent improvements in imaging techniques and more frequent use of cross-sectional imaging have led to an increase in the identification of benign and low-grade lesions of the pancreas. Patients with resectable cancers are commonly treated by either a Whipple procedure or distal pancreatectomy (DP) based on the location of the tumor. Central pancreatectomy (CP) is a less commonly performed operation that has recently been utilized for resection of these now more frequently diagnosed low-grade and benign lesions located in the mid pancreas. Lesions that may have a relatively more indolent nature include branch-type intraductal papillary mucinous neoplasm (IPMNs), mucinous cystic neoplasms, neuroendocrine tumors, and solid pseudopapillary tumors. The goal of a CP is complete extirpation of the lesion, while preserving pancreatic parenchyma to reduce the risks of developing diabetes and exocrine insufficiency (EI). Although open CP has been shown to be safe and efficacious, the outcomes of a minimally invasive approach are still relatively underreported and therefore unknown. In this paper, we describe our surgical approach to performing a CP with an accompanying video demonstration of the key portions of the operation.


title: Gastrointestinal Symptoms and outcomes in hospitalized COVID-19 patients.

text: INTRODUCTION Gastrointestinal (GI) symptoms are increasingly being recognized in coronavirus disease 2019 (COVID-19). It is unclear if the presence of GI symptoms is associated with poor outcomes in COVID-19. We aim to assess if GI symptoms could be used for prognostication in hospitalized patients with COVID-19. METHODS We retrospectively analyzed patients admitted to a tertiary medical center in Brooklyn, NY, from March 18, 2020, to March 31, 2020, with COVID-19. The patients' medical charts were reviewed for the presence of GI symptoms at admission, including nausea, vomiting, diarrhea, and abdominal pain. COVID-19 patients with GI symptoms (cases) were compared with COVID-19 patients without GI symptoms (control). RESULTS A total of 150 hospitalized COVID-19 patients were included, of which 31 (20.6%) patients had at least one or more of the GI symptoms (cases). They were compared with the 119 COVID-19 patients without GI symptoms (controls). The average age among cases was 57.6 years (SD 17.2) and, control was 63.3 years (SD 14.6). No statistically significant difference was noted in comorbidities and laboratory findings. The primary outcome was mortality, which did not differ between cases and controls (41.9% vs. 37.8%, p=0.68). No statistically significant differences were noted in secondary outcomes, including the length of stay (LOS, 7.8 days vs. 7.9 days, p=0.87) and need for mechanical ventilation (29% vs. 26.9%, p=0.82). DISCUSSION In our study, the presence of GI manifestations in COVID-19 at the time of admission was not associated with increased mortality, LOS, or mechanical ventilation.


title: Achieving Quality in Cardiovascular Imaging II: proceedings from the Second American College of Cardiology -- Duke University Medical Center Think Tank on Quality in Cardiovascular Imaging.

text: Despite rapid technologic advances and sustained growth, less attention has been focused on quality in imaging than in other areas of cardiovascular medicine. To address this deficit, representatives from cardiovascular imaging societies, private payers, government agencies, the medical imaging industry, and experts in quality measurement met in the second Quality in Cardiovascular Imaging Think Tank. The participants endorsed the previous consensus definition of quality in imaging and proposed quality measures. Additional areas of needed effort included data standardization and structured reporting, appropriateness criteria, imaging registries, laboratory accreditation, partnership development, and imaging research. The second American College of Cardiology-Duke University Think Tank continued the process of the development, dissemination, and adoption of quality improvement initiatives for all cardiovascular imaging modalities.


title: Erratum: Investigation of Turkish dentists' clinical attitudes and behaviors towards the COVID-19 pandemic: a survey study. Braz Oral Res. 2020;34:e054 DOI: 10.1590/1807-3107bor-2020.vol34.0054.

text: [This corrects the article doi: 10.1590/1807-3107bor-2020.vol34.0054].


title: Optimal pediatric dosing of anti-platelet agents for pipeline stent embolization -a case report and review of the literature.

text: BACKGROUND Various strategies are emerging for dosing antiplatelet therapies in preparation for pipeline stent embolization in adults. Hyper-response is associated with hemorrhagic complications. Hypo-response is associated with thromboembolic events. Dosing of antiplatelet agents is highly variable, with little consensus among experts for adults-and even more so for children. To date, pipeline stents have been deployed in 11 pediatric patients, ages 4-15. A variety of clopidogrel and aspirin dosing regimens have been used, with response tested in only three patients, who were all therapeutic. Thrombotic events occurred in two patients, neither of whom were tested. CASE We describe here the first case of a hemorrhagic complication in a hyper-responsive pediatric patient undergoing placement of a pipeline stent. DISCUSSION As the use of endovascular therapies requiring dual anti-platelet agents becomes more established, there is an increasing need to develop titration protocols that minimizes the risk of thrombotic and hemorrhagic events.


title: Endotherapy in case of relapse of neoplastic Barrett's esophagus after successful initial endoscopic resection.

text: BACKGROUND Endotherapy in cases of neoplastic Barrett esophagus (BE) relapse after successful initial endoscopic management is commonly accepted, but few studies analyze this topic and also take into account the metachronous lesions. AIMS To evaluate the efficiency of endotherapy in the case of neoplastic BE relapse after successful complete endoscopic eradication of neoplastic BE and metaplastic BE. METHODS Retrospective review of medical records was collected in a computerized and prospective manner between 2000 and 2015, in a single tertiary care center. Recurrence was defined by histological presence of high-grade dysplasia or superficial adenocarcinoma at least 6 months after the end of successful initial endotherapy. RESULTS Eighteen patients were assessed (1F/17 M). Delay between initial treatment and relapse was 16.6 months (range 6-33). Endotherapy for relapse obtained a sustained and complete remission for 8/18 (44%) patients, with an average endoscopic follow-up of 28 months. The complication rate of endotherapy was 6%. Surgical management was required in 33% (2 pT2N0M0, 2 pTisN0M0, 1 pTm2N0M0 and 1 pTm3N0M0) and salvage radiochemotherapy in 17% (3/18). One patient treated by 6 sessions of ER was considered as a failure given the multiple sessions of endotherapy. Multivariate analysis showed that length of BE (>5 cm), late stenosis adverse events and the quality of vertical margin during initial ER are predictive factors for disease-free survival (p value < 0.01, Hazard Ratio up to 0.076). CONCLUSION Endotherapy could be a treatment for management of neoplastic BE relapse, but should be carefully used, with strict follow-up.


title: Epicardial adipose tissue and carotid artery disease: Protocol for systematic review and meta-analysis.

text: BACKGROUND Atherosclerosis is now widely recognized as a multifactorial disease with outcomes that arise from complex factors such as plaque components, blood flow, and inflammation. Epicardial adipose tissue (EAT) is a metabolically active fat depot, abundant in proinflammatory cytokines, and has been correlated with the extent and severity of carotid artery disease (CD). The locations most frequently affected by carotid atherosclerosis are the proximal internal carotid artery (ie, the origin) and the common carotid artery bifurcation. Progression of atheromatous plaque at the carotid bifurcation results in luminal narrowing, often accompanied by ulceration. However, there are no systematic analyses or well-conducted meta-analyses to evaluate the relationship between EAT and CD. The aim of this study is to examine this association of EAT with CD in different ages and sex. METHODS This systematic review and meta-analysis will be conducted using published studies that will be identified from electronic databases (ie, PubMed, EMBASE, Web of Science, and Google Scholar. Studies that (1) examined the association between EAT and CD, (2) focus on cohort, case-control and cross-sectional studies, (3) will conducted among in adults aged 40 to 70 years, (4) provided sufficient data for calculating ORs or relative risk with a 95% CI, (5) will published as original articles written in English or other languages, and (6) have been published until January 2018 will be included. Study selection, data collection, quality assessment and statistical syntheses will be conducted based on discussions among investigators. RESULTS We propose the current protocol to evaluate the evaluation of EAT with ED. CONCLUSION This systematic review will not need ethical approval, because it does not involve human beings. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. ETHICS AND DISSEMINATION Ethics approval was not required for this study because it was based on published studies. The results and findings of this study will be submitted and published in a scientific peer-reviewed journal. TRIAL REGISTRATION NUMBER PROSPERO (CRD42018083458).


Ebola and ethics.


A young male with bilateral chest pain.


Stability and Viability of SARS-CoV-2.


title: A rare type of double aortic arch diagnosed by echocardiography in an asymptomatic 9-year-old patient.

text: A case of double aortic arch with an atretic left arch distal to the origin of the left subclavian artery was suspected by echocardiography (ECHO) in an asymptomatic 9-year-old girl and confirmed by magnetic resonance imaging (MRI). The authors report their ECHO findings, which could be an important diagnostic tool for symptomatic patients because confusion exists in the literature regarding the differentiation of the aforementioned rare malformation from a right arch with mirror image branching. The authors support their ECHO proposal with an explanation based on the hypothetical double aortic arch plan set by Edwards.


title: A one-step conversion from gastric banding to laparoscopic Roux-en-Y gastric bypass is as safe as a two-step conversion: A comparative analysis of 885 patients.

text: AIMS To achieve additional weight loss or to resolve band-related problems, a laparoscopic adjustable gastric banding (LAGB) can be converted to a laparoscopic Roux-en-Y gastric bypass (RYGB). There is limited data on the feasibility and safety of routinely performing a single-step conversion. We assessed the efficacy of this revisional approach in a large cohort of patients operated in a high-volume bariatric institution. METHODS Between October 2004 and December 2015, a total of 885 patients who underwent LAGB removal with RYGB were identified from a prospectively collected database. In all cases, a single-stage conversion procedure was planned. The feasibility of this approach and peri-operative outcomes of these patients were evaluated and analyzed. RESULTS A single-step approach was successfully achieved in 738 (83.4%) of the 885 patients. During the study period, there was a significant increase in performing the conversion from LAGB to RYGB single-staged. No mortality or anastomotic leakage was observed in both groups. Only 45 patients (5.1%) had a 30-d complication: most commonly hemorrhage (N = 20/45), with no significant difference between the groups. CONCLUSION Converting a LAGB to RYGB can be performed with a very low morbidity and zero-mortality in a high-volume revisional bariatric center. With increasing experience and full standardization of the conversion, the vast majority of operations can be performed as a single-stage procedure. Only a migrated band remains a formal contraindication for a one-step approach.


title: Middle East respiratory syndrome coronavirus: five years later.

text: INTRODUCTION In the past five years, there have been 1,936 laboratory-confirmed cases of Middle East Respiratory Syndrome coronavirus (MERS-CoV) in 27 countries, with a mortality rate of 35.6%. Most cases have arisen in the Middle East, particularly the Kingdom of Saudi Arabia, however there was a large hospital-associated outbreak in the Republic of Korea in 2015. Exposure to dromedary camels has been recognized by the World Health Organization (WHO) as a risk factor in primary cases, but the exact mechanisms of transmission are not clear. Rigorous application of nationally defined infection prevention and control measures has reduced the levels of healthcare facility-associated outbreaks. There is currently no approved specific therapy or vaccine available. Areas covered: This review presents an overview of MERS-CoV within the last five years, with a particular emphasis on the key areas of transmission, infection control and prevention, and therapies and vaccines. Expert commentary: MERS-CoV remains a significant threat to public health as transmission mechanisms are still not completely understood. There is the potential for mutations that could increase viral transmission and/or virulence, and zoonotic host range. The high mortality rate highlights the need to expedite well-designed randomized clinical trials for direct, effective therapies and vaccines.


Coagulopathy associated with COVID-19.


title: Radiofrequency ablation: technique and clinical applications.

text: Radiofrequency ablation is the most commonly used percutaneous ablation technique and well-documented in the literature on focal therapies. It has become the image-guided ablation method of choice because of its efficacy, safety, and ease of use. Radiofrequency ablation has shown promise in treating selected solid tumors, particularly those involving the liver, kidneys, lungs, and the musculoskeletal system. It is a minimally invasive technique often used in inoperable patients with other comorbidities. Radiofrequency ablation requires a minimal hospital stay or can be performed on an outpatient basis. The aim of this article is to review radiofrequency ablation techniques and their clinical applications.


title: Drivers of disease emergence and spread: is wildlife to blame?

text: The global focus on wildlife as a major contributor to emerging pathogens and infectious diseases (EIDs) in humans and domestic animals is not based on field, experimental or dedicated research, but mostly on limited surveys of literature, opinion and the assumption that biodiversity harbours pathogens. The perceived and direct impacts of wildlife, from being a reservoir of certain human and livestock pathogens and as a risk to health, are frequently overstated when compared to the Global burden of disease statistics available from WHO, OIE and FAO. However organisms that evolve in wildlife species can and do spill-over into human landscapes and humans and domestic animal population and, where these organisms adapt to surviving and spreading amongst livestock and humans, these emerging infections can have significant consequences. Drivers for the spill-over of pathogens or evolution of organisms from wildlife reservoirs to become pathogens of humans and domestic animals are varied but almost without exception poorly researched. The changing demographics, spatial distribution and movements, associated landscape modifications (especially agricultural) and behavioural changes involving human and domestic animal populations are probably the core drivers of the apparent increasing trend in emergence of new pathogens and infectious diseases over recent decades.


title: Determining the microbiological cause of a chest infection.

text: Over recent years non-culture techniques such as specific viral and bacterial nucleic acid amplification, serology and antigen detection have considerably developed and been applied within research studies to clinical samples, significantly increasing pathogen detection in pneumonia. There are promising signs of improved diagnostic yields for pneumococcal pneumonia when using molecular techniques to detect pneumococcal gene sequences in blood or by combining serum biomarkers with rapid pneumococcal urinary antigen testing. Pathogens have traditionally been difficult to detect in pneumonia and treatment is usually successful with empiric antibiotics. However, directed antibiotic treatment has significant benefits in terms of antibiotic stewardship and these new technologies make this goal a possibility, though not yet a reality.


title: Unusual venous route of pulmonary artery catheter in a liver transplant recipient: pericardiophrenic or highest intercostal vein?: a case report.

text: We report an extraordinary case in which the venous route for pulmonary artery catheterization was unusual. A 41 year-old woman with an end-stage liver disease underwent a living-donor liver transplantation. After induction of anesthesia, the pulmonary artery catheter was revealed to be advanced into the left brachiocephalic vein and then slipped into another vein that drains into the left brachiocephalic vein. In this case, we assumed that the catheter had most likely slipped into the left pericardiophrenic vein since the catheter follows the left heart border similarly to the route of this vein according to the chest X-ray. Patients with liver cirrhosis develop many collateral vessels and have enlarged veins due to portal hypertension, which makes this vascular route possible. We present this case for anesthesiologists to be aware of the possibilities of unusual venous route due to dilated collateral vessels especially in liver transplant patients.


title: Higher anti-TNF serum levels are associated with perianal fistula closure in Crohn's disease patients.

text: Objectives: Anti-TNF agents are effective to treat perianal Crohn's disease (CD). Evidence suggests that Crohn's disease patients with perianal fistulas need higher infliximab (IFX) serum concentrations compared to patients without perianal CD to achieve complete disease control. Our aim was to compare anti-TNF serum concentrations between patients with actively draining and closed perianal fistulas. Methods: A retrospective survey was performed in CD patients with perianal disease treated with IFX or adalimumab (ADL). Fistula closure was defined as absence of active drainage at gentle finger compression and/or fistula healing on magnetic resonance imaging. Results: We identified 66 CD patients with a history of perianal fistulas treated with IFX (n = 47) and ADL (n = 19). Median IFX serum trough concentrations ([interquartile range]) were higher in patients with closed fistulas (n = 32) compared to patients with actively draining fistulas (n = 15): 6.0 µg/ml [5.4-6.9] versus 2.3 µg/ml [1.1-4.0], respectively (p < .001)). A similar difference was seen in patients treated with ADL: median serum concentrations were 7.4 µg/ml [6.5-10.8] in 13 patients with closed fistulas versus 4.8 µg/ml [1.7-6.2] in 6 patients with producing fistulas (p = .003). Serum concentrations of ≥5.0 µg/ml for IFX (area under the curve of 0.92; 95% CI: 0.82-1.00)) and 5.9 µg/ml for ADL (area under the curve of 0.89; 95% CI 0.71-1.00) were associated with fistula closure. Conclusion: Cut-off serum concentrations ≥5.0 µg/ml for IFX and ≥5.9 µg/ml for ADL were associated with perianal fistula closure. Hence, patients with producing perianal fistulas may benefit from anti-TNF dose intensification to achieve fistula closure.


title: Sports: The Infectious Hazards.

text: Although the medical complications of sports are usually traumatic in nature, infectious hazards also arise. While blood-borne pathogens such as HIV, hepatitis B, and hepatitis C, cause significant illness, the risk of acquiring these agents during sporting activities is minimal. Skin infections are more commonplace, arising from a variety of microbial agents including bacterial, fungal, and viral pathogens. Sports involving water contact can lead to enteric infections, eye infections, or disseminated infections such as leptospirosis. Mumps, measles, and influenza are vaccine-preventable diseases that have been transmitted during sporting events, both in players and in spectators. Prevention is the key to many of these infections. Players should be vaccinated and should not participate in sports if their infection can be spread by contact, airborne, or droplet transmission.


Community Obstetrical Units Less Likely than Academic Units to Have Universal COVID-19 Testing.


title: An empirical study of the toxic capsule crisis in China: risk perceptions and behavioral responses.

text: The outbreak of the toxic capsule crisis during April 2012 aroused widespread public concern about the risk of chromium-contaminated capsules and drug safety in China. In this article, we develop a conceptual model to investigate risk perceptions of the pharmaceutical drug capsules and behavioral responses to the toxic capsule crisis and the relationship between associated factors and these two variables. An online survey was conducted to test the model, including questions on the measures of perceived efficacy of the countermeasures, trust in the State FDA (Food and Drug Administration), trust in the pharmaceutical companies, trust in the pharmaceutical capsule producers, risk perception, concern, need for information, information seeking, and risk avoidance. In general, participants reported higher levels of risk perception, concern, and risk avoidance, and lower levels of trust in the three different stakeholders. The results from the structural equation modeling procedure suggest that perceived efficacy of the countermeasures is a predictor of each of the three trust variables; however, only trust in the State FDA has a dampening impact on risk perception. Both risk perception and information seeking are significant determinants of risk avoidance. Risk perception is also positively related to concern. Information seeking is positively related to both concern and need for information. The theoretical and policy implications are also discussed.


title: Regional Differences in Antithrombotic Treatment for Atrial Fibrillation: Insights from the GLORIA-AF Phase II Registry.

text: Introduction Although guideline-adherent antithrombotic therapy (ATT) for stroke prevention in atrial fibrillation (AF) is associated with lower mortality and thromboembolism, ATT uptake shows geographic variation worldwide. We aimed to assess thromboembolic risk and baseline ATT by geographic region and identify factors associated with prescription of ATT in a large, truly global registry of patients with recently diagnosed AF. Methods and Results Our analysis comprises 15,092 patients newly diagnosed with non-valvular AF at risk for stroke, enrolled in Phase II of Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation (GLORIA-AF). Global oral anticoagulation (OAC) use was 79.9%, being highest in Europe (90.1%), followed by Africa/Middle East (87.4%) and Latin America (85.3%), North America (78.3%) and Asia (55.2%). Among OAC users, vitamin K antagonists (VKAs) have been replaced by non-VKA OACs (NOACs) as the more prevalent OAC option in all regions, with highest use in North America (66.5%) and lowest in Asia (50.2%). In Asia, OAC was 80.4% in community hospitals but only 49.8% in university hospitals and 42.6% in specialist offices, and varied from 21.0% in China to 89.7% in Japan (NOACs at 5.8% in China and 83.3% in Japan). Globally, 76.5% of low-risk patients were prescribed ATT (46.1% OAC), whereas 17.7% high-risk patients were not anticoagulated (Europe 8.8%; North America 18.9%; Asia 42.4%). Conclusion Substantial inter- and intra-regional differences in ATT for stroke prevention in AF are evident in this global registry. While guideline-adherent ATT can be further improved, NOACs are the main contributor to high OAC use worldwide.


title: A novel method for evaluating natural and vaccine induced serological responses to Bordetella pertussis antigens.

text: We studied the time course of serum IgG antibodies against 3 different pertussis vaccine antigens: PT (pertussis toxin), FHA (filamentous hemagglutinin), Prn (pertactin) in sera from individuals vaccinated with four different pertussis vaccines at 4 years of age: (N=44, 44, 23 and 23, respectively,) and compared the responses to/after natural infection with Bordetella pertussis (N=44, age 1-8 years). These longitudinal data were analyzed with a novel method, using a mathematical model to describe the observed responses, and their variation among subjects. This allowed us to estimate biologically meaningful characteristics of the serum antibody response, like peak level and decay rate, and to compare these among natural infections and vaccine responses. Compared to natural infection, responses to PT after vaccination with the tested vaccines are smaller in magnitude and tend to decay slightly faster. When present in vaccines, FHA and Prn tend to produce high peak levels, higher than those in naturally infected patients, but these decay faster. As expected, the Dutch whole cell vaccine produced lower antibody responses than the acellular vaccines. This model allows a better comparison of the kinetics of vaccine induced antibody responses and after natural infection over a long follow up period.


title: Single-port access total laparoscopic hysterectomy with Korean-made OCTO Port: Turkish surgeons' initial experience.

text: We present our initial experience with single-port access total laparoscopic hysterectomy (TLH) surgery using a Korean-made laparoscopic port (OCTO™ Port). In a retrospective study, single-port access TLH (SPA-TLH) with the OCTO Port was performed on 34 patients with benign gynaecological indications from July 2013 to May 2014 by two surgeons (Ahmet Kale and Hasan Terzi). All patients were divided into two groups. The first 15 patients who underwent SPA-TLH were classified as Group 1, and the second 19 patients who underwent SPA-TLH were classified as Group 2. Patient data were analyzed for age, body mass index (BMI, kg/m(2)), weight of uterus, vaginal cuff suturation time, estimated blood loss, operation time, hysterectomy indications and operative outcomes. The median time needed for the surgery was 75 min in both groups. The duration of suturing of the vaginal cuff was shorter in Group 2 compared with that in Group 1. The estimated blood loss was less in Group 2 compared with Group 1: Four patients in Group 1 required blood transfusion while none of the patients in Group 2 required blood transfusion. The OCTO Port has soft and flexible instrumental movements, which can reduce crowding of instruments during surgery, and the cap rotates 360 degrees. The OCTO Port might facilitate the learning curve of single-port laparoscopic hysterectomy surgery.


title: Impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists.

text: OBJECTIVES To evaluate the impact of COVID-19 on clinical practice, income, health and lifestyle behavior of Brazilian urologists during the month of April 2020. MATERIALS AND METHODS A 39-question, web-based survey was sent to all urologist members of the Brazilian Society of Urology. We assessed socio-demographic, professional, health and behavior parameters. The primary goal was to evaluate changes in urologists' clinical practice and income after two months of COVID-19. We also looked at geographical differences based on the incidence rates of COVID-19 in different states. RESULTS Among 766 urologists who completed the survey, a reduction ≥ 50% of patient visits, elective and emergency surgeries was reported by 83.2%, 89.6% and 54.8%, respectively. An income reduction of ≥ 50% was reported by 54.3%. Measures to reduce costs were implemented by most. Video consultations were performed by 38.7%. Modifications in health and lifestyle included weight gain (32.9%), reduced physical activity (60.0%), increased alcoholic intake (39.9%) and reduced sexual activity (34.9%). Finally, 13.5% of Brazilian urologists were infected with SARS-CoV-2 and about one third required hospitalization. Urologists from the highest COVID-19 incidence states were at a higher risk to have a reduction of patient visits and non-essential surgeries (OR=2.95, 95% CI 1.86 - 4.75; p< 0.0001) and of being infected with SARS-CoV-2 (OR=4.36 95%CI 1.74-10.54, p=0.012). CONCLUSIONS COVID-19 produced massive disturbances in Brazilian urologists' practice, with major reductions in patient visits and surgical procedures. Distressing consequences were also observed on physicians' income, health and personal lives. These findings are probably applicable to other medical specialties. Available at. .


title: Incidence of iatrogenic ureteral injury after laparoscopic colectomy.

text: OBJECTIVE To compare the incidence of iatrogenic ureteral injury between laparoscopic and open colectomies at a single institution. DESIGN From June 1, 2005, through July 31, 2010, patients were identified from a prospectively maintained database and hospital records were retrospectively reviewed. SETTING Mount Sinai Medical Center. PATIENTS Fourteen patients who underwent colectomy complicated by a ureteral injury. MAIN OUTCOME MEASURES A significant increase in ureteral injuries occurred after laparoscopic vs open procedures (0.66% vs 0.15%, P = .007). RESULTS A total of 5729 colectomies were performed during the study period. Fourteen ureteral injuries occurred, resulting in a 0.244% incidence of iatrogenic ureteral injury. Patient demographics demonstrated that 9 injuries (64%) occurred in females and 7 patients (50%) had undergone prior abdominal operations. Operative indications were inflammatory bowel disease (n = 7), diverticulitis (n = 2), and malignant neoplasm (n = 4). Thirteen operations (87%) in this study were elective colectomies, and 7 patients (50%) underwent laparoscopic procedures, with 2 open conversions. Of the 5729 colectomies, 4669 were open and 1060 laparoscopic. Regarding ureteral injuries, no difference was observed in intraoperative identification of ureteral injury in patients who underwent preoperative ureteral stent placement (n = 4) vs those who did not (50% [2 of 4] vs 50% [5 of 10]). CONCLUSIONS A significant increase was found in the incidence of iatrogenic ureteral injuries with laparoscopy compared with open colectomies. Preoperative stent placement did not ensure intraoperative identification of injury. Female sex and increased operative blood loss appear to predispose patients to injury.


title: Dexamethasone treatment for the acute respiratory distress syndrome: a multicentre, randomised controlled trial.

text: BACKGROUND There is no proven specific pharmacological treatment for patients with the acute respiratory distress syndrome (ARDS). The efficacy of corticosteroids in ARDS remains controversial. We aimed to assess the effects of dexamethasone in ARDS, which might change pulmonary and systemic inflammation and result in a decrease in duration of mechanical ventilation and mortality. METHODS We did a multicentre, randomised controlled trial in a network of 17 intensive care units (ICUs) in teaching hospitals across Spain in patients with established moderate-to-severe ARDS (defined by a ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen of 200 mm Hg or less assessed with a positive end-expiratory pressure of 10 cm H2O or more and FiO2 of 0·5 or more at 24 h after ARDS onset). Patients with brain death, terminal-stage disease, or receiving corticosteroids or immunosuppressive drugs were excluded. Eligible patients were randomly assigned based on balanced treatment assignments with a computerised randomisation allocation sequence using blocks of 10 opaque, sealed envelopes to receive immediate treatment with dexamethasone or continued routine intensive care (control group). Patients in the dexamethasone group received an intravenous dose of 20 mg once daily from day 1 to day 5, which was reduced to 10 mg once daily from day 6 to day 10. Patients in both groups were ventilated with lung-protective mechanical ventilation. Allocation concealment was maintained at all sites during the trial. Primary outcome was the number of ventilator-free days at 28 days, defined as the number of days alive and free from mechanical ventilation from day of randomisation to day 28. Secondary outcome was all-cause mortality 60 days after randomisation. All analyses were done according to the intention-to-treat principle. This study is registered with ClinicalTrials.gov, NCT01731795. FINDINGS Between March 28, 2013, and Dec 31, 2018, we enrolled 277 patients and randomly assigned 139 patients to the dexamethasone group and 138 to the control group. The trial was stopped by the data safety monitoring board due to low enrolment rate after enrolling more than 88% (277/314) of the planned sample size. The mean number of ventilator-free days was higher in the dexamethasone group than in the control group (between-group difference 4·8 days [95% CI 2·57 to 7·03]; p<0·0001). At 60 days, 29 (21%) patients in the dexamethasone group and 50 (36%) patients in the control group had died (between-group difference -15·3% [-25·9 to -4·9]; p=0·0047). The proportion of adverse events did not differ significantly between the dexamethasone group and control group. The most common adverse events were hyperglycaemia in the ICU (105 [76%] patients in the dexamethasone group vs 97 [70%] patients in the control group), new infections in the ICU (eg, pneumonia or sepsis; 33 [24%] vs 35 [25%]), and barotrauma (14 [10%] vs 10 [7%]). INTERPRETATION Early administration of dexamethasone could reduce duration of mechanical ventilation and overall mortality in patients with established moderate-to-severe ARDS. FUNDING Fundación Mutua Madrileña, Instituto de Salud Carlos III, The European Regional Development's Funds, Asociación Científica Pulmón y Ventilación Mecánica.


title: Clinical presentation and course of COVID-19.

text: Information about the clinical presentation and course of COVID-19 is rapidly evolving. Data are emerging from retrospective clinical studies conducted in Wuhan, China, showing the symptoms and characteristics of COVID-19 caused by severe acute respiratory virus coronavirus 2 (SARS-CoV-2) infection, including fever, cough, and shortness of breath. Radiographic data on COVID-19 cases reveal bilateral opacities on chest radiography and ground-glass opacities on computed tomography. Data on laboratory markers and mortality and morbidity are also emerging.


title: Mechanism underlying accelerated arterial oxygen desaturation during recurrent apnea.

text: RATIONALE Brief recurrent apneas in preterm infants and adults can precipitate rapid and severe arterial O(2) desaturation for reasons that remain unclear. OBJECTIVES We tested a mathematically derived hypothesis that when breathing terminates apnea, mixed-venous hypoxemia continues into the subsequent apnea; as a result, there is a surge in pulmonary O(2) uptake that rapidly depletes the finite alveolar O(2) store, thereby accelerating arterial O(2) desaturation. METHODS Recurrent apneas were simulated in an experimental lamb model. Pulmonary O(2) uptake was calculated from continuously measured arterial and mixed-venous O(2) saturation and cardiac output. MEASUREMENTS AND MAIN RESULTS Direct measurements revealed that asynchrony in the desaturation and resaturation of arterial and venous blood gave rise to dips and surges in O(2) uptake. After desaturation to 50%, a typical nadir in preterm infants, O(2) uptake surged to a peak of 176.9 ± 7.8% of metabolic rate. During subsequent apneas, desaturation rate was increased two- to threefold greater than during isolated apneas, in direct proportion to the magnitude of the surge in O(2) uptake (P < 0.001; R(2) = 0.897). Application of our mathematical model to a published recording of cyclic apneas in a preterm infant precisely reproduced the accelerated desaturation rates of up to 15% · s(-1) observed clinically. CONCLUSIONS Rapid depletion of alveolar O(2) stores by surges in O(2) uptake almost completely explains the acceleration of desaturation that occurs during recurrent apnea. This powerful mechanism is likely to explain the severity of intermittent hypoxemia that is associated with neurocognitive and cardiovascular morbidities in preterm infants and adults.


title: Vaccines for the common cold.

text: BACKGROUND The common cold is a spontaneously remitting infection of the upper respiratory tract, characterised by a runny nose, nasal congestion, sneezing, cough, malaise, sore throat and fever (usually < 37.8˚C). The widespread morbidity it causes worldwide is related to its ubiquitousness rather than its severity. The development of vaccines for the common cold has been difficult because of antigenic variability of the common cold virus and the indistinguishable multiple other viruses and even bacteria acting as infective agents. There is uncertainty regarding the efficacy and safety of interventions for preventing the common cold in healthy people. OBJECTIVES To assess the clinical effectiveness and safety of vaccines for preventing the common cold in healthy people. SEARCH METHODS We searched CENTRAL (2012, Issue 12), MEDLINE (1948 to January week 1, 2013), EMBASE (1974 to January 2013), CINAHL (1981 to January 2013) and LILACS (1982 to January 2013). SELECTION CRITERIA Randomised controlled trials (RCTs) of any virus vaccines to prevent the common cold in healthy people. DATA COLLECTION AND ANALYSIS Two review authors independently evaluated methodological quality and extracted trial data. Disagreements were resolved by discussion or by consulting a third review author. MAIN RESULTS This review included one RCT with 2307 healthy participants; all of them were analysed. This trial compared the effect of an adenovirus vaccine against a placebo. No statistically significant difference in common cold incidence was found: there were 13 events in 1139 participants in the vaccines group and 14 events in 1168 participants in the placebo group; risk ratio (RR) 0.95, 95% confidence interval (CI) 0.45 to 2.02, P = 0.90). No adverse events related to the live vaccine were reported. AUTHORS' CONCLUSIONS This Cochrane review has found a lack of evidence on the effects of vaccines for the common cold in healthy people. Only one RCT was found and this did not show differences between comparison groups; it also had a high risk of bias. There are no conclusive data to support the use of vaccines for preventing the common cold in healthy people. We identified the need for well-designed, adequately powered RCTs to investigate vaccines for the common cold in healthy people. Unless RCTs provide evidence of a treatment effect and the trade-off between potential benefits and harms is established, policy-makers, clinicians and academics should not recommend the use of vaccines for preventing the common cold in healthy people. Any future trials on medical treatments for preventing the common cold should assess a variety of virus vaccines for this condition. Outcome measures should include common cold incidence, vaccine safety and mortality related to the vaccine.


Covid-19 is threatening the survival of US primary care.


title: Accuracy of neutrophil gelatinase-associated lipocalin for acute kidney injury diagnosis in children: systematic review and meta-analysis.

text: OBJECTIVE To estimate the accuracy of Neutrophil Gelatinase-Associated Lipocalin (NGAL) as a biomarker for acute kidney injury (AKI) in children. METHODS A systematic review of the literature was performed. The review protocol was registered at PROSPERO (CRD 42015024153). We conducted searches in the following databases: Medline (PubMed), LILACS (BVS), SCOPUS (Elsevier), Embase (OVID), Cochrane Central Register of Controlled Trials (CENTRAL), Biomed Central, and ISI Web of Science, from January 1990 to October 2016. For inclusion, studies measured NGAL levels in plasma and urine for AKI in children. For each study, 2 × 2 contingency tables were developed. For statistical analysis we calculated the sensitivity, specificity and diagnostic odds ratio. For methodological assessment, we used Quality Assessment of Diagnostic Accuracy Studies-2. Software used for analysis was Stata 14, and RevMan 5.3. RESULTS In total 13 studies were analyzed, which included 1629 children. For urinary NGAL, the pooled sensitivity was 0.76 (95% CI 0.62-0.85) and a pooled specificity 0.93 (95% CI 0.88-0.96). The diagnostic odds ratio (DOR) for the detection of AKI was 43 (95% CI 16-115) and the Area under the curve (AUC) was 0.94 (95% CI 0.92-0.96). For plasma NGAL the combined sensitivity was 0.80 (95% CI 0.64-0.90) and a combined specificity was 0.87 (95% CI 0.74-0.94). The DOR was 26 (95% CI 8.0-82) and AUC was 0.90 (95% CI 0.87-0.94) for the detection of AKI in children. CONCLUSION The data suggest that NGAL levels can be an important biomarker for the early detection of AKI in children.


Law as a Social Medicine: Enhancing International Inter-regime Regulatory Coopetition as a Means for the Establishment of a Global Health Governance Framework.


Responding to COVID-19: Agile Use of Information Technology to Serve Patients With Diabetes.