title: Physical rehabilitation interventions in the intensive care unit: a scoping review of 117 studies.

text: Background Physical rehabilitation (PR) interventions in the intensive care unit (ICU) can improve patients' functional outcomes, yet systematic reviews identified discordant effects and poor reporting. We conducted a scoping review to determine the extent of ICU PR interventions and how they were reported and measured. Methods We searched five databases from inception to December 2016 for prospective studies evaluating adult ICU PR interventions. Two independent reviewers screened titles, abstracts, and full texts for inclusion. We assessed completeness of reporting using the Consolidated Standards of Reporting Trials, Strengthening the Reporting of Observational Studies in Epidemiology, or Standards for Quality Improvement Reporting Excellence guidelines, as appropriate. For planned PR interventions, we evaluated reporting with the Consensus on Exercise Reporting Template (CERT) and assessed intervention and control groups separately. We calculated completeness of reporting scores for each study; scores represented the proportion of reported items. We compared reporting between groups using Kruskal-Wallis with Bonferroni corrections and t tests, α = 0.05. Results We screened 61,774 unique citations, reviewed 1429 full-text publications, and included 117: 39 randomized trials, 30 case series, 9 two-group comparison, 14 before-after, and 25 cohort. Interventions included neuromuscular electrical stimulation (NMES) (14.5%), passive/active exercises (15.4%), cycling (6.8%), progressive mobility (32.5%), and multicomponent (29.9%). The median (first,third quartiles) study reporting score was 75.9% (62.5, 86.7) with no significant differences between reporting guidelines. Of 87 planned intervention studies, the median CERT score was 55.6%(44.7,75.0); cycling had the highest (85.0%(62.2,93.8)), and NMES and multicomponent the lowest (50.0% (39.5, 70.3) and 50.0% (41.5, 58.8), respectively) scores. Authors reported intervention groups better than controls (p < 0.001). Conclusions We identified important reporting deficiencies in ICU PR interventions, limiting clinical implementation and future trial development.


title: Opioid use after propofol or sevoflurane anesthesia: a randomized trial.

text: BACKGROUND The intravenous anesthetic propofol is a gamma-aminobutyric acid A receptor agonist. Propofol promotes analgesia by depressing nociceptive transmission in peripheral neurons, antagonizing N-methyl-D-aspartate receptors, and activating gamma-aminobutyric acid A receptors in dorsal root ganglion receptor cells. Nevertheless, it remains unclear whether intraoperative propofol causes clinically meaningful postoperative analgesia. We therefore tested the hypothesis that patients anesthetized with sevoflurane require a greater quantity of postoperative opioids (from the end of surgery until the next postoperative morning) than those anesthetized with propofol. METHODS With Institutional Review Board and EudraCT Number approval (2009-011038-82) and patients' informed consent, ninety patients scheduled for open vein stripping were randomized to either sevoflurane or propofol anesthesia at the Medical University of Vienna General Hospital and the Danube Hospital, the largest regional hospital in Vienna. Pain was treated with bolus piritramide and patient-controlled morphine hydrochloride. The primary outcome was total opioid use from the end of surgery until the first postoperative morning. For the initial four postoperative hours and on the first postoperative morning, a blinded investigator recorded pain scores on an 11-point Likert verbal response scale. RESULTS The median [interquartile range] morphine sulfate equivalents were 9.8 [4-19] mg in the sevoflurane group and 10 [6-20] mg in the propofol group. Sevoflurane was not superior to propofol on postoperative opioid consumption, giving a ratio of means of 0.91 (95% interim-adjusted confidence interval [CI], 0.33 to 2.45; P = 0.74). Additionally, no difference in pain scores was found over time between the two groups, with a mean difference on an 11-point scale of 0.20 (95% interim-adjusted CI, -0.36 to 0.73; P = 0.31). CONCLUSION Intraoperative sevoflurane did not reduce postoperative analgesia. This finding is consistent with the results in most previous reports. This trial was registered at ClinicalTrials.gov: NCT00712517.


Laryngectomy Care in the COVID-19 Era.


title: Use of a flow-diverting stent for ruptured dissecting aneurysm treatment in a patient with sickle cell disease.

text: INTRODUCTION Sickle cell disease (SCD) is a clinical phenotype that presents a unique challenge to the interventionalist, particularly when stent therapy is contemplated. Homozygous individuals are likely at increased risk for thromboembolic complications. There are no formal guidelines regarding antiplatelet therapy in the short or long term for intracranial stent use in SCD. The authors describe the novel use of a pipeline embolization device (PED) to treat a ruptured dissecting bilobed/fusiform vertebral artery V4 aneurysm in an SCD patient complicated by tortuous proximal anatomy and the anterior spinal artery arising from the diseased segment. Considerations regarding antiplatelet therapy in this scenario are discussed. CASE REPORT A 50-year-old woman with homozygous recessive SCD was transported to the emergency department and presented with diffuse subarachnoid hemorrhage. CT angiography demonstrated a left-sided 3 × 5 mm fusiform bi-lobulated presumed dissecting vertebral artery aneurysm, immediately distal to the origin of the posterior inferior cerebellar artery (PICA). A PED was deployed within the V4 segment across the aneurysm. Post-treatment angiography showed patency of the parent artery, and patency of the "jailed" anterior spinal artery and of the PICA. DISCUSSION Selecting a treatment method in SCD patients with a ruptured intracranial aneurysm is challenging and there are no clinical trials comparing treatment methods in this population. The authors demonstrate that flow diversion is feasible in SCD, which has not been described in the literature. Additionally, the case stresses the peri- and post-procedural management of SCD, as well as long-term considerations with a flow-diverting stent in place.


title: Glenohumeral Function of the Long Head of the Biceps Muscle: An Electromyographic Analysis.

text: BACKGROUND Optimal treatment of superior labral anterior-posterior (SLAP) tears is controversial, in part because the dynamic role of the long head of the biceps muscle (LHBM) in the glenohumeral joint is unclear. The aim of this study was to determine dynamic LHBM behavior during shoulder activity by studying (1) the electromyographic activity of the LHBM during shoulder motion, (2) the effect of elbow immobilization on this activity, and (3) the effect of a load applied to the distal humerus on this activity. HYPOTHESIS The LHBM would not play a significant role in active glenohumeral range of motion. STUDY DESIGN Controlled laboratory study. METHODS Thirteen normal volunteers underwent surface electromyography (EMG) measurement of the LHBM, short head biceps muscle (SHBM), deltoid, infraspinatus, and brachioradialis during shoulder motion from the neutral position (0° of rotation, flexion, and abduction) to 45° of flexion, 90° of flexion, 45° of abduction, and 90° of abduction. These motions were repeated both with and without splint immobilization of the forearm and elbow at 100° of flexion and neutral rotation and with and without a 1-kg weight placed on the lateral distal humerus. RESULTS Mean EMG activity within the LHBM and the SHBM was low (≤11.6% ± 9.1%). LHBM activity was significant increased by flexion and abduction (P < .049 in all cases), while SHBM activity was not. EMG activity from the middle head of the deltoid was significantly increased by loading with the shoulder positioned away from the body (ie, in abduction or flexion). When compared with the unloaded state, the addition of a distal humeral load significantly increased LHBM activity in 45° of abduction (P = .028) and 90° of flexion (P = .033) despite forearm and elbow immobilization. The SHBM showed similar trends. CONCLUSION In normal volunteers with forearm and elbow immobilization and application of a load to the distal humerus, LHBM EMG activity is increased by both glenohumeral flexion and abduction, suggesting that this muscle plays a dynamic role in glenohumeral motion with higher demand activities. CLINICAL RELEVANCE Biceps tenodesis may result in dynamic change within the glenohumeral joint with higher demand activities.


China Coronavirus Outbreak: All the Latest Updates.


title: Early identification of patients requiring massive transfusion, embolization, or hemostatic surgery for traumatic hemorrhage: a systematic review protocol.

text: BACKGROUND Hemorrhage is a major cause of early mortality following a traumatic injury. The progression and consequences of significant blood loss occur quickly as death from hemorrhagic shock or exsanguination often occurs within the first few hours. The mainstay of treatment therefore involves early identification of patients at risk for hemorrhagic shock in order to provide blood products and control of the bleeding source if necessary. The intended scope of this review is to identify and assess combinations of predictors informing therapeutic decision-making for clinicians during the initial trauma assessment. The primary objective of this systematic review is to identify and critically assess any existing multivariable models predicting significant traumatic hemorrhage that requires intervention, defined as a composite outcome comprising massive transfusion, surgery for hemostasis, or angiography with embolization for the purpose of external validation or updating in other study populations. If no suitable existing multivariable models are identified, the secondary objective is to identify candidate predictors to inform the development of a new prediction rule. METHODS We will search the EMBASE and MEDLINE databases for all randomized controlled trials and prospective and retrospective cohort studies developing or validating predictors of intervention for traumatic hemorrhage in adult patients 16 years of age or older. Eligible predictors must be available to the clinician during the first hour of trauma resuscitation and may be clinical, lab-based, or imaging-based. Outcomes of interest include the need for surgical intervention, angiographic embolization, or massive transfusion within the first 24 h. Data extraction will be performed independently by two reviewers. Items for extraction will be based on the CHARMS checklist. We will evaluate any existing models for relevance, quality, and the potential for external validation and updating in other populations. Relevance will be described in terms of appropriateness of outcomes and predictors. Quality criteria will include variable selection strategies, adequacy of sample size, handling of missing data, validation techniques, and measures of model performance. DISCUSSION This systematic review will describe the availability of multivariable prediction models and summarize evidence regarding predictors that can be used to identify the need for intervention in patients with traumatic hemorrhage. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42017054589.


Declining cholesterol levels in US youths: a reason for optimism.


title: Patient and public involvement in patient safety research: a workshop to review patient information, minimise psychological risk and inform research.

text: PLAIN ENGLISH SUMMARY Patient safety is a growing research area. However, although patients and the public are increasingly involved in clinical research, there is little guidance on how best to involve patients in patient safety research. Here we focus on how patients can contribute to the design of patient safety research. We conducted a workshop with patients as part of a project exploring errors and safety in the delivery of intravenous medication (medication given via a vein). The workshop was designed to explore how best to engage with hospital inpatients about these issues, to generate research topics, and to inform researchers about patients' experiences. Nine patients participated, each of whom had previously received intravenous medication. Participants advised against using terms such as 'error'; they also advocated caution when using terms such as 'safety' when describing the study to patients as this may worry some who had not thought about these issues before. We received thorough and useful feedback on our patient information sheets to ensure they were clear and understandable to patients. Patients also shared rich experiences with us about their treatment, which emphasised the need to extend our research focus to include a wider range of factors affecting quality and safety. ABSTRACT Background Patient safety has attracted increasing attention in recent years. This paper explores patients' contributions to informing patient safety research at an early stage, within a project on intravenous infusion errors. Currently, there is little or no guidance on how best to involve patients and the wider public in shaping patient safety research, and indeed, whether such efforts are worthwhile. Method We ran a 3-hour workshop involving nine patients with experience of intravenous therapy in the hospital setting. The first part explored patients' experiences of intravenous therapy. We derived research questions from the resulting discussion through qualitative analysis. In the second part, patients were asked for feedback on patient information sheets considering both content and clarity, and on two potential approaches to framing our patient information: one that focused on research on safety and error, the other on quality improvement. Results The workshop led to a thorough review of how we should engage with patients. Importantly, there was a clear steer away from terms such as 'error' and 'safety' that could worry patients. The experiences that patients revealed were also richer than we had anticipated, revealing different conceptions of how patients related to their treatment and care, their role in safety and use of medical devices, the different levels of information they preferred, and broader factors impacting perceptions of their care. Conclusion Involving patients at an early stage in patient safety research can be of great value. Our workshop highlighted sensitivities around potentially worrying patients about risks that they might not have considered previously, and how to address these. Patient representatives also emphasised a need to expand the focus of patient safety research beyond clinicians and error, to include factors affecting perceptions of quality and safety for patients more broadly.


Allergic contact dermatitis to 2-octyl cyanoacrylate after surgical repair: Humidity as a potential factor.


title: A new system of microwave ablation at 2450 MHz: preliminary experience.

text: The aim of this study was to assess the feasibility of the application of the new system (Emprint Microwave Ablation System, Covidien Boulder, CO, USA) and to identify its advantages. In particular the attention was focused to the spherical ablation zone obtained and its usefulness in terms of effectiveness. The new system is composed of: a 2450 MHz generator that delivers a maximum power of 100 W, a fiberglass antenna and a pump for internally cooled antenna. Ten liver nodules (8 hepatocellular carcinomas and 2 metastasis) were percutaneously treated (mean diameter 24.9 mm, range 16-35 mm). Technical success, ablation duration time, overall procedure time and safety were registered. To define the shape of the ablation zone, multiplanar reformatting (MPR) was performed. Roundness index transverse was calculated: a value near 1 represents a more spherical ablation zone shape, and a value distant from 1 implies an oval configuration. Technical success was 100%. Mean ablation time was of 3.85 min (range 3-5 min), mean overall procedure time was 30.5 min (range 25-40 min). No major complications were recorded. Roundness index transverse presented a mean value of 0.94, meaning that a spherical shape of ablation zone was achieved. One of the most promising innovations of the new microwave technology is the spherical shape of the ablation volume that could be related with an improving of the effectiveness and safety.


Embolization of cardiac arteriovenous malformation with onyx.


COVID-19 in People With Diabetes: Urgently Needed Lessons From Early Reports.


title: Video-assisted thoracoscopic surgery is a safe option for benign lung diseases requiring lobectomy.

text: BACKGROUND Lobectomy for benign lung disease is renowned to be technically complex and to be subjected to an increased complication rate. The objective of this study was to evaluate whether the results obtained with video-assisted surgery (VATS) in benign disease are comparable to those obtained in oncologic surgery, where VATS has been validated. METHODS We have reviewed the files of 246 consecutive patients who underwent VATS lobectomy from January 2012 to August 2015. The cohort was divided into two groups according to pathology (benign or malignant). Outcome parameters on scrutiny were demographics, pathology, duration of air leak, drainage and hospital stay, conversion, and perioperative complication rate. Comparisons were made with the χ 2 test and Student's t test; any p value ≤0.05 was considered as significant. RESULTS Group 1 (36 patients) included patients who underwent lobectomy for benign disease and group 2 (210 patients) patients affected by lung cancer or pulmonary metastases. The two groups differed with reference to age (p < 0.001), history of cancer (p < 0.001), history of stroke (p = 0.05), and the presence of pleural adhesions (p = 0.03). There was no difference for duration of air leaks, chest tube drainage and hospital stay, conversion rate, and perioperative complication rate. CONCLUSIONS We conclude that pathology did not impact on outcomes after VATS lobectomy. This study suggests that VATS is as a safe option in selected patients with benign disease requiring lobectomy, despite a more complex technical context.


title: Dual antiplatelet therapy dilemmas: duration and choice of antiplatelets in acute coronary syndromes.

text: Dual antiplatelet therapy (DAPT) is a key component of therapy for acute coronary syndromes managed with and without percutaneous coronary intervention. Recent advances have given patients a wider variety of therapeutic options including the use of combinations of agents, dosing strategies, and durations of therapy. The optimal regimen minimizes thrombotic risk without increasing the risk of bleeding. Choosing the best therapy for each patient is an individualized dilemma that requires new, evidence-based tools to support regimen decision-making.


title: Detection of porcine epidemic diarrhea virus-neutralizing antibody using high-throughput imaging cytometry.

text: Porcine epidemic diarrhea virus (PEDV) is an emerging porcine coronavirus that causes a tremendous economic burden on the swine industry. The assessment of PEDV-neutralizing antibody levels provides a valuable tool to assess and predict herd immunity. We evaluated the performance of a PEDV imaging cytometry-based high-throughput neutralization test (HTNT) and compared the HTNT to a fluorescent focus neutralization (FFN) assay using serum samples from pigs of known PEDV infection status (n = 159). Estimates of diagnostic sensitivity and specificity for HTNT and FFN assays derived from receiver-operator characteristic (ROC) curve analyses showed that both PEDV FFN and HTNT provided excellent diagnostic performance. However, in the laboratory, imaging cytometry provided an objective and semi-automated approach that removed human subjectivity from the testing process and reduced the read-time of a 96-well plate to < 4 min. In addition, imaging cytometry facilitated the rapid collection and long-term storage of test images and data for further evaluation or client consultation. For PEDV and other pathogens, imaging cytometry could provide distinct advantages over classic virus neutralization or FFN assays for the detection and quantitation of neutralizing antibody.


title: Chloroquine analogues in drug discovery: new directions of uses, mechanisms of actions and toxic manifestations from malaria to multifarious diseases.

text: Antimalarial drugs (e.g. chloroquine and its close structural analogues) were developed primarily to treat malaria; however, they are beneficial for many dermatological, immunological, rheumatological and severe infectious diseases, for which they are used mostly today. Chloroquine and hydroxychloroquine, two of the most fascinating drugs developed in the last 50 years, are increasingly recognized for their effectiveness in myriad non-malarial diseases. In advanced research, chloroquine and hydroxychloroquine have been shown to have various immunomodulatory and immunosuppressive effects, and currently have established roles in the management of rheumatic diseases, lupus erythematosus (different forms) and skin diseases, and in the treatment of different forms of cancer. Recently, chloroquine analogues have also been found to have metabolic, cardiovascular, antithrombotic and antineoplastic effects. This review is concerned with the lysosomotropic, anti-inflammatory and immunomodulatory mechanisms of chloroquine, hydroxychloroquine, quinacrine and related analogues, and the current evidence for both their beneficial effects and potential adverse manifestations in various diseases.


Novel Reassortant Avian Influenza A(H5N1) Virus in Human, Southern Vietnam, 2014.


Dynamic Trainee Support for Residents Involved in COVID-19 Treatment and Response.


title: The impact of environmental factors in pre-hospital thermistor-based tympanic temperature measurement: a pilot field study.

text: BACKGROUND Few pre-hospital services have the possibility to accurately measure core temperature (T core). Non-invasive estimation of T core will improve pre-hospital decision-making regarding the triage and management of hypothermic patients. Thermistor-based tympanic temperature (T tymp) correlates well with T core in controlled studies; however, little is known about the feasibility of using T tymp under field conditions. This study assessed the impact of pre-hospital environmental factors on the accuracy of T tymp . Deep rectal temperature (T rect) was used as a substitute for T core . METHODS Normothermic volunteers (n = 13) were exposed to four simulated field conditions producing local cooling of the head and ear canal. After exposure, T tymp was recorded every 15 s for 10 min and compared with T rect . Descriptive analysis and Bland-Altman plots were used to assess agreement. RESULTS Immediately after exposure mean T tymp was low, but increased rapidly and reached an apparent steady state after 3-5 min. After 5 and 10 min, the mean temperature difference (∆T rect-tymp) ranged from 1.5-3.2 °C (SD = 0.5) and 1.2-2.0 °C, respectively. T rect remained unchanged throughout the study period. CONCLUSIONS After surface cooling of head and neck, T tymp did not accurately reflect core temperature within the first 10 min of measurement. The variation of ∆T rect-tymp was low after 10 min, regardless of the initial degree of cooling. With the risk of over-triage, T tymp may at this point provide an indication of T core and also exhibit a trend. TRIAL REGISTRATION ClinicalTrials.gov: NCT02274597.


title: Ethical triage during the COVID-19 pandemic: a toolkit for neurosurgical resource allocation.

text: BACKGROUND The COVID-19 pandemic confronts healthcare workers, including neurosurgeons, with difficult choices regarding which patients to treat. METHODS In order to assist ethical triage, this article gives an overview of the main considerations and ethical principles relevant when allocating resources in times of scarcity. RESULTS We discuss a framework employing four principles: prioritizing the worst off, maximizing benefits, treating patients equally, and promoting instrumental value. We furthermore discuss the role of age and comorbidity in triage and highlight some principles that may seem intuitive but should not form a basis for triage. CONCLUSIONS This overview is presented on behalf of the European Association of Neurosurgical Societies and can be used as a toolkit for neurosurgeons faced with ethical dilemmas when triaging patients in times of scarcity.


title: Correlation between changes in thyromental distance and distance of migration of oral Ring-Adair-Elwyn tubes during neck extension with a shoulder positioner in patients undergoing neck procedures.

text: OBJECTIVES To measure the migration of oral Ring-Adair-Elwyn (RAE) preformed tracheal tubes during neck extension compared with the neutral neck position, and to assess the correlation between changes in the thyromental distance (TMD) during changes in neck position and tracheal tube migration. METHODS This prospective observational study enrolled adult patients undergoing elective neck or thyroid procedures below the mandible. Using fibreoptic bronchoscopy, distances from the RAE tube adapter to the carina and to the tube tip were measured in the neutral position and after neck extension with a 10 cm D-shaped gel shoulder positioner. The change in distance of the RAE tube tip migration was compared with the change in TMD in each patient. RESULTS This study enrolled 106 patients. During neck extension with a 10-cm shoulder positioner, RAE tubes cranially migrated 2.7 cm from the neutral position, but RAE tube migration was not correlated with the change in external TMD. CONCLUSION Oral RAE tube migration was not significantly correlated with the change in external TMD. Due to their large variability, changes in TMD were not useful predictors of RAE tube migration.


title: Living with a disability during the pandemic. "Instant paper from the field" on rehabilitation answers to the COVID-19 emergency.

text: COVID-19 pandemic is creating collateral damage to persons with disabling conditions of different aetiology. The restrictions imposed to contain the spread of infection is limiting the access to many health services, including rehabilitation. It is expected that such situation will lead to long lasting negative consequences for persons with disability, increasing functional limitations in chronic conditions and hindering the recovery after acute events. The aim of this paper is to explore the impact on people with disability, reporting the contents of the sixth Italian Society of Physical and Rehabilitation Medicine (SIMFER) webinar on the COVID-19 impact on rehabilitation ("Covinars"). Seven representatives of Associations of persons affected by different disabling conditions described the difficulties they are facing during the pandemic, the initiatives undertaken to support their members and their future perspectives and expectations. The users' inputs will be helpful in planning the future phases of the emergency and improve preparedness for other emergencies.


title: Encephalomyelitis associated with Covid-19 infection: case report.

text: We describe a COVID-19 patient who presented with persistent headache and anosmia that was related to viral encephalomyelitis with acute lesions on MRI in both the brain and upper cervical cord.


title: Development of a cytotoxic T-lymphocyte-based, broadly protective influenza vaccine.

text: The current vaccination strategy against influenza is to induce production of antibodies directed against the surface antigens of these viruses. However, frequent changes in the surface antigens of influenza viruses allow them to avoid antibody-mediated immunity. On the other hand, it is known that cytotoxic T-lymphocyte (CTL) populations directed against internal antigens of influenza A virus are broadly cross-reactive to influenza virus subtypes. The present authors have previously demonstrated that antigens chemically coupled to the surface of liposomes made using unsaturated fatty acids are cross-presented by APCs via MHC class I to CD8(+) T cells and induce antigen-specific CTLs. Based on this finding, a liposome vaccine that is capable of inducing CTL response against internal antigens of influenza viruses and removing virus-infected cells in the host has been developed. The CTL-based liposomal technique might be applicable for developing vaccines against influenza and other viruses, such as hepatitis C, HIV, and severe acute respiratory syndrome corona virus, which frequently change their surface antigenic molecules.


title: Burkholderia mallei CLH001 Attenuated Vaccine Strain Is Immunogenic and Protects against Acute Respiratory Glanders.

text: Burkholderia mallei is the causative agent of glanders, an incapacitating disease with high mortality rates in respiratory cases. Its endemicity and ineffective treatment options emphasize its public health threat and highlight the need for a vaccine. Live attenuated vaccines are considered the most viable vaccine strategy for Burkholderia, but single-gene-deletion mutants have not provided complete protection. In this study, we constructed the select-agent-excluded B. mallei ΔtonB Δhcp1 (CLH001) vaccine strain and investigated its ability to protect against acute respiratory glanders. Here we show that CLH001 is attenuated, safe, and effective at protecting against lethal B. mallei challenge. Intranasal administration of CLH001 to BALB/c and NOD SCID gamma (NSG) mice resulted in complete survival without detectable colonization or abnormal organ histopathology. Additionally, BALB/c mice intranasally immunized with CLH001 in a prime/boost regimen were fully protected against lethal challenge with the B. mallei lux (CSM001) wild-type strain.


title: Activated carbon fiber filters could reduce the risk of surgical smoke exposure during laparoscopic surgery: application of volatile organic compounds.

text: BACKGROUND Generation of smoke is inevitable during surgical procedures. Some volatile organic compounds (VOCs) in surgical smoke are known to be strong carcinogens. We used a prototype of a multi-layered complex filter in an attempt to eliminate VOCs. METHODS From June 2015 to July 2015, 20 patients underwent transperitoneal laparoscopic nephrectomy for renal cell carcinoma. Smoke (pre-filter) was collected 20 min after the electrocautery device was first used during the surgery, by the direct collection method, with a 5-L Tedlar® gas-sampling bag. Twenty and 120 min after the filter was applied, smoke (post-filter) was again collected using the same method. The sample was analyzed by gas chromatography and mass spectrography. The cancer risk and hazard quotient were analyzed based on US Environmental Protection Agency guidelines. RESULTS Twenty patients with a median age of 54.5 (30-80) years were enrolled in the study. Eighteen VOCs were detected using the Japanese indoor air standards mix analysis. The total elimination rate of the VOCs was 86.49 ± 2.83%. The post-filter (120 min) cancer risk (mean ± standard deviation) reduced to a negligible level for benzene, ethylbenzene, and styrene except 1,2-dichloroethane. The post-filter (120 min) hazard quotient for each compound decreased to levels posing a negligible risk for acetone, hexane, benzene, toluene, p-xylene, o-xylene, and styrene. CONCLUSION Strong carcinogens, such as 1,2-dichloroethane, benzene, and ethylbenzene, were eliminated by more than 85% by using this activated carbon fiber filter and the risks from these compounds decreased to an almost negligible level. We suggest using every measure, including these filters, to protect the health of operating room personnel.


title: Lactobacillus helveticus and Bifidobacterium longum taken in combination reduce the apoptosis propensity in the limbic system after myocardial infarction in a rat model.

text: Myocardial infarction (MI) stimulates the release of pro-inflammatory substances that induce apoptosis in the limbic system. Pro-inflammatory cytokines are considered as the root cause of apoptosis, although the mechanism is not fully explained and/or understood at this time. In addition, depression may induce gastrointestinal perturbations that maintain the elevated levels of pro-inflammatory cytokines. It has been shown that some specific probiotic formulations may reduce gastrointestinal problems induced by stress and the pro/anti-inflammatory cytokine ratio. Therefore, we hypothesised that probiotics, when given prophylactically, may diminish the apoptosis propensity in the limbic system following a MI. Male adult Sprague-Dawley rats were given probiotics (Lactobacillus helveticus and Bifidobacterium longum in combination) or placebo in their drinking-water for four consecutive weeks. A MI was then induced in the rats by occluding the left anterior coronary artery for 40 min. Rats were killed following a 72 h reperfusion period. Infarct size was not different in the two groups. Bax/Bcl-2 (pro-apoptotic/anti-apoptotic) ratio and caspase-3 (pro-apoptotic) activity were reduced in the amygdala (lateral and medial), as well as in the dentate gyrus in the probiotics group when compared with the placebo. Akt activity (anti-apoptotic) was increased in these same three regions. No significant difference was observed in Ca1 and Ca3 for the different markers measured. In conclusion, the probiotics L. helveticus and B. longum, given in combination as preventive therapy, reduced the predisposition of apoptosis found in different cerebral regions following a MI.


title: Transanal endoscopic video-assisted excision: application of single-port access.

text: BACKGROUND Transanal endoscopic microsurgery is a safe and efficacious surgical approach for local excision of benign adenomas and early-stage rectal cancer. However, utilization of the technique has been limited due to the unavailability of high-priced specialized instrumentation at many institutions and the technically demanding training required. To avoid these obstacles, we have explored an alternative approach called Transanal Endoscopic Video-Assisted excision, which combines the merits of singleport access and local transanal excision. METHODS A disposable single-incision port is inserted into the anal canal for transanal access. The port contains 3 cannulae for introducing instrumentation into the rectal lumen, and a supplementary cannula for carbon dioxide insufflation. Pneumorectum results in rectal distention and optimizes the visual field during the procedure. Standard laparoscopic instrumentation is utilized for visualization and transanal excision of rectal pathologies. CONCLUSIONS Transanal endoscopic video-assisted excision is an innovative approach to local excision of benign and malignant rectal lesions. The approach averts several of the pitfalls commonly experienced with transanal endoscopic microsurgery. Continued investigation and development of this novel modality will be important in establishing its role in minimally invasive surgery.


Covid-19: GPs can't get results of tests carried out at drive-through centres.


title: Use of the informational spectrum methodology for rapid biological analysis of the novel coronavirus 2019-nCoV: prediction of potential receptor, natural reservoir, tropism and therapeutic/vaccine target.

text: A novel coronavirus recently identified in Wuhan, China (2019-nCoV) has expanded the number of highly pathogenic coronaviruses affecting humans. The 2019-nCoV represents a potential epidemic or pandemic threat, which requires a quick response for preparedness against this infection. The present report uses the informational spectrum methodology to identify the possible origin and natural host of the new virus, as well as putative therapeutic and vaccine targets. The performed in silico analysis indicates that the newly emerging 2019-nCoV is closely related to severe acute respiratory syndrome (SARS)-CoV and, to a lesser degree, Middle East respiratory syndrome (MERS)-CoV. Moreover, the well-known SARS-CoV receptor (ACE2) might be a putative receptor for the novel virus as well. Additional results indicated that civets and poultry are potential candidates for the natural reservoir of the 2019-nCoV, and that domain 288-330 of S1 protein from the 2019-nCoV represents promising therapeutic and/or vaccine target.


title: Self-reported symptoms of infection among travelers departing from Sydney and Bangkok airports.

text: BACKGROUND Data on the burden of illness in travelers departing from both developing and developed countries within the Asia-Pacific region is scarce. We conducted a survey to assess symptoms of infection among travelers within the region. METHODS A self-administered questionnaire was distributed to travelers departing Sydney airport, Australia, for destinations in Asia and departing Bangkok Airport, Thailand, for Australian destinations during the respective winter months of 2007. A two-stage cluster sampling technique was developed to ensure representativeness and a weighting was applied to the Sydney sample. Travelers were assessed for symptoms of infection (fever, sore throat, diarrhea, rash, and myalgia), travel activities, and social contact in the 2 weeks prior to departure. RESULTS A total of 843 surveys was included in the final sample (Sydney 729, response rate 56%; Bangkok 114, response rate 60%). Overall, 45.6% of respondents were Australian residents and 26.7% were residents of countries in Asia. At least one symptom of infection was reported by 23.8% of respondents and 5.4% reported two or more symptoms of infection in the 2 weeks prior to departure. The proportion reporting symptoms was higher in those departing Bangkok compared to Sydney. Significant risk factors for the reporting of symptoms differed between residents and visitors departing each study site. Activities resulting in high rates of social contact prior to travel, particularly contact with febrile persons, were found to be independent predictors of reported symptoms. CONCLUSIONS Self-reported symptoms of infection were common in our sample of travelers. Infectious diseases in travelers can result in spread across international borders and may be associated with the frequency of social contacts and reported illness among travelers.


title: Will changes in alcohol and tobacco use be seen during the COVID-19 lockdown?

text: Editorial of vol. 32-2.


title: Comparison of C-MAC D-blade videolaryngoscope and McCoy laryngoscope efficacy for nasotracheal intubation in simulated cervical spinal injury: a prospective randomized comparative study.

text: BACKGROUND Immobilization with cervical spine worsens endotracheal intubation condition. Though various intubation devices have been demonstrated to perform well in oral endotracheal intubation, limited information is available concerning nasotracheal intubation (NTI) in patients with cervical spine immobilization. The present study compared the performance of the C-MAC D-Blade videolaryngoscope with the McCoy laryngoscope for NTI in patients with simulated cervical spine injuries. METHODS This was a prospective, randomized, controlled, study done in a tertiary hospital. Ninety-five patients requiring NTI were included in data analysis: McCoy group (group M, n = 47) or C-MAC D-Blade videolaryngoscope group (group C, n = 48). A Philadelphia neck collar was applied before anesthetic induction to immobilize the cervical spine. Single experienced anesthesiologist performed NTI. The primary outcome was duration of intubation divided by three steps: nose to oropharynx; oropharynx into glottic inlet; and glottic inlet to trachea. Secondary outcomes included glottic view as percentage of glottis opening (POGO) score and Cormack-Lehance (CL) grade, modified nasal intubation-difficulty scale (NIDS) rating, hemodynamic changes before and after intubation, and complications. RESULTS Total intubation duration was significantly shorter in group C (39.5 ± 11.4 s) compared to group M (48.1 ± 13.9 s). Group C required significantly less time for glottic visualization and endotracheal tube placement in the trachea. More patients in group C had CL grade I and higher POGO scores (P < 0.001, for both measures). No difficulty in NTI (modified NIDS = 0) was more in group C than group M. Hemodynamic changes and incidence of complications were comparable between groups. CONCLUSION The C-MAC D-Blade videolaryngoscope is an effective tool for NTI in a simulated difficult airway, which improves glottic visualization and shortens intubation time relative to those with McCoy laryngoscope. TRIAL REGISTRATION Clinical Research Information Service of the Korea National Institute of Health, Identification number: KCT 0004535, Registered December 10, 2019, Retrospectively registered, http://cris.nih.go.kr.


title: Previous and Recent Evidence of Endovascular Therapy in Acute Ischemic Stroke.

text: The ideal therapy of acute ischemic stroke is achieved by early recanalization that finally leads to good clinical outcome. The recombinant intravenous tissue plasminogen activator (rtPA) within 4.5 hours was approved as an important thrombolytic treatment. However, the recanalization rate was low in patients with a large artery occlusion. The efficacy of intravenous rtPA regarding recanalization of a large artery occlusion was limited. In several clinical trials, pharmacological and mechanical intra-arterial thrombolytic therapy showed improved recanalization rates, but the favorable outcome had not been achieved. Through those trials and errors, researchers have learned that speed of treatment initiation, patient selection by documentation of large artery occlusion and the use of effective devices could be crucial for good clinical outcomes. Finally, five recent randomized controlled trials of endovascular therapy compared to standard medical care have been published. The superiority of endovascular thrombolysis to standard medical care was proved. In this article, we reviewed previous and recent clinical evidence about endovascular thrombolytic therapy of acute ischemic stroke.


title: [Effect of heat inactivation of blood samples on the efficacy of three detection methods of SARS-CoV-2 antibodies].

text: OBJECTIVE To evaluate the effects of heat inactivation of blood samples at 56℃ for 30 min on the results of SARS-CoV-2 antibody detection using different methods. METHODS This retrospective study was conducted in 11 patients with established diagnosis of COVID-19 and 10 patients with diseases other than COVID- 19 in our hospital. We collected samples of serum, plasma and whole blood from each patient between February, 12 and 18, 2020, and with a double- blind design, the samples were examined for SARS-CoV-2 antibodies before and after heat inactivation at 56 ℃ for 30 min. In all the samples, the total SARS-CoV-2 antibodies were detected using immunochromatography, and the IgM antibodies were detected using fluorescence immunochromatography; the IgM and IgG antibodies in the serum and plasma samples detected with chemiluminescence immunoassay. We compared the detection results and analyzed the correlation of semi-quantitative detection results of IgM and IgG antibodies before and after heat inactivation of the samples. RESULTS With immuno-chromatography, the coincidence rate of the total SARS-CoV-2 antibody detection before and after heat inactivation of the serum and plasma samples was 90.0% in COVID-19 cases and 100.0% in the negative cases, resulting in a total coincidence rate 95.2%; for the whole blood samples, the total coincidence rates of the total SARS-CoV-2 antibodies were 100.0%. For detection of IgM antibodies in the serum, plasma and whole blood samples using fluorescence immunochromatography, the coincidence rates in SARS-CoV-2-positive and negative cases and the total coincidence rate before and after inactivation were 100.0%, 0 and 47.6%, respectively. For detection of serum IgM and IgG antibodies and plasma IgG antibodies with chemiluminescence immunoassay, the coincidence rates in SARS-CoV-2-positive and negative cases and the total coincidence rate before and after inactivation were all 100.0%, and the total coincidence rate of plasma IgM antibodies was 95.2%. Pearson correlation analysis of the semi-quantitative results of IgM and IgG detection in the serum and plasma samples showed a correlation coefficient of 0.9999 (95%CI: 0.9998-1.000, P < 0.001) between the results before and after sample inactivation. CONCLUSIONS Heat inactivation of blood samples at 56 ℃ for 30 min does not obviously affect the results of immunochromatography and chemiluminescent immunoassay for detection of SARS-COV-2 antibodies but can reduce the risk of infection for the operators. Heat-inactivated samples can not be used in fluorescence immunochromatography for SARS-CoV-2 antibody detection.


Plastics recycling with a difference.


title: Analytical sensitivity and efficiency comparisons of SARS-CoV-2 RT-qPCR primer-probe sets.

text: The recent spread of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exemplifies the critical need for accurate and rapid diagnostic assays to prompt clinical and public health interventions. Currently, several quantitative reverse transcription-PCR (RT-qPCR) assays are being used by clinical, research and public health laboratories. However, it is currently unclear whether results from different tests are comparable. Our goal was to make independent evaluations of primer-probe sets used in four common SARS-CoV-2 diagnostic assays. From our comparisons of RT-qPCR analytical efficiency and sensitivity, we show that all primer-probe sets can be used to detect SARS-CoV-2 at 500 viral RNA copies per reaction. The exception for this is the RdRp-SARSr (Charité) confirmatory primer-probe set which has low sensitivity, probably due to a mismatch to circulating SARS-CoV-2 in the reverse primer. We did not find evidence for background amplification with pre-COVID-19 samples or recent SARS-CoV-2 evolution decreasing sensitivity. Our recommendation for SARS-CoV-2 diagnostic testing is to select an assay with high sensitivity and that is regionally used, to ease comparability between outcomes.


title: Who's afraid of noncommunicable diseases? Raising awareness of the effects of noncommunicable diseases on global health.

text: Public-health priorities are in part driven by fear, yet fear has long been recognized as posing a threat to effective public health interventions. In this article, the authors review the role of fear in global health by focusing on the leading global cause of death and disability: noncommunicable diseases. Taking an historical perspective, first the authors review Samuel Adams' 1911 analysis of the role of fear in generating public health priority and his recommendations about mass educating the public. Next, they show that Adams' analysis still applies today, drawing on contemporary responses to H1N1 and HIV, while illustrating the ongoing neglect of long-term threats such as noncommunicable diseases. Then, they pose the question, "Is it possible, necessary, or useful to create a fear factor for noncommunicable diseases?" After reviewing mixed evidence about the effects of fear on social change (on individual behaviors and on building a mass movement to achieve collective action), the authors conclude by setting out an evidence-based, marketing strategy to generate a sustained, rational response to the noncommunicable disease epidemic.


title: Trials of endovascular therapies or collaterals?

text: Several landmark clinical trials of endovascular therapy for acute ischemic stroke have recently jolted the concerted multidisciplinary efforts to develop effective revascularization strategies. Further consideration of these four endovascular stroke trials published in the last year suggests a more fundamental question: are these trials of specific treatments or have the results simply reflected the importance of underlying pathophysiology? Data from IMS III, MR RESCUE, SWIFT and TREVO2 consistently demonstrate the dramatic impact of collateral perfusion in acute ischemic stroke. Such collateral, or parallel, trials of the underlying pathophysiology in stroke reveal that diagnosis or selection of optimal candidates may be paramount to the specific drug or device therapy. Future trials of endovascular therapies may harness the influential role of collaterals as critical selection criteria for intervention, with triage based on imaging rather than time alone. Treating the optimal patient may be more important than chasing an elusive magical therapy.


Molecular characterisation of calicivirus and astrovirus in puppies with enteritis.


title: [Evaluation of postoperative myocardial injury by heart-type fatty acid-binding protein in off-pump coronary artery bypass grafting surgery].

text: BACKGROUND AND GOAL OF STUDY Postoperative myocardial infarction is a serious and frequent complication of cardiac surgery. Nonetheless, diagnosis in this context it is occasionally challenging. We sought to evaluate the kinetics and diagnostic accuracy of the new biomarker « heart-type fatty acid-binding protein » (h-FABP) in the early detection of myocardial injury in patients undergoing off-pump coronary artery bypass grafting, compared with classical biomarkers. MATERIALS AND METHODS A prospective study was conducted on 17 consecutive patients who underwent off-pump coronary artery bypass grafting during a 2 month period. Blood samples were drawn for measurement of myocardial ischemic injury biomarkers (h-FABP, troponin, creatine kinase [CK] and CK-MB), at baseline (T1), immediate post-coronary artery bypass grafting (T2), on ICU admission (T3), and after 4 (T4), 8 (T5), 24 (T6) and 48 h (T7). Perioperative ischemic complications, defined according to electrocardiographic, echocardiographic and hemodynamic criteria, were recorded. RESULTS Earlier biomarkers peak plasma values occurred at T4 with troponin (2.9 ± 5.2 ng/mL), and at T5 with h-FABP (37.9 ± 55.5 ng/mL). Maximum values of CK and CK-MB occurred later, both in T6 (741 ± 779 and 37 ± 51 U/L, respectively). The optimized cut-off obtained for h-FABP was 19 ng/mL, providing a sensitivity and specificity of 77 and 75%, respectively, for diagnosis of perioperative ischemic injury, with an area under the ROC curve for h-FABP of 0.83 (95% CI 0.6-1.0) vs. 0.63 (95% CI 0.33-0.83) for troponin. This cut-off value for h-FABP is reached on average at T2 (mean value of h-FABP at T2: 18.9 ± 21.5 ng/mL). CONCLUSION This is the first study evaluating the kinetics of h-FABP biomarker in perioperative off-pump coronary artery bypass grafting, and the cut-off value established could help to extend earlier detection of myocardial ischemia in this context.


title: Clinical Features of COVID-19 in Patients With Essential Hypertension and the Impacts of Renin-angiotensin-aldosterone System Inhibitors on the Prognosis of COVID-19 Patients.

text: Hypertension is one of the most common comorbidities in patients with coronavirus disease 2019 (COVID-19). This study aimed to clarify the impact of hypertension on COVID-19 and investigate whether the prior use of renin-angiotensin-aldosterone system (RAAS) inhibitors affects the prognosis of COVID-19. A total of 996 patients with COVID-19 were enrolled, including 282 patients with hypertension and 714 patients without hypertension. Propensity score-matched analysis (1:1 matching) was used to adjust the imbalanced baseline variables between the 2 groups. Patients with hypertension were further divided into the RAAS inhibitor group (n=41) and non-RAAS inhibitor group (n=241) according to their medication history. The results showed that COVID-19 patients with hypertension had more severe secondary infections, cardiac and renal dysfunction, and depletion of CD8+ cells on admission. Patients with hypertension were more likely to have comorbidities and complications and were more likely to be classified as critically ill than those without hypertension. Cox regression analysis revealed that hypertension (hazard ratio, 95% CI, unmatched cohort [1.80, 1.20-2.70]; matched cohort [2.24, 1.36-3.70]) was independently associated with all-cause mortality in patients with COVID-19. In addition, hypertensive patients with a history of RAAS inhibitor treatment had lower levels of C-reactive protein and higher levels of CD4+ cells. The mortality of patients in the RAAS inhibitor group (9.8% versus 26.1%) was significantly lower than that of patients in the non-RAAS inhibitor group. In conclusion, hypertension may be an independent risk factor for all-cause mortality in patients with COVID-19. Patients who previously used RAAS inhibitors may have a better prognosis.


title: Clinical utility of radiofrequency ablation following transarterial injection of miriplatin-iodized oil suspension in small hepatocellular carcinoma.

text: PURPOSE To retrospectively evaluate the clinical utility of radiofrequency ablation (RFA) following transarterial injection of miriplatin-iodized oil suspension (MPT-RFA) for hepatocellular carcinoma treatment. MATERIALS AND METHODS We evaluated clinical outcomes of MPT-RFA for three or fewer hepatocellular carcinomas. Twenty-one patients with 30 tumors (maximum diameter: mean 1.4 ± 0.4 cm, range 0.7-2.2 cm) received MPT-RFA. RESULTS Nineteen patients (90.5 %, 19/21) achieved complete ablation at the first RFA session. Two patients (9.5 %, 2/21) required a second RFA session but achieved complete ablation. Primary and secondary technical success rates were 90.5 and 100 %. There were no deaths related to the procedures performed. Grade 3 or 4 increases in the serum aspartate aminotransferase, alanine aminotransferase, and bilirubin levels were found in six patients (38.1 %, 8/21). There were no liver infarctions. During the median follow-up period of 24.1 months (mean ± SD 24.7 ± 6.9 months, range 13.8-38.9 months), the local tumor progression rate and overall survival rate at 2 years was 5.0 % (95 % confidence interval 0.3-20.6 %) and 86.7 % (95 % confidence interval 56.3-96.5 %), respectively. The mean hospital stay was 8.4 ± 3.1 days (range 5-18 days). CONCLUSION MPT-RFA is a safe therapeutic option that initially provides therapeutic results.


title: [Modified-release hydrocortisone for glucocorticoid deficiency].

text: BACKGROUND The central circadian pacemaker in the suprachiasmatic nucleus and interaction of clock genes with the hypothalamus pituitary adrenal axis are responsible for very distinct cortisol concentrations. Unphysiologically high doses of glucocorticoids that do not follow the circadian rhythm lead to increased rates of morbidity, mortality and reduced quality of life. OBJECTIVES Does a switch to modified-release hydrocortisone in multimorbid elderly patients offer benefits compared to a conventional therapy regime? METHODS Evaluation, analysis and discussion of statistics, recent research results and expert advice. RESULTS Overdosage and unphysiological timing of cortisol administration result in higher incidences of obesity, hypertension, hyperglycemia, coronary heart disease and cardiac events. Body weight, body mass index and HbA1c decline with Plenadren® (Shire Pharmaceuticals Ireland Limited, Dublin, Ireland) treatment compared to conventional therapy. CD16+ natural killer cells and natural killer cytotoxycity are reduced, and the incidence of respiratory-tract infections is increased, with conventional therapy compared to Plenadren®. Cortisol influences sleep pattern and sleep quality by its circadian secretion. CONCLUSION Novel modified-release hydrocortisone preparations offer diverse benefits with regard to their effect on metabolism, cardiovascular risk, immunity and sleep, which might be beneficial in particular in multimorbid elderly.


title: Advances in peripheral arterial disease endovascular revascularization.

text: Significant advances have been made in the endovascular treatment of lower extremity arterial occlusive disease. Since the 2011 update, technologies has developed and allowed for the revascularization of complex vascular lesions. Although this technical success is encouraging, these technologies must provide measurable long-term clinical success at a reasonable cost. Large, randomized, controlled trials need to be designed to focus on clinical outcomes and success rates for treatment. These future studies will serve as the guide by which clinicians can provide the most successful clinical and cost effect care in treating patients with lower-extremity peripheral artery disease.


title: Optimal cutoff points of entropy indices for use in predicting responses elicited during determination of minimum alveolar concentration of sevoflurane in dogs.

text: OBJECTIVE To investigate values of spectral indices for use in predicting responses in dogs during determination of minimum alveolar concentration (MAC) of sevoflurane. ANIMALS 15 healthy German Shepherd Dogs. PROCEDURES :Sevoflurane MAC was determined by use of tail clamping. Entropy indices consisting of response entropy and state entropy were recorded during MAC determination. Optimal cutoff points of response entropy and state entropy for use in predicting responses to tail clamping were analyzed with multiple logistic regression. RESULTS Sevoflurane MAC ranged from 1.8% to 2.6% (mean ± SD, 2.2 ± 0.3%). Response entropy and state entropy were significantly higher during positive responses to tail clamping (88 ± 2 and 76 ± 2, respectively) than during negative responses to tail clamping (63 ± 3 and 52 ± 3, respectively). The difference between the 2 entropy indices did not differ between positive (11 ± 1) and negative (13 ± 1) responses to tail clamping. Response entropy and state entropy served as independent predictors of a positive response, with areas under the curve for receiver operating characteristic curves 0.810 (95% confidence interval, 0.716 to 0.903) and 0.828 (95% confidence interval, 0.741 to 0.916), respectively. Optimal cutoff points to predict a positive response were 75 for response entropy and 65 for state entropy, which corresponded to mean ± SD ORs of 25.2 ± 15.6 and 14.9 ± 7.9, respectively. CONCLUSIONS AND CLINICAL RELEVANCE Response entropy and state entropy were good predictors of responses to tail clamping elicited during determination of sevoflurane MAC in healthy dogs.


Support the global public health community.


Cone-beam CT for Diagnosis of Avulsion Injuries of the Hand and Wrist.


An Easy and Cost-Effective Method to Perform the "No-Touch" Technique in Saline Breast Augmentation.


title: Probability estimation with machine learning methods for dichotomous and multicategory outcome: applications.

text: Machine learning methods are applied to three different large datasets, all dealing with probability estimation problems for dichotomous or multicategory data. Specifically, we investigate k-nearest neighbors, bagged nearest neighbors, random forests for probability estimation trees, and support vector machines with the kernels of Bessel, linear, Laplacian, and radial basis type. Comparisons are made with logistic regression. The dataset from the German Stroke Study Collaboration with dichotomous and three-category outcome variables allows, in particular, for temporal and external validation. The other two datasets are freely available from the UCI learning repository and provide dichotomous outcome variables. One of them, the Cleveland Clinic Foundation Heart Disease dataset, uses data from one clinic for training and from three clinics for external validation, while the other, the thyroid disease dataset, allows for temporal validation by separating data into training and test data by date of recruitment into study. For dichotomous outcome variables, we use receiver operating characteristics, areas under the curve values with bootstrapped 95% confidence intervals, and Hosmer-Lemeshow-type figures as comparison criteria. For dichotomous and multicategory outcomes, we calculated bootstrap Brier scores with 95% confidence intervals and also compared them through bootstrapping. In a supplement, we provide R code for performing the analyses and for random forest analyses in Random Jungle, version 2.1.0. The learning machines show promising performance over all constructed models. They are simple to apply and serve as an alternative approach to logistic or multinomial logistic regression analysis.


title: Secretion of thymidine kinase to increase the effectivity of suicide gene therapy results in the loss of enzymatic activity.

text: Low efficiency of gene transfer is one of the major limitations of gene therapy. A solution to this problem may be transmission; by modification of the transgene, the gene product can be secreted and internalized by the surrounding cells. Cancer gene therapy using the herpes simplex thymidine kinase (HSV-TK) suicide gene is a promising treatment, and TK has been used in clinical trials with some success. However, this kind of therapy has limited efficacy due to the low level of gene transfer reached. A modified TK protein, capable of migrating from the producing cell to neighboring cells, would result in a greater proportion of cells affected by the treatment. As a first step towards transmission, we constructed a secretory form of HSV-TK by including the Igkappa leader peptide in the gene. An endoplasmatic reticulum export signal was added to the construct to further improve its secretion. Secretion and protein production in cancer cells, the enzymatic activity of the modified proteins and the ability of the modified TK to sensitize cancer cells to ganciclovir were tested. Addition of the Igkappa leader resulted in high levels of secretion of HSV-TK, with up to 70% of the total amount of protein secreted. Inclusion of an ER export signal did not further improve secretion. The enzyme activity of the secreted TK however, was decreased when compared to native TK. This study is the first to report on secretion of TK, and provides a first step in a novel strategy to improve the efficiency of cancer gene therapy. The loss of function in secreted TK however, may present a major hurdle in the development of a transmitted form of TK.


title: Outbreak of diarrhea among preweaning alpacas (Vicugna pacos) in the southern Peruvian highland.

text: INTRODUCTION Infections, particularly diarrheal infections, are a major cause of neonatal death in South American camelids. The aim of this study was to identify the pathogens that could have caused the recent diarrhea outbreak among the alpacas in Silli, Cusco, located in the southern Peruvian highland. METHODOLOGY Spleen, kidney, and intestine tissue along with fecal and intestinal lavage samples were obtained from 50 one- to five-week-old alpacas and analyzed for the presence of parasites, bacteria, and viruses. RESULTS Laboratory testing of the 50 crias included in this study revealed that 80% were infected with Eimeria spp., 40% with coronavirus, 34% with E. coli, 32% with rotavirus, 22% with Clostridium spp., and 20% with Cryptosporidium spp. Of these 50 alpaca crias, 20 presented with a single infection (19 positive for Eimeria spp. and 1 positive for rotavirus). Co-infections with up to four pathogens occurred in 60% of the samples. The significance of such infections is not clear, but it is noteworthy that the animals suffering from necrotic and/or hemorrhagic enteritis presented with quadruple infections. It is likely that co-infections increase the severity of the disease. CONCLUSIONS These data show that multiple pathogens circulate among young alpaca crias and could be associated with diarrheal disease in these animals. The findings from this study warrant the provision of subsidies for future assessment of the potential economic impact of these infections on the productivity of the Peruvian alpaca industry.


title: Better Prepare Than React: Reordering Public Health Priorities 100 Years After the Spanish Flu Epidemic.

text: This commentary argues that 100 years after the deadly Spanish flu, the public health emergency community's responses to much more limited pandemics and outbreaks demonstrate a critical shortage of personnel and resources. Rather than relying on nonpharmaceutical interventions, such as quarantine, the United States must reorder its health priorities to ensure adequate preparation for a large-scale pandemic.


title: Patient Portal Use and Experience Among Older Adults: Systematic Review.

text: BACKGROUND The older adult population (65 years or older) in the United States is growing, and it is important for communities to consider ways to support the aging population. Patient portals and electronic personal health records (ePHRs) are technologies that could better serve populations with the highest health care needs, such as older adults. OBJECTIVE The aim of this study was to assess the existing research landscape related to patient portal and ePHR use and experience among older adults and to understand the benefits and barriers to older adults' use and adoption of patient portals and ePHRs. METHODS We searched six pertinent bibliographic databases for papers, published from 2006 to 2016 and written in English, that focused on adults 60 years or older and their use of or experience with patient portals or ePHRs. We adapted preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines to review papers based on exclusion and inclusion criteria. We then applied thematic analysis to identify key themes around use, experience, and adoption. RESULTS We retrieved 199 papers after an initial screening and removal of duplicate papers. Then we applied an inclusion and exclusion criteria, resulting in a final set of 17 papers that focused on 15 separate projects. The majority of papers described studies involving qualitative research, including interviews and focus groups. They looked at the experience and use of ePHRs and patient portals. Overall, we found 2 main barriers to use: (1) privacy and security and (2) access to and ability to use technology and the Internet. We found 2 facilitators: (1) technical assistance and (2) family and provider advice. We also reported on older adults' experience, including satisfaction with the system and improvement of the quality of their health care. Several studies captured features that older adults wanted from these systems such as further assistance managing health-related tasks and contextual health advice and tips. CONCLUSIONS More research is needed to better understand the patient portal experience among older adults from initial use to adoption. There are also opportunities to explore the role of design in addressing barriers and supporting facilitators to patient portal and ePHR use. Finally, the future use of these systems by older adults should be anticipated and considered in the design process.


title: Community psychological and behavioral responses through the first wave of the 2009 influenza A(H1N1) pandemic in Hong Kong.

text: BACKGROUND Little is known about the community psychological and behavioral responses to influenza pandemics. METHODS Using random digit dialing, we sampled 12,965 Hong Kong residents in 13 cross-sectional telephone surveys between April and November 2009, covering the entire first wave of the 2009 influenza A(H1N1) pandemic. We examined trends in anxiety, risk perception, knowledge on modes of transmission, and preventive behaviors. RESULTS Respondents reported low anxiety levels throughout the epidemic. Perceived susceptibility to infection and perceived severity of H1N1 were initially high but declined early in the epidemic and remained stable thereafter. As the epidemic grew, knowledge on modes of transmission did not improve, the adoption of hygiene measures and use of face masks did not change, and social distancing declined. Greater anxiety was associated with lower reported use of hygiene measures but greater social distancing. Knowledge that H1N1 could be spread by indirect contact was associated with greater use of hygiene measures and social distancing. CONCLUSIONS The lack of substantial change in preventive measures or knowledge about the modes of H1N1 transmission in the general population suggests that community mitigation measures played little role in mitigating the impact of the first wave of 2009 influenza A(H1N1) pandemic in Hong Kong.


title: Equine disease surveillance: quarterly summary.

text: This quarterly equine disease surveillance report, prepared by Defra, the Animal Health Trust and the British Equine Veterinary Association, covers: Summary of surveillance testing, January to March 2017International disease occurrence in the first quarter of 2017Focus on the diagnosis of equine influenza.


title: Endovascular stroke intervention in young patients with large vessel occlusions.

text: OBJECT Endovascular therapy has become a widely used method for achieving arterial recanalization in patients who are ineligible for intravenous thrombolysis or those in whom it is unsuccessful. Young stroke patients with large vessel occlusions may particularly benefit from endovascular intervention. This study aims to assess the authors' experience with the use of modern endovascular techniques to treat young patients (≤ 55 years old) with acute ischemic stroke and large vessel occlusions. METHODS Young patients (≤ 55 years old) undergoing endovascular intervention for acute ischemic stroke at the authors' institution were identified from a prospectively maintained database. Only those patients with a confirmed large vessel occlusion were included. Modified Rankin Scale (mRS) scores were determined at 90 days during a follow-up visit. A multivariate analysis was performed to determine predictors of outcome (mRS score 0-2). RESULTS A total of 45 patients met the inclusion criteria. The mean age of the patients in this series was 45 ± 9.6 years. The mean admission NIH Stroke Scale score was 14.1 ± 5 (median 13.5). Mechanical thrombectomy was performed using the Solitaire FR device in 13 (29%) patients and the Merci/Penumbra systems in 32 (71%) patients. The rate of successful recanalization (Thrombolysis In Myocardial Infarction [TIMI] scale Grade II-III) was 93% (42/45). Only 1 patient (2.2%) had a symptomatic intracranial hemorrhage following intervention. One patient (2.2%) sustained a vessel perforation intraoperatively. The rate of 90-day favorable outcome (mRS score 0-2) was 77.5% and the rate of 90-day satisfactory outcome (mRS score 0-3) was 90%. The 90-day mortality rate was 7.5%. In multivariate analysis, postprocedure TIMI grade was the only statistically significant independent predictor of 90-day outcome (OR 3.3, 95% CI 1.01-1.19; p = 0.05). CONCLUSIONS The results of this study demonstrate that endovascular therapy provides remarkably high rates of arterial recanalization and favorable outcomes in young patients with acute ischemic stroke and large vessel occlusions. These findings support aggressive interventional strategies in these patients. Randomized, controlled trials reflecting modern acute ischemic stroke treatment will be needed to confirm the findings of this study.


title: Comparing lignocaine-adrenaline-tetracaine gel with lignocaine infiltration for anesthesia during repair of lacerations: A randomized trial.

text: BACKGROUND This study aimed to compare the topical anesthetic lignocaine, adrenaline, and tetracaine (LAT) (4% lignocaine, 1:2 000 adrenaline, 1% tetracaine) with the conventional lignocaine infiltration(LI) for repair of minor lacerations, for the comfort of anesthetic administration, efficacy, adverse effects and cost. METHODS This was a prospective randomized clinical trial. Forty Asian patients who required toilet and suture for minor lacerations in the emergency department of the Singapore General Hospital over a 4-month period. The patients were assigned randomly to 2 arms of treatment. The first was the LAT gel group who had LAT gel applied to the laceration prior to suturing. The second was the control group in whom the anesthetic administered was lignocaine infiltration (LI) via a syringe. The pain of the process of administering anesthetic and efficacy of anesthesia were scored using the visual pain scale included within. The efficacy of LAT vs. lignocaine infiltration as an anesthetic prior to the toilet and suture of minor lacerations and complications of therapy. RESULTS Twenty patients were randomized to LAT gel and 16 to LI on an intention to treat analysis. The mean pain score by patients in the LAT gel group was 2.5 (0.52 SE), and 2.5 (0.58 SE) in the LI group. The pain score for pain during application of the anesthetic was 1.5 (0.40) in the LAT gel group, and 3.5 (0.46) in the LI group. There was no difference in complications between the LAT and LI groups. CONCLUSION LAT gel prior to the toilet and suture of minor lacerations is proven to be as efficacious as LI in terms of patient comfort and effectiveness of anesthesia. The complications are also comparable to those treated with LI.


title: Racial Disparities in COVID-19 Deaths Reveal Harsh Truths About Structural Inequality in America.

text: The Coronavirus disease 2019 (COVID-19) pandemic has unveiled the stark racial disparities that are present in United States (US) and other developed countries today. In recent weeks, several states have released demographic data that highlights the disproportionate rate of COVID-19 infections in racial/ethnic minorities1 . These disparities are likely a result of the structural inequities that minorities face due to factors such as racism, neighborhood segregation, income, housing and education inequality, and poor access to medical care.


title: Anticipation of the difficult airway: preoperative airway assessment, an educational and quality improvement tool.

text: BACKGROUND Assessment of the potentially difficult airway (DA) is a critical aspect of resident education. We investigated the impact of a new assessment form on airway prediction and management by anaesthesia residents. We hypothesized that residents would demonstrate improvement in evaluation of DAs over the study duration. METHODS After IRB approval, anaesthesia residents were randomized into two groups: control (existing form) and experimental (new form). Data were collected prospectively from August 2008 to May 2010 on all non-obstetric adult patients undergoing non-emergent surgery. RESULTS Eight thousand three hundred and sixty-four independent preoperative assessments were collected and 8075 were analysed. The experimental group had the higher completion rate than the control group (94.3% vs 84.3%, P=0.001). DA prediction was higher for the control group (71.2%) compared with the experimental group (69.1%; P=0.032). A significant improvement in prediction rates was found over time for the experimental group (likelihood estimate=0.00068, P=0.031). CONCLUSIONS The use of a comprehensive airway assessment did not improve resident ability to predict a DA in an academic, tertiary-based hospital, anaesthesiology residency training programme.


Calling it what it is.


title: Stent Retriever Thrombectomy with Mindframe Capture LP in Isolated M2 Occlusions.

text: BACKGROUND AND PURPOSE Mechanical thrombectomy is an effective recanalization technique in acute ischemic stroke patients with large vessel occlusions; however, it is unclear to what extent stent retriever thrombectomy may be applicable to occlusions of smaller peripheral cerebral vessels. The outcome of patients with isolated M2 occlusions treated with the Mindframe Capture low profile (LP) stent retriever was reviewed. MATERIAL AND METHODS A retrospective review of prospectively collected data on all consecutive patients treated for isolated M2 occlusions between June 2013 and December 2017 using the Mindframe Capture LP was performed. Technical aspects of the recanalization procedure, recanalization rate, complication rate, and clinical outcome were analyzed. RESULTS Mechanical thrombectomy with the Mindframe Capture LP was performed in 38 patients (median age 79 years) with an isolated M2 occlusion. The median National Institutes of Health Stroke Scale (NIHSS) score on admission was 7.5 (interquartile range, IQR 5-12) and successful reperfusion modified Thrombolysis in Cerebral Infarction (mTICI 2b or 3) was achieved in 28 patients (74%). A compensated/adjusted modified Rankin Scale (mRS) 0-2 at 3 months was observed in 65% when taking pre-stroke disability into account. Symptomatic intracranial hemorrhage (sICH) occurred in 1 patient (2.6%). Asymptomatic intracranial hemorrhage (aICH) was noted in 8 patients (21%) and a small subarachnoid hemorrhage (SAH) in the immediate vicinity of the target vessel was apparent in 8 patients (21%). CONCLUSION The Mindframe Capture LP is a technically effective thrombectomy device for the treatment of isolated M2 occlusions. The lower profile of the device is advantageous when targeting peripheral intracranial occlusions.


title: Potential benefits of laparoscopy-assisted proximal gastrectomy with esophagogastrostomy for cT1 upper-third gastric cancer.

text: BACKGROUND Few reports have compared laparoscopy-assisted proximal gastrectomy (LAPG) with laparoscopy-assisted total gastrectomy (LATG) in patients with cT1N0 gastric cancer. This study assessed the safety and feasibility of LAPG with esophagogastrostomy in these patients and compared postgastrectomy disturbances and nutritional status following LAPG and LATG. METHODS This study compared 40 patients who underwent LAPG with esophagogastrostomy and 59 who underwent LATG with esophagojejunostomy, both with OrVil™. Surgical outcomes, postoperative complications, nutritional status at 1 and 2 years, and relapse-free survival were compared in these two groups. RESULTS Operation time was significantly shorter in the LAPG group than in the LATG group (280 min vs. 365 min, P < 0.001). Although the rate of surgical complications was similar in the two groups, the rate of anastomotic stricture was significantly higher in the LAPG group than in the LATG group (28 vs. 8.4 %; P = 0.012). Rates of reflux esophagitis graded A or higher in the Los Angeles classification were 10 and 5.1 %, respectively. Hemoglobin levels 2 years after surgery, relative to baseline levels, were significantly higher in the LAPG group than in the LATG group (98.6 vs. 92.9 %, P = 0.020). Body weight, albumin and total protein concentrations, and total lymphocyte count 1 and 2 years after surgery were slightly, but not significantly, higher in the LAPG group. Relapse-free survival rates were similar, as were 5-year overall survival rates (86 vs. 79 %, P = 0.42). CONCLUSIONS LAPG with esophagogastrostomy using OrVil™ was safe and feasible for patients with cT1N0 gastric cancer. LAPG may have nutritional advantages over LATG, but the rate of anastomotic stricture was significantly higher for LAPG than for LATG.


title: Effects of dexmedetomidine on postoperative cognitive function in patients undergoing coronary artery bypass grafting.

text: Effects of dexmedetomidine on postoperative cognitive function in patients undergoing coronary artery bypass grafting were investigated. Eighty patients undergoing systemic anesthesia with extracorporeal coronary artery bypass grafting in The People's Hospital of Guangxi Zhuang Autonomous Region from January 2015 to August 2017 were selected and randomly divided into the observation group (n=40) and control group (n=40). The two groups were treated with dexmedetomidine and equal volume of normal saline, respectively. Moreover, safety indexes including EEG bispectral index (BIS) at 30 min before induction of anesthesia (T0), immediately after intubation (T1), when incision was made (T2), when chest was closed (T3), when operation was completed (T4) and at 6 h after operation (T5), intraoperative circulatory system-related complications, cortisol, epinephrine and norepinephrine levels at the end of surgery as well as anesthesia recovery time and postoperative mechanical ventilation time were recorded and compared. All the patients were followed up for 1 week. Mini-mental state examination (MMSE) and Montreal cognitive assessment (MoCA) were administered at 1, 3 and 7 days after operation, and the incidence of intraoperative awareness and postoperative cognitive dysfunction was recorded. BIS value in the observation group was lower than that in the control group (P<0.05) at T1-T4 time points, and the BIS value in the observation group was higher than that in the control group (P<0.05) at T5. Incidence rates of intraoperative arrhythmia, hypertension and hypotension in the observation group was significantly lower than those in the control group (P<0.05). At the end of operation, levels of cortisol, epinephrine and norepinephrine in the observation group were significantly lower than those in the control group (P<0.05). Anesthesia recovery time and postoperative mechanical ventilation time in the observation group was significantly shorter than the time in the control group (P<0.05). MMSE and MoCA scores of the observation group were better than those of the control group (P<0.05). The incidence of cognitive impairment and postoperative cognitive impairment in the observation group was significantly lower than those in the control group (P<0.05). Therefore, it is concluded that dexmedetomidine can effectively reduce the incidence of postoperative cognitive impairment in patients undergoing coronary artery bypass grafting, and it is of high safety for circulatory function.


title: Sustained analgesia achieved through esterase-activated morphine prodrugs complexed with PAMAM dendrimer.

text: PURPOSE Design and evaluate the in vitro and in vivo efficacy of two extended release morphine formulations developed for IV administration by complexing esterase activated morphine prodrugs to surface-modified, generation 5 (G5) poly(amidoamine) (PAMAM) dendrimer. METHODS Prodrugs were synthesized, complexed with PAMAM dendrimer, characterized via ultra performance liquid chromatography (UPLC), nuclear magnatic resonance (NMR), and tested in vitro using rat plasma vs. saline control and in an in vivo rat and guinea pig pain model (modified Randall and Selitto test). RESULTS We demonstrated that complexation with dendrimer allowed the solubilization of the prodrugs for in vivo applications without the need for salt, and that the structural design of the morphine prodrugs allowed the controlled release of morphine which extended the action of morphine-induced analgesia in an animal pain model from 2 h (control) to 6 h (Morphine Prodrug A). CONCLUSION The concept of complexing/solubilizing appropriately designed esterase-sensitive prodrugs with dendrimer to enhance the sustained release of these drugs may be a useful pharmacokinetic strategy for a range of therapeutics.


title: The Canadian general surgery resident: defining current challenges for surgical leadership.

text: BACKGROUND Surgery training programs in Canada and the United States have recognized the need to modify current models of training and education. The shifting demographic of surgery trainees, lifestyle issues and an increased trend toward subspecialization are the major influences. To guide these important educational initiatives, a contemporary profile of Canadian general surgery residents and their impressions of training in Canada is required. METHODS We developed and distributed a questionnaire to residents in each Canadian general surgery training program, and residents responded during dedicated teaching time. RESULTS In all, 186 surveys were returned for analysis (62% response rate). The average age of Canadian general surgery residents is 30 years, 38% are women, 41% are married, 18% have dependants younger than 18 years and 41% plan to add to or start a family during residency. Most (87%) residents plan to pursue postgraduate education. On completion of training, 74% of residents plan to stay in Canada and 49% want to practice in an academic setting. Almost half (42%) of residents identify a poor balance between work and personal life during residency. Forty-seven percent of respondents have appropriate access to mentorship, whereas 37% describe suitable access to career guidance and 40% identify the availability of appropriate social supports. Just over half (54%) believe the stress level during residency is manageable. CONCLUSION This survey provides a profile of contemporary Canadian general surgery residents. Important challenges within the residency system are identified. Program directors and chairs of surgery are encouraged to recognize these challenges and intervene where appropriate.


title: COVID-19: An Update on the Epidemiological, Clinical, Preventive and Therapeutic Evidence and Guidelines of Integrative Chinese-Western Medicine for the Management of 2019 Novel Coronavirus Disease.

text: As of 22 February 2020, more than 77662 cases of confirmed COVID-19 have been documented globally with over 2360 deaths. Common presentations of confirmed cases include fever, fatigue, dry cough, upper airway congestion, sputum production, shortness of breath, myalgia/arthralgia with lymphopenia, prolonged prothrombin time, elevated C-reactive protein, and elevated lactate dehydrogenase. The reported severe/critical case ratio is approximately 7-10% and median time to intensive care admission is 9.5-10.5 days with mortality of around 1-2% varied geographically. Similar to outbreaks of other newly identified virus, there is no proven regimen from conventional medicine and most reports managed the patients with lopinavir/ritonavir, ribavirin, beta-interferon, glucocorticoid and supportive treatment with remdesivir undergoing clinical trial. In China, Chinese medicine is proposed as a treatment option by national and provincial guidelines with substantial utilization. We reviewed the latest national and provincial clinical guidelines, retrospective cohort studies, and case series regarding the treatment of COVID-19 by add-on Chinese medicine. We have also reviewed the clinical evidence generated from SARS and H1N1 management with hypothesized mechanisms and latest in silico findings to identify candidate Chinese medicines for the consideration of possible trials and management. Given the paucity of strongly evidence-based regimens, the available data suggest that Chinese medicine could be considered as an adjunctive therapeutic option in the management of COVID-19.


title: Effects of low and high dose intraarticular tiludronate on synovial fluid and clinical variables in healthy horses-a preliminary investigation.

text: To determine effects of intraarticularly administered tiludronate on articular cartilage in vivo, eight healthy horses were injected once with tiludronate (low dose tiludronate [LDT] 0.017 mg, n = 4; high dose tiludronate [HDT] 50 mg, n = 4) into one middle carpal joint and with saline into the contralateral joint. Arthrocentesis of both middle carpal joints was performed pre-treatment, and 10 min, 24 h, 48 h, 7 and 14 days after treatment. Synovial nucleated cell counts and total solids, tiludronate, sulfated glycosaminoglycan (sGAG), chondroitin sulfate 846 epitope (CS-846, a measure of aggrecan synthesis), and collagen type II cleavage neoepitope (C2C) concentrations were determined. Histologic analysis of joint tissues and sGAG quantitation in cartilage was performed at 14 days in HDT horses. Data were analyzed by repeated measures non-parametric ANOVA and Wilcoxon signed-rank test. High dose tiludronate administration produced synovial fluid tiludronate concentrations of 2,677,500 ng/mL, exceeding concentrations that were safe for cartilage in vitro, and LDT administration produced synovial fluid concentrations of 1,353 ng/mL, remaining below concentrations considered potentially detrimental to cartilage. With HDT, synovial fluid total solids concentration was higher at 24 h and 7 days and sGAG concentration was higher at 48 h, compared to control joints. Synovial fluid CS-846 concentration was increased over pre-treatment values in HDT control but not in HDT treated joints at 24 and 48 h. All joints (HDT and LDT control and treated) showed a temporary decrease in synovial fluid C2C concentration, compared to pre-treatment values. Histologic features of articular cartilage and synovial membrane did not differ between HDT treated and control joints. High dose tiludronate treatment caused a transient increase in synovial total solids and temporarily increased proteoglycan degradation in cartilage. Although clinical significance of these changes are questionable, as they did not result in articular cartilage damage, further investigation of the safety of intraarticular HDT in a larger number of horses is warranted.


title: A 56-year-old man with RT-PCR negative nasopharyngeal swabs with Coronavirus Disease 2019 (COVID-19) Pneumonia.

text: INTRODUCTION Diagnostic procedure in Coronavirus Disease 2019 (COVID-19) is based mainly on performing real-time-reverse transcription-polymerase chain-reaction (RT-PCR), which has been accepted as the gold standard method. In some cases, such as mutations of the SARS-CoV-2 genome, variable viral load kinetics or laboratory errors, it can be false-negative. CASE REPORT The case is presented of a 56-year-old man with respiratory tract symptoms, with twice negative results of real-time-reverse transcription-polymerase chain-reaction of nasopharyngeal swabs and positive chest computed tomography, with typical findings for COVID-19 pneumonia. CONCLUSIONS Patients with negative RT-PCR results, but with positive computed tomography findings characteristic for COVID-19, should be treated as well as those infected.


title: A first-in-human study investigating biodistribution, safety and recommended dose of a new radiolabeled MAb targeting FZD10 in metastatic synovial sarcoma patients.

text: BACKGROUND Synovial Sarcomas (SS) are rare tumors occurring predominantly in adolescent and young adults with a dismal prognosis in advanced phases. We report a first-in-human phase I of monoclonal antibody (OTSA-101) targeting FZD10, overexpressed in most SS but not present in normal tissues, labelled with radioisotopes and used as a molecular vehicle to specifically deliver radiation to FZD10 expressing SS lesions. METHODS Patients with progressive advanced SS were included. In the first step of this trial, OTSA-101 in vivo bio-distribution and lesions uptake were evaluated by repeated whole body planar and SPECT-CT scintigraphies from H1 till H144 after IV injection of 187 MBq of 111In-OTSA-101. A 2D dosimetry study also evaluated the liver absorbed dose when using 90Y-OTSA-101. In the second step, those patients with significant tumor uptake were randomized between 370 MBq (Arm A) and 1110 MBq (Arm B) of 90Y-OTSA-101 for radionuclide therapy. RESULTS From January 2012 to June 2015, 20 pts. (median age 43 years [21-67]) with advanced SS were enrolled. Even though 111In-OTSA-101 liver uptake appeared to be intense, estimated absorbed liver dose was less than 20 Gy for each patient. Tracer intensity was greater than mediastinum in 10 patients consistent with sufficient tumor uptake to proceed to treatment with 90Y-OTSA-101: 8 were randomized (Arm A: 3 patients and Arm B: 5 patients) and 2 were not randomized due to worsening PS. The most common Grade ≥ 3 AEs were reversible hematological disorders, which were more frequent in Arm B. No objective response was observed. Best response was stable disease in 3/8 patients lasting up to 21 weeks for 1 patient. CONCLUSIONS Radioimmunotherapy targeting FZD10 is feasible in SS patients as all patients presented at least one lesion with 111In-OTSA-101 uptake. Tumor uptake was heterogeneous but sufficient to select 50% of pts. for 90Y-OTSA-101 treatment. The recommended activity for further clinical investigations is 1110 MBq of 90Y-OTSA-101. However, because of hematological toxicity, less energetic particle emitter radioisopotes such as Lutetium 177 may be a better option to wider the therapeutic index. TRIAL REGISTRATION The study was registered on the NCT01469975 website with a registration code NCT01469975 on November the third, 2011.


title: A scoping review on the roles and tasks of peer reviewers in the manuscript review process in biomedical journals.

text: BACKGROUND Although peer reviewers play a key role in the manuscript review process, their roles and tasks are poorly defined. Clarity around this issue is important as it may influence the quality of peer reviewer reports. This scoping review explored the roles and tasks of peer reviewers of biomedical journals. METHODS Comprehensive literature searches were conducted in Cochrane Library, Cumulative Index to Nursing and Allied Health Literature, Educational Resources Information Center, EMBASE, MEDLINE, PsycINFO, Scopus and Web of Science from inception up to May 2017. There were no date and language restrictions. We also searched for grey literature. Studies with statements mentioning roles, tasks and competencies pertaining to the role of peer reviewers in biomedical journals were eligible for inclusion. Two reviewers independently performed study screening and selection. Relevant statements were extracted, collated and classified into themes. RESULTS After screening 2763 citations and 600 full-text papers, 209 articles and 13 grey literature sources were included. A total of 1426 statements related to roles were extracted, resulting in 76 unique statements. These were grouped into 13 emergent themes: proficient experts in their field (3 items), dutiful/altruistic towards scientific community (7 items), familiar with journal (2 items), unbiased and ethical professionals (18 items), self-critical professionals (4 items), reliable professionals (7 items), skilled critics (15 items), respectful communicators (6 items), gatekeepers (2 items), educators (2 items), advocates for author/editor/reader (3 items) and advisors to editors (2 items). Roles that do not fall within the remit of peer reviewers were also identified (5 items). We also extracted 2026 statements related to peer reviewers' tasks, resulting in 73 unique statements. These were grouped under six themes: organisation and approach to reviewing (10 items), make general comments (10 items), assess and address content for each section of the manuscript (36 items), address ethical aspects (5 items), assess manuscript presentation (8 items) and provide recommendations (4 items). CONCLUSIONS Peer reviewers are expected to perform a large number of roles and tasks for biomedical journals. These warrant further discussion and clarification in order not to overburden these key actors.


title: Crystal Structure of Feline Infectious Peritonitis Virus Main Protease in Complex with Synergetic Dual Inhibitors.

text: UNLABELLED Coronaviruses (CoVs) can cause highly prevalent diseases in humans and animals. Feline infectious peritonitis virus (FIPV) belongs to the genus Alphacoronavirus, resulting in a lethal systemic granulomatous disease called feline infectious peritonitis (FIP), which is one of the most important fatal infectious diseases of cats worldwide. No specific vaccines or drugs have been approved to treat FIP. CoV main proteases (M(pro)s) play a pivotal role in viral transcription and replication, making them an ideal target for drug development. Here, we report the crystal structure of FIPV M(pro) in complex with dual inhibitors, a zinc ion and a Michael acceptor. The complex structure elaborates a unique mechanism of two distinct inhibitors synergizing to inactivate the protease, providing a structural basis to design novel antivirals and suggesting the potential to take advantage of zinc as an adjunct therapy against CoV-associated diseases. IMPORTANCE Coronaviruses (CoVs) have the largest genome size among all RNA viruses. CoV infection causes various diseases in humans and animals, including severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). No approved specific drugs or vaccinations are available to treat their infections. Here, we report a novel dual inhibition mechanism targeting CoV main protease (M(pro)) from feline infectious peritonitis virus (FIPV), which leads to lethal systemic granulomatous disease in cats. M(pro), conserved across all CoV genomes, is essential for viral replication and transcription. We demonstrated that zinc ion and a Michael acceptor-based peptidomimetic inhibitor synergistically inactivate FIPV M(pro). We also solved the structure of FIPV M(pro) complexed with two inhibitors, delineating the structural view of a dual inhibition mechanism. Our study provides new insight into the pharmaceutical strategy against CoV M(pro) through using zinc as an adjuvant therapy to enhance the efficacy of an irreversible peptidomimetic inhibitor.


Finerenone for Albuminuria in Patients With Diabetic Nephropathy--Reply.


A brave new world: the new normal for general practice after the COVID-19 pandemic.


title: Coronavirus disease 2019 (COVID-19) pandemic: Review of guidelines for resuming non-urgent imaging and procedures in radiology during Phase II.

text: Since the spread of the coronavirus disease 2019 (COVID-19) was designated as a pandemic by the World Health Organization, health care systems have been forced to adapt rapidly to defer less urgent care during the crisis. The United States (U.S.) has adopted a four-phase approach to decreasing and then resuming non-essential work. Through strong restrictive measures, Phase I slowed the spread of disease, allowing states to safely diagnose, isolate, and treat patients with COVID-19. In support of social distancing measures, non-urgent studies were postponed, and this created a backlog. Now, as states transition to Phase II, restrictions on non-essential activities will ease, and radiology departments must re-establish care while continuing to mitigate the risk of COVID-19 transmission all while accommodating this backlog. In this article, we propose a roadmap that incorporates the current practice guidelines and subject matter consensus statements for the phased reopening of non-urgent and elective radiology services. This roadmap will focus on operationalizing these recommendations for patient care and workforce management. Tiered systems are proposed for the prioritization of elective procedures, with physician-to-physician communication encouraged. Infection control methods, provision of personal protective equipment (PPE), and physical distancing measures are highlighted. Finally, changes in hours of operation, hiring strategies, and remote reading services are discussed for their potential to ease the transition to normal operations.