title: Evolving guidelines in the use of topical nonsteroidal anti-inflammatory drugs in the treatment of osteoarthritis.

text: BACKGROUND Nonsteroidal anti-inflammatory drugs (NSAIDs) are a standard treatment for osteoarthritis (OA), but the use of oral NSAIDs has been linked to an elevated risk for cardiovascular and gastrointestinal adverse events and renal toxicity. Topical NSAIDs are thought to afford efficacy that is comparable to oral formulations while reducing widespread systemic drug exposure, which may provide a benefit in terms of safety and tolerability. As a result, European treatment guidelines have, for many years, recommended the use of topical NSAIDs as a safe and effective treatment option for OA. Following the recent approval of several topical NSAID formulations by the US Food and Drug Administration, US treatment guidelines are increasingly recommending the use of topical NSAIDs as an alternative therapy and, in some cases, as a first-line option for OA. This commentary summarizes OA treatment guidelines that are currently available and discusses their potential evolution with regard to the increased inclusion of topical NSAIDs.


title: COVID-19 pandemic predictions using the modified Bateman SIZ model and observational data for Heidelberg, Germany: Effect of vaccination with a SARS-CoV-2 vaccine, coronavirus testing and application of the Corona-Warn-App.

text: AIMS OF THE STUDY Published data show that the current progression of the COVID-19 pandemic in Heidelberg, Germany, despite the current lockdown, could continue into 2021 and become more severe. We have used the modified Bateman SIZ algorithm to predict the effects of interventional measures to control the COVID-19 pandemic. MATERIALS AND METHODS Model parameters, e.g., doubling time and rate of decrease in the number of infectious persons were obtained from published reports. Predictions were made for the status quo on June 1, 2020, and for interventional measures obtained for 4 scenarios. These included vaccination of the whole population using a SARS-CoV-2 vaccine having an efficacy of 50% and 100%, mass-testing for COVID-19 coronavirus and application of the Corona-Warn-App. RESULTS The principle findings were 1) without new measures to control the pandemic, the daily number of infectious persons could reach a peak of > 4,500 daily within 18 months when > 67,000 persons would have been infected. This could be prevented by using a vaccine with 50% efficacy which was almost equally effective as a vaccine with 100% efficacy. Application of the Corona-Warn-App was the most effective method and more effective than testing for COVID-19. The methodology used has been described in detail to enable other researchers to apply the modified Bateman SIZ model to obtain predictions for COVID-19 outbreaks in other regions. Application of the model has been verified by independent investigators using different commercial software packages. CONCLUSION The modified Bateman SIZ model has been verified and used to predict the course of the COVID-19 pandemic in Heidelberg. Lockdown measures alone are insufficient to control the pandemic during 2021. Vaccination, diagnostic tests, and use of the Corona-Warn-App with quarantine could successfully control the spread of the coronavirus infection in the community. The Corona-Warn-App applied correctly may be the most effective. The model showed that vaccination with 50% efficacy is almost as effective as vaccination with 100% efficacy.


FAO calls for more surveillance and research on MERS.


title: Ammonia disinfection of hatchery waste for elimination of single-stranded RNA viruses.

text: Hatchery waste, an animal by-product of the poultry industry, needs sanitation treatment before further use as fertilizer or as a substrate in biogas or composting plants, owing to the potential presence of opportunistic pathogens, including zoonotic viruses. Effective sanitation is also important in viral epizootic outbreaks and as a routine, ensuring high hygiene standards on farms. This study examined the use of ammonia at different concentrations and temperatures to disinfect hatchery waste. Inactivation kinetics of high-pathogenic avian influenza virus H7N1 and low-pathogenic avian influenza virus H5N3, as representatives of notifiable avian viral diseases, were determined in spiked hatchery waste. Bovine parainfluenza virus type 3, feline coronavirus, and feline calicivirus were used as models for other important avian pathogens, such as Newcastle disease virus, infectious bronchitis virus, and avian hepatitis E virus. Bacteriophage MS2 was also monitored as a stable indicator. Coronavirus was the most sensitive virus, with decimal reduction (D) values of 1.2 and 0.63 h after addition of 0.5% (wt/wt) ammonia at 14 and 25°C, respectively. Under similar conditions, high-pathogenic avian influenza H7N1 was the most resistant, with D values of 3.0 and 1.4 h. MS2 was more resistant than the viruses to all treatments and proved to be a suitable indicator of viral inactivation. The results indicate that ammonia treatment of hatchery waste is efficient in inactivating enveloped and naked single-stranded RNA viruses. Based on the D values and confidence intervals obtained, guidelines for treatment were proposed, and one was successfully validated at full scale at a hatchery, with MS2 added to hatchery waste.


False Negative Tests for SARS-CoV-2 Infection - Challenges and Implications.


title: Sevoflurane remifentanil interaction: comparison of different response surface models.

text: BACKGROUND Various pharmacodynamic response surface models have been developed to quantitatively describe the relationship between two or more drug concentrations with their combined clinical effect. We examined the interaction of remifentanil and sevoflurane on the probability of tolerance to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy in patients to compare the performance of five different response surface models. METHODS Forty patients preoperatively received different combined concentrations of remifentanil (0-12 ng/ml) and sevoflurane (0.5-3.5 vol.%) according to a criss-cross design (160 concentration pairs, four per patient). After having reached pseudosteady state, the response to shake and shout, tetanic stimulation, laryngeal mask airway insertion, and laryngoscopy was recorded. For the analysis of the probability of tolerance, five different interaction models were tested: Greco, Reduced Greco, Minto, Scaled C50(O) Hierarchical, and Fixed C50(O) Hierarchical model. All calculations were performed with NONMEM VI (Icon Development Solutions, Ellicott City, MD). RESULTS The pharmacodynamic interaction between sevoflurane and remifentanil was strongly synergistic for both the hypnotic and the analgesic components of anesthesia. The Greco model did not result in plausible parameter estimates. The Fixed C50(O) Hierarchical model performed slightly better than the Scaled C50(O) Hierarchical and Reduced Greco models, whereas the Minto model fitted less well. CONCLUSION We showed the importance of exploring various surface model approaches when studying drug interactions. The Fixed C50(O) Hierarchical model fits our data on sevoflurane remifentanil interaction best and appears to be an appropriate model for use in hypnotic-opioid drug interaction.


title: Intranasal oxytocin reduces heart rate variability during a mental arithmetic task: A randomised, double-blind, placebo-controlled cross-over study.

text: Heart rate variability (HRV) refers to variation in the interval between successive heart beats. Low HRV is an indicator of potential autonomic nervous system dysfunction. People with chronic pain often display autonomic dysregulation, especially in the parasympathetic nervous system. The hormone oxytocin has been shown to increase HRV in non-clinical samples, but its potential impact on HRV in persons with chronic pain is unknown. This study investigated the impact of intranasal oxytocin on HRV in persons with chronic neck and shoulder pain. Participants included 24 individuals with chronic neck and shoulder pain lasting >12months and 24 age- and sex-matched pain-free controls. In a randomised double-blind, placebo-controlled, cross-over study, participants self-administered intranasal oxytocin (24IU) in one session, and placebo in another, before HRV was recorded at rest and during a mental arithmetic task. Intranasal oxytocin did not influence HRV at rest. However, compared to placebo, intranasal oxytocin elicited small decreases in low-frequency and high-frequency HRV in both groups during the mental arithmetic task. These results suggest that intranasal oxytocin may enhance the salience of the mental arithmetic task, leading to reduced engagement of the parasympathetic nervous system when completing the task. Further investigation and replication of these findings are required to improve our understanding of the effects of intranasal oxytocin on autonomic functioning both at rest and under cognitive stress.


title: Initial experiences using robot-assisted central pancreatectomy with pancreaticogastrostomy: a potential way to advanced laparoscopic pancreatectomy.

text: BACKGROUND Benign and borderline malignant pancreatic tumors are increasing. Function-preserving and minimally invasive pancreatectomy may be an ideal approach for these tumors. METHODS The authors retrospectively evaluated their initial experiences with five consecutive robotic central pancreatectomies (CPs). They also compared the perioperative outcome for open CPs performed in their institution. RESULTS The five women in the study had a median age of 45 years (range 36-64 years). A solid pseudopapillary tumor of the pancreas was found in four patients, and a pancreatic endocrine tumor was found in one patient. The tumor was relatively small (median size, 1.5 cm; range, 1-2 cm). All remnant pancreases were managed using pancreaticogastrostomy. The median operation time was 480 min (range 360-480 min), and the median estimated intraoperative bleeding was 200 ml (range 100-600 ml). No transfusion was given during the perioperative period. The median hospital stay was 12 days (range 9-28 days). Only one patient experienced postoperative pancreatic fistula (grade B), which was managed using the percutaneous drainage procedure. No operative morality was noted. In a comparative analysis with open CP, the robotic CP group demonstrated a smaller asymptomatic (17 out of 10 patients vs none, p = 0.026) tumor (5.9 ± 6.4 vs 1.4 ± 0.4 cm; p = 0.055), a longer operation time (286.5 ± 90.2 vs 432.0 ± 65.7 min, p = 0.013), and less intraoperative bleeding (432.0 ± 65.7 vs 286.5 ± 90.2 ml, p = 0.013). CONCLUSION Central pancreatectomy can be selected carefully as an appropriate surgical option for benign and borderline malignant lesions limited to the pancreatic neck area. The robotic surgical system may allow surgeons to perform complex and difficult laparoscopic procedures more easily, effectively, and precisely.


Superficial temporal artery haemorrhage caused by neurophysiological monitoring: a unique MRI finding.


title: Laparoendoscopic single-site retroperitoneoscopic adrenalectomy versus conventional retroperitoneoscopic adrenalectomy: initial experience by the same laparoscopic surgeon.

text: PURPOSE The purpose of this study was to demonstrate our initial experience with and the feasibility of laparoendoscopic single-site retroperitoneoscopic adrenalectomy (LESS-RA). PATIENTS AND METHODS 54 patients undergoing conventional retroperitoneoscopic adrenalectomy were compared with 27 patients undergoing LESS-RA. The adrenal tumors were considered to be benign preoperatively and <6 cm. Age, sex, laterality, body mass index, surgical indications, time to resuming oral intake, tumor size, operation time, estimated blood loss, intravenous or intramuscular analgesics (pethidine) and postoperative hospital stay were compared between the two groups. Analysis of covariance was applied to analyze postoperative hospital stay and time to resuming oral intake. RESULTS The length of postoperative hospital stay was significantly higher in the conventional retroperitoneoscopic adrenalectomy group in the adjusted and unadjusted model. The time to resuming oral intake was significant shorter in the LESS-RA group, but was not significant after adjusting opioid analgesics dosage. No conversions to an open or conventional retroperitoneoscopic approach were necessary. There were neither complications nor blood transfusions in both groups. CONCLUSIONS LESS-RA for benign adrenal tumors is a feasible surgical procedure when tumors are <6 cm. Further clinical research is warranted to define the role of LESS in adrenal surgery and to prove its efficacy over conventional laparoscopic surgery.


title: Observational Study Design in Veterinary Pathology, Part 1: Study Design.

text: Observational studies are the basis for much of our knowledge of veterinary pathology and are highly relevant to the daily practice of pathology. However, recommendations for conducting pathology-based observational studies are not readily available. In part 1 of this series, we offer advice on planning and conducting an observational study with examples from the veterinary pathology literature. Investigators should recognize the importance of creativity, insight, and innovation in devising studies that solve problems and fill important gaps in knowledge. Studies should focus on specific and testable hypotheses, questions, or objectives. The methodology is developed to support these goals. We consider the merits and limitations of different types of analytic and descriptive studies, as well as of prospective vs retrospective enrollment. Investigators should define clear inclusion and exclusion criteria and select adequate numbers of study subjects, including careful selection of the most appropriate controls. Studies of causality must consider the temporal relationships between variables and the advantages of measuring incident cases rather than prevalent cases. Investigators must consider unique aspects of studies based on archived laboratory case material and take particular care to consider and mitigate the potential for selection bias and information bias. We close by discussing approaches to adding value and impact to observational studies. Part 2 of the series focuses on methodology and validation of methods.


title: Single-port video-assisted thoracoscopic wedge resection: novel approaches in different genders.

text: OBJECTIVES To discuss the feasibility, safety and superiority of novel approaches in single-port video-assisted thoracoscopic wedge resection in different genders. METHODS The clinical data of patients who underwent thoracoscopic pulmonary wedge resection were analysed. A total of 197 consecutive male patients from January 2012 to December 2014, and 72 female patients from June 2013 to December 2014 were included retrospectively. Of the males, 65 received a transareolar single-port procedure (TASP Group) and 132 received a standard two-port procedure (Standard Group A). Among the females, 18 were treated with a subxiphoid single-port procedure (SXSP Group), and 54 were treated with the standard procedure (Standard Group B). The general clinical materials and surgical outcomes were evaluated. RESULTS All patients underwent total thoracoscopic wedge resection successfully, and no severe complications were observed. In men, there were no significant differences in operation time, blood loss, postoperative drainage amount, chest drainage duration, postoperative hospital stay or pain score on the first postoperative day (P = 0.827; 0.423; 0.174; 0.440; 0.115; 0.159, respectively). The pain scores of the TASP Group on the day before and after removal of the chest tube were lower (P = 0.006; 0.023, respectively) than those of Standard Group A, and the incision-associated paraesthesia in the third and sixth month after operation was reduced (P = 0.041; 0.026, respectively). The incision satisfaction degree was significantly improved in the TASP Group (P = 0.001). In women, there were no significant differences in blood loss, drainage amount, chest drainage duration or postoperative hospital stay (P = 0.680; 0.757; 0.651; 0.608, respectively). The operation time of the SXSP Group was longer (P = 0.000), and the pain scores on the first postoperative day and the days before and after removal were all significantly lower (P = 0.000; 0.000; 0.000, respectively) than those of the Standard Group B. Furthermore, the incision paraesthesia 3 and 6 months after surgery was greatly reduced (P = 0.001; 0.001, respectively), although the patients were not very satisfied with the cosmetic results (P = 0.577). CONCLUSIONS In single-port thoracoscopic pulmonary wedge resection, we performed 'individualized' procedures based on gender, namely, the transareolar approach in males and the subxiphoid approach in females. These procedures were considered feasible and safe, and showed superiority in reducing postoperative pain. However, the cosmetic results of the subxiphoid approach require further improvement.


title: Occupational health nursing and the quest for professional authority.

text: Occupational health nurses provide most of the in-plant health care services in U.S. industry but have dubious credentials to provide care for many of the injuries and illnesses they encounter. The nurses work directly for the employer in an atmosphere designed to control employer costs and employee benefits. Their loyalty to the company and limited autonomy make it unlikely that they will represent the workers' interests. They generally embrace any expansion of their roles within the company. However, employers and government have made no serious effort to determine whether nurses can adequately take on these new functions and advance occupational health. A nurse-directed model carries the risk that nurses who are not knowledgeable enough about the law, or are overly committed to reducing costs, may overdelegate responsibilities, thereby aiding and abetting the unlicensed practice of nursing. This overreaching is part of an ill-conceived effort to establish nursing as a profession with the greater independence, expertise, and control over training that longstanding professions such as medicine and law have achieved. An extensive literature devoted to the approval and acceptance of occupational health nursing exists, yet constructive criticism of occupational health nursing is almost nonexistent. Occupational health and safety is much too important to be largely relegated to an inadequately defined semi-profession, striving to attain higher professional status and control while lacking the expertise, power, professional standards, and autonomy required of a profession.


title: Tissue reaction induced by implanted venous access ports in adult patients after infection of the implantation site.

text: Implantable long-term central venous port systems (CVPS) are widely used as a permanent means of accessing the vascular system for intravenous delivery of drugs, parenteral nutrition, blood transfusion, and blood sampling. These systems allow easy and repetitive puncture without causing much damage to the vessels. However, the body foreign surface of CVPS induces an inflammatory response with varying intensity (depending on the implant materials) that leads to formation of a fibrous tissue capsule around the implant. This study was designed to investigate the influence of bacterial infection on the tissue reaction induced by implanted CVPS in adult patients. 20 patients (9 women, 11 men, 58 ± 14 yrs of age) were included in this study. These patients received explantation of a polysulfone based CVPS (ChemoSite™, Covidien, Mansfield, USA) due to port related infections (patients with bacterial infections at the implantation site: group A, 5 men, 1 women) or to other reasons such as termination of treatment, thrombosis, or CVPS dysfunction (patients without bacterial infections, group B, 6 men, 8 women) 299.9 ± 261.2 days after CVPS implantation. A sample of the encapsulating tissue covering the CVPS together with surrounding tissue (at least 1 × 1 cm2) was placed in a small container with fixing agent, a buffered neutral 4% formalin solution (pH 7). Histological sections of the samples were prepared for light microscopic analysis after paraffin embedding. Sections of 3 μm were cut and stained with haematoxylin and eosin, Weigert's elastic stain, and Heidenhain's azan stain. There was no difference in thickness, collagen and elastin content, or cell and capillary density of the fibrous capsule between both groups. Due to the wound healing reaction involving angiogenesis and fibroblast activation cell density and number of capillaries in the capsule tissue of all patients showed a positive correlation (r = 0.45, p < 0.05). However, the study demonstrated that at the end of the foreign body reaction the artificial tissue layer which covers the CVPS after implantation due to foreign body reaction shows only low reactivity towards infections.


title: Appropriate Antibiotic Use for Acute Respiratory Tract Infection in Adults: Advice for High-Value Care From the American College of Physicians and the Centers for Disease Control and Prevention.

text: BACKGROUND Acute respiratory tract infection (ARTI) is the most common reason for antibiotic prescription in adults. Antibiotics are often inappropriately prescribed for patients with ARTI. This article presents best practices for antibiotic use in healthy adults (those without chronic lung disease or immunocompromising conditions) presenting with ARTI. METHODS A narrative literature review of evidence about appropriate antibiotic use for ARTI in adults was conducted. The most recent clinical guidelines from professional societies were complemented by meta-analyses, systematic reviews, and randomized clinical trials. To identify evidence-based articles, the Cochrane Library, PubMed, MEDLINE, and EMBASE were searched through September 2015 using the following Medical Subject Headings terms: "acute bronchitis," "respiratory tract infection," "pharyngitis," "rhinosinusitis," and "the common cold." HIGH-VALUE CARE ADVICE 1 Clinicians should not perform testing or initiate antibiotic therapy in patients with bronchitis unless pneumonia is suspected. HIGH-VALUE CARE ADVICE 2 Clinicians should test patients with symptoms suggestive of group A streptococcal pharyngitis (for example, persistent fevers, anterior cervical adenitis, and tonsillopharyngeal exudates or other appropriate combination of symptoms) by rapid antigen detection test and/or culture for group A Streptococcus. Clinicians should treat patients with antibiotics only if they have confirmed streptococcal pharyngitis. HIGH-VALUE CARE ADVICE 3 Clinicians should reserve antibiotic treatment for acute rhinosinusitis for patients with persistent symptoms for more than 10 days, onset of severe symptoms or signs of high fever (>39 °C) and purulent nasal discharge or facial pain lasting for at least 3 consecutive days, or onset of worsening symptoms following a typical viral illness that lasted 5 days that was initially improving (double sickening). HIGH-VALUE CARE ADVICE 4 Clinicians should not prescribe antibiotics for patients with the common cold.


title: Feasibility and safety of laparoscopic colorectal surgeries for patients with left ventricular assist device.

text: PURPOSE There is limited literature regarding the feasibility and safety of laparoscopic procedures in patients having mechanical circulatory support, especially colonic resections. METHODS The aim of this study is to present the case of a laparoscopic colectomy for cancer undergone in a 69-year-old patient having a HeartWare II at our institution without any postoperative major complications and to describe the perioperative management and outcome of these patients according to the literature, regarding the hemodynamic, hemorrhagic, and infectious risks and the safety of this procedure. RESULTS There was no 90-day postoperative morbidity or death. A total of six patients including ours were identified in the study. This study has a limited number of patients and relatively short follow-up time. CONCLUSION Even though the management of patients having a LVAD is challenging and needs a multidisciplinary approach, reported literatures have shown the safety and feasibility of laparoscopic interventions for colorectal surgeries.


title: EFFECTS OF PLANT PROTEIN DIETS ON THE HEALTH OF FARMED AMERICAN ALLIGATORS (ALLIGATOR MISSISSIPPIENSIS).

text: The objective of this prospective, blinded study was to compare plasma biochemical values and gross and histologic evaluation of kidney and liver from American alligators ( Alligator mississippiensis ) fed extruded diets with protein derived from animal or plant sources. Alligators in two treatment groups were fed an extruded diet with protein derived primarily from plant products for 7 (n = 20) or 10 (n = 20) mo prior to harvest. A control group (n = 20) was fed a commercial diet with protein derived from animal products for the duration of the study. Plasma biochemistry panels were obtained and gross and histologic examination of kidney and liver tissues was conducted for each animal. No differences were found between alligators fed diets with animal or plant protein in terms of either biochemistry profiles or gross or histologic examination of kidney and liver. Plant-based diets, fed for up to 10 mo, do not appear to have any ill effects on the kidney or liver of American alligators.


title: The THRIVE score strongly predicts outcomes in patients treated with the Solitaire device in the SWIFT and STAR trials.

text: BACKGROUND The Totaled Health Risks in Vascular Events (THRIVE) score strongly predicts clinical outcome, mortality, and risk of thrombolytic haemorrhage in ischemic stroke patients, and performs similarly well in patients receiving intravenous tissue plasminogen activator, endovascular stroke treatment, or no acute treatment. It is not known if the THRIVE score predicts outcomes with the Solitaire endovascular stroke treatment device. AIMS To validate the relationship between the THRIVE score and outcomes after treatment with the Solitaire endovascular stroke treatment device. METHODS The study conducted a retrospective analysis of the prospective SWIFT and STAR trials to examine the relationship between THRIVE and outcomes after treatment with the Solitaire device. We examined the relationship between THRIVE and clinical outcomes (good outcome or death at 90 days) among patients in SWIFT and STAR. Receiver-operator characteristics curve analysis was used to compare THRIVE score performance with other stroke prediction scores. Multivariable modeling was used to confirm the independence of the THRIVE score from procedure-specific predictors (successful recanalization or device used) and other predictors of functional outcome. RESULTS The THRIVE score strongly predicts good outcome and death among patients treated with the Solitaire device in SWIFT and STAR (Mantel-Haenszel chi-square test for trend P < 0·001 for good outcome, P = 0·01 for death). In receiver-operator characteristics (ROC) curve comparisons, totaled health risks in vascular events score is superior to Stroke Prognostication using Age and NIH Stroke Scale score-100 (P < 0·001) and performed similarly to Houston Intra-Arterial Therapy score (HIAT) (P = 0·98) and HIAT-2 (P = 0·54). In multivariable models, THRIVE's prediction of good outcome is not altered after controlling for recanalization or after controlling for device used. The THRIVE score remains a strong independent predictor after controlling for the above predictors together with time to procedure, rate of symptomatic haemorrhage, and use of general anesthesia. Of note, use of general anesthesia was not an independent predictor of outcome in SWIFT + STAR after controlling for totaled health risks in vascular events and other factors. CONCLUSIONS The THRIVE score strongly predicts clinical outcome and mortality in patients treated with the Solitaire device in the SWIFT and STAR trials. The lack of interaction between THRIVE and procedure-specific elements such as vessel recanalization or device choice makes the THRIVE score a reasonable candidate for use as a patient selection criterion in stroke clinical trials.


title: Interventions to Prevent and Reduce Burnout Among Undergraduate and Graduate Medical Education Trainees: a Systematic Review.

text: OBJECTIVE The authors conducted a systematic review of the published literature to identify interventions to prevent and/or reduce burnout among medical students and residents. METHODS The authors searched 10 databases (from the start of each through September 21, 2016) using keywords related to burnout, medical education, and prevention. Teams of two authors independently reviewed the search results to select peer-reviewed, English language articles describing educational interventions to prevent and/or reduce burnout among medical students and/or residents that were evaluated using validated burnout measures. They assessed study quality using the Medical Education Research Study Quality Instrument and the Cochrane Risk of Bias Tool. RESULTS Fourteen studies met inclusion criteria and all used the Maslach Burnout Inventory as at least one measure of burnout. Four were single group pre-post studies, 6 non-randomized two-group studies, and 4 randomized controlled trials. None of the studies were designed specifically to target burnout prevention. In 12 studies, residents were the targeted learners. Six of the 14 studies reported statistically significant changes in burnout scores: 5 reported improvement and 1 reported worsening of burnout. Of the 5 studies that reported statistically significant benefit, 1 studied a complementary and alternative medicine elective, 1 studied the Respiratory One Meditation method, and 3 studied duty hour changes. CONCLUSIONS This review highlights the need for rigorously designed studies in burnout prevention and reduction among residents and especially medical students.


title: Technical Evaluation of Soft Mist Inhaler Use in Patients with Chronic Obstructive Pulmonary Disease: A Cross-Sectional Study.

text: Background Proper inhaler technique is highly relevant to the effective management of chronic obstructive pulmonary disease (COPD). The tiotropium bromide spray (TBS) (Spiriva® Respimat®) is a soft mist inhaler (SMI) preferred by patients to pressurized metered-dose inhalers (pMDIs) and dry powder inhalers (DPIs) because of its convenience in use. However, the technique of using TBS inhaler in the real world is unclear. Objective To evaluate techniques in using TBS inhaler and investigate the association between the patient characteristics and the correct use of TBS inhaler. Methods This cross-sectional study enrolled 74 COPD patients who used TBS inhaler device for more than 3 months. The sociodemographic and clinical characteristics of the patients were recorded. The technique of using TBS inhaler was evaluated step by step. Incorrect use was defined as the patient's inability to complete the key steps in the inhalation manoeuvre. The percentage of incorrect use was compared between the groups. Risk factors related to incorrect use were analyzed by logistic regression analysis. Results Of the 74 participants, only 2 (2.7%) patients completed all the steps correctly, and 48 (64.9%) patients misused the key steps in the inhalation manoeuvre. Incorrect preparation of the TBS inhaler for the first use was the most frequently misused step, accounting for 77.0%. Factors associated with misuse of TBS inhaler included the educational background (p=0.010), living state (p=0.031) and COPD assessment test (CAT) score (p=0.005) of the patients. Additionally, logistic regression analysis showed that the COPD duration was significantly associated with the incorrect use (p=0.019). Compared with patients with a higher educational background, patients with an elementary school background [OR 11652.99, CI: 22.72-5975697.72], junior high school background [OR 7187.78, CI: 16.41-3146787] and high school background [OR 1563, CI: 4.27-572329.67] were more likely to misuse TBS inhaler. Patients living with their spouses alone were also more likely to commit errors in using TBS inhaler as compared with those living with their children [OR 12.29, CI of 1.14-1.96]. Clinical factors like the COPD symptoms were relative to the technical use of the device. Better technique was accompanied by a lower CAT score [OR 1.49, CI of 1.14-1.96]. Conclusion The incorrect use of TBS inhaler was common in COPD patients. Healthcare providers should not only teach the patients about the drug preparation but help them use the inhaler correctly. Special attention should be paid to patients with a short COPD duration and a low educational background and those who live without the company of their children. Proper use of TBS inhaler can significantly improve the symptom control of COPD patients.


title: TIM3 comes of age as an inhibitory receptor.

text: T cell immunoglobulin and mucin domain-containing protein 3 (TIM3), a member of the TIM family, was originally identified as a receptor expressed on interferon-γ-producing CD4+ and CD8+ T cells. Initial data indicated that TIM3 functioned as a 'co-inhibitory' or 'checkpoint' receptor, but due to the lack of a definable inhibitory signalling motif, it was also suggested that TIM3 might act as a co-stimulatory receptor. Recent studies have shown that TIM3 is part of a module that contains multiple co-inhibitory receptors (checkpoint receptors), which are co-expressed and co-regulated on dysfunctional or 'exhausted' T cells in chronic viral infections and cancer. Furthermore, co-blockade of TIM3 and programmed cell death 1 (PD1) can result in tumour regression in preclinical models and can improve anticancer T cell responses in patients with advanced cancers. Here, we highlight the developments in understanding TIM3 biology, including novel ligand identification and the discovery of loss-of-function mutations associated with human disease. In addition, we summarize emerging data from human clinical trials showing that TIM3 indeed acts as a 'checkpoint' receptor and that inhibition of TIM3 enhances the antitumour effect of PD1 blockade.


title: Trends in patient reported outcomes of conservative and surgical treatment of primary chronic venous disease contradict current practices.

text: OBJECTIVE To analyze patient-reported quality of life (QOL) and symptoms in a prospective cohort of CVD patients who was managed within the framework of existing policies. STUDY DESIGN Prospective cohort study of 150 patients with C2-C4 clinical class of primary chronic venous disease (CVD). Management consisted of initial conservative measures, following which, the patients were given a choice of continuing conservative therapy, or surgical treatment. Patients completed Specific Quality of Life and Outcome Response--Venous (SQOR-V) tool before initial visit, after completion of conservative treatment, and at 1 and 12 month follow up visits after surgical treatment. Management consisted of initial conservative measures. QOL score and symptom score (SS) part of this instrument was analyzed separately. RESULTS Conservative treatment resulted in improvement of symptom score in 85(57%) patients, and the QOL in 111(74%) patients. Despite this improvement, the majority of patients (121) chose surgical option. At the 1-month follow up after surgical treatment 97 (80%) patients reported significant improvement of their symptoms and 114 (94%) in the QOL compare to their status after conservative therapy. The QOL improvement was due mainly to improvement in symptom score. Patients who improved after conservative therapy were more than 15 times more likely to have symptoms relief at 1 month (RR = 15.6, 95% CI 4.3-56.5), and 21 times higher at 1 year after surgery (RR = 21.3, 95% CI 4.7-96.9) compared with those who did not change the SS. CONCLUSIONS Surgical treatment resulted in a better relief of symptoms compare to conservative therapy. The relief of symptoms after conservative therapy predicts better outcomes of surgical treatment. These findings suggest that success of conservative therapy should be considered as an indication, and the failure of conservative therapy should not be an indication to surgical treatment.


title: Severe SARS-CoV-2 Infection in Children With Suspected Acute Abdomen: A Case Series From a Tertiary Hospital in Spain.

text: We describe 5 children with severe SARS-CoV-2 infection, hemodynamic instability and suspected acute abdomen. This form of the disease has not been previously documented. Four of the cases were confirmed SARS-CoV-2 infection and 1 probable. All of them were previously healthy and needed a pediatric critical care unit admission. The respiratory symptoms were not dominant or were absent. Also, fever was observed. Laboratory testing revealed lymphopenia and high levels of C-reactive protein and procalcitonin with D-dimer, ferritin and interleukin-6 usually elevated. Respiratory support and inotropic support were almost always necessary. In all of them, deterioration occurred on the day of admission.


title: Single-port access laparoscopic reversal of Hartmann operation.

text: BACKGROUND Single-port access offers cosmetic advantages in addition to the well-recognized benefits of standard multiport laparoscopic surgery, and can be performed with the use of standard straight instruments. We describe a technique of single-port access reversal of Hartmann colostomy by use of the colostomy site for access. METHODS After routine skin preparation and laparoscopic setup, the colostomy is mobilized from its mucocutaneous border, and the anvil of a circular stapler is secured to the distal lumen. By the use of a GelPoint system with 3 or 4 trocars, the intra-abdominal adhesions are divided and the splenic flexure is mobilized to achieve sufficient access to the abdominal and pelvic cavities and proximal colonic mobility. The rectal stump is mobilized to the mid rectum, starting from the posterior mesorectal fascia around to the anterior rectal wall. A tension-free colorectal anastomosis is secured with a standard circular stapling device inserted transanally, and leak tested. The colostomy wound is closed in standard fashion. RESULTS Five patients underwent single-port access reversal of Hartmann resection (4 diverticular perforations and 1 pT3N0 colon cancer), with a mean operating time of 155 (range, 137-187) minutes and a median length of stay of 3 (range, 2-11) days. There were no conversions, major surgical morbidity, or deaths. CONCLUSION Single-port access reversal of Hartmann colostomy through the stoma site is safe, and it offers additional cosmetic advantages with no apparent additional morbidity in comparison with standard multiport surgery.


title: Six Propositions against Ageism in the COVID-19 Pandemic.

text: The risk of developing severe illness from COVID-19 and of dying from it increases with age. This statistical association has led to numerous highly problematic policy suggestions and comments revealing underlying ageist attitudes and promoting age discrimination. Such attitudes are based on negative stereotypes on the health and functioning of older adults. As a result, the lives of older people are disvalued, including in possible triage situations and in the potential limitation of some measures against the spread of the pandemic to older adults. These outcomes are unjustified and unethical. We develop six propositions against the ageism underlying these suggestions to spur a more adequate response to the current pandemic in which the needs and dignity of older people are respected.


Pandemic carves gaps in long-term field projects.


title: Robotic extrahepatic Glissonean pedicle approach for anatomic liver resection in the right liver: techniques and perioperative outcomes.

text: BACKGROUND The Glissonean pedicle approach is one of the most popular methods of anatomic liver surgery. Liver surgeons have attempted to reproduce this method laparoscopically. In this study, we introduce our technique of the extrahepatic Glissonean approach for anatomic liver resections, using a robotic system, and report on short-term perioperative outcomes. METHODS From December 2008 to July 2014, 10 patients underwent robotic anatomic liver resection in the right liver. The procedure is as follows: (1) mobilization of the liver and isolation and clamping of a selected Glissonean pedicle; (2) transection of the liver parenchyma using a rubber band retraction technique; (3) division of the Glissonean pedicle after full exposure, followed by completion of parenchymal transection. RESULTS The median age of the patients was 52.50 (range 28-59) years, and seven were male. All patients had hepatocellular carcinoma. The types of resections performed were as follows: segmentectomy 6 (n = 1), segmentectomy of 4b + 5 ventral segments (n = 2), right posterior sectionectomy (n = 3), extended right hepatectomy (n = 1), extended right posterior sectionectomy (n = 2), and central bisectionectomy (n = 1). Only one case was converted to open surgery due to severe tumor adhesions on the diaphragm. The median operative time was 555 min (range 413-848), and the median estimated blood loss was 225 ml (range 30-700), with no perioperative transfusions. The overall complication rate was 70 % (grade I, 5; grade II, 1; grade III, 1; grade IV, 0). The median length of hospital stay postsurgery was 7 days (range 6-11). CONCLUSION Robotic surgery allowed for successful anatomic liver resections via an extrahepatic Glissonean pedicle approach in the right liver and can be safely performed in selected patients.


title: Scientific Advances in Thoracic Oncology 2016.

text: Lung cancer care is rapidly changing with advances in genomic testing, the development of next-generation targeted kinase inhibitors, and the continued broad study of immunotherapy in new settings and potential combinations. The International Association for the Study of Lung Cancer and the Journal of Thoracic Oncology publish this annual update to help readers keep pace with these important developments. Experts in thoracic cancer and care provide focused updates across multiple areas, including prevention and early detection, molecular diagnostics, pathology and staging, surgery, adjuvant therapy, radiotherapy, molecular targeted therapy, and immunotherapy for NSCLC, SCLC, and mesothelioma. Quality and value of care and perspectives on the future of lung cancer research and treatment have also been included in this concise review.


Validation: The Use of Google Trends as an Alternative Data Source for COVID-19 Surveillance in Indonesia.


title: Single-incision laparoscopic Heller myotomy and Dor fundoplication for achalasia: report of a case.

text: Our objective was to establish the efficiency of single-incision laparoscopic Heller myotomy and Dor fundoplication (SILHD) as treatment for esophageal achalasia. A 58-year-old man underwent SILHD for achalasia. The left triangular ligament was retracted using a suture thread and fixed to the body surface, providing a good operative field at the cardia. We performed a 7-cm long myotomy, extending 2 cm into the gastric wall, using a tissue-sealing device or L-shaped electrocautery. Oral intake resumed on postoperative day 1, and hospital stay was 4 days. No morbidity was observed. Based on our experience, we believe that the SILHD can be performed safely and seems to offer at least short-term benefits for selected patients with esophageal achalasia, when performed by surgeons experienced in laparoscopic and esophageal surgery.


title: Validation of the Hologic's Aptima Unisex and Multitest Specimen collection kits used for Endocervical and Male Urethral Swab Specimen (Aptima Swab) for sample collection of SARS-CoV-2.

text: Recent events have seen the rise of SARS-CoV-2 all across the world affecting the lives and economies of every nation.….


title: Migration of health workers in the Pacific Islands: a bottleneck to health development.

text: Human resources for health (HRH) are a crucial component of a well-functioning health system. Problems in the global HRH supply and distribution are an obstacle to achieving the health-related Millennium Development Goals and other health outcomes. The Pacific Island region, covering 20,000 to 30,000 islands in the South Pacific Ocean, is suffering a serious HRH crisis. Yet updated evidence and data are not available for the 22 Pacific Island Countries and Territories. The objective of this study was thus to explore the current HRH situation in the Pacific Island region, focusing particularly on the issue of health workforce migration. HRH trends and gaps differ by country, with some showing increases in HRH density over the past 20 years whereas others have made negligible progress. Currently, three Pacific Island countries are facing critical HRH shortages, a worsening of the situation from 2006, when HRH issues were first brought to widespread global attention. In this region, skilled personnel migration is a major issue contributing to the limited availability of HRH. Political commitment from source and destination countries to strengthen HRH would be a key factor toward increasing efforts to train new health personnel and to implement effective retention strategies.


title: A conserved domain in the coronavirus membrane protein tail is important for virus assembly.

text: Coronavirus membrane (M) proteins play key roles in virus assembly, through M-M, M-spike (S), and M-nucleocapsid (N) protein interactions. The M carboxy-terminal endodomain contains a conserved domain (CD) following the third transmembrane (TM) domain. The importance of the CD (SWWSFNPETNNL) in mouse hepatitis virus was investigated with a panel of mutant proteins, using genetic analysis and transient-expression assays. A charge reversal for negatively charged E(121) was not tolerated. Lysine (K) and arginine (R) substitutions were replaced in recovered viruses by neutrally charged glutamine (Q) and leucine (L), respectively, after only one passage. E121Q and E121L M proteins were capable of forming virus-like particles (VLPs) when coexpressed with E, whereas E121R and E121K proteins were not. Alanine substitutions for the first four or the last four residues resulted in viruses with significantly crippled phenotypes and proteins that failed to assemble VLPs or to be rescued into the envelope. All recovered viruses with alanine substitutions in place of SWWS residues had second-site, partially compensating, changes in the first TM of M. Alanine substitution for proline had little impact on the virus. N protein coexpression with some M mutants increased VLP production. The results overall suggest that the CD is important for formation of the viral envelope by helping mediate fundamental M-M interactions and that the presence of the N protein may help stabilize M complexes during virus assembly.


title: Angiotensin-converting enzyme 2 ectodomain shedding cleavage-site identification: determinants and constraints.

text: ADAM17, also known as tumor necrosis factor α-converting enzyme, is involved in the ectodomain shedding of many integral membrane proteins. We have previously reported that ADAM17 is able to mediate the cleavage secretion of the ectodomain of human angiotensin-converting enzyme 2 (ACE2), a functional receptor for the severe acute respiratory syndrome coronavirus. In this study, we demonstrate that purified recombinant human ADAM17 is able to cleave a 20-amino acid peptide mimetic corresponding to the extracellular juxtamembrane region of human ACE2 between Arg(708) and Ser(709). A series of peptide analogues were also synthesized, showing that glutamate subtitution at Arg(708) and/or Arg(710) attenuated the cleavage process, while alanine substitution at Arg(708) and/or Ser(709) did not inhibit peptide cleavage by recombinant ADAM17. Analysis of CD spectra showed a minimal difference in the secondary structure of the peptide analogues in the buffer system used for the ADAM17 cleavage assay. The observation of the shedding profiles of ACE2 mutants expressing CHO-K1 and CHO-P cells indicates that the Arg(708) → Glu(708) mutation and the Arg(708)Arg(710) → Glu(708)Glu(710) double mutation produced increases in the amount of ACE2 shed when stimulated by phorbol ester PMA. In summary, we have demonstrated that ADAM17 is able to cleave ACE2 peptide sequence analogues between Arg(708) and Ser(709). These findings also indicate that Arg(708) and Arg(710) play a role in site recognition in the regulation of ACE2 ectodomain shedding mediated by ADAM17.


title: Help-Seeking Behavior of Returning to Work in Healthcare Workers and its Influencing Factors During COVID-19 Subsiding.

text: OBJECTIVES To explore the level and influencing factors of help-seeking behavior of returning to work in healthcare Workers (HCWs). METHODS A total of 861 HCWs were surveyed. A structured self-administered questionnaire was used to collect data. Multivariable logistic regression was performed to examine the influencing factors of help-seeking behavior. RESULTS HCWs sought help with respect to COVID-19-diagnosised problem most. Help-seeking intention, problems encountered after return, test for return, work condition during COVID-19, relatives or friends diagnosed or suspected as COVID-19 and socio-demographic characteristics such as occupation, education, title and marriage status are predictors of help-seeking behavior. CONCLUSIONS Education and intervention should lay particular stress on HCWs featured rest at home before return, doctor, lower education and lower title to ensure the safety, accuracy and quality of work after they return to work for a better occupational environment.


Perspectives on personal protective equipment in acute-care facilities during the COVID-19 pandemic.


title: Endoscopic slip-knot clip suturing method: prospective pilot study (with video).

text: BACKGROUND AND AIMS We developed a suturing method with a slip-knot string and clips for a single-channel endoscope. The feasibility of the slip-knot clip suturing method was evaluated in this clinical pilot study. METHODS Ten patients underwent endoscopic submucosal dissection for colorectal and duodenal tumors 5 cm or less. A slip-knot loop can be tightened when tension is applied to the free end of the string. A clip and string can be passed through an instrument channel (3.2 mm) of a single-channel endoscope. The slip-knot loop is anchored onto the mucosal defect's proximal margin with the clip. Additional clips anchoring the slip-knot loop are placed at the opposite side of the margin. The slip-knot loop is tightened by pulling the string. Additional clips are placed to achieve complete closure. RESULTS The mean size of resected specimen was 34.4 ± 10.0 mm. The success rate of the slip-knot clip suturing method was 90% (9/10). In the first patient, the string was cut because of friction, and the patient dropped out of the study. After the failure of the first patient, we used wet string to reduce friction, and slip-knot string worked effectively. The mean procedure time was 18.2 ± 3.3 minutes. CONCLUSION The slip-knot clip suturing method could close large mucosal defects completely using a single-channel endoscope. (Clinical trial registration number: UMIN000017583.).


title: Positive impact of the participation in the ENCHANTED trial in reducing Door-to-Needle Time.

text: Door-to-needle time (DNT) is a key performance indicator for efficient use of intravenous thrombolysis in acute ischemic stroke (AIS). We aimed to determine whether DNT improved over time in the Enhanced Control of Hypertension and Acute Stroke Study (ENCHANTED) and the clinical predictors of DNT. Temporal trends in DNT were assessed across fourths of time since activation of study centers using generalized linear model. Predictors of long DNT (>60 min) were determined in logistic regression models. Overall mean DNT (min) was 71.8 (95% confidence interval [CI] 70.4-73.2), but decreased significantly over time (fourths): 77.9 (74.9-80.9), 69.3 (66.7-72.0), 69.1 (66.5-71.8) and 71.4 (68.7-74.2) (P for trend, 0.003). The reduction in DNT was particularly marked in China (P for trend, 0.001), but was not significant across the other participating countries (P for trend, 0.065). Independent predictors of long DNT were recruitment from China, short onset-to-door time, lower numbers of patients treated per center, higher diastolic blood pressure, off-hour admission, and absence of proximal clot occlusion. DNT in ENCHANTED declined progressively during the trial, especially in China. However, DNT in China is still longer than the key performance parameter of ≤60 minutes recommended in guidelines. Effective national programs are needed to improve DNT in China.


title: Severe cerebral involvement due to idiopathic systemic capillary leak syndrome.

text: The idiopathic systemic capillary leak syndrome (ISCLS) is a rare disorder, characterized by recurrent attacks of hypotension, hypoalbuminemia, and hemoconcentration, which is often misdiagnosed due to overlapping features with other diseases. Even though cerebral involvement is uncommon, a broad awareness is crucial, because of its life-threatening character.


Covid-19: UK's chief scientific officer defends make up of advisory group.


title: Rapid detection and subtyping of human papillomaviruses in condyloma acuminatum using loop-mediated isothermal amplification with hydroxynaphthol blue dye.

text: Objective Condyloma acuminatum (CA) is a common, viral, sexually transmitted disease worldwide. Human papillomavirus (HPV) genotyping has important clinical implications for the treatment of CA. We developed a loop-mediated isothermal amplification (LAMP) method for the detection of HPV. Methods We collected 294 cervical scrape samples, including 30 HPV-6-positive, 30 HPV-11-positive, 22 HPV-16-positive, 20 HPV-42-positve, 30 HPV-43-positive, 20 HPV-44-positive and 142 HPV-negative samples. Tissues from 40 patients with a pathological diagnosis of CA were paraffin-embedded and analyzed by LAMP and Luminex. Hydroxynaphthol blue (HNB) and electrophoresis were used to detect the results of LAMP. Results LAMP and Luminex systems were compared in detecting six subtypes of HPV. LAMP reactions were specific for each subtype. The sensitivity of LAMP for HPV-6, as determined by the HNB indicator assay, was 1000 copies/tube. The kappa value between the two methods was 0.98 (HPV-6), 0.94 (HPV-11), 0.89 (HPV-43), 0.87 (HPV-42) 0.79 (HPV-16) and 0.68 (HPV-44). Among the 142 HPV-negative samples determined by the Luminex assay, HPV-6 was detected in eight and HPV-11 in one by LAMP. Among the 40 CA samples, the results of LAMP and Luminex were in agreement in 38 (95%). Conclusion The results of this study indicated that the LAMP assay with HNB is superior to the Luminex method in terms of sensitivity and specificity. The specificity of LAMP was 100% and the sensitivity of LAMP was 1000 copies/tube using HNB. LAMP is therefore a useful, quick and accurate method for the clinical diagnosis of HPV subtypes.


title: The effects of the combination of sodium ferulate and oxymatrine on lipopolysaccharide-induced acute lung injury in mice.

text: In our previous study, the remarkable analgesic and anti-inflammatory effects of the combination of sodium ferulate (SF) and oxymatrine (OMT) had been found. In this study, we investigated the effect of the combination of SF and OMT on acute lung injury using lipopolysaccharide (LPS)-induced acute lung injury (ALI) mouse model. The cell counting and the protein concentration in the bronchoalveolar lavage fluid (BALF) were measured. The animal lung edema degree was evaluated by wet/dry weight (W/D) ratio. The superoxidase dismutase (SOD) activity and myeloperoxidase (MPO) activity was assayed by SOD and MPO kits, respectively. The levels of inflammatory mediators including C-reactive protein (CRP) and tumor necrosis factor-α (TNF-α) were assayed by enzyme-linked immunosorbent assay method. The data showed that treatment with the combination of SF and OMT markedly attenuated inflammatory cell numbers and protein concentration in the BALF and improved SOD activity and inhibited MPO activity compared to LPS group. Moreover, the combination significantly inhibited the production of CRP and TNF-α in lung homogenate. The histological changes of the lungs were also more significantly improved by the combination. At the same dose, the obvious protective effect was not found in SF or OMT-treated alone group except that the protein concentration slightly decreased in SF group. The results indicated that the combination SF and OMT had a protective effect on LPS-induced ALI in mice, and the effect was much better than that of SF or OMT used alone.


title: Microvascular fluid exchange during CPB with deep hypothermia circulatory arrest or low flow.

text: OBJECTIVE Use of deep hypothermic low-flow (DHLF) cardiopulmonary bypass (CPB) has been associated with higher fluid loading than the use of deep hypothermia circulatory arrest (DHCA). We evaluated whether these perfusion strategies influenced fluid extravasation rates and edema generation differently per-operatively. MATERIALS AND METHODS Twelve anesthetized pigs, randomly allocated to DHLF (n = 6) or DHCA (n = 6), underwent 2.5 hours CPB with cooling to 20°C for 30 minutes (min), followed by 30 min arrested circulation (DHCA) or 30 min low-flow circulation (DHLF) before 90 min rewarming to normothermia. Perfusion of tissues, fluid requirements, plasma volumes, colloid osmotic pressures and total tissue water contents were recorded and fluid extravasation rates calculated. During the experiments, cerebral microdialysis was performed in both groups. RESULTS Microvascular fluid homeostasis was similar in both groups, with no between-group differences, reflected by similar fluid extravasation rates, plasma colloid osmotic pressures and total tissue water contents. Although extravasation rates increased dramatically from 0.10 (0.11) ml/kg/min (mean with standard deviation in parentheses) and 0.16 (0.02) ml/kg/min to 1.28 (0.58) ml/kg/min and 1.06 (0.41) ml/kg/min (DHCA and DHLF, respectively) after the initiation of CPB, fluid filtrations during both cardiac arrest and low flow were modest and close to baseline values. Cerebral microdialysis indicated anaerobic metabolism and ischemic brain injury in the DHCA group. CONCLUSION No differences in microvascular fluid exchange could be demonstrated as a direct effect of DHCA compared with DHLF. Thirty minutes of DHCA was associated with anaerobic cerebral metabolism and possible brain injury.


title: [Progress and challenge of vaccine development against 2019 novel coronavirus (2019-nCoV)].

text: The outbreak of 2019 novel coronavirus (2019-nCoV) infection poses a serious threat to global public health. Vaccination is an effective way to prevent the epidemic of the virus. 2019-nCoV along with severe acute respiratory syndrome coronavirus (SARS-CoV) and Middle East respiratory syndrome coronavirus (MERS-CoV) belong to the same β-genus of coronavirus family. Base on the previous experience and the technical platform of developing SARS-CoV and MERS-CoV vaccines, scientists from all over the world are working hard and quickly on the related fields. There are substantial progress in these fields including the characterizing the 2019-nCoV virus, identification of candidate antigens and epitopes, establishment of animal models, characterizing the immune responses, and the design of vaccines. The development of 2019-nCoV vaccines cover all types: inactivated virus vaccine, recombinant protein vaccine, viral vector-based vaccine, mRNA vaccine, and DNA vaccine, et al. As of March 2020, two 2019-nCoV vaccines have entered phase I clinical trials. One is named as Ad5-nCoV developed by the Chinese Institute of Biotechnology of the Academy of Military Medical Sciences and Tianjin Cansino Biotechnology Inc. Ad5-nCoV is based on the replication-defective adenovirus type 5 as the vector to express 2019-nCoV spike protein. The another vaccine is mRNA-1273 developed by the National Institute of Allergy and Infectious Diseases and Moderna, Inc.. RNA-1273 is an mRNA vaccine expressing 2019-nCoV spike protein. Although the rapid development of 2019-nCoV vaccine, it still faces many challenges with unknown knowledge, including the antigenic characteristics of the 2019-nCoV, the influence of antigenic variation, the protective immune response of host, the protection of the elderly population, and the downstream manufacturing process of the new vaccine. The safety and efficacy of vaccines are the first priority for vaccine development and should be carefully evaluated.


title: Interventions to Enhance Patient and Family Engagement Among Adults With Multiple Chronic Conditions: A Systematic Scoping Review.

text: PURPOSE In the United States, 42% of adults, and 81% of adults over 65 years of age live with multiple chronic condition (MCC). Current interventions to facilitate engagement in care focus primarily on the patient; however, many individuals with MCC manage and live with their conditions within the context of their family. This review sought to identify interventions used to facilitate patient and/or family engagement among adults with MCC. METHODS We adhered as closely as possible to PRISMA guidelines and conducted a systematic scoping review using a modified approach by Arksey and O'Malley. We searched PubMed, Web of Science, and Scopus using terms related to MCC, patient and family engagement, and intervention. We included articles that: (1) were published in English; (2) were peer-reviewed; (3) described an engagement intervention (with or without a comparator); and (4) targeted individuals with MCC. We abstracted data from included articles and classified them using the Multidimensional Framework for Patient and Family Engagement in Health and Health Care, and the Classification Model of Patient Engagement. RESULTS We identified 21 discrete interventions. Six (29%) were classified as having the highest degree of engagement. Eighteen (85%) focused on engagement at the direct care level. Only one was specifically designed to engage families. CONCLUSIONS Many engagement interventions currently exist for adults with MCC. Few of these interventions foster the highest degree of engagement; most focus on engagement at the level of direct care and do not specifically target family member involvement.


title: e-learning comes of age: Web-based education provided by the International League Against Epilepsy.

text: Education tools and programs using interactive digital content, distributed on the internet, are increasingly becoming an integral part of postgraduate medical education. The coronavirus pandemic and global lockdown hoisted a major challenge for traditional teaching courses. A timely solution is to focus attention and reinforce web-based teaching programs. For more than 15 years, the ILAE has been developing and managing a wide range of e-learning programs. This paper provides an overview on the e-learning portfolio of the ILAE, including tutored e-courses, self-paced interactive e-courses and online multimedia resources, all linked to the ILAE curriculum and learning objectives addressing specific levels of professional experience. All e-learning programs will become available through the new ILAE Academy platform (www.ilae-academy.org), in July 2020. E-learning is an important tool for reaching the global educational mission of the ILAE.


title: Stabilization of a steerable sheath during retrograde access to antegrade-oriented branches in complex endovascular aortic aneurysm repair.

text: During branched endovascular aneurysm repair, cannulation of the visceral target vessels through antegrade branches and insertion of bridging stents are frequently done from an upper extremity access. A retrograde femoral approach is a challenging alternative when an antegrade approach is not preferred. Herein, we describe a technique to increase stability of a steerable sheath, using a single suture, for bridging antegrade-facing branches from a retrograde access. This technique secures the sheath's deflected tip and provides more pushability to the steerable sheath.


title: Pipeline Embolization Device for Small Intracranial Aneurysms: Evaluation of Safety and Efficacy in a Multicenter Cohort.

text: BACKGROUND To date, the use of the flow-diverting Pipeline Embolization Device (PED) for small intracranial aneurysms (≤ 7 mm) has been reported only in single-center series. OBJECTIVE To evaluate the safety and efficacy of the PED in a multicenter cohort. METHODS Five major academic institutions in the United States provided data on patient demographics, aneurysm features, and treatment characteristics of consecutive patients with aneurysms ≤ 7 mm treated with a PED between 2009 and 2015. Radiographic outcome was assessed with digital subtraction angiography. Clinical outcome was measured with the modified Rankin Scale. RESULTS The cumulative number of aneurysms ≤ 7 mm treated with PED at the 5 institutions was 149 in 117 patients (age, 54 years [range, 29-87 years]; male to female, 1-5.9). Aneurysms were most commonly located in the paraophthalmic segment (67.1%) of the internal carotid artery. Radiographic outcome at last follow-up was available for 123 aneurysms (82.6%), with a complete occlusion rate of 87%. Thromboembolic and symptomatic procedural complications occurred in 8.7% and 6% of the aneurysms treated, respectively. There was 1 mortality (0.9%) unrelated to the PED procedure. Multivariable logistic regression identified size < 4 mm, balloon angioplasty to open the device, and simultaneous treatment of multiple aneurysms as predictors of procedural complications. Good clinical outcome was achieved in 96% of electively treated patients. CONCLUSION In the largest series on PED for small aneurysms to date, data suggest that treatment with the flow-diverting PED is safe and efficacious, with complication rates comparable to those for traditional endovascular techniques.


title: Coagulation dysfunction: A hallmark in COVID-19.

text: Context: The coronavirus disease 2019 (COVID-19) is a highly contagious respiratory disease caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Coagulation dysfunction is a hallmark in patients with COVID-19. Fulminant thrombotic complications emerge as critical issues in patients with severe COVID-19. Objective: To present a review of the literature and discuss the mechanisms of COVID-19 underlying coagulation activation and the implications for anticoagulant and thrombolytic treatment in the management of COVID-19. Data Sources: We performed a systemic review of scientific papers on the topic of COVID-19, online available via the PubMed NCBI, medRxiv, and Preprints as of May 15, 2020. We also shared our experience on the management of thrombotic events in patients with COVID-19. Conclusions: COVID-19-associated coagulopathy ranges from mild laboratory alterations to disseminated intravascular coagulation (DIC) with a predominant phenotype of thrombotic/multiple organ failure. Characteristically, high D-dimer levels on admission and/or continuously increasing concentrations of D-dimer is associated with disease progression and poor overall survival. SARS-CoV-2 infection triggers the immune-hemostatic response. Drastic inflammatory responses including, but not limited to, cytokine storm, vasculopathy, and NETosis may contribute to an overwhelming activation of coagulation. Hypercoagulability and systemic thrombotic complications necessitate anticoagulant and thrombolytic interventions, which provide opportunities to prevent or reduce "excessive" thrombin generation, while preserving "adaptive" hemostasis and bring additional benefit via their anti-inflammatory effect in the setting of COVID-19.


title: Neurosurgical activity during COVID-19 pandemic: an expert opinion from China, South Korea, Italy, United Stated of America, Colombia and United Kingdom.

text: BACKGROUND More than a million and a half people are infected worldwide with more than 90.000 casualties. The ongoing COVID-19 pandemic is radically altering both socio-economic and health care scenarios. METHODS On April 4, 2020, at 13.30 CET, a webinar was broadcasted, organized by Global Neuro and supported by WFNS. Expert neurosurgeons from 6 different countries (China, Italy, South Korea, USA, Colombia and United Kingdom) reported on the impact of the COVID-19 pandemic on their health care systems and neurosurgical activity. RESULTS The first part focused on the epidemiology until that date. The USA were the most affected State with 450.000 cases, followed by Italy (140.000 cases and 19.000 casualties), China (83.305 cases and 3.345 had died), South Korea (10.156 cases with 177 casualties), the UK (38.168 cases and 3.605 deaths) and Colombia (1.267 cases and 25 deaths). The second part concerned Institution and staff reorganization. In every country all surgical plans have been modified. In Wuhan the staff was enrolled in COVID-units. In New York, the Mount Sinai Health System was in lockdown mode. In South Korea, sterilizing chambers have been placed. In Italy some Departments were reorganized in a Hub and Spoke fashion. In the Latin American region, they adopted special measures for every case. In the UK a conference center has been used to accommodate intensive care unit (ICU) beds. The third part was about neurosurgical practice during the COVID-19 pandemic. In Wuhan the main hospital was used for urgent non-COVID patients. In New York the neurosurgeon staff work in ICU as advanced practitioner (APP). In South Korea every patient is screened. In Italy the on-duty Hub neurosurgeons have been doubled. In the Latin American region recommendations have been developed by some neurosurgical societies. In the UK local non-specialists and traumatologists neurosurgical experts are collaborating in terms of best practice. The final part touched upon how to perform safe surgery and re-start after the pandemic. In China elective surgical procedures are performed very carefully. In New York, surgery planning will be based on patient's viral load. In South Korea and in Italy disinfection plans and negative-pressure O.R. were created. In the Latin American region, the aim is to have a rapid testing system. In the UK they have developed flowcharts to guide trauma patient management. CONCLUSIONS In general, the pandemic scenario was presented as a thought-provoking challenge in all countries which requires tireless efforts for both maintaining emergency and elective neurosurgical procedures.


title: Prevention of intracranial in-stent restenoses: predilatation with a drug eluting balloon, followed by the deployment of a self-expanding stent.

text: PURPOSE Stenting in intracranial atherosclerotic disease (ICAD) is increasingly debated, due to issues of procedural safety, technical efficacy, and in-stent recurrent stenoses (ISR). In the present study, feasibility, safety, and efficacy of angioplasty using a drug-eluting balloon (DEB) followed by the implantation of a self-expanding stent (Enterprise) were evaluated for the treatment of ICAD lesions. METHODS Fifty-two patients (median age: 71 years; range: 54-86 years; male/female ratio 37:15) underwent stenting of high-grade ICAD lesions between February 2010 and November 2011 in a single center. Angioplasty using a paclitaxel coated SeQuent Please (B. Braun, Germany) or DIOR (Eurocor, Germany) coronary PTCA balloon, followed by the implantation of a self-expanding stent (Enterprise, Codman, USA) was performed in 54 lesions. Angiographic and clinical follow-up was performed at 6 and 12 weeks, 6 and 12 months, and yearly thereafter. Technical success rate, periprocedural complications, occurrence of recurrent ischemic symptoms, and the development of an ISR were analyzed. RESULTS Angioplasty using a DEB followed by stent implantation was successfully performed in 44 (81 %) cases. DEB insertion failed in 19 % of the cases and angioplasty was finally performed using a conventional PTCA balloon. The combined procedure related permanent neurologic morbidity and mortality rate (stroke, ICH, and subarachnoid hemorrhage) at 30 days and beyond was 5 %. Angiographic and clinical follow-up were obtained in 33 (61 %) lesions in 32 patients. Recurrent stenosis was seen in one (3 %) lesion. CONCLUSION Angioplasty and stenting using a DEB is safe and yields encouragingly low ISR rates. Further technical developments to improve lesion accessibility are, nevertheless, mandatory.


Coronavirus in charts: historical funding for coronavirus research has been tiny.


Novel coronavirus SARS-CoV-2: familial spread resulting in COVID-19 pneumonia in a pediatric patient.


title: Full-length cloning, sequence analysis and expression detection of the β-tubulin gene from the Chinese gall aphid (Schlechtendalia chinensis).

text: Some insect galls are formed on sumac plants by certain aphid species and have been used for medicinal and chemical purposes as they are rich in tannins. The most prominent species among gall aphids in China is Schlechtendalia chinensis, which formed horn-shaped galls on the winged rachis of Rhus chinensis. S. chinensis has a complex life cycle, with a switch of hosts between R. chinensis and certain mosses, and a switch of sexual and asexual reproduction (cyclical parthenogenesis). We have cloned a full-length cDNA of the β-tubulin gene from S. chinensis, using qPCR and RACE. This cDNA has 1606 base pairs with a 251 bp 5'-untranslated region (5'-UTR) and a 15 bp 3'-untranslated region (3'-UTR). The gene encodes a protein with 376 amino acids residues. The expression levels of the β-tubulin gene in S. chinensis were investigated among fundatrigeniae and overwintering larvae rearing under either natural conditions, or at 7.5 °C and 18 °C. No significant differences (P > 0.01) in gene expression levels were found in insects under these conditions. It is indicates that the β-tubulin gene is highly conserved and then it may be used as a reference for further research in gene expression and reproduction determination in this important aphid.


Screening for COVID-19 at childbirth: does it deliver?


Insights from Italy: the Novara-COVID score for rapid destination of COVID-19 patients at emergency department presentation.


Covid-19 fatality is likely overestimated.


title: Breast Contrast Enhanced MR Imaging: Semi-Automatic Detection of Vascular Map and Predominant Feeding Vessel.

text: PURPOSE To obtain breast vascular map and to assess correlation between predominant feeding vessel and tumor location with a semi-automatic method compared to conventional radiologic reading. METHODS 148 malignant and 75 benign breast lesions were included. All patients underwent bilateral MR imaging. Written informed consent was obtained from the patients before MRI. The local ethics committee granted approval for this study. Semi-automatic breast vascular map and predominant vessel detection was performed on MRI, for each patient. Semi-automatic detection (depending on grey levels threshold manually chosen by radiologist) was compared with results of two expert radiologists; inter-observer variability and reliability of semi-automatic approach were assessed. RESULTS Anatomic analysis of breast lesions revealed that 20% of patients had masses in internal half, 50% in external half and the 30% in subareolar/central area. As regards the 44 tumors in internal half, based on radiologic consensus, 40 demonstrated a predominant feeding vessel (61% were supplied by internal thoracic vessels, 14% by lateral thoracic vessels, 16% by both thoracic vessels and 9% had no predominant feeding vessel-p<0.01), based on semi-automatic detection, 38 tumors demonstrated a predominant feeding vessel (66% were supplied by internal thoracic vessels, 11% by lateral thoracic vessels, 9% by both thoracic vessels and 14% had no predominant feeding vessel-p<0.01). As regards the 111 tumors in external half, based on radiologic consensus, 91 demonstrated a predominant feeding vessel (25% were supplied by internal thoracic vessels, 39% by lateral thoracic vessels, 18% by both thoracic vessels and 18% had no predominant feeding vessel-p<0.01), based on semi-automatic detection, 94 demonstrated a predominant feeding vessel (27% were supplied by internal thoracic vessels, 45% by lateral thoracic vessels, 4% by both thoracic vessels and 24% had no predominant feeding vessel-p<0.01). An excellent agreement between two radiologic assessments (k = 0.81) and between radiologic consensus and semi-automatic assessment (k = 0.80) was found to identify origin of predominant feeding vessel. An excellent reliability for semi-automatic assessment (Cronbach's alpha = 0.96) was reported. CONCLUSIONS Predominant feeding vessel location was correlated with breast lesion location: internal thoracic artery supplied the highest proportion of breasts with tumor in internal half and lateral thoracic artery supplied the highest proportion of breasts with lateral tumor.


title: Development of a high-throughput real-time PCR system for detection of enzootic pathogens in pigs.

text: Respiratory and intestinal diseases in pigs can have significant negative influence on productivity and animal welfare. A wide range of real-time PCR (rtPCR) assays are used in our laboratory (National Veterinary Institute, Technical University of Denmark) for pathogen detection, and PCR analyses are performed on traditional rtPCR platforms in which a limited number of samples can be analyzed per day given limitations in equipment and personnel. To mitigate these restrictions, rtPCR assays have been optimized for the high-throughput rtPCR BioMark platform (Fluidigm). Using this platform, we developed a high-throughput detection system that can be used for simultaneous examination of 48 samples with detection specificity for 18 selected respiratory and enteric viral and bacterial pathogens of high importance to Danish pig production. The rtPCR assays were validated and optimized to run under the same reaction conditions using a BioMark 48.48 dynamic array (DA) integrated fluidic circuit chip, and the sensitivity and specificity were assessed by testing known positive samples. Performance of the 48.48DA was similar to traditional rtPCR analysis, and the specificity of the 48.48DA was high. Application of the high-throughput platform has resulted in a significant reduction in cost and working hours and has provided production herds with a new innovative service with the potential to facilitate the optimal choice of disease control strategies such as vaccination and treatment.


title: Immune evasion and counteraction of restriction factors by HIV-1 and other primate lentiviruses.

text: Retroviruses have evolved effective strategies to evade the host immune response, such as high variability and latent infection. In addition, primate lentiviruses, such as HIV-1, have acquired several "accessory" genes that antagonize antiviral host restriction factors and facilitate viral immune evasion, thereby allowing continuous and efficient viral replication despite apparently strong innate and acquired immune responses. Here, I summarize some of our current knowledge on the acquisition and function of the viral vif, vpr, vpu, and nef genes, with a particular focus on the evolution and specific properties of pandemic HIV-1 strains that may contribute to their efficient spread and high virulence.


title: Neurologists and Covid-19: A note on courage in a time of uncertainty.

text: Neurologists are used to uncertainty - diagnoses are frequently challenging, too often there are limited treatment options, and unpredictable prognoses are our bread and butter. When colleagues struggle to communicate bad news, they regularly turn to us. We practice staying steady and calm amidst our patients' fears, confusion, suffering, and anxiety. We listen, perform detailed exams, and do our best to provide helpful insights. This emphasis on listening and thoughtful problem solving is the core of our art and should be front and center as we partner with colleagues to face an unprecedented set of challenges related to the Covid-19 pandemic.


title: Procoagulation, hypercoagulation and fibrinolytic “shut down” detected with ClotPro® viscoelastic tests in COVID-19 patients.

text: INTRODUCTION International data indicate that arterial, venous and microvascular thrombosis or disseminated intravascular coagulation occur in more than 30% of hospitalized patients with COVID-19. This condition is characterized by high levels of D-dimer and fibrinogen, prolonged prothrombin time and activated partial thromboplastin time. METHOD Blood samples from three COVID-19 patients treated in a Hungarian intensive care unit were collected and analyzed with ClotPro® tests. EX-tests, IN-test, FIB-tests, RVV-tests, and TPA-tests were performed. The results were interpreted with respect to the clinical condition of the patients. RESULTS Procoagulation, hypercoagulation and either fibrinolysis or a "shut down" phenomenon of the fibrinolytic process were found with ClotPro®. The ClotPro® parameters were consistent with the conventional coagulation tests and corresponded with the criteria of non-overt disseminated intravascular coagulation. CONCLUSION These findings encourage further investigations to elucidate the underlying pathophysiology of thromboembolic events in COVID-19 patients and may support the introduction of full dose anticoagulation with or without antiplatelet therapy. Interventional clinical trials may be helpful in defining the appropriate drug(s), for this purpose, the algorithms of administration, and the optimal duration of therapy. At present, the authorization of a clinical trial that attempts to answer these questions is in progress. Orv Hetil. 2020; 161(22): 899-907.


Video consultations for triage of patients with covid-19.


Covid-19 Pandemic-An Opportunity to Reduce and Eliminate Low-Value Practices in Oncology?


title: Gastric Band Removal in Revisional Bariatric Surgery, One-Step Versus Two-Step: a Systematic Review and Meta-analysis.

text: We aimed to systematically review the literature comparing the safety of one-step versus two-step revisional bariatric surgery from laparoscopic adjustable gastric banding (LAGB) to Roux-en-Y gastric bypass (RYGB) or sleeve gastrectomy (SG). There is debate on the safety of removing the gastric band and performing revisional surgery immediately or in a delayed, two-step fashion due to potential higher complications in one-step revisions. A systematic and comprehensive search of the literature was conducted. Included studies directly compared one-step and two-step revisional surgery. Eleven studies were included with 1370 patients. Meta-analysis found comparable rates of complications, morbidity, and mortality between one-step and two-step revisions for both RYGB and SG groups. This suggests that immediate or delayed revisional bariatric surgeries are both safe options for LAGB revisions.


title: The unique immunological and microbial aspects of pregnancy.

text: The comparison of the immunological state of pregnancy to an immunosuppressed host-graft model continues to lead research and clinical practice to ill-defined approaches. This Review discusses recent evidence that supports the idea that immunological responses at the receptive maternal-fetal interface are not simply suppressed but are instead highly dynamic. We discuss the crucial role of trophoblast cells in shaping not only the way in which immune cells respond to the invading blastocyst but also how they collectively react to external stimuli. We also discuss the role of the microbiota in promoting a tolerogenic maternal immune system and highlight how subclinical viral infections can disrupt this status quo, leading to pregnancy complications.


[Festschrift for Thomas Deitmer].


title: Thrombectomy within 8 hours after symptom onset in ischemic stroke.

text: BACKGROUND We aimed to assess the safety and efficacy of thrombectomy for the treatment of stroke in a trial embedded within a population-based stroke reperfusion registry. METHODS During a 2-year period at four centers in Catalonia, Spain, we randomly assigned 206 patients who could be treated within 8 hours after the onset of symptoms of acute ischemic stroke to receive either medical therapy (including intravenous alteplase when eligible) and endovascular therapy with the Solitaire stent retriever (thrombectomy group) or medical therapy alone (control group). All patients had confirmed proximal anterior circulation occlusion and the absence of a large infarct on neuroimaging. In all study patients, the use of alteplase either did not achieve revascularization or was contraindicated. The primary outcome was the severity of global disability at 90 days, as measured on the modified Rankin scale (ranging from 0 [no symptoms] to 6 [death]). Although the maximum planned sample size was 690, enrollment was halted early because of loss of equipoise after positive results for thrombectomy were reported from other similar trials. RESULTS Thrombectomy reduced the severity of disability over the range of the modified Rankin scale (adjusted odds ratio for improvement of 1 point, 1.7; 95% confidence interval [CI], 1.05 to 2.8) and led to higher rates of functional independence (a score of 0 to 2) at 90 days (43.7% vs. 28.2%; adjusted odds ratio, 2.1; 95% CI, 1.1 to 4.0). At 90 days, the rates of symptomatic intracranial hemorrhage were 1.9% in both the thrombectomy group and the control group (P=1.00), and rates of death were 18.4% and 15.5%, respectively (P=0.60). Registry data indicated that only eight patients who met the eligibility criteria were treated outside the trial at participating hospitals. CONCLUSIONS Among patients with anterior circulation stroke who could be treated within 8 hours after symptom onset, stent retriever thrombectomy reduced the severity of post-stroke disability and increased the rate of functional independence. (Funded by Fundació Ictus Malaltia Vascular through an unrestricted grant from Covidien and others; REVASCAT ClinicalTrials.gov number, NCT01692379.).


title: Inferior vena cava thrombosis: a review of current practice.

text: Inferior vena cava (IVC) thrombosis remains under-recognised as it is often not pursued as a primary diagnosis. The aetiology of IVC thrombosis can be divided into congenital versus acquired, with all aetiological factors found among Virchow's triad of stasis, injury and hypercoagulability. Signs and symptoms are related to aetiology and range from no symptoms to cardiovascular collapse. Painful lower limb swelling combined with lower back pain, pyrexia, dilatation of cutaneous abdominal wall veins and a concurrent rise in inflammatory markers are suggestive of IVC thrombosis. Following initial lower limb venous duplex, magnetic resonance imaging (MRI) is the optimal non-invasive imaging tool. Aetiology directs treatment, which ranges from anticoagulation and lower limb compression to open surgery, with endovascular therapies increasingly favoured. The objective of this review is to assess current literature on the aetiology, presentation, investigation, treatment, prognosis and other factors pertaining to IVC thrombosis.


title: A Highly Sensitive Molecular Detection Platform for Robust and Facile Diagnosis of Middle East Respiratory Syndrome (MERS) Corona Virus.

text: Trail polymerization enables a significant enhancement of the DhITACT system. DhITACT-Trail (DNA hydrogel formation by isothermal amplification of complementary targets trail polymerization) offers a robust diagnosis of target RNA strands in pseudo-serum specimen. This system requires minimum liquid handling as compared to conventional analysis. In addition, a definitive diagnostic result can be achieved within 30 min by an optical detection.


title: Vulnerability to severe forms of COVID-19: an intra-municipal analysis in the city of Rio de Janeiro, Brazil.

text: Given the characteristics of the COVID-19 pandemic and the limited tools for orienting interventions in surveillance, control, and clinical care, the current article aims to identify areas with greater vulnerability to severe cases of the disease in Rio de Janeiro, Brazil, a city characterized by huge social and spatial heterogeneity. In order to identify these areas, the authors prepared an index of vulnerability to severe cases of COVID-19 based on the construction, weighting, and integration of three levels of information: mean number of residents per household and density of persons 60 years or older (both per census tract) and neighborhood tuberculosis incidence rate in the year 2018. The data on residents per household and density of persons 60 years or older were obtained from the 2010 Population Census, and data on tuberculosis incidence were taken from the Brazilian Information System for Notificable Diseases (SINAN). Weighting of the indicators comprising the index used analytic hierarchy process (AHP), and the levels of information were integrated via weighted linear combination with map algebra. Spatialization of the index of vulnerability to severe COVID-19 in the city of Rio de Janeiro reveals the existence of more vulnerable areas in different parts of the city's territory, reflecting its urban complexity. The areas with greatest vulnerability are located in the North and West Zones of the city and in poor neighborhoods nested within upper-income parts of the South and West Zones. Understanding these conditions of vulnerability can facilitate the development of strategies to monitor the evolution of COVID-19 and orient measures for prevention and health promotion.


title: Kawasaki-like diseases and thrombotic coagulopathy in COVID-19: delayed over-activation of the STING pathway?

text: As healthy young adults can die of COVID-19, whereas old COVID-19 patients can have mild symptoms only, genetic variances probably contribute to the severity of this emerging infection. We previously put forward the hypothesis that gain of function variants of TMEM 173, which encodes STING, contribute to COVID-19, since bats are protected from coronaviruses due to loss of function mutations of this gene. The present review detail new arguments for the contribution of the STING pathway to COVID-19, following the description of hyper-coagulability and Kawasaki-like diseases in children with COVID-19. Indeed, Kawasaki disease is induced by overreaction of innate cells following exposition to various viruses, including herpes viruses which trigger STING. It predisposes to diffuse vasculitis and aneurysms, whereas STING is over-expressed in arterial aneurisms. The redness at the inoculation site of bacillus Calmette-Guérin, a specific feature of Kawasaki disease, is reproduced by activation of the STING pathway, which is inhibited upstream by aspirin, intravenous immunoglobulins, and Vitamin-D. SARS-CoV2 binding to ACE2 can lead to excessive angiotensin II signaling, which activates the STING pathway in mice. Overactivation of the STING-pathway promotes hyper-coagulability through release of interferon-β and tissue factor by monocytes-macrophages. Aspirin and dipyridamole, besides their anti-platelet activity, also reduce tissue factor procoagulant activity, and aspirin inhibits the STING pathway upstream of STING. Aspirin and dipyridamole may be used, in combination with drugs blocking downstream the activation of the STING pathway, like inhibitors of IL-6R and JAK/STAT pathways. The risk of bleeding should be low as bleeding has not been reported in severe COVID-19 patients.


title: Herbal medicine (Shaofu Zhuyu decoction) for treating primary dysmenorrhea: A systematic review of randomized clinical trials.

text: Shaofu Zhuyu decoction (SFZY) or Sobokchugeo-tang, a traditional herbal formula, is used as a treatment for primary dysmenorrhea. We searched four English, seven Korean, three Chinese, and one Japanese database from inception through January 2016 without a language restriction. All randomized controlled trials (RCTs) of SFZY or modified SFZY (MSFZY) were included. Data extraction and risk of bias assessments were performed by two independent reviewers. A total of 51 potentially relevant studies were identified, and 9 RCTs met our inclusion criteria. Seven RCTs tested the effects of SFZY or modified SFZY in treating dysmenorrhea. Three RCTs showed superior effects of (M)SFZY on the response rate, while the other three RCTs failed to do so (n=531, RR: 1.17, 95% CI: 1.09 to 1.26, P<0.0001, I(2)=0%). Three RCTs showed favorable effects of MSFZY for pain reduction compared with conventional drugs (n=340, SMD: -1.39, 95% CI: -2.23 to -0.55, P=0.01). Two RCTs examined the effects of modified SFZY plus conventional drugs and conventional drugs alone. The meta-analysis showed favorable effects of MSFZY (n=206; RR, 1.12; 95% CI 1.08 to 1.36; P=0.0009, I(2)=0%). Our systemic review and meta-analysis provide suggestive evidence of the superiority of SFZY over conventional drugs for treating primary dysmenorrhea. However, the level of evidence is low because of a high risk of bias.


title: Gastric emptying is delayed in transgastric NOTES: a randomized study in swine.

text: AIM The aim of this study was to evaluate the restoration of gastrointestinal motility after NOTES using capsule endoscopy (CE). MATERIALS AND METHODS Twenty adult Yorkshire pigs were randomly assigned to four groups: transgastric NOTES (gNOTES), transrectal NOTES (rNOTES), transvaginal NOTES (vNOTES), and laparoscopy (LAP). At the end of a 30-min peritoneoscopy with identification of seven predetermined organs, an array of eight receivers and the recorder were attached to the abdominal wall. The CE was delivered into the antrum with the help of an endoscope and a polypectomy snare. Animals were kept alive for 14 d. RESULTS Median time for surgery was longer in gNOTES (56 min, range 47-63) and vNOTES (54 min, range 44-79) than in LAP (32 min, range 32-33; P < 0.05 and P < 0.01) and in rNOTES (45.5 min, range 33-56) (P = ns). This increase was related to a larger incision and longer closure times. Images from the CE were successfully retrieved in 19 cases. The CE was retained in the stomach in all animals in gNOTES (459 min; range 360-600), but only in one animal in rNOTES and vNOTES and in none in the LAP group. Failure of passage of the CE beyond the stomach was associated with gNOTES and longer closure of the incision. Animals in the gNOTES group gained less weight than the others and this change was statistical significant when compared with vNOTES animals (1.7 kg, range -1.98 to 4.5 versus 8.4 kg, range 5.8 to 11.45; P < 0.01). CONCLUSION Gastric emptying is delayed after gNOTES peritoneoscopy compared with rNOTES, vNOTES, and LAP and this effect is associated with less weight gain.


title: Extracorporeal Membrane Oxygenation for Coronavirus Disease 2019-Induced Acute Respiratory Distress Syndrome: A Multicenter Descriptive Study.

text: OBJECTIVES Severe acute respiratory distress syndrome is complicated with coronavirus disease 2019 and extracorporeal membrane oxygenation support may be necessary in severe cases. This study is to summarize the clinical features, extracorporeal membrane oxygenation characteristics, and outcomes of patients with severe acute respiratory syndrome coronavirus 2 pneumonia received extracorporeal membrane oxygenation. DESIGN Descriptive study from two hospitals. SETTING The ICUs from university hospitals. PATIENTS Patients with severe acute respiratory syndrome coronavirus 2 pneumonia received mechanical ventilation, including those underwent extracorporeal membrane oxygenation from Zhongnan Hospital of Wuhan University and Wuhan Pulmonary Hospital from January 8, 2020, to March 31, 2020. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS Clinical records, laboratory results, ventilator parameters, and extracorporeal membrane oxygenation-related data were abstracted from the medical records. One-hundred twenty-nine critically ill patients with severe acute respiratory syndrome coronavirus 2 pneumonia were admitted to ICU of the two referral hospitals. Fifty-nine patients received mechanical ventilation and 21 of them received extracorporeal membrane oxygenation support (fourteen from Zhongnan hospital and seven from Wuhan pulmonary hospital). Compared to mechanical ventilation patients without extracorporeal membrane oxygenation support, there was a tendency of decline in mortality but with no significant difference (no-extracorporeal membrane oxygenation group 24/38 [63.2%] vs extracorporeal membrane oxygenation group 12/21 [57.1%]; p = 0.782). For those patients with extracorporeal membrane oxygenation, 12 patients died and nine survived by April 7, 2020. Among extracorporeal membrane oxygenation patients, the PaCO2 prior to extracorporeal membrane oxygenation was lower (54.40 mm Hg [29.20-57.50 mm Hg] vs 63.20 mm Hg [55.40-72.12 mm Hg]; p = 0.006), and pH prior to extracorporeal membrane oxygenation was higher (7.38 [7.28-7.48] vs 7.23 [7.16-7.33]; p = 0.023) in survivors than nonsurvivors. CONCLUSIONS Extracorporeal membrane oxygenation might be an effective salvage treatment for patients with severe acute respiratory syndrome coronavirus 2 pneumonia associated with severe acute respiratory distress syndrome. Severe CO2 retention and acidosis prior to extracorporeal membrane oxygenation indicated a poor prognosis.


title: Host factors in enterovirus 71 replication.

text: Enterovirus 71 (EV71) infections continue to remain an important public health problem around the world, especially in the Asia-Pacific region. There is a significant mortality rate following such infections, and there is neither any proven therapy nor a vaccine for EV71. This has spurred much fundamental research into the replication of the virus. In this review, we discuss recent work identifying host cell factors which regulate the synthesis of EV71 RNA and proteins. Three of these proteins, heterogeneous nuclear ribonucleoprotein A1 (hnRNP A1), far-upstream element-binding protein 2 (FBP2), and FBP1 are nuclear proteins which in EV71-infected cells are relocalized to the cytoplasm, and they influence EV71 internal ribosome entry site (IRES) activity. hnRNP A1 stimulates IRES activity but can be replaced by hnRNP A2. FBP2 is a negative regulatory factor with respect to EV71 IRES activity, whereas FBP1 has the opposite effect. Two other proteins, hnRNP K and reticulon 3, are required for the efficient synthesis of viral RNA. The cleavage stimulation factor 64K subunit (CstF-64) is a host protein that is involved in the 3' polyadenylation of cellular pre-mRNAs, and recent work suggests that in EV71-infected cells, it may be cleaved by the EV71 3C protease. Such a cleavage would impair the processing of pre-mRNA to mature mRNAs. Host cell proteins play an important role in the replication of EV71, but much work remains to be done in order to understand how they act.