title: Software tools for literature screening in systematic reviews in biomedical research.

text: Systematic Reviews (SRs) hold promise for implementing the 3Rs in animal sciences: they can retrieve available alternative models, help refining experiments, and identify insufficiencies, or an excess of, scientific knowledge on a particular topic. Unfortunately, SRs can be labour- and time-intensive, especially the reference screening and data extraction phases. Fortunately, there are several software tools available that help make screening faster and easier. However, it is not always clear which features the tools offer. Therefore, a feature analysis was performed to compare different reference screening tools as objectively as possible. This analysis enables researchers to select the most appropriate tool for their needs. Fifteen different tools were compared: CADIMA, Covidence, DistillerSR, Endnote, Endnote using Bramer's method, EROS, HAWC, Microsoft Excel, Excel using VonVille's method, Microsoft Word, Rayyan, RevMan, SyRF, SysRev.com, and SWIFT Active Screener. Their support of 21 features was tested. Features were categorised as mandatory, desirable, and optional. DistillerSR, Covidence, and SWIFT Active Screener are the tools that support all mandatory features. These tools are preferred for screening references, but none of them are free. The best scoring free tool is Rayyan, which lacks one mandatory function: distinct title/abstract and full-text phases. The lowest scoring tools are those not specifically designed for SRs, like Microsoft Word and Endnote. Their use can only be advised for small and simple SRs. A well-informed selection of SR screening tools will benefit review quality and speed, which can contribute to the advancement of the 3Rs in animal studies.


title: Establishing a Porcine Model of Small for Size Syndrome following Liver Resection.

text: BACKGROUND Small for size syndrome (SFSS) is responsible for a high proportion of mortalities and morbidities following extended liver resection. AIM The aim of this study was to establish a porcine model of SFSS. METHODS Twenty-four Landrace pigs underwent liver resection with a remnant liver volume of 50% (group A, n = 8), 25% (group B, n = 8), and 15% (group C, n = 8). After resection, the animals were followed up for 8 days and clinical, laboratory, and histopathological outcomes were evaluated. RESULTS The survival rate was significantly lower in group C compared with the other groups (p < 0.001). The international normalized ratio, bilirubin, aspartate transaminase, alanine transaminase, and alkaline phosphatase levels increased shortly after surgery in groups B and C, but no change was observed in group A (p < 0.05 for all analyses). The histopathological findings in group A were mainly mild mitoses, in group B severe mitoses and hepatocyte ballooning, moderate congestion, and hemorrhage, along with mild necrosis, and in group C extended tissue damage with severe necrosis, hemorrhage, and congestion. CONCLUSIONS Combination of clinical, laboratory, and histopathological evaluations is needed to confirm the diagnosis of SFSS. 75% liver resection in porcine model results in SFSS. 85% liver resection causes irreversible liver failure.


title: Three-year follow-up and quality of life of endovenous radiofrequency ablation of the great saphenous vein with the ClosureFast™ procedure: Influence of BMI and CEAP class.

text: Purpose Endovascular ablation of the great saphenous vein has been proposed as a less invasive alternative to conventional ligation and stripping of varicose veins. Outcomes of patients treated with the radiofrequency ablation ClosureFast™ system over an eight-year period from a single-center were evaluated. Methods Three-year follow-up data included duplex ultrasound scan, complication rate, and questionnaires to assess patients' QOL, level of pain, and days off work. Results A total of 1080 consecutive patients (49.5 ± 18.6 years, 72% female, mean body mass index: 25.44 ± 4.1 kg m-2) underwent radiofrequency ablation for incompetent saphenous veins in a single institution. Occlusion of the great saphenous vein was obtained in 98.6% and 93.8% cases at the end of the procedures and within 36 months, respectively. Only three deep venous thromboses and minor complications occurred in this series throughout the first week from the procedure. A decrease of the external vein diameter, equal to 72.7% and 31.1% of the pretreatment diameter, was observed at 1 week and 36 months, respectively. The average Aberdeen Varicose Vein Questionnaire score improved from 18.06 ± 9.47 before treatment to 11.56 ± 10.23 at 12 months, with no significant differences in the subsequent follow-up. SF-36 QOL scores significantly improved after the procedure in all domains, while there were no changes over time. Patients reported a prompt return to normal daily activities (1.5 ± 0.7 days) and work (3.1 ± 1.9 days). Body mass index influenced QOL scores, while it did not affect great saphenous vein diameter reduction during the follow-up. On the contrary, Clinical Etiologic Anatomic Pathophysiologic class significantly influenced both great saphenous vein diameter reduction after the treatment and QOL scores within 36 months. Conclusion Results of this retrospective monocentric, large patients study suggest that radiofrequency ablation of the great saphenous vein may be a safe and efficient alternative to conventional surgery.


title: Validating a standardized laparoscopy curriculum for gynecology residents: a randomized controlled trial.

text: BACKGROUND Residency programs struggle with integrating simulation training into curricula, despite evidence that simulation leads to improved operating room performance and patient outcomes. Currently, there is no standardized laparoscopic training program available for gynecology residents. OBJECTIVE The purpose of this study was to develop and validate a comprehensive ex vivo training curriculum for gynecologic laparoscopy. STUDY DESIGN In a prospective, single-blinded randomized controlled trial (Canadian Task Force Classification I) postgraduate year 1 and 2 gynecology residents were allocated randomly to receive either conventional residency training or an evidence-based laparoscopy curriculum. The 7-week curriculum consisted of cognitive didactic and interactive sessions, low-fidelity box trainer and high-fidelity virtual reality simulator technical skills, and high-fidelity team simulation. The primary outcome measure was the technical procedure score at laparoscopic salpingectomy with the use of the objective structured assessment of laparoscopic salpingectomy tool. Secondary outcome measures related to performance in multiple-choice questions and technical performance at box trainer and virtual reality simulator tasks. A sample size of 10 residents per group was planned (n = 20). Results are reported as medians (interquartile ranges), and data were compared between groups with the Mann-Whitney U, chi-square, and Fisher's exact tests (P ≤ .05). RESULTS In July 2013, 27 residents were assigned randomly (14 curriculum, 13 conventional). Both groups were similar at baseline. Twenty-one residents (10 curriculum, 11 conventional) completed the surgical procedure-based assessment in the operating room (September to December 2013). Our primary outcome indicated that curriculum-trained residents displayed superior performance at laparoscopic salpingectomy (P = .043). Secondary outcomes demonstrated that curriculum-trained residents had higher performance scores on the cognitive multiple-choice questions (P < .001), the nontechnical skills multiple-choice questions (P = .016), box trainer task time (P < .001), and all virtual reality simulator parameters. CONCLUSION Participation in a comprehensive simulation-based training curriculum for gynecologic laparoscopy leads to a superior improvement in knowledge and technical performance in the operating room compared with conventional residency training.


title: Prevention of periprosthetic joint infection: what are the effective strategies?

text: Periprosthetic joint infection (PJI) following total knee arthroplasty is a major burden for patients and health systems. Prevention of this challenging complication through implementation of effective strategies should be a priority. These strategies should encompass various levels of patient care. Multiple modifiable risk factors such as uncontrolled hyperglycemia, obesity, smoking, substance abuse, and nasal colonization with Staphylococcus aureus have been described for PJI. Preoperative recognition and mitigation of these risk factors along with optimization of nonmodifiable risk factors such as kidney, liver, or immune system insufficiency can considerably decrease the risk of PJI. A comprehensive perioperative protocol should involve optimization of the operative environment to reduce the number of bacteria and particulates in the air. Several surgical and nonsurgical details of intraoperative care such as maintenance of normothermia, skin preparation, surgical field irrigation, wound closure, and duration of surgical and anesthetic procedure can influence the occurrence of PJI. Prophylactic perioperative antibiotic administration is probably one of the most important strategies in preventing PJI. Implementation of surgical safety checklist can diminish the risk of perioperative complications, particularly surgical site infection. Controversy regarding efficacy, efficiency, and optimization of some preventive measures continues to exist due to inconsistency or inadequacy of available evidence. Novel research has focused on designing PJI-resistant implants and developing vaccines that target molecule components with major role in the process of bacterial adhesion to the implant or periprosthetic tissues.


title: New and Established Technology in Focal Ablation of the Prostate: A Systematic Review.

text: CONTEXT Focal therapy of prostate cancer has been proposed as an alternative to whole-gland treatments. OBJECTIVE To summarize the evidence regarding sources of energy employed in focal therapy. EVIDENCE ACQUISITION Embase and Medline (PubMed) were searched from 1996 to October 31, 2015 following the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement. Ongoing trials were selected from electronic registries. The stage of assessment of each source of energy was determined using the Idea, Development, Exploration, Assessment, Long-term study recommendations. EVIDENCE SYNTHESIS Thirty-seven articles reporting on 3230 patients undergoing focal therapy were selected. Thirteen reported on high-intensity focused ultrasound, 11 on cryotherapy, three on photodynamic therapy, four on laser interstitial thermotherapy, two on brachytherapy, three on irreversible electroporation, and one on radiofrequency. High-intensity focused ultrasound, cryotherapy, photodynamic therapy, and brachytherapy have been assessed in up to Stage 2b studies. Laser interstitial thermotherapy and irreversible electroporation have been evaluated in up to Stage 2a studies. Radiofrequency has been evaluated in one Stage 1 study. Median follow-up varied between 4 mo and 61 mo, and the median rate of serious adverse events ranged between 0% and 10.6%. Pad-free leak-free continence and potency were obtained in 83.3-100% and 81.5-100%, respectively. In series with intention to treat, the median rate of significant and insignificant disease at control biopsy varied between 0% and 13.4% and 5.1% and 45.9%, respectively. The main limitations were the length of follow-up, the absence of a comparator arm, and study heterogeneity. CONCLUSIONS Focal therapy has been evaluated using seven sources of energy in single-arm retrospective and prospective development studies up to Stage 2b. Focal therapy seems to have a minor impact on quality of life and genito-urinary function. Oncological effectiveness is yet to be defined against standard of care. PATIENT SUMMARY Seven sources of energy have been employed to selectively ablate discrete areas of prostate cancer. There is high evidence that focal therapy is safe and has low detrimental impact on continence and potency. The oncological outcome has yet to be evaluated against standard of care.


How COVID-19 lockdowns could lead to a kinder research culture.


Intensive care unit disaster preparation: keep it simple.


title: Contagion: epidemiological models and financial crises.

text: Since the 1990s, economists have drawn on the epidemiology of emerging infectious diseases to explain the diffusion of shock through an increasingly complex financial system. The successful coordination of public health responses to disease threats, and in particular the epidemiological modelling underpinning infection control, has influenced economists' understanding of the risks posed to the stability of the financial system by 'contagion'. While the exportation of analytic models and frames of reference can be fruitful, reinvigorating the destination domain, such analogizing can have a distorting effect. There are differences between biological and financial systems. Moreover, the migration of highly context-specific epidemiological models may undermine the basis of the analogy. Finally, there may be repercussions for the efficacy of public health in the way that its aims are misconstrued in financial analyses.


title: Recurrence of biliary disease following non-operative management in elderly patients.

text: INTRODUCTION The purpose of this study was to determine the proportion of symptomatic recurrence following initial non-operative management of gallstone disease in the elderly and to test possible predictors. METHODS This is a single institution retrospective chart review of patients 65 years and older with an initial hospital visit (V1) for symptomatic gallstone disease, over a 4-year period. Patients with initial "non-operative" management were defined as those without surgery at V1 and without elective surgery at visit 2 (V2). Baseline characteristics included age, sex, Charlson comorbidity index (CCI), diagnosis, and interventions (ERCP or cholecystostomy) at V1. Outcomes assessed over 1 year were as follows: recurrence (any ER/admission visit following V1), surgery, complications, and mortality. A survival analysis using a Cox proportional hazards model was performed to assess predictors of recurrence. RESULTS There were 195 patients initially treated non-operatively at V1. Mean age was 78.3 ± 7.8 years, 45.6% were male, and the mean CCI was 2.1 ± 1.9. At V1, 54.4% had a diagnosis of biliary colic or cholecystitis, while 45.6% had a diagnosis of cholangitis, pancreatitis, or choledocholithiasis. 39.5% underwent ERCP or cholecystostomy. Excluding 10 patients who died at V1, 31.3% of patients had a recurrence over the study period. Among these, 43.5% had emergency surgery, 34.8% had complications, and 4.3% died. Median time to first recurrence was 2 months (range 6 days-4.8 months). Intervention at V1 was associated with a lower probability of recurrence (HR 0.3, CI [0.14-0.65]). CONCLUSION One-third of elderly patients will develop a recurrence following non-operative management of symptomatic biliary disease. These recurrences are associated with significant rates of emergency surgery and morbidity. Percutaneous or endoscopic therapies may decrease the risk of recurrence.


How to defend a PhD remotely.


title: COVID-19: The Need for Rational Use of Face Masks in Nigeria.

text: Because of the pandemic of COVID-19, the federal government of Nigeria has instituted a mandatory policy requiring everyone going out in public to wear face masks. Unfortunately, the Nigeria media is awash with images of misuse and abuse of face masks by the public, government officials, and healthcare workers. Medical masks are used widely in community settings amid reported scarcity within healthcare facilities. It is observed that some people wear face masks on their chin and neck, and mask wearers give no attention to covering their mouth and nose, especially when talking. Used face masks are kept with personal belongings or disposed indiscriminately in public spaces, leading to self and environmental contamination. Inappropriate use and disposal of face masks in Nigeria could promote the spread of the novel coronavirus in the country and negate the country's efforts to contain the COVID-19 pandemic. In the implementation of the universal masking policy in Nigeria, federal and state governments ought to consider local applicability, feasibility, and sustainability, as well as identify and mitigate all potential risks and unintended consequences. Also critical is the need for intensive public sensitization and education on appropriate use and disposal of face masks in the country.


title: Safety and efficacy of perioperative benzodiazepine administration: study protocol for a systematic review and meta-analysis.

text: INTRODUCTION Perioperative benzodiazepines are used because of their anxiolytic, sedative and amnestic effects. Evidence has demonstrated an association of benzodiazepines with adverse neuropsychiatric effects. Nonetheless, because of their potential benefits, perioperative benzodiazepines continue to be used routinely. We seek to evaluate the body of evidence of the risks and benefits of benzodiazepine use during the perioperative period. METHODS AND ANALYSIS We will search Cochrane CENTRAL, MEDLINE, EMBASE, PsychINFO, CINAHL and Web of Science from inception to March 2019 for randomised controlled trials (RCTs) and observational studies evaluating the administration of benzodiazepine medications as compared with all other medications (or nothing) in patients undergoing cardiac and non-cardiac surgery. We will exclude studies assessing the use of benzodiazepines for procedural sedation or day surgery. We will examine the impact of giving these medications before, during and after surgery. Outcomes of interest include the incidence of delirium, duration of delirium, postprocedure cognitive change, the incidence of intraoperative awareness, patient satisfaction/quality of life/quality of recovery, length-of-stay (LOS) in the intensive care unit (ICU), hospital LOS and in-hospital mortality.Reviewers will screen references and assess eligibility using predefined criteria independently and in duplicate. Two reviewers will independently collect data using prepiloted forms. We will present results separately for RCTs and observational studies. We will pool data using a random effect model and present results as relative risk with 95% CIs for dichotomous outcomes and mean difference with 95% CI for continuous outcomes. We will pool adjusted ORs for observational studies. We will assess risk of bias for individual studies using the Cochrane Collaboration tool for RCTs. For observational studies, we will use tools designed by the Clinical Advances through Research and Information Translation group. Quality of evidence for each outcome will be assessed using the Grading of Recommendations Assessment, Development and Evaluation approach. ETHICS AND DISSEMINATION This systematic review involves no patient contact and no interaction with healthcare providers or systems. As such, we did not seek ethics board approval. We will disseminate the findings of our systematic review through the presentation at peer-reviewed conferences and by seeking publication in a peer-reviewed journal. PROSPERO REGISTRATION NUMBER CRD42019128144.


title: Supporting women of childbearing age in the prevention and treatment of overweight and obesity: a scoping review of randomized control trials of behavioral interventions.

text: BACKGROUND Women of childbearing age are vulnerable to weight gain. This scoping review examines the extent and range of research undertaken to evaluate behavioral interventions to support women of childbearing age to prevent and treat overweight and obesity. METHODS Eight electronic databases were searched for randomized controlled trials (RCT) or systematic reviews of RCTs until 31st January 2018. Eligible studies included women of childbearing age (aged 15-44 years), evaluated interventions promoting behavior change related to diet or physical activity to achieve weight gain prevention, weight loss or maintenance and reported weight-related outcomes. RESULTS Ninety studies met the inclusion criteria (87 RCTs, 3 systematic reviews). Included studies were published from 1998 to 2018. The studies primarily focused on preventing excessive gestational weight gain (n = 46 RCTs, n = 2 systematic reviews), preventing postpartum weight retention (n = 18 RCTs) or a combination of the two (n = 14 RCTs, n = 1 systematic review). The RCTs predominantly evaluated interventions that aimed to change both diet and physical activity behaviors (n = 84) and were delivered in-person (n = 85). CONCLUSIONS This scoping review identified an increasing volume of research over time undertaken to support women of childbearing age to prevent and treat overweight and obesity. It highlights, however, that little research is being undertaken to support the young adult female population unrelated to pregnancy or preconception.


title: Neutral Position Facilitates Nasotracheal Intubation with a GlideScope Video Laryngoscope: A Randomized Controlled Trial.

text: The optimal head position for GlideScope facilitated nasotracheal intubation has not yet been determined. We compared the neutral and sniffing positions to establish the degree of intubation difficulty. A total of 88 ASA I-II patients requiring nasotracheal intubation for elective dental surgery with normal airways were divided into two groups according to head position, neutral position (group N), and sniffing position (group S). The primary outcome was the degree of intubation difficulty according to the Intubation Difficulty Scale (IDS): Easy (IDS = 0), mildly difficult (IDS = 1 to 4), and moderately to severely difficult (IDS ≥ 5). Eighty-seven patients completed the study and their data were analyzed. The degree of intubation difficulty was significantly different between the two groups (p = 0.004). The frequency of difficult intubation (IDS > 0) was 12 (27.9%) in group N and 28 (63.6%) in group S (difference in proportion, 35.7%; 95% confidence interval [CI], 14.8 to 52.6%; p = 0.001). The neutral position facilitates nasotracheal intubation with GlideScope by aligning the nasotracheal tube and the glottis inlet more accurately than the sniffing position.


title: Tackers versus glue mesh fixation: an objective assessment of postoperative acute and chronic pain using inflammatory markers.

text: PURPOSE Laparoscopic hernioplasty has become a popular choice for inguinal hernia repair since its advent in 1990s. Postoperative pain is an undesirable clinical outcome impairing daily activity of 22.5% of patients. The aim of this study is to evaluate postoperative acute and chronic pain via inflammatory markers as an objective assessment following tacks or glue mesh fixation in TEP repair. METHODS Sixty-six (66) patients with unilateral uncomplicated inguinal hernia were randomized into 34 patients in the tacker and 32 patients in cyanoacrylate glue mesh fixation in TEP repair. The extent of surgical trauma was evaluated by measuring inflammatory markers of C-reactive protein, white blood cell count at 48 h, and ESR at 3 months postoperatively. Postoperative acute and chronic pain was assessed by recording the visual analogue scale scores and surgical complications were recorded over 3 months of the study period. RESULTS The median CRP and WBC levels at postoperative 48 h in both groups raised significantly from the baseline values (p < 0.05), however, did not differ significantly between the two study groups at 48 h (p > 0.05). The median ESR level increased significantly at 3 months postoperatively from baseline in the glue mesh fixation group only (p < 0.05), however, did not differ significantly between the two study groups (p > 0.05). There was no significant difference for VAS scores at all timelines between the tacker and glue mesh fixation group (p > 0.05). CONCLUSION Cyanoacrylate glue mesh fixation technique as an alternative method to mechanical fixation in TEP repair is comparable to tacker and can be considered to be safe and feasible.


title: Prevalence of psychiatric disorders among Toronto hospital workers one to two years after the SARS outbreak.

text: OBJECTIVE This study aimed to determine the incidence of psychiatric disorders among health care workers in Toronto in the one- to two-year period after the 2003 outbreak of severe acute respiratory syndrome (SARS) and to test predicted risk factors. METHODS New-onset episodes of psychiatric disorders were assessed among 139 health care workers by using the Structured Clinical Interview for DSM-IV and the Clinician-Administered PTSD Scale. Past history of psychiatric illness, years of health care experience, and the perception of adequate training and support were tested as predictors of the incidence of new-onset episodes of psychiatric disorders after the SARS outbreak. RESULTS The lifetime prevalence of any depressive, anxiety, or substance use diagnosis was 30%. Only one health care worker who identified the SARS experience as a traumatic event was diagnosed as having PTSD. New episodes of psychiatric disorders occurred among seven health care workers (5%). New episodes of psychiatric disorders were directly associated with a history of having a psychiatric disorder before the SARS outbreak (p=.02) and inversely associated with years of health care experience (p=.03) and the perceived adequacy of training and support (p=.03). CONCLUSIONS Incidence of new episodes of psychiatric disorders after the SARS outbreak were similar to or lower than community incidence rates, which may indicate the resilience of health care workers who continued to work in hospitals one to two years after the SARS outbreak. In preparation for future events, such as pandemic influenza, training and support may bolster the resilience of health care workers who are at higher risk by virtue of their psychiatric history and fewer years of health care experience.


Covid-19: Scotland recommends face coverings, but England does not follow suit.


title: Secondary attack rate of hepatitis A, varicella and mumps in household settings and reliability of family history to detect seronegative children for necessity of vaccination.

text: Hepatitis A, varicella, and mumps are common in countries without universal immunization against these infections. Information about secondary household attack rates is limited. A prospective study was conducted in children <16 y of age who had household contact with the above infections. History for previous infections and vaccination was obtained from the parents. Specific antibodies in the sera during enrollment and at the end of the longest incubation periods were determined. A total of 113 children who had household contact with cases of varicella, hepatitis A, or mumps were enrolled. Secondary attack rate (SAR) was lower in hepatitis A (43.3%) than those for varicella (75.0%) and mumps (65.3%) (p<0.05). Rate of secondary asymptomatic infections was 25.6% in the hepatitis A group, 3.1% in the varicella group, and 16.6% in the mumps group. Positive predictive value (PPV) of the history was 100% for all 3 diseases and negative predictive value (NPV) was 85% for hepatitis A, 80.0% for varicella, and 56.2% for mumps. In conclusion, asymptomatic infections are important in the calculation of SARs in household contacts. PPV and NPV of medical history taken from parents might be useful when deciding the need for vaccination.


title: Cytokines and 90Y-Radioembolization: Relation to Liver Function and Overall Survival.

text: BACKGROUND To evaluate the course of pro- and anti-inflammatory cytokines after 90Y-radioembolization (RE) of liver malignancies and to identify prognosticators for liver-related adverse events and survival. METHODS In 34 consecutive patients with secondary or primary liver tumors scheduled for RE, the following cytokines were measured prior to and 2 h, 3 days, and 6 weeks after RE: interleukin (IL) -1, IL-2, IL-4, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), and interferon-γ. Liver function impairment was defined as an elevation of liver-related laboratory values as graded by CTCAE ≥ 2 and/or serum bilirubin ≥30 µmol/l and/or development of ascites at 6-week follow-up. RESULTS Significant changes over time were seen in IL-1 (increase from 0.4 pg/ml (±0.7) at baseline to 1.1 pg/ml (±1.4) 3 days after RE (p = 0.02)), and in IL-6 (increase from 16.8 pg/ml (±21.8) at baseline to 54.6 pg/ml (±78.2) 3 days after RE (p = 0.003)). Baseline values of IL-6 and IL-8 were independently associated with liver function impairment at follow-up as well as decreased survival with an optimal cutoff at 6.53 and 60.8 pg/ml, respectively. CONCLUSION Expected changes in pro- and anti-inflammatory cytokines after RE were shown. Furthermore, baseline values of IL-6 and IL-8 were associated with later liver dysfunction and survival. We hypothesize that these biomarkers are potential prognosticators and might help in patient selection for RE.


title: Significance of surgical plume obstruction during laparoscopy.

text: With the advent of laparoscopic surgery, the need of optimal visualization and efficient instrumentation has created a need for better understanding of the characteristics of the surgical plume. Despite the technological advances of digital imaging and dissector technology (ultrasonic, radiofrequency electrical, and bipolar), the inconvenient and sometimes harmful generation of a surgical plume decreases visualization, often requiring the surgeon to remove the scope from the surgical field and remove the obstructing particles. If visualization is suboptimal or lost during bleeding, the outcome can be deadly. Therefore, we reviewed the available reports in the literature focused on the quantification of surgical plumes.


Declarations of pharma funding to doctors are hit by covid-19 crisis.


title: Application of metabolomics to drug discovery and understanding the mechanisms of action of medicinal plants with anti-tuberculosis activity.

text: Human tuberculosis (TB) is amongst the oldest and deadliest human bacterial diseases that pose major health, social and economic burden at a global level. Current regimens for TB treatment are lengthy, expensive and ineffective to emerging drug resistant strains. Thus, there is an urgent need for identification and development of novel TB drugs and drug regimens with comprehensive and specific mechanisms of action. Many medicinal plants are traditionally used for TB treatment. While some of their phytochemical composition has been elucidated, their mechanisms of action are not well understood. Insufficient knowledge on Mycobacterium tuberculosis (M.tb) biology and the complex nature of its infection limit the effectiveness of current screening-based methods used for TB drug discovery. Nonetheless, application of metabolomics tools within the 'omics' approaches, could provide an alternative method of elucidating the mechanism of action of medicinal plants. Metabolomics aims at high throughput detection, quantification and identification of metabolites in biological samples. Changes in the concentration of specific metabolites in a biological sample indicate changes in the metabolic pathways. In this paper review and discuss novel methods that involve application of metabolomics to drug discovery and the understanding of mechanisms of action of medicinal plants with anti-TB activity. Current knowledge on TB infection, anti-TB drugs and mechanisms of action are also included. We further highlight metabolism of M. tuberculosis and the potential drug targets, as well as current approaches in the development of anti-TB drugs.


title: [Several suggestion of operation for colorectal cancer under the outbreak of Corona Virus Disease 19 in China].

text: Pneumonia caused by SARS-Cov-2 infection has been reported in Wuhan since December 2019, and spread rapidly across the country. The radical operation of colorectal cancer is confine operation. Patients with colorectal cancer should receive operation as soon as possible after elective operation is resumed in each hospital. SARS-Cov-2 virus can be transmitted by asymptomatic infectors, and it has been confirmed to be transmitted by droplets and contact. However, fecal-oral transmission and aerosol transmission have not been excluded. Based onLaparoscopic colorectal operation experiences, the author suggests that the surgery strategy for colorectal cancer patients under the COVID-19 situation. Recommending laparoscopy-assisted radical surgery for colorectal cancer patients. The aerosols need to be strictly managed during operation. NOSES and TaTME should be carried out with cautious during the epidemic period. Protective stoma should be carried out scientifically and reasonably, and the protection of operating room personnel should be strengthened.


title: Pedagogical foundations to online lectures in health professions education.

text: Professional and tertiary health professions education (HPE) has been markedly challenged by the current novel coronavirus (COVID-19). Mandates for training organisations to reduce social contact during the global pandemic, and make learning available online, provide an opportunity for regional, rural and remote clinicians and students to more easily access learning and professional development opportunities. Online lectures, while posing an opportunity for regional, rural and remote HPE, entail potential risks. Educators who are familiar with face-to-face pedagogies may find a transition to remote, digital interaction unfamiliar, disarming, and therefore they may not design maximally engaging lectures. The strategies used in a face-to-face lecture cannot be directly transferred into the online environment. This article proposes strategies to ensure the ongoing effectiveness, efficiency and engagement of lectures transitioning from face-to-face to online delivery. Cognitive learning theory, strategies to promote learner engagement and minimise distraction, and examples of software affordances to support active learning during the lecture are proposed. This enables lecturers to navigate the challenges of lecturing in an online environment and plan fruitful online lectures during this disruptive time. These suggestions will therefore enable HPE to better meet the existing and future needs of regional, rural and remote learners who may not be able to easily access face-to-face learning upon the relaxation of social distancing measures. Strategies to provide equitable HPE to learners who cannot access plentiful, fast internet are also discussed.


title: A method for reliable voluntary oral administration of a fixed dosage (mg/kg) of chronic daily medication to rats.

text: Stress can influence a number of physiological processes including adult neurogenesis, metabolism, cardiovascular function, immune function, neurophysiological function, endocrine function and inflammatory processes following injury. In testing drugs which may be used to treat various diseases or injuries, reducing stress associated with chronic drug delivery to animal models should then be an imperative, which led us to design a reliable voluntary oral drug delivery method. Various drug combinations were tested versus vehicle controls in four different rat stocks or strains (Wistar, Fisher, Long Evans and Sprague Dawley) with our voluntary oral delivery system. Oral medications were placed into a store-bought sugar cookie dough ball (~4 g), thoroughly integrating the dry drugs with the dough. This method has worked consistently to deliver the medication (complete ingestion) in four different stocks or strains of rats, with reliabilities ranging from 98.6% to 100%. The percentage of rats in each stock or strain that have at any time during the study had incomplete ingestion of the drugs ranged from 1% in Sprague Dawley, approximately 4% in Wistar and Fisher, to approximately 16% in Long Evans. Both serum and brain samples were analysed for high-performance liquid chromatography (HPLC) detection of one of our administered drugs: 5 mg/kg fluoxetine. HPLC analysis shows that serum levels are detectable 2-4 h after ingestion, but not 24 h after ingestion. Brain samples however, showed detectable levels of both fluoxetine and norfluoxetine more than a week following ingestion of a single dose, with higher norfluoxetine levels seen following a month of daily administered drugs.


title: Outcomes of Open, Laparoscopic, and Robotic Abdominoperineal Resections in Patients With Rectal Cancer.

text: BACKGROUND There are limited available data comparing open, laparoscopic, and robotic approaches for rectal cancer surgery. OBJECTIVE We sought to investigate outcomes of different surgical approaches to abdominoperineal resection in patients with rectal cancer. DESIGN The nationwide inpatient sample database was used to examine the clinical data of patients with rectal cancer who underwent elective abdominoperineal resection between 2009 and 2012 in the United States. Multivariate regression analysis was performed to compare outcomes of different surgical approaches. SETTINGS A retrospective review according to the national inpatient sample database was designed. PATIENTS We included patients with rectal cancer who underwent elective abdominoperineal resection between 2009 and 2012. MAIN OUTCOME MEASURES Outcomes of different surgical approaches to abdominoperineal resection were investigated. RESULTS We sampled 18,359 patients with rectal cancer who underwent elective abdominoperineal resections. Of these, 69.5% had open surgery, 25.8% had laparoscopic surgery, and 4.7% had robotic surgery. The rate of robotic procedures increased >4-fold, from 2.1% to 8.1%, from 2009 to 2012. The conversion rate in robotic surgery was significantly lower compared with laparoscopic surgery (5.7% vs 13.4%; p < 0.01). After risk adjustment, patients who underwent laparoscopic and robotic approaches had lower morbidity risks compared with those who underwent the open approach (adjusted OR = 0.77 (95% CI, 0.65-0.92), 0.57 (95% CI, 0.40-0.80); p < 0. 01). There were no significant differences in the morbidity rate of patients who underwent laparoscopic or robotic approaches (adjusted OR = 0.79 (95% CI, 0.55-1.14); p = 0.21). However, patients who underwent the robotic approach had significantly higher total hospital charges compared with those who underwent the laparoscopic approach (mean difference, $24,890; p < 0.01). LIMITATIONS We could not adjust the results with some important factors, such as the tumor stage and BMI. CONCLUSIONS The use of robotic and laparoscopic approaches to abdominoperineal resection have increased between 2009 and 2012. Both minimally invasive approaches decrease morbidity rates of patients undergoing abdominoperineal resection. The robotic approach has a significantly lower conversion rate compared with the laparoscopic approach. However, it had significantly higher total hospital charges compared with the laparoscopic approach.


title: Development of a multi-epitope antigen of S protein-based ELISA for antibodies detection against infectious bronchitis virus.

text: An indirect enzyme-linked immunosorbent assay (ELISA) method based on a novel multi-epitope antigen of S protein (SE) was developed for antibodies detection against infectious bronchitis virus (IBV). The multi-epitope antigen SE protein was designed by arranging three S gene fragments (166-247 aa, S1 gene; 501-515 aa, S1 gene; 8-30 aa, S2 gene) in tandem. It was identified to be approximately 32 kDa as a His-tagged fusion protein and can bind IBV positive serum by western blot analysis. The conditions of the SE-ELISA method were optimized. The optimal concentration of the coating antigen SE was 3.689 μg/mL and the dilution of the primary antibodies was identified as 1:1000 using a checkerboard titration. The cut-off OD450 value was established at 0.332. The relative sensitivity and specificity between the SE-ELISA and IDEXX ELISA kit were 92.38 and 89.83%, respectively, with an accuracy of 91.46%. This assay is sensitive and specific for detection of antibodies against IBV.


title: Association between postoperative troponin levels and 30-day mortality among patients undergoing noncardiac surgery.

text: CONTEXT Of the 200 million adults worldwide who undergo noncardiac surgery each year, more than 1 million will die within 30 days. OBJECTIVE To determine the relationship between the peak fourth-generation troponin T (TnT) measurement in the first 3 days after noncardiac surgery and 30-day mortality. DESIGN, SETTING, AND PARTICIPANTS A prospective, international cohort study that enrolled patients from August 6, 2007, to January 11, 2011. Eligible patients were aged 45 years and older and required at least an overnight hospital admission after having noncardiac surgery. MAIN OUTCOME MEASURES Patients' TnT levels were measured 6 to 12 hours after surgery and on days 1, 2, and 3 after surgery. We undertook Cox regression analysis in which the dependent variable was mortality until 30 days after surgery, and the independent variables included 24 preoperative variables. We repeated this analysis, adding the peak TnT measurement during the first 3 postoperative days as an independent variable and used a minimum P value approach to determine if there were TnT thresholds that independently altered patients' risk of death. RESULTS A total of 15,133 patients were included in this study. The 30-day mortality rate was 1.9% (95% CI, 1.7%-2.1%). Multivariable analysis demonstrated that peak TnT values of at least 0.02 ng/mL, occurring in 11.6% of patients, were associated with higher 30-day mortality compared with the reference group (peak TnT ≤ 0.01 ng/mL): peak TnT of 0.02 ng/mL (adjusted hazard ratio [aHR], 2.41; 95% CI, 1.33-3.77); 0.03 to 0.29 ng/mL (aHR, 5.00; 95% CI, 3.72-6.76); and 0.30 ng/mL or greater (aHR, 10.48; 95% CI, 6.25-16.62). Patients with a peak TnT value of 0.01 ng/mL or less, 0.02, 0.03-0.29, and 0.30 or greater had 30-day mortality rates of 1.0%, 4.0%, 9.3%, and 16.9%, respectively. Peak TnT measurement added incremental prognostic value to discriminate those likely to die within 30 days for the model with peak TnT measurement vs without (C index = 0.85 vs 0.81; difference, 0.4; 95% CI, 0.2-0.5; P < .001 for difference between C index values). The net reclassification improvement with TnT was 25.0% (P < .001). CONCLUSION Among patients undergoing noncardiac surgery, the peak postoperative TnT measurement during the first 3 days after surgery was significantly associated with 30-day mortality.


title: Reading First Coordinates from the Nephrogenic Zone in Human Fetal Kidney.

text: While substantial information is available on organ anlage and the primary formation of nephrons, molecular mechanisms acting during the late development of the human kidney have received an astonishing lack of attention. In healthy newborn babies, nephrogenesis takes place unnoticed until birth. Upon delivery, morphogenetic activity in the nephrogenic zone decreases, and the stem cell niches aligned beyond the organ capsule vanish by an unknown signal. However, this signal also plays a key role in preterm and low birth weight babies. Although they are born in a phase of active nephrogenesis, pathological findings illustrate that they evolve to a high incidence oligonephropathy and prematurity of renal parenchyma. Different extra- and intrauterine influences seem to be responsible, but independent from chemical nature, all of them culminate in the nephrogenic zone. One assumes that the marred development is caused either by an overshoot of metabolites, misleading signaling of morphogens, unbalanced synthesis of extracellular matrix or restricted contact between mesenchymal and epithelial stem cells. Even more surprising is that there is only a few vague morphological information of the nephrogenic zone in the human fetal kidney available and ultrastructural data is severely lacking. On this account, the first coordinates were determined by optical microscopy and morphometry. Without claiming to be complete, generated results made it possible to create schematic illustrations true to scale for orientation. It will help graduating students, young pediatricians, pathologists, and scientists working in the field of biomedicine to interpret professionally the nephrogenic zone and contained niches.


title: Time scale for resolution of olfactory dysfunction in COVID-19.

text: By now, the 2019 novel coronavirus disease (COVID-19), caused by the SARS-CoV-2 virus, is widely recognized around the world as a pandemic that has infected millions and claimed the lives of hundreds of thousands (1). Despite months of mitigation strategies, COVID-19 continues to spread and ascertainment of new knowledge about the disease process continues to be a priority of the medical community. Originally described by characteristic symptoms of fever, cough and/or shortness of breath that can rapidly progress to acute respiratory distress syndrome, it has become clear that COVID-19 has manifold clinical presentations (2-4). Notably, olfactory dysfunction (OD)-decreased sense of smell-has been reported to occur in up to 85.6% of COVID-19 patients (2,5).


title: Novel technique for relieving anastomotic tension using halo-vest immobilization after tracheal sleeve resection.

text: We describe a novel technique of using halo-vest-enforced immobilization to relieve anastomotic tension after tracheal sleeve resection. Immediately after the tracheal sleeve resection, four halo titanium pins were inserted in the skulls of the patients to secure the halo-vest. All patients fitted with halo-vests were able to eat and drink and their clinical course was good. Bronchoscopy confirmed the absence of anastomotic leaks and stenoses, and there were no complications associated with the halo-vest. We believe that ensuring neck flexion using a halo-vest after tracheal sleeve resection is an excellent way of relieving anastomotic tension that would predispose the wound to dehiscence.


title: Dynamic imaging of the hepatitis C virus NS5A protein during a productive infection.

text: UNLABELLED Hepatitis C virus (HCV) NS5A is essential for viral genome replication within cytoplasmic replication complexes and virus assembly at the lipid droplet (LD) surface, although its definitive functions are poorly understood. We developed approaches to investigate NS5A dynamics during a productive infection. We report here that NS5A motility and efficient HCV RNA replication require the microtubule network and the cytoplasmic motor dynein and demonstrate that both motile and relatively static NS5A-positive foci are enriched with host factors VAP-A and Rab5A. Pulse-chase imaging revealed that newly synthesized NS5A foci are small and distinct from aged foci, while further studies using a unique dual fluorescently tagged infectious HCV chimera showed a relatively stable association of NS5A foci with core-capped LDs. These results reveal new details about the dynamics and maturation of NS5A and the nature of potential sites of convergence of HCV replication and assembly pathways. IMPORTANCE Hepatitis C virus (HCV) is a major cause of serious liver disease worldwide. An improved understanding of the HCV replication cycle will enable development of novel and improved antiviral strategies. Here we have developed complementary fluorescent labeling and imaging approaches to investigate the localization, traffic and interactions of the HCV NS5A protein in living, virus-producing cells. These studies reveal new details as to the traffic, composition and biogenesis of NS5A foci and the nature of their association with putative sites of virus assembly.


Emerging human middle East respiratory syndrome coronavirus causes widespread infection and alveolar damage in human lungs.


title: Subtotal ureteral substitution with ileum for patients with multiple ureteral stenosis.

text: The use of small bowel for ureteral substitution in patients with ureteral stenosis can, nowadays, be safely performed with a laparoscopic or robotic mini-invasive approach. To date, this technique required a complete substitution of the ureter with ileum. In this work we present our robotic intracorporeal sub-total ureteral substitution preserving the distal part of the ureter with the aim to reduce the risk of vescico-ureteral reflux. We report the case of a 65-years old male with a "functional" right single kidney and multiple recurrent stenosis. Our technique seems to be feasible and safe, no intra or postoperative complication were recorded. At 3 months of follow-up the trans-nephrostomic enhanced CT showed a completely opacification of ileal ureter, thus the nephrostomic tube was removed. At 6 and 12 months the patient was asymptomatic and with a level of serum creatinine 1.9 and 1.6 mg/dL, respectively. In conclusion the sub-total ureteral substitution with ileum can be a safety and effective procedure for patients who require a mandatory preservation of homolateral renal function.


title: Fetal surgery for myelomeningocele: patient selection, perioperative management and outcomes.

text: Myelomeningocele (MMC), one of the most common congenital malformations, can result in severe lifelong disabilities,including paraplegia, hydrocephalus, Chiari II malformation(CM-II), incontinence, sexual dysfunction, skeletal deformations and mental impairment. MMC was the first nonlethal anomaly to be treated by fetal surgery. Experimental and clinical evidence suggests that the primary cause of the neurologic deficit associated with MMC is not simply incomplete neurulation but rather chronic mechanical injury and amniotic fluid-induced chemical trauma that progressively damages the exposed neural tissue during gestation. Case series and a prospective, randomized study show that fetal surgery for MMC before 26 weeks' gestation may preserve neurologic function, reverse the hindbrain herniation of the CM-II and obviate the need for postnatal placement of a ventriculoperitoneal shunt. However, these studies also demonstrate that fetal surgery is associated with significant maternal and fetal risks. Consequently, further research is warranted to further expand our understanding of the pathophysiology of MMC, to evaluate the long-term impact of in utero intervention and to refine the timing and technique of fetal MMC surgery.


title: Ocular Manifestations of COVID-19 (SARS-CoV-2): A Critical Review of Current Literature.

text: The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in China in the city of Wuhan in December of 2019 and since then more than 5,000,000 people have been infected, with approximately 338,000 deaths worldwide. The virus causes the coronavirus disease 2019 (COVID-19), which is characterized by fever, myalgia and cough, with severe acute respiratory syndrome being the most fearsome complication. Nevertheless, the vast majority of cases present mild symptoms or none. Central nervous system and cardiovascular manifestations have been reported. The range of ocular manifestations, either as a result of the infection or as a result of the treatment, has not yet been discussed. In this study, a systematic review of current literature relevant to COVID-19 was performed with focus on modes of transmission, ocular manifestations related to infection and medications, as well as the control of infection in ophthalmic practice.


Collateral damage of the covid-19 pandemic: a Dutch perinatal perspective.


Augmenting surgical capacity in resource-limited settings.


title: A model for treating COVID-19-related guilt, shame, and moral injury.

text: During the unprecedented COVID-19 pandemic, people around the world have faced a myriad of heart-rending and ethically difficult scenarios (e.g., not being able to tend to a sick or dying loved one) that may lead to subsequent guilt, shame, or moral injury. Trauma-informed guilt reduction therapy is a brief intervention that helps clients accurately appraise their role in a stressful event (such as those experienced during the COVID-19 pandemic) and find positive ways to express important values going forward. Future studies of trauma-informed guilt reduction therapy with those affected by COVID-19 will be helpful for clarifying its effectiveness with this population. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: A study of psychomotor skills in minimally invasive surgery: what differentiates expert and nonexpert performance.

text: BACKGROUND A high level of psychomotor skills is required to perform minimally invasive surgery (MIS) safely. To assure high quality of skills, it is important to be able to measure and assess these skills. For that, it is necessary to determine aspects that indicate the difference between performances at various levels of proficiency. Measurement and assessment of skills in MIS are best done in an automatic and objective way. The goal of this study was to investigate a set of nine motion-related metrics for their relevance to assess psychomotor skills in MIS during the performance of a labyrinth task. METHODS Thirty-two surgeons and medical students were divided into three groups according to their level of experience in MIS; experts (>500 MIS procedures), intermediates (31-500 MIS), and novices (no experience in MIS). The participants performed the labyrinth task in the D-box Basic simulator (D-Box Medical, Lier, Norway). The task required bimanual maneuvering and threading a needle through a labyrinth of 10 holes. Nine motion-related metrics were used to assess the MIS skills of each participant. RESULTS Experts (n = 7) and intermediates (n = 14) performed significantly better than the novices (n = 11) in terms of time and parameters measuring the amount of instrument movement. The experts had significantly better bimanual dexterity, which indicated that they made more simultaneous movements of the two instruments compared to the intermediates and novices. The experts also performed the task with a shorter instrument path length with the nondominant hand than the intermediates. CONCLUSIONS The surgeon's performance in MIS can be distinguished from a novice by metrics such as time and path length. An experienced surgeon in MIS can be differentiated from a less experienced one by the higher ability to control the instrument in the nondominant hand and the higher degree of simultaneous (coordinated) movements of the two instruments.


title: Sugary drink warnings: A meta-analysis of experimental studies.

text: BACKGROUND Policymakers worldwide are considering requiring warnings for sugary drinks. A growing number of experimental studies have examined sugary drink warnings' impacts, but no research to our knowledge has synthesized this literature. To inform ongoing policy debates, this study aimed to identify the effects of sugary drink warnings compared with control conditions. METHODS AND FINDINGS We systematically searched 7 databases on June 21, 2019, and October 25, 2019. We also searched reference lists of relevant articles. Two investigators independently screened titles, abstracts, and full texts to identify peer-reviewed articles that used an experimental protocol to examine the effects of sugary drink warnings compared to a control condition. Two investigators independently extracted study characteristics and effect sizes from all relevant full-text articles. We meta-analyzed any outcome assessed in at least 2 studies, combining effect sizes using random effects meta-analytic procedures. Twenty-three experiments with data on 16,241 individuals (mean proportion female, 58%) were included in the meta-analysis. Most studies took place in Latin America (35%) or the US or Canada (46%); 32% included children. Relative to control conditions, sugary drink warnings caused stronger negative emotional reactions (d = 0.69; 95% CI: 0.25, 1.13; p = 0.002) and elicited more thinking about the health effects of sugary drinks (d = 0.65; 95% CI: 0.29, 1.01; p < 0.001). Sugary drink warnings also led to lower healthfulness perceptions (d = -0.22; 95% CI: -0.27, -0.17; p < 0.001) and stronger disease likelihood perceptions (d = 0.15; 95% CI: 0.06, 0.24; p = 0.001). Moreover, sugary drink warnings reduced both hypothetical (d = -0.32; 95% CI: -0.44, -0.21; p < 0.001) and actual consumption and purchasing behavior (d = -0.17; 95% CI: -0.30, -0.04; p = 0.012). Statistically significant effects were not observed for perceptions of added sugar or positive sugary drink attitudes (p's > 0.10). Moderation analyses revealed that health warnings (e.g., "Beverages with added sugar contribute to obesity") led to greater reductions in hypothetical sugary drink purchases than did nutrient warnings (e.g., "High in sugar"; d = -0.35 versus -0.18; Qb = 4.04; p = 0.04). Limitations of this study include that we did not review grey literature and that we were unable to conduct moderation analyses for several prespecified moderators due to an insufficient number of studies. CONCLUSIONS This international body of experimental literature supports sugary drink warnings as a population-level strategy for changing behavior, as well as emotions, perceptions, and intentions. PROTOCOL REGISTRY PROSPERO ID 146405.


title: The value of 18F-FDG PET/CT in diagnosing infectious endocarditis.

text: PURPOSE Early detection of infectious endocarditis is challenging. For diagnosing infectious endocarditis, the revised Duke criteria are the gold standard. Evidence of endocardial involvement on echocardiography is a major criterion, but sensitivity and specificity of echocardiography are not optimal. Here we investigated the utility of (18)F-fluorodeoxyglucose (FDG) positron emission tomography and computed tomography (PET/CT) to diagnose infectious endocarditis in patients with gram-positive bacteraemia. METHODS Seventy-two patients with gram-positive bacteraemia were prospectively included. Patients with a positive blood culture growing Staphylococcus aureus, Streptococcus species or Enterococcus species were eligible when a risk factor for developing metastatic infectious foci was present. Infectious endocarditis was defined according to the revised Duke criteria. All patients underwent (18)F-FDG PET/CT and echocardiography. (18)F-FDG uptake in or around the heart valves was evaluated independently by two nuclear medicine physicians. RESULTS Sensitivity for diagnosing infectious endocarditis with (18)F-FDG PET/CT was 39% and specificity was 93%. The positive predictive value was 64% and negative predictive value was 82%. The mortality rate in patients without infectious endocarditis and without increased (18)F-FDG uptake in or around the heart valves was 18%, and in patients without infectious endocarditis but with high (18)F-FDG uptake in or around the heart valves the mortality rate was 50% (p = 0.181). CONCLUSION (18)F-FDG PET/CT is currently not sufficiently adequate for the diagnosis of infectious endocarditis because of its low sensitivity. Improvements such as patient preparation with low carbohydrate-fat allowed diet and technical advances in the newest PET/CT scanners may increase sensitivity in future studies.


title: Monitoring respiratory virus infection in the metropolitan area of Belo Horizonte, Brazil, 2011-2013.

text: OBJECTIVE to analyze the circulation of respiratory viruses in people living in the metropolitan area of Belo Horizonte, Brazil, and hospitalized in Belo Horizonte from 2011 to 2013. METHODS this is a descriptive study of 5,158 patients with Severe Acute Respiratory Syndrome; a comparison was made between the characteristics of confirmed cases and those of discarded cases or cases without swab samples. RESULTS Influenza A virus accounted for half the isolated viruses, especially subtype A(H1N1)pdm09 among patients aged 20-59 years old, and subtype A(H3N2) in those aged 60 or over; the most frequently identified respiratory virus among children under five years old was respiratory syncytial virus (65.6%), followed by influenza A virus (21.2%); influenza virus circulated in all seasons of the year and its periods of greatest incidence were interspersed with those of higher Respiratory Syncytial Virus activity. CONCLUSION monitoring respiratory viruses contributes to knowledge about periods of virus circulation and the adoption of specific control measures.


A case of Covid19 infection manifesting itself with only abdominal symptoms.


Covid-19 and alcohol-a dangerous cocktail.


title: Delayed antibiotic prescribing for respiratory tract infections: protocol of an individual patient data meta-analysis.

text: INTRODUCTION Delayed prescribing can be a useful strategy to reduce antibiotic prescribing, but it is not clear for whom delayed prescribing might be effective. This protocol outlines an individual patient data (IPD) meta-analysis of randomised controlled trials (RCTs) and observational cohort studies to explore the overall effect of delayed prescribing and identify key patient characteristics that are associated with efficacy of delayed prescribing. METHODS AND ANALYSIS A systematic search of the databases Cochrane Central Register of Controlled Trials, Ovid MEDLINE, Ovid Embase, EBSCO CINAHL Plus and Web of Science was conducted to identify relevant studies from inception to October 2017. Outcomes of interest include duration of illness, severity of illness, complication, reconsultation and patient satisfaction. Study authors of eligible papers will be contacted and invited to contribute raw IPD data. IPD data will be checked against published data, harmonised and aggregated to create one large IPD database. Multilevel regression will be performed to explore interaction effects between treatment allocation and patient characteristics. The economic evaluation will be conducted based on IPD from the combined trial and observational studies to estimate the differences in costs and effectiveness for delayed prescribing compared with normal practice. A decision model will be developed to assess potential savings and cost-effectiveness in terms of reduced antibiotic usage of delayed prescribing and quality-adjusted life years. ETHICS AND DISSEMINATION Ethical approval was obtained from the University of Southampton Faculty of Medicine Research Ethics Committee (Reference number: 30068). Findings of this study will be published in peer-reviewed academic journals as well as General Practice trade journals and will be presented at national and international conferences. The results will have important public health implications, shaping the way in which antibiotics are prescribed in the future and to whom delayed prescriptions are issued. PROSPERO REGISTRATION NUMBER CRD42018079400.


title: Superparamagnetic nanoparticle capture of prions for amplification.

text: Prion diseases are associated with the presence of PrP(Sc), a disease-associated misfolded conformer of the prion protein. We report that superparamagnetic nanoparticles bind PrP(Sc) molecules efficiently and specifically, permitting magnetic separation of prions from a sample mixture. Captured PrP(Sc) molecules retain the activity to seed protein misfolding cyclic amplification (PMCA) reactions, enabling the rapid concentration of dilute prions to improve detection. Furthermore, superparamagnetic nanoparticles clear contaminated solutions of PrP(Sc). Our findings suggest that coupling magnetic nanoparticle capture with PMCA could accelerate and improve prion detection. Magnetic nanoparticles may also be useful for developing a nontoxic prion decontamination method for biologically derived products.


title: Transglanular repair of impending penile prosthetic cylinder extrusion.

text: INTRODUCTION Penile prosthetic devices are highly satisfactory in the management of erectile dysfunction but carry a number of risks including the potential for erosion. In some cases, impending extrusion can be identified and managed before frank erosion occurs. AIMS To report our results using a transglanular approach for management of impending distal erosion of penile prosthetic devices. METHODS Patients who presented with impending erosion of penile prosthetics were identified by retrospective chart review. Patients who were managed with a transglanular surgical approach constitute the study group. MAIN OUTCOME MEASURES Clinical data were culled from the charts. Identified patients were contacted and were asked a battery of questions regarding their subjective assessment of the treatment's efficacy. RESULTS Six men were identified. Mean age at time of surgery was 56 years. Four men had had implants placed within the past 2 years and two had implants that had been in place for greater than 12 years. Mean operative time was 25 minutes. Four patients were successfully managed with a single repair procedure. Two men required repeat revision surgery. Of men that were available for additional postoperative contact, three of four reported satisfaction with the procedure. CONCLUSIONS The transglanular approach for repair of impending distal erosion of penile prosthetics is a quick and minimally morbid procedure that produces satisfactory results in the majority of patients. Further refinements of technique will likely lead to greater overall improvement in outcomes.


title: Flexor tendon injuries in the child.

text: This review aims to highlight the differences in the management of flexor tendon injuries between children and adults. These include differences in epidemiology, anatomy, classification, diagnosis, incisions and skin closure, the size of the flexor tendons, technical aspects of zones I and II repairs, core suture purchase length, rehabilitation, results, and complications of primary flexor tendon repair. Finally, one- versus two-stage flexor tendon reconstruction in children is reviewed.


title: Coil Embolization for Ruptured Basilar Tip Aneurysm After Mechanical Thrombectomy for Acute Basilar Artery Occlusion.

text: BACKGROUND There is no published report of ruptured cerebral aneurysm accompanied by target vessel occlusion. We present a case of ruptured basilar tip aneurysm with concomitant basilar artery (BA) occlusion. CASE DESCRIPTION A 53-year-old man presented to our emergency room with the acute onset of disturbance. Plain head computed tomography showed diffuse subarachnoid hemorrhage. Computed tomography angiography and digital subtraction angiography showed a BA tip aneurysm with BA trunk occlusion. Endovascular treatment with mechanical thrombectomy using a stent retriever and coil embolization was performed. Clinical and radiologic results were good. The patient was discharged 30 days after onset (modified Rankin Scale score = 1). CONCLUSIONS We were able to recanalize the BA trunk and perform coil embolization of the ruptured BA tip aneurysm. Our case is the first published report of a ruptured aneurysm with target large-vessel occlusion. Awareness of the issues raised in this case is required to determine the best treatment strategy, and preoperative consideration allows neurointerventionalists to avoid unpleasant surprises in the angiography suite.


title: Unbiased Detection of Respiratory Viruses by Use of RNA Sequencing-Based Metagenomics: a Systematic Comparison to a Commercial PCR Panel.

text: Current infectious disease molecular tests are largely pathogen specific, requiring test selection based on the patient's symptoms. For many syndromes caused by a large number of viral, bacterial, or fungal pathogens, such as respiratory tract infections, this necessitates large panels of tests and has limited yield. In contrast, next-generation sequencing-based metagenomics can be used for unbiased detection of any expected or unexpected pathogen. However, barriers for its diagnostic implementation include incomplete understanding of analytical performance and complexity of sequence data analysis. We compared detection of known respiratory virus-positive (n= 42) and unselected (n= 67) pediatric nasopharyngeal swabs using an RNA sequencing (RNA-seq)-based metagenomics approach and Taxonomer, an ultrarapid, interactive, web-based metagenomics data analysis tool, with an FDA-cleared respiratory virus panel (RVP; GenMark eSensor). Untargeted metagenomics detected 86% of known respiratory virus infections, and additional PCR testing confirmed RVP results for only 2 (33%) of the discordant samples. In unselected samples, untargeted metagenomics had excellent agreement with the RVP (93%). In addition, untargeted metagenomics detected an additional 12 viruses that were either not targeted by the RVP or missed due to highly divergent genome sequences. Normalized viral read counts for untargeted metagenomics correlated with viral burden determined by quantitative PCR and showed high intrarun and interrun reproducibility. Partial or full-length viral genome sequences were generated in 86% of RNA-seq-positive samples, allowing assessment of antiviral resistance, strain-level typing, and phylogenetic relatedness. Overall, untargeted metagenomics had high agreement with a sensitive RVP, detected viruses not targeted by the RVP, and yielded epidemiologically and clinically valuable sequence information.


COVID-19 and district and community nursing.


title: Evaluation of the Renal Arteries of 2,144 Living Kidney Donors Using Computed Tomography Angiography and Comparison with Intraoperative Findings.

text: OBJECTIVES A carefully chosen and suitably prepared kidney donor is essential in living-donor kidney transplantation. Computed tomography angiography (CTA) is an effective imaging method for evaluating the renovascular morphology of donor candidates. The aim of this study was to evaluate renal artery variations in kidney donors using CTA and compare the findings with the number of arteries detected during laparoscopic donor nephrectomy. MATERIALS AND METHODS The study included 2,144 living donors who underwent pretransplant renovascular assessment using CTA and laparoscopic donor nephrectomy in our center between August 2012 and October 2018. The number of renal arteries to the donor kidney detected on CTA was compared with the number of arteries discovered intraoperatively. RESULTS The mean age of the 2,144 living kidney donors included in the study was 47.19 ± 13.3 (18-87) years. According to CTA findings, 81.1% (n = 1,738) had a single renal artery, 17.2% (n = 369) had double renal arteries, 1.6% (n = 35) had triple renal arteries, and 0.1% (n = 2) had quadruple renal arteries. The same number of renal arteries were detected by CTA and in laparoscopic donor nephrectomy in 97.9% (n = 2,099) of the donors. In the other 2.1% (n = 45), fewer renal arteries were detected intraoperatively compared to their CTA findings. None of the donors included in the study had a greater number of renal arteries discovered during nephrectomy than by CTA. CONCLUSION CTA is a highly accurate method for the evaluation of renovascular variations in donor candidates for living-donor kidney transplantation. However, it must be kept in mind that double or multiple renal artery variations may be detected on CTA in 18.9% of donor candidates.


title: Chikungunya virus emergence is constrained in Asia by lineage-specific adaptive landscapes.

text: Adaptation of RNA viruses to a new host or vector species often results in emergence of new viral lineages. However, lineage-specific restrictions on the adaptive processes remain largely unexplored. Recently, a Chikungunya virus (CHIKV) lineage of African origin emerged to cause major epidemics of severe, persistent, debilitating arthralgia in Africa and Asia. Surprisingly, this new lineage is actively replacing endemic strains in Southeast Asia that have been circulating there for 60 y. This replacement process is associated with adaptation of the invasive CHIKV strains to an atypical vector, the Aedes albopictus mosquito that is ubiquitously distributed in the region. Here we demonstrate that lineage-specific epistatic interactions between substitutions at amino acid positions 226 and 98 of the E1 envelope glycoprotein, the latter of which likely resulted from a founder effect, have for 60 y restricted the ability of endemic Asian CHIKV strains to adapt to this new vector. This adaptive constraint appears to be allowing invasion of the unoccupied vector niche by Ae. albopictus-adapted African strains. These results underscore how different adaptive landscapes occupied by closely related viral genotypes can profoundly affect the outcome of viral evolution and disease emergence.


title: The Diagnostic Efficiency of 99mTc-EDDA/HYNIC-Octreotate SPECT-CT in Comparison with 111In-Pentetrotide in the Detection of Neuroendocrine Tumours.

text: OBJECTIVE The aim of this study was to assess the diagnostic efficiency of (99m)Tc-EDDA/HYNIC-Octreotate in comparison with (111)Inpentetrotide scintigraphy in the detection of neuroendocrine tumors. This study also evaluates the impact of SPECT-CT hybrid imaging on somatostatin receptor scintigraphy (SRS) interpretation and clinical management of these tumors. METHODS Fourteen patients were included in the study. All patients underwent a whole body and SPECT-CT imaging with both (99m)Tc- EDDA/HYNIC-octreotate and (111)In-pentetrotide. Images were evaluated both visually and semiquantitatively. RESULTS On patient basis, the diagnostic results of both studies were similar. The number of lesions detected by (99m)Tc- EDDA/HYNICOctreotate were higher than the number of lesions detected by (111)In-pentetrotide however the difference was not significant (40/43( 93%), 36/43 (83%) p=0.109). Semiquantitative analysis showed higher tumor/organ count ratios for both whole-body and SPECT (99m)Tc- EDDA/HYNIC-Octreotate scans. CONCLUSION The results of this study suggested that, (99m)Tc- EDDA/HYNIC-Octreotate may be a better alternative to (111)In- pentetrotide due to high image quality and lower radiation dose. SPECT/CT is a valuable tool for the assessment of neuroendocrine tumors by providing the precise anatomic localization of scintigraphic findings thus improving lesion detectability and characterization. CONFLICT OF INTEREST None declared.


Mental Health of Communities during the COVID-19 Pandemic.


title: Identification of a coronavirus transcription enhancer.

text: Coronavirus (CoV) transcription includes a discontinuous mechanism during the synthesis of sub-genome-length minus-strand RNAs leading to a collection of mRNAs in which the 5' terminal leader sequence is fused to contiguous genome sequences. It has been previously shown that transcription-regulating sequences (TRSs) preceding each gene regulate transcription. Base pairing between the leader TRS (TRS-L) and the complement of the body TRS (cTRS-B) in the nascent RNA is a determinant factor during CoV transcription. In fact, in transmissible gastroenteritis CoV, a good correlation has been observed between subgenomic mRNA (sg mRNA) levels and the free energy (DeltaG) of TRS-L and cTRS-B duplex formation. The only exception was sg mRNA N, the most abundant sg mRNA during viral infection in spite of its minimum DeltaG associated with duplex formation. We postulated that additional factors should regulate transcription of sg mRNA N. In this report, we have described a novel transcription regulation mechanism operating in CoV by which a 9-nucleotide (nt) sequence located 449 nt upstream of the N gene TRS core sequence (CS-N) interacts with a complementary sequence just upstream of CS-N, specifically increasing the accumulation of sg mRNA N. Alteration of this complementarity in mutant replicon genomes showed a correlation between the predicted stability of the base pairing between 9-nt sequences and the accumulation of sg mRNA N. This interaction is exclusively conserved in group 1a CoVs, the only CoV subgroup in which the N gene is not the most 3' gene in the viral genome. This is the first time that a long-distance RNA-RNA interaction regulating transcriptional activity specifically enhancing the transcription of one gene has been described to occur in CoVs.


title: Embolization of cerebral arteriovenous malformations with silk suture particles prior to stereotactic radiosurgery.

text: We aimed to determine the long term durability of silk suture and polyvinyl alcohol (PVA) particle embolization (SPE) of arteriovenous malformations (AVM), and to evaluate the outcomes following multimodality management of AVM with combined SPE and stereotactic radiosurgery (SRS). A general supposition among neurointerventionalists is that embolization of cerebral AVM with silk sutures and PVA particles does not yield a durable occlusion. We performed a retrospective review of all AVM patients treated at our institution with combined SPE and SRS. After extracting the baseline, embolization and SRS data for each patient, the durability of SPE was determined by evaluating the postembolization recanalization between the last procedural angiogram and the most recent neuroimaging. Four AVM patients who underwent a total of nine SPE procedures through 21 arterial pedicles were included for the analyses. The nidus volumes were 5.8-75 cm(3) and the Spetzler-Martin grades were II and V in one patient and III in two patients. The median degree of devascularization per procedure was <25%. There were no procedural complications, with all patients maintaining functional independence after embolization (modified Rankin scale score 0-2). After a median follow-up duration of 27 months (range: 23-36), there were no patients with recanalization. SRS (marginal dose 13-18 Gy) resulted in 40 to >95% volume reduction. Following SRS, one patient remained asymptomatic, two patients improved, and one patient deteriorated due to a latency period AVM hemorrhage. In conclusion, SPE can safely provide durable AVM devascularization, therefore, appropriately selected nidi can be effectively treated with combined SPE and SRS.


Vascular perforation by enterprise stent during stent-assisted coil embolization for intracranial aneurysm.


title: Coronavirus Host Range Expansion and Middle East Respiratory Syndrome Coronavirus Emergence: Biochemical Mechanisms and Evolutionary Perspectives.

text: Coronaviruses have frequently expanded their host range in recent history, with two events resulting in severe disease outbreaks in human populations. Severe acute respiratory syndrome coronavirus (SARS-CoV) emerged in 2003 in Southeast Asia and rapidly spread around the world before it was controlled by public health intervention strategies. The 2012 Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak represents another prime example of virus emergence from a zoonotic reservoir. Here, we review the current knowledge of coronavirus cross-species transmission, with particular focus on MERS-CoV. MERS-CoV is still circulating in the human population, and the mechanisms governing its cross-species transmission have been only partially elucidated, highlighting a need for further investigation. We discuss biochemical determinants mediating MERS-CoV host cell permissivity, including virus spike interactions with the MERS-CoV cell surface receptor dipeptidyl peptidase 4 (DPP4), and evolutionary mechanisms that may facilitate host range expansion, including recombination, mutator alleles, and mutational robustness. Understanding these mechanisms can help us better recognize the threat of emergence for currently circulating zoonotic strains.


Chinese Officials Investigate Cause of Pneumonia Outbreak in Wuhan.


Chronic wounds?


Correction to Considering the Effects of Microbiome and Diet on SARS-CoV-2 Infection: Nanotechnology Roles.


title: Contraception and reproductive planning during the COVID-19 pandemic.

text: INTRODUCTION The coronavirus disease (COVID-19) is a global health emergency. Major disruption to healthcare services during the current COVID 19 pandemic will last even after its peak. Sexual and reproductive health (SRH), specially contraception, needs to be understood as an essential service. AREAS COVERED This paper is a narrative review. Data from PubMed/MEDLINE, Scopus, and websites of scientific societies were screened during the months of April and May 2020. It addresses the main aspects related to contraception during the COVID-19 pandemic, with special emphasis on family planning services, extended use of long-acting reversible contraceptive (LARC) methods, drug interactions and thromboembolism risk. We also specified some issues focused on the Brazilian reality. EXPERT OPINION Ensuring proper contraception use in the COVID-19 time is very important. We encourage women, healthcare providers, policy makers, and the society to consider SRH services as priority.


title: Epidemiology of outpatient and inpatient eye injury in Taiwan: 2000, 2005, 2010, and 2015.

text: PURPOSE To estimate the incidence rate of eye injuries (EI) requiring inpatient and outpatient treatment in Taiwan and compare the epidemiologic characteristics of EI (age, sex, treatment setting, seasonality, occupation, external cause, diagnosis, and surgery) in the years 2000, 2005, 2010, and 2015. METHODS We analyzed four random samples of 1,000,000 beneficiaries each from 2000, 2005, 2010, and 2015 of the Taiwan National Health Insurance Program. The direct age-standardized rate, with 95% confidence interval (CI), was used to compare EI rates for the four calendar years. The chi-square test and chi-square test for trend were used to compare data for the four calendar years. RESULTS Annual EI incidence rates were between 2.57% in 2000 and 3.28% in 2015. The age-standardized rates were 2.73% (95% CI, 2.70%-2.76%) in 2000, 3.37% (95% CI, 3.33%-3.41%) in 2005, 3.31% (95% CI, 3.28%-3.35%) in 2010, and 3.02% (95% CI, 2.99%-3.06%) in 2015. Manual workers had the highest EI incidence rate, followed by non-manual workers and civil servants. The proportion of EI requiring inpatient treatment declined from 1.34% in 2000 to 0.63% in 2015 (P <0.0001). Analysis of seasonality showed a consistent decrease in February in the four sampling years; however, this decrease in EI was only seen in outpatients, not in EI requiring hospitalization. The proportion of outpatients requiring surgery significantly decreased, from 2.53% in 2000 to 1.2% in 2015 (P<0.0001). However, the proportion of inpatients requiring surgery for EI as the principal diagnosis increased from 69.32% in 2000 to 83.02% in 2015 (P = 0.29), and the proportion of inpatients requiring surgery for EI as a secondary diagnosis increased from 54.86% in 2000 to 71.6% in 2015 (P = 0.0019). Among inpatients with EI, the most common cause of EI was a traffic accident (44.79%, especially motorcycles), followed by falls (9.75%) and homicide (6.05%). CONCLUSION In Taiwan, the annual EI incidence rate slightly increased from 2000 to 2005 and then decreased through 2015. The proportion of EI patients requiring hospitalization decreased from 1.34% in 2000 to 0.63% in 2015, but the percentage of inpatients requiring surgery increased. Traffic accidents (especially those involving motorcyclists) remained the predominant external cause of EI requiring hospitalization during the study period.


title: Validated computed cleansing score for video capsule endoscopy.

text: BACKGROUND AND AIM Diagnostic yield of video capsule endoscopy may be hampered by intestinal content or air bubbles. A major limitation in video capsule-related study is the lack of a validated objective score for bowel preparation quality. We aimed to design and validate a computed small bowel preparation score for research and clinical use. METHODS Two experienced physicians reached a consensus regarding bowel preparation quality based on known criteria used in previous studies and their confidence of an accurate medical interpretation of the procedure. A computed algorithm based on the pixels in the color bar was created and validated. Concordance between the gastroenterologists' agreement (gold standard) and the computed analysis was assessed. RESULTS Of 85 videos studied, 44 (52%), 13 (15%) and 28 (33%) had adequate, borderline and inadequate bowel preparation, respectively, according to the gastroenterologists' agreement. Computer analysis restricted to adequate and inadequate cases yielded accurate classification of bowel preparation in 65/72 cases (90% agreement, sensitivity 95%, specificity 82%, total accuracy 90%, Kappa 0.79). When adding the borderline definition, the computer analysis correctly classified 71/85 of the cases, yielding an overall agreement of 84% (Kappa 0.72). Minute-by-minute analysis of 10 cases also yielded an agreement of 91.4%. CONCLUSION The present study introduces a user-friendly computer analysis-based small bowel preparation score, which demonstrated excellent concordance with the physician's assessment. This score holds promise as a standardization tool in research and clinical practice of video capsule endoscopy. Further validation is warranted.


title: Overactive Epidermal Growth Factor Receptor Signaling Leads to Increased Fibrosis after Severe Acute Respiratory Syndrome Coronavirus Infection.

text: Severe acute respiratory syndrome coronavirus (SARS-CoV) is a highly pathogenic respiratory virus that causes morbidity and mortality in humans. After infection with SARS-CoV, the acute lung injury caused by the virus must be repaired to regain lung function. A dysregulation in this wound healing process leads to fibrosis. Many survivors of SARS-CoV infection develop pulmonary fibrosis (PF), with higher prevalence in older patients. Using mouse models of SARS-CoV pathogenesis, we have identified that the wound repair pathway, controlled by the epidermal growth factor receptor (EGFR), is critical to recovery from SARS-CoV-induced tissue damage. In mice with constitutively active EGFR [EGFR(DSK5) mice], we find that SARS-CoV infection causes enhanced lung disease. Importantly, we show that during infection, the EGFR ligands amphiregulin and heparin-binding EGF-like growth factor (HB-EGF) are upregulated, and exogenous addition of these ligands during infection leads to enhanced lung disease and altered wound healing dynamics. Our data demonstrate a key role of EGFR in the host response to SARS-CoV and how it may be implicated in lung disease induced by other highly pathogenic respiratory viruses.IMPORTANCE PF has many causative triggers, including severe respiratory viruses such as SARS-CoV. Currently there are no treatments to prevent the onset or limit the progression of PF, and the molecular pathways underlying the development of PF are not well understood. In this study, we identified a role for the balanced control of EGFR signaling as a key factor in progression to PF. These data demonstrate that therapeutic treatment modulating EGFR activation could protect against PF development caused by severe respiratory virus infection.


title: A multicenter single-arm Phase II clinical trial of second-line FOLFIRI plus panitumumab after first-line treatment with FOLFOX plus panitumumab for initial RAS wild-type colorectal cancer with evaluation of circulating tumor DNA: A protocol study.

text: The efficacy and safety of the continuous use of panitumumab in first- and second-line treatments for colorectal cancer (CRC) have yet to be determined. Liquid biopsy of circulating tumor DNA is capable of assessing the gene mutation status at several time-points, and could predict the efficacy of ongoing panitumumab treatment. To address these two points, a multicenter single-arm Phase II clinical trial will be conducted by evaluating the effect of FOLFIRI with panitumumab as second-line chemotherapy in patients with CRC, after failure or intolerance of first-line treatment with FOLFOX with panitumumab. The primary endpoint is the 6-month progression-free survival rate. Gene mutation status using circulating tumor DNA will be assessed at multiple time-points during the study period as one of the secondary endpoints. The observed 6-month PFS rate will be compared with the threshold 6-month PFS rate of 35% with a one-sided significance level of 10% using the binomial exact test. The target number of cases in this study is 55 patients. The study protocol was approved by the Institutional Review Board of the Epidemiological and Clinical Research Information Network (17-0601-1) and will be conducted after approval by the Institutional Review Board of each participating institute. This study is registered in UMIN (UMIN000026817, March 31, 2017). The results of the present study will be presented at related international congresses, and will be disseminated in peer-reviewed journals.


title: Clamp-crushing versus stapler hepatectomy for transection of the parenchyma in elective hepatic resection (CRUNSH)--a randomized controlled trial (NCT01049607).

text: BACKGROUND Hepatic resection is still associated with significant morbidity. Although the period of parenchymal transection presents a crucial step during the operation, uncertainty persists regarding the optimal technique of transection. It was the aim of the present randomized controlled trial to evaluate the efficacy and safety of hepatic resection using the technique of stapler hepatectomy compared to the simple clamp-crushing technique. METHODS/DESIGN The CRUNSH Trial is a prospective randomized controlled single-center trial with a two-group parallel design. Patients scheduled for elective hepatic resection without extrahepatic resection at the Department of General-, Visceral- and Transplantation Surgery, University of Heidelberg are enrolled into the trial and randomized intraoperatively to hepatic resection by the clamp-crushing technique and stapler hepatectomy, respectively. The primary endpoint is total intraoperative blood loss. A set of general and surgical variables are documented as secondary endpoints. Patients and outcome-assessors are blinded for the treatment intervention. DISCUSSION The CRUNSH Trial is the first randomized controlled trial to evaluate efficacy and safety of stapler hepatectomy compared to the clamp-crushing technique for parenchymal transection during elective hepatic resection. TRIAL REGISTRATION ClinicalTrials.gov: NCT01049607.


title: Impact of COVID-19 pandemic on people living with visual disability.

text: People living with visual disabilities/impairment are more likely vulnerable to get contracted from the severe acute respiratory syndrome coronavirus-2 (SARS-CoV 2) than people without visual impairment. This means more than 253 million people globally will be at higher risk of affecting by the COVID-19. The current pandemic, followed by a nationwide emergency lockdown to slow the unprecedented spread of the virus, will have a serious impact on people living with visual disabilities and even endangers their lives in the long run. Many restrictive and control measures, including the adoption of new behavioural changes (for example, social distance during outdoor movement, limiting touch or tactile contact) recommended by the government will pose immense challenges to individuals with a visual loss. This serious impact, including challenges in healthcare access, can be minimized through inclusive service approaches, involving persons with visual disabilities, caregivers, family members, and healthcare providers, along with the community to a large extent, and finally, support to improve the overall outcomes. The government, along with profit or non-profit private sectors, should consider initiating such inclusive approaches while planning responses to the pandemic. Indeed, the present COVID-19 pandemic provides an opportunity for health care planners and decision-makers of various organizations across India for a reformation of disabilities care. Impacts due to the pandemic and lockdown can be reduced substantially if planning and policy are in place before any emergency happened in the future.


Tens of thousands of scientists are redeploying to fight coronavirus.


title: Community-acquired pneumonia.

text: PURPOSE OF REVIEW Community-acquired pneumonia (CAP) is a major cause of morbidity, mortality and expenditure of resources. When followed, guidelines for CAP management have been demonstrated to improve clinical outcomes; however, several issues are still open. This review summarizes the recent advances in this field and the priority needs for future research. RECENT FINDINGS Recently identified clinical and biochemical tools promise to improve the assessment of CAP severity; however, definition of the most accurate and feasible rule(s) for clinical practice is now necessary. Some empirical antimicrobial regimens are still being debated, such as the need for atypical pathogen coverage in home-treated and nonsevere hospitalized patients and the inclusion of respiratory fluoroquinolones among first-choice molecules. New drugs such as tigecycline and cethromycin appear promising. Pharmacokinetically enhanced amoxicillin/clavulanate is highly effective, even for treating CAP caused by multiple-drug-resistant Streptococcus pneumoniae. Other aspects recently clarified include the inappropriateness of rigid time-to-first-antibiotic-dose rules, the advantages of shorter antibiotic treatments for nonsevere patients and the need of special clinical attention for acute myocardial infarction among patients with severe CAP or clinical failure. SUMMARY Recent developments have significantly contributed to refine the management of CAP patients. However, various hot topics remain undefined as yet and urgently require ad-hoc research in order to optimize the outcomes and the costs of this highly social-impacting disease.


Critically ill patients with influenza A(H1N1)pdm09 virus infection in 2014.


title: Sublingual microcirculatory changes during high-volume hemofiltration in hyperdynamic septic shock patients.

text: INTRODUCTION Previous studies have suggested that high volume hemofiltration (HVHF) may contribute to revert hypotension in severe hyperdynamic septic shock patients. However, arterial pressure stabilization occurs due to an increase in systemic vascular resistance, which could eventually compromise microcirculatory blood flow and perfusion. The goal of this study was to determine if HVHF deteriorates sublingual microcirculation in severe hyperdynamic septic shock patients. METHODS This was a prospective, non-randomized study at a 16-bed, medical-surgical intensive care unit of a university hospital. We included 12 severe hyperdynamic septic shock patients (norepinephrine requirements > 0.3 μg/kg/min and cardiac index > 3.0 L/min/m2) who underwent a 12-hour HVHF as a rescue therapy according to a predefined algorithm. Sublingual microcirculation (Microscan for NTSC, Microvision Medical), systemic hemodynamics and perfusion parameters were assessed at baseline, at 12 hours of HVHF, and 6 hours after stopping HVHF. RESULTS Microcirculatory flow index increased after 12 hours of HVHF and this increase persisted 6 hours after stopping HVHF. A similar trend was observed for the proportion of perfused microvessels. The increase in microcirculatory blood flow was inversely correlated with baseline levels. There was no significant change in microvascular density or heterogeneity during or after HVHF. Mean arterial pressure and systemic vascular resistance increased while lactate levels decreased after the 12-hour HVHF. CONCLUSIONS The use of HVHF as a rescue therapy in patients with severe hyperdynamic septic shock does not deteriorate sublingual microcirculatory blood flow despite the increase in systemic vascular resistance.


title: Structure of replicating SARS-CoV-2 polymerase.

text: The coronavirus SARS-CoV-2 uses an RNA-dependent RNA polymerase (RdRp) for the replication of its genome and the transcription of its genes1-3. Here we present the cryo-electron microscopic structure of the SARS-CoV-2 RdRp in active form, mimicking the replicating enzyme. The structure comprises the viral proteins nsp12, nsp8, and nsp7, and over two turns of RNA template-product duplex. The active site cleft of nsp12 binds the first turn of RNA and mediates RdRp activity with conserved residues. Two copies of nsp8 bind to opposite sides of the cleft and position the second turn of RNA. Long helical extensions in nsp8 protrude along exiting RNA, forming positively charged 'sliding poles'. These sliding poles can account for the known processivity of the RdRp that is required for replicating the long coronavirus genome3. Our results enable a detailed analysis of the inhibitory mechanisms that underlie the antiviral activity of substances such as remdesivir, a drug for the treatment of coronavirus disease 2019 (COVID-19)4.


title: Drug-eluting balloon versus standard balloon angioplasty for infrapopliteal arterial revascularization in critical limb ischemia: 12-month results from the IN.PACT DEEP randomized trial.

text: BACKGROUND Drug-eluting balloons (DEB) may reduce infrapopliteal restenosis and reintervention rates versus percutaneous transluminal angioplasty (PTA) and improve wound healing/limb preservation. OBJECTIVES The goal of this clinical trial was to assess the efficacy and safety of IN.PACT Amphirion drug-eluting balloons (IA-DEB) compared to PTA for infrapopliteal arterial revascularization in patients with critical limb ischemia (CLI). METHODS Within a prospective, multicenter, randomized, controlled trial with independent clinical event adjudication and angiographic and wound core laboratories 358 CLI patients were randomized 2:1 to IA-DEB or PTA. The 2 coprimary efficacy endpoints through 12 months were clinically driven target lesion revascularization (CD-TLR) and late lumen loss (LLL). The primary safety endpoint through 6 months was a composite of all-cause mortality, major amputation, and CD-TLR. RESULTS Clinical characteristics were similar between the 2 groups. Significant baseline differences between the IA-DEB and PTA arms included mean lesion length (10.2 cm vs. 12.9 cm; p = 0.002), impaired inflow (40.7% vs. 28.8%; p = 0.035), and previous target limb revascularization (32.2% vs. 21.8%; p = 0.047). Primary efficacy results of IA-DEB versus PTA were CD-TLR of 9.2% versus 13.1% (p = 0.291) and LLL of 0.61 ± 0.78 mm versus 0.62 ± 0.78 mm (p = 0.950). Primary safety endpoints were 17.7% versus 15.8% (p = 0.021) and met the noninferiority hypothesis. A safety signal driven by major amputations through 12 months was observed in the IA-DEB arm versus the PTA arm (8.8% vs. 3.6%; p = 0.080). CONCLUSIONS In patients with CLI, IA-DEB had comparable efficacy to PTA. While primary safety was met, there was a trend towards an increased major amputation rate through 12 months compared to PTA. (Study of IN.PACT Amphirion™ Drug Eluting Balloon vs. Standard PTA for the Treatment of Below the Knee Critical Limb Ischemia [INPACT-DEEP]; NCT00941733).


Covid-19: Don't apply advance care plans to groups of people, doctors' leaders warn.