title: Efficacy and Tolerability of Evolocumab vs Ezetimibe in Patients With Muscle-Related Statin Intolerance: The GAUSS-3 Randomized Clinical Trial.

text: IMPORTANCE Muscle-related statin intolerance is reported by 5% to 20% of patients. OBJECTIVE To identify patients with muscle symptoms confirmed by statin rechallenge and compare lipid-lowering efficacy for 2 nonstatin therapies, ezetimibe and evolocumab. DESIGN, SETTING, AND PARTICIPANTS Two-stage randomized clinical trial including 511 adult patients with uncontrolled low-density lipoprotein cholesterol (LDL-C) levels and history of intolerance to 2 or more statins enrolled in 2013 and 2014 globally. Phase A used a 24-week crossover procedure with atorvastatin or placebo to identify patients having symptoms only with atorvastatin but not placebo. In phase B, after a 2-week washout, patients were randomized to ezetimibe or evolocumab for 24 weeks. INTERVENTIONS Phase A: atorvastatin (20 mg) vs placebo. Phase B: randomization 2:1 to subcutaneous evolocumab (420 mg monthly) or oral ezetimibe (10 mg daily). MAIN OUTCOME AND MEASURES Coprimary end points were the mean percent change in LDL-C level from baseline to the mean of weeks 22 and 24 levels and from baseline to week 24 levels. RESULTS Of the 491 patients who entered phase A (mean age, 60.7 [SD, 10.2] years; 246 women [50.1%]; 170 with coronary heart disease [34.6%]; entry mean LDL-C level, 212.3 [SD, 67.9] mg/dL), muscle symptoms occurred in 209 of 491 (42.6%) while taking atorvastatin but not while taking placebo. Of these, 199 entered phase B, along with 19 who proceeded directly to phase B for elevated creatine kinase (N = 218, with 73 randomized to ezetimibe and 145 to evolocumab; entry mean LDL-C level, 219.9 [SD, 72] mg/dL). For the mean of weeks 22 and 24, LDL-C level with ezetimibe was 183.0 mg/dL; mean percent LDL-C change, -16.7% (95% CI, -20.5% to -12.9%), absolute change, -31.0 mg/dL and with evolocumab was 103.6 mg/dL; mean percent change, -54.5% (95% CI, -57.2% to -51.8%); absolute change, -106.8 mg/dL (P < .001). LDL-C level at week 24 with ezetimibe was 181.5 mg/dL; mean percent change, -16.7% (95% CI, -20.8% to -12.5%); absolute change, -31.2 mg/dL and with evolocumab was 104.1 mg/dL; mean percent change, -52.8% (95% CI, -55.8% to -49.8%); absolute change, -102.9 mg/dL (P < .001). For the mean of weeks 22 and 24, between-group difference in LDL-C was -37.8%; absolute difference, -75.8 mg/dL. For week 24, between-group difference in LDL-C was -36.1%; absolute difference, -71.7 mg/dL. Muscle symptoms were reported in 28.8% of ezetimibe-treated patients and 20.7% of evolocumab-treated patients (log-rank P = .17). Active study drug was stopped for muscle symptoms in 5 of 73 ezetimibe-treated patients (6.8%) and 1 of 145 evolocumab-treated patients (0.7%). CONCLUSIONS AND RELEVANCE Among patients with statin intolerance related to muscle-related adverse effects, the use of evolocumab compared with ezetimibe resulted in a significantly greater reduction in LDL-C levels after 24 weeks. Further studies are needed to assess long-term efficacy and safety. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT01984424.


title: High-resolution genotyping of Campylobacter species by use of PCR and high-throughput mass spectrometry.

text: In this work we report on a high-throughput mass spectrometry-based technique for the rapid high-resolution identification of Campylobacter jejuni strain types. This method readily distinguishes C. jejuni from C. coli, has a resolving power comparable to that of multilocus sequence typing (MLST), is applicable to mixtures, and is highly automated. The strain typing approach is based on high-performance mass spectrometry, which "weighs" PCR amplicons with enough mass accuracy to unambiguously determine the base composition of each amplicon (i.e., the numbers of A's, G's, C's, and T's). Amplicons are derived from PCR primers which amplify short (<140-bp) regions of the housekeeping genes used by conventional MLST strategies. The results obtained with a challenge panel that comprised 25 strain types of C. jejuni and 25 strain types of C. coli are presented. These samples were parsed and resolved with demonstrated sensitivity down to 10 genomes/PCR from pure isolates.


Will antibody tests for the coronavirus really change everything?


The psychological impact of quarantine on coronavirus disease 2019 (COVID-19).


title: Bariatric surgical anatomy and mechanisms of action.

text: Because bariatric surgery is becoming increasingly common, gastroenterologists need to be familiar with the surgical and endoscopic anatomy of the operations in use today. This review focuses on the 4 most commonly performed bariatric operations in the United States: Roux-en-Y gastric bypass, adjustable gastric band, sleeve gastrectomy, and biliopancreatic diversion with duodenal switch. The anatomy and mechanism of action of each procedure is discussed and illustrated. Emphasis is placed on the endoscopic anatomy, with review of the commonly encountered complications. Emerging techniques and devices are reviewed.


Covid-19 may be exacerbated by right-to-left interatrial shunt.


Covid-19: trials of four potential treatments to generate "robust data" of what works.


title: Infectious disease outbreaks and increased complexity of care.

text: AIM This study examined the effects of healthcare-associated infectious disease outbreaks on nurses' work in a large acute care hospital in Ontario, Canada. BACKGROUND The incidence of healthcare-associated infections has increased. Previous research focuses on epidemiology, healthcare systems, and the economic burden of outbreaks. Few published studies focus on the impact of outbreaks on nurses' work in acute care facilities. INTRODUCTION Since the severe acute respiratory syndrome epidemic in 2003, combating infectious diseases has become a key issue. Hospitals have implemented measures related to healthcare-associated infections. However, nurses experience challenges in preventing, controlling, and contending with outbreaks. METHODS A retrospective exploratory case study approach was used. Data were collected over a 4-month period in 2012. The incidence rates of site-specific HAIs were analysed, and individual interviews were held with 23 bedside nurses and five nurse managers. FINDINGS Five themes emerged from the interviews: comparison of healthcare-associated infections outbreaks; the nature of nurses' work; impact of outbreaks on patient care; innovation and quality control in clinical practice; and increased and expanded IPAC measures. The incidence rates of methicillin-resistant Staphylococcus aureus, Clostridium difficile and vancomycin-resistant enterococci at the study site decreased, but remained above provincial benchmarks. Nurses experienced workload challenges, time pressures and psychological effects stemming from outbreaks and developed various innovations in response. Patient care was also affected. CONCLUSION Nurses' work has been impacted by healthcare-associated infectious disease outbreaks. Nursing workloads should be quantified to facilitate the development of guidelines for optimum nurse-patient ratio during outbreaks. IMPLICATIONS FOR NURSING AND/OR HEALTH POLICY A strong evidence-based policy framework is required to address healthcare-associated infectious disease outbreaks. Infection prevention and control guidelines and procedures should be established provincially and nationally. An interdisciplinary approach is essential for the creation of comprehensive and innovative strategies. Nursing research has increased understanding of the implications of infectious diseases in hospitals. Building on the literature, findings from this study can be used to influence policies on the care of patients who have secondary infections. Nurse-driven protocols are important and can lead to the creation of best practice guidelines that can be implemented across settings.


title: International Union of Basic and Clinical Pharmacology. LXXIII. Nomenclature for the formyl peptide receptor (FPR) family.

text: Formyl peptide receptors (FPRs) are a small group of seven-transmembrane domain, G protein-coupled receptors that are expressed mainly by mammalian phagocytic leukocytes and are known to be important in host defense and inflammation. The three human FPRs (FPR1, FPR2/ALX, and FPR3) share significant sequence homology and are encoded by clustered genes. Collectively, these receptors bind an extraordinarily numerous and structurally diverse group of agonistic ligands, including N-formyl and nonformyl peptides of different composition, that chemoattract and activate phagocytes. N-formyl peptides, which are encoded in nature only by bacterial and mitochondrial genes and result from obligatory initiation of bacterial and mitochondrial protein synthesis with N-formylmethionine, is the only ligand class common to all three human receptors. Surprisingly, the endogenous anti-inflammatory peptide annexin 1 and its N-terminal fragments also bind human FPR1 and FPR2/ALX, and the anti-inflammatory eicosanoid lipoxin A4 is an agonist at FPR2/ALX. In comparison, fewer agonists have been identified for FPR3, the third member in this receptor family. Structural and functional studies of the FPRs have produced important information for understanding the general pharmacological principles governing all leukocyte chemoattractant receptors. This article aims to provide an overview of the discovery and pharmacological characterization of FPRs, to introduce an International Union of Basic and Clinical Pharmacology (IUPHAR)-recommended nomenclature, and to discuss unmet challenges, including the mechanisms used by these receptors to bind diverse ligands and mediate different biological functions.


title: Epidemic dynamics at the human-animal interface.

text: Few infectious diseases are entirely human-specific: Most human pathogens also circulate in animals or else originated in nonhuman hosts. Influenza, plague, and trypanosomiasis are classic examples of zoonotic infections that transmit from animals to humans. The multihost ecology of zoonoses leads to complex dynamics, and analytical tools, such as mathematical modeling, are vital to the development of effective control policies and research agendas. Much attention has focused on modeling pathogens with simpler life cycles and immediate global urgency, such as influenza and severe acute respiratory syndrome. Meanwhile, vector-transmitted, chronic, and protozoan infections have been neglected, as have crucial processes such as cross-species transmission. Progress in understanding and combating zoonoses requires a new generation of models that addresses a broader set of pathogen life histories and integrates across host species and scientific disciplines.


title: PREVENTion of a parastomal hernia with a prosthetic mesh in patients undergoing permanent end-colostomy; the PREVENT-trial: study protocol for a multicenter randomized controlled trial.

text: BACKGROUND Parastomal hernia is a common complication of a colostomy. Ultimately, one-third of patients with a parastomal hernia will need surgical correction due to frequent leakage or life-threatening bowel obstruction or strangulation. However, treatment remains a challenge resulting in high recurrence rates. Two single center trials demonstrated that the frequency of parastomal hernias decreases by prophylactic placement of a mesh around the stoma at the time of formation. Unfortunately, both studies were small-sized, single-center studies and with these small numbers less common complications could be missed which were the reasons to initiate a prospective randomized multicenter trial to determine if a retromuscular, preperitoneal mesh at the stoma site prevents parastomal hernia and does not cause unacceptable complications. METHODS One hundred and fifty patients undergoing open procedure, elective formation of a permanent end-colostomy will be randomized into two groups. In the intervention group an end-colostomy is created with placement of a preperitioneal, retromuscular lightweight monofilament polypropylene mesh, and compared to a group with a traditional stoma without mesh. Patients will be recruited from 14 teaching hospitals in the Netherlands during a 2-year period. Primary endpoint is the incidence of parastomal hernia. Secondary endpoints are stoma complications, cost-effectiveness, and quality of life. Follow-up will be performed at 3 weeks, 3 months and at 1, 2, and 5 years. To find a difference of 20% with a power of 90%, a total number of 134 patients must be included. All results will be reported according to the CONSORT 2010 statement. DISCUSSION The PREVENT-trial is a multicenter randomized controlled trial powered to determine whether prophylactic placement of a polypropylene mesh decreases the incidence of a parastomal hernia versus the traditional stoma formation without a mesh. TRIAL REGISTRATION The PREVENT-trial is registered at: http://www.trialregister.nl/trialreg/admin/rctview.asp?TC=2018.


title: A novel low-cost simulator for laparoscopic inguinal hernia repair.

text: Despite the advantages of laparoscopic inguinal hernia repair over the open approach in selected situations, laparoscopic inguinal hernia repair (LIHR) remains a challenge to teach and learn. The purpose of this study was to develop and validate a low-cost adaptable simulator for evaluation and training of LIHR. McGill Laparoscopic Inguinal Hernia Simulator (MLIHS) is a physical simulator that accurately represents inguinal anatomy. MLIHS permits to perform both transabdominal pre-peritoneal (TAPP) and totally extraperitoneal (TEP) repairs. Six experienced surgeons performed TAPP repairs using MLIHS. They were surveyed to establish face validity, and were scored using a previously validated global rating scale (maximum score = 25). Experienced surgeons considered MLIHS a useful tool for evaluating and training of LIHR. The mean (SD) global rating scores were 24.0 (± 0.6). The experienced surgeons considered MLIHS very useful for training and assessment. MLIHS is a valuable and affordable tool for training and evaluation of LIHR.


title: Proximal to distal approach in the treatment of tandem occlusions causing an acute stroke.

text: INTRODUCTION A tandem occlusion is a rare presentation of acute stroke that involves an occlusion of the internal carotid artery at the bifurcation with an intracranial middle cerebral artery occlusion. This study describes the experience at our institution in treating tandem occlusions with a proximal to distal approach in the acute stroke setting. METHODS A retrospective review of acute strokes caused by tandem occlusions requiring thrombectomy were performed. RESULTS 16 cases were identified with a mean National Institutes of Health Stroke Scale score at presentation of 13.1 ± 3.9. The proximal occlusion was crossed initially with a microwire in all cases. All carotid occlusions were treated with stenting, and intracranial vessel thrombectomy was performed with a variety of devices. Procedure related complications occurred in two (12.5%) patients. Eight patients (50%) achieved a good outcome (modified Rankin Scale score of 0-2). CONCLUSIONS A tandem occlusion of the carotid artery at the bifurcation with a concomitant intracranial occlusion is a relatively rare and complex presentation of acute stroke. We have found that addressing the proximal lesion first and covering it with a stent prior to performing distal thrombectomy appears to be a safe and effective option in the treatment algorithm.


title: Acquisition of sensorimotor fMRI under general anaesthesia: Assessment of feasibility, the BOLD response and clinical utility.

text: We evaluated whether task-related fMRI (functional magnetic resonance imaging) BOLD (blood oxygenation level dependent) activation could be acquired under conventional anaesthesia at a depth enabling neurosurgery in five patients with supratentorial gliomas. Within a 1.5 T MRI operating room immediately prior to neurosurgery, a passive finger flexion sensorimotor paradigm was performed on each hand with the patients awake, and then immediately after the induction and maintenance of combined sevoflurane and propofol general anaesthesia. The depth of surgical anaesthesia was measured and confirmed with an EEG-derived technique, the Bispectral Index (BIS). The magnitude of the task-related BOLD response and BOLD sensitivity under anaesthesia were determined. The fMRI data were assessed by three fMRI expert observers who rated each activation map for somatotopy and usefulness for radiological neurosurgical guidance. The mean magnitudes of the task-related BOLD response under a BIS measured depth of surgical general anaesthesia were 25% (tumour affected hemisphere) and 22% (tumour free hemisphere) of the respective awake values. BOLD sensitivity under anaesthesia ranged from 7% to 83% compared to the awake state. Despite these reductions, somatotopic BOLD activation was observed in the sensorimotor cortex in all ten data acquisitions surpassing statistical thresholds of at least p < 0.001uncorr. All ten fMRI activation datasets were scored to be useful for radiological neurosurgical guidance. Passive task-related sensorimotor fMRI acquired in neurosurgical patients under multi-pharmacological general anaesthesia is reproducible and yields clinically useful activation maps. These results demonstrate the feasibility of the technique and its potential value if applied intra-operatively. Additionally these methods may enable fMRI investigations in patients unable to perform or lie still for awake paradigms, such as young children, claustrophobic patients and those with movement disorders.


title: [2019 novel coronavirus, angiotensin converting enzyme 2 and cardiovascular drugs].

text: 2019年底，武汉出现了由2019新型冠状病毒（2019-nCoV）引发的新型冠状病毒肺炎（COVID-19）。该疫情在短时间内迅速蔓延，严重威胁着公共卫生安全，目前，COVID-19尚无有效的治疗手段。血管紧张素转化酶2（ACE2）作为受体介导2019-nCoV进入细胞，是目前最有可能防治COVID-19的靶点之一。中老年人是COVID-19的易感人群，多伴有基础疾病，且大部分为心血管疾病，因此这部分人更容易发展为重症和危重症，造成严重的临床后果。ACE2是肾素-血管紧张素系统重要的组成部分，以此系统为靶点的ACE抑制剂和血管紧张素受体阻断剂等药物，是目前临床治疗高血压、心肌重构和心力衰竭等心血管疾病的最主要的药物之一。本文系统的介绍了COVID-19以及肾素-血管紧张素系统相关药物及其临床应用，并且分析了肾素-血管紧张素系统相关药物在COVID-19防治中的价值，以及并发心血管疾病的COVID-19患者用药方面需要注意的问题。.


title: Uterine artery ligation at the beginning of total laparoscopic hysterectomy reduces total blood loss and operation duration.

text: The purpose of this study was to compare the feasibility, blood loss, duration of surgery and complications between patients in whom both uterine arteries were ligated by surgical clips and cut using a 5-mm ligature at the beginning of total laparoscopic hysterectomy (TLH) and patients in whom uterine arteries were not ligated at the beginning of TLH. In our prospective study, a total of 60 women underwent TLH. Uterine artery ligation (UAL) was done at the beginning of the procedure. Women were divided into TLH + UAL (n = 30) and TLH (n = 30) groups. In TLH group, TLH was done without ligating the uterine arteries at the beginning of the procedure. In TLH + UAL group, TLH was done with ligation of both uterine arteries at the beginning of the procedure. The mean operating time was longer for the TLH group (99.16 ± 7.01) than TLH + UAL group (63.27 ± 7.16). The median total blood loss was higher in TLH group (109.38 ± 33.03 mL) than TLH + UAL group (47.50 ± 8.12 mL). UAL at the beginning of TLH is a technically feasible procedure. It reduces the total blood loss and decreases the time taken for the procedure and length of hospital stay.


title: Respiratory viruses associated with community-acquired pneumonia in children: matched case-control study.

text: BACKGROUND Community-acquired pneumonia (CAP) is the leading cause of death in children worldwide and a substantial proportion of childhood CAP is caused by viruses. A better understanding of the role of virus infections in this condition is needed to improve clinical management and preventive measures. The aim of the study was therefore to assess the association between specific respiratory viruses and childhood CAP. METHODS A case-control study was conducted during 3 years in Stockholm, Sweden. Cases were children aged ≤5 years with radiological CAP. Healthy controls were consecutively enrolled at child health units during routine visits and matched to cases on age and calendar time. Nasopharyngeal aspirates were obtained and analysed by real-time PCR for 15 viruses. Multivariate conditional logistic regression was used to account for coinfections with other viruses and baseline characteristics. RESULTS A total of 121 cases, of which 93 cases met the WHO criteria for radiological pneumonia, and 240 controls were included in the study. Viruses were detected in 81% of the cases (n=98) and 56% of the controls (n=134). Influenza virus, metapneumovirus and respiratory syncytial virus were detected in 60% of cases and were significantly associated with CAP with ORs >10. There was no association with parainfluenza virus, human enterovirus or rhinovirus and coronavirus and bocavirus were negatively associated with CAP. CONCLUSIONS Our study indicates viral CAP is an underestimated disease and points out hMPV as a new important target for the prevention of childhood CAP.


title: Oxygenation time course and neuromuscular fatigue during repeated cycling sprints with bilateral blood flow restriction.

text: The aim was to evaluate changes in peripheral and cerebral oxygenation, cardiorespiratory, and performance differences, as well as neuromuscular fatigue across multiple levels of blood flow restriction (BFR) during a repeated cycling sprint test to exhaustion (RST). Participants performed three RST (10-sec maximal sprints with 20-sec recovery until exhaustion) with measurements of power output and V̇O2peak as well as oxygenation (near-infrared spectroscopy) of the vastus lateralis and prefrontal cortex. Neuromuscular fatigue was assessed by femoral nerve stimulation to evoke the vastus lateralis. Tests were conducted with proximal lower limb bilateral vascular occlusion at 0%, 45%, and 60% of resting pulse elimination pressure. Total work decreased with BFR (52.5 ± 22.9% at 45%, 68.6 ± 32.6% at 60%, P < 0.01 compared with 0%) as V̇O2peak (12.6 ± 9.3% at 45%, 18.2 ± 7.2% at 60%, compared with 0%, P < 0.01). Decreased changes in muscle deoxyhemoglobin (∆[HHb]) during sprints were demonstrated at 60% compared to 0% (P < 0.001). Changes in total hemoglobin concentrations (∆[tHb]) increased at both 45% and 60% compared with 0% (P < 0.001). Cerebral ∆[tHb] increased toward exhaustion (P < 0.05). Maximal voluntary contraction (MVC), voluntary activation level (VAL), and root mean square (RMS)/M-wave ratio decreased at 60% compared with 0% (P < 0.001, all). MVC and VAL decreased between 45% and 60% (P < 0.05, both). The application of BFR during RST induced greater changes in tissue perfusion (via blood volume, ∆[tHb]) suggesting a possible stimulus for vascular blood flow regulation. Additionally, high-intensity sprint exercise with partial ischemia may challenge cerebral blood flow regulation and influence local fatigue development due to protection of cerebral function.


title: Indocyanine green reinjection technique for use in fluorescent angiography concomitant with cholangiography during laparoscopic cholecystectomy.

text: BACKGROUND For safe laparoscopic cholecystectomy, surgeons must possess detailed knowledge of the anatomy of the bile duct and arterial system as seen through a laparoscope. STUDY DESIGN We developed an indocyanine green (ICG) reinjection technique for use in fluorescent angiography. Here, we evaluated the efficacy of the ICG reinjection technique in fluorescent angiography in discriminating the arterial system with the concomitant use of fluorescent cholangiography. RESULTS Twenty-eight patients were enrolled in the study. All patients underwent laparoscopic cholecystectomy without complication. After reinjection of ICG during surgery, fluorescence of the cystic artery was visualized in 25 patients (89%). CONCLUSIONS Fluorescent angiography using this ICG reinjection technique might enhance the safety of laparoscopic cholecystectomy.


title: Current status of pneumococcal vaccines: lessons to be learned and new insights.

text: One of the great success stories in pneumococcal vaccines is the 7-valent conjugated pneumococcal vaccine (PCV-7); and with wider coverage, the broad prevention it offers would be possible with new vaccines. The 7th International Symposium on Pneumococci and Pneumococcal Diseases (ISPPD-7) was held on the 14-18 March 2010 in Tel Aviv, Israel. During this symposium, clinical and epidemiological features in the post-PCV-7 era, current studies about two new approved PCVs (PHiD-CV and PCV-13) and new data about protein-based vaccines were extensively evaluated. Routine surveillance for pneumococcal infections is essential for all countries whether pneumococcal vaccines are available or not, and long-term results of surveillance help us to understand the PCVs potential benefits. Current epidemiological data about serotype 6C have also been presented from different countries and existing PCVs' efficacy against serotype 6C should be evaluated. In the post-PCV7 era, we have some new emerging serotypes and we also need new vaccines or interventions focused on protection for children against serotypes prevalent in the developing world or broad protection across all pneumococcal serotypes. Effectiveness of the new PCVs against nasopharyngeal carriage, acute otitis media and invasive infections need to be investigated in the real world; immunogenicity of investigational protein-based vaccines, are still evaluated in different settings. We will have a chance to hear and discuss all the new achievements in the many aspects related to pneumococcal diseases at the next ISPPD-8, which will be held in Iguaçu Falls in 2012.


Don't forget about head and neck cancer.


title: Echinacea for preventing and treating the common cold.

text: CLINICAL QUESTION Are Echinacea products associated with a reduced incidence and a shorter duration of common colds compared with placebo? BOTTOM LINE Individual prophylaxis trials show no association with prevention of the common cold, but exploratory meta-analysis suggests that Echinacea products may be associated with a small reduction in cold incidence. In treatment trials, there was no association of Echinacea products with a shorter duration of colds.


title: Huge pseudomyxoma peritonei: Surgical strategies and procedures to employ to optimize the rate of complete cytoreductive surgery.

text: BACKGROUND Complete cytoreductive surgery (CCRS) plus Hyperthermic Intraperitoneal Chemotherapy (HIPEC) is the best-known treatment for pseudomyxoma peritonei (PMP). In 30% of the cases, PMP realize a widespread involvement of the peritoneal cavity. In these extreme situations, we developed, devoted strategies to optimize the feasibility and safety of CCRS. This study describes the surgical resections required for CCRS and the consequent approaches that we propose to achieve CCRS. MATERIALS AND METHODS We defined "huge PMP" by a peritoneal cancer index (PCI) ≥ 28. Surgical procedures of patients operated on between 1994 and 2014 were retrospectively reviewed from a prospective database in a single institution. RESULTS During this period, 311 patients were operated on and 247 (79%) underwent CCRS + HIPEC. Among them, 100 patients presented "huge" PMP and 54 patients underwent CCRS + HIPEC. In patients with "huge" PMP, the rate of CCRS + HIPEC was 25% before 2002 and reached 71% between 2011 and 2014. We identified 3 conditions for CCRS 1) to guaranty a sufficient length of residual small bowel 2) to preserve the left gastric vessels in order to preserve the superior third of the stomach 3) to ensure that the hepatic pedicle can be entirely cleared from its tumor involvement. None of the other peritonectomy procedures were decisional for CCRS. CONCLUSION Our learning curve improved the selection and completion rate of CCRS + HIPEC for "huge PMP". Some anatomical and physiological prerequisites guarantee the feasibility and safety of such extensive surgeries.


Mortality rate and gender differences in COVID-19 patients dying in Italy: A comparison with other countries.


title: The vaccine journey for COVID-19: a comprehensive systematic review of current clinical trials in humans.

text: INTRODUCTION Since December 2019, there has been an outbreak of a novel beta-coronavirus (SARS-CoV-2) in Wuhan, China. On March the 11th the World Health Organization (WHO) declared COVID-19 as a pandemic, with over 118,000 cases in more than 110 countries around the world. In response to the global coronavirus disease 2019 (COVID-19) emergency, clinical trial research assessing the efficacy and safety of experimental vaccines to prevent COVID-19 are emerging at an unprecedented rate. The aim of this systematic review is to summarize the preliminary experiences and ongoing clinical trials of the major candidates and challenges of the vaccine strategies in humans. EVIDENCE ACQUISITION After a priori protocol registration with PROSPERO (181483), a systematic research of the published literature was conducted on 24 April 2020 using Medline (via PubMed), Embase (via Ovid), and WHO databases. Moreover, to explore the more recent literature we also searched the preprint server medRxiv. Finally, we scrutinized the Cochrane COVID-19 study register and the COVID-19 section of ClinicalTrials.gov database for identifying relevant ongoing clinical trials. Thereafter we selected the articles according to the PRISMA guidelines. Animal or in-vitro experimental studies were excluded. Moreover editorials, commentaries, abstracts, reviews, book chapters, and articles not in English were not included. EVIDENCE SYNTHESIS Our search identified 1359 published papers, 478 pre-print articles and 367 ongoing clinical trials. Finally, only ten ongoing clinical trials met the inclusion criteria. Specifically, seven developed vaccines for the S protein of SARS-CoV-2 and three clinical trials assessed the protective role of BCG vaccine against COVID-19. The first group included phase I/II trials with different types of molecules (DNA or mRNA vaccine, bacterial plasmid or viral vectors), the latter were phase III/IV trials designed on the basis of a heterologous lymphocyte activation by the BCG vaccine. CONCLUSIONS This new disease is pushing the scientific community to develop swiftly a safe and effective vaccine. Notwithstanding the limitations of our analysis, given by the absence of available results, we try to provide a comprehensive view of the ongoing clinical trials in humans. Our analysis reveals a worldwide effort of both scientists and enterprises to achieve one of the most challenging goals of our century.


The fight to end tuberculosis must not be forgotten in the COVID-19 outbreak.


title: The incidence of ventilator-associated pneumonia using the PneuX System with or without elective endotracheal tube exchange: A pilot study.

text: BACKGROUND The PneuX System is a novel endotracheal tube and tracheal seal monitor, which has been designed to minimise the aspiration of oropharyngeal secretions. We aimed to determine the incidence of ventilator-associated pneumonia (VAP) in patients who were intubated with the PneuX System and to establish whether intermittent subglottic secretion drainage could be performed reliably and safely using the PneuX System. FINDINGS In this retrospective observational study, data was collected from 53 sequential patients. Nine (17%) patients were initially intubated with the PneuX System and 44 (83%) patients underwent elective exchange to the PneuX System. There were no episodes of VAP while the PneuX System was in situ. On an intention to treat basis, the incidence VAP was 1.8%. There were no complications from, or failure of, subglottic secretion drainage during the study. CONCLUSIONS Our study demonstrates that a low incidence of VAP is possible using the PneuX System. Our study also demonstrates that elective exchange and intermittent subglottic secretion drainage can be performed reliably and safely using the PneuX System.


Life after COVID-19: preparing for changes in mental healthcare service demand.


title: Long-term use of noble metal alloy coated urinary catheters reduces recurrent CAUTI and decreases proinflammatory markers.

text: Background The objective of this study was to investigate a case of a permanently (suprapubic) catheterized woman with neurogenic bladder dysfunction. The patient had suffered from recurrent catheter-associated urinary tract infections (CAUTIs) since 2009, despite several prevention approaches and attempts. In 2013, the patient's catheter was substituted for the BIP Foley Catheter, coated with a noble metal alloy (NMA) of gold, silver, and palladium. Method This is a retrospective-prospective clinical case study covering 4 years history for the control catheters and up to 2.5 years for the anti-infective BIP Foley Catheter. CAUTI incidences, symptoms, antibiotics, catheter performance, and comfort were evaluated. Levels of proinflammatory cytokines were measured pre- and post-substitution to BIP Foley Catheter in urine of the case and of four other permanently catheterized patients. In addition, the levels of noble metals were assessed in urine of the case subject during use of the BIP Foley Catheter. Results While using control catheters, the patient experienced symptomatic CAUTIs requiring antibiotics almost every month for 4 years. After 1 month with the BIP Foley Catheter, the symptoms disappeared, and the patient remained free of symptomatic CAUTIs and antibiotic treatment for the following 2.5 years, despite bacteriuria. The patient was satisfied with the comfort during insertion, use, and removal of the BIP Foley Catheter. Urinary levels of the proinflammatory cytokines interleukin (IL)-6, IL-8, and tumor necrosis factor alpha (TNFα) decreased towards normal levels post catheter type substitution. Traces of noble metals detected in a few urine samples were ⩽4% of the permitted daily exposure. The levels of the noble metals gold, silver, and palladium remaining on the BIP Foley Catheter after use were the same as for unused catheters. Conclusion Long-term use of a NMA-coated catheter was associated with cessation of frequent CAUTIs. The catheter was experienced as comfortable and inflammatory markers were reduced with time. The coating was stable, with no significant metal release into urine and is therefore safe for patient use.


title: Hospital Preparedness for Outbreak at Patan Hospital: Lesson Learnt from COVID-19.

text: Patan Academy of Health Sciences started preparedness for COVID-19 in response to increasing number of patient in neighboring country. Outbreak preparedness in resource limited setup is challenging. Despite this, preparedness was done in reference to WHO interim guidance utilizing best available resources. During this preparedness, one patient was isolated as suspected COVID-19. This paper presents level of preparedness achieved with the limited resources and the lesson learned while isolating the patient. Keywords: COVID-19; Disaster; hospital preparedness.


docid: voizdqjp

title: The usefulness of the McGrath MAC laryngoscope in comparison with Airwayscope and Macintosh laryngoscope during routine nasotracheal intubation: a randomaized controlled trial.

text: BACKGROUND McGrath MAC video laryngoscope offers excellent laryngosopic views and increases the success rate of orotracheal intubation in some cases. The aim of this study was to determine the usefulness of McGrath MAC for routine nasotracheal intubation by comparing McGrath MAC with Airway scope and Macintosh laryngoscope. METHODS A total of 60 adult patients with ASA physical status class 1 or 2, aged 20-70 years were enrolled in this study. Patients were scheduled for elective oral surgery under general anesthesia with nasotracheal intubation. Exclusion criteria included lack of consent and expected difficult airway. Patients were randomly allocated to three groups: McGrath MAC (n = 20), Airway scope (n = 20), and Macintosh laryngoscope (n = 20). After induction, nasotracheal intubation was performed by six expert anesthesiologists with more than 6 years of experience. RESULTS There were no significant differences in preoperative airway assessment among the three groups. Successful tracheal intubation time was 26.8 ± 5.7 (mean ± standard deviation) s for McGrath MAC, 36.4 ± 11.0 s for Airway scope, and 36.5 ± 8.9 s for Macintosh laryngoscope groups. The time for successful tracheal intubation for McGrath MAC group was significantly shorter than that for Airway scope and Macintosh laryngoscope (p < 0.01). McGrath MAC significantly improved the Cormack Lehane grade for nasotracheal intubation compared with Macintosh laryngoscope (p < 0.05). CONCLUSION McGrath MAC significantly facilitates routine nasotracheal intubation compared with Airwayscope and Macintosh laryngoscope by shortening the tracheal intubation time and improving the Cormack Lehane grade. TRIAL REGISTRATION UMINCTR Registration number UMIN000023506 . Registered 5 Aug 2016.


title: Competence and training in interventional pulmonology.

text: Interventional Pulmonology (IP) is experiencing a rapid evolution of new technologies. There is a need to develop structured training programs, organized in high volume expert centres in order to improve trainee education, and including the development of validated metrics for their competency assessment. Concerning teaching methods, a gradual progression from theory to practice, using new teaching techniques, including live sessions and low and high fidelity simulation, flipped classroom models and problem-based learning (PBL) exercises would provide a training setting more suitable for our current need to improve skills and update professionals. Training programs should be learner centered and competence-oriented, as well as being based on a spiral-shaped approach in which the same subject is addressed many times, from new and different perspectives of knowledge, ability, behaviour and attitude, until the trainee has demonstrated a high degree of skill and professionalism5. Furthermore there is a need to standardize the training programs as guide for physicians wishing to undertake a gradual and voluntary improvement of their own competencies, and assist those planning and organizing training programs in IP. The article includes a general part on Core Curriculum contents, innovative training methods and simulation, and introduces the following articles on the skills hat the Interventional Pulmonologist must master in order to perform the different procedures. This monography should be considered a starting point that will evolve over time and results in better training for practitioners and better care for our patients. The task of establishing a trainee's competence to practice independently as an Interventional Pulmonologist remains the responsibility of the IP fellowship program director and faculty, who validate logbooks and assess competence for each procedure. These standards need to be reviewed and approved by national and International Scientific Societies and Healthcare Institutions with the aim to improve, disseminate and incorporate them in healthcare programs.


Covid-19: Two antibody tests are "highly specific" but vary in sensitivity, evaluations find.


Public Health Interventions for COVID-19: Emerging Evidence and Implications for an Evolving Public Health Crisis.


title: Bypasses and reconstruction for complex brain aneurysms.

text: Microsurgery for brain aneurysms is a current relevant technique, as advances in endovascular and stent-assisted coiling have not solved many of the difficulties inherent in the management of complex brain aneurysms. The following review highlights the importance of microsurgical bypass techniques for the management of complex cerebrovascular aneurysms and emphasizes, through two clinical cases, the technical difficulties and indications for bypass surgery. These cases demonstrate that in selected scenarios, bypass microsurgery still offers the only viable treatment for complex aneurysms.


The limits to our capacity: reflections on resiliency, community engagement, and recovery in 21st-century crises.


title: Both the middle and distal sections of the urethra may be regarded as optimal targets for 'outside-in' transobturator tape placement.

text: PURPOSE To investigate whether the position of the tape under the urethra may influence 'outside-in' transobturator sling (TOT) outcome. METHODS The study comprised 141 women who underwent TOT for clinically and urodynamically proved stress urinary incontinence. The postoperative ultrasound examination with an endovaginal biplane probe was performed before discharging the patients from hospital. The measurements obtained described the position of the tape relative to the urethra and pubic symphysis, as well as anatomical relationships in the anterior compartment. RESULTS Ninety-six (68.1 %) patients were cured, 27 (19.1 %) significantly improved, and in 18 cases (12.7 %), the surgery failed. The tape position under the midurethra (40-70th percentile of the urethral length) or distal urethra (>70th percentile) coincided with better results (cure rate 67.1 and 82.4 %, respectively) than the location in the proximity of the bladder neck (<40th percentile) (21.4 % cured, p = 0.0015 and p < 0.001, respectively). However, the risk of failure was the lowest when the tape was located under the distal urethra. Other ultrasonographic findings were not related to treatment results. CONCLUSIONS The highest failure rate for 'outside-in' TOT is associated with the location of the tape under the proximal third of the urethra. Both the middle and distal sections of the urethra may be regarded as targets for transobturator tape placement.


title: Semaglutide for type 2 diabetes mellitus: A systematic review and meta-analysis.

text: AIMS To assess the efficacy and safety of semaglutide, a recently approved glucagon-like peptide 1 receptor agonist (GLP-1 RA) for type 2 diabetes. MATERIALS AND METHODS We searched major electronic databases and grey literature sources for randomized controlled trials comparing semaglutide with placebo or other antidiabetic agents. Primary outcome was change from baseline in HbA1c. Secondary endpoints included change from baseline in body weight, blood pressure, heart rate and incidence of hypoglycaemia, gastrointestinal adverse effects, pancreatitis and diabetic retinopathy. RESULTS A total of 6 placebo-controlled and 7 active-controlled studies with subcutaneous semaglutide were included. We identified only 1 trial with oral semaglutide. Compared with placebo, subcutaneous semaglutide 0.5 and 1 mg reduced HbA1c by 1.01% (95% CI, 0.56-1.47) and 1.38% (1.05-1.70), respectively. Both doses demonstrated superior glycaemic efficacy compared to other antidiabetic agents, including sitagliptin, exenatide, liraglutide, dulaglutide and insulin glargine. Semaglutide also had a beneficial effect on body weight (mean difference vs placebo -4.11 kg, 95% CI -4.85 to -3.37 for semaglutide 1 mg) and systolic blood pressure. We did not observe increased hypoglycaemia rates with semaglutide; nevertheless, we noted an increased incidence of nausea, vomiting and diarrhoea. Cases of pancreatitis were infrequent and the odds ratio for diabetic retinopathy compared with placebo was 1.32 (95% CI, 0.98-1.77). CONCLUSIONS Semaglutide is a potent once-weekly GLP-1 RA, significantly reducing HbA1c, body weight and systolic blood pressure. However, it is associated with increased incidence of gastrointestinal adverse events. Results for pancreatitis and retinopathy require further assessment in post-approval pharmacovigilance studies.


title: The thromboembolism in COVID-19: the unsolved problem.

text: INTRODUCTION The recent Sars-Cov-2 pandemic (COVID-19) has led to growing research to explain the poor clinical prognosis in some patients. EVIDENCE ACQUISITION While early observational studies highlighted the role of the virus in lung failure, in a second moment thrombosis emerged as a possible explanation of the worse clinical course in some patients. Despite initial difficulties in management of such patients, the constant increase of literature in the field is to date clarifying some questions from clinicians. However, several other questions need answer. EVIDENCE SYNTHESIS A novel disease (Covid-19) due to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was responsible for thousands of hospitalizations for severe acute respiratory syndrome, with several cases of thrombotic complications due to excessive inflammation, platelet activation, endothelial dysfunction, and stasis. Covid-19 and hospitalizations for Covid-19 may carry several potential risk factors for thrombosis. Severe coagulation abnormalities may occur in almost all of the severe and critical ill COVID-19 cases. CONCLUSIONS Despite a strong pathophysiological rationale, the evidences in literature are not enough to recommend an aggressive antithrombotic therapy in COVID- 19. However, it is our opinion that an early use, even at home at the beginning of the disease, could improve the clinical course.


docid: gdcbgamw

title: COVID-19 and spontaneous singing to decrease loneliness, improve cohesion, and mental well-being: An Italian experience.

text: Since March 2020, Italy has been in lockdown due to COVID-19, and individuals have missed all kinds of networking opportunities. Already in the 1st weeks of March, Italian cities' silence was broken by singing. The use of singing as a coping strategy as well as to improve the sense of cohesion is evident. Greater attention should be paid to the development of social cohesion and to social support in terms of social networks and the development of social capital. (PsycInfo Database Record (c) 2020 APA, all rights reserved).


title: Key elements of interventions for heart failure patients with mild cognitive impairment or dementia: A systematic review.

text: BACKGROUND The purpose of this systematic review was to (a) examine the effects of interventions delivered by a heart failure professional for mild cognitive impairment and dementia on cognitive function, memory, working memory, instrumental activities of daily living, heart failure knowledge, self-care, quality of life and depression; and (b) identify the successful elements of these strategies for heart failure patients with mild cognitive impairment or dementia. METHODS AND RESULTS During March 2018, an electronic search of databases including CINAHL, MEDLINE, EMBASE and PsycINFO was conducted. All randomised controlled trials, which examined an intervention strategy to help heart failure patients with mild cognitive impairment or dementia cope with self-care, were included. An initial search yielded 1622 citations, six studies were included (N= 595 participants, mean age 68 years). There were no significant improvements in cognitive function and depression. However, significant improvements were seen in memory (p=0.015), working memory (p=0.029) and instrumental activities of daily living (p=0.006). Nurse led interventions improved the patient's heart failure knowledge (p=0.001), self-care (p<0.05) and quality of life (p=0.029). Key elements of these interventions include brain exercises, for example, syllable stacks, individualised assessment and customised education, personalised self-care schedule development, interactive problem-solving training on scenarios and association techniques to prompt self-care activities. CONCLUSIONS Modest evidence for nurse led interventions among heart failure patients with mild cognitive impairment or dementia was identified. These results must be interpreted with caution in light of the limited number of available included studies.


title: Venous thromboembolism in adult elective spinal surgery: a tertiary centre review of 2181 patients.

text: AIMS To evaluate the incidence of primary venous thromboembolism (VTE), epidural haematoma, surgical site infection (SSI), and 90-day mortality after elective spinal surgery, and the effect of two protocols for prophylaxis. PATIENTS AND METHODS A total of 2181 adults underwent 2366 elective spinal procedures between January 2007 and January 2012. All patients wore anti-embolic stockings, mobilised early and were kept adequately hydrated. In addition, 29% (689) of these were given low molecular weight heparin (LMWH) while in hospital. SSI surveillance was undertaken using the Centers for Disease Control and Prevention criteria. RESULTS In patients who only received mechanical prophylaxis, the incidence of VTE was 0.59% and that of SSI 2.1%. In patients who were additionally given LMWH, the incidence of VTE was 0% and that of SSI 0.7%. The unadjusted p-value was 0.04 for VTE and 0.01 for SSI. There were no cases of epidural haematoma or 90-day mortality in either group. When adjusted for case-mix, LMWH remained a significant factor (p = 0.006) for VTE, but not for SSI. CONCLUSION A peri-operative protocol involving mechanical anti-embolism stockings, adequate hydration, and early post-operative mobilisation is effective in significantly reducing the incidence of VTE. The addition of LMWH is safe in patients at higher risk of developing VTE. Cite this article: Bone Joint J 2017;99-B:1204-9.


title: (99m)Tc(CO)3(NTA): a (99m)Tc renal tracer with pharmacokinetic properties comparable to those of (131)I-OIH in healthy volunteers.

text: UNLABELLED Studies in rats showed that the pharmacokinetics of the tricarbonyl core radiopharmaceutical (99m)Tc(CO)(3)-nitrilotriacetic acid, (99m)Tc(CO)(3)(NTA), were essentially identical to those of (131)I ortho-iodohippuran ((131)I-OIH), the clinical gold standard for the measurement of effective renal plasma flow. Our objective was to compare the pharmacokinetics of these 2 tracers in healthy volunteers. METHODS (99m)Tc(CO)(3)(NTA) was prepared with commercially available NTA and a commercially available kit and isolated by reversed-phase high-performance liquid chromatography. Approximately 74 MBq (2 mCi) of (99m)Tc(CO)(3)(NTA) were coinjected with 9.25 MBq (250 microCi) of (131)I-OIH in 9 volunteers, and simultaneous imaging of each tracer was performed for 24 min. Plasma clearances were determined from 8 blood samples obtained 3-90 min after injection using the single-injection, 2-compartment model. Plasma protein binding, red cell uptake, and percentage injected dose in the urine at 30 and 180 min were determined. RESULTS There was no difference in the plasma clearances of (99m)Tc(CO)(3)(NTA) and (131)I-OIH, 475 +/- 105 mL/min versus 472 +/- 108 mL/min, respectively. The plasma protein binding and red cell uptake of (99m)Tc(CO)(3)(NTA) were 43% +/- 5% and 9% +/- 6%, respectively; both values were significantly lower (P < 0.001) than the plasma protein binding (75% +/- 3%) and red cell uptake (17% +/- 5%) of (131)I-OIH. There was no significant difference in the percentage injected dose recovered in the urine at 30 min and at 3 h; for comparison, the percentage dose in the urine at 3 h was 91% +/- 4% for (99m)Tc(CO)(3)(NTA) and 91% +/- 6% for (131)I-OIH (P = 0.96). Image quality with (99m)Tc(CO)(3)(NTA) was excellent, and the renogram parameters were similar to those of (131)I-OIH. CONCLUSION Preliminary results in healthy volunteers suggest that the pharmacokinetic behavior of (99m)Tc(CO)(3)(NTA) is comparable to that of (131)I-OIH.


docid: qoinntar

title: Lopinavir-ritonavir versus hydroxychloroquine for viral clearance and clinical improvement in patients with mild to moderate coronavirus disease 2019.

text: Background/Aims The efficacies of lopinavir-ritonavir or hydroxychloroquine remain to be determined in patients with coronavirus disease 2019 (COVID-19). To compare the virological and clinical responses to lopinavir-ritonavir and hydroxychloroquine treatment in COVID-19 patients. Methods This retrospective cohort study included patients with COVID-19 treated with lopinavir-ritonavir or hydroxychloroquine at a single center in Korea from February 17 to March 31, 2020. Patients treated with lopinavir-ritonavir and hydroxychloroquine concurrently and those treated with lopinavir-ritonavir or hydroxychloroquine for less than 7 days were excluded. Time to negative conversion of viral RNA, time to clinical improvement, and safety outcomes were assessed after 6 weeks of follow-up. Results Of 65 patients (mean age, 64.3 years; 25 men [38.5%]), 31 were treated with lopinavir-ritonavir and 34 were treated with hydroxychloroquine. The median duration of symptoms before treatment was 7 days and 26 patients (40%) required oxygen support at baseline. Patients treated with lopinavir-ritonavir had a significantly shorter time to negative conversion of viral RNA than those treated with hydroxychloroquine (median, 21 days vs. 28 days). Treatment with lopinavir-ritonavir (adjusted hazard ratio [aHR], 2.28; 95% confidence interval [CI], 1.24 to 4.21) and younger age (aHR, 2.64; 95% CI 1.43 to 4.87) was associated with negative conversion of viral RNA. There was no significant difference in time to clinical improvement between lopinavir-ritonavir- and hydroxychloroquine-treated patients (median, 18 days vs. 21 days). Lymphopenia and hyperbilirubinemia were more frequent in lopinavir-ritonavir-treated patients compared with hydroxychloroquine-treated patients. Conclusions Lopinavir-ritonavir was associated with more rapid viral clearance than hydroxychloroquine in mild to moderate COVID-19, despite comparable clinical responses. These findings should be confirmed in randomized, controlled trials.


title: Comparison of oximeters for the detection of critical congenital heart diseases.

text: Introduction and objectives In some centers, the pulse oximetry is not performed with the justification of lack of the adequate oximeter. We compared the effectiveness of two brands of oximeters to perform it. Methods In neonates, a term of the joint housing service of the Hospital General de Occidente in Zapopan, Jalisco, Mexico, from May to November 2018, an examination of the characteristics of the American Academy of Pediatrics with both oximeters (ChoiceMMed® and Masimo SET®) was carried out, comparing the detection of critical congenital heart disease, time of intake, and false positives. Results In each group, 1022 patients were analyzed; with the Masimo SET® oximeter, 83 positive tests were obtained (8.12%), of which 22 cases had some heart disease (26.5%), which represents a sensitivity of 100%, specificity of 93.9%, positive predictive value of 26.5%, and negative predictive value of 100% (odds ratio [OR]: 0.73; 95% confidence interval [CI] 0.6-0.8). With the ChoiceMMed® oximeter, 168 positive tests were obtained (16.4%), of which 22 cases had some heart disease (13.09%), with a sensitivity of 100%, specificity of 85.4%, positive predictive value of 13.09%, and negative predictive value 100% (OR: 0.86; 95%CI: 0.8-0.92). Regarding the time to perform the cardiac sieve, the mean in minutes of the Masimo SET® oximeter was 5.38 and the ChoiceMMed® oximeter was 9.7 min. Conclusions The ChoiceMMed® oximeter contains a large number of false positives and a greater number of echocardiograms and comparatively longer cardiac screen printing with Masimo SET®, however, both with a negative predictive value of 100% eliminating such excuses.


title: ICP-MS determination of serum aluminum in monkeys subcutaneously administered an alhydrogel-formulated drug candidate.

text: AIM To develop and validate an inductively coupled plasma-mass spectrometry method for quantitative bioanalysis of aluminum (Al) in monkey serum in support of a GLP TOX study with alhydrogel-formulated drug candidate. METHODS & RESULTS The method was linear over a dynamic range of 10-1000 ng/ml using a 50-μl sample volume. The intra-/inter-run precision (%CV) of the quality control sample results were ≤7.9% (CV) and the accuracy (%bias) within ±11.0% across all quality control concentrations evaluated. Other validation parameters, including stability under various conditions, extraction recovery and matrix effect, all met the acceptance criteria. CONCLUSION The validated method was successfully implemented for the quantitative analysis of Al in monkey serum to assess the systemic exposure to Al.


docid: vkojivfl

title: The optimal diagnostic methods for COVID-19.

text: As the world continues to study and understand coronavirus disease (COVID-19), existing investigations and tests have been used to try and detect the virus to slow viral transmission and its global spread. A 'gold-standard' investigation has not yet been identified for detection and monitoring. Initially, computed tomography (CT) was the mainstay investigation as it shows the disease severity and recovery, and its images change at different stages of the disease. However, CT has been found to have limited sensitivity and negative predictive value in the early stages of the disease, and the value of its use has come under debate due to whether its images change the treatment plan, the risk of radiation, as well as its practicality with infection control. Therefore, there has been a shift to the use of other imaging modalities and tests, such as chest X-rays and ultrasound. Furthermore, the use of nucleic acid-based testing such as reverse-transcriptase polymerase chain reaction (RT-PCR) have proven useful with direct confirmation of COVID-19 infection. In this study, we aim to review and analyse current literature to compare RT-PCR, immunological biomarkers, chest radiographs, ultrasound and chest CT scanning as methods of diagnosing COVID-19.


title: Development and Angiographic Use of the Rabbit VX2 Model for Liver Cancer.

text: The rabbit VX2 tumor is an animal model commonly utilized for translational research regarding hepatocellular carcinoma (HCC) in the field of Interventional Radiology. This model employs an anaplastic squamous cell carcinoma that is easily and reliably propagated in the skeletal muscle of donor rabbits for eventual harvest and allograft implantation into the liver of naïve recipients. This tumor graft rapidly grows within the liver of recipient rabbits into an angiographically identifiable tumor characterized by a necrotic core surrounded by a viable hypervascular capsule. The physical size of the rabbit anatomy is sufficient to facilitate vascular instrumentation allowing for the application and testing of various interventional techniques. Despite these benefits, there exists a paucity of technical resources to act as a concrete reference for researchers working with the model. Herein, we present a comprehensive visual outline for the technical aspects of development, growth, propagation, and angiographic utilization of the rabbit VX2 tumor model for use by novice and experienced researchers alike.


It is irrational to exclude vets from Covid-19 control.


docid: fgtkveos

title: Endovascular techniques for the management of wide-neck intracranial bifurcation aneurysms: A critical review of the literature.

text: Endovascular treatment is the first line treatment for intracranial aneurysms, but wide-neck aneurysms are often difficult to treat due to the difficulty in stabilizing the coils inside the aneurysm. It is singularly true for wide-neck bifurcation aneurysms (WNBA) as bifurcation branches often arise from the aneurysm neck. To overcome these difficulties, several approaches are available to treat both ruptured and unruptured aneurysms (balloon-assisted coiling and intra-aneurysmal flow disruption), while some techniques are essentially restricted to unruptured aneurysms due to the need of concomitant use of antiplatelet medications (stent-assisted coiling and flow diversion). Several ways of performing balloon-assisted coiling have been proposed for WNBA. Two stent-assisted techniques are available for WNBA (Y-stenting and the waffle-cone technique), but these techniques have yet to be evaluated in large, prospective series. Off-label use of flow diverters in WNBA has been proposed but efficacy has still to be established, and the technique presents unique potential safety issues (the potential modifications of bifurcation branches covered by the flow diverter) that has to be assessed. Intrasaccular flow disruption devices are promising tools for the endovascular treatment of WNBA. The WEB device has been extensively evaluated with prospective, multicenter studies showing high safety and good efficacy.


title: The cohort effect in childhood disease dynamics.

text: The structure of school terms is well known to influence seasonality of transmission rates of childhood infectious diseases in industrialized countries. A less well-studied aspect of school calendars that influences disease dynamics is that all children enter school on the same day each year. Rather than a continuous inflow, there is a sudden increase in the number of susceptible individuals in schools at the start of the school year. Based on the standard susceptible-exposed-infectious-recovered (SEIR) model, we show that school cohort entry alone is sufficient to generate a biennial epidemic pattern, similar to many observed time series of measles incidence. In addition, cohort entry causes an annual decline in the effective transmission that is evident in observed time series, but not in models without the cohort effect. Including both cohort entry and school terms yields a model fit that is significantly closer to observed measles data than is obtained with either cohort entry or school terms alone (and just as good as that obtained with Schenzle's realistic age-structured model). Nevertheless, we find that the bifurcation structure of the periodically forced SEIR model is nearly identical, regardless of whether forcing arises from cohort entry, school terms and any combination of the two. Thus, while detailed time-series fits are substantially improved by including both cohort entry and school terms, the overall qualitative dynamic structure of the SEIR model appears to be insensitive to the origin of periodic forcing.


title: Seroepidemiologic Study Designs for Determining SARS-COV-2 Transmission and Immunity.

text: Serologic studies are crucial for clarifying dynamics of the coronavirus disease pandemic. Past work on serologic studies (e.g., during influenza pandemics) has made relevant contributions, but specific conditions of the current situation require adaptation. Although detection of antibodies to measure exposure, immunity, or both seems straightforward conceptually, numerous challenges exist in terms of sample collection, what the presence of antibodies actually means, and appropriate analysis and interpretation to account for test accuracy and sampling biases. Successful deployment of serologic studies depends on type and performance of serologic tests, population studied, use of adequate study designs, and appropriate analysis and interpretation of data. We highlight key questions that serologic studies can help answer at different times, review strengths and limitations of different assay types and study designs, and discuss methods for rapid sharing and analysis of serologic data to determine global transmission of severe acute respiratory syndrome coronavirus 2.


title: Heparin protects against septic mortality via apoE-antagonism.

text: BACKGROUND Apolipoprotein E (apoE), a component of plasma lipoproteins, increases septic mortality in a rodent model of sepsis, presumably by enhancing lipid antigen presentation to antigen-presenting cells via the low-density lipoprotein receptor (LDLR). Downstream, this culminates in natural killer T (NKT) cell activation and cytokine secretion. To determine whether apoE antagonism would protect against septic mortality in mice, apoE-LDLR binding was antagonized using heparin, which can inhibit apoE's LDLR-binding site. METHODS C57BL/6 mice underwent cecal ligation and puncture (CLP) and heparin infusion. Serum partial thromboplastin time and alanine aminotransferase were measured at 24 hours, and survival was monitored for 7 days after CLP. LDLR+/+ and LDLR-/- fibroblasts were incubated with apoE and heparin to measure apoE internalization. Hepatic NKT cells and cytokine levels were quantified via fluorescence-activated cell sorting. RESULTS Heparin decreased CLP-induced mortality by 50% versus saline-treated controls, independent of anticoagulation. LDLR+/+ fibroblasts displayed decreased uptake of apoE when treated concurrently with heparin for 12 hours. In septic mice, hepatic alanine aminotransferase levels, hepatic NKT cells, and plasma cytokine levels decreased after heparin treatment. CONCLUSIONS This study demonstrates that heparin protects against septic mortality independent of its anticoagulant effect. This protective effect is associated with the inhibition of apoE-LDLR binding, diminished NKT proliferation and cytokine production, and hepatic dysfunction. These findings indicate a potential clinical role for apoE antagonism in the treatment of sepsis.


title: Phase I trial of stereotactic MR-guided online adaptive radiation therapy (SMART) for the treatment of oligometastatic or unresectable primary malignancies of the abdomen.

text: PURPOSE/OBJECTIVES SBRT is used to treat oligometastatic or unresectable primary abdominal malignancies, although ablative dose delivery is limited by proximity of organs-at-risk (OAR). Stereotactic, magnetic resonance (MR)-guided online-adaptive radiotherapy (SMART) may improve SBRT's therapeutic ratio. This prospective Phase I trial assessed feasibility and potential advantages of SMART to treat abdominal malignancies. MATERIALS/METHODS Twenty patients with oligometastatic or unresectable primary liver (n = 10) and non-liver (n = 10) abdominal malignancies underwent SMART. Initial plans prescribed 50 Gy/5 fractions (BED 100 Gy) with goal 95% PTV coverage by 95% of prescription, subject to hard OAR constraints. Daily real-time online-adaptive plans were created as needed, based on daily setup MR-image-set tumor/OAR "anatomy-of-the-day" to preserve hard OAR constraints, escalate PTV dose, or both. Treatment times, patient outcomes, and dosimetric comparisons between initial and adaptive plans were prospectively recorded. RESULTS Online adaptive plans were created at time of treatment for 81/97 fractions, due to initial plan violation of OAR constraints (61/97) or observed opportunity for PTV dose escalation (20/97). Plan adaptation increased PTV coverage in 64/97 fractions. Zero Grade ≥ 3 acute (<6 months) treatment-related toxicities were observed. DISCUSSION SMART is clinically deliverable and safe, allowing PTV dose escalation and/or simultaneous OAR sparing compared to non-adaptive abdominal SBRT.


title: Strengthening the core health research capacity of national health systems helps build country resilience to epidemics: a cross-sectional survey.

text: Background: TDR, The Special Programme for Research and Training hosted at the World Health Organization, has long supported Low- and Middle-Income Countries in strengthening research capacity through three training programmes: the Postgraduate Training Scheme (PGTS), the Clinical Research and Development Fellowship (CRDF), and the Structured Operational Research Training InitiaTive (SORT IT). In the advent of the COVID-19 pandemic, we assessed whether those trained through these programmes were involved in the COVID-19 response and if so, in which area(s) of the emergency response they were applying their skills. Methods: From the records for each training programme, we identified the individuals who had completed training during the relevant timespan of each programme: 1999-2018 for the CRDF scheme, 2015-2020 for PGTS, and 2009-2019 for SORT-IT. Between March and April 2020, we sent trainees an online questionnaire by e-mail. Results: Out of 1254 trained, 1143 could be contacted and 699 responded to the survey. Of the latter, 411 were involved with the COVID-19 response, of whom 315 (77%) were applying their acquired skills in 85 countries. With some overlap between programmes, 84% of those trained through CRDF were applying their skills in 27 countries, 91% of those trained through PGTS were applying their skills in 19 countries, and through SORT IT, this was 73% in 62 countries. Skills were being applied in various areas of the emergency response, including: emergency preparedness, situation analysis/surveillance, infection control and clinical management, data generation, mitigating the effect of COVID on the health system, and research. Depending on the type of training programme, 26-74% were involved in implementation, operational or clinical research. Conclusion: Research training programmes build research capacity and equip health workers with transferable core competencies and skillsets prior to epidemics. This becomes invaluable in building health system resilience at a time of pandemics.


docid: sxtspcmy

title: Alcohol-Branded Merchandise Ownership and Drinking.

text: CONTEXTS Alcohol-branded merchandise (ABM) has a longer shelf-life than other forms of alcohol marketing and the potential to become integrated into children's self-identities. OBJECTIVE This review sought to explore the current literature on children's exposure to, and the impact of, ABM. DATA SOURCES PsycInfo, Proquest, Science Direct, and ABI-Inform databases were searched from the earliest available date to May 2015. Additional studies were identified by a manual review of the reference lists of retrieved articles and contacting the corresponding author of each included study. STUDY SELECTION Articles that reported on child or adolescent ownership of ABM and/or the relationship between ABM ownership and drinking were included. DATA EXTRACTION Data on key measures were tabulated; where data of interest were not reported, requests for further information were sent to the articles' authors. RESULTS Nine cross-sectional and 4 longitudinal studies were identified. ABM ownership ranged from 11% to 59% and was higher among older children and males. Seven cross-sectional studies reported associations between ABM ownership and drinking-related behaviors. All 4 longitudinal studies reported a significant relationship between ownership at baseline and drinking initiation at follow-up. LIMITATIONS The small number of available studies, with different measures of ABM ownership and of associations/effects. CONCLUSIONS The few studies exploring ABM ownership are consistent in showing high rates of ownership and associations between ownership and current and future drinking. There is a need for further research into specific aspects of ABM ownership. However, there is also a need for policy interventions to reduce children's access to and ownership of ABM.


Catheter-based renal denervation: a word of caution.


title: The most cited and co-cited COVID-19 articles: Knowledge base for rehabilitation team members.

text: BACKGROUND The COVID-19 outbreak pandemic is a situation without a tested action plan. Rehabilitation team members have been called for duty with new responsibilities in addition to their conventional roles in the healthcare system. The infectious disease specialists are updating the knowledge base in limited time in clinical settings. The number of articles in PubMed grows at an increasing rate. OBJECTIVE The purpose of this study is to identify core COVID-19 articles by citation and co-citation network analysis in PMC subset of PubMed. METHODS Citation and co-citation network analysis methods were used to identify core articles and knowledge base. RESULTS COVID-19 terms query retrieved 15,387 articles in PubMed. These articles formed a citation network with 6,778 articles and 25,163 PMC-PubMed citations. The main article cluster in the co-citation network consists of 2,811 articles and 78,844 co-citations. CONCLUSIONS The number of COVID-19 articles in PubMed is increasing at a very high rate. Citation and co-citation network analysis are advantageous techniques to identify knowledge base in a scientific discipline. These techniques may help rehabilitation specialists to identify core articles efficiently.


title: Development and Initial Validation of the COVID-19 Anxiety Scale.

text: Background Safeguarding the psychological well-being of the public is also an integral component of fighting COVID-19. However, there is limited availability of psychometric measures to document COVID-19-related anxiety among the general public. Objectives This study was aimed at developing a validated scale to measure COVID-19-related anxiety. Methods Three hundred and seven subjects from different gender, educational categories participated in the study. Exploratory factor analysis for the determination of factor structure, Pearson's correlation test, and Kruskal-Wallis ANOVA were employed in data analysis using SPSS version 20 software. Results COVID-19 Anxiety Scale (CAS) demonstrated a two-component structure identified as: "fear of social interaction;" "illness anxiety." The final scale with seven items demonstrated good internal consistency reliability (Cronbach's Alpha 0.736). CAS exhibited good construct validity showing moderately negative correlation (Pearson's r = -0.417) with the self-rated mental health and resulted in higher scores among individuals with lower educational qualification (Kruskal-Wallis ANOVA χ2 [2, 303] = 38.01; P = 0.001). Conclusion CAS is a rapidly administrable, valid, and reliable tool that can be used to measure COVID-19-related anxiety among the Indian population.


title: Intracorporeal versus extracorporeal anastomosis in right hemicolectomy: a systematic review and meta-analysis.

text: BACKGROUND Laparoscopic right hemicolectomy for colon cancer is associated with substantial morbidity despite the introduction of enhanced recovery protocols and laparoscopic surgery. Laparoscopic right hemicolectomy with an intracorporeal anastomosis (IA) is less invasive than laparoscopic assisted hemicolectomy, possibly leading to further decrease in post-operative morbidity and faster recovery. The current standard technique includes an extracorporeal anastomosis with mobilization of the colon, mesenteric traction and a extraction wound located in the mid/upper abdomen with relative more post-operative morbidity compared to extraction wounds located in the lower abdomen. METHODS A systematic review of PubMed and Embase databases was performed on studies comparing the intracorporeal versus the extracorporeal performed anastomosis in laparoscopic right hemicolectomy. Primary outcomes were mortality, short-term morbidity and length of stay. For quality assessment, the MINORS checklist was used. Meta-analysis was performed using a random-effects model, and a subgroup analysis was performed for data regarding short-term morbidity and length of stay in studies published in 2012≥. RESULTS A total of 2692 papers were identified, 12 non-randomized comparative studies were included in the analysis with a total number of 1492 patients. No significant change in mortality was found (OR 0.36, 95 % CI 0.09-1.46; I 2 = 0 %). Short-term morbidity decreased significantly in favour of IA (OR 0.68, 95 % CI 0.49-0.93; I 2 = 20 %). Length of stay was decreased, but with serious risk of heterogeneity (MD -0.77 days, 95 % CI -1.46 to -0.07; I 2 = 81 %). Subgroup analysis for papers published in 2012≥ resulted in an even larger decrease in short-term morbidity (OR 0.65, 95 % CI 0.50-0.85; I 2 = 0 %) and a significant decrease in length of stay with low risk of heterogeneity (MD -0.77 days, 95 % CI -1.17 to -0.37; I 2 = 4 %). CONCLUSION Intracorporeal anastomosis in laparoscopic right hemicolectomy is associated with reduced short-term morbidity and decreased length of hospital stay suggesting faster recovery as shown in this meta-analysis.


docid: jsnzbuee

title: A Review of Methanol Poisoning: A Crisis Beyond Ocular Toxicology.

text: At first blush, methanol poisoning may be seen as an arcane problem generally associated with rapid ocular neuropathy. The emerging clinical reality is that methanol poisoning around the globe has claimed increasingly large numbers of deaths largely due to the press of poverty and the delay in suspecting and diagnosing methanol toxicity. With the onset of the COVID-19 pandemic, false beliefs about methanol's preventive potential vs viral infection of have arisen. In March of this year, more than 300 Iranians died and 1,000 became ill after consuming methanol in the hope that it would protect them against the novel coronavirus. We review the context and magnitude methanol toxicity, pathophysiology, principal medical issues, and human variability in metabolism. While toxicologists and clinicians may need to be especially attentive to this problem, it is becoming clear that the social and economic underpinnings of the methanol poisoning crisis must be actively and urgently explored and managed as vigorously as its toxicologic and pathophysiologic components.


docid: gpjbkved

title: PRESCIENT: platform for the rapid evaluation of antibody success using integrated microfluidics enabled technology.

text: Identifying antibodies (Abs) that neutralize infectious agents is the first step for developing therapeutics, vaccines, and diagnostic tools for these infectious agents. However, current approaches for identifying neutralizing Abs (nAbs) typically rely on dilution-based assays that are costly, inefficient, and only survey a small subset of the entire repertoire. There are also intrinsic biases in many steps of conventional nAb identification processes. More importantly, conventional assays rely on simple Ab-antigen binding assays, which may not result in identifying the most potent nAbs, as the strongest binder may not be the most potent nAb. Droplet microfluidic systems have the capability to overcome such limitations by conducting complex multi-step assays with high reliability, resolution, and throughput in a pico-liter volume water-in-oil emulsion droplet format. Here, we describe the development of PRESCIENT (Platform for the Rapid Evaluation of antibody SucCess using Integrated microfluidics ENabled Technology), a droplet microfluidic system that can enable high-throughput single-cell resolution identification of nAb repertoires elicited in response to viral infection. We demonstrate PRESCIENT's ability to identify Abs that neutralize a model viral agent, Murine coronavirus (murine hepatitis virus), which causes high mortality rates in experimentally infected mice. In-droplet infection of host cells by the virus was first demonstrated, followed by demonstration of in-droplet neutralization by nAbs produced from a single Ab-producing hybridoma cell. Finally, fluorescence intensity analyses of two populations of hybridoma cell lines (nAb-producing and non-nAb-producing hybridoma cell lines) successfully discriminated between the two populations. The presented strategy and platform have the potential to identify and investigate neutralizing activities against a broad range of potential infectious agents for which nAbs have yet to be discovered, significantly advancing the nAb identification process as well as reinvigorating the field of Ab discovery, characterization, and development.


title: The European response to the WHO call to eliminate cervical cancer as a public health problem.

text: The age-standardised incidence of cervical cancer in Europe varies widely (between 3 and 25/100000 women-years) in 2018. HPV vaccine coverage is low in countries with the highest incidence and screening performance is heterogeneous among European countries. A broad group of delegates of scientific professional societies and cancer organisations endorse the principles of the WHO call to eliminate cervical cancer as a public health problem, also in Europe. All European nations should, by 2030, reach at least 90% HPV vaccine coverage among girls by the age of 15 years and also boys, if cost-effective; they should introduce organised population-based HPV-based screening and achieve 70% of screening coverage in the target age group, providing also HPV testing on self-samples for non- or under-screened women; and to manage 90% of screen-positive women. To guide member states, a group of scientific professional societies and cancer organisations engage to assist in the roll-out of a series of concerted evidence-based actions. European health authorities are requested to mandate a group of experts to develop the third edition of European Guidelines for Quality Assurance of Cervical Cancer prevention based on integrated HPV vaccination and screening and to monitor the progress towards the elimination goal. The occurrence of the COVID-19 pandemic, having interrupted prevention activities temporarily, should not deviate stakeholders from this ambition. In the immediate post-epidemic phase, health professionals should focus on high-risk women and adhere to cost-effective policies including self-sampling. This article is protected by copyright. All rights reserved.


title: Adenoid ciliostimulation in children with chronic otitis media.

text: OBJECTIVE Adenoid hypertrophy and chronic adenoiditis are associated with an increased incidence of chronic otitis media. This study intends to determine the relationship between chronic otitis media and dynamic ciliary beat frequency in children undergoing adenoidectomy. STUDY DESIGN Prospective, controlled study. SETTING Pediatric tertiary care hospital. SUBJECTS AND METHODS Children undergoing adenoidectomy were enrolled. Patients were stratified according to their indication for surgery, including adenotonsillar hypertrophy with obstructive sleep apnea, chronic otitis media with effusion, or recurrent episodes of acute otitis media. Adenoids were harvested using the curette. Tissue was sectioned and allowed to equilibrate in basal media for 24 hours. Cilia-bearing tissue was then stimulated using isoproterenol or methacholine. Ciliary beat frequency was serially reordered and analyzed using the Sisson-Ammons Video Analysis software program. RESULTS Baseline ciliary beat frequency was similar in all groups (N = 47, total). Using isoproterenol, children with chronic otitis media with effusion demonstrated a blunted dynamic ciliary response at 2 and 3 hours relative to control (P = .0176 and P = .0282). Methacholine-stimulated ciliary beat frequency was not different between each group. CONCLUSION At 2 and 3 hours following isoproterenol stimulation, there was a significant blunting of dynamic ciliary beat frequency in children with chronic otitis media with effusion. This ciliary dysfunction may provide a physiological explanation related to chronic adenoiditis in children with chronic otitis media.


title: Robot-assisted upper extremity rehabilitation for cervical spinal cord injuries: a systematic scoping review.

text: Abstact Purpose: To provide an overview of the feasibility and outcomes of robotic-assisted upper extremity training for individuals with cervical spinal cord injury (SCI), and to identify gaps in current research and articulate future research directions. MATERIALS AND METHODS A systematic search was conducted using Medline, Embase, PsycINFO, CCTR, CDSR, CINAHL and PubMed on June 7, 2017. Search terms included 3 themes: (1) robotics; (2) SCI; (3) upper extremity. Studies using robots for upper extremity rehabilitation among individuals with cervical SCI were included. Identified articles were independently reviewed by two researchers and compared to pre-specified criteria. Disagreements regarding article inclusion were resolved through discussion. The modified Downs and Black checklist was used to assess article quality. Participant characteristics, study and intervention details, training outcomes, robot features, study limitations and recommendations for future studies were abstracted from included articles. RESULTS Twelve articles (one randomized clinical trial, six case series, five case studies) met the inclusion criteria. Five robots were exoskeletons and three were end-effectors. Sample sizes ranged from 1 to 17 subjects. Articles had variable quality, with quality scores ranging from 8 to 20. Studies had a low internal validity primarily from lack of blinding or a control group. Individuals with mild-moderate impairments showed the greatest improvements on body structure/function and performance-level measures. This review is limited by the small number of articles, low-sample sizes and the diversity of devices and their associated training protocols, and outcome measures. CONCLUSIONS Preliminary evidence suggests robot-assisted interventions are safe, feasible and can reduce active assistance provided by therapists. Implications for rehabilitation Robot-assisted upper extremity training for individuals with cervical spinal cord injury is safe, feasible and can reduce hands-on assistance provided by therapists. Future research in robotics rehabilitation with individuals with spinal cord injury is needed to determine the optimal device and training protocol as well as effectiveness.


title: Robotic appendicovesicostomy revision in children: description of technique and initial results.

text: PURPOSE To report our initial results of robotic appendicovesicostomy (APV) revision in children. PATIENTS AND METHODS Three patients (median age 6 years; range 6-13) underwent robot-assisted APV surgery for bladder dysfunction because of posterior urethral valves, myelomeningocele, and traumatic spinal cord transection. Leakage developed in each patient from the APV. After failing more conservative treatments, the patients subsequently underwent robot-assisted APV revision. RESULTS Robot-assisted APV revision was conducted at a median 14 months (range 6-34 mos) after initial surgery. Median operative time was 165 minutes (range 106-232 min), and blood loss was ≤5 mL for all patients. Intraoperative findings ranged from partial to complete separation of the APV from the bladder tunnel. APV leakage resolved for all patients at last follow-up (median 5 months; range 2-9 mos). CONCLUSION This initial series expands the scope of robotic surgical procedures in children. Robot-assisted APV revision was technically feasible and safe in this early experience.


title: The future is now: a call for action for cardiac telerehabilitation in the COVID-19 pandemic from the secondary prevention and rehabilitation section of the European Association of Preventive Cardiology.

text: The role of comprehensive cardiac rehabilitation is well established in the secondary prevention of cardiovascular diseases such as coronary artery disease and heart failure. Numerous trials have demonstrated both the effectiveness as well as the cost-effectiveness of comprehensive cardiac rehabilitation in improving exercise capacity and quality of life, and in reducing cardiovascular mortality and morbidity. However, the current COVID-19 pandemic has led to closure of many cardiac rehabilitation centres in Europe resulting in many eligible patients unable to participate in the optimisation of secondary prevention and physical performance. This elicits an even louder call for alternatives such as cardiac telerehabilitation to maintain the delivery of the core components of cardiac rehabilitation to cardiovascular disease patients. The present call for action paper gives an update of recent cardiac telerehabilitation studies and provides a practical guide for the setup of a comprehensive cardiac telerehabilitation intervention during the COVID-19 pandemic. This set up could also be relevant to any cardiovascular disease patient not able to visit cardiac rehabilitation centres regularly after the COVID-19 pandemic ceases.


title: Effectiveness and tolerance of anti-inflammatory drugs' add-on therapy in major mental disorders: a systematic qualitative review.

text: OBJECTIVE To provide a systematic review of the literature regarding the efficacy of anti-inflammatory drugs in three major mental disorders [major depressive disorder (MDD), schizophrenia and bipolar disorders]. METHOD Four databases were explored, without any year or language restrictions. The baseline search paradigm was limited to open-labelled clinical and randomized controlled trials (RCTs). RESULTS Four major classes of anti-inflammatory drugs were identified, namely polyunsaturated fatty acids (PUFAs), cyclooxygenase (COX) inhibitors, anti-TNFalpha and minocycline. Effectiveness and benefit/risk ratio of each class in MDD, bipolar disorders and schizophrenia was detailed when data were available. Several meta-analyses indicated effectiveness of PUFAs in MDD with a good tolerance profile. One meta-analysis indicated that COX-2 specific inhibitors showed effectiveness in schizophrenia. Anti-TNFalpha showed important effectiveness in resistant MDD with blood inflammatory abnormalities. Minocycline showed effectiveness in schizophrenia. CONCLUSION Polyunsaturated fatty acids seem to have the best benefit/risk ratio profile but proved their effectiveness only in MDD. A number of anti-inflammatory drugs are available as adjunct treatment for treatment-resistant patients with MDD, schizophrenia and bipolar disorder. If used with caution regarding their possible side-effects, they may be reasonable therapeutic alternatives for resistant symptomatology.


title: Enteral refeeding is useful for promoting growth in neonates with enterostomy before stoma closure.

text: BACKGROUND Enterostomy may lead to fluid and electrolyte imbalance, or impaired absorption of nutrition followed by impairment of growth. This study aimed to clarify the effectiveness of enteral refeeding (ER) in premature and full-term neonates. METHODS A retrospective database of all consecutive neonates who had enterostomy during 2000-2014 in a regional center was analyzed. Thirteen patients with ER (ER group) and 14 patients without ER (control group) were included. Detailed clinical data were evaluated with reference to the increment in body weight during ER. RESULTS The ER group had a significantly higher rate in weight gain compared with the control group (P=0.0012), despite the gestational age (<37weeks: P=0.0012, ≥37weeks: P=0.029). ER starting at a lower body weight was also associated with a higher weight gain (P=0.0002). Moreover, univariate and multivariate analyses showed that only the ER procedure (P<0.0001) and birth weight (P=0.049) were significantly independent predictors of good weight gain. CONCLUSIONS Using ER, low-birth-weight infants may have benefits, such as better acceleration of growth, than normal-birth-weight infants. We do not hesitate to perform ER, even in low-birth-weight neonates or those with low body weight, when starting ER.


title: Comparison of Changes in Respiratory Dynamics Immediately After the Start of Propofol Sedation With or Without Midazolam.

text: PURPOSE The aim of this study was to compare changes in respiratory dynamics starting immediately after administration of propofol alone or a combination of propofol and midazolam. MATERIALS AND METHODS Twenty-seven healthy adult volunteers participated in a randomized crossover study of undergoing sedation with propofol alone (P group) or with a combination of propofol and midazolam (PM group). In the P group, continuous infusion of propofol through a target-controlled infusion (TCI) pump was started with the target effect site (ES) concentration set at 1.2 μg/mL. In the PM group, participants received a bolus administration of midazolam 0.02 mg/kg simultaneously with the start of continuous infusion of propofol through a TCI pump with the target ES concentration set at 0.8 μg/mL. The variables measured included the bispectral index (BIS) value, tidal volume (VT), percutaneous arterial oxygen saturation (SpO2), respiratory rate (RR), end-tidal carbon dioxide tension (ETCO2), estimated ES propofol concentration, and minute volume. RESULTS BIS value, VT, SpO2, and ETCO2 decreased after sedative administration in the 2 groups. RR increased in the 2 groups. These changes occurred sooner in the PM group than in the P group. The ratio of change in VT to change in BIS value decreased in the 2 groups and was markedly smaller in the PM group than in the P group. Ratios of changes in SpO2, RR, and ETCO2 to change in BIS value increased in the 2 groups and were larger in the PM group than in the P group. CONCLUSION Changes in respiratory dynamics occurred sooner in the PM group than in the P group. In the PM group, although VT began to decrease before the change in BIS value, the increase in RR caused the rate of decrease in SpO2 to be smaller than the rate of decrease in BIS value.


title: Crystal structure of herpes simplex virus 2 gD bound to nectin-1 reveals a conserved mode of receptor recognition.

text: UNLABELLED Herpes simplex virus 1 (HSV-1) and HSV-2 are among the most prevalent human pathogens. Both viruses can recognize, via the surface envelope glycoprotein D (gD), human nectin-1 as a functional receptor. Previous studies have successfully elucidated the molecular basis of the binding between HSV-1 gD and nectin-1 by cocrystallography. Despite a high sequence identity between HSV-1 and HSV-2 gDs, the atomic intermolecule details for the HSV-2-gD/nectin-1 interaction remain elusive. Here, we report the crystal structures of both the unbound and the nectin-1-bound HSV-2 gDs. The free-gD structure expectedly comprises an IgV-like core and the surface-exposed terminal extensions as observed in its HSV-1 counterpart but lacks traceable electron densities for a large portion of the terminal elements. These terminal residues were clearly traced in the complex structure as a definitive loop in the N terminus and an α-helix in the C terminus, thereby showing a conserved nectin-1-binding mode as reported for HSV-1 gD. The interface residues in nectin-1 were further mutated and tested for the gD interaction by surface plasmon resonance. The resultant binding patterns were similar for HSV-1 and HSV-2 gDs, further supporting a homologous receptor-binding basis by the two viruses for nectin-1. These data, together with a cell-based fusion assay showing a cross-inhibition of the gD/nectin-1-mediated cell-cell fusion by soluble HSV-1 and HSV-2 gDs, provided solid structural and functional evidence that HSV-1 and HSV-2 recognize nectin-1 via the same binding mode. Finally, we also demonstrated that nectin-1 I80 is an important residue involved in gD interaction. IMPORTANCE Despite intensified studies, a detailed picture of the molecular features in the HSV-2-gD/nectin-1 interaction remains unavailable. Previous work focused on HSV-1 gD, which folds into an IgV-like core with large terminal extensions and utilizes the extension elements to engage nectin-1. Here, we report the crystal structures of HSV-2 gD in both the free and the nectin-1-bound forms. The atomic intermolecule details for HSV-2-gD/nectin-1 interaction are clearly presented. The observed binding mode is identical to that reported for its HSV-1 counterpart. This structural observation was further supported by our comparative functional assays showing that nectin-1 mutations similarly affect the ligand-receptor interaction of both virus gDs. Taken together, we provide comprehensive structural and functional data demonstrating a conserved receptor-binding mode between HSV-1 and HSV-2 for nectin-1. Our results also indicate that the tropism difference between the two viruses likely arises from aspects other than the gD/nectin-1 binding features.


title: Infection Prevention and Control in Pediatric Ambulatory Settings.

text: Since the American Academy of Pediatrics published its statement titled "Infection Prevention and Control in Pediatric Ambulatory Settings" in 2007, there have been significant changes that prompted this updated statement. Infection prevention and control is an integral part of pediatric practice in ambulatory medical settings as well as in hospitals. Infection prevention and control practices should begin at the time the ambulatory visit is scheduled. All health care personnel should be educated regarding the routes of transmission and techniques used to prevent the transmission of infectious agents. Policies for infection prevention and control should be written, readily available, updated every 2 years, and enforced. Many of the recommendations for infection control and prevention from the Centers for Disease Control and Prevention for hospitalized patients are also applicable in the ambulatory setting. These recommendations include requirements for pediatricians to take precautions to identify and protect employees likely to be exposed to blood or other potentially infectious materials while on the job. In addition to emphasizing the key principles of infection prevention and control in this policy, we update those that are relevant to the ambulatory care patient. These guidelines emphasize the role of hand hygiene and the implementation of diagnosis- and syndrome-specific isolation precautions, with the exemption of the use of gloves for routine diaper changes and wiping a well child's nose or tears for most patient encounters. Additional topics include respiratory hygiene and cough etiquette strategies for patients with a respiratory tract infection, including those relevant for special populations like patients with cystic fibrosis or those in short-term residential facilities; separation of infected, contagious children from uninfected children when feasible; safe handling and disposal of needles and other sharp medical devices; appropriate use of personal protective equipment, such as gloves, gowns, masks, and eye protection; and appropriate use of sterilization, disinfection, and antisepsis. Lastly, in this policy, we emphasize the importance of public health interventions, including vaccination for patients and health care personnel, and outline the responsibilities of the health care provider related to prompt public health notification for specific reportable diseases and communication with colleagues who may be providing subsequent care of an infected patient to optimize the use of isolation precautions and limit the spread of contagions.