title: Systematic review of the influence of enhanced recovery pathways in elective lung resection.

text: OBJECTIVE Enhanced-recovery pathways aim to accelerate postoperative recovery and facilitate early hospital discharge. The aim of this systematic review was to summarize the evidence regarding the influence of this intervention in patients undergoing lung resection. METHODS The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Eight bibliographic databases (Medline, Embase, BIOSIS, CINAHL, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials) were searched for studies comparing postoperative outcomes in adult patients treated within an enhanced-recovery pathway or traditional care. Risk of bias was assessed using the Cochrane Collaboration risk of bias tool. RESULTS Six studies fulfilled our selection criteria (1 randomized and 5 nonrandomized studies). All the nonrandomized studies reported shorter length of stay in the intervention group (difference, 1.2-9.1 days), but the randomized study reported no differences. There were no differences between groups in readmissions, overall complications, and mortality rates. Two nonrandomized studies reported reduction in hospital costs in the intervention group. Risk of bias favoring enhanced recovery pathways was high. CONCLUSIONS A small number of low-quality comparative studies have evaluated the influence of enhanced-recovery pathways in patients undergoing lung resection. Some studies suggest that this intervention may reduce length of stay and hospital costs, but they should be interpreted in light of several methodologic limitations. This review highlights the need for well-designed trials to provide conclusive evidence about the role of enhanced-recovery pathways in this patient population.


title: Detection of respiratory viruses in sputum from adults by use of automated multiplex PCR.

text: Respiratory tract infections (RTI) frequently cause hospital admissions among adults. Diagnostic viral reverse transcriptase PCR (RT-PCR) of nose and throat swabs (NTS) is useful for patient care by informing antiviral use and appropriate isolation. However, automated RT-PCR systems are not amenable to utilizing sputum due to its viscosity. We evaluated a simple method of processing sputum samples in a fully automated respiratory viral panel RT-PCR assay (FilmArray). Archived sputum and NTS samples collected in 2008-2012 from hospitalized adults with RTI were evaluated. A subset of sputum samples positive for 10 common viruses by a uniplex RT-PCR was selected. A sterile cotton-tip swab was dunked in sputum, swirled in 700 μL of sterile water (dunk and swirl method) and tested by the FilmArray assay. Quantitative RT-PCR was performed on "dunked" sputum and NTS samples for influenza A (Flu A), respiratory syncytial virus (RSV), coronavirus OC43 (OC43), and human metapneumovirus (HMPV). Viruses were identified in 31% of 965 illnesses using a uniplex RT-PCR. The sputum sample was the only sample positive for 105 subjects, including 35% (22/64) of influenza cases and significantly increased the diagnostic yield of NTS alone (302/965 [31%] versus 197/965 [20%]; P = 0.0001). Of 108 sputum samples evaluated by the FilmArray assay using the dunk and swirl method, 99 (92%) were positive. Quantitative RT-PCR revealed higher mean viral loads in dunked sputum samples compared to NTS samples for Flu A, RSV, and HMPV (P = 0.0001, P = 0.006, and P = 0.011, respectively). The dunk and swirl method is a simple and practical method for reliably processing sputum samples in a fully automated PCR system. The higher viral loads in sputa may increase detection over NTS testing alone.


title: Subgenomic messenger RNA amplification in coronaviruses.

text: Coronaviruses possess the largest known RNA genome, a 27- to 32-kb (+)-strand molecule that replicates in the cytoplasm. During virus replication, a 3' coterminal nested set of five to eight subgenomic (sg) mRNAs are made that are also 5' coterminal with the genome, because they carry the genomic leader as the result of discontinuous transcription at intergenic donor signals during (-)-strand synthesis when templates for sgmRNA synthesis are made. An unanswered question is whether the sgmRNAs, which appear rapidly and abundantly, undergo posttranscriptional amplification. Here, using RT-PCR and sequence analyses of head-to-tail-ligated (-) strands, we show that after transfection of an in vitro-generated marked sgmRNA into virus-infected cells, the sgmRNA, like the genome, can function as a template for (-)-strand synthesis. Furthermore, when the transfected sgmRNA contains an internally placed RNA-dependent RNA polymerase template-switching donor signal, discontinuous transcription occurs at this site, and a shorter, 3' terminally nested leader-containing sgmRNA is made, as evidenced by its leader-body junction and by the expression of a GFP gene. Thus, in principle, the longer-nested sgmRNAs in a natural infection, all of which contain potential internal template-switching donor signals, can function to increase the number of the shorter 3'-nested sgmRNAs. One predicted advantage of this behavior for coronavirus survivability is an increased chance of maintaining genome fitness in the 3' one-third of the genome via a homologous recombination between the (now independently abundant) WT sgmRNA and a defective genome.


title: Metal composition of fine particulate air pollution and acute changes in cardiorespiratory physiology.

text: BACKGROUND Studying the physiologic effects of components of fine particulate mass (PM2.5) could contribute to a better understanding of the nature of toxicity of air pollution. OBJECTIVES We examined the relation between acute changes in cardiovascular and respiratory function, and PM2.5-associated-metals. METHODS Using generalized linear mixed models, daily changes in ambient PM2.5-associated metals were compared to daily changes in physiologic measures in 59 healthy subjects who spent 5-days near a steel plant and 5-days on a college campus. RESULTS Interquartile increases in calcium, cadmium, lead, strontium, tin, vanadium and zinc were associated with statistically significant increases in heart rate of 1-3 beats per minute, increases of 1-3 mmHg in blood pressure and/or lung function decreases of up to 4% for total lung capacity. CONCLUSION Metals contained in PM2.5 were found to be associated with acute changes in cardiovascular and respiratory physiology.


title: Strokes in the anterior circulation: comparison between bridging and intravenous thrombolysis.

text: BACKGROUND AND PURPOSE To compare safety and efficacy of bridging approach with intravenous (IV) thrombolysis in patients with acute anterior strokes and proximal occlusions. PATIENTS AND METHODS Consecutive patients with ischemic anterior strokes admitted within a 4 h 30 min window in two different centers were included. The first center performed IV therapy (alteplase 0.6 mg/kg) during 30 min and, in absence of clinical improvement, mechanical thrombectomy with flow restoration using a Solitaire stent (StS); the second carried out IV thrombolysis (alteplase 0.9 mg/kg) alone. Only T, M1 or M2 occlusions present on CT angiography were considered. Endpoints were clinical outcome and mortality at 3 months. RESULTS There were 63 patients in the bridging and 163 in the IV group. No significant differences regarding baseline characteristics were observed. At 3 months, 46% (n = 29) of the patients treated in the combined and 23% (n = 38) of those treated in the IV group had a modified Rankin scale (mRS) of 0-1 (P < 0.001). A statistical significant difference was observed for all sites of occlusion. In a logistic regression model, National Institute of Health Stroke Scale (NIHSS) and bridging therapy were independent predictors of good outcome (respectively, P = 0.001 and P = 0.0018). Symptomatic hemorrhage was documented in 6.3% vs 3.7% in the bridging and in the IV group, respectively (P = 0.32). There was no difference in mortality. CONCLUSIONS Our results suggest that patients treated with a bridging approach were more likely to have minimal or no deficit at all at 3 months as compared to the IV treated group.


title: Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.

text: BACKGROUND Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase. METHODS We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3-6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality. FINDINGS Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35-2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05-1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95-1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01-7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11-10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98-12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99-1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3-6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h. INTERPRETATION Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits. FUNDING UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.


docid: fstdwcco

title: Towards the rational utilization of SARS-CoV-2 serological tests in clinical practice.


title: Ethics, pandemics, and the duty to treat.

text: Numerous grounds have been offered for the view that healthcare workers have a duty to treat, including expressed consent, implied consent, special training, reciprocity (also called the social contract view), and professional oaths and codes. Quite often, however, these grounds are simply asserted without being adequately defended or without the defenses being critically evaluated. This essay aims to help remedy that problem by providing a critical examination of the strengths and weaknesses of each of these five grounds for asserting that healthcare workers have a duty to treat, especially as that duty would arise in the context of an infectious disease pandemic. Ultimately, it argues that none of the defenses is currently sufficient to ground the kind of duty that would be needed in a pandemic. It concludes by sketching some practical recommendations in that regard.


title: A Randomized Controlled Trial Comparison of NeuroSENSE and Bispectral Brain Monitors During Propofol-Based Versus Sevoflurane-Based General Anesthesia.

text: BACKGROUND NeuroSENSE is a depth of anesthesia monitor that uses automated electroencephalogram quantification. The Wavelet-based Anesthetic Value for Central Nervous System (WAVCNS) index calculated by this monitor is based on wavelet analysis of a normalized electroencephalogram signal in the γ-frequency band. The aim of this study was to determine the extent of disagreement between the Bispectral Index (BIS) and the WAVCNS index during propofol-based and sevoflurane-based maintenance of general anesthesia in a routine surgical population. METHODS Patients undergoing elective surgery were enrolled in the study and randomly assigned to receive either propofol or sevoflurane for the maintenance of anesthesia and remifentanil in both groups. Anesthesiologists were blinded to monitors in both groups. Discordance between the 2 monitors was assessed by the count of discrepancy in recommendation (DR) (type 1 defined as one parameter <40 and the other >60, or type 2 defined as BIS and WAVCNS values on different sides of a threshold [40 or 60]) and also by the proportion of agreement (P0) between WAVCNS and BIS, obtained every 5 seconds, in 3 categories of index (<40, 40-60, and >60). RESULTS The analyzed data set consisted of 22 patients (36,872 data pairs) in the propofol group and 24 patients (32,826 data pairs) in the sevoflurane group. The type 1 DR rarely occurred in both the groups (<1%); however, the median (interquartile range) type 2 DR was significantly more frequent in the propofol group (20.6% [7.0-36.9] vs 4.5% [2.3-12.4]; P = 0.0005). The median difference in P0 was 11.53% (95% confidence interval, 0.57-21.32). Major disagreement between WAVCNS index and BIS was related to the weight of burst suppression pattern for the index calculation. CONCLUSIONS Disagreement between BIS and NeuroSENSE during the maintenance of general anesthesia was worse in the propofol group than that in the sevoflurane groups. The disagreement increases during deep anesthesia or in the occurrence of burst suppression.


title: Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials.

text: BACKGROUND Randomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation. METHODS PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial. RESULTS Four eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75). CONCLUSIONS Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels. TRIAL REGISTRATION NUMBER CRD42014013953.


title: Patient-generated health data and electronic health record integration: protocol for a scoping review.

text: INTRODUCTION The objective of this study is to determine the extent and describe the nature of patient-generated health data (PGHD) integration into electronic health records (EHRs) using systematic scoping methods to review the available literature. PGHD have the potential to enhance decision making by providing the valuable information that may not be ordinarily captured during a routine care visit. These data which are captured from mobile devices, such as smartphones, activity trackers and other sensors, should be integrated into clinical workflows to allow for optimal use by clinicians. METHODS AND ANALYSIS This study aims to conduct a rigorous scoping review to explore evidence related to the integration of PGHD into EHRs. Using the framework developed by Arksey and O'Malley, we will create a systematic search strategy, chart data from the relevant articles, and use a qualitative, thematic approach to analyse the data. This review will enable the identification of types of integration and describe challenges and barriers to integrating PGHD. ETHICS AND DISSEMINATION Database searches will be initiated in June 2019. The review is expected to be completed by October 2019. As the content of the full-text articles emerges, the authors will summarise the characteristics related to the integration of PGHD. The findings of this scoping review will identify research gaps and present implications for future research.


title: Successful endovascular treatment of a holo-hemispheric cerebral arteriovenous fistula in an infant.

text: A cerebral arteriovenous fistula (CAVF) is a rare abnormality representing only 4.7% of all cerebral arteriovenous malformations. In this report a unique case is presented of a giant holo-hemispheric CAVF in an infant who presented with congestive heart failure and was successfully treated endovascularly with transarterial and transvenous embolization. A 4-day-old girl presented with lethargy and poor feeding and was found to be in congestive heart failure secondary to a large left hemispheric vascular malformation. Embolization was performed via a transarterial route on days of life (DOL) 11 and 18, a transvenous route on DOL 54 and a final transarterial treatment on DOL 76. After all treatment the patient was discharged home on minimal cardiac medications. At 2-year follow-up the patient had moderate motor delays and mild speech delays, but she continued to meet milestones and her cardiac failure was completely resolved. This case demonstrates one of the largest CAVFs treated successfully in the neonatal population.


title: Effect of sevoflurane on systemic and cerebral circulation, cerebral autoregulation and CO2 reactivity.

text: BACKGROUND Sevoflurane is one of the most frequently used inhaled anesthetics for general anesthesia. Previously it has been reported that at clinically used doses of sevoflurane, cerebral vasoreactivity is maintained. However, there are no data how sevoflurane influences systemic and cerebral circulation in parallel. The aim of our study was to assess systemic and cerebral hemodynamic changes as well as cerebral CO2-reactivity during sevoflurane anesthesia. METHODS Twenty nine patients undergoing general anesthesia were enrolled. Anesthesia was maintained with 1 MAC sevoflurane in 40% oxygen. Ventilatory settings (respiratory rate and tidal volume) were adjusted to reach and maintain 40, 35 and 30 mmHg EtCO2 for 5 min respectively. At the end of each period, transcranial Doppler and hemodynamic parameters using applanation tonometry were recorded. RESULTS Systemic mean arterial pressure significantly decreased during anesthetic induction and remained unchanged during the entire study period. Central aortic and peripherial pulse pressure and augmentation index as markers of arterial stiffness significantly increased during the anesthetic induction and remained stable at the time points when target CO2 levels were reached. Both cerebral autoregulation and cerebral CO2-reactivity was maintained at 1 MAC sevoflurane. DISCUSSION Cerebral autoregulation and CO2-reactivity is preserved at 1 MAC sevoflurane. Cerebrovascular effects of anesthetic compounds have to be assessed together with systemic circulatory effects. TRIAL REGISTRATION The study was registered at http://www.clinicaltrials.gov , identifier: NCT02054143, retrospectively registered. Date of registration: February 4, 2014.


title: [Comparison of two epidemic patterns of COVID-19 and evaluation of prevention and control effectiveness: an analysis based on Guangzhou and Wenzhou].

text: Objective: To compare the epidemiological characteristics of COVID-19 in Guangzhou and Wenzhou, and evaluate the effectiveness of their prevention and control measures. Methods: Data of COVID-19 cases reported in Guangzhou and Wenzhou as of 29 February, 2020 were collected. The incidence curves of COVID-19 in two cities were constructed. The real time reproduction number (R(t)) of COVID-19 in two cities was calculated respectively. Results: A total of 346 and 465 confirmed COVID-19 cases were analysed in Guangzhou and Wenzhou, respectively. In two cities, most cases were aged 30-59 years (Guangzhou: 54.9%; Wenzhou: 70.3%). The incidence curve peaked on 27 January, 2020 in Guangzhou and on 26 January, 2020 in Wenzhou, then began to decline in both cities. The peaks of imported COVID-19 cases from Hubei occurred earlier than the peak of COVID-19 incidences in two cities, and the peak of imported cases from Hubei occurred earlier in Wenzhou than in Guangzhou. In early epidemic phase, imported cases were predominant in both cities, then the number of local cases increased and gradually took the dominance in Wenzhou. In Guangzhou, the imported cases was still predominant. Despite the different epidemic pattern, the R(t) and the number of COVID-19 cases declined after strict prevention and control measures were taken in Guangzhou and in Wenzhou. Conclusion: The time and scale specific differences of imported COVID-19 resulted in different epidemic patterns in two cities, but the spread of the disease were effectively controlled after taking strict prevention and control measures.


title: The need for a systematic approach to disaster psychosocial response: a suggested competency framework.

text: Competency models attempt to define what makes expert performers "experts." Successful disaster psychosocial planning and the institutionalizing of psychosocial response within emergency management require clearly-defined skill sets. This necessitates anticipating both the short- and long-term psychosocial implications of a disaster or health emergency (ie, pandemic) by developing effective and sustained working relationships among psychosocial providers, programs, and other planning partners. The following article outlines recommended competencies for psychosocial responders to enable communities and organizations to prepare for and effectively manage a disaster response. Competency-based models are founded on observable performance or behavioral indicators, attitudes, traits, or personalities related to effective performance in a specific role or job. After analyzing the literature regarding competency-based frameworks, a proposed competency framework that details 13 competency domains is suggested. Each domain describes a series of competencies and suggests behavioral indicators for each competency and, where relevant, associated training expectations. These domains have been organized under three distinct categories or types of competencies: general competency domains; disaster psychosocial intervention competency domains; and disaster psychosocial program leadership and coordination competency domains. Competencies do not replace job descriptions nor should they be confused with performance assessments. What they can do is update and revise job descriptions; orient existing and new employees to their disaster/emergency roles and responsibilities; target training needs; provide the basis for ongoing self-assessment by agencies and individuals as they evaluate their readiness to respond; and provide a job- or role-relevant basis for performance appraisal dimensions or standards and review discussions. Using a modular approach to psychosocial planning, service providers can improve their response capacity by utilizing differences in levels of expertise and training. The competencies outlined in this paper can thus be used to standardize expectations about levels of psychosocial support interventions. In addition this approach provides an adaptable framework that can be adjusted for various contexts.


title: Oncologic outcomes for complete robot-assisted laparoscopic management of upper-tract transitional cell carcinoma.

text: BACKGROUND AND PURPOSE The gold standard for treatment of upper-tract transitional cell carcinoma (TCC) is nephroureterectomy. For distal ureteral TCC, distal ureterectomy with ureteral reimplantation represents a treatment option. Multiple minimally invasive techniques have been introduced with the goal of replicating these open procedures. Currently, there is a paucity of literature for the use of robot-assisted laparoscopic (RAL) management of upper-tract TCC. We evaluated our experience with RAL management of upper-tract TCC. PATIENTS AND METHODS A retrospective chart review was performed on all patients who underwent complete RAL nephroureterectomy or distal ureterectomy with ureteral reimplantation at our institution. RESULTS Eleven patients with a mean age of 67.4 years underwent RAL nephroureterectomy. Mean operative time was 326 minutes (range 243-470 minutes), estimated blood loss 200 mL (range 100-400 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 15.2 months (range 2-31 months), four patients experienced recurrence, and two ultimately died from metastatic disease. Four patients with a mean age of 73.5 years underwent RAL distal ureterectomy with ureteral reimplantation for distal ureteral TCC. Mean operative time was 311 minutes (range 225-446 minutes), estimated blood loss 200 mL (range 100-350 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 30.5 months (range 12-48 months), only one patient, whose pathology exhibited carcinoma in situ within periureteral tissue, required adjuvant treatment for recurrent disease. CONCLUSIONS RAL nephroureterectomy and distal ureterectomy with ureteral reimplantation are feasible options for patients with upper-tract TCC with promising short-term oncologic outcomes.


title: Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion.

text: BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.


title: Analysis of outcomes for single-incision laparoscopic surgery (SILS) right colectomy reveals a minimal learning curve.

text: BACKGROUND Single-incision right colectomy has emerged as a safe and feasible alternative to standard laparoscopic resection. As with any new surgical approach, definition of the number of procedures required to optimize the technique is an important goal. Data on this learning curve for single-incision right colectomy are lacking; therefore, we report the outcomes of consecutive single-incision right colectomies to identify the procedural learning curve. METHODS We retrospectively reviewed consecutive single-incision right colectomies performed by a single surgeon from May 2010 to May 2013. Patients were evaluated in groups of ten to minimize individual patient variability and selection bias. Demographics and peri-operative outcomes among groups were evaluated using ANOVA or Kruskal-Wallis. Statistical improvement was assessed between groups using Student T tests or Mann-Whitney U tests. RESULTS Seventy consecutive single-incision right colectomies were performed during the study period. There were no differences in patient demographics over the course of the experiences, suggesting that the selection bias did not influence the outcomes. There was a statistical improvement in operative time after the first 10 cases (103 vs. 130 min, p = 0.01). A second statistical improvement in operative time occurred after 40 cases (97 vs. 114 min, p = 0.03). There was no statistical improvement in estimated blood loss, lymph node harvest, conversion rate, length of stay, or post-operative morbidity throughout the experience. CONCLUSIONS Analysis of our large series of consecutive cases indicates that for a surgeon trained in advanced laparoscopic techniques and given adequate case volume, the outcomes from the procedure are quickly optimized with a minimal learning curve. Operative time is optimized following 40 procedures. Identification of the learning curve is critical for surgeons wishing to implement a single-incision approach and to ensure that the outcomes are optimized prior to thorough comparison with standard laparoscopic or open approaches.


title: Novel in vitro model for assessing susceptibility of synthetic hernia repair meshes to Staphylococcus aureus infection using green fluorescent protein-labeled bacteria and modern imaging techniques.

text: BACKGROUND Mesh infection complicating hernia repair is a major cause of patient morbidity and results in substantial healthcare expenditures. The various constructs of prosthetic mesh may alter the ability of bacteria to attach and form a biofilm. Few data exist evaluating biofilm formation. Using the Maestro in-Vivo Imaging System (CRi, Inc., Woburn, MA) to detect green fluorescent protein (GFP)-expressing Staphylococcus aureus, we studied the ability of synthetic mesh to withstand bacterial biofilm formation in an in vitro model. METHODS We included four meshes: Polypropylene (PP), polypropylene/expanded PTFE (PX), compressed PTFE (cPTFE), and polyester/polyethylene glycol and collagen hydrogel (PE). Five samples of each mesh were exposed to GFP-expressing S. aureus for 18 h at 37°C. Next, green fluorescence was measured using the Maestro Imaging System, with the results expressed in relative fluorescence units (RFU), subtracting the fluorescence of uninfected mesh (control). Each mesh subsequently underwent sonication and quantitative culture of the released bacteria, with the results expressed in colony-forming units (CFU). Analysis of variance was performed to compare the mean values for the different meshes. RESULTS There was a statistically significant difference in bacterial fluorescence for the four meshes: PE (49.9 ± 25.5 [standard deviation] RFU), PX (30.8 ± 9.4 RFU), cPTFE (10.1 ± 4.0 RFU), and PP (5.8 ± 7.5 RFU)(p = 0.001). Bacterial counts also were significantly different: PE (2.2 × 10(8) CFU), PX (8.6 × 10(7) CFU), cPTFE (3.7 × 10(7) CFU), and PP (9.1 × 10(7) CFU)(p < 0.001). CONCLUSION Using novel imaging technology, this study documented significantly different amounts of S. aureus biofilm formation and proliferation on different mesh constructs, with good agreement between imaging and culture results. A multifilament woven mesh (PE) had the highest degree of biofilm formation. These findings are being evaluated in a clinical infection model.


title: Statins for the primary prevention of cardiovascular disease: an overview of systematic reviews.

text: OBJECTIVE To synthesise evidence from exclusively primary prevention data on the effectiveness of statins for prevention of cardiovascular disease (CVD), including stroke, and outcomes stratified by baseline risk and gender. DESIGN Overview of systematic reviews (SRs) using Revised-AMSTAR approach to assess quality. DATA SOURCES Cochrane Database of Systematic Reviews, MEDLINE, Embase, PubMed, Scopus and PROSPERO to June 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES SRs of randomised control trials (RCTs) or individual patient data (IPD) from RCTs, examining the effectiveness of statins versus placebo or no treatment on all-cause mortality, coronary heart disease, CVD (including stroke) and composite endpoints, with stratification by baseline risk and gender. DATA EXTRACTION AND SYNTHESIS Two independent reviewers extracted data and assessed methodological quality. A narrative synthesis was conducted. RESULTS Three SRs were included. Quality of included SRs was mixed, and none reported on the risk of bias of included trials.We found trends towards reduced all-cause mortality in all SRs (RR 0.91 [95% CI 0.85 to 0.97]), (RR 0.91 [95% CI 0.83 to 1.01]) and (RR 0.78 [95% CI 0.53 to 1.15]) though it was not statistically significant in two SRs. When stratified by baseline risk, the effect on all-cause mortality was no longer statistically significant except in one medium risk category. One review reported significant reductions (RR 0.85 [95% CI 0.77 to 0.95]) in vascular deaths and non-significant reductions in non-vascular deaths (RR 0.97 [95% CI 0.88 to 1.07]). There were significant reductions in composite outcomes overall, but mixed results were reported in these when stratified by baseline risk. These reviews included studies with participants considered risk equivalent to those with established CVD. CONCLUSIONS There is limited evidence on the effectiveness of statins for primary prevention with mixed findings from studies including participants with widely ranging baseline risks. Decision making for the use of statins should consider individual baseline risk, absolute risk reduction and whether risk reduction justifies potential harms and taking a daily medicine for life. TRIAL REGISTRATION NUMBER CRD42017064761.


The hand-sewn gastrojejunostomy: braided suture or monofilament suture?


docid: lotadmbm

title: Morbidity and mortality after closure of loop ileostomy.

text: BACKGROUND A temporary loop ileostomy is commonly used to protect low pelvic anastomoses. Closure is associated with morbidity and mortality. This study investigated patterns of complications after loop ileostomy closure and factors associated with morbidity and mortality. METHOD A review was performed of patients who underwent loop ileostomy closure between 1999 and 2005. RESULTS Three hundred and twenty-five patients underwent closure of loop ileostomy. Reasons for primary surgery were: anterior resection for cancer (n = 160, 49%), ileal pouch-anal anastomosis (n = 114, 35%), diverticular disease (n = 25, 8%), Crohn's colitis (n = 4, 1%) and other conditions (n = 22, 7%). Overall mortality was 2.5% (n = 8) and morbidity was 22.8% (n = 74). Thirty-two patients (10%) developed small bowel obstruction, of whom seven required operative intervention. Overall, the re-operation rate in this series was 28 patients (8.6%). Thirteen (4%) patients had an anastomotic leak of whom 12 patients had re-operation. Preoperative anaemia was significantly associated with leakage (Hb < 11 g/dl; n = 65, P = 0.033). The leakage rate was lower after a stapled anastomosis than a hand-sutured anastomosis (4/203 vs 9/122; P = 0.039). Hypo-albuminaemia (albumin < 34 g/l) was significantly associated with mortality (n = 46, P < 0.001). CONCLUSIONS Loop ileostomy closure is associated with morbidity and mortality. Anaemia and hypo-albuminaemia may be associated with poor outcome.


title: Respiratory performance offered by N95 respirators and surgical masks: human subject evaluation with NaCl aerosol representing bacterial and viral particle size range.

text: OBJECTIVES This study aimed at determining the protection factors (PFs) provided by N95 filtering facepiece respirators and surgical masks against particles representing bacterial and viral size ranges (aerodynamic size: 0.04-1.3 mum). METHODS The protection levels of N95 filtering facepiece respirators (four models) and surgical masks (three models) were investigated while they were donned by 12 subjects performing the OSHA (US Occupational Safety and Health Administration) fit-testing exercises in a test chamber. RESULTS About 29% of N95 respirators and approximately 100% of surgical masks had PFs <10, which is the assigned PF designated for this type of respirator by the OSHA. On average, the PFs of N95 respirators were 8-12 times greater than those of surgical masks. The minimum PFs were observed in the size range of 0.04-0.2 mum. No significant difference in PF results was found between N95 respirators with and without an exhalation valve. CONCLUSIONS The study indicates that N95 filtering facepiece respirators may not achieve the expected protection level against bacteria and viruses. An exhalation valve on the N95 respirator does not affect the respiratory protection; it appears to be an appropriate alternative to reduce the breathing resistance.


Concerns and needs of patients with systemic lupus erythematosus regarding hydroxychloroquine supplies during the COVID-19 pandemic: results from a patient-centred survey.


title: Short self-interacting N-terminal region of rubella virus capsid protein is essential for cooperative actions of capsid and nonstructural p150 proteins.

text: UNLABELLED Nucleocapsid formation is a primary function of the rubella virus capsid protein, which also promotes viral RNA synthesis via an unknown mechanism. The present study demonstrates that in infected cells, the capsid protein is associated with the nonstructural p150 protein via the short self-interacting N-terminal region of the capsid protein. Mutational analyses indicated that hydrophobic amino acids in this N-terminal region are essential for its N-terminal self-interaction, which is critical for the capsid-p150 association. An analysis based on a subgenomic replicon system demonstrated that the self-interacting N-terminal region of the capsid protein plays a key role in promoting viral gene expression. Analyses using a virus-like particle (VLP) system also showed that the self-interacting N-terminal region of the capsid protein is not essential for VLP production but is critical for VLP infectivity. These results demonstrate that the close cooperative actions of the capsid protein and p150 require the short self-interacting N-terminal region of the capsid protein during the life cycle of the rubella virus. IMPORTANCE The capsid protein of rubella virus promotes viral RNA replication via an unknown mechanism. This protein interacts with the nonstructural protein p150, but the importance of this interaction is unclear. In this study, we demonstrate that the short N-terminal region of the capsid protein forms a homo-oligomer that is critical for the capsid-p150 interaction. These interactions are required for the viral-gene-expression-promoting activity of the capsid protein, allowing efficient viral growth. These findings provide information about the mechanisms underlying the regulation of rubella virus RNA replication via the cooperative actions of the capsid protein and p150.


title: Testicular perfusion after standing laparoscopic peritoneal flap hernioplasty in stallions.

text: Acquired inguinal herniation is a very common condition in stallions, usually leading to unilateral or bilateral castration to prevent future recurrence. Recently, several surgical techniques such as the standing laparoscopic peritoneal flap hernioplasty (SLPFH) have been developed to avoid herniation recurrence and also preserve the breeding activity of high economic value stallions. However, studies on SLPFH lack more comprehensive and systematic data about reproductive-related adverse effects and outcomes. The aim of this study was to evaluate whether SLPFH of the internal inguinal rings produces changes in the testicular blood flow in a 1-year follow-up. For that purpose, six healthy stallions were used and testicular blood flow was assessed before, 3, 6, and 12 months (T0, T3, T6, and T12) after the procedure. Blood flow was evaluated ultrasonographically, using the pulsed-wave color Doppler mode. Peak systolic velocity, end-diastolic velocity, the time-averaged maximum velocity, and the derived indexes (resistive index) and pulsatility index) of the testicular artery were measured in two localizations: in the spermatic cord and on the caudal epididymal edge of the testicle. On the spermatic cord, the peak systolic velocity of the testicular artery increased significantly at T12. However, on the epididymal edge location of the artery, the pulsatility and resistive indexes were decreased at T12 (P < 0.05). This pattern of blood flow was related to a hyperemic process. Furthermore, SLPFH might have compressed the spermatic cord, causing a slight occlusion of the testicular artery and triggering a compensatory hyperemia to compensate the deficit of blood flow that supplies the testes. The SLPFH of the internal inguinal ring affected the testicular perfusion in stallions in a 1 year follow-up, although there was no effect on sperm production during this time. The spectral Doppler ultrasound is a useful tool to asses the testicular perfusion after reproductive surgical procedure and provides information which anticipates vascular supply compromise of the stallion testicles.


title: Successful closed suction drain management of a canine elbow hygroma.

text: A 1-year-old castrated male St. Bernard dog presented to Angell Animal Medical Center with bilateral elbow hygromas which had been present for several weeks. The largest hygroma involving the left elbow was managed with a closed suction (active) drain system to continuously collapse the hygroma pocket over a 3-week period. Soft bedding was used to protect the elbows from further impact trauma to the olecranon areas. Following drain removal, there was no evidence of hygroma recurrence based on periodic examinations over an 18-month period. The smaller non-operated right elbow hygroma had slightly enlarged during this period. Closed suction drain management of the hygroma proved to be a simple and economical method of collapsing the left elbow hygroma. This closed drainage system eliminated the need for the postoperative bandage care required with the use of the Penrose (passive) drain method of managing elbow hygromas. The external drain tube should be adequately secured in order to minimise the risk of its inadvertent displacement.


title: Quantitative proteomics identifies host factors modulated during acute hepatitis E virus infection in the swine model.

text: UNLABELLED Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In industrialized countries, HEV is considered an emerging zoonotic disease, with swine being the principal reservoir for human contamination. The viral and cellular factors involved in the replication and/or pathogenesis of HEV are still not fully known. Here we report that several cellular pathways involved in cholesterol and lipid metabolism or cell survival were modulated during HEV infection in the swine model. Moreover, we observed a difference between the different swine strains, suggesting that HEV's genetic variability could play a role in pathogenesis. We also identified some proteins known to be involved in other viral cycles. Our study provides insight into the mechanisms modulated during HEV infection and constitutes a useful reference for future work on HEV pathogenesis and virulence.


title: Modified esophagogastrostomy in laparoscopy-assisted proximal gastrectomy: A reverse-Tornado anastomosis.

text: INTRODUCTION The aim of this study was to introduce and examine a modified mechanical end-to-side esophagogastrostomy method ("reverse-Tornado" anastomosis) in laparoscopy-assisted proximal gastrectomy. METHODS Five patients with gastric cancer who underwent laparoscopy-assisted proximal gastrectomy were analyzed retrospectively. Esophagogastrostomy in the anterior wall was performed in three patients, and esophagogastrostomy in the posterior wall was performed in two patients. Clinicopathological features, operative outcomes (operative time, operative blood loss), and postoperative outcomes (complications, postoperative hospital stay, reflux esophagitis) were evaluated. RESULTS Operative time was normal (278 min). There was no marked operative blood loss, postoperative complications, prolonged hospital stay, or reflux esophagitis. CONCLUSION Esophagogastrostomy was completed in a normal time with reverse-Tornado anastomosis. This method can be safe and can enable good postoperative quality of life.


title: Ophthalmology and SARS-CoV-2: Blind toward those who fight blindness?

text: SARS-CoV-2 infection recently reached pandemic proportions, with high risk of death for the worldwide population. In this dramatic scenario, all the resources are addressed to the intensive care units for the assessment of the emergency. However, more attention should be paid with respect to the risk of viral diffusion among asymptomatic people. Italy is the second most involved country in the world, and we needed to gain a lot of experience in a very limited time. At least 1 m of distance among people is recommended; however, some clinical practices cannot allow this distance. In this context, we believe that the careful safety assessment of clinical settings, like ophthalmologic ones, may have a remarkable impact on the fight against SARS-CoV-2 spread.


title: Partially Uncleaved Alphavirus Replicase Forms Spherule Structures in the Presence and Absence of RNA Template.

text: Alphaviruses are positive-strand RNA viruses expressing their replicase as a polyprotein, P1234, which is cleaved to four final products, nonstructural proteins nsP1 to nsP4. The replicase proteins together with viral RNA and host factors form membrane invaginations termed spherules, which act as the replication complexes producing progeny RNAs. We have previously shown that the wild-type alphavirus replicase requires a functional RNA template and active polymerase to generate spherule structures. However, we now find that specific partially processed forms of the replicase proteins alone can give rise to membrane invaginations in the absence of RNA or replication. The minimal requirement for spherule formation was the expression of properly cleaved nsP4, together with either uncleaved P123 or with the combination of nsP1 and uncleaved P23. These inactive spherules were morphologically less regular than replication-induced spherules. In the presence of template, nsP1 plus uncleaved P23 plus nsP4 could efficiently assemble active replication spherules producing both negative-sense and positive-sense RNA strands. P23 alone did not have membrane affinity, but could be recruited to membrane sites in the presence of nsP1 and nsP4. These results define the set of viral components required for alphavirus replication complex assembly and suggest the possibility that it could be reconstituted from separately expressed nonstructural proteins.IMPORTANCE All positive-strand RNA viruses extensively modify host cell membranes to serve as efficient platforms for viral RNA replication. Alphaviruses and several other groups induce protective membrane invaginations (spherules) as their genome factories. Most positive-strand viruses produce their replicase as a polyprotein precursor, which is further processed through precise and regulated cleavages. We show here that specific cleavage intermediates of the alphavirus replicase can give rise to spherule structures in the absence of viral RNA. In the presence of template RNA, the same intermediates yield active replication complexes. Thus, partially cleaved replicase proteins play key roles that connect replication complex assembly, membrane deformation, and the different stages of RNA synthesis.


title: Transcatheter or Surgical Aortic Valve Replacement in Patients With Prior Coronary Artery Bypass Grafting.

text: BACKGROUND Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are treatment options for aortic stenosis in patients with prior coronary artery bypass graft surgery. We assessed the major clinical outcomes of such patients enrolled in the CoreValve High Risk (CHR) study. METHODS Of the 795 CHR study patients, 226 had prior coronary artery bypass graft surgery; 115 underwent TAVR and 111 underwent SAVR. The primary endpoint was a comparison of all-cause mortality at 1 year. Important secondary clinical endpoints were assessed. RESULTS At 1 year, all-cause mortality was 9.6% for TAVR versus 18.1% for SAVR (p = 0.06); cardiovascular mortality was 7.0% for TAVR versus 13.8% for SAVR (p = 0.09). A combination of The Society of Thoracic Surgeons risk score greater than 7 and age greater than 80 years was a significant predictor of mortality, with TAVR demonstrating a survival advantage (p = 0.03). No differences were seen for stroke. The SAVR group had longer intensive care unit and hospital stays, increased incidence of acute kidney injury, life-threatening or disabling bleeding, and major adverse cardiac and cerebrovascular events (p < 0.05). Pacemaker implantation and paravalvular regurgitation were greater with TAVR at all timepoints. CONCLUSIONS For patients with prior coronary artery bypass graft surgery and aortic stenosis, TAVR offers a significant morbidity advantage and a strong trend toward improved survival over SAVR at 1 year.


title: Tele-Neuro-Ophthalmology: Vision for 20/20 and Beyond.

text: BACKGROUND Telehealth provides health care to a patient from a provider at a distant location. Prior to the COVID-19 pandemic adoption of telehealth modalities was increasing slowly but steadily. During the public health emergency rapid widespread telehealth implementation has been encouraged to promote patient and provider safety and preserve access to health care. EVIDENCE ACQUISITION Evidence was acquired from English language Internet-searches of medical and business literature and following breaking news on the COVID-19 pandemic and responses from health care stakeholders including policy makers, payers, physicians and health care organizations, and patients. We also had extensive discussions with colleagues who are developing telehealth techniques relevant to neuro-ophthalmology. RESULTS Regulatory, legal, reimbursement and cultural barriers impeded the widespread adoption of telehealth prior to the COVID-19 pandemic. With the increased use of telehealth in response to the public health emergency, we are rapidly accumulating experience and an evidence base identifying opportunities and challenges related to the widespread adoption of tele-neuro-ophthalmology. One of the major challenges is the current inability to adequately perform funduscopy remotely. CONCLUSIONS Telehealth is an increasingly recognized means of healthcare delivery. Tele-neuro-ophthalmology adoption is necessary for the sake of our patients, the survival of our subspecialty, and the education of our trainees and students. Telehealth does not supplant but supplements and complements in-person neuro-ophthalmologic care. Innovations in digital optical fundus photography, mobile vision testing applications, artificial intelligence and principles of channel management will facilitate further adoption of tele-neuro-ophthalmology and bring the specialty to the leading edge of healthcare delivery.


title: Endovascular Reperfusion and Cooling in Cerebral Acute Ischemia (ReCCLAIM I).

text: BACKGROUND The efficacy of hypothermia as a neuroprotectant has yet to be demonstrated in acute ischemic stroke. We conducted a phase I pilot study to assess the feasibility and safety of performing intravascular hypothermia after definitive intra-arterial reperfusion therapy (IAT). METHODS ReCCLAIM (Reperfusion and Cooling in Cerebral Acute Ischemia) is a prospective single-arm open-label clinical trial conducted between May and August 2012 at Grady Memorial Hospital. Twenty patients with Alberta Stroke Program Early CT Score (ASPECTS) 5-7 and NIH Stroke Scale (NIHSS) score > 13 were enrolled and treated with intravascular cooling immediately after IAT. The incidence of pneumonia, deep vein thrombosis, cardiac arrhythmias and postoperative hemorrhages was documented for the entire length of stay. Secondary outcomes included blood-brain barrier (BBB) breakdown on gadolinium-enhanced MRIs and 90-day modified Rankin scores (mRS). RESULTS The mean age, median NIHSS score and median final infarct volume were 59.7 ± 14.6 years, 19 (IQR16-22) and 78 cm(3) (IQR 16-107), respectively. The average time to the target temperature (33 °C) was 64 ± 50 min. Intracranial hemorrhages were found in three patients, of which one was symptomatic. Evidence of BBB breakdown was observed on 3 of 14 MRIs (21%). Six patients died due to withdrawal of care, whereas six patients (30%) achieved mRS of 0-2 at 90 days. In a binary logistical regression model comparing ReCCLAIM patients with 68 historical controls at our institution, hypothermia was protective against intracerebral hemorrhages (OR 0.09, 95% CI 0.02 to 0.56; p<0.01). CONCLUSIONS Hypothermia can be safely performed after definitive IAT in patients with large pretreatment core infarcts. A phase II study randomizing patients to hypothermia or normothermia is needed to properly assess the efficacy of hypothermia as a neuroprotectant for reperfusion injury. TRIAL REGISTRATION NUMBER NCT01585597.


docid: goxenjlq

title: Efficacy and safety of Chinese herbal medicine for Coronavirus disease 2019: A protocol for systematic review and meta-analysis.

text: BACKGROUND Coronavirus disease 2019 (COVID-19) is a global pandemic caused by the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). There is no specific cure for this disease, and the clinical management mainly depends on supportive treatment. Traditional Chinese medicines (CHM) is widely used in treating COVID-19 in China. METHODS A comprehensive literature search will be conducted. Two methodological trained researchers will read the title, abstract, and full texts and independently select the qualified literature according to inclusion and exclusion criteria. After assessment of the risk of bias and data extraction, we will conduct meta-analyses for outcomes related to COVID-19. The heterogeneity of data will be investigated by Cochrane χ and I tests. Then publication bias assessment will be conducted by funnel plot analysis and Egger test. RESULTS The results of our research will be published in a peer-reviewed journal. CONCLUSION Our study aims to systematically present the clinical evidence of CHM in the treatment of COVID-19, which will be of guiding significance for further research and clinical practice. OSF REGISTRATION NUMBER 10.17605/OSF.IO/H7GMU.


title: Apixaban for treatment of embolic stroke of undetermined source (ATTICUS randomized trial): Rationale and study design.

text: Rationale Optimal secondary prevention of embolic stroke of undetermined source is not established. The current standard in these patients is acetylsalicylic acid, despite high prevalence of yet undetected paroxysmal atrial fibrillation. Aim The ATTICUS randomized trial is designed to determine whether the factor Xa inhibitor apixaban administered within 7 days after embolic stroke of undetermined source, is superior to acetylsalicylic acid for prevention of new ischemic lesions documented by brain magnetic resonance imaging within 12 months after index stroke. Design Prospective, randomized, blinded, parallel-group, open-label, German multicenter phase III trial in approximately 500 patients with embolic stroke of undetermined source. A key inclusion criterion is the presence or the planned implantation of an insertable cardiac monitor. Patients are 1:1 randomized to apixaban or acetylsalicylic acid and treated for a 12-month period. It is an event-driven trial aiming for core-lab adjudicated primary outcome events. Study outcomes The primary outcome is the occurrence of at least one new ischemic lesion identified by axial T2-weighted FLAIR magnetic resonance imaging and/or axial DWI magnetic resonance imaging at 12 months when compared with the baseline magnetic resonance imaging. Key secondary outcomes are the combination of recurrent ischemic strokes, hemorrhagic strokes, systemic embolism; combination of MACE including recurrent stroke, myocardial infarction, and cardiovascular death and combination of major and clinically relevant non-major bleeding defined according to ISTH, and change of cognitive function and quality of life (EQ-5D, Stroke Impact Scale). Discussion Embolic stroke of undetermined source is caused by embolic disease and associated with a high risk of recurrent ischemic strokes and clinically silent cerebral ischemic lesions. ATTICUS will investigate the impact of atrial fibrillation detected by insertable cardiac monitor and the effects of early anticoagulation with apixaban compared with antiplatelet therapy with acetylsalicylic acid on the incidence of new ischemic lesion after embolic stroke of undetermined source.


title: Exercise Training in Elderly People Undergoing Hemodialysis: A Systematic Review and Meta-analysis.

text: Introduction Previous reviews have indicated the effectiveness of exercise in people undergoing hemodialysis. However, these analyses did not take into account whether the subjects were elderly. We performed a systematic review of the effects of exercise training in elderly people undergoing hemodialysis and updated the evidence of exercise for people undergoing hemodialysis by adding recent research data. Methods We searched 8 electronic databases up to June 2016. Inclusion criteria were as follows: randomized controlled trial, English publication, subjects aged 18 and older undergoing hemodialysis, evaluation of physical function as an outcome of exercise intervention. We defined elderly as age 60 years and older. The main outcomes were exercise tolerance (peak/maximum oxygen consumption) and walking ability (6-minute walk distance). Secondary outcomes were lower extremity muscle strength and quality of life. Results After screening of 10,923 references, 30 comparisons were entered into the analysis. However, because we found only 1 study in which elderly subjects were treated, we could not perform a meta-analysis for these people. For the general population undergoing hemodialysis, supervised exercise training was shown to significantly increase peak/maximum oxygen consumption (standard mean difference, 0.62; 95% confidence interval 0.38-0.87; P < 0.001), 6-minute walk distance (standard mean difference, 0.58; 95% confidence interval 0.24-0.93; P < 0.001), lower extremity muscle strength (standard mean difference, 0.94; 95% confidence interval 0.67-1.21; P < 0.001), and quality of life (standard mean difference, 0.53; 95% confidence interval 0.52-0.82; P < 0.001). Discussion Our analysis on the effectiveness of exercise training in elderly people undergoing hemodialysis as compared with nonelderly people was somewhat inconclusive. Future studies should be carried out for elderly people to identify the most favorable exercise program for this population.


Prevalence of COVID-19 in Out-of-Hospital Cardiac Arrest: Implications for Bystander CPR.


title: Predictive Value of Anastomotic Blood Supply for Anastomotic Stricture After Esophagectomy in Esophageal Cancer.

text: BACKGROUND Insufficient blood supply in the gastric tube is considered as a risk factor for postoperative anastomotic strictures in patients receiving esophagectomy, but the direct evidence is lacking. AIMS We aimed to investigate the correlation between perioperative blood supply in the anastomotic area of the gastric tube and the formation of anastomotic strictures in the patients undergoing esophagectomy. METHODS This prospective study included 60 patients with esophageal squamous cell carcinoma undergoing Ivor Lewis esophagectomy between March 2014 and February 2016, which were divided into stricture group (n = 13) and non-stricture group (n = 47) based on their severity of anastomotic strictures at 3 months post-operation. The perioperative anastomotic blood supply was measured using a laser Doppler flowmetry. The gastric intramucosal pH (pHi) was measured by a gastric tonometer within 72 h post-operation. The perfusion index and gastric pHi were compared between groups. RESULTS The stricture group had a significantly lower blood flow index (P < 0.001) and gastric pHi values from day 1 to day 3 post-operation than the non-stricture group (all P < 0.001). In addition, Pearson correlation analysis showed that both the perfusion index and gastric pHi were significantly correlated with stricture size and stricture scores, respectively (r = 0.65 - 0.32, all P < 0.05). Furthermore, the multivariate logistic regression analysis showed that perfusion index was an influential factor associated with postoperative anastomotic strictures (OR 0.84. 95% CI 0.72-0.98, P = 0.026). CONCLUSION These results suggested that poor blood supply in the anastomotic area of the gastric tube in the perioperative period was a risk factor for postoperative anastomotic strictures.


Gastric antral vascular ectasia: a rare manifestation for gastrointestinal bleeding in left ventricular assist device patients--an initial report.


Quantification of myocardial blood flow and flow reserve: Technical aspects.


title: Analytical comparisons of SARS-COV-2 detection by qRT-PCR and ddPCR with multiple primer/probe sets.

text: Different primers/probes sets have been developed all over the world for the nucleic acid detection of SARS-CoV-2 by quantitative real time polymerase chain reaction (qRT-PCR) as a standard method. In our recent study, we explored the feasibility of droplet digital PCR (ddPCR) for clinical SARS-CoV-2 nucleic acid detection compared with qRT-PCR using the same primer/probe sets issued by Chinese Center for Disease Control and Prevention (CDC) targeting viral ORF1ab or N gene, which showed that ddPCR could largely minimize the false negatives reports resulted by qRT-PCR [1]. Here, we further stringently compared the performance of qRT-PCR and ddPCR for 8 primer/probe sets with the same clinical samples and conditions. Results showed that none of 8 primer/probe sets used in qRT-PCR could significantly distinguish true negatives and positives with low viral load (10-4 dilution). Moreover, false positive reports of qRT-PCR with UCDC-N1, N2 and CCDC-N primers/probes sets were observed. In contrast, ddPCR showed significantly better performance in general for low viral load samples compared to qRT-PCR. Remarkably, the background readouts of ddPCR are relatively lower, which could efficiently reduce the production of false positive reports.


title: Applying principles of behaviour change to reduce SARS-CoV-2 transmission.

text: Human behaviour is central to transmission of SARS-Cov-2, the virus that causes COVID-19, and changing behaviour is crucial to preventing transmission in the absence of pharmaceutical interventions. Isolation and social distancing measures, including edicts to stay at home, have been brought into place across the globe to reduce transmission of the virus, but at a huge cost to individuals and society. In addition to these measures, we urgently need effective interventions to increase adherence to behaviours that individuals in communities can enact to protect themselves and others: use of tissues to catch expelled droplets from coughs or sneezes, use of face masks as appropriate, hand-washing on all occasions when required, disinfecting objects and surfaces, physical distancing, and not touching one's eyes, nose or mouth. There is an urgent need for direct evidence to inform development of such interventions, but it is possible to make a start by applying behavioural science methods and models.


title: Reverse transcription polymerase chain reaction (RT-PCR) analysis of proteolytic enzymes in cultures of human respiratory epithelial cells.

text: BACKGROUND Pancreatic proteolytic digestive enzymes are a major extracellular barrier to the sucessful systemic delivery of biopharmaceuticals via the oral route, whereas in health in the lungs these powerful proteases are virtually absent from the extracellular fluids. Despite this, the absorption of some (but not all) natural peptides and proteins from the lungs may be poor, and one has to acknowledge that information on the activity and spatial distribution of proteolytic enzymes in the human lung is scarce. Here, we investigated expression patterns of a series of proteolytic enzymes in several human respiratory cell types on mRNA level in an attempt to better understand the fate of inhaled biopharmaceuticals. METHODS The mRNA expression of proteolytic enzymes (i.e., carboxypeptidases: CPA1, CPA2, CPB, CPM; gamma-glutamyltransferases: GGT1, GGT2; angiotensin-converting enzymes: ACE, ACE2; aminopeptidases: APA, APB, APN, APP1, APP2, APP3; endopeptidases: 24.11 (neprilysin), 24.15 (thimet oligopeptidase), 24.18 (meprin A); enteropeptidase; trypsin 1, trypsin 2; neutrophilic elastase; dipeptidyl peptidase 4; gamma-glutamylhydrolase) was investigated by semiquantitative RT-PCR in human bronchial (hBEpC, Calu-3, 16HBE14o-) and alveolar (A549) epithelial cells, respectively. Gastrointestinal Caco-2 cells were used as comparison. RESULTS Obvious differences were observed in proteinases' expression pattern between the investigated cell types. Although considered to be of bronchial epithelial phenotype, neither Calu-3 nor 16HBE14o- cells matched the mRNA expression pattern of hBEpC in primary culture. Of all investigated cell lines, Caco-2 expresses the highest number of proteases and peptidases. CONCLUSIONS Although mRNA expression does not necessarily signify enzyme functionality, our results provide the first comprehensive analysis of peptidase and protease expression and distribution in human lung epithelial cells and are the basis for further investigations.


title: Combining dose and injection volume for good performance of a specific radiopharmaceutical for sentinel node detection.

text: INTRODUCTION The aim of this work was to quantify the effects of injection volume at different technetium-99m specific radiotracer doses on its lymphatic movement in animal model. PROCEDURES Effects of injection volume (50, 100 μl) at different doses (0.05, 0.135, 0.22 nmol) on popliteal node (PN) detection were studied in rats. The radiotracer under study was (99m)Technetium-cysteine-mannose-dextran conjugate (30 kDa). RESULTS At 0.05 nmol dose, higher PN uptake was observed at 50 μl injection volume (2.6 fold increase). Conversely, at 0.135 nmol dose, an increase of radiotracer retention in PN was achieved at 100 μl volume, 78% higher than 50 μl. However, at 0.22 nmol dose, the injection volume changes did not influence on the PN uptake. Considering as suitable radiotracer performance: high PN uptake and extraction, better combinations were 0.05 nmol/50 μl, 0.135 nmol/100 μl, 0.22/50 μl. CONCLUSION Suitable performances could be reached by proper combinations of dose, injection volume and concentration for a specific radiotracer used in sentinel lymph node detection.


title: Acute necrotizing encephalopathy with SARS-CoV-2 RNA confirmed in cerebrospinal fluid.

text: Here we report a case of Covid-19-related acute necrotizing encephalopathy (ANE) where SARS-CoV-2 RNA was found in cerebrospinal fluid (CSF) 19 days after symptom onset after testing negative twice. Even though monocytes and protein levels in CSF were only marginally increased, and our patient never experienced a hyperinflammatory state, her neurological function deteriorated into coma. Magnetic resonance imaging of the brain showed pathological signal symmetrically in central thalami, subinsular regions, medial temporal lobes and brain stem. Extremely high concentrations of the neuronal injury markers neurofilament light (NfL) and tau, as well as an astrocytic activation marker, glial fibrillary acidic protein (GFAp), were measured in CSF. Neuronal rescue proteins and other pathways were elevated in the in-depth proteomics analysis. The patient received intravenous immunoglobulins (IVIG) and plasma exchange (PLEX). Her neurological status improved and she was extubated four weeks after symptom onset. This case report highlights the neurotropism of SARS-CoV-2 in selected patients and emphasizes the importance of repeated lumbar punctures and CSF analyses in patients with suspected Covid-19 and neurological symptoms.


An affordable videolaryngoscope for use during the COVID-19 pandemic.


title: Relationship between clinical signs and transmission of an infectious disease and the implications for control.

text: Control of many infectious diseases relies on the detection of clinical cases and the isolation, removal, or treatment of cases and their contacts. The success of such "reactive" strategies is influenced by the fraction of transmission occurring before signs appear. We performed experimental studies of foot-and-mouth disease transmission in cattle and estimated this fraction at less than half the value expected from detecting virus in body fluids, the standard proxy measure of infectiousness. This is because the infectious period is shorter (mean 1.7 days) than currently realized, and animals are not infectious until, on average, 0.5 days after clinical signs appear. These results imply that controversial preemptive control measures may be unnecessary; instead, efforts should be directed at early detection of infection and rapid intervention.


title: Genomic characteristics of adhesion molecules in patients with symptomatic pulmonary embolism.

text: The aim of this study was to identify the differences in the expression of cell adhesion molecule-related mRNAs between symptomatic pulmonary embolism (PE) and a control group, and to investigate the interactions among activated leukocytes, platelets and endothelial cells. Whole human gene chip was applied to detect the expression of cell adhesion molecule-related mRNAs in symptomatic PE and in the control group, and statistical analysis was performed. In patients with PE, the expression of the majority of integrin mRNAs located on leukocytes and platelets was significantly upregulated. The expression of mRNAs related to L-selectin and P-selectin glycoprotein ligand was significantly upregulated, while the expression of mRNA related to E-selectin was significantly downregulated. The expression of mRNAs related to classic cadherins and protocadherins was downregulated, and the expression of mRNAs related to vascular endothelial cadherin was significantly downregulated; the expression of mRNAs related to the immunoglobulin superfamily had no obvious difference between the 2 groups. In conclusion, we demonstrated that, in symptomatic PE patients, the adhesion of leukocytes and platelets was enhanced; the activation of endothelial cells was obviously weakened; the adherens junctions among endothelial cells were weakened, with the endothelium becoming more permeable.


title: Distal macro- and microembolization during subintimal recanalization of femoropopliteal chronic total occlusions.

text: PURPOSE To investigate the phenomenon of distal embolization during subintimal angioplasty with or without stenting of femoropopliteal chronic total occlusions (CTOs). METHODS This prospective study included 40 consecutive patients (35 men; mean age 65.4±9.3 years) who underwent subintimal angioplasty alone (n=14) or with stenting (n=26) of CTOs in the femoropopliteal segment. A Spider protection filter was used to capture any possible macro- or microemboli generated during balloon inflation/stenting. Arterial outflow was angiographically checked during each consecutive procedural step. All filters were examined on site for macroscopic material, while the first 20 filters underwent further histopathological qualitative and semiquantitative analysis using a 0+ to 3+ score. RESULTS There was no angiographically or clinically evident distal embolization. Macroscopic particulate debris was not detected in any filter. Histopathology confirmed the absence of macroemboli but revealed microembolic material (diameter <100 μm) in all filters (20/20). The mean number of particles detected was 9.4±4.5 (range 5-17). Histopathological findings included fibrin conglomerates (20/20), trapped erythrocytes (19/20), inflammatory cells (16/20), calcification minerals (6/20), extracellular matrix (6/20), cholesterol clefts (6/20), and endothelial cells (6/20). Captured material was classified as fresh and old thrombus in 7/20 and 4/20 cases, respectively. Semiquantitative analysis demonstrated that the collected microparticles consisted primarily of fibrin conglomerates (median score 2+), trapped erythrocytes (median score 1+), and inflammatory cells (median score 1+). CONCLUSION Macroscopically evident emboli were not detected following subintimal angioplasty or stenting of femoropopliteal CTOs. Microscopic debris was present in all filters. The clinical significance of the phenomenon remains to be determined.


title: Laparoscopic anti-reflux procedures with hepatic shoulder technique in the surgical management of large hiatal hernias and paraesophageal hernias: a follow-up study.

text: BACKGROUND Numerous techniques have been historically proposed in the management of gastroesophageal reflux and paraesophageal hernias (PEH). A follow-up study (Quilici et al. in Surg Endosc 23(11):2620-2623, 2009) to a novel laparoscopic approach introduced in 2009 and performed in 49 patients is presented. METHODS All procedures were performed via laparoscopy. Thirty-two patients underwent a Nissen Fundoplication, eleven a reduction of the PEH with a Nissen fundoplication, two without a fundoplication, and four with a Collis-Nissen fundoplication. In all patients, the left hepatic lobe was freed, repositioned, and anchored under and inferior to the gastroesophageal junction, propping the gastroesophageal junction anteriorly. This maneuver entirely covers and closes the diaphragmatic defect. RESULTS At the time of laparoscopy, several patients were found not to be suitable candidates for this procedure (morphology of the left hepatic lobe). Forty-nine procedures were completed. One patient was re-explored on POD 2 for a tight hiatus post-Collis fundoplication. Post-operatively, all other patients did well without notable, unusual complaints. The average length of stay was 2.2 days. Although not statistically significant, 43 patients had no recurrence of symptoms with the longest follow-up at 10 years, two patients were lost to follow-up, one patient had a recurrence of the PEH and three patients stated they were experiencing some form of gastroesophageal reflux requiring medical management. CONCLUSION In selected patients, patients with an "at-risk" crural closure during a laparoscopic anti-reflux procedure or PEH can safely be managed via a laparoscopic anti-reflux procedure with the hepatic shoulder technique. This technique has shown good early post-operative results and could be used as an alternative to a laparoscopic mesh-reinforced fundoplication in difficult crural closures or in the management of large paraesophageal hernias.


title: Design of engineered surfaces for prospective detection of Sars-CoV-2 using quartz crystal microbalance based techniques.

text: INTRODUCTION Rapid transmission of the severe acute respiratory syndrome coronavirus 2 has affected the whole world and forced it to a halt (lockdown). A fast and label free detection method for the novel coronavirus needs to be developed along with the existing enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR) based methods. AREAS COVERED In this report, biophysical aspects of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike glycoprotein are outlined based on its recent reported electron microscopy structure. Protein binding sites are analyzed theoretically, which consisted of hydrophobic and positive charged amino acid residues. Different strategies to form mixed self-assembled monolayers (SAMs) of hydrophobic (CH3) and negatively charged (COOH) groups are discussed to be used for the specific and strong interactions with spike protein. Bio-interfacial interactions between the spike protein and device (sensor) surface and its implications towards designing suitable engineered surfaces are summarized. EXPERT OPINION Implementation of the engineered surfaces in quartz crystal microbalance (QCM) based detection techniques for the diagnosis of the novel coronavirus from oral swab samples is highlighted. The proposed strategy can be explored for the label free and real time detection with sensitivity up to ng level. These engineered surfaces can be reused after desorption.


title: Biochemical characterization of a novel α-L-fucosidase from Pedobacter sp. and its application in synthesis of 3'-fucosyllactose and 2'-fucosyllactose.

text: Fucosyllactoses have gained much attention owing to their multiple functions, including prebiotic, immune, gut, and cognition benefits. In this study, human milk oligosaccharide (HMO) 2'-fucosyllactose (α-L-Fuc-(1,2)-D-Galβ-1,4-Glu, 2'FL) and its isomer 3'-fucosyllactose (α-L-Fuc-(1,3)-D-Galβ-1,4-Glu, 3'FL) with potential prebiotic effect were synthesized efficiently by a novel recombinant α-L-fucosidase. An α-L-fucosidase gene (PbFuc) from Pedobacter sp. CAU209 was successfully cloned and expressed in Escherichia coli (E. coli). The deduced amino acid sequence shared the highest identity of 36.8% with the amino sequences of other reported α-L-fucosidases. The purified α-L-fucosidase (PbFuc) had a molecular mass of 50 kDa. The enzyme exhibited specific activity (26.3 U/mg) towards 4-nitrophenyl-α-L-fucopyranoside (pNP-FUC), 3'FL (8.9 U/mg), and 2'FL (3.4 U/mg). It showed the highest activity at pH 5.0 and 35 °C, respectively. PbFuc catalyzed the synthesis of 3'FL and 2'FL through a transglycosylation reaction using pNP-FUC as donor and lactose as acceptor, and total conversion ratio was up to 85% at the optimized reaction conditions. The synthesized mixture of 2'FL and 3'FL promoted the growth of Lactobacillus delbrueckii subsp. bulgaricus NRRL B-548, L. casei subsp. casei NRRL B-1922, L. casei subsp. casei AS 1.2435, and Bifidobacterium longum NRRL B-41409. However, the growths of E. coli ATCC 11775, S. enterica AS 1.1552, L. monocytogenes CICC 21635, and S. aureus AS 1.1861 were not stimulated by the mixture of 2'FL and 3'FL. Overall, our findings suggest that PbFuc possesses a great potential for the specific synthesis of fucosylated compounds.Key Points• A novel α-L-fucosidase (PbFuc) from Pedobacter sp. was cloned and expressed.• PbFuc showed the highest hydrolysis activity at pH 5.0 and 35 °C, respectively.• It was used for synthesis of 3'-fucosyllactose (3'FL) and 2'-fucosyllactose (2'FL).• The mixture of 3'FL and 2'FL promoted the growth of some Lactobacillus sp. and Bifidobacteria sp.


Herd Immunity: Knowns, Unknowns, Challenges, and Strategies.


title: Early Outcomes of Roux-en-Y Gastric Bypass in a Publically Funded Obesity Program.

text: Background. There is limited literature assessing the outcomes of bariatric surgery in a publically funded, North American, multidisciplinary bariatric program. Our objective was to assess outcomes of roux-en-Y gastric bypass (RYGB) in a publically funded bariatric program through a retrospective review of patient records. Methods. 293 patients spent a median of 13 months attending a multidisciplinary obesity clinic prior to undergoing laparoscopic RYGB surgery. The hospital was a Canadian, publically funded, level 2 trauma center with university teaching services. Results. 79% of the patients were female and the average BMI at first visit to clinic was 55.3 kg/m2. The average decrease in BMI was 19.2 ± 0.9 kg/m(2). This was an average absolute weight loss of 56.1 kg or 35.5% of initial weight. The average excess weight loss was 63.4 ± 20.4%. Improvement or resolution of obesity related comorbidities occurred in 65.9% of type 2 diabetics and in 50% of hypertensive patients. Conclusion. Despite this being an unconventional setting of a publically funded program in a large Canadian teaching hospital, early outcomes following RYGB were appropriate in severely obese patients. Ongoing work will identify areas of improvement for enhanced efficiencies within this system.


title: Ovarian endometrioma but not deep infiltrating endometriosis is associated with increased serum levels of interleukin-8 and interleukin-6.

text: Cytokines, and specifically interleukin 6 (IL-6) and interleukin 8 (IL-8), have been associated with the pathogenesis of endometriosis. We studied serum concentrations of IL-6 and IL-8 in patients with deep infiltrating endometriosis (DIE) or ovarian endometriomas (OE), but no other forms of associated endometriosis disease type. We carried out a case-control study including 19 patients with OE alone (OE group), 14 patients with DIE alone (DIE group) and 24 healthy patients without endometriosis (C group). Serum concentrations of IL-6 and IL-8 were measured in the three groups of patients. Serum levels of both IL-6 and IL-8 were significantly higher in the OE group. A high positive correlation was found between serum IL-6 and IL-8 levels in the OE group but not in the DIE and C groups. Serum IL-8 alone achieved the highest predictive value of the presence of OE (adjusted OR: 1.44; sensitivity: 78.2%; specificity: 76.2%). The combination of IL-6 and IL-8 levels did not significantly improve the discrimination between subjects with OE and those with DIE over that of IL-8. OE but not DIE are associated with increased serum levels of IL-6 and IL-8, and thus these may become useful tools for discriminating OE alone from DIE.


title: Persistence With Dabigatran Therapy at 2 Years in Patients With Atrial Fibrillation.

text: BACKGROUND Guidelines recommend long-term oral anticoagulation therapy for stroke prevention in patients with atrial fibrillation (AF). Treatment discontinuation rates in vitamin K antagonist (VKA)-treated patients are high but may be lower with non-VKA oral anticoagulant agents. OBJECTIVES The goal of this study was to describe and explore predictors of dabigatran etexilate persistence in patients with newly diagnosed AF over 2 years of follow-up. METHODS Consecutive patients newly diagnosed with AF and ≥1 stroke risk factor were followed up for 2 years. Dabigatran nonpersistence was defined as discontinuation of dabigatran for >30 days. A multivariable Cox regression model included region as well as patient clinical and sociodemographic characteristics to explore predictors of nonpersistence. RESULTS Eligible patients (N = 2,932) took ≥1 dabigatran dose; their mean age was 70.3 ± 10.2 years, and 55.3% were male. The 2-year probability of dabigatran persistence was 69.2%. Approximately 7% switched to a factor Xa inhibitor and 6% to a VKA. Approximately one-third of dabigatran discontinuations were primarily due to serious or nonserious adverse events. Patients from North America had the highest discontinuation risk, and Latin America had the lowest. Minimally symptomatic or asymptomatic AF and permanent AF were associated with a lower risk for dabigatran nonpersistence. Previous proton pump inhibitor use was associated with a higher risk for dabigatran nonpersistence. CONCLUSIONS Probability of treatment persistence with dabigatran after 2 years was approximately 70%. Nearly one-half of the patients who stopped dabigatran switched to another oral anticoagulant agent. Patients from North America, and those with paroxysmal, persistent, or symptomatic AF, may be at a higher risk for discontinuing dabigatran.


title: Coaching skills for medical education in a VUCA world.

text: The world is in the midst of the COVID-19 pandemic. Healthcare professionals and students globally are experiencing an increasingly 'VUCA' (volatile, uncertain, complex and ambiguous) healthcare and educational climate. Our future medical workforce needs skillsets to manage the personal and emotional challenges of work, uncertainty and change. These include organization, time management, proactive and consistent clinical skill development, effective communication, person-centred approaches, self-reflection and self-care. This is critical for success during undergraduate medical education and ongoing clinical practice to build personal resilience, provide the best possible clinical care in a different healthcare ecosystem, innovate for better healthcare systems and advocate for more vulnerable communities. Our faculty and students have been eager to learn and apply solution-oriented coaching skills to help to mitigate against burnout, hold more rewarding, person-centred conversations in clinical practice and enable them personally to respond flexibly and adapt constructively to change. Coaching training should comprise an essential component of the undergraduate medical curriculum and continuing professional development, supporting our medical workforce to derive joy from the practice of humanistic healthcare and develop the leadership skills to help shape a way forward through the challenges we are experiencing in an increasingly VUCA healthcare climate.


title: Machine learning approach for prediction of hearing preservation in vestibular schwannoma surgery.

text: In vestibular schwannoma patients with functional hearing status, surgical resection while preserving the hearing is feasible. Hearing levels, tumor size, and location of the tumor have been known to be candidates of predictors. We used a machine learning approach to predict hearing outcomes in vestibular schwannoma patients who underwent hearing preservation surgery: middle cranial fossa, or retrosigmoid approach. After reviewing the medical records of 52 patients with a pathologically confirmed vestibular schwannoma, we included 50 patient's records in the study. Hearing preservation was regarded as positive if the postoperative hearing was within serviceable hearing (50/50 rule). The categorical variable included the surgical approach, and the continuous variable covered audiometric and vestibular function tests, and the largest diameter of the tumor. Four different algorithms were lined up for comparison of accuracy: support vector machine(SVM), gradient boosting machine(GBM), deep neural network(DNN), and diffuse random forest(DRF). The average accuracy of predicting hearing preservation ranged from 62% (SVM) to 90% (DNN). The current study is the first to incorporate machine learning methodology into a prediction of successful hearing preservation surgery. Although a larger population may be needed for better generalization, this study could aid the surgeon's decision to perform a hearing preservation approach for vestibular schwannoma surgery.


title: Lung volume assessment in acute respiratory distress syndrome.

text: PURPOSE OF REVIEW Measurements of lung volumes allow evaluating the pathophysiogical severity of acute respiratory distress syndrome (ARDS) in terms of the degree of reduction in aerated lung volume, calculating strain, quantifying recruitment and/or hyperinflation, and gas volume distribution. We summarize the current techniques for lung volume assessment selected according to their possible usage in the ICU and discuss the recent findings obtained with implementation of these techniques in patients with ARDS. RECENT FINDINGS Computed tomography technique remains irreplaceable in terms of quantitative aeration of different lung regions, but the commonly used cut-offs for classification may be questioned with recent findings on nonpathological lungs. Monitoring end expiratory lung volume using nitrogen washout technique enhanced our understanding on lung volume change during positioning, pleural effusion drainage, intra-abdominal hypertension, and recruitment maneuver. Recent studies supported that tidal volume could not surrogate tidal strain, which needs measurement of functional residual capacity and which is correlated with pro-inflammatory lung response. SUMMARY Although lung volume measurements are still limited to research area of ARDS, recent progress in technology provides clinicians more opportunities to evaluate lung volumes noninvasively at the bedside and may facilitate individualization of ventilator settings based on the specific physiological understandings of a given patient.


title: Very short-term reactive forecasting of the solar ultraviolet index using an extreme learning machine integrated with the solar zenith angle.

text: Exposure to erythemally-effective solar ultraviolet radiation (UVR) that contributes to malignant keratinocyte cancers and associated health-risk is best mitigated through innovative decision-support systems, with global solar UV index (UVI) forecast necessary to inform real-time sun-protection behaviour recommendations. It follows that the UVI forecasting models are useful tools for such decision-making. In this study, a model for computationally-efficient data-driven forecasting of diffuse and global very short-term reactive (VSTR) (10-min lead-time) UVI, enhanced by drawing on the solar zenith angle (θs) data, was developed using an extreme learning machine (ELM) algorithm. An ELM algorithm typically serves to address complex and ill-defined forecasting problems. UV spectroradiometer situated in Toowoomba, Australia measured daily cycles (0500-1700h) of UVI over the austral summer period. After trialling activations functions based on sine, hard limit, logarithmic and tangent sigmoid and triangular and radial basis networks for best results, an optimal ELM architecture utilising logarithmic sigmoid equation in hidden layer, with lagged combinations of θs as the predictor data was developed. ELM's performance was evaluated using statistical metrics: correlation coefficient (r), Willmott's Index (WI), Nash-Sutcliffe efficiency coefficient (ENS), root mean square error (RMSE), and mean absolute error (MAE) between observed and forecasted UVI. Using these metrics, the ELM model's performance was compared to that of existing methods: multivariate adaptive regression spline (MARS), M5 Model Tree, and a semi-empirical (Pro6UV) clear sky model. Based on RMSE and MAE values, the ELM model (0.255, 0.346, respectively) outperformed the MARS (0.310, 0.438) and M5 Model Tree (0.346, 0.466) models. Concurring with these metrics, the Willmott's Index for the ELM, MARS and M5 Model Tree models were 0.966, 0.942 and 0.934, respectively. About 57% of the ELM model's absolute errors were small in magnitude (±0.25), whereas the MARS and M5 Model Tree models generated 53% and 48% of such errors, respectively, indicating the latter models' errors to be distributed in larger magnitude error range. In terms of peak global UVI forecasting, with half the level of error, the ELM model outperformed MARS and M5 Model Tree. A comparison of the magnitude of hourly-cumulated errors of 10-min lead time forecasts for diffuse and global UVI highlighted ELM model's greater accuracy compared to MARS, M5 Model Tree or Pro6UV models. This confirmed the versatility of an ELM model drawing on θsdata for VSTR forecasting of UVI at near real-time horizon. When applied to the goal of enhancing expert systems, ELM-based accurate forecasts capable of reacting quickly to measured conditions can enhance real-time exposure advice for the public, mitigating the potential for solar UV-exposure-related disease.