• Poole Corcoran posted an update 6 months, 1 week ago

    Men undergoing RTSA had a higher revision rate than men undergoing SHA (hazard ratio 6, 95% confidence interval 2-19). 454 (62%) patients returned a complete WOOS questionnaire. The mean WOOS score was 53 for SHA and 53 for RTSA. Patients who were 65 years or older had a better WOOS score than younger patients (mean difference 7, CI 1-12). Half of patients had WOOS scores below 50.Interpretation – Shoulder arthroplasty for PHF sequelae was associated with a high risk of revision and a poor patient-reported outcome. Men treated with RTSA had a high risk of revision.The primary aim around developing and optimizing an electronic health record is to improve patient care and population health. The objective of this study is to design and evaluate an action research approach for the optimization of the design of a summary page artefact within an electronic health record for newborn healthcare. An action research approach was chosen for its participatory democratic process for developing practical knowledge and solutions. Collaborative workshops lead by an independent graphic facilitator with a ‘bottom up’ approach, involving self-selected motivated members from multidisciplinary healthcare teams, were designed and conducted. To evaluate this approach, insights were drawn from behavioural and design science paradigms to demonstrate that knowledge and understanding of the design problem and its solution were acquired in building the optimized summary page artefact. Information system development for healthcare requires consideration not just of what we do but how and why we do things. Our analysis demonstrates that action design research represents an agile and lean approach for successful optimization and implementation of information system development in healthcare.Fibroblast growth factor receptor-like-1 (FGFRL1) is important to cell motility and links with tumorigenic potential in various types of cancers. buy FIN56 To investigate the biological function and underlying mechanism of FGFRL1 in rectal adenocarcinoma, we conducted this study. TCGA and Oncomine databases were used to analyze FGFRL1 expression and its association with clinical characteristics or overall survival (OS) in rectal adenocarcinoma patients. siRNA strategy was implemented to knockdown FGFRL1 expression in rectal adenocarcinoma cells. CCK8, colony formation, wound healing, and transwell assays were implemented to measure cell behaviors. qRT-PCR and western blot were utilized to identify mRNA and protein expression levels. FGFRL1 was significantly increased in rectal adenocarcinoma tissue samples, either colon or rectum. High-regulation of FGFRL1 expression induced poorer outcome of rectal adenocarcinoma patients. Downregulation of FGFRL1 inhibited the proliferation, colony formation, migration, and invasion of SW837 cells. The MAPK pathway-related proteins, phosphorylation of MEK and ERK, were also decreased after si-FGFRL1 transfection. These findings demonstrated that FGFRL1, acting as a potential inducator, may promote the progression of rectal adenocarcinoma via activating the MAPK signaling pathway.Background Pediatric-onset restrictive cardiomyopathy (RCM) is associated with high mortality, but underlying mechanisms of disease are under investigated. RCM-associated diastolic dysfunction secondary to variants in TNNT2-encoded cardiac troponin T (TNNT2) is poorly described. Methods and Results Genetic analysis of a proband and kindred with RCM identified TNNT2-R94C, which cosegregated in a family with 2 generations of RCM, ventricular arrhythmias, and sudden death. TNNT2-R94C was absent among large, population-based cohorts Genome Aggregation Database (gnomAD) and predicted to be pathologic by in silico modeling. Biophysical experiments using recombinant human TNNT2-R94C demonstrated impaired cardiac regulation at the molecular level attributed to reduced calcium-dependent blocking of myosin’s interaction with the thin filament. Computational modeling predicted a shift in the force-calcium curve for the R94C mutant toward submaximal calcium activation compared within the wild type, suggesting low levels of muscle activation even at resting calcium concentrations and hypercontractility following activation by calcium. Conclusions The pathogenic TNNT2-R94C variant activates thin-filament-mediated sarcomeric contraction at submaximal calcium concentrations, likely resulting in increased muscle tension during diastole and hypercontractility during systole. This describes the proximal biophysical mechanism for development of RCM in this family.INTRODUCTION Lactate, a product of anaerobic metabolism, is a biomarker and indicator for tissue hypoperfusion and oxygen debt. An elevated blood lactate level has been associated with poor outcome in many clinical conditions, including cardiac surgery. Nevertheless, debate exists regarding which blood lactate concentration is most indicative of poor outcomes. We evaluate the impact of hyperlactatemia, defined as a peak arterial blood concentration ⩾2.0 mmol/L during cardiopulmonary bypass, on surgical results with a focus on long-term outcome. METHODS We reviewed 1,099 consecutive adult patients who underwent cardiac surgery on pump. The patients were divided into two groups based on the presence or not of hyperlactatemia. Pre- and intraoperative risk factors for hyperlactatemia were identified, and the postoperative outcome of patients with or without hyperlactatemia was compared. RESULTS Hyperlactatemia was present in 372 patients (33.8%). Factors independently associated with hyperlactatemia were urgent/emergency procedure, cardiopulmonary bypass duration and aortic cross-clamp time. Patients with hyperlactatemia had significantly higher rate of prolonged mechanical ventilation time, in-hospital stay and requirement of inotropes and intra-aortic balloon pump support (p  less then  0.001). Operative (30-day) mortality was higher in the group of patients with hyperlactatemia (7.8% vs. 1.1%; p  less then  0.001). Kaplan-Meier curve showed worse long-term survival (mean follow-up 4.02 ± 1.58 years) in patients with hyperlactatemia. CONCLUSION Hyperlactatemia during cardiopulmonary bypass has a significant association with postoperative morbidity and mortality. Correction of risk factors for hyperlactatemia, together with prompt detection and correction of this condition, may control complications and improve outcome.

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