89X (calibrators) + 32.6. Control samples and CSF pools yielded imprecision ranging from 6.5 to 10.2% (Aβ42) and 2.2 to 7.0% (Aβ40). None of the CSF pools showed statistically significant differences in Aβ42 concentrations across 2 different calibrator lots. Comparison of Aβ42 with Aβ42/Aβ40 showed that the ratio improved concordance with concurrent [18F]-florbetapir PET as a measure of fibrillar Aβ (n = 766) from 81 to 88%. CONCLUSIONS Long-term performance assessment substantiates our modified LC-MS/MS reference method for 3 Aβ peptides. The improved diagnostic performance of the CSF ratio Aβ42/Aβ40 suggests that Aβ42 and Aβ40 should be measured together and supports the need for an Aβ40 CRM. © American Association for Clinical Chemistry 2020. All rights reserved. For permissions, please email journals.permissions@oup.com.A lack of reliable laryngeal thermal injury models precludes laryngeal burn wound healing studies and investigation of novel therapeutics. We hypothesize that a swine laryngeal burn model can allow for laryngeal burn evaluation over time. Twelve Yorkshire crossbreed swine underwent tracheostomy and endoscopically directed laryngeal burns using heated air (150-160°C). Swine larynges were evaluated and sectioned/stained at 12 hours, 1, 3, 7, 14, and 21 days. A board-certified veterinary pathologist assessed anatomic regions (left and right epiglottis, true/false vocal folds, and subglottis) using a nine criteria histological injury scoring scale. Six swine were euthanized at scheduled endpoints, three prematurely (airway concerns), and three succumbed to airway complications after 16 to 36 hours. Endoscopic and gross examination from scheduled endpoints revealed massive supraglottic edema and tissue damage, particularly around the arytenoids, extending transglottically. Swine from premature endpoints had comparatively increased edema throughout. Microscopic evaluation documented an inverse relationship between injury severity score and time from injury. Inflammation severity decreased over time, nearly resolving by 14 days. Neutrophils predominated early with histiocytes appearing at 3 days. Granulation tissue appeared at 3 days, and early epiglottic and/or subglottic fibrosis appeared by 7 days and matured by 14 days. Edema, abundant initially, decreased by day 3 and resolved by day 7. This approach is the first to provide longitudinal analysis of laryngeal thermal injuries, reflecting some of the first temporal wound healing characteristic data in laryngeal thermal injuries and providing a platform for future therapeutic studies. Published by Oxford University Press on behalf of the American Burn Association 2020.The present study compares the net portal appearance of dietary iron (Fe) and selenium (Se) after meals containing different sources and levels of these minerals. Twelve pigs (55.1 ± 3.7 kg) were used in a cross-over design to assess the 11-h net portal-drained viscera (PDV) flux of serum Fe and Se after ingestion of boluses containing inorganic (I) or organic (O) dietary Fe and Se at industry average (A; 200 and 0.6 mg, respectively) or high (H; 400 and 1.2 mg, respectively) levels. Arterial serum Fe concentrations increased by an average of 158% within 6 h post-meal and gradually decreased thereafter (P less then 0.001). Values were greater (P less then 0.001) for I than for O until 6 h post-meal and greater (P ≤ 0.001) for A than for H from 4 to 8 h post-meal. For the whole post-prandial period (11 h), arterial serum Fe concentrations tended (P = 0.06) to be greater for I than for O and were lowest for HO (P ≤ 0.03). Net PDV flux of Fe tended to be greater for AI than for AO (P ≥ 0.07). Cumulative apperation and percentage of intestinal absorption, this was not the case for dietary Se. The postabsorptive availability of dietary I was greater than O for both minerals and, particularly for Fe, at low levels. © Crown copyright 2020.Impella® pumps are increasingly utilized in patients in cardiogenic shock. We report on a case series where Impella support was insufficient, and a switch to venoarterial extracorporeal membrane oxygenation (VA ECMO) became necessary. ECMO patients with previous Impella devices were identified utilizing our institutional ECMO database. Since 2014, 10 patients with a mean age of 62 ± 3 years were identified. Despite correct placement of all Impella pumps, cardiogenic shock persisted with progressive multi-organ failure (Impella type 2.5/CP n = 6/4 patients). Femoro-femoral VA ECMO was implanted percutaneously on the contralateral side with the Impella initially left on standby but retracted into the descending aorta for transport reasons after a mean support time of 20 ± 8 h. All patients were able to unload their heart by left ventricular ejection with a blood pressure amplitude of 15 ± 3 mmHg on VA ECMO support. After VA ECMO implantation haemodynamic parameters improved significantly within 24 h of support (mean serum lactate levels decreased from 92 ± 17 to 44 ± 10 mg/dl, P = 0.031). Survival to hospital discharge was 70%. These data indicate that the Impella 2.5® and CP® might not be sufficient in profound cardiogenic shock. Comparative studies are necessary to specify which patient population benefits from which type of circulatory support. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.OBJECTIVE This study was designed to investigate the role of mucosal-associated invariant T (MAIT) cells in gouty arthritis (GA) and their effects on osteoclastogenesis. METHODS Patients with GA (n = 61), subjects with hyperuricaemia (n = 11) and healthy controls (n = 30) were enrolled in this study. MAIT cells, cytokines, CD69, programmed death-1 (PD-1) and lymphocyte-activation gene 3 (LAG-3) levels were measured by flow cytometry. In vitro osteoclastogenesis experiments were performed using peripheral blood mononuclear cells in the presence of M-CSF and RANK ligand. RESULTS Circulating MAIT cell levels were significantly reduced in GA patients. However, their capacities for IFN-γ, IL-17 and TNF-α production were preserved. Expression levels of CD69, PD-1 and LAG-3 in MAIT cells were found to be elevated in GA patients. In particular, CD69 expression in circulating MAIT cells was increased by stimulation with MSU crystals, suggesting that deposition of MSU crystals might contribute to MAIT cell activation. Interestingly, MAIT cells were found to be accumulated in synovial fluid and infiltrated into gouty tophus tissues within joints. Furthermore, activated MAIT cells secreted pro-resorptive cytokines (i.e. IL-6, IL-17 and TNF-α) and facilitated osteoclastogenesis. CONCLUSION This study demonstrates that circulating MAIT cells are activated and numerically deficient in GA patients. In addition, MAIT cells have the potential to migrate to inflamed tissues and induce osteoclastogenesis. These findings provide an important role of MAIT cells in the pathogenesis of inflammation and bone destruction in GA patients. https://www.selleckchem.com/products/pim447-lgh447.html © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology. All rights reserved. For permissions, please email journals.permissions@oup.com.OBJECTIVES Our aim was to investigate the outcome of patients with diabetes undergoing coronary artery bypass grafting (CABG) surgery in a whole population with main focus on long-term mortality and complications. METHODS This was a nationwide retrospective analysis of all patients who underwent isolated primary CABG in Iceland between 2001 and 2016. Overall survival together with the composite end point of major adverse cardiac and cerebrovascular events was compared between patients with diabetes and patients without diabetes during a median follow-up of 8.5 years. Multivariable regression analyses were used to evaluate the impact of diabetes on both short- and long-term outcomes. RESULTS Of a total of 2060 patients, 356 (17%) patients had diabetes. Patients with diabetes had a higher body mass index (29.9 vs 27.9 kg/m2) and more often had hypertension (83% vs 62%) and chronic kidney disease (estimated glomerular filtration rate ≤60 ml/min/1.73 m2, 21% vs 14%). Patients with diabetes had an increased risk of operative mortality [odds ratio 2.52, 95% confidence interval (CI) 1.27-4.80] when adjusted for confounders. 5-Year overall survival (85% vs 91%, P  less then  0.001) and 5-year freedom from major adverse cardiac and cerebrovascular events were also inferior for patients with diabetes (77% vs 82%, P  less then  0.001). Cox regression analysis adjusting for potential confounders showed that the diagnosis of diabetes significantly predicted all-cause mortality [hazard ratio (HR) 1.87, 95% CI 1.53-2.29] and increased risk of major adverse cardiac and cerebrovascular events (HR 1.47, 95% CI 1.23-1.75). CONCLUSIONS Patients with diabetes have significantly lower survival after CABG, both within 30 days and during long-term follow-up. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.OBJECTIVES Serum CA72-4 levels are elevated in some gout patients but this has not been comprehensively described. The present study profiled serum CA72-4 expression in gout patients and verified the hypothesis that CA72-4 is a predictor of future flares in a prospective gout cohort. METHODS To profile CA72-4 expression, a cross-sectional study was conducted in subjects with gouty arthritis, asymptomatic hyperuricaemia, four major arthritis types (OA, RA, SpA, septic arthritis) and healthy controls. A prospective gout cohort study was initiated to test the value of CA72-4 for predicting gout flares. During a 6-month follow-up, gout flares, CA72-4 levels and other gout-related clinical variables were observed at 1, 3 and 6 months. RESULTS CA72-4 was highly expressed in patients with gouty arthritis [median (interquartile range) 4.55 (1.56, 32.64) U/ml] compared with hyperuricaemia patients [1.47 (0.87, 3.29) U/ml], healthy subjects [1.59 (0.99, 3.39) U/ml] and other arthritis patients [septic arthritis, 1.38 (0.99, 2.66) U/ml; RA, 1.58 (0.95, 3.37) U/ml; SpA, 1.56 (0.98, 2.85) U/ml; OA, 1.54 (0.94, 3.34) U/ml; P 6.9 U/ml) was the strongest predictor of gout flares (hazard ratio = 3.889). Prophylactic colchicine was effective, especially for patients with high CA72-4 levels (P = 0.014). CONCLUSION CA72-4 levels were upregulated in gout patients who experienced frequent flares and CA72-4 was a useful biomarker to predict future flares. © The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Rheumatology.It has long been recognized that sample size calculations for cluster randomized trials require consideration of the correlation between multiple observations within the same cluster. When measurements are taken at anything other than a single point in time, these correlations depend not only on the cluster but also on the time separation between measurements and additionally, on whether different participants (cross-sectional designs) or the same participants (cohort designs) are repeatedly measured. This is particularly relevant in trials with multiple periods of measurement, such as the cluster cross-over and stepped-wedge designs, but also to some degree in parallel designs. Several papers describing sample size methodology for these designs have been published, but this methodology might not be accessible to all researchers. In this article we provide a tutorial on sample size calculation for cluster randomized designs with particular emphasis on designs with multiple periods of measurement and provide a web-based tool, the Shiny CRT Calculator, to allow researchers to easily conduct these sample size calculations.