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S TRO19622 improves mitochondrial dysfunction but enhances Aβ levels in disease models of AD. Further studies must evaluate whether TRO19622 offers benefits at the mitochondrial level despite the increased formation of Aβ, which could be harmful. BACKGROUND Cognitive impairment and frailty are highly prevalent in older adults undergoing transcatheter aortic valve replacement. This study aimed to investigate the relationship of cognitive impairment and frailty with functional recovery after transcatheter aortic valve replacement. METHODS This was a single-center prospective cohort study of 142 patients who were ≥70 years old and underwent transcatheter aortic valve replacement for aortic stenosis. Before transcatheter aortic valve replacement, cognitive impairment was defined as Mini-Mental State Examination score less then 24 points (range 0-30) and moderate-to-severe frailty was defined as a deficit-accumulation frailty index ≥0.35 (range 0-1). The functional status composite score, the number of 22 daily and physical tasks that a patient could perform independently, measured at baseline and 1, 3, 6, 9, and 12 months postoperatively were analyzed using linear mixed-effects model. RESULTS The mean age was 84.2 years, with 74 women (51.8%). Patients with moderate-to-severe frailty and cognitive impairment (n=27, 19.0%) had the lowest functional status at baseline and throughout 12 months, while patients with mild or no frailty and no cognitive impairment (n=48, 33.8%) had the best functional status. Patients with cognitive impairment alone (n=19, 13.4%) had better functional status at baseline than those with moderate-to-severe frailty alone (n=48, 33.8%), but their functional status scores merged and remained similar during the follow-up. CONCLUSIONS Preoperative cognitive function plays a vital role in functional recovery after transcatheter aortic valve replacement, regardless of baseline frailty status. Impaired cognition may increase functional decline in the absence of frailty, whereas intact cognition may mitigate the detrimental effects of frailty. Cognitive assessment should be routinely performed before transcatheter aortic valve replacement. BACKGROUND Low plasma sodium concentration has been recognized as a prognostic factor in several disorders but never evaluated in sickle cell disease. The present study evaluates its value at admission to predict a complication in adult sickle cell disease patients hospitalized for an initially uncomplicated acute painful episode. METHODS The primary endpoint of this retrospective study, performed between 2010 and 2015 in a French referral center for sickle cell disease, was a composite criterion including acute chest syndrome, intensive care unit transfer, red blood cell transfusion or inpatient death. Analyses were adjusted for age, sex, hemoglobin genotype and concentration, LDH concentration, and white blood cell count. RESULTS We included 1218 stays (406 patients). [https://www.selleckchem.com/products/GDC-0449.html Wnt inhibitor] No inpatient death occurred during the study period. Hyponatremia (plasma sodium ≤ 135 mmol/L) at admission in the center was associated with the primary endpoint (adjusted odds ratio (OR) 1.95 [95% confidence interval (CI) 1.3-2.91, p=0,001]), and with acute chest syndrome (OR 1.95 [95% CI 1.2-3.17, p=0.008]) and red blood cell transfusion (OR 2.71 [95% CI 1.58-4.65, p less then 0.001]), but not significantly with intensive care unit transfer (OR 1.83 [95% CI 0.94-3.79, p=0.074]). Adjusted mean length of stay was longer by 1.1 days (95% CI 0.5-1.6, p less then 0.001) in patients with hyponatremia at admission. CONCLUSIONS Hyponatremia at admission in the medical department for an acute painful episode is a strong and independent prognostic factor of unfavorable outcome, and notably acute chest syndrome. It could help targeting patients who may benefit from closer monitoring. BACKGROUND To describe age differences in patient's chief complaint related to a first myocardial infarction, and how the "typicality" of patient's acute symptoms relates to extent of pre-hospital delay. METHODS The medical records of 2,586 central Massachusetts residents hospitalized at 11 greater Worcester medical centers with a first myocardial infarction on a biennial basis between 2001 and 2011 were reviewed. RESULTS The average age of the study population was 66.4 years, 39.6% were women, 40.2% were diagnosed with a STEMI, and 72.0 % presented with typical symptoms of myocardial infarction, namely acute chest pain/pressure. Patients were categorized into five age strata those less than 55 years old (23%), 55-64 years (20%), 65-74 years (19%), 75-84 years (22%), and those 85 years and older (16%). The lowest proportion (11%) of atypical symptoms of myocardial infarction was observed in patients less then 55 years, increasing to 17%, 28%, 40%, and 51% across our respective age groups. The most prevalent chief complaint reported at the time of hospitalization was chest pain but the proportion of patients reporting this symptom decreased from the youngest (83%) to the oldest patient groups (45%). There was a slightly increased risk of prehospital delay across the different age groups (higher in the oldest old) in those who presented with atypical rather than typical symptoms of myocardial infarction. CONCLUSIONS The present results provide insights to the presenting chief complaint of patients hospitalized with a first myocardial infarction according to age and the relation of symptom presentation to patient's care seeking behavior. BACKGROUND In clinical trials, first-line treatment with pembrolizumab improved overall survival (OS) in patients with advanced non-small-cell lung cancer (NSCLC) with a programmed death ligand 1 (PD-L1) tumor proportion score of&nbsp;≥ 50%. However, data on the efficacy of this treatment between clinical trials and actual clinical practice are inconsistent. PATIENTS AND METHODS Ninety-five patients with histologically diagnosed advanced or recurrent NSCLC and a PD-L1 tumor proportion score of&nbsp;≥ 50% who received pembrolizumab as first-line treatment were consecutively enrolled onto this multicenter retrospective study from February 2017 to December 2018. Clinical data were collected from electronic medical records. We assessed the objective response rate, progression-free survival (PFS), OS, and immune-related adverse events (irAE), and determined their associations with clinical characteristics. RESULTS The objective response rate was 40.0%. The median PFS was 6.1 months, and OS did not reach the median. Multivariate analyses revealed that nonadenocarcinoma histology (hazard ratio, 1.