Thorntonswanson9342

In the entire cohort, MF+ was significantly associated with poorer LV function, higher extent of pathological LV remodelling, and more pronounced clinical heart failure at BL. After TAVI, MF+ was associated with a delay in normalization of LV geometry and function but not per se with absence of reverse remodelling and clinical improvement. However, 22 patients died during follow-up (mean, 11 months), and 14 deaths were classified as cardiovascular (CV) (n = 9 arrhythmia-associated). Importantly, 13 of 14 CV deaths occurred in MF+ patients (CV mortality 26.5% in MF+ vs. ANA-12 nmr 2% in MF- patients, P = 0.0003). Multivariate analysis identified MF+ as independent predictor of CV mortality [hazard ratio (HR) 27.4 (2.0-369), P = 0.01]. CONCLUSION Histological MF is associated with AS-related pathological LV remodelling and independently predicts CV mortality after TAVI. © The Author(s) 2020. Published by Oxford University Press on behalf of the European Society of Cardiology.Importance Identifying psychosis subgroups could improve clinical and research precision. Research has focused on symptom subgroups, but there is a need to consider a broader clinical spectrum, disentangle illness trajectories, and investigate genetic associations. Objective To detect psychosis subgroups using data-driven methods and examine their illness courses over 1.5 years and polygenic scores for schizophrenia, bipolar disorder, major depression disorder, and educational achievement. Design, Setting, and Participants This ongoing multisite, naturalistic, longitudinal (6-month intervals) cohort study began in January 2012 across 18 sites. Data from a referred sample of 1223 individuals (765 in the discovery sample and 458 in the validation sample) with DSM-IV diagnoses of schizophrenia, bipolar affective disorder (I/II), schizoaffective disorder, schizophreniform disorder, and brief psychotic disorder were collected from secondary and tertiary care sites. Discovery data were extracted in September 2016 amptoms (R2 = 0.41; 95% CI, 0.38-0.44), depression symptoms (R2 = 0.28; 95% CI, 0.25-0.32), global functioning (R2 = 0.16; 95% CI, 0.14-0.20), and quality of life (R2 = 0.20; 95% CI, 0.17-0.23). The depressive and severe psychosis subgroups exhibited the lowest functioning and quadratic illness courses with partial recovery followed by reoccurrence of severe illness. Differences were found for educational attainment polygenic scores (mean [SD] partial η2 = 0.014 [0.003]) but not for diagnostic polygenic risk. Results were largely replicated in the validation cohort. Conclusions and Relevance Psychosis subgroups were detected with distinctive clinical signatures and illness courses and specificity for a nondiagnostic genetic marker. New data-driven clinical approaches are important for future psychosis taxonomies. The findings suggest a need to consider short-term to medium-term service provision to restore functioning in patients stratified into the depressive and severe psychosis subgroups.The intraluminal vesicles (ILVs) of endosomes mediate the delivery of activated signaling receptors and other proteins to lysosomes for degradation, but they also modulate intercellular communication when secreted as exosomes. The formation of ILVs requires four complexes, ESCRT-0, -I, -II, and -III, with ESCRT-0, -I, and -II presumably involved in cargo sorting and ESCRT-III in membrane deformation and fission. Here, we report that an active form of the ESCRT-associated protein ALIX efficiently recruits ESCRT-III proteins to endosomes. This recruitment occurs independently of other ESCRTs but requires lysobisphosphatidic acid (LBPA) in vivo, and can be reconstituted on supported bilayers in vitro. Our data indicate that this ALIX- and ESCRT-III-dependent pathway promotes the sorting and delivery of tetraspanins to exosomes. We conclude that ALIX provides an additional pathway of ILV formation, secondary to the canonical pathway, and that this pathway controls the targeting of exosomal proteins. © 2020 Larios et al.Importance Older adults, especially those with frailty, have a higher risk for complications and death after emergency surgery. Acute Care for the Elderly models have been successful in medical wards, but little evidence is available for patients in surgical wards. Objectives To develop and assess the effect of an Elder-Friendly Approaches to the Surgical Environment (EASE) model in an emergency surgical setting. Design, Setting, and Participants This prospective, nonrandomized, controlled before-and-after study included patients 65 years or older who presented to the emergency general surgery service of 2 tertiary care hospitals in Alberta, Canada. Transfers from other medical services, patients undergoing elective surgery or with trauma, and nursing home residents were excluded. Of 6795 patients screened, a total of 684 (544 in the nonintervention group and 140 in the intervention group) were included. Data were collected from April 14, 2014, to March 28, 2017, and analyzed from November 16, 2018, through Mreased by 12.2 (2.5) points (P  less then  .001; DID P  less then  .001). Median length of stay decreased by 3 days (10 [interquartile range (IQR), 6-17] days to 7 [IQR, 5-14] days; P = .001; DID P = .61), and fewer patients required an alternative level of care at discharge (61 of 153 [39.9%] vs 29 of 140 [20.7%]; P  less then  .001; DID P = .11). Conclusions and Relevance To our knowledge, this is the first study to examine clinical outcomes associated with a novel elder-friendly surgical care delivery redesign. The findings suggest the clinical effectiveness of such an approach by reducing major complications or death, decreasing hospital stays, and returning patients to their home residence. Trial Registration ClinicalTrials.gov Identifier NCT02233153.Importance Vasopressors are commonly administered to intensive care unit (ICU) patients to raise blood pressure. Balancing risks and benefits of vasopressors is a challenge, particularly in older patients. Objective To determine whether reducing exposure to vasopressors through permissive hypotension (mean arterial pressure [MAP] target, 60-65 mm Hg) reduces mortality at 90 days in ICU patients aged 65 years or older with vasodilatory hypotension. Design, Setting, and Participants A multicenter, pragmatic, randomized clinical trial was conducted in 65 ICUs in the United Kingdom and included 2600 randomized patients aged 65 years or older with vasodilatory hypotension (assessed by treating clinician). The study was conducted from July 2017 to March 2019, and follow-up was completed in August 2019. Interventions Patients were randomized 11 to vasopressors guided either by MAP target (60-65 mm Hg, permissive hypotension) (n = 1291) or according to usual care (at the discretion of treating clinicians) (n = 1307).