BackgroundAtrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all‐cause mortality may guide interventions.Methods and ResultsIn the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose‐adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all‐cause mortality in the 14 171 participants in the intention‐to‐treat population. The median age was 73 years, and the mean CHADS
2 score was 3.5. Over 1.9 years of median follow‐up, 1214 (8.6%) patients died. Kaplan–Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all‐cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33–1.70, P<0.0001) and age ≥75 years (hazard ratio 1.69, 95% CI 1.51–1.90, P<0.0001) were associated with higher all‐cause mortality. Multiple additional characteristics were independently associated with higher mortality, with decreasing creatinine clearance, chronic obstructive pulmonary disease, male sex, peripheral vascular disease, and diabetes being among the most strongly associated (model C‐index 0.677).ConclusionsIn a large population of patients anticoagulated for nonvalvular atrial fibrillation, ≈7 in 10 deaths were cardiovascular, whereas <1 in 10 deaths were caused by nonhemorrhagic stroke or systemic embolism. Optimal prevention and treatment of heart failure, renal impairment, chronic obstructive pulmonary disease, and diabetes may improve survival.Clinical Trial Registration
URL: https://www.clinicaltrials.gov/. Unique identifier: NCT00403767.
Background:
This study aimed to investigate the effect of long noncoding ribonucleic acids
(RNAs) metastasis-associated lung adenocarcinoma transcript 1 (lnc-MALAT1) on regulating neuron
apoptosis, neurite outgrowth and inflammation, and further explore its molecule mechanism in Alzheimer’s
disease (AD).
Methods:
Control overexpression, lnc-MALAT1 overexpression, control shRNA, and lnc-MALAT1
shRNA were transfected into NGF-stimulated PC12 cellular AD model and cellular AD model from
primary cerebral cortex neurons of rat embryo, which were established by Aβ1-42 insult. Rescue experiments
were performed by transferring lnc-MALAT1 overexpression and lnc-MALAT1 overexpression
& miR-125b overexpression plasmids. Neuron apoptosis, neurite outgrowth and inflammation were
detected by Hoechst-PI/apoptosis marker expressions, and observations were made using microscope
and RT-qPCR/Western blot assays. PTGS2, CDK5 and FOXQ1 expressions in rescue experiments were
also determined.
Results:
In two AD models, lnc-MALAT1 overexpression inhibited neuron apoptosis, promoted neurite
outgrowth, reduced IL-6 and TNF-α levels, and increased IL-10 level compared to control overexpression,
while lnc-MALAT1 knockdown promoted neuron apoptosis, repressed neurite outgrowth, elevated
IL-6 and TNF-α levels, but reduced IL-10 level compared to control shRNA. Additionally, lnc-
MALAT1 reversely regulated miR-125b expression, while miR-125b did not influence the lnc-
MALAT1 expression. Subsequently, rescue experiments revealed that miR-125b induced neuron apoptosis,
inhibited neurite outgrowth and promoted inflammation, also increased PTGS2 and CDK5
expressions but decreased FOXQ1 expression in lnc-MALAT1 overexpression treated AD models.
Conclusion:
Lnc-MALAT1 might interact with miR-125b to inhibit neuron apoptosis and inflammation
while promote neurite outgrowth in AD.
Introduction: Drug-induced acute kidney injury (D-AKI) is one of the important types of AKI. The incidence of D-AKI in China has rarely been studied. Objective: This study aims to explore the disease burden, related drugs, and risk factors of D-AKI. Methods: A nationwide cross-sectional survey was conducted in adult patients from 23 academic hospitals in 17 provinces in China. Suspected AKI was screened based on serum creatinine changes in accordance with the 2012 Kidney Disease: Improving Global Outcomes Clinical Practice Guideline for AKI, patients who met the diagnosis of hospital-acquired AKI in January and July of 2014 were defined. Suspected AKI was firstly evaluated for the possibility of D-AKI by pharmacists using the Naranjo Scale and finally defined as D-AKI by nephrologists through reviewing AKI clinical features. Results: Altogether 280,255 hospitalized patients were screened and 1,960 cases were diagnosed as hospital-acquired AKI, among which 735 cases were defined as having D-AKI (37.50%, 735/1,960) with an in-hospital mortality rate of 13.88% and 54.34% of the survivors did not achieve full renal recovery. 1,642 drugs were related to AKI in these patients. Anti-infectives, diuretics, and proton pump inhibitors were the top 3 types of drugs relevant to D-AKI, accounting for 66.63% cumulatively. Besides age, AKI staging, severe disease, hypoalbuminemia, plasma substitute, and carbapenem related D-AKI were independent risk factors for in-hospital mortality of D-AKI patients. Conclusion: In China, D-AKI has caused a substantial medical burden. Efforts should be made to pursue nephrotoxic drug stewardship to minimize attributable risk and improve the prevention, diagnosis, and treatment of D-AKI.
A visible-light-mediated photocatalytic strategy for the radical–radical cross-coupling of acetenyl ketones with benzyl trifluoroborate has been described.
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