Dysnatremia is associated with increased risk of all-cause mortality within 365 days post-discharge in patients with atrial fibrillation without heart failure: A prospective cohort study

Aim: The aim of this study is to evaluate the association between serum sodium concentrations at hospital admission and all-cause mortality within 365 days post-discharge in patients with atrial fibrillation (AF) without heart failure (HF). Methods: The prospective cohort study enrolled 1,446 patients with AF without HF between November 2018 and October 2020. A follow-up was performed 30, 90, 180, and 365 days after enrollment through outpatient visits or telephone interviews. All-cause mortality was estimated in three groups according to serum sodium concentrations: hyponatremia ( \u3c 135 mmol/L), normonatremia (135 – 145 mmol/L), and hypernatremia ( \u3e 145 mmol/L). We estimated the risk of all-cause mortalities using univariable and multivariable Cox proportional hazards models with normonatremia as the reference. Results: The all-cause mortalities of hyponatremia, normonatremia, and hypernatremia were 20.6, 9.4, and 33.3 % within 365 days post-discharge, respectively. In the univariable analysis, hyponatremia (HR: 2.19, CI 1.5 – 3.2) and hypernatremia (HR: 4.03, CI 2.32 – 7.02) increased the risk of all-cause mortality. The HRs for hyponatremia and hypernatremia were 1.55 (CI 1.05 – 2.28) and 2.55 (CI 1.45 – 4.46) after adjustment for age, diabetes mellitus, loop diuretics, antisterone, antiplatelet drugs, and anticoagulants in the patients with AF without HF. The association between serum sodium concentrations and the HRs of all-cause mortality was U-shaped. Conclusion: Dysnatremia at hospital admission was an independent factor for all-cause mortality in patients with AF without HF within 365 days post-discharge

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Nicorandil in Patients with Acute Myocardial Infarction Undergoing Primary Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis

<div><p>Background</p><p>Nicorandil, as an adjunctive therapy with primary percutaneous coronary intervention (PCI), had controversial benefits in cardioprotection in patients with acute myocardial infarction (AMI).</p> <p>Methods and Results</p><p>We performed a systematic review of randomized controlled trials (RCTs) comparing treatment with nicorandil prior to reperfusion therapy with control (placebo or no nicorandil) in patients who suffered from AMI and performed primary PCI. PubMed, EMBASE and CENTRAL databases and other sources were searched without language and publication restriction. 14 trials involving 1680 patients were included into this meta-analysis. Nicorandil significantly reduced the incidence of thrombolysis in myocardial infarction (TIMI) flow grade ≤2 (risk ratio [RR], 0.57; 95% confidence interval [CI]: 0.42 to 0.79), the Timi frame count (TFC) (mean difference [MD], -5.19; 95% CI: -7.13 to -3.26), increased left ventricular ejection fraction (LVEF) (%) (MD, 3.08; 95% CI: 0.79 to 5.36), and reduced the incidence of ventricular arrhythmia (RR, 0.53; 95% CI: 0.37 to 0.76) and congestive heart failure (CHF) (RR, 0.41; 95% CI: 0.22 to 0.75). No difference in the pear creatine kinase (CK) value (MD, -290.19; 95% CI: -793.75 to 213.36) or cardiac death (RR, 0.39; 95% CI: 0.09 to 1.67) was observed.</p> <p>Conclusions</p><p>Nicorandil prior to reperfusion is associated with improvement of coronary reflow as well as suppression of ventricular arrhythmia, and further improves left ventricular function in patients who suffered from AMI and underwent primary PCI. But the definite clinical benefits of nicorandil were not found, which may be due to the small sample size of the selected studies.</p> </div

Risk of Bias Summary.

<p>Risk of Bias Summary.</p

MD of LVEF.

<p>Forest plot of MD (with 95% CI) for LVEF in patients receiving nicorandil compared with those receiving no nicorandil. Significant increase in LVEF (MD: 3.08; 95% CI: 0.79 to 5.36; p=0.008) was observed in nicorandil group. CI = confidence interval; LVEF = left ventricular ejection fraction; MD = mean difference.</p

Funnel Plot for the Incidence of TIMI Flow Grade ≤ 2.

<p>RR = risk ratio; SE = standard error.</p

RR of the Incidence of TIMI Flow Grade ≤ 2.

<p>Forest plot of RR (with 95% CI) for TIMI flow grade ≤ 2 in patients receiving nicorandil compared with those receiving no nicorandil. Significant reduction in TIMI flow grade ≤ 2 (RR: 0.57; 95% CI: 0.42 to 0.79; p=0.0006) was observed in nicorandil group. CI = confidence interval; RR = risk ratio; TIMI = thrombolysis in myocardial infarction.</p

MD of TIMI Frame Count.

<p>Forest plot of MD (with 95% CI) for TIMI frame count in patients receiving nicorandil compared with those receiving no nicorandil. Significant reduction in TIMI frame count (MD: -5.19; 95% CI: -7.13 to -3.26; p<0.00001) was observed in nicorandil group. CI = confidence interval; MD = mean difference, TIMI = thrombolysis in myocardial infarction.</p