Outcomes of coronary artery bypass grafting in patients with heart failure with a midrange ejection fraction

BackgroundCoronary artery bypass grafting (CABG) improves survival in patients with heart failure and severely reduced left ventricular systolic function (LVEF). Limited data exist regarding adverse cardiovascular event rates after CABG in patients with heart failure with midrange ejection fraction (HFmrEF; LVEF > 40% and < 55%).MethodsWe analyzed data on isolated CABG patients from the Veterans Affairs national database (2010-2019). We stratified patients into control (normal LVEF and no heart failure), HFmrEF, and heart failure with reduced LVEF (HFrEF) groups. We compared all-cause mortality and heart failure hospitalization rates between groups with a Cox model and recurrent events analysis, respectively.ResultsIn 6533 veterans, HFmrEF and HFrEF was present in 1715 (26.3%) and 566 (8.6%) respectively; the control group had 4252 (65.1%) patients. HFrEF patients were more likely to have diabetes mellitus (59%), insulin therapy (36%), and previous myocardial infarction (31%). Anemia was more prevalent in patients with HFrEF (49%) as was a lower serum albumin (mean, 3.6 mg/dL). Compared with the control group, a higher risk of death was observed in the HFmrEF (hazard ratio [HR], 1.3 [1.2-1.5)] and HFrEF (HR, 1.5 [1.2-1.7]) groups. HFmrEF patients had the higher risk of myocardial infarction (subdistribution HR, 1.2 [1-1.6]; P = .04). Risk of heart failure hospitalization was higher in patients with HFmrEF (HR, 4.1 [3.5-4.7]) and patients with HFrEF (HR, 7.2 [6.2-8.5]).ConclusionsHeart failure with midrange ejection fraction negatively affects survival after CABG. These patients also experience higher rates myocardial infarction and heart failure hospitalization.     

Social cognitive correlates of device-measured and self-reported physical activity in Black and White individuals with multiple sclerosis

BackgroundThere is increasing research interest regarding physical activity behavior among persons with multiple sclerosis (MS), yet there is little known about physical activity and its correlates in Black persons with MS.ObjectiveThis cross-sectional study assessed associations among social cognitive theory (SCT) variables and device-measured and self-reported physical activity in samples of Black and White persons with MS.MethodsParticipants included 67 Black and 141 White persons with MS who wore an ActiGraph accelerometer on a belt around the waist measuring moderate-to-vigorous physical activity (MVPA) for seven days and completed a battery of questionnaires. Questionnaires included demographic and clinical characteristics, leisure-time exercise, exercise self-efficacy, overcoming barriers self-efficacy, function, social support, exercise outcome expectations, and goal setting and planning.ResultsBlack participants with MS engaged in significantly less MVPA, but not sedentary behavior or light physical activity, than the White participants with MS. Black participants further had significantly lower levels of exercise self-efficacy and outcome expectations than the White sample. All SCT correlates were significantly correlated with self-reported physical activity, but only exercise and barriers self-efficacy, perceived function, and exercise goal setting were associated with device-measured MVPA. The difference in physical activity between Black and White participants with MS was accounted for by differences in exercise self-efficacy and outcome expectations.ConclusionsResearchers should consider developing behavioral interventions that target exercise self-efficacy and outcome expectations as SCT variables for increasing physical activity in Black persons with MS.     

Dual-target inhibitors of bromodomain-containing protein 4 (BRD4) in cancer therapy: Current situation and future directions

Bromodomain-containing protein 4 (BRD4) is emerging as a therapeutic target that acts synergistically with other targets of small-molecule drugs in cancer. Therefore, the discovery of potential new dual-target inhibitors of BRD4 may be a promising strategy for cancer therapy. In this review, we highlight a series of strategies to design therapeutic dual-target inhibitors of BRD4 that focus on the synergistic functions of this protein. Drug combinations that exploit synthetic lethality, protein–protein interactions, functional complementarity, and blocking of resistance mechanisms could ultimately overcome the barriers inherent to the development of BRD4 inhibitors as future cancer drugs.