Left ventricular assist devices: A comprehensive review of major clinical trials, devices, and future directions.

Heart failure is an increasingly prevalent medical condition associated with significant morbidity and mortality. In spite of optimal medical therapy, a large number of patients continue to deteriorate clinically and could potentially benefit from advanced therapies. While cardiac transplantation is an established therapy for end-stage heart failure, there are a limited number of donor hearts, and many patients may not be candidates. Over the past two decades, mechanical circulatory support and left ventricular assist devices (LVAD) have altered the heart failure management landscape. Herein we review the indications for LVAD implantation and how they have changed over time. We will also outline major technological evolutions in LVADs and summarize the landmark clinical trials pertaining to them. We also highlight the adverse events associated with LVADs and assess the limitations of the existing literature. Finally, we look ahead to the future of LVAD therapy for patients with advanced heart failure.

Surgical Treatment for Ischemic Heart Failure (STICH) trial: A review of outcomes.

Coronary artery disease (CAD) is a significant source of morbidity and mortality in developed countries. The landmark Surgical Treatment for Ischemic Heart Failure (STICH) trial has provided greatly needed evidence in the management of patients with severe left ventricle (LV) dysfunction (LVEF ≤ 35%) and CAD amenable to revascularization. The trial investigated two primary hypotheses: (i) that coronary artery bypass grafting (CABG) with optimal medical therapy (OMT) was superior to OMT alone, and (ii) that CABG with surgical ventricular reconstruction (SVR) would be superior to CABG alone. The results of the 10-year follow-up demonstrated significant long-term benefits with the addition of CABG to OMT. However, the second hypothesis yielded controversial results as the study found no difference between CABG with SVR and SVR alone. The STICH trial, and the numerous subanalyses that followed have reinforced and challenged a number of widely held beliefs regarding the management of patients with severe LV dysfunction and ischemic heart failure. The purpose of this comprehensive review is to outline the published data from the STICH trial and its substudies while providing a balanced assessment of the evidence-based conclusions and criticisms that have followed.

Molecular mechanisms underlining the role of metformin as a therapeutic agent in lung cancer.

BACKGROUND: Metformin, a first-line therapeutic for type 2 diabetes, has been studied for its potential use in cancer treatment following a number of epidemiological studies that have demonstrated reduced cancer incidence and mortality rates among patients treated with the drug. As yet, however, there remains significant uncertainty about the molecular mechanisms by which metformin exerts its anti-cancer effects. Herein, we summarize the evidence surrounding the anti-lung cancer effects of metformin. CONCLUSIONS: Specifically, we explore protein targets of metformin, including AMPK, PP2A, IRF-1/YAP and HGF and we outline the proposed mechanisms of action for metformin in lung cancer, with particular attention given to apoptosis and autophagy. We also closely examine the synergistic activity of metformin with existing cancer treatment regimens, such as TKI's, platinum-based agents and immune therapeutics. In addition to considering preclinical and clinical studies, we also dissect and contextualize the limitations and inconsistencies of the current literature, especially those of epidemiological studies. Finally, we offer a potential trajectory for future research in this rapidly evolving area of basic and clinical oncology.