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Introduction: Adverse ventricular remodeling may occur after myocardial infarction (MI) and is associated with an increased risk of heart failure and death. Extracellular vesicles (EVs) derived exogenously from pluripotent stem cells exert cardioprotective effects after injury and being tested for therapeutic efficacy for MI. However role of endogenous EVs from MI patients in this regard is not yet addressed. Hypothesis: We aim to characterize EVs derived from MI patients and explore their cardioprotective potential on human primary cardiomyocytes (HCM) upon chemically induced cell death. Methods: The EVs from plasma of MI patients with preserved or reduced left ventricular ejection fraction (LVEF) and healthy controls (HC) were purified and characterized by flow cytometry and transmission electron microscopy (TEM). HCM and human cardiac microvascular endothelial cells (hCMVECs) were used to study functional effects of EVs upon staurosporin (STS), etoposide and rapamycin induced cell death. Results: Higher concentrations of platelet-, leukocyte-, endothelial- and erythrocyte-derived EVs were found in MI patients compared to HC. TEM analysis demonstrated the presence of heterogenous vesicles of different sizes (50-1000-nm) across all tested samples. Human cardiac cells- hCMVECs and HCM when pre-incubated with both preserved and reduced LVEF MI EVs showed significant attenuation to STS-induced caspase 3 activity compared to HC EVs or mock treatment. Lactate dehydrogenase (LDH) release, as a marker for membrane integrity, upon etoposide stimulation was not affected in hCMVECs and partly increased in HCM, whereas pre-incubation with HC EVs or MI EVs did not affect eotoposide treatment outcome by these cells. While rapamycin induced cleavage of LC3-I to LC3-II in hCMVECs, the presence of EVs from either HC or MI patients did not influence autophagic response. Whereas, baseline LC3-II expression in HCM was observed to be too high to be perturbed by the presence of rapamycin. Conclusions: Diverse nature of MI EVs in terms of cells of origin can be further elaborated to consolidate their biomarker potential. Cardioprotective ability of endogenously presented heterogenous mixture of MI EVs opens new avenues to consider in preclinical EV/MI research.

Background: NT-proBNP is elevated in patients with a diagnosis of atrial fibrillation (AF) and associated with risk of stroke and other outcomes. The associations have mainly been studied in patients on oral anticoagulation and not considering if samples were obtained during AF or sinus rhythm. We investigated the association of NT-proBNP with heart rhythm and cardiovascular (CV) events in patients with AF without oral anticoagulation. Methods: Plasma samples were obtained at baseline in 3184 patients with diagnosis of AF (2142 in AF rhythm at blood sampling) receiving aspirin in two multicenter randomized clinical trials with median follow-up 1.2 years (AVERROES) and 3.8 years (ACTIVE A), respectively. NT-proBNP was analyzed using Elecsys electrochemiluminescence immunoassay. Association of NT-proBNP with clinical variables was assessed with multivariable linear regression models. Association with outcomes were estimated with Cox-regression models adjusting for clinical variables. Results: Median age was 71 years, 57.8% were men, and median NT-proBNP 713 ng/L (25 th -75 th percentiles, 282-1388 ng/L). Variables contributing to NT-proBNP level were, in reducing order: AF rhythm (ratio of geometric means 2.9), age, creatinine, and prior heart failure. Levels of NT-proBNP were significantly associated with ischemic stroke (HR 3 rd vs 1 st quartile 2.1, 95%CI 1.5-3.0), heart failure hospitalizations (HR 2.2, 95%CI 1.6-2.9), and CV death (HR 2.4, 95% CI 1.8-3.3), all p Conclusion: In patients with a diagnosis AF, plasma levels of NT-proBNP are three times higher during AF rhythm compared with sinus rhythm. Higher levels of NT-proBNP are independently associated with ischemic stroke, heart failure hospitalizations, and CV death in AF patients without oral anticoagulation treatment, irrespective of heart rhythm.

To date, the virtual multidisciplinary tumor boards (vMTBs) are increasingly used to achieve high-quality treatment recommendations across health-care regions, which expands and develops the local MTB team to a regional or national expert network. This review describes the process of lung cancer-specific MTBs and the transition process from face-to-face tumor boards to virtual ones. The review also focuses on the project organization's description, advantages, and disadvantages. Semi-structured interviews identified five major themes for MTBs: current practice, attitudes, enablers, barriers, and benefits for the MTB. MTB teams exhibited positive responses to modeled data feedback. Virtualization reduces time spent for travel, allowing easier and timely patient discussions. This process requires a secure web platform to assure the respect of patients’ privacy and presents the same unanswered problems. The implementation of vMTB also permits the implementation of networks especially in areas with geographical barriers facilitating interaction between large referral cancer centers and tertiary or community hospitals as well as easier access to clinical trial opportunities. Studies aimed to improve preparations, structure, and conduct of MTBs, research methods to monitor their performance, teamwork, and outcomes are also outlined in this article. Analysis of literature shows that MTB participants discuss 5–8 cases per meeting and that the use of a vMTB for lung cancer and in particular stage III NSCLC and complex stage IV cases is widely accepted by most health professionals.Despite still-existing gaps, overall vMTB represents a unique opportunity to optimize patient management in apatient-centeredapproach.