METABOLIC HETEROGENEITY IN ISCHEMIA REPERFUSION INJURY: THE INSIDE STORY

It is well established that ischemia reperfusion (IR) injury can lead to life-threatening arrhythmias. Our group introduced the theory of metabolic sinks as a novel cause of arrhythmogenesis in a heart exposed to IR injury. Metabolic sinks are clusters of myocytes in which ischemia-induced reduction of ATP:ADP ratio increases open probability of sarcolemmal ATP-sensitive K+ channels. This in turn leads to hyperpolarization of membrane potential that reduces or ablates electrical excitability within the affected region of myocardium. To date, studies of metabolic sinks in intact hearts have been largely limited to use of fluorescent indicators to image mitochondrial membrane potential on the epicardial surface. This has revealed the existence of spatio-temporally evolving regions of myocardium within which mitochondrial membrane potential is depolarized, and whose presence influences electrical conduction and action potential duration. In order to explore the three-dimensional structure of metabolic sinks within the myocardium, we have developed a protocol for labeling an intact guinea pig heart exposed to IR injury and imaging any portion of the labeled heart using a custom designed automated volume imaging microtome (AVIM) to overcome the limited imaging field of laser scanning microscopy (LSM). Our AVIM is composed of low-cost components that can be easily installed and removed from a shared microscope. We have developed an open-source software signal processing pipeline to correct for imaging artifacts inherent to LSM and effectively reconstruct the acquired image volumes. Using this approach, we show that hearts undergoing reperfusion arrhythmias have an endocardium containing mostly depolarized mitochondria, with an abrupt transition to repolarized mitochondria in mid-myocardial to epicardial regions. Hearts not exhibiting reperfusion arrhythmias show a much more uniform distribution of depolarized mitochondria as a function of transmural location. These results show different stereotypical patterns of mitochondrial depolarization that are correlated with the presence and absence of reperfusion arrhythmias

CODE-EHR best-practice framework for the use of structured electronic health-care records in clinical research.

Big data is important to new developments in global clinical science that aim to improve the lives of patients. Technological advances have led to the regular use of structured electronic health-care records with the potential to address key deficits in clinical evidence that could improve patient care. The COVID-19 pandemic has shown this potential in big data and related analytics but has also revealed important limitations. Data verification, data validation, data privacy, and a mandate from the public to conduct research are important challenges to effective use of routine health-care data. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including representation from patients, clinicians, scientists, regulators, journal editors, and industry members. In this Review, we propose the CODE-EHR minimum standards framework to be used by researchers and clinicians to improve the design of studies and enhance transparency of study methods. The CODE-EHR framework aims to develop robust and effective utilisation of health-care data for research purposes

CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research.

Big data is central to new developments in global clinical science aiming to improve the lives of patients. Technological advances have led to the routine use of structured electronic healthcare records with the potential to address key gaps in clinical evidence. The covid-19 pandemic has demonstrated the potential of big data and related analytics, but also important pitfalls. Verification, validation, and data privacy, as well as the social mandate to undertake research are key challenges. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including patient representatives, clinicians, scientists, regulators, journal editors and industry. We propose the CODE-EHR Minimum Standards Framework as a means to improve the design of studies, enhance transparency and develop a roadmap towards more robust and effective utilisation of healthcare data for research purposes

CODE-EHR best practice framework for the use of structured electronic healthcare records in clinical research

Big data is central to new developments in global clinical science aiming to improve the lives of patients. Technological advances have led to the routine use of structured electronic healthcare records with the potential to address key gaps in clinical evidence. The covid-19 pandemic has demonstrated the potential of big data and related analytics, but also important pitfalls. Verification, validation, and data privacy, as well as the social mandate to undertake research are key challenges. The European Society of Cardiology and the BigData@Heart consortium have brought together a range of international stakeholders, including patient representatives, clinicians, scientists, regulators, journal editors and industry. We propose the CODE-EHR Minimum Standards Framework as a means to improve the design of studies, enhance transparency and develop a roadmap towards more robust and effective utilisation of healthcare data for research purposes

The Changing Landscape for Stroke\ua0Prevention in AF: Findings From the GLORIA-AF Registry Phase 2

Background GLORIA-AF (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients with Atrial Fibrillation) is a prospective, global registry program describing antithrombotic treatment patterns in patients with newly diagnosed nonvalvular atrial fibrillation at risk of stroke. Phase 2 began when dabigatran, the first non\u2013vitamin K antagonist oral anticoagulant (NOAC), became available. Objectives This study sought to describe phase 2 baseline data and compare these with the pre-NOAC era collected during phase 1. Methods During phase 2, 15,641 consenting patients were enrolled (November 2011 to December 2014); 15,092 were eligible. This pre-specified cross-sectional analysis describes eligible patients\u2019 baseline characteristics. Atrial fibrillation disease characteristics, medical outcomes, and concomitant diseases and medications were collected. Data were analyzed using descriptive statistics. Results Of the total patients, 45.5% were female; median age was 71 (interquartile range: 64, 78) years. Patients were from Europe (47.1%), North America (22.5%), Asia (20.3%), Latin America (6.0%), and the Middle East/Africa (4.0%). Most had high stroke risk (CHA2DS2-VASc [Congestive heart failure, Hypertension, Age  6575 years, Diabetes mellitus, previous Stroke, Vascular disease, Age 65 to 74 years, Sex category] score  652; 86.1%); 13.9% had moderate risk (CHA2DS2-VASc = 1). Overall, 79.9% received oral anticoagulants, of whom 47.6% received NOAC and 32.3% vitamin K antagonists (VKA); 12.1% received antiplatelet agents; 7.8% received no antithrombotic treatment. For comparison, the proportion of phase 1 patients (of N = 1,063 all eligible) prescribed VKA was 32.8%, acetylsalicylic acid 41.7%, and no therapy 20.2%. In Europe in phase 2, treatment with NOAC was more common than VKA (52.3% and 37.8%, respectively); 6.0% of patients received antiplatelet treatment; and 3.8% received no antithrombotic treatment. In North America, 52.1%, 26.2%, and 14.0% of patients received NOAC, VKA, and antiplatelet drugs, respectively; 7.5% received no antithrombotic treatment. NOAC use was less common in Asia (27.7%), where 27.5% of patients received VKA, 25.0% antiplatelet drugs, and 19.8% no antithrombotic treatment. Conclusions The baseline data from GLORIA-AF phase 2 demonstrate that in newly diagnosed nonvalvular atrial fibrillation patients, NOAC have been highly adopted into practice, becoming more frequently prescribed than VKA in Europe and North America. Worldwide, however, a large proportion of patients remain undertreated, particularly in Asia and North America. (Global Registry on Long-Term Oral Antithrombotic Treatment in Patients With Atrial Fibrillation [GLORIA-AF]; NCT01468701

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In 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= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Wirtliche Ökonomie. Philosophische und dichterische Quellen [Hospitable Economics. Philosophical and Poetic Sources], Volume II, Elementa Œconomica 1.2

Dieser Band stellt die erste Fortsetzung der 2013 begonnenen Publikation zur „Wirtlichen Ökonomie“ dar. Er dient der sich fortsetzenden Frage nach der Wirtlichkeit. Zu dieser Frage gehört es, das Ökonomische aus einer notwendig gewordenen Zurückhaltung gegenüber dem methodischen Vorgriff der modernen Wirtschaftswissenschaften zu denken. Die Zurückhaltung verleiht, indem sie den Fragebereich der Wirtlichkeit eröffnet, den hier versammelten Beiträgen ihren wahren Zusammenhan

Ökonomie als Problem. Interdisziplinäre Beiträge zu einer Kritik ökonomischen Wissens

Der interdisziplinär ausgerichtete Band zielt nicht auf die Korrektur oder Ergänzung des herrschenden ökonomischen Paradigmas. Vielmehr gilt es neu zu bestimmen, was ökonomisches Wissen, was seine Quellen und Methoden sein sollen. Wie lässt sich eine solche Neubestimmung im Rückgang auf Werke der Dichtung und Kunst gewinnen? Welche fruchtbaren Impulse können aus interkulturellen Aspekten hervorgehen? Sind klassische philosophische Positionen überhaupt noch relevant für aktuelle ökonomische Problemstellungen und, wenn ja, in welcher Weise? Somit wird die weithin bestehende Akzeptanz, mit der jenem Paradigma und dem Problem seines Wirklichkeitsbezugs begegnet wird, in Frage gestellt