Circulating exosomal microRNA expression patterns distinguish cardiac sarcoidosis from myocardial ischemia.

Objective: Cardiac sarcoidosis is difficult to diagnose, often requiring expensive and inconvenient advanced imaging techniques. Circulating exosomes contain genetic material, such as microRNA (miRNA), that are derived from diseased tissues and may serve as potential disease-specific biomarkers. We thus sought to determine whether circulating exosome-derived miRNA expression patterns would distinguish cardiac sarcoidosis (CS) from acute myocardial infarction (AMI).

CaMKII Met281/282 oxidation is not required for recovery of calcium transients during acidosis.

CaMKII is needed for the recovery of Ca transients during acidosis but also mediates postacidic arrhythmias. CaMKIIδ can sustain its activity following Met281/282 oxidation. Increasing cytosolic Na during acidosis as well as postacidic pH normalization should result in prooxidant conditions within the cell favoring oxidative CaMKIIδ activation.

Directed, Elliptic, and Higher Order Flow Harmonics of Protons, Deuterons, and Tritons in Au+Au Collisions at sqrt[s_{NN}]=2.4 GeV.

Flow coefficients v_{n} of the orders n=1-6 are measured with the High-Acceptance DiElectron Spectrometer (HADES) at GSI for protons, deuterons, and tritons as a function of centrality, transverse momentum, and rapidity in Au+Au collisions at sqrt[s_{NN}]=2.4  GeV. Combining the information from the flow coefficients of all orders allows us to construct for the first time, at collision energies of a few GeV, a multidifferential picture of the angular emission pattern of these particles.

Extracorporeal life support in patients with acute myocardial infarction complicated by cardiogenic shock - Design and rationale of the ECLS-SHOCK trial.

Background: In acute myocardial infarction complicated by cardiogenic shock the use of mechanical circulatory support devices remains controversial and data from randomized clinical trials are very limited. Extracorporeal life support (ECLS) - venoarterial extracorporeal membrane oxygenation - provides the strongest hemodynamic support in addition to oxygenation. However, despite increasing use it has not yet been properly investigated in randomized trials.

Secondary hemophagocytic lymphohistiocytosis and severe liver injury induced by hepatic SARS-CoV-2 infection unmasking Wilson's disease: Balancing immunosuppression.

A 21-year-old woman was hospitalized due to coronavirus disease 2019 (COVID-19)-associated respiratory and hepatic impairment concomitant with severe hemolytic anemia. Upon diagnosis of secondary hemophagocytic lymphohistiocytosis, immunosuppression with anakinra and steroids was started, leading to a hepatic severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and viremia. Subsequent liver biopsy revealed virus particles in hepatocytes by electron microscopy and SARS-CoV-2 virus could be isolated and cultured.

Proteomic and functional mapping of cardiac NaV1.5 channel phosphorylation sites.

Phosphorylation of the voltage-gated Na+ (NaV) channel NaV1.5 regulates cardiac excitability, yet the phosphorylation sites regulating its function and the underlying mechanisms remain largely unknown. Using a systematic, quantitative phosphoproteomic approach, we analyzed NaV1.

Acquired von Willebrand syndrome and factor VIII in patients with moderate to severe mitral regurgitation undergoing transcatheter mitral valve repair.

Background And Hypothesis: The acquired von Willebrand syndrome (AvWS), which predisposes to bleeding events, is often related to valvular heart diseases. We investigated possible implications of AvWS and factor VIII levels in patients with moderate to severe mitral regurgitation (MR) undergoing transcatheter mitral valve repair (TMVR).

Methods And Results: 123 patients with moderate to severe MR were prospectively enrolled.

Diagnostic value of FDG PET/CT imaging in patients with surgically managed infective endocarditis: results of a retrospective analysis at a tertiary center.

Background: We assessed the diagnostic value of FDG PET/CT in a real-world cohort of patients with surgically managed infective endocarditis (IE).

Methods: We performed a retrospective analysis of all patients hospitalized in a tertiary IE referral medical center from January 2014 to October 2018 fulfilling the following criteria: ICD-10 code for IE and OPS code for both, heart surgery and FDG PET/CT.

Results: Final analysis included 29 patients, whereof 28 patients had surgically proven IE.

A novel mouse model of obstructive sleep apnea by bulking agent-induced tongue enlargement results in left ventricular contractile dysfunction.

Aims: Obstructive sleep apnea (OSA) is a widespread disease with high global socio-economic impact. However, detailed pathomechanisms are still unclear, partly because current animal models of OSA do not simulate spontaneous airway obstruction. We tested whether polytetrafluoroethylene (PTFE) injection into the tongue induces spontaneous obstructive apneas.

Genetic determinants of clinical phenotype in hypertrophic cardiomyopathy.

Background: Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiovascular disease that affects approximately one in 500 people. HCM is a recognized genetic disorder most often caused by mutations involving myosin-binding protein C (MYBPC3) and β-myosin heavy chain (MYH7) which are responsible for approximately three-quarters of the identified mutations.

Methods: As a part of the international multidisciplinary SILICOFCM project ( www.

Association of inhaled and systemic corticosteroid use with Coronavirus Disease 2019 (COVID-19) test positivity in patients with chronic pulmonary diseases.

Background: The effects of chronic inhaled and systemic corticosteroids use on COVID-19 susceptibility and severity are unclear. Since many patients with chronic pulmonary diseases rely on corticosteroids to control disease, it is important to understand the risks of their use during the pandemic. We aim to study if the use of inhaled or systemic corticosteroids affects the likelihood of developing COVID-19 infection.

Decreased GLUT1/NHE1 RNA expression in whole blood predicts disease severity in patients with COVID-19.

Aims: We aimed to assess whether expression of whole-blood RNA of sodium proton exchanger 1 (NHE1) and glucose transporter 1 (GLUT1) is associated with COVID-19 infection and outcome in patients presenting to the emergency department with respiratory infections. Furthermore, we investigated NHE1 and GLUT1 expression in the myocardium of deceased COVID-19 patients.

Methods And Results: Whole-blood quantitative assessment of NHE1 and GLUT1 RNA was performed using quantitative PCR in patients with respiratory infection upon first contact in the emergency department and subsequently stratified by SARS-CoV-2 infection status.

Restarting Respiratory Clinical Research in the Era of the Coronavirus Disease 2019 Pandemic.

The clinical research we do to improve our understanding of disease and to develop new therapies has temporarily been delayed as the global health-care enterprise has focused its attention on those impacted by coronavirus disease 2019 (COVID-19). Although rates of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection are decreasing in many areas, many locations continue to have a high prevalence of infection. Nonetheless, research must continue and institutions are considering approaches to restarting non-COVID-related clinical investigation.

Disease Phenotypes and Mechanisms of iPSC-Derived Cardiomyocytes From Brugada Syndrome Patients With a Loss-of-Function SCN5A Mutation.

Brugada syndrome (BrS) is one of the major causes of sudden cardiac death in young people, while the underlying mechanisms are not completely understood. Here, we investigated the pathophysiological phenotypes and mechanisms using induced pluripotent stem cell (iPSC)-derived cardiomyocytes (CMs) from two BrS patients (BrS-CMs) carrying a heterozygous mutation p.S1812X.

Patterns of methamphetamine production among an international sample of methamphetamine 'cooks'.

Introduction And Aims: The illicit manufacture of methamphetamine in clandestine laboratories is associated with significant risks to the community and environment. Currently little is known about clandestine laboratories or the individual 'cooks' who operate them; current research directly engaging with cooks is limited to three qualitative studies with small samples (n < 24) of cooks based in the USA. This descriptive brief report starts to address this knowledge gap by exploring characteristics of an international sample of self-identified methamphetamine cooks.

Oxidized CaMKII and O-GlcNAcylation cause increased atrial fibrillation in diabetic mice by distinct mechanisms.

Diabetes mellitus (DM) and atrial fibrillation (AF) are major unsolved public health problems, and diabetes is an independent risk factor for AF. However, the mechanism(s) underlying this clinical association is unknown. ROS and protein O-GlcNAcylation (OGN) are increased in diabetic hearts, and calmodulin kinase II (CaMKII) is a proarrhythmic signal that may be activated by ROS (oxidized CaMKII, ox-CaMKII) and OGN (OGN-CaMKII).

Inhibition of cardiac potassium currents by oxidation-activated protein kinase A contributes to early afterdepolarizations in the heart.

Reactive oxygen species (ROS) have been shown to prolong cardiac action potential duration resulting in afterdepolarizations, the cellular basis of triggered arrhythmias. As previously shown, protein kinase A type I (PKA I) is readily activated by oxidation of its regulatory subunits. However, the relevance of this mechanism of activation for cardiac pathophysiology is still elusive.

Long-term effects of empagliflozin on excitation-contraction-coupling in human induced pluripotent stem cell cardiomyocytes.

The SGLT2 inhibitor empagliflozin improved cardiovascular outcomes in patients with diabetes. As the cardiac mechanisms remain elusive, we investigated the long-term effects (up to 2 months) of empagliflozin on excitation-contraction (EC)-coupling in human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CM) in a blinded manner. IPSC from 3 donors, differentiated into pure iPSC-CM (4 differentiations), were treated with a clinically relevant concentration of empagliflozin (0.

Effects of visualization of successful revascularization on chest pain and quality of life in chronic coronary syndrome: study protocol for the multi-center, randomized, controlled PLA-pCi-EBO-pilot-trial.

Background: Stable coronary artery disease (CAD), recently termed chronic coronary syndrome (CCS), is a highly prevalent disease. Current treatment strategies often include a relevant placebo effect. The hypothesis is that visual angiographic demonstration of the coronary arteries before and after successful percutaneous coronary intervention (PCI) by itself reduces the symptom burden of stable CAD/CCS.

Angiotensin-converting enzyme inhibitor/angiotensin II receptor blocker treatment and haemodynamic factors are associated with increased cardiac mRNA expression of angiotensin-converting enzyme 2 in patients with cardiovascular disease.

Aims: Coronavirus disease 2019 (COVID-19) is a widespread pandemic with an increased morbidity and mortality, especially for patients with cardiovascular diseases. Angiotensin-converting enzyme 2 (ACE2) has been identified as necessary cell entry point for SARS-CoV-2. Previous animal studies have demonstrated an increased ACE2 expression following treatment with either angiotensin-converting enzyme inhibitors (ACEi) or angiotensin II receptor blockers (ARB) that have led to a massive precariousness regarding the optimal cardiovascular therapy during this pandemic.

Evaluating the Minimal Clinically Important Difference of the King's Sarcoidosis Questionnaire in a Multicenter Prospective Study.

Improvement of quality of life (QoL) in patients with sarcoidosis is an important goal of management. The King's Sarcoidosis Questionnaire (KSQ) and Patient Global Assessment (PGA) are instruments that have been used in sarcoidosis. We defined the minimal clinically important difference (MCID) as the within-patient clinically meaningful change threshold and determined the MCID of KSQ general health (KSQ GH), KSQ lung, and PGA using both anchor and distribution methods.

Protected complex percutaneous coronary intervention and transcatheter aortic valve replacement using extracorporeal membrane oxygenation in a high-risk frail patient: a case report.

Background: Transcatheter aortic valve replacement has become a routine procedure for patients with severe symptomatic aortic stenosis at increased surgical risk. Not much is known about using prophylactic support with venoarterial extracorporeal membrane oxygenation in patients undergoing transcatheter aortic valve replacement and eventually concomitant complex percutaneous coronary intervention.

Case Presentation: We present a successful procedure of transcatheter aortic valve replacement and high-risk percutaneous coronary intervention utilizing venoarterial extracorporeal membrane oxygenation for hemodynamic support in a very frail 88-year-old Caucasian woman with severe symptomatic aortic stenosis and coronary bypass grafting in the past.

Empagliflozin inhibits Na /H exchanger activity in human atrial cardiomyocytes.

Aims: Recent clinical trials have proven gliflozins to be cardioprotective in diabetic and non-diabetic patients. However, the underlying mechanisms are incompletely understood. A potential inhibition of cardiac Na /H exchanger 1 (NHE1) has been suggested in animal models.

Association of candidate pharmacogenetic markers with platinum-induced ototoxicity: PanCareLIFE dataset.

Genetic association studies suggest a genetic predisposition for cisplatin-induced ototoxicity. Among other candidate genes, thiopurine methyltransferase () is considered a critical gene for susceptibility to cisplatin-induced hearing loss in a pharmacogenetic guideline. The PanCareLIFE cross-sectional cohort study evaluated the genetic associations in a large pan-European population and assessed the diagnostic accuracy of the genetic markers.