Proinflammatory cytokines driving cardiotoxicity in COVID-19.

Aims: Cardiac involvement is common in patients hospitalized with COVID-19 and correlates with an adverse disease trajectory. While cardiac injury has been attributed to direct viral cytotoxicity, serum-induced cardiotoxicity secondary to serological hyperinflammation constitutes a potentially amenable mechanism that remains largely unexplored.

Methods And Results: To investigate serological drivers of cardiotoxicity in COVID-19 we have established a robust bioassay that assessed the effects of serum from COVID-19 confirmed patients on human embryonic stem cell (hESC)-derived cardiomyocytes.

Epicardially secreted fibronectin drives cardiomyocyte maturation in 3D-engineered heart tissues.

Ischemic heart failure is due to irreversible loss of cardiomyocytes. Preclinical studies showed that human pluripotent stem cell (hPSC)-derived cardiomyocytes could remuscularize infarcted hearts and improve cardiac function. However, these cardiomyocytes remained immature.

FXR inhibition may protect from SARS-CoV-2 infection by reducing ACE2.

Preventing SARS-CoV-2 infection by modulating viral host receptors, such as angiotensin-converting enzyme 2 (ACE2), could represent a new chemoprophylactic approach for COVID-19 that complements vaccination. However, the mechanisms that control the expression of ACE2 remain unclear. Here we show that the farnesoid X receptor (FXR) is a direct regulator of ACE2 transcription in several tissues affected by COVID-19, including the gastrointestinal and respiratory systems.

Cardiovascular ACE2 receptor expression in patients undergoing heart transplantation.

Aims: Membrane-bound angiotensin-converting enzyme (ACE)2 is the main cellular access point for SARS-CoV-2, but its expression and the effect of ACE inhibition have not been assessed quantitatively in patients with heart failure. The aim of this study was to characterize membrane-bound ACE2 expression in the myocardium and myocardial vasculature in patients undergoing heart transplantation and to assess the effect of pharmacological ACE inhibition.

Methods And Results: Left ventricular (LV) tissue was obtained from 36 explanted human hearts from patients undergoing heart transplantation.

SARS-CoV-2 Infects Human Pluripotent Stem Cell-Derived Cardiomyocytes, Impairing Electrical and Mechanical Function.

COVID-19 patients often develop severe cardiovascular complications, but it remains unclear if these are caused directly by viral infection or are secondary to a systemic response. Here, we examine the cardiac tropism of SARS-CoV-2 in human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) and smooth muscle cells (hPSC-SMCs). We find that that SARS-CoV-2 selectively infects hPSC-CMs through the viral receptor ACE2, whereas in hPSC-SMCs there is minimal viral entry or replication.

Cholangiocyte organoids can repair bile ducts after transplantation in the human liver.

Organoid technology holds great promise for regenerative medicine but has not yet been applied to humans. We address this challenge using cholangiocyte organoids in the context of cholangiopathies, which represent a key reason for liver transplantation. Using single-cell RNA sequencing, we show that primary human cholangiocytes display transcriptional diversity that is lost in organoid culture.

Familial Evaluation in Idiopathic Ventricular Fibrillation: Diagnostic Yield and Significance of J Wave Syndromes.

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Epicardial cells derived from human embryonic stem cells augment cardiomyocyte-driven heart regeneration.

The epicardium and its derivatives provide trophic and structural support for the developing and adult heart. Here we tested the ability of human embryonic stem cell (hESC)-derived epicardium to augment the structure and function of engineered heart tissue in vitro and to improve efficacy of hESC-cardiomyocyte grafts in infarcted athymic rat hearts. Epicardial cells markedly enhanced the contractility, myofibril structure and calcium handling of human engineered heart tissues, while reducing passive stiffness compared with mesenchymal stromal cells.

Reconstruction of the mouse extrahepatic biliary tree using primary human extrahepatic cholangiocyte organoids.

The treatment of common bile duct (CBD) disorders, such as biliary atresia or ischemic strictures, is restricted by the lack of biliary tissue from healthy donors suitable for surgical reconstruction. Here we report a new method for the isolation and propagation of human cholangiocytes from the extrahepatic biliary tree in the form of extrahepatic cholangiocyte organoids (ECOs) for regenerative medicine applications. The resulting ECOs closely resemble primary cholangiocytes in terms of their transcriptomic profile and functional properties.

Predictors of Suboptimal Gain in Exercise Capacity After Cardiac Rehabilitation.

Cardiac rehabilitation (CR) improves exercise capacity (EC), but not all CR participants achieve such improvements. Our primary aim was to develop a tool to identify those with suboptimal improvement in EC after CR. We retrospectively analyzed 541 patients enrolled in a phase-II CR program after a cardiac event or intervention from 2003 to 2014.

Embryological Origin of Human Smooth Muscle Cells Influences Their Ability to Support Endothelial Network Formation.

Unlabelled: Vascular smooth muscle cells (SMCs) from distinct anatomic locations derive from different embryonic origins. Here we investigated the respective potential of different embryonic origin-specific SMCs derived from human embryonic stem cells (hESCs) to support endothelial network formation in vitro. SMCs of three distinct embryological origins were derived from an mStrawberry-expressing hESC line and were cocultured with green fluorescent protein-expressing human umbilical vein endothelial cells (HUVECs) to investigate the effects of distinct SMC subtypes on endothelial network formation.

Preexisting atrial fibrillation and cardiac complications after liver transplantation.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, and it is associated with increased cardiovascular morbidity and all-cause mortality. Our aim was to determine the impact of preexisting AF on patients undergoing liver transplantation (LT). A retrospective case-control study was performed.

Reversible non-ischaemic cardiomyopathy and left ventricular dysfunction after liver transplantation: a single-centre experience.

Background & Aims: Non-ischaemic cardiomyopathy (NIC) is an early complication of liver transplantation (LT). Our aims were to define the prevalence, associated clinical factors, and prognosis of this condition.

Methods: A retrospective study was performed on patients undergoing LT at our institution from January 2005 to December 2012.

Axillary Lymph Node Status in Early-Stage Breast Cancer Patients with Sentinel Node Micrometastases (0.2-2 mm).

Background: Omission of axillary lymph node dissection (ALND) is increasingly becoming the new standard of care for patients with sentinel lymph node micrometastases (SNMMs). However, a formidable proportion of patients is afflicted with non-sentinel node (NSN) macrometastatic tumor burden.

Methods: Over 1 decade 5,000 patients underwent sentinel node biopsies (SNB) at 2 certified breast cancer centers in Austria.