Abstract: Systemic inflammation is a key characteristic of sepsis but also also in non-infectious conditions such as post-cardiac arrest syndrome. Cytokine adsorption and extracorporeal membrane oxygenation are emerging therapies applied in these critically ill patients, but the experience with their concurrent use is limited. We evaluated cytokine adsorption in critically ill patients requiring support with either veno-venous (vv) or veno-arterial (va) extracorporeal membrane oxygenation (ECMO) support and hypothesized that adsorber incorporation into the ECMO circuit was technically feasible and not associated with imminent risk. We analyzed data from the first six cases of a prospective single-center registry of patients undergoing veno-venous (vv) or veno-arterial (va) ECMO therapy. While in most published cases cytokine adsorbers were inserted into a hemofiltration circuit, we directly incorporated the adsorber into the ECMO circuit without interruption of continuous ECMO support. We observed no relevant side effects attributable to cytokine adsorption. Thirty-day mortality was 83% (predicted mortality 87%), indicating that the decision for adding cytokine adsorption may have been considered as an ultima ratio decision in severe cases with poor prognosis. Vasopressor or inotrope use, lactate level, and fluid balance did not change significantly when comparing pre- vs. post-cytokine adsorption values. Interestingly, the real-time course of the mentioned three surrogate parameters remained unaltered in all but two cases, regardless of cytokine removal. Beneficial effects of cytokine adsorption are plausible in two va-ECMO-treated patient, where increasing lactate began to drop after initiation of cytokine adsorption. Taken together, these data suggest that incorporation of cytokine adsorption into the management of critically ill patients requiring continued ECMO support is feasible and easy to handle. Whether cytokine removal improves clinical outcome in ECMO-treated patients should now be investigated in randomized controlled trials

Abstract: Pulmonary hypertension (PH) is characterized by pulmonary vascular remodeling and associated with adverse outcomes. In patients with PH, plasma aldosterone levels are elevated, suggesting that aldosterone and its receptor, the mineralocorticoid receptor (MR), play an important role in the pathophysiology of PH. The MR plays a crucial role in adverse cardiac remodeling in left heart failure. A series of experimental studies from the past few years indicate that MR activation promotes adverse cellular processes that lead to pulmonary vascular remodeling, including endothelial cell apoptosis, smooth muscle cell (SMC) proliferation, pulmonary vascular fibrosis, and inflammation. Accordingly, in vivo studies have demonstrated that pharmacological inhibition or cell-specific deletion of the MR can prevent disease progression and partially reverse established PH phenotypes. In this review, we summarize recent advances in MR signaling in pulmonary vascular remodeling based on preclinical research and discuss the potential, but also the challenges, in bringing MR antagonists (MRAs) into clinical application

Abstract: The heterocellular nature of the heart has been receiving increasing attention in recent years. In addition to cardiomyocytes as the prototypical cell type of the heart, non-myocytes such as endothelial cells, fibroblasts, or immune cells are coming more into focus. The rise of single-cell sequencing technologies enables identification of ever more subtle differences and has reignited the question of what defines a cell's identity. Here we provide an overview of the major cardiac cell types, describe their roles in homeostasis, and outline recent findings on non-canonical functions that may be of relevance for cardiology. We highlight modes of biochemical and biophysical interactions between different cardiac cell types and discuss the potential implications of the heterocellular nature of the heart for basic research and therapeutic interventions

Abstract: Background C-type natriuretic peptide (CNP) is an endothelium-derived paracrine molecule with an important role in vascular homeostasis. In septic patients, the serum level of the amino-terminal propeptide of CNP (NT-proCNP) shows a strong positive correlation with inflammatory biomarkers and, if elevated, correlates with disease severity and indicates a poor outcome. It is not yet known whether NT-proCNP also correlates with the clinical outcome of patients suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In the current study, we aimed to determine possible changes in the NT-proCNP levels of patients with coronavirus disease 2019 (COVID-19), with special regard to disease severity and outcome. Methods In this retrospective analysis, we determined the serum level of NT-proCNP in hospitalized patients with symptoms of upper respiratory tract infection, using their blood samples taken on admission, stored in a biobank. The NT-proCNP levels of 32 SARS-CoV-2 positive and 35 SARS-CoV-2 negative patients were measured to investigate possible correlation with disease outcome. SARS-CoV-2 positive patients were then divided into two groups based on their need for intensive care unit treatment (severe and mild COVID-19). Results The NT-proCNP was significantly different in the study groups (e.g. severe and mild COVID-19 and non-COVID-19 patients), but showed inverse changes compared to previous observations in septic patients: lowest levels were detected in critically ill COVID-19 patients, while highest levels in the non-COVID-19 group. A low level of NT-proCNP on admission was significantly associated with severe disease outcome. Conclusions Low-level NT-proCNP on hospital admission is associated with a severe COVID-19 disease course. The pathomechanism underlying this observation remains to be elucidated, while future studies in larger patient cohorts are necessary to confirm these observations and reveal therapeutic importance. Trial registration DRKS00026655 Registered 26. November 2021