Transcatheter aortic valve replacement in patients with severe aortic valve stenosis and concomitant mitral valve regurgitation - 5 years follow-up.

Objectives: To investigate the change in severity of mitral regurgitation (MR) after transcatheter aortic valve replacement (TAVR) and its effect on 5-year mortality. Background: There is inconsistency in literature on pre-existing MR influencing long-term survival in patients who undergo TAVR. Methods: Patients who underwent TAVR at the University Hospital Schleswig-Holstein (USKH) Campus Kiel between March 2009 and February 2018 have been enrolled. Echocardiography determined the degree of MR before and within 7 days after TAVR. Patients were divided into two groups according to their MR at baseline: MR-grade ≤ 2 (non-relevant MR, nr-MR) and baseline MR-grade > 2 (relevant MR, r-MR). Primary endpoint was a composite of MR baseline influence on mortality and MR reduction and its' impact on mortality. Results: A total of 820 patients (642 nr-MR and 178 in r-MR) were included in this study. Of these, 167 patients showed an improvement in MR-grade. Thereof 106 (63.5 %) referred to r-MR with a significant decrease in mean MR-grade (p < 0.01). Systolic pulmonary artery pressure (sPAP) (p < 0.01) and NT-proBNP (p = 0.03) decreased in patients who had an improvement. There was no significant difference in 5-year mortality for MR at baseline (p = 0.35) or reduction in mortality for r-MR patients with an MR improvement compared to patients with worsening or equal MR status (p = 0.80). Conclusion: In patients undergoing TAVR, 63.5 % of patients with MR-grade ≥ 2 at baseline showed an improvement of grade of MR after TAVR with reduction of their sPAP and NT-proBNP values but there was no significant difference in mortality.

The Intersectoral Coordination Unit for the Sustainable Intensification of Peritoneal Dialysis in Schleswig-Holstein (SKIP-SH) cohort study.

BACKGROUND: Peritoneal dialysis (PD) remains underutilised in Germany, prompting the initiation of the Sustainable Intensification of Peritoneal Dialysis in Schleswig-Holstein (SKIP-SH) project. The SKIP-SH cohort study aims to demonstrate the presumed benefits of PD, including enhanced quality of life and reduced healthcare personnel requirements, and to generate data to strengthen the use of PD. METHODS: The prospective SKIP-SH cohort study recruits patients with advanced chronic kidney disease (CKD) and their caregivers. Comprehensive data, including demographic information, medical history, clinical course, laboratory data, and quality-of-life assessments, are collected. Additionally, biomaterials will be obtained. Primary study objectives are documenting the clinical course and complications, time on therapy for new dialysis patients, reasons influencing treatment modality choices, circumstances at the initiation of dialysis, and quality of life for patients with CKD and their caregivers. The collected biomaterials will serve as a basis for further translational research. Secondary objectives include identifying factors impacting disease-related quality of life, clinical complications, and therapy dropout, estimating ecological footprints, and evaluating healthcare costs and labour time for initiating and sustaining PD treatment. DISCUSSION: PD is notably underutilised in Germany. The current therapy approach for advanced CKD often lacks emphasis on patient-focused care and quality-of-life considerations. Furthermore, adequate explorative research programs to improve our knowledge of mechanisms leading to disease progression and therapy failure in PD patients are scarce. The overarching goal of the SKIP-SH cohort study is to address the notably low PD prevalence in Germany whilst advocating for a shift towards patient-focused care, quality-of-life considerations, and robust translational research. TRIAL REGISTRATION: This study was registered with the German trial registry (Deutsches Register klinischer Studien) on November 7, 2023, under trial number DRKS00032983.

Epidemiology of haemophagocytic lymphohistiocytosis at the population level in Germany.

We retrospectively analysed all German inpatient cases of haemophagocytic lymphohistiocytosis (HLH) from 2014 to 2020 to describe the epidemiology, clinical course, and underlying diseases of 4065 HLH patients. The age-standardized incidence rate of HLH in Germany was 0.52/100 000 people in 2014 and steadily increased by 10% per year to 0.97/100 000 in 2020 (mean 0.70/100 000). Inpatient deaths related to HLH increased from 0.84/1 000 000 people in 2014 to 2.32/1 000 000 people in 2020, caused by rising numbers of older HLH patients. Overall, HLH is more frequent than previously expected and incidence as well as HLH-related deaths increased significantly.

RhoA: a dubious molecule in cardiac pathophysiology.

The Ras homolog gene family member A (RhoA) is the founding member of Rho GTPase superfamily originally studied in cancer cells where it was found to stimulate cell cycle progression and migration. RhoA acts as a master switch control of actin dynamics essential for maintaining cytoarchitecture of a cell. In the last two decades, however, RhoA has been coined and increasingly investigated as an essential molecule involved in signal transduction and regulation of gene transcription thereby affecting physiological functions such as cell division, survival, proliferation and migration. RhoA has been shown to play an important role in cardiac remodeling and cardiomyopathies; underlying mechanisms are however still poorly understood since the results derived from in vitro and in vivo experiments are still inconclusive. Interestingly its role in the development of cardiomyopathies or heart failure remains largely unclear due to anomalies in the current data available that indicate both cardioprotective and deleterious effects. In this review, we aimed to outline the molecular mechanisms of RhoA activation, to give an overview of its regulators, and the probable mechanisms of signal transduction leading to RhoA activation and induction of downstream effector pathways and corresponding cellular responses in cardiac (patho)physiology. Furthermore, we discuss the existing studies assessing the presented results and shedding light on the often-ambiguous data. Overall, we provide an update of the molecular, physiological and pathological functions of RhoA in the heart and its potential in cardiac therapeutics.