Acute leukaemias are rare but highly aggressive malignancies, but only limited population-level data are available for Germany. We aimed to describe epidemiology, survival, and therapies of acute myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL) in Germany using nationwide cancer registry data. We conducted a population-based analysis of all incident cases of AML and ALL in Germany, identified via ICD codes from mandatory cancer registry reporting, to assess incidence, treatment, and survival outcomes. We identified 25,788 patients with AML and 6480 patients with ALL diagnosed between 2016 and 2021 aged 0–101 years. The age-standardized incidence rate was 4.72/100,000 for AML (median age 72.8 years, IQR 61.0–80.3) and 1.36/100,000 for ALL (median age 19.4 years, IQR 5.2–58.6). The three- and five-year overall survival was 29.0% (95% CI: 28.3–29.7) and 23.8% (95% CI: 23.1–24.7) in AML, and 64% (95% CI: 62.2–65.9) and 58% (95% CI: 55.7–60.2) in ALL. Survival was highly dependent on age, with children (0–18 years) showing the highest three-year survival rates in AML (76.4%, 95% CI: 70.2–83.2) and ALL (91.9%, 95% CI: 89.8–94.1) compared to older adults. Moreover, area-based income and social deprivation were linked to survival, with three-year survival reduced by up to 4% in lower-income counties. Based on German federal population estimates, AML cases are expected to rise by 14.6%, while ALL cases will decline by 2.3% between 2020 and 2050. We provide incidence and survival data to inform future clinical trials, guide resource allocation, and support healthcare planning to improve real-world outcomes and address disparities in acute leukaemia. 10.13039/501100001659 German Research Foundation (DFG).

Background: Heavy calcifications in severe aortic stenosis (AS) pose a major challenge in patients undergoing transcatheter aortic valve replacement (TAVR). Only a few studies have addressed the performance of different transcatheter heart valves (THV) in this subgroup of patients. Objectives: We aimed to investigate the outcomes of the self-expanding Medtronic CoreValve Evolut valve frame and the balloon-expandable Edwards SAPIEN-3/3 Ultra THV in this challenging patient population. Materials and methods: This was a multicenter registry including a total of 1513 patients with heavily calcified AS undergoing TAVR. The primary endpoint was the incidence and degree of paravalvular leak (PVL) after TAVR. Secondary endpoints were post-implant hemodynamics as well as clinical endpoints according to the VARC-3 definitions. Results: The CoreValve Evolut R but not the Evolut PRO showed significantly higher rates of PVL compared to the SAPIEN-3/3 Ultra (44.8% vs. 29.5% for mild PVL, p < 0.001), while there was no significant difference in ≥ moderate PVL between both groups (p = 0.399). The CoreValve Evolut R and Evolut PRO showed superior THV hemodynamics compared to the SAPIEN-3/3 Ultra group. These findings were confirmed in a propensity score-matched analysis. There were no significant differences regarding short-term outcomes including permanent pacemaker implantation and all-cause mortality between the three groups. Conclusion: In patients with severely calcified AS, both CoreValve Evolut PRO and SAPIEN-3/3 Ultra THV showed lower rates of PVL than the CoreValve Evolut R. The self-expanding CoreValve platform had superior post-implant hemodynamics than the SAPIEN-3/3 Ultra system. Graphical

Targeted gene delivery to vascular smooth muscle cells (VSMCs) could prevent or improve a variety of diseases affecting the vasculature and particularly the aorta. Thus, we aimed to develop a delivery vector that efficiently targets VSMCs. We selected engineered adeno-associated virus (AAV) capsids from a random AAV capsid library and tested the top enriched motifs in parallel screening through individual barcoding. This approach allowed us to distinguish capsids that only transduce cells based on genomic DNA (gDNA) from those also mediating transgene expression based on transcribed cDNA reads. After three rounds of selection on primary murine VSMCs (mVSMCs), we identified a novel targeting motif (RFTEKPA) that significantly improved transduction and gene expression efficiency over AAV9-wild type (WT) and increased expression in mVSMCs by 70% compared to the previously identified SLRSPPS peptide. Further analysis showed that the novel motif also improved expression in human aortic smooth muscle cells (HAoSMCs) and human aortic tissue ex vivo up to threefold compared to SLRSPPS and approximately 70-fold to AAV9-WT. This high cross-species transduction efficiency makes the novel capsid motif a potential candidate for future clinical application in vascular diseases.

Aims: CAR-T cell therapy is becoming a key pillar of medical oncology, used for an expanding range of indications. Considering the increased risk of cardiovascular disease with increasing age, assessing the impact of cardiac comorbidities can help minimizing complications and improve treatment outcomes. Methods: We evaluated cardiovascular outcomes in patients undergoing CD19- or BCMA-directed CAR T-cell therapy from two large independent databases (DESTATIS (Germany) and the TriNetX network (US)). Results: Among 2,545 CAR T-cell cases from Germany and 1,335 patients from the US, we identified 51 respective 20 short-term severe cardiac events with early death documented in 135 (5%) and 16 (1.2%) patients. Patients with preexisting cardiac conditions did not show an increased risk for immune-related complications like cytokine release (OR 1.19, 95%CI 0.77-1.82) or neurotoxicity syndrome (OR 1.59, 95%CI 0.94-2.69). They faced higher long-term risks for major cardiovascular events (OR 1.89, 95%CI 1.23-2.91) and kidney failure (OR 2.98, 95%CI 1.85-4.81). Conclusion: Cardiovascular complications in CAR T-cell therapy were rare and primarily affected patients with preexisting cardiac conditions. Serious cardiac events were uncommon acutely but increased over time. The analysis underscores the need for risk-adapted follow-up and cardiological assessments to improve outcomes in patients with cardiac comorbidities. Inherent with the databases used, these results should be interpreted with caution, as underreporting and overreporting could introduce bias regarding risik factors and outcomes in both directions.

This comparative study examines the transition from isolated registries to a consolidated data-centric approach at University Hospital Schleswig-Holstein, focusing on migrating the Atrioventricular Valve Intervention Registry (AVIR) from REDCap to a Medical Data Integration Center based openEHR registry. Through qualitative analysis, we identify key disparities and strategic decisions guiding this transition. While REDCap has historical utility, its limitations in automated data integration and traceability highlight the advantages of a data-centric approach, which include streamlined data (integration) management at a single-point-of-truth based on e.g., centralized consent management. Our findings lay the groundwork for the AVIR project and a proof-of-concept data-centric registry, reflecting a broader industry trend towards data-centric healthcare initiatives.

Understanding the molecular mechanisms that maintain protein homeostasis in cardiomyocytes is fundamental for the development of causal therapies for heart failure. Chaperones, the ubiquitin–proteasome system and autophagy are major regulators of cardiac homeostasis and are crucial for cardiomyocyte function and survival. In this context, myeloid leukaemia factor 2 (MLF2) emerged as a candidate of interest, as we found it overrepresented in protein aggregates in the hearts of mouse models of desmin-related cardiomyopathies (DRM), and it has also been suggested to be associated with dilated cardiomyopathy (DCM). Here, we identified αB-crystallin (CryAB), among other proteins, as a potential interaction partner of MLF2. Functionally, MLF2 was significantly upregulated in mouse models of heart failure and in two in vitro models of cardiomyocyte hypertrophy, and its overexpression resulted in attenuation of pro-hypertrophic gene expression. Taken together, these findings provide initial evidence supporting a role for MLF2 in regulating protein homeostasis and in modulating hypertrophic signalling in cardiomyocytes.