The Rechts der Isar Hospital (Hospital to the right of the Isar) is a hospital in the Haidhausen district of Munich, Germany. It is the teaching hospital and biomedical research facility of the TUM School of Medicine.
GPR3 belongs to the protein superfamily of G protein-coupled receptors (GPCRs) and plays a central role in both benign and malignant physiological processes, such as energy expenditure in adipocytes and Alzheimer's disease pathology, respectively. Despite the therapeutic potential of both receptor agonists and inverse agonists, GPR3 so far has lacked drug-like ligands and innovative screening technologies, hindering effective drug discovery efforts targeting this receptor. To overcome the limitations of conventional ligand screening techniques based on cAMP accumulation or β-arrestin recruitment, we developed a conformational GPR3 biosensor to monitor receptor activity in living cells with high-throughput screening (HTS)-compatible sensitivity and robustness. Combined with virtual compound screening against homology models of GPR3 and classical medicinal chemistry, this biosensor enabled us to identify new ligands, one of which (compound 33) modulates GPR3-dependent Gs activity with an average potency in the nanomolar range. Our study not only presents novel GPR3 ligands for future optimization efforts and paves the way for even further expansion of the GPR3 ligand repertoire, but our sensor approach also provides a blueprint for targeting other therapeutically attractive yet challenging orphan GPCRs.
Background:Understanding the prevalence of pneumococcal serotypes in hospitalised patients with community-acquired pneumonia (CAP) is critical for vaccine development and implementation of future public health policies. Pneumococcal conjugate vaccines (PCVs) have been implemented to decrease the burden of pneumococcal disease. This study aims to identify the serotype distribution of pneumococcal CAP in Germany. Methods:This interim analysis of a multicentre, prospective, active observational study includes patients aged ≥18 years hospitalised with CAP in seven German hospitals. Patients were enrolled between August 2022 and September 2024. To determine CAP aetiology, microbiological tests were performed according to local standard of care. Urinary antigen testing for Streptococcus pneumoniae (BinaxNOW) was performed in all patients, and two serotype-specific urinary antigen detection (SSUAD) assays were used to detect serotypes in pneumococcal vaccines PCV15 and PCV20. Results:S. pneumoniae was detected in 16.5% (85/514) of participants by all diagnostic tests. SSUAD assays detected S. pneumoniae as pathogen in 13.2% (68/514) of participants. In six patients, two pneumococcal serotypes were detected. The seven most detected serotypes were: 3, 11A, 8, 23B, 9N, 18C and 22F. Among 74 serotype detections, 64 (86.9%) are included in V116 compared with 56 (75.8%) in PCV20. The difference in coverage between PCV20 and V116 was 10.8% (95% CI -3.2-24.8%). Conclusion:Among adults hospitalised with CAP in Germany, S. pneumoniae was detected in 13% of cases by SSUAD assays. While the findings suggest that V116 may offer broader serotype coverage compared with PCV20, these differences were not statistically significant.
In Deutschland sind gegenwärtig mindestens 1,8 Millionen von Demenz betroffen; bis 2060 droht ein Anstieg auf 2,1 Millionen Betroffene. Prävention bietet die derzeit beste Möglichkeit zur effektiven Linderung der Krankheitslast. Das Krankheitsrisiko und der Krankheitsverlauf sowie die Effektivität von Präventionsmaßnahmen werden von diversen Faktoren beeinflusst; in Kombination ergeben diese potenziell individuelle Risikoprofile als Grundlage für eine effektive Demenzprävention. Die Hebung dieser Potenziale erfordert kurzfristig insbesondere eine bessere Nutzung bestehender Daten inklusive einer erweiterten Datenerfassung und Nutzbarmachung für die Forschung, wodurch bevölkerungsbasierte Screening- und Interventionsmaßnahmen entwickelt und eine Strategie zur personalisierten Demenzprävention realisiert werden können.
Background Venous thromboembolism (VTE) is a major cause of preventable in-hospital mortality, yet disease-specific risk profiles remain poorly defined. In pancreatitis, one of the most common gastrointestinal causes of hospitalisation, thromboembolic complications are under-recognised, with limited data, especially on extrasplanchnic events. Evidence guiding screening and management remains scarce. We analysed VTE events in a large prospective cohort of patients with acute and chronic pancreatitis and derived a simple admission-time clinical risk score to support early identification of high-risk individuals.Methods We performed a retrospective analysis of a prospectively recruited cohort at LMU Klinikum Munich, a referral centre for pancreatic diseases. Patients with acute, acute-on-chronic or chronic pancreatitis evaluated between January 2018 and June 2023 were included. Comprehensive clinical, laboratory, imaging and outcome data were extracted. The primary objective was to identify admission-time factors associated with VTE and develop a clinically actionable risk score. Continuous variables were dichotomised using receiver operating characteristic (ROC)-derived optimal cut-points. Binary predictors were entered into a multivariable logistic regression model, and coefficients were scaled to generate an integer-based point score. Discrimination was assessed using the area under the ROC curve (AUC), and patients were stratified into low-risk, intermediate-risk and high-risk groups.Results Among 647 patients, 114 (17.6%) developed VTE, with similar incidence rates in acute (59, 16.2%) and chronic pancreatitis (55, 19.5%). Deep vein thrombosis (5.9%) and pulmonary embolism (4.2%) were the most frequent events. Patients with VTE experienced significantly worse clinical courses, including longer hospitalisation (15 vs 7 days, p<0.001), higher rates of severe pancreatitis and increased need for advanced analgesia. Thrombosis was associated with lower diastolic blood pressure, reduced oxygen saturation, tachycardia, older age and lower body mass index at admission as well as higher rates of systemic and local complications. Mortality was markedly higher in patients with VTE (8.8% vs 2.1%, p=0.029). A six-item admission-only risk score (0–8 points) demonstrated good discrimination (AUC 0.71) and effectively stratified patients into low-risk (7.6%), intermediate-risk (22.0%) and high-risk groups (38.5%).Conclusion VTE is common in pancreatitis and strongly associated with adverse outcomes. A simple admission-time clinical score reliably identifies high-risk patients and may support earlier recognition, targeted diagnostic evaluation and risk stratification.
