Assessment of the potential of the MET inhibitor tepotinib to affect the pharmacokinetics of CYP3A4 and P-gp substrates.

Tepotinib is a highly selective, potent, mesenchymal-epithelial transition factor (MET) inhibitor, approved for the treatment of non-small cell lung cancer harboring MET exon 14 skipping alterations. The aims of this work were to investigate the potential for drug-drug interactions via cytochrome P450 (CYP) 3A4/5 or P-glycoprotein (P-gp) inhibition. In vitro studies were conducted in human liver microsomes, human hepatocyte cultures and Caco-2 cell monolayers to investigate whether tepotinib or its major metabolite (MSC2571109A) inhibited or induced CYP3A4/5 or inhibited P-gp.

Meta-analysis of full ROC curves using bivariate time-to-event models for interval-censored data.

Systematic reviews and meta-analyses are the cornerstones of evidence-based medicine and inform treatment, diagnosis, or prevention of individual patients as well as policy decisions in health care. Statistical methods for the meta-analysis of intervention studies are well established today. Meta-analysis for diagnostic accuracy trials has also been a vivid research area in recent years, which is especially due to the increased complexity of their bivariate outcome of sensitivity and specificity.

Alternative technique of the right atrial anastomosis (cavo-atrial) in orthotopic heart transplantation.

An alternative technique of the right atrial anastomosis in heart transplantation, which allows a more anatomical reconstruction of the right atrium and is easier in handling than bi-caval anastomoses is described.

Differential coupling of m-cholinoceptors to Gi/Go-proteins in failing human myocardium.

Muscarinic acetylcholine receptors (mAChRs) mediate their main cardiac effects via pertussis toxin-sensitive G-proteins. Physiological effects differ considerably between atrium and ventricle, and it is unknown to which extent these differences derive from selective receptor-G-protein coupling or further downstream events. We have characterized specific coupling between mAChRs and Gi/Go-protein isoforms in atrial and ventricular myocardium by agonist-dependent photoaffinity labeling with [(32)P]azidoanilido GTP (aaGTP) and immunoprecipitation in sarcolemmal membranes from terminally failing human hearts.