Impact of hemoadsorption with CytoSorb® on meropenem and piperacillin exposure in critically ill patients in a post-CKRT setup: a single-center, retrospective data analysis.

Purpose: CytoSorb® (CS) adsorbent is a hemoadsorption filter for extracorporeal blood purification often integrated into continuous kidney replacement therapy (CKRT). It is primarily used in critically ill patients with sepsis and related conditions, including cytokine storms and systemic inflammatory responses. Up to now, there is no evidence nor recommendation for the use of CS filters in sepsis (22).

First Clinical Application of Aztreonam-Avibactam in Treating Carbapenem-Resistant Enterobacterales: Insights from Therapeutic Drug Monitoring and Pharmacokinetic Simulations.

: A novel fixed combination of aztreonam (ATM) and avibactam (AVI) offers promising potential to treat infections with carbapenem-resistant (CRE) producing metallo-β-lactamases (MBL). This study aimed to assess the accuracy of population pharmacokinetic (PK) models for ATM-AVI in predicting in vivo concentrations in a critically ill patient with CRE infection during its first clinical use. : A 70-year-old male with septic shock due to hospital-acquired pneumonia (HAP) caused by MBL-producing was treated with ATM-AVI.

Understanding Voriconazole Metabolism: A Middle-Out Physiologically-Based Pharmacokinetic Modelling Framework Integrating In Vitro and Clinical Insights.

Background And Objective: Voriconazole (VRC), a broad-spectrum antifungal drug, exhibits nonlinear pharmacokinetics (PK) due to saturable metabolic processes, autoinhibition and metabolite-mediated inhibition on their own formation. VRC PK is also characterised by high inter- and intraindividual variability, primarily associated with cytochrome P450 (CYP) 2C19 genetic polymorphism. Additionally, recent in vitro findings indicate that VRC main metabolites, voriconazole N-oxide (NO) and hydroxyvoriconazole (OHVRC), inhibit CYP enzymes responsible for VRC metabolism, adding to its PK variability.

Validating a composite endpoint for acceptability evaluation of oral drug formulations in the pediatric population: a randomized, open-label, single dose, cross-over study.

Objective: This study aimed to validate the newly developed composite acceptability endpoint to investigate acceptability of oral pediatric drug formulations that integrates swallowability and palatability assessments.

Methods: In this open-label study acceptability of oral formulations was tested in three age groups (1-<6 months, 6-<12 years, and 12-<18 years) with a 2-way cross-over design in children aged 1-<6 months (syrup and mini-tablets), and with an incomplete block design of four sequences with three out of four formulations (syrup, mini-tablets, oblong tablet, and round tablet) each in children aged 6-<18 years. The primary endpoint was acceptability derived from the composite acceptability endpoint.

Novel mathematical approach to accurately quantify 3D endothelial cell morphology and vessel geometry based on fluorescently marked endothelial cell contours: Application to the dorsal aorta of wild-type and Endoglin-deficient zebrafish embryos.

Endothelial cells, which line the lumen of blood vessels, locally sense and respond to blood flow. In response to altered blood flow dynamics during early embryonic development, these cells undergo shape changes that directly affect vessel geometry: In the dorsal aorta of zebrafish embryos, elongation of endothelial cells in the direction of flow between 48 and 72 hours post fertilization (hpf) reduces the vessel's diameter. This remodeling process requires Endoglin; excessive endothelial cell growth in the protein's absence results in vessel diameter increases.