Association between continuity of care and inappropriate prescribing in outpatient care in Germany: a cross-sectional analysis conducted as part of the LoChro trial.

Objectives: Potentially inappropriate medications (PIMs) and potential prescribing omissions (PPOs) are common in multimorbid patients. This study aims to describe PIMs and PPOs in an open-access outpatient setting and to investigate any association between continuity of care (CoC) and PIMs and PPOs in multimorbid older patients.

Design: Cross-sectional study using patient-confirmed outpatient medication plans to describe PIMs and PPOs using the 'Screening Tool of Older Person's Prescription/Screening Tool to Alert to Right Treatment' version 2.

Pan-cancer profiling of tumor-infiltrating natural killer cells through transcriptional reference mapping.

The functional diversity of natural killer (NK) cell repertoires stems from differentiation, homeostatic, receptor-ligand interactions and adaptive-like responses to viral infections. In the present study, we generated a single-cell transcriptional reference map of healthy human blood- and tissue-derived NK cells, with temporal resolution and fate-specific expression of gene-regulatory networks defining NK cell differentiation. Transfer learning facilitated incorporation of tumor-infiltrating NK cell transcriptomes (39 datasets, 7 solid tumors, 427 patients) into the reference map to analyze tumor microenvironment (TME)-induced perturbations.

Egr2 to the rescue: nanoparticles revitalize natural killer cells in the fight against cancer.

Reversal of tumor-induced natural killer (NK) cell dysfunction remains a major hurdle to overcome for the clinical success of immunotherapies based on NK cells targeting solid tumors. New research in The EMBO Journal identifies the transcription factor early growth response gene 2 (Egr2) and diacylglycerol kinase DGKα as two negative regulators of NK cell dysfunction (Sabag et al, 2024).

Optimisation of a primary human CAR-NK cell manufacturing pipeline.

Objectives: Autologous chimeric antigen receptor (CAR) T-cell therapy of B-cell malignancies achieves long-term disease remission in a high fraction of patients and has triggered intense research into translating this successful approach into additional cancer types. However, the complex logistics involved in autologous CAR-T manufacturing, the compromised fitness of patient-derived T cells, the high rates of serious toxicities and the overall cost involved with product manufacturing and hospitalisation have driven innovation to overcome such hurdles. One alternative approach is the use of allogeneic natural killer (NK) cells as a source for CAR-NK cell therapy.

Cell-cycle inhibition and immune microenvironment in breast cancer treated with ribociclib and letrozole or chemotherapy.

In this study, we performed genomic analyses of cell cycle and tumor microenvironment changes during and after ribociclib and letrozole or chemotherapy in the CORALLEEN trial. 106 women with untreated PAM50-defined Luminal B early breast cancers were randomly assigned to receive neoadjuvant ribociclib and letrozole or standard-of-care chemotherapy. Ki67 immunohistochemistry, tumor-infiltrating lymphocytes quantification, and RNA sequencing were obtained from tissue biopsies pre-treatment, on day 14 of treatment, and tumor specimens from surgical resection.