Academic medical centres in the Netherlands: muddling through or radical change?

Introduction: Academic medical centres (AMCs) are designed to perform multiple tasks within a single organisation. This institutional complexity gives rise to intricate governance challenges and promotes incrementalism and muddling.

Method: In this study, we hypothesised that radical change could provide a solution to the current incrementalism and we explored the conditions under which such changes could or could not be achieved.

Case Report: A severe case of immunosuppressant-refractory immune checkpoint inhibitor-mediated colitis rescued by tofacitinib.

Immune checkpoint inhibitor therapy for cancer treatment can give rise to a variety of adverse events. Here we report a male patient with metastatic melanoma who experienced life-threatening colitis and duodenitis following treatment with ipilimumab and nivolumab. The patient did not respond to the first three lines of immunosuppressive therapy (corticosteroids, infliximab, and vedolizumab), but recovered well after administration of tofacitinib, a JAK inhibitor.

Identification of Fusion Genes and Targets for Genetically Matched Therapies in a Large Cohort of Salivary Gland Cancer Patients.

Salivary gland cancer (SGC) is a rare cancer for which systemic treatment options are limited. Therefore, it is important to characterize its genetic landscape in search for actionable aberrations, such as gene fusions. This research aimed to identify these actionable aberrations by combining NGS-based analysis of RNA (gene fusions) and DNA (single and multiple nucleotide variants, copy number variants, microsatellite instability and tumor mutational burden) in a large cohort of SGC patients.

Drug Discovery and Repurposing Inhibits a Major Gut Pathogen-Derived Oncogenic Toxin.

The human intestinal microbiome plays an important role in inflammatory bowel disease (IBD) and colorectal cancer (CRC) development. One of the first discovered bacterial mediators involves toxin (BFT, also named as fragilysin), a metalloprotease encoded by enterotoxigenic (ETBF) that causes barrier disruption and inflammation of the colon, leads to tumorigenesis in susceptible mice, and is enriched in the mucosa of IBD and CRC patients. Thus, targeted inhibition of BFT may benefit ETBF carrying patients.