Iron Regulatory Protein 1 is Required for the Propagation of Inflammation in Inflammatory Bowel Disease.

Inflammatory bowel diseases (IBD) are complex disorders. Iron accumulates in the inflamed tissue of IBD patients, yet neither a mechanism for the accumulation nor its implication on the course of inflammation are known. We hypothesized that the inflammation modifies iron homeostasis, affects tissue iron distribution and that this in turn perpetuates the inflammation. This study analyzed human biopsies, animal models and cellular systems to decipher the role of iron homeostasis in IBD. We found inflammation-mediated modifications of iron distribution, and iron-decoupled activation of the iron regulatory protein (IRP)1. To understand the role of IRP1 in the course of this inflammation-associated iron pattern, a novel cellular co-culture model was established, that replicated the iron-pattern observed in vivo, and supported involvement of nitric oxide in the activation of IRP1 and the typical iron pattern in inflammation. Importantly, deletion of IRP1 from an IBD mouse model completely abolished both, the misdistribution of iron and intestinal inflammation. These findings suggest that IRP1 plays a central role in the coordination of the inflammatory response in the intestinal mucosa and that it is a viable candidate for therapeutic intervention in IBD.

Comparative evaluation of a language model and human specialists in the application of European guidelines for the management of inflammatory bowel diseases and malignancies.

BACKGROUND: Society guidelines on colorectal dysplasia screening, surveillance, and endoscopic management in inflammatory bowel disease (IBD) are complex, and physician adherence to them is suboptimal. We aimed to evaluate the use of ChatGPT, a large language model, in generating accurate guideline-based recommendations for colorectal dysplasia screening, surveillance, and endoscopic management in IBD in line with European Crohn's and Colitis Organization (ECCO) guidelines. METHODS: 30 clinical scenarios in the form of free text were prepared and presented to three separate sessions of ChatGPT and to eight gastroenterologists (four IBD specialists and four non-IBD gastroenterologists). Two additional IBD specialists subsequently assessed all responses provided by ChatGPT and the eight gastroenterologists, judging their accuracy according to ECCO guidelines. RESULTS: ChatGPT had a mean correct response rate of 87.8%. Among the eight gastroenterologists, the mean correct response rates were 85.8% for IBD experts and 89.2% for non-IBD experts. No statistically significant differences in accuracy were observed between ChatGPT and all gastroenterologists (P=0.95), or between ChatGPT and the IBD experts and non-IBD expert gastroenterologists, respectively (P=0.82). CONCLUSIONS: This study highlights the potential of language models in enhancing guideline adherence regarding colorectal dysplasia in IBD. Further investigation of additional resources and prospective evaluation in real-world settings are warranted.