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Background: The risk of immune-related colitis (IRC) and efficacy of immune checkpoint inhibitors (ICIs) in patients with gastrointestinal cancers and preexisting ulcerative colitis (UC) has not been well described.
Patients And Methods: We divided the patients with gastrointestinal cancers and preexisting UC who received ICIs between January 2021 and May 2024 into two groups as IRC group and non-IRC group. The electronic medical records were reviewed to compare the risk of IRC between two groups. Survival analysis and COX regression was conducted to assess clinical efficacy.
Results: Of the 138 patients in study, 31 patients had a history of UC prior to initiation of immunotherapy. IRC occurred in 22 patients (71.0%) and over half experienced severe IRC (54.5%), a rate higher than that among similar patients without underlying UC (17.4%, = 0.013). Compared with patients without UC who did not experience IRC, PFS and OS of patients with UC who had mild IRC were longer (PFS: 170 vs 96 days, < 0.001; OS: 261 vs 172 days, = 0.021) and those with severe IRC demonstrated merely a marginal advantage in terms of PFS (147 vs 96 days, = 0.001), but no significant difference was observed in OS (171 vs 172 days, = 0.851). The Multivariate analysis affirmed that mild IRC were correlated with a favorable prognosis (HR = 0.286, 95%CI: 0.106-0.769, = 0.013), whereas severe IRC was not sufficient to be recognized as independent risk factors affecting survival outcomes. (HR = 1.149, 95%CI: 0.502-2.633, = 0.742). The result of serum cytokines showed that the levels of IL-6 and IL-17A in patients with IRC were significantly elevated.
Conclusion: For preexisting UC patients treated with ICIs, the risk of IRC is increased. Mild IRC may suggest a favorable prognosis, and being vigilant and effectively managing the occurrence of severe IRC is crucial for maximizing clinical benefits. Targeting the IL-6 pathway may be a potential new strategy for treating IRC in the future.
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http://dx.doi.org/10.3389/fimmu.2025.1627680 | DOI Listing |
Transl Psychiatry
August 2025
Social Stress and Family Health Research Group, Max Planck Institute for Human Cognitive and Brain Sciences, Leipzig, Germany.
Many refugees experience multiple traumatic events, which set them at increased risk to develop post-traumatic stress disorder (PTSD). To refine interventions aimed at improving refugees' mental health, a better understanding of the factors modulating vulnerability to war-related trauma is needed. In the present study, we focused on stress resonance as a potential vulnerability factor.
View Article and Find Full Text PDFEMBO Mol Med
August 2025
VIB Center for Inflammation Research, VIB, Ghent, Belgium.
Geranylgeranyl pyrophosphate, a non-sterol intermediate of the mevalonate pathway, serves as the substrate for protein geranylgeranylation, a process catalyzed by geranylgeranyl transferase I (GGTase-I). Myeloid-specific deletion of Pggt1b, the gene coding for GGTase-I, leads to spontaneous and severe erosive arthritis in mice; however, the underlying mechanisms remained unclear. In this study, we demonstrate that arthritis in mice with myeloid-specific Pggt1b deficiency is driven by unprenylated GTP-bound small RHO family GTPases, which in turn trigger Pyrin (Mefv) inflammasome activation, GSDMD-dependent macrophage pyroptosis, and IL-1β secretion.
View Article and Find Full Text PDFBiomedicines
August 2025
Department of Medicine, Surgery and Health Sciences, University of Trieste, 34149 Trieste, Italy.
North Carolina Macular Dystrophy (NCMD) is a non-progressive inherited macular dystrophy characterized by marked phenotypic variability. The genetic etiology of NCMD remains largely unknown, and only a limited number of families have been reported in Europe. : We performed an in-depth investigation of an Italian family affected by NCMD using an integrated approach that combined SNP-array analysis, whole-exome sequencing, and long-read whole-genome sequencing.
View Article and Find Full Text PDFBMC Public Health
August 2025
Department of Public health, College of Health Science, Salale University, Fiche, Ethiopia.
Background: Maintaining a healthy lifestyle is essential to lowering the global burden of non-communicable diseases. Living a healthy lifestyle reduces the likelihood of developing a severe illness or passing away too soon. Public officials frequently lead unhealthy lifestyles because they are time-pressed and face many challenges that could negatively impact their health.
View Article and Find Full Text PDFFront Immunol
August 2025
Department of Gastroenterology and Hepatology, Jinling Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China.
Background: The risk of immune-related colitis (IRC) and efficacy of immune checkpoint inhibitors (ICIs) in patients with gastrointestinal cancers and preexisting ulcerative colitis (UC) has not been well described.
Patients And Methods: We divided the patients with gastrointestinal cancers and preexisting UC who received ICIs between January 2021 and May 2024 into two groups as IRC group and non-IRC group. The electronic medical records were reviewed to compare the risk of IRC between two groups.