{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T10:10:48Z","timestamp":1779358248461,"version":"3.51.4"},"reference-count":43,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T00:00:00Z","timestamp":1779321600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JPM"],"abstract":"<jats:p>Background: Persistent histologic inflammation may remain present in patients with inflammatory bowel disease (IBD) despite endoscopic remission. This study evaluated a clinically interpretable cytokine-based framework for risk stratification of residual histologic activity. Methods: In this prospective cohort study, 59 patients with IBD undergoing colonoscopy were included. Primary analyses were restricted to patients with ulcerative colitis (UC) in endoscopic remission (n = 31). Histologic activity was assessed using the Geboes score. Serum interleukin-10 (IL-10), interleukin-23 (IL-23), and C-reactive protein (CRP) were measured prior to endoscopy. Receiver operating characteristic (ROC) analysis and ROC-derived thresholds were used to evaluate biomarker performance and construct a cytokine-based risk stratification framework. Results: Among patients with UC in endoscopic remission, 14\/31 (45.2%) demonstrated persistent histologic activity. IL-10 showed the strongest discriminatory performance for histologic activity (AUC 0.850), with a threshold &lt; 3.9 pg\/mL associated with sensitivity of 84.6% and specificity of 77.8%. Similar performance was observed using raw assay-reported IL-10 values (AUC 0.906). IL-23 showed limited overall discrimination (AUC 0.615). A combined IL-10\/IL-23 framework stratified patients into progressively higher-risk subgroups, with histologic activity observed in 1\/14 patients (7.1%) in the low-risk subgroup, 1\/2 patients (50.0%) in the Intermediate A subgroup, 9\/12 patients (75.0%) in the Intermediate B subgroup, and 3\/3 patients (100%) in the high-risk subgroup (p &lt; 0.001), although estimates for smaller subgroups should be interpreted cautiously. Reduced IL-10 levels were independently associated with histologic activity, whereas IL-23 primarily refined subgroup classification without substantially improving discrimination. Conclusions: An exploratory cytokine-based framework incorporating IL-10 and IL-23 may support risk stratification of residual histologic activity in UC during endoscopic remission. Larger multicenter studies are required to validate these findings and define their clinical utility.<\/jats:p>","DOI":"10.3390\/jpm16050275","type":"journal-article","created":{"date-parts":[[2026,5,21]],"date-time":"2026-05-21T09:29:58Z","timestamp":1779355798000},"page":"275","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Personalized Risk Stratification of Residual Histologic Activity in IBD Using Circulating Cytokines"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0009-0006-6090-6076","authenticated-orcid":false,"given":"Nikolaos","family":"Martinos","sequence":"first","affiliation":[{"name":"Gastroenterology Department, Naval Hospital of Athens, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5876-2599","authenticated-orcid":false,"given":"Christos","family":"Kroupis","sequence":"additional","affiliation":[{"name":"Department of Clinical Biochemistry, Attikon University General Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilena","family":"Stamouli","sequence":"additional","affiliation":[{"name":"Department of Biochemistry, Athens Naval and Veterans Hospital, 11521 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8118-7780","authenticated-orcid":false,"given":"Andreas C.","family":"Lazaris","sequence":"additional","affiliation":[{"name":"First Department of Pathology, School of Medicine, National and Kapodistrian University of Athens, 11527 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Georgia-Eleni","family":"Thomopoulou","sequence":"additional","affiliation":[{"name":"Cytopathology Department, Attikon University General Hospital, National and Kapodistrian University of Athens, 12462 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,21]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1570","DOI":"10.1053\/j.gastro.2020.12.031","article-title":"STRIDE-II: An update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) initiative of the IOIBD","volume":"160","author":"Turner","year":"2021","journal-title":"Gastroenterology"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1324","DOI":"10.1038\/ajg.2015.233","article-title":"Selecting therapeutic targets in inflammatory bowel disease (STRIDE): Determining therapeutic goals for treat-to-target","volume":"110","author":"Sandborn","year":"2015","journal-title":"Am. 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