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Background and Aims During early phases of inflammation, activated neutrophils extrude neutrophil extracellular traps (NETs) in a peptidyl arginine deiminase 4 (PAD4)-dependent manner, aggravating tissue injury and remodeling. In this study, we investigated the potential pro-fibrotic properties and signaling of NETs in Crohn's disease (CD). Methods NETs and activated fibroblasts were labeled on resected ileum from CD patients by multiplex immunofluorescence staining. NETs-treated human primary intestinal fibroblasts were analyzed by bulk RNA sequencing to uncover cell signaling pathways, and by high-throughput imaging to assess collagen production and migratory activity. Consequentially, TLR2/NF-κB pathway was evaluated by transfection of CCD-18Co fibroblasts with an NF-κB-luciferase reporter plasmid, incorporating C29 to block TLR2 signaling. A chronic dextran sulfate sodium (DSS) mouse model was used to define the specific role of PAD4 deletion in neutrophils (MRP8 -Cre, Pad4 fl/fl). Results Immunofluorescence showed spatial colocalization of NETs and activated fibroblasts in ileal ulcerations of CD patients. Transcriptomic analysis revealed upregulation of pro-fibrotic genes and activation of Toll-like receptor signaling pathways in NETs-treated fibroblasts. NETs treatment induced fibroblast proliferation, diminished migratory capability, and increased collagen release. Transfection experiments indicated a substantial increase in an NF-κB expression with NETs, whereas C29 led to decreased expression and release of collagen. In line, a significant reduction in collagen content was observed in the colon of MRP8 -Cre, Pad4 fl/fl mice subjected to chronic DSS colitis. Conclusions NETs potentially serve as an initial stimulus for pathological activation of fibroblasts within the intestine via the TLR2/NF-κB pathway. Given their early involvement in inflammation, inhibition of PAD4 might offer a strategy to modulate both inflammation and fibrogenesis in CD. [ABSTRACT FROM AUTHOR]

Introduction Total colectomy for ulcerative colitis (UC) is associated with postoperative morbidity, including venous thromboembolic events (VTE). In light of recent concerns on increased major adverse events associated with JAK inhibitor exposure, we aimed to evaluate the postoperative VTE risk as well as other complications in UC patients undergoing colectomy. Methods This single-center retrospective cohort study included all UC patients who underwent (procto)colectomy between 2013 and March 2022, and documented the 180-day postoperative non-infectious and infectious complications. Results One hundred seventy-five UC patients (43.4% women, median age 41.0 years) underwent colectomy. Forty-nine patients (28.0%) were operated in an urgent setting. In the twelve weeks prior to surgery, 53 (30.3%) patients had received anti-TNF agents, 40 (22.9%) anti-adhesion therapy, 16 (9.1%) anti-IL12/23 and 34 (19.4%) JAK inhibitors. Preoperatively, 26 patients (14.9%) received moderate to high doses of systemic corticosteroids. All except two patients received prophylactic LMWH postoperatively. During the 180-day postoperative period, 2 patients developed a thrombosis, all incidental findings on abdominal CT scan. No VTE was seen in the patients who underwent colectomy while on JAK inhibitor. Three out of 34 JAK-inhibitor treated patients (8.8%) developed a postoperative infectious complication, while the overall incidence of infectious complications was 17.1%. Conclusion Our findings suggest that the overall VTE risk in UC patients undergoing colectomy is low with adequate antithrombotic prophylaxis. JAK inhibitor use prior to surgery was not linked to increased short-term thromboembolic or infectious complications. However, the limited sample size warrants further study in larger cohorts., (S. Karger AG, Basel.)

Background: We aimed to evaluate the impact of advanced medical therapies (biologicals and small molecules) on time to colectomy and oncological outcomes in ulcerative colitis (UC)., Methods: This cohort study included UC patients who underwent colectomy between 2003 and 2022 at 2 referral centers in Belgium and the Netherlands. Exposure was the use of advanced medical therapies. Primary outcomes were time to colectomy and colorectal cancer (CRC) rate, compared between 4 periods: P1 (2003-2007), P2 (2008-2012), P3 (2013-2017), and P4 (2018-2022). Secondary outcomes were oncological outcomes, including incidental cancers found unexpectedly in resection specimens or during endoscopic follow-up for medication switch., Results: Among 716 patients, the usage of advanced therapies increased from 36.8% in P1 to 89.7% in P4 (P < .0001). Median time to colectomy remained comparable (P1: 7.1 years [interquartile ranges (IQR), 2.8-12.9] vs P4: 7.2 years [IQR, 2.7-14.6]; P = not significant). Colectomy and colorectal cancer was diagnosed in 72 (10.1%) patients, with no significant change over time (P = .44). Proportion of CRC was lower in patients treated with advanced therapies (4.7% vs 23.6%, P < .0001) and related to a shorter follow-up (median 6.1 vs 10.3 years, P < .0001). Advanced therapy patients had higher incidental cancer rates (37.5% vs 8.3%, P = .002), which was associated with reduced CRC-related survival (HR for CRC-related death: 3.3, 95% CI 1.17-9.4; P = .02)., Conclusion: Despite increased usage of advanced medical therapies, time to resection and CRC rates have remained unchanged in UC patients undergoing colectomy over the past 2 decades. Advanced therapy patients had higher incidental cancers rates, associated with decreased CRC survival. Awareness of timely colectomy is crucial for this group., (© The Author(s) 2025. Published by Oxford University Press on behalf of European Crohn’s and Colitis Organisation.)

Background: Ventral rectopexy has become increasingly utilized in the surgical management of rectal prolapse. There is a need for a contemporary evaluation of the role of the procedure and description of its use in clinical practice., Objective: To create an international consensus on ventral rectopexy., Design: An expert panel undertook a scoping review of the literature to identify subject domains of interest. Literature reviews were completed for each domain with subsequent development of evidence-based and practice-based statements. These were compiled and reviewed by the group over a total of nine meetings. Once statements were confirmed, supportive text was finalized, and an anonymous vote was completed using REDCap to record consensus., Setting: An international expert panel comprising colorectal surgeons who perform ventral rectopexy in a high-volume center., Main Outcome Measures: Statements and associated expert consensus., Results: Eleven experts identified ten domains for review: indications, contraindications, assessment and planning, consent, operative details, prostheses, complications, follow-up, recurrence and reoperative surgery and specific considerations. After round-table review, there were 17 resultant statements for consideration. Experts agreed unanimously with the thirteen of the statements and their accompanying text, with different experts disagreeing each with four statements (91% consensus each)., Limitations: Paucity of high-quality data., Conclusion: This international group developed 17 statements with high consensus. These statements provide an up-to-date summary of the literature, identify key areas for research development and a reference point for colon and rectal surgeons who undertake ventral rectopexy as part of their practice. See Video Abstract., (Copyright © 2025 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Society of Colon and Rectal Surgeons.)