Ouali, Sara El

INTRODUCTION: Computed tomography enterography (CTE) is a noninvasive cross-sectional imaging modality routinely used for diagnosis of Crohn's disease (CD) strictures. However, CTE is limited in individually defining the severity of inflammation, fibrosis, or smooth muscle hyperplasia/hypertrophy (SMH) within such strictures. We developed and internally validated a radiomics-based machine learning model for separately characterizing the degree of histopathological inflammation, fibrosis, and SMH in CD strictures and compared it with centrally read visual radiologist scoring of CTE. METHODS: This single-center, cross-sectional study included 100 patients with CD (n = 66 for discovery; n = 34 for validation) with terminal ileal strictures confirmed on diagnostic CTE within 15 weeks of intestinal resection. Histopathological specimens were scored for inflammation, fibrosis, and SMH and spatially linked with corresponding pre-surgical CTE sequences. Annotated stricture regions on CTE were scored visually by radiologists as well as underwent three-dimensional radiomics-based machine-learning analysis; both evaluated against histopathology scoring. RESULTS: Three distinct sets of radiomic features capturing textural heterogeneity within strictures were separately linked with severe inflammation, fibrosis, and SMH across both discovery (accuracy = 0.74, 0.71, 0.71, respectively) and validation (accuracy = 0.74, 0.68, 0.68, respectively) cohorts. Radiologist visual scoring was limited, with accuracy of 0.51 for identifying severe inflammation, 0.48 for severe fibrosis, and 0.58 for severe SMH. Augmenting radiologist scoring with radiomic features yielded improved performance in identifying severe inflammation, fibrosis, or SMH compared to radiologist scoring alone. DISCUSSION: Radiomic features of CD strictures on CTE can identify severe histopathological fibrosis, inflammation, and smooth muscle hyperplasia and perform better than radiologist visual scoring in stricture characterization.

Abstract Background & Aims Stricturing Crohn’s disease (CD) is a significant problem, and no selective anti-fibrotic therapies are available. Anti-inflammatory approaches are the mainstay of medical treatment. However, data on the efficacy of ustekinumab (USTE) in ileal stricturing CD are lacking. Our aim was to assess its efficacy in this setting. Methods We performed an international multicenter observational cohort study evaluating adult CD patients who received USTE within 6 months of imaging-confirmed symptomatic stricturing small bowel disease. Outcomes were rates of endoscopic balloon dilation (EBD), surgery, intervention (defined as the composite need for EBD or surgery), recurrent obstructive symptoms, and USTE persistence. Results Fifty-seven patients were included (51% female, median age 43 years). Median follow-up was 17 months. Intervention rates were 35%, 45%, and 69% of patients, at 12, 24, and 48 months, respectively. USTE persistence was 78%, 76%, and 52% at 12, 24, and 48 months. Estimated obstructive symptoms rates were 31% and 49% at 12 and 24 months, respectively. EBD within 6 months prior to starting USTE was associated with an increased risk of intervention. Increased bowel wall thickness on imaging, prior biologic use, and obstructive symptom duration were associated with USTE discontinuation. Occurrence of obstructive symptoms during treatment was associated with prior biologic use, EBD within 6 months of starting USTE, and a lower BMI. Conclusions USTE appears to be an appropriate medical option in biologic-experienced CD patients with ileal strictures. Further prospective data are needed to better define outcomes and predictors of response in this setting.

Abstract Background Global data demonstrate an inverse relationship between hospital ileoanal pouch volume and adverse outcomes, highlighting the need for quality metrics for this technically demanding procedure.1-4 Currently, there are no standardised quality indicators to define high-quality pouch surgery. This study aimed to establish international consensus on key performance indicators (KPIs) in pouch surgery. Methods A modified Delphi process was conducted among an international, multidisciplinary panel of experts. Participants were identified through professional networks, literature review, and direct email invitation; additional participants recruited via a snowball sampling approach over one month. Candidate KPIs were generated from literature review and expert input across 5 domains. Each item was rated on a 9-point Likert scale (1 = not important, 9 = critically important); consensus was predefined as ≥ 80% of respondents rating an item 7–9. Items not reaching consensus were re-rated in a second round following anonymized group feedback. Results Round 1 included 312 participants from 37 countries. Demographics (Table 1): 53% were age 45 years, 35.2% were female, and included surgeons (68.6%) and gastroenterologists (31.1%). Most (76.6%) practice at academic or university hospitals, with a median of 11 (5–17) years in practise; 78.9% perform >1 pouchoscopy per month, and 39.5% of surgeons perform 5 pouches/year. Respondents’ regions included North America (51%), Europe (26%), Oceania (9%), Asia (6%), Latin America (4%), and the Middle East/Africa (4%). Seven (18%) countries (Denmark, Lithuania, Malaysia, Norway, United Arab Emirates, Sweden, and Switzerland) reported pouch surgery is already centralised, while 70.6% agreed pouch centralisation should be implemented. Cost/logistics and professional autonomy were the most important barriers to centralisation, whereas capacity and training exposure were least important. Overall, 37/59 (62.7%) candidate KPIs reached consensus after Round 1. The Round 2 response rate was 61%, and 2 additional KPIs reached consensus (preop ileitis and long-term risk of pouchitis). Additionally, 14 of 25 (56%) informed consent items reached consensus, and 64% of respondents felt informed consent for pouch surgery requires 2 or more office visits. Consensus items were used to populate a KPIPS Checklist (Figure 1). Conclusion Through an international Delphi process, the KPIPS study identified a consensus-derived set of key performance indicators to measure quality in pouch surgery. These quality metrics provide a foundation for benchmarking outcomes and represent a critical step towards centralization and the development of designated pouch centres of excellence to improve global standards of care for pouch patients. References: 1. Worley GHT, Fearnhead NS, Brown SR, et al. Review of current practice and outcomes following ileoanal pouch surgery: Lessons learned from the ileoanal pouch registry and the 2017 ileoanal pouch report. Colorectal Dis 2018;20:913–22. 2. Giddings HL, Yang PF, Steffens D, Solomon MJ, Ng KS. Influence of hospital-level and surgeon factors on the outcomes after ileo-anal pouch surgery for inflammatory bowel disease: Systematic review. Br J Surg 2024;111. 3. Hoang CM, Maykel JA, Davids JS, et al. Distribution of elective ileal pouch-anal anastomosis cases for ulcerative colitis: A study utilizing the university health system consortium database. J Gastrointest Surg 2020;24:2613–9. 4. Moojen TB, Visser E, Reijntjes MA, et al. One-year stoma-free survival of ileoanal pouches for uc in european centers: The miracle project. Ann Surg Open 2025;6:e596. Conflict of interest: Prof. Holubar, Stefan: No conflict of interest Soop, Mattias: No conflict of interest Poskus, Tomas: No conflict of interest Neary, Peter: No conflict of interest Uchino, Tairin: No conflict of interest Yang, Song-soo: No conflict of interest Adamina, Michel: No conflict of interest Avellaneda, Nicolas Luis: No conflict of interest Barnes, Edward: No conflict of interest Brouquet, Antoine: No conflict of interest Brown, Steven Ross: No conflict of interest De Buck Van Overstraeten, Anthony: No conflict of interest Buskens, Christianne J.: No conflict of interest Chiorean, Michael: No conflict of interest Clark, David: No conflict of interest Cohen, Benjamin: No conflict of interest El Ouali, Sara: No conflict of interest Faiz, Omar Darius: No conflict of interest Fichera, Alessandro: No conflict of interest Hahnloser, Dieter: No conflict of interest Hancock, Laura: No conflict of interest Herfarth, Hans: No conflict of interest Johnston, Michael: No conflict of interest Kayal, Maia: No conflict of interest Laharie, David: No conflict of interest Liberman, Sender: No conflict of interest Loftus, Jr, Edward: No conflict of interest Moeslein, Gabriela: No conflict of interest Myrelid, Pär: No conflict of interest Poylin, Vitaliy: No conflict of interest Qazi, Taha: No conflict of interest Raffals, Laura: No conflict of interest Rubin, David T.: No conflict of interest Spinelli, Antonino: No conflict of interest Steinhagen, Emily: No conflict of interest Tozer, Philip: No conflict of interest Verstockt, Bram: No conflict of interest Warusavitarne, Janindra: No conflict of interest Wexner, Steven: No conflict of interest Winter, Desmond: No conflict of interest

Abstract Background Colonic strictures in Crohn’s disease (CD) present a complex and relatively underexplored clinical issue. Imaging modalities such as computed tomography (CT), magnetic resonance imaging (MRI), and intestinal ultrasound (IUS), have established criteria for evaluating small bowel CD strictures. However, radiologic definitions of benign colonic strictures and their diagnostic accuracy are not well-developed. Endoscopic definitions of colonic strictures are the most well-described. We conducted a systematic review to summarize definitions, diagnosis, and identification of inflammation and fibrosis of colonic strictures on endoscopy, CT, MR, and IUS. Methods A systematic review following PRISMA guidelines, from inception to October 6, 2024, was conducted using MEDLINE, Scopus, CINAHL, and CENTRAL databases to identify literature on diagnostic imaging of patients with colonic CD strictures. Only studies with comparison to endoscopy or imaging to a full-thickness histologic gold standard to differentiate fibrosis from inflammation were included. Two stage screening was completed in duplicate, and risk of bias was assessed using QUADAS-2. Results 46 studies were eligible for inclusion of 4623 abstracts screened. Definitions of colonic strictures on CT, MR, and IUS were highly variable with combinations of bowel wall thickness, luminal narrowing, and pre-stenotic dilation. Endoscopic definitions of colonic strictures were the most consistently reported as lack of passage of a colonoscope through a narrowed lumen. Diagnostic imaging definitions used various combinations of increased bowel wall thickness, luminal narrowing, and pre-stenotic dilation with no clear cutoffs. Few studies directly compared imaging features with histologic or endoscopic gold standards, limiting evaluation of diagnostic accuracy. Meta-analyses were not conducted due to methodological heterogeneity of grading fibrosis across studies. In addition, statistical heterogeneity of sensitivity, specificity, and accuracy of colonic stricture diagnoses was limited by pooling with small bowel strictures in the studies. Conclusion This systematic review highlighted the absence of standardized definitions for diagnosing colonic Crohn’s disease strictures, particularly on diagnostic imaging, and the limited data distinguishing inflammatory from fibrotic components. Bowel wall thickening, luminal narrowing, and pre-stenotic dilation are key features of small bowel strictures, but their relevance to the colon requires further assessment. Establishing standardized definitions for colonic strictures that incorporate both endoscopic and imaging modalities is essential to advancing the field. Conflict of interest: Dr. Lu, Cathy: Advisory board - Abbvie, Johnson and Johnson, Takeda, Ferring, Merck, Celltrion, Lilly, Pfizer, Pendopharm, Agomab. Research Funding - Abbvie, Helmsley Charitable Trust, Alberta Innovates Dhaliwal, Ravdip: No conflict of interest Kellar, Amelia: No conflict of interest Rowan, Catherine: No conflict of interest St-Pierre, Joelle: Consultant for Pfizer, Abbvie, Eli Lilly and Pendopharm, and speaker for Takeda. Ernest-Suárez, Kenneth: Consulting/Advisory Board fees: Abbvie, AstraZeneca, Johnson & Johnson, Pfizer, Ferring, Sandoz, SatisfAI, Takeda O’Brien, Maureen: No conflict of interest Rosentreter, Ryan: No conflict of interest Gulhati, Vishrut: No conflict of interest Baker, Mark: No conflict of interest Bettenworth, Dominik: DB is on the advisory board or consultant for AbbVie, Amgen, Arena, Atheneum, BNG Service GmbH, Bristol Myers Squibb, CED-Service GmbH, Celltrion, Doctorflix, DGVS, Diaplan, Else Kröner-Fresenius Foundation, Falk Foundation, Galapagos, Guidepoint, Impulze, Ferring, Janssen Cilag, Lilly, Medical Tribune, MedTriX, MSD, Mylan, Onkowissen, Pharmacosmos, Pfizer, Roche, Sandoz, Takeda, Tetrameros, Thieme, Tillotts Pharma, UCB Biopiharma, Viatris and Vifor Pharma. Bruining, David: Advisory board fees from Janssen Bari, Dane: Grant from Helmsley Charitable Trust speaker honorarium from Siemens Healthineers support for attending meetings or travel from Siemens Healthineers member of the Olympus advisory board co-chair Society of Abdominal Radiology (SAR) Inflammatory Bowel Disease Disease Focused Panel (IBD DFP) and SAR Photon-Counting Detector CT Emerging Technology Commission and chair of the Society for Advanced Body Imaging Scientific Committee. Dillman, Jonathan: Grants from Philips Healthcare, GE HealthCare, Motilent, Perspectum, Guerbet, and Bracco. El Ouali, Sara: Speaker and/or consulting fees from Takeda, Eli Lilly, Janssen, Abbvie. Fletcher, John: Grant supports from Siemens Healthineers Gordon, Ilyssa: Grants to institution from Morphic Therapeutics, Alimentiv, Pliant Therapeutics, and UCB patent pending with Case Western Reserve University on radiomics signatures Jairath, Vipul: Consulting Fees: Abbvie, Alimentiv, Amgen, Anaptys Bio, Asahi Kasei, Asieris, Astra Zeneca, Attovia, Blackbird Labs, BMS, Boehringer Ingleheim, Biomebank, Caldera, Calluna, Catalytic Health, Celltrion, Ensho, Enthera, Exeliome Biosciences, Ferring, Fresenius Kabi, Gilead, Granite Bio, GSK, Janssen, Lilly, Merck, Mountainfield, MRM Health, Nxera, Organon, OSE Immunotherapeutics, Pendopharm, Pioneering Medicine, Pfizer, Prometheus, Roche/Genentech, Sanofi, SCOPE, Shattuck Labs, Sorriso, Spyre, Synedgen, Takeda, Teva, Tillotts, Union Therapeutics, Ventus, Ventyx, Vividion, Xencor, Zealand Pharma. Feagan, Brian Gordon: Consulting Fees: AbbVie, Abivax, Adaxion, Adiso, AgomAB Therapeutics, Akros, Alira Health, Ally Bridge Group, Apini Therapeutics, Argenx, Attovia Tx, Avoro Capital Advisors, Belmore Law, Biora Therapeutics, Blackbird Laboratories, Boehringer-Ingelheim, BMS, Boxer Capital, Celgene/BMS, Clarivate, Connect Biopharm, EcoR1, Eli Lilly, Ensho Therapeutics, Equillium, Evida, Enveda, Evommune Inc. Faes Farma, First Wave, Forbion, Galapagos, Genentech/Roche, General Atlantic, Genesis Therapeutics, Gerson Lehrman Group, Gilead, Guidepoint, Imhotex, ImiDomics, Immunic Therapeutics, Janssen, Japan Tobacco Inc., LifeMine Therapeutics, Mage Biologics, Merck, Mirador Therapeutics, Mobius Care, Monte Rosa Tx, Morphic Therapeutics, Nimbus Therapeutics, Novartis, Nxera, OncoC3, Palisade Bio, Pendopharm, Pfizer,Q32 Bio, REDX, Roche, Sanofi, Sobi, Sorriso, Spyre Therapeutics, Sun Pharma, Surrozen Inc., Synedgen, Takeda, Tegus Inc., Teva, Tillotts, Trex Bio, TR1X Inc. TVM Lifesciences, Ventyx Biosciences, Versant Ventures, Vida Ventures, Ysios Capital, Zagbio Stock Shareholder: Connect Biopharm, EnGene, Evida, SRT, Imidomics, Enveda Rieder, Florian: Personal Fees: Adiso, Adnovate, Agomab, Allergan, AbbVie, Arena, Astra Zeneca, Boehringer-Ingelheim, Celgene/BMS, Celltrion, CDISC, Celsius, Cowen, Ferring, Galapagos, Galmed, Genentech, Gilead, Gossamer, Granite, Guidepoint, Helmsley, Horizon Therapeutics, Image Analysis Limited, Index Pharma, Landos, Jannsen, Koutif, Mestag, Metacrine, Mopac, Morphic, Organovo, Origo, Palisade, Pfizer, Pliant, Prometheus Biosciences, Receptos, RedX, Roche, Samsung, Sanofi, Surmodics, Surrozen, Takeda, Techlab, Teva, Theravance, Thetis, UCB, Ysios, 89Bio

Abstract During the 20th century, inflammatory bowel disease (IBD) was considered a disease of early-industrialized regions in North America, Europe, and Oceania. At the turn of the 21st century, incidence of IBD increased in newly-industrialized and emerging regions in Africa, Asia, and Latin America, while prevalence in early-industrialized regions started to grow steadily. Changes in incidence and prevalence denote evolution of IBD across four epidemiologic stages: Stage 1 (Emergence), characterized by low incidence and prevalence; stage 2 (Acceleration in Incidence), characterized by rapidly rising incidence and low prevalence; and stage 3 (Compounding Prevalence), characterized by decelerating, plateauing, or declining incidence and steadily rising prevalence. A fourth stage (Prevalence Equilibrium) has been proposed where the slope of prevalence plateaus due to shifting demographics of an aging IBD population, but it has not yet been evidenced. To date, these stages have been theoretical without specific incidence/prevalence indicators defining transition points. Using real-world data from 490 population-based studies comprising 80 global regions and spanning over a century (1920–2023), we show spatiotemporal transitions across stages 1–3 and model transition towards stage 4. Understanding the evolution of IBD across epidemiologic stages allows healthcare systems to better prepare for the future worldwide burden of IBD.

AbstractBackgroundRisk factors for intervention in terminal ileal (TI) stricturing Crohn's disease (CD) are poorly defined. Novel and rigorous definitions for TI strictures recently became available.ObjectiveWe aimed to describe the rates of symptoms or need for endoscopic balloon dilation (EBD) or surgery as well as risk factors of progression in a well‐defined stricturing CD cohort.MethodsConsecutive adult patients with non‐penetrating stricturing TI CD, as defined by centrally‐read magnetic resonance enterography CONSTRICT criteria, were separated into a derivation and validation cohort. Clinical and imaging characteristics were collected following prespecified scoring conventions. Primary outcome was a composite endpoint of EBD or surgery (“intervention”). Multivariable analysis was performed.ResultsEighty‐six patients (48.8% female, median age 36 years) met selection criteria, 17.4% had prior EBD, 59.3% previously received biologics and 58.1% of strictures were anastomotic. Median follow‐up was 63.4 [95% CI: 57, 68.9] months. In the derivation cohort, at 12 and 48 months, 26% and 45% of patients had intervention, respectively. Multivariable analysis showed obstructive symptoms (Hazard ratio [HR] 1.444; 95% CI 1.126–1.852), stricture duration (HR 0.974; 95% CI, 0.954–0.995) and length (HR 1.039; 95% CI, 1.011–1.069) predicted intervention. The concordance index for split‐sample validation was 0.74 and 0.67, respectively. Biologics were not associated with intervention. An online risk calculator was constructed.ConclusionIn patients with TI stricturing CD, 26% and 45% required intervention at 1 and 4 years. Obstructive symptoms, stricture duration and length were independent and validated predictors of the need for intervention. These findings are important for clinical practice and aid in the design of future trials for CD strictures.