bluuebunny/crossref_metadata_2025 huggingface dataset:
P0212 Non-canonical STING signaling in intestinal epithelial cells guides DNA damage-driven stem cell function and protects from intestinal carcinogenesis
Authors: Xiang H , Woitaske-Proske C , Bernardes J P , Martini G R , Wottawa F , Bornhaeuser J , Kakavand N , Guang Y , Wu Q , Kugler J , Welz L , Konukiewitz B , Peifer C , Schreiber S , Tschurtschenthaler M , Rosenstiel P , Aden K
Published: January 2025

Background

RNaseH2 plays a critical role in removing mis-bounded RNA from the DNA double strand helix1. Absence of RNaseH2 results in spontaneous double-stranded DNA breaks and cytosolic release of dsDNA2. We have previously shown that epithelial deficiency of RNaseH2b (H2bΔIEC) leads to a p53-dependent stem cell suppression and additional deficiency of p53 results in spontaneous intestinal carcinogenesis3. Due to the central role of cGAS/STING in sensing dsDNA, we aim to investigate the role of epithelial STING in a mouse model of chronic epithelial DNA damage and tumor prevention in this study.

Methods

DNA damage was assessed using comet assay in ModeK cell line with cGAS and STING knock out. Protein kinase activity were assessed by Pamgene Kinase Assay. Intestinal organoids were generated from H2bΔIEC and H2bΔIEC/Tmem173-/-mice. Colony forming assay and EdU staining were performed in all genotypes to assess the impact of STING on epithelial stem cell function and proliferation were assessed by CellTiter Glo assay.

RNA sequencing was performed in intestinal organoids. Spontaneous carcinogenesis was assessed in 1-year aged mice.

Results

Loss of RNaseH2b results in activation of cGAS/STING pathway and subsequent upregulation of IFN-I signature. Deficiency of cGAS/STING lead to impaired IFN-I independent DNA damage repair which were accessed by WB and comet assay. During the DNA damage response, STING but not cGAS mediates the P53 pathway and the P21-CDK axis. Organoid EdU stanning displayed restored proliferation in H2bΔIEC/Tmem173-/- compared to H2bΔIEC. RNA sequencing from H2bΔIEC/Tmem173-/-organoid further confirmed decreased G2/M DNA damage checkpoint and P53 signature compared to H2bΔIEC. In vivo, we show that H2bΔIEC/Tmem173-/- mice have downregulated DNA damage repair and developed spontaneous small bowel adenocarcinoma after 53 weeks. Tumor derived from H2bΔIEC/Tmem173-/- mice show sensitivity to CDK inhibitor consistent with in vitro validation.

Conclusion

We provide evidence that non-canonical role of epithelial STING mediates DNA damage response and guides P21-CDK1 axis in preventing tumor genesis. Our research provided evidence understand the role of STING in DNA damage response and intestine carcinogenesis.

References

1.Reijns, Martin A.M., et al., Enzymatic Removal of Ribonucleotides from DNA Is Essential for Mammalian Genome Integrity and Development. Cell, 2012. 149(5): p. 1008-1022.

2.Bartsch, K., et al., Absence of RNase H2 triggers generation of immunogenic micronuclei removed by autophagy. Hum Mol Genet, 2017. 26(20): p. 3960-3972.

3.Aden, K., et al., Epithelial RNase H2 Maintains Genome Integrity and Prevents Intestinal Tumorigenesis in Mice. Gastroenterology, 2019. 156(1): p. 145-159 e19.
P0214 Notch Pathway-Mediated epithelial-mesenchymal transition and Fibrosis in Complicated Crohn’s Disease
Authors: Patel J , Cejudo-Garcés A , Jarén A , Macias-Ceja D C , Manresa M , López A , Cosin-Roger J , Calatayud S , Barrachina M D , Ortiz-Masiá D
Published: January 2025

Background

The dysregulation of epithelial-mesenchymal transition (EMT) is linked to numerous pathologies, including fibrotic diseases. The Notch pathway may selectively mediate fibrogenic processes, such as EMT. Previous studies by our group have demonstrated elevated expression of NOTCH3, NOTCH4 receptors, and the DLL4 ligand in the intestines of patients with complicated Crohn’s disease (CD)1. This study aims to explore the potential of the Notch pathway as a therapeutic target in intestinal fibrosis associated with CD.

Methods

We analyzed ileal samples from Crohn’s disease patients with complicated lesions to assess the localization of NOTCH3/4 receptors using immunohistochemistry (IHQ) and performed RT-qPCR and Western blot (WB) analysis. In vitro studies were conducted using DLL4-coated plates (1 µg/ml), with or without the γ-Secretase Inhibitor DAPT (10 μL/ml), to evaluate protein and mRNA expression of HES1 and EMT markers (VIMENTIN, SNAIL, and E-CADHERIN) in two primary epithelial cell lines: small intestine (HIEC6) and colon (CoEpi) cells over 48 hours. Data, presented as fold induction (mean ± SEM) relative to water-treated cells or control tissues, were analyzed using parametric or non-parametric ANOVA (Kruskal-Wallis) based on normality testing (*P < 0.05).

Results

RT-qPCR analysis revealed significantly increased mRNA levels of the Notch receptors NOTCH3 and NOTCH4. WB analysis showed elevated levels of NOTCH3 (235±87*), but not NOTCH4 (87±13), protein in affected versus control tissues (100±8 and 100±7, respectively). In terms of cellular localization, NOTCH3 was detected in endothelial and smooth muscle cells, lamina propria cells, and with lower intensity in the epithelium. NOTCH4 was primarily found in cells of the lamina propria. In vitro assays indicated that DLL4 significantly altered mRNA and protein expression of HES1 and certain EMT markers (VIMENTIN and SNAIL) in both epithelial cell lines. Co-treatment with DAPT significantly reversed some EMT markers induced by DLL4 (VIMENTIN and SNAIL) (Figure 1).

Conclusion

NOTCH3 may play a role in the fibrogenic processes of CD, with elevated expression observed. The activation of EMT markers by DLL4 suggests that Notch signaling has a critical function in driving fibrosis and tissue remodeling in CD.

References

M Rodriguez-Antequera, J Cosin-Roger, D Macias-Ceja, P Salvador, L Gisbert-Ferrándiz, S Coll, J Manyé, R Alós, F Navarro-Vicente, S Calatayud, M D Barrachina, D Ortiz-Masia, P041 Differences in NOTCH signalling between stricturing and penetrating behaviour in Crohn’s disease, Journal of Crohn’s and Colitis, Volume 13, Issue Supplement_1, March 2019, Page S107, https://doi.org/10.1093/ecco-jcc/jjy222.165
P0224 Learning Curve in Intestinal Ultrasound: Advancing from Basic Skills to Advanced Competencies – Insights from the IUS IG-IBD (Italian Group for the Study of Inflammatory Bowel Disease) Master Program
Authors: Bezzio C , Pitoni D , Ribaldone D G , Vernero M , Castiglione F , Rispo A , Saibeni S , Maconi G , Terracciano F , Bossa F , Allocca M , Furfaro F , Calabrese E , Zorzi F , Fraquelli M , Caprioli F , Rizzello F , Mazzotta E , Orlando A , Grova M , Massironi S , Viganò C , Armuzzi A
Published: January 2025

Background

Intestinal ultrasound (IUS) is increasingly used in assessing Crohn’s disease (CD) and ulcerative colitis (UC) due to its accessibility, low cost and absence of radiation. However, its operator dependency necessitates targeted training programs. This study aimed to evaluate the learning curve of gastroenterology trainees in IUS, determining the number of exams required to achieve diagnostic agreement with expert tutors.

Methods

This study was conducted at eight Italian referral centers for intestinal ultrasound as part of the IUS Master promoted by IG-IBD. Eight gastroenterology trainees with significant experience in abdominal ultrasound but limited exposure to IUS each performed 99 consecutive examinations. The trainees received an eight-hour course on IUS and one week of hands-on training with the expert sonographer. The exams were divided into three periods of 33. After each examination, an expert sonographer reassessed the findings and Cohen's Kappa coefficient was used to measure the agreement between the trainee and the expert operator for all the parameters considered. The parameters considered were bowel wall thickening, vascularity, Limberg score and complications (fistulas, stenosis, abscesses).

Results

A progressive improvement in concordance was observed across all parameters from period 1 to period 3 for all learners (Table 1). Overall agreement in identifying pathological findings increased from K=0.778 to K=0.911. Specifically, concordance for bowel wall thickening improved from K=0.558 in the first 33 exams to K=0.780 in later periods. Vascularity reached K=0.909 and the Limberg score achieved K=0.879. For complications, agreement on fistulas increased from K=0.765 to K=0.893, while stenosis improved from K=0.583 to K=0.872. Abscesses consistently demonstrated high concordance (K=0.855). The number of examinations required to achieve good agreement with the expert operator for detecting bowel wall thickening was at least 66, while 69 were needed for the accurate assessment of increased vascularity. However, detecting intra-abdominal complications required at least 99 examinations.

Conclusion

The time required to achieve proficiency in assessing intestinal ultrasound parameters related to the bowel wall is shorter than the time needed to detect the presence of complications. These findings highlight the importance of structured and supervised practice to achieve proficiency in both basic and advanced IUS competencies, providing a foundation for the development of standardized training programs in gastroenterology.
P0226 Postoperative recurrence after a definitive ostomy in Crohn's disease. A nationwide retrospective series from the Eneida registry
Authors: Calafat Sard M , Mañosa M , Fernández-Clotet A , Pasanau L , Matallana V , Iglesias E , Hernández-Camba A , Ucha P , Nos P , Barrio J , Gutiérrez A , Merino V , Barreiro-de Acosta M , Cudero L , Casanova M J , González-Muñoza C , Bujanda L , Varela P , Bermejo F , Torres N , Mesonero F , Calvet X , Rivas C , Pérez C , Alonso-Abreu I , Rodríguez-Lago I , Vega P , Zabana Y , Mora M , Busquets D , Rodríguez-Gutiérrez C , Torres G , Valldosera G , Ponferrada Á , Ceballos D , Martínez Pascual C , Jiménez N , Sampedro M , Irabien M , Domènech E
Published: January 2025

Background

Although the concept of postoperative recurrence (POR) in Crohn’s disease (CD) has been limited to patients undergoing intestinal resection with anastomosis, some small-sized retrospective series with short follow-up periods suggest that clinical POR may occur in up to 30% of patients with a definitive ostomy. This may explain the lack of recommendations for monitoring and preventive strategies in this clinical setting. Our aim was to assess the risk of POR and current monitoring strategies in this population.

Methods

Retrospective study from the ENEIDA database of GETECCU. Patients with CD and a permanent ostomy were included. Demographic, clinical characteristics, evolution, and monitoring data were analyzed.

Results

Overall, 263 patients who underwent permanent ostomy between 1979 and 2023 were included, of whom 70% had an ileostomy and 30% a colostomy with 65% having previous ileal involvement in both groups. Proctectomy had been performed in 57% of them. Medical prevention for POR was started in 38% of patients (44% thiopurines, 43% biologics, and 13% 5ASA). Regarding monitoring strategies in asymptomatic patients, 25% underwent ileoscopy, 43% had radiological examinations and 53% faecal calprotectin measurements. Moreover, 37% underwent radiological examinations and 55% ileoscopy due to the development of symptoms or elevation of biomarkers.

After a median follow-up of 142 months (IQR 75-267), 32% developed clinical POR, 16% biological POR, 37% endoscopic POR, 37% radiological POR, and 14% surgical POR. Among those with POR, 37% started medical therapy (9% 5ASA, 24% thiopurines, 65% biologics). The cumulative probability of clinical POR at 3, 5, and 10 years was 16%, 20%, and 28%, respectively. The cumulative probability of surgical POR at 3, 5, and 10 years was 5%, 8%, and 12%, respectively. In the multivariate analysis, risk factor for clinical POR was having colostomy vs. ileostomy (OR 2.05, 95% CI 1.05-3.99; P=0.035).

As for complications during follow-up, 40%, 24%, and 18% of patients developed iron-deficiency anemia, vitamin B12 deficiency, or renal insufficiency, respectively.

Conclusion

More than one third of patients with CD and a permanent ostomy develop POR in the long-term, and 10% requiring a new resection. These findings underscore the need for recommendations on monitoring strategies and preventive approaches n this clinical scenario.
P0230 Prognostic factors and predictive model development for pediatric Inflammatory Bowel Disease with IL-10RA deficiency: A retrospective cohort study
Authors: Shi X , Qian L , Wu H , Wang L , Ye Z , Dong K , Sun S , Zhai X , Qian X , Huang Y
Published: January 2025

Background

Patients with IL10RA-deficient inflammatory bowel disease (IBD) generally have a poor prognosis, with high mortality and a significant rate of intestinal surgeries. Hematopoietic stem cell transplantation (HSCT) is currently the main cure, but most patients still face death after transplantation. The study analyzes the prognosis of patients without HSCT, aiming to explore factors associated with both mortality and the need for intestinal surgery, as well as to establish short-term prognostic models.

Methods

The study retrospectively enrolled 138 patients admitted to our center from January 2012 to July 2024. We defined death and intestinal surgery as outcomes and used competing risks analysis, cox regression models, and random survival forest algorithm to explore prognostic factors. Additionally, optimal subset regression, and logistic regression were employed to establish a short-term prognostic model, with the goal of better assessing the severity of the patients' conditions and evaluating the likelihood of long-term survival, as well as the risks of short-term death or surgery.

Results

The median age of onset of 138 patients was 0.3 months (range: 0.2-1 months), and the median age of admission was 8.1 months (range: 3.0-15.2 months). 21.7% had pure homozygous mutations. The most frequent was c.301C>T，c.537G>A. 32.6% of patients died, of which 73.3% were transplant-related. 35.5% of patients had undergone intestinal surgery. In patients without HSCT, most deaths occurred within the first year, while intestinal surgeries were mainly performed by age four. Cox multivariate analysis identified thalidomide used as an independent protective factor against mortality (HR = 0.09, 95% CI: 0.02-0.46, P = 0.004). Intestinal perforation was a significant risk factor (HR = 9.39, 95% CI: 3.49-25.30, P < 0.001) for the outcome of intestinal surgery. The random survival forest model highlighted thalidomide, mesalazine, intestinal perforation and gross bloody stool as key variables affecting mortality or surgery risk, with thalidomide having the greatest impact. Short-term death model (age of admission, ALB, intestinal perforation) was well distinguished (AUC: 0.945), but poorly calibrated; Short-term surgical models (CRP, PLT, perianal lesions) were moderately distinguished (AUC: 0.799), and the calibration was reasonable.

Conclusion

Long-term survival is possible for IL10RA-deficient patients without HSCT. However, due to the risk of early-life adverse outcomes, close follow-up remains essential. Thalidomide appears to have the most significant impact on prognosis and may improve disease outcomes. The short-term prognostic assessment model demonstrates good discriminatory ability for distinguishing high-risk from low-risk patients.
P0232 Increasing awareness of joint symptoms in Inflammatory Bowel Disease clinic using recognised clinical joint pain scoring symptoms may aid early diagnosis of spondyloarthropathy
Authors: Kerr H , Clarke M , Connaughton R , Elsiddig M , Hall B , Farrell R , Smyth C , Kelly O
Published: January 2025

Background

Axial spondyloarthropathy(axSpA) is under-recognised and underdiagnosed in lnflammatory Bowel Disease (IBD) patients. The aim of our study is to assess the prevalence of subclinical axSpA in our IBD patient cohort, assess risk factors and improve patient health through early recognition and referral.

Methods

A prospective observational study assessing presence of clinical symptoms suggestive of spondyloarthropathy was performed. Patients with established IBD and no previous history of joint pain or documented rheumatological disease attending a specialist IBD clinic were screened over a 6 month period from January to July 2024. All patients reporting lower back pain were assessed with a screening questionnaire using the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) score. BASDAI score ≥ 4 suggests moderate activity of axial spondyloarthropathy. Radiographic imaging of the sacroiliac joints were performed. BASDAI scores were correlated with CRP and calprotectin levels. Other demographic factors were also recorded from patient records.

Results

590 patient visits for IBD were recorded from January to July 2024. 320 patients were screened for the study. 34 (10.6%) patients reported symptoms suggestive of axial spondyloarthropathy when questioned. The mean age was 45 years of age (19-82). 55.9% of patients were female. 14.7% of patients had symptoms of other extra-intestinal manifestations (EIMs). 50% of patients had Ulcerative colitis, 44% of patients had Crohn’s disease and 6% had IBD-U. Mean CRP level was 2.36 (0.5–7). Mean calprotectin was 151 (13-1100). 21/34 (62%) of patients had a BASDAI score suggestive of moderately active clinical symptoms of arthropathy. Mean BASDAI score was 4.97. 2/21 (9.5%) of those with BASDAI ≥ 4 had radiographic evidence of sacroiliitis. Of those patients with radiographic axSpA, the mean BASDAI was 5.1. Patients with radiographic axSpA were referred to the rheumatology outpatient service. 84% females screened had BASDAI ≥ 4 compared to 40 % males (Fisher exact test, p=0.015). There was no correlation noted between reporting of joint symptoms and age, CRP or calprotectin nor did it correlate with disease type or behaviour.

Conclusion

The use of rheumatological screening tests in the IBD clinic could contribute to the early diagnosis of axial spondyloarthropathy in IBD patients. Raising awareness of musculoskeletal manifestations of IBD could improve diagnosis, early involvement of the multidisciplinary team and improve disease burden.
P0236 Diaphragmatic ultrasound investigation to discriminate sarcopenic index in a population of patients with ibd
Authors: Palmisano C M , Dell'Aquila P , Cormio S , Borraccino A V , Squeo F , Savino F , Novielli D , Forastiere D , Principi M R D
Published: January 2025

Background

Sarcopenia is prevalent in patients with inflammatory bowel disease (IBD) and impacts surgical and therapeutic outcomes.The use of different muscles for the study of sarcopenia is described in the literature. The ultrasound study of the diaphragm is a rapid, reproducible, non-invasive with a rapid learning curve.The aim of this work was to evaluated whether the ultrasound diameter of the diaphragm muscle (DM) correlated with the clinical SARC-F score in patients with IBD, in order to use DM measurement as a tool in the diagnosis of sarcopenia in this population.

Methods

Consecutive IBD patients were enrolled.All patients underwent ultrasound of the diaphragm muscle.The diameters during exhalation and during inspiration were assessed, then from these two values it was possible to extrapolate the diaphragm thickness fraction.We calculated the diaphragm-to-height ratio in the US as the average diaphragm thickness fraction divided by the patient's height (mm/m).As previous studies have shown, a cut-off of 1 cm above which one speaks of a normal diaphragmatic excursion has been considered. All patients underwent a clinical questionnaire to calculate the SARC-F score. A SARC-F value≥4 was significant of sarcopenia.

Results

A total of 353 IBD patients (170 CD and 183 UC), 54,55% male, with a mean age of 44.78 years were enrolled.The diaphragm index had a mean value of 0.70cm/m (±.024cm/m). The Pearson test showed a significant negative correlation between the sarcopenia score SARC-F and the diaphragm index (r: -0.42; p-value ˂ 0.05).Of the 353 patients enrolled, 98 had a diaphragmatic excursion of less than 1 cm.Of these, when subjected to the SARC-F score, 57 patients (16.19%) showed positive results with a score above 4, while the remainder had a score of 3, just below the cut-off. These were patients who all had a diaphragmatic excursion index of less than 1 cm. The mean sarcopenia score was 1.51 (±2.02), with a median of 1 (IQR: 0 – 2). Cohen’s Kappa statistics used using the fifth percentile as a threshold, it yielded a significant 80.80% agreement rate (expected: 80.35; Kappa: 0.55; p-value ˂ 0.05).

Conclusion

The study shows a significant correlation between the diaphragmatic index and the SARC-F clinical score,suggesting how reliable the use of diaphragmatic ultrasound is for the study of sarcopenia in patients with IBD. This research could take significant implications for disease management in IBD patients and underscores the importance of further investigations to validate these findings in larger cohorts.
P0243 Evaluation of liver fibrosis and steatohepatitis associated with metabolic dysfunction (MASH) in patients with inflammatory bowel disease (IBD) and steatotic liver disease associated with metabolic dysfunction (MASLD)
Authors: Oliveira E C S D , Lopes M A , Beraldo R F , Castelhano N S , Baima J P , Herrerias G S P , Quaglio A E V , Di Stasi L C , Barbosa W F , Silva G F , Sassaki L Y
Published: January 2025

Background

Inflammatory bowel disease (IBD) is associated with a systemic inflammatory state and dysbiosis, which may increase the risk of metabolic dysfunction-associated steatotic liver disease (MASLD). This occurs through intestinal bacterial translocation and the increased entry of lipopolysaccharides, free fatty acids, and other toxins into the liver via the portal circulation. One significant complication of MASLD is metabolic dysfunction-associated steatohepatitis (MASH), which can progress to cirrhosis. This study aimed to evaluate the prevalence of MASLD in IBD patients and assess the frequency of complications, such as MASH and liver fibrosis.

Methods

The presence of MASLD was based on the presence of NAFLD associated with the metabolic criterion in outpatients with IBD. The presence of NAFLD was confirmed using liver ultrasound. Noninvasive estimate of liver fibrosis (FIB-4) Index and NAFLD Fibrosis Score (NFS) were used as indirect scores of liver fibrosis. Patients with scores greater than NFS > 0.675 and/or FIB-4 > 2.67; and patients with indeterminate or discordant scores were indicated for liver biopsy to quantify liver fibrosis and evaluate MASH. Liver elastography was not performed due to unavailability in our center.

Results

A total of 179 patients underwent liver ultrasound, with 72 (40.2%) diagnosed with MASLD, including 33 with Crohn’s disease (CD) and 39 with ulcerative colitis (UC). Regarding disease activity, 36.11% were clinically active and 50% were endoscopically active. Biological therapy was used by 54.2% of patients. The degree of steatosis was mild (41.67%), moderate (44.4%) and intense (13.89%). According to the FIB-4 Index, patients were classified as low risk of fibrosis (72.22%), intermediate risk (26.32%) and high risk (1.39%). According to the NFS, the risks for fibrosis were low (53.52%), undetermined (38.08%) and high (8.45%). Sixteen (22.22%) patients underwent liver biopsy, and the presence of fibrosis was observed in 11 (68.75%) patients. The histological stage of fibrosis was F1 (n=6, 54.5%), F2 (n=3, 27,3%), F3 (n=1, 9.1%) and F4 (n=1, 9.1%) according to Kleiner's classification. 4 patients (25%) met criteria for MASH.

Conclusion

A high prevalence of MASLD was observed in patients with IBD. Among patients with MASLD, we must be aware of the risk of liver fibrosis and MASH. Routine monitoring of liver function and fibrosis, including liver biopsy or elastography when appropriate, is crucial for early detection and management of complications. Due to the lack of routine elastography in our center in Brazil, liver biopsy remains essential for accurate assessment in those patients.
P0244 Serum IgLC Levels in Ulcerative Colitis: Limited Utility as Biomarkers for Disease Activity
Authors: Oh J E , Park J J , Choi S , Park J , Park S J , Kim T I , Cheon J H
Published: January 2025

Background

Immunoglobulin free light chains (IgLC), which are surplus light chains produced by plasma cells that fail to bind to heavy chains, have been reported to be elevated in Crohn's disease. However, the presence and clinical significance of serum IgLC levels in ulcerative colitis (UC) remains unclear. We investigated serum IgLC levels and their association with disease activity in UC patients.

Methods

In this prospective study, we enrolled consecutive UC patients (n=25) and assessed disease activity using the partial Mayo score. Serum IgLC kappa and lambda levels were measured using immunoturbidimetric assay. Inflammatory markers including erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) were also evaluated. Disease extent was classified as proctitis, left-sided colitis, or pancolitis.

Results

Mean serum IgLC lambda levels were significantly higher in active UC compared to remission (29.8 ± 20.2 mg/L vs. 14.4 ± 3.0 mg/L, P = 0.044). However, IgLC kappa levels showed no significant difference between the two groups (36.0 ± 37.6 mg/L vs. 22.5 ± 7.4 mg/L, P = 0.330). In correlation analysis, CRP and ESR demonstrated strong correlations with disease activity (r = 0.573 and r = 0.517, respectively), while IgLC lambda showed only weak correlation (r = 0.315, P = 0.125). Subgroup analysis by disease extent revealed different patterns: while no biomarkers correlated with disease activity in proctitis, CRP alone showed significant correlation in left-sided colitis (r = 0.718) and pancolitis (r = 0.693), with ESR and IgLC lambda showing no significant associations.

Conclusion

Despite elevated serum IgLC lambda levels in active UC, its correlation with clinical disease activity was limited. These findings suggest that B-cell activity markers may not serve as reliable biomarkers for UC disease activity assessment.
P0246 Predicting Operative Recurrence in Crohn's Disease Using a Nomogram Incorporating Histopathological Factors
Authors: Zhang C , Zhang Y , Xiong S , Zhang P , Cao Q , Ye Z , Qiu Y
Published: January 2025

Background

Crohn's disease (CD) poses a substantial risk of disability and often necessitates recurrent surgical interventions. To date, no association between histologic activity and relapse in CD were found.

Methods

Data were retrieved from a prospective inflammatory bowel disease registry. Two blinded pathologists graded the inflammation and fibrosis of archived specimens from primary ileal or ileocolonic resections based on an established histopathological score. Factors associated with earlier operative recurrence were identified using a multivariate logistic regression model. A nomogram was constructed to predict reoperation, with model performance assessed using receiver-operating characteristic (ROC) curves and decision curve analysis (DCA).

Results

Among the 133 patients (68.4% male), the median time to reoperation was 31.9 months (IQR, 14.1-65.7 months). Fourteen reoperations were detected, 4 for abscess/fistula/perforation and 10 for stricture/stenosis. Fifty-four patients experienced endoscopic recurrence within a median time of 10.7 months (IQR, 4.53-18.9 months). Factors associated with reoperation included disease behavior (stricturing, OR 12.1, 95% CI 1.8-80.9; penetrating, OR 9.9, 95% CI 1.4-67.9) and the degree of intestinal fibrosis in the resected specimens (OR 12.1, 95%CI 1.2-126.6). A nomogram, incorporating fibrosis scores, smoking status, disease behavior, and perianal lesions, was established. Both ROC curve and DCA analysis indicated that the nomogram provided increased benefits for predicting reoperation.

Conclusion

The established nomogram, integrating fibrosis grading from resected specimens, serves as a practical tool for predicting reoperation in CD patients. This nomogram enables the identification of high-risk patients, facilitating proactive postoperative interventions to mitigate operative recurrence.
P0247 Clinical and Colonoscopic Features of Colitis in HIV-Positive Patients Mimicking Inflammatory Bowel Disease Over the Past 12 Years
Authors: Kim Prof. Dr. W J , Choi Y S , Kim J K , Paik N
Published: January 2025

Background

Not only the incidence of inflammatory bowel disease(IBD) but also that of HIV-positive colitis is increasing as individual freedom is emphasized, making the diagnosis of IBD more challenging nowadays.

Methods

We reviewed the data of 75 HIV-positive patient at Daehang Hospital, Seoul, from January 2012 to October 2024. Ten patients were filtered from retrospective medical records analysis who were suspected to have IBD before the HIV-positive diagnosis.

Results

Among the 10 patients suspected to have IBD, all were men with a median age of 27, ranging from 22 to 62. Symptom complaints started 2 week ago(2 men), 1 month ago(6 men), 2months ago(1 man), 6month ago(1 man). Initial diagnoses from personal history were ulcerative colitis(5 men), Crohn’s disease(3 men), irritable bowel syndrome(1 man), infectious colitis(1 man). Anal sex history could be obtained from 5 patients. Colonoscopy revealed rectal ulcers(4 men), whole colon ulcers or erosions(4 men), left colon erythema, edema (1 man), and anal abscess(1 man). One patient was found to have amebiasis from cecum tissue.

Conclusion

HIV-positive colitis is very rare but now increasing, necessitating differential diagnosis. Initial suspicion through careful history taking and close observation of colonic mucosal lesions could reduce the misdiagnosis of IBD. Further large-scale cases are needed to identify the characteristics of HIV-positive colitis to exclude the diagnosis of IBD.
P0248 Insomnia as a determinant of poor IBD disease course
Authors: Weintraub Y , Tauman R , Shouval D S , Shamir R , Kwapisz L , Rosenberg S , Dunietz G L
Published: January 2025

Background

Insomnia is one of the most common sleep disorders, affecting up to 30% of the adult population worldwide. Sleep disorders can have a marked impact on immune functions and inflammation, including in patients with inflammatory bowel diseases (IBD) in both active and inactive disease states. Whether insomnia preceding IBD flares affects clinical outcomes is unknown. We examined the association between insomnia and IBD-related outcomes in adults diagnosed with of Crohn’s disease (CD) or ulcerative colitis (UC).

Methods

A retrospective, real-world, cohort study utilizing the Lynx MD’s electronic medical record dataset, provided by a US-based community gastroenterology practice. Deidentified patient charts were analyzed to identify patients with a confirmed diagnosis of IBD (either CD or UC). Eligibility criteria included: ≥3 diagnoses of IBD, ≥1 diagnoses of IBD and: histopathologic diagnosis of IBD; or IBD related surgery; or ≥ 3 months of treatment with standard accepted therapies for IBD; and ≥3 years of follow-up. IBD-related events of hospitalization and/or surgery were recorded. The cohort was classified into two groups based on insomnia diagnosis, prior to IBD related hospitalizations or surgeries. We implemented Cox Proportional Regression models to estimate Hazard Ratios for the IBD-related outcomes.

Results

Among 20,011 patients with IBD, 10,775 (54%) were women, at a mean age of 48.2 ± 18.2 years old, 11,842 (59%) were diagnosed with UC and 8,169 (41%) with CD. Over 3,100 patients (16%) were diagnosed with insomnia prior to the first IBD related hospitalization or surgery.

In an unadjusted model, insomnia was significantly associated with IBD-related hospitalizations - hazard ratio (HR) of 1.43 (95% CI 1.28, 1.59) and IBD related surgeries - HR of 1.42 (95% CI 1.12, 1.81). After adjustment for age, sex, race, body mass index, anxiety and type of IBD (CD vs. UC), IBD-affected patients with insomnia had a higher HR of hospitalization and surgery: HR of 1.35 (95% CI 1.2,1.51) and 1.29 (95% CI 1.01,1.66), respectively, compared to those without insomnia.

Conclusion

In a large real-life dataset of patients with IBD, we found higher rates of IBD-related hospitalizations and surgeries among patients with comorbid insomnia, suggesting that insomnia may be associated with a more severe course of IBD.
P0249 The Impact of Obesity on the Persistence of Advanced Therapies in Inflammatory Bowel Disease
Authors: Hsu W C , Lin S H , Chiu H Y , Kuo C J , Chen C M , Su M Y , Wu R C , Chiu C T , Chang C W , Huang T Y , Pan Y B , Le P H
Published: January 2025

Background

Obesity has emerged as a factor influencing outcomes in inflammatory bowel disease (IBD), yet its effect on the persistence of advanced biologic therapies, especially in Asian populations, remains unclear. This study evaluates obesity’s impact on clinical outcomes and treatment persistence among Taiwanese IBD patients on advanced biologic therapies.

Methods

This retrospective cohort study was conducted at Chang Gung Memorial Hospital, Taiwan, involving IBD patients on advanced biologics between April 2017 and October 2024. Patients were categorized by BMI into obesity (≥27 kg/m²) and control (<27 kg/m²) groups. Outcomes included one-year therapy persistence, infections, IBD-related hospitalizations, surgeries, and flare-ups, with persistence compared across biologic agents.

Results

Among 555 IBD patients, 68 were obese. Obese patients had distinct characteristics: higher male prevalence (86.8% vs. 65.3%), smoking rates (20.6% vs. 7.8%), and comorbidities such as hypertension (30.6% vs. 13.6%) and cardiovascular disease (11.8% vs. 2.5%). Lab results indicated elevated white blood cells, hemoglobin, albumin, and triglycerides, and lower HDL cholesterol in the obesity group. While overall one-year persistence rates were similar, Ustekinumab showed a lower persistence in obese patients.

Conclusion

Obesity in Asian IBD patients is linked to specific clinical traits and comorbidities. Although obesity did not affect overall therapy persistence, Ustekinumab’s lower persistence among obese patients suggests the need for tailored treatments. Future studies should explore optimal therapies for obese IBD patients.
P0251 Inter-rater disagreements in applying the Montreal classification for Crohn’s disease: The Five-Nations Survey Study
Authors: Ukashi O , Amiot A , Laharie D , Menchén L , Gutierrez A , Fernandes S , Pessarelli T , Correia F , Gonzalez-Muñoza C , López-Cardona J , Barreiro-de Acosta M , Yanai H , Armuzzi A , Magro F , Kopylov U
Published: January 2025

Background

The Montreal classification has been widely used in Crohn’s disease (CD) since 2005 to categorize patients by the age of onset (A), disease location (L), behavior (B), and upper gastrointestinal tract and perianal involvement. With evolving management paradigms in CD, we aimed to assess the performance of gastroenterologists in applying the Montreal classification.

Methods

An online survey was conducted among participants in an international educational conference on inflammatory bowel diseases (IBD). Participants classified 20 theoretical CD cases using the Montreal classification. Agreement rates with the IBD board (three expert gastroenterologists whose consensus rating was considered the gold standard) were calculated for gastroenterologist specialists and fellows/specialists with ≤2 years of clinical experience. A majority vote<75% among participants was considered a notable disagreement. The same cases were classified using three large language models (LLMs), ChatGPT-4, Claude-3, and Gemini-1.5, and assessed for agreement with the board and gastroenterologists. Fleiss Kappa was used to assess within-group agreement.

Results

Thirty-eight participants from five countries completed the survey. In defining the Montreal classification as a whole, specialists (21/38 [55%]) had a higher agreement rate with the board compared to fellows/young specialists (17/38 [45%]) [58% vs. 49%, p=0.012] and to LLMs (58% vs. 18%, p<0.001). Disease behavior classification was the most challenging, with 76% agreement among specialists and fellows/young specialists and 48% among LLMs compared to the IBD board. Regarding disease behavior within-group agreement was moderate (specialists: k=0.522, fellows/young specialists: k=0.532, LLMs: k=0.577; p<0.001 for all). Notable points of disagreement included: defining disease behavior concerning obstructive symptoms, assessing disease extent via video capsule endoscopy, and evaluating treatment-related reversibility of the disease phenotype.

Conclusion

There is significant inter-rater disagreement in applying the Montreal classification, particularly for disease behavior in CD. Improved education or revisions to phenotype criteria may be needed to enhance consensus on the Montreal classification.
P0256 Histologically-proven isolated cuffitis and quality of life among patients with ileoanal pouch
Authors: Fischman M , Codish M , Barkan R , White I , Wasserberg N , Rabinowitz K , Avni-Biron I , Banai H , Snir Y , Yanai H , Dotan I , Ollech J
Published: January 2025

Background

Patients with ulcerative colitis (UC) undergoing ileal pouch-anal anastomosis (IPAA) may develop inflammation of the ileal pouch (pouchitis), rectal cuff (cuffitis), or both. We aimed to evaluate how isolated cuffitis impacts patients' quality of life (QoL).

Methods

In a comprehensive pouch clinic at a tertiary referral center (Rabin Medical Center), consenting patients were followed prospectively, with routine clinical, laboratory, endoscopic, and QoL evaluations. Patients undergoing IPAA due to UC and having ≥1 cuff biopsy during follow-up were included. Patients with isolated cuffitis (cuff inflammation but no pouch inflammation) were compared to patients with isolated pouchitis (inflammation of the pouch with a normal cuff). Pouch endoscopy findings were defined based on the Pouchitis Disease Activity Index (PDAI) endoscopic and histologic subscores. Cuff endoscopy findings were defined based on Mayo endoscopic subscore and NANCY histological index. Cuffitis was defined as evidence of moderate-to-severe histologic inflammation (NANCY score 3-4).

Results

The cohort included 116 patients (median age 50 years, IQR 42-64; 60% females, n=68) who underwent 250 endoscopies (median 2, range 1-3). Isolated cuffitis (Mayo≥2) was diagnosed in 7 endoscopies, and isolated pouchitis (PDAI>2) in 33. Histologically, isolated cuffitis was detected in 39 biopsies, and isolated pouchitis in 72 biopsies.

Patients with isolated cuffitis had higher body mass index (27 [23–29] vs. 23 [21–27], p=.03). Inflammatory markers, including C-reactive protein (0.61 [0.32–1.27] vs. 0.64 [0.31–1.03], p=.98) and fecal calprotectin (135.5 [53.25–347.5] vs. 276.0 [131.0–553.0], p=.21), were similar.

Both groups had comparable daily bowel movements (BMs); 39% of patients with isolated cuffitis vs. 42% of those with isolated pouchitis had >10 BM/day (p=.79). Bristol stool scale scores 6-7 were reported in 94% of patients with isolated cuffitis compared to 76% with pouchitis (p=.04). Both groups had similar PDAI clinical sub-scores (p=.98).

Patients with isolated cuffitis were more likely to report overall (22% vs. 7%, p=.08) and current (31% vs. 16%, p=.13) poor well-being. QoL scores were comparable: median Short Inflammatory Bowel Disease Questionnaire (SIBDQ) 46.5 vs. 50.5, (p=.53) and IBD-Control score of 10.0 vs. 7.0, (p=.6).

Conclusion

Cuff histology reveals higher rates of inflammation than endoscopy alone. Patients with histologically-proven isolated cuffitis and a normal pouch experience a negative impact on QoL as those with an inflamed pouch only. These findings suggest that greater attention to identifying cuffitis and effective management are required.
P0257 Correlation of biochemical, endoscopic and histologic endpoints in vedolizumab-treated patients with ulcerative colitis: a post-hoc analysis from the VIEWS randomised controlled trial
Authors: Pudipeddi A , Dhanji P , Paramsothy S , Kariyawasam V , Paramsothy R , Ghaly S , Haifer C , An Y K , Begun J , Connor S , Corte C , Ward M , De Cruz P , Fung C , Redmond D , Chan W , Mourad F , Kermeen M , Leong R
Published: January 2025

Background

Biochemical, endoscopic and histologic endpoints are commonly used to objectively define remission status in ulcerative colitis (UC). Little data exists on the correlation of these endpoints from prospectively collected samples based on a well-defined protocol. Also, optimal faecal calprotectin (FC) values that predict histo-endoscopic remission are lacking.

Methods

The phase IV Vedolizumab Immunomodulator Enforced Withdrawal Study (VIEWS) prospectively recruited 62 patients with UC on vedolizumab in steroid-free clinical remission. Treatment endpoints were assessed at week 0 and 48. Biopsies for histology were standardised using strict protocolised criteria. Definitions of remission using treatment endpoints were C-reactive protein (CRP)<5mg/L, FC<150µg/g, centrally-read Mayo endoscopic score (MES)=0, centrally-read Nancy Index (NI)=0, and histo-endoscopic remission (MES=0 and NI=0). Correlation was assessed using phi (ϕ) co-efficient analysis (value between -1 and 1 reflecting strength of correlation). Receiver operating characteristic (ROC) analysis was performed to determine optimal FC cutoffs to predict histo-endoscopic outcomes (IBM SPSS Statistics, version 30).

Results

A total of 124 datapoints were obtained from paired endpoints. From these, CRP remission was noted in 81%, FC remission 82%, endoscopic remission 66%, histologic remission 61% and histo-endoscopic remission in 54%. Strong correlations were found between endoscopy and histology (ϕ=0.447, P<0.001), and between FC and endoscopy (ϕ=0.395, P<0.001). FC had moderate correlation with histology (ϕ=0.204, P=0.03). CRP had weaker correlations with FC (ϕ=0.158, P=0.08), endoscopy (ϕ=0.111, P=0.24), and histology (ϕ=0.196, P=0.04) (Figure 1). A FC cut-off of 62.6 µg/g (sensitivity 78%, specificity 54%) predicted endoscopic remission (AUC 0.72 [95%CI: 0.61-0.84], P<0.001). A FC cut-off of 34.2µg/g (sensitivity 65%, specificity 60%) predicted histologic remission (AUC 0.66 [95%CI: 0.55-0.77], P=0.006). A FC cut-off of 23.7µg/g (sensitivity 60%, specificity 63%) predicted histo-endoscopic remission (AUC 0.65 [95%CI: 0.54-0.76], P=0.006) (Figure 2).

Conclusion

Endoscopic and histologic endpoints correlate strongly when standardised in a trial setting. FC values below 34.2µg/g and 23.7µg/g best predicted for histologic and histo-endoscopic remission respectively.
P0259 Iron deficiency anemia patterns and outcomes in Romanian inflammatory bowel disease patients: results of a prospective cohort study
Authors: State R M , Marinica A , Mateescu R B
Published: January 2025

Background

Iron deficiency anemia (IDA) is the most frequent complication of inflammatory bowel disease (IBD), with several contributing mechanisms: iron loss from bleeding, decreased iron intake from enterocytes, impaired iron absorption. Our main objective is to study the prevalence and evolution patterns over time of IDA in Romanian patients with IBD.

Methods

We conducted a retrospective analysis of prospectively collected data of ulcerative colitis and Crohn’s disease patients included in the local IBD cohort. Clinical data about disease activity and laboratory data (including CBC, serum CRP levels and ferritin levels) was collected at baseline and follow-up visits. We defined anemia according to the ECCO guidelines as hemoglobin levels < 13g/dL for male and 12g/dL for female patients, and iron deficiency using a serum ferritin level < 100µg/ml [1].

Results

We included in the final analysis 168 patients, totaling 331 patient-visits. 27 female patients (50%) were anemic at their baseline visit and 67% of patients showed ferritin levels < 100µg/ml at baseline. Overall criteria for anemia were fulfilled at 26.6% of patient-visits, while 71.8% of patient-visits showed ferritin levels < 100ug/ml. Over time, the percentage of patients with anemia significantly improved (27.3% and 16.6% at first and second follow up visits respectively, p=0.048 Chi Square) but iron deficiency as reflected by ferritin levels < 100 did not significantly improve over time (75.6% and 81.8% at first and second follow-up visits respectively, p=0.119) despite a significant decrease in the proportion of patients with clinical activity at follow up visits (52% at first visit vs 32% at second visit, p=0.001).

Conclusion

The prevalence of anemia among IBD patients shows a decreasing trend over time as disease control improves; iron deficiency however remains an unmet problem among a majority of IBD patients despite clinical improvement over time.

References

[1]Dignass AU, Gasche C, Bettenworth D, et al. European consensus on the diagnosis and management of iron deficiency and anaemia in inflammatory bowel diseases. J Crohns Colitis. 2015;9(3):211-222. doi:10.1093/ecco-jcc/jju009
P0261 The hidden impact of surgery for inflammatory bowel disease: a qualitative exploration of sexual function and intimacy
Authors: Joshi S , Pelly T , Alrubaiy L , Dames N , Dibley L , Fourie S , Rajeswaran K , White I , Hart A , Tozer P ,   Sex-PROM
Published: January 2025

Background

Surgery for inflammatory bowel disease (IBD) often carries a hidden cost in terms of sexual function. Traditionally, when measuring outcomes, the focus has been on those easily measured, quantified, analysed and applied to health economics, such as mortality, morbidity and disease recurrence. Whilst research in this subject area is expanding, there are limited qualitative data specifically investigating patient experiences of sexual dysfunction post-surgery for IBD. This study aims to produce an in-depth exploration of patient perspectives of sexual dysfunction after surgery, and to assess the broader impact on relationships, intimacy and quality of life.

Methods

An exploratory qualitative study was performed following the ‘Standards for reporting qualitative research’ (SRQR) recommendations. Purposive sampling was employed to recruit a diverse group with differing ages, genders, ethnicities, sexual orientations, religions and relationship status. Participants were recruited from clinical settings, social media and national IBD charities. An interview guide was developed iteratively, with input from an expert patient, qualitative researchers, sexual function experts, gastroenterologists and colorectal surgeons. Semi-structured interviews were conducted via Microsoft Teams/Zoom and audio-recorded, transcribed and analysed. Thematic analysis was conducted using the Framework analysis method (open coding with an inductive approach).

Results

Qualitative interviews were conducted (n=10, 5 females, 5 males, median age 47, age range 24-69), including patients with Crohn’s disease (n=6) and ulcerative colitis (n=4). Participants were of varying sexualities: heterosexual (n=8), pansexual (n=1) and asexual (n=1). Surgeries included fistula surgery, stoma formation, proctectomy and ileo-anal pouch formation. Thematic analysis revealed physical dysfunction including loss of sensation, impaired pelvic muscle control, erectile and ejaculatory dysfunction, diminished orgasmic sensation and adjustments to sexual positions. Psychological impacts were prominent, including loss of desire, altered body image and a sense of shame/stigma. The impact on spontaneity, intimacy and the overall sexual experience was substantial. Crucially, this often led to relationship strain and breakdown, resulting in further isolation and frustration.

Conclusion

Patients who retain ‘normal’ sexual function after surgery can still experience psychological challenges that significantly impact their sexual desire, spontaneity, relationships, intimacy, and sexual experience. These interviews have revealed the often unspoken effects of surgery for inflammatory bowel disease, emphasising the need for healthcare professionals to address these issues in clinical practice.