bluuebunny/crossref_metadata_2025 huggingface dataset:
P0190 Hypoglycemia induces SLC7A11-dependent disulfidptosis to regulate intestinal inflammation in IBD
Authors: Chen C , Tao M , Fu Y
Published: January 2025

Background

IBD is an autoimmune disease related to intestinal mucosal immune dysregulation, and cellular metabolism is an important factor affecting intestinal immunity[1]. Previous studies have shown that the low-glucose environment inhibits the intestinal immune response to IBD, and the specific mechanism is unknown. Recently, a new mode of cell death has been discovered in the study of tumor cells, which is cytotoxic death caused by cysteine accumulation in cells with high expression of SLC7A11 in a low-glucose environment[2]. Therefore, we wanted to explore whether the phenomenon of disulfidptosis with low glucose environmental effects also exists in IBD and whether it has an impact on the regulation of intestinal inflammation in IBD.

Methods

We intend to explore the role and mechanism of SLC7A11-dependent disulfidptosis in low-glucose environment in regulating intestinal inflammation in IBD through mass spectrometry, multi-omics and cryo-electron microscopy, and further explore the molecular mechanism of regulating SLC7A11 at the protein structure level, so as to provide a solid theoretical basis for exploring new cell death modes in different glucose environments in IBD.

Results

We found that the expression of SLC7A11 in the colon of IBD patients and mice with DSS-induced colitis increased, the glucose content of the intestinal mucosa increased, and the genes related to disulfidptosis were down-regulated, suggesting that there may be inhibition of disulfide death in the high-glucose environment in IBD. We further showed that the low-glucose environment may induce disulfidptosis and inhibit inflammation in macrophages under inflammatory conditions, suggesting that the hypoglucose environment may inhibit IBD inflammation by promoting disulfidptosis.

Conclusion

The hypoglycemic environment in IBD may induce slc7a11-dependent disulfidptosis, thereby inhibiting intestinal inflammation.

References

1. Jung, J., et al. Metabolism as a guiding force for immunity. Nat. Cell Biol. 21, 85-93 (2019).

2. Liu, X., et al. Actin cytoskeleton vulnerability to disulfide stress mediates disulfidptosis. Nat. Cell Biol. 25, 404-414 (2023).
P0195 Immune reconstitution following autologous hematopoietic stem cell transplantation with cyclophosphamide-free mobilization for refractory Crohn’s disease
Authors: Saager E , Lutter L , Mahmmod N , Hoytema van Konijnenburg D , Delemarre E , van der Wal M , Oldenburg B , van Wijk F , Fidder H
Published: January 2025

Background

Autologous hematopoietic stem cell transplantation (aHSCT) has emerged as an effective therapeutic strategy for patients with severe chronic inflammatory conditions that are refractory to conventional treatment, including Crohn’s disease. The success of aHSCT is thought to be grounded in resetting the break of immunological tolerance, but the exact mechanisms underlying a favourable response remain incompletely understood.

Methods

We followed the immune reconstitution of 9 patients with severe refractory Crohn’s disease from one month until more than 2 years post-aHSCT. We performed flow cytometry to follow immune cell populations and functional T cells markers over time, in addition to Olink proteomics to study the inflammatory response in serum.

Results

Transplantation proceeded safely, without major adverse events in any of the 9 patients. aHSCT resulted in considerable improvement of disease status in 6 patients, with 3 patients classified as non-responders. After transplantation, we observed a strong change in the peripheral T-cell subset composition, with a reduction of the CD4/CD8 ratio and a reduction of naïve over effector memory (EM) T cells. Non-responders appeared distinct by a higher CD4/CD8 ratio and higher naïve over T-EM frequencies already before transplantation, and a smaller change in subset composition after transplantation. Remarkably, the local T-cell composition did not mirror the changes in the periphery, with an increased CD4/CD8 ratio in intestinal biopsies post-aHSCT, underscoring that a more detailed study of local versus peripheral responses to aHSCT is essential in aiding our understanding of its efficacy. Functionally, the changes in the peripheral T-cell profile were minimal and not clearly related to response. Although the pro-inflammatory profile was not altered, we did find a small but significant increase in the expression of regulatory markers.

Conclusion

aHSCT resulted in strong changes in the T-cell subset composition of Crohn’s disease patients, but only small changes in functional markers related to inflammation, regulation and homing. Non-responders could be distinguished at baseline by a different T-cell composition and also experienced less profound changes herein upon transplantation.
P0200 Evaluating the efficacy of tonsil-derived mesenchymal stem cells and intestinal stem cells-like cells in modulating fibrosis and inflammation in murine colitis models
Authors: Byeon J R , Song E M , Joo Y H , Choe A R , Park Y , Tae C H , Kim S E , Jung H K , Shim K N , Park Y S , Jung S A
Published: January 2025

Background

Current treatments in inflammatory bowel disease (IBD) primarily target inflammation, but effective anti-fibrotic treatments are limited. This study evaluates the therapeutic potential of tonsil derived mesenchymal stem cell (TMSCs) and TMSC induced intestinal stem cell-like cell (T-ISCs) in treating intestinal fibrosis and inflammation using two murine colitis models.

Methods

Two chronic colitis models were established using dinitrobenzene sulfonic acid (DNBS) and dextran sulfate sodium (DSS) in mice. TMSCs and T-ISCs were administered intraperitoneally, with mice divided into seven groups, including control and treatment groups. Colitis symptoms were assessed using disease activity index (DAI) and colon length. After euthanasia on day 30, colon tissues were collected for analysis. Fibrosis markers and inflammatory cytokines were assessed using real-time PCR, while fibrosis severity was evaluated through Masson’s Trichrome staining. In addition, immunofluorescence and western blotting was performed to confirm the fibrosis-related protein expression.

Results

The therapeutic effects of TMSCs and T-ISCs were confirmed in both DNBS and DSS colitis models. In the DNBS colitis model, both TMSCs and T-ISCs treatments significantly reduced DAI and restored colon length compared to the PBS group (colitis control group) (all p < 0.05). TMSCs treatment markedly decreased three fibrosis markers, including COL1A1, Vimentin, and TGF-β, with statistical significance (p < 0.01, p < 0.01, and p < 0.05, respectively), while T-ISCs significantly reduced only COL1A1 expression (p < 0.05). Histological analyses using Masson’s Trichrome staining showed decreased fibrosis scores in both TMSCs- and T-ISCs-treated groups, and protein expression analysis via immunofluorescence and western blot also confirmed reductions in a-SMA, Vimentin, COL1A1, and TGF-β in both TMSCs- and T-ISCs-treated groups, with a particularly pronounced reduction observed in the TMSCs-treated group. In the DSS colitis model, both TMSCs and T-ISCs treatments significantly decreased the colon shortening compared to the PBS group (all p < 0.05). Although fibrosis markers and scores showed no significant changes, inflammatory cytokine levels were markedly reduced in the DSS colitis model. Notably, T-ISCs demonstrated significant reductions in both IL-1β (p < 0.01) and IL-6 (p < 0.05).

Conclusion

TMSCs and T-ISCs demonstrate therapeutic effects in murine colitis models mimicking IBD, with fibrosis reduction in the DNBS model and inflammation reduction in the DSS model. These findings suggest that TMSC-based stem cell therapies are promising strategies for treating fibrosis and inflammation in IBD.
P0211 Characterization of drug-specific CD4+ T cells in patients with inflammatory bowel diseases
Authors: Weichberger A , Rios Martini G , Namuch Castro D M , Funcke N , Müller S , Marutz H , Sokolova M , Stamer N , Riffert J , Bergfeld A , Schulze Dieckhoff T , Nikolaus S , Aden K , Tran F , Schreiber S , Bacher P
Published: January 2025

Background

Biologicals are commonly used to treat chronic inflammatory diseases. Treatment failure is a major limitation for the efficacy of biologicals, which can be caused by the development of anti-drug antibodies. The formation of high-affinity anti-drug antibodies suggests the involvement of specific CD4+ T cell responses. However, the CD4+ T cell reaction against biologicals remains poorly characterized. Therefore, in this study we analyzed CD4+ T cells specific to various biologicals and investigated potential differences of drug-specific CD4+ T cells in patients with continued remission versus those with secondary nonresponses or allergic reactions.

Methods

Peripheral blood samples were collected at baseline and at week 6, week 14, week 22, week 30 after biological treatment. Drug-specific CD4+ T cells were analyzed using Antigen-Reactive T cell Enrichment (ARTE) directly ex vivo from human peripheral blood. To detect immunogenic regions, drug-specific CD4+ T cells were expanded and restimulated with individual peptides covering the whole variable chain of the therapeutic antibodies. Additionally, single-cell RNA sequencing was performed to investigate the gene expression profiles of drug-specific CD4+ T cells.

Results

Of the analyzed biological agents, the chimeric antibody infliximab showed significantly higher activation of reactive CD4+ T cells compared to other humanized or fully human biological agents. Notably, this response was characterized by a highly proliferative Th1 phenotype with evidence of long-term memory. In patients with secondary nonresponses or allergic reactions infliximab-specific CD4+ T cells showed elevated gene and protein expression of TNF-a, IFN-g and IL-21. Restimulation experiments indicated that drug-specific CD4+ T cell responses are driven by small immunodominant peptide regions.

Conclusion

Infliximab exhibits a higher activation of specific CD4+ T cell reactions compared to other biologicals, characterized by a proliferative Th1 response with long-term memory capabilities. Infliximab is a chimeric antibody consisting of murine variable regions, which likely contributes to its immunogenicity. The increased production of TNF-a, IFN-g and IL-21 in patients experiencing secondary nonresponses or allergic reactions highlights the potential role of drug-specific CD4+ T cells in treatment outcomes and formation of anti-drug antibodies. Overall, our data identifies differences in anti-drug CD4+ T cell reactions for different biologicals as well as different treatment outcomes which may contribute to enhance drug efficacy and improve long-term success with immunogenic biologicals.
P0220 Anti-TNFα, anti-integrin α4β7 and anti-IL23p19 biologic treatment dose optimization in a dextran sodium sulphate (DSS)-induced colitis mouse model
Authors: Suarez-Trujillo F , Orejudo M , Soleto I , Ramírez C , Baldán-Martín M , Martínez P J , Gordillo-Vélez C H , Cibrián D , Gisbert J P , Chaparro M ,   *These authors share senior authorship
Published: January 2025

Background

Current immunotherapy for inflammatory bowel disease (IBD) treatment is based on anti-TNFα, anti-integrin α4β7, anti-IL12/IL23 and anti-IL23 antibodies that have demonstrated to be safe and effective. In vivo models are crucial for research with biologics, but the literature on doses of above-mentioned drugs in in vivo IBD models is scarce, highly variable and covers wide ranges. Thus, we aim to find the optimal dose for biologic treatment in a DSS-induced colitis model.

Methods

C57BL/6 mice were randomized into a control group and treatment groups receiving 3% DSS combined with varying doses of neutralizing antibodies against TNFα, integrin α4β7, and IL-23p19. Treated mice received 3% DSS ad libitum for 5 days and clean water for another 3 additional days (5 + 3 model). Neutralizing antibodies were injected intraperitoneally on days 2 and 5 of the experiment. Doses used for optimization were set for each dose at 100, 250 and 500 μg/mouse for anti-integrin α4β7 and anti-IL23p19 antibodies, and at 10, 25 and 50 μg/mouse for anti-TNFα antibody for covering ranges found in bibliography. Weight loss, fecal consistency and fecal occult blood parameters were measured every day of experiment to elaborate a disease activity index (DAI). Mice were sacrificed at day 8 and the colon was obtained for histological evaluation by H/E staining, and for extraction of lamina propria mononuclear cells (LPMCs). Longitude was also measured. Blood was obtained by intracardiac punction and peripheral blood mononuclear cells (PBMCs) were obtained. Distal and proximal colon sections were fixed in 4% paraformaldehyde and embedded in paraffin. 4 μm sections were hydrated and H/E stained for histological score assessment. Extracted LPMCs and PBMCs were stained for flow cytometry evaluation of inflammation markers.

Results

Proximal and distal colon of mice treated with two doses of 10 μg/mouse of anti-TNFα, 250 μg/mouse of anti-integrin α4β7 and 100 μg/mouse of anti-IL23p19 showed the greatest tissue conservation and repair (Figure 1). In addition, these groups had less weight loss throughout the experiment as well as a reduced DAI (Figure 2). LPMCs and PBMCs inflammatory markers were also decreased in these groups in comparison with the others. Slight differences were found in 250 and 500 μg/mouse anti-integrin α4β7 treated mice.

Conclusion

The optimal treatment doses of neutralizing anti-TNFα, anti-integrin α4β7 and anti-IL23p19 antibodies are set at two doses of 10, 250 and 100 μg/mouse respectively for this 5 + 3 model of DSS-induced colitis. By establishing precise dosimetry baselines, our work provides a robust framework for combinatorial therapies, which could unlock novel approaches for IBD treatment.
P0222 Predicting corticosteroid failure in Acute Severe Ulcerative Colitis at admission using the ADMIT-ASC score
Authors: Chan P , Ajmera R , Thin L
Published: January 2025

Background

The treatment paradigm for Acute Severe Ulcerative Colitis (ASUC) continues to evolve in the era of biologics and small molecules, with corticosteroids forming the initial foundation of treatment. A significant proportion of patients fail to improve on corticosteroid therapy alone1 and are at subsequent risk of colectomy, requiring treatment escalation. We applied the recently developed ADMIT-ASC2 model to an Australian cohort of ASUC patients to further validate its role in predicting steroid failure.

Methods

158 admissions (147 patients) that met the modified Truelove and Witts’ criteria for ASUC between 2016-2023 at a Western Australian tertiary hospital were retrospectively analysed. The previously described ADMIT-ASC model was applied to our cohort: CRP ≥100mg/L (1 point), albumin ≤25g/L (1 point), UCEIS ≥4 (1 point) or ≥7 (2 points). Baseline patient data including demographic, disease characteristics, and prior treatment information were collected. Steroid-failure was defined as requiring a lack of clinical improvement (defined by the Oxford Criteria) necessitating medical rescue therapy or surgery.

Results

In our cohort, 158 admissions for ASUC were analysed and 46 (29%) patients were new diagnoses of ulcerative colitis at the time of admission. Of those, 99 patients (62.7%) received medical rescue therapy (95% infliximab, 4% tofacitinib, 1% cyclosporine). Twenty-two (13.9%) patients underwent a colectomy within 30 days and an additional 12 (7.6%) required colectomy within 12 months of discharge. The ADMIT-ASC score was applied to our cohort. A score of ≥3 yielded a 94.1% positive predictive value for steroid failure (OR 9.56). A score of 0 predicted steroid response in 100% of the cohort. The baseline characteristics of the steroid responsive and non-steroid responsive groups are shown in Table 1.

Conclusion

The ADMIT-ASC score provides a simple scoring system available from initial endoscopic and biochemical evaluation. Increased utilisation of this validated tool potentially allows for day 1 prediction of patients at high risk of steroid failure to prompt earlier treatment escalation to advanced therapies.

References

[1]Adams, A., Gupta, V., Mohsen, W., Chapman, T. P., Subhaharan, D., Ramaswamy, P. K., ... & Satsangi, J. (2023). Early management of acute severe UC in the biologics era: development and international validation of a prognostic clinical index to predict steroid response. Gut, 72(3), 433-442.Chicago

[2]Ho, G. T., Mowat, C., Goddard, C. J. R., Fennell, J. M., Shah, N. B., Prescott, R. J., & Satsangi, J. (2004). Predicting the outcome of severe ulcerative colitis: development of a novel risk score to aid early selection of patients for second-line medical therapy or surgery. Alimentary pharmacology & therapeutics, 19(10), 1079-1087.
P0223 In Vitro Fertilization in Women with Inflammatory Bowel Disease – Clinical Characteristics and Outcomes
Authors: Ashkenazi A , Ron Y , Skornick-Rapaport A , Leibovitzh H , Thurm T , Hirsch A , Maharshak N , Cohen N A
Published: January 2025

Background

Inflammatory Bowel Disease (IBD) most commonly affects women of reproductive age. While considered effective, there are limited data concerning IBD and pregnancy-related outcomes in patients receiving in vitro fertilization (IVF). This study compares the characteristics and outcomes of pregnant women with IBD who conceived spontaneously with those who required IVF.

Methods

This retrospective study included pregnant women with IBD who visited the IBD Mom Clinic at the Tel Aviv Sourasky Medical Center (TLVMC). The cohort consists of two groups - women who conceived spontaneously (IBD-spon) or through IVF therapy (IBD-IVF). Demographics, clinical characteristics, as well as pregnancy and IBD-related outcomes were collected from electronic medical records.

Results

A total of 269 IBD pregnancies from September 2017 to December 2023 were reviewed; 53 women (19.7%) conceived via IVF. Among the IBD-IVF group, there was a lower rate of Crohn’s disease (54.7% vs 67%, P=0.02), similar rate of ulcerative colitis (35.8% vs 31%, p=0.347) and lower rate of patients with pouch (9.4% vs 1.9%, p=0.005). Disease duration was longer in IBD-IVF (10.5 ± 6.9 vs. 8.3 ± 6.0 years, p<0.05) and the IBD-IVF group was significantly older (mean 34.5 ± 5.4 years vs. 31.6 ± 4.4 years, p<0.001) and independently associated with a 10% increase in IVF conception likelihood per additional year of age (OR=1.10, p<0.001). Patients with CD who received IVF had higher rates of peri-anal involvement compared to those who conceived spontaneously (37.9% vs. 19.5% p<0.05). Table 1 summarizes these findings.

First-trimester fecal calprotectin levels were elevated in the IBD-IVF group (684.1 ± 1003.5 vs. 373.8 ± 529.6 μg/g, p<0.001). Despite that, no significant differences in IBD exacerbations, advanced therapy adjustments, or hospitalizations were observed. Adverse pregnancy outcomes were more frequent in the IBD-IVF group. These includes lower mean fetal weight (2999.7 ± 493 vs. 3185.6 ± 524.6 g, p=0.05), spontaneous abortions (9.4% vs. 1.9%, p=0.03), and pregnancy losses before 20 weeks (7.5% vs. 1.5%, p=0.03), as detailed in Table 2.

Conclusion

In this study, significantly higher rates of adverse pregnancy outcomes were observed in patients conceiving through IVF. Older age was independently associated with IVF conception. No increased adverse IBD-related outcomes were observed. These data suggest that the complications in the IVF group, are more related to underlying maternal risk factors and emphasize the importance of close monitoring and follow-up in this population.
P0233 Prevalence and characteristics of short bowel syndrome in Crohn's disease: a retrospective observational single centre study
Authors: Laffusa A , Viganò C , Pirola L , Hu W , Mulinacci G , Gallo C , Savino A , Fichera M , Sampietro G M , Invernizzi P , Massironi S
Published: January 2025

Background

Despite a wide range of treatment options for Crohn’s Disease (CD), over half of patients require bowel resection within five years of diagnosis, with one-third needing additional surgery. Even with conservative surgical techniques, these patients remain at risk of Short Bowel Syndrome (SBS), defined as a residual small bowel length of less than 200 cm, potentially leading to intestinal failure (IF), characterized by reduced absorption of macronutrients, water or electrolytes. The prevalence and risk factors for SBS in CD patients remain unclear. Available retrospective studies report an SBS prevalence in operated CD patients ranging from 3.3% to 5.9 %. Our study aimed at describing the prevalence and characteristics of SBS, IF and Intestinal Functional Deficiency (IFD), defined as the need of any chronic enteral supplementation of macro and/or micronutrients, in a cohort of CD patients.

Methods

We conducted a retrospective observational cohort study, including all adult patients with CD referred to the Gastroenterology Department at IRCCS San Gerardo dei Tintori (Monza - Italy) between September 2014 and April 2022. Data were collected through the Electronic Medical Records.

Results

456 CD patients were included with a mean age of 52 years (±18 SD). 221 (48.5%) patients underwent bowel surgery with a median resection length of 63 cm (IQR 60.75); the ileocecal valve was preserved in 49 (22.1%) patients. Four patients (1.8% of operated CD patients) developed SBS, after two to four surgeries over a median follow-up of 18 (IQR 15) years. Of these, three presented with type 2 SBS (jejuno-colonic anastomosis) and one with type 1 SBS (jejunostomy). Three patients had ileocolonic disease and one ileal disease, upper disease was present in three. Two SBS patients had stricturing disease, and the remaining two a penetrating phenotype. Perianal involvement was present in two patients. Only one patient (0.5%) developed permanent IF. On the other hand, 110 (49.7%) of operated patients presented post-surgical IFD: 109 (99.1%) received vitamins, 7 (6.4%) proteo-caloric, and 3 (2.7%) electrolytes supplements. These patients had a higher median age (62 vs 51.5 years, p=0.001), longer small bowel resections (60 vs 20 cm, p<0.0001) and more frequent ileocecal valve resections (91.8% vs 63.9%, p<0.0001) than patients without deficiency.

Conclusion

SBS and IF are rare conditions in CD patients following surgical bowel resection, prevalence is lower than previously reported. Whereas IFD affects about half of resected CD patients, highlighting the importance of prevention, early diagnosis and treatment of nutritional deficit.
P0234 Predicting factors for long-term outcomes of intestinal Behçet's disease in Japan
Authors: Murakami K , Ihara S , Fujishiro M
Published: January 2025

Background

This study aimed to investigate long-term prognosis and predictive factors for relapse in patients with intestinal Behçet's disease (BD) who initiated conventional therapy (5-ASA, oral steroids, and azathioprine) in Japan.

Methods

Sixty-three patients with intestinal BD treated at Tokyo University Hospital in Japan from 2005 to 2024 were included. Patients who required anti-TNFα agents were classified as the Advanced Therapy (AT) group, while those controlled with conventional therapy were classified as the Conventional Therapy (CT) group. Cumulative relapse rates and risk factors for relapse were analyzed by Kaplan-Meier method and Cox proportional hazards Regression.

Results

The median follow-up was 93 months (range, 4-231), with 28 patients (44%) in the AT group and 35 patients (56%) in the CT group. At the time of diagnosis of intestinal BD, there were no significant differences between the two groups in terms of sex, age, and BD subtypes. The cumulative relapse rates at 1, 3, 5, and 10 years were 22.6%, 35.9%, 40.0%, and 50.8%, respectively. Univariate and multivariate analyses identified concomitant use of PPIs (HR: 2.65, 95% CI: 1.06-6.58, p=0.036), the presence of bloody stool (HR: 2.40, 95% CI: 1.05-5.46, p=0.037), CRP ≥ 4 mg/dL (HR: 2.56, 95% CI: 1.04-6.31, p=0.042), and maximum ulcer size ≥ 3 cm (HR: 2.68, 95% CI: 1.05-6.84, p=0.039) as independent risk factors for transitioning to AT. A predictive model incorporating these factors demonstrated good diagnostic ability (AUC = 0.847).

Conclusion

PPI use, bloody stool, high CRP, and large ulcer size were considered risk factors for resistance to conventional therapy and the need for anti-TNFα agents in patients with intestinal BD.
P0239 Sexual quality of life and patient-healthcare communication in Inflammatory Bowel Disease: a comprehensive single-center analysis
Authors: Saidani R , Cherif D , Hassine H , Yacoub H , Debbabi H , Kchir H , Maamouri N
Published: January 2025

Background

Sexual health concerns significantly impact quality of life in inflammatory bowel disease (IBD), yet remain insufficiently addressed in clinical practice. We aimed to assess sexual quality of life (SQoL) in IBD patients compared to healthy controls while exploring patient-healthcare communication patterns.

Methods

We conducted a prospective single-center study of 78 IBD patients (45 with Crohn's disease [CD] and 33 with ulcerative colitis [UC]) and 49 healthy controls. Participants completed a comprehensive assessment including sociodemographic data and validated instruments: Short IBD Questionnaire (SIBDQ), Sexual QoL Questionnaire-Male/Female (SQoL-M/F), Nine-item Patient Health Questionnaire (PHQ-9), and specific questions about sexual health communication with healthcare providers. Disease characteristics and surgical history were also collected.

Results

The cohort included 43 females (55.1%) and 35 males (44.9%), with a mean age of 46.3 ± 13.8 years. IBD patients reported significantly lower SQoL scores compared to controls (males: 77.29 vs 83.83, p<0.001; females: 70.40 vs 81.63, p<0.001). A majority of patients (76.9%, 60/78) reported specific sexual health concerns.

Physical symptoms affecting sexual life included pain during intercourse (34.6%), fatigue (42.3%), and incontinence concerns (29.5%). Psychological impacts were more prevalent, with fear of symptom occurrence during intimacy (51.3%) and decreased sexual drive (47.4%) being the most common concerns. Perianal disease (present in 23.1%, 18/78) significantly impacted male SQoL scores (70.2 vs 79.8, p=0.003) but not female scores.

Depression symptoms (PHQ-9 ≥10) were present in 35.9% of patients and strongly correlated with reduced SQoL (r=-0.62, p<0.001). While 82.1% of patients desired healthcare provider-initiated discussions about sexual health, only 15.4% had raised these concerns themselves, citing embarrassment (56.4%) and perceived time constraints (41.0%) as main barriers.

In multivariate analysis, independent predictors of reduced SQoL in males included age (β=-0.31, p=0.02), depression (β=-2.101, 95% CI: -2.505 to -1.696, p<0.001), and perianal disease (β=-0.28, p=0.03). In females, depression remained the sole independent predictor (β=-1.973, 95% CI: -2.313 to -1.632, p<0.001).

Conclusion

IBD patients experience significantly impaired sexual quality of life compared to healthy controls, with distinct gender-specific patterns in predictive factors. Despite high prevalence of sexual health concerns, there remains a substantial communication gap between patients and healthcare providers. These findings emphasize the need for routine screening of sexual health issues and proactive healthcare provider-initiated discussions as integral components of IBD care.
P0241 The DETECTION Study: DETection by Endoscopy of Colitis in Screening ImplementaTION
Authors: Lloyd A , Hanly M , Nolan B , Doran R , McCarville L , Macmathuna P , Coffey H , Adetona O , Rajan M , Dokic D , Manj J , Morahan F , Lucey M , Walsh N , Musial O , Sugrue K , Twomey R , O'Sullivan C , O'Brien L , Gleeson S , Sheehan D , McDonald C , Moran C , Buckley M , Iacucci M , McDermott E , Cullen G , Horgan G , Mulcahy H , Buckley M , Sheridan J , Egan L , Kevans D , McCarthy J , Leydan J , O'Toole A , Macnamara D , Slattery E , Boland K , Doherty G
Published: January 2025

Background

The National Bowel Screening Program (Bowelscreen), a nationwide initiative program, aims to provide direct access to those aged 55-74 (currently 59-69) for colonoscopy assessment deemed high risk for colorectal cancer via positive faecal immunochemical test (FIT). Inflammatory Bowel Disease (IBD) follows a bimodal distribution of onset with European studies reporting 10-15% diagnosis after age 60. Limited published research exists on IBD incidence in Ireland via FIT-based population screening and associated outcomes. We aim to dtermine incidence rates/severity of incident IBD cases found via FIT-based colorectal screening programme and hRetrospective review was conducted of all index colonoscopes conducted in FIT positive screening participants (aged 59-69) in multiple Irish centres between 2015-2024. Inclusion criteria: histological diagnosis of colitis. Parameters measured: distribution of colitis, histology, clinical sequalae/IBD history, faecal calprotectin (FCP) and treatment escalation based on screening colonoscopyow often screening colonoscopy is performed for patients with known IBD and positive FIT.

Methods

Retrospective review was conducted of all index colonoscopes conducted in FIT positive screening participants (aged 59-69) in multiple Irish centres between 2015-2024. Inclusion criteria: histological diagnosis of colitis. Parameters measured: distribution of colitis, histology, clinical sequalae/IBD history, faecal calprotectin (FCP) and treatment escalation based on screening colonoscopy.

Results

203/8070 (2.52%) of index screening colonoscopies analysed reported endoscopic diagnosis of colitis. 105/8070 (1.3%) satisfied diagnostic criteria for classic IBD (65.7% UC; 34.2% Crohn’s), of which the majority were new diagnosis (73.3%). 32% cases of segmental colitis associated with diverticulosis (SCAD) were identified. 21% cases of NSAID induced colitis were identified. UC Colitis distribution: 18.8% pancolitis, 38.4% proctitis and 42.8% left-sided. Crohn’s distribution: 8.3% small bowel solely; 89% colonic and 2.7% mixed. 48% reported symptoms at endoscopy. Median FCP following diagnostic colonoscopy was 216.5μg/g. 10% of newly diagnosed IBD patients required biologic escalation.

Conclusion

Incidental diagnosis of colitis occurs in 3% of FIT-positive screening participants in a population based screening programme with new diagnoses of IBD including UC, Crohn’s and SCAD requiring treatment. This is a novel, unintended benefit to FIT-based population screening.
P0245 Analysis of quality measurements of colonoscopy at different levels of care in IBD
Authors: Bacsur P , Farkas B , Ivány E , Fábián A , Bor R , Szepes Z , Farkas K , Molnár T
Published: January 2025

Background

High-quality endoscopy in IBD is associated with better clinical outcomes, while quality measurement supports effective quality control. The European Society of Gastrointestinal Endoscopy recommends using nine performance measures, depending on the indication for endoscopic examination in IBD. Our study aimed to compare colonoscopy quality between tertiary and secondary referral centers for IBD patients, based on endoscopic reports.

Methods

In this cross-sectional study, colonoscopy reports of IBD patients were analyzed. At our tertiary center, we consecutively enrolled patients over 18 years old with established IBD between July and October 2024, using their available colonoscopy reports. The secondary care group included patients referred to our tertiary center, with the last existing report from secondary care used for analysis, while the tertiary care group consisted of our patients whose most recent report was similarly used. Nine key performance measures (indication, bowel preparation, photo documentation, ileal intubation, biopsy, endoscopic activity score, high-definition and chromoendoscopy use, and neoplasia detection) were evaluated based on colonoscopy reports. Patients were stratified by procedure indication (diagnostic, activity assessment, or surveillance) as well. Descriptive statistics, Welch’s, and Fisher’s exact tests were used to compare groups, with p-values <0.05 considered significant.

Results

Overall, 207 colonoscopy reports were assessed, of which 68/207 were performed at secondary care level. A total of 78/207 patients were diagnosed with Crohn’s disease, while unclassified diagnoses were noted only at secondary centers. Activity control (88% vs. 38%, p<0.001) and surveillance (8% vs. 0%, p=0.02) examinations were more common at the tertiary level. Bowel preparation was better at tertiary centers (Boston Bowel Preparation Scale [BBPS] 8.3±2.3 vs. 7.2±1.2; p=0.003), and use of BBPS was more frequent at higher levels of care (p<0.001). Disease activity scores were more commonly used at the tertiary level during activity control examinations (51.2% vs. 19.2%, p=0.004), while ileal intubation was also more frequent at the tertiary level (53% vs. 28%; p<0.001). Procedure and withdrawal times did not differ between levels in diagnostic or activity control examinations. Neoplasia detection was low, and biopsy rates were similar.

Conclusion

Quality indicator targets were met in neither secondary nor tertiary centers; however, wider investigation is needed to verify these results. Broad education can help to improve the quality of colonoscopy in IBD care.
P0252 Mild Crohn’s disease is associated with altered sphingolipid metabolism and reduced neutrophilic inflammation
Authors: Bourgonje A R , Ibing S , Argmann C , Sands B E , Dubinsky M C , Jacobsen H A , Larsen L , Jess T , Rajauria P , Shapiro J M , Shah S A , Ananthakrishnan A N , Suarez-Fariñas M , Renard B Y , Colombel J F , Ungaro R C
Published: January 2025

Background

Around 20-30% of patients with Crohn's disease (CD) experience a mild disease course. However, identifying patients likely to maintain a mild course is challenging. This study aimed to identify molecular features of mild CD by exploring biological datasets from two large patient cohorts.

Methods

Patients with mild CD were analysed from two longitudinal cohorts: the Mount Sinai Crohn's and Colitis Registry (MSSCR) observational cohort and the Ocean State Crohn’s and Colitis Registry (OSCCAR) inception cohort. Baseline assessments in both cohorts included biological/immunomodulator use, history of IBD-related surgeries, and complications (stricturing, penetrating, and perianal CD). Mild CD was defined by the absence of these variables at baseline and after five years of follow-up (Fig. 1A). The remaining patients were mild at baseline but progressed during follow-up. Patients with mild CD and those who progressed after being mild at baseline were evaluated for potential molecular biomarkers including circulating metabolites (metabolomics), immune cell profiles (multiparametric flow cytometry), serum proteomics, and intestinal transcriptomics.

Results

In total, 100 (MSSCR) and 152 (OSCCAR) patients were characterized, with 55 (55.0%) and 74 (48.7%) classified as mild CD, respectively. Intestinal transcriptomic analysis revealed downregulation of genes associated with neutrophilic inflammation and innate immunity, including SAA, DUOXA2, FCGR3B, LCN2, S100A8, and AQP9 (Fig. 1B). Flow cytometry showed lower frequencies of neutrophils (CD16+), lower neutrophil-to-lymphocyte ratios (NLR), and higher counts of NK and total B cells in mild CD (Fig. 1C). Metabolomic analysis identified ceramide- and sphingomyelin compounds (particularly acyl-CoA chain lengths C14-16 and C22-26) as positively associated with mild CD (odds ratios [OR] >2.0), whereas primary and secondary bile acids and amino acid derivatives from lysine, tyrosine, and proline metabolism were inversely associated (Fig. 1D). Proteomic analysis in OSCCAR demonstrated associations between C-X-C motif chemokine ligand 9 (CXCL9), macrophage colony stimulating factor (CSF-1), and TGF-β1 latency-associated peptide (LAP-TGF-β), and an inverse association for Delta and Notch-like epidermal growth factor-related receptor (DNER) with mild CD (adjusted P<0.05) (Fig. 1E).

Conclusion

This study provides multi-omics-based biomarker signatures of mild CD, which primarily relate to altered ceramide- and sphingomyelin metabolites and lower systemic neutrophilic inflammation. Future studies focusing on the biological significance and potential clinical impact on disease monitoring and therapeutic strategies are warranted.
P0253 Identification of baseline Pediatric Crohn’s disease location and complications: How do intestinal ultrasound and magnetic resonance enterography compare?
Authors: Morrissey M , Hudson A , Huynh H Q , Carroll M W , Wine E , Thompson A , Isaac D
Published: January 2025

Background

Pediatric patients with newly diagnosed Crohn’s disease (CD) often undergo magnetic resonance enterography (MRE) to assess bowel not accessible by endoscopy and to evaluate for CD complications. In contrast to intestinal ultrasound (IUS), MRE access is quite limited, expensive, and not feasible for young patients. Little is known about how MRE and IUS compare, with a recent systematic review reporting inconclusive results when comparing diagnostic accuracy in pediatric CD. This study therefore aimed to compare MRE and IUS at diagnosis of pediatric CD.

Methods

Pediatric patients (≤18 years old) seen for suspected CD were prospectively consecutively enrolled (2019-2022) and underwent endoscopy (Simple Endoscopic Score for Crohn Disease (SES-CD)), MRE, IUS (performed by IUS trained pediatric gastroenterologists), calprotectin, blood work and assessment (weighted Pediatric Crohn Disease Activity Index (wPCDAI)). A blinded pediatric radiologist read all MREs. An interim analysis was done after 21 patients before the final analysis. Statistical analyses included descriptive statistics and Pearson chi-square.

Results

58 patients (n=38, 66% male) were included; median age 13 years (IQR 10-15, range 6-17). Disease activity at diagnosis was moderate: median SES-CD 14 (IQR 10-21), wPCDAI 48 (IQR 34-59), calprotectin 1455ug/g (IQR 840-2454), C-reactive protein 47mg/L (IQR 27-72), and erythrocyte sedimentation rate 33mm/hr (IQR 18-46). Jejunum and proximal ileum involvement had high levels of agreement between MRE and IUS for non-inflamed bowel, but less agreement for inflammation (Figure 1). There was higher agreement for inflamed distal ileum compared to proximal ileum or jejunum (Figure 1). MRE and IUS performed similarly in identifying endoscopically inflamed bowel, with the highest accuracy for the terminal ileum (TI) (Figure 2). Both were more accurate for moderate/severe (segment SES-CD≥7) vs. mild/moderate/severe disease (segment SES-CD≥3) (Figure 2). For patients with endoscopic TI strictures (n=8/58, 14%), this was seen on MRE (n=8/8, 100%) more often than IUS (n=5/8, 63%). Those without endoscopic TI strictures were still reported on MRE (n=15/50, 30%), more than IUS (n=2/50, 4%). There were no significant differences in MRE vs. IUS bowel wall thickness measurements in all segments of the small and large bowel (p>0.05).

Conclusion

IUS and MRE performed similarly in distal small bowel and colonic CD assessment in both the identification and measurement of inflamed bowel. More proximal small bowel disease may be over reported by MRE or under reported by IUS. MRE also over reported TI stricturing disease. Both may miss mild CD. For initial and longitudinal pediatric CD assessment, repeating IUS rather than MRE is a viable option.
P0262 Analysis of remission maintenance rate according to the extent of MES 1 inflammation in ulcerative colitis
Authors: Kanazawa M , Tominaga K , Tanaka T , Kojimahara S , Masuyama S , Watanabe S , Sugaya T , Haruyama Y , Irisawa A
Published: January 2025

Background

Endoscopic evaluation of inflammation in ulcerative colitis (UC) is important as a predict marker for relapse and maintenance of remission. Mayo endoscopic subscore (MES) is frequently used for endoscopic evaluation in UC, and MES 0 and MES 1 are often considered endoscopic healing. Although MES is evaluated based on findings in the most intense areas, a partial decrease in vascular pattern is rated as MES 1, even if MES 0 is seen in most areas. There are no reports detailing the long-term prognosis of patients with extensive or partial MES 1. In this study, we investigated the remission maintenance rate according to the extent of inflammation in UC patients and analyzed the usefulness of this method.

Methods

This retrospective study was conducted at a single institution in accordance with the ethical principles associated with the Declaration of Helsinki. It was approved by the Dokkyo Medical University Hospital Ethics Committee (approval no. 29002). This study included 285 of 549 UC patients treated at Dokkyo Medical University Hospital. They were diagnosed as MES 0 or MES 1 at the first colonoscopy after remission induction, and their clinical course was followed for 2 years after the colonoscopy. The colon was divided into six segments: cecum, ascending colon, transverse colon, descending colon, sigmoid colon, and rectum. Based on ROC analysis and Youden index results, patients with MES 1 were divided into the 1-3 segment inflammation group and the 4-6 segment inflammation group, and the remission maintenance rate was examined according to the extent of inflammation. In addition, the remission maintenance rates of the MES 0 vs. the MES 1 1-3 segment inflammation group were analyzed (Figure 1).

Results

The remission maintenance rate during the 2-year follow-up period was significantly higher in the 1-3 segment inflammation group than the 4-6 segment inflammation group (P < 0.001). Comparing the MES 0 vs. MES 1 1-3 segment inflammation group, the 2-year remission maintenance rate was significantly higher in the MES 0 group (P < 0.001).

Conclusion

The result of this study suggests that the additional evaluation of MES 1 inflammation range may be a more accurate predictor of remission maintenance.
P0266 Ultrasound Spectroscopy for the detection of inflammation in inflammatory bowel disease
Authors: Petzsche J , Chaghaneh O , Kegel J , Koop P H , Gabriel T , Pfeifer J , Kampfrath N , Queck A , Arsova M , Büttner M , Nauber R , Fettweis G , Siegmund B , Hampe J , Lehmann M , Herzog M ,   HybridEcho
Published: January 2025

Background

Accurate assessment of inflammation within the intestinal wall is crucial in managing patients with Inflammatory Bowel Disease (IBD), a condition with rising incidence and prevalence worldwide. Ultrasound offers an effective, non-invasive diagnostic option to diagnose and monitor the disease. However, traditional ultrasound is highly user-dependent and requires considerable experience to accurately determine the degree of inflammation. As an extension, Quantitative Ultrasound (QUS), the analysis of raw ultrasound data consisting of unprocessed acoustic signals, contains both frequency and phase information, enabling spectroscopy. We hypothesize that these signals allow a precise estimation of inflammation within the intestinal wall.

Methods

The study was conducted at the Sonography Departments of University Clinic Dresden and Charité- Universitätsmedizin Berlin, where patients attended bowel examinations. In addition to the Limberg-Score acquired with a Highend-Ultrasound-Systems, raw data were obtained using a handheld ultrasound device (Clarius L15). For spectroscopy analysis, time-gain compensation was first reversed from the radio frequency data, followed by frequency analysis using short-time fast Fourier transformation.

Results

We included 35 patients (22 male, 13 female) aged 19 to 85 years. They were either diagnosed with Crohn’s disease (24) or ulcerative colitis (11). Our results indicate a positive correlation between the Limberg score (0–4) and peak frequency in MHz, as determined through the raw ultrasound data spectroscopy. Pairwise comparisons applying analysis of variance (ANOVA) testing, followed by a t-test with Benjamini-Hochberg correction as post hoc, revealed statistically significant differences between Limberg scores 0 and 2 (p ≤ 0.05), 0 and 3 (p ≤ 0.01) and scores 0 and 4 (p ≤ 0.05). The comparison between groups 0 and 1 demonstrated a trend but did not reach statistical significance (p=0.058).

Conclusion

Our findings indicate that higher Limberg scores are associated with increased center frequency, with statistically significant differences evident at advanced inflammation levels. This exploratory study demonstrates, for the first time, the capability of QUS to detect changes in intestinal tissues, offering an innovative approach for objectively monitoring inflammatory bowel disease. However, potential confounders such as attenuation in varying imaging depths and mixed causality of the inflammation need to be considered. A reevaluation after including larger sample sizes is required to reinforce the study’s findings and further explore the potential of QUS in the context of IBD.
P0267 Proactive Remote Monitoring of Inflammatory Bowel Disease for Improved Outcomes and Flare Prediction
Authors: Goren M , Talan Asher A , Haj O , Godis T , Briskman Shakhnovsky N , Levi T , Fizdel B , Shtein I , Galper A , Albshesh A , Barda L , Ben Shalom Y , Laks D , Tzur M , Ungar B , Sagi M , Sina S , Goshen G , Ben-Horin S , Zimlichman E , Kopylov U
Published: January 2025

Background

This study evaluated a remote monitoring program for IBD patients, using a mobile app to track disease activity and improve patient-provider communication. The app included disease activity questionnaires, quality of life assessments, and home-based calprotectin tests. we aimed to develop a data-driven, patient-reported care management system for early detection of clinical flares in IBD patients, enabling timely treatment adjustments.

Methods

A 12-month prospective cohort study included 100 adult IBD patients. Participants completed monthly online questionnaires via the “DATOS” platform, assessing disease activity (PRO2/SCCAI), quality of life (PROMIS-10, SIBDQ), emotional state (DASS-21), and perceived disease control (IBD CONTROL). Home calprotectin tests were performed at baseline, 6 months, and 12 months. Data from 533 monthly observations were used to develop a machine learning model to predict flares.

Results

Among 100 patients (74% Crohn’s, 26% ulcerative colitis; median age 31 years), 94% were on biological therapy. Adherence to the remote platform declined over time (86% at 0 months, 53% at 6 months, 30% at 12 months). Over the study period, 40 flares, 14 hospitalizations, 6 surgeries, and 31 changes in biological therapy occurred. Patients experiencing a flare had significantly higher fecal calprotectin levels (mean: 901.8 vs. 330.6 mg/kg, p=0.044), as well as increased anxiety, depression, and stress (DASS-21, p<0.05), poorer quality of life (PROMIS-10, p=0.005; SIBDQ, p<0.001), and reduced perceived disease control (IBD-Control, p<0.001). A machine learning model incorporating calprotectin and patient-reported outcomes demonstrated a 0.85 accuracy in predicting flares.

Conclusion

This study demonstrates the feasibility of a remote monitoring program for IBD patients. Although the program facilitated streamlined patient follow-up, long-term adherence was challenging, highlighting the need for improvements in system usability and patient engagement. The machine-learning model, which combined fecal calprotectin and patient-reported outcomes, showed good accuracy in identifying patients at risk of flares. These findings suggest that remote monitoring, supported by machine learning, could enhance IBD management.