bluuebunny/crossref_metadata_2025_split huggingface dataset:
OP07 Psychosocial factors are associated with risk of flare in IBD; results from the PREdiCCt study
Authors: Derikx L , Cotronei C , Gros B , Plevris N , Elford A , Blackwell J , Gaya D , Constantine-Cook N , Lees C ,   PREdiCCt Study Group
Published: January 2025

Abstract

Background
Patients with IBD suffer a high prevalence of psychological disorders. The impact of psychosocial factors on the risk of a disease flare is unknown. We aimed to assess associations between psychosocial factors and disease flare.

Methods
The PREdiCCt study is the largest prospective study of the causes of IBD flare. 2629 patients in clinical remission were recruited from 47 UK sites and followed up for 24 months. At study entry, patients completed questionnaires evaluating anxiety (HADS-A), depression (HADS-D), sleep quality (PSQI), physical activity (GPAQ) and somatization (PHQ15). We investigated associations between psychosocial factors and risk of clinical flare (patient-reported from IBD-Control 8 score) and hard flare (clinical flare and CRP &gt;5 mg/L or faecal calprotectin (FC) &gt;250 mcg/g and change in treatment). Survival analyses with Cox frailty models were performed, separately for Crohn’s disease (CD) and UC/IBDU, adjusting for baseline FC, sex, index of multiple deprivation, hospital site + age.

Results
We included 1641 patients [CD=830, UC/IBDU=811] who had a complete dataset for analysis (Table 1). Clinical flares were reported by 595 patients [CD=280, UC/IBDU=315], with an overall two-year flare rate of 36%. Hard flares were recorded for 219 patients [CD=99, UC/IBDU=120; two-year flare rate: 13%].
UC patients with higher depression scores had an increased risk of both clinical [elevated HADS-D scores of 8-10: aHR 1.72 (95%CI 1.21-2.43, p=0.002)] and hard flare [aHR 2.50 (p&lt;0.001); Figure 1]. Anxiety was associated with an increased risk of clinical flare [elevated HADS-A scores of 11-21: UC/IBDU: aHR 1.46 (1.08-1.99, p=0.01); CD: aHR 1.86 (1.38-2.52, p&lt;0.001)]. In addition, IBD patients with higher somatization scores were at increased risk for clinical flare [CD: aHR 3.86 (2.33-6.40, p&lt;0.001); UC/IBDU: aHR 1.96 (1.25-3.07, p=0.003)], with a borderline effect for hard flare only in CD [aHR 2.34 (1.02-5.38, p=0.05)]. Significant associations were found between sleep deprivation and clinical flare risk in CD [aHR 1.58 (1.22-2.04, p&lt;0.001)]. UC/IBDU patients who did not meet WHO-recommended exercise levels were at increased risk of hard flare [aHR 1.55 (1.03-2.32, p=0.03)].

Conclusion
In this large prospective IBD cohort study we demonstrated a significant burden of several psychosocial factors. Anxiety, depression, somatization, and sleep disturbances were associated with an increased clinical flare risk. Depression and lack of exercise were associated with an increased hard flare risk in UC patients. These findings emphasize the need for a holistic IBD treatment approach.
Table 1: baseline characteristics

Figure 1: Clinical flare risk (left) and hard flare risk (right adjusted for site [fixed effect], sex, IMD, FC + age)
OP13 Higher neoplasia detection rate and lower number of targeted biopsies associated with virtual chromoendoscopy in IBD surveillance: a real-world, multicentre UK study
Authors: Radia C , King A , Harlow C , Yeo J H , Hickey A , Wyatt N , Michael E , Gerard P , Colwill M , Patel C , Patel K , Speight A , Harrow P , Kandiah K , Samaan M , Kent A J , Pavlidis P 
Published: January 2025

Abstract

Background
Dye chromoendoscopy (DCE) with targeted biopsies has traditionally been considered the gold standard for optimal detection of dysplasia in the context of inflammatory bowel disease (IBD) surveillance. Randomised trials have challenged this with both virtual chromoendoscopy (VCE) and high-definition white light endoscopy (WLE) appearing to have comparable yield. This multicentre UK study aims to test the hypothesis that neoplasia detection rate (NDR) in IBD surveillance as part of routine clinical care is not affected by the modality used.

Methods
IBD surveillance colonoscopy procedures for patients with ulcerative colitis (UC) and colonic Crohn’s disease (CD) performed in five UK centres between 2018 and 2024 were reviewed. For procedures with polypectomy or missing data, median withdrawal times for each modality from non-polypectomy cases were imputed. Significant variables in a univariate analysis were included in a logistic regression model to adjust NDR in the three modalities.

Results
A total of 2,673 IBD surveillance colonoscopies in 2,050 patients were included: 1,275 (48%) WLE, 1,032 (38%) DCE, 366 (14%) VCE. Disease breakdown included 74% UC and 26% CD, and 25% of patients had concomitant primary sclerosing cholangitis. The majority (67%) were performed by endoscopists with expertise in IBD surveillance. Median (IQR) withdrawal time in minutes without polypectomy was DCE: 17 (13, 22), VCE: 14 (12, 20), WLE: 11 (8, 14). Neoplasia was detected in 305 (11%) procedures. The NDR (95% CI) were VCE: 19% (15.3, 23.6), DCE: 12% (9.9, 13.9) and WLE: 9% (7.5, 10.7), p&lt;0.001 (figure 1A).
In a univariate analysis, 8 variables were significantly associated with NDR. A logistic regression model including these variables (figure 2) showed that VCE significantly increased dysplasia detection (p&lt;0.001). Older age, previous dysplasia, and longer withdrawal time also significantly increased NDR (p&lt;0.001), with active disease having the opposite effect (p=0.035). Adjustment for these variables did not change modality related NDR substantially (figure 1B). A higher number of targeted biopsies per procedure were taken with DCE 0.52 (SD 1.68) compared to VCE 0.33 (SD 1.59) or WLE 0.13 (SD0.78), p &lt;0.001. However, this did not improve dysplasia yield within these biopsies: DCE 3.2%, VCE 5.7%, WLE 5.0%, (p=0.248).

Conclusion
In this study of IBD surveillance in routine clinical practice VCE has higher NDR than DCE and WLE. DCE was associated with more targeted biopsies without greater dysplasia detection.
OP14 The United European Gastroenterology green paper—climate change and gastroenterology
Authors: Duijvestein M , Sidhu R , Zimmermann K , Carrington E V , Hann A , Sousa P , Touw H R , van Hooft J E , Müller M 
Published: January 2025

Abstract

Background
The 2024 Lancet Countdown highlights the urgent need for aligned structural and sustained changes to avoid the most severe global health impacts. According to the latest Emissions Gap Report from 2024 by the UN Environment Programme, the continuation of current policies would lead to 3.1°C of global warming. Climate change exacerbates extreme weather, food insecurity, and disease prevalence, thereby affecting human health, medical practice, and healthcare stability. Physicians increasingly encounter these effects in daily patient care, with alterations in the gut microbiome, air pollution, heatwaves, and shifts in infectious disease patterns affecting gastrointestinal and hepatic health.

Methods
The United European Gastroenterology (UEG) conducted a comprehensive literature review to assess the climate change associated health hazards and outcomes in gastroenterology as well as the environmental impact of gastroenterology practices. Additionally, the review aimed to identify research gaps and barriers to the implementation of eco-friendly practices in gastroenterology.

Results
Climate change and healthcare exist in a bidirectional feedback loop: healthcare: emissions, waste and resource consumption from the healthcare sector amplify climate change, which subsequently increases the incidence of GI and liver diseases, heat-related illnesses, zoonoses, vector-borne diseases, and malnutrition. The healthcare sector contributes to 4.4% of global carbon emissions, with gastroenterology procedures, particularly endoscopy as the third highest generator with 3.09 kg of waste per day per bed. The "5 Rs of Greener Gastroenterology" framework—reduce, reuse, recycle, rethink, and research—offer a pathway towards reducing the environmental footprint of gastroenterology. These include minimizing unnecessary procedures, advocating for the Planetary Health Diet, and integrating eco-friendly practices such as telemedicine, digitalization, and sustainability-focused education and research. Promoting roles such as "eco-gastroenterologists," "eco-endoscopists", “eco-intensivist” and "eco-surgeons" is essential to advancing sustainable healthcare on both personal and institutional levels.

Conclusion
The United European Gastroenterology Green Paper aims to raise awareness and outline key principles that the GI workforce can adopt to tackle the climate crisis together. To facilitate adoption and transformation into clinical practice, UEG has developed a toolkit for stakeholders to promote such concepts and provide possible solutions at any structural level. This is a call to joint action between national und specialist gastroenterology societies.
OP15 ECCO Topical Review on Pouch Disorders
Authors: Kayal M , Bislenghi G , Adamina M , Ardalan Z , Avallaneda N , de Buck van Overstraeten A , Duijvestein M , Estevinho M M , Furfaro F , Hart A , Holubar S , Lobaton T , Ollech J , Vavricka S , Ferrante M 
Published: January 2025

Abstract

Background
Pouch disorders are common and may present with symptoms of increased stool frequency, urgency, incontinence, pelvic cramping, and perianal drainage, leading to poor sleep, fatigue, and disability. This topical review provides expert consensus recommendations for the diagnosis and management of the most common inflammatory, functional, structural and neoplastic pouch disorders.

Methods
An open-call for participation was made to all ECCO members. Four working groups were formed each focusing on a specific category of pouch disorders. Each group member performed a comprehensive literature review for their assigned disorder using appropriate key words and drafted summary texts. Sections were reviewed and integrated into a single manuscript by MK, GB, and MF.

Results
Symptoms that arise and persist immediately following pouch construction may indicate surgical issues, while those that gradually develop after a prolonged period of wellness may suggest inflammatory or functional disorders. Symptoms of increased stool frequency, abdominal cramping, and urgency are suggestive of an inflammatory disorder, and a short trial of oral antibiotics may confirm the most likely diagnosis of pouchitis, though a pouchoscopy is preferable to exclude other causes. In case of persistent or recurrent symptoms of pouchitis, additional evaluation via stool studies, pouchoscopy and cross-sectional imaging should be considered to rule out chronic antibiotic-dependent or –refractory pouchitis, or Crohn’s-like disease of the pouch. Symptoms of chronic pelvic pain, intermittent obstruction, and incomplete evacuation suggest a structural disorder. Evaluation with pouchography, MR defaecography, pouchoscopy and examination under anaesthesia should be performed to evaluate for pouch prolapse or volvulus, afferent or efferent limb syndrome, anastomotic leakage, strictures or fistulae. Symptoms of incomplete evacuation, incontinence, and pelvic pain that occur in the absence of an inflammatory or structural abnormality point to a functional disorder. Assessment with anorectal manometry, balloon expulsion tests, and defaecography should be conducted to evaluate pelvic floor dynamics and rule out pelvic floor dyssynergia or irritable pouch syndrome.

Conclusion
A multidisciplinary approach is essential for the diagnosis and management of most pouch disorders. Centres with a specialized pouch care team are often best equipped to manage these complex cases, providing the expertise necessary for accurate diagnosis and tailored interventions.
OP21 MIF-CD74 signaling promotes intestinal LTi-like ILC3s activation and gut fibrosis via upregulating pSTAT3
Authors: Zhao Y , Tu Y , Yang Q , Zhang Y , Zou D 
Published: January 2025

Abstract

Background
Intestinal fibrosis is a common complication of inflammatory bowel disease, and its core pathogenesis is fibroblast activation and massive extracellular matrix (ECM) deposition. In recent years, innate lymphoid cells (ILCs) have been shown to be an important source of fibroblast activation signals in fibrotic diseases. This study aims to explore the heterogeneity of ILC3 (the main ILC subgroup in the human intestine) in the intestinal fibrosis and the mechanism of its interaction with stromal cells.

Methods
The intestinal fibrosis model was constructed with ILC3 deficiency mice (Rorc knock out) treated with chronic DSS/TNBS. Flow cytometry was performed to detect the proportion of ILC3 subsets and cytokine expression level. ILC3 were sorted out for transcriptome sequencing and co-culture experiment with primary intestinal fibroblasts.

Results
In chronic DSS/TNBS models, the colon CCR6+ILC3 significantly expanded (p&lt;0.05), and the expression of cytokine IL-22 was upregulated (p&lt;0.05). ILC3 deficiency mice showed lower degree of intestinal fibrosis, including decrease in collagen involvement area (p&lt;0.05) and decrease in ECM-related genes expression(p&lt;0.05). After adoptively transferred of CCR6+ILC3, the severity of intestinal fibrosis in mice increases again. Flow cytometry revealed that CCR6+ILC3 was the main source of IL-22 in the mouse colon. CCR6+ILC3 cells were then sorted by flow cytometry, and co-cultured with mouse intestinal fibroblasts in vitro. Results shown that CCR6+ILC3 can activate fibroblasts. The expression level of α-SMA protein was significantly upregulated (p&lt;0.05). Cell migration ability was also improved in the scratch experiment (p&lt;0.05). Blocking IL-22 could inhibit the effects above. Transcriptome sequencing analysis of sorted ILC3 revealed a significant upregulation in signaling pathways related to cell activation, proliferation and adhesion, with CD74 existing in all of them. Flow cytometry confirmed the expression of CD74 on ILC3 for the first time, which specifically present on CCR6+ILC3 within RORγt+ cells. Cell stimulation experiments in vitro showed that macrophage migration inhibitory factor (MIF)-CD74 signal upregulated IL-22 level of ILC3 cells and was associated with increased phosphorylation of STAT3 signaling pathway. And MIF, the CD74 ligand, significantly increased in both mouse intestinal fibrosis models and stenosis tissue samples from CD patients (p&lt;0.05).

Conclusion
CCR6+ILC3 is enriched in the intestinal fibrotic microenvironment and can continuously promote disease progression by activating fibroblasts through IL-22. CCR6+ILC3 can sense the pathogenic inflammatory factor MIF in chronic colitis through CD74, and increase IL-22 expression by promote STAT3 phosphorylation.
OP22 NR1D1 Deficiency Induces CD47 Upregulation Impairing Macrophage Efferocytosis and Exacerbating Intestinal Inflammation in Ulcerative Colitis
Authors: Chen Y , Liangru Z 
Published: January 2025

Abstract

Background
Ulcerative colitis (UC) is marked by excessive apoptosis of colonic epithelial cells, driven by intrinsic epithelial defects and impaired macrophage efferocytosis. Inefficient clearance of apoptotic cells perpetuates inflammation and obstructs tissue resolution. NR1D1, a nuclear receptor involved in cellular homeostasis and inflammation, has been implicated in immune regulation, but its role in UC pathogenesis, particularly in macrophage efferocytosis, remains poorly understood.

Methods
A clinical cohort of 300 individuals (200 UC patients and 100 healthy controls) was analyzed to assess the relationship between NR1D1 expression and disease severity, using the Mayo score as a measure of clinical progression. In parallel, dextran sulfate sodium (DSS) was used to induce acute colitis in wild-type and NR1D1-knockout mice. Proteomic profiling was employed to elucidate the effects of NR1D1 deficiency on intestinal inflammation. Mechanistic insights into NR1D1 regulation of CD47 expression were obtained using CUT&Tag, chromatin immunoprecipitation (ChIP), and dual-luciferase reporter assays in colonic epithelial cells from UC patients and healthy controls. The impact of NR1D1 deficiency on macrophage efferocytosis was explored in vitro using co-cultures of macrophages and organoids. Therapeutic potential was evaluated by administering a hydrogel loaded with SR9009, an NR1D1 agonist, to DSS-treated mice, followed by single-cell RNA sequencing (scRNA-seq) to assess cellular and molecular changes.

Results
NR1D1 expression was significantly reduced in UC patients and inversely correlated with disease severity, as reflected by the Mayo score. Proteomic analysis in DSS-treated mice confirmed that NR1D1 deficiency aggravated intestinal inflammation. CUT&Tag and ChIP assays identified CD47 as a direct transcriptional target negatively regulated by NR1D1. Loss of NR1D1 led to elevated CD47 expression in epithelial cells, which impaired macrophage efferocytosis and disrupted the resolution of inflammation. Administration of SR9009 via a hydrogel delivery system restored NR1D1 activity, reduced CD47 expression, and improved efferocytosis. scRNA-seq of colonic tissues from treated mice revealed a shift toward anti-inflammatory cellular states, with enhanced macrophage functionality and improved epithelial integrity.

Conclusion
NR1D1 deficiency exacerbates epithelial apoptosis and inflammation in UC by upregulating CD47, thereby impairing macrophage efferocytosis. Restoring NR1D1 activity with SR9009 ameliorates inflammation and promotes resolution through improved apoptotic cell clearance. Targeting the NR1D1-CD47 axis represents a promising therapeutic strategy for UC.
OP29 Young Researcher Award: Breaking New Ground in IBD Research: Organoid Models as the Vanguard for Personalized Therapies
Authors: Verstockt B 
Published: January 2025

Abstract

Background
Organoid technology has emerged as a pivotal tool in IBD research, offering unparalleled insights into disease mechanisms, mechanisms-of-action, and host-microbiota interactions. Advances in these models enable the establishment of co-cultures in dynamic and IBD-specific intestinal environments.

Methods
Intestinal crypts from biopsies of IBD patients were isolated, adult stem cells expanded into 3D organoids and differentiated to reflect epithelial subtypes. To enable easy basolateral and apical access, organoid-derived epithelial cells were cultured in Transwells. For enhanced physiological relevance, organoids were integrated into gut-on-a-chip platforms featuring microfluidic flow and peristalsis, and prolonged co-cultures with stimuli and cell types of interest. Advanced imaging techniques, including high-resolution microscopy, were used to evaluate epithelial dynamics, barrier integrity, and inflammatory responses. These models were utilized to test therapeutic compounds and assess personalized responses based on patient-specific profiles (Figure 1).

Results
Organoid-based models replicated key features of IBD pathology, including inflammation-induced epithelial dysfunction and barrier loss. Imaging provided critical insights into cell-cell interactions and mucus expression under inflammatory conditions and therapeutic interventions. Barrier integrity was rigorously assessed using transepithelial electrical resistance in Transwells, confirming functional disruptions associated with inflammation or ER-stress. Transcriptomic analyses revealed patient- and disease-specific responses to cytokines, microbial metabolites, and environmental stressors, demonstrating the relevance for personalized therapeutic strategies. Early gut-on-a-chip experiments validated the integration of intact (Papp) organoid-derived epithelial monolayers with stromal components and dynamic flow.

Conclusion
The convergence of organoid technology and gut-on-a-chip systems heralds a new era in IBD translational research. These platforms provide complementary strengths, enabling researchers to tailor models to specific investigative needs. Gut-on-a-chip models integrate organoid-derived epithelial layers with stromal, vascular, and/or immune components under dynamic flow conditions, offering unparalleled insight into the spatial and functional complexities of the gut environment. Together, these systems support personalized exploration of disease pathways and (preclinical) therapeutic efficacy, bridging the gap between in vitro modeling and clinical application. This convergence establishes a versatile foundation for precision medicine, addressing individual variability and driving transformative advances in patient care.
OP35 Low remission recapture after ustekinumab dose optimization in Crohn’s disease: results of the randomized placebo-controlled double-blind REScUE study.
Authors: Bossuyt MD PhD P , Rahier J F , Baert F , Louis E , Macken E , Lobaton T , Busschaert J , Peeters H , Dewint P , Franchimont D , Dutré J , Willandt B , Claessens C , Dewit O , Ferrante M , Vermeire S 
Published: January 2025

Abstract

Background
In Crohn’s disease (CD), an exposure-response relationship exists for ustekinumab, with higher serum levels associated with better outcomes. Although several retrospective and observational studies demonstrate dose-escalation of ustekinumab can be effective in case of secondary loss of response (LOR), prospective placebo-controlled data are lacking. The aim of the REScUE study (NCT04245215) was to investigate the effect of 2 different re-induction regimens with ustekinumab on clinical, endoscopic, biological and pharmacological outcomes in patients with CD.

Methods
This Belgian multicentre prospective double-blind randomized placebo-controlled trial included adult patients with CD treated with ustekinumab who presented with secondary LOR to ustekinumab after documented primary response. Secondary LOR was defined by PRO-2 (AP&gt; 1 AND SF&gt; 3) and confirmed by either an elevated biomarker (CRP &gt;5 mg/L or faecal calprotectin &gt;250 µg/mg) or endoscopic signs of inflammation. All patients received a single IV re-induction with ustekinumab (≈6mg/kg) and were then randomized 1:1 to blinded maintenance ustekinumab 90 mg SC Q4W (intervention) or 90 mg SC Q8W (control) for 48 weeks. Primary endpoint was proportion of patients with steroid-free clinical remission (definition in fig 1) at week 48, with missing data were handled using non-responder imputation.

Results
In total, 132 patients were screened, and 108 patients were included: 67% female, median [IQR] age 41 [32-54] year, median disease duration 14 [7-22] years. Prior anti-TNF exposure was reported in 92% of patients, while ustekinumab was the first-line advanced treatment in 7% of patients. The primary endpoint of steroid-free clinical remission at week 48 was achieved by 9/54 (17%) patients in the q4w regimen vs 8/54 (16%) in the q8w regimen (p=0.96) (fig 1). Endoscopic remission (SES-CD &lt;3) was achieved in 5/54 (10%) vs 3/54 (6%) (p=0.52), endoscopic response (≥50% decrease in SES-CD from baseline) was achieved in 11/54 (22%) vs 6/54 (12%) (p=0.23) and 0.52biomarker remission was achieved in 20/54 (38%) vs 13/54 (26%) (p=0.19) in the q4w regimen vs the q8w regimen, respectively. Time to first clinical remission was similar between groups (fig 2). Association with ustekinumab serum levels will be reported. No new safety signals were observed.

Conclusion
In patients with CD experiencing secondary LOR to ustekinumab, dose optimization with a single IV re-induction followed by intensified maintenance dosing (90 mg SC q4W) was not superior to a single IV re-induction followed by conventional maintenance dosing (90 mg SC q8W) in achieving steroid-free clinical remission. The secondary endpoints were numerically higher but not significant in the intensified regimen.