bluuebunny/crossref_metadata_2025 huggingface dataset:
P0047 Understanding the pathogenic role of inflammatory fibroblasts in Inflammatory Bowel Disease
Authors: Matellan C , Nwaezeigwe M , Doherty G , Manresa M
Published: January 2025

Background

TWEAK (TNF-like weak inducer of apoptosis), a member of the tumor necrosis factor superfamily, has been found to be upregulated in IBD biopsies and to promote chronic inflammation in in vivo murine models.

Previous work by our group has identified that TWEAK represses the expression of homeostatic factors in colonic fibroblasts, and it promotes inflammatory fibroblast-monocyte crosstalk.

The aim of this study was to translate in vitro observations into a clinical setting by investigating the presence of TWEAK in the healthy and inflamed gut and its correlation with inflammatory fibroblasts.

Methods

Fresh colonic biopsies were enzymatically digested and processed to extract single cells.

Isolated cells were analysed by flow cytometry to characterise the expression and cellular source of TWEAK, as well as changes in structural cell compartments, including inflammatory polarisation in colonic fibroblasts.

Flow cytometry was conducted on 31 colonic samples of patients with known IBD (inflamed n=11, noninflamed n=10, remission, n=10) as well as 4 healthy controls with no history of IBD

Results

We observed an increased number of TWEAK+ myeloid cells (CD45+/CD11b+/TWEAK+) in inflamed segments compared to non-involved sections, or to biopsies from healthy donors or patients in remission (Figure 1A).

Similarly, inflamed biopsies showed an increase in CD90+/PDPN+ stromal cells, which is consistent with an expansion in inflammatory fibroblasts (Figure 1B), and highly correlates with the accumulation of TWEAK+ myeloid cells (Figure 1C).

Conclusion

The accumulation of TWEAK+ myeloid cells in inflamed tissues is concomitant with the expansion of the inflammatory stroma in ulcerative colitis, positioning TWEAK as a potential driver of inflammatory fibroblast polarisation.

Understanding the effect of TWEAK in stromal remodelling is of key importance both to understanding intestinal physiology and to developing potential therapeutic strategies in diseases as diverse as inflammatory bowel disease.
P0194 Osteoporosis and osteopenia as extraintestinal manifestations in ulcerative colitis
Authors: Andronic A M , Andronic C , Toader E
Published: January 2025

Background

Inflammatory bowel diseases (IBD) are often characterized by associated conditions with extraintestinal manifestations that can make diagnosis and treatment difficult. It is known that chronic inflammation, nutritional deficiencies and corticosteroid treatment in IBD are the main risk factors for developing metabolic bone diseases. This study aims to evaluate ulcerative colitis (UC) patients with osteoporosis and osteopenia as extraintestinal manifestation.

Methods

We analyzed 79 patients (mean age 42 years) with UC and we measured bone mineral density by dual energy X-ray absorptiometry (DXA). Patients who received treatment with corticosteroids were not included in the study. 25(OH)D levels were also measured in all patients enrolled in the study. The patients did not follow vitamin D supplementation treatment. Disease remission was defined with partial Mayo score ≤2. Among the patients included in the study, 52 were under biologic therapy.

Results

Among the patients included in the study 55 patients (69%) were in remission and 49 patients (62%) with low vitamin D levels <20 ng/ml. Osteoporosis (T score <-2.5) was found in 24% of patients at the lumbar-sacral spine and in 13.9% of patients at the femoral neck; osteopenia (T score between -1.0 and -2.5) was also found in 40.5% of patients at the lumbar-sacral spine and in 35.5% of patients at the femoral neck. All patients with osteoporosis had vitamin D deficiency (p=0.01) and osteopenia was present in 61% of patients with vitamin D deficiency (p=0.05). Regarding disease activity, 23.6% patients in remission and 29.1% patients with active ulcerative colitis were diagnosed with osteoporosis (p=0.69), meanwhile in the osteopenia group, 38.1% patients were in remission and 41.6% patients were with active disease (p=0.84). From the patients included in the study, 65.8% were following biological therapy of which only 3.8% were diagnosed with osteoporosis (p=0.007) and 11.5% were diagnosed with osteopenia (p=0.006).

Conclusion

Our data confirm that osteoporosis and osteopenia are common extraintestinal manifestations in ulcerative colitis. Patients with vitamin D deficiency were more likely to develop metabolic bone diseases without statistically significant differences between ulcerative colitis patients with active disease or those in remission. Patients who follow biological therapy have a lower risk of developing metabolic bone disease. Screening for osteoporosis and osteopenia is indicated in UC patients and vitamin D supplements are mandatory.
P0196 Metabolic dysregulation in Crohn’s disease fibrosis: Targeting WISP1 to restore ECM homeostasis
Authors: Buck A , Widemann K , Weber M C , Friess H , Neumann P A
Published: January 2025

Background

In patients with Crohn’s disease (CD), homeostasis of the extracellular matrix (ECM) is significantly disrupted, frequently leading to severe complications such as intestinal stenosis. The maintenance of organ functionality depends on a delicate balance between inflammatory mediators, ECM production, and degradation processes. However, these mechanisms remain poorly understood. This study investigates the dynamic interplay between ECM homeostasis and metabolic pathways in CD, providing novel insights into their role in disease pathogenesis and potential therapeutic intervention.

Methods

Bulk RNA sequencing was performed to compare fibrotic and non-fibrotic intestinal tissues from CD patients undergoing ileocecal resection, aiming to identify key metabolic and ECM-related pathways. Primary matrix-producing fibroblasts were studied in 2D cultures and spheroids to characterize their metabolic activity, with a focus on fatty acid oxidation (FAO) and glycolysis through gene and protein analysis, metabolic assays, and fatty acid profiling (GC-FID). Chronic intestinal fibrosis was modelled in vivo using dextran sodium sulfate (DSS)-treated mice, allowing therapeutic evaluation of WISP1 neutralisation. The in vivo model was characterized using histological and clinical scoring, as well as gene and protein expression analysis.

Results

Gene set enrichment analysis revealed increased WNT signaling coupled with a reduction in fatty acid metabolism. Additionally, fibrotic tissue exhibited elevated levels of oleic acid and palmitate, indicative of increased lipid accumulation. WISP1, a WNT mediator, was identified as an adipokine and a key regulator of the metabolic shift from fatty acid oxidation to glycolysis. The disruption of FAO-related genes, including PPARγ, CPT1A, CPT2, and ACOX1, demonstrated reciprocal effects on fibroblast activity: pharmacological inhibition of FAO increased matrix production by fibroblasts, whereas activation of FAO via the PPARα agonist fenofibrate induced a catabolic fibroblast phenotype. This phenotype was characterized by suppressed ECM expression and enhanced ECM degradation via MMP1. Importantly, therapeutic neutralization of WISP1 significantly reduced fibrosis in a chronic DSS-induced colitis model.

Conclusion

This study presents a novel therapeutic strategy for managing fibrosis in Crohn’s disease. By pharmacologically neutralizing WISP1, this approach aims to correct the underlying metabolic dysfunction, thereby restoring metabolic balance and ECM homeostasis.
P0203 Unique faecal & oral microbiota signatures in first degree relatives of inflammatory bowel disease patients
Authors: Koentgen S , Zhang F , Wu N , Jayawardana T , Little R , Tavakoli P , Ghaly S , Connor S J , Hold G L
Published: January 2025

Background

While the aetiology of IBD is unknown, a range of genetic and environmental risk factors have been described. First-degree relatives (FDRs; siblings, parents and children) of IBD patients share many of these factors. To better understand the interplay between environmental and genetic risk factors, we evaluated the gut microbial profiles of an FDR cohort, their IBD probands and healthy controls (HC). The aim was to identify whether FDRs of IBD patients have healthy or IBD-like microbial features.

Methods

All participants were recruited as part of the Australian IBD Microbiome (AIM) study. Participants were selected based on self-reported first-degree relative status (n=68) and, where possible, affected IBD relatives (n=24) were included for comparison. All participants were antibiotic free for 3-months prior to baseline sampling. Oral and faecal samples underwent 16S rRNA sequencing. The Microbiome Research Centre 16S analysis pipeline and R studio were used for statistical analysis and data visualisation.

Results

The FDR group was predominantly female (63%) with a mean age of 49.7 years and BMI of 25.5 kg/m2. The IBD cohort was significantly different in age to FDR (mean 36.7; p < 0.05) but not controls (mean 40.4 years) and BMI was comparable between groups. European Australians were the most represented ethnic group (47.6%) and 98.6% of participants were non-smokers. Oral microbiota profiles showed no significant difference in alpha diversity across FDR, IBD and HC groups. Differential abundance analysis of the oral microbiota revealed FDRs had increased abundance of Oribacterium, Granulicatella, Lachnoanaerobaculum and Rothia compared to HC, and increased levels of Capnocytophaga, Tannerella and Abiotrophia compared to the IBD group. In agreement with other studies, faecal microbial profiles in the IBD group had significantly reduced alpha diversity compared to both FDR and HC groups. All groups were compositionally different by Bray-Curtis beta dissimilarity analysis (p<0.018). FDRs had higher abundance of Akkermansia, Alistipes and Monoglobus compared to IBD and HC groups. FDRs and IBD shared similar abundance of Butyricicoccus which was lower than the HCs.

Conclusion

FDR oral microbiome signatures had greater variance from HC than IBD groups. Faecal microbial analysis showed distinct differences with enrichment of key beneficial genera in the FDR group. FDR profiles however still shared significant gut microbial features with the IBD group, remaining distinct from healthy controls. FDRs oral microbiome was higher in opportunistic pathogens and IBD-like whereas faecal composition was protective, rich in beneficial metabolite producing genera.
P0206 Skin deep connections: patients with stricturing Crohn’s disease are more likely to have a history of skin scarring than those with non-stricturing Crohn’s and non-IBD controls
Authors: Mohamedrashed M , Yogakanthi S , Chauhan A , Lucas S , Robinson A , Garg M
Published: January 2025

Background

The mechanism and prediction of stricturing Crohn’s disease (CD) to guide medical therapy remains elusive. Formation of hypertrophic and keloid skin scars have not been previously studied in IBD. This study aimed to evaluate the nature of skin scars in patients with CD, and their association with different phenotypes.

Methods

Adult patients attending a tertiary IBD service were invited to participate in this cross-sectional observational study. Patients were divided into three groups (non-IBD controls, non-structuring/non-penetrating CD and stricturing/penetrating CD). A patient survey tool, consisting of 8 questions was administered to assess for the presence of scars and their type. Disease characteristics were ascertained using electronic medical records. The primary outcome of the study was the prevalence of either hypertrophic or keloid scarring across the 3 groups. Secondary outcomes included the rates of scarring overall as well as keloid and hypertrophic scars individually between the three groups. The chi-square test along with pair-wise comparison differences was used to assess for differences between groups.

Results

189 patients were recruited for this study with baseline characteristics presented in table 1 below. Control patients were older than the other groups (p = 0.013). Patients with stricturing/penetrating CD were more likely to be male. Patients with stricturing/penetrating CD (36.5%) were more likely to have either hypertrophic or keloid scars than those with non-stricturing/non-penetrating CD (11.1%) and non-IBD controls (6.3%), p = <0.0001. Pairwise comparisons revealed differences individually between the stricturing/penetrating and non-stricturing/non-penetrating (p = 0.001) and healthy controls (p < 0.001), but not between the latter two groups (p = 0.52). 8 patients with structuring/penetrating CD had a history of keloid scars, but none in the other 2 groups (p < 0.001). Across the 3 groups, there was no difference in the rates of normal scars (p = 0.112).

Conclusion

In this pilot cross-sectional study, a higher rate of hypertrophic or keloid scarring was demonstrated in patients with stricturing or penetrating disease in comparison to healthy controls and those with non-stricturing/non-penetrating disease, suggesting potential underlying common pathophysiology. Future studies confirming this novel association may provide an avenue for further study of predictive and therapeutic targets for IBD.
P0207 Ex-vivo colonoids derived from ulcerative colitis patients retain epithelial inflammatory “memory” even after several passages, which may contribute to UC chronicity
Authors: Abbas-Egbariya H , Braun T , Granot M , Weiss B , Gal-Mor O , Amir A , VanDussen K , Haberman Ziv Y
Published: January 2025

Background

Intestinal epithelia is key in ulcerative colitis (UC) pathogenesis. However, epithelial models that capture the human variations for pre-clinical screening of epithelial-directed interventions are limited. We aimed to determine whether ex-vivo colonoids derived from different UC patients, maintain inflammatory signals associated with UC.

Methods

Rectal biopsies-derived epithelial colonoids were maintained through 4-9 passages (>1 month in culture) using an L-WRN-conditioned medium, differentiated for 48h, and were either left untreated or treated with inflammatory cocktails for an additional 24h. ELISA quantified CXCL1 secretion, mRNAseq and qPCR assessed mRNA levels

Results

7 controls and 9 UC colonoids were generated from different subjects (median age was 16 years, 56% females). After 4-9 passages, untreated colonoids from UC patients secreted significantly higher levels of the CXCL1 chemokine compared to colonoids obtained from non-IBD controls (Fig. 1A). This phenomenon was also observed when colonoids were treated with INFγ and TNFα to mimic gut inflammation (Fig. 1B). mRNAseq further confirmed differences between UC and non-IBD colonoids. Unsupervised PCA analyses indicated the separation of 4/8 UC organoids from control organoids on PC1 (explaining 39% variance) and toward organoids treated ex-vivo with INFγ and TNFα (Fig. 1C). Differential expression (fold change >1.5 and FDR <0.05) identified 800 genes significantly upregulated, and 263 genes downregulated in untreated UC compared to control colonoids following passaging (Fig. 2A). Upregulated genes included DUOX2, DUOXA2, VDAC2, TJP1 (ZO1), TGM2, CXCL1, and IL8, as previously observed in mucosal biopsies from UC (PMID: 36655602) (Fig. 2B). Functional annotation of the upregulated genes highlighted pathways related to responses to wounding, bacterial signals, and cell-cell junctions (FDR<1E-10) (Fig. 2C). Conversely, downregulated genes included lipoprotein lipase (LPL), a key enzyme in lipid metabolism, the sulfate/anion transporter gene SLC26A1, and the mitochondrial coenzyme A transporter SLC25A42 (Fig. 2A-B). Functional enrichment analysis of the downregulated genes revealed associations with rRNA binding (FDR=1E-12) and mitochondrial gene expression (FDR=1E-6), all of which are relevant to UC pathogenesis (Fig. 2C). The expression of these genes and pathways were further induced with inflammatory triggering (Fig. 2D).

Conclusion

UC epithelial cells maintain a heightened inflammatory response ex-vivo after several passaging. This suggests an "inflammatory" epithelial transcriptional memory that may contribute to UC chronicity, justifying the use of this model for testing interventions targeted at the epithelium.
P0276 Psoriasis is more frequently induced and displays a distinct phenotype in patients with Inflammatory Bowel Disease.
Authors: Lhermet M , Castagna J , Puyraveau M , Gallais-Serezal I , Mauny F , Meyer F , Andre M , Clairet V , Aubin F , Toussirot E , Prati C , Vuitton L
Published: January 2025

Background

Specific psoriasis (Pso) phenotypes seem to emerge in inflammatory bowel disease (IBD) patients. Our study explored Pso phenotypes under and outside biologic therapy in IBD, comparing them to those in chronic inflammatory rheumatism (IRD).

Methods

From a prospective university hospital cohort of patients with IBD, IRD, and Pso, we selected those with IBD and/or IRD (axial and peripheral spondyloarthritis or rheumatoid arthritis) associated with Pso, excluding psoriatic arthritis cases. Each case was reviewed to classify psoriasis as therapy-induced or not, define prevalence with phenotype description, examine treatments responsible for induced Pso, and assess risk factors for therapy-induced Pso in IBD.

Results

Among 2,412 patients in the database, 237 (9.8%) had psoriasis associated with IBD and/or IRD: 98 with IBD, 110 with IRD, and 29 with both IBD and IRD. Pso prevalence was 12.1% in IBD vs. 8.5% in IRD (p=0.0056). After analysis, 92 (93.9%) IBD and 86 (78.2%) IRD patients had been exposed to systemic therapy (p=0.0013). The mean age for IBD+Pso and IRD+Pso was 46.4 (±15.8) and 52.8 (±15.5) years, respectively (p=0.0034); 62 (63.3%) and 49 (45%) were women (p=0.0083).

Phenotypic details of Pso were available in 97/98 IBD and 90/110 IRD cases: 70 (71.4%) vs. 33 (30%) were therapy-induced Pso, respectively (p<0.0001). The main systemic therapy linked to induced Pso was biologics: adalimumab in 44 (62.9%) IBD and 15 (45.5%) IRD patients (p=0.0957).

Plaque and inverse psoriasis were noted in 72 (73.5%) and 39 (39.8%) IBD vs. 53 (48.2%) and 6 (5.4%) IRD patients (p=0.0002 and p<0.0001). Lesions appeared on the face in 26 (26.5%) IBD vs. 6 (5.4%) IRD (p<0.0001), on the scalp in 40 (40.8%) IBD vs. 30 (27.3%) IRD (p=0.0391), and on nasal wings in 13 (13.3%) IBD patients only (p<0.0001), suggesting this as a specific site. In IBD, inverse and scalp Pso were more frequent in therapy-induced cases.

Regarding Pso treatments, biologic therapy was discontinued in 13 (13.3%) IBD patients vs. 2 (1.8%) IRD patients (p=0.0014), and a swap out of biologic class was made in 32 (32.7%) IBD patients vs. 5 (4.5%) IRD patients (p<0.0001).

Factors associated to therapy-induced Pso in IBD were active smoking (OR= 2.02, 95% CI [1.14–3.56], p=0.0193), inflammatory phenotype in Crohn’s disease (OR=1.94, 95% CI [1.21;3.10], p=0.0047), and female sex (OR=2.04 [1.25–3.31], p=0.0041).

Conclusion

In this large cohort, Pso prevalence in IBD was high, with therapy-induced Pso being more frequent among women and smokers. Specific phenotypes were observed (induced, inverse, scalp, nasal wings), suggesting a common pathophysiology with the underlying inflammatory disease.
P0281 Comparison of disease characteristics and disease course between paediatric and adult onset Primary Sclerosing Cholangitis and Inflammatory Bowel Disease
Authors: Khan R , Ellen Kuenzig E , Aganya V , Tang A , Jimenez C , Crowley E , Sherlock M , Zachos M , Mulder D , Brill H , Sharma R , Otley A , El-Matary W , DeBruyn J , Abdulaziz Alkhalifa M , Alhashimalsayed Z , Wine E , Carol M , Huynh H , Murthy S , Narula N , Carman N , Griffiths A , Benchimol E , Ricciuto A
Published: January 2025

Background

Primary sclerosing cholangitis (PSC) is a rare cholestatic liver disease that frequently coexists with inflammatory bowel disease (IBD). Data comparing the paediatric- and adult-onset PSC-IBD are lacking. We compared disease characteristics and the clinical course of PSC-IBD between Canadian children and adults.

Methods

This was a multi-center retrospective cohort study including eight paediatric centers from different provinces across Canada including (Ontario, Alberta, Nova Scotia, Manitoba) and four adult centers from the province of Ontario, including patients diagnosed with PSC-IBD from 1985-2023. Patient and disease characteristics and outcome data were extracted from the clinical charts. We compared patient demographics, disease course, laboratory and imaging results, and complications including liver transplant among paediatric- and adult-onset PSC-IBD. Continuous data were reported as median (Q1-Q3) and compared with the Wilcoxon Rank Sum test, and categorical data were reported as number (%) and compared with chi-square or Fisher exact tests. We compared the time to transplant with the log-rank test.

Results

We included 521 patients (228 children, median follow-up 3.3 (Q1-Q3 1.5-5.8) years; 293 adults, median follow-up 9.8 (Q1-Q3 4.3-16.0) years (Table-1). The interval between PSC and IBD diagnosis was longer in adults. Small duct disease and PSC with autoimmune hepatitis (AIH) features were more common in children, with corresponding higher ALT and more frequently positive autoantibodies. Rates of portal hypertension at PSC diagnosis were similar in both groups. Ulcerative colitis predominated in both groups with more IBD-unclassified in children. Colitis was most severe in the right colon in a third of children and adults. Children were more often treated with ursodeoxycholic acid, vancomycin, corticosteroids and immunomodulators. Adult patients experienced a higher proportion of adverse liver events over the entire follow-up duration, but time to event analysis showed similar rates of progression to liver transplant (log-rank p=0.075; 2- and 5-year survival with native liver in paediatric vs. adult: 97% and 90% vs. 94% and 84%). (Figure-1)

Conclusion

In this large Canadian multi-center cohort of PSC-IBD, paediatric-onset disease was characterized by more frequent small duct disease and features of AIH. The interval between IBD and PSC diagnosis was far longer in adults. Although a greater proportion of adult-onset patients experienced adverse liver outcomes overall, rates of transplant at 2 and 5 years were similar between groups, suggesting that PSC progression may in fact be similar.
P0285 Long-term outcome of children with very early-onset non-monogenic colitis: a single center retrospective study
Authors: Pigneur B , Logrieco G , Cucinotta U , Ruemmele F , Charbit-Henrion F
Published: January 2025

Background

Very early-onset inflammatory bowel disease (VEOIBD), defined by IBD diagnosed before the age of 6 years, is a challenging condition with complex clinical features and limited long-term data. Our study describes the long-term outcome of patients diagnosed with VEOIBD without any identified genetic mutation.

Methods

Data on all consecutive patients aged 0–6 years diagnosed with colitis (CD, UC, or IBD-U) at Necker-Enfants Malades Hospital (Paris, France) between 2013 and 2023 were retrospectively reviewed. Patients with monogenic forms of VEOIBD and perianal disease were excluded. Clinical, biological, and endoscopic data were collected at diagnosis and during follow-up (1, 3 and 5 years). Comparisons were made between patients in remission and those with active disease at 3 years of follow up and between age groups (diagnosis before 2 and after2 years). A standardised questionnaire regarding environmental factors during pregnancy and infancy was sent to parents.

Results

Sixty-five patients (49% male, mean follow-up 4.8 ± 2.9 years, including 28 [41%]) with infantile IBD (diagnosed before the age of 2 years) were included. There were 8 (12%) patients with Crohn’s disease (CD), 21 (34%) with ulcerative colitis (UC) and 35 (54%) with IBD unclassified (IBDU). Most of the patients had pancolitis.

Only 3 patients underwent colectomy and diversion during follow-up. Corticosteroid-free remission rates were 48% at 1 year, 71% at 3 years, and 76% at 5 years.

64% of patients were treated with an immunosuppressant during follow-up, mainly azathioprine.

Earlier initiation of corticosteroids was associated with better 1-year remission rates.

Patients with infantile-onset IBD (IO-IBD) had more severe disease at diagnosis (higher disease activity and endoscopic scores, greater need for steroids; p=0.04). However, IO-IBD patients had better long-term outcomes, with lower anti-TNF-alpha use and fewer therapy escalations at 3 and 5 years (p<0.05).

Finally, poorer outcomes were associated with maternal consumption of processed foods, paternal smoking and western lifestyle.

Conclusion

Patients with VEOIBD without genetic mutation exhibit low rate of complications and surgical interventions at the long term. Environmental factors seem to impact the disease burden even in VEOIBD.
P0319 The Fuction of Serological Biomarkers in Assessing Endoscopic Activity in Inflammatory Bowel Disease
Authors: Zhao Y , Liu X , Pu T , Wen H T
Published: January 2025

Background

Identifying IBD and evaluating disease activity depend critically on endoscopy. But it is expensive and intrusive, which emphasizes the need for more easily available and non-invasive biomarkers to help in IBD diagnosis and assessment. This work seeks to investigate their correlation with endoscopic activity and assess the diagnostic relevance in IBD.

Methods

Between January 2022 and September 2024, we registered 365 UC patients, 319 CD patients and 100 control patients at the First Affiliated Hospital of Zhengzhou University. The subsequent biomarkers were examined:WBC, Hb, PLT, N, L, HCT, EOS, ALB, GLB, CRP, ESR, ALB/GLB (AGR), CRP/ALB (CAR), CRP/L (CLR), PLT/ALB (PAR), PLT/L(PLR), N/L (NLR). MES, SES-CD were respectively utilized to evaluate endoscopic activity in UC and CD. Mild endoscopic activity was characterized by MES=1 or SES-CD=3-6, moderate activity by MES=2 or SES-CD=7-15, and severe activity by MES=3 or SES-CD≥16. Biomarker comparions were conducted among UC, CD, and control groups, and between biomarkers and endoscopic activity were examined.

Results

1. While Hb, HCT, L, ALB, and AGR were significantly lower (P<0.05) in both UC and CD groups compared with controls, N, PLT, GLB, CRP, ESR, CAR, CLR, PLR, PAR, and NLR were significantly raised (P<0.001). EOS levels in UC group averaged 0.19×109/L while in CD group they averaged 0.14×109/L, with this difference reaching statistical significance (P<0.01).

2. Whereas WBC, PLT, N, CRP, ESR, GLB, CAR, CLR, PLR, PAR, and NLR were significantly increased (P<0.01), Hb, HCT, ALB, and AGR were significantly lowered in those with moderate to severe disease compared to mild group. Significant variations in N, CRP, ESR, ALR, GLB, AGR, CAR, CLR, and PAR were noted among mild, moderate, and severe disease categories for CD patients (P<0.05).

3. ESR (OR=1.09, P=0.0015), CAR (OR=381.71, P=0.0018) and PAR (OR=1.27, P=0.0072) were independent risk factors for UC endoscopic activity. The AUC of their combination (0.87; 95%CI 0.82-0.92) surpassed the individual values of ESR(0.81; 95%CI 0.75-0.87), CAR(0.84; 95%CI 0.79-0.89), and PAR(0.81; 95%CI 0.76-0.87). AGR (OR=0.05, P<0.001) and CAR (OR=1.72, P=0.0117) were independent risk factors for endoscopic activity in CD. The AUC for the combination (0.81; 95%CI 0.75-0.86) was also higher than only AGR (0.80; 95%CI 0.74-0.85) or CAR (0.74; 95%CI 0.68-0.80).

Conclusion

IBD endoscopic activity was substantially correlated with biomarkers WBC, Hb, HCT, PLT, N, CRP, ESR, ALB, GLB, AGR, CAR, CLR, PLR, PAR, and NLR. While a lower AGR and a higher CAR may indicate more severe endoscopic activity in CD patients, elevated ESR, CAR, and PAR may point to more severe endoscopic activity in UC patients. Their amalgamation can enhance diagnostic efficacy.
P0321 Early improvement of mental health is associated with long-term disease remission in Ulcerative Colitis
Authors: Zheng J , Huang P , Feng R , Li L L , Chen M , Chen R , Zhang S
Published: January 2025

Background

Emerging evidence underscore the critical role of mental health in managing ulcerative colitis. However, the potential impact of early mental health improvement on long-term therapeutic outcomes remains poorly understood. This study aimed to explore the association between early mental health improvements and long-term disease remission.

Methods

This was a post hoc analysis using data from the SELECTION trial (NCT02914522) involving 381 patients treated with filgotinib. Mental health was assessed using the mental health subscale of the 36-item Short-Form Survey. Endoscopic, clinical, and histologic outcomes were assessed at week 58. Multivariable logistic regression was used to calculate adjusted odds ratios (aOR) with 95% confidence intervals (95% CI). Receiver operating characteristic curves, combined with bootstrap resampling, were employed to determine the mental health response threshold.

Results

Early mental health improvements at week 10 were significantly associated with disease remission at week 58. After adjusting for potential confounders, the aOR of mental health improvements was 1.03 (95% CI: 1.00–1.06) for endoscopic remission, 1.03 (95% CI: 1.01–1.05) for clinical remission, 1.03 (95% CI: 1.01–1.05) for histologic remission, and 1.04 (95% CI: 1.01–1.07) for disease clearance at week 58. Patients who exhibited a mental health response at week 10 (defined as an increase in the mental health subscale score of ≥7.85) were more likely to achieve long-term endoscopic remission (aOR 2.67, 95% CI: 1.43–5.25), clinical remission (aOR 1.91, 95% CI: 1.22–2.99), histologic remission (aOR 1.98, 95% CI: 1.27–3.12), and disease clearance (aOR 3.48, 95% CI: 1.74–7.50). Additionally, incorporating mental health response assessment along with clinical remission significantly enhanced outcome predictions. Specifically, patients with only clinical remission at week 10 were approximately half as likely to achieve week-58 endoscopic remission (aOR 0.45, 95% CI: 0.21–0.91) compared to those who attained both mental health response and clinical remission.

Conclusion

Early mental health improvements independently predicted long-term disease remission in ulcerative colitis. Integrating mental health assessments into the management strategies may provide valuable insights beyond physical symptoms.
P0414 Serum Activin-A level as a new biomarker in active Ulcerative Colitis patients
Authors: Ayyildiz T , Ketenci Y B , Duygulu M E , Zorlu B Ş , Avcı B
Published: January 2025

Background

Ulcerative colitis is a lifelong inflammatory disease affecting the rectum and colon to varying degrees. Multiple scoring-classification methods, including endoscopic, clinical, and combined methods, have been used to assess disease severity. Various biomarkers are used for diagnosis and subtyping in ulcerative colitis, including fecal calprotectin, C-reactive protein, p-ANCA, ESR, anti-integrin αvβ6, and serum trefoil factor 3. In this study, we investigated whether there was a significant difference in serum activin-A levels, considered an indicator of intestinal inflammation, between symptomatic active ulcerative colitis patients and a control group.

Methods

The study included 34 patients and 18 controls, Patients were analyzed for serum Activin-A levels, symptomatic assessment, endoscopic evaluation, and laboratory parameters.

Results

Serum Activin-A levels in the patient group were significantly higher than those in the control group (p=0.034). Accordingly, with a sensitivity of 55.9% and a specificity of 72.2%, the cut-off value for Activin-A was found to be 486.925 pg/mL.

Conclusion

Serum activin A level has been associated with active ulcerative colitis

References

Namwanje M, Brown CW. Activins and inhibins: roles in development, physiology, and disease. Cold Spring Harb Perspect Biol. 2016;8(7):a021881. https://www.doi.org/10.1101/cshperspect.a021881

Sonoyama K, Rutatip S, Kasai T. Gene expression of activin, activin receptors, and follistatin in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol. 2000;278(1):G89-97. https://www.doi.org/10.1152/ajpgi.2000.278.1.G89

Dignass AU, Jung S, Harder-d’Heureuse J, Wiedenmann B. Functional relevance of activin A in the intestinal epithelium. Scand J Gastroenterol. 2002;37(8):936-943. https://doi.org/10.1080/003655202760230900

Ogihara, R., Kurumi, H., Kanda, T., Yashima, K., Isomoto, H., & Yamaguchi, N. (2023). Serum Activin A Is a Novel Biomarker of Endoscopic Activity in Ulcerative Colitis. Gastroenterology research, 16(6), 334–341. https://doi.org/10.14740/gr1677
P0415 Bone turnover biomarkers alteration in patients with Inflammatory Bowel Disease
Authors: Omran S , Gamal Eldeen H , Abdel Latif Z , Abdou D , Hamdy R , Gaber A , Ali A , Shehab H , El Raziky M
Published: January 2025

Background

Because of glucocorticoids, chronic inflammation, malabsorption, and other factors, patients with inflammatory bowel disease (IBD) are at varying risk for osteoporosis (OP) and decreased bone mineral density. This puts individuals at risk for osteoporotic fractures, which have a negative impact on their quality of life. The purpose of this study is to measure bone turnover markers (BTMs) representing bone resorption and formation in an Egyptian cohort of IBD patients, compare them to healthy controls, and investigate their relationship to disease activity, extension, and treatment modalities.

Methods

The cross-sectional study included 92 participants: 45 IBD patients, 25 ulcerative colitis (UC), 20 Crohn’s disease (CD), and 47 controls. Overnight fasting blood samples were withdrawn for BTMs including bone formation markers (Procollagen I N-terminal propeptide {PINP} and bone specific alkaline phosphatase {BSAP}), bone resorptive marker (C-terminal telopeptide of type I collagen {CTX}).

Results

Serum CTX, PINP, and BALP levels increased significantly in IBD patients, indicating increased turnover and metabolic bone disease, but there were no significant differences between the UC and CD groups. In terms of disease activity and intestinal involvement, BTM levels in UC and CD patients were comparable. Anti-tumour necrosis-α (anti-TNF-α) users had considerably reduced CTX and PINP increases compared to non-users.

Conclusion

Biochemical testing with BTMs may be useful in the initial evaluation of bone health in IBD patients. Anti-TNF-α users were less likely to experience bone alterations compared to non-users.
P0422 CROHN-PREP study: Simplified bowel preparation adapted to small bowel capsule endoscopy in patients with Crohn’s disease; comparison with the reference method
Authors: Rouveyre R , Collins M , De Maissin A , Flamant M , Trang C , Bouguen G , Dib N , Bourreille A , Le Berre C
Published: January 2025

Background

Ileal involvement is common in Crohn’s disease (CD), affecting two-thirds of patients, of whom 10-15% also present with associated proximal small bowel (SB) lesions that are inaccessible to conventional endoscopy. This proximal location is associated with poorer outcomes, including higher risk of strictures and surgery. Therefore, regular monitoring of these patients is crucial, and SB capsule endoscopy (SBCE) has emerged as a valuable tool for assessing mucosal activity. Its acceptability greatly depends on prior bowel preparation. However, the latter remains debated, and data on this specific population of patients with CD are scarce. The CROHN-PREP study aimed to compare the efficacy of a simplified preparation to a polyethylene glycol (PEG)-based preparation in patients with an established diagnosis of CD.

Methods

This prospective, multicenter, single-blind, randomized controlled trial was conducted across six centers in France between June 2022 and April 2024. Patients were randomly assigned either to a simplified preparation (clear liquid diet + 500 mL + 1L of water) or a PEG-based preparation (24h-residue-free diet + 2L of PEG) in a 1:1 ratio with stratification on disease activity. Intestinal cleanliness (as quantified by the KODA score or qualitatively evaluated), patient’s acceptability of preparation and examination, diagnostic yield, capsule completion rate and SB transit time were compared between both groups.

Results

In total, 148 patients were included, in whom 142 SBCE were analyzable. Terminal ileal involvement was observed in 132 patients (93.0%), with proximal SB lesions associated in 10.6% of cases. No difference was observed in terms of intestinal cleanliness between the two groups. Patient acceptability of the preparation was twice as high—and nearly perfect—among those receiving the simplified preparation (P<0.001). Similarly, acceptability of the examination itself was significantly higher in the simplified preparation group (P<0.001) (Figure 1). The diagnostic yield, the rate of complete examinations, and intestinal transit time were comparable between the two groups.

Conclusion

CROHN-PREP is the first randomized controlled trial to evaluate SB cleanliness prior to SBCE exclusively in a CD patient population. A simplified preparation consisting of a clear liquid diet and water offers a viable alternative to a PEG-based preparation, offering comparable SB cleanliness and diagnostic outcomes while doubling patient’s acceptability. These findings are particularly relevant given the necessity of repeated examinations in patients with CD, in whom acceptability is critical to ensure continuity of care.
P0425 Factors Associated with Biopsy-Proven Cuffitis in Ulcerative Colitis Patients Following Colectomy with Ileal Anal-Pouch Anastomosis
Authors: Fishman M , Codish M , Rabinowitz K , Avni-Biron I , Godny L , Yanai H , Dotan I , Ollech J
Published: January 2025

Background

Total proctocolectomy with ileal pouch-anal anastomosis (IPAA) is the standard surgical treatment in patients with refractory/complicated ulcerative colitis (UC). Inflammation of the small rectal remnant below IPAA lines (“cuff”) is designated cuffitis. Despite its clinical significance and characteristic endoscopic and histologic features, risk factors are vague. This study aimed to decipher demographic, disease, and surgery-related risk factors for histologically proven cuffitis.

Methods

In a comprehensive pouch clinic at a tertiary referral center (Rabin Medical Center), consenting patients were followed prospectively, with routine clinical, laboratory, and endoscopic evaluations. Patients after IPAA due to UC having≥1 cuff biopsy during follow-up were included. Histological cuff samples were scored based on the validated NANCY index. Cuffitis, the primary outcome, was defined as evidence of moderate-to-severe histologic inflammation (NANCY score 3-4). Univariate Cox models were used to assess hazard ratios (HRs) of various factors with the occurrence of cuffitis.

Results

Of 400 patients followed at the pouch clinic, 182 consented to prospective follow-up, and 116 underwent cuff biopsy, each having a median of 2 biopsies. Most patients had histological evidence of moderate-to-severe cuffitis (n=76, 65.5%). Significant associations with cuffitis included disease duration ≤10 years before surgery (HR 15.4, 95%CI; 4.0-59.1, p<0.001); body mass index ≤ 18.5 (HR 3.83, 95%CI; 1.75-8.4, p<0.001); Arab descent (HR 3.2, 95%CI; 1.1-9, p=0.03); immediate postoperative complications (HR 2.0, 95%CI; 1.24-3.2, p=0.004); strong association with pre-operative biologic treatment was observed, with a single biologic (anti-TNF 90%) used before colectomy having a HR of 5 (95%CI;2.6-9.7, p<0.001) and multiple biologics having a HR of 14 (95%CI; 6.1-34, p<0.001). Interestingly, refractory UC as the indication for IPAA (vs dysplasia) was not independently associated with an increased risk of cuffitis.

Conclusion

Several demographic, disease, and surgery-related factors associated with post-IPAA cuffitis were identified. These may be incorporated into decision-making processes. Furthermore, closer postoperative follow-up may be warranted in specific patient subgroups. ese patients may benefit from closer post-operative follow-up.
P0428 Validation of the Urgency-Numeric Rating Scale in Ulcerative Colitis and correlation with endoscopic, histological and manometric activity
Authors: Guimaraes A , Leal T , Caetano A C , Barbosa I , Costa D , Carvalho T , Mendes S , Soares J , Rodrigues Â , Gonçalves R
Published: January 2025

Background

The Urgency-Numeric Rating Scale (NRS) is a scale that assesses the severity of bowel urgency (BU), a common symptom in ulcerative colitis (UC) associated with significant morbidity. The aim of this study was to translate and validate this scale into Portuguese, as well as to assess the prevalence of BU in a cohort of UC patients and, in those in clinical remission, to evaluate its relation with endoscopic and histological activity and manometric changes.

Methods

After translation of the Urgency-NRS into Portuguese, patients with UC seen at the outpatient clinic were asked to complete the scale at T0, after 2 weeks (T1) and after 3 months (T2). PRO2, EQ-5D, EQ-VAS, IBD-Disk and the Global Perceived Effect (GPE) scale were also completed. Acceptability, reliability, construct validity, responsiveness and interpretability were assessed. A subgroup of patients in clinical remission with BU underwent rectosigmoidoscopy with rectal biopsies and anorectal manometry and were compared with a control group (in clinical remission without BU).

Results

126 patients were included (56,3% female), of whom 49,21% (n=62) had BU. Test- retest reliability was excellent (intraclass correlation coefficient 0,823). The Urgency-NRS scores correlated significantly with the PRO-2 (p<0,001), IBD-Disk (p<0,001), EQ-VAS (p<0,001) and EQ-5D (p<0,001), demonstrating construct validity. There were no differences in the Nancy histological index (p=1,000) between patients in clinical remission with urgency (n=14) and the control group (n=16). The Urgency-NRS values correlated with the volume of the first sensation on anorectal manometry (p=0,032).

Conclusion

The Urgency-NRS scale is an easy and quick tool for assessing BU and can be incorporated into clinical practice for the Portuguese population.
P0434 Clinical patterns and prognosis according to the time of diagnosis in Korean IBD Patients with over 10 years of disease duration
Authors: Park Y E , Park S B , Kang S B , Park Y , Kim D , Na S Y , Moon W ,   IBD Research Group of the Korean Association for the Study of Intestinal Diseases (KASID)
Published: January 2025

Background

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic condition marked by intestinal inflammation. IBD diagnosed in children tends to more extensive involvement, but generally responds well to treatment than adult-onset cases. This study aims to compare the long-term clinical characteristics, treatment patterns, and prognosis of IBD in patients diagnosed before and after age 18.

Methods

A retrospective study was conducted using data from 352 IBD patients with a disease duration exceeding 10 years across four hospitals. Baseline characteristics, disease status, and treatment patterns were analyzed at diagnosis, 5 years, 10 years, and currently.

Results

Of the 352 patients, 80 (22.7%) were diagnosed before the age of 18, and 272 (77.3%) were diagnosed at age 18 or older. Patients diagnosed before 18 years of age presented more frequently with CD (82.5% vs. 40.1%), while UC was predominant in those diagnosed later (17.5% vs. 59.9%). Younger patients had a significantly higher prevalence of abdominal pain (66.3% vs. 49.3%), malnutrition/weight loss (22.8% vs. 9.6%), and anal fistula/abscess (25.0% vs. 4.8%) at diagnosis. Younger patients had more pancolitis type in UC (50% vs. 31.9%), and more perianal disease in CD (53% vs 20.7%). Younger patients exhibited higher rates of steroid usage initially, with a gradual shift towards biologics such as infliximab. Over time, disease behavior in CD patients often progressed, especially among those diagnosed at age 18 or older. Multivariate analysis identified fever, fistula/abscess at diagnosis, and biologic use or discontinuation as significant risk factors for recurrence.

Conclusion

In patients diagnosed with IBD before the age of 18, Crohn’s disease (CD) is more common, often presenting with abdominal pain, perianal disease, and extensive involvement. However, with appropriate treatment can maintain remission and achieve better long-term outcomes. In conclusion, these findings suggest that age at IBD onset significantly impacts disease progression and treatment outcomes, underscoring the need for age-tailored management strategies in long-term IBD care.

References

1.Thia KT, Loftus EV, Jr., Sandborn WJ, Yang SK (2008) An update on the epidemiology of inflammatory bowel disease in Asia. Am J Gastroenterol 103(12):3167-3182.

2.Duricova D, Burisch J, Jess T, et al. Age-related differences in presentation and course of pediatric inflammatory bowel disease; an update on the populationbased literature. J Crohns Colitis 2014;8(11):1351–61. 5.

3.Carroll MW, Kuenzig ME, Mack DR, et al. The impact of inflammatory bowel disease in Canada 2018: children and adolescents with IBD. J Can Assoc Gastroenterol 2019;2:S49–S67.
P0437 Positive anti-Saccharomyces cerevisiae antibodies do not affect clinical outcomes in pediatric patients with Crohn’s disease treated with anti-TNF therapy
Authors: LIng D , Grabovski R , Matar M , Shamir R , Shouval D S , Weintraub Y
Published: January 2025

Background

Anti-Saccharomyces cerevisiae antibodies (ASCA) have been associated with a more aggressive Crohn’s disease (CD) phenotype. However, the effect of ASCA serology on the response to biologic therapy, specifically in children on anti-TNF therapy, is unknown. Our goal was to assess whether ASCA levels are associated with clinical outcomes in pediatric CD patients treated with anti-TNF antibodies.

Methods

A single center retrospective study. Demographic, clinical and laboratory data were collected from pediatric CD patients (aged 2.2-17.9 years) treated with anti-TNF therapy, who were tested for IgG ASCA levels upon diagnosis, between 2010-2023. The cut-off value for a positive ASCA result was defined as 30 EU/mL. Clinical outcomes included durability of anti-TNF therapy, corticosteroid-free survival (CSFS) at week 52 of therapy, IBD-associated hospitalizations and IBD related surgery.

Results

One hundred seventy-two patients with CD (69 ,39% females) with a median age at diagnosis of 13.5 (11.1-15.4) years were included. Ninety-two (52%) patients had positive ASCA (> 30 EU/mL). ASCA positivity was associated with female sex (p=0.02) and ileocolonic disease location at diagnosis (p=0.02). Sixty-six (37%) patients were treated with infliximab and 111 (63%) with adalimumab. The median time of follow-up in our cohort was 115 (65-174) weeks. Time to discontinuation of anti-TNF was comparable between patients with ASCA positive and negative levels (97.8% vs. 97.4% and 89.3% vs. 87.4% at 1 and 3 years, respectively). In addition, time to IBD-associated hospitalization and surgery were also similar. Interestingly, patients with positive ASCA achieved CSFR more often, compared to patients with ASCA negative (P=0.04). Sub-analysis of patients with high ASCA values, the top 20%, (>80 EU/mL) demonstrated significantly longer durability of anti-TNF, compared to the patients with lower ASCA levels (<80 EU/mL,p= 0.02).

Conclusion

ASCA positivity is not associated with worse outcomes in pediatric patients with CD treated with TNF antagonists.