bluuebunny/crossref_metadata_2025 huggingface dataset:
P137 Salivary calprotectin: a potential biomarker in inflammatory bowel disease?
Authors: Rodrigues C , Gomes A , Leal J , Mendes K , Correia M J , Pereira P , Martins R , Nélio V , Rosa N , Soares C , Ministro P
Published: January 2024

Background

Background: Biomarkers are used frequently for evaluation and monitoring of IBD. Fecal calprotectin (FCP) is an already established biomarker in IBD, nevertheless patients often do not feel comfortable with stool manipulation. A saliva sample collection is particularly interesting due to its noninvasiveness and readiness of collection. We aimed to assess if salivary calprotectin (SCP) could be used as a new biomarker to assess disease activity.

Methods

In this observational cohort study, saliva was collected through the passive drool technique from adult IBD patients. All patients were submitted to a previous oral examination performed by a dentist. Recent history of antibiotic treatment (within the preceding month), proton pump inhibitors or non-steroidal anti-inflammatory drugs were exclusion criteria. Determination of FCP and SCP levels was accomplished using Elia Stool Extraction Kit and Elia Calprotectin 2 test. Intestinal disease activity was assessed with fecal calprotectin levels and the Harvey-Bradshaw Index (HBI) or Partial Mayo score (PMS). Ethical approval was obtained.

Results

92 patients (56 with CD and 36 with UC) were included. Clinical characteristics are presented in Table 1. Patients had a median FCP of 45 mg/Kg and a median SCP of 206.5 mg/Kg. No significant correlations between SCP and FCP, CRP (C-reactive protein), ferritin and ESR (erythrocyte sedimentation rate) were found. However, there was a significant correlation between fecal calprotectin and CRP (p<0.001) and ESR (p=0.011). Disease activity scores did not correlate significantly with SCP, although there was a significant correlation between FCP and PMS (p=0.006).

IBD patients were stratified based on a composite criterion for inactive disease HBI score <5 for CD or a PMS ≤ 2 for UC, and FCP cutoff value of 150 mg/Kg), with no significant difference in SCP between the two groups, despite the significant difference in FCP (p<0.001). No significant differences between different treatments groups or no treatment in salivary calprotectin concentration were found using Kruskal–Wallis H tests (CD (χ2(4) = 6.211, p = 0.184; UC group (χ2(3) = 1.201, p = 0.753)). 77% of patients with IBD do not have periodontal health. Nonetheless, there was no significant difference in the median SCP value between patients with or without periodontal health. Although the median SCP value was higher in patients with UC without periodontal health, the difference was not statistically significant (0.484).

Conclusion

SCP does not correlate with FCP and do not represent a reliable biomarker to distinguish disease activity in patients with IBD patients. Moreover, according to our results, it cannot be used as a marker of lack of oral health, namely periodontitis.
P157 Differentiation of Tonsil-derived mesenchymal stem cells to intestinal stem cells-like cells for cell therapy of inflammatory bowel disease
Authors: Song E M , Joo Y H , Byeon J , Choe A R , Park Y , Moon C M , Kim S E , Jung S A
Published: January 2024

Background

Tonsil-derived mesenchymal stem cells (TMSCs) were found to exhibit a faster growth rate compared to mesenchymal stem cells derived from other tissues. This is attributed to the relatively younger age of the tonsil tissue donors. Moreover, it has been verified that TMSCs possess the capability to undergo differentiation into endoderm lineages, giving rise to cell types like parathyroid glands and insulin-producing cells. In this study, we explored the possibility of differentiation of TMSCs into intestinal stem cells-like cells (ISC-like cells), a cell type of endoderm lineages for utilizing these cells for therapeutic applications in inflammatory bowel disease (IBD).

Methods

TMSCs were cultivated in DMEM (10% FBS) and used in the experiment when 90-100% confluency was observed. Adipose-derived mesenchymal stem cells (AMSCs) were used as the control for assessing the differentiation efficacy of TMSCs. The morphology of cells was verified at each differentiation stage, and the expression of endoderm and intestinal stem cell markers was confirmed using real-time PCR (qPCR), western blotting, and immunofluorescence (IF) staining.

Results

Subjected to 100ng/ml of Activin A for endoderm differentiation and cultured for 2 to 5 days, TMSCs exhibited an upregulation in endoderm markers (SOX17, FOXA2), as confirmed by real-time PCR. Specifically, under the influence of Activin A at 100ng/ml and cultured for 5 days, there was a significant increase in the expression of SOX17 (pre-differentiation vs. endoderm-differentiation, 0.999 vs. 3.610, P=0.0394) and FOXA2 (1.047 vs. 3.912, P=0.0297). Following the endoderm differentiation phase, the medium was changed to include 500ng/ml of FGF4 and 500ng/ml of Wnt3a for a 7-day period. Post-culture, the expression level of Lgr5, an intestinal stem cell (ISC) marker, was significantly increased in TMSCs (1.061 vs. 134.0, P<0.001). Notably, AMSCs displayed a lower expression rate compared to TMSCs (TMSCs vs. AMSCs, 134.0 vs. 9.819, P<0.001). Moreover, the spheroids formation was observed 7 days after the initiation of FGF4 and Wnt3a treatment, a phenomenon absent in AMSCs differentiation. Immunofluorescence staining for differentiation markers further validated these findings: the expression of SOX17, an endoderm marker, and the fluorescence density of LGR5, an ISC marker, were notably higher in TMSCs compared to AMSCs. Protein expression levels also confirmed the upregulation of each marker in TMSCs.

Conclusion

This study validated the potential of TMSCs to differentiate into ISC-like cells, with a higher efficiency observed compared to AMSCs. The prospect of differentiating into ISC positions TMSCs as promising candidates for use as a tool in IBD.
P160 Integrative transcriptional analysis to identify predictive biomarkers for IBD severity and subtyping
Authors: Balasubramanian B , Patel S , Gall L , Parker S , Carpenter A , Hannan N , Pin C , Moran G , Ordóñez Morán P
Published: January 2024

Background

Conventional diagnostic strategies for Inflammatory Bowel Diseases (IBD) heavily rely on invasive biopsy procedures and subjective questionnaires, thereby introducing intrinsic limitations in the context of precision medicine. By understanding the molecular mechanisms behind IBD disease biology, we aim to identify certain signalling pathways relevant for epithelial tissue regeneration under chronic inflammation conditions.

Methods

To address these limitations, we compared gene expression in a large cohort of IBD patients, utilizing the IBD Plexus database (Crohn’s & Colitis Foundation, US) as well as other publicly available datasets. We further validated our results derived from the transcriptional programs by using patient derived advanced 3D-organoid models (Hospital of Nottingham, UK). These models, derived from ulcerated and normal tissue regions of IBD patients, serve as a sophisticated platform for robust validation, bridging the gap between molecular insights and clinical applications.

Results

Our primary objective was to discern putative biomarkers that are capable of effectively stratifying IBD subtypes. We further identified the genes that were upregulated exclusively in each subtypes and the gene signature that is elevated in inflamed samples compared to non-inflamed samples. We found that either the chemokine and interleukin (IL-17) signalling pathways which have known roles in recruitment of immune cells thereby perpetuating chronic inflammation and several key chemokines influence the integrity of the epithelial barrier function and regeneration. We are also analysing non-invasive biomarkers by using samples such as blood, plasma and stool and employ machine learning methods to correlate with established clinical indicators such as sCDAI, PRO2, PRO3, and MAYO categories.

Conclusion

Hence, in identifying specific targets we can introduce novel therapeutic strategies to mitigate inflammation and restore integrity of the gut epithelial barrier. With this research we aim to improve the current IBD diagnostics landscape as well propels it towards precision medicine by offering precise subtyping and predictive markers for disease severity, ultimately contributing to more personalised and effective therapeutics interventions.
P172 Spatial Transcriptomics Characterization of S1P Pathway Genes in Ulcerative Colitis and Crohn’s Disease Colon Tissues
Authors: Zhang J , Maddux R , Petersen A , Mehandru S , Stauffer W , Baichwal V , Harris S
Published: January 2024

Background

Inflammatory bowel diseases (IBD), such as ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory diseases of the gastrointestinal tract, related to the confluence of environmental and immunological factors in genetically predisposed individuals. Activated T and B cells migrate from the lymphoid tissue into the circulation through the interaction of Sphingosine-1-phosphate (S1P) and the S1P1 receptor (S1P1), which can perpetuate inflammation and lead to tissue damage. Targeting of cellular migratory pathways has emerged as a novel therapeutic paradigm in IBD. The aim of this study is to characterize the S1P pathway-related genes and signaling pathways driving the pathogenesis of UC and CD.

Methods

Spatial transcriptomics analysis was performed in health volunteer (HV, n=2), UC (n=4) and CD (n=2) FFPE colon tissues using the GeoMX platform and NanoString whole transcriptome atlas (WTA) assay. The WTA panel was run on 8 samples stained with antibodies to S1P1, pan Cytokeratin, and CD45. Six regions of interests (ROIs) were selected in each sample based on the staining and each ROI were split into two areas (CD45+ or CD45-). Differential gene expression and enriched pathways analysis including S1P pathway genes were performed in CD45+ and CD45- segments in HV, UC and CD colon tissues.

Results

A total of 6085 and 6054 differentially expressed genes were identified from the CD45+ segments in UC and CD respectively, compared to HV colon (P=0.05), including the genes that are involved in T cell activation (e.g., HLA-DPA1, CCDC13), immune cell migration (e.g., ADAM15, CCL5) and tissue damage (e.g., FABP6, PDK4). Interestingly, significant differences were identified in UC and CD in S1P pathway gene expression. Specifically, SMPD1, a gene involved in generating ceramide and regulating inflammatory responses, was the most significantly up-regulated gene from both CD45+ and CD45- compartments in UC compared to HV colon. While CERS2 and CERS6, genes related to S1P metabolism, were significantly down-regulated genes in CD45+ and CD45- compartment in UC respectively, as compared to HV colon. Additionally, RTN4 (participates in the intestinal epithelial barrier function) and PLPP3 (dephosphorylates extracellular S1P to sphingosine) were most significantly down-regulated genes from CD45+ segments in both UC and CD compared to HV colon.

Conclusion

In summary, our study successfully validated the GeoMx transcriptome analysis approach in FFPE colon tissue and assessed the S1P pathway gene signature difference in HV, UC and CD colon tissues supporting the pathway’s role in IBD. Results could also facilitate the identification of potential S1P pathway UC and CD disease biomarkers.
P181 Combination of EPIC-CD epigenetic signatures accurately identifies non-response to multiple biologics in patients with active Crohn’s disease
Authors: Joustra V , Li Yim A , Henneman P , Ishtu H , de Waard T , Evgeni L , Noble A , van Zon S , Chapman T , McGregor C , Adams A , Satsangi J , de Jonge W , D'Haens G
Published: January 2024

Background

While the introduction of biologicals has revolutionized Crohn’s disease (CD) care, the current trial-and-error approach to treatment selection is insufficient, emphasizing the unmet need for predictive biomarkers. We previously developed 2 distinct panels of 25- and 68 epigenetic markers that were accurately associated with (non-)response to vedolizumab (VDZ) or ustekinumab (USTE) in both anti-TNF naïve and experienced patients. In this analysis of the EPIC-CD study, we examined how both models performed in detecting Crohn’s disease patients unresponsive to treatment with multiple biological agents.

Methods

We measured peripheral blood DNA methylation profiles in an independent cohort of adult CD patients that were sequentially treated with anti-TNF (infliximab, adalimumab), VDZ and/or USTE using the Illumina EPIC BeadChip array. Treatment failure was determined using objective outcome measures including endoscopy, MRI or the need for resection combined with clinical- and biochemical parameters (CRP and/or fecal calprotectin (FCP)). Using raw methylation data and our previously developed VDZ and USTE models, predictions were generated, and the percentages of true and false negatives were subsequently calculated.

Results

We included 34 CD patients (53% females, median age 36, median disease duration 13 years). Of these, 27 patients had a history of VDZ failure, 26 had experienced USTE failure, and 19 had failed both VDZ and USTE determined with endoscopy (82%), MRI (6%), or surgical resection (12%) and supplemented by CRP (35%) and/or FCP (47%) and clinical outcome assessment (94%). Notably, we observed a substantial proportion of patients with extensive disease location (67.6%), perianal disease (52.9%), and/or a history of IBD-related surgery (70.6%), underscoring the therapy-refractory nature of this cohort. Both VDZ- and USTE-response prediction models demonstrated accurate prediction of non-response, with a true negative rate of 89% (24 out of 27) for VDZ and 92% (24 out of 26) for USTE. When specifically targeting patients who failed both VDZ and USTE, the models correctly identified 16 out of 19 (84%) as non-responders. Twelve of these 19 patients (75%) had previously failed anti-TNF treatment.

Conclusion

We demonstrate the predictive power of the EPIC-CD epigenetic signatures to effectively identify patients that failed both VDZ and USTE treatment. Our results hold considerable clinical significance, as accurately pinpointing non-response to a combination of multiple biological agents enables clinicians to directly consider alternative modes-of-action, such as JAK inhibitors.
P182 Hepatic lesions in chronic inflammatory bowel disease revealed by liver biopsy during surgery
Authors: Siham B , zazour A , koulali H , Ismaili Z , Kharrasse G
Published: January 2024

Background

Chronic inflammatory bowel diseases are complicated in 10 to 30% cases by hepatobiliary abnormalities, the aim of this study was to evaluate the prevalence of histological liver abnormalities and demonstrate the advantages of performing a systematic liver biopsy during surgery.

Methods

from 2018 to 2022,twenty patients underwent surgery for inflammatory bowel disease (IBD) with systematically liver biopsy during the procedure .

Results

Twenty IBD patients were operated (sex ratio M / F: 1.5),the mean age was 31.7 years, during a mean follow-up of three years before surgery ; occlusive syndrome was the dominated indication of surgery in 90% cases, and acute colitis in 10% cases,two patients had cytolysis,and one patient had cholestasis,four patients had radiologically steatosis.Histologically,fourteen patients had small duct cholangitis (chronic or subacute portitis, portal fibrosis),five patients had steatosis and one patient presented with primary sclerosing cholangitis .

Conclusion

peroperative liver biopsy identify liver diseases in an early diagnosis and as a result medical treatment was adapted and regular surveillance of the liver was ensured.
P199 External validation of Intestinal Ultrasound score: IBUS-SAS with clinical (CDAI), biomarkers and endoscopic scoring system (SES-CD)
Authors: Nagarajan K V , Yelsangikar A , Nagar A , Bhat N
Published: January 2024

Background

Intestinal ultrasound (IUS) is a non-invasive tool for assessing disease activity in patients with Inflammatory bowel disease. International Bowel Ultrasound Segmental Activity Score (IBUS-SAS) is a comprehensive score proposed by an expert consensus with good reliability. We aim to assess the correlation of the IBUS-SAS with clinical and endoscopic scores and biomarkers in patients with Crohn’s disease (CD) in a point-of-care setting.

Methods

This retrospective study was conducted from October 2021 to September 2023. All patients with CD who underwent colonoscopy at initial presentation or assessing disease activity on follow-up were included. At the clinic visit, Crohn’s disease activity index (CDAI), C-reactive protein levels (CRP), Faecal calprotectin (FC) were documented. IUS was performed in the clinic and IBUS-SAS was documented. A colonoscopy was done within 1 week of the clinic visit. Endoscopic disease activity was documented using Simple Endoscopic Score in Crohn’s disease (SES-CD).

Statistical Analysis

Pearson’s correlation was performed between IBUS-SAS and the clinical and endoscopic scores and the biomarkers. ROC analysis was done to assess the threshold value of IBUS-SAS to predict the presence of endoscopic disease activity.

Results

181 patients were included in the study.

In patients with clinical remission, the median IBUS-SAS was 8 (± 23.5). The median IBUS-SAS was 62 (± 21.47), 70 (± 15.47) & 64 (± 0.58) in patients with mild, moderate to severe & severe CDAI respectively. The Pearson correlation coefficient between IBUS-SAS & CDAI was 0.7 (95% CI 0.62-0.77; p < 0.001).

The IBUS-SAS in patients with normal CRP levels (< 5mg/L) was 8 (± 19.54) & in patients with elevated CRP was 64 (± 18.99). The IBUS-SAS in patients with normal FC was 8 (± 19.65) & elevated FC (>250mcg/g) was 64.5 (± 22.66). The Pearson correlation coefficient between IBUS-SAS & CRP was 0.49(95% CI 0.37-0.60; p < 0.001) and with FC was 0.58 (95% CI 0.46-0.68; p < 0.001).

The IBUS-SAS correlated well with SES-CD score with IBUS SAS scores of 8 (± 12.92), 53.5 (± 16.35), 65 (± 20.83) & 65 (± 8.62) in patients with inactive, mild, moderate, & severe SES-CD respectively. The Pearson correlation coefficient between IBUS-SAS & SES-CD was 0.77 (95% CI 0.7-0.82; p < 0.001).

The IBUS-SAS score of > 37.5 revealed an area under the curve of 0.96 (95% CI 0.92 – 0.99) with a sensitivity of 94% & specificity of 91% to predict endoscopic disease activity (SES-CD > 3).

Conclusion

The IBUS-SAS score correlated very well with clinical and endoscopic disease activity as well as biomarkers. A score > 37.5 had a sensitivity of 94% and specificity of 91% to predict the presence of endoscopic disease activity.
P205 Histologic image-based ensemble model to identify myenteric plexitis and predict endoscopic postoperative recurrence in Crohn’s disease: a multicentre, retrospective study
Authors: Li Y , Wang Y
Published: January 2024

Background

Myenteric plexitis is correlated with postoperative recurrence of Crohn’s disease (CD) when relying on traditional statistical methods. However, comprehensive assessment of the myenteric plexus remains challenging. This study aimed to develop and validate a deep learning system to predict postoperative recurrence through automatic screening and identification of features of the muscular layer and myenteric plexus.

Methods

In this study, we retrospectively reviewed 205 CD patients who underwent bowel resection surgery from 2 hospitals. Patients were divided into a training cohort (n=108), an internal validation cohort (n=47) and an external validation cohort (n=50). A total of 190960 patches from 278 whole-slide images of surgical specimens were analysed using ResNet50, and 6144 features were extracted after transfer learning. Spearman correlation analysis, LASSO logistic regression and the interclass correlation coefficient test were utilized for feature selection. We used five robust algorithms to construct classification models. The performances of the models were evaluated by the area under the receiver operating characteristic curve (AUC) in three cohorts.

Results

The stacking model achieved satisfactory accuracy in predicting postoperative recurrence of CD in the training cohort (AUC: 0.980; 95% CI 0.960-0.999), internal validation cohort (AUC: 0.908; 95% CI 0.823-0.992), and external validation cohort (AUC: 0.868; 95% CI 0.761-0.975). The accuracy for identifying the severity of myenteric plexitis was 0.833, 0.745, and 0.694 in the training cohort, internal validation cohort and external validation cohort, respectively.

Conclusion

Our work initially established an interpretable stacking model based on muscular layer and myenteric plexus features extracted from histologic images to identify the severity of myenteric plexitis and predict postoperative recurrence of CD.
P210 Association between Non-Alcoholic Fatty Liver Disease and Related Factors in Patients with Idiopathic Chronic Ulcerative Colitis
Authors: Sánchez Rosado R R , Martínez Gonzalez H , Dosal Limón S K , Higuera de la Tijera M D F , Villanueva Herrero J A , Jiménez Bobadilla B , De León Rendón J L
Published: January 2024

Background

UC is an immunomodulated inflammatory intestinal disease that can involve systemic or extraintestinal manifestations. Few studies have evaluated the possible association between UC and nonalcoholic fatty liver disease (NAFLD). However, the prevalence of NAFLD among patients with UC has been reported to be higher than in the general population. Objetive: To determine the frequency of NAFLD in patients with UC and the factors associated with the simultaneous presence of both diseases.

Methods

This was an observational, cross-sectional, relational, and analytical study that included 40 patients with UC. Data on demographics, clinical information, biochemical parameters, endoscopic findings, and histological features were collected for each patient. Disease activity was assessed using the Truelove and Witts scales, Mayo endoscopic scale, and Riley histological index. NAFLD was evaluated using transient elastography (FibroScan®), determining the controlled attenuation parameter (CAP) with a cutoff score of 248 dB/m to define steatosis. Hepatic fibrosis was considered when the measurement exceeded 6.5 kPa. The risk of steatohepatitis was estimated using the FAST index. Data were analyzed using the MyFibroScan® app, selecting "multi-etiology" as a parameter. Statistical analysis was performed using SPSS version 26, calculating correlation coefficients using Spearman's Rho. A value of p < 0.05 was considered significant.

Results

The clinical and demographic characteristics of the patients are described in Table 1. A positive correlation was found between CAP and Body Mass Index (r = 0.36; p = 0.02). Statistically significant differences were observed between CAP and Truelove and Witts scale (p = 0.02). Differences were also noted between kPa value (p = 0.03) and FAST index (p < 0.001) and the medical treatment used to control UC. No associations or correlations were observed between CAP, kPa, FAST index, and endoscopic or histological severity or other clinical characteristics of the patients.

Conclusion

The presence of NAFLD in patients with UC may be of metabolic origin, predominantly associated with overweight/obesity, and determined by the clinical-biochemical immunomodulated inflammatory activity of the disease and the concurrent treatment used. These findings highlight the importance of a multidisciplinary approach in the care of patients with UC.
P211 Impact of celiac disease on the outcome of Inflammatory Bowel Disease
Authors: Alonso I , Ramos L , Hernández-Camba A , Yagüe-Caballero C , Vicente Lidón R , Taxonera C , García-Brenes M A , Gisbert J P , Chaparro M , Madero Velázquez L , Carrillo-Palau M , Arranz Hernández L , Castro Senosiain B , García de la Filia Molina I , Rojas-Feria M , López Romero-Salazar F , Bastón-Rey I , Sánchez-Azofra M , Riestra S , Pérez-Galindo P , Ortega Moya S P , Brunet-Mas E , Sanz Segura P , Caballero-Mateos A M , Calafat M , Botella Mateu B , Manceñido Marcos N , Rodríguez-Lago I , Suárez-Ferrer C , Gutiérrez Casbas A
Published: January 2024

Background

Inflammatory bowel disease (IBD) and celiac disease (CeD) are digestive disorders that share common genetic, immunological, and environmental factors in their pathogenesis.

Objective

To investigate whether the concurrent diagnosis of CeD and IBD predisposes to a more aggressive phenotype of IBD.

Methods

A multicenter case-control study was performed including cases (celiac IBD) and controls (non-celiac IBD) (paired 1:2, matched for sex, year of diagnosis, and IBD type). CeD diagnosis was established if Marsh score was > 1. Disease phenotype and IBD outcomes, including mortality and neoplasm development, were ascertained from medical records.

Results

66 patients with celiac IBD (39 females; 30 ulcerative colitis-UC/6 indeterminate colitis-IC/30 Crohn disease-CD; age at diagnosis 30±14 years) and 132 matched non-celiac IBD patients (85 females; 68 UC/4 IC/60 CD; age at diagnosis 32±14 years) were included. The diagnosis of CeD was confirmed by gastroscopy and duodenal biopsy in 97% of cases, and the most common histological lesion was Marsh 3. Overall, there were no significant differences in the duration of IBD (median 11±8 years vs 9±8 years; p=0.81), IBD extension (UC (E1/E2/E3): 6 (20.7%)/14 (48.3%)/9 (31%) vs 19 (29.2%)/22 (33.8%)/24 (36.9%); p=0.39); CD (L1/L2/L3/L4): 17 (56.7%)/3 (10%)/8 (26.7%)/2 (6.7%) vs 27 (45%)/6 (10%)/23 (38.3%)/4 (6.4%); p=0.71), extra-intestinal manifestations (10 (15,2%) vs 20 (12,8%); p=0.96) and other autoimmune diseases (8 (12%) vs 16 (12.1%); p=1) between celiac and non-celiac IBD, respectively.

In terms of disease outcome, no differences were found either globally or by IBD subtype in terms of perianal disease, use of mesalamine, exposure to immunomodulators, receipt of biologic agents, need for IBD surgery, and development of neoplasm during follow-up (Table 1). There was no mortality in any of the cohorts.

Conclusion

No significant differences in disease outcome were observed in patients with a concurrent diagnosis of CeD and IBD compared with non-celiac IBD patients. In our large multicenter cohort of patients with celiac IBD and IBD controls, coexisting CeD did not show an impact on the natural history of IBD.
P223 Early prediction and objective criteria to define failure of rescue medical therapy in acute severe ulcerative colitis
Authors: Kakkadasam Ramaswamy P , Subhaharan D , Edwards J , White L , Patrick D , Shahzad A , Willmann L , Shukla D , Ishaq N , Bhullar M , Dorrington A , Satsangi J , Mohsen W
Published: January 2024

Background

Medical rescue therapy (MRT) is effective in intravenous corticosteroid refractory acute severe ulcerative colitis (ASUC). We recently described the ADMIT-ASC score to identify patients on admission at high risk of steroid failure. In this setting, our primary objective in this analysis is now to identify parameters at admission which could identify non-response to MRT, following corticosteroid failure. Co-primary objective is to develop and validate a model to identify non-responders to MRT.

Methods

Two cohorts were studied, for discovery and validation. Retrospective analysis of 66 adult ASUC admissions receiving MRT between 2015-19 at Gold Coast University Hospital and Logan Hospital was first performed. Clinical, endoscopic and laboratory data were collected. Non-response was defined as undergoing colectomy during the index admission. Univariable and multivariable logistic regression were employed to identify predictors of non-response. A predictive model was developed based on thresholds obtained from ROC curves. The predictive model was validated in 99 patients admitted to Gold Coast University Hospital and Sunshine Coast University Hospital between 2020-23.

Results

In the 2015-19 cohort, out of 66 episodes who received MRT, 11 episodes (16.7%) underwent colectomy during the same admission. UCEIS at admission was the strongest predictor of non-response to MRT [OR 3.03 (95%CI 1.47-6.22), p 0.033), AUROC 0.7552 (95%CI 0.6271 – 0.8832]. UCEIS score ≥6 had sensitivity 100%, specificity 41.7%, PPV 26.3%, NPV 100%, to predict non-response to MRT. CRP on day 3 after commencing rescue therapy (CRP Day R+3) was also a predictor for non-response to MRT (OR 1.02 (95%CI 1.00-1.05), p 0.015). A score comprising 2 points involving UCEIS ≥ 6 and CRP value of ≥ 22 mg/L on day R +3 was developed (1 point each). Score of 2 points had accuracy 79.6%, specificity 75%, sensitivity 100%, PPV 47.4%, NPV 100%, AUROC 0.8750 (95%CI 0.8070-0.9429) for non-response to MRT. In the validation cohort, 6 (6.1%) patients underwent colectomy during the same admission after failing MRT. On implementing the score, a score of 2 points had accuracy 86.7%, specificity 88.1%, sensitivity 66.7%, PPV 28.6%, NPV 97.4%, AUROC 0.8095 (95%CI 0.6423-0.9768) for predicting non-response to MRT.

Conclusion

UCEIS score at admission and CRP on day 3 after commencing MRT are predictors of non-response to MRT. We have developed and validated a model to identify non-response to medical rescue therapy, and objective criteria to mandate surgical intervention.
P238 Autoimmune comorbidities in microscopic colitis: retrospective analysis of consecutive single centre patients
Authors: Kiudelis V , Kiudeliene E , Kupcinskas J , Kupcinskas L
Published: January 2024

Background

Microscopic colitis (MC) is an autoimmune inflammatory condition that causes watery diarrhoea along with other symptoms like bowel incontinence, resulting in impaired quality of life and morbidity. MC is localized to the colon, although other autoimmune disorders are known to be more prevalent among MC patients.

Methods

A retrospective analysis of consecutive MC patients treated in Lithuanian University of Health Sciences Hospital Kauno Klinikos over the last 6 years was performed. Patient information was obtained from electronic records and reviewed for demographic characteristics and diagnosed conditions.

Results

94 MC patients were treated in our centre since 2017, 46 (49 %) with collagenous colitis (CC), 39 (41.5 %) with lymphocytic colitis (LC), 2 (2.1 %) with incomplete CC and 7 (7.4 %) with incomplete LC. 77 patients were female (82 %). Median age was 59 years [44.8-70.3]. There was a tendency for men to be younger (median 42 [37-68]) than women (median 60 [50-70.5]) but not significantly (p>0.05).

31 MC patients (33 %) we diagnosed with concomitant autoimmune disorders. 20 patients (21.3 %) had autoimmune thyroiditis, 7 (7.4 %) had coeliac disease, 7 (7.4 %) had autoimmune skin conditions, 5 (5.3 %) had rheumatoid arthritis, 1 (1.1 %) had spondyloarthritis and 2 (2.1 %) had autoimmune hepatitis. 9 patients (9.6 %) had 2 autoimmune conditions in addition to MC and 1 patient (1.1 %) had 3.

16 (34.8 %) CC patients, 11 (28.2 %) LC patients and 4 (57 %) incomplete LC patients had autoimmune comorbidities. 3 (6.5 %) CC patients, 3 (7.7 %) LC patients and 1 (14.3) incomplete LC patient had coeliac disease. Autoimmune thyroiditis was observed in 11 (23.9 %) CC patients, 6 (15.4 %) LC patients and 3 (42.9 %) incomplete LC patients. 2 (4.3 %) CC patients and 3 (7.7 %) LC patients had rheumatoid arthritis. 5 (10.9 %) CC patients and 2 (5.1 %) LC patients has autoimmune skin disorders. The differences between CC and LC patients were not statistically significant. Both patients with autoimmune hepatitis had LC and the patient with spondyloarthritis had incomplete LC.

Conclusion

MC patients in our centre were frequently diagnosed with additional autoimmune disorders warranting vigilance in clinical practice. There was no difference between CC and LC patients. Incomplete LC patients had a higher proportion of autoimmune comorbidities and though the number of cases was low, this opens up prospects for future investigation.
P239 Characteristics and outcomes of portal vein thrombosis in patients with Inflammatory Bowel Disease in Korea
Authors: Kim K J , Song S , Park J B , Bae J H , Baek J E , Kim G H , Kim M , Hong S W , Hwang S W , Yang D H , Ye B D , Byeon J S , Myung S J , Yang S K , Yu C S , Yoon Y S , Lee J L , Kim M H , Park S H
Published: January 2024

Background

Portal vein thrombosis (PVT) is known to occur frequently in patients with inflammatory bowel disease (IBD), particularly when compounded by factors such as abdominal infection, IBD flares, or intra-abdominal surgery. However, PVT can lead to diverse complications, causing acute issues like intestinal ischemia or necrosis and long-term problems such as portal hypertension, varices, and ascites. Nevertheless, there is a significant shortage of research regarding the characteristics and prognosis of PVT in the context of IBD. Particularly, with the rising prevalence of IBD patients in Asia, the authors conducted an evaluation of clinical presentation and prognosis of PVT in IBD patients at a large tertiary hospital in South Korea.

Methods

This study is a retrospective study conducted at a single tertiary center in South Korea. It examined patients aged 18 and above diagnosed with inflammatory bowel disease (IBD) who had confirmed portal vein thrombosis (PVT) between June 1, 1989, and December 15, 2021. The study focused on investigating patient characteristics, PVT characteristics, treatment methods, and outcomes. The diagnosis and resolution of PVT were confirmed using enhanced CT imaging.

Results

A total of 78 patients met the inclusion criteria for this study. Only 21% (16/78) received oral anticoagulants, yet nearly all patients (96%; 75/78) achieved Complete Radiologic Resolution (CRR). When comparing baseline characteristics between the anticoagulation use group and the non-use group, a trend was observed with a higher utilization of anticoagulants in cases where the main portal vein was involved rather than only the left or right portal vein (p-value 0.006). However, when conducting multivariable analysis, no factors significantly influenced CRR, especially anticoagulant use and surgery status.

Conclusion

PVT concomitant with IBD demonstrated favorable outcomes regardless of anticoagulation use.
P250 Geriatric impairments associate with mortality and hospitalisations during follow-up in older IBD outpatients
Authors: Fons A , Asscher V , Stuyt R , Baven-Pronk M , van der Marel S , Jacobs R , van der Meulen-de Jong A , Mooijaart S , Kalisvaart K , Maljaars J
Published: January 2024

Background

We aimed evaluate the association between impairments found in a geriatric assessment and the risk for adverse outcomes in older patients with Inflammatory Bowel Disease (IBD).

Methods

In a prospective multicenter cohort study, a geriatric assessment was performed at baseline in 405 older (≥ 65 years) patients with IBD. Linear-and cox regression analyses were used to study the association between impairment in five geriatric domains measured in the geriatric assessment (somatic-, functional-, mental-, and social domain, physical capacity) and adverse outcomes occurring during 18 months of follow-up. Adverse outcomes were defined as all-cause-, acute-, and IBD-related hospitalisations and all-cause mortality. All analyses were adjusted for age, sex and biochemical disease activity (C-reactive protein ≥10 mg/L and/or fecal calprotectin ≥250 μg/g).

Results

Of 405 patients at baseline (median age: 70 years), 11 patients (2.7%) died and follow-up was conducted in 356 patients (87.9%). During 18 months, 136 all-cause hospitalizations occurred in 96 patients (23.7%), of which 103 (75.7%) were acute, occurring in 74 patients (18.3%). Forty-one hospitalizations (30.1%) in 28 patients (6.9%) were IBD-related. The number of impaired domains at baseline was independently associated with mortality (p=0.001, B=2.76), all-cause hospitalisation (p=0.016, B=1.28) and acute hospitalisation (p=0.02, B=1.3), but not with IBD-related hospitalisation (p=0.06, B=1.37). On domain level, mortality was associated with impaired mental- (p=0.002, B=8.9) and physical domains (p=0.006, B=9.5), all-cause hospitalisation with an impaired somatic domain (p=0.002, B=2.13), and acute hospitalisation with an impaired somatic domain (p=0.02, B=2.49).

Conclusion

Geriatric impairments in geriatric assessment are independently associated with adverse outcomes in older patients with IBD, including an increased risk of mortality, all-cause and acute hospitalizations. Therefore, this study provides the first prospective evidence for the predictive value of the geriatric assessment, enhancing risk stratification in older patients with IBD.
P259 Clinical characteristics and long-term disease course in patients with Crohn’s disease diagnosed by video capsule endoscopy; A retrospective multicentre matched case-control study
Authors: Bae J H , Park S H , Kim K O , Jang B I , Lee M R , Park J B , Baek J E , Hong S W , Hwang S W , Yang D H , Ye B D , Byeon J S , Myung S J , Yang S K , Kim E S , Park S H
Published: January 2024

Background

Video capsule endoscopy (VCE) is a non-invasive and accurate diagnostic modality that allows for direct visualization of the small intestinal mucosa in Crohn’s disease (CD). In rare cases, lesions not detected by other diagnostic modalities in patients suspected to have CD are solely identified through VCE. We aim to evaluate the clinical characteristics and long-term outcomes of these rare cases.

Methods

A retrospective multicentre matched case-control analysis was conducted in patients with CD across three hospitals in Korea, from January 2007 to April 2023. To perform a matched case-control study, we defined cases (VCE group) as patients with normal findings at colonoscopy and cross-sectional imaging, ultimately diagnosed with CD by VCE; the controls were patients with CD diagnosed with specific findings at endoscopy or cross-sectional imaging (non-VCE group). Controls were matched to cases with a ratio of 3:1 for sex, calendar year of diagnosis, and age at diagnosis. Clinical characteristics and outcomes between the two groups were compared.

Results

Of the 3,137 patients diagnosed with CD during the study period, 24 were diagnosed solely by VCE. When compared to 72 matched patients with CD, the mean duration from symptom onset to diagnosis did not significantly differ (27.2 months [SD 10.2] vs. 25.3 months [SD 8.9], p=0.394). There was a significant difference in the proportion of Montreal behaviour (p<0.001). In the VCE group, non-stricturing and non-penetrating (B1) type and stricturing (B2) type accounted for 91.7 and 8.3%, respectively. However, there was no significant difference in the perianal fistula modifier (25% vs. 33.3%, p=0.446). Within the VCE group, 45.8% underwent the examination due to abdominal pain with diarrhoea, followed by 25.0% with perianal disease, and 20.8% with unexplained iron deficiency anaemia. Regarding capsule findings, the ileum was mostly involved (87.5%), while the jejunum and duodenum were affected in 70.8 and 16.7% of cases, respectively. Fifteen patients had two or three segments affected. The Median Lewis score was 838 [IQR 393–1803]. Concerning the cumulative incidence of clinical outcomes over 10 years, complicated behaviour, need for biologics, and CD-related hospitalization and surgery were all significantly lower in the VCE group than in the non-VCE group (p<0.005).

Conclusion

Patients diagnosed with CD solely by VCE are rare. In this study, they exhibited different clinical characteristics and a more favourable long-term disease course compared to the general population of patients with CD. This included a lower incidence of complicated behaviour, reduced need for biologics, and CD-related hospitalization and surgery.
P262 Differences in the Management and Demographics of Adult Inflammatory Bowel Disease in Older-Onset and Younger-Onset
Authors: Kivrakoğlu F , Kilic V , Ergin M , Kucuk H , Yuksel I
Published: January 2024

Background

The goal of this study was to investigate differences in the management and demographic characteristics of older-onset and younger-onset adult patients with Ulcerative Colitis (UC) and Crohn’s Disease (CD).

Methods

We retrospectively compared the management and distinguishing characteristics of UC and CD patients who were older-onset (≥60 years) and younger-onset (18-60 years) between June 1993 and October 2023.

Results

A total of 1245 patients with 56 (4.5%) older-onset adults (Male 41, 73%) and 1189 (95.5%) younger-onset adults (Male 725, 58%) were admitted to the study. The median follow-up time was 11 years (Older-onset 6 and younger-onset 11 years) for both groups. Prevalence of UC 39 (69.6%) in the older-onset group was more common than that of younger-onset group 579 (48.7%), (p=0.002). There were no significant differences between the two disease onset groups in terms of UC extension, CD location, behavior, and perianal involvement. In younger-onset, active smokers 277 (23%) was more frequent than older-onsets 6 (10%) (p= 0.003). A family history of IBD in older onsets 2 (4%) was less common than younger-onsets 155 (13%) (p= 0.037). Prior major abdominal surgery was detected similar (Older-onset 20, 35.7% and younger-onset 464, 39%). At least one extraintestinal manifestation exist was less common in older-onsets 18 (32.1%) than younger-onsets 606 (51%) (p= 0.006). Baseline partial MAYO score 7 and CDAI 302 in older-onsets, and 297 in younger-onsets were similar in both groups.

Thiopurine usage 391 (32.9%) in younger-onsets was the most frequent than in older-onsets 9 (16.1%) (p=0.008). There was no difference in both groups in terms of other conventional medications. At least one biological experience was less common in older-onsets 15 (26.8%) than the younger-onsets group 586 (49.3%) (p=0.001). The two biological therapies that were used the most frequently were adalimumab (Older-onset; 6, 10.7% and younger-onset; 384, 32.8%) (p=0.001) and infliximab (Older-onset; 15, 26.8% and younger-onset; 586, 49.3%) (p=0.02).

Conclusion

Our study showed that the prevalence of UC in older-onsets was more common than younger-onsets. A family history, extraintestinal manifestation, thiopurine, and biological usage in older-onsets were less common than in younger-onsets. Major abdominal surgery was similar in both groups. Older-onset patients demonstrated significant differences in medication utilization, including less thiopurine and biological therapy compared with younger-onset groups, these utilization patterns may have long-term effects on disease outcomes. Further investigation is needed to optimize care pathways in the older-onset population.
P265 Factors affecting patient perception and acceptance of colonoscopy in patients with inflammatory bowel disease
Authors: Huang T Y , Liao C H , Chen Y J
Published: January 2024

Background

Inflammatory bowel disease (IBD) is characterized by chronic idiopathic inflammation of the gut. Colonoscopy is the mainstay procedure for managing and monitoring IBD patients. However, many patients with IBD do not comply with routine or surveillance colonoscopies, and the underlying reasons have not been determined for Asian patients with IBD. Therefore, this study analyzed IBD patients' perceptions of bowel preparation and colonoscopy procedures and attitudes toward examination intervals, using a questionnaire.

Methods

This cross-sectional study included 94 patients with IBD (41 with Crohn’s disease and 53 with ulcerative colitis) presenting at one medical center between July 2020 and May 2022. The patients’ perceptions of the four components associated with the colonoscopy procedure (embarrassment, pain, use of bowel-cleansing agents, and stress) were assessed via a questionnaire. Patients were asked to indicate the frequency at which they had scheduled a colonoscopy and the frequency at which they desired to undergo the procedure.

Results

“Bowel cleansing” and “pain” were most uncomfortable during the colonoscopy procedure. Younger age and younger age at diagnosis were associated with a greater burden of bowel preparation and painful sensations. Regarding examination intervals, male patients were more compliant with colonoscopies within shorter timeframes than female patients. Additionally, younger patients and those diagnosed at an earlier age tended to prefer longer examination intervals.

Conclusion

This study provides insights into the perception of colonoscopy in Taiwanese patients with IBD. Our findings would promote the adherence to colonoscopy and facilitate early detection of major complications in high-risk and long-term IBD patients.
P269 Harnessing Natural Language Processing for Structured Information Extraction from Radiology Reports in Crohn's Disease: A Nationwide Study From the epi-IIRN
Authors: Hazan L , Focht G , Gavrielov N , Reichart R , Friss C , Cytter Kuint R , Turner D , Freiman M
Published: January 2024

Background

Large-scale analyses of imaging in Crohn's disease (CD) hold promise for advancing research on the inflammatory burden in the bowel as well as developing predictive models of disease progression. However, the lack of structured human annotations in these datasets limits the ability use these for research. This study from epi-IIRN nationwide cohort, aims to develop and evaluate Natural Language Processing (NLP) algorithms for extracting structured information from unstructured radiology reports on CT and MR enterography.

Methods

We identified radiology reports of all patients diagnosed with inflammatory Bowel Disease (IBD) in the nationwide epi-IIRN cohort, which includes data from the four Israeli HMOs, covering 98% of the population. We developed an in-house NLP platform using a publicly available Hebrew pretrained BERT model. After annotating a small portion of the reports for validation, we fine-tuned the model on our dataset through a masked language task, followed by a few-shot approach based on the Next Sentence Prediction (NSP) pretraining objective for classification model fine-tuning. The platform extracts radiological indicators related to inflammation, stenosis, and location, including wall thickening, enhancement, lumen narrowing, and dilation in the following locations: jejunum, ileum, colon, sigmoid, and rectum. We validated our models using a 5-fold cross-validation experimental setup, employing accuracy, PPV, NPV, F1 score and Cohen’s kappa score as the evaluation metrics.

Results

We extracted 9,704 radiology reports (6,299 MRE, 2,405 CTE) of 7,062 IBD patients (5,972 were diagnosed with CD, and 1,076 with ulcerative colitis). The mean age on the first imaging study was 36.8±17.1 years and 52% were male. We selected 500 studies for being annotated for the radiological indicators. The most common label was wall thickening in the ileum (215 positive patients vs.285 negative) while the least common was lumen narrowing in the jejunum (1 positive patient vs. 499 negative). Table 1 summarizes the results and label distributions. The mean [95% CI] accuracy/PPV/NPV/F1/Cohen's kappa score averaged over all labels was 0.98 [0.95,1]/0.99 [0.96,1]/0.83 [0.56,1]/0.86 [0.6,1]/0.63 [0.16,1]. The labels with the highest F1/Cohen's kappa score were wall thickening, enhancement, and narrowing in the Ileum while the label with the lowest F1/Cohen's kappa score were dilation in the Colon and the Jejunum.

Conclusion

NLP methods can extract structured information from radiology reports with high accuracy. Few-shot approaches based on the Next Sentence Prediction can alleviate the need for large scale data annotation for training. NLP offers exciting possibilities for large-scale studies utilizing imaging data in CD.