bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &lt; 0.001).
The IBUS-SAS in patients with normal CRP levels (&lt; 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 (&gt;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 &lt; 0.001) and with FC was 0.58 (95% CI 0.46-0.68; p &lt; 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 &lt; 0.001).
The IBUS-SAS score of &gt; 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 &gt; 3).

Conclusion
The IBUS-SAS score correlated very well with clinical and endoscopic disease activity as well as biomarkers. A score &gt; 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

Abstract

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

Abstract

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 &lt; 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 &lt; 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

Abstract

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 &gt; 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

Abstract

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

Abstract

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&gt;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.