bluuebunny/crossref_metadata_2025 huggingface dataset:
P0336 From inflammation to depression: key biomarkers for Inflammatory Bowel Disease-related Major Depressive Disorder
Authors: Hu C , Guo H
Published: January 2025

Background

Inflammatory bowel disease (IBD) is a chronic, inflammatory, and autoimmune disorder[1], and its incidence of comorbid with major depressive disorder (MDD) is significantly higher than the general population[2]. However, many patients lack proper recognition and necessary psychological health treatments. We aimed to identify potential biomarkers and mechanisms involved in the development of IBD comorbid with MDD (IBD-MDD).

Methods

We utilized IBD and MDD-related datasets from the GEO database for differential gene expression analysis, protein-protein interaction (PPI) and pathway enrichment analysis, random forest algorithm, LASSO regression analysis, and construction of a disease prediction model. We assessed the accuracy of the model using ROC curve, explored potential mechanisms through immune infiltration analysis, and validated candidate biomarkers using peripheral blood samples from patients in our center’s cohort.

Results

We identified 484 IBD-related secreted proteins and 142 key module genes associated with MDD. PPI analysis revealed two crucial modules primarily involved in inflammation and immune regulation. We identified four diagnostic genes (HGF, SPARC, ADAM12, and MMP8) from the 21 shared genes between IBD-related secreted proteins and MDD key module genes, constructed a nomogram model and confirmed its accuracy using ROC curve from an external independent dataset. Immune infiltration analysis revealed significant associations between the four diagnostic genes, and cellular immune dysregulation in MDD.

Finally, we validated the expression patterns of the four diagnostic genes in our cohort.The results showed that the serum levels of HGF and MMP8 were significantly elevated in IBD patients with comorbid MDD, SPARC and ADAM12 showed an increasing trend (Figure 1A). Meanwhile, we developed a predictive model for IBD-related MDD based on our cohort (Figure 1B). The calibration curve suggests that the predictive probability of the nomogram model is nearly the same as that of the ideal model (Figure 1C). ROC curve analysis of the efficacy of the joint predictive model based on the 4 diagnostic markers showed that the AUC value was 0.87, indicating that the nomogram have strong diagnostic value for IBD-related MDD (Figure 1D).

Conclusion

Our study discovered four candidate biomarkers for IBD-MDD, providing new insights for the diagnosis and therapeutic intervention of serum-based IBD comorbid with MDD.

References

[1] Khor B, Gardet A, Xavier RJ. Genetics and pathogenesis of inflammatory bowel disease. Nature. 2011; 474:307-317.

[2] Neuendorf R, Harding A, Stello N, Hanes D, Wahbeh H. Depression and anxiety in patients with Inflammatory Bowel Disease: A systematic review. J Psychosom Res. 2016; 87:70-80.
P0338 Early identification of pediatric inflammatory bowel disease based on machine learning with non-invasive data
Authors: Wu H , Sun Y H , Tang Z F , Qin X J , Wang Y H , Huang Y
Published: January 2025

Background

Early identification of pediatric inflammatory bowel disease (IBD) can improve long-term prognosis, yet significant diagnostic delays persist. This study aims to develop an effective early identification tool using machine learning with non-invasive testing.

Methods

This retrospective study collected data from 314 pediatric patients (109 with IBD and 205 without IBD) hospitalized in Fudan University Children’s Hospital, to serve as the training dataset. We developed machine learning classifiers using support vector machine, artificial neural network, extreme gradient boosting, decision tree, random forest, k-nearest neighbors, logistic model, and gradient boosting machine methods, incorporating easily obtainable clinical examination tools. Participant data included age, sex, and three groups of features across different dimensions: IBD symptoms (diarrhea lasting ≥1 month; blood in stool for ≥1 week; recurrent perianal abscesses or fistulas; delayed growth; abdominal pain lasting ≥1 month; >10% weight loss; first-degree family history; arthritis, uveitis, erythema nodosum without definitive rheumatologic diagnosis; recurrent aphthous ulcers; unexplained fever), inflammatory biomarkers (elevated fecal calprotectin; elevated serum inflammatory markers; anemia; hypoalbuminemia; ANCA positivity), and transabdominal bowel ultrasound parameters (Limberg level >1 indicating bowel wall thickening with vascularity; mesenteric fat wrapping; bowel wall stratification disorder or loss; lymphadenopathy). We evaluated the performance of each feature group and their combinations, optimized hyperparameters, internal validation, and performed sequential validation with 66 prospectively recruited pediatric patients from the same center. The final model was selected based on optimal and stable performance in both the development and external validation cohorts, with Shapley values used to interpret feature importance.

Results

The support vector machine outperformed other algorithms, achieving an area under the curve of 0.95 in both internal and external validation datasets. The five most important features based on Shapley values were Limberg level >1, elevated ESR, elevated fecal calprotectin, recurrent perianal disease, and elevated CRP. Additionally, combining all three feature dimensions outperformed any single or paired combination. The probability of IBD classification showed moderate correlation with clinical, endoscopic, and histologic scores .

Conclusion

The machine learning model based on non-invasive data has the potential to become a low-cost and time-efficient tool for early identification of IBD. Ultrasound examination plays a significant role in distinguishing children with IBD from those without.
P0341 Variation in healthcare utilisation amongst IBD care centres in Australia and New Zealand, Crohn’s Colitis Care Data Insight’s Program
Authors: Su W K , Wilson W , Wark G , Walker G , Su H , Forbes A , Kim A , Giles E , Lawrance I , Dutt S , Brett L , Begun J , Lynch K , Andrews J M , Connor S J
Published: January 2025

Background

Inflammatory bowel disease (IBD) is a global health issue with Australia (AUS) and New Zealand (NZ) having amongst the highest prevalence rates worldwide. Due to a paucity of externally visible data on how care is delivered within individual sites, little is known about utilisation of various care inputs and the presence and/or magnitude of any variation in this amongst centres. We therefore examined the use of various documented care inputs amongst 11 Australasian IBD centres over a 12-month period.

Methods

Crohn’s Colitis Care (CCCare) is a cloud-based IBD-specific electronic medical record (EMR) used in Australasia. Deidentified data prospectively entered by clinicians and consumers during routine clinical practice from September 2023 to September 2024 were retrospectively analysed. Centres with over 100 people with IBD with an assessment during the last 14-month period were included.

Results

A total of 7119 eligible people with IBD from 11 centres were included; of those, 55.9% (n=3982) had Crohn’s Disease, 41.3% (n=2938) had Ulcerative Colitis, and 2.8% (n=199) had IBD-Unclassified. There was an even gender distribution with 49.3% (n=3508) male, 48.0% (n=3420) female; 2.8% (n=199) did not have gender documented. Most resided in AUS (71.9%, n=5120) and 28.1% (n=1999) in NZ. Their median age was 42 years (IQR 31 – 57), and the median disease duration was 10.8 years (IQR 5.2 – 19.2). The number of eligible people with IBD included per centre ranged from 165 to 1421 (median 729, IQR 350 – 805).

A total of 10,910 clinical assessments (in-person and telehealth) were conducted and documented in CCCare; with centre variation from 1.0 per person (pp) to 2.4 pp (p<0.001). Nine centres documented Helpline contacts which varied from 0.0 pp to 7.8 pp (p< 0.001). The number of endoscopies performed varied from 0.2 pp to 0.5 pp (p<0.001) and the number of radiological investigations performed varied from 0.0 pp to 0.8 pp (p<0.001). Admission rates across the sites were similar, ranging from 0.0 pp to - 0.1 pp (p=0.88).

Conclusion

There was significant variation in healthcare utilisation across 11 IBD centres in AUS and NZ. Despite large variation in rates of radiology and endoscopy, admission rates did not differ, suggesting that, at least in the short term, greater use of these resources did not improve outcomes at cohort level. Further analyses are required to understand this variability, which may include specific patient needs, site-specific practices, or differences in access to healthcare services and resources. A tool like CCCare, is key to enabling health services research across centres and will support us with data to develop evidence-based IBD care guidelines to achieve equitable, cost-effective care.
P0345 Tailoring Crohn’s disease surveillance in clinical remission: new insights from the Lewis score
Authors: Ferreira A I , Lima Capela T , Xavier S , Arieira C , Rosa B , Cotter J
Published: January 2025

Background

Optimal thresholds for Lewis score in the surveillance of patients with known Crohn’s disease (CD) in clinical remission remain uncertain. The aim of this study was to evaluate predictive factors of clinical exacerbation in patients with small bowel inflammatory-type CD in clinical remission, focusing on the yield of the Lewis score.

Methods

Retrospective, unicentric cohort study including adult patients with known small bowel inflammatory-type, non-stricturing and non-penetrating CD, in clinical remission, who were submitted to small bowel capsule endoscopy for evaluation of mucosal healing. Clinical exacerbation was defined as the need for corticosteroid administration, biological/immunomodulator treatment initiation, intensification or switch, intestinal surgery, or CD-related hospitalization, with a minimum follow-up time of 24 months.

Results

A total of 63 patients were included, and clinical exacerbation occurred in 18 patients (28.6%), with 8 patients requiring oral corticosteroid administration (12.7%), 12 needing biological/immunomodulator treatment initiation or switch (19.0%), and 2 needing both (3.2%). An age ≤33 years and a Lewis score >225 were found to be independent predictive factors of clinical exacerbation (OR 7.145, p=0.028 and OR 12.585, p=0.005, respectively). Patients who were not in biochemical remission were 14 times more likely to have a clinical exacerbation during follow-up (83.3% vs 42.2%, p=0.003). Furthermore, patients who were not in biochemical remission and who had a Lewis score >225 were 16 times more likely to have a clinical exacerbation (66.7% vs 13.3%, p<0.001). Patients with a Lewis score >225 had an overall risk for clinical exacerbation of 59.1%, compared to 12.2% in those with a Lewis score ≤225 (p<0.001). Additionally, patients with a Lewis score >225 had a shorter period of time free from clinical exacerbation (32±5 vs 80±5 months, χ2=22.414, p<0.001) (figure 1).

Conclusion

Clinical exacerbation occurred in almost one third of patients with small bowel inflammatory-type CD in clinical remission. An age ≤33 years and a Lewis score >225 were independent predictive factors of clinical exacerbation. The absence of biochemical remission was also associated with clinical exacerbation. A Lewis score >225 was the best threshold to predict clinical exacerbation and shorter period of time free from clinical exacerbation. Therefore, in small bowel CD patients with a Lewis score <225, a wait and watch therapeutic strategy can be applied, since the risk of clinical exacerbation for a minimum 24-month follow-up period is low. However, those with a Lewis score >225 should be considered for therapeutic intensification, especially if younger, in order to prevent clinical exacerbation in the long term.
P0348 Ultrasound enterography with a novel ultrasound contrast agent for Crohn’s Disease
Authors: Gjengstoe A J , Volkmann H L V , Aziz A , Dimcevski G , Gilja O H , Nylund K
Published: January 2025

Background

Gastrointestinal ultrasound (GIUS) is a method with both high sensitivity and specificity for evaluating disease activity in patients with Crohn’s disease. However, detecting and classifying stenosis and ulcerations can be challenging with GIUS. Developing an ultrasound method for detecting and categorising these findings would be of significant benefit to these patients. GIUS using an oral ultrasound contrast agent containing microbubbles is a new method with the potential to improve the intestinal ultrasound examination in patients with Crohn’s disease. The goal of this study is to investigate if intestinal ultrasound with oral contrast containing Sonazoid microbubbles in a PEG solution is a feasible and safe method in patients with Crohn’s disease.

Methods

24 patients with Crohn’s disease in the terminal ileum (TI) was examined with ileocolonoscopy and intestinal ultrasound with oral contrast in a phase 2, single centre prospective cross-sectional drug trial. The ultrasound examination was done using Logiq E10 in contrast hybrid mode after ingestion of 1ml Sonazoid mixed with 500ml of PEG. The quality of the examination was graded 0-3 based on the amount of contrast in the lumen. In grade 3 the terminal ileum filled completely with contrast, and this was considered a successful examination. The contrast grade and transit time to TI after ingestion was documented along with symptoms, side effects and disease activity using "Mobile Health Index for Crohn’s Disease" before and after the study visit (1).

Results

All the included patients completed the ultrasound examination. The examination had a feasibility of 96 % as 23/24 patients achieved contrast effect grade 3 in TI with a clear separation of the intestinal wall and lumen. Average time from ingestion to grade 3 contrast effect in the TI was 20.8 min. Average duration of contrast effect grade 3 in the TI was 50.4 min. 50% of the patients had self-limiting diarrhea after the examination, however using paired samples T test there was no significant difference in average disease activity measured by MHICD before and after the examination (p=0.685). 96% of the patients agreed or completely agreed to undergo the examination again.

Conclusion

All except one patient achieved successful grade 3 contrast effect in the terminal ileum with a clear separation of the lumen and intestinal wall. Half of the patients had self-limiting diarrhea, but there was no increase in Crohn’s disease activity after the contrast examination. According to our study, ultrasound with oral contrast consisting of 1ml Sonazoid and 500ml PEG is a feasible and safe method to examine patients with Crohn’s disease.

References

1. Van Deen WK et. Al. Development and Validation of an Inflammatory Bowel Diseases Monitoring Index for Use With Mobile Health Technologies. Clin Gastroenterol Hepatol. 2016 Dec;14(12):1742-1750.e7. doi: 10.1016/j.cgh.2015.10.035.
P0350 Asia Pacific Association of Gastroenterology consensus statements on histopathological evaluation of Inflammatory Bowel Diseases
Authors: Leong R , Chaemsupaphan T , Lin H , Lim W C , Ooi C J , Chetwood J D , Mao R , Wu H Y , Wei S C , Makharia G , Ahuja V , Banerjee R , Limsrivilai J , Aniwan S , Pisespongsa P , Hilmi I , Raja Ali R A , Leung W K , Ng S , Ye B D , Kobayashi T , Matsuoka K , Chau C , Sanpavat A , Shun C T , Puspanathan P , Gearry R B , Danese S , Ma C , Pudipeddi A , Paramsothy S
Published: January 2025

Background

Mucosal histological activity is increasingly valued as a treatment endpoint in inflammatory bowel diseases (IBD). In the Asia Pacific region, however, the utility and acceptability of IBD histology as a treatment endpoint is uncertain due to the heterogeneity of IBD prevalence, resourcing, and level of knowledge among practitioners. There is an opportunity to engage clinicians to harmonise histology reporting and collaborate with pathologists in this field. To this end, we developed statements to determine their consensus through anonymous voting on histological features, processing, reporting, and relevance to treatment outcomes in ulcerative colitis and Crohn’s disease.

Methods

Representatives of the Asia Pacific Association of Gastroenterology, in collaboration with pathologists, voted anonymously in accordance with modified Delphi methodology on statements relevant to IBD and histology. Domains of interest were histological features of ulcerative colitis and Crohn’s disease, relevance to clinical management, and the potential utility of artificial intelligence in grading histological disease severity. Level of evidence and recommendation grade were included in accordance with the NHMRC guidelines of Australia.

Results

Consensus was reached on 37 statements concerning definitions, pathology processing and reporting, scoring system, and relevance to clinical outcomes (Figure). There was uncertainty on escalating treatment when histological remission is not achieved, preventing consensus on this statement. Knowledge gaps were identified over the role of artificial intelligence.

Conclusion

These consensus statements provide recommendations, with specific relevance to the Asia Pacific region, on the role of histology in IBD ways to harmonise its use. The consensus statements will promote understanding and applicability in research and in the routine management of IBD.
P0351 Differential Cutoff Values of Fecal Calprotectin Based on Disease Extent of Ulcerative Colitis
Authors: Lee J , Kim S J , Lee M H
Published: January 2025

Background

Fecal calprotectin (FC) is a well-established biomarker for bowel inflammation in ulcerative colitis (UC). However, its utility across different disease extents remains poorly defined. This study investigates the correlation between FC levels and endoscopic severity according to disease extent in UC, aiming to establish specific cutoff values for each disease extent

Methods

From January 2013 to December 2020, UC patients slated for colonoscopy at our institution were recruited. Fecal samples were collected pre-procedure for FC analysis. Demographic and clinical data were recorded, categorizing patients by UC extent. Disease activity was evaluated using the Partial Mayo Score and Mayo Endoscopic Subscore (MES).

Results

We performed 404 colonoscopies on 165 UC patients. Analysis demonstrated varying correlations between FC and MES, particularly showing diminished correlation in patients with proctitis (E1/E2/E3 correlations: 0.298/0.533/0.574; p-values: 0.010/0.001/0.001). Cutoff values for FC varied with disease extent: 77 for proctitis (AUC: 0.752; Sensitivity: 64%; Specificity: 84%), 164 for left-sided colitis (AUC: 0.821; Sensitivity: 83%; Specificity: 100%), and 222 for pancolitis (AUC: 0.870; Sensitivity: 86%; Specificity: 83%). FC was superior to C-reactive protein in discriminating remission across all extents.

Conclusion

FC levels correlate with UC disease extent, suggesting that differential cutoff values should be utilized to enhance diagnostic accuracy. Specifically, lower correlations in proctitis highlight the need for adjusted diagnostic thresholds, underlining FC’s varied utility in managing UC.

References

1.Lichtenstein GR, Rutgeerts P. Importance of mucosal healing in ulcerative colitis. Infamm Bowel Dis. 2010;16:338–46.

2.Lee J. [Fecal Calprotectin in Inflammatory Bowel Disease]. Korean J Gastroenterol. 2016 May 25;67(5):233-7.

3.Walsh A, Kormilitzin A, Hinds C, et al. Defning faecal calprotectin thresholds as a surrogate for endoscopic and histological disease activity in ulcerative colitis—a prospective analysis. J Crohn’s Colitis. 2019;13:424–30.

4.Mosli MH, Zou G, Garg SK, et al. C-Reactive Protein, Fecal Calprotectin, and Stool Lactoferrin for Detection of Endoscopic Activity in Symptomatic Inflammatory Bowel Disease Patients: A Systematic Review and Meta-Analysis. Am J Gastroenterol. 2015 Jun;110(6):802-19

5.Sonoyama H, Kawashima K, Ishihara S, et al. Capabilities of fecal calprotectin and blood biomarkers as surrogate endoscopic markers according to ulcerative colitis disease type. J Clin Biochem Nutr. 2019 May;64(3):265-270
P0352 Fecal calprotectin and pseudopolyps in Ulcerative Colitis: Is there a relationship?
Authors: Crespo A , Pèlach A , Vidal M , Calafat M , Llaó J , Domènech E , Mañosa M
Published: January 2025

Background

Fecal calprotectin (FC) is the main biomarker of inflammatory bowel disease (IBD). Pseudopolyps are lesions that arise after repeated episodes of inflammation following healing processes. The impact of the presence of pseudopolyps on FC levels in patients with ulcerative colitis (UC) is not established.

The aim of the study was to analyze FC levels in relation to the presence of pseudopolyps and to investigate the association between these and the risk of relapse.

Methods

Retrospective study of patients with UC followed up at the IBD unit of a tertiary hospital. We selected adult patients in clinical and endoscopic remission (Mayo endoscopic score 0-1), with a quality screening colonoscopy between 2015 and 2024. Demographic, clinical, analytical and endoscopic variables were analyzed.

Results

The study included 147 patients with UC, of whom 51 (35%) presented pseudopolyps. Patients with pseudopolyps had a significant proportion of extensive UC, hospitalizations due to UC, and use of immunomodulators and biological drugs. The median FC levels pericolonoscopy were 32 µg/g (IQR 15-53) in those with pseudopolyps and 28 µg/g (IQR 20-42) in those without (P = 0.464). There were also no differences in CF levels according to the use of NSAIDs (P = 0.722) or PPIs (P = 0.945). The median follow-up was 23 months (IQR 13-45). The presence of pseudopolyps was not associated with a greater risk of clinical relapse during follow-up (P = 0.425), neither the time to relapse (P = 0.937). In contrast, the condition of ex-smoker or non-smoker (P = 0.003) and extensive UC (P = 0.007) were associated with relapse.

Conclusion

In patients in clinical and endoscopic remission, the presence of pseudopolyps is not associated with higher levels of fecal calprotectin neither an increased risk of clinical relapse in the medium term.
P0353 Correlation between qUality of life and point of cAre intestinaL ultrasound In patients wiTh inflammatorY bowel disease (CUALITY)
Authors: Parra Izquierdo L V , Ernest Suarez K , Argollo M , Frías-Ordoñez J , Orduz G , Puentes Manosalva F , Cubillos S , Verstockt B
Published: January 2025

Background

Inflammatory bowel disease (IBD) impairs patients’ quality of life, and hence, there is increased awareness of patient-reported outcomes (PRO). Intestinal ultrasound (IUS) is becoming increasingly important as a noninvasive patient monitoring strategy. However, no data exist on the concordance between PRO and IUS findings. Therefore, we investigated the association between PRO, assessed by the IBD Questionnaire-32 (IBDQ-32), and IUS parameters.

Methods

This prospective study recruited patients with IBD who underwent IUS assessment, while subsequently, an IBDQ-32 was recorded. The IUS parameters captured were bowel wall thickening (BWT), colour doppler sign using the modified Limberg score and color wall flow (CWF) absent or present, also, presence of lymphadenopathies, and mesenteric fat hypertrophy. We performed uni- and bivariate analysis. A p-value <0.05 was considered significant.

Results

A total of 55 patients were included [37 with ulcerative colitis (UC); 18 with Crohn’s disease (CD)]. In UC, we observed a significant association between IBDQ-32 and BWT (P=0.049), CWF (P=0.02) (Figure 2). and mesenteric fat hypertrophy (P=0.040) respectively. Exploring the dimensions of the IBDQ-32, there was a statistically significant association between the dimension of gastrointestinal symptoms (P= 0.002) and systemic symptoms (P=0.003) with CWF, as well a with BWT respectively (P= 0.013). No association between IUS features and emotional and social dimensions was observed. The validated MUC score (cutoff 6.2) associated significantly with IBDQ-32 (P=0.010) (Figure 1). No associations were observed in patients with CD.

Conclusion

The quality of life assessed by IBDQ-32 is associated with intestinal ultrasound parameters that reflect disease activity in UC.
P0359 Characteristics and long-term outcomes of biopsy proven serrated epithelial change in patients with inflammatory bowel disease: a retrospective analysis
Authors: Vaitiekunas L , Kakkadasam Ramaswamy P , Pillai S , Willis T , Mohsen W
Published: January 2025

Background

Serrated epithelial change (SEC) is an increasingly recognised histologic finding in patients with inflammatory bowel disease (IBD) and may be associated with an increased risk of synchronous or metachronous colorectal dysplasia.1,2 The aims of this study were to characterise the clinical and histologic features of IBD patients with SEC and determine the incidence of dysplasia.

Methods

We performed a retrospective, observational, single-centre study at a tertiary referral hospital. IBD patients with SEC were identified by searching the pathology database for ‘serrated’, ‘epithelial’ and ‘change’ in pathology reports. The first colonic biopsy showing SEC between 2015 to 2023, was designated as the index SEC. SEC was defined as colonic mucosa with goblet cell-rich epithelium, disorganised crypt architecture and irregular serrations without distortion of basal aspects of crypts or features of dysplasia. Patients without follow-up colonoscopy or flexible sigmoidoscopy were excluded (see Figure 1). Clinical and histological data were extracted from electronic medical records and endoscopy reports.

Results

The cohort included 26 IBD patients (16 with Crohn’s Disease and 10 with ulcerative colitis), consisting of 14 males (53.8%) with a median age of 58 years at the time of the index SEC diagnosis. See Table 1 for patient characteristics. A total of 30 specimens with SEC were identified among the 26 patients, and all patients had at least one follow-up colonoscopy or flexible sigmoidoscopy. The mean disease duration was 15 years, and the median follow-up time was 24.5 months. SEC was detected on high-definition white light endoscopy in 61.5% of cases. SEC was primarily located in the cecum (30%), rectum (23.3%) and transverse colon (16.7%), detected on nodular or polypoid mucosa (60%), and exhibited multifocal distribution (19.2%). In patients with SEC, endoscopic and histologic inflammation was demonstrated in 50% and 46.2% of cases, respectively. One case (3.8%) of low-grade dysplasia in the caecum was observed in a patient with Crohn’s disease.

Conclusion

SEC was predominantly found as polypoid or nodular lesions proximal to the splenic flexure and associated with endoscopic and histologic inflammation. Larger, prospective, multi-centre studies are necessary to clarify the clinical implications of SEC in IBD, its potential role in carcinogenesis and dysplasia surveillance strategies.

References

1.Johnson DH, Khanna S, Smyrk TC, et al. Detection rate and outcome of colonic serrated epithelial changes in patients with ulcerative colitis or Crohn’s colitis. Alimentary Pharmacology & Therapeutics. 2014;39(12):1408-1417. doi:10.1111/apt.12774

2 Parian A, Koh J, Limketkai BN, et al. Association between serrated epithelial changes and colorectal dysplasia in inflammatory bowel disease. Gastrointestinal Endoscopy. 2015;84(1):87-95.e1. doi:10.1016/j.gie.2015.12.010
P0364 Establishment and validation of a central reader pool for magnetic resonance enterography (MRE) for use in Crohn’s disease clinical trials
Authors: Pillay L , Paverd H , Noor N , Hickman K , De Paepe K , Godfrey E M , Khwaja S , Upponi S , Kennedy N A , Parkes M , Raine T
Published: January 2025

Background

Clinical trials in Crohn’s disease (CD) currently rely on ileocolonoscopy to assess disease activity and monitor treatment response. There is growing interest in utilising non-invasive tests for this purpose. Magnetic resonance enterography (MRE) is non-invasive, more tolerable for patients, and allows assessment of all bowel layers and surrounding tissues. Validated systems for scoring CD severity on MRE enable standardised reporting and include Magnetic Resonance Index of Activity (MaRIA), a simplified version (MaRIAs) and the Lemann Index (LI). However, to be utilized in clinical trials, inter-reader reliability needs to be established. Here, we report the use of a standardised protocol to create a central reader pool for MRE scoring in CD and report its validation by application to the PROFILE1 clinical trial cohort.

Methods

Five accredited gastrointestinal radiologists blindly reported a total of 18 scans across 2 rounds of reading, with a consensus meeting between the rounds (Table 1). Each scan was scored using MaRIAs, MaRIAs-E (modified MaRIAs which includes small bowel segments), and LI. Intraclass correlation coefficient (ICC) was calculated to assess inter-reader reliability. To validate this reliability assessment in a clinical trial cohort, 71 scans from the PROFILE trial were double-read and ICC calculated.

Results

The central reader pool showed good inter-reader reliability after two rounds of training (ICC>0.70, with 95%CI lower bound>0.5). This high level of reliability was maintained in the trial validation (Figure 1).

Conclusion

Using this protocol we have successfully validated a central reader pool dedicated to severity scoring of CD that can be utilised in clinical trial setting. The ICC metrics in training rounds reflect good agreement between readers, suggesting that any single reader chosen from the pool would return a similar result to any other reader. The similarly high ICC calculated from the trial validation set suggests that the protocol used for establishing the central reader pool was robust, and high reliability of readers persisted during the PROFILE trial. Importantly, this methodology is transferable to other modalities where expert readers are asked to score images against validated scoring systems.

References

Nurulamin M. Noor et al., “A Biomarker-Stratified Comparison of Top-down versus Accelerated Step-up Treatment Strategies for Patients with Newly Diagnosed Crohn’s Disease (PROFILE): A Multicentre, Open-Label Randomised Controlled Trial,” The Lancet Gastroenterology & Hepatology 9, no. 5 (May 1, 2024): 415–27
P0365 The evolution of Geldof fistula class in patients with Crohn’s disease perianal fistula
Authors: Ibrahim F A E , Sebastian S
Published: January 2025

Background

Progressing the evaluation and management of Perianal fistulizing Crohn’s disease ( CD-pAF ) , an aggressive phenotype of CD , is one of the key unmet needs in Inflammatory Bowel Disease (IBD). There is sub-optimal understanding of the behavior of CD-pAF with some patients having rapid velocity of disease progression needing radical surgery such as proctectomy or diverting stoma. More recently, a practical patient-centric classification has been developed recently by Geldof et al has been used to classify patients underpinned by the behavior of CD-pAF(1). We aimed to evaluate the fistula class trajectory using Geldof classification in a large cohort of CD-pAF patients.

Methods

Data for 997 patients with Crohn’s disease perianal fistula (CD-pAF) included in a cohort study of patients with existing diagnosis of CD-pAF. Data was entered to predefined time points starting at the date of diagnosis of Cd-pAF and onward until entry into the cohort. We analysed the change in fistula classification using Geldof classification over 2 years.

Results

Data at entry to the cohort of 997 ( Males 52% , Females 48%) patients were included in the analysis The median age at fistula diagnosis was 31 years (23, 42). Among the 997 patients 686 had their Geldof class identified at baseline and 665 at 6-12 months. Class 2a followed by class 1 were the most frequent classes reported (Class 2a at baseline 376/686(55%) and Class 1 167/686(24%), at 6-12 months class 2a were 286/665(43%) and class 1 were 252/665(38%). At 12-24 months from fistula diagnosis 599 patients’ classes were reported, the most frequent being class 1 279/599(47%). There were minimal variations in Class 2b and class 2ci over the 3 time periods. (Class 2b [112/686(16%], [92/665(14%)]and [82/549(15%)] respectively, class 2ci [21/686(3%)], [20/665(3%)] [14/549(3%)] respectively). 15/686(2.1%) had proctectomy in the first 2 years.

Conclusion

While there are dynamic changes in fistula classification over 2 year period from fistula diagnosis there seems to be clustering among some classes. This indicates potential opportunity for identifying distinct classes which may have refractory course and tailor therapies accordingly.

References

(1)Geldof J, Iqbal N, LeBlanc JF, et al. Classifying perianal fistulising Crohn’s disease: an expert consensus to guide decision-making in daily practice and clinical trials. Lancet Gastroenterol Hepatol. 2022;7(6):576-584. doi:10.1016/S2468-1253(22)00007-3
P0369 The use of exhaled volatile organic compounds for the non-invasive assessment of endoscopic inflammation in patients with ileal pouch anal anastomosis (IPAA)
Authors: Qazi T , Cohen B , Ma J , Yang Q , Grove D , Regueiro M , Dweik R , Rieder F
Published: January 2025

Background

The incidence of inflammatory conditions in patients with ileal pouch-anal anastomosis (IPAA) constructed for the treatment of refractory ulcerative colitis (UC) and its complications is increasing. Objective assessment of IPAA inflammation is limited to surrogate markers in blood and stool which lack sensitivity and specificity or invasive endoscopic evaluations. Measurement of exhaled breath volatile organic compounds (VOCs) in breath shows promise for the assessment of inflammation. Our study aims to evaluate the pattern of VOCs in the exhaled breath of patients with IPAA and assess whether exhaled breath analysis can effectively distinguish patients with endoscopically active IPAA inflammation from patients without IPAA inflammation.

Methods

We conducted a cross-sectional study of patients with IPAA created for the management of UC. Exhaled breath samples were obtained from patients presenting for endoscopic pouch evaluation. Samples were analyzed using selective ion flow tube mass spectrometry (SIFT-MS) to measure constituent VOCs. Patients were dichotomized into subjects with significant endoscopic pouch inflammation, endoscopic pouch disease activity index greater than or equal to 4 (ePDAI ≥ 4) or patients with minimal pouch inflammation (ePDAI ≤ 1) . Similar analyses were performed in subjects with a ePDAI greater than or equal to 5. Principle component analysis (PCA) was conducted to reveal the most important VOCs that differentiate two cohorts. Principle component regression (PCR) was performed to assess the prediction performance of exhaled breath VOC analysis in differentiating the groups.

Results

In the final analysis, 70 subjects presenting for pouch endoscopic evaluation were included in the study. 29 subjects had an ePDAI less than or equal to 1 and 41 subjects had and ePDAI greater than or equal to 4. Demographics are provided in table 1. Key VOCs—ethane, octanoic acid, and propylcyclohexane—were found to differ significantly between the two groups. Figure 1 shows the receiver operating curve (ROC) of the PCR model for the full mass scan, showing an area under the curve (AUC) of 0.77 (0.66-0.88). A similar analysis in patients with PDAI of greater than equal to 5, demonstrated and AUC of 0.83 (0.72-0.94).

Conclusion

Exhaled breath VOC analysis effectively differentiates between patients with significant pouch inflammation and those with minimal inflammation. This non-invasive method shows promise as a reliable tool for assessing ileal pouch inflammation, with high patient acceptance. Further research is warranted to validate these findings and explore the potential of VOC analysis in clinical practice.
P0370 Transmural healing in Ulcerative Colitis patients improves long-term outcomes compared to endoscopic healing alone
Authors: Lim C T , Teichert C , Pruijt M , de Voogd F , D’Haens G , Gecse K
Published: January 2025

Background

Endoscopic healing (EH) is recognised as a long-term treatment goal for patients with ulcerative colitis (UC).1 We investigated whether transmural healing (TH) in UC as assessed by intestinal ultrasound (IUS) is associated with improved outcomes compared to EH alone.

Methods

We performed a retrospective study on patients with left-sided or extensive UC on stable maintenance treatment who had EH (Mayo Endoscopic Sub score [MES] ≤1) and an intestinal ultrasound (IUS) performed within six months of an endoscopy with no treatment alterations between IUS and endoscopy. Patients with ulcerative proctitis or on corticosteroids were excluded. TH was defined as bowel wall thickness (BWT) < 3mm. The primary outcome was relapse-free survival in patients with and without TH. UC relapse was defined as at least two of the following: Simple Clinical Colitis Activity Index of ≥ 5 or physician’s global assessment of relapse; fecal calprotectin ≥ 250 ug/g; MES of ≥ 2 on any bowel segment; BWT of ≥ 3mm on any bowel segment (excluding the rectum).

Results

A total of 61 patients with a median follow up of 20 months were included (Table 1). The relapse risk for the first and second year was 7.5% and 20.5% for the TH group, respectively, compared to 29.4% and 64.3% for the non-TH group (p=0.004, Figure 1). The mean time to the first relapse, was 20.9 ± 11.1 months for the TH group and 12.2 ± 7.8 months for the non-TH group (p=0.042).

The risk of relapse for MES 0 at the first year was lower than MES 1 (3.7% compared to 20.8%), although this was not statistically significant (p=0.059). When stratifying for MES 1, TH showed improved relapse free survival for patients with MES 1 compare to those without TH (p=0.045, Figure 1). Moreover, there was a trend towards shorter time to relapse for patients with MES 1 without TH compared to those with TH (12.2 ± 7.8 months vs 18.4 ± 7.6 months)

In multivariate Cox regression, female gender (hazard ratio [HR], 2.63; 95% CI, 1.05-6.58; p=0.039), ≥ 2 previous advance therapies (HR, 4.06; 95% CI 1.08-15.28; p=0.038) and non-TH (HR, 3.99; 95% CI 1.31-12.20; p=0.015) were associated with a relapse whereas EH level (MES 0 vs MES 1) was not an associated factor (HR, 1.06; 95% CI 0.32-3.55; p=0.924).

Conclusion

In UC patients, transmural healing is associated with lower relapse risk compared to endoscopic healing alone. These findings implicate that intestinal ultrasound is a non-invasive, low-cost alternative to endoscopy for stratifying UC patients for risk of relapse.

References

1.Turner D, Ricciuto A, Lewis A, et al. STRIDE-II: An Update on the Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) Initiative of the International Organization for the Study of IBD (IOIBD): Determining Therapeutic Goals for Treat-to-Target strategies in IBD. Gastroenterology. 2021;160(5):1570-1583. doi:10.1053/j.gastro.2020.12.031
P0371 Building a Robust Artificial Intelligence Solution for Use in Ulcerative Colitis Clinical Trials
Authors: Byrne M , Requa J , Panés J , Bressler B , Panaccione R , Mendel R , East J E , Parsa N , Banerjee R , Kalapala R , Reddy D N , Rughwani H R , Flegg D , Moran G , Gallinger Z , Cheung V , Tan M , Ma C , Travis S P , Jairath V
Published: January 2025

Background

Artificial Intelligence (AI) is increasingly used to assess Ulcerative Colitis (UC) disease activity in clinical trials, with the goal of matching or exceeding expert performance in a reproducible manner. Certai has been created from previous AI work as a model that conforms to the new definitions within the Modified Mayo Endoscopic Score criteria.

Methods

Using the self-supervised DINOv2 method, Certai was pre-trained on 845 colonoscopic procedures and then refined with annotations from the proprietary Software for Intelligent Annotation (SIA) platform. This browser-based tool, with advanced playback controls and a UC scoring interface, enabled video annotation by eight global IBD specialists and central readers, and seven additional specialists in training on SIA. Labellers underwent rigorous onboarding to meet minimum thresholds for Intra-Class Correlation Coefficient (ICC) and Quadratic Weighted Kappa (QWK).

Certai’s architecture features two Vision Transformer models: a Quality Control (QC) model and a Scoring model. The QC model excludes frames with poor clarity, inadequate bowel prep, non-colonic views, chromoendoscopy, or biopsy procedures. The Scoring model uses multi-headed outputs to assess UC severity, grading vascular pattern, bleeding, ulcers/erosions, friability, and erythema.

Results

A total of 8.9 million frames from 39 videos were labelled across six categories, resulting in 2.17 million merged labels determined by majority vote. For inter-rater agreement on modified MES in the labelling process, the overall ICC among the onboarded labellers was 0.86, and the QWK was 0.88.

On a validation set of colonoscopy procedures, Certai achieved 100% agreement with human central readers on modified MES scores. The ICC among three expert labellers was 0.922 and rose to 0.942 with the addition of Certai. There was an additional increase of the ICC to 0.955 when Certai was paired with just one expert labeller. Similarly, QWK scores rose from 0.914 for two expert labellers to 0.961 with Certai and one expert labeller.

Conclusion

Certai represents an advance in UC disease activity assessment, meeting modified MES requirements. With further specialist labelling of an additional several hundred videos at the detailed frame level, a robust version of Certai will enable new quality standards in speed of central reading and consistency. Future applications may include stand-alone AI reads with human sign-off or a 2 + 1 reader model incorporating AI as one reader.
P0372 Fatigue in Swedish patients with Inflammatory bowel disease
Authors: Jäghult S , Pilhl Lesnovska K , Marsal J
Published: January 2025

Background

Fatigue is characterized as an overwhelming sense of tiredness, weakness, or exhaustion, which can be physical, psychological, or a combination of both. Fatigue is a common symptom and a significant concern for patients with IBD. International studies indicate that between 44% and 86% of patients with active disease, and 22% to 41% of those in remission, experience fatigue. This symptom can limit individual activities and negatively impact health-related quality of life. Despite its profound effects on patients, fatigue is often overlooked by healthcare professionals, who find it challenging to measure and manage. The aim of this study is to assess the prevalence of fatigue in Swedish IBD patients, both in active disease and in remission.

Methods

The study was conducted using a disease-specific questionnaire, the IBD-Fatigue Scale, which has been translated and validated into Swedish. The IBD-Fatigue Scale and questions concerning demographic data was distributed electronically to IBD patients in Stockholm and Linköping. The IBD Fatigue Scale consists of three sections. Section I assess frequency and severity of fatigue. Section II is rating experience and impact of fatigue, and section III is asking for patients’ comments and issues related to fatigue. This study will show the results of section I. A total of 2208 patients were asked to participate in the study.

Results

A total of 760 (34%) patients accepted to participate in the study and of 674 of those answered the questionnaire. The IBD-Fatigue Scale´s first section shows that fatigue is a burdensome symptom in IBD patients (figure 1). The scoring ranges between 0-20, where 0 means no fatigue and 20 means severe fatigue. The mean value showed 12,1 in the Swedish population. When comparing between sex, diagnosis and active vs remission, the patients who perceived most fatigue were woman and those with active disease (table 1).

Conclusion

This study shows that IBD-patients in Sweden suffer from fatigue to similar extent as in international studies. Those with highest perceived fatigue are women and those with active disease and those with continuous symptoms.No studies have examined the prevalence of fatigue among Swedish patients with IBD or its impact on their lives, and there is a pressing need to explore the extent of fatigue among this population and to understand their experiences and the effects of fatigue on their daily lives.
P0377 Development of Crohn’s Aid mobile application based on AI algorithms to make an early diagnosis of Crohns Disease in TB endemic regions
Authors: Mohta S , Kutum R , Pendyala R , Dev H , Kante B , Kumar Vuyyuru S , Kumar P , Virmani S , Kumar M , Bahl S , Makharia G , Chaudhury S , Kedia S , Sethi T , Ahuja V
Published: January 2025

Background

Intestinal tuberculosis (ITB) and Crohn’s disease (CD) mimic each other clinically, endoscopically, and radiologically and are difficult to differentiate. This is a major barrier to make an early diagnosis of CD in TB endemic areas. We aimed to develop a high accuracy machine learning-based model which could be easily implemented in an innovative way.

Methods

We retrospectively analyzed data from 1066 patients. After data cleaning, 796 patients (514 CD & 282 ITB) and data from 28 variables were included. A super learner approach using random forest and support vector machine was used for differentiating ITB from CD. Data was divided into 80 percent training and 20 percent testing data sets followed by 10-fold cross validation. The optimal cut-off for the diagnosis was obtained using the Youden index-measure to optimize the balance between sensitivity and specificity and the model was evaluated at multiple thresholds for clinical utility. The best performing model was incorporated into a mobile phone-based application. Prospective validation on 37 patients was carried out with similar accuracy.

Results

The random forest model achieved a sensitivity, specificity and accuracy of 0.92, 0.83, 0.86 respectively and performed better than the support vector machine model trained with linear and radial basis functions. The random forest model was found to have the best AUROC with a cutoff of 0.4, predicting the diagnosis of CD with a sensitivity of 93%, specificity of 83%, and accuracy of 86%, positive predictive value of 76%, and negative predictive value of 95%. The random forest model was used for creation of the application. The app is being made available on smartphones free of cost for use by any physician.

Conclusion

Our model differentiated between ITB and CD with high accuracy and has the potential to makean early diagnosis of CD. The free to use mobile application would make implementation of thisalgorithm much easier, allowing for widespread use in clinical practice and helping make moreinformed decisions. More data from multiple centers and different geographical locationswould aid in further improving the model performance.

Figure 1: Overall model training approach

Figure 2: Model performance and selection of appropriate cut-off