Active Colitis Research Articles

Bile acid profiling as an effective biomarker for staging in pediatric inflammatory bowel disease

ABSTRACT Rapid and accurate clinical staging of pediatric patients with inflammatory bowel disease (IBD) is crucial to determine the appropriate therapeutic approach. This study aimed to identify effective, convenient biomarkers for staging IBD in pediatric patients. We recruited cohorts of pediatric patients with varying severities of IBD to compare the features of the intestinal microbiota and metabolites between the active and remitting disease stages. Metabolites with potential for staging were targeted for further assessment in both patients and colitis model mice. The performance of these markers was determined using machine learning and was validated in a separate patient cohort. Pediatric patients with IBD exhibited distinct gut microbiota structures at different stages of disease activity. The enterotypes of patients with remitting and active disease were Bacteroides-dominant and Escherichia-Shigella-dominant, respectively. The bile secretion pathway showed the most significant differences between the two stages. Fecal and serum bile acid (BA) levels were strongly related to disease activity in both children and mice. The ratio of primary BAs to secondary BAs in serum was developed as a novel comprehensive index, showing excellent diagnostic performance in stratifying IBD activity (0.84 area under the receiver operating characteristic curve in the primary cohort; 77% accuracy in the validation cohort). In conclusion, we report profound insights into the interactions between the gut microbiota and metabolites in pediatric IBD. Serum BAs have potential as biomarkers for classifying disease activity, and may facilitate the personalization of treatment for IBD.

Endoscopic scoring system utilization for inflammatory bowel disease activity assessment: A multicenter real-world study from Argentina

BackgroundThe frequency and patterns of use of scores for the assessment of endoscopic activity in inflammatory bowel disease patients are not known. AimTo describe the prevalence of adequate use of endoscopic scores in IBD patients who underwent colonoscopy in a real-life setting. Materials and methodsA multicenter observational study comprising six community hospitals in Argentina was undertaken. Patients with a diagnosis of Crohn's disease or ulcerative colitis who underwent colonoscopy for endoscopic activity assessment between 2018 and 2022 were included. Colonoscopy reports of included subjects were manually reviewed to determine the proportion of colonoscopies that included an endoscopic score report. We determined the proportion of colonoscopy reports that included all of the IBD colonoscopy report quality elements proposed by BRIDGe group. Endoscopist's specialty, years of experience as well as expertise in IBD were assessed. ResultsA total of 1556 patients were included for analysis (31.94% patients with Crohn's disease). Mean age was 45.94±15.46. Endoscopic score reporting was found in 58.41% of colonoscopies. Most frequently used scores were Mayo endoscopic score (90.56%) and SES-CD (56.03%) for ulcerative colitis and Crohn's disease, respectively. In addition, 79.11% of endoscopic reports failed to comply with all recommendations on endoscopic reporting for inflammatory bowel disease. ConclusionsA significant proportion of endoscopic reports of inflammatory bowel disease patients do not include the description of an endoscopic score to assess mucosal inflammatory activity in a real-world setting. This is also associated with a lack of compliance in recommended criteria for proper endoscopic reporting.

Inflammatory bowel disease activity threatens ankylosing spondylitis: implications from Mendelian randomization combined with transcriptome analysis.

Inflammatory bowel disease (IBD) and ankylosing spondylitis (AS) share common traits of chronic recurrent inflammation affecting both the intestines and joints. Epidemiological studies have revealed that the incidence of AS has jumped from 0.3% to 3% among patients with IBD. However, these findings do not definitively establish a causal relationship whereby IBD directly leads to the development of AS. Moreover, whether the activity of IBD will have an impact on this process remains a pending question. Two-sample Mendelian randomization (MR) analyses were employed across multiple datasets to investigate the potential of IBD as a risk factor for AS. The pathogenic genes of AS were identified by MR analysis of expression quantitative trait locus. Risk scores for active and inactive patients were calculated by single-sample gene set enrichment analysis. Comparative assessments encompassing alterations in risk transcription factor activity, shifts in signaling pathways, and variances in immune cell profiles were conducted between active and inactive patients. Moreover, the correlation of immune cells and risk genes was quantified. A total of 6 MR analyses, conducted across 3 exposure datasets and 2 outcome datasets, consistently revealed that IBD substantially elevates the risk of AS development. The MR analysis of the two outcome datasets identified 66 and 54 risk genes, respectively. Notably, both the risk scores computed from the two distinct sets of risk genes were notably higher in active patients compared to their inactive counterparts. Discernible variations in the activity of risk-associated transcription factors were observed between active and inactive patients. In addition, three inflammatory pathways exhibited marked activation in active patients. Moreover, seven specific immune cell types, closely linked to disease activity, exhibited statistically significant correlations with the identified risk genes. By combining Mendelian randomization with transcriptome analysis, this study postulates IBD as a significant risk factor for AS, and further presents innovative evidence for the impact of IBD activity on the progression of AS.

Частота тривожно-депресивного синдрому в дітей, хворих на запальні захворювання кишечника

Inflammatory bowel diseases (IBD) have been spreading rapidly in industrialized countries since the beginning of the 21st century. Purpose - to determine the frequency of symptoms of anxiety and depression in children with IBD, in order to optimize treatment. Materials and methods. 18 patients aged 10-17 years were surveyed: 10 people with ulcerative colitis (UC) and 8 people with Crohn’s disease (CD), symptoms of anxiety and depression were studied using PHQ-2, PHQ-9 questionnaires (Patient Health Questionnaire) and GAD-7 (Generalized Anxiety Disorder). The obtained results were analyzed using SPSS 26.0 programs. The odds ratio (OR) was considered significant if the 95% confidence interval (CI) did not include 1. The difference in samples was considered significant at p<0.05. Results. Of the 18 patients who were surveyed using the PHQ-2 questionnaire, 13 (72.2%) were screened for further investigation using the PHQ-9 questionnaire. The prevalence of anxiety symptoms was 55.5% (95% CI: 38.3-66.5), depressive symptoms - 34.8% (95% CI: 21.4-45.8). Patients with CD had higher odds of anxiety symptoms (OR: 1.2, 95% CI: 1.1-3.6) and depressive symptoms (OR: 1.3, 95% CI: 1.1-1.7) than children with UC. There were differences in the severity of anxiety and depression in different pathological conditions (IBD: p<0.01; UC: p<0.05; CD: p=0.05). The frequency of symptoms of anxiety or depression was higher in patients with active IBD than in children with inactive disease (100% and 33.3% and 100% and 45.8%, respectively). Minimal (0-4 points) and mild (5-9) degrees of anxiety and depression prevailed. Conclusions. The frequency of detection of symptoms of anxiety and depression in children with CD and UC in the active stage of the disease is 55.5% and 34.8%, respectively, with a predominance of minimal (0-4 points) and mild (5-9) degrees. Patients with CD are higher odds of anxiety and depression symptoms than children with UC. The research was carried out in accordance with the principles of the Helsinki Declaration. The study protocol was approved by the Local Ethics Committee of the participating institution. The informed consent of the patient was obtained for conducting the studies. No conflict of interests was declared by the authors.

Identification of immune cell markers associated with ulcerative colitis histological disease activity in colonic biopsies

AimsAccurate determination of histological activity in ulcerative colitis (UC) is essential given its diagnostic and prognostic importance. Data on the relationship between histology and immune cell markers are limited. We...

Comparison of Fecal Calprotectin and Myeloperoxidase in Predicting Outcomes in Inflammatory Bowel Disease.

Biomarkers have been proposed as surrogate treatment targets for the management of inflammatory bowel disease (IBD); however, their relationship with IBD-related complications remains unclear. This study investigated the utility of neutrophil biomarkers fecal calprotectin (fCal) and fecal myeloperoxidase (fMPO) in predicting a complicated IBD course. Participants with IBD were followed for 24 months to assess for a complicated IBD course (incident corticosteroid use, medication escalation for clinical disease relapse, IBD-related hospitalizations/surgeries). Clinically active IBD was defined as Harvey-Bradshaw index >4 for Crohn's disease (CD) and simple clinical colitis activity index >5 for ulcerative colitis (UC). Area under the receiver-operating-characteristics curves (AUROC) and multivariable logistic regression assessed the performance of baseline symptom indices, fCal, and fMPO in predicting a complicated disease IBD course at 24 months. One hundred and seventy-one participants were included (CD, n = 99; female, n = 90; median disease duration 13 years [interquartile range, 5-22]). Baseline fCal (250 μg/g; AUROC = 0.77; 95% confidence interval [CI], 0.69-0.84) and fMPO (12 μg/g; AUROC = 0.77; 95% CI, 0.70-0.84) predicted a complicated IBD course. Fecal calprotectin (adjusted OR = 7.85; 95% CI, 3.38-18.26) and fMPO (adjusted OR = 4.43; 95% CI, 2.03-9.64) were associated with this end point after adjustment for other baseline variables including clinical disease activity. C-reactive protein (CRP) was inferior to fecal biomarkers and clinical symptoms (pdifference < .05) at predicting a complicated IBD course. A combination of baseline CRP, fCal/fMPO, and clinical symptoms provided the greatest precision at identifying a complicated IBD course. Fecal biomarkers are independent predictors of IBD-related outcomes and are useful adjuncts to routine clinical care.

The role of endoscopic ultrasonography for assessing the activity of ulcerative colitis in children

Background. Endoscopic diagnostic methods, namely ileocolonoscopy with biopsy, are the „gold standard“ in the diagnosis of ulcerative colitis. Due to the improvement of methods for the diagnosis of ulcerative colitis, the use of endoscopic ultrasonography, that combines endoscopic and ultrasound diagnostic methods, has attracted widespread attention. Endoscopic ultrasonography allows examination of the mucous membrane and the underlying layers of the intestinal wall, which makes it possible to measure the thickness of the intestinal wall. Both in Russia and abroad, there are no publications on the use of endoscopic ultrasonography for ulcerative colitis in children, and that requires further research in this area.&#x0D; Aim. To evaluate the possibilities of endoscopic ultrasonography in order to determine the activity of ulcerative colitis in children.&#x0D; Materials and methods. The study includes 97 children with an established diagnosis of ulcerative colitis. All children underwent ileocolonoscopy and endoscopic ultrasonography. The UCEIS scale (Ulcerative Colitis Endoscopic Index of Severity) was used to assess endoscopic activity. During endoscopic ultrasonography, the thickness of the intestinal wall and blood flow were evaluated using the color Doppler mapping mode.&#x0D; Results. According to the study, there was a statistically significant increase in the thickness of the intestinal wall amid the development of endoscopic activity. The statistically significant increase in the activity of blood flow in the intestinal wall was found.&#x0D; Conclusion. Endoscopic ultrasonography is a relatively new research method with a number of functions that can be used to solve complex diagnostic problems in children with ulcerative colitis. The ability to measure the thickness of the intestinal wall and assess the severity of blood flow allows endoscopic ultrasonography to assess patients with ulcerative colitis dynamically, which makes it a promising method in primary diagnosis.

Immune checkpoint inhibitor-related colitis in patients on immunotherapy for cancer.

Immune checkpoint inhibitors, a revolutionary class of cancer immunotherapy drugs, have transformed cancer treatment by bolstering antitumor immunity for various advanced-stage solid cancers. The US Food and Drug Administration has approved 7 immune checkpoint inhibitors that target 3 major immune checkpoint proteins: cytotoxic T-lymphocyte-associated protein 4, programmed cell death 1 protein, and programmed cell death 1 ligand 1. In addition to their remarkable efficacy, however, these inhibitors have been observed causing immune-related adverse events, particularly immune checkpoint inhibitor-related colitis, which often results in severe or life-threatening clinical issues. The diagnosis of immune checkpoint inhibitor-related colitis relies on incorporation of clinical evaluation as well as endoscopic and histopathologic examination, with exclusion of other potential etiologies. The common histopathologic manifestations of immune checkpoint inhibitor-related colitis are acute active colitis, chronic active colitis, microscopic colitis (collagenous or lymphocytic), and ischemic colitis, with patterns overlapping. Notably, enterocyte apoptosis is a unique feature of immune checkpoint inhibitor toxicity. The proposed mechanisms for the pathogenesis of immune checkpoint inhibitor-related colitis are primarily associated with autoimmune-type dysregulation and gut microbiome alteration. This review summarizes the clinical and pathologic characteristics of immune checkpoint inhibitor-related colitis and elucidates its underlying pathogenic mechanisms. Future successful management of this form of colitis relies on our comprehension of the intricate interplay between tumoral and systemic immune responses to immune checkpoint inhibitors and innovative approaches to modify these responses, along with specific immune cell populations, to preclude immune-related adverse events while achieving antitumor therapeutic outcomes.

Enhancing Calprotectin's Predictive Power as a Biomarker of Endoscopic Activity in Ulcerative Colitis: A Machine Learning Use Case.

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by periods of exacerbation and remission, making disease monitoring and management challenging. Endoscopy, the gold standard for assessing disease activity and severity, involves invasive procedures and is associated with patient discomfort and risks. Using machine learning (ML) to combine fecal calprotectin with other clinical or biological tests can significantly enhance the non-invasive prediction of endoscopic disease activity (EDA) in UC. Aim: To prove that by fusing fecal calprotectin with other clinical data into an ML model, the performance of the non-invasive prediction of EDA can be significantly improved. Methods: We conducted a prospective, observational, single-center study encompassing 103 patients diagnosed with UC. We employed multilayer perceptron models as the core ML algorithm for predicting EDA. For the constructed models, we utilized the varImp function from the caret library in R to assess the significance of each variable in predicting the outcome. Results: Calprotectin as a sole predictor obtained an accuracy of 70% and an area under the curve (AUC) of 0.68. Combining calprotectin with the list of selected predictors that were fed to the MLP models improved accuracy and the AUC. The accuracy of the algorithm on the test set was 85%. Similarly, the AUC increased to 0.93. This is the first study to propose the use of calprotectin as a predictor in an ML model to estimate UC endoscopic disease activity. Conclusion: The deployment of this ML model can furnish doctors and patients with valuable evaluation of endoscopic disease activity which can be highly beneficial for individuals with UC who need long-term treatment.

Single-cell and spatial multi-omics highlight effects of anti-integrin therapy across cellular compartments in ulcerative colitis

Ulcerative colitis (UC) is driven by immune and stromal subsets, culminating in epithelial injury. Vedolizumab (VDZ) is an anti-integrin antibody that is effective for treating UC. VDZ is known to inhibit lymphocyte trafficking to the intestine, but its broader effects on other cell subsets are less defined. To identify the inflammatory cells that contribute to colitis and are affected by VDZ, we perform single-cell transcriptomic and proteomic analyses of peripheral blood and colonic biopsies in healthy controls and patients with UC on VDZ or other therapies. Here we show that VDZ treatment is associated with alterations in circulating and tissue mononuclear phagocyte (MNP) subsets, along with modest shifts in lymphocytes. Spatial multi-omics of formalin-fixed biopsies demonstrates trends towards increased abundance and proximity of MNP and fibroblast subsets in active colitis. Spatial transcriptomics of archived specimens pre-treatment identifies epithelial-, MNP-, and fibroblast-enriched genes related to VDZ responsiveness, highlighting important roles for these subsets in UC.

New trends associated with disease activity in patients with ulcerative colitis

Background/Aim: The severity and extent of ulcerative colitis (UC) guide us in determining the treatment method for each case. It has been suggested in the literature that high neutrophil-lymphocyte and platelet-lymphocyte ratios can serve as markers of active ulcerative colitis. This study retrospectively analyzes the relationship between neutrophil-lymphocyte ratio and platelet-lymphocyte ratio with clinical activity indices and endoscopic activity indices in predicting disease severity in patients with ulcerative colitis. There are few studies in the literature regarding the relationship between platelet-lymphocyte ratio (PLR) and disease activation in ulcerative colitis. This study contributes to the follow-up and outcomes of these patients, as there is a lack of sufficient retrospective studies on the platelet/lymphocyte ratio in patients diagnosed with UC in our country and worldwide. Methods: This study is a population-based, single-center, case-controlled study. It was conducted by retrospectively analyzing the hospital information system for data recorded during the routine diagnosis and treatment of ulcerative colitis patients followed and treated at Celal Bayar University Medical Faculty Gastroenterology Division between January 2014 and December 2021. A total of 135 patients with ulcerative colitis were included in the study. The patients were divided into 2 groups, active disease and disease in remission, based on clinical activity indices and endoscopic activity indices. Erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), hemoglobin (Hb), white blood cell (WBC), neutrophil-lymphocyte ratio (NLR), and platelet-lymphocyte ratio (PLR) levels were checked during routine follow-up of patients with ulcerative colitis. These values were recorded at the first presentation to the hospital and 3 months after treatment. Results: Laboratory values at presentation were compared with those at the third month of treatment in a group of 113 patients with UC in remission: NLR (5.529 (3.485) and 4.374 (2.335), [P&lt;0.001]), erythrocyte sedimentation rate (26.81 (20.42) and 21.78 (19.32), [P=0.015]), C-reactive protein (4.087 (6.729) and 1.696 (3.525), [P&lt;0.001]), and white blood cell count (9,864 (3,514) and 8,067 (1,927), [P&lt;0.001]) were found to be lower than the baseline values. As expected, decreases in inflammatory markers were observed in patients in remission. In a group of 22 patients with active disease, values at presentation were compared with those at the third month of treatment: neutrophil count (8,508 (2,908) and 9,646 (3,265), [P=0.037]) and platelet count (289,591 (95,123) and 323,364 (127,647), [P=0.010]) were found to be high. Similarly, ESR (19.63 (15.43) and 27.89 (21.11), [P=0.036]) was found to be high. These values were higher in active disease compared to the time of admission. Conclusion: In our study, neutrophil-lymphocyte ratios and platelet-lymphocyte ratios were significantly higher in patients with active ulcerative colitis. The level of inflammatory markers in ulcerative colitis patients at the time of diagnosis and in the early stages of the disease is helpful in predicting the course of the disease, and this was shown to be related to clinical, endoscopic, and laboratory indices. These inflammatory markers can predict disease activity alone or in combination. However, a threshold value could not be calculated due to the insufficient number of patients, and thus, more comprehensive prospective studies are needed.

A79 PATIENT AND PHYSICIAN PERSPECTIVES ON IMPLEMENTION OF BEDSIDE INTESTINAL ULTRASOUND FOR THE ASSESSMENT OF INFLAMMATORY BOWEL DISEASE

Abstract Background New tools for evaluating Inflammatory Bowel Disease (IBD) activity and complications are needed to deliver timely disease management and improve patient outcomes. Point of care (POC) intestinal ultrasound (IUS) is safe, inexpensive, and less invasive compared to standard endoscopy and imaging. Aims To evaluate the implementation of POC IUS within an ambulatory IBD clinic at the QEII Health Sciences Center. Methods This was a retrospective evaluation of a cohort of patients who had undergone IUS within the Nova Scotia Collaborative Inflammatory Bowel Diseases Clinic (NSCIBD) between January 18, 2023 and August 13, 2023. Medical records were reviewed retrospectively. Patient demographics, disease-related characteristics, perceived impact of IUS on need for endoscopy, perceived impact of IUS on IBD management, and clinical utility of IUS were collected. Surveys were administered prospectively to referring care providers and patients following IUS. Patient surveys assessed IUS satisfaction, acceptance of other methods to assess IBD activity, whether IUS improved knowledge of illness, and impact on quality of life (QoL). Results One physician completed 107 IUS exams on 92 patients at the NSCIBD clinic over a nine-month period. Of 92 patients, 47 (51%) were male and 78 (85%) had Crohn’s disease. 53 patients provided an email and consented to survey participation. 34 responses were submitted (64%). There were 97 responses (91%) from 12 referring gastroenterology specialist clinicians. Ninety-three percent of responses show IUS reports were very helpful (60%) or somewhat helpful (33%). More than a third (37%) of IUS exams were reported to delay or prevent the need for endoscopic evaluation, and 34% were reported to prompt a therapeutic change. Of available tools, IUS had the highest proportion of patients who felt it was completely acceptable (77%), compared to colonoscopy (41%), stool sampling (50%), blood tests (71%), and computed tomography/magnetic resonance imaging (47%). Most (89%) indicated IUS caused either no discomfort (68%) or little discomfort (21%), with no patient reporting a lot of discomfort. Some patients (41%) reported that IUS improved their understanding of their illness, and 38% believe it improved their QoL. Conclusions POC IUS offers an accurate, less invasive option for monitoring IBD activity compared to traditional investigations. There is limited data on implementation of, and patient and clinician perspectives regarding use of IUS and its clinical implications. Even early in implementation, POC IUS has clear benefits. This study suggests that IUS is highly acceptable to patients for investigating/monitoring their illness. Treating clinicians find significant value in IUS and report that it can prevent the need for endoscopic evaluation and prompt changes in therapeutic management. Funding Agencies None

A250 CYTOKINE MULTI-OMICS AND MACHINE LEARNING IDENTIFY MIP1ALPHA AS A NOVEL MEDIATOR IN INFLAMMATORY BOWEL DISEASE

Abstract Background Macrophage inflammatory protein 1 alpha (MIP1a) is a proinflammatory cytokine previously related to murine models of inflammatory bowel disease (IBD), but not definitively in the human disease. MIP1a acts as a chemoattractant of immune cells from the blood to the gut mucosa. We aimed to delineate the alterations to MIP1a and macrophages in relation to a range of IBD severity. Aims To characterize the changes to MIP1a production and localization in response to disease activity in IBD. Methods Both IBD (n=63) and control patients (n=118) were enrolled in this study (HSREB 6033229). Cytokine profiles were investigated using a 17-plex multi-fluorescent bead-based immunoassay (FirePlex, Abcam, Cambridge, UK) on serum from a subset of patients. Disease activity and macrophage levels were extracted from the clinical record. Activity was quantified using the Physician Global Assessment Score. Machine learning (ML) was performed with custom R scripts utilizing the tidymodels package (version 1.1) to determine the optimal model. Immunohistochemistry (IHC) was used to localize MIP1a in patient biopsies and quantified using QuPath software (v0.4). Results An extreme gradient boost ML model was found to have optimal sensitivity and specificity for predicting disease activity based on serum cytokine levels. Within this model lower levels of serum MIP1a were associated with higher severity of IBD activity. However, in GI mucosal biopsies, the percentage of MIP1a positive cells in colon tissue increased with the severity of IBD. Macrophage concentrations in the peripheral blood were higher in patients on prednisone, and relatively similar across all other medications used in our cohort. Conclusions With the data collected, we identify MIP1a as a possible prognostic tool for quantifying IBD activity. Funding Agencies CIHR

A225 ASSESSMENT OF BEDSIDE INTESTINAL ULTRASOUND IN MONITORING CROHN’S DISEASE ACTIVITY

Abstract Background Bedside intestinal ultrasound (IUS) is an evolving modality in monitoring disease activity and assessing complications in inflammatory bowel disease (IBD). The easy-tolerability and immediate accessibility to results for expedited clinical decision-making contribute to the growing global attraction of IUS integration into IBD care. Fecal calprotectin (FC) is a known, non-invasive tool to assess disease activity in IBD. However, it comes with limitations. Aims To assess the efficacy of IUS in monitoring Crohn’s Disease (CD) compared to FC level. Methods We conducted a retrospective observational study in patients with confirmed CD at a certified IUS gastroenterologist’s outpatient clinic in Saskatoon. Patients’ charts undergoing IUS between February 2022 and April 2023 were reviewed. Patients with CD and available FC results within a month of IUS performance were identified. Age, gender, disease character, clinical symptoms (Harvey-Bradshaw Index (HBI)), FC levels, and IUS bowel wall thickening (BWT) were collected. The cut-off for FC levels and BWT for disease activity were ampersand:003E250 μg/g and ampersand:003E3 mm, respectively. The correlation between IUS BWT and FC levels was analyzed based on the Pearson correlation. Results Among a total of 178 chart reviews, 71 patients were identified. The median age was 49 years, 52.1% were males and 47.8% were females. 35 (49.3%) ileal CD, 35 (49.3%) ileocolonic and 1 (1.4%) colonic CD were identified. The HBI score verified 67.6% mild disease, 19.7% moderate, 11.2% in remission, and 1.4% severe disease. The Pearson correlation coefficient (r) between FC levels and BWT findings on IUS was r = 0.29 (P ampersand:003C0.0001), indicating a weak positive correlation. Conclusions A positive but weak correlation exists between bowel wall thickening in IUS and FC level in monitoring CD. Recognizing FC limitations, future multi-center, larger cohort studies need to be done to investigate this correlation further. Funding Agencies None

A222 CLINICAL EFFECTIVENESS AND SAFETY OF USTEKINUMAB IN YOUTH WITH REFRACTORY INFLAMMATORY BOWEL DISEASE IN SAUDI ARABIA: A RETROSPECTIVE COHORT STUDY

Abstract Background Inflammatory bowel disease (IBD) incidence and prevalence have been increasing worldwide with higher disease severity observed in pediatrics. Limited data exists on the effectiveness of ustekinumab (UST) in children. Aims To describe the effectiveness and safety of UST in pediatric patients with IBD. Methods A retrospective, single-center cohort study was conducted between January 2017 and February 2022. The study included patients ≤16 years of age who were treated with off-label UST and followed up for a minimum of one year. Clinical remission was defined as a decrease in the score on the Pediatric Crohn's Disease (CD) and Pediatric Ulcerative Colitis (UC) Activity Indices to ≤10 at week 52. Results A total of 13 patients who had failed anti-TNFα therapy were included, 8 (61.5%) with CD and 5 (38.5%) with UC. The median age of the patients was 13y (IQR: 11.5 to 14). UST treatment was initiated at a median of 3y (IQR: 2.3 to 7) after diagnosis. Ten patients (76.9%) achieved clinical remission. There were no statistically significant differences in baseline characteristics between patients who achieved and did not achieve clinical remission. Biochemical remission was achieved in 6 patients (46.2%). C-reactive protein levels decreased significantly in the remission group and insignificantly in the non-remission group. No significant changes were observed in erythrocyte sedimentation rate, albumin, or hemoglobin. BMI improved (Fig 1) and the need for corticosteroids significantly decreased after UST therapy in the remission group (P = 0.014). Endoscopy conducted post-treatment in 7 patients confirmed remission in 6 patients, with one patient showing clinical remission but not endoscopic remission. Adverse events included two instances of infection and once case of headache. Conclusions UST was effective as a secondary biologic therapy for the induction and maintenance of remission in patients with anti-TNFα refractory IBD. At one year, 84% of patients remained on UST with no severe adverse reactions reported. Future prospective large-scale studies are necessary to assess the therapeutic positioning and optimal dosing regimens of UST in pediatric IBD. Figure 1. Change in BMI Z-score throughout the study (P value of interaction = 0.049). Funding Agencies None

A260 ADVANCING INFLAMMATORY BOWEL DISEASE DIAGNOSIS THROUGH STOOL PROTEOMIC SIGNATURES OBTAINED VIA DIA-MASS SPECTROMETRY AND MACHINE LEARNING

Abstract Background Resembling symptoms between flare-up Inflammatory bowel disease (IBD) and other gastrointestinal diseases and conditions, make the initial diagnosis and accurate treatment of this disease challenging. Currently, the most common clinical methods used for diagnosing and monitoring IBD are colonoscopy and biopsy, which are invasive and uncomfortable procedures, and the fecal calprotectin test, which is not sufficiently accurate. Therefore, it is necessary to develop an alternative method. Aims In this study, our aim was to develop a robust predictive model for a noninvasive and accurate test to distinguish active IBD from non-IBD controls. Methods A total of 120 samples were collected, with 78 samples separated for retrospective analysis and model training, while 42 samples were set aside for prospective validation. We employed SWATH mass spectrometry for the identification and quantification of the stool proteome. The obtained data underwent multiple stages, including data preprocessing, feature selection, model training, and performance evaluation. We optimized data processing procedures through advanced bioinformatics, selecting an appropriate pipeline that included data normalization, batch effect correction, and missing value imputation. Subsequently, we assessed various machine learning algorithms to determine the most effective classifier for predicting IBD based on the selected proteins. Results After data preprocessing, we identified 48 differentially abundant proteins (DAPs). To eliminate redundant proteins, we employed Correlation-based Feature Selection (CFS), resulting in selecting 7 proteins. To identify the most suitable predictive model for our dataset, we assessed five popular machine learning methods: Support Vector Machines (SVM), Random Forests, Logistic Regression, k-nearest neighbors (KNN), and Naive Bayes. Among these, SVM exhibited the highest performance. Finally, we evaluated the model's performance by applying the selected algorithm to 42 prospective blind samples. The results revealed a sensitivity of 96% and a specificity of 76%, highlighting its strength and effectiveness. Conclusions In conclusion, this study offers a proof of concept for the application of SWATH for precise IBD diagnosis using stool proteomics and showcases the effectiveness of our data processing and machine learning approach. Additionally, it highlights the potential of this method for classifying Crohn's Disease (CD) vs. Ulcerative Colitis (UC) and distinguishing active IBD from remission. Workflow of study Funding Agencies CIHRCrohn's and Colitis Canada , Studentship from CRMUS,

A72 THE ENDOSCOPIC YIELD OF PRIORITIZED INDICATIONS USING A PROVINCIAL-WIDE COLONOSCOPY REFERRAL FORM

Abstract Background The widespread use of a standardized and validated province-wide colonoscopy referral form (PCRF), regrouping mutually exclusive indications into suggested priority wait time categories, has allowed for a more comprehensive assessment of routine colonoscopy practice Aims To validate the Quebec PCRF by better characterizing endoscopic finding yields according to specific clinical indications. Methods This retrospective cohort study includes consecutive adult patients with available data from the PCRF from two tertiary hospitals. The primary outcome was the diagnostic rates of colorectal cancer (CRC). Secondary outcomes assessed incidences of clinically significant lesions (CSL) on endoscopy and confirmed at pathology. These are CRC, advanced adenomas, sessile serrated polyps, polyps ≥ 5mm, colitis, colonic strictures, and miscellaneous other findings excluding hemorrhoids and diverticulosis. Descriptive and inferential statistics, and multivariable regression predictive modeling are reported. Results Overall, 14,657 patients (mean age 59.2 ± 14.0 years, 50.9% female) were included from September 2018 to August 2022. The most frequent indications for colonoscopy were polyp surveillance (IN13, 20.8%), recent change in bowel habits (IN7, 11.9%), a positive fecal immunochemical test (IN5, 8.3%), a family history of CRC or polyps (first-degree relative) (IN8, 6.4%), and suspected active inflammatory bowel disease (IBD) (IN3, 5.8%). Overall, 40.6% had CSL, including CRCs in 0.8%. CRCs were found more frequently for IN2 (19.7% vs 2.0%, pampersand:003C0.01), IN5 (29.9% vs 8.2%, pampersand:003C0.01), and an unexplained documented iron deficiency anemia (IN6) (11.8% vs 5.2%, pampersand:003C0.01). CSLs were more frequent for IN3 (1.6% vs 5.8%, p=0.04), IN7 (4.7% vs 12.0%, p=0.01), IN8 (0.8% vs 6.5%, p=0.01), IN13 (7.1% vs 20.9%, pampersand:003C0.01), IBD surveillance (IN15, 0.0% vs 4.0%, p=0.02), and surveillance for a significant family history (IN21, 0.0% vs 3.7%, p=0.02). On multivariable analysis, CRC was significantly associated with IN2 OR=31.8 (4.86; 208.7), IN5 OR=19.2 (3.86; 95.7), and IN6 OR=15.7 (2.37; 78.0) - (all are high priority PCRF referrals with a suggested shorter wait time than for most other indications). CSLs were significantly associated with age (OR=1.03 (1.02; 1.03)), IN2 (OR=2.32 (1.35; 3.99)), IN5 (OR=2.37 (1.74; 3.22)), and IN13 (OR= 1.66 (1.36; 2.02)). Conclusions This large cohort study confirms the validity of indications and corresponding prioritization of wait times of a PCRF. Funding Agencies CPAC and MSSS

A71 IMPACT OF THE COVID-19 PANDEMIC ON WAIT TIMES, AND CLINICALLY RELEVANT FINDINGS AT COLONOSCOPY

Abstract Background The widespread use of a standardized and validated province-wide colonoscopy referral form (PCRF), regrouping mutually exclusive indications into suggested priority wait times categories (P1 to P5), has allowed for a more comprehensive description of routine colonoscopy practice. Aims To better understand the impact of COVID-19 on the routine practice of colonoscopy. Methods This is a multicenter retrospective cohort study of consecutive adult patients referred with PCRF data available from two Quebec tertiary hospitals. Patient and procedural characteristics were recorded. The primary outcomes were the diagnostic rates of colorectal cancers (CRC) and clinically significant lesions (CSF), defined as endoscopic findings affecting subsequent patient management, excluding hemorrhoids and diverticulosis. The secondary outcome was procedural wait times. We compared endpoints contrasting colonoscopy findings pre-COVID (before March 15th, 2020) to intra-COVID (after April 15th, 2020). Results 7,476 pre-COVID and 7,181 Intra-COVID patients (mean age 59.2 ± 14.0 years, 50.9% female) were included from 2018 to 2022. There were no clinically relevant between-group differences in patient characteristics. CRC detection remained similar (0.9% pre- vs 0.8% intra-COVID, p=0.69), while CSF were diagnosed more frequently intra-COVID (41,2% vs 39.7%, p=0.02). There were higher rates of indications performed for urgent and semi-elective priorities (P2, P3) intra-COVID (2.9% vs 1.3%, pampersand:003C0.01, and 50.5% vs 47.9%, pampersand:003C0.01). Corresponding intra- vs pre-COVID differences in indications (all Pampersand:003C0.01) included a clinical suspicion of active inflammatory bowel disease (6.4% vs 5.2%), a high index of suspicion for cancer based on imaging, endoscopy or clinical exam (2.9% vs 1.3%), suspicion of occult colorectal cancer (1.4% vs 0.9%), and doing a repeat endoscopy because of a prior inadequate bowel preparation (1.3% vs 0.8%). In contradistinction, more elective colonoscopies had been performed pre-COVID (P4: 15.5% vs 8.6%, pampersand:003C0.01, and P5: 5.2% vs 3.8%, pampersand:003C0.01. COVID Colonoscopy wait times grew significantly longer intra- vs pre-COVID (176.3 ± 252.4 days vs 78.6 ± 110.2 days, pampersand:003C0.01). Conclusions We witnessed significant changes in indications and referral priorities distributions for colonoscopy pre- vs intra-COVID, amidst longer wait times. These practice modifications did not alter CRC diagnostic yields, but resulted in greater proportions of CSF detection Funding Agencies CPAC and MSSS

Efficacy and tolerance of oral versus parenteral cyanocobalamin supplement in hypocobalaminaemic dogs with chronic enteropathy: a controlled randomised open-label trial.

Determine comparative tolerance of daily oral and weekly parenteral cobalamin supplementation, in hypocobalaminaemic dogs with chronic enteropathy. Determine whether oral is as effective as parenteral supplementation at achieving eucobalaminaemia, in hypocobalaminaemic dogs with protein-losing enteropathy, severe hypocobalaminaemia or high canine inflammatory bowel disease activity index at inclusion. Thirty-seven client-owned dogs with hypocobalaminaemia and clinical signs of chronic enteropathy were prospectively enrolled in three UK referral centres. Dogs were randomly allocated to daily oral for 12 weeks or weekly parenteral cobalamin supplementation for 6 weeks and one additional dose 4 weeks later. Serum cobalamin, body condition score, canine inflammatory bowel disease activity index and bodyweight were assessed at inclusion, weeks 7 and 13. Serum methylmalonic acid concentration was evaluated at inclusion and at week 13. Owners completed treatment adherence, palatability, tolerance and satisfaction questionnaires at week 13. Nineteen dogs completed the study. All dogs orally supplemented achieved normal or increased cobalaminaemia at weeks 7 and 13. There was no statistical difference in cobalamin concentration at week 13 in dogs treated with oral or parenteral supplementation, regardless of presence of protein-losing enteropathy, severity of hypocobalaminaemia or canine inflammatory bowel disease activity index at inclusion. Serum methylmalonic acid concentration was not significantly different between oral and parenteral groups, neither were treatment adherence, satisfaction, and tolerance scores at week 13. Oral is as effective and as well-tolerated as parenteral cobalamin supplementation in hypocobalaminaemic dogs with chronic enteropathy and severe clinical or biochemical phenotypes, and should be considered as a suitable treatment option regardless of disease severity.

A268 1 YEAR FOLLOW-UP OF PEDIATRIC ULCERATIVE COLITIS USING INTESTINAL ULTRASOUND

Abstract Background Intestinal ultrasound (IUS) is an emerging tool that offers a non-invasive method for monitoring inflammatory bowel disease in pediatric patients, with increasing popularity worldwide. Assessment of IUS for monitoring pediatric Ulcerative Colitis (UC) has been previously limited to small samples of patients with no long-term follow up. Aims This project aims to utilize intestinal ultrasound assessments obtained at routine time points to determine changes in IUS parameters within 12 months of study enrollment in newly diagnosed children with UC, and their relationship to biochemical markers, clinical assessments, and endoscopic findings. Methods Pediatric patients with suspected ulcerative colitis were prospectively enrolled through the Edmonton Pediatric IBD Clinic. Participants underwent IUS, clinical assessments, bloodwork for biomarkers, and fecal calprotectin (FCP) testing at baseline, 1-, 3-, 6-, and 12-month visits, as well as endoscopy at baseline and 6-12 months. In each IUS assessment, the bowel wall thickness (BWT), presence of hyperemia, abnormal haustrations, and fat wrapping was determined in 4 bowel segments (right, transverse, descending, and sigmoid colon). The Pediatric Ulcerative Colitis Activity Index (PUCAI) scores and Ulcerative Colitis Intestinal Ultrasound Scores (UC-IUS) were calculated at each visit. Results 42 patients (55% male) were included. Median UC-IUS total scores and BWT alone improved in all bowel segments over the study period. For the most affected bowel segment for all patients, median percent reduction of BWT was 39.6%, 34.2%, 33.7%, and 42.5%, at the 1-, 3-, 6-, and 12-month assessment respectively. The biggest decrease in UC-IUS scores and BWT occurred with the initiation of therapy between baseline and 1-month. UC-IUS scores significantly correlated with endoscopy at 12-months, clinical assessments at all time points, and biochemical markers of disease at all time points over the 12-month study period (pampersand:003C0.05). BWT measurement alone also had significant correlation with endoscopy at 12 months; clinical assessment at 1-, 3-, and 6-months; and with biochemical markers at every time point (pampersand:003C0.05). Patients with inflammatory bowel markers (indicated by elevated FCP (ampersand:003E250)) at 12-months were found to have significantly thicker BWT and UC-IUS scores at 3- and 6-months. Conclusions BWT and UC-IUS performed well in pediatric patients with newly-diagnosed UC, with UC-IUS scores and BWT measurements alone correlating significantly with endoscopic, clinical, and biochemical disease activity over the 12-month study period. BWT alone performed similarly to total UC-IUS scores. This data suggests that IUS can offer a non-invasive method to monitor long-term pediatric UC disease severity. Funding Agencies TRIANGLE, WCHRI, Stollery Children's Hospital Foundation.