bluuebunny/crossref_metadata_2025 huggingface dataset:
A62 UNCOVERING MICROBIAL DETERMINANTS OF IBS FLARE-UPS: COHORT-LEVEL VS PATIENT-SPECIFIC APPROACHES
Authors: Mohan V , pinto-sanchez M , Nardelli A , Borojevic R , Magee M , Shanmuganathan M , Kroezen Z , De Palma G , Moayyedi P , Britz Mckibbin P , Collins S , Bercik P
Published: February 2025

Background

Irritable bowel syndrome (IBS) is a complex gastrointestinal disorder with a global prevalence of 3.8% (5.8% in Canada, using Rome IV criteria), with the gut microbiota implicated in its pathophysiology. Despite extensive research in the last decade, the microbial mechanisms underlying symptom flares remain unclear. We showed in the previous analysis of our longitudinal study that the strongest factors responsible for separating IBS flare-ups from asymptomatic periods were stool appearance (Bristol stool scale) and somatization, followed by pain scores. Although there were no significant differences in alpha microbial diversity, beta diversity changes associated to symptom flares occurred in 25% of patients.

Aims

Explore cohort-level versus personalized analyses in identifying microbial and metabolic predictors of flares in IBS patients.

Methods

Twenty-eight IBS patients (IBS-D n=20; IBS-C n=8) and 10 healthy controls (HC) were followed for 25 weeks, with weekly symptom assessment (Birmingham IBS, HAD, STAI questionnaires) and stool sample collected (950 samples), analyzed by 16S rRNA sequencing and metabolomics profiling. Discriminatory taxa and metabolites among groups and within individuals were identified using sparse PLS-DA and mixed-effect models.

Results

The integrated stool microbiome-metabolome analysis revealed 6 taxa and 8 metabolites in IBS-D, and 10 taxa and 18 metabolites in IBS-C cohort, that differed from HC (adjusted p<0.05). However, when comparing asymptomatic and flare-up timepoints within IBS cohorts, these microbial taxa and metabolites lost significance. Variance partitioning from mixed models indicated that individuals accounted for a larger share of the variance than cohort-level differences. Consequently, we performed time-course individual analysis in several patients, which identified about 40 bacterial taxa and 33 metabolites being altered during flare-up timepoints among both IBS-D and IBS-C patients. Furthermore, alterations in specific metabolic pathways were more prominent in individuals than in cohort comparisons.

Conclusions

Our results suggest that personalized analysis is essential for better understanding of symptom dynamics within individual patients. Group-level differences may highlight general alterations in microbiome that make IBS patients more susceptible to the effects of transient taxa and metabolites identified in individual analyses, which might then contribute to symptom flares in that individual. While these microbial and metabolic predictors still require further investigation, they emphasize the complexity of IBS pathophysiology and the need for a hybrid approach to improve biomarker discovery.

Funding Agencies

CIHR
A64 VALIDATION OF THE MODIFIED MULTIPLIER OF SES-CD (MM-SES-CD) TO PREDICT ENDOSCOPIC REMISSION IN CROHN’S DISEASE: A POST HOC ANALYSIS OF THE SEAVUE TRIAL
Authors: Anvari S , Ahuja D , Wong E , Dubai P , Marshall J , Jairath V , Reinisch W , Narula N
Published: February 2025

Background

The modified multiplier of the SES-CD (MM-SES-CD) has been shown to have prognostic value for predicting endoscopic healing (EH) in patients with Crohn’s disease.

Aims

The purpose of this analysis was to validate baseline categories of endoscopic disease severity using the MM-SES-CD and determine their prognostic value for predicting one-year EH.

Methods

Participants in the SEAVUE trial (n = 386) were categorized based on baseline endoscopic disease severity using MM-SES-CD cut-offs into mild (≥22.5 to < 31), moderate (≥ 31 to < 45) and severe (≥45) disease. The primary outcome was achievement of endoscopic healing (EH) based on MM-SES-CD score (< 22.5) at one year. Secondary outcomes included achieving clinical remission based on patient-reported outcomes and normalization of fecal calprotectin in patients with raised baseline levels at one year.

Results

MM-SES-CD < 22.5 at one year was achieved in 62.0% of patients with baseline mild endoscopic disease, 48.6% with moderate disease and 33.8% with severe disease (p <0.001). Similarly, a trend was observed for patient-reported outcome (PRO-2) clinical remission, which was achieved in 78.9% of patients with baseline mild endoscopic disease, 72.9% of those with moderate and 66.2% of those with severe disease (p=0.09). Likelihood of fecal calprotectin (FCP) normalization was significantly associated with baseline endoscopic disease severity (p=0.008).

Conclusions

Baseline MM-SES-CD-based cutoffs for endoscopic disease severity demonstrate prognostic value for achieving one-year EH, PRO2 remission, and FCP normalization. These findings suggest that the MM-SES-CD can be used both to measure baseline endoscopic disease severity and predicts post-maintenance outcomes in patients with CD.

Figure 1: Percentage of patients in MM-SES-CD remission (<22.5) at week 52 stratified by baseline MM-SES-CD categories (Mild ≥ 22.5 to < 31, moderate ≥ 31 to < 45, severe ≥ 45)

Funding Agencies:
A69 UVB SKIN EXPOSURE MODULATES INTESTINAL METABOLISM AND HOST DEFENSE
Authors: Jimenez Sanchez M C , Yang H , Sham H , Dutz J , vallance B
Published: February 2025

Background

Gastrointestinal (GI) diseases are rising in Western societies, alongside environmental changes like reduced exposure to ultraviolet (UV) B light. UVB light affects the skin through vitamin D (vitD) and Aryl hydrocarbon receptor (Ahr) signaling, but its potential influence on distant sites, like the gut, is not well studied, despite GI and skin diseases often co-occurring (O’Neill et al, 2016). Patients not only suffer from GI symptoms but also may experience various mood disorders such as anxiety and depression (Graff et al, 2009). We aimed to explore how UVB skin exposure influences gut health, microbiota and its metabolic by-products, and hypothesize that UVB may also affect the gut-brain axis, influencing mood and cognition.

Aims

Test the (1) effect of UVB light using vitD deficient (-) and sufficient (+) diets on the metabolomic profile and gut microbiome, and (2) the impact of vitD levels and UVB on susceptibility to Citrobacter rodentium infection.

Methods

Female C57BL/6J mice were fed either vitD (+) or (-) diets. They were anaesthetized, and then 8 cm2 of their dorsal skin was shaved and exposed to UVB. Mice were euthanized to collect serum, cecal content, and stool (FI-ToF metabolomics analysis and 16S sequencing). Ingenuity Pathway Analysis (IPA) was used to predict the impact of metabolic changes.

Mice were infected by oral gavage using 2x108 colony-forming units of WT C. rodentium, monitored daily and euthanized on day 10 post-infection. Samples (cecum, colon, and stool) were collected for CFU, histology, immunostaining, and qPCR analysis.

Results

In vitD (-) fed mice, UVB skin exposure raised vitD levels to match those on vitD (+) diets. Untargeted metabolomics detected ~1,630 stool metabolites at baseline, and following one UVB exposure, 266 metabolites changed in the vitD (-) group, 297 in the vitD (+), with 47 overlapping. After 6 exposures, 449 metabolites changed in the vitD (-) group, 138 in the vit D (+), with 61 overlapping. Pathway analysis revealed significant alterations in purine, tryptophan, and alanine-aspartate-glutamate metabolism. IPA determined that changes in these pathways in the vitD (-) group were associated with mood disorders and colorectal tumor inhibition. 16S microbiome analysis showed changes in the Bacteroidota phylum. Finally, vitD (-) group showed increased susceptibility to C. rodentium infection, while UVB light skin exposure reduced intestinal pathology in the vitD (-) group, suggesting a protective role of UVB light against intestinal infection.

Conclusions

The study demonstrates that UVB exposure significantly alters the GI metabolome and microbiome, with a greater impact in vitD (-) mice. These findings highlight the complex interplay between UVB exposure, vitD status, and host metabolism and immunity.

Funding Agencies

NSERC
A78 INTESTINAL AND PANCREATIC HNF4A ACTING TOGETHER TO MANAGE BLOOD GLUCOSE LEVELS
Authors: Rodriguez Rodriguez N , de Castro A , Jones C , Pupo D , Boudreau F
Published: February 2025

NOT PUBLISHED AT AUTHOR’S REQUEST

Please acknowledge all funding agencies listed below

Funding Agencies: Bourses d’excellence de l’Université de Sherbrooke
A79 EAT, SLEEP, WORK, REPEAT! WEARABLES AND APPS TO TRACK IBD PATIENTS’ SYMPTOMS, DIET, SLEEP, AND PHYSICAL ACTIVITY
Authors: Miranda P M , Fernando I , Armstrong D
Published: February 2025

Background

Lifestyle factors like diet, physical activity, and sleep patterns are known to influence symptoms and progression in Inflammatory Bowel Disease (IBD). However, accurately determining temporal relationships between these factors and symptoms has been hampered by a lack of reliable data collection methods. New technologies, such as wearables and smartphone apps, offer real-time, remote monitoring and allow for better understanding of their relationship with IBD symptoms.

Aims

To assess the feasibility of using remote monitoring tools (wearables and mobile apps) to explore the temporal relationships between symptoms, diet, and sleep in IBD patients.

Methods

Adult IBD patients participated in a 3-month pilot study (Track-IBD), during which they wore a fitness monitor (Oura Ring) and tracked their diet and symptoms in real-time using Keenoa (diet tracking) and Zamplo (symptom tracking) smartphone apps.

Results

Fifteen IBD patients (9 - Crohn’s disease, 6 - ulcerative colitis; 8 female; 12 Caucasian; mean age 41.2 years) were enrolled. The usage rates were 69.8% for Zamplo, 77.0% for Keenoa, and 77.0% for the Oura Ring. The most commonly reported symptoms were abdominal pain, diarrhea, and fatigue, which together accounted for 67% of all recorded symptoms. Symptoms were predominantly reported in the afternoon (30.1%) and late-night (49.2%), while morning and early-night periods saw fewer reports (20.7%). Most symptoms occurred within 5 hours of a meal, with peaks in meal-to-symptom latency (MTSL) at 0.5–1 hour and 4–5 hours post-meal, demonstrating an association between meal timing and symptoms. No correlation was found between MTSL and the nature of the symptoms (upper, lower, or extra-intestinal) or macronutrient intake. Wearable data analysis revealed decreased sleep quality and increased average heart rate on symptomatic days (p<0.04). Most participants found the apps easy to use (Oura: 100%, Zamplo: 93%, Keenoa: 73%) and helpful in managing their IBD (Oura: 100%, Zamplo: 87%, Keenoa: 60%).

Conclusions

The Track-IBD study demonstrates high adherence to monitoring diet, symptoms, and physiological measures by IBD patients over 3 months. It also shows the feasibility of combining multiple tracking technologies to assess lifestyle patterns, physiological parameters, and symptoms in real-time. Preliminary analyses identified relationships between symptoms, diet and sleep quality, highlighting the potential to identify lifestyle triggers of disease and symptom flares and provide personalized therapeutic advice to IBD patients.

Funding Agencies

Balsam Foundation
A87 LEVERAGING DIGITAL HEALTH: SYMPTOM TRACKING IN PEDIATRIC IBD USING A SMARTPHONE APP FOR ENHANCED PATIENT-REPORTED OUTCOMES
Authors: L’Heureux-Hubert É , Mah T , Fleur-Aimé M , Louis P , Vaccarino C , Khouna H , Martin R , Kubinski R , Chapuy L , Cuccia L , Deslandres C , Jantchou P
Published: February 2025

Background

Patient-reported outcome measures (PROMs) are essential for managing chronic diseases, as they provide valuable insights into patients’ perspectives on their condition’s impact and help tailor treatments accordingly. However, collecting this information from pediatric patients with inflammatory bowel disease (IBD) presents several challenges, such as the reluctance of patients to discuss sensitive topics such as bowel movements, defecation, and rectal bleeding. Additionally, the subjective nature of physicians’ evaluations compared to the experiences of patients affect the symptom assessment. An IBD app could help teenagers to routinely assess the clinical symptoms.

Aims

The objectives of the study were twofold: first, to describe the trajectory of symptoms as self-reported by patients through a digital application, and second, to compare these symptoms with those evaluated by physicians during medical visits.

Methods

We conducted a prospective study involving teenagers with IBD aged 15-18 years old. All participants had a smartphone and an understanding of English. They received an app (Injoy Gut Health tracking by Phyla Technologies Inc.) that allowed for the collection of symptoms at home, which they were asked to use daily. At inclusion, participants completed the IBD Control questionnaire. Additionally, we collected information on disease status such as the physician global assessment (PGA).

Results

We included 25 children (60% female) with a median age at diagnosis of 14.5 years (interquartile range (IQR): 13.2-14.5) for IBD (64% Crohn’s disease) for a median of 3.6 years (IQR: 2.7-5.4). Most participants (84%) were in complete remission and 16% had mild active disease, according to the PGA. The teenagers completed the app survey for a median of 122 (IQR: 44-200) days.

Participants reported gastrointestinal symptoms during daily data collection: 48% experienced rectal pain, 64% experienced nausea, 96% experienced gas, 76% experienced bloating and 80% experienced abdominal pain. Finally, 28% noted blood in their stools representing a median of 7.8% (IQR 8.88-11.9) of their stools. The PROMs filled at baseline depicted a spectrum of disease activity. The median IBD-control-8 subscore was 12 (IQR: 10-15).

The PROMs and the data self-collected daily at home were not in agreement with the PGA. Indeed, symptom data showed that participants experienced a median of 7 (IQR: 4-8) symptoms while 92% (23) of patients reported more than two symptoms.

Conclusions

These results highlight the importance of incorporating PROMs for more precise and personalized management of IBD in children. The use of an app for at-home daily data collection proved to be a valuable tool in capturing real-time symptomatology.

Funding Agencies:
A88 PATIENT-CENTRIC VALIDATION OF A PROVINCE-WIDE COLONOSCOPY REFERRAL SHEET DETERMINING WAIT-TIME PROCEDURAL ALLOCATION
Authors: Barkun A , Aprikian S , Hansen-Barkun C , Kim D , Milky G , Beauchesne-Blanchet J , Martel M , Menard C , von Renteln D
Published: February 2025

Background

The widespread use of a standardized, validated province-wide colonoscopy referral form (PCRF), regrouping mutually exclusive indications into suggested priority wait time categories has allowed for a more comprehensive, patient-centric assessment of routine colonoscopy practice

Aims

To better characterize colonoscopic finding yields based on specific clinical indications (PCRF) determined by patient symptoms’ questionnaire-generated indications rather than referring physician-based indications. We also attempt further validation of the PCRF.

Methods

Prospective cohort of consecutive adult patients from two hospitals. Information collected from PCRF (therefore referring physician assessment) but also additional symptoms from a patient questionnaire. The primary outcome was the colonoscopy findings. Descriptive and inferential statistics and multivariable regression analyze predictive modeling of different indications and symptoms.

Results

Overall, 5979 patients (mean age 59.2±14.2years, 49.8% female, mean BMI 26.7±5.2) were included from June 2022 to February 2024. Duration between colonoscopy referral and colonoscopy (days) was 266.7 ± 405.9 (median=138 days). Excluding diverticulosis and non-bleeding hemorrhoids, 41.3% of patients had clinically significant lesions and 0.9% adenocarcinomas. The main indication according to patients was surveillance of polyps (IN13 - 35.7%), surveillance for significant family history (IN21 - 21.2%), IBD surveillance (IN15 - 11.7%). Based on additional questions of the patient questionnaire that did not correspond to any indication on the PCRF, 70.0% had no additional symptoms while 13.3% experienced abdominal pains, and 11.1% cramping, with 4.8% reporting weight loss. Between-group comparisons for adenocarcinoma and clinically significant lesions are described in figure 1. Models with the best fit for predicting adenocarcinoma were associated with the combinations of age>40, and presence of IN2, IN5, IN6 and IN17 with OR=7.74 (4.45; 13.46) (or OR=6.46 (2.78; 15.14) for age>60). Clinically significant lesions were associated with the combinations of age>60, IN5, IN17 and IN13 with OR=2.05 (1.83; 2.90).

Conclusions

This exercise has allowed further validation of recently adopted provincial changes in PCRF priorities attributed to some indications. Addition of symptoms not captured in PCRF indications did not improve prediction using existing indications in multivariable modelling. The use of multiple PCRF indication in allocating waiting priorities rather than choosing the sole perceived most urgent one (which is how the PCRF is used) now requires prospective validation.

Funding Agencies

CPAC and MSSS
A95 APPROACH AND OUTCOMES OF PATIENTS WITH NON-VARICEAL UPPER GASTROINTESTINAL BLEEDING: ANALYSIS OF 50 CASES IN A TERTIARY CARE CENTRE
Authors: Labib K A , Zepeda-Gomez S , aldaihani a , Fazal M , Hashmi A
Published: February 2025

Background

Non-variceal upper gastrointestinal bleeding (NVUGIB) is a significant cause of morbidity and mortality worldwide. NVUGIB refers to bleeding occurring above the ligament of Treitz, excluding variceal causes. Despite improvements in management, the incidence and mortality of NVUGIB remain high. Key challenges include determining optimal treatment strategies and predicting patient outcomes.

Aims

To analyze clinical presentation, management strategies, endoscopic findings, treatment and outcomes of NVUGIB patients.

Methods

A retrospective review was conducted at the University of Alberta Hospital on 50 patients diagnosed with NVUGIB who underwent endoscopy within 48 hours of presentation. We analyzed clinical presentation, management strategies, endoscopic findings, treatment and outcomes to assess their impact on patient care.

Results

Of the 50 patients, 54% were male, and melena was the most frequent presenting symptom (56%). Sixty-two percent of patients received intravenous proton pump inhibitors (IV PPI) during initial management, while 42% were on NSAIDs without concurrent PPI therapy. Peptic ulcer disease was the leading cause of bleeding (90%), followed by vascular lesions (6%) and Mallory-Weiss tears (4%). Among ulcers, 66.7% were classified as Forrest III. Nine patients (18%) underwent urgent endoscopy within 6-12 hours, while 30% had early endoscopy (12-24 hours), and 52% had late endoscopy (after 24 hours). High-risk lesions (Forrest Ia, Ib, IIa) were identified in 32% of patients. The early endoscopy group had the highest rate of high-risk lesions (53%), compared to the urgent group (33%) and the late group (19%). Patients with high-risk lesions experienced significantly longer hospital stays, averaging 7.8 days compared to 4.9 days for those without high-risk findings (p < 0.005). Re-bleeding occurred in 16% of patients after initial endoscopy. Six patients received successful repeat endoscopic therapy, while two required embolization for bleeding duodenal ulcers. No further episodes of bleeding occurred in the re-bleeding group, and one patient died within 30 days of presentation, the cause was unrelated to bleeding.

Conclusions

Peptic ulcer disease remains the most common cause of NVUGIB, with NSAID use as a key risk factor. Timely endoscopy and appropriate initial management are critical for optimizing outcomes. High-risk lesions are found in approximately 30% of patients and are associated with longer hospital stays. Physicians should be aware of embolization as a rescue therapy for patients who experience re-bleeding.

Funding Agencies

None
A102 NOVICE ENDOSCOPISTS EXPERIENCE AND PERFORMANCE ON A NOVEL PHYSICAL-COMPUTER COLONOSCOPY SIMULATOR
Authors: Almneni A , Gimpaya N , Tran W , Tham D , Wiggins A , Ibrahim A , Sondawle R , Sinanian G , Lisondra J , Dang F , Samarasena J , Grover S
Published: February 2025

Background

Simulation-based training mitigates safety risks for patients in the early stages of endoscopic training. The MIKOTO colonoscopy simulator is a hybrid physical-computer model that assesses forces applied during simulated procedures via sensor-generated feedback to the user.

Aims

To describe the technical performance and self-reported experience of novice endoscopists when using the MIKOTO.

Methods

24 novices attended a simulation course in Toronto which included activities on benchtop, colon phantoms, and the MIKOTO. Trainees completed MIKOTO’s easiest case in 10 minutes. The primary outcome measure was the self-reported user experience using a 5-point Likert scale. Other outcomes included relevant DOPS items rated by an expert, and a MIKOTO-generated score integrating colon elongation and completion time.

Results

11 Gastroenterology and 13 General Surgery novices (<500 procedures) attended. The median rating for “feels like the low-fidelity (wooden simulator)” was 2 with an IQR of 2 (Table 1). The median rating for “looks like performing colonoscopy on a live patient” was 4 with an IQR of 2. The median score for “Further use of the Mikoto will help improve my overall colonoscopy performance” was 5. The median ratings on relevant DOPS items ranged from 1 to 2. The median MIKOTO score was 27.5 with an interquartile range (IQR) of 5.

Conclusions

The expert-assessed DOPS rating and Mikoto-generated scores indicate the ability of the Mikoto to show the skill level of the novice trainees. Self-reported experiences indicate similarity of visual and haptic realism compared to live procedures. The MIKOTO, however, was distinct from the low-fidelity benchtop simulator. A limitation of this study is the brief time spent on the simulator and the lack of orientation to the MIKOTO. Further studies are needed to compare technical performance and subjective experience between novices, intermediate and expert endoscopists. Different forms of validity must be investigated. The experience of the novice endoscopists provide insight on future integration of the MIKOTO into training programs.

Table 1. Mikoto Experience Form

Demographics and DOPS Ratings

Funding Agencies

None
A121 DEVELOPMENT OF COLON CANCER MODELS TO STUDY THE INTERACTION BETWEEN CANCER STEM CELLS AND THE MICROENVIRONMENT
Authors: Sedeuil M G , Grenier E , Giroux V
Published: February 2025

Background

Colon cancer is the 2nd deadliest cancer worldwide. The main treatment combines surgery with 5-fluorouracil (5-FU) chemotherapy. However, the number of relapses remains frequent due to a loss of sensitivity to treatment, known as chemoresistance. Over the last decades, studies have highlighted the importance of two tumoral components: cancer stem cells (CSC) and the microenvironment. CSC are tumor cells characterized by their enhanced capacity for self-renewal, potency and resistance to anti-cancer treatments. The microenvironment, for its part, comprises all components surrounding the tumor cells including cancer-associated fibroblasts (CAF). While their respective importance in resistance has been studied, it is important to better understand their interactions during resistance and how this could affect their respective functions.

Aims

Identify the specific changes occurring in CSC and the impact of their interaction with CAF during the induction of 5-FU resistance in colon cancer.

Methods

To achieve this goal, we established a model of colon cancer organoids resistant to 5-FU.

Results

First, we validated that the parental organoids maintained their expected cellular heterogeneity. Indeed, the presence of proliferative cells (Ki67+) and CSC (ALDH1+) was confirmed by immunofluorescence. We also confirmed that they are sensitive to 5-FU by assessing cell survival using a WST1 assay. With a baseline IC50 of 7µM, we concluded that they can be used to generate a 5-FU resistant line. To induce 5-FU resistance, we performed cyclic treatments to mimic clinical reality using a 5-FU dose 4-5 times greater than the baseline IC50. Resistance is currently being validated by WST1 assay to compare IC50. Second, our initial findings indicate that the conditioned media of CAF cultures reduce the sensitivity of parental organoids to 5-FU, highlighting the necessity for further exploring the interaction between these two tumor components.

Conclusions

In summary, our preliminary results suggest that the interaction between tumor cells and CAF influences the sensitivity to chemotherapy. We are currently investigating the interaction between CAF and CSC with secretome and surfaceome analysis. Additionally, we are investigating the phenotypic and transcriptomic changes occurring specifically in CSC isolated from resistant organoids. Ultimately, the aim of this project is to enhance our understanding of the changes required for resistance, paving the way for new targeted therapies.

Funding Agencies

Canada foundation for innovation, Canada Research Chairs
A127 PEMBROLIZUMAB-ASSOCIATED IMMUNE CHECKPOINT INHIBITOR GASTRITIS AND DUODENITIS: A CASE REPORT
Authors: Zhen J , Canning S , Rushton M
Published: February 2025

Background

Advancements in immunotherapy have revolutionized the treatment of cancer. However, innate to their mechanism of action, these therapies are associated with various immune-related adverse effects which present challenges to their use. While immune checkpoint inhibitor-associated colitis is the most common gastrointestinal toxicity, upper gastrointestinal involvement, such as esophagitis, gastritis, and duodenitis remains considerably rare.

Aims

The aim of this case report is to describe a severe case of immune checkpoint inhibitor-associated gastritis/duodenitis and highlight some of the challenges linked with its diagnosis and management.

Methods

We performed a retrospective chart review of the described patient and conducted a review of the relevant literature.

Results

A 65-year-old female was diagnosed with triple-negative, invasive ductal carcinoma and had been undergoing adjuvant treatment with pembrolizumab. Ten months after initiating therapy, she presented with epigastric pain, nausea/vomiting, and poor appetite. She subsequently underwent an esophagogastroduodenoscopy (EGD) which revealed a firm and friable stomach with thickened mucosa and significant edema of the duodenal cap. An initial review of the biopsies taken during upper endoscopy demonstrated non-specific gastric and duodenal inflammation without a definitive diagnosis. However, a subsequent review at consensus rounds suggested severe immune checkpoint inhibitor-associated gastritis/duodenitis and she was started on corticosteroid therapy. While her symptoms were refractory to high-dose intravenous methylprednisolone, she showed marked improvement after two infusions of infliximab (5mg/kg and 10mg/kg, respectively).

Conclusions

This case highlights the importance of increasing awareness of immune checkpoint inhibitor-associated gastritis and duodenitis, involving a multidisciplinary team to help facilitate its diagnosis, and emphasizes the role of repeated doses of biologic therapy in steroid-refractory cases.

Figure 1. Endoscopic findings of immune checkpoint inhibitor-associated gastritis (1) Diffuse edema and friability in the gastric fundus. (2) Diffusely edematous gastric body with loss of the typical gastric folds. (3) Mild edema along the gastric antrum. (4) Normal appearing duodenal mucosa in the second portion of the duodenum.

Funding Agencies

None
A158 APPLYING MACHINE LEARNING FOR PREDICTING TREATMENT RESPONSE TO VEDOLIZUMAB IN PEDIATRIC IBD BY SERUM METABOLOMICS
Authors: Suarez Suarez R G , Bar Or O , Focht G , Shavit Z , Orlanski-Meyer E , Broide E , Urlep D , Hyams J , Levine J , Rosh J , Turner D , Wine E
Published: February 2025

Background

Vedolizumab (VDZ) is effective to induce remission in children with Crohn disease (CD) and ulcerative colitis (UC), but effectiveness varies.

Metabolites produced by interactions between intestinal microbiota and host metabolic processes can be useful to identify metabolome signatures that may preferentially favor response to a specific therapeutic class. Therefore, metabolomic studies can potentially inform precision medicine in Inflammatory Bowel Diseases (IBD).

Aims

This study aimed to apply machine learning to assess metabolites as potential predictors for forecasting the response to VDZ treatment.

Methods

VedoKids is a multicenter, prospective, observational cohort study, designed to report the effectiveness and safety of VDZ. Children aged 0-18 years, diagnosed with IBD, who initiated VDZ treatment at any stage of their condition, were subjected to comprehensive assessments at the onset and subsequently at 2, 6, 14, 30, 54 weeks and thereafter. Detailed demographic, clinical, and safety information was meticulously recorded in a prospective manner throughout the study period. Metabolomic profiling was conducted in serum at three time points: baseline, 14 weeks, and 30 weeks. Metabolites were identified using a quantitative metabolomics approach utilizing DI/LC-MS/MS technology for the analysis of serum samples.

We constructed a learning algorithm to predict treatment response to identify the most relevant serum metabolites subset. The algorithm consisted of a Random Fores (RF) model and maximum relevance minimum redundancy (mRMR) feature selection. Response was defined as decrease of ≥20 points in PUCAI or >20 points in wPCDAI and clinical remission as PUCAI<10 or wPCDAI<12.5.

Results

We were able to train different RF models using clinical, pre-treatment, and serum metabolite data. Results for the experiment performed with CD patients at week 14 shows an AUC = 0.95 with N-Acetyl-Aspartic acid, Fumaric acid, and Glutamine scoring among the features with highest predictive importance. Results for the experiment performed with UC patients at week 30 shows an AUC = 0.81 with Isoleucine, Malic acid, and N-Acetyl-Glutamic acid scoring among the features with highest predictive importance.

Conclusions

Our results suggest that it is possible to produce predictor capable of predicting response to VDZ treatment using clinical and metabolome data in children with IBD. Importantly, some of the identified metabolites have been previously associated with IBD pathophysiology.

Funding Agencies

CIHR
A167 DIETARY BRANCHED-CHAIN AMINO ACIDS MEDIATE THE IMPACT OF HIGH PROTEIN DIET ON COLITIS SEVERITY THROUGH MTOR ACTIVATION
Authors: Kan K , Rondeau L E , Muppidi P , Barbosa da Luz B , Dang R , Caminero A
Published: February 2025

Background

Dysregulated inflammation in inflammatory bowel disease (IBD) can be triggered by environmental exposures such as dietary and microbial factors. The prevalence of IBD continues to increase in Western countries, where individuals consume the western diet, characterized by high dietary intake of animal protein, fat, and sugar. Our lab has recently found that diets high in protein and animal protein promote intestinal inflammation and exacerbate colitis severity through mechanistic target of rapamycin (mTOR) activation and autophagy impairment. The mTOR pathway crucially regulates cellular growth and development through the recycling of essential components mediated by autophagy. Branched-chain amino acids (BCAAs) are potent activators of the mTOR pathway and are abundant in high protein diets and animal protein. Thus, we hypothesize that the BCAA content of these diets may contribute to the previously observed mTOR hyperactivation, autophagy inhibition, and worsened colitis severity associated with excess protein and animal protein intake.

Aims

To determine the impact of dietary BCAA-enrichment on colitis severity, mTOR activation, and autophagy.

Methods

Specific pathogen free C57BL/6 mice were fed a control diet (CD) (n=6/diet) or a BCAA-enriched diet (BCAA) (n=6/diet) for four weeks prior to tissue collection or three weeks prior to colitis induction. Colitis was induced through the administration of 2% w/v dextran sulfate sodium (DSS) in drinking water for 5 days, followed by 2 days of water before tissue collection. Disease activity was monitored for changes in body weight, stool consistency, and rectal bleeding, and microscopic damage scores were evaluated through histology. Colon tissues were analyzed by western blotting against mTOR proteins (p-mTOR, mTOR) and autophagy proteins (LC3-I, LC3-II). Immunohistochemistry was used to analyze colon tissue for mTOR activation levels (p-S6).

Results

BCAA consumption increased levels of p-mTOR and p-S6 within colon tissue compared to the CD in groups with and without colitis. Levels of LC3-I and LC3-II decreased in groups fed the BCAA diet compared to the CD with and without colitis induction. Following colitis induction, mice fed the BCAA diet experienced increased weight loss, stool consistency, and rectal bleeding compared to mice fed the CD. BCAA consumption also elevated microscopic tissue damage compared to CD consumption.

Conclusions

These findings demonstrate that BCAAs, which are enriched in high protein and animal protein diets, increase intestinal inflammation and worsen colitis severity in mice, paralleled by increased mTOR activation and impaired autophagy.

Funding Agencies

CCC, CIHRCFI
A170 DISTRIBUTION OF PHARMACOGENETIC VARIANTS IN PEOPLE SUFFERING FROM ULCERATIVE COLITIS TREATED WITH TARGETED MOLECULAR THERAPIES IN QUEBEC
Authors: Tessier L , Fortin E , Michaud-Herbst A , Tremblay K
Published: February 2025

Background

Ulcerative colitis (UC) is a chronic inflammatory bowel disease characterized by continuous colonic inflammation. In Canada, ~160,000 people suffer from its symptoms, such as diarrhea, blood in the stool and abdominal pain, which can highly impact their quality of life. For moderate to severe forms of the disease, molecular targeted therapies (MTT) are used to control symptoms and achieve remission. There is a large variability in treatment response to MTT. Indeed, ~20-50% MTT users don’t improve following drug initiation and 50-90% suffer from adverse events. Multiple factors, such as age, sex, tobacco use and pharmacogenetic (PGx) variants, may influence response. However, genetic variants may also impact UC development which may become a confounding factor in treatment response studies.

Aims

Therefore, the aim of this study is to validate PGx variants associated with nonresponse by comparing their distribution in UC patients with a populational cohort.

Methods

A cohort of 101 people using MTT in UC in Saguenay–Lac-St-Jean was recruited and compared to the populational cohort of CARTaGENE (representing Quebec population, n = 1879). The patients were genotyped for eight PGx variants, distributed across four genes (TNF, TNFAIP3, TNFRSF1A et TNFRSF1B), which were selected as candidates for their previous association with MTT response phenotypes.

Results

The variant TNFRSF1B-rs1061622, previously associated with nonresponse to infliximab (a type of MTT) in a previous study by our team, was comparable between the recruited and populational cohorts. The alternative allele of variant TNFRSF1B-rs3397 was more frequent in the recruited cohort compared to the populational cohort (80,0 vs 67,0 %, p = 0.0001). No other tested variants were differently distributed.

Conclusions

Next steps are to compare these PGx variants with a populational cohort of healthy individuals (exclude individuals suffering from UC in CARTaGENE cohort) to eliminate as many confounding factors as possible. The variant TNFRSF1B-rs1061622 would then be validated and become a great lead to better comprehend treatment response to infliximab in UC. The variant TNFRSF1B-rs3397 needs to be studied more to clarify its potential link to UC development.

Funding Agencies

CCCFRQS, IRSC, Fondation de ma vie
A191 REAL WORLD USE OF ADALIMUMAB BIOSIMILAR AMGEVITA® (ABP-501) IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE IN CANADA
Authors: Chohan M , Wani R J , Copeman J , Martinez D , Lukanova R , Dawod F , Mooney O
Published: February 2025

Background

ABP-501 (AMGEVITA®), biosimilar to adalimumab reference product (RP), was approved by Health Canada in 2021 for use in different immune diseases, including inflammatory bowel disease (IBD), comprising Crohn’s disease (CD) and ulcerative colitis (UC).

Aims

To assess the real-world use, effectiveness and satisfaction of ABP-501 in adalimumab naïve and switch patients with IBD across Canada.

Methods

Data were drawn from the Adelphi IBD Disease Specific ProgrammeTM, a cross-sectional survey with retrospective data collection from physicians conducted in Canada between July 2023 and June 2024. Gastroenterologists (GIs) provided data on their patients with IBD including demographics, clinical characteristics, and treatment satisfaction. Analyses were descriptive.

Results

Overall, 10 GIs reported data on 101 patients (60 CD and 41 UC): 80 initiated ABP-501 as first adalimumab therapy (initiators) and 21 switched directly to ABP-501 from RP (switchers) (Table 1).

Mean [standard deviation; SD] time receiving ABP-501 at consultation was 13.2 [11.6] and 21.6 [9.9] months for initiators and switchers, respectively. Switchers received RP for 48 [27.1] months before switching to ABP-501. Most patients were receiving adalimumab as their first advanced therapy (70% initiators, 90% switchers). The main reasons for switching from RP to ABP-501 were cost effectiveness for the healthcare system (57%) and insurance coverage (43%).

At consultation, most initiators and switchers had mild disease (92%, 95%, respectively), were in clinical (91%; 95%, respectively) and endoscopic (66%; 81% respectively) remission (Figure 1) and had an improving/stable disease (97%; 100%, respectively). Treatment targets for initiators and switchers included maintaining clinical remission (n=54; n=18, achieved by 100%, respectively) and maintaining endoscopic remission (n=37; n=17, achieved by 86% and 100%, respectively). GIs were satisfied with ABP-501 treatment (99% initiators, 100% switchers).

Conclusions

Most patients with IBD treated with ABP-501 as initiating or continuing adalimumab therapy in a real-world setting had mild disease, were in remission and had an improving/stable disease. Patients who switched from RP to ABP-501 switched mainly for economic reasons. GIs reported high levels of satisfaction.

Table 1. Demographics and clinical characteristics of patients with IBD receiving ABP-501 at consultation

Funding Agencies

None
A199 MODELS OF OUTPATIENT INFLAMMATORY BOWEL DISEASE CARE DELIVERY: A SCOPING REVIEW
Authors: Kuenzig E , Rohatinsky N , Sheekha T A , Im J , Huestis M , Seow C , Kaplan G G , Nguyen G , Benchimol E
Published: February 2025

Background

The rapidly increasing prevalence of inflammatory bowel disease (IBD) in Canada, combined with an aging population at higher risk of age-related comorbidities, will place a significant strain on gastroenterology clinics and the broader healthcare system. Changes in care delivery are necessary to meet the growing demand for health services among people living with IBD.

Aims

To understand the extent and type of evidence focused on models of outpatient care delivery for disease management in individuals with IBD.

Methods

A scoping review was conducted by searching MEDLINE, EMBASE, CINAHL, and PsycINFO (from inception to March 4, 2024) to identify studies describing or evaluating models of care for managing people with IBD in outpatient settings. We included English language published studies of any type (primary studies, reviews, and opinion pieces) focusing on any age group, specific aspects of care (e.g., preconception, transition from pediatric to adult care), or setting (e.g., remote care or monitoring). Studies were screened for eligibility in duplicate, and conflicts were resolved by consensus. Heat maps were created to synthesize the evidence and summarize the literature recommendations.

Results

Our search yielded 13,146 records, of which 209 met our inclusion criteria. These included 88 quantitative studies, 11 qualitative studies, 18 mixed methods studies, and 21 systematic or scoping reviews; the remaining studies consisted of clinical practice guidelines, narrative reviews, or perspectives. The models of care evaluated, along with their outcomes, are summarized in Figure A. Many interventions resulted in high levels of patient and clinician satisfaction, as well as reduced healthcare utilization and costs (direct, indirect, and out-of-pocket). However, data on other outcomes were mixed, with many studies being underpowered to detect significant improvements in patient outcomes. Gastroenterologists, nurses, mental health professionals (e.g., social workers, psychologists, psychiatrists), and dietitians were consistently identified as key members of multidisciplinary teams (Figure B).

Conclusions

Several innovative outpatient models of IBD care have been proposed. The recommendations from these studies can guide adaptations in the Canadian healthcare system, addressing the growing healthcare needs of the increasing number of people living with IBD.

Heat maps describing (A) the evaluated models of outpatient inflammatory bowel disease care and their outcomes and (B) the recommended core and auxiliary members of multidisciplinary teams included in the described and evaluated models of care

Funding Agencies

None
A204 THE EARLY POST-DISCHARGE PERIOD IS A VULNERABLE PERIOD FOR VENOUS THROMBOEMBOLISM IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE.
Authors: Seeraj A A , McCurdy J , Siegal D , Kuenzig E , Ghasemi R , Tennakoon G
Published: February 2025

Background

Patients with inflammatory bowel disease (IBD) have an increased risk of venous thromboembolism (VTE). The temporal relationship between VTE and hospitalization is poorly understood.

Aims

To determine the proportion of VTE events that are associated with hospitalization in patients with IBD.

Methods

We performed a retrospective cohort study of individuals with Crohn’s disease or Ulcerative Colitis (UC) who developed a VTE between January 1, 2009 and December 31, 2024 at a Canadian academic institution, the Ottawa Hospital. Patients with IBD and VTE events were identified by ICD-10 codes and confirmed with chart review. VTE events were categorized as ambulatory or hospital-associated (within the hospital admission or 90 days of discharge). To account for diagnostic delay at the time of hospitalization, VTE events within 48 hours of admission were categorized as ambulatory events. We determined demographics, comorbidities, medication exposure, anticoagulation and IBD disease activity at the time of VTE diagnosis. Differences between cohorts was determined using Chi-squared or Fisher’s exact test where appropriate.

Results

We identified 275 IBD patients with a VTE event: mean age (SD) was 55 (15.8),132 (48%) female,168 (62%) CD and 103 (38%) UC. The types of VTE included: 49% pulmonary embolism (PE) ± deep vein thrombosis (DVT), 24% DVT alone, 13% portal vein thrombosis and 14 % other VTE (splenic vein, hepatic vein, superior mesenteric vein, cerebral venous sinus). A total of 150 (55%) VTE events were categorized as hospital associated (33 patients (22%) during hospitalization and 117 patients (78%) within 90 days after hospital discharge). 30% of patients in the ambulatory category and 71% of patients in the hospital-associated category (94% during hospitalization and 30% after hospital discharge) were receiving anticoagulation (prophylaxis or therapeutic) prior to the VTE diagnosis. Patients in the hospital-associated category were significantly more likely to have a current malignancy (p=0.01), a severe flare of UC (p=0.008) and receive corticosteroids (p=0.002). There were no differences between cohorts in age, sex, comorbidities, smoking status and anti-TNF exposure.

Conclusions

Our study demonstrates that a large percentage of VTE events in patients with IBD are hospital-associated with the majority occurring early after hospital discharge. Importantly, only a minority of patients received VTE prophylaxis during this period, suggesting the post-discharge period is a vulnerable time for patients with IBD.

Funding Agencies

None
A212 ROLE OF UPADACITINIB AND IUS IN PEDIATRIC PATIENTS WITH REFRACTORY ACUTE SEVERE COLITIS: SINGLE-CENTER CASE SERIES
Authors: Alrwili R , Prowse K , Zachos M , Sharma R
Published: February 2025

Background

Inflammatory Bowel Disease (IBD) refractory to first-line agents is challenging in pediatrics due to limited therapeutic options, especially in Acute Severe Colitis (ASC). Upadacitinib (UPA) is a selective Janus-Kinase (JAK) inhibitor approved for use in adults. Its use in pediatrics for refractory moderate to severe colitis is off label, but its oral route of administration and quick onset of action make it a promising therapy. Intestinal Ultrasound (IUS) in this context may be a useful tool for monitoring treatment response.

Aims

To describe the efficacy of UPA as a second-line agent for pediatric ASC and report IUS findings to demonstrate its use in monitoring IBD.

Methods

Single-center chart and literature review of pediatric patients with IBD on UPA.

Results

Case 1: A 12-year-old female with pancolonic Ulcerative Colitis (UC) since age 9 maintained on Infliximab (IFX). Despite adequate IFX levels, re-induction and steroids, she had a Pediatric Ulcerative Colitis Activity Index (PUCAI) of 50, elevated C-Reactive Protein (CRP) and fecal calprotectin (FC) leading to repeat admissions. Intravenous (IV) steroids, followed by UPA 45mg for 8 weeks, led to rapid clinical response by Day 4. At discharge, PUCAI was 5 and CRP <5. On Day 20 of UPA, IUS showed normal bowel wall thickness (BWT) and Modified Limberg (ML) score of 0. At 6 months, she remains in steroid-free remission with a normal FC.

Case 2: A 16-year-old female presented with a Pediatric Crohn’s Disease Activity Index (PCDAI) of 45 and was diagnosed with Crohn’s colitis with perianal fistula. Due to inadequate response to 6 days of IV steroids, she received IFX. Despite robust IFX levels, IUS showed pancolonic inflammation with increased BWT of 4.6 mm and ML score of 1-2. [1] She was readmitted with severe anemia and elevated CRP. Concurrent C. jejuni infection was treated without symptom resolution. Given severe colitis despite IFX and steroids, UPA 45mg for 12 weeks was started with clinical response and discharge by Day 4; PCDAI of 20. At 1 month, she remains asymptomatic on a steroid taper with a normal hemoglobin. Repeat IUS and FC is pending.

Case 3: A 15-year-old male with IBD favouring UC since age 14, who initially did well on steroids and IFX was re-admitted with a PUCAI of 65 and elevated FC while weaning steroids. Repeat endoscopy showed Mayo 2 colitis to hepatic flexure correlating to increased BWT of 3.5 mm and ML score of 2 on IUS. Despite appropriate IFX levels, due to steroid dependence at discharge (PUCAI 25), UPA 45mg for 8 weeks was started as an outpatient. By Day 21 his PUCAI was 0, with normal FC. At 2 months, IUS showed normal BWT and ML Score 0 with steroid-free remission.

Conclusions

These cases demonstrate the efficacy of UPA in refractory pediatric ASC with rapid clinical response, normalization of biochemical tests and IUS findings.

Funding Agencies

None