bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 (&lt;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

Abstract

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

Abstract

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

Abstract

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 &gt;20 points in wPCDAI and clinical remission as PUCAI&lt;10 or wPCDAI&lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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