bluuebunny/crossref_metadata_2025 huggingface dataset:
A51 DEFINING THE ROLE OF THE SPDEF TRANSCRIPTION FACTOR IN INTESTINAL INFLAMMATION
Authors: Jamal A , Wang H , Grondin J , Seto T , Kamal A , Khan W I
Published: February 2025

Background

The intestinal mucus layer prevents commensal microbes and luminal pathogens from interacting with and invading into the underlying epithelium. Goblet cells are predominantly responsible for maintaining this mucus layer through the production and secretion of mucins. Alterations in goblet cell responses are observed in various gastrointestinal disorders including inflammatory bowel disease (IBD). The differentiation and maturation of goblet cells is controlled by several genes. Recently it was shown that the SAM pointed domain ETS factor (SPDEF), an ETS family transcription factor plays a key role in terminal differentiation and maturation of goblet cells. The role of SPDEF in goblet cell responses in intestinal inflammation remains to be determined. Understanding its role in regulating goblet cell responses and mucins production will provide new insight into the mechanisms of dysregulated mucus barrier in intestinal inflammation.

Aims

This study aimed to investigate the severity of a commonly employed chemical model of colitis, dextran sodium sulphate (DSS), in SPDEF knockout (KO) mice compared to wild-type (WT) littermate controls. It was hypothesized that the SPDEF KO mice will exhibit a heightened severity of DSS-induced colitis than the WT mice.

Methods

SPDEF KO and WT mice were treated with DSS in the drinking water for seven consecutive days then euthanized. Disease activity index (DAI), comprising of body weight, stool consistency, and fecal bleeding was assessed over the course of DSS administration. The severity of intestinal inflammation was further assessed by checking macroscopic scores, histological damage scores, myeloperoxidase (MPO) assay, and various pro-inflammatory cytokines in the colonic tissues by ELISA.

Results

SPDEF KO mice exhibited a heightened sensitivity to DSS-induced colitis compared to WT controls. The SPDEF KO mice show a much more dramatic decline in body weight and a substantial increase in DAI, most prominently during the later stages of DSS administration. Additionally, SPDEF KO mice exhibited a greater degree of colonic, fecal, and rectal bleeding than the WT mice, reflected by a higher macroscopic score. Levels of MPO and certain pro-inflammatory cytokines were significantly elevated in the colon tissues of SPDEF KO as compared to WT mice. Histologically, SPDEF KO also displayed decreased goblet cell counts compared to WT mice.

Conclusions

These findings suggest that disruption of the SPDEF transcription factor aggravates DSS-colitis. Defining the role of SPDEF in intestinal inflammation provides a deeper understanding of the mechanism of dysregulated mucus barrier in colitis which may ultimately lead to identifying potential new targets to restore barrier integrity in colitis.

Funding Agencies

NRC
A54 INFLAMMATORY BOWEL DISEASE IN INDIGENOUS POPULATIONS: A SCOPING REVIEW
Authors: Munir O , Condray C , Souza Lira A P , Fowler S , Brass C , Butterworth H , Hourston A , Porter L , Porter R , Sanderson R , Peña-Sánchez J
Published: February 2025

Background

Globally, Inflammatory Bowel Disease (IBD) rates have surged; however, Indigenous/Native/Aboriginal populations (i.e., the original inhabitants of a geographical region) are underrepresented in research and often face unique challenges in accessing healthcare due to socioeconomic barriers stemming from historic inequities.

Aims

This scoping review aimed to synthesize available literature on IBD in Indigenous populations globally, identify research gaps, and propose recommendations to improve research inclusivity.

Methods

A literature search was conducted across eight online databases: MEDLINE, EMBASE, CINAHL, SCOPUS, Web of Science, i-portal, Native Health Database, and ASTIS. We included qualitative, quantitative, and mixed-method research in this review, as well as commentaries, editorials, and abstracts published between 1960 and 2023. Eligibility criteria included publications in English focused on IBD Indigenous populations. Two reviewers independently screened titles and abstracts. The included publications were summarized and appraised using the Joanna Briggs Institute critical appraisal tools.

Results

Eighteen publications were included in the review, with most originating from Canada (n=7), New Zealand (n=5), and Australia (n=4). There was one study from Chile and another from the United States. Results showed a lower prevalence of IBD in Indigenous populations compared to the general population, but some recent studies reported an increasing prevalence of IBD among Indigenous populations from different countries. These changes are hypothesized to result from urbanization, changes in diet, sanitation, or other environmental changes. Also, a study from Canada showed that Indigenous peoples face inequities in accessing IBD care. Apart from 3 papers from Canada, 15 of the 18 publications had no evidence of working with Indigenous community members during the research process.

Conclusions

This scoping review highlights gaps in the literature about IBD in Indigenous populations. While the prevalence of IBD among Indigenous peoples is low, evidence demonstrates that rates are rising. Further research is required to continue studying the rising rates of IBD in Indigenous populations, alongside the genetic and environmental factors contributing to these trends. A focus on patient-centered research should also be emphasized. Indigenous peoples must be included as research partners and Indigenous research protocols must be followed to address health inequities and improve the health and well-being of Indigenous peoples living with IBD.

Funding Agencies

None
A56 THE ROLE OF THE STERILE ALPHA MOTIF (SAM) POINTED DOMAIN ETS FAMILY TRANSCRIPTION FACTOR (SPDEF) ON GOBLET CELL BIOLOGY AND INTESTINAL MUCUS PRODUCTION IN THE CONTEXT OF PARASITIC HOST DEFENSE.
Authors: Seto T , Haider Z , Grondin J , Wang H , Haq S , Banskota S , Khan W I
Published: February 2025

Background

The intestinal mucus layer in the gastrointestinal (GI) tract acts as a physical protective barrier against luminal contents and potential invaders. Goblet cells, a specialized subset of intestinal epithelial cells, play a large role in synthesizing and secreting mucins, which are the structural building blocks of the intestinal mucus layer. The terminal differentiation and maturation of these goblet cells are regulated by sterile alpha motif (SAM) pointed domain ETS family transcription factor (SPDEF). Goblet cell biology and the intestinal mucus barrier is one of the most effective host response mechanisms against enteric parasitic infections, including Trichuris muris. However, no study has evaluated the relationship between SPDEF, goblet cell biology, and mucus production in the context of parasitic host defense.

Aims

To identify the relationship between SPDEF, goblet cell biology, and mucus production during T. muris infection and how this contributes to parasitic host defence.

Methods

For infection experiments, BALB/c mice were gavaged with ~300 T. muris eggs in 200 µl autoclaved distilled water. To explore the role of SPDEF in goblet cell and mucin responses during T. muris infection, SPDEF-/- and SPDEF+/+ mice were administered ~300 T. muris eggs and were sacrificed at days 14 and 21 post-infection (p.i) along with uninfected controls. Periodic Acid Schiff (PAS) staining was used to quantify goblet cells and immunofluorescence was used to identify Muc2+ and SPDEF+ cells. Enzyme-linked immunosorbent assays were used to evaluate Th2 cytokines, and qPCR was used to evaluate Muc2 and SPDEF expression.

Results

BALB/c mice infected with T. muris displayed increased SPDEF expression. On days 14 and 21 p.i., SPDEF-/- mice harboured significantly more worms than their SPDEF+/+ counterparts. These mice also displayed diminished levels of IL-4 and IL-13 at day 14 p.i. as well as decreased PAS+ and MUC2+ goblet cell numbers. Compared to SPDEF+/+ mice, on day 21 p.i., IL-4 was increased in infected SPDEF-/- mice, whereas levels of PAS+ and MUC2+ goblet cells retained a similar pattern to that of day 14 p.i. Interestingly, the number of PAS+ goblet cells, MUC2+ cells and Muc2 expression significantly increased after infection in SPDEF+/+ mice at day 14 and day 21 p.i.

Conclusions

Together, these results suggest that SPDEF is an important regulator of goblet cell function and mucus production during T. muris infection, ultimately contributing to parasitic host defense.

Funding Agencies:
A58 LOW TTG-IGA ASSOCIATED WITH ISOLATED BULB PATHOLOGY IN PEDIATRIC CELIAC DISEASE: IMPLICATIONS IN A NO-BIOPSY APPROACH ERA
Authors: Wang Q , Jantchou P , Dirks M , Lavoie S , Oligny L , Dal Soglio D , Patey N
Published: February 2025

NOT PUBLISHED AT AUTHOR’S REQUEST

Funding Agencies: None
A60 ANXIETY AND DEPRESSION ARE ASSOCIATED WITH POOR ADHERENCE TO THE GLUTEN-FREE DIET, GREATER SYMPTOMS SEVERITY, AND REDUCED QUALITY OF LIFE IN TREATED CELIAC DISEASE PATIENTS
Authors: Echagüe F J , Verma A K , Leong R , Aman A , Blom J , Noejovich V , Daca R , Armstrong D , Pinto-Sanchez M
Published: February 2025

Background

Studies have reported an association between celiac disease (CeD) and anxiety and depression. However, how this impacts symptoms and disease management is unknown.

Aims

To assess 1) the prevalence of anxiety and depression in adult patients with celiac disease and 2) the association of anxiety and depression with CeD outcomes including symptoms, disease activity, treatment adherence and quality of life.

Methods

Consecutive patients attending the adult Celiac Disease Clinic at a tertiary care hospital were enrolled in the Celiac Registry. Participants completed the gluten-free diet (GFD) adherence (CDAT), Quality of Life (CD-QoL), Celiac Symptom (CSI), and Anxiety and Depression Scale (HADS) questionnaires. Anxiety or depression were defined based on a HADS score ≥ 7 for each subscale. CDAT <13 was considered good adherence to the GFD. CSI score ≤30 was considered a low CeD-symptom burden. Continuous variables were expressed as median (IQR) and categorical variables as percentages.

Results

From October 2020 to October 2024, 673 CeD patients, [38 (31) years] were enrolled in the study. Of these, 251 (37%) met the criteria for anxiety and 109 (16%) for depression. Anxiety and depression were associated with lower adherence to a gluten-free diet (anxiety OR=0.7, p<0.001; depression OR=0.5, p<0.001), reduced QoL (anxiety OR=1.07, p<0.001; depression OR=1.03, p<0.001) and increased celiac-related symptoms (anxiety OR=0.56, p<0.001; depression OR=0.2, p<0.001). A non-significant trend of increasing weight was observed in CeD patients with anxiety and depression. Regression analysis showed QoL, diet adherence, and weight changes were predictors for an increased risk of anxiety and depression in CeD patients.

Conclusions

Anxiety and depression are common in CeD patients, and they are associated with poor adherence to a GFD, symptom control, and worse quality of life. Addressing mental health in CeD is crucial for the management of celiac disease and has the potential to improve celiac outcomes.

Funding Agencies:
A68 CROSSING PATHS: THE OVERLAP BETWEEN INTESTINAL TB AND CROHN’S DISEASE, A CASE REPORT
Authors: Denier D , O’Donnell J , Griffiths A , Walters T
Published: February 2025

Background

We report the case of a 17-year-old female, who initially presented with a 3-week history of abdominal pain to a hospital in India, an area endemic for tuberculosis (TB). An abdominal CT scan and endoscopy showed circumferential narrowing involving the cecum and terminal ileum (TI). A tuberculin skin test was positive, while PCR from biopsies was negative. The differential diagnosis was Intestinal TB versus Ileocecal Crohn’s disease (CD). Empirical TB treatment was started, resulting in rapid symptom improvement. She presented to our hospital after immigration with increasing abdominal pain, vomiting and findings of a short, narrowed segment of TI on ultrasound. The patient developed two subsequent episodes of complete bowel obstruction, prompting urgent IC resection. At operation there was a stricture at the level of the cecum, the TI was noted to be thickened with proximal dilatation. Pathology showed inconclusive results with acute and chronic inflammation, possibly inflammatory bowel disease (IBD) or infectious etiology. Repeat quantiferon test was positive with high titre.

Aims

Abdominal TB can uncommonly cause intestinal stricturing during the active phase of disease. The potential for a very similar presentation to CD makes differentiation challenging. In this case report we discuss the background and potential approaches to stricturing intestinal disease in patients from a TB endemic area and the implications for post-operative management.

Methods

Case report with literature review

Results

Gastrointestinal TB can occur as a primary infection or in the context of active pulmonary disease. TB PCR is highly specific but with low sensitivity and Quantiferon Test may be negative in patients with extra pulmonary manifestations. Differentiating between intestinal TB and CD is challenging. In TB endemic areas, the standard approach is to treat for intestinal TB first, only considering CD if symptoms persist; a markedly different approach than practiced in Canada.

Our patient primarily presented with intestinal obstruction showing initial improvement after anti-TB treatment, followed by rapid evolution of fibrostenosis. Confirmation of TB diagnosis was complicated by limited evaluation prior to anti-TB therapy and inconclusive test results subsequently. Although surgical resection was inevitable in this case, post-operative medical management becomes problematic in the absence of a confirmed diagnosis where the choices include ongoing anti-TB therapy versus the initiation of CD post-operative prophylaxis with anti-TNF therapy.

Conclusions

Clinicians should be aware that intestinal TB can cause intestinal stenosis, especially in the IC region. Diagnostic clarity should be top priority, in order to provide the best possible long-term outcomes.

Funding Agencies

None
A70 EXPLORING THE ROLE OF MICROBIAL PHOSPHOLIPIDS IN VISCERAL HYPERSENSITIVITY AND ALTERED EMOTIONAL BEHAVIOUR INDUCED BY INFLAMMATORY BOWEL DISEASE (IBD)-ASSOCIATED MICROBIOTA
Authors: Vicentini F A , Hall-Bruce M , Pujo J , Rueda G H , Nardelli A , Jiang A , De Palma G , Verdu E , Collins S , Bercik P
Published: February 2025

Background

IBD is characterized by relapsing episodes of inflammation in the gastrointestinal tract. Abdominal pain is common in IBD and often persists without overt inflammation. Moreover, patients with IBD often develop anxiety and depression, further impairing their quality of life. Recently, gut microbiota emerged as a tentative pathophysiological factor in pain and mood disorders. However, little is known about the specific mechanisms by which microbiota modulate pain and mental health in IBD.

Aims

We hypothesized that bacteria contribute to visceral hypersensitivity and behavioural abnormalities in IBD via modulation of bioactive phospholipids, focusing on lysophosphatidylcholine (LPC) and its metabolite lysophosphatidic acid (LPA), which were previously linked to chronic pain, anxiety and depression.

Methods

Fecal samples from healthy controls (HC n=15) and IBD patients (n=35; Crohn’s Disease (CD) n=18, Ulcerative Colitis (UC) n=17) were collected to assess the levels of LPC and LPA via mass-spectrometry. Samples from selected donors (HC n=5, CD n=6, UC n=5) were used to colonize germ-free C57BL/6 mice (n=115) of both sexes. After 3 weeks, the light preference and tail suspension tests were performed to assess anxiety- and depression-like behaviour. Visceral sensitivity was assessed by visceromotor responses to colorectal distension (100-300 μL). Gut inflammation was evaluated by histology. Microbiota composition was assessed via 16S rRNA gene sequencing.

Results

Fecal concentrations of LPC and LPA were higher in patients with IBD, mainly in those with chronic abdominal pain. Mice colonized with IBD microbiota displayed a reduced preference for the light compartment and increased immobility, suggestive of anxiety- and depression-like behaviour, respectively. Mice with IBD microbiota had higher visceromotor responses to colorectal distension. Interestingly, we observed increased responses to non-noxious stimuli (100 μL), suggestive of visceral allodynia. Microbiota profiles differed between mice colonized with IBD or HC microbiota. Also, mice with increased visceral sensitivity had lower abundance of Bacteroidales taxa, which contains genes related to the catabolism of LPC and LPA. Histology analysis did not show signs of overt inflammation in the jejunum, ileum, or colon.

Conclusions

Microbiota from patients with IBD negatively affect the gut-brain axis by inducing changes in anxiety- and depression-like behaviour and triggering visceral hypersensitivity. Bacterial production of LPC and LPA may be responsible for these deleterious effects.

Funding Agencies

CCC, CIHRCrohn’s & Colitis Foundation
A75 EARLY-LIFE IRON SUPPLEMENTATION SHAPES GUT MICROBIOTA AND MODULATES RECOVERY FROM GUT DYSBIOSIS
Authors: Maumy T , Santos M M
Published: February 2025

Background

Iron is an essential micronutrient, but its supplementation carries significant risks to intestinal health. Excess free iron in the gut fosters pathogenic bacterial growth, disrupting the microbiota and increasing susceptibility to future intestinal stresses. Early life represents a critical window for microbiota establishment, yet little is known about the long-term effects of iron supplementation during this period. This raises concerns about how early iron exposure may impact the gut’s resilience to future stressors, such as gut dysbiosis, especially given the prevalence of intestinal stress and the widespread availability of over-the-counter iron supplements.

Aims

Our study aims to investigate how early-life iron excess influences the gut microbiota and its capacity to recover from two distinct dysbiosis models:

1- Colitis-induced dysbiosis via dextran sulfate sodium (DSS)

2- Antibiotic-induced dysbiosis via a metronidazole and ciprofloxacin cocktail.

We hypothesize that early exposure to excess iron impairs microbiota recovery compared to exposure during adult life.

Methods

Using C57BL/6 mice, we compared the outcomes of iron-sufficient and iron-excess diets initiated at weaning and continued into adulthood. After a 5 week exposure and an iron-sufficient period of two weeks, dysbiosis was induced, followed by an 8-week recovery phase, with frequent stool sampling for 16S rRNA sequencing to track gut microbiota composition. A bioinformatic pipeline was developed to analyze microbiota recovery and the influence of iron exposure. Parallel experiments on adult mice were conducted to explore the role of age in recovery outcomes.

Results

Preliminary data indicate that the colitis model was effective, with disease severity scores confirming a stronger inflammatory response in mice exposed to excess iron during early life. Young mice in the iron-excess group showed heightened susceptibility to DSS-induced colitis compared to their iron-sufficient counterparts. Our bioinformatics workflow has been optimized for other datasets, showing reduced computational time while maintaining analytical precision.

Conclusions

These findings suggest that early-life iron excess impairs gut resilience, potentially predisposing individuals to heightened responses to gut stresses like colitis or antibiotic exposure. Ongoing 16S analysis will further delineate recovery patterns, providing critical insights into how iron supplementation during infancy may influence long-term intestinal health and informing future dietary recommendations for young infants.

Funding Agencies

Institut du Cancer de Montreal, Centre de recherche du CHUM, University of Montreal
A76 MODULATING THE PREOPERATIVE GUT MICROBIOTA USING DIETARY FIBER TO IMPROVE COLORECTAL CANCER SURGICAL OUTCOMES
Authors: McCartney C , Fragoso G , Calve A , Gerkins C , Cuisiniere T , Ajayi A S , Alaoui A , Hajjar R , Taleb N , Richard C , Santos M M
Published: February 2025

Background

Anastomotic leak (AL) is a postoperative complication that occurs in up to 20% of patients undergoing surgery for colorectal cancer (CRC). It is characterized by the poor healing of the intestinal reconnection and is associated with increased mortality, morbidity, and cancer recurrence. The gut microbiota plays a key role in anastomotic healing, potentially mediated by the production of beneficial short-chain fatty acids (SCFA). Supplementation with the dietary fiber inulin was shown to increase SCFA as well as improve microscopic and macroscopic anastomotic healing in a mouse surgical model. However, when considering clinical applications, differences in baseline microbiota composition and patient ability to respond to a dietary fiber must be taken into account.

Aims

In order to differentiate between responders and non-responders prior to surgery, we tested patient responses to different fibers in a mouse fecal microbiota transplantation (FMT) model. Our overall objective is to identify microbial or systemic markers that could predict patient response to different fibers, allowing for personalized dietary interventions.

Methods

Wild-type C57BL/6 mice received FMT from a human donor. Following a 2 week engraftment period, mice received supplementation with one of four dietary fibers for 2 weeks, after which fecal samples were collected for SCFA analysis using HPLC-MS.

Results

The microbiota response to each dietary fiber was estimated based on increased fecal SCFA levels at endpoint for each FMT donor.

Conclusions

Our FMT mouse model is able to detect increased SCFA levels in response to dietary fiber supplementation. Future validation will include measuring post-operative intestinal healing parameters in a mouse surgical model and comparing these results with an ongoing clinical trial. By lowering the risk of AL, we aim to decrease treatment burden for CRC patients and improve their quality of life post treatment.

Funding Agencies

CIHRFRQS
A77 THE INFLUENCE OF IRON SUPPLEMENTATION IN EARLY LIFE ON COLORECTAL CANCER PROGRESSION
Authors: Gerkins C , Cuisiniere T , Maumy T , McCartney C , Fragoso G , Calve A , Santos M M
Published: February 2025

Background

During the first years of life, the immune system develops simultaneously with the gut microbiota, and it has been previously shown that perturbations to gut microbiota development can lead to altered immune phenotypes later in life. One factor that may influence the gut microbiota in early life, and therefore immune development, is iron supplementation.

Aims

We aim to evaluate how iron supplementation in early life affects immune system development and therefore cancer progression in adulthood.

Methods

BALB/c mice were given either an iron sufficient or an iron excess diet beginning at weaning until adulthood at 8 weeks of age. All mice were then placed on the iron sufficient diet for two weeks prior to beginning the experimental model in order to establish the effect of iron only during the early life period. Mice were then injected subcutaneously with the murine colon carcinoma cell line CT-26.

Results

Mice that recieved iron supplementation in early life had significantly higher levels of iron in both the liver and spleen, indicating that this diet was successful in increasing iron levels. Furthermore, mice given iron supplementation had significantly more sebaceous glands per mm ear tissue than mice given the iron sufficient diet. Sebaceous glands are structures in the skin important for coordination of the innate immune response and regulation of the skin microbiota. We next measured several cytokines by ELISA. Mice supplemented with iron had significantly lower levels of interleukin (IL)-4, IL-10, and interferon (IFN)-γ.

Conclusions

Considering that mice given the iron excess diet had significantly altered skin immune structures and significantly decreased basal cytokine levels in ear tissue, we conclude that iron supplementation in early life modulates immune system development. Next, we will evaluate how iron supplementation in early life affects colorectal cancer development and progression.

Funding Agencies

CIHRFRQS, NSERC
A89 PREVALENCE AND OUTCOMES OF SERRATED POLYPOSIS SYNDROME IN TERTIARY GASTROENTEROLOGY PRACTICES: A RETROSPECTIVE ANALYSIS
Authors: Jiang S X , Zarrin A , Taylor E , Tavakoli P , Bell S , Walia A , Pang S , Rui Xuan Yu M , Motomura D , Lam E , Enns R , Telford J , Xiong W , Shahidi N
Published: February 2025

Background

While serrated polyposis syndrome (SPS) is associated with an increased risk of colorectal cancer (CRC), incident CRC can be mitigated through programmatic endoscopic surveillance. Diagnosing SPS remains challenging due to physician awareness and the logistics of cumulative polyp tracking. There is a lack of data on SPS prevalence and outcomes outside of established cohorts.

Aims

To evaluate the prevalence and outcomes of SPS within tertiary gastroenterology practices.

Methods

Using a validated histopathology database, all patients with at least 1 sessile serrated lesion (SSL) removed by 1 of 11 gastroenterologists in a tertiary centre between 2013-2023 were considered for evaluation. All patients were subsequently screened for SPS based on the 2019 World Health Organization (WHO) criteria. Patients meeting SPS criteria underwent full chart review for demographic, procedural, and clinical outcomes. Analysis was based on serrated class lesions (SCLs), which included sessile serrated lesions, hyperplastic polyps, and traditional serrated adenomas.

Results

A total of 6117 patients had at least 1 SSL of which 178 (3%) met SPS criteria (110 WHO I, 10 WHO II, 58 WHO I/II). Median age at first colonoscopy was 62 years (IQR 54-71 years) and 115 (65%) were female. Diagnostic criteria were achieved over a median of 3 years (IQR 1-9 years) and a median of 3 colonoscopies (IQR 2-4 colonoscopies). On index colonoscopy, patients eventually meeting SPS criteria had a median of 3 SCLs (IQR 2-6 SCLs) with median largest lesion size of 11mm (IQR 5-18mm) whereas patients without SPS had a median of 1 SCL (IQR 1-2 SCLs) with median largest lesion size of 5mm (IQR 4-8mm) (p<0.001). SPS was diagnosed by the gastroenterologist in only 132 (74%) patients. SPS was managed by endoscopy and surgery in 157 (88%) and 21 (12%) respectively. Reasons for surgery included polyp burden (9, 5%), endoscopic adverse event (1, 0.5%) and CRC (11, 6%). CRC was diagnosed either before or concurrent to SPS diagnosis in 7 (63.6%).

Conclusions

In patients with at least 1 SSL, the prevalence of SPS was 3% and the diagnosis was recognized in 74% by the primary gastroenterologist. Increased awareness of SPS criteria alongside consideration for modified surveillance intervals based on index SCL size and number may improve patient outcomes.

Funding Agencies

None
A94 ASSOCIATION OF BOWEL URGENCY WITH OTHER DISEASE ACTIVITY MEASURES IN ULCERATIVE COLITIS
Authors: Gill P , Finch H , Stein L , Ma C
Published: February 2025

Background

The presence of bowel urgency and fecal incontinence negatively impacts quality of life in patients with ulcerative colitis (UC).

Aims

We aimed to characterize the assessment of urgency and incontinence in routine clinical care.

Methods

We conducted a retrospective cohort study of prevalent cases of UC evaluated in the University of Calgary IBD Clinic from December 2022 to May 2023, with at least 12 months of follow-up to May 2024. Data on the evaluation of bowel urgency was collected, as were other patient-, disease-, and outcome-related parameters. We aimed to evaluate (1) the proportion of clinic visits where bowel urgency was assessed and documented; (2) the methods for evaluating urgency; (3) the correlation between bowel urgency and other patient-reported outcome measures (including stool frequency and rectal bleeding); and (4) the correlation between bowel urgency and endoscopic appearance.

Results

A total of 274 patients with UC who attended 435 clinic visits were included in this analysis (126 [46.0%] male, mean age at diagnosis 33.2 years [SD 15.5], 104 [40.3%] pancolitis. At the index visit, bowel urgency was evaluated in 160/274 visits (58.4%) and was present in 24.4% (39/160). Most cases were evaluated using the presence/absence of bowel urgency, rather than using a Likert or ordinal scale. In 416 follow-up visits, bowel urgency was assessed in 231 (55.5%) of visits and was present in 75 cases (33.0%). There were moderate-to-strong correlations between bowel urgency and stool frequency (Spearman correlation coefficient 0.54, p<0.001) and rectal bleeding (0.53, p<0.001), but only weak correlation with endoscopic evaluation (Spearman 0.20, p=0.08). Among 136 patients with normal or near normal stool frequency, 16.2% (22/136) had persistent bowel urgency. Among 59 patients with normal or near normal endoscopy, 20.3% (12/59) had persistent bowel urgency.

Conclusions

Bowel urgency remains inconsistently evaluated in clinical care, representing an important area for quality improvement. Although bowel urgency was significantly associated with other patient-reported outcome measures, approximately 1 in 5 patients will have persistent bowel urgency despite minimal endoscopic activity.

Funding Agencies

None
A104 ADENOMATOUS POLYPOSIS WITHIN TERTIARY GASTROENTEROLOGY PRACTICES: A RETROSPECTIVE STUDY
Authors: Jiang S X , Tavakoli P , Rui Xuan Yu M , Ten-Pow M , Flegg D , Taylor E , Walia A , Pang S , Motomura D , Lam E , Enns R , Telford J , Xiong W , Shahidi N
Published: February 2025

Background

Adenomatous polyposis (AP) is defined as ≥ 10 cumulative colorectal adenomas. Despite its clinical relevance, its prevalence, genetic implications, and optimal management remains unknown.

Aims

Evaluate the prevalence and outcomes of AP within a tertiary gastroenterology referral center.

Methods

Patients with at least 1 adenomatous colorectal polyp removed by 1 of 11 gastroenterologists at a tertiary referral center between 2013-2023 were screened for AP using a validated histopathology database. Patients with a known adenomatous polyposis syndrome and/or previous colorectal surgery prior to referral were excluded from analysis. All patients with AP (defined as ≥ 10 adenomatous colorectal polyps) underwent full chart review. Data were extracted for demographic and clinical outcomes.

Results

Of 10,603 patients with at least 1 colorectal adenoma, 330 (3.1%) were diagnosed with AP. AP patients were diagnosed over a median of 5 years (IQR 1-9 years) and a median of 3 colonoscopies (IQR 2-4 colonoscopies). The frequencies of an advanced adenoma and colorectal cancer (CRC) were 236 (71.5%) and 23 (7.0%), respectively. 78.2% of CRC diagnosed before or concurrent to AP diagnosis. Genetic analysis was completed in 22 (6.8%) patients, with a deleterious mutation found in 10 (45.4%). 276 (83.6%) patients were managed endoscopically with 24 (7.3%) referred to surgery and 30 (9.1%) discharged due to age. 300 (90.9%) patients had 10-20 adenomas and 30 (9.1%) patients had > 20 adenomas. Patients with > 20 adenomas were more commonly referred to surgery (6, 20% vs. 18, 6%; p = 0.014). There was no difference in the frequency of CRC between groups (21, 7.0% in 10-20 adenomas and 2, 6.7% in >20 adenomas; p=0.195).

Conclusions

In patients with ≥ 1 colorectal adenoma, the prevalence of AP was 3.1%, with an overall CRC risk of 7.0%. The majority of patients can be successfully managed endoscopically with further evidence needed to delineate appropriate surveillance interval recommendations.

Funding Agencies

CAG
A129 CLINICAL RELIABILITY OF LOWERED ANTI-TISSUE TRANSGLUTAMINASE LEVEL FOR SEROLOGIC DIAGNOSIS OF PEDIATRIC CELIAC DISEASE
Authors: Lang A , Wiepjes M , Zarrabi M , Isaac D M , Turner J
Published: February 2025

Background

The most recent North American pediatric gastroenterology guidelines on diagnosing celiac disease (CD) published in 2016 recommend endoscopic diagnosis (ED) with histologic evaluation as the gold standard in all patients. This contrasts with European guidelines, which have advocated for a serologic diagnosis (SD) in eligible patients, since 2012. The Stollery Children’s Hospital (Edmonton, Alberta), has incorporated SD following internal validation since 2016. Until 2020, SD used an anti-tissue transglutaminase (aTTG) >200 IU/mL with confirmatory HLA typing. After 2020, SD used aTTG >10x the upper limit of normal (ULN) on 2 separate blood-draws.

Aims

The aim of this study was to determine the clinical reliability of a lowered threshold of aTTg >5x ULN for SD in our centre. A secondary aim was to determine estimated healthcare cost savings if this change were implemented.

Methods

We completed a retrospective chart review on pediatric patients (<18 years) diagnosed with CD at our centre from 2018-2021. Patients who underwent endoscopy for suspected CD were included. The costing method was a mix of aggregate costing for endoscopy performed in ambulatory care of the hospital plus micro-costing of other service utilizations such as physician fee for endoscopy, anesthesiologist fee, lab test and processing fees. To calculate the estimated cost savings, we subtracted the estimated costs of diagnosis in our population when all those meeting SD avoided endoscopy from the estimated total cost of diagnosis if these patients had all undergone ED.

Results

In total, 507 patients underwent endoscopy (Figure 1). In patients with aTTG >10x ULN, specificity for CD diagnosis was 99.2% with positive predictive value (PPV) 98.5%. In patients with aTTG >5x ULN, specificity remained 99.2% with PPV 99.5%. There was one false positive case (aTTG 104 IU/L, negative biopsies).

In our study population, use of lowered SD threshold from 2020-2021 would lead to 34 (10.8%) fewer endoscopies, with associated healthcare cost savings of an estimated $88,919 (Table 1).

Conclusions

In our centre, a lower cut-off value for SD may improve time to diagnosis and initiation of a gluten-free diet, and is cost saving. Preliminary results show comparable performance to the currently accepted diagnostic approach used at our centre. Future directions include validating these findings with a larger sample size, as well as determining acceptance of this diagnostic method by patients and families, given the rare but real potential for false positive diagnoses.

Estimated Cost Savings of ED vs SD

*Average cost of ED= $2642.13, Estimated cost of SD = $26.86

Funding Agencies

None
A131 ENDOSCOPIC SUBMUCOSAL DISSECTION: EXPERIENCE AT A LOCAL CANADIAN CENTER
Authors: Ching Hui Yee C , Bechara R
Published: February 2025

Background

Endoscopic Submucosal Dissection (ESD) was established in Japan. There exist few formalized training programs compared to the growing need for its expertise internationally, with many learning through observation and in-vivo training courses. According to Oyama et. al. (1), western centers conducting ESD have learning curves which were inferior when compared to leading Japanese centers. The proposed quality metrics for a proficient operator in ESD are en bloc resection rates of 90%, complications <5%, curative resection rates of 80%, and resection speed of 9cm2/hr. Whereas, the proposed quality metrics for competency are en bloc resection rates of 80% and complication rates of <10%. (1) Here, we present ESD data from a local Canadian center performed by an expert who underwent formal training in ESD at a expert Japanese center.

Aims

We aim to assess if internationally proposed quality metrics of an operator proficient in ESD were met.

Methods

We retrospectively reviewed all patients who underwent ESD between October 2016 up till September 2024 at the Kingston Health Sciences Center. 324 consecutive ESDs were performed on the esophagus, stomach, duodenum, colon and rectum. Primary outcomes include resection speed calculated as centimeters squared per hour (cm2/hr). Secondary outcomes include the number of successful en block and R0 resections, total procedure time, and procedure-related adverse events. Demographic and procedural variables were compared with descriptive statistics (mean ± SD; median, interquartile range), two-sample t-test, and chi-square test.

Results

324 (62.7% male) (67.6 ± 11.8 years) consecutive ESDs were performed, consisting of esophageal (n=109), gastric (n=55), duodenal(n=1), rectal (n=80), and colonic (n=79) ESDs. The overall mean resection speed was 10.9 ± 6.9 cm2/hr. The rate of successful en bloc resections was 96%, and R0 resections were 88.6%. Curative resection rates were 82.4%. The total procedure-related adverse events were at 4%, Notably, 1 of the perforations were delayed, requiring surgical intervention.

When the ESD data was divided into early (first 160 cases) and late (later 164 cases) groups, there was a significant improvement in the resection speed (10.1 ± 7.1 cm2/hr vs 11.7 ± 6.7 cm2/hr, p = 0.05), while maintaining a consistently high rate of en bloc resection (94.4% vs 98.2%) and a low rate of adverse events (4.4% vs 3.7%).

Conclusions

This study demonstrates that ESDs conducted after formal training not only met proficiency quality metrics from the outset, but also exhibited improvements in resection speed and en bloc resection rates as experience increased.

Characteristics of ESD

Funding Agencies

None
A133 QUALITY INDICATOR ADHERENCE FOR BARRETT’S ESOPHAGUS: A RETROSPECTIVE ANALYSIS
Authors: Roda C , Koerber D , Walia A , Tavakoli P , Taylor E , Rui Xuan Yu M , Pang S , Motomura D , Lam E , Enns R , Xiong W , Shahidi N
Published: February 2025

Background

Consensus guidelines advocate for quality indicator adherence in patients with Barrett’s Esophagus (BE). This includes documentation of landmarks/extent of BE, adherence to biopsy protocols and recommended surveillance intervals.

Aims

Evaluate adherence to established quality indicators for patients with BE in a tertiary referral centre.

Methods

Between 01/2012 - 01/2024, consecutive patients with intestinal metaplasia with goblet cells on esophageal biopsies were identified using a validated histopathology registry at St. Paul’s Hospital (Vancouver, BC, Canada). After confirming the diagnosis of BE (≥ 1cm of columnar epithelium above the top of the gastric folds on index esophagogastroduodenoscopy), quality indicator adherence was evaluated (documentation of landmarks/extent of BE (Prague Classification), adherence to biopsy protocols (Seattle Protocol) and recommended surveillance intervals). Continuous variables were summarised using median (IQR). Categorical variables were summarised as frequencies (%).

Results

Preliminary analysis between 01/2012 - 03/2015 identified 253 patients with BE. Median age was 61 years (IQR 17), with 196 (77.5%) being male. Of these, 81 patients were diagnosed with neoplastic BE (33.3% referred for neoplastic BE management; 24.7% at index esophagogastroduodenoscopy; 42.0% during surveillance). The median time to low-grade dysplasia, high-grade dysplasia and esophageal adenocarcinoma from BE diagnosis was 12 months (IQR 48 months), 13 months (IQR 47 months) and 48 months (IQR 33 months), respectively. At index or follow-up evaluation, landmark delineation/extent of BE was documented in 23.3%. Biopsy protocol adherence was 86.6%. Adherence to surveillance recommendations was 57.7%.

Conclusions

Quality Indicators for BE are poorly adhered to, outside of established biopsy protocols. Programmatic BE management may carry the potential to improve patient outcomes and resource utilization.

Funding Agencies

None
A145 EFFECT OF DUPILUMAB ON WEIGHT IN PATIENTS AGED 1 TO 11 YEARS WITH ACTIVE EOSINOPHILIC ESOPHAGITIS (EOE): RESULTS FROM THE PHASE 3 EOE KIDS STUDY
Authors: Chehade M , Pesek R D , Menard-Katcher C , Gutmark-Little I , Fugere N , Liu R , Robinson L , Maloney J , Louisias M , Radin A
Published: February 2025

Background

During the phase 3 eosinophilic esophagitis (EoE) KIDS study (NCT04394351), dupilumab improved histologic and endoscopic endpoints and quality of life vs placebo in children aged 1 to 11 years with active EoE.

Aims

This analysis assessed the effect of higher-exposure dupilumab vs placebo on weight in children with EoE enrolled in the KIDS study.

Methods

Part A was a 16-week, double-blind treatment period; patients were randomized to receive weight-tiered dupilumab or placebo. Patients who completed Part A were eligible to enter a 36-week, extended treatment period (Part B) in which dupilumab patients continued the same dupilumab regimen and placebo patients switched to pre-assigned dupilumab. Outcomes at Weeks 16 and 52 included mean absolute and percent change from baseline in: body weight-for-age percentile, body mass index (BMI)-for-age z-score for patients aged ≥2 years, weight-for-age z-score, and weight-for-length z-score.

Results

At Week 16, mean percent changes (standard deviation) from Part A baseline for higher-exposure dupilumab vs placebo were +3.09 (+21%) vs +0.29 (+5%) in body weight-for-age percentile; +0.10 (+27%) vs -0.14 (+6%) in BMI-for-age z-score, and +0.12 (-20%) vs -0.01 (-1%) in weight-for-age z-score. At Week 52, improvements were maintained or increased with continued higher-exposure dupilumab; improvements were also observed in placebo patients who switched to higher-exposure dupilumab (Table). Dupilumab safety was consistent with its known safety profile.

Conclusions

Higher-exposure dupilumab was associated with a greater increase vs placebo in body weight-for age percentile at Weeks 16 and 52, and sustained trends for increased BMI-for-age and weight-for-age z-scores, in children with EoE aged 1 to 11 years.

Table. Effect of higher-exposure dupilumab on outcomes associated with weight increases at Weeks 16 and 52

Data are mean (standard deviation). n=number of patients at each visit. aPart A full analysis set. bPart B safety analysis set. cn=8.

BMI, body mass index.

Funding Agencies

Research sponsored by Sanofi and Regeneron Pharmaceuticals Inc.
A147 CHARACTERIZATION OF EPIGENETIC MODIFICATIONS OF HUMAN COLONOID MONOLAYERS ESTABLISHED AS IN VITRO CHRONIC DAMAGE MODEL
Authors: Sandilya S , Dever K , Jiang J , Rees B , Kobor M , Steiner T
Published: February 2025

Background

Our lab established an in vitro damage model using human colonoids grown as 2D Intestinal Epithelial Cells (IECs) monolayers in Air-Liquid Interface (ALI) culture. Upon repeated injury by submergence, these colonoid monolayers lost their epithelial barrier integrity and regrowth potential. Changes in mRNA expression and global proteomic profiling of this human model of injury were found to be very similar to those found in Inflammatory Bowel Disease (IBD) and pre-colon cancer like state.

Aims

Preliminary proteomics studies on these monolayers is suggestive of significant changes in expression of key proteins after progressive rounds of injury. These are quite similar to that seen in IBD. These could be strongly associated with epigenetic modifications, such as, DNA methylation and chromatin accessibility which would impact the gene expression, in these epithelial monolayers.

This study aims to assess the epigenetic modifications of these injured IECs monolayers which will help in identification and validation of methylation at specific sites.

Methods

To assess the epigenetic modifications, these IEC monolayers from 2 human colonoid lines were analyzed pre-ALI, during growth and differentiation in ALI before injury, and after 1st, 3rd and 5th round of injury and recovery.

Global methylation, at each of the conditions was assessed using the Illumina Infinium Methylation EPIC BeadChip, an array based technology, to assess the bisulphite-converted cellular DNA for methylation at CpG sites. Genomic DNA was extracted and bisulfite conversion was done using Zymo EZ DNA methylation kit. Methylation at specific sites has been calculated using the fluorescence intensity of methylated and unmethylated alleles. DNAm age estimator software, HOMER, was used to calculate the epigenetic age.

Open chromatin accessibility for the viable cells was measured using bulk ATAC-Seq, which uses transposon based barcoding to build a library for sequencing of chromatin-accessible genes. Gene ontology process enrichment analysis has been used to identify changes in gene expression pathways at above mentioned stages.

Results

Progressive rounds of submergence injury lead to loss of barrier integrity, strongly correlated with significant genotypic and phenotypic changes.Increased DNA methylation and histone assembly found in our studies are reflective of chronic damage. Epigenetic characterization has helped in identfication of key specific targets which play modify pathways leading to chronic epithelial injury.

Conclusions

Correlative evidence from proteomics profiling and epigenetic characterization of this in vitro chronic damage model provides for an enhanced understanding of the initiation and progression of IBD and IBD associated colorectal cancer.

Upregulated proteins after 5th round of damage

Funding Agencies

CCC
A156 FECAL PROTEOLYTIC ACTIVITY IS ASSOCIATED WITH SYMPTOMATIC STATUS IN CROHN’S DISEASE
Authors: Hann A , Bording-Jorgensen M , Constante M , Moayyedi P , Surette M G , Galipeau H , Verdu E
Published: February 2025

Background

An imbalance in host proteolytic activity (PA) has been reported in patients with inflammatory bowel disease (IBD) versus healthy controls (HCs). Fecal PA increases before the diagnosis of ulcerative colitis (UC) which is proinflammatory and has a microbial component. High microbial PA is also present in Crohn’s disease (CD), and when transferred to germ-free mice, induces inflammation through protease receptor-2 signaling. However, whether high PA associates with symptoms in IBD is unknown.

Aims

To investigate whether patients with IBD and high PA have higher symptoms as assessed by Symptom IBD Short Index (SIBDSI).

Methods

Patients with IBD and HCs were recruited and followed for >4 years in the MAGIC study via the IMAGINESPOR network (www.imaginespor.com). Ethnicity, sex, and age information were collected at the initial visit and stool donations were collected at baseline and at each yearly visit. IBD patients completed the SIBDSI survey at each fecal donation and were classified as asymptomatic (UC <13, CD <14) or symptomatic (UC >13, CD >14). From the larger cohort, 60 HC, 60 CD patients, and 60 UC patients were selected and fecal samples from baseline and 1-year follow up visits were used for proteolytic activity assays. Total proteolytic (trypsin), elastase-like (N-Suc-Ala3-pNA), and mucolytic (bioassay) activities were measured in the feces at baseline and follow up from IBD patients and HCs.

Results

Demographic information, SIBDSI scores, and fecal donations from 60 HCs (39F/22M), 60 CD (33F/24M), and 60 UC (33F/25M) patients were analyzed from baseline and 1-year follow up. The average age for HCs, CD patients, and UC patients was 55, 51, and 45, respectively, and most patients were Caucasian. Overall proteolytic activity and mucolytic activities were (p=0.0001) in IBD patients compared with HCs. From baseline to follow up, 27 CD and 24 UC patients had a change in their symptom status classification. In symptomatic CD patients compared with asymptomatic CD patients, total fecal PA was higher (p=0.04).

Conclusions

Dysregulated PA is emerging as a potential mediator of inflammation in some patients with IBD. Our data suggest that high overall proteolytic activity may be linked with symptomatic status in a subset of CD patients. PA activity may constitute a novel non-invasive biomarker for monitoring CD disease activity that could therapeutically be targeted in patients with proteolytic-driven disease.

Funding Agencies

CCC, CIHR