bluuebunny/crossref_metadata_2025_split huggingface dataset:
A175 MACHINE LEARNING MODELLING OF MULTIMORBIDITY PATTERNS AND PREMATURE MORTALITY IN INFLAMMATORY BOWEL DISEASE
Authors: Tennakoon G , Postill G , Harish V , Itanyi I , Tang F , Buajitti E , Kuenzig E , Rosella L , Benchimol E 
Published: February 2025

Abstract

Background
Multimorbidity is the co-occurrence of two or more chronic conditions in one individual. It is associated with reduced quality of life, poorer disease outcomes, increased hospitalizations, and polypharmacy. Although linked to premature mortality in general populations, the relationship between multimorbidity and premature mortality in inflammatory bowel disease (IBD) is unknown.

Aims
(1) characterize multimorbidity patterns across the life course within the context of IBD; (2) identify how the sequence of condition accumulation contributes to premature death.

Methods
We conducted a population-based retrospective matched cohort study using health administrative data from Ontario, Canada, including decedents with IBD between 2010 and 2020. Consensus K-Means Clustering was employed to characterize multimorbidity patterns, allowing us to identify potential groups of patients with similar condition profiles. Recurrent Neural Network (RNN) and Long Short-Term Memory (LSTM) models were trained to analyze the impact of the sequence of condition accumulation on premature mortality, considering either early-onset (diagnosed before 60 years of age) or all life conditions. These models were chosen for their ability to process sequential data, which is crucial for understanding how the order and timing of condition onset in multimorbidity progression impacts premature mortality.

Results
Among 9,278 IBD decedents (49% female), we identified three multimorbidity clusters: (α) mood disorders and/or osteo- and other arthritis, (β) cancer with low multimorbidity, and (γ) cardiovascular comorbidities (Figure 1). Premature deaths accounted for 47.2% (n=4,380) of all deaths. All models performed well, with Area Under the Curve (AUC) values ranging from 0.84 to 0.88. The LSTM model achieved the best performance (AUC 0.88) in predicting premature mortality, using data from early-onset conditions. Key predictors of premature mortality were young ages of diagnosis for mood disorder, osteoarthritis, other mental health disorders, hypertension, and male sex.

Conclusions
This study provides novel insights into multimorbidity patterns in IBD. Our findings reveal three specific multimorbidity clusters in the IBD population and we identified conditions important for predicting premature mortality. These results highlight the importance of providing multidisciplinary care for patients with IBD throughout their lives.

Figure 1. IBD patient multimorbidity clusters. (A) Consensus matrix showing three patient clusters based on comorbidities. Darker blue indicates more consistent patient pairing. (B) Heatmap showing chronic condition prevalence in the three clusters (α, β, γ). Darker blue indicates higher prevalence.

Funding Agencies
None
A177 RESILIENCE AND EMPOWERMENT OF INDIGENOUS PERSONS LIVING WITH INFLAMMATORY BOWEL DISEASE: A PHOTOVOICE STUDY FROM CANADA
Authors: Teucher U , Jennings D , Gannon A , Andkhoie M , Brass C , Fowler S , Johnson-Jennings M , Osei J , Porter L , Porter R , Sanderson R , Souza Lira A P , Peña-Sánchez J 
Published: February 2025

Abstract

Background
There is limited evidence about inflammatory bowel disease (IBD) among Indigenous peoples (Inuit, Métis, and First Nations [FN]). Healthcare utilization inequities between FN and non-FN individuals with IBD have been documented.

Aims
We aimed to explore the perceptions of FN persons living with IBD, including identifying barriers and facilitators to access healthcare and understanding their expectations of healthcare for IBD.

Methods
Six FN community members shared their experiences and perspectives about IBD. Four were individuals living with IBD and two were parents of FN persons living with IBD. Participants were asked to make photos in response to: “What is IBD for you?”, “What does it mean to be healthy and unhealthy when living with the diagnosis of IBD?”, “What do you expect when looking for healthcare at a clinic or a hospital?”, and “What are your challenges when accessing care?”. Then, they participated in semi-structured group reflections about their photo selections. Reflexive thematic analysis was utilized to analyze photographs, questionnaires, and reflections.

Results
The analysis revealed five themes: 1. Diagnosing IBD; 2. Living with IBD; 3. The Health-Sickness Dichotomy; 4. Healthcare Enablers and Barriers; and 5. Advocacy. The 1st theme encapsulates participants’ experiences regarding delays in diagnosis, the tendency of healthcare practitioners to focus on symptoms rather than the underlying disease, and the emotional responses to receiving an IBD diagnosis. The 2nd theme traces participants’ experiences as they navigate a changed reality, confront issues of bodily betrayal, dignity, and resilience. The 3rd theme highlights the contrasts between health and illness as experienced through physical symptoms, dietary choices, and social interactions. The 4th theme captures participants’ experiences within the healthcare system, including their expectations, positive encounters, and challenges such as inadequate knowledge among some healthcare providers, negative interactions, finding adequate language and use of metaphors to speak about a stigmatizing illness, and the use of humor as a coping mechanism and a barrier. The 5th theme reflects participants’ experiences advocating for themselves or relying on supportive networks to advocate on their behalf. Participants recognized the value of patients and advocates as experts in navigating their health journeys.

Conclusions
Drawing on participants’ lived experiences, this study highlights the gaps in the healthcare system faced by Indigenous patients living with IBD, while revealing potential solutions to enhance their healthcare experiences and outcomes.

Funding Agencies
SHRF-SCPOR
A184 DISCOVERY OF POTENTIAL LGR5 LIGANDS
Authors: Gendron F , Arguin G , Acosta Montalvo J , Boudreau P 
Published: February 2025

Abstract

Background
LGR5, an intestinal stem cell marker, is crucial in mediating R-spondin (RSPO) signaling, supporting canonical WNT signaling for tissue development and renewal. This pathway is pivotal in gastrointestinal (GI) disease, assisting wound healing and playing a role in cancer progression and chemoresistance. While modulating the WNT pathway holds therapeutic potential, directly targeting it risks disrupting cell differentiation and organ function. LGR5, whose activity complements but does not fully overlap with the WNT pathway, represents a safer target for therapeutic intervention.

Aims
This study seeks to identify novel ligands for LGR5, focusing on bioactive molecules in the gut lumen and secreted soluble factors from epithelial cells. In addition, RSPO-derived peptidomimetics were designed and assessed as potential LGR5 ligands.

Methods
Luminal lavages from mice intestines were subjected to size-exclusion chromatography, and their activity was tested using impedance assays in HEK293 cells expressing human LGR5 (HEK293/LGR5). Active fractions were further analyzed using pull-down assays and LC-MS/MS to identify LGR5 interacting proteins. Media from cultured IECs were also processed and evaluated for potential LGR5 ligands using LC-MS/MS. Protein-protein interactions (PPIs) were confirmed via immunoprecipitation (IP). Finally, RSPO peptidomimetics based on the FU2 domain, known to bind LGR5, were tested for their ability to modulate β-catenin activity through luciferase reporter assays.

Results
An isoform of Urotensin II (iUTS2) from the cell culture media and three proteins from intestinal luminal extracts were identified as potential LGR5 ligands. The interaction between iUTS2 and LGR5 was confirmed through IP. As a proof of concept, six RSPO peptidomimetics were designed and tested. Although none of the peptides fully replicated RSPO1 activity, three were found to enhance the effect of RSPO1 on WNT3a-induced β-catenin activity, indicating their potential as modulators of LGR5.

Conclusions
This study presents the first identification of potential endogenous and peptidomimetic LGR5 ligands. Although in the preliminary stages, these findings represent a significant step toward developing selective LGR5 ligands, offering insight into LGR5 receptor functions. Such discoveries hold promise for future LGR5-targeted therapies, which could restore tissue homeostasis in conditions like inflammatory bowel disease or impede cancer progression by preventing cell adaptation and dissemination.
This work was funded by a CCC-GIA research grant (2022-2025) and NSERC (RGPIN-2019-05294).

Funding Agencies
CCCNSERC
A186 BALLOON-ASSISTED ENDOSCOPY IN THE MANAGEMENT OF SMALL BOWEL CROHN’S DISEASE – AN OVERALL EXPERIENCE FROM A CANADIAN TERTIARY CARE HOSPITAL
Authors: Fazal M , Bowron J C , Reeson M , Zepeda-Gomez S , Halloran B 
Published: February 2025

Abstract

Background
Crohn’s disease (CD) is a chronic inflammatory disease of the gastrointestinal tract with a wide spectrum of gastrointestinal symptoms and disease complications including strictures, fistulae, malabsorption etc. Balloon-Assisted Endoscopy (BAE) at our institution plays a vital role in managing small bowel Crohn’s disease, to which conventional endoscopy has limited access. It allows better diagnostic and therapeutic abilities through better visualization, biopsies, and endoscopic balloon dilations of strictures.

Aims
Our aim is to evaluate the efficacy and safety of Balloon-Assisted Endoscopy, including Single-Balloon Endoscopy (SBE) and Double-Balloon Endoscopy (DBE), in patients with Small Bowel Crohn’s disease by analyzing the demographics, indications, complications, and endoscopic therapies performed.

Methods
Retrospective analysis of 231 patients who underwent a total of 532 BAE procedures between April 2012 – January 2024 at the University of Alberta Hospital (a tertiary care referral centre). The cohort included both DBE (344) and SBE (188) procedures and clinical findings and outcomes were analyzed.

Results
A total of 532 BAE procedures (344 DBE, 188 SBE) were performed on 231 patients during April 2012 – January 2024. Out of 231 patients, 126 (54.5%) were males and the mean age of the cohort was 52.96 years. The mean duration of disease was 17.55 years and 109 patients (47.18%) had history of surgical resection before their first DBE. 94 patients (40.6%) underwent diagnostic DBE out of which 56 patients had single and 38 patients had multiple endoscopies. Whereas, 137 patients (59.3%) underwent therapeutic DBE with 60 patients undergoing single and 77 patients requiring multiple therapeutic procedures. Obstructive symptoms were reported before 96 procedures (18%). We were able to diagnose Adenocarcinoma (3 patients), Meckel’s Diverticulum (2 patients), retrieve Video-Capsule (1 patient) and achieve hemostasis via hemoclips in 4 patients. A total of 398 strictures were encountered out of which 16 (4.02%) were non-traversable and 3 (0.75%) were failed dilations. We had a &gt; 95% successful dilation rate. Adverse events included aspiration leading to termination of procedure (n=3, 0.56%), mucosal/submucosal tears (n=4, 0.75%), bleeding requiring clips (n=3, 0.56%) and perforation requiring emergent surgery (n=1, 0.18%).

Conclusions
We are reporting on one of the largest single center cohorts of BAE done in IBD patients in the literature. Overall, BAE has a strong safety profile in retrospective analysis of our cohort with a high success rate in both assessing disease and dilating the majority of strictures encountered. 40.6 % of our patients benefited from BAE as an ongoing diagnostic modality: assessing disease status and response to therapy.

Funding Agencies
None
A197 ASSOCIATION BETWEEN ANTIMICROBIAL SEROLOGIES AND IBD LOCATION AND BEHAVIOUR: DATA FROM THE CIDSCANN INCEPTION COHORT
Authors: Fanous Vukas E , Muise A , Jacobson K , Huynh H , Otley A , deBruyn J , Mack D , Deslandres C , El-Matary W , Walters T , Griffiths A , Ricciuto A 
Published: February 2025

Abstract

Background
Antimicrobial serologies have been associated with Inflammatory Bowel Disease (IBD) type and Crohn’s disease (CD) progression. However, prospective pediatric data examining these associations while considering disease location are sparse.

Aims
1) Describe rates of serology positivity by disease location; 2) Assess the ability of serologies to predict CD progression to stricturing (B2) /penetrating (B3) behaviour, while accounting for IBD location.

Methods
Children with CD enrolled in the prospective multicentre Canadian Children IBD Network (CIDsCaNN) were included. ASCA IgA and IgG, CBir1, OmpC and ANCA positivity were measured centrally at Cedars-Sinai. We assessed variables at diagnosis and last follow up. We used Pearson’s Chi-Squared test to compare proportions and Mann-Whitney U test to compare medians between groups. We used multivariable Cox regression to determine the association between serologies and progression to B2/B3 amongst CD patients with B1 at diagnosis, while accounting for L1 location. We calculated area under the ROC curve (AUC) to quantify predictive ability.

Results
There were 512 CD patients included: median age 13 y (IQR 10.8-14.9), follow up 3.3 y (IQR 1.9-5.0). There were 50/452 (11%) B1 CD patients who progressed (L1: 16/77 (21%); L2: 7/112 (6%); L3: 27/241 (11%)). ASCA+ was more frequent among patients with L1/L3 compared to L2 CD (28% vs 13%, p=0.009), while CBir1+ and OmpC+ rates did not differ by CD location (55% vs 48%, p=0.19 and 9% vs 9%, p=0.85). ANCA+ rate was higher among L2 CD compared to L1/L3 CD (30% vs 10%, p&lt;0.001). In univariate survival analysis, CBir1+, ASCA+ and L1 were associated with progression to B2/B3 (Table 1). In multivariable analysis, only positivity for CBir1+ and L1 were associated with progression. CBir1 titre had only moderate ability to predict progression (AUC 0.65 (95%CI 0.57-0.72)).

Conclusions
While ASCA and CBir1 are associated with complicated CD in univariate analysis, this appears to be mediated by small bowel location for ASCA. While CBir1 was independently associated with B2/B3 disease, its predictive ability alone was limited.
Table 1. Unadjusted and Adjusted Hazard Ratios for Progression to B2 or B3 Complications

Funding Agencies
CIHRCh.I.L.D Foundation
A207 INFLIXIMAB IN VERY EARLY ONSET INFLAMMATORY BOWEL DISEASE (VEO-IBD), DOSING AND OUTCOME: A RETROSPECTIVE CROSS-SECTIONAL STUDY
Authors: Sethuraman A , Kishore S B , Binomar H , Jacobson K 
Published: February 2025

Abstract

Background
VEO-IBD patients defined as children with IBD diagnosed before 6rys of age, account for approximately 10% of pediatric IBD patients. They are uniquely at risk of inadequate infliximab (IFX) exposure. We report the dosing patterns, efficacy and safety of IFX use in a cohort of patients with VEO-IBD.

Aims
To study the response rate and outcome of IFX in VEOIBD patients with active therapeutic drug monitoring. Our primary aim was to study the rate of clinical remission and outcome of patients with VEOIBD on IFX. Our secondary aim was to study the IFX failure rate in VEOIBD children and also to study the association of body weight (BW) and body surface area (BSA) dosing.

Methods
A retrospective chart review was conducted for all children with VEOIBD diagnosed between 1st January 2013 to 31st December 2022 with a minimum follow up of one year at a single centre. The patients were identified from the British Columbia paediatric IBD database. Clinical data, including IBD medication use and response were collected from the medical record. REB approval was obtained for this study.

Results
A total of 77 patients were identified and reviewed in our study with 28 (34.1%) exposed to infliximab, with a mean follow up of 65.6 months (±31.7mo). The mean age at diagnosis was 45.9 months (SD±18.5m). Among them, 14 (50%) were diagnosed with Crohn’s disease and 11 (39%) and 3 (11%) with ulcerative colitis and IBD-U respectively. 19/28 (67.8%) patients were started on IFX below 6yrs of age. The median time from diagnosis to IFX commencement was 11.9 months (IQR 3.9-11.9mo). The median pre dose 3 and pre dose 4 infliximab trough levels were 4.35 μg/mL and 5.2 μg /mL respectively with a mean IFX induction dose of 6.7 mg/kg (SD ±2.14mg/kg) and 160.6 mg/m2 body surface area. 18/28 (64.3%) patients needed a dose change after induction with the rest needing dose optimization at follow up. 12/28 (42.8%) were on concomitant therapy with methotrexate or azathioprine. 17/28 (60.7%) continued on IFX as their therapy, with a mean IFX dose of 300mg/m2 and 10.25 mg/kg to achieve clinical remission at last follow. The median drug level for these patients was 7.15 μg/mL.
Clinical remission at last follow up on IFX was achieved in all 17/28 patients with 7/17 in biochemical remission, defined at fecal calprotectin &lt;250μg/g. Infliximab failure occurred in 11/28 (39.3%) of patients with 10/11 due to secondary loss of response. Among those 11, 7 were exposed to a 2nd biologic and 4 to a 3rd biologic with response in 7. Three patients required a colectomy and 1 underwent a bone marrow transplant.

Conclusions
Infliximab trough levels pre dose 3 and 4 are often low in VEO-IBD patients and dose optimization is very common.

Funding Agencies
None
A225 UPTAKE AND OUTCOMES OF MENTAL HEALTH AND NUTRITION COUNSELLING FOR RECENTLY DIAGNOSED IBD PATIENTS.
Authors: Narous M , Ly G , vagianos K , Kredentser M , Graff L , Shaffer S , Singh H , Bernstein C N 
Published: February 2025

Abstract

Background
Inflammatory bowel disease (IBD) significantly impacts both physical and mental health, with patients experiencing elevated levels of anxiety and depression. Nutritional management is also crucial, as dietary choices can influence physical symptoms. Despite the importance of integrated mental health and nutrition services, numerous barriers, such as limited awareness and access, contribute to suboptimal engagement among patients with IBD.

Aims
We sought to assess the uptake of integrated psychologist and dietician services in a clinical setting, and to further understand the mental health and nutrition needs of individuals with IBD.

Methods
In a pilot study initiated in May 2022, recruiting from an IBD clinic at Manitoba’s provincial tertiary hospital, consecutive individuals ages 16+ with IBD diagnosed within 3 years were invited to enrol. Participants completed baseline screening tools including the DASS-21, PHQ8, GAD7, PROMIS, and SaskIBD (nutrition risk) and were offered appointments with an IBD psychologist, dietitian or both, when flagged through the screening tools. Descriptive data were collected regarding clinical screening, psychological diagnoses and interventions, as well as dietary needs and nutrition counselling provided.

Results
Of 226 eligible, 101 were enrolled (42% Crohn’s disease), and 64 accepted referral to clinical psychology. Of those, &gt;50% and 36-49% met screening criteria for moderate to severe depression and anxiety, respectively. Median scores (± std dev) for DASS-21 were 14 ±9.6 (depression), 8 ±6.6 (anxiety), and 16 ±7.9 (stress); PHQ8 10 ±5.2; and GAD7 8 ±4.7. At an initial semi-structured diagnostic interview, approximately 50% of patients were confirmed to have a psychological diagnosis, most commonly depression (20.6%), anxiety (31.7%) and insomnia/sleep disorder (15.9%). Median number of psychologist visits was 1 ±4.13 (range 0-19); 44.4% of patients returned for follow-up. Of the 37 patients who were not flagged/declined to proceed with the psychologist, only 4 screened positive (1 moderate depression; 3 moderate-severe anxiety). Almost all participants (n=84) were flagged to see the dietitian, with the main needs relating to types of food to avoid and strategies for weight gain or loss. Of those, 52% screened positive for moderate to severe risk of malnutrition, with a median SaskIBD score of 3 ±2.1.

Conclusions
In a prospective cohort of recently diagnosed IBD patients, there is a demonstrable need for integrated mental health and dietitian expertise with excellent uptake of these services when easily accessible in an outpatient gastroenterology clinic. Ongoing data are being collected to characterize outcomes of this comprehensive model of care for IBD patients.

Funding Agencies
CCC
A244 EVIDENCE THAT IMPAIRED VAGAL SATIETY SENSING IN OBESITY IS DRIVEN BY LUMINAL MEDIATORS
Authors: Chakraborty A , Sachdev S , Reed D E , Lomax A E 
Published: February 2025

Abstract

Background
Obesity occurs when energy intake exceeds energy expenditure. The physiological changes causing excess energy intake are unclear. Satiety is conveyed from the gut to the brain by vagal afferent neurons (VANs) that have cell bodies in the nodose (NG) and axons that connect the gut and brain stem. There is evidence of diminished satiety sensation in obesity. In the current study, we characterised VAN activity in the jejunum of obese mice and investigated whether mediators secreted into the lumen contribute to this effect. We hypothesized that obese mice would have diminished VAN activity and secrete luminal mediators that inhibit VAN signalling.

Aims
Characterise changes in VAN satiety sensing in obese mice and determine if luminal mediators can induce these changes.

Methods
Genetically leptin-deficient male [N = 6] and female obese (Ob) [N = 8] mice were used, with heterozygous littermates (Het) [male N = 7, female N = 7] serving as controls. Ex-vivo afferent nerve recordings were conducted on VAN axons attached to the mouse jejunum. Changes in firing frequency were assessed in response to meal-related hormonal and mechanical stimuli, namely 100 nM cholecystokinin (CCK) and distension to 60 mmHg. Additionally, naïve NG neurons were incubated in luminal contents collected from the small intestine of Ob and Het mice to determine the potential role of luminal mediators. Patch clamp recordings were carried out on these cells and changes in excitability were assessed using rheobase (higher rheobase indicates decreased excitability).

Results
Ob mice had rates of basal jejunal afferent discharge 70% lower than Het mice (p &lt;0.01) and showed 60% less activation in response to 100 nM CCK (p &lt;0.05). Ob mice also showed a 40% attenuation in distension response compared to Het mice (p &lt;0.01). In patch clamp experiments, NG cells from Ob mice (n = 23 cells from N = 8 mice) had a 33% higher rheobase than Het (n = 18 cells from N = 8 mice; p &lt;0.01). Overnight incubation of NG neurons from naïve mice with luminal contents collected from the jejunum of Ob mice increased the rheobase to over double the rheobase of cells incubated with samples from Het control mice (Ob n = 12, het n = 12, p &lt;0.05). These changes to rheobase were blocked by pre-incubation of NG neurons with the orexin-1 receptor agonist SB-334867 (p &lt;0.01).

Conclusions
Our findings suggest that during obesity, mediators are produced that can attenuate vagal satiety signaling. The ability to inhibit these changes using the orexin-1 receptor antagonist implicate orexin receptors in impaired vagal satiety signaling during obesity.

Funding Agencies
None