bluuebunny/crossref_metadata_2025 huggingface dataset:
A18 EARLY LIFE EXPOSURE TO PARENTAL CROHN'S DISEASE IS ASSOCIATED WITH GUT MICROBIAL COMPOSITION AND FUNCTION, GUT PERMEABILITY AND INCREASED RISK OF FUTURE CROHN'S DISEASE
Authors: Bushra M , Shao J , Qiu L , Olivera P A , Leibovitzh H , Xue M , Neustaeter A , Xu W , Espin-Garcia O , Aumais G , Huynh H , Panaccione R , Steinhart H , Cino M , Mack D , Marshall J , Ropeleski M , Bitton A , Jacobson K , Mcgrath J , Yerushalmi B , Abreu M , Bernstein C , Radford-Smith G , Lees C , Turner D , Silverberg M , Turpin W , Croitoru K , Lee S
Published: February 2024

Background

Previous studies show that offspring of persons with Crohn’s disease (CD) have a 7-fold higher risk of incident CD than the general population. Newborns of women with CD (vs healthy women) have altered stool microbiome composition and elevated fecal calprotectin (FCP). The perinatal period (pregnancy and first year postpartum) is critical for the development of the gut microbiome and immune system.

Aims

We investigated whether perinatal exposure to parental CD (compared to exposure later in life) has an impact on offspring’s gut barrier function, microbiome composition, and risk of future CD.

Methods

We assessed 1252 healthy offspring of persons with CD who were recruited in the CCC-GEM Project. We classified offspring into "perinatally exposed (pregnancy and first year postpartum)" vs "exposed later in life" to parental CD diagnosis. We measured baseline FCP and urinary fractional excretion ratio of lactulose to mannitol (marker of intestinal permeability, LMR). Fecal microbiome composition was determined by 16S rRNA gene sequencing. Microbiome function was imputed by PICRUSt2 (q value defined as false discovery rate-adjusted p<0.05). Multivariable regression and Cox proportional-hazards analyses were used to assess if peri-natal exposure to parental CD is associated with LMR, FCP, altered microbial composition, and future CD onset.

Results

Offspring exposed to a CD parent perinatally had a 4.7-fold higher risk (aHR 95%CI 1.3-17.5) of developing CD compared to those exposed to a parent who developed CD later in life (11/586 vs 3/666). LMR was significantly higher in the offspring exposed to parental CD perinatally (p=0.003), while no significant difference was observed for FCP at recruitment (p=0.94). Five bacterial taxa were significantly increased in the perinatally exposed group (q<0.05). The microbial functions such as glycine amidinotransferase, serine protein kinase and cyanophycin synthase were significantly increased in the perinatally exposed group (q<0.05).

Conclusions

Offspring exposed to parental CD perinatally had a higher risk of developing CD than those exposed to parental CD later in life. Early life exposure to parental CD was associated with higher baseline LMR, altered bacterial taxa and functional capacities. Environmental exposure during the perinatal period may determine the offspring’s risk of developing CD.

Funding Agencies

CAG, CCC, CIHRCanada Research Chair
A19 THE IMPACT OF FOOD INSECURITY ON ADHERENCE TO A GLUTEN-FREE DIET IN THE ADULT CELIAC DISEASE POPULATION ATTENDING A DEDICATED CELIAC CLINIC
Authors: Leong R , Tandon S , Khaouli M , Blom J , Daca R , Verdu E , Armstrong D , Pinto-Sanchez M
Published: February 2024

Background

A strict gluten-free diet (GFD) is currently the only treatment for celiac disease (CeD), but a GFD can be inconvenient and expensive. CeD patients who are food insecure (FI) face threats to GFD adherence, overall health, and quality of life.

Aims

To evaluate the prevalence of FI in patients with CeD attending a dedicated Adult Celiac Disease Clinic (ACDC) at an academic hospital and to examine the relationship between FI and GFD adherence, quality of life and various gastrointestinal symptoms.

Methods

Patients were invited to participate in the CeD registry when they attended the ACDC; those who agreed to participate then provided verbal and signed consent. Patients had the option to complete the CeD registry forms in the clinic on an iPad or at home using a card with a QR code and a unique ID to access the online CeD registry. The CeD registry uses REDCap (v. 11.1, 2021, US) and includes six validated questionnaires (Celiac Diet Adherence Test (CDAT), Celiac Disease Quality of Life Questionnaire (CD QoL), Celiac Symptom Index (CSI), Gastrointestinal Symptom Rating Scale (GSRS), Hospital Anxiety and Depression Scale (HADS), and Household Food Security Survey Module (HFSSM)). Continuous data are expressed as mean (SD), and categorical data as proportions of patients. The chi-squared test with Fisher correction and t-test were used to assess differences between groups.

Results

A total of 653 patients attended the ACDC from November 2, 2022, to September 20, 2023, and 411 patients were invited to participate in this study. Of them, 204 completed the CeD registry. Food insecurity was identified in 16% of CeD patients, of whom 11 (5%) were marginally FI, 16 (8%) were moderately FI, and 7 (3%) were severely FI. Compared to CeD patients who are food secure, a greater proportion of FI CeD patients reported nonadherence to GFD (26/34 vs 70/170; p<0.001), reduced QoL (32/34 vs 98/170; p<0.001), greater anxiety (27/34 vs 84/170; p=0.001) and greater depression (13/34 vs 26/170; p=0.004) compared with normal values. CeD patients with FI also reported lower QoL [61.0(14.9) vs 49.6(16.7); p=0.001] and increased gastrointestinal symptoms [GSRS 37.7(14.7) vs 29.0(12.8); p=0.001] compared with food secure CeD patients.

Conclusions

Food insecurity is common in patients with CeD and is associated with significantly worse adherence to treatment, symptom control, and quality of life. There is an important need for programs and societal measures to abolish food insecurity and ensure adequate access to treatment for patients with CeD.

Funding Agencies

TRIANGLE Summer Studentship
A20 FECAL MICROBIOTA TRANSPLANTATION FORMULATIONS DO NOT AFFECT BACTERIAL VIABILITY OR TREATMENT OUTCOMES IN RECURRENT C. DIFFICILE INFECTION
Authors: Chan L , Franz R , McDougall C , Wong K , Kao D
Published: February 2024

Background

Fecal microbiota transplantation (FMT) is the most effective therapy for recurrent Clostridioides difficile infections (rCDI) with multiple RCTs showing efficacy of 80-90%. Frozen FMT is a commonly used formulation but requires storage at -80°C, creating barriers to storage and transportation. More recently, lyophilized FMT (LFMT) has shown promise as an alternative formulation, but little data exists as to how bacterial viability may be affected compared to fresh or frozen FMT by different storage temperatures and duration, and real-world outcome data is sparse. As such, this study aims to evaluate the viability and efficacy of LFMT compared to fresh and frozen FMT.

Aims

To 1) compare bacterial viability in 3 FMT formulations: fresh, frozen and lyophilization, at varying storage temperatures and duration, and 2) correlate different formulations with treatment outcomes.

Methods

We compared bacterial viability using flow cytometry to determine the proportion of live vs dead bacteria on fresh, frozen and lyophilized donor stool samples stored at different temperatures (-80°C for frozen, -80°C and +4°C for LFMT) and duration (up to 12 months). We then retrospectively examined treatment success rates in rCDI patients who received fresh, frozen or LFMT at the University of Alberta since inception of the FMT program in 2012. Success is defined as no recurrence of CDI 8 weeks after receiving a single FMT treatment.

Results

Compared to fresh FMT (20% live cells), the proportions of live cells in frozen formulation stored at -80°C and lyophilized formulations stored at -80°C and 4°C did not diminish over time for up to 12 months as shown in Figure 1. Between 2013-2022, outcome data was available in 503 rCDI patients with baseline characteristics and treatment outcomes shown in Table 1. A logistic regression analysis comparing LFMT to frozen FMT resulted in an odds ratio of 0.14, indicating that success rate of LFMT is 14% higher than frozen FMT.

Conclusions

Our study showed that LFMT stored at either -80°C or 4°C over 12 months did not result in diminished bacterial viability compared with frozen FMT. Furthermore, treatment success rate following LFMT in rCDI patients was not lower than with frozen FMT. This finding has implication for stool banks and FMT programs as LFMT can be stored and shipped at 4°C, facilitating use in outpatient settings.

Table 1. Baseline characteristics and success rates of rCDI patients who received fresh, frozen or LFMT.

Figure 1. Proportions of live cells in frozen FMT stored at -80°C, LFMT stored at -80°C and 4°C, at 1, 3, 6, 9 and 12 months.

Funding Agencies

None
A26 BIOLOGICAL CHARACTERIZATION OF THE INTERACTION BETWEEN SIRT1 AND HNF4Α2 IN INTESTINAL EPITHELIAL CELLS
Authors: Herrera Pulido J A , Jones C , Boudreau F
Published: February 2024

Background

Colorectal cancer (CRC) is the third most common cancer in Canada. HNF4A locus is amplified in CRC, while additional reports suggest that hepatocyte nuclear factor 4 alpha (HNF4α) is associated with increased proliferation and disease development. This dual role as a tumor suppressor or oncoprotein might be due to the production of 12 spliced isoforms with structural differences and variable tissue expression. It suggests distinct functions for each isoform according to their specific interaction complexes. However, little is known about the nature of these protein complexes and their biological functions during intestinal physiopathology. Recently, using a BioID2 and mass spectrometry approach, our laboratory showed a possible interaction between HNF4α2 and sirtuin 1 (SIRT1) in intestinal epithelial cells from a colon carcinoma (HCT116). HNF4α2 is one of the most potent isoforms in the control of transcriptional activity of multiple intestinal epithelial genes related to regulating cell death, angiogenesis, apoptosis, response to injury, and response to drugs, among others.

Aims

To characterize the possible interaction between HNF4α2 and SIRT1 in intestinal epithelial cells at the biological level.

Methods

We performed SIRT1 knockdown using shRNAs in HCT116 cells expressing the HNF4α2 isoform in an inducible manner by doxycycline (DOX). Subsequently, we conducted a proximity ligation assay to validate the interaction between HNF4α2 and SIRT1 in HCT116 cells. Additionally, protein purification was performed to validate their physical interaction through EMSA. A transcriptome analysis was carried out using RNA-seq to define the biological processes involved in the interaction between the two proteins.

Results

We observed an interaction signal between HNF4α2 and SIRT1 in HCT116 cells, similar to that observed for IRFBB2, whose interaction with HNF4α2 has been previously validated. This signal decreased when cells were treated with shRNA for SIRT1 and was not observed in cells not induced by DOX. EMSA analyses revealed a direct interaction signal between HNF4α2 and SIRT1. RNA-seq analyses showed a loss in the regulation of over 95% of genes targeted by HNF4α2 when cells were treated with shRNA for SIRT1. An enrichment analysis for GO annotations using ShyniGO v. 0.77 software showed an enrichment of genes for biological processes such as apoptosis, inflammation, cell migration, cell invasion, cell death, and various cancer-related signaling pathways.

Conclusions

SIRT1 displays physical interaction with HNF4α2 and significantly affects the transcriptional regulation of this isoform in the context of epithelial cells. Their interaction is involved in processes related to intestinal inflammation and cancer progression. Pharmacological targeting of SIRT1 could represent a viable strategy in treating CRC and other intestinal diseases

Funding Agencies

CIHRNSERC
A34 DEVELOPING A NOVEL MOUSE MODEL TO ELUCIDATE MECHANISMS OF ORAL TOLERANCE IN EARLY LIFE
Authors: FitzPatrick R D , Cartwright R A , Gatti D M , Reynolds L
Published: February 2024

Background

Oral tolerance is the active suppression of immune responses to antigens that are first encountered in the gastrointestinal tract. When this process fails, food allergies can arise. Food allergies affect up to 6% of Canadian children underlining the need for a thorough understanding of how oral tolerance develops in childhood. Despite this, tolerance has historically been studied using adult rodent models instead of focusing on more physiologically relevant early-life time points.

Aims

Our research aims to develop a robust mouse model to elucidate mechanisms of oral tolerance development in early life and we hypothesize that the mesenteric lymph nodes are a major site of food antigen-specific T cell development in early life.

Methods

Prior to weaning, actively suckling mouse pups were orally gavaged with ovalbumin (OVA), an egg white component and common food allergen or water as a control. Following a series of systemic challenges with OVA, circulating antibody levels were quantified by ELISA to measure the development of oral tolerance to OVA. Additionally, splenocytes isolated from tolerized and control mice were stimulated in vitro with exogenous OVA and cytokines were quantified in culture supernatants via a cytometric bead array assay to assess the suppression of T cell responses to OVA in tolerized mice. One week following oral OVA exposure flow cytometry was used to characterize the expansion of T cell populations in the mesenteric lymph nodes, spleen and thymus.

Results

Mice orally gavaged with OVA in early life show reduced systemic antibody production after subsequent challenges with OVA, compared to mice not orally exposed to OVA. We determined the minimum dosage of OVA required to confer tolerance in these mice and confirmed the validity of this model in both male and female C57BL/6 and BALB/c mice. Further, we detected an active suppression of IL-5 production, a cytokine indicative of a Type 2 immune response, in OVA-stimulated splenocyte cultures isolated from mice tolerized to OVA. We found a significant increase in the frequency of CD4 T cells in the mesenteric lymph nodes just 1-week following oral OVA exposure.

Conclusions

We have developed a robust mouse model of oral tolerance where mice are directly exposed to OVA in an early life period while they are still actively ingesting breastmilk, and their mucosal immune system and intestinal microbiota composition are under significant development. To date, our data suggests that the gut draining mesenteric lymph nodes may be a site of food antigen-specific T cell expansion in early life.

Funding Agencies

CIHRTRIANGLE
A39 DEVELOPMENTALLY REGULATED CECAL CONTENT MICRO-RNAS CORRELATE WITH MATURING MICROBIOTA GENES AND FUNCTIONS IN JUVENILE MICE
Authors: Cuinat C , Taibi A , Tremblay J , Gargari G , Guglielmetti S , Tompkins T , Comelli E
Published: February 2024

Background

The gut microbiome establishment in early life is critical to life-long health and influenced by the maternal gut ecosystem. MicroRNAs (miRNAs) have emerged as a new player in host-microbiota interaction due to their regulatory effect on bacterial genes. We previously found that maternal supplementation with a probiotic mix of Lacticaseibacillus rhamnosus R0011 and Lactobacillus helveticus R0052 supported the maturation of microbial metabolic activity and altered the cecal content miRNA profile in juvenile mice.

Aims

To investigate the relationship between cecal content miRNAs and inferred microbiota genes and functions in early life and identify potential miRNA-bacterial gene targets.

Methods

We generated 16S rRNA gene sequencing and NanoString nCounter® data from the cecal content of 14, 21, and 36-days-old C57BL/6 mice born to dams receiving or not probiotic-supplemented water since preconception. Taxa contributions to bacterial enzyme-encoding genes and pathways were inferred with PICRUSt2. Time or group-altered genes, pathways, and miRNAs were identified with DESeq2. Spearman correlations were performed between miRNAs and bacterial genes or pathways (n= 3-5 male offspring/PND/group) and significant correlations (q ampersand:003C 0.05) were visualized with NAViGaTOR. Potential miRNA binding sites on bacterial genes were investigated using the ViennaRNA Package.

Results

Time-associated miR-433 positively correlated with two time-altered genes involved in the TCA and glyoxylate cycles. Group-associated miR-691 was positively correlated with genes related to tRNA charging pathway, pyruvate fermentation to acetate and lactate, and amino acids biosynthesis. Additionally, miR-691 was negatively correlated with six group-altered genes involved in myo-inositol degradation. We identified potential miRNA binding sites (total free energy of binding ampersand:003C -10 kcal/mol) for miR-691 with genes involved in pyruvate fermentation, lysine biosynthesis, and myo-inositol degradation, and for miR-433 with genes annotated to the TCA and glyoxylate cycles.

Conclusions

Host miRNAs correlate with bacterial pathways and genes maturing during the weaning transition, highlighting their potential to regulate microbial metabolic activity. Maternal probiotics supplementation may accelerate the development of microbial metabolic pathways through epigenetic mechanisms, independently of weaning dietary shift. Correlations identified include energy production pathways and may become clinical targets in infants with delayed maturation of the intestinal ecosystem.

Funding Agencies

NSERC
A42 A HIGH SALT DIET INCREASES ELASTOLYTIC ACTIVITY AND WORSENS COLITIS IN GNOTOBIOTIC MICE
Authors: Hann A , Bording Jorgensen M , Santiago Badenas A , Constante M , Jackson K , Bercik P , Galipeau H , Verdu E
Published: February 2024

Background

Recent evidence has linked ultra-processed foods, which are high in salt, to increased risk of inflammatory bowel disease (IBD). A high salt diet (HSD) was also shown to be colitogenic in specific pathogen-free mice, in part, through modulation of the microbiota. We recently described high microbial proteolytic activity (PA) in feces from IBD patients, that when transferred to germ-free mice, increased acute colitis severity. However, the drivers of high microbial PA are unknown.

Aims

To determine whether HSD increases proteolytic activity, thereby exacerbating colitis.

Methods

Adult germ-free (GF) C57BL/6 mice were colonized with feces from a patient with UC in flare (n=13). Mice were fed either a control diet (CD; 7004, Teklad) or a HSD (7004 supplemented with 4% NaCl) plus 1% NaCl in drinking water. Three weeks following colonization, chronic colitis was induced in half of the mice by three cycles (five days each; 2.0%, 1.5% and 1.5%, respectively) of DSS in drinking water with a five-day wash-out period between cycles. Fecal PA and predicted microbial protease profiles were measured before colitis induction. Weight loss and disease activity (e.g., occult blood in feces and stool consistency) was evaluated for the duration of colitis and microscopic colitis was evaluated at endpoint.

Results

In mice colonized with UC microbiota, a HSD increased elastolytic activity (p=.03 versus CD) and induced a unique predicted protease and peptidase profile. After colitis induction, mice consuming a HSD lost more weight than mice consuming the CD (p=.0001) and had higher disease activity (p=.0004). Additionally, HSD induced more severe microscopic colitis scores compared with the CD (p=.0001).

Conclusions

These results raise the hypothesis that a HSD drives microbial proteolytic activity of IBD microbiota. However, whether this shift is causally associated with the worsening of colitis remains unclear. Mechanistic insight underlying this HSD-microbial proteolytic function could lead to specific dietary modifications or anti-proteolytic therapies for IBD in patients with proteolytic-driven inflammation.

Funding Agencies

CCC, CIHR
A47 A PRELIMINARY ANALYSIS OF THE CROHN'S DISEASE THERAPEUTIC INTERVENTION TRIAL (CD-TDI) IN MILD-TO-MODERATE CROHN'S DISEASE
Authors: Haskey N , Bruno A , Ramay H , Munazza Y , Taylor L M , Ohland C , McCoy K , Ma C , Ghosh S , Veniamin S , Dieleman L , Raman M
Published: February 2024

Background

Studies show a diet-CD remission link, yet a lack of clinical trials exists. The CD Therapeutic Dietary Intervention (CD-TDI) is an evidence-based dietary regimen based on the principles of the Mediterranean diet and incorporates insights from our pilot data as well as the scientific literature about mitigating inflammation through diet in CD.

Aims

To explore the efficacy of the CD-TDI compared with conventional management (CM) to induce clinical and biochemical remission in patients with active, mild-to-moderate luminal CD.

Methods

Participants (n=28) were randomly assigned (2:1 ratio) to either CD-TDI (n=16) or conventional management (CM) (n=12) for 13 weeks. Stool and blood samples were collected at the start and end of the 13 weeks, and fecal bacteriome was analyzed by 16S rRNA.

Results

At baseline, fecal calprotectin (FCP) or C-reactive protein (CRP) levels were not significantly different. By W13, the CD-TDI group's FCP decreased (△ -113±237 µg/g), whereas the CM group experienced an increase (△ 337±1224 µg/g) (p=0.04). CD-TDI significantly reduced CRP (1.0 mg/L, IQR: 0.6-2.4) compared to the CM (4.5 mg/L, IQR: 2.6-13.0, p=0.007). In the CD-TDI group, zonulin decreased (-43 vs. +26, p=0.04) and increased in the CM group (-43 vs. +26, p=0.04), respectively. Lipopolysaccharide-binding protein (LBP) significantly increased in the CM group compared to CD-TDI (CD-TDI = 17 vs. CM = 26; p=0.03). Differential abundance analysis identified a higher abundance of Lachnospiraceae, Selenomonadaceae, Sutterella spp., and Akkermansia muciniphila in the CD-TDI group, whereas Collinsella intestinalis was more prevalent in the CM group.

Conclusions

The CD-TDI demonstrated a reduction in markers of inflammation and intestinal permeability in patients with mild-to-moderately active CD, along with alterations in the composition of bacterial taxa. These initial findings strongly indicate that CD-TDI holds promise for alleviating the inflammatory burden in CD patients and warrants further exploration as a valuable adjunctive therapy.

Funding Agencies

Crohn's Colitis Foundation of America; IMAGINE
A50 PRODUCTION OF A PANCREATIC AND INTESTINAL HEPATOCYTE NUCLEAR FACTOR 4A DOUBLE KNOCKOUT MOUSE MODEL TO UNRAVEL NEW MECHANISMS CONTROLLING METABOLISM
Authors: Rodriguez Rodriguez N , Di Castro A , Jones C , Pupo Gómez D , Boudreau F
Published: February 2024

Background

Hepatocyte nuclear factor (HNF) 4A is a transcription factor mainly found within endodermal organs, including the intestine and pancreas. HNF4A controls the expression of genes associated with glucose transit, glycolytic enzymes, lipid and drug metabolism, and incretin production from intestinal enteroendocrine cells. Mutations within this are linked to various diseases, including maturity-onset diabetes of the young and increased risk of Type 2 diabetes mellitus. However, it remains unclear whether intestinal and pancreatic HNF4A is functionally involved in glucose metabolism. This could be partly due to the lack of suitable experimental model that allow recreating phenotypes associated with hnf4a lost in two key organs involved in controlling body glucose levels.

Aims

To generate a conditionally mutant mouse line that does not express HNF4A in the intestine or the pancreas and to investigate how glucose metabolism is affected in these mice.

Methods

Conditional deletion in each organ was achieved by mating VillinCre or InsCreER with Hnf4αloxP/loxP C57BL/6 mice, respectively. The mutant mouse line was then generated by crossing mice Hnf4αloxP/loxP+VillinCre and Hnf4αloxP/loxP+InsCreER. PCR was performed to confirm all genotypes. Male and female mice around 2-3 months were distributed in four groups, including controls, Hnf4α-deleted intestine only, Hnf4α-deleted pancreas only, and Hnf4α-deleted in both organs. HNF4A expression was measured by qPCR, immunoblot and immunofluorescence. Glucose metabolism tests, including oral glucose tolerance (2g/kg) and insulin tolerance (0.75 International Units/kg) were performed. The blood glucose levels were measured after overnight fasting at 15, 30, 60, and 120 min.

Results

The body weight of four groups of mice remained comparable over experimental time. HNF4A expression was not detected from double mutant mice’s gut epithelial or pancreatic β cells. The oral glucose challenge showed a difference among the group of experimental mice as compared to the control group. After 15 min, blood glucose values of double mutant mice remained higher than control mice, for which glucose clearance was less efficient in the mutants. Insulin tolerance tests demonstrated that double mutant mice behave differently than control mice, suggesting a defect in insulin response.

Conclusions

These promising preliminary results allow us to obtain and characterize a novel murine model to study glucose metabolic syndrome that could be related to hnf4a gene deletion in both the gut and pancreas. Further studies are needed to establish a mechanism by which the HNF4A transcription factor could interplay between the intestine and the pancreas during whole-body glucose metabolism.

Funding Agencies

CIHRBourses d’excellence de l'Université de Sherbrooke
A69 EXPANDED ROLE OF THE DIETITIAN IN THE CLINICAL MANAGEMENT OF PATIENTS WITH CELIAC DISEASE
Authors: Asaria I , Blom J , Morgan J , Khaouli M , Armstrong D , Pinto-Sanchez M
Published: February 2024

Background

The only available treatment for Celiac Disease (CeD) is adhering to a strict gluten-free diet (GFD). However, a GFD has been associated with multiple nutrient imbalance and deficiencies, which are often under-recognized and remain untreated.

Aims

To identify the reasons for referral to a registered dietitian (RD) and RD-recommended dietary interventions for patients with CeD attending a specialised Adult Celiac Disease Clinic.

Methods

We conducted a retrospective chart review using nutrition assessment forms completed by the RD between November 2021 and May 2022. CeD diagnosis was performed through specific serology (anti-tissue transglutaminase IgA and anti-deamidated gliadin peptide IgG) and confirmed by duodenal biopsies demonstrating villous atrophy. We collected data on demographics, diagnosis date, nutritional status (BMI), micronutrients measured in serum, gastrointestinal (GI) symptoms, reason for consult, and the recommendations made by the RD. Data was collected in RedCap (v. 11.1, 2021, US) and expressed as both a proportion and Median (IQR).

Results

A total of 136 visits from 102 patients were included in the analysis. Of them, 77 were female (75.5%) with a mean age of 40.3 yrs (+/- 16.0). The median year of CeD diagnosis was 4 (IQR= 6) from 2002-2022. Patients reported various symptoms including bloating (50.9%), abdominal pain (34.3%), and constipation (23.5%). 56% of patients were overweight or obese (BMI ampersand:003E25), and 4.9% were undernourished (BMIampersand:003C18). The most common nutrient deficiencies were ferritin below 30 ng/mL (58.8%), zinc below 9.4 µmol/L (23.5%), and suboptimal levels of vitamin D (38.2%). The most common reasons for referral to the RD were to assess GFD adherence (44.1%), dietary management of GI symptoms (30.4%) and nutritional optimization (24.5%). We identified 18 different interventions recommended by the RD, the most common being how to prevent gluten cross-contamination (58.8%), tips for dining out (43.1%), GF diet education (32.4%), and increasing fibre intake (30.4%). The most common reasons for follow up visits (n=34) included dietary management of GI symptoms (60.9%) and GFD adherence (43.5%).

Conclusions

Patients with CeD face multiple nutritional challenges associated with following a GFD, and a number of GI symptoms. Although the GFD is the only available treatment, this review identifies the need for multiple individualized dietary interventions, which require and encourage the inclusion of a specialized RD to ensure personalized, effective care and support in the management of CeD.

Funding Agencies

None
A71 IMPACT OF THE COVID-19 PANDEMIC ON WAIT TIMES, AND CLINICALLY RELEVANT FINDINGS AT COLONOSCOPY
Authors: Barkun A , Ravanbakhsh K , Kim D , Milky G , Stanowski P , Geraci O , Martel M , Menard C , von Renteln D
Published: February 2024

Background

The widespread use of a standardized and validated province-wide colonoscopy referral form (PCRF), regrouping mutually exclusive indications into suggested priority wait times categories (P1 to P5), has allowed for a more comprehensive description of routine colonoscopy practice.

Aims

To better understand the impact of COVID-19 on the routine practice of colonoscopy.

Methods

This is a multicenter retrospective cohort study of consecutive adult patients referred with PCRF data available from two Quebec tertiary hospitals. Patient and procedural characteristics were recorded. The primary outcomes were the diagnostic rates of colorectal cancers (CRC) and clinically significant lesions (CSF), defined as endoscopic findings affecting subsequent patient management, excluding hemorrhoids and diverticulosis. The secondary outcome was procedural wait times. We compared endpoints contrasting colonoscopy findings pre-COVID (before March 15th, 2020) to intra-COVID (after April 15th, 2020).

Results

7,476 pre-COVID and 7,181 Intra-COVID patients (mean age 59.2 ± 14.0 years, 50.9% female) were included from 2018 to 2022. There were no clinically relevant between-group differences in patient characteristics. CRC detection remained similar (0.9% pre- vs 0.8% intra-COVID, p=0.69), while CSF were diagnosed more frequently intra-COVID (41,2% vs 39.7%, p=0.02).

There were higher rates of indications performed for urgent and semi-elective priorities (P2, P3) intra-COVID (2.9% vs 1.3%, pampersand:003C0.01, and 50.5% vs 47.9%, pampersand:003C0.01). Corresponding intra- vs pre-COVID differences in indications (all Pampersand:003C0.01) included a clinical suspicion of active inflammatory bowel disease (6.4% vs 5.2%), a high index of suspicion for cancer based on imaging, endoscopy or clinical exam (2.9% vs 1.3%), suspicion of occult colorectal cancer (1.4% vs 0.9%), and doing a repeat endoscopy because of a prior inadequate bowel preparation (1.3% vs 0.8%). In contradistinction, more elective colonoscopies had been performed pre-COVID (P4: 15.5% vs 8.6%, pampersand:003C0.01, and P5: 5.2% vs 3.8%, pampersand:003C0.01. COVID Colonoscopy wait times grew significantly longer intra- vs pre-COVID (176.3 ± 252.4 days vs 78.6 ± 110.2 days, pampersand:003C0.01).

Conclusions

We witnessed significant changes in indications and referral priorities distributions for colonoscopy pre- vs intra-COVID, amidst longer wait times. These practice modifications did not alter CRC diagnostic yields, but resulted in greater proportions of CSF detection

Funding Agencies

CPAC and MSSS
A77 COMPLICATIONS OF DUODENAL DIVERTICULA: A SYSTEMATIC REVIEW ON CLINICAL PRESENTATION AND MANAGEMENT OF ENTEROLITH ILEUS SECONDARY TO DUODENAL DIVERTICULA FORMATION
Authors: Miranda C J , Carlson A M , Hossein-Javaheri N , Aijaz A , Ali M H , Ismail M
Published: February 2024

Background

Duodenal diverticula (DD) are relatively common findings in the gastrointestinal (GI) tract with their presence noted in up to 20% of the population. Rarely, however, these diverticula predispose to enterolith formation which can lead to small bowel obstruction, a phenomenon termed “enterolith ileus”. Both surgical and non-surgical approaches have been espoused in tackling this complication but definitive literature on optimal management is lacking and is limited to scattered case reports and case series. With this phenomenon carrying significant morbidity and mortality, we have conducted a comprehensive review of all available case reports to summarize our understanding of this condition.

Aims

To investigate the prevalance and clinical presentation of enterolith ileus secondary to duodenal diverticula and their optimal management whether that be medical or surgical.

Methods

A comprehensive search of PubMed, OVID, CINAHL, and Cochrane databases up to February 2023 was conducted to identify all studies reporting clinical information on enterolith formation in DD leading to small bowel obstruction. Each article was qualitatively assessed, and relevant data were extracted from selected studies to determine clinical courses and optimal management.

Results

Our literature review identified 17 case reports of enterolith ileus secondary to DD. The mean age of the patients was 72 years (SD 11.43), with 59% of them being female. Three patients had previously undergone Roux-en-Y gastric bypass, while one patient had undergone a distal gastrectomy. The most common symptoms reported were abdominal pain, nausea, and vomiting (88%), followed by abdominal distension (47%). Dilated bowel loops was the most common finding on X-rays, while CT scans revealed signs of small bowel obstruction and DD with an endoluminal mass in most of the cases. Upper GI series was performed in five cases, revealing multiple duodenal diverticula. Despite initial conservative management, 16 out of 17 patients eventually required surgical intervention. Enteroliths were extracted via enterotomy in 14 out of 17 cases, while surgical resection of the bowel was performed in three cases due to suspicion of tumor or perforation.

Conclusions

Our findings highlight the importance of prompt diagnosis and management of DD leading to enterolith ileus, particularly in elderly patients and those with a history of gastric surgery. Surgical intervention is almost always required and therefore early recognition and intervention can help minimize the risk of morbidity and mortality associated with this condition.

Funding Agencies

None
A78 VALIDITY EVIDENCE FOR OBSERVATIONAL EUS COMPETENCY ASSESSMENT: A SYSTEMATIC REVIEW
Authors: Ceccacci A , Hothi H , Khan R , Gimpaya N , Chan B , Forbes N , James P D , Mosko J , Yeung E , Walsh C M , Grover S C
Published: February 2024

Background

Endoscopic ultrasound (EUS) encompasses a range of diagnostic and therapeutic procedures that require technical, cognitive, and non-technical skills. The implementation of competency-based frameworks in endoscopic education has emphasized trainee assessment based on predefined milestones, rather than procedure volume. Observational assessment tools with strong validity evidence are needed to achieve this goal.

Aims

To systematically identify and evaluate observational competency assessment tools employed in EUS using an established validity framework. The secondary aim is to evaluate the educational utility of assessment tools.

Methods

We searched three databases (MEDLINE, EMBASE, and Evidence-Based Medicine Reviews) and the grey literature from inception to May 2023. Messick’s unified framework was used to evaluate validity evidence based on content, response process, internal structure, relations to other variables, and consequences. Each domain was scored from 0 to 3 with a maximum score of 15 points. Educational utility was evaluated using the Accreditation Council for Graduate Medical Education Standards considering ease of use, ease of interpretation, resources required, and educational impact. Study quality was assessed using the Medical Education Research Quality Instrument.

Results

Our search identified 2081 records. We screened 44 full texts and included 5 observational EUS assessment tools from 10 studies. All 5 tools are formative assessments, with 4 employed in clinical settings and one in a simulated setting. All tools use Likert rating scales and are rater-based, with 2 having additional self-assessment components. Validity evidence scores ranged from 3 to 13, with the EUS Assessment Tool (EUSAT), Global Assessment of Performance and Skills in EUS (GAPS-EUS), and The EUS and ERCP Skills Assessment Tool (TEESAT) scoring highest, with 10, 11, and 13 points, respectively. Overall educational utility was high across studies given ease of tool use. The TEESAT had the strongest educational impact considering its influence on credentialing and competence thresholds. Study quality was high overall, with scores ranging from 9.5 to 12 (maximum 13.5 points). Inter-rater agreement for validity evidence and educational utility scoring was substantial (k=0.73, raw agreement 80%) and almost perfect (k=0.92, raw agreement 96%), respectively.

Conclusions

The EUSAT, GAPS-EUS, and TEESAT demonstrate the strongest validity evidence for observational competency assessment of EUS and are easy to implement in educational settings. Future work should investigate barriers to implementation and evaluate utility of these tools for summative assessment.

EUS Observational Competency Assessment Tool Validity Evidence Scores

Funding Agencies

None
A79 PATIENT AND PHYSICIAN PERSPECTIVES ON IMPLEMENTION OF BEDSIDE INTESTINAL ULTRASOUND FOR THE ASSESSMENT OF INFLAMMATORY BOWEL DISEASE
Authors: Chan R , Stewart M , Jones J
Published: February 2024

Background

New tools for evaluating Inflammatory Bowel Disease (IBD) activity and complications are needed to deliver timely disease management and improve patient outcomes. Point of care (POC) intestinal ultrasound (IUS) is safe, inexpensive, and less invasive compared to standard endoscopy and imaging.

Aims

To evaluate the implementation of POC IUS within an ambulatory IBD clinic at the QEII Health Sciences Center.

Methods

This was a retrospective evaluation of a cohort of patients who had undergone IUS within the Nova Scotia Collaborative Inflammatory Bowel Diseases Clinic (NSCIBD) between January 18, 2023 and August 13, 2023. Medical records were reviewed retrospectively. Patient demographics, disease-related characteristics, perceived impact of IUS on need for endoscopy, perceived impact of IUS on IBD management, and clinical utility of IUS were collected. Surveys were administered prospectively to referring care providers and patients following IUS. Patient surveys assessed IUS satisfaction, acceptance of other methods to assess IBD activity, whether IUS improved knowledge of illness, and impact on quality of life (QoL).

Results

One physician completed 107 IUS exams on 92 patients at the NSCIBD clinic over a nine-month period. Of 92 patients, 47 (51%) were male and 78 (85%) had Crohn’s disease. 53 patients provided an email and consented to survey participation. 34 responses were submitted (64%). There were 97 responses (91%) from 12 referring gastroenterology specialist clinicians.

Ninety-three percent of responses show IUS reports were very helpful (60%) or somewhat helpful (33%). More than a third (37%) of IUS exams were reported to delay or prevent the need for endoscopic evaluation, and 34% were reported to prompt a therapeutic change.

Of available tools, IUS had the highest proportion of patients who felt it was completely acceptable (77%), compared to colonoscopy (41%), stool sampling (50%), blood tests (71%), and computed tomography/magnetic resonance imaging (47%). Most (89%) indicated IUS caused either no discomfort (68%) or little discomfort (21%), with no patient reporting a lot of discomfort. Some patients (41%) reported that IUS improved their understanding of their illness, and 38% believe it improved their QoL.

Conclusions

POC IUS offers an accurate, less invasive option for monitoring IBD activity compared to traditional investigations. There is limited data on implementation of, and patient and clinician perspectives regarding use of IUS and its clinical implications. Even early in implementation, POC IUS has clear benefits. This study suggests that IUS is highly acceptable to patients for investigating/monitoring their illness. Treating clinicians find significant value in IUS and report that it can prevent the need for endoscopic evaluation and prompt changes in therapeutic management.

Funding Agencies

None
A81 GASTROINTESTINAL (GI) FEATURES OF HYPERMOBILE EHLERS-DANLOS SYNDROME (HEDS) AND HYPERMOBILITY SPECTRUM DISORDER (HSD): A SCOPING REVIEW
Authors: Chang N , Borovsky D , Yuan Y , Armstrong D
Published: February 2024

Background

Ehlers-Danlos syndromes (EDS) are a varied group of hereditable connective tissue disorders (HCTD) typified by skin, joint and vascular features, along with less well-recognized features of chronic pain, immunological dysfunction and chronic GI symptoms.

The latest EDS classification (2017) lists 13 EDS types and 19 genetic factors but there is no identified genetic basis for hEDS, the most common type and the most-commonly associated with GI symptoms. There is a need for robust data on the prevalence of GI symptoms and diagnoses in hEDS and HSD.

Aims

To investigate the extent of evidence on GI symptom prevalence and methods used to establish GI diagnoses in patients with hEDS and HSD.

Methods

Following the JBI (Joanna Briggs Institute) guide for scoping reviews, a systematic search of Ovid Medline, Embase and Cochrane Library retrieved scoping and systematic reviews, published in English (1974 – Sept 2023), reporting GI symptom prevalence, assessment and complications in EDS or HSD. Abstracts of identified papers were reviewed by NC & DB and discrepancies resolved by YY & DA. As a scoping review, it required no statistical comparisons.

Results

Duplicate screening of 410 abstracts yielded 10 papers that met inclusion criteria: 1 scoping and 9 systematic reviews. Four systematic reviews reported GI surgical issues related to vascular EDS; none was evaluated further. Two papers reported, specifically, on GI symptoms in patients with postural tachycardia syndrome or eating disorders, some of whom had hEDS or HSD and two papers reported on multiple GI and non-GI symptoms associated with fibromyalgia or functional somatic symptoms. The final 2 papers reported on multiple GI and non-GI symptoms in patients with HSD or multiple EDS types, limited in the latter case to papers published after the latest EDS classification (2017). In general, GI symptoms were characterised as IBS-like symptoms (Rome III or Rome IV) or as typical GI symptoms but without using a validated symptom questionnaire.

Conclusions

There are few data on GI symptom prevalence in hEDS or HSD and no standardised methods for identifying or characterizing GI symptoms or function in hEDS. The evaluation of GI function and symptoms in EDS is hampered by the absence of a definitive genetic or diagnostic test for hEDS or HSD and by changes in EDS classification over the last 50 years.

There is a need for targeted systematic reviews of the prevalence of various GI symptoms in hEDS individuals and of relevant diagnostic methods, to guide further research into the causes of GI dysfunction in hEDS or HSD.

Funding Agencies

None
A85 PERCEIVED FOOD INTOLERANCES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE COMPARED TO HEALTHY CONTROLS
Authors: Dang R , Boron D , Linton J , Mundra P , Narula N , Caminero A
Published: February 2024

Background

Inflammatory bowel disease (IBD) patients commonly exhibit food intolerance. However, the precise dietary triggers and mechanistic pathways responsible for food intolerances are unknown. The characterization of the main offending foods in intestinal inflammation could guide targeted dietary interventions in IBD management.

Aims

To examine self-reported food intolerances in IBD participants compared to healthy controls.

Methods

IBD participants (18-75 years old with a confirmed ulcerative colitis (UC) or Crohn’s disease (CD) diagnosis) were recruited from the Gastroenterology clinic at McMaster University from August 2021 to September 2023. Healthy controls (18-75 years old with medical condition) were recruited through recruitment posters at McMaster University. Participants completed questionnaires pertaining to self-reported food intolerances, gastrointestinal rating symptoms, demographic information, and past medical conditions.

Results

A total of 80 IBD participants (48 CD and 32 UC) and 26 controls completed the questionnaires. We found that IBD participants (88% CD and 90% UC) reported at least one food intolerance compared to controls (30%). The mean number of food intolerances IBD participants reported was 3 (SD=1.78). The most common adverse reactions were reported to dairy (60% CD and 63% UC), wheat (37% CD and 40% UC), peanuts/tree nuts (27% CD and 25% UC), caffeine (27% CD and 25% UC) and fiber (22% CD and 28% UC). The rates of intolerances to all of the food groups were higher than reported by controls. The most common symptoms include discomfort (75% CD and 50% UC), bloating (66% CD and 62% UC), diarrhea (62% CD and 56% UC) and pain (56% CD and 37% UC) when consuming offending foods. About half of IBD participants had these symptoms before their diagnosis and 30% reported worsening of intolerances after their IBD diagnosis.

Conclusions

Our current findings reveal that IBD participants commonly report food intolerances that are associated with symptomatology. Common offending foods include dairy, wheat, peanuts/tree nuts and caffeine. IBD participants commonly experience discomfort, bloating and diarrhea when eating offending foods, which can persist after diagnosis. Ongoing studies will provide insights into the relationship between stool bacterial composition and food intolerance symptoms.

Funding Agencies

CCC
A92 THE CURRENT STATE OF PEDIATRIC TO ADULT TRANSITION OF CARE: A ROUND TABLE DISCUSSION WITH KEY STAKEHOLDER GROUPS
Authors: Hu M , Gakhal N , Kabakulak C , LoMonaco J , Bollegala N
Published: February 2024

Background

There is a severe paucity in available resources to facilitate a safe and effective pediatric to adult health care transition for patients with chronic disease.

Aims

This study aims to better understand the experiences of key stakeholder groups involved in pediatric to adult transition of care across various chronic disease specialties within a tertiary care urban environment.

Methods

A focus group was conducted on July 12th, 2018 at Women’s College Hospital with key stakeholder groups. Questions focused on the top issues related to pediatric to adult transition of care and an ideal transition model for their respective patient populations. The second part of this study included individual interviews with patients and carepartners. Focus group meetings and individual interviews were both audio-recorded and transcribed for qualitative thematic analysis.

Results

Seventeen pediatric and adult care physicians representing ten chronic disease specialties were represented. Seven patients and care partners were interviewed. Major focus group themes included: disproportionate access to resources between and within specialties (n=10), lack of mental health support in the adult setting (n=8), fragmentation of care due to multiple providers as a result of patients leaving for employment or education (n=6), patients feeling alienated due to decrease in allied health support or due to shorter appointment times (n=8), and difficulty retaining consistent care due to missed appointments as a result of inconsistent communications or change in location for education or employment (n=7). Ideal care models were suggested to include: centralized intake procedure to identify patients who may require extra support (n=9), education for scheduling administrators about second chances after a no-show (n=5), implementation of joint clinics with pediatric and adult care teams or back-and-forth clinic sessions to ensure bidirectional provider comfort before discharge to adult care system (n=4), and implementation of a dedicated transitions navigator or point of contact for patients (n=10).

The individual patient and carepartner interviews emphasized the need for: centralized and comprehensive online resource (n=7), simple and clear educational content introducing the adult healthcare system (n=7), opportunities to meet and share information with other individuals in a similar position (n=3), and availability of a transitions navigator (n=4).

Conclusions

Current pediatric to adult transition of care resources are fragmented, allocated inefficiently, difficult to ascertain and often constrained to a specific condition or location. Future efforts should focus on improving the care transition process for high-risk patient populations by taking a comprehensive approach utilizing innovative, and multidisciplinary solutions.

Funding Agencies

None