bluuebunny/crossref_metadata_2025 huggingface dataset:
A128 PATIENT CHARACTERIZATION AND ASSESSMENT OF REMISSION RATES IN CHILDREN WITH EOSINOPHILIC ESOPHAGITIS AFTER INITIAL TREATMENT AND 1-YEAR POST-DIAGNOSIS
Authors: Da Silva S , Bortolin K , Afzal N , Marcon P , Hulst J
Published: February 2022

Background

Eosinophilic esophagitis (EoE) is a chronic immune- or antigen-mediated esophageal disorder characterized by symptoms of esophageal dysfunction and eosinophil-predominant inflammation. With incidence rates rapidly increasing, EoE is the leading cause of food bolus impaction and the second leading cause of chronic esophagitis. The treatment of EoE includes both induction and maintenance therapy to prevent complications including esophageal fibrosis and strictures. Despite significant advances in the diagnosis and treatment of EoE, the natural history and long-term management of the disease remains poorly understood.

Aims

To describe the clinical characterization of children with EoE, and to assess remission rates after initial treatment and 1-year post-diagnosis.

Methods

In this ongoing, single-center retrospective study, the electronic medical charts of children newly diagnosed with EoE between January 2017-March 2021 participating in the EoE-AHEAD Registry study were reviewed. Children aged 6 months-18 years with a confirmed diagnosis of EoE based on consensus guidelines and receiving outpatient care at the SickKids EoE clinic were included.

Results

A total of 37 children with a median age of 11 years (IQR: 4.5, 12.5) were included, the majority of which were male (86.5%). Demographic and clinical characteristics are shown in Table 1. On initial treatment, 2.7% of children were on an elemental diet, 18.9% on a food elimination diet, 40.5% on proton-pump inhibitor (PPI) therapy, 16.2% on topical steroids, 8.1% on systemic steroids, and 13.5% on a combination therapy. Of the 30 children with a second endoscopy (mean interval since diagnosis of 6.1 months (3.9)), 30% achieved histological remission after the initial treatment (see Figure 1). Of the 14 children with a one-year follow-up endoscopy, 14.2% were in remission, 3 of which had relapsed. No significant differences in treatment modality were found between those who achieved remission and those who did not.

Conclusions

This is the first Canadian registry study to examine the longitudinal outcomes of EoE in a pediatric setting. Our preliminary results show that only 30% of children achieved histological remission following first-line treatment. The choice of initial therapy varied, although the majority of patients (62.2%) were prescribed a PPI and/or a topical steroid. Our findings highlight the importance of identifying different disease phenotypes to develop personalized therapeutic approaches for the management of EoE.

Funding Agencies

SickKids start-up funds (JM Hulst) and the Comprehensive Research Experience for Medical Students (CREMS) Program
A131 ESOPHAGEAL MUCOSAL BIOPSIES FOR THE DIAGNOSIS OF NON-EROSIVE REFLUX DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Rodrigues D , Kataria J , Rivera D
Published: February 2022

Background

Non-erosive reflux disease (NERD) accounts for over half of all cases of gastroesophageal reflux disease (GERD). It is characterized by symptoms of GERD with pathologic acid exposure on ambulatory pH monitoring and no evidence of erosive esophagitis on upper endoscopy. Symptoms and negative endoscopy alone are insufficient to diagnose NERD. Ambulatory pH monitoring is limited due to availability and patient tolerance. Conventional histologic analysis of mucosal esophageal biopsies has been studied in this context but there is no clear guidance as to its utility in diagnosing NERD.

Aims

The purpose of this study was to conduct a systematic review and meta-analysis to determine the sensitivity and specificity of esophageal biopsy histology in diagnosing NERD.

Methods

Data were obtained from Embase (1947- April 2021) and Ovid MEDLINE (1946 – April 2021). We included all studies where esophageal mucosal biopsies were taken and light microscopy was used to analyze histopathology in symptomatic adult NERD patients (i.e., no evidence of erosive esophagitis and ambulatory pH testing confirmed the presence of pathologic acid exposure). Papers were sorted in duplicate. Relevant data was extracted from papers meeting inclusion criteria, including histologic abnormalities and the location of the biopsy. Sensitivities and specificities were calculated from raw data and pooled using RevMan 5.4 software, using asymptomatic patients with no significant esophageal acid exposure and/or patients with functional heartburn (i.e., symptoms but no elevated acid exposure on ambulatory pH testing) as controls.

Results

The search yielded 2871 studies after the removal of duplicates, of which 158 were eligible for full text review. In total, 12 papers met our stringent inclusion criteria and contained raw data that allowed for sensitivity calculations. Histological abnormalities that were commonly reported included gross morphological scores, papillary elongation, basal cell hyperplasia and dilated intraepithelial spaces. Biopsies were taken at <3cm in 5 studies, ≥3cm in 5 studies, and at multiple sites in 2 studies, and all were reviewed by a blinded pathologist. When assessing for the presence of any abnormality in the histological analysis, biopsies taken at <3cm had a pooled sensitivity of 0.70 (95% CI 0.64 – 0.75) and specificity of 0.72 (95% CI 0.63 – 0.77). Biopsies taken at ≥3cm revealed a pooled sensitivity of 0.39 (95% CI 0.32 – 0.47) and specificity of 0.63 (95% CI 0.51 – 0.74).

Conclusions

Esophageal mucosal biopsies have poor sensitivity and specificity at diagnosing non-erosive gastroesophageal reflux disease. Biopsies taken below 3cm appear to have a higher sensitivity and specificity than those taken more proximally.

Funding Agencies

None
A139 EQUITY IN ACCESS TO COLORECTAL CANCER SCREENING IN NOVA SCOTIA
Authors: Sullivan R , Jones J , Williams C , Kilfoil E , MacIntosh D , Stewart M J
Published: February 2022

Background

Population-based colorectal cancer (CRC) screening programs aim to minimize inequities in participation through universal access, however, there remain disparities associated with low education, socio-economic status, and population centre. In the United States racialized groups have lower screening participation, and Black and Indigenous adults have higher CRC mortality. There is no Canadian data on racialized group participation in CRC screening because racial and ethnic data is not routinely collected. The Nova Scotia Colon Cancer Prevention Program (NSCCPP) mails fecal immunochemical tests (FIT) biennially to all residents aged 50–74 and allows for optional self-identified race and ethnicity.

Aims

To determine whether participation rates in the NSCCPP differ on the basis of race/ethnicity, age, sex, or population centre. In this preliminary analysis we report screening participation on the basis of race/ethnicity.

Methods

A retrospective cohort study was performed using the NSCCPP database to identify screen-eligible adults who returned a FIT to the program (i.e. participated) from 2011 to 2021. Racialized groups were identified based on self-identification form results allowing for multiple category selections. Race/Ethnicity was categorized as White, Black/African Canadian, Indigenous, Asian, Middle Eastern. The 2016 Canadian census was used to estimate the screen-eligible population (age 50–74) and race/ethnicity group population sizes. Unique participants were identified as individuals who returned one or more FITs in the study period. Unique participants were compared to the screen-eligible population to estimate participation over the 10-year study period.

Results

508,533 FITs were returned over 10 years by 208,702 unique participants. The number of annual FITs returned ranged from 14,066 in 2011 to 65,746 in 2019. Participants were 56% female, 44% male, with a mean age 62.8 (± 7.0). FIT status was 89% negative, 7% positive, and 4% indeterminate. 96% (n=490,398) of participants provided self-identification data. Table 1 provides the screen-eligible population, unique participants, and FIT participation over the 10-year study period all characterized by race/ethnicity. Over 10 years, 59% of the eligible population participated in CRC screening by returning at least one FIT.

Conclusions

CRC screening participation by race/ethnicity in Canada is unknown. This analysis of the NSCCPP suggests that participation by racialized individuals including Black/African Canadian, Asian, and Indigenous, are lower relative to White individuals. Further analyses will explore race/ethnicity and gender in terms of temporal and geographic trends.

Table 1.

Funding Agencies

None
A143 SAFETY OF BIOLOGICAL THERAPIES IN ELDERLY IBD: A SYSTEMATIC REVIEW
Authors: Golovics P , Drügg Hahn G , Wetwittayakhlang P , Wild G , Afif W , Bitton A , Bessissow T , Lakatos P L
Published: February 2022

Background

There was a significant progress in the medical therapy of inflammatory bowel disease(IBD) with the advent of biological compounds, yet patients may experience adverse events(AE): infusion reactions, serious infections and malignancies, understudied in vulnerable patient populations (e.g. elderly).

Aims

Our aim was to perform a systematic review to assess the safety of the biologic therapies in the elderly IBD population.

Methods

Medline databases and conferences proceedings were searched between January 1, 2010, and June 1, 2021. Two reviewers independently evaluated the collected studies based on inclusion and exclusion criteria. Search was focused on IBD/CD/UC, any biological therapy, and adverse events in the elderly. The methodological quality of the included studies was assessed using the Newcastle– Ottawa Scale (NOS). This study was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (PRISMA).

Results

Our search identified 2885 articles and 12 congress abstracts trough the data base search, finally 14 peer reviewed papers and 3 abstracts met the inclusion criteria. The majority of the studies were retrospective, merging IBD patients, with an age limit of 60 or 65 years for elderly, from Europe or North America. The gender ratio was equal except in the USA veteran database. The identified studies collected safety data on anti-TNF therapy, vedolizumab and ustekinumab. We selected studies with at least 1 year follow-up period. Ranges of AE rates(infliximab/adalimumab 6–39/100patient-years (PY), vedolizumab 6–26/100 PY and ustekinumab 6–18.2/100 PY), infection rates (anti TNF 2.5–31/100PY, vedolizumab 2.6–77/100 PY and ustekinumab 5.2–35.7/100 PY) or infusion/injection reactions (anti TNF 0–14/100PY, vedolizumab 0.9–5/100 PY and ustekinumab 0–2.6/100 PY), were not different among the biological medication.

Conclusions

We report for the first time the comparative safety of biological therapies in elderly IBD patients. Ranges of adverse events or infections were wide but not different among the medications. Current data are insufficient to suggest prioritizing among biologicals in the elderly based on the safety, larger studies in elderly IBD patients are warranted.

Funding Agencies

None
A146 THE EFFECTIVENESS OF USTEKINUMAB DOSE ESCALATION IN PATIENTS WITH ULCERATIVE COLITIS
Authors: Albino L , Rosentreter R , Lu C , Siffledeen J , Dieleman L A , Ma C , Baugmart D C , Du L , Halloran B , Kroeker K , Peerani F , Wong K
Published: February 2022

Background

Ustekinumab (UST), an IgG1 antibody that targets IL-12/23, is an effective and safe treatment option for patients with inflammatory bowel disease (IBD). Cohort studies have shown that dose escalation is an effective strategy for reinducing and maintaining remission in Crohn’s disease patients who do not respond or lose response to standard dosing of UST. There are currently no published studies evaluating effectiveness of UST dose escalation in ulcerative colitis (UC) patients.

Aims

To assess the effectiveness of UST dose escalation in patients with moderate-to-severe UC who have not responded to or lost responsiveness to standard maintenance dosing (90mg SC every 8 weeks).

Methods

A retrospective cohort study was conducted at three centers. Consecutive patients with moderate-to-severe UC initiated on ustekinumab were enrolled.

Results

Data on 43 patients (26 males) are reported (to date, patients from 1 of 3 centres have been reviewed). Mean age was 40.2 years (±15.6). Mean duration of disease was 8.5 years (±5.8). Mean duration of follow up while on UST was 8.8 months (±7.2). In total, 28% (12) of patients underwent dose escalation: 8% (1) by way of IV reinduction, 58% (7) through interval shortening (every 4 weeks), and 33% (4) by both interval shortening and IV reinduction. Mean time to first dose escalation was 6.2 months (±4.1). Mean time to second dose escalation was 5.1 months (±1.2). Seven percent (3) of patients discontinued UST, with the mean timeframe being 5.3 months (±2.9). Three patients discontinued UST due to primary non-response with one proceeding onto surgery.

Time to normalization of CRP and FCP after initiation of UST is shown in Table 1.

Conclusions

Preliminary data demonstrates that 28% of patients in this cohort required UST dose escalation, with 33% requiring a second dose escalation. Only 7% of patients discontinued UST at 9 months of follow up. Longer term follow up of this cohort would determine if dose escalation is an effective strategy to extend durability of ustekinumab.

Table 1. Normalization of CRP and FCP

Funding Agencies

None
A156 MUCOSA-ASSOCIATED MICROBIOTA OF ILEOCOLONIC CROHN’S DISEASE PATIENTS IS DISTINCT FROM COLONIC CROHN’S DISEASE AND ULCERATIVE COLITIS PATIENTS INDEPENDENT OF BIOPSY SITE, ENDOSCOPIC INFLAMMATION AND HOST GENETICS
Authors: Hernandez-Rocha C , Nayeri S , Turpin W , Borowski K , Stempak J , Silverberg M S
Published: February 2022

Background

Colonic IBD encompassing ulcerative colitis (UC) and isolated colonic Crohn’s disease (cCD) shows significant clinical, therapeutic response and genetic differences compared to ileocolonic CD (icCD). Elucidating the microbial signatures characterizing these subphenotypes could help to understand the causal factors underlying these clinical dissimilarities

Aims

We compared the mucosal microbial diversity and differential abundance (DA) among disease locations (UC, cCD and icCD) accounting for potential clinical, endoscopic, and genetic confounders

Methods

Healthy control (HC), UC, cCD and icCD patients (including ileal and ileocolonic involvement) underwent colonoscopy. Biopsy samples were obtained from terminal ileum (TI), ascending colon (AC) and sigmoid colon (SC) for 16s rRNA gene profiling. Patients with prior ileocecal resection, IBD-unclassified and antibiotic exposure within 3 months before colonoscopy were excluded. Endoscopic inflammation was defined as a segmental Mayo endoscopic subscore = 0 in UC and a simple endoscopic score ≤ 2 in CD. A blood sample was drawn for genotyping and a weighted genetic risk score (GRS) was built based on 169 IBD risk variants found in our cohort. Alpha diversity (Chao1) and DA between IBD subphenotypes were compared using a linear mixed-effects model with subjects as random effect and adjusted for biopsy site, endoscopic inflammation, age, sex, and GRS. For DA analysis, the MaAsLin2 protocol was applied. All p-values were corrected by false discovery rate (FDR) with < 0.05 considered significant

Results

A total of 199 IBD patients and 44 HC with a mean age of 37.2 ± 14 were recruited. Of these, 113 (46.5%) were female. At colonoscopy, 535 biopsy samples (TI = 178, AC = 123 and SC = 234) were obtained. Considering disease location, 254, 55 and 148 samples were obtained from UC, cCD and icCD patients, respectively. A total of 168 samples (31.4%) showed endoscopic inflammation. Alpha diversity was significantly reduced in icCD when compared to either HC, UC or cCD. MaAsLin2 identified that the genera Agathobacter and Faecalibacterium, as well as the family Ruminococacceae and the order Oscillospirales were significantly reduced in icCD when compared to either HC, UC or cCD. These findings were independent of age, sex, endoscopic inflammation, biopsied site, and GRS. UC and cCD did not show differences in their microbial profile

Conclusions

Mucosal samples from UC and cCD patients showed marked similarities in their microbial profile while icCD is characterized by a significant decrease in diversity and beneficial microbes. These data suggest that disease location is the main driver of the mucosal microbial landscape independent of IBD GRS

Funding Agencies

NoneNIDDK IBD Genetics Consortium
A159 OPIOID USE IS DECLINING AMONG PEOPLE WITH INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED STUDY
Authors: Kuenzig E , Mason J , Bernstein C N , Gomes T , Juurlink D , Kaplan G G , Peña-Sánchez J , Targownik L E , Vigod S , Begum J , Nugent Z , Benchimol E I
Published: February 2022

Background

Patients with inflammatory bowel disease (IBD) are more likely to use opioids than those without IBD and are more susceptible to the negative consequences of opioid use, including increased risk of death.

Aims

Examine trends in the use of opioids among people with and without IBD, where opioids were prescribed, and who prescribed them.

Methods

We identified Ontarians with IBD (7/2012–3/2017) from population-based health administrative data using validated algorithms. We matched each patient with IBD on age and sex to 5 people without IBD. We calculated age- and sex-standardized quarterly rates of patients taking opioids, characterized as any, chronic (>90 days), or acute (≤90 days) among people with and without IBD. Among people with IBD, we identified the location of the last healthcare interaction prior to filling the prescription (hospital, emergency department [ED], outpatient clinic), presuming this was where the opioid was prescribed. Opioids prescribed after outpatient visits were stratified by specialty (gastroenterologist, family physician/internist, surgeon, other). Average quarterly percentage change was calculated using Poisson regression, adjusting for age, sex, income, and rural/urban household.

Results

Of 92,233 IBD patients (mean 47 y at study entry, 45% male, 50% Crohn’s), 56% had at least 1 opioid prescription during the study period. Opioid use was more common among people with IBD (any: IRR 2.11, 95% CI 2.08–2.14; chronic: IRR 2.61, 95% CI 2.54–2.69; acute: IRR 1.82, 95% CI 1.79–1.94), Figure A. Among IBD patients, any opioid use decreased by 0.5% (95%CI 0.4–0.5) per quarter, from 13.4% (95%CI 13.1–13.6) to 12.7% (95%CI 12.5–13.0). Chronic opioid use decreased by 0.3% (95%CI 0.2–0.4) per quarter while acute opioid use among IBD patients decreased by 0.6% (95% CI 0.5–0.7) per quarter. Most opioids were prescribed after an outpatient visit (70.2%), most often (82.7%) by a family physician or internist. Total outpatient prescriptions declined by 1.9% (95%CI 1.7–2.0) per quarter, from 5.8% (95%CI 5.6–5.9) to 3.8% (95%CI 3.7–3.9). Relative quarterly decreases were similar across all specialties, Figure B.

Conclusions

Opioid use remains common among IBD patients but has decreased since 2012. The prescriptions most often originated after outpatient visits to family physicians and internists rather than gastroenterologists or surgeons.

Trends in (A) the acute and chronic opioid use among those with and without IBD and (B) the specialist prescribing opioids to IBD patients when the most recent healthcare contact was an outpatient visit.

Funding Agencies

American College of Gastroenterology
A170 SERUM ALBUMIN AS A MEASURE OF INFLAMMATION OR MALNUTRITION IN INFLAMMATORY BOWEL DISEASE: A CROSS SECTIONAL STUDY
Authors: Squirell E , Fardy J , Borgaonkar M , McGrath J S
Published: February 2022

Background

Albumin may be both a marker of malnutrition and a marker of inflammation in various disease states but there has been little study of the precise etiology of hypoalbuminemia in patients with Crohn’s disease (CD). Malnutrition, a common complication of active CD, can lead to hypoalbuminemia. Inflammation can also lead to low albumin levels, and previous literature in other inflammatory diseases has suggested that inflammation may be more likely than malnutrition to be a primary driver of hypoalbuminemia.

Aims

In order to investigate the association between serum albumin and disease activity in individuals with Crohn’s disease, we proposed the following research question:

1. In Crohn’s disease, what is the association between serum albumin and two factors – (1) inflammation and (2) malnutrition, and;

2. Is serum albumin an appropriate diagnostic measure of one or both of these factors in patients with CD.

Methods

This study was a single centre cross sectional study of patients with Crohn’s disease in St. John’s, NL. A total of 45 patients with Crohn’s disease were enrolled in the study. Serum albumin was compared with the subjective global assessment (SGA) for nutritional status, the Crohn’s disease activity index (CDAI), and C- Reactive Protein (CRP), a marker of inflammation.

Results

Simple correlation found negative relationships between albumin and inflammation (r = -0.44, p = 0.002) and between albumin and nutritional status (r = -0.406, p = 0.006). Multiple linear regression confirmed independent effect of both inflammation and malnutrition in the model. Participants who were both malnourished and had active inflammation had a mean serum albumin that was 5.32 g/L lower than those who were malnourished but had no active inflammation (p = 0.009) and 4.3 g/L lower than those who had active inflammation but were well-nourished (p = 0.005).

Conclusions

In our study, hypoalbuminemia was independently associated with both malnutrition and inflammation in patients with Crohn’s disease but was most profound in subjects with both malnutrition and active inflammation. These results suggest that although a low serum albumin in Crohn’s disease may be a marker of either malnutrition or active disease, the lowest levels will be seen in patients with both. There are limitations to most surrogate markers of inflammation and malnutrition in inflammatory bowel disease. Serum albumin is a nonspecific marker in this setting but hypoalbuminemia in patients with Crohn’s disease should prompt further investigation with both inflammation and malnutrition in mind.

Funding Agencies

None
A173 EVALUATING VACCINATION IN INFLAMMATORY BOWEL DISEASE – A QUALITY ASSESSMENT STUDY IN THE WINNIPEG HEALTH REGION
Authors: Kundapur P , Ilnyckyj A
Published: February 2022

Background

The Canadian Association of Gastroenterology published a two-part clinical practice guideline, highlighting that IBD patients may be more susceptible to vaccine preventable diseases. Various studies have demonstrated shortcomings in vaccination rates amongst IBD patients. It is imperative to ensure that an individual’s vaccination status be known prior to starting immunosuppressive therapy; and deficiencies be addressed to optimize patient outcomes.

Aims

Identify physician perceived barriers to vaccinations in the IBD cohort.

Determine discrepancies in vaccination rates in IBD patients, pre and post-introduction of the clinical tool.

Methods

Gastroenterologists in the Winnipeg Health Region (WRHA) will be provided with a survey to assess barriers to vaccination. This survey will be used to inform the clinical tool that will be developed to support physicians. The study is divided into a retrospective component (“pre-clinical tool”) and a prospective component (“post-clinical tool”). In the pre-clinical tool assessment, patient charts of new biological starts at St. Boniface Hospital (SBGH); between January – December 2020, will be reviewed to determine vaccination discussions. For the post-clinical tool assessment, SBGH Gastroenterologists will be provided a document containing guideline recommended vaccination schedule for IBD patients. Subsequently, vaccination rates in IBD patients starting biological therapy will be evaluated over the following 3 months.

Results

Response rates were 90% for the 10 WRHA Gastroenterologists surveyed. Only 55% felt comfortable providing vaccine related care to their IBD patients. Despite being comfortable, 40% correctly identified recommended annual vaccination and 60% accurately identified vaccines that were contraindicated in IBD patients on immunosuppressive therapy. 55% would assess vaccination status with their IBD patients “sometimes,” and 33% state they have “never” provided age-appropriate vaccinations prior to initiation of immunosuppression. Physician related factors (Physician Knowledge) was the most commonly cited obstacle faced in providing immunization care. 80% believed that Primary Care Physicians should keep track and be responsible for administering vaccines to IBD patients. 88% specified that having a clinical tool describing vaccine recommendations would be useful in their practice. Retrospective chart review is in progress and prospective data collection is scheduled to be completed in February 2022.

Conclusions

Survey analysis demonstrates that vaccine practices in WRHA are inadequately addressed; the leading obstacle for physician related factors was knowledge. Though chart review is underway, we anticipate that current vaccination assessments in IBD patients undergoing biological starts are low. We anticipate that rates of vaccinations will improve with the provision of a clinical tool.

Funding Agencies

None
A175 DISEASE ACTIVITY IN FIRST TRIMESTER IS ASSOCIATED WITH REDUCED GROWTH IN INFANTS BORN TO WOMEN WITH INFLAMMATORY BOWEL DISEASE
Authors: Wu R Y , Tandon P , Ambrosio L , Dunsmore G , Wang G , Hotte N , Dieleman L A , Elahi S , Madsen K , Huang V
Published: February 2022

Background

Ulcerative colitis (UC) and Crohn’s disease (CD) are chronic inflammatory bowel diseases (IBD) that affect a significant portion of women in childbearing years. It is known that disease activity in early pregnancy negatively impacts obstetrical and perinatal outcomes, but the impact on infant growth is largely unknown.

Aims

The objective of this study was to compare the growth of infants born to women with active IBD during pregnancy versus those born to women with IBD in remission during pregnancy.

Methods

We conducted a prospective cohort study in a Canadian tertiary centre comprised of 98 pregnant women with IBD (63 with UC and 35 with CD) and 13 healthy pregnant women. We collected maternal demographic at trimester 1 and assessed disease activity at each trimester using clinical disease scores and fecal calprotectin. We then collected perinatal outcomes at delivery and followed the infants’ growth and feeding habits up to 12 months of age.

Results

A total of 103 mother-infant pairs were included in the study, of which 88 infants were born to women with IBD, and 15 born to women with active disease at trimester 1. Active disease at trimester 1 was associated with more adverse obstetrical outcomes, reduced 1-minute and 5-minute APGAR scores and more frequent NICU admissions. Infants born to women with active trimester 1 disease had reduced weight-for-age and length-for-age Z scores up to 6 months of age, in the absence of difference in feeding patterns. In addition, women with active disease at trimester 1 had increased expression of IL-8 and IFN-γ compared to those with trimester 1 remission.

Conclusions

Active IBD during first trimester is correlated with decreased infant weight and height up to 6 months of age, suggesting that strict disease control during first trimester, or even preconception, is essential for optimizing infant growth and perinatal outcomes.

Funding Agencies

None
A176 UTILITY OF MACHINE LEARNING FOR SERUM METABOLOMIC DATA ANALYSIS IN PEDIATRIC CROHN DISEASE
Authors: Suarez Suarez R G , Dijk S I , Zhang Z , Focht G , Navas-López V , Koletzko S , Griffiths A , Wishart D S , Greiner R , Turner D , Wine E
Published: February 2022

Background

The pathogenesis of pCD remains poorly understood, but evidence suggests roles for genetics, environment, immune response, and gut microbes. Microbial changes can contribute to chronic inflammation and correlate with disease severity. Metabolomics reflects interactions between host immune and gut microbial function by quantifying compounds in biological samples. Therefore, metabolomics provides a unique opportunity to gain insight into pCD pathogenesis.

Aims

To correlate disease severity, metabolites, and clinical data by applying machine learning algorithms in pediatric Crohn Disease (pCD).

Methods

ImageKids is a multicenter, prospective, cohort observational study, conducted to develop magnetic resonance enterography (MRE) indices for pCD. Paired serum specimens were collected at study initiation (Visit One; V1) and completion (Visit Four; V4; 18 months) for 120 pCD patients. Serum from patients with representative clinical scenarios and paired samples was analyzed at The Metabolomics Innovation Centre (TMIC; University of Alberta) and 131 metabolites were identified. Metabolites were analyzed via Unsupervised (U.ML) and Supervised (S.ML) Machine Learning algorithms based on Scikit-learn library in Python. Principal Component Analysis (PCA) was used to identify the variation pattern of the patients’ metabolome. Classifiers and regression algorithms were trained to assess correlation with disease activity.

Results

Results were available for the 56 paired samples. U.ML demonstrated distinct metabolome profiles with V1 clustering mainly attributed to aspartic acid, glutamic acid, and kynurenine. V4 clustering was mainly attributed to spermidine, spermine, total dimethylarginine. Furthermore, demographics was found as an important environmental factor driving distinct patterns of the metabolomics profile.

After training different classifiers and regressors with S. ML algorithms, metabolome data were correlated with disease severity (defined by C-reactive protein and fecal calprotectin). Isoleucine, p-hydroxyhippuric acid, and putrescine were the top three compounds associated with disease severity. The accuracy of our classification models was of 80% and the coefficient of determination of our regression models was 0.5

Conclusions

Metabolomic analysis can provide insight into disease pathogenesis and help predict disease severity among pCD patients. The correlation between metabolomics and disease severity might allow a better understanding of changes in host-microbe interactions and introduce new diagnostic or therapeutic options.

Funding Agencies

CIHR
A181 INFECTION WITH THE RAT TAPEWORM HYMENOLEPIS DIMINUTA REVEALS AN INTERLEUKIN-4 INDEPENDENT TUFT CELL ASSOCIATED WITH PEYER’S PATCHES
Authors: Li S , Rajeev S , Wang A , Mckay D M
Published: February 2022

Background

Infection with the rat tapeworm Hymenolepis diminuta elicits a T helper 2 (Th2) imunity and suppresses dinitrobenzene sulphonic-acid-induced colitis in mice. However, the signaling cascade in an immunocompetent host that recognizes and mobilizies early immune events to expel the worm is poorly understood. To fully understand how helminth-infection can ameliorate concomitant disease, it is important to elucidate key cells/mediators in the detection of the worm and early events in the local anti-worm response. Here, we assess the chemosensory epithelial tuft cell and Peyer’s patches (PP) as the primary inductive sites of mucosal immunity in H. diminuta-infected mice.

Aims

To assess the role of tuft cells in PP development and worm expulsion following infection of H. diminuta.

Methods

BALB/c, BALB/c Il-4receptor-a-/-, C57Bl/6 and C57Bl/6 pou2f3-/- (transcription factor critial for tuft cell development) mice were infected with 5 cysticercoids of H. diminuta and necropsied 5-, 8- and 11-days post-infection (dpi); time-matched non-infected mice served as controls. PP number and size were counted and measured. Enteric tuft cells were assessed by immunostaining for the canonical marker double cortin like kinase (dclk)-1, and enumerated in PP-associated epithelium and villous epithelium distant from PP.

Results

Dclkl+ tuft cells were sparse throughout villus epithelium of control mice, but were notably aggregrated over PPs. Infection with H. diminuta resulted in more detectable PPs by visual inspection, but did not result in a statistically significant increase in either size or number of PP. Infected mice showed increased numbers of dclk1+ tuft cells in villus epithelium and PP-associated epithelium (n=3–6). Tuft cells were absent in pou2f3-/- mice, that showed normal size and number of PPs ± infection with H. diminuta. Unexpectedly, analysis of small intestine from il4ra-/- mice revealed dclk1+ tuft cells in association with PPs; perhaps a unique sub-type of this sentinel cell.

Conclusions

Analysis of tuft cells after infection with H. diminuta revealed that these cells aggregate around PPs under homeostatic conditions, and future studies will explore if this distrirbution is important for ‘M’ cell development and/or PP immune reactivity. Intrigingly, an il-4ra-independent tuft cell subtype was observed that awaits fuller characterization. Understanding the tuft cell may reveal novel aspects of development of mucosal immunity relevant to combating helminth-infection and perhaps autoinflammatory enteric disease.

Funding Agencies

NSERC
A188 FACTORS ASSOCIATED WITH CLINICAL REMISSION IN PEDIATRIC LUMINAL CROHN’S DISEASE: A RETROSPECTIVE COHORT STUDY
Authors: Sassine S , Fadela Zekhnine S , Qaddouri M , Djani L , Cambron-Asselin C , Savoie-Robichaud M , Lin Y , Grzywacz K , Groleau V , Dirks M , Drouin É , Halac U , Marchand V , Girard C , Courbette O , Patey N , Dal Soglio D , Deslandres C , Jantchou P
Published: February 2022

Background

The natural evolution of Crohn’s disease is incompletely understood in the pediatric population. Data on factors influencing time-to-remission are very limited in the literature.

Aims

The aim of this retrospective cohort study was to describe the time to clinical remission in children with Crohn’s disease as well as changes over the past decade and to identify factors associated with time to clinical remission.

Methods

Patients under 18 years old diagnosed between 2009 and 2019 were included. All data were collected from the patients’ medical records and the CHU Sainte-Justine inflammatory bowel disease registry. Survival analyses and linear regression models were used to assess the impact of clinical, laboratory, endoscopic, histological and therapeutic factors on time to clinical remission.

Results

654 patients were included in the study. There was no change in the time to clinical remission over the past decade. Female sex in adolescents (ajusted bêta regression coefficient (aβ)= 31.8 days, p= 0.02), upper digestive tract involvement (aβ= 46.4 days, p= 0.04), perianal disease (aβ= 32.2 days, p= 0.04), presence of active inflammation on biopsies (aβ= 46.7 days, p= 0.01) and oral 5-ASA exposure (aβ=56.6 days, p= 0.002) were all associated with longer time to clinical remission. However, antibiotic exposure (aβ= -29.3 days, p=0.04), increased eosinophils on biopsies (aβ= -29.6 days, p=0.008) and combination of exclusive enteral nutrition and TNF- alpha inhibitors as induction therapy (aβ= -36.8, p=0.04) were associated with shorter time to clinical remission.

Conclusions

Time to clinical remission did not improve during the decade and was associated with baseline clinical and histological data and treatment strategies. Combination of enteral nutrition and TNF-alpha inhibitors was associated with faster clinical remission.

Kaplan-Meier curve representing the time to clinical remission of patients according to the first induction treatment administered.

Funding Agencies

NoneFonds Recherche Santé Québec / Fondation du CHU Sainte-Justine
A192 CONSUMPTION OF FOOD LOWER IN TRYPTOPHAN IS ASSOCIATED WITH SIGNIFICANT ANXIETY IN PATIENTS WITH CELIAC DISEASE
Authors: Gupta V , Jivraj A , Armstrong D , Verdu E , Pinto-Sanchez M I
Published: February 2022

Background

Tryptophan, an essential amino acid found in many protein-based foods, has been involved in the pathogenesis of mood disorders and celiac disease (CeD). However, dietary tryptophan consumption has not been investigated in CeD.

Aims

To estimate 1) differences in tryptophan content in food consumed in CeD patients compared to matched healthy controls (HC), and 2) whether consumption of tryptophan is associated with the presence of anxiety and depression in patients with CeD.

Methods

This prospective observational study examined adult patients with a diagnosis of CeD, based on positive specific serology and confirmed by duodenal biopsies, enrolled in the Celiac Registry at McMaster University. A group of sex matched HC were recruited from within the community. Participants completed several questionnaires to evaluate, gastrointestinal symptoms (GSRS), Anxiety and Depression (HADS), and dietary intake of tryptophan (Modified Food Frequency Questionnaire). In addition, CeD patients were assessed for celiac disease activity (CSI), gluten-free diet (GFD) adherence (CDAT) and nutritional status. HADs >11 denoted significant anxiety or depression. Cut-off for low vs high amount of tryptophan content in food was established based on the median tryptophan food content in the HC population.

Results

A total of 443 participants were enrolled in the study; 222 with CeD and 221 controls. The majority of participants were female (74.3%) and the adherence to the GFD was very good (Median CDAT=13; IQR 11–15). The CeD patients were older than HC (Median age, yrs. CD= 40 vs HC= 35; p<0.01). Patients with CeD consumed higher amount of tryptophan compared with HC (Median tryptophan g/day CeD=4.41 vs HC=3.31; p<0.01). There were 157 active CeD patients (CSI ≧ 30). There was no difference in tryptophan consumption between patients with and without active CeD (OR=1.021; 95%CI 0.86–1.21; p=0.88). There was no association between tryptophan consumption and gastrointestinal symptoms or depression scores. Fifteen % of the overall population and 18% of the CeD population had anxiety. There was an increased risk of anxiety in the overall population that consumed low amount of tryptophan (OR=1.87; 95%CI 1.01–3.11; p=0.04), and the risk was greater in the CeD population (OR=4.57; 95%CI 1.26–16.41; p<0.01).

Conclusions

Consumption of food with lower amounts of tryptophan in patients with CeD is associated with significant anxiety, which may influence disease management. Future studies should evaluate whether increasing tryptophan in the diet compared to supplements improves outcomes in CeD population, especially in those with anxiety.

Funding Agencies

None
A193 PERCEIVED BARRIERS TO GLUTEN-FREE FOOD ACCESS ON-CAMPUS EXPERIENCED BY STUDENTS FROM DIFFERENT CANADIAN UNIVERSITIES AND COLLEGES
Authors: Mistry J , Khaouli M , Weiten D , Case S , Gidrewicz D , Turner J , Duerksen D , Pinto-Sanchez M I
Published: February 2022

Background

Students with gluten-related disorders (GRD), a spectrum of conditions including celiac disease (CeD) and non-celiac wheat sensitivity (NCWS), often experience challenges when accessing gluten-free (GF) foods.

Aims

To identify barriers perceived by students with GRD to access GF products on-campus of universities and colleges across Canada.

Methods

We conducted a cross sectional survey using the RedCap platform and distributed it to the Canadian Celiac Association community. We included students who reported adopting a GFD for various reasons including CeD and other GRD. We collected data on adherence to the GFD using a validated questionnaire (CDAT), presence of perceived barriers to follow a GFD while dining on campus, persistent symptoms, and altered quality of life. Continuous data are expressed as median (IQR), and categorical data as proportions of patients. Mann-Whitney U and Chi2 with Fisher correction were used to assess differences between groups.

Results

Seventy nine students responded to the survey (5% male and median age = 25 yrs) and 78 had complete data for analysis. Of the 78 students, 52 (66.6%) reported a diagnosis of CeD, while 26 were adopting a GFD for other reasons (non-CeD). The majority were enrolled in university programs (72/78) and 18% were living on-campus. Almost 90% reported difficulties maintaining a GFD while dining on-campus. Similar proportion of CeD and non-CeD reported eating gluten accidentally (75% vs 80%), while 15% reported eating gluten intentionally on-campus at least a few times per week. This was observed more frequently in non-CeD compared with students with CeD (61% vs 17%; p=0.04). Barriers identified in CeD versus non-CeD groups were related to a reduced GF-food variety (48% vs 69%), lack of availability of GF food (21% vs 46%) and increased cost (46% vs 81%) compared with gluten-containing counterparts. The majority of participants were concerned whether the food available on-campus was truly GF (80% vs 54%) as they reported foods not properly labelled. The majority of participants considered their overall health (79%) and quality of life (65%) was fair to terrible while dining on campus. During the pandemic, 76% of them perceived that it was easier to stick to a GF diet.

Conclusions

Students from various universities and colleges across Canada experience barriers to access GF food on-campus. This has a significant impact on their overall health and quality of life. Proper food labeling, GF certification and improving the variety of GF food on-campus are options for improvement.

Funding Agencies

None
A194 THE ADDITION OF DEAMIDATED GLIADIN PEPTIDE TO TISSUE TRANSGLUTAMINASE ANTIBODIES DOES NOT INCREASE THE ODDS OF CELIAC DISEASE DIAGNOSIS IN AN IGA SUFFICIENT POPULATION
Authors: Moss K , Russell L , Mehta K , Faisal M , Armstrong D , Verdu E , Dowhaniuk J , Pinto-Sanchez M I
Published: February 2022

Background

Previous studies proposed that the combination of IgA anti-tissue transglutaminase 2 IgA (TTG) and IgG deamidated gliadin peptide IgG (DGP) antibodies increases celiac disease (CeD) detection rates. However, this remains controversial.

Aims

To evaluate the performance of adding DGP to TTG antibodies, for the diagnosis of celiac disease (CeD) in the immunoglobulin A (IgA)-sufficient population.

Methods

We included consecutive patients with suspected CeD who had both TTG and DGP serology performed simultaneously from 2017–2020 in Hamilton, Canada. Chart review was performed by 3 reviewers to extract data on biopsies, diagnosis of CeD and genetic HLA-DQ2/DQ8. CeD was defined as positive serology (either TTG and/or DGP) and villous atrophy in duodenal biopsies (≥Marsh-3a). A case was defined as an instance of TTG and DGP performed at a single timepoint. A single patient could have represented multiple cases if TTG and DGP were measured at multiple time points. Sensitivity, specificity, negative and positive predictive values were calculated, and ROC curves were generated. Diagnostic odds ratios (DOR) assessed the performance of each serological strategy compared to duodenal biopsies.

Results

There were 580 patients constituting 823 cases that met inclusion criteria, of whom 441 had CeD. IgA-deficient patients (n=100) were excluded. Of the 723 cases remaining, 337 (214 adult;123 pediatric) had serology performed at the time of CeD diagnosis. TTG increased the odds of CeD diagnosis compared with DGP, Diagnostic Odds Ratio (DOR)=53.22 (95% CI 22.63–119.80) vs DOR=21.28 (95% CI 10.67–42.46). The addition of DGP to TTG did not increase the odds of CeD diagnosis [DGP+TTG DOR=51.39 (95% CI 19.36–135.61) vs TTG alone DOR=53.22 (95% CI 22.63–119.80)]. There were 37 discordant cases where only one of either TTG or DGP was positive. HLA-DQ2/DQ8 were absent in 2/9 cases with isolated increased DGP. Among the discordant cases, TTG outperformed DGP (DOR TTG= 4.29; 95% CI 1.09–16.83 vs DOR DGP=0.23; 95% CI 0.06–0.92).

Conclusions

In the IgA-sufficient population, the addition of DGP to TTG testing does not increase the diagnostic accuracy of CeD serologic screening. This has implications in health-care costs as false positive results prompt further investigations. Given these findings, larger prospective studies should be completed prior to adding DGP antibodies to routine TTG serology.

Funding Agencies

None
A218 THE RISK OF RECURRENT HEPATOCELLULAR CARDINOMA IN POST-LIVER TRANSPLANT PATIENTS RECEIVING CAPECITABINE TREATMENT
Authors: Alsager M , Chaitanya V , Gandhi R , Puka K , Tang E , Teriaky A , Qumosani K , Skaro A , Parfitt J , Brahmania M
Published: February 2022

Background

Little is known on how to reduce the risk of hepatocellular carcinoma (HCC) recurrence post liver transplantation (LT). We examined if adjuvant oral Capecitabine reduces the risk of recurrent HCC in a high-risk group post-LT.

Aims

To examine if adjuvant oral Capecitabine reduces the risk of recurrent HCC in a high-risk group post-LT.

Methods

A retrospective study was performed from a pre-existing liver transplant database from the Liver Transplant Unit at London Health Sciences Center, London; Canada. This database contains demographic, clinical parameters and follow-up of all patients transplanted for HCC. Data was extracted for patients who underwent LT between January 2000 – April 2018 and included follow up until May 31st, 2020. High-risk of tumor recurrence was defined as a RETREAT score ≥5 or PARFITT score ≥10.5. Log rank test compared the recurrence of HCC or death among patients who were and were not prescribed Capecitabine.

Results

Out of 168 LT for HCC, 25 patients were identified as high-risk group for recurrence. The median age was 63 years (IQR=60–65). 19 (76%) patients had viral hepatitis including Hepatitis B and Hepatitis C as their primary disease while 4 (16%) patients had NASH. The remaining 2 (8%) patients had Autoimmune Hepatitis. 7 (28%) patients received Capecitabine while 18 (72%) did not. All patients were followed for a median of 22 months (IQR=8.9–57.5). No statistical significance difference was found between the two groups with respect to HCC recurrence or death (p=0.56).

Conclusions

Among patients with high risk features for recurrence of HCC, adding Capecitabine therapy added to conventional immunosuppression had no overall effect on reducing overall tumor recurrence or survival.

Funding Agencies

None