bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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 &lt; 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

Abstract

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 (&gt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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

Abstract

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