bluuebunny/crossref_metadata_2025_split huggingface dataset:
A129 CLINICAL RELIABILITY OF LOWERED ANTI-TISSUE TRANSGLUTAMINASE LEVEL FOR SEROLOGIC DIAGNOSIS OF PEDIATRIC CELIAC DISEASE
Authors: Lang A , Wiepjes M , Zarrabi M , Isaac D M , Turner J 
Published: February 2025

Abstract

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

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

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

Results
In total, 507 patients underwent endoscopy (Figure 1). In patients with aTTG &gt;10x ULN, specificity for CD diagnosis was 99.2% with positive predictive value (PPV) 98.5%. In patients with aTTG &gt;5x ULN, specificity remained 99.2% with PPV 99.5%. There was one false positive case (aTTG 104 IU/L, negative biopsies).
In our study population, use of lowered SD threshold from 2020-2021 would lead to 34 (10.8%) fewer endoscopies, with associated healthcare cost savings of an estimated $88,919 (Table 1).

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

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

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

Abstract

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

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

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

Results
324 (62.7% male) (67.6 ± 11.8 years) consecutive ESDs were performed, consisting of esophageal (n=109), gastric (n=55), duodenal(n=1), rectal (n=80), and colonic (n=79) ESDs. The overall mean resection speed was 10.9 ± 6.9 cm2/hr. The rate of successful en bloc resections was 96%, and R0 resections were 88.6%. Curative resection rates were 82.4%. The total procedure-related adverse events were at 4%, Notably, 1 of the perforations were delayed, requiring surgical intervention.
When the ESD data was divided into early (first 160 cases) and late (later 164 cases) groups, there was a significant improvement in the resection speed (10.1 ± 7.1 cm2/hr vs 11.7 ± 6.7 cm2/hr, p = 0.05), while maintaining a consistently high rate of en bloc resection (94.4% vs 98.2%) and a low rate of adverse events (4.4% vs 3.7%).

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

Characteristics of ESD

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

Abstract

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

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

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

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

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

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

Abstract

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

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

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

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

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

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

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

Abstract

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

Aims
Preliminary proteomics studies on these monolayers is suggestive of significant changes in expression of key proteins after progressive rounds of injury. These are quite similar to that seen in IBD. These could be strongly associated with epigenetic modifications, such as, DNA methylation and chromatin accessibility which would impact the gene expression, in these epithelial monolayers.
This study aims to assess the epigenetic modifications of these injured IECs monolayers which will help in identification and validation of methylation at specific sites.

Methods
To assess the epigenetic modifications, these IEC monolayers from 2 human colonoid lines were analyzed pre-ALI, during growth and differentiation in ALI before injury, and after 1st, 3rd and 5th round of injury and recovery.
Global methylation, at each of the conditions was assessed using the Illumina Infinium Methylation EPIC BeadChip, an array based technology, to assess the bisulphite-converted cellular DNA for methylation at CpG sites. Genomic DNA was extracted and bisulfite conversion was done using Zymo EZ DNA methylation kit. Methylation at specific sites has been calculated using the fluorescence intensity of methylated and unmethylated alleles. DNAm age estimator software, HOMER, was used to calculate the epigenetic age.
Open chromatin accessibility for the viable cells was measured using bulk ATAC-Seq, which uses transposon based barcoding to build a library for sequencing of chromatin-accessible genes. Gene ontology process enrichment analysis has been used to identify changes in gene expression pathways at above mentioned stages.

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

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

Upregulated proteins after 5th round of damage

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

Abstract

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

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

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

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

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

Funding Agencies
CCC, CIHR
A159 SERUM IGG RESPONSE TO THE D0-D1 HINGE PEPTIDE OF COMMENSAL FLAGELLIN PREDICTS THE FUTURE ONSET OF CROHN’S DISEASE IN HEALTHY FIRST-DEGREE RELATIVES
Authors: Wu R Y , Xue M , Zhao Q , Jeong S , Griffiths A , Dieleman L , Steinhart A , Aumais G , Bressler B , Panaccione R , Deslandres C , Mack D , Bernstein C N , Marshall J , Turner D , Xu W , Duck L W , Elson C , Turpin W , Lee S , Croitoru K 
Published: February 2025

Abstract

Background
Elevated antimicrobial antibody levels have been reported up to 6 years before diagnosis of Crohn’s disease (CD), but the specific antibody response is poorly defined.

Aims
Here, we characterized the nature of the antimicrobial antibody responses before the diagnosis of CD in healthy first-degree relatives (FDR) of CD patients.

Methods
The CCC-GEM Project nested case-control cohort consisted of FDRs who later developed CD (n=77), matched 1:4 by age, sex, follow-up duration, and geographical location with FDRs who remained healthy (n=304). Sera at enrollment were probed for antimicrobial reactivity using a microbiota antigen microarray and a flagellin peptide cytometric bead array. Conditional logistic regression was used to assess association with CD onset and partial Spearman was used to correlate the serologic responses with gut permeability (fractional urinary excretion of lactulose-to-mannitol ratio (LMR)) and fecal calprotectin (FCP).

Results
19 (out of 49) IgG antimicrobial antibody responses were significantly associated with the risk of CD; these antibodies were reactive to Lachnospiraceae family, particularly Roseburia-derived flagellins (q&lt;0.02); 5 antibodies positively correlated with FCP (q&lt;0.046), whereas 3 antibodies positively correlated with LMR (q&lt;0.049). These IgG-seroreactive flagellins shared significant amino acid sequence homology, characterized by a conserved “hinge peptide” within D0-D1 domains of the amino-terminus. Elevated IgG seroreactivity to this hinge peptide (determined by cytometric bead array) was associated with multi-flagellin reactivity and future risk of CD.

Conclusions
Increased antibody response in healthy asymptomatic FDRs towards Lachnospiraceae flagellins is associated with future risk of CD, and markers of gut inflammation and altered intestinal permeability. Importantly, pre-CD participants shared seroreactivity towards a conserved bacterial flagellin epitope, suggesting a possible role in the early immunopathogenesis of CD.

Funding Agencies
CCC, CIHRThe Leona M. and Harry B. Helmsley Charitable Trust
A160 PATIENT SATISFACTION WITH NUTRITIONAL COUNSELLING IN MULTIDISCIPLINARY CARE FOR INFLAMMATORY BOWEL DISEASE
Authors: Majdzadeh Z , Pulver C , Rosenfeld G 
Published: February 2025

Abstract

Background
The exact role of diet in inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), remains uncertain with no definitive dietary guidelines established. Nutritional interventions in IBD aim to address nutrient deficiencies, alleviate symptoms, and promote long-term remission. Despite the increasing recognition of nutrition in IBD management, evidence on the impact of nutritional counselling in multidisciplinary IBD care centres on patient-reported outcomes remains limited.

Aims
The primary objective of this study is to determine patient satisfaction with nutrition counselling as an adjunct therapy for IBD and explore its potential to improve patient-reported outcomes.

Methods
The IBD Centre of British Columbia (IBDC) is a multi-disciplinary, tertiary care centre in Vancouver, British Columbia that offers nutritional counselling by a registered dietician with experience in managing IBD. Adult patients of the IBDC, who completed at least 3 nutrition counselling sessions for IBD management, were invited to complete an online survey using a 5-point Likert scale that focused on 4 themes: whether the sessions provided new personalized information to patients, their effectiveness in improving patients’ dietary needs, impact on IBD symptoms, and overall patient satisfaction.1 Patients who had previously consented to research were invited to participate; ethics was obtained from the Providence Health research ethics board.

Results
A total of 69 patients (44 females, 25 males) completed the survey, with a mean age of 43.440 (+/- 15.48) years, and mean disease duration of 12.6 (+/- 11.23) years. Among these, 41 (59.4%) had CD, and 28 (40.6%) had UC. For the purposes of analysis, responses were categorized as positive, negative or neutral. A significant portion of patients (88.4%) reported that the dietitian sessions successfully managed their IBD related nutritional needs. Additionally, 78.3% incorporated the dietary recommendations into their daily dietary routines. Notably, more than 68% of participants reported that nutritional counselling sessions were effective in improving their symptoms. Overall, patient satisfaction with the dietitian sessions was high, at 76.8%.

Conclusions
High patient satisfaction and symptom relief were reported by patients when surveyed about nutritional counselling as an adjunct therapy in their multidisciplinary IBD care. These findings underscore the importance of integrating personalized dietary interventions into standard IBD care and support the growing recognition that nutrition improves patient-reported outcomes. Future research should explore the impact of nutrition counselling on IBD disease outcomes.

References
1. Craven, Meredith et al. Inflammatory Bowel Disease Patient Experiences with Psychotherapy in the Community. J Clin Psychol Med Settings. 2019;26(2):183-193.

Funding Agencies
None