bluuebunny/crossref_metadata_2025_split huggingface dataset:
A51 INTESTINAL MICROBIOTA DETERMINES ARYL HYDROCARBON RECEPTOR ACTIVATION AND SUSCEPTIBILITY TO COLITIS
Authors: Rondeau L , Haas D , Wang X , Caminero A 
Published: March 2023

Abstract

Background
Intestinal microbiota, diet, and the immune system have been proposed to contribute to the development of inflammatory bowel diseases (IBD). The aryl hydrocarbon receptor (AhR) is a critical regulator of intestinal immunity and mucosal barrier homeostasis that is activated by agonists such as host and microbial tryptophan metabolites. IBD patients have altered microbiota and reduced AhR agonists in intestinal content resulting in the downregulation of AhR. These findings necessitate further study to understand how diet-microbiota interactions contribute to intestinal inflammation.

Purpose
To study the influence of intestinal microbiota on tryptophan metabolism, AhR activation, and colitis severity.

Method
8- to 10-week-old germ-free C57BL/6 mice were colonized with cecal content of mice harbouring specific pathogen-free (SPF) or a limited and well-defined altered Schaedler flora (ASF) microbiota. Germ-free mice were used as controls. Three weeks following colonization, mucosal injury was induced in a subset of mice with dextran sulfate sodium (DSS) in drinking water for five days followed by two days of water recovery. Activation of AhR was measured in stool using an in vitro AhR luciferase reporter assay. Stool AhR agonists were determined using high-performance liquid chromatography coupled to high-resolution mass spectrometry. Colonic expression of AhR pathway genes Cyp1a1, Il22, Ahrr, Ahr, and Il17 was evaluated by RT-qPCR. Susceptibility to colitis was assessed by analysing stool consistency and stool blood, colonic microscopic damage, immune infiltration by immunohistochemistry, and pro-inflammatory gene expression (NanoString). Fecal microbiota was analysed by 16S rRNA gene sequencing (Illumina).

Result(s)
AhR agonists, AhR activation in vitro, and AhR pathway gene expression were elevated in mice colonized with SPF microbiota in comparison to mice colonized with ASF microbiota and germ-free mice. In ASF-colonized mice, DSS induced more severe inflammation than in SPF-colonized mice, as demonstrated by worsened mucosal injury, greater weight loss, and softer stools. SPF-colonized mice developed less mucosal immune cell infiltration and pro-inflammatory gene signaling.

Conclusion(s)
Our findings suggest that intestinal microbiota composition determines the metabolic capacity to degrade tryptophan into agonists that homeostatically activate AhR. When mucosal injury is induced, mice with elevated microbiota-derived AhR agonists and AhR activation develop less severe mucosal injury and signs of colitis. This study presents a useful tool for evaluating dietary and microbial therapies in the context of a microbiota with impaired tryptophan metabolism.

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CCC, CIHR

Disclosure of Interest
None Declared
A52 SEX DIFFERENCES IN POST-INFLAMMATORY VISCERAL PAIN IN A MOUSE MODEL OF INFLAMMATORY BOWEL DISEASE (IBD)
Authors: Arzamendi M , Shute A , Chan R , Defaye M , Altier C , Sharkey K A , Geuking M B , Nasser Y 
Published: March 2023

Abstract

Background
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract. Despite achieving endoscopic remission, up to 50% of IBD patients continue to experience chronic abdominal pain, with female patients displaying an increased prevalence. The reason underlying these differences in pain perception is unknown, but the influence of sex hormones represents an important biological source for variability in pain sensitivity. To date, few studies have examined sex differences in chronic visceral pain in IBD.

Purpose
Examine sex-specific differences in post-inflammatory chronic visceral pain in IBD.

Method
We used the post-inflammatory DSS mouse model of chronic visceral pain. Ovariectomy was performed to study the effects of estrogen deficiency; sham surgery was performed as a control. Male, cycling female and ovariectomized female mice were given 2.5% DSS for five days and allowed to recover for 5 weeks. Somatic pain was evaluated using the hot plate and von Frey hair tests. Visceral pain was evaluated using the visceral motor reflex (VMR) to colorectal distension five weeks after DSS treatment. Visceral and somatic pain testing in cycling females was performed in diestrus.

Result(s)
Male, cycling female and ovariectomized female mice given DSS initially lost weight when compared to controls (p&lt;0.0001). Cycling females displayed significantly decreased colitis severity when compared to males [Disease Activity Index at Day 12: 1.41 ± 0.41 cycling females, n=12; 4.41 ± 0.31 males, n=12; p&lt;0.001] but increased severity compared to ovariectomized females [Disease Activity Index at Day 12: 2.0 ± 0.41 ovariectomized females, n=13; 4.77 ± 0.6 cycling females, n=13, p=0.0005]. Increased visceral hypersensitivity was seen in post-inflammatory cycling females compared to post-inflammatory males [VMR at 60mmHg, post-inflammatory cycling females 0.10 ± 0.016, n=10; post-inflammatory males 0.07 ± 0.007, n=10; p=0.032] and post-inflammatory ovariectomized females [VMR at 60mmHg, post-inflammatory sham females 0.072 ± 0.005, n=8; post-inflammatory ovariectomized females 0.047 ± 0.005, n=8; p=0.019]. Thermal hyperalgesia and mechanical allodynia were similar across all groups.

Conclusion(s)
These data suggest that estrogen plays an important role in the severity of colitis severity and post-inflammatory visceral pain. Understanding sex-specific differences in post-inflammatory visceral pain in IBD may allow us to define novel therapeutic approaches for IBD patients.

Disclosure of Interest
None Declared
A59 GLOBAL PROTEOMIC PROFILING OF HUMAN COLONOID MONOLAYERS UNDERGOING IN VITRO CHRONIC DAMAGE
Authors: Sandilya S , Steiner T , Lange P , Rees W 
Published: March 2023

Abstract

Background
An in vitro damage model has been established in our lab using human colonoids grown as 2D monolayers. Upon being subjected to repeated rounds of air-liquid interface (ALI) growth and injury by submergence, these colonoid monolayers lost their barrier integrity and regrowth potential. Changes in mRNA expression and DNA methylation in genes from this human model of injury were similar to those that occur in Inflammatory Bowel Disease (IBD) and colon cancer. Significant morphological changes were observed in these monolayers after they were subjected to subsequent rounds of submergence injury, compared to when they were differentiated in ALI.

Purpose
Submergence injury is predicted to be involved in unfolded protein response (UPR) activation which can specifically alter translation. Hence proteomics studies will help undertand these changes.

Method
To determine if these changes are mirrored in the proteomes of damaged colonoids, we employed a Single-Plot, Solid-Phase-enhanced Sample Preparation (SP3) technology for Mass Spectrometry (MS) based proteomics analysis to characterize these monolayers at baseline, once they were differentiated in ALI, after one and five rounds of injury after differentiation in ALI, and after stimulation with the Toll-like receptor 5 (TLR5) agonist FliC. Hierarchical clustering, enrichment analysis, volcano plot analysis after pre-processing and normalization of the proteomics data set revealed differentially expressed proteins across various groups of monolayers.

Result(s)
Preliminary proteomic data analysis revealed changes in the profile of proteins involved in cellular differentiation, mitochondrial proteins, hypoxia upregulated proteins, those responsible for the maintenance and reorganization of the cytoskeletal structure and Golgi structure. These changes in protein profile may account for the significant morphological changes observed in these monolayers when subjected to submergence injury. Some outliers in monolayers subjected to microbial stimulation included proteins involved in regulation of extracellular matrix dependent motility and components of Adaptor Protein Complexes. Further studies are needed to ascertain if these account for the protective effect of FliC on these monolayers.

Conclusion(s)
This study suggests that the submergence injury to these healthy human derived colonoid monolayers leads to changes in their protein profile which mirror those seen in case of acute and chronic inflammation like IBD and colon cancer. It corroborates with the findings of gene expression and epigenetic analyses using the in vitro model established in our lab.

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CCC

Disclosure of Interest
None Declared
A74 URGENCY FOR BOWEL MOVEMENTS IS A HIGHLY DISCRIMINATORY SYMPTOM FOR ACTIVE DISEASE IN PERSONS WITH IBD (THE MANITOBA LIVING WITH IBD STUDY)
Authors: Kulyk A , Shafer L A , Graff L A , Stone J , Witges K , Targownik L E , Bernstein C 
Published: March 2023

Abstract

Background
The Inflammatory Bowel Disease Symptom Inventory (IBDSI) is a validated patient self-reported measure used to assess IBD disease activity.

Purpose
We aimed to assess the prevalence of symptoms, and examine which symptoms are most associated with disease activity as measured by a symptom index and objective measure of inflammation.

Method
The Manitoba Living with IBD Study is a prospective study of 156 participants with confirmed IBD who completed bi-weekly Inflammatory Bowel Disease Symptom Inventory (IBDSI) surveys. Relative risks (RR) (with 95% confidence interval (CI)), positive and negative predictive values (PPV, NPV), and area under receiver operator curve (AUC) were reported for each symptom to predict active disease defined as: (1) active IBDSI, (2) self-reported flare, and (3) elevated fecal calprotectin (FCAL) (&gt;250µg/g). Analyses were undertaken following stratification based on sex, and disease type (Crohn’s disease (CD) and ulcerative colitis (UC)).

Result(s)
In total, 69.2% of participants were female; 64.7% had CD. Fatigue was the most prevalent symptom in both inactive and active disease, across all 3 disease measures (IBDSI: 24.5% and 75.1%, self-reported flare: 42.2% and 72.2%, FCAL: 46.0% and 60.6%). Absence of fatigue had a high NPV for active IBDSI and self-reporting a flare in both CD and UC. Urgency had a consistently strong NPV, RR and AUC across all three disease measures in both IBD subtypes and sexes. The number of loose/liquid bowel movements predicted elevated FCAL in UC (RR in men = 3.5, 95% CI 1.2-9.9, RR in women = 1.8, 95% CI 1.2-2.7, AUC in men = 0.73, 95% CI 0.59-0.84, AUC in women = 0.65, 95% CI 0.56-0.72), as did blood in stool in females with UC (RR = 1.8, 95% CI 1.2-2.7). In men with CD, excessive bowel gas (RR = 2.0, 95% CI 1.2-3.4) and urgency (RR = 3.9, 95% CI 1.6-9.3) best predicted an elevated FCAL. No symptom was strongly predictive of elevated FCAL in females with CD.

Conclusion(s)
Fatigue was the most prevalent symptom irrespective of disease activity. Urgency stood out as being consistently associated with disease activity, irrespective of the disease measure. Individual symptoms have different impacts on subjective (IBDSI) and objective (FCAL) measures in IBD.

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None

Disclosure of Interest
None Declared
A92 FEMALE AUTHORSHIP IN GASTROENTEROLOGY RANDOMIZED CONTROL TRIALS: 2011 - 2021
Authors: Liu C S , Lin Z X , Kroeker K 
Published: March 2023

Abstract

Background
Although tremendous strides have been made in the participation of women in medicine, female continues to be underrepresented in leadership positions and higher-level academic medicine. An important factor in determining career advancement in academic medicine is the quality and quantity of an individual’s scholarly publications. To date, no study has looked at female authorship in gastroenterology (GI) randomized control trials (RCTs), which remains the gold standard for evaluating intervention effectiveness.

Purpose
The primary outcome is to assess female authorship in gastroenterology randomized control trials from 2011 to 2021, and the secondary outcome is to assess female authorship within GI subspecialty RCT publications.

Method
In this observational study, the gender of the first and last author of gastroenterology RCTs from January 1, 2011 to December 31, 2021 was assessed. Python (v3.8.12) was used to extract publication data from PubMed. A validated algorithm, genderize.io, was used to determine gender. Author first names that cannot be determined by the algorithm were manually searched on publicly-available profiles.

Result(s)
A total of 5690 original gastroenterology RCTs were included from January 1, 2011 to December 31, 2021. The gender of the first and senior authors of the papers was determined for 5668 (99.6%) first authors and 5656 (99.4%) senior authors. Overall, 1937 (34.1%) of the first authors and 1138 (20.0%) of senior authors were female.
There was an increase in the proportion of female first authors over the past decade, from 25.4% in 2011 to 37.8% in 2021 (p&lt;0.05). For senior authors, there was a more gradual increase in female authorship from 14.2% in 2011 to 21.6% in 2021 (p&lt;0.05). (Figure 1)
Within GI subspecialties, 612 RCTs were included for inflammatory bowel disease, 1143 RCTs were included for hepatology, and 1856 RCTs were included for therapeutic endoscopy from January 1, 2011 to December 31, 2021. Further analysis will be performed to determine the gender trend for GI subspecialties.

Image

Conclusion(s)
Female authorship in gastroenterology RCTs has increased from 2011 to 2021, although the rate of senior authorship has increased to a slower extent compared to first authors. Across all years, female authorship in gastroenterology RCTs has been lower than males.

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None

Disclosure of Interest
None Declared
A112 MEASURING COLORECTAL POLYP SIZE USING A NOVEL VIRTUAL SCALE FUNCTION DURING ENDOSCOPIES: A CLINICAL PILOT STUDY
Authors: Djinbachian R , Zarandi-Nowroozi M , Taghiakbari M , von Renteln D 
Published: March 2023

Abstract

Background
Although accurate polyp size measurement is essential for adequately managing patients, we still rely on the endoscopists' subjective visual estimation of polyp size in routine practice.

Purpose
We therefore conducted a clinical pilot study to evaluate relative accuracy of measuring colorectal polyp size during live colonoscopies using a novel virtual scale endoscope (VSE) that superimposes a virtual linear or circular ruler onto objects in the endoscopist's field of view.

Method
We conducted a pilot phase 1 study to evaluate the relative accuracy of VSE for polyp size measurement. We measured polyp size from fresh polypectomy specimens before formalin fixation using a digital vernier caliper. These reference measurements were compared to visual size estimations and VSE measurements obtained during live colonoscopies. The primary outcome was the relative accuracy of visual size estimation versus size estimation using VSE. The secondary outcome was the percentage of measurements that fall within 25% of true polyp size.

Result(s)
43 patients (mean age: 63.3 years; 44.2% male) undergoing screening, surveillance, or diagnostic colonoscopies were included in the pilot study. Colonoscopies were performed by two endoscopists, including one trainee and one staff gastroenterologist. Visual, VSE, and reference size measurements was performed for 17 polyps. VSE during live colonoscopies had a higher relative accuracy of polyp size measurements when compared with visual polyp size estimation 84.3% (95% confidence interval (CI) 77.22% to 91.41%) vs 69.3% (95%CI 61.13% to 77.39%) (p=0.005). The percentage of size measurements that were within 25% of sizes as measured by caliper were 41.2% for visual polyp size estimation and 88.2% for VSE (p=0.02).

Conclusion(s)
We found that a novel endoscope equipped with a virtual scale allowed for significantly higher accuracy in polyp size measurement. A prospective randomized controlled trial is currently underway to validate these results.

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Other

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Fujifilm

Disclosure of Interest
R. Djinbachian: None Declared, M. Zarandi-Nowroozi: None Declared, M. Taghiakbari: None Declared, D. von Renteln Grant / Research support from: Daniel von Renteln is supported by a “Fonds de Recherche du Québec Santé” (FRQS) career development award and has received research funding from ERBE, Ventage, Pendopharm, Fujifilm, and Pentax., Consultant of: Boston Scientific and Pendopharm,
A116 OPTIMIZING CROHN’S DISEASE ENDOSCOPIC SCORING OPERATING CHARACTERISTICS TO ASSIST WITH THE ADVENT OF ARTIFICIAL INTELLIGENCE
Authors: Galts C , Narula N , Wong E , Reinisch W 
Published: March 2023

Abstract

Background
To date, no studies have used Artificial Intelligence (AI) to produce standard endoscopic scores for Crohn’s Disease (CD). These scores are essential to clinical practice and have a major cost in clinical trials.

Purpose
We aimed to re-examine the components of the Simple Endoscopic Score for Crohn’s Disease (SES-CD) and Modified Multiplier (MM-SES-CD) to see if scoring of individual colonic segments could be combined while maintaining predictive value accuracy, thus simplifying scoring for AI.

Method
Data from 279 participants in the UNITI and EXTEND trials as well as an infliximab biosimilar trial (NCT02096861) were used in this retrospective study. The primary outcome was endoscopic remission (ER-1) of the colon, defined as absence of ulcers. Secondary outcomes included alternative definitions of colonic endoscopic remission including SES-CD score of 0 (ER-2), SES-CD &lt;3 (ER-3), and SES-CD reduction by 50% or greater from baseline (colonic endoscopic response).

Result(s)
The mean baseline SES-CD score was 13.7 (SD 7.7) and the mean MM-SES-CD score was 22.8 (SD 12.4). Among all possible colonic segment combinations, the combination of Right + Rectum + worst of Left or Transverse performed best for prediction of one-year ER-1, with fair accuracy (AUC 0.71, 95% CI 0.65-0.78, p &lt; 0.0001). Accuracy of prediction of one-year ER-2 was poor (AUC 0.68, 95% CI 0.62-0.75, p &lt; 0.0001), ER-3 was fair (AUC 0.71, 95% CI 0.65-0.77, p &lt; 0.0001), and prediction of endoscopic response was poor (AUC 0.64, 95% CI 0.56-0.72, p &gt; 0.01). These results were very similar to conventional scoring (without combining any “worst of” segments) with all of the colonic MM-SES-CD scores, with AUCs of 0.70, 0.69, 0.71, and 0.61 for the respective outcomes. Assessing only for the presence of ulcers was as accurate as the full assessment and exclusion of scoring stenosis had minimal impact on scores.

Image

Conclusion(s)
By combining assessment of colonic segments accuracy was maintained compared with currently used endoscopic scoring. Assessing for features other than ulceration had no significant impact on overall scores. By combining colonic segments and limiting assessment to ulceration, it may be simpler to develop AI algorithms reliably scoring endoscopic severity of CD for clinical practice and trials.

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None

Disclosure of Interest
None Declared
A120 ENDOSCOPIC CLOSURE TECHNIQUES FOLLOWING ACUTE IATROGENIC PERFORATION -- AN UPDATED SYSTEMATIC REVIEW
Authors: Buttar J , Enns R , Lam E , Shahidi N 
Published: March 2023

Abstract

Background
Iatrogenic perforation is arguably the most feared adverse event associated with endoscopy. Current American Society for Gastrointestinal Endoscopy (ASGE) and European Society of Gastroenterology Endoscopy (ESGE) guidelines recommend endoscopic closure as the first-line treatment strategy. Historically, this has been achieved using through-the-scope clips (TTSC). Given the emergence of alternative endoscopic closure techniques including over-the-scope clips (OTSC) and endoscopic suturing, we sought to provide an updated review of the literature.

Purpose
To review endoscopic closure techniques following iatrogenic perforation during screening or therapeutic endoscopy.

Method
Based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) Guidelines, an electronic search of MEDLINE and EMBASE from June 1st, 1946 – Oct 10th, 2022 was performed. Inclusion criteria was limited to English full-text original citations, with case reports, and cohorts with &lt; 3 patients excluded. Our primary objective was to assess complete defect closure after attempted endoscopic treatment. Outcomes were stratified by modality (TTSC, OTSC, endoscopic suturing) and chronologically based on a previous well received systematic review.

Result(s)
A total of 2549 citations were identified in our electronic search, of which 34 were included representing 830 perforations. Overall, successful endoscopic closure was achieved in 763 cases (91.9%). When stratified by endoscopic closure techniques, range estimates for successful endoscopic closure was 71% – 100%, 57% - 100%, and 100% for TTSC, OTSC and endoscopic suturing respectively. When stratifying chronologically, an improvement in TTSC closure was identified.

Conclusion(s)
Endoscopic defect closure, including TTSC, OTSC and endoscopic suturing, are effective in the management of iatrogenic perforations with increasing TTSC performance over time. It remains the primary treatment strategy for iatrogenic perforation.

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None

Disclosure of Interest
None Declared
A122 MINIMALLY INVASIVE ENDOSCOPIC RESECTION TECHNIQUES FOR ANORECTAL JUNCTION NEOPLASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Arif A A , Donaldson K , Qian H , Lam E , Shahidi N 
Published: March 2023

Abstract

Background
The management of neoplastic lesions at the anorectal junction remains debated. Endoscopic submucosal dissection (ESD) and endoscopic mucosal resection (EMR) have emerged as the primary endoscopic modalities of choice.

Purpose
We sought to compare the performance of ESD and EMR in resection of anorectal neoplasia.

Method
Two authors independently searched MEDLINE, EMBASE and Cochrane Libraries (Jan 2000 – Aug 2021) for citations evaluating the performance of endoscopic resection techniques (ESD, EMR) for lesions involving the anorectal junction (defined as within 20mm of the dentate line). The frequencies and 95% confidence intervals (95% CI) of technical success (complete removal of all neoplastic tissue at index procedure), clinically significant post-endoscopic resection bleeding (CSPEB), delayed perforation, recurrence and referral to surgery were assessed using random-effects modelling.

Result(s)
We included 11 studies (total 563 patients: 414 ESD, 149 EMR) of which nine were ESD and two were EMR studies. Technical success was achieved in 97.2% overall (95% CI 94.8%-98.5%, ESD 97.5% and EMR range 93.9%-98.0%). Clinically significant post-endoscopic resection bleeding occurred in 4.3% (95% CI 1.6%-11.1%, ESD 3.0% and EMR range 8.2%-11.0%). Delayed perforation was not identified. Recurrence at first screening colonoscopy occurred in 4.8% (95% CI 1.9%-11.7%, ESD 3.0% and EMR range 15.4%-18.4%). Referral to surgery for any reason occurred in 5.9% (95% CI 4.3%-8.0%, ESD 6.9%, EMR range 2.0%-3.0%).

Conclusion(s)
ESD and EMR demonstrate high frequencies of technical success but may have different rates of adverse events and recurrence. More studies investigating lesions at the anorectal junction should be conducted including head-to-head analyses between ESD and EMR for low-risk anorectal junction neoplasia.

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None

Disclosure of Interest
None Declared