bluuebunny/crossref_metadata_2025_split huggingface dataset:
A107 VISCERAL ADIPOSE TISSUE VOLUME DIFFERENTIATES BETWEEN FIBROSTENOTIC AND INFLAMMATORY CROHN’S DISEASE
Authors: Rosentreter R , Cheng E , Shen H , Ma C , Bhayana D , Panaccione R , Raman M , Medellin A , Lu C 
Published: March 2023

Abstract

Background
Creeping fat, a form of visceral adipose tissue (VAT) that wraps the intestinal wall, influences the formation of Crohn’s disease (CD) strictures. The degree of fat wrapping from intestinal stricture resections is correlated with the extent of chronic inflammation, fibrosis, stricture formation, and response to biologic therapy. VAT and subcutaneous adipose tissue (SAT) ratios from CTE (computed tomography) scans are elevated in CD strictures. However, the definition of strictures in these studies has been poorly defined and not included current well-recognized criteria: 1) bowel wall thickness (BWT), 2) narrowed luminal diameter, and 3) pre-stenotic dilation. (PSD).

Purpose
The objective of this pilot study was to assess the relationship of 2D and 3D VAT:SAT ratios with CT stricture parameters in patients with terminal ileal (TI) CD strictures.

Method
2D VAT:SAT ratios from CT’s of CD patients with TI strictures defined as increased BWT, narrowed luminal diameter (&lt; 50% relative to normal adjacent distended loop), and PSD greater than the stricture diameter were retrospectively obtained from a database and chart review. CT’s from fibrostenotic CD patients were sex and BMI matched to patients with only TI inflammatory behaviour. Patient demographics, medication, smoking, and surgical history were also obtained. Analyses were adjusted for age, sex, and BMI covariates. Unpaired t-tests and multi-variable logistic regression analyses were conducted.

Result(s)
Twenty-eight patients with stricturing CD had a significantly greater mean VAT:SAT volume ratio than 29 non-stricturing CD (41.5 cm3 vs 34.2 cm3, p=0.03). Thirty-six percent (10/28) of CD stricture patients had prior ileocolic resection with a mean disease duration of 13.5 years (range 0-48). The median ileal BWT (7.0 mm, range 4.0-13.0 mm) for the stricturing group was significantly greater than those with inflammatory behaviour (BWT 2.0 mm, p&lt;0.0001). The median luminal diameter and PSD for the stricture group was 2.0 mm (range 0 - 14.0 mm), and 3.0 cm (range 1.0 - 7.3 cm), respectively.

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Conclusion(s)
Fibrostenotic TI CD patients have increased VAT:SAT ratios in comparison to those with only inflammatory behaviour. These pilot VAT:SAT results provide an initial foundation for further studies to assess its predictive role in responsiveness of medical or surgical therapies in stricturing CD.

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None

Disclosure of Interest
None Declared
A123 COMPARING SIZE MEASUREMENT OF SIMULATED COLORECTAL POLYPS WHEN USING A NOVEL VIRTUAL SCALE ENDOSCOPE, ENDOSCOPIC RULER OR FORCEPS: A BLINDED RANDOMIZED TRIAL
Authors: Djinbachian R , Taghiakbari M , Haumesser C , Zarandi-Nowroozi M , Abou-Khalil M , Sidani S , Liu J , Panzini B , von Renteln D 
Published: March 2023

Abstract

Background
Accurate polyp size measurement is important for guideline conforming choice of polypectomy techniques and subsequent surveillance interval assignments. Some endoscopic tools (forceps or endoscopic rulers [ER]) exist to help with visual size estimation. A virtual scale endoscope (VSE) has been developed that allows superimposing a virtual measurement scale during live endoscopies.

Purpose
Our aim was to evaluate the performance of VSE when compared to ER and forceps-based measurement.

Method
We conducted a randomized trial to evaluate the relative accuracy of size measurement of simulated colorectal polyps when using: VSE, ER, and forceps. Six endoscopists performed 60 measurements randomized at a 1:1:1 ratio using each method. Primary outcome was relative accuracy in polyp size measurement. Secondary outcomes included misclassification of sizes at the 5, 10, and 20mm thresholds.

Result(s)
A total of 360 measurements were performed. The relative accuracy of biopsy forceps, ER, and VSE was 78.9% (95%CI=76.2-81.5), 78.4% (95%CI=76.0-80.8), and 82.7% (95%CI=80.8-84.8). VSE had significantly higher accuracy compared to biopsy forceps (p=0.02) and ER (p=0.006). VSE misclassified a lower percentage of polyps &gt;5mm as ≤5mm (9.4%) compared to forceps (15.7%) and ER (20.9%). VSE misclassified a lower percentage of ≥20mm polyps as &lt;20mm (8.3%) compared with forceps (66.7%) and ER (75.0%). 25.6%, 25.5%, and 22.5% of polyps ≥10mm were misclassified as &lt;10mm with ER, forceps, and VSE, respectively.

Conclusion(s)
VSE had significantly higher relative accuracy in measuring polyps compared to ER or forceps assisted measurement. VSE improves correct classification of polyps at clinically important size thresholds.

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None

Disclosure of Interest
R. Djinbachian: None Declared, M. Taghiakbari: None Declared, C. Haumesser: None Declared, M. Zarandi-Nowroozi: None Declared, M. Abou-Khalil: None Declared, S. Sidani: None Declared, J. Liu: None Declared, B. Panzini: 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,
A132 A CASE OF COLONIC MALAKOPLAKIA PRESENTING AS A LARGE CECAL MASS : NOT EVERY POLYP HAS TO LOOK LIKE A NAIL
Authors: Jiang S X , Xiong W , Shahidi N 
Published: March 2023

Abstract

Background
Malakoplakia is a rare inflammatory condition, commonly affecting the genitourinary system of immunocompromised patients. Gastrointestinal malakoplakia has been reported in the literature, with previous endoscopic findings mimicking mass lesions.

Purpose
To describe a case of colonic malakoplakia after referral for endoscopic management of a large non-pedunculated colorectal polyp.

Method
Case report and review of the literature.

Result(s)
Case Report
An 80-year-old male with chronic kidney disease and remote renal transplant on immunosuppressive therapy (mycophenolate mofetil, tacrolimus, prednisone) was referred for endoscopic resection for a large non-pedunculated colorectal polyp in the cecum. Original presenting symptoms included chronic diarrhea, iron deficiency anemia, and fecal immunochemical test (FIT) positivity. A repeat colonoscopy demonstrated a 40mm Paris 0-IIA plaque-like lesion in the cecum with optical features not in keeping with adenomatous or serrated histopathology. Biopsies were performed with histopathology demonstrating normal colonic mucosa with confluent sheets of histiocytes with concentrically layered cytoplasmic inclusions, in keeping with malakoplakia.
Literature review
Malakoplakia, Greek for “soft plaque”, is a rare inflammatory condition characterized by impaired dysfunction in macrophages leading to the accumulation of incompletely degraded bacteria in phagolysosomes. Histologically, this appears as concentrically layered cytoplasmic inclusions, comprising the pathognomonic Michaelis-Gutmann bodies. Many bacterial organisms have been implicated in the development of malakoplakia, with E. coli being the most common; specifically in immunocompromised patients, whether from immunosuppressive medications, immunodeficiency syndromes, or clinical conditions precluding effective immune function. Malakoplakia commonly presents as a mass-like lesion and has been found in all organs, most commonly in the genitourinary system. Diagnosis is made by biopsy and allows for appropriate treatment, which is most commonly a reduction in immunosuppressive therapy and antibiotic therapy.

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Conclusion(s)
Malakoplakia is rare but should be considered when a lesion with atypical optical evaluation features is found in immunocompromised individuals or those with recurrent infections.

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None

Disclosure of Interest
None Declared
A178 ELUCIDATING THE ROLE OF THE LEUCINE-RICH REPEAT KINASE 2 G2019S MUTATION IN CROHN’S DISEASE PATHOGENESIS USING A CITROBACTER RODENTIUM INFECTIOUS COLITIS MODEL
Authors: Samman B , Yadav J , Bayer G , Foerster E G , Chen L , Rocha J D B , Girardin S E , Philpott D J 
Published: March 2023

Abstract

Background
Associations have been found linking certain LRRK2 kinase domain gain-of-function variants, such as G2019S, to the development of Crohn’s disease and Parkinson’s disease, yet their exact roles in pathogenesis remains elusive. LRRK2 is most robustly expressed in circulating and tissue-resident immune cells, such as neutrophils, lymphocytes, and macrophages. Myeloid cells deficient in LRRK2 exhibit defective antimicrobial responses, such as reduced production of reactive oxygen species in response to microbial stimuli and reduced bactericidal activity in response to infection. As an enteric colitis-inducing extracellular pathogen, Citrobacter rodentium can help us better understand the consequences of LRRK2 kinase hyperactivity on intestinal inflammation by correlating pathogen burden with key host response parameters over the course of infection.

Purpose
To investigate the effects of the Crohn’s and Parkinson’s disease-associated Lrrk2 G2019S hyper-kinase mutation on pathogen burden and colonic inflammation in the context of C. rodentium-induced infectious colitis.

Method
Wild-type and Lrrk2 G2019S mutant mice (7-8 weeks old) were fasted for 4 hours then infected with 1 x 108 CFU of C. rodentium in a 3% NaHCO3 solution by oral gavage. Body weight, faecal pathogen burden, and faecal lipocalin-2 (Lcn2) concentrations were measured at 2, 4, 7, 9, 10, 12, and 14 days post-infection (DPI). Systemic pathogen burden (as measured in the mesenteric lymph nodes and spleen), colon length, colonic inflammatory gene expression, and histopathological scoring were assessed at 7, 10, and 14 DPI.

Result(s)
While G2019S mice exhibited marginally higher C. rodentium loads at certain timepoints, no significant differences were found in overall pathogen burden or pathogen clearance rates between genotypes over the first 14 days of infection. Faecal pathogen load peaked at 7-9 DPI in both WT and G2019S mice, which correlated with detectable levels of C. rodentium in the mesenteric lymph nodes and spleens of some mice at 7 DPI. Lcn2 secretion and the expression of inflammatory and antimicrobial genes of interest were induced robustly over the course of infection. They peaked and ebbed at timepoints correlating well with pathogen burden; however, no significant differences were observed between WT and G2019S mutant mice at the various timepoints assessed.

Conclusion(s)
Mice expressing the G2019S Lrrk2 mutation exhibit neither defective pathogen control nor deleterious hyperinflammation – compared to WT mice – when infected with C. rodentium. Further research will aim to investigate the role of this Lrrk2 variant in additional models of intestinal inflammation.

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CCC, CIHR

Disclosure of Interest
None Declared
A204 COST-EFFECTIVENESS OF THERAPIES AFTER FAILURE OF CONVENTIONAL THERAPY FOR PATIENTS WITH MODERATE-TO-SEVERE ULCERATIVE COLITIS IN THE CANADIAN HEALTHCARE SYSTEM
Authors: Hagerman C , Kroeker K I , Dieleman L , Peerani F , Baumgart D C , Wong K , Halloran B 
Published: March 2023

Abstract

Background
Ulcerative colitis (UC) is a chronic inflammatory disease of the colon which requires ongoing medical therapy. The therapeutic options for moderate-to-severe UC include biologics and small molecules, which are effective but come with a significant cost. As such, their exact positioning in the therapeutic algorithm remains unclear.

Purpose
The aim of our study was to assess and compare the cost-effectiveness of infliximab, adalimumab, vedolizumab, golimumab, ustekinumab and tofacitinib for the management of moderate-to-severe UC from the perspective of the Canadian public healthcare system.

Method
A Markov model was constructed to simulate the disease course of UC patients after initiating each available therapy. Drug costs were obtained from the Alberta Health Drug Benefit List and the remaining costs were determined from the CIHI Patient Cost Estimator. Transition probabilities were obtained from a review of the literature, and loss of response and complication rates were obtained from randomized controlled trials. Our main analysis used a time horizon of 5 years, and time horizons of 1- and 10-years were also assessed in our sensitivity analysis. Probabilistic sensitivity analysis was performed to characterize uncertainty related to all parameters.

Result(s)
Infliximab costs $26,611 per quality-adjusted life year (QALY) using a 5-year time horizon. Adalimumab costs $20,783 per QALY. Vedolizumab costs $40,553 per QALY. Golimumab costs $34,316 per QALY. Ustekinumab costs $26,366 per QALY. Lastly, tofacitinib costs $25,572 per QALY. At a willingness-to-pay threshold of $50,000 per QALY, sensitivity analysis revealed that infliximab, adalimumab, vedolizumab, golimumab, ustekinumab and tofacitinib had a 36%, 12%, 1%, 1%, 44% and 6% probability of being cost-effective, respectively.

Conclusion(s)
Our economic model concluded that adalimumab is the most cost-effective first-line therapy for UC patients who have failed conventional therapy.

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None

Disclosure of Interest
None Declared
A219 BIOLOGIC USE DURING PREGNANCY IN WOMEN WITH INFLAMMATORY BOWEL DISEASE AND ASSOCIATED NEONATAL OUTCOMES: A RETROSPECTIVE CHART REVIEW
Authors: Jeyakumar Y , O'Connor K , Huang V 
Published: March 2023

Abstract

Background
Biologics are the mainstay of therapy for patients with advanced inflammatory bowel disease (IBD). Most biologics readily undergo placental transfer during the second trimester and remain detectable in infant serum for up to 12 months. Therefore, most clinical guidelines currently recommend avoiding live vaccines in the first 6 to 12 months for exposed infants. In Canada, the rotavirus vaccine is the only live vaccine administered before 6 months. Emerging evidence is suggesting that the vaccine may safely be given to infants with normal immune function, even if serum biologic level is detectable. Specialist assessment of infant immune function may help guide decision-making about rotavirus vaccine administration, but there remains a large gap in our knowledge of the impact of biologic exposure on the immune function of infants, necessitating further study.

Purpose
In this single-centre retrospective chart review, we aim to study the clinical outcomes, immune function, and rotavirus vaccine recommendations for infants exposed to biologics in utero during their first year of life.

Method
The study included mothers seen at the Pregnancy IBD Clinic at Mount Sinai Hospital in Toronto, ON, who were offered a referral to the Special Immunization Clinic (SIC) at The Hospital for Sick Children due to biologic exposure in utero. Data was collected on the recommendations made by paediatric specialists at SIC, based on complete blood count, lymphocyte phenotyping, and T-cell receptor excision analysis. Data was obtained on adverse neonatal outcomes in the first year of life, including prematurity, congenital malformations, and infections based on post-partum surveys completed by mothers and follow-up letters from SIC.

Result(s)
43 patients were referred to and seen by paediatric specialists at SIC between 2 to 12 months of age. 18 infants (42%) were exposed to Adalimumab in utero, 16 (37%) to Infliximab, 5 (12%) to Vedolizumab, and 4 (9%) to Ustekinumab. The rotavirus vaccine was recommended to 34 infants (81%) and not recommended to 3 (7%) for reasons including gastrointestinal illness, neutropenia, and low lymphocyte counts. Recommendation is pending for 6 infants (14%). Two infants (5%) had premature births. Four infants (9%) were admitted to the NICU for reasons including respiratory distress, and prematurity (9%). One infant (2%) had a congenital malformation, specifically bilateral sensorineural hearing loss. Six infants (14%) had upper respiratory tract infections, none of which required hospital admission or antibiotics.

Conclusion(s)
This study is currently in progress. Further data is required to assess whether biologic exposure in utero has a significant impact on neonatal immune function, especially beyond the first year of life, and whether there is a significant difference in vaccine recommendations and response based on the type of biologic received.

Disclosure of Interest
None Declared
A226 EFFECT OF PHYSICAL ACTIVITY AMONG INDIVIDUALS WITH QUIESCENT OR MILDLY ACTIVE INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW
Authors: Oketola B , Akinrolie O , Webber S , Singh H , Askin N , Rabbani R , Abou-Setta A 
Published: March 2023

Abstract

Background
Individuals with quiescent inflammatory bowel diseases (IBD) can continue to have several symptoms. Physical activity (PA) can improve immunological response and psychological health.

Purpose
We performed a systematic review of trials investigating the safety and efficacy of PA as an adjunct therapy to manage persistent symptoms in quiescent or mildly active IBD.

Method
We searched for randomised controlled trials (RCTs) and nonrandomised non-controlled trials (non-RCTs) in eight databases, trial registries and conference proceedings, published in English between 2011 and 2021. We focused on trials in adults (&gt;18 years) using any form of PA as an adjunct therapy to medical therapy. Outcomes of interest were health-related quality of life, fatigue, joint pain, abdominal pain, stress, anxiety, and depression.

Result(s)
From 10,862 retrieved citations, we identified seven RCTs and one non-RCT that met our inclusion criteria. All trials deemed PA safe for individuals with quiescent or mildly active IBD. Clinical heterogeneity was noted among the trials for all outcomes. Six RCTs utilized parallel-group design while one utilized a cross-over design. Seven trials provided partially or fully supervised PA interventions, and one provided no supervision. All trials used different types of PA, which varied between running, resistance training, yoga, and aerobic exercises. The trials used different parameters to measure PA intensity including Peak Power Output, Resistance Intensity Scale for Exercise, percentage of maximum heart rate, ability to talk while running. Heterogeneity was noted in the duration and frequency of PA.

Conclusion(s)
Even though PA is safe for individuals with quiescent or mildly active IBD, heterogeneity in available trials make it difficult to ascertain precise estimates of treatment effect. This also presents a challenge when determining the specific modes of PA that are beneficial for individuals with quiescent or mildly active IBD. This highlights the need for standardization of the definitions of parameters involved in PA in IBD research.

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CAG

Disclosure of Interest
None Declared
A230 A MISSENSE MUTATION IN GOBLET CELL PROTEIN FCGBP ALTERS THE GLYCOMIC PROFILE AND FUNCTION OF THE COLONIC MUCUS BARRIER
Authors: Gorman H , Moreau F , Zandberg W , Bergstrom K , Chadee K 
Published: March 2023

Abstract

Background
MUC2 mucin, produced by colonic goblet cells, forms a mucus bilayer that provides a physical barrier between potential pathogens in the lumen and the underlying epithelial cells. Mucus is thus the first line of innate host defense in the gastrointestinal (GI) tract. Many GI diseases including inflammatory bowel disease and colon cancer affect the glycosylation of mucus. Goblet cells produce a variety of proteins that are associated with the mucus layer. Of these proteins, FCGBP is of significant interest due to its structural similarities to MUC2 mucin with unknown functions. In this study, we investigated how a missense mutation in FCGBP altered the glycosylation of goblet cell MUC2 and affected its barrier functions.

Purpose
Hypothesis: A missense mutation in FCGBP results an impaired mucus layer by the altering glycomic profiles of goblet cell mucins. Specific aims:
1) To determine mechanistically how FCGBP impeded the structural integrity of the mucus layer
2) To quantify MUC2 glycoprotein modifications in the altered mucus layer

Method
To investigate whether FCGBP impaired mucus barrier functions, two cell types were investigated: wildtype LS174T (WT) MUC2 mucus-producing goblet cells and LS174T cells with a missense mutation in FCGBP (FCGBP MS). To determine if FCGBP MS led to loss in barrier function in the mucus layer, the penetration of 0.2, 1, and 2 μm fluorescent beads (to mimic bacteria) through the mucus layer were quantified. To determine if the differences in penetrability were caused by differences in MUC2 glycosylation in the goblet cell lines, sensitive glycomic analyses were performed by high-performance liquid chromatography-mass spectrometry (HPLC-MS) and capillary electrophoresis with laser-induced fluorescence detection (CE-LIF). Both intact cells and isolated MUC2 mucin granules were analyzed. To determine if differences in the glycomic profiles was caused by differences in glycotransferases, RT-PCR was performed on over 30 human glycosyltransferases.

Result(s)
FCGBP MS cells exhibited significant loss in MUC2 mucus barrier function as quantified by fluorescent beads penetration through the mucus layer in a temporal manner. FCGBP MS cells exhibited an altered glycomic profile with a notable increase in sialylated glycans as quantified by HPLC-MS. The increase in sialylated glycans was associated with a significant increase in sialyl-transferase expression in FCGBP MS cells.

Conclusion(s)
These data demonstrate that a single missense mutation in FCGBP altered the penetrability of the mucus layer associated with an increase in sialylated proteins, a signature hallmark of numerous colonic diseases. FCGBP was critical in providing structural integrity of the mucus layer and maintenance of goblet cell glycosylation profiles.

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CIHR

Disclosure of Interest
None Declared