bluuebunny/crossref_metadata_2025 huggingface dataset:
A104 PATIENT AND PUBLIC INVOLVEMENT (PPIN) IN IBD RESEARCH - A SCOPING REVIEW
Authors: Elsolh K , Neary E , Seleq S , Gimpaya N , Scaffidi M , Khan R , Grover S
Published: February 2022

Background

Over the past 10 years, interest in patient and public involvement (PPIn) in research has grown. Several arguments support the engagement of patients as partners in the research process. Patients with lived experience of a condition can offer their knowledge to study design as experience-based experts, helping researchers incorporate patient-pertinent outcomes. PPIn has also been shown to boost patient enrolment and retention in clinical trials. Benefits, challenges, and best practices of PPIn have been examined in other fields. However, to date, no study has examined PPIn in inflammatory bowel disease (IBD) research. Many factors amenable to research involvement may impact IBD patients’ quality of life, including disease morbidity, complications, and efficacy/side effects of therapy.

Aims

This review aims to characterize methods of PPIn in IBD research and highlight themes relating to best practices, benefits, and challenges.

Methods

We ran a systematic search on MEDLINE, EMBASE, and Cochrane for all IBD research studies in which IBD patients were involved in the research process. PPIn included but was not limited to patient input in one of the following 3 stages: Study Design (prioritization of research topics, outcome selection, study tool development), Study Execution (recruitment, data collection & analysis), and Dissemination of Research. After abstract and full-text screening, 14 studies were selected.

Results

Patients were recruited for PPIn through IBD and patient organizations (7/14), outpatient clinics (4/14), tertiary care sites (2/14), and pre-existing patient advisory groups (1/14). The majority of studies (11/14) engaged patients in the development of study materials, which included a physical activity intervention for stoma patients, an IBD pregnancy decision aid, and a quality of life questionnaire. Two studies interviewed patients to determine comprehensibility of survey items and guide revisions. One study involved patients in data analysis and manuscript development. Most consultations were open-ended, including focus groups (8/14) and semi-structured interviews (3/14). According to study authors, PPIn helps guide IBD research priorities by focusing on patient-relevant issues. Authors also cited the role of PPIn in designing patient-friendly study tools. One challenge reported by 2 studies was that PPIn requires patients to have access to high-quality information and requires a significant time commitment, which may contribute to demographic biases.

Conclusions

The majority of IBD studies engaged patients in an open-ended format and were engaged in study design, particularly in developing study materials. Authors recommend continuous involvement of patients throughout the research process to address their research priorities.

Funding Agencies

None
A105 ENDOSCOPIC MUCOSAL RESECTION AND ENDOSCOPIC SUBMUCOSAL DISSECTION FOR ILEOCECAL VALVE NEOPLASIA: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Donaldson K , Arif A A , Qian H , Lam E , Shahidi N C
Published: February 2022

Background

Neoplastic lesions at the ileocecal valve (ICV) represent a complex lesion subgroup given the unique anatomical characteristics of this location. Both endoscopic mucosal resection (EMR) and endoscopic submucosal dissection (ESD) are established techniques for colorectal neoplasia but comparative analyses for ICV lesions are lacking.

Aims

Evaluate the performance of EMR and ESD for ICV neoplasia.

Methods

Between Jan 2000 to Aug 2021, two authors independently searched MEDLINE, EMBASE and Cochrane Libraries for relevant citations evaluating the performance of either EMR and/or ESD for ICV neoplasia; defined as lesions involving at least one component of the ICV complex. The rate of technical success (complete removal of all neoplastic tissue during index procedure of those lesions deemed amenable to endoscopic resection), clinically significant post-endoscopic resection bleeding (CSPEB), delayed perforation, and recurrence were assessed. Meta-analysis was performed using a random-effects model.

Results

Nine studies (367 patients, 252 EMR, 115 ESD) were included in the analysis. Successful removal of all visible neoplastic tissue of those deemed amenable to endoscopic resection was 98.1% (EMR 99.6%, ESD 97.4%). Of note, only 2 studies, both assessing EMR, provided data on lesions which were not considered for endoscopic resection ranging from 5.6–23.7%. Average procedure time ranged from 45–49 minutes for EMR and 52–191 minutes for ESD. Clinically significant post-endoscopic resection bleeding occurred in 6.2% (EMR 9.4%, ESD 4.4%). Delayed perforation occurred in 0.6% (EMR 0.4%, ESD 2.0%). Recurrence occurred in 3.1% (EMR 13.2%, ESD 1.9%).

Conclusions

Endoscopic resection, both with EMR and ESD, demonstrates high technical success and good adverse event profiles amongst ICV neoplasia deemed amenable for endoscopic resection.

Funding Agencies

None
A107 WHAT SIZE CUT-OFF LEVEL SHOULD BE USED TO IMPLEMENT OPTICAL POLYP DIAGNOSIS?
Authors: Taghiakbari M , Pohl H , Djinbachian R , Anderson J , Metellus D , Barkun A N , Bouin M , von Renteln D
Published: February 2022

Background

The risk of advanced pathology and potential mismanagement increases with polyp size while performing optical diagnosis. We hypothesized that a lower polyp size cut-off (e.g., 1–3 mm) would be associated with a lower risk of misclassifying advanced neoplasia or even cancer when using optical diagnosis.

Aims

This study aimed to evaluate the proportion of patients undergoing inadequate surveillance intervals associated with different size cut-offs when using optical diagnosis.

Methods

In a post-hoc analysis of three prospective studies, the use of optical diagnosis was evaluated for three polyp size groups: 1–3, 1–5, and 1–10 mm. The primary outcome was the proportion of patients in which advanced adenomas were found and optical diagnosis resulted in delayed surveillance in each group. Secondary outcomes included agreements between surveillance intervals based on high-confidence optical diagnosis and pathology outcomes, reduction in histopathological examinations, and proportion of patients who could receive an immediate surveillance recommendation.

Results

We included 3374 patients (7291 polyps ≤10 mm) undergoing complete colonoscopies (median age 66.0 years, 75.2% male, 29.6% for screening). Among polyp sized 1–3 mm, 1–5 mm, and 1–10 mm, 0.5%, 0.6%, and 1.2% of polyps, respectively, were found to have advanced pathology ( P <.0001). The percentage of patients with advanced adenomas and either 2- or 7- year delayed surveillance intervals (n=79) was 3.8%, 15.2%, and 25.3% for size cut-offs of 1–3, 1–5, and 1–10 mm polyps, respectively ( P<.0001). Surveillance interval agreements between pathology and high-confidence optical diagnosis for the three groups were 97.2%, 95.5%, and 94.2%, respectively. In the cohort of patients in which patients with normal colonoscopy, polyps >10 mm, and poor bowel preparation were excluded, the surveillance interval agreements between pathology and high-confidence optical diagnosis for the three groups were 96.2%, 93.6%, and 92.1%, respectively. Total reduction in pathology examinations for the three groups were 33.5%, 62.3%, and 78.2%, respectively. Furthermore, optical diagnosis could have allowed 41.0%, 58.2%, and 73.3% of patients, respectively, to be given immediate surveillance interval recommendations.

Conclusions

This study showed that limiting optical diagnosis to polyps 1–3 mm resulted in an excellent safety profile with a very low risk for inappropriate management of advanced adenomas, which makes routine clinical implementation of the “resect and discard” strategy feasible. Implementing a 3 mm cut-off could be a starting point for endoscopists to feel comfortable with the “resect and discard” strategy, with the potential of implementing a 5 mm cut-off, once optical diagnosis becomes more popular, and endoscopists become more comfortable with its use.

Funding Agencies

NoneNA
A116 CLINICAL OUTCOMES OF PATIENTS UNDERGOING BALLOON-ASSISTED ENDOSCOPY FOR SUSPECTED SMALL BOWEL BLEEDING
Authors: Guo J , Cave K , Halloran B , Zepeda-Gomez S
Published: February 2022

Background

Obscure gastrointestinal bleeding (OGIB) accounts for approximately 50% of all GI bleeds. This refers to bleeding from an unknown etiology despite initial investigations with upper endoscopy and colonoscopy, of which 75–80% is attributed to a small bowel source, also termed as small bowel bleeding. Various diagnostic and therapeutic modalities have been used to investigate sources of OGIB. Balloon-assisted enteroscopy (BAE) is a useful procedure for managing small bowel bleeding, with reported diagnostic and therapeutic rates up to 87% and 80%, respectively.

Aims

The aims of this study are to evaluate the outcomes of patients with OGIB who have undergone BAE, as well as to explore correlations between the timing of BAE and clinical outcomes.

Methods

We performed a retrospective review of 342 patients who underwent BAE at a tertiary referral centre between 2016 to 2021, of which 116 underwent evaluation for OGIB. Aside from gender and age, preprocedural variables including endoscopy indication, timing from video capsule endoscopy (VCE) and overt GI bleed were collected to allow for further stratification of data. Endoscopic variables including modality, findings, and therapeutic interventions were used to calculate diagnostic and therapeutic yields. Furthermore, the association between timing of BAE after VCE and clinical outcomes including rebleeding rate, diagnostics and therapeutic yields were assessed. All data analyses were performed with SPSS.

Results

The overall diagnostic yield was 70.3%. Patients with active overt bleeding were found to have a higher yield compared to those with occult and inactive overt bleeding (78.6% vs 72.5% vs 64.6%, respectively). Amongst all OGIB presentations, the most common findings were vascular lesions including angiodysplasia, arteriovenous malformations, and dieulafoy lesions. The majority of lesions were found within the proximal jejunum. Subgroup analysis did not show a statistically significant difference in diagnostic yields between BAE with and without prior VCE (75.9% vs 77.8, P = 0.605). The therapeutic yield was 51.1% with a higher yield found in those presenting with active overt bleeds compared to occult and inactive overt cases. Compared to BAE performed after 30 days of overt GI bleeding, those completed within 30 days was found to have a higher diagnostic and therapeutic rate (80.0% vs 60.0%, 70.0 vs 30.0%, respectively).

Conclusions

Balloon-assisted enteroscopy continues to be an effective diagnostic and therapeutic modality for the investigation of obscure gastrointestinal bleeding. Our retrospective study shows a higher diagnostic and therapeutic rate in those presenting with active overt GI bleed as well as those who underwent BAE within 30 days of overt GI bleeding

Funding Agencies

None
A126 ONCE IS BY CHANCE, TWO IS A TREND: A RECURRING FINDING WITHIN THE POST-RESECTION DEFECT
Authors: Alshihry I A , Tomaszewski M , Shahidi N C
Published: February 2022

Background

A 74-year-old male was referred for the management of a large non-pedunculated colorectal polyp in the transverse colon. On optical evaluation, including high-definition white-light and narrow-band imaging (NBI), a 30mm 0-IIA non-granular large non-pedunculated colorectal polyps (LNPCP) was identified with optical features in keeping with adenomatous histopathology (NBI International Colorectal Endoscopic II, Japan NBI Expert Team IIA, Kudo Pit Pattern III/IV). Endoscopic mucosal resection (EMR) was performed. During sequential tissue transection and evaluation of the expanding submucosal defect a hole with a surrounding white-cautery ring was identified in keeping with significant deep mural injury. However, on careful evaluation a cystic structure was identified with a viscous amorphous substance emanating from it. Endoscopic resection of the lesion was completed with subsequent through-the-scope mechanical clip closure of the area of concern.

Aims

case report showing unique finding of intra-cellular mucin emanating from the post-resection defect has been identified as a potential intra-procedural finding of a mucinous adenocarcinoma

Methods

Endoscopic mucosal resection of a mid transverse colon polyp

Results

Histopathology identified a villous adenoma with high-grade dysplasia with submucosal mucin and an indeterminate focus of carcinoma; highly suspicious for a mucinous adenocarcinoma. No muscularis propria was identified. After multi-disciplinary review, the patient underwent laparoscopic right hemicolectomy with no evidence of invasive disease.

Conclusions

Recently coined as the “fish-eye” polypectomy defect, intra-cellular mucin emanating from the post-resection defect has been identified as a potential intra-procedural finding of a mucinous adenocarcinoma; specifically, in an otherwise benign appearing LNPCP based on real-time optical evaluation. Herein we describe the second case in the literature. This reinforces the importance of meticulous evaluation of the post-resection defect to stratify this finding from deep mural injury. Moreover, further understanding of the clinical ramifications of this unique intra-procedural finding is needed.

Funding Agencies

None
A132 ACHALASIA FOLLOWING A SARS-COV-2 INFECTION: A CASE REPORT
Authors: Zeidan E , Desilets E , Bouin M , Maniere T
Published: February 2022

Background

SARS-CoV-2 is a novel virus currently causing a major pandemic. Recent studies have shown that SARS-CoV-2 has an affinity to ACE2 receptors which are present in the olfactory epithelium as well as the pulmonary and gastrointestinal (GI) systems. It is stipulated that these receptors are responsible for the entry of the virus into cells explaining the respiratory and GI symptoms of this infection. The anosmia related to COVID-19 is likely due to an aberrant immune response to the virus rather than direct damage to the olfactory epithelium. Similarly, achalasia is also believed to result from an aberrant immune response through which there is degeneration of inhibitory neurons in the myenteric plexus. In this case report, we present the first case of achalasia thought to be linked to a SARS-CoV-2 infection in contemporary literature.

Aims

We hypothesize that SARS-CoV-2 caused an aberrant immune response in our patient, leading him to develop achalasia. We hope to expose clinicians to this potential complication of COVID-19, allowing them to consider it sooner in their differential.

Methods

The patient’s file was reviewed to extract the relevant information. A second gastroenterologist’s opinion was obtained on the manometry to confirm the diagnosis of type III achalasia.

Results

A 61-year-old man with a medical history of myasthenia gravis, chronic obstructive pulmonary disease, hypothyroidism, and chronic renal failure was treated in our establishment for a SARS-CoV-2 pneumonia. He experienced new severe dysphagic symptoms, regurgitations, and lost 10 pounds during his hospitalization. He also developed anosmia and diarrhea. A CT-scan of his neck and thorax showed no extrinsic compression of his esophagus. No neoplasm was found on his gastroscopy. A barium study was then conducted showing a stagnation of contrast in the distal third of his esophagus. No relaxation of the inferior gastroesophageal sphincter was noted. A manometry was then performed and confirmed a type III achalasia. The mean lower esophageal sphincter residual pressure was elevated at 43.7 mmHg. A calculated 69% of wet swallows were premature contractions with a distal latency value less than 4.5 seconds. The mean distal contractile integral was 13613 mmHg. This corroborates the spastic nature of type III achalasia.

Conclusions

Considering that our patient developed anosmia and knowing its pathogenesis in the context of COVID-19, an inappropriate immune response to SARS-CoV-2 could have equally taken place in the esophagus. This inflammatory response might have caused the degeneration of the inhibitory neurons in the myenteric plexus responsible for the achalasia. Furthermore, given the fact that our patient had diarrhea, this suggests that the virus has a GI tropism supporting our hypothesis. We therefore believe that achalasia may be a potential complication of COVID-19.

High resolution esophageal motility study showing a type III achalasia pattern.

Funding Agencies

None
A134 UES MANOMETRIC PARAMETERS IN ESOPHAGEAL MOTILITY DISORDERS
Authors: Woo M , Randall D , Gupta M , Miles M , Li D Y , Nasser Y , Andrews C N
Published: February 2022

Background

Upper esophageal sphincter (UES) function may be evaluated manometrically using a solid-state high-resolution manometry (HRM) system, which allows for the measurement of manometric parameters specific to the UES. While many of these parameters have yet to be validated for use in clinical practice, there is some suggestion that there may be an association between esophageal motility and UES function.

Aims

We aimed to identify the relationship between UES manometric variables and high-resolution esophageal manometry (HREM) diagnoses.

Methods

A retrospective analysis of HREM studies was performed between 2019 and 2021. Extraction of esophageal and UES manometric variables were performed. UES manometric values of interest included: mean basal pressure (mmHg), mean residual pressure (mmHg), relaxation time-to-nadir (ms), relaxation duration (ms), and recovery time (ms). Relationships between manometric diagnosis (Chicago Classification version 3) and UES manometric variables were explored. All values are expressed a medians and group means were compared with the non-parametric Mann-Whitney U test.

Results

2119 symptomatic patients underwent HREM over the study period. Manometric diagnoses were achalasia (72 patients), esophagogastric junction outflow obstruction (286), absent contractility (108), distal esophageal spasm (53), jackhammer esophagus (32), and ineffective esophageal motility (694). 886 patients had no specific motility disorder; 643 of whom had ≤ 20% ineffective swallows and were considered symptomatic controls.

Patients with achalasia had significantly higher mean basal pressures (63.2 vs. 54.4, p = .001), mean residual pressure (3.8 vs. -1.9, p < .001), relaxation-time-to-nadir (182.0 vs. 142.0, p = .005), relaxation duration (820.5 vs. 708.0, p < .001) and recovery time (623.0 vs. 562, p < .001) compared to control patients. Among patients with achalasia, the presence of panesophageal pressurization correlated weakly with recovery time (R2 .3, p = .03). Patients with ineffective esophageal motility had significantly higher mean basal pressures (61.7 vs. 54.0, p < .001).

Among all patients, patients with incomplete bolus clearance (≥ 30%) had significantly higher UES mean basal pressure (58.9 vs. 54.6, p = .004), mean residual pressure (-.62 vs. -2, p < .001), relaxation duration (724.0 vs. 707.0, p = .014) and recovery time (580 vs. 558.0, p < .001).

Conclusions

Patients with achalasia may have higher basal and residual UES pressures, and slower relaxation compared to patients with normal esophageal motility. This may reflect dynamic changes of the UES in response to obstruction at the esophagogastric junction. Elevated UES pressures are also seen in patients with ineffective esophageal motility, potentially reflecting a response to poor bolus clearance. More work needs to be done to validate these parameters in clinical practice.

Funding Agencies

None
A138 TEMPORAL CHANGES IN SURVIVAL OF METASTATIC COLORECTAL CANCER PATIENTS: A POPULATION BASED STUDY
Authors: Wang C , Ghosh S , Abdelsalam O , Karachiwala H
Published: February 2022

Background

Colorectal cancer (CRC) remains a significant cause of morbidity and mortality in Canada. While early screening programs and improvements in surgical and oncologic therapies have led to a steady decline in the mortality rate of CRC, survival in metastatic stage IV disease remains low. Furthermore, it is unclear which factors have the largest impact on survival leading to a wide range in quoted survival times between studies.

Aims

This study examines the impact of various disease, patient, and treatment factors on the outcomes and survival of stage IV CRC patients in Alberta, Canada from 2004–2014 and compares the survival data of this population to the most current statistics from clinical trials. It is hypothesized that survival should increase over the past decade and factors such as age, presence of comorbidities, number of metastases, and chemmotherapy regimen chosen will have significant impacts on overall survival.

Methods

A registry-based analysis was conducted identifying patients diagnosed with advanced colorectal cancer in Alberta. Specifically, we collected demographic information for patients in 3 time intervals: 2004–2006, 2008–2010, and 2012–2014. Data collected included year of diagnosis, age, sex, number of metastatic sites at diagnosis (single vs multiple), area of residence (rural vs urban), Charlson comorbidity index, and primary site of disease. The survival data from the three timeframes were compared.

Results

A total of 1476 patients were studied across the 3 time intervals. Over the three time periods examined in this study, there was essentially no clinically significant difference in the survival curves. Median survival from 2004–2006 was 22.3 months, from 2008–2010 was 24.4 months, and from 2012–2014 was 24.0 months. While median survival did increase over the 3 time periods, the improvement was not statistically significant (p=0.196). Overall survival in this cohort was 23.9 months. Patients who were >68 years old or those who had multiple sites of metastases and multiple comorbidities had a worse overall survival (p<0.05).

Conclusions

Despite a decade of advances in both the surgical and medical management of Stage IV CRC, the overall survival remains low. Furthermore, there remains a wide range in the quoted survival for studies performed with this cohort. This variation is almost certainly due to the heterogeneity of the study population in stage IV disease. Future studies should employ broad inclusion criteria in order to address these important gaps in the external validity of oncology trials.

Survival of Stage IV Colorectal Cancer Over One Decade (2004–2014)

Funding Agencies

None
A141 IS SURGERY STILL THE ONLY TREATMENT OPTION FOR CURABLE RECTAL CANCER?
Authors: Vuong T , Garant A , Khosrow-Khavar F , Devic S , Enger S , Boutros M , Cohen A , Miller C S , Friedman G , Galiatsatos P , Nguyen V , Benoit N , Lan Thai H , Diec H , Desgroseilliers C , Faria J , Vasilevsky C
Published: February 2022

Background

Rectal cancer is curable by standard surgery with Total Mesorectal Excision (TME). However, there are well known associated long-term bowel and sexual dysfunctions. Non-operative management (NOM) is an emerging treatment for patients with operable rectal cancer. There is evidence supporting dose response for tumor control in rectal adenocarcinoma.

Aims

In the era of modern technologies, Image-guided adaptive endorectal brachytherapy is a means to deliver local radiotherapy boost treatments. We explored its role in a randomized phase II/III trial (NCT03051464) for patients aiming to achieve cure without surgery. Total Mesorectal Excision (TME) free survival at 2 years was the primary endpoint. We now present the interim analysis upon accrual of the first 40 patients.

Methods

In randomized trial, patients with operable cT2-3ab N0 M0 rectal cancer received 45 Gy in 25 fractions of pelvic external beam radiotherapy (EBRT) with concurrent 5-FU/ Capecitabine. They were randomized to receive either an EBRT boost of 9 Gy in 5 fractions (Arm A), or three weekly adaptive brachytherapy boosts for a total of 30 Gy in 3 fractions (Arm B).

Results

Forty patients were included (20 per arm). The median age was 66 years; baseline characteristics were well balanced in terms of age, tumor location, T stage and tumor size (Table 1). The acute treatment related toxicities are similar as shown in table 2 but in arm B, there were two deaths: one patient died during his chemotherapy and external beam treatment from congestive heart failure and one patient from a heart attack after treatment prior to salvage TME surgery. The proportion of complete clinical response was 50% (n=10/20) in Arm A and 90% in Arm B (n=18/20). With a median follow-up of 2.2 years, local regrowth at 2 years occurred in 4/10 patients (40%) in Arm A and 4/18 patients (22%) in Arm B. TME-free survival rate at 2 years was 45.9% in Arm A and 85.1% in Arm B (p=0.0036) (Figure 1).

Conclusions

The interim analysis of this trial suggests that these two strategies of radiation dose escalation are feasible and lead to high chances of organ preservation in patients with operable rectal cancer. The Independent Monitoring Comittee (IDMC) approved the continuation of patient recruitment in the phase III study as planned.

Funding Agencies

Elekta
A144 CHRONIC DSS LEADS TO ALTERED EXPRESSION OF IRAK4/TPL2 PATHWAYS IN UC-COLONIZED MICE
Authors: Hann A , Santiago A , Galipeau H J , Constante M , Jackson K , Bercik P , Verdu E
Published: February 2022

Background

Ulcerative colitis (UC) is one of two forms of inflammatory bowel disease (IBD). The exact cause of IBD is unknown but altered host-microbe interactions and genetic susceptibility are involved in its pathogenesis. Many patients with IBD do not respond to biological therapies targeting single cytokines, therefore new therapies that target common immune pathways are being developed and need to be tested in relevant preclinical models. Previously we have shown that mice colonized with UC microbiota upregulated genes related to inflammation without induction of colitis compared to healthy volunteer-colonized mice. We thus investigated whether IRAK4 and TPL2-induced pathways, new therapeutic targets in development upstream of inflammatory cytokine gene activation, are upregulated in mice colonized with UC microbiota and chronic colitis.

Aims

Our aim was to characterize TPL2 and IRAK4 signalling pathways and T cell phenotypes in UC-colonized mice following chronic low-dose dextran sodium sulfate (DSS) colitis.

Methods

10-16-week-old germ-free C57BL/6 mice were colonized with fecal microbiota from a patient with UC experiencing a flare (n=16). Mice were housed in a gnotobiotic facility during the experiment. Three weeks following colonization, colitis was induced in half of the mice by three cycles (5 d each; 2.0%, 1.5% and 1.5%, respectively) of DSS in drinking water with a 5-d wash-out period between cycles. All mice were fed a control diet (7004, Teklad). Fecal samples were collected weekly. At sacrifice, disease activity (colon length, occult blood in feces, stool consistency, and spleen weight) was measured and colon tissue was collected for histological analysis and RNA sequencing. Mesenteric lymph nodes (MLNs) were acquired for flow cytometry to analyze T cell phenotypes.

Results

In UC-colonized mice, chronic low-dose DSS induced softer feces (p<0.0001), shorter colon length (p<0.0001), and increased spleen weight (p<0.0001), compared with water treated mice. This was paralleled by detectable blood in stool, development of moderate colitis (DSS: 1.9+/-1.4 vs H2O: 0.5+/-0.2; p<0.02) and higher proportion of IL-17 (p=0.003) and IFN-γ-producing T cells (p=0.06) in MLNs compared with water treated mice. RNA sequencing revealed that inflammatory genes, mainly related to the IRAK4/TPL2 pathway (e.g., Gadd45b, Socs3, Il1b), were significantly increased (p≤0.05) in the colon of mice treated with DSS compared with water.

Conclusions

When challenged with a chronic low-dose chemical injury agent, mice colonized with UC microbiota develop clinical and histological signs of colitis and upregulation of genes involved in inflammation like Gadd45b, Socs3, and Il1b. Thus, this model represents a new valuable tool for preclinical testing of new drug candidates, such as those related to the modulation of IRAK4/TPL2 pathways.

Funding Agencies

CCC
A153 STRATEGIES TO DISTINGUISH PERIANAL FISTULAS RELATED TO CROHN’S DISEASE FROM CRYPTOGLANDULAR DISEASE: SYSTEMATIC REVIEW WITH META-ANALYSIS
Authors: Chin Koon Siw K , Engel J , Visva S , Mallick R , Hart A , de Buck van Overstraeten A , McCurdy J
Published: February 2022

Background

Differentiating between perianal fistulas related to cryptoglandular disease (CGD) and Crohn’s disease (CD) is essential to guide disease specific management.

Aims

We aimed to assess the ability of diagnostic strategies to differentiate between CD from CGD in patients with perianal fistulas.

Methods

We performed a diagnostic accuracy systematic review and meta-analysis. Electronic databases (MEDLINE, Embase, Web of Science, CENTRAL) were systematically searched from inception through February 2021 for studies that assessed a diagnostic test’s ability to distinguish fistula types. We calculated weighted summary estimates with 95% confidence intervals for sensitivity and specificity by bivariate analysis, using fixed effects models when data was available from two or more studies. The QUADAS tool was used to assess study quality.

Results

Twenty-one studies were identified and included: clinical symptoms (2 studies; n = 154 patients), MRI characteristics (3 studies; n = 296 patients), ultrasound characteristics (7 studies; n = 1003 patients), video capsule endoscopy (2 studies; n = 44 patients), fecal calprotectin (1 study; n = 56 patients) and various biomarkers (8 studies; n = 440 patients). MRI and ultrasound characteristics had the most robust data. Rectal inflammation, multiple-branched fistula tracts and abscesses on pelvic MRI, and the Crohn’s Ultrasound Fistula Sign, fistula debris and bifurcated fistulas on pelvic ultrasonography had high specificity (range, 80–95% vs. 89–96%) but poor sensitivity (range, 17–37% vs. 31–63%), respectively. Fourteen of twenty-one studies had risk of bias on at least one of the QUADAS domains.

Conclusions

Limited high-quality evidence suggest that imaging characteristics may help discriminate CD from CGD in patients with perianal fistulas. Larger, prospective studies are needed to confirm these findings and to evaluate if combining multiple diagnostic tests can improve diagnostic sensitivity.

Funding Agencies

None
A154 COMPARING RESPONSE TO INTRAVENOUS IRON INFUSION IN CROHN’S DISEASE AND ULCERATIVE COLITIS
Authors: Su S , Stone J , Bernstein C N
Published: February 2022

Background

Iron deficiency anemia (IDA) is common in persons with inflammatory bowel disease (IBD). Current evidence-based guidelines suggest iron replacement therapy in IBD patients with IDA. Intravenous (IV) iron has been demonstrated to be more effective than oral iron replacement in the IBD population, and this is thought to be related to oral iron being poorly tolerated, absorbed, and possibly having an adverse impact on the gut microbiome. Studies have not directly compared the response of IV iron between persons with ulcerative colitis (UC) and Crohn’s disease (CD).

Aims

(1) To compare the increase in serum hemoglobin and ferritin following IV iron therapy between persons with UC and CD. (2) To determine factors associated with response to IV iron (other than disease type), including age, sex, IBD therapies, abdominal surgeries, and IBD phenotype.

Methods

In a retrospective chart review, we evaluated 536 IV iron infusions (iron sucrose) prescribed to 117 IBD patients by a single gastroenterologist between 2012–2020, and collected data on IBD type, age, sex, medications (IBD therapies, NSAIDs, ASA, oral iron), abdominal surgeries, and IBD phenotype. Statistical analysis was performed using SPSS version 26.

Results

Most IV iron infusions were given to patients with CD (77% of infusions, 68% of persons). The majority of infusions were given as a series of multiple iron infusions (84%) over a mean of 27 weeks, rather than a single infusion. Persons with UC had a greater increase in serum ferritin than those with CD (mean difference ± SE of 13.2 ± 5.6 µg/L, p = 0.02). There was no significant difference in the increase in serum hemoglobin between UC and CD (UC= 6.5 ± 1.0 g/L; CD 4.9 ± 2.1 g/L; p = 0.62).

Conclusions

Persons with UC had a better ferritin response to IV iron therapy than persons with CD. Patients with UC were prescribed less IV iron than those with CD. In summary, persons with CD may require greater dosing of IV iron therapy than patients with UC. Further studies are needed to discern if this difference is secondary to CD being associated with a greater extent of mucosal disease burden, impaired iron absorption, or a greater intolerance to oral iron.

Funding Agencies

Fellowship Funding from Pfizer Canada
A167 CATEGORIZING ENDOSCOPIC SEVERITY OF CROHN’S DISEASE USING THE MODIFIED MULTIPLIER SES-CD (MM-SES-CD)
Authors: Pray C , Narula N , Wong E C , Colombel J , Marshall J , Daperno M , Reinisch W , Dulai P S
Published: February 2022

Background

The modified multiplier of the Simple Endoscopic Score for Crohn’s Disease (MM-SES-CD) is a novel internally validated endoscopic scoring tool that quantifies the endoscopic burden of Crohn’s Disease (CD). The MM-SES-CD considers the same endoscopic parameters and anatomical locations of the commonly used SES-CD, but acknowledges the different prognostic value of each parameter by assigning an individual weight to each category based on its impact on probability of achieving ER. Previous published work has demonstrated the MM-SES-CD can predict one-year endoscopic remission. This analysis aims to establish thresholds of the MM-SES-CD to classify CD endoscopic burden into very mild or inactive disease, mild, moderate, and severe disease based on the probability of achieving ER on active therapy at one-year.

Aims

The purpose of this analysis was to assess for numerical cut-offs of baseline MM-SES-CD to distinguish between mild, moderate and severe endoscopic CD activity based on the likelihood of one year ER. Additionally, the relationship between baseline MM-SES-CD score and likelihood of one-year CR (CDAI <150) was evaluated.

Methods

This post-hoc analysis included pooled data from three CD clinical trials including the UNITI studies, the EXTEND study, and a biosimilar infliximab study, referred to as ‘CT-P13 study’ (n=350 patients, baseline SES-CD ≥3 with confirmed ulceration). Maximum Youden Index calculations were used to determine thresholds for severity. Chi-square tests of trend were used to compare achievement of ER between severity categories, and Kaplan-Meier survival curve analysis was used to compare time to clinical remission (CR).

Results

MM-SES-CD severity categories were established as very mild or in remission (score <14), mild (score ≥14 to <31), moderate (≥31 to <45), and severe (score ≥45), which were predictive of one-year ER (50%, 30.3%, 21.7%, 8.8% respectively p<0.001). Lower MM-SES-CD scores had numerically higher rates of one-year CR, and time to CR over 52 weeks was superior to those with higher scores (p=0.0492).

Conclusions

We have established numerical cut-offs of the MM-SES-CD that categorize endoscopic disease severity and are prognostic for one-year ER and CR.

Achievement of one-year outcomes stratified by baseline MM-SES-CD

Funding Agencies

None
A171 EXPLORING PATIENT PERSPECTIVES ON A 12-WEEK, ONLINE STRESS REDUCTION INTERVENTION IN INFLAMMATORY BOWEL DISEASE
Authors: Hyde A , Watt M , Peerani F , Madsen K , Siffledeen J , Kroeker K , Lim A , Tandon P
Published: February 2022

Background

Inflammatory bowel disease (IBD) which includes Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic relapsing-remitting or progressive inflammatory condition. In addition to physical symptoms, individuals with IBD experience uncertainty about their future, social isolation, and increased psychological stress. Conventional medical and surgical IBD treatment does not adequately address the the impact of psychological stress. Online stress reduction interventions may therefore be useful adjuncts to standard medical therapies for IBD. The Peace Power Pack (PPP) trial was a 12-week RCT testing a stress reduction intervention with two core components: (i) a yoga, breathwork and meditation video, and (ii) a behavior-change facilitation informed by cognitive behavioral therapy.

Aims

The aims of this qualitative study, which was carried out alongside the PPP trial was to: (i) explore the experience of living with IBD, (ii) understand the impacts of the PPP program, and (iii) identify potential improvements to the program.

Methods

Upon completion of the 12-week RCT, all intervention participants were invited to participate in semi-structured interviews. A qualitative descriptive approach was used. Interviews were analyzed through a theoretical thematic analysis process, whereby transcripts were coded, and codes then grouped into larger categories and themes.

Results

Of the 56 participants interviewed, 52% had CD and 48% had UC. Participants ranged in age from 23 to 73 years, were predominantly female (70%) and had been diagnosed with IBD 14.3 years ago. Three main themes (Table 1) were identified: (i) IBD as a source of stress and uncertainty, (ii) understanding the positive impacts of the stress reduction program, and (iii) suggested strategies to enhance program desirability. IBD was described as causing uncertainty, significant disruptions to daily activities, and stress. The online program was associated with a perceived reduction in IBD symptom burden, an increased ability to manage daily and disease-associated stressors, and a more positive mindset. Variation in program content and fostering connections with others in the IBD community were identified as potential strategies to enhance future programming.

Conclusions

This study highlights the power of the patient voice to deepen our understanding of the impact of IBD, and the potential benefit of an online stress reduction program including suggestions for iterative refinement.

Table 1. Themes identified with sample quotations

Funding Agencies

University of Alberta Hospital Foundation, the American College of Gastroenterology and the Inflammation, Microbiome, and Alimentation: Gastrointestinal and Neuropsychiatric Effects (IMAGINE) Network CIHR grant
A190 EPIDEMIOLOGY OF MUSCULOSKELETAL MANIFESTATIONS IN PAEDIATRIC INFLAMMATORY BOWEL DISEASE: A SYSTEMATIC REVIEW
Authors: Ali A , Schmidt M , Piskin D , Crowley E , Berard R
Published: February 2022

Background

Paediatric inflammatory bowel disease (p-IBD) is a chronic and relapsing gastrointestinal disorder of childhood with associated long-term morbidity. Several extraintestinal manifestations (EIMs) are described, the most common being joint pain and/or inflammation. In 1986, Passo et al. were the first to describe the association of arthritis in p-IBD patients. However, since then, data on the epidemiology, patient and disease factors associated with, treatments for, and outcomes of p-IBD associated musculoskeletal (MSK) disease are not well-established.

Aims

Our study aims to summarize the literature on the epidemiology of MSK EIMs in p-IBD in the era of biologics.

Methods

A systematic review of the literature was performed. PubMed, Embase, Cochrane Library, Web of Science Core Collection, and CINAHL databases were searched with relevant keywords. Studies in English published from January 1, 2000 to December 21, 2020 were included. In total, 3893 papers were identified and screening was performed by two independent reviewers (AA, MS). Conflicts were resolved by a third reviewer (EC, RB). Study and population characteristics were recorded. The primary outcomes of interest were MSK symptoms at presentation and their course, method of diagnosis and definitions used for MSK EIMs. Risk of bias assessment was performed using the JBI Critical Appraisal Tools.

Results

Thirteen studies were included for full review, which were primarily single-centre observational studies with retrospective or cross-sectional design. The method of diagnosis for MSK EIMs varied across the studies, with only 4 studies stating the involvement of a rheumatologist in diagnosis. The definitions also varied, with MSK EIMs such as peripheral arthritis, axial arthritis, enthesopathy, and arthralgia included. Only 7 studies focused on MSK EIMs as their primary outcome, while the remainder reported on all p-IBD associated EIMs. There was a wide range in the prevalence of MSK EIMs from 2–35% (Figure 1). Four studies reported on the therapeutic response of MSK EIMs, and only 3 of those reported on biologic use. Risk of bias demonstrated heterogeneity in the quality of included studies.

Conclusions

This is the first systematic review of the literature for MSK EIMs in p-IBD. Analysis was limited due to variability in study design and data-reporting methods. Included studies reported prevalence of MSK EIMs, but the ascertainment of MSK EIMs, both method and definition varied with a clear lack in standardization. Our study demonstrates the need for further research of the MSK associations of p-IBD and to explore optimal management to advance care for this group of children.

Funding Agencies

None
A196 DIARRHEA AS A PRESENTING SYMPTOM OF RELAPSED GRANULOMATOSIS WITH POLYANGIITIS
Authors: Tan J , Bercik P , Khalidi N , Armstrong D
Published: February 2022

Background

Granulomatosis with polyangiitis (GPA) is a rare, small-to-medium sized-vessel vasculitis that typically involves the sinus, respiratory, and renal systems. The gastrointestinal (GI) tract is rarely involved, but its exact frequency is poorly characterized. GI symptoms have been reported to occur in up to 10% of acute presentations, and a historic series of 56 autopsies of GPA patients found 24% to have focal necrotizing arteriolitis of the intestine (Storesund, 1998). There are few case reports of colitis associated with GPA. They commonly describe abdominal pain, rectal bleeding, and less frequently, perforation, early in the disease course in conjunction with other classic systems involvement which aid in the diagnosis of GPA.

Aims

We present the case of a 77 year-old woman with lung biopsy-proven cANCA-positive GPA who was found to have colonic vasculitis after she had been in remission for several years.

Methods

Case report and literature review

Results

The patient presented with a 1-month history of progressive back pain, followed by 1 week of severe abdominal pain and watery diarrhea. She was afebrile, with a leukocyte count of 13.8x109/L, C-reactive protein of 213 mg/L, and fecal calprotectin of 669mg/kg. cANCA was strongly positive at 5.4 AI. Computed tomography scan revealed focal inflammatory change at the cecum and terminal ileum. Stool cultures were negative. Colonoscopy showed a polypoid, inflammatory-appearing hard mass at the ileocecal valve with surrounding fragile mucosa. Ileocecal valve biopsies described fibropurulent material and granulation tissue consistent with ulcer bed with surrounding mucosa showing chronic ischemic colitis with various degrees of acute cryptitis. The most likely etiology was speculated by the pathologist to be involvement of the colon by vasculitis, as other etiologies appeared to be ruled out. The patient had mild kidney injury, but no additional lung findings, in contrast to her initial presentation of GPA. She was started on prednisone 50mg/day. Her back pain, abdominal pain, and diarrhea resolved within 1 week, and renal function improved. Currently, there is a plan to start Rituximab for chronic treatment.

Conclusions

Our case of GPA-associated colitis is unique for several reasons. First, most case reports describe rectal bleeding as the presenting symptom of GPA colitis, whereas our patient presented with non-hemorrhagic diarrhea. Second, where available, reports of colitis correlated endoscopically with colonic ulcerations, whereas our patient had an ileocecal mass. Third, most reports present colitis associated with a new diagnosis of GPA, whereas our patient presented with colitis as new GI system involvement with likely inflammatory back pain as the presenting feature of GPA relapse. While a rare feature, colitis secondary to GPA can be considered in the appropriate context.

Funding Agencies

None
A198 COLONIC MUC2 MUCIN IS STABILIZED BY FCGBP TO RESIST SALMONELLA TYPHIMURIUM INVASION IN GOBLET CELLS
Authors: Gorman H , Moreau F , Beaupre E , Chadee K
Published: February 2022

Background

The colonic mucus bilayer is the first line of innate defense against pathogen invasion in the gut by forming a physical barrier between the lumen and the underlying single layer of mucosal epithelial cells. While MUC2 mucin is the primary component of the mucus layer, it also contains several mucus associated proteins of which FCGBP is of significant interest due to its structural similarities to MUC2 with unknown functions. Here we elucidated the functions of FCGBP in MUC2 mucin in response to S. typhimurium ( St) adherence and invasion in human colonic goblet cells.

Aims

Hypothesis: FCGBP is coordinately produced with MUC2 mucin and plays an important role in innate host defense. The specific aims are:

1. To determine if FCGBP alters the structural integrity of the mucus layer

2. To determine the role of FCGBP in St adherence and invasion of goblet cells

Methods

To investigate whether FCGBP impaired mucus barrier functions, wildtype LS174T (WT) MUC2 mucus-producing goblet cells and LS174T cells with a missense mutation in FCGBP (FCGBP MS) were used. To determine if FCGBP MS led to loss in barrier function, St adherence and invasion, and 0.2, 1, and 2 μM fluorescent bead penetration through the mucus monolayers were quantified. MUC2 and FCGBP mRNA and protein expression induced by St were analysed by RT-PCR and Western blotting. St-induced pro-inflammatory cytokines responses were analyzed by RT-PCR and human focus 15-plex cytokine and chemokine array. Cell killing was enumerated by LDH assay.

Results

FCGBP MS cells exhibited significant loss in MUC2 mucus barrier function as quantified by fluorescent beads penetration closer towards the epithelial cell surface temporally as compared to WT cells independent of bead size. Adherence of St was significantly increased in FCGBP MS cells and induced robust MUC2 mRNA and protein expressions in a time-dependent manner. Similarly, St elicited robust expression of pro-inflammatory cytokine mRNA and protein release in FCGBP MS as compared to WT cells. FCGBP MS were readily invaded by St that resulted in increased cell death as compared to WT cells.

Conclusions

Loss of function by FCGBP MS, but not in WT cells, showed increased penetration of fluorescent beads through the mucus layer that resulted in increased St adherence, invasion, and cell death. In WT cells, FCGBP and MUC2 were coordinately upregulated in response to St. The concurrent increase in pro-inflammatory cytokine expression in FCGBP MS cells in response to St suggests that bacteria directly interacted with the cell surface indicative of an impaired mucus layer. The overall trend for increased bacterial invasion, pro-inflammatory response and cell death in FCGBP MS demonstrates that FCGBP was critical in providing structural integrity and protective functions of the mucus layer.

Funding Agencies

CIHR