bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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

Abstract

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 &lt;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 &lt;14), mild (score ≥14 to &lt;31), moderate (≥31 to &lt;45), and severe (score ≥45), which were predictive of one-year ER (50%, 30.3%, 21.7%, 8.8% respectively p&lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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
A199 UTILIZATION OF MUCUS-DERIVED O-GLYCAN SUGARS BY THE PATHOGEN C. RODENTIUM FACILITATE ITS COLONIZATION OF THE MURINE GUT
Authors: Mslati M , Yu H , Ma C , Vallance B 
Published: February 2022

Abstract

Background
The ability of enteric pathogens to colonize and expand within the mammalian gastrointestinal (GI) tract is determined by several factors, including the ability to find and acquire nutrients. The thick mucus layer that lines the inner surface of the large intestine is rich in sugars that can serve as nutrient sources for several members of the microbiota. Whether these sugars can also be used by invading bacterial pathogens to colonize the GI tract is still unclear, in particular for the family of attaching and effacing (A/E) bacterial pathogens, including the human diarrheal pathogens EHEC and EPEC.

Aims
To investigate the ability of the murine A/E pathogen Citrobacter rodentium to use mucin-derived sugars as a nutrient source, and the importance of these sugars in the virulence of C. rodentium during in-vivo infection.

Methods
To identify which sugar(s) are required for C. rodentium to colonize and grow in the murine GI tract, we generated mutants lacking single or multiple genes involved in the uptake and catabolism of mucin-derived O-glycan sugars. This was followed by in-vitro growth assays in minimal media supplemented with mucin sugars to investigate the growth properties of C. rodentium and the generated mutants on mucin sugars.

Results
We determined that C. rodentium was able to use three mucin O-glycan sugars: sialic acid, galactose, and N-acetylglucosamine (GlcNAc) as both carbon and nitrogen sources for in-vitro growth. C. rodentium exhibited the maximal growth rate and density on GlcNAc, followed by sialic acid, and finally galactose. A mutant C. rodentium strain carrying a deletion in the nagA gene was unable to grow on both GlcNAc and sialic acid, confirming that the breakdown pathways for these two sugars merge and are processed by shared suite of enzymes. As for galactose, combined deletions in the genes mglB and galP were required to abolish growth on this sugar. Notably, a mutant strain carrying simultaneous deletions in nagA, mglB, and galP was unable to grow on all three mucin sugars, as well as on purified mucin.

Conclusions
Our results demonstrate that intestinal mucin sugars serve as potential nutrient sources for C. rodentium and that C. rodentium can catabolize three of these sugars. Future work will examine whether these sugar pathways contribute to C. rodentium colonization of the murine GI tract.

Funding Agencies
CCC, CIHRCH.I.L.D. Fdn
A203 INCIDENCE AND PREDICTORS OF NON-HEPATIC CANCERS IN ALCOHOL RELATED LIVER DISEASE IN THE WALDO COHORT
Authors: Hindi Z , Brahmania M , Arab J , Shi N , Rajoriya N , Aithal G , Allison M , Hagström H , Likhitsup A , McCune A , Masson S , Parker R 
Published: February 2022

Abstract

Background
Alcohol-related liver disease (ArLD) accounts for 48% of cirrhosis-related deaths in the world. Alcohol is a known contributor to hepatocellular carcinoma (HCC) and non-hepatic cancers (NHC).

Aims
We aimed to describe the incidence and predictors of NHC in patients with histologically characterized ArLD.

Methods
Data came from an international, multicenter retrospective cohort study of patients with histologically characterized ArLD. We excluded all patients with clinical, biochemical, or histologic evidence of liver disease due to another etiology noted either at diagnosis or during follow-up. The primary outcome was incidence of the first of NHC. To identify risk factors of NHC, baseline characteristics of patients with and without NHC were compared. Outcomes were presented as unadjusted and adjusted hazard ratios (HR) based on COX analysis. All statistical analysis was done in R using the ‘cmprsk’ package.

Results
A total of 633 patients with histologically characterized ArLD were included. The mean age was 51 years, 64% of patients were male and 58% had cirrhosis on biopsy. We found that 69 patients with ArLD (11%) developed NHC during a median follow-up of 8.8 years. The most common NHC was lung cancer (19%). Other cancers are shown in Figure 2. Patients who developed NHC were older (55 vs. 50 years old; p&lt;0.0001) compared to those without NHC. BMI, current or past smoking status, peak alcohol use, absence of cirrhosis and histological findings did not differ between groups. On multivariable analysis, past smoking status (HR 5.70, p=0.002) and current smoking status (HR 4.95; p = 0.003) were associated with higher rates of NHC.

Conclusions
In this large multicenter cohort study, we found ArLD is associated with an increased incidence of NHCs, primarily lung cancer. Past and current smoking are risk factors associated with an increased risk of NHC in ArLD.

Funding Agencies
None