bluuebunny/crossref_metadata_2025 huggingface dataset:
A21 VITAMIN D DEFICIENCY AND ITS ASSOCIATION WITH CLINICAL OUTCOMES IN PRIMARY SCLEROSING CHOLANGITIS
Authors: Wang S , Montano-Loza A J , Ebadi M
Published: February 2020

Background

Primary sclerosing cholangitis (PSC) is a progressive cholestatic disease involving chronic inflammation and fibrosis of intra- and extra-hepatic ducts. Vitamin D is a secosteroid implicated in anti-inflammatory and anti-fibrotic pathways, and its deficiency has been associated with worse outcomes in chronic liver disease. Vitamin D status may also influence the course of PSC but studies evaluating this link are scarce.

Aims

To determine the association of vitamin D deficiency with the development of cirrhosis, mortality, and need for liver transplantation in patients with PSC.

Methods

Ninety-four patients with the diagnosis of PSC were evaluated and followed by the autoimmune liver disease clinic at the University of Alberta, Edmonton, Canada. Clinical data were recovered from medical charts. Vitamin D status was defined by the serum concentration of 25-hydroxyvitamin D3. Patients with levels <50 nmol/L (10 ng/ml) were defined as deficient. Univariate and multivariate analyses were constructed using the Cox proportional hazards regression models. Event-free survival was defined as time from vitamin D assessment to the time of liver transplant or death.

Results

Mean age at PSC diagnosis was 32±14 years, with 67% of patients being male. The mean vitamin D level was 69±33 nmol/L (range, 4–163 nmol/L) and 26 patients (28%) had vitamin D deficiency (<50 nmol/L). Among 85 patients without cirrhosis at diagnosis, 43 patients (51%) developed cirrhosis. By univariate Cox analysis, serum ALP, albumin, bilirubin and vitamin D deficiency were predictors of cirrhosis development. Vitamin D deficiency was independently associated with higher risk of developing cirrhosis (HR 2.11, 95% CI 1.002–4.44, P=0.049) after adjusting for other predictors. Median time to develop cirrhosis was shorter in patients with vitamin D deficiency (6.8 years; 95% CI, 1.7–11.8) compared to those without (10.8 years; 95% CI, 9.2 -12.4; P=0.007). Over a median follow-up period of 5.6 years, adverse outcomes (liver transplant or death) were observed in 34 patients (36%). Serum levels of albumin, ALP, bilirubin, INR, platelet count, ascites, variceal bleeding and vitamin D deficiency were associated with adverse outcomes in univariate analysis. Vitamin D deficiency was independently associated with higher risk of adverse endpoints (HR 2.87, 95% CI, 1.16–7.12, P=0.02) after adjusting for confounding factors. Event-free survival was shorter in the patients with vitamin D deficiency compared to those without deficiency (7.1 years; 95% CI, 2.4–11.9 vs. 11.4 years; 95% CI, 8.9–13.9, P=0.03, Figure 1).

Conclusions

Vitamin D deficiency was frequent in patients with PSC and was associated with higher risk of progression to cirrhosis, as well as decreased time to death and liver transplantation. The possibility of improving outcomes in PSC by vitamin D supplementation awaits further investigation.

Funding Agencies

Food and Health Innovation Initiative (Vitamin Fund), University of Alberta
A29 HOPX LABELS A COLONIC STEM CELL THAT CONTRIBUTES TO COLONIC REGENERATION BUT NOT COLONIC TUMORS
Authors: Iablokov V , Good H J , Shin A E , Fazio E N , Loggie J W , Zhang L , Asfaha S
Published: February 2020

Background

Colorectal cancer is the 2nd leading cause of cancer death in Canada. In rapidly dividing tissues such as the intestine or colon, only long-lived, multipotent, self-renewing tissue stem cells have longevity to accumulate mutations and serve as the cellular origin of cancer. In the small intestine, genetic fate mapping studies have demonstrated that there are at least two principal stem cell pools: actively cycling, crypt base cells expressing Lgr5, and quiescent cells situated above the crypt base. Clevers and colleagues have previously shown that Lgr5-expressing cells can give rise to cancer upon mutation. Interestingly, when Lgr5+ stem cells are selectively “killed”, intestinal integrity remains intact and other stem cells restore homeostasis. To determine whether another stem cell population can give rise to cancer in the colon, we examined whether the atypical homeobox protein Hopx, marks stem cells in the colon and whether these cells can give rise to colon cancer.

Aims

In the present study, we aim to determine whether Hopx-expressing cells are colonic stem cells that contribute to gut healing and can give rise to colonic tumours following the loss of APC.

Methods

To determine whether Hopx expressing cells show stemness, we crossed Hopx-CreERT mice to R26-TdTomato reporter mice. We then conducted genetic lineage tracing studies in the colon during homeostasis and following dextran sodium sulphate (DSS)-induced colitis. To test the function of Hopx expressing cells, Hopx-CreERT mice were also crossed to R26DTR mice and treated with diphtheria toxin (DT) following tamoxifen. These mice were then exposed to either normal drinking water or DSS to determine the role of Hopx+ cells in colonic regeneration. To test whether Hopx expressing cells can serve as a cellular origin for colon cancer, Hopx-CreERT mice were crossed to Apcf/f (floxed) mice.

Results

Consistent with the labeling of a stem cell, following tamoxifen, Hopx+ cells expressing tdTomato expanded to lineage trace full colonic crypts within 7 days, and labelling was persistent for greater than 6 months. Interestingly, ablation of Hopx+ cells with DT did not alter weight, histological damage or survival during normal homeostasis, however, Hopx+ cell ablation in mice treated with DSS resulted in increased histological damage. Surprisingly, loss of APC in Hopx-expressing cells did not induce colonic adenomas even after 8 months following tamoxifen administration.

Conclusions

These findings prove that Hopx expressing cells identify a novel colonic stem cell pool that is redundant in homeostasis, but in the context of injury, are essential for epithelial regeneration. Interestingly, Hopx+ cells do not have the capacity to give rise to colorectal adenomas upon loss of the APC gene.

Funding Agencies

CIHR
A33 THE ROLE OF A HOMOZYGOUS PROTEIN CODING VARIANT OF EPS8 IN THE PATHOGENESIS OF PEDIATRIC IBD
Authors: Long K , Warner N , Pan J , Guo C , Muise A
Published: February 2020

Background

The rate of onset for Inflammatory Bowel Disease (IBD) is rising worldwide—most significantly in the pediatric population. The pathogenesis of the disease involves a complicated interaction between the environment and genetics. Recent findings suggest that there is a broad range of rare, single-gene mutations that correlate with the IBD phenotype in children. Some of these single-gene defects can disrupt the epithelial barrier, which alters intestinal immune homeostasis. Epidermal Growth Factor Receptor Kinase Substrate 8 (EPS8) is crucial for the stabilization of F-actin by capping and bundling the barbed end. Previous literature shows that loss of expression of EPS8 disrupts the polymerization of F-actin in intestinal microvilli resulting in shortened brush borders. We identified a pediatric IBD patient with a homozygous missense EPS8 mutation(c.2099C>T, I700T) in the actin-binding domain. The patient presented with pancolitis, colonic strictures and other IBD-like symptoms at 6 weeks of age. Currently, the functional role of EPS8 in the pathogenesis of very early-onset IBD remains elusive.

Aims

1)To investigate if the patient with EPS8 mutation has microvilli disorganization.

2)To determine EPS8 localization in patient samples and cell models.

3)To clarify the mechanism of how the EPS8 mutation affects F-actin in vitro.

Ultimately, we want to clarify how the mutation of EPS8 might contribute to the onset of pediatric IBD.

Methods

A rare, damaging mutation in EPS8 was identified in a very early-onset IBD patient by Whole Exome Sequencing. From patient-derived colon biopsy samples, the localization of EPS8 and actin was visualized by immunofluorescence (IF) microscopy. The morphology of the patient’s intestinal microvilli was assessed using transmission electron microscopy (TEM). EPS8 expression was measured using western blot. An F-actin polymerization assay was performed comparing purified WT and mutant EPS8 protein to assess the rate of polymerization from monomeric G-actin to F-actin.

Results

IF microscopy of the colonic sections revealed lower co-localization of EPS8 and actin on the apical surfaces, compared to IBD and normal controls. Closer examination of the cell structure using TEM showed disruption of the microvilli in the EPS8 mutant, but not in IBD or normal controls. Western blots showed no differences in protein expression between wildtype and mutant EPS8 in HEK293T cells. F-actin polymerization assay revealed differences in the rate of G-actin to F-actin polymerization between wildtype and mutant EPS8.

Conclusions

The patient with EPS8 mutation had microvilli disorganization. EPS8 localized differently in the patient colon tissues compared to normal and IBD control samples. The EPS8 mutation may affect F-actin polymerization, which may lead to disruption of the microvilli.

Funding Agencies

CIHR
A35 MICROBIAL PROTEOLYTIC SIGNATURE IN ULCERATIVE COLITIS INDUCES AN INFLAMMATORY SIGNATURE IN MICROBIOTA-HUMANIZED MICE
Authors: Galipeau H J , Turpin W , Caminero Fernandez A , Santiago A , Libertucci J , Bermudez-Brito M , Armstrong S , Bedrani L , Croitoru K , Verdu E
Published: February 2020

Background

Altered gut microbiota composition has been associated with inflammatory bowel diseases (IBD) including ulcerative colitis (UC), but causality and bacterially-driven mechanisms, are unclear. Proteases within the gastrointestinal tract play a critical role in maintaining homeostasis and are tightly regulated by anti-proteases. Host-derived proteolytic imbalances have been described in IBD, including UC, however, the role of intestinal microbiota as a source of proteases and anti-proteases has largely been ignored.

Aims

To study microbial proteolytic activity and intestinal microbiota profiles in a cohort of individuals at-risk for IBD, and in those individuals that develop UC at follow-up.

Methods

Fecal samples were collected from healthy individuals at-risk for IBD and who went on to develop UC (pre-UC; n=14) and again after UC diagnosis (post-UC, n=10). Fecal samples from matched at-risk individuals that did not develop UC were used as healthy controls (n=52). Overall fecal proteolytic and elastolytic activity was measured. We performed metagenomics sequencing in 4 UC subjects (pre and post) and 4 matched HC using Illumina Hi-Seq from stool DNA. To investigate bacterial origin and functional significance, pregnant germ-free (GF) mice were colonized with a fecal sample from a selected UC subject (pre and post) and a matched HC. Naturally colonized litters were followed for 12 weeks, after which proteolytic activities and signs of inflammation were measured.

Results

Fecal proteolytic and elastase activity was increased in pre- and post-UC samples compared to HCs. Metagenomics revealed over 20k genes were significantly different between HC and pre-UC samples, and of these, 440 related to proteases and peptidases. Increased fecal proteolytic activity, higher lipocalin levels, and increased colonic polymorphonuclear cells in colonic H&E sections was observed in pre- and post-UC colonized mice compared to HC colonized mice. Mice colonized with pre-UC microbiota showed increased mRNA expression of genes linked to immunological disease, antimicrobial and inflammatory responses (ie. Tlr2, Tlr5, Nod2, and Il1b) as compared to HC colonized mice.

Conclusions

These results suggest increased fecal proteolytic activity is observed prior to the onset and clinical diagnosis of UC in patients at-risk for IBD, and upon transfer to mice born from colonized GF dams, low-grade inflammation develops. These pathways could be developed as novel non-invasive biomarkers to monitor at-risk populations. Submitted on behalf of the CCC-GEM Project consortium. Supported by CCC GIA to EF Verdu

Funding Agencies

CCC
A43 β-DEFENSINS AS MARKERS OF INTESTINAL DYSBIOSIS: THE NATURE OF CHANGES IN β-DEFENSINS IS DEPENDENT ON THE PROCESS UNDERLYING THE INDUCTION OF DYSBIOSIS
Authors: Saqib Z , De Palma G , Lu J , Bercik P , Collins S M
Published: February 2020

Background

Dysbiosis may be defined as a change in the microbial composition or function that results in altered host function. Defensins are antimicrobial peptides, are part of innate immunity, and are important in host defense and maintaining homeostasis. Dysbiosis is a putative mechanism underlying the expression of many functional GI disorders like Irritable Bowel Syndrome (IBS) for which no biomarkers exist. Previous studies have revealed increased β-defensin (β-Def) levels in IBS patients, most likely due to changes in the microbiota.

Aims

We examined the hypotheses that: 1) Changes in β-Def are dependent on the manner in which dysbiosis is induced, and that 2) the direction of the change in β-Def depends on how dysbiosis was induced.

Methods

We used 4 models of experimentally induced dysbiosis to determine changes in fecal β-Def and to characterize the microbiota composition before and during the induction of dysbiosis. We used: 1) an antimicrobial cocktail (AC) in water; 2) a high-fat/ high-sugar diet (HFHSD); 3) a high salt diet (HSD) that we previously showed to induce a pro-inflammatory microbiota; and 4) mild restraint stress (MRS). All studies were performed in C57/BL6 mice except studies using MRS that were performed in NIH Swiss mice. In the AC or dietary studies, we employed a one-week intervention preceded by one-week baseline and recovery periods. In MRS studies, mice comparisons were made between a control and a stressed group. Stool samples were collected every 24 hours and were assayed for fecal β-Def levels analysis by an ELISA and microbial composition by 16S gene profiling.

Results

Exposure to AC or dietary change, but not MRS, resulted in significant decreases in fecal β-Def. Additionally, bacterial composition and diversity profiles were different in all mice except MRS mice (control vs. MRS males: p=0.414; control vs. MRS females: p=0.96). In contrast, mice exposed to the HSD revealed a significant increase in β-Def during treatment compared to baseline in both males (p=0.025) and females (p= 0.0019). The AC mice showed the largest changes and significant correlations between changes in β-Def levels and bacterial diversity (males: p=0.013, r=0.6; females: p=0.007, r=0.6) and richness (males: p=0.0008, r=0.70; females: p=0.003, r=0.62). However, no significant correlations were found between specific bacteria and β-Def levels in the HFHSD group.

Conclusions

We conclude that directional changes in fecal β-Def levels are dependent on the manner in which dysbiosis is induced. The use of β-Def as a biomarker requires comparisons with baseline levels obtained during remission in order to identify dysbiosis presence in microbiota-associated chronic GI conditions like IBS. Such an approach will identify patient subgroups that may benefit from microbiota-directed therapies.

Funding Agencies

CIHR
A52 BUTYRATE SUPPLEMENTATION AMELIORATES DAMAGE CAUSED BY ENTERIC CITROBACTER RODENTIUM INFECTION
Authors: Celiberto L S , Healey G , Xu J , Xia L , Vallance B
Published: February 2020

Background

Patients with inflammatory bowel disease (IBD) often display a dysbiotic microbiome as well as a defective intestinal mucus layer, which appears thinner and more penetrable than the mucus layer of healthy subjects. Tributyrin (TB), a prodrug of butyric acid, has shown beneficial effects in models of IBD due to its anti-inflammatory effects. We previously showed that mice lacking the major intestinal mucin Muc2 (Muc2-/-) or lacking the “Core1” enzyme responsible for glycosylating Muc2 (C1galt1-/-) were highly susceptible to infection by Citrobacter rodentium, a murine model of intestinal inflammation.

Aims

The study explored the role of gut mucus in providing host defense against C. rodentium, as well as the effects of TB supplementation in the prevention of mucosal damage in this model.

Methods

Six to ten week old wildtype (WT), Muc2-/-, flox control (C1galt1f/f) and C1galt1-/- mice were infected with C. rodentium (∼2.5 × 108 CFU) by oral gavage. For TB supplementation experiments, mice received 100µL of TB or glycerol as a control by oral gavage every other day starting on day 1 post infection. Mice were monitored daily throughout the experiment and were euthanized at day 6 of infection. Several tissues of interest were collected to verify bacterial colonization in the gut and at systemic sites as well as histological tissue damage. Cecal contents were collected for the analysis of short chain fatty acids, while blood was collected by cardiac puncture after oral gavage with FITC-dextran to measure intestinal permeability.

Results

While WT and C1galt1f/f mice were only modestly susceptible to C. rodentium infection, Muc2-/- and C1galt1-/- mice displayed dramatically (100 fold) increased pathogen burdens, significantly greater intestinal macroscopic and histopathology scores, and heightened barrier disruption as compared to controls. Moreover, Muc2-/- and C1galt1-/- mice showed significantly lower levels of butyric acid as compared to control mice under baseline conditions. Interestingly, when supplemented with TB, Muc2-/- and C1galt1-/- proved less susceptible to C. rodentium infection, as indicated by reduced weight loss and clinical signs of colitis, while pathogen burdens were greatly reduced as was histological tissue damage, and epithelial barrier dysfunction. The same protection was conferred when TB was administered as a dietary supplementation, thus confirming its beneficial effect in protecting mice against C. rodentium infection.

Conclusions

These findings demonstrate that intestinal mucus controls host susceptibility to C. rodentium infection via control over butyrate levels, and highlight the need to explore the mechanisms by which gut mucus modulates the resident microbiota and its metabolites.

Funding Agencies

CCC, CIHR
A55 LACK OF EXPERIMENTAL REPRODUCIBILITY IN PRECLINICAL RESEARCH IS INFLUENCED BY THE NUTRITIONAL PROFILE OF STANDARD RODENT CHOWS
Authors: Tuck C J , De Palma G , Takami K , Brant B J , Caminero Fernandez A , Reed D E , Muir J , Gibson P , Winterborn A , Bercik P , Verdu E , Vanner S
Published: February 2020

Background

Lack of experimental reproducibility, particularly in studies investigating the microbiota, is of growing concern to the scientific community. Factors such as environment, stress, and sex have been identified as contributors, whereas dietary composition has received less attention.

Aims

To profile the use of standard rodent chows in research institutions, analyze the nutrient content of common rodent chows, and assess the impact of different chows on microbiota profiles.

Methods

A survey was conducted to evaluate which rodent chows are used by research institutions worldwide. Seven standard rodent chows were selected for analysis of ingredients, fermentable carbohydrate (FODMAP) and gluten content. FODMAP content was measured by high-performance liquid-chromatography and enzymatic assays, and gluten content was assessed by a commercial kit using G12 antibody. Forty C57BL/6 mice were randomized to 4 groups of 10 mice (5 male, 5 female). Group A was euthanized at baseline. Group B received the breeding institution chow (LabDiet 5066). Group C received ResearchDiets AIN93G (low FODMAP and gluten content). Group D received LabDiet 5001 (high FODMAP and gluten content). After 3 weeks, cecal contents were collected and analyzed by 16S rRNA gene sequencing; short- and branched-chain fatty acids (SCFA, BCFAs) content was also determined.

Results

Twenty-eight different types of rodent chows were reported to be used by 45 international survey respondents. Ingredient composition of the standard chows varied widely, resulting in differences in FODMAP and gluten content. Microbiota analysis of cecal contents revealed that gut microbiota composition was altered by the standard chows, as reflected by significantly different clusters in β-diversity analysis as well as by altered α-diversity. Microbiota diversity was also influenced by sex in Groups A and B (p<0.01). Total SCFA levels were lower (p=0.03) and BCFA levels were higher (p=0.01) in Group C compared to Group B.

Conclusions

Our results suggest that the composition of the diet not only significantly impacts gut microbiota profiles and fermentation patterns but may also emphasize sex differences in preclinical studies, with major implications for the reproducibility of results across laboratories.

Funding Agencies

CIHRThe Canadian Nutrition Society
A60 THE INCIDENCE OF INFLAMMATORY BOWEL DISEASE IS DECREASING IN SASKATCHEWAN: A POPULATION-BASED COHORT STUDY
Authors: Osei J A , Peña-Sánchez J , Fowler S , Muhajarine N , Kaplan G G , Lix L M
Published: February 2020

Background

Canada has one of the highest inflammatory bowel disease (IBD) incidence rates worldwide, although within Canada rates vary. Evidence show increasing incidence rates of IBD in Ontario (i.e. adults aged 30–60), stable in Alberta and decreasing in Manitoba. Additionally, higher incident rates of IBD have been identified among urban regions compared to rural regions. There is limited data on the incidence of IBD in Saskatchewan.

Aims

The study objectives were to 1) estimate IBD incidence rates in Saskatchewan from 1999 to 2016, and 2) test for differences in IBD incidence rates for rural and urban regions of Saskatchewan.

Methods

A population-based study was conducted using linked provincial administrative health databases. Individuals age 18+ old with newly diagnosed Crohn’s disease (CD) or ulcerative colitis (UC) were identified using a validated case definition. Generalized linear models with a negative binomial distribution were used to estimate incidence rates and incidence rate ratios (IRR) adjusted for age group, sex, and rurality with 95% confidence intervals (95%CI).

Results

In total, 4,908 newly diagnosed individuals with IBD were included. The average annual incidence rate of IBD decreased from 75 (95%CI 67–84) per 100,000 people in 1999 to 15 (95%CI 12–18) per 100,000 population in 2016. This decrease was evident in both UC (from 36/100,000 [95%CI 31–42] in 1999 to 6/100,000 [95%CI 4–8] in 2016) and CD (37/100,000 [95%CI 32–42] in 1999 to 8/100,000 [95%CI 6–10] in 2016). A significant decline of 6.9% (95%CI 6.2–7.6) in the average annual incidence of IBD was estimated between 1999 and 2016 (see Figure 1). Urban residents had a greater overall risk of IBD (IRR=1.19, 95%CI 1.11–1.27) than rural residents. This risk difference was statistically significant for CD (IRR=1.25, 95%CI 1.14–1.36), but not UC (IRR=1.08, 95%CI 0.97–1.19).

Conclusions

A decreasing trend in IBD incidence in Saskatchewan was identified after adjusting for age group, sex, and rural/urban region of residence. Around 150 new cases of IBD are still diagnosed annually in Saskatchewan, but this estimate is lower than estimates from other provinces. Urban dwellers have a 25% higher risk of CD onset compared to their rural counterparts. This finding could suggest the presence of specific risk factors in urban settings that require further investigation. Health care providers and decision-makers should plan IBD-specific health care programs taking into account these specific IBD rates in Saskatchewan.

Funding Agencies

College of Medicine, University of Saskatchewan
A65 VARIATION IN THE CARE OF CHILDREN WITH INFLAMMATORY BOWEL DISEASE: A CANGIEC POPULATION-BASED STUDY
Authors: Kuenzig E , Singh H , Bitton A , Kaplan G G , Carroll M W , Otley A , Stukel T A , Spruin S , Griffiths A , Mack D , Jacobson K , Nguyen G C , Targownik L , El-Matary W , Nasiri S , Benchimol E I
Published: February 2020

Background

Inflammatory bowel disease (IBD) is rising rapidly in Canadian children. These children require consistent high-quality specialized care to prevent long-term complications.

Aims

Evaluate variation in health services utilization and surgery rates across pediatric IBD centres in Ontario.

Methods

Incident cases of IBD <16y (1999–2010), identified from health administrative data using a validated algorithm, were assigned to pediatric IBD centres based on location of IBD hospitalization, endoscopy and outpatient care. Children receiving IBD-specific care outside pediatric centres were also grouped. Frailty models, median hazard ratios (MHR), and Kendall’s t described variation in IBD-related ED visits, hospitalizations, and surgery 6–60 months after diagnosis, adjusting for age, sex, rural/urban household, and income. Mean diagnostic lag (time from first health system contact for an IBD symptom to final IBD diagnosis) and proportion of children with IBD care by gastroenterologists (GIs) at each centre were evaluated as centre-level predictors of variation.

Results

Of 2584 IBD cases, 73.4% were treated in a pediatric IBD centre. Between-centre differences accounted for 0.18% (MHR 1.06) and 0.41% (MHR 1.09) of variation in hospitalizations and ED visits, respectively. Children treated at centres where a higher proportion of children were cared for by GIs were more likely to be hospitalized (HR 2.09, 95% CI 1.26–3.45). Children treated at centres with a longer mean diagnostic lag were also more likely to be hospitalized (HR 1.01, 95% CI 1.003–1.02). ED visits were not associated with the proportion of children cared for by gastroenterologists or diagnostic lag. Among 1529 CD cases, 14.1% required intestinal resection; 1.79% of variation in the risk of surgery resulted from between-centre differences (MHR 1.20). Surgery was less common among patients at centres where more children were cared for by GIs (HR 0.24, 95% CI 0.07–0.84) and with a longer mean diagnostic lag (HR 0.98, 95% CI 0.97–0.99). After adjusting for these, between-centre differences accounted for 0.005% (MHR 1.01) of variation in care. Minimal variation was observed among the 11.0% of 872 UC cases requiring colectomy, with 0.37% of variation due to between-centre differences (MOR 1.09). Colectomy risk was not associated with GI care or diagnostic lag.

Conclusions

Variation in ED visits, hospitalizations, and surgery among children with IBD is small; however, centre-level differences in GI specialist care use and time to diagnosis were associated with hospitalization and surgery. It is essential to understand between-centre differences to reduce variation and ensure high-quality care.

Funding Agencies

CCC
A67 EVALUATING ACCESS TO IBD CARE ACROSS CANADA: PROCEEDINGS FROM THE 2017 IBD ACCESS SUBMMIT
Authors: MacDonald S , Heisler C , Mathias H , Mirza R , Jones J
Published: February 2020

Background

Inflammatory Bowel Disease (IBD) is a chronic, immune-mediated disease, with Canada demonstrating the highest incidence and prevalence rates in the world. Patients with IBD often require lifelong treatment and, therefore, lifelong interactions with the healthcare system. Access to care can have a direct impact on patient health-related outcomes. Although acknowledged as a problem, the complexity of accessing IBD specialty care in Canada has not been reviewed. This lack of understanding presents a barrier in evaluating and implementing changes in IBD specialty care.

Aims

To identify key barriers and facilitators for and to develop a national working strategy to address limitations in access to IBD specialty care by exploring the perceptions and experiences of key stakeholders (pediatric and adult gastroenterologists, IBD patients, researchers, and policy makers).

Methods

The IBD Summit was held in Toronto, Ontario in November 2017, sponsored by SPOR-CIHR catalyst funding and in partnership with Crohn’s & Colitis Canada. Perceptions and experiences of key stakeholders were gathered during two audio-recorded stakeholder dialogues held during the Summit. The audio recordings were transcribed and coded to compare and contrast between key stakeholders to determine potential differences in access to IBD care. Five final themes are highlighted in this report.

Results

A total of 21 key stakeholders attended, including pediatric and adult gastroenterologists, patients, researchers, and policy makers. Five key themes of importance relating to access to IBD care arose from The IBD Summit:(1) Integrated Models of Care, (2) IT Enhanced Care, (3) Health System Process, (4) Communication and Advocacy, and (5) Community Supports. The IBD Summit identified similar perceptions and experiences, highlighting common barriers and facilitators that transcend provincial borders. Shared perceptions included a need for common medical records and overall improved IT-enhanced care for managing IBD; improved centralized triage systems; increased comprehensive care support for patients and primary care physicians; and increased community supports for patients and providers.

Conclusions

Highlights from the IBD Summit present several clinically relevant and actionable suggestions for improved access to IBD speciality care across Canada. The suggestions provided by key stakeholders highlight the need for a system-level redesign in order to improve access to enhanced models of care. Improvements in access to IBD specialty care can only occur through partnerships between those working within the healthcare system and those within the community. Future research will involve pursuing deeper insight into the experience of patient and provider stakeholders as they navigate the healthcare system in order to access and provide care.

Funding Agencies

CIHRNova Scotia Health Authority Research Fund
A76 INCOMPLETE RESECTION OF 1-20MM COLORECTAL POLYPS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Djinbachian R , Iratni R , Durand M , Marques P , von Renteln D
Published: February 2020

Background

Colonoscopy has been used as a screening or surveillance tool for colorectal cancer (CRC), however, a minority of patients develop post-colonoscopy interval CRC. Incomplete resection of colorectal polyps is thought to be a major cause of post-colonoscopy interval CRC.

Aims

We were interested in studying the incomplete resection rate (IRR) of colorectal polyps and factors associated with incomplete resection in a systematic review and meta-analysis.

Methods

We conducted a systematic review and meta-analysis using MEDLINE, EMBASE, EBM Reviews, and CINAHL of all studies reporting on IRR of polyps 1-20mm published until March 2019. Exclusion criteria were: Inclusion of IBD cohorts; referrals for difficult polypectomy; polyp size >20mm; endoscopic submucosal dissection; conference abstracts; non-english language. Primary outcome was histologic IRR for polypectomies. Secondary outcomes included IRR for all studies; IRR for polyps 1-10mm and 10-20mm; IRR with or without submucosal injection; IRR based on assessment method of completeness; IRR for different polypectomy methods.

Results

6148 records were identified through initial search and 37 studies with a total of 11962 polyps were included in our quantitative analysis. Histologic IRR for polypectomies (snare and forceps) was 10.54% (95%CI 8.56–12.53). IRR for all included studies was 9.05% (95%CI 7.54–10.56). IRR was lower for polyps 1-10mm than polyps 10-20mm; 8.85% (95%CI 7.27–10.44) vs 18.08% (95%CI 10.30–25.87). IRR was statistically significantly lower when only evaluated using imaging enhanced endoscopy (IEE) (0.69%; 95%CI 0.02–1.35) compared to post polypectomy margin biopsies (7.19%; 95%CI 5.39–8.99). Histologic IRR for snare polypectomy (8.79%; 95%CI 6.96–10.62) was lower than histologic IRR for forceps polypectomy (17.75; 95%CI 10.49–25.01).

Conclusions

Incomplete resection of 1-20mm colorectal polyps occurs in a significant proportion of polypectomies. Incomplete resection occurs more frequently in larger (10-20mm) polyps. Visual inspection with IEE after polypectomy underestimates IRR in comparison to post polypectomy biopsies. Snare polypectomy had lower IRR when compared with forceps.

Funding Agencies

None
A79 CLINICAL VALIDATION OF THE SIMPLE CLASSIFICATION FOR OPTICAL DIAGNOSIS OF DIMINUTIVE AND SMALL COLORECTAL POLYPS
Authors: Alaoui A , Oumedjbeur K , Djinbachian R , Marchand E , Marques P , Hammar C , Pohl H , Bouin M , Deslandres E , Bouchard S , von Renteln D
Published: February 2020

Background

Image enhanced endoscopy (IEE) allows for real-time optical diagnosis of colorectal polyps in order to replace histopathology. A novel classification system (SIMPLE classification) has recently been developed for optical diagnosis when using the novel Pentax Optivista IEE platform.

Aims

The aim of this study was to evaluate the SIMPLE classification for optical polyp diagnosis in a prospective clinical study.

Methods

Patients undergoing screening, diagnostic or surveillance colonoscopies were enrolled in the study. All colorectal polyps 1-10mm found underwent optical polyp diagnosis using the SIMPLE classification with either iScan or Optivista for image-enhanced endoscopy (IEE). Polyps were resected as per standard care and sent for histopathology analysis. Optical diagnosis and surveillance intervals were calculated based on SIMPLE criteria and compared to pathology-based results as reference. Primary outcome was the agreement of the surveillance intervals based on the SIMPLE classification with pathology-based surveillance intervals for 1-5mm colorectal polyps. Secondary outcomes included negative predictive value (NPV) for rectosigmoid adenoma, percentage of pathology avoided, percentage of post-colonoscopy immediate recommendations, and surveillance interval agreement, rectosigmoid NPV for 1-10mm polyps.

Results

399 patients (mean age: 62.4, 55.6% female) with 278 diminutive and 364 small polyps were evaluated in the study cohort. For ≤5mm polyps, agreement with pathology-based surveillance intervals was 93.5% [95% CI 91.1–95.9] (shorter: 4.5% [95% CI 2.5–6.5]; longer: 1.8% [95% CI 0.5–3.0]). NPV for rectosigmoid adenomatous polyps (including SSA) was 85.5% [95% CI 77.6–93.4]. Using Optical diagnosis and the SIMPLE classification, pathology analysis could be avoided in 61.5% [95% CI 56.9–66.2] of polyps and post-colonoscopy immediate surveillance interval recommendation could be given in 70.9% [95% CI 66.5–75.4] of patients. For ≤10mm polyps, agreement with pathology-based surveillance intervals was 92.2% [95% CI 89.6–94.9] (shorter: 5.5% [95% CI 3.3–7.8]; longer: 2.3% [95% CI 0.8–3.7]). NPV for rectosigmoid adenomatous polyps (including SSA) was 83.7% [95% CI 75.9–91.5].

Conclusions

The first clinical validation study using the SIMPLE classification in combination with Optivista or iScan IEE showed a high (≥90%) surveillance interval agreement compared to pathology. More than 60% of pathology could be avoided, and most patients could be given immediate surveillance intervals when using IEE in combination with the SIMPLE classification.

Funding Agencies

NonePentax
A85 COLON CANCER SCREENING IN PATIENTS ASSESSED FOR LUNG TRANSPLANTATION
Authors: Sanders D , Telford J J , Levy R
Published: February 2020

Background

Colorectal Cancer (CRC) mortality is significantly higher after a lung transplant (1). CRC screening for average risk patients in British Columbia is done with Fecal Immunochemical Testing (FIT) every two years (2), however colonoscopy is currently the standard modality in patients undergoing lung transplant assessments in British Columbia. The yield of using FITs or Fecal Occult Blood Testing (FOBT) and colonoscopy in screening for lung transplant assessments in Canada is unknown.

Aims

To review the colon cancer screening results for all lung transplants done in British Columbia from 2013 to 2018.

Methods

This is a retrospective chart review of the 222 lung transplants done from January 2013 to December 2019.

Results

220 patients were transplanted during this time period. 2 patients were re-transplanted. 136 of the 220 lung transplant patients were male (62%). The most common indication for transplantation was interstitial lung disease (44%), followed by chronic obstructive pulmonary disease (30%), cystic fibrosis (7%), and pulmonary hypertension (4%). Colonoscopies were performed in 127 of the 220 patients. Computed tomography (CT) colonography was performed in 15 of the 220 patients, and a FOBT or FIT was performed in 200 of the 220 patients. No colon cancers were found by colonoscopy or CT colonography (0/142). Of the colonoscopies performed, 38 % (49/127) had adenomatous or serrated polyps removed. Of these 36% (18/49) had high risk pathology. The positive predictive value of a FIT/FOBT positive for a polyp was 51.4 % (CI 37.6–65.1%).

Conclusions

The value of non-invasive screening modalities in pre-lung transplant patients are modest. Program screening should be tailored to the lung transplant candidate’s risk of CRC and the risk of an invasive procedure with a known complication rate.

Funding Agencies

None
A117 A CASE OF ADULT AUTOIMMUNE ENTEROPATHY AND PRIMARY SCLEROSING CHOLANGITIS
Authors: Lei Y , Azhari H , Raman M
Published: February 2020

Background

Autoimmune enteropathy (AIE) is a rare, immune-mediated condition causing severe diarrhea and mucosal damage. The diagnostic criteria are chronic diarrhea with malabsorption, blunting of the small bowel villi, specific histologic changes, and the exclusion of other causes of villous atrophy. Anti-enterocyte and anti-goblet cell antibodies are supportive of the diagnosis, but not specific or sensitive enough to make the diagnosis. It has several clinical and histologic phenotypes and affects children more than adults. To our knowledge, there are only 2 published cases of AIE with concurrent primary sclerosing cholangitis (PSC).

Aims

To review the literature for adult AIE, any previous cases of concurrent PSC, and present a case of both conditions.

Methods

We searched PubMed for “autoimmune enteropathy psc”, “autoimmune enteropathy”, “autoimmune enteropathy case report”, “autoimmune enteropathy adult” and collected all the relevant articles. Relevant clinical features of demographics, IBD status, liver diseases, immune conditions, antibody status, and treatment agents were summarized.

Results

A 31-year-old man presented with a 20-year history of diarrhea and 11kg weight loss over 3 months. He had gout, no regular medications, and relevant no family history. All initial investigations were normal. Repeat endoscopy showed increased intra-epithelial lymphocytes (IEL) in the colon consistent with lymphocytic colitis. He was given budesonide with moderate improvement. He then developed biliary stasis, and was found to have early PSC. Repeat colonoscopy for ongoing diarrhea showed increased colonic IEL. Ulcerative colitis (UC) was suspected, and he was given oral 5-ASA and prednisone, with subsequent switch to vedolizumab. He then relapsed, requiring IV fluids, total parenteral nutrition (TPN), and IV steroids. Repeat endoscopy showed persistent colonic IEL, and villous blunting in the terminal ileum and duodenum. Celiac disease, IBD, combined variable immunodeficiency (CVID), and enteric infections were excluded. In this context, AIE was considered. He improved with IV steroids, and was switched to infliximab. Despite initial improvement, he had worsening diarrhea and malnutrition. After dose escalation of infliximab, and further IV steroids and TPN, he was started on a trial of ustekinumab. We found 35 articles that reported on 100 adult cases of AIE. There were two previous adult cases of concurrent PSC. We found 7 cases where TNF-alpha inhibitors were used, one case where vedolizumab was used, and no cases using ustekinumab. Details are in Table 1.

Conclusions

AIE is a rare condition causing chronic diarrhea and gut mucosal damage reported only in case reports and series. There have only been 2 other reported cases of concurrent PSC with AIE in adults. This is the first reported case of ustekinumab being tried to control symptoms.

Funding Agencies

None
A123 GASTROINTESTINAL SYMPTOMS AND DISORDERS OF GUT BRAIN INTERACTION ARE COMMON IN PATIENTS WITH EHLERS-DANLOS SYNDROME (EDS) IN TERTIARY REFERRAL CENTER
Authors: Abu-Farhaneh E , Tse Y , Parker C H , Liu L W
Published: February 2020

Background

Ehlers Danlos Syndrome (EDS) is a group of rare connective tissue disorders. Gastrointestinal (GI) symptoms such as abdominal pain, nausea, vomiting, bloating and altered bowel habits are common in patients with EDS. Specifically, disorders of gut brain interaction (DGBI) appear to be more common in this patient population. The University Health Network (UHN) has the first and only multi-disciplinary clinic, including specialized gastroenterology services, in Canada for the management of EDS.

Aims

The aim of this study is to describe the GI symptoms and DGBI that are present in our cohort of EDS patients.

Methods

A retrospective chart review of all EDS who were seen in the gastroenterologist clinic of the GoodHope EDS clinic at UHN were reviewed from November 1, 2017 to September 26, 2019. Demographic information including age, sex and EDS subtype were collected. GI symptoms that were collected include constipation, diarrhea, fecal incontinence, nausea, vomiting, bloating, abdominal pain, early satiety, heart burn, dysphagia and regurgitation. A physician made diagnosis of irritable bowel syndrome (IBS) was recorded. Descriptive statistics were performed.

Results

The charts of 79 EDS patients were reviewed; 4 were excluded due to missing data. 75 patients were included in the final analysis. 93.3% of patients were female with a mean age of 36.4 +/- 12.5 years. Of these 75 patients, 43 (57.3%) had EDS-hypermobile subtype, 13 (17.3%) EDS-classic, 3 (4%) EDS-vascular, 3 (4%) unknown EDS subtype and 13 (17.3%) were categorized as having a hypermobile spectrum disorder. The most common GI symptoms observed in this patient group included abdominal pain in 85.5%, bloating in 64.4%, heartburn in 61.8%, constipation in 57.9%, nausea in 50%, diarrhea 43.4%, dysphagia in 43.4%, regurgitation in 34.2%, early satiety in 32.89%, vomiting in 30.2%,and fecal incontinence in 13.1%. It was also observed that 50.7% (n=38) had a physician made diagnosis of IBS. Of these patients with IBS, 16 (42.1%) had IBS constipation, 12 (31.5%) had IBS mixed, and 10 (26.3%) had IBS diarrhea.

Conclusions

Our study demonstrated that GI symptoms are common in patients with EDS. In our cohort, abdominal pain is the most commonly reported GI symptom, though other various GI symptoms are also reported in high numbers. DGBI are also common, with IBS being much more common than what has been reported in the general population. Further studies are needed to better understand the pathophysiology and impact of these GI symptoms and DGBI in patients with EDS.

Funding Agencies

UNH Foundation Goodhope Fund
A131 MALNUTRITION FOLLOWING IMPLEMENTATION OF A STRICT LOW FODMAP DIET FOR IBS
Authors: Woodman K , Bercik P
Published: February 2020

Background

Low fermentable oligosaccharides, disaccharides, monosaccharides and polysaccharides, polyols (FODMAP) diet is an elimination diet recommended for the symptom management of irritable bowel syndrome (IBS). It involves reducing the amount of unabsorbed and fermentable carbohydrates in attempt to decrease osmotic overload and gas production. This diet may be deficient in calcium and carbohydrates and alter the gut microbiota, however, its long-term nutritional implications are unknown. Thus, the 2019 CAG Guidelines for management of IBS suggest its short-term use with dietician supervision. To our knowledge, no previous cases of malnutrition secondary to a low FODMAP diet have been reported.

Aims

We report of case of severe weight loss and laboratory evidence of malnutrition following a low FODMAP diet in a patient with IBS.

Methods

Data was obtained by chart review, patient interview and review of relevant literature.

Results

A 40-year-old otherwise healthy female presented to the outpatient gastroenterology clinic for assessment of IBS in fall of 2018. At that time, she had been moderately restricting FODMAPs for several months to reduce abdominal pain and bloating. After her initial clinic visit, she followed a strict low FODMAP diet for 1 month, followed by slow and gradual re-introduction of high FODMAP containing foods. This was self-implemented without the supervision of a dietician, using on-line resources. From fall of 2018 to early 2019, she lost 12 percent of her body weight secondary to dietary restriction. While there was some improvement in bloating and pain, she developed significant fatigue.

Blood work prior to implementation of low FODMAPs diet was normal, including INR of 1.2, albumin of 45 g/L, neutrophil count 2.2 x 10E9/L, and alkaline phosphatase 31 U/L (30–110 U/L). In spring of 2019, 5 months after starting a low FODMAP diet, her INR was elevated at 1.4, neutrophils low at 1.6 x 10^9/L, alkaline phosphatase low at 32 U/L (35 U/L – 120 U/L), with normal albumin of 45 g/L. After consulting a hematology specialist, she was advised to resume adequate dietary intake.

She slowly returned to her baseline diet, but excluded lactose, beans, fruit, eggs, nuts and oats. While she restored her body weight by Fall 2019, her gut symptoms returned, although had improved overall. Her lab work showed normal neutrophils of 2.7 x 10^9/L, INR 1.3, with unchanged albumin at 45g/L.

Conclusions

While these are indirect markers of nutritional adequacy, the timeline and associated weight loss are highly suggestive of dietary inadequacy secondary to FODMAP restriction. Serum albumin remained normal as FODMAP restriction does not affect dietary protein intake. This case exemplifies the danger of initiating extreme dietary restriction in self-management manner and stresses the need of dietician supervision of such a restrictive diet.

Funding Agencies

None