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  • Wong, K  (28)
  • 1
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2018
    In:  Journal of the Canadian Association of Gastroenterology Vol. 1, No. suppl_1 ( 2018-03-01), p. 180-181
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 1, No. suppl_1 ( 2018-03-01), p. 180-181
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 2
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2024
    In:  Journal of the Canadian Association of Gastroenterology Vol. 7, No. Supplement_1 ( 2024-02-14), p. 220-220
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 7, No. Supplement_1 ( 2024-02-14), p. 220-220
    Abstract: FMT has shown promise at inducing remission in ulcerative colitis. The effect of FMT on inducing remission in Crohn’s disease however remains unknown. Aims To evaluate the efficacy of FMT at inducing remission in mild-to-moderate Crohn’s disease Methods This double-blind, randomized, trial conducted at 3 Canadian academic centers (Edmonton, Hamilton and Calgary) randomized. Adult patients with mild-to-moderate Crohn’s disease with modified Harvey Bradshaw Index (mHBI) score of ampersand:003E5 and at least one objective measure of inflammation (CRP ≥ 8mg/L or fecal calprotectin (FCP) ≥ 250 ug/g) on stable dosing of concomitant therapy were assigned to FMT or placebo. First assigned treatment was by colonoscopy followed by 20 [DK1] capsules weekly for 7 weeks. Endoscopic severity (SES-CD) was assessed at baseline during colonoscopic delivery of assigned treatment and at week 8 by a blinded central reader using video recording. The primary endpoint was the proportion of patients in both clinical (mHBI ampersand:003C 5) and endoscopic remission (SES-CD ≤ 5) at week 8. Responders (reduction of HBI ≥ 3 or HBI ≤ 5 and reduction of CRP or FCP by ≥ 10%) in FMT group were eligible to continue with open-label FMT capsule every 2 weeks. Non-responders in the placebo group were permitted to restart the trial at week 0 with open-label FMT. Secondary outcomes included patient reported outcomes and safety outcomes. Results Between July 2017 to Jun 2021, 28 were randomized (16 to FMT and 12 to placebo). The study team voluntarily suspended the trial twice due to Health Canada safety warnings regarding potential transmission of multi-drug resistant organisms and SARS-CoV-2 through FMT. At week 8, 0% (0/16) of patients in the FMT group versus 8.3% (1/12) in the placebo group reached the primary endpoint of combined clinical and endoscopic remission. Of the 50% (8/16) in the FMT group who achieved a clinical response and continued on open-label FMT every 2 weeks, 12.5% (1/8) achieved the primary endpoint. Of the 7 non-responders in the placebo group who restarted the trial at week 0 and received open-label FMT, 28.6% (2/7) achieved primary endpoint at week 8 on open-label FMT. No death or hospitalization were observed. The study was terminated early at the recommendation of the Data Safety Monitoring Board. Conclusions FMT was not effective at inducing remission in Crohn’s disease using the FMT regimen in this study. However, this study was limited by a small sample size and recruitment barrier during the COVID pandemic. Future studies may consider other strategies to potentially enhance treatment response, including antibiotic pre-treatment, optimized donor-recipient pairing, and concomitant anti-inflammatory diet. Funding Agencies CIHR
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2024
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  • 3
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2018
    In:  Journal of Crohn's and Colitis Vol. 12, No. supplement_1 ( 2018-01-16), p. S297-S298
    In: Journal of Crohn's and Colitis, Oxford University Press (OUP), Vol. 12, No. supplement_1 ( 2018-01-16), p. S297-S298
    Type of Medium: Online Resource
    ISSN: 1873-9946 , 1876-4479
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2389631-0
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  • 4
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 1, No. suppl_1 ( 2018-03-01), p. 188-190
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
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  • 5
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Journal of the Canadian Association of Gastroenterology Vol. 5, No. Supplement_1 ( 2022-02-21), p. 65-67
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 5, No. Supplement_1 ( 2022-02-21), p. 65-67
    Abstract: Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colonic epithelium, with potential roles for the inflammasome, complement activation, T cells, and the microbiome in pathogenesis. We applied an established method of microarray-based gene expression analysis to a set of 128 UC biopsies (from 113 patients), to elucidate the molecular changes associated with active UC. Aims Our aim was to describe the molecules most associated with UC disease activity (the endoscopic Mayo score) and to annotate these molecules into biological processes. Methods 128 UC colonic biopsies were collected at the University of Alberta Hospital (Edmonton, Alberta) and Cedars-Sinai Hospital (Los Angeles, California) during standard of care colonoscopy. Biopsies were processed using Affymetrix microarrays. Gene expression data from the population was visualized using volcano plots (showing fold change and association between genes and endoscopic Mayo score), and heatmaps (showing expression of the top 30 genes in a previously established cell panel). Overexpression of top genes was analyzed using Gene Ontology and KEGG pathways. Results The volcano plot (Figure 1A) showed strong associations between the endoscopic Mayo score and components of innate immunity, e.g. complement factor B (CFB), C1-inhibitor (also known as SERPING1), chitinase 3-like 1 (CHI3L1), and inflammasome genes (ZBP1 and PIM2). Moderate associations with calprotectin (S100A8 and S100A9), other inflammasome components (CASP1 and NLRP3), and T cell transcripts (i.e. CTLA4, PDL1) were observed. Targets of biologic therapy (TNFA, ITGA4/B7, IL12B) were weakly associated with the endoscopic Mayo score. Expression of the top genes in a cell panel (Figure 1B) showed primary expression in monocytes, macrophages, dendritic cells, and polymorphonucleocytes, with some expression in colon epithelial and endothelial cells. Minimal expression was found in CD4/CD8 T cells or NK cells. Pathway analysis represented extracellular matrix remodeling, complement regulation, and TNFA signaling, but revealed no pathways associated with adaptive immunity (Table 1). Conclusions UC disease activity, as assessed by the endoscopic Mayo score, was strongly associated with tissue remodeling and molecules of innate immunity that were largely found in myeloid cells, colon epithelium, and endothelium. Cognate T cells were not dominant features of UC disease activity. These data suggest that the driver of ongoing UC activity is independent of the cognate T cell response. Funding Agencies None
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
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  • 6
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2022
    In:  Journal of the Canadian Association of Gastroenterology Vol. 5, No. Supplement_1 ( 2022-02-21), p. 37-38
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 5, No. Supplement_1 ( 2022-02-21), p. 37-38
    Abstract: Ulcerative colitis (UC) is a chronic inflammatory condition affecting the colonic epithelium. We used an established microarray-based system to analyze a set of 128 UC biopsies (113 patients), assessing gene expression associated with the colon’s response to injury in UC. Aims Our aim was to describe the burden of injury in UC biopsies and to explore molecular heterogeneity across disease activity, as assessed by the endoscopic Mayo score. Methods 128 UC colon biopsies were collected at the University of Alberta Hospital (Edmonton, AB) and Cedars-Sinai Hospital (Los Angeles, CA) during standard of care colonoscopy and processed using Affymetrix microarrays. Principal component analysis (PCA) and archetypal analysis (AA) visualized relationships between biopsies and previously annotated injury-associated transcript sets. AA assigned each biopsy to one of three groups, and scores to each biopsy relating it to all three groups. Results Spearman correlations (Table 1A) were highest between the endoscopic Mayo score and the injury-repair-associated transcripts (IRRAT, 0.64, P=4.7x10-16), immunoglobulin transcripts highly associated with chronic injury and fibrosis (IGT, 0.63, P=3.0x10-15), endothelial transcripts (ENDAT, 0.61, P=1.8x10-14), and parenchymal dedifferentiation i.e. epithelial solute carrier loss (CT2, -0.60, P=6.5x10-14). PCA separated injury from no injury in PC1 (Figure 1A). T cell transcripts (QCATs), interferon-gamma inducible transcripts (GRITs) and targets of biologics (IL12, TNFA, ITGA4/B7) separated from injury transcripts in PC2. We assigned three AA groups and visualized biopsies in PCA (Figure 1B, colored by AA membership). Group 1 (grey, N=44) biopsies had little parenchymal dedifferentiation and low expression of injury-associated transcripts. Groups 2 (red, N=44) and 3 (blue, N=40) had increased expression of injury-associated transcript sets and dedifferentiation compared to Group 1 (Table 1). Although Group 3 was endoscopically similar to Group 1 (P & gt;0.05), Group 3 showed elevated injury-associated transcript set expression (e.g. IRRAT) and increased parenchymal dedifferentiation (CT2). Conclusions Assessment of UC biopsies using AA and previously annotated injury-associated gene sets reveals two groups of biopsies that are endoscopically similar though one group has increased molecular abnormalities, thus revealing heterogeneity unrelated to the Mayo score. A molecular system based around PCA and AA could enhance and refine UC disease assessment by allowing for quantitation and qualification of injury in biopsies obtained at endoscopy i.e. a level of resolution beyond conventional endoscopic scoring. Funding Agencies None
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2022
    detail.hit.zdb_id: 2940642-0
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  • 7
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2018
    In:  Journal of the Canadian Association of Gastroenterology Vol. 1, No. suppl_2 ( 2018-03-01), p. 215-215
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 1, No. suppl_2 ( 2018-03-01), p. 215-215
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2940642-0
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  • 8
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 1, No. suppl_1 ( 2018-03-01), p. 182-184
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2940642-0
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  • 9
    Online Resource
    Online Resource
    Oxford University Press (OUP) ; 2020
    In:  Journal of the Canadian Association of Gastroenterology Vol. 3, No. Supplement_1 ( 2020-02-26), p. 96-98
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 3, No. Supplement_1 ( 2020-02-26), p. 96-98
    Abstract: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), may affect multiple organ systems. The extraintestinal manifestations (EIMs) occur frequently, considerably increase morbidity and mortality, and strongly influence the quality of life in IBD patients. Aims To establish the all-time prevalence of EIMs in a large cohort of IBD patients and assess risk factors contributing to their development. Methods We conducted a retrospective cohort study of IBD patients followed at the Division of Gastroenterology, University of Alberta, diagnosed between 1954 and 2019. We recorded demographic, clinical, and biochemical data. The EIMs included dermatological, musculoskeletal, ophthalmological, hepatobiliary, urogenital, and pulmonary manifestations. The chi-square and Mann-Whitney tests (median, IQR) were used to evaluate differences. Univariate logistic regression was used to determine the association of EIMs with demographic and disease-specific variables across CD and UC, with predictors (p≤0.05) further incorporated into multivariate regression models. Results We analyzed data of 4493 IBD patients: 2354 with CD and 2139 – with UC, aged 18–96 years. Males were underrepresented in the CD cohort compared to the UC (47.8% vs 52.8%; p=0.001), with longer disease duration (16.3, IQR 16.1 vs 12.3, IQR 12.4 years; p≤0.001). The EIMs were slightly more prevalent in the CD group compared to UC (22.2% vs 20.4%; p=0.134), along with a significantly higher proportion of patients with over two EIMs (4.1% vs 1.7%; p≤0.001). The EIMs’ pattern varied substantially between the IBD subtypes (Figure). In the CD cohort, the most common EIM was peripheral arthropathy (4.1%), followed by ankylosing spondylitis (4.0%) and nephrolithiasis (3.6%). Among CD patients, disease duration ≥20 years (OR 1.70, 95% CI 1.17–2.48; p=0.006), iron (OR 1.54, 95%CI 1.13–2.09; p=0.006) and calcium (OR 2.28, 95% CI 1.21–4.27; p=0.010) deficiencies were identified as risk factors for EIMs. The UC patients most frequently had primary sclerosing cholangitis (9.6%) with peripheral arthropathy and nephrolithiasis each being present in 2.2% of patients. In the UC cohort, three variables demonstrated the most significant associations with EIMs: male sex (OR 1.75, 95% CI 1.32–2.32; p≤0.001), disease duration ≥20 years (OR 1.93, 95% CI 1.35–2.74; p≤0.001), and pan-colonic disease extent (OR 2.12, 95% CI 1.03–4.36; p=0.041) (Table). Conclusions Our data demonstrate that over one-fifth of IBD patients had at least one EIM over the course of the disease and the EIMs pattern varies substantially across CD and UC. Identification of risk factors allowing prediction of EIMs would increase awareness, assist in their early recognition, and tailor further management. Funding Agencies AbbVie
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2020
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  • 10
    In: Journal of the Canadian Association of Gastroenterology, Oxford University Press (OUP), Vol. 1, No. suppl_1 ( 2018-03-01), p. 225-226
    Type of Medium: Online Resource
    ISSN: 2515-2084 , 2515-2092
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2018
    detail.hit.zdb_id: 2940642-0
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