Publications by authors named "Brian Bressler"

123 Publications

Providing Hospitalized Ulcerative Colitis Patients With Practice Guidelines Improves Patient-Reported Outcomes.

J Can Assoc Gastroenterol 2021 Jun 9;4(3):131-136. Epub 2020 Jun 9.

Division of Gastroenterology, Mount Sinai Hospital, Department of Medicine, University of Toronto, Toronto, Ontario, Canada.

Background And Aims: Variation in care has been demonstrated among hospitalized patients with ulcerative colitis. Guidelines aim to reduce variation; however, it is known that the uptake of guidelines by physicians is variable. Providing patients with guidelines is a strategy that has not been extensively studied in inflammatory bowel disease (IBD). Our aim was to evaluate the impact of a patient-directed educational intervention that included treatment guidelines among hospitalized ulcerative colitis patients.

Methods: We performed a quality improvement, cluster-randomized trial at seven tertiary IBD centres. Sites were randomized to implement an educational intervention or standard care for a 6-month period between January 2017 and January 2018. The educational intervention consisted of a patient-directed video that provided a summary of inpatient management guidelines for ulcerative colitis. Primary outcome measures included the length of stay and colectomy at discharge and 6 months. Patient-reported outcomes included trust in physician and patient satisfaction at discharge and at 6 months.

Results: Ninety-one patients were enrolled. No statistically significant differences in length of stay or colectomy were noted. Patients who received the intervention had higher trust in physician as measured by Trust in Physician Score at discharge (69.5 vs. 62.6, = 0.028) and at 6 months (77.7 vs. 68, = 0.008). Patient satisfaction as measured by the CACHE questionnaire in the intervention group was higher at discharge (72.8 vs. 67.1, = 0.04); however, this difference was not sustained.

Conclusion: Empowering patients with guidelines through an educational intervention resulted in differences in trust in physician and patient satisfaction. Further studies are needed for evaluating a strategy of engaging IBD patients to take a more active role in their care. (clinicaltrials.gov, NCT02569333).
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http://dx.doi.org/10.1093/jcag/gwaa019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8158645PMC
June 2021

Clinical Implications of Recent Findings From the EVOLVE Study.

Authors:
Brian Bressler

Gastroenterol Hepatol (N Y) 2020 Aug;16(8):420-422

Clinical Associate Professor of Medicine Division of Gastroenterology University of British Columbia Vancouver, British Columbia, Canada.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8132657PMC
August 2020

Interleukin-37 regulates innate immune signaling in human and mouse colonic organoids.

Sci Rep 2021 Apr 15;11(1):8206. Epub 2021 Apr 15.

Department of Pediatrics, BC Children's Hospital, University of British Columbia, Vancouver, BC, Canada.

Intestinal epithelial cells (IEC) reside in close proximity to the gut microbiota and are hypo-responsive to bacterial products, likely to prevent maladaptive inflammatory responses. This is in part due to their strong expression of Single Ig IL-1 related receptor (SIGIRR), a negative regulator of interleukin (IL)-1 and toll-like receptor signaling. IL-37 is an anti-inflammatory cytokine that inhibits innate signaling in diverse cells by signaling through SIGIRR. Despite the strong expression of SIGIRR by IEC, few studies have examined whether IL-37 can suppress their innate immune signaling. We characterized innate immune responses of human and murine colonoids to bacteria (FliC, LPS) and host (IL-1β) products and the role of IL-37/SIGIRR in regulating these responses. We demonstrated that human colonoids responded only to FliC, but not to LPS or IL-1β. While colonoids derived from different donors displayed significant inter-individual variability in the magnitude of their innate responses to FliC stimulation, all colonoids released a variety of chemokines. Interestingly, IL-37 attenuated these responses through inhibition of p38 and NFκB signaling pathways. We determined that this suppression by IL-37 was SIGIRR dependent, in murine organoids. Along with species-specific differences in IEC innate responses, we show that IL-37 can promote IEC hypo-responsiveness by suppressing inflammatory signaling.
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http://dx.doi.org/10.1038/s41598-021-87592-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8050237PMC
April 2021

Vedolizumab and Anti-TNFα Real-World Outcomes in Biologic-Naïve Inflammatory Bowel Disease Patients: Results from the EVOLVE Study.

J Crohns Colitis 2021 Mar 31. Epub 2021 Mar 31.

Evangelismos Hospital, Athens, Greece.

Background And Aims: This study aimed to compare real-world clinical effectiveness and safety of vedolizumab, an α4β7-integrin inhibitor, and anti-tumour necrosis factor-α (anti-TNFα) agents in biologic-naïve ulcerative colitis (UC) and Crohn's disease (CD) patients.

Methods: This was a 24-month retrospective medical chart study in adult UC and CD patients treated with vedolizumab or anti-TNFα in Canada, Greece and the United States. Inverse probability weighting was used to account for differences between groups. Primary outcomes were cumulative rates of clinical effectiveness (clinical response, clinical remission, mucosal healing) and incidence rates of serious adverse events (SAEs) and serious infections (SIs). Secondary outcomes included cumulative rates of treatment persistence (patients who did not discontinue index treatment during follow-up) and dose escalation and incidence rates of disease exacerbations and disease-related surgeries. Adjusted analyses were performed using inverse probability weighting.

Results: A total of 1095 patients (604 UC, 491 CD) were included. By 24 months, rates of clinical effectiveness were similar between groups, but incidence rates of SAEs (HR=0.42 [0.28-0.62]) and SIs (HR=0.40 [0.19-0.85]) were significantly lower in vedolizumab vs anti-TNFα patients. Rates of treatment persistence (p<0.01) by 24 months were higher in vedolizumab patients with UC. Incidence rates of disease exacerbations were lower in vedolizumab patients with UC (HR=0.58 [0.45-0.76]). Other outcomes did not significantly differ between groups.

Conclusion: In this real-world setting, first-line biologic therapy in biologic-naïve patients with UC and CD demonstrated that vedolizumab and anti-TNFα treatments were equally effective at controlling disease symptoms, but vedolizumab has a more favourable safety profile.
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http://dx.doi.org/10.1093/ecco-jcc/jjab058DOI Listing
March 2021

International Perspectives on Management of Inflammatory Bowel Disease: Opinion Differences and Similarities Between Patients and Physicians From the IBD GAPPS Survey.

Inflamm Bowel Dis 2021 Jan 29. Epub 2021 Jan 29.

The Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Background: Inflammatory bowel diseases (IBD), including Crohn disease (CD) and ulcerative colitis (UC), are complex disorders with multiple comorbidities. We conducted international patient and physician surveys to evaluate current experiences and perceptions of patients with CD or UC and physicians who treat IBD.

Methods: The IBD Global Assessment of Patient and Physician Unmet Need Surveys comprised a patient survey and a physician survey, fielded in North America and Europe between August 16, 2019, and November 10, 2019. Adults with CD or UC (targeted 1:1 ratio) were recruited from physicians, patient advocacy groups, and recruitment panels; physicians were recruited by recruitment agencies and panels.

Results: In total, 2398 patients with IBD (1368 CD, 1030 UC) and 654 physicians completed surveys. Anxiety and depression were the most common comorbidities among patients with IBD. Patients and physicians were generally aligned on treatment goals and patient-physician communication. Patients with IBD reported high quality-of-life impact by rectal urgency and need to use the toilet, which were rated as lower-impact by physicians. Patients defined remission based on symptoms; physicians defined remission based primarily on clinical tests. Patients expected current treatments to control their disease for a longer duration than did physicians. Patients expressed more concern about corticosteroid use compared with physicians; many physicians reported prescribing corticosteroids for more than 4 months per year in some patients.

Conclusions: Patients could benefit from education about disease remission and expectations for current therapies. High corticosteroid use is concerning to patients, and physicians should minimize the use of corticosteroids for extended periods of time.
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http://dx.doi.org/10.1093/ibd/izab006DOI Listing
January 2021

Do You See What I See? An Assessment of Endoscopic Lesions Recognition and Description by Gastroenterology Trainees and Staff Physicians.

J Can Assoc Gastroenterol 2020 Oct 19;3(5):216-221. Epub 2019 Jun 19.

Division of Gastroenterology, McGill University Health Center, Montreal, Quebec, Canada.

Background: Gastroenterologists should accurately describe endoscopic findings and integrate them into management plans. We aimed to determine if trainees and staff are describing inflammatory bowel disease (IBD) lesions in a similar manner.

Methods: Using 20 ileocolonoscopy images, participants described IBD inflammatory burden based on physician severity rating, and Mayo endoscopic score (MES) (ulcerative colitis [UC]) or simple endoscopic score (SES-CD) (Crohn's disease [CD]). Images were selected based on agreement by three IBD experts. Findings of varying severity were presented; 10 images included a question about management. We examined inter-observer agreement among trainees and staff, compared trainees to staff, and determined accuracy of response comparing both groups to IBD experts.

Results: One hundred and twenty-nine staff and 47 trainees participated from across Canada. There was moderate inter-rater agreement using physician severity rating (κ = 0.53 UC and 0.52 CD for staff, κ = 0.51 UC and 0.43 CD for trainees). There was moderate inter-rater agreement for MES for staff and trainees (κ = 0.49 and 0.48, respectively), but fair agreement for SES-CD (κ = 0.37 and 0.32, respectively). For accuracy of response, the mean score was 68.7% for staff and 63.7% for trainees ( = 0.028). Both groups identified healed bowel or severe disease better than mild/moderate ( < 0.05). There was high accuracy for management, but staff scored higher than trainees for UC ( < 0.01).

Conclusion: Inter-rater agreement on description of IBD lesions was moderate at best. Staff and trainees more accurately describe healed and severe disease, and better describe lesions in UC than CD.
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http://dx.doi.org/10.1093/jcag/gwz022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7465549PMC
October 2020

Pharmacological inhibition of RORC2 enhances human Th17-Treg stability and function.

Eur J Immunol 2020 09 10;50(9):1400-1411. Epub 2020 Jun 10.

Department of Surgery, The University of British Columbia, Columbia, Vancouver, British Columbia, Canada.

Inflammatory bowel diseases (IBD) are chronic conditions that result from uncontrolled intestinal inflammation. Pathogenic Th17 cells, characterized by production of IL-17A in the absence of IL-10, are thought to contribute to this inflammation, but in humans, antibody-mediated blockade of IL-17A is an ineffective IBD therapy whereas IL-23 blockade is effective. Here, we investigated the effects of pharmacological inhibition of RORC2, the Th17 cell lineage-defining transcription factor, on in vivo-differentiated human Th17 cells and Th17-like Tregs (Th17-Tregs). BMS-336, a small molecule RORC2 inverse agonist, inhibited expression of RORC2-regulated genes in peripheral Th17 cells (CD4 CD25 CD127 CXCR3 CCR4 CCR6 ) in a dose-dependent manner, with similar inhibitory effects on laminar propria mononuclear cells from IBD and non-IBD subjects. Exposure of peripheral Th17-Tregs (CD4 CD25 CD127 CXCR3 CCR4 CCR6 ) to BMS-336 also inhibited IL-17A production and prevented inflammatory cytokine-induced destabilization, as evidenced by preserved FOXP3 expression and epigenetic status of the Treg-specific demethylation region. In parallel, RORC2 inhibition increased the production of IL-10 in Th17-Tregs, resulting in enhanced suppression of inflammatory cytokines from myeloid cells. Thus, via its ability to simultaneously inhibit Th17 cells and enhance the stability and function of Th17-Tregs, pharmacological inhibition of RORC2 is a promising approach to suppress inflammation and promote immune regulation in IBD.
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http://dx.doi.org/10.1002/eji.201948435DOI Listing
September 2020

Validation of the St. Paul's Endoscopy Comfort Scale (SPECS) for Colonoscopy.

J Can Assoc Gastroenterol 2020 Apr 21;3(2):91-95. Epub 2018 Dec 21.

Department of Internal Medicine, Division of Gastroenterology, University of British Columbia, Vancouver, British Columbia, Canada.

Aims: Patient comfort during colonoscopy is an important measure of quality, which can improve patient satisfaction and compliance with future procedures. Our aim was to develop and validate a pain assessment tool based on objective behavioural cues tailored to outpatients undergoing colonoscopy: St. Paul's endoscopy comfort score (SPECS).

Methods: A single-centre, prospective study was conducted in consecutive adults undergoing planned outpatient colonoscopy. Patient comfort was independently assessed by the physician, nurse and a research assistant (observer) using the SPECS and the Gloucester scale (GS). In addition, the nurse-assessed patient comfort score (NAPCOMS), nonverbal pain Assessment tool (NPAT) and Richmond agitation sedation scale (RASS) were completed by the observer. Data on subject demographics, sedation dose and duration of the procedure were collected. Following the procedure, patients completed a patient satisfaction questionnaire, including a visual analogue scale (VAS) to measure their overall perceived pain during the procedure.

Results: The study enrolled 350 subjects. The SPECS showed excellent inter-rater reliability among all three raters with an intra-class coefficient (ICC) of 0.81 (95% CI, 0.78-0.84), while the GS showed good reliability with an ICC of 0.77 (95% CI, 0.73-0.80). The SPECS demonstrated moderate agreement with the patient-reported VAS ratings.

Conclusions: The St. Paul's endoscopy comfort score was successfully validated, demonstrating excellent inter-rater reliability.
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http://dx.doi.org/10.1093/jcag/gwy073DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7165262PMC
April 2020

Improvement of Endoscopic Reports with Implementation of a Dictation Template.

J Can Assoc Gastroenterol 2021 Feb 19;4(1):21-26. Epub 2019 Dec 19.

St. Paul's Hospital, Vancouver, Canada.

Aims: Completeness of procedure reports is an important quality indicator in endoscopy. A dictation template was developed to ensure key elements were included in colonoscopy and esophagogastroduodenoscopy (EGD) reports. Endoscopy reports were reviewed prior to and following implementation of the dictation templates to determine whether report completeness improved.

Methods: Key elements in an endoscopic report were identified from published guidelines and posted at dictation stations. Colonoscopy and EGD reports were reviewed for the nine physicians performing endoscopy at St. Paul's Hospital prior to and following implementation of dictation templates. Dictation completeness was defined as inclusion of all key elements. Dictation completeness and inclusion of individual key elements at the two time points were compared using the -test and Chi-square test.

Results: Reports for 4648 procedures undertaken by nine endoscopists were reviewed for completeness at each time point (2008 and 2014). Colonoscopy report completeness increased from 65.8% to 83.2% ( < 0.001). Items that improved included documentation of consent, endoscope used, complications, withdrawal time and rectal retroflexion. EGD report completeness increased from 72.7% to 77.3% ( < 0.001) with improvement in documentation of consent and complications. Items consistently underreported for colonoscopy and EGD at both time points included: patient age, comorbidities, current medications and patient comfort.

Conclusion: There was an association between the use of a posted dictation template at dictation stations and the improved completeness of endoscopic reports.
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http://dx.doi.org/10.1093/jcag/gwz033DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7898381PMC
February 2021

Clinical Practice Guideline for the Medical Management of Perianal Fistulizing Crohn's Disease: The Toronto Consensus.

J Can Assoc Gastroenterol 2018 Dec 14;1(4):141-154. Epub 2018 Sep 14.

Division of Digestive Care & Endoscopy, Department of Medicine, Dartmouth General Hospital, Halifax, Nova Scotia, Canada.

Background: Fistulas occur in about 25% of patients with Crohn's disease (CD) and can be difficult to treat. The aim of this consensus was to provide guidance for the management of patients with perianal fistulizing CD.

Methods: A systematic literature search identified studies on the management of fistulizing CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform using a modified Delphi process, then finalized, and voted on by a group of specialists.

Results: The quality of evidence for treatment of fistulizing CD was generally of very low quality, and because of the scarcity of good randomized controlled trials (RCTs), these consensus statements generally provide conditional suggestions (5 of 7 statements). Imaging and surgical consultations were recommended in the initial assessment of patients with active fistulizing CD, particularly those with complicated disease. Antibiotic therapy is useful for initial symptom control. Antitumor necrosis factor (anti-TNF) therapy was recommended to induce symptomatic response, and continued use was suggested to achieve and maintain complete remission. The use of concomitant immunosuppressant therapies may be useful to optimize pharmacokinetic parameters when initiating anti-TNF therapy. When there has been an inadequate symptomatic response to medical management strategies, surgical therapy may provide effective fistula healing for some patients.

Conclusions: Optimal management of perianal fistulizing CD requires a collaborative effort between gastroenterologists and surgeons and may include the evidence-based use of existing therapies, as well as surgical assessments and interventions when needed.
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http://dx.doi.org/10.1093/jcag/gwy047DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6542243PMC
December 2018

Enteroids Derived From Inflammatory Bowel Disease Patients Display Dysregulated Endoplasmic Reticulum Stress Pathways, Leading to Differential Inflammatory Responses and Dendritic Cell Maturation.

J Crohns Colitis 2020 Jul;14(7):948-961

Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.

Background And Aims: Endoplasmic reticulum [ER] stress in intestinal epithelial cells [IECs] contributes to the pathogenesis of inflammatory bowel disease [IBD]. We hypothesized that ER stress changes innate signalling in human IECs, augmenting toll-like receptor [TLR] responses and inducing pro-inflammatory changes in underlying dendritic cells [DCs].

Methods: Caco-2 cells and primary human colon-derived enteroid monolayers were exposed to ATP [control stressor] or thapsigargin [Tg] [ER stress inducer], and were stimulated with the TLR5 agonist flagellin. Cytokine release was measured by an enzyme immunoassay. ER stress markers CHOP, GRP78 and XBP1s/u were measured via quantitative PCR and Western blot. Monocyte-derived DCs [moDCs] were cultured with the IEC supernatants and their activation state was measured. Responses from enteroids derived from IBD patients and healthy control participants were compared.

Results: ER stress enhanced flagellin-induced IL-8 release from Caco-2 cells and enteroids. Moreover, conditioned media activated DCs to become pro-inflammatory, with increased expression of CD80, CD86, MHCII, IL-6, IL-15 and IL-12p70 and decreased expression of CD103 and IL-10. Flagellin-induced IL-8 production correlated with DC activation, suggesting a common stress pathway. Moreover, there were distinct differences in cytokine expression and basal ER stress between IBD and healthy subject-derived enteroid monolayers, suggesting a dysregulated ER stress pathway in IBD-derived enteroids.

Conclusions: Cellular stress enhances TLR5 responses in IECs, leading to increased DC activation, indicating a previously unknown mechanistic link between epithelial ER stress and immune activation in IBD. Furthermore, dysregulated ER stress may be propagated from the intestinal epithelial stem cell niche in IBD patients.
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http://dx.doi.org/10.1093/ecco-jcc/jjz194DOI Listing
July 2020

Analysis of Flagellin-Specific Adaptive Immunity Reveals Links to Dysbiosis in Patients With Inflammatory Bowel Disease.

Cell Mol Gastroenterol Hepatol 2020 30;9(3):485-506. Epub 2019 Nov 30.

Department of Medicine, University of British Columbia, Vancouver, British Columbia, Canada; British Columbia Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background & Aims: Bacterial flagellin is an important antigen in inflammatory bowel disease, but the role of flagellin-specific CD4 T cells in disease pathogenesis remains unclear. Also unknown is how changes in intestinal microbiome intersect with those in microbiota-specific CD4 T cells. We aimed to quantify and characterize flagellin-specific CD4 T cells in Crohn's disease (CD) and ulcerative colitis (UC) patients and study their relationship with intestinal microbiome diversity.

Methods: Blood was collected from 3 cohorts that included CD patients, UC patients, and healthy controls. Flow cytometry analyzed CD4 T cells specific for Lachnospiraceae-derived A4-Fla2 and Escherichia coli H18 FliC flagellins, or control vaccine antigens. Serum antiflagellin IgG and IgA antibodies were detected by enzyme-linked immunosorbent assay and stool samples were collected and subjected to 16S ribosomal DNA sequencing.

Results: Compared with healthy controls, CD and UC patients had lower frequencies of vaccine-antigen-specific CD4 T cells and, as a proportion of vaccine-specific cells, higher frequencies of flagellin-specific CD4 T cells. The proportion of flagellin-specific CD4 T cells that were CXCR3CCR4CCR6 Th17 cells was reduced in CD and UC patients, with increased proportions of CD39, PD-1, and integrin β7 cells. Microbiome analysis showed differentially abundant bacterial species in patient groups that correlated with immune responses to flagellin.

Conclusions: Both CD and UC patients have relative increases in the proportion of circulating Fla2-specific CD4 T cells, which may be associated with changes in the intestinal microbiome. Evidence that the phenotype of these cells strongly correlate with disease severity provides insight into the potential roles of flagellin-specific CD4 T cells in inflammatory bowel disease.
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http://dx.doi.org/10.1016/j.jcmgh.2019.11.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7036547PMC
May 2021

Efficacy and safety of tofacitinib dose de-escalation and dose escalation for patients with ulcerative colitis: results from OCTAVE Open.

Aliment Pharmacol Ther 2020 01 29;51(2):271-280. Epub 2019 Oct 29.

Pfizer Inc, Collegeville, PA, USA.

Background: For patients with UC, flexible maintenance dosing therapy may confer advantages for safety, efficacy, costs and patient preference. Tofacitinib is an oral, small molecule JAK inhibitor for the treatment of UC.

Aim: To assess the efficacy and safety of tofacitinib dose de-escalation and escalation in patients with UC.

Methods: We evaluated data (November 2017 data cut-off) from OCTAVE Open, an ongoing, open-label, long-term extension study. The dose de-escalation group comprised 66 tofacitinib induction responders in remission following 52 weeks' tofacitinib 10 mg b.d. maintenance therapy, subsequently de-escalated to 5 mg b.d. in OCTAVE Open. The dose escalation group comprised 57 tofacitinib induction responders who experienced treatment failure while receiving 5 mg b.d. maintenance therapy, subsequently escalated to 10 mg b.d. in OCTAVE Open.

Results: After tofacitinib de-escalation, 92.4% (61/66) and 84.1% (53/63) of patients maintained clinical response and 80.3% (53/66) and 74.6% (47/63) maintained remission, at months 2 and 12, respectively. After dose escalation, 57.9% (33/57) and 64.9% (37/57) of patients recaptured clinical response and 35.1% (20/57) and 49.1% (28/57) were in remission, at months 2 and 12, respectively. The incidence rate of herpes zoster with dose escalation (7.6 patients with events/100 patient-years) was numerically higher than in the overall tofacitinib UC programme.

Conclusions: Following tofacitinib de-escalation in patients already in remission on 10 mg b.d., most maintained remission, although 25.4% lost remission, at month 12. For induction responders who dose-escalated following treatment failure on 5 mg b.d. maintenance therapy, 49.1% achieved remission by month 12. (ClinicalTrials.gov number: NCT01470612).
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http://dx.doi.org/10.1111/apt.15555DOI Listing
January 2020

Editorial: aminosalicylates and nephrotoxicity-an issue put to rest.

Aliment Pharmacol Ther 2019 11;50(9):1059

University of British Columbia, Vancouver, Canada.

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http://dx.doi.org/10.1111/apt.15474DOI Listing
November 2019

Vaccination Guidelines for Patients with Immune-Mediated Disorders on Immunosuppressive Therapies-Executive Summary.

J Can Assoc Gastroenterol 2019 Dec 1;2(4):149-152. Epub 2019 Feb 1.

Faculty of Medicine, University of British Columbia, Vancouver, British Columbia, Canada.

The use of immunosuppressive therapies for immune-mediated disease (IMD) is associated with an elevated risk of infections and related comorbidities. While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal, due in part to uncertainty about their efficacy or safety under these clinical situations. To address this concern, a multidisciplinary group of Canadian physicians with expertise in dermatology, gastroenterology, infectious diseases and rheumatology developed evidence-based clinical guidelines on vaccinations featuring 13 statements that are aimed at reducing the risk of preventable infections in individuals exposed to immunosuppressive agents.
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http://dx.doi.org/10.1093/jcag/gwy069DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6785689PMC
December 2019

Suppressive and Gut-Reparative Functions of Human Type 1 T Regulatory Cells.

Gastroenterology 2019 12 10;157(6):1584-1598. Epub 2019 Sep 10.

BC Children's Hospital Research Institute, University of British Columbia, Vancouver, British Columbia, Canada; School of Biomedical Engineering, University of British Columbia, Vancouver, British Columbia, Canada; Department of Surgery, University of British Columbia, Vancouver, British Columbia, Canada. Electronic address:

Background & Aims: T-regulatory (Treg) cells suppress the immune response to maintain homeostasis. There are 2 main subsets of Treg cells: FOXP3 (forkhead box protein 3)-positive Treg cells, which do not produce high levels of effector cytokines, and type 1 Treg (Tr1) cells, which are FOXP3-negative and secrete interleukin (IL) 10. IL10 is an anti-inflammatory cytokine, so Tr1 cells might be used in the treatment of inflammatory bowel diseases. We aimed to develop methods to isolate and expand human Tr1 cells and define their functions.

Methods: We obtained blood and colon biopsy samples from patients with Crohn's disease or ulcerative colitis or healthy individuals (controls). CD4 T cells were isolated from blood samples and stimulated with anti-CD3 and anti-CD28 beads, and Tr1 cells were purified by using an IL10 cytokine-capture assay and cell sorting. FOXP3-positive Treg cells were sorted as CD4CD25CD127 cells from unstimulated cells. Tr1 and FOXP3-positive Treg cells were expanded, and phenotypes and gene expression profiles were compared. T cells in peripheral blood mononuclear cells from healthy donors were stimulated with anti-CD3 and anti-CD28 beads, and the suppressive abilities of Tr1 and FOXP3-positive Treg cells were measured. Human colon organoid cultures were established, cultured with supernatants from Tr1 or FOXP3-positive cells, and analyzed by immunofluorescence and flow cytometry. T84 cells (human colon adenocarcinoma epithelial cells) were incubated with supernatants from Tr1 or FOXP3-positive cells, and transepithelial electrical resistance was measured to determine epithelial cell barrier function.

Results: Phenotypes of Tr1 cells isolated from control individuals vs patients with Crohn's disease or ulcerative colitis did not differ significantly after expansion. Tr1 cells and FOXP3-positive Treg cells suppressed proliferation of effector T cells, but only Tr1 cells suppressed secretion of IL1B and tumor necrosis factor from myeloid cells. Tr1 cells, but not FOXP3-positive Treg cells, isolated from healthy individuals and patients with Crohn's disease or ulcerative colitis secreted IL22, which promoted barrier function of human intestinal epithelial cells. Tr1 cell culture supernatants promoted differentiation of mucin-producing goblet cells in intestinal organoid cultures.

Conclusions: Human Tr1 cells suppress proliferation of effector T cells (adaptive immune response) and production of IL1B and TNF by myeloid cells (inmate immune response). They also secrete IL22 to promote barrier function. They might be developed as a cell-based therapy for intestinal inflammatory disorders.
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http://dx.doi.org/10.1053/j.gastro.2019.09.002DOI Listing
December 2019

Internet-Based Patient Education Prior to Colonoscopy: Prospective, Observational Study of a Single Center's Implementation, with Objective Assessment of Bowel Preparation Quality and Patient Satisfaction.

J Can Assoc Gastroenterol 2020 Dec 4;3(6):274-278. Epub 2019 Sep 4.

Division of Gastroenterology, Department of Medicine, St. Paul's Hospital, University of British Columbia, Vancouver, British Columbia.

Background: Nonpharmacologic factors, including patient education, affect bowel preparation for colonoscopy. Optimal cleansing increases quality and reduces repeat procedures. This study prospectively analyzes use of an individualized online patient education module in place of traditional patient education.

Aims: To determine the effectiveness of online education for patients, measured by the proportion achieving sufficient bowel preparation. Secondary measures include assessment of patient satisfaction.

Methods: Prospective, single-center, observational study. Adults aged 19 years and over, with an e-mail account, scheduled for nonurgent colonoscopy, with English proficiency (or someone who could translate for them) were recruited. Demographics and objective bowel preparation quality were collected. Patient satisfaction was assessed via survey to assess clarity and usefulness of the module.

Results: Nine hundred consecutive patients completed the study. 84.6% of patients achieved adequate bowel preparation as measured by Boston bowel preparation score ≥ 6 and 90.1% scored adequately using Ottawa bowel preparation score ≤7. 94.2% and 92.1% of patients rated the web-education module as 'very useful' and 'very clear', respectively (≥8/10 on respective scales).

Conclusions: Our analysis suggests that internet-based patient education prior to colonoscopy is a viable option and achieves adequate bowel preparation. Preparation quality is comparable to previously published trials. Included patients found the process clear and useful. Pragmatic benefits of a web-based protocol such as time and cost savings were not formally assessed but may contribute to greater satisfaction for endoscopists and patients.
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http://dx.doi.org/10.1093/jcag/gwz026DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7678736PMC
December 2020

Use of Vedolizumab for the Treatment of Crohn's Disease.

Authors:
Brian Bressler

Gastroenterol Hepatol (N Y) 2019 Apr;15(4):204-206

Clinical Associate Professor of Medicine Division of Gastroenterology University of British Columbia Vancouver, British Columbia, Canada.

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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6696600PMC
April 2019

Novel Microbial-Based Immunotherapy Approach for Crohn's Disease.

Front Med (Lausanne) 2019 19;6:170. Epub 2019 Jul 19.

Qu Biologics Inc., Vancouver, BC, Canada.

Current Crohn's disease (CD) therapies focus on suppressing immune function and come with consequent risk, such as infection and cancer. Notwithstanding, most CD patients still experience disease progression. There is a need for new CD treatment strategies that offer better health outcomes for patients. To assess safety, efficacy, and tolerability of a novel microbial-derived immunotherapy, QBECO, that aims to restore rather than suppress immune function in CD. A randomized, double-blind, placebo-controlled trial was conducted in 68 patients with moderate-to-severe CD. Primary endpoints: safety and Week 8 clinical improvement. Secondary endpoints: Week 8 clinical response and remission. Week 8 responders continued blinded treatment through Week 16; non-responders received open-label QBECO from Weeks 9-16. Exploratory analyses included immune biomarker and genotype assessments. QBECO was well-tolerated. Mean reduction in Crohn's Disease Activity Index (CDAI) score was -68 for QBECO vs. -31 for placebo at Week 8. Improvement with QBECO continued through Week 16 (-130 CDAI reduction). Week 8 QBECO clinical response, improvement and remission rates were 41.2%, 32.4%, 29.4% vs. 26.5%, 23.5%, 23.5% for placebo. TNFα inhibitor-naïve subjects achieved higher response rates at Week 8 with QBECO (64%) vs. placebo (26%). Specific immune biomarkers were identified that linked to QBECO response. This proof-of-concept study supports further investigation for the use of QBECO as a novel immunotherapy approach for CD. Biomarker analyses suggests it may be feasible to personalize CD treatment with QBECO. Larger trials are now needed to confirm clinical improvement and the unique biological findings. NCT01809275 (https://clinicaltrials.gov/ct2/show/NCT01809275).
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http://dx.doi.org/10.3389/fmed.2019.00170DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659126PMC
July 2019

Rate of Corticosteroid-Induced Mood Changes in Patients with Inflammatory Bowel Disease: A Prospective Study.

J Can Assoc Gastroenterol 2018 Sep 4;1(3):99-106. Epub 2018 Jun 4.

University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada.

Background: Corticosteroid is an effective therapeutic option for inflammatory bowel disease flares, but its adverse effects may compromise treatment adherence and reduce patients' quality of life. There is lack of data on the incidence of corticosteroid-induced mood changes in this patient population, which may be underappreciated by healthcare providers in clinical practice and interfere with optimal care. This study aimed to determine the rate of mood changes in this patient population.

Methods: In this prospective observational study, adult outpatients treated with prednisone for inflammatory bowel disease flares were considered for inclusion. Participants completed validated questionnaires (Beck Depression Inventory-II and Activation Subscale of Internal State Scale version two) before starting prednisone, after two weeks of prednisone, and at the end of prednisone taper to assess for mood changes. Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index were used to monitor clinical disease activity.

Results: Fifty-three subjects were included in the analyses. The rate of mood change after two weeks of prednisone was 49.1%, primarily driven by increase in mood towards (hypo)mania. Younger age was an independent risk factor. Mood state returned to pretreatment level at the end of treatment. There was no correlation between clinical disease activity change and mood change.

Conclusions: Oral prednisone for inflammatory bowel disease flare is associated with high rate of mood change. As prednisone is a critical part of induction therapy, ways to minimize this adverse event must be studied. For now, healthcare providers should inform patients and monitor closely for this adverse event.
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http://dx.doi.org/10.1093/jcag/gwy023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507281PMC
September 2018

Rate of Corticosteroid-Induced Mood Changes in Patients with Inflammatory Bowel Disease: A Prospective Study.

J Can Assoc Gastroenterol 2018 Sep 4;1(3):99-106. Epub 2018 Jun 4.

University of British Columbia, Faculty of Medicine, Department of Medicine. St. Paul's Hospital, Vancouver, B.C. Canada.

Background: Corticosteroid is an effective therapeutic option for inflammatory bowel disease flares, but its adverse effects may compromise treatment adherence and reduce patients' quality of life. There is lack of data on the incidence of corticosteroid-induced mood changes in this patient population, which may be underappreciated by healthcare providers in clinical practice and interfere with optimal care. This study aimed to determine the rate of mood changes in this patient population.

Methods: In this prospective observational study, adult outpatients treated with prednisone for inflammatory bowel disease flares were considered for inclusion. Participants completed validated questionnaires (Beck Depression Inventory-II and Activation Subscale of Internal State Scale version two) before starting prednisone, after two weeks of prednisone, and at the end of prednisone taper to assess for mood changes. Harvey-Bradshaw Index and Simple Clinical Colitis Activity Index were used to monitor clinical disease activity.

Results: Fifty-three subjects were included in the analyses. The rate of mood change after two weeks of prednisone was 49.1%, primarily driven by increase in mood towards (hypo)mania. Younger age was an independent risk factor. Mood state returned to pretreatment level at the end of treatment. There was no correlation between clinical disease activity change and mood change.

Conclusions: Oral prednisone for inflammatory bowel disease flare is associated with high rate of mood change. As prednisone is a critical part of induction therapy, ways to minimize this adverse event must be studied. For now, healthcare providers should inform patients and monitor closely for this adverse event.
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http://dx.doi.org/10.1093/jcag/gwy023DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507281PMC
September 2018

Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease.

J Can Assoc Gastroenterol 2019 Aug 10;2(3):e1-e34. Epub 2018 Jul 10.

Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada.

Background & Aims: Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD.

Methods: We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists.

Results: The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent.

Conclusions: Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.
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http://dx.doi.org/10.1093/jcag/gwz019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6619415PMC
August 2019

Real World Effectiveness of Golimumab Therapy in Ulcerative Colitis Regardless of Prior TNF Exposure.

J Can Assoc Gastroenterol 2018 Sep 10;1(3):129-134. Epub 2018 May 10.

Division of Gastroenterology, Mount Sinai Hospital IBD Centre, Toronto, Ontario, Canada.

Background: The efficacy of golimumab to induce and maintain remission in biologic-naïve patients with ulcerative colitis (UC) is established from placebo-controlled trials. However, golimumab's real-world effectiveness, important to physicians and payers, remains unexplored.

Aim: The goal of this study was to describe real-world use and rate of persistence among UC patients with golimumab therapy and to assess factors that predict discontinuation during golimumab maintenance treatment.

Methods: A retrospective study of UC patients receiving golimumab maintenance therapy (August 2012-August 2015) was conducted on dosing data from a national case management program. Treatment persistence, defined as time from index prescription to the last dose (gap in dose >60 days), was assessed using Kaplan-Meier survival analysis. Predictors of treatment persistence were explored with Cox proportional hazards regression.

Results: One hundred thirty-six patients (50.7% male) with a mean (SD) age of 44.4 (15.6) years were included. At golimumab initiation, 72.1% were naïve to anti-TNFs; 77.2% received 200 mg, while 4.4% and 18.4% received 50 mg and 100 mg, respectively, every 4 weeks (induction therapy). The median time to discontinuation was 530 days, with a cumulative probability of 63% to remain on therapy at one year. Age, gender, golimumab induction, golimumab maintenance dose and prior anti-TNF exposure were not significantly associated with treatment persistence. Dose adjustment occurred in 7.4% of patients during maintenance treatment.

Conclusions: Overall, the persistence rate of golimumab observed in the current real-world study is similar to that described in previous single-centre UC cohorts and consistent with that seen in controlled clinical trials.
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http://dx.doi.org/10.1093/jcag/gwy019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6507284PMC
September 2018

Development of a Global Rating Scale for Inflammatory Bowel Disease.

J Can Assoc Gastroenterol 2020 Feb 11;3(1):4-16. Epub 2019 Jun 11.

Division of Gastroenterology, Department of Medicine, Mount Sinai Centre for Inflammatory Bowel Disease, University of Toronto, Toronto, Ontario, Canada.

Background: The Global Rating Scale (GRS) is a web-based self-assessment quality improvement tool used to identify gaps in health care, change the focus to patient-centred care and standardize care. There are four levels of achievement ranging from basic-(D) to excellent-(A) service delivery. The goal was to develop a GRS for inflammatory bowel disease (IBD) to improve the quality of care for patients on a system level.

Methods: The IBD GRS was developed through an iterative process and modeled upon the successful endoscopy GRS programs in the United Kingdom and Canada. Dimensions, items and statements were drafted based on expert opinions, patient-informed quality indicators and best available evidence, then reviewed and modified by a core committee. A working group of IBD and GRS experts voted in-person to establish consensus on the inclusion and quality of statements.

Results: Two dimensions (Clinical Quality and Quality of Patient Experience), 10 items and 89 statements made up the IBD GRS. There was a 100% response rate for each of the 40 votes for statements in the IBD GRS. All statements within each level received a mean rating score between four (agree) and five (strongly agree). Revisions agreed upon during the voting process were incorporated into the IBD GRS. Group consensus was achieved on the inclusion of statements, and 10 items were selected as standards within the two dimensions.

Conclusions: We have developed the first IBD GRS with the aim of improving quality of care through ongoing evaluations and improvements by health care teams, focusing on patient-centred care.
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http://dx.doi.org/10.1093/jcag/gwz017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8218537PMC
February 2020

Acute Severe Ulcerative Colitis: The Oxford Criteria No Longer Predict In-Hospital Colectomy Rates.

Dig Dis Sci 2020 02 15;65(2):576-580. Epub 2019 May 15.

Department of Gastroenterology, Faculty of Medicine, University of British Columbia, 2775 Laurel Street, 10th Floor, Vancouver, BC, V5Z 1M9, Canada.

Background: Patients admitted to hospital with acute severe ulcerative colitis have a short-term in-hospital colectomy rate of 30%. The Oxford criteria state that if the CRP is greater than 45 mg/l or there are more than eight bowel movements in 24 h at day 3 of intravenous corticosteroids, there is an 85% risk of an in-hospital colectomy.

Aim: The aim of this study was to determine whether this high rate of colectomy continues to be accurate in this medically refractory patient population.

Methods: We performed a retrospective chart review of 80 patients admitted to a tertiary hospital between 2013 and 2017 with acute severe ulcerative colitis.

Results: Sixteen (20%) patients required an in-hospital colectomy. Of the 33 patients that fulfilled the Oxford criteria, 12 (36%) patients required a colectomy during admission. Only four (9.5%) patients who did not fulfill the Oxford criteria required a colectomy during admission. Twenty-two patients that had fulfilled the Oxford criteria received infliximab as second-line medical therapy.

Conclusion: In a patient population that fulfilled the Oxford criteria, the in-hospital colectomy rate has reduced from 85% in 1996 to 36% in 2017. These results should be considered when discussing with patients the opportunity to commence infliximab or cyclosporine as second-line medical therapy.
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http://dx.doi.org/10.1007/s10620-019-05668-6DOI Listing
February 2020

Appropriate Therapeutic Drug Monitoring of Biologic Agents for Patients With Inflammatory Bowel Diseases.

Clin Gastroenterol Hepatol 2019 08 27;17(9):1655-1668.e3. Epub 2019 Mar 27.

Dartmouth-Hitchcock Medical Center, Lebanon, New Hampshire.

Background & Aims: Therapeutic drug monitoring (TDM) is widely available for biologic therapies in patients with inflammatory bowel disease (IBD). We reviewed current data and provided expert opinion regarding the clinical utility of TDM for biologic therapies in IBD.

Methods: We used a modified Delphi method to establish consensus. A comprehensive literature review was performed regarding the use of TDM of biologic therapy in IBD and presented to international IBD specialists. Subsequently, 28 statements on the application of TDM in clinical practice were rated on a scale of 1 to 10 (1 = strongly disagree and 10 = strongly agree) by each of the panellists. Statements were accepted if 80% or more of the participants agreed with a score ≥7. The remaining statements were discussed and revised based on the available evidence followed by a second round of voting.

Results: The panel agreed on 24 (86%) statements. For anti-tumor necrosis factor (anti-TNF) therapies, proactive TDM was found to be appropriate after induction and at least once during maintenance therapy, but this was not the case for the other biologics. Reactive TDM was appropriate for all agents both for primary non-response and secondary loss of response. The panellists also agreed on several statements regarding TDM and appropriate drug and anti-drug antibody (ADA) concentration thresholds for biologics in specific clinical scenarios.

Conclusion: Consensus was achieved towards the utility of TDM of biologics in IBD, particularly anti-TNF therapies. More data are needed especially on non-anti-TNF biologics to further define optimal drug concentration and ADA thresholds as these can vary depending on the therapeutic outcomes assessed.
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http://dx.doi.org/10.1016/j.cgh.2019.03.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6661210PMC
August 2019

Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Luminal Crohn's Disease.

Clin Gastroenterol Hepatol 2019 08 7;17(9):1680-1713. Epub 2019 Mar 7.

Section of Gastroenterology, University of Manitoba, Winnipeg, Manitoba, Canada.

Background & Aims: Crohn's disease (CD) is a lifelong illness with substantial morbidity, although new therapies and treatment paradigms have been developed. We provide guidance for treatment of ambulatory patients with mild to severe active luminal CD.

Methods: We performed a systematic review to identify published studies of the management of CD. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a group of specialists.

Results: The consensus includes 41 statements focused on 6 main drug classes: antibiotics, 5-aminosalicylate, corticosteroids, immunosuppressants, biologic therapies, and other therapies. The group suggested against the use of antibiotics or 5-aminosalicylate as induction or maintenance therapies. Corticosteroid therapies (including budesonide) can be used as induction, but not maintenance therapies. Among immunosuppressants, thiopurines should not be used for induction, but can be used for maintenance therapy for selected low-risk patients. Parenteral methotrexate was proposed for induction and maintenance therapy in patients with corticosteroid-dependent CD. Biologic agents, including tumor necrosis factor antagonists, vedolizumab, and ustekinumab, were recommended for patients failed by conventional induction therapies and as maintenance therapy. The consensus group was unable to clearly define the role of concomitant immunosuppressant therapies in initiation of treatment with a biologic agent.

Conclusions: Optimal management of CD requires careful patient assessment, acknowledgement of patient preferences, evidence-based use of existing therapies, and thorough assessment to define treatment success.
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http://dx.doi.org/10.1016/j.cgh.2019.02.043DOI Listing
August 2019

Innate Control of Tissue-Reparative Human Regulatory T Cells.

J Immunol 2019 04 8;202(8):2195-2209. Epub 2019 Mar 8.

Department of Surgery, University of British Columbia, Vancouver, British Columbia V5Z 4H4, Canada;

Regulatory T cell (Treg) therapy is a potential curative approach for a variety of immune-mediated conditions, including autoimmunity and transplantation, in which there is pathological tissue damage. In mice, IL-33R (ST2)-expressing Tregs mediate tissue repair by producing the growth factor amphiregulin, but whether similar tissue-reparative Tregs exist in humans remains unclear. We show that human Tregs in blood and multiple tissue types produced amphiregulin, but this was neither a unique feature of Tregs nor selectively upregulated in tissues. Human Tregs in blood, tonsil, synovial fluid, colon, and lung tissues did not express ST2, so ST2 Tregs were engineered via lentiviral-mediated overexpression, and their therapeutic potential for cell therapy was examined. Engineered ST2 Tregs exhibited TCR-independent, IL-33-stimulated amphiregulin expression and a heightened ability to induce M2-like macrophages. The finding that amphiregulin-producing Tregs have a noneffector phenotype and are progressively lost upon TCR-induced proliferation and differentiation suggests that the tissue repair capacity of human Tregs may be an innate function that operates independently from their classical suppressive function.
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http://dx.doi.org/10.4049/jimmunol.1801330DOI Listing
April 2019

Vaccination Guidelines for Patients with Immune-mediated Disorders Taking Immunosuppressive Therapies: Executive Summary.

J Rheumatol 2019 07 1;46(7):751-754. Epub 2019 Feb 1.

From K. Papp Clinical Research; Probity Medical Research, Waterloo; University Health Network; Faculty of Medicine, University of Toronto; Mount Sinai Hospital, Toronto; Department of Medicine and Farncombe Family Digestive Health Research Institute, McMaster University, Hamilton; Faculty of Medicine, Queen's University, Kingston; Faculty of Medicine, University of Western Ontario; St. Joseph's Health Care, London, Ontario; Centre Hospitalier de l'Université de Montréal; Innovaderm Research Inc.; McGill University Health Centre; Research Institute - McGill University Health Centre, Montreal, Quebec; Faculty of Medicine, University of British Columbia; St. Paul's Hospital; Vancouver Coastal Health; Vancouver General Hospital, Vancouver, British Columbia, Canada.

The use of immunosuppressive therapies for immune-mediated disease is associated with an elevated risk of infections and related comorbidities. While many infectious diseases can generally be prevented by vaccines, immunization rates in this specific patient population remain suboptimal, due in part to uncertainty about their efficacy or safety under these clinical situations. To address this concern, a multidisciplinary group of Canadian physicians with expertise in dermatology, gastroenterology, infectious diseases, and rheumatology developed evidence-based clinical guidelines on vaccinations featuring 13 statements that are aimed at reducing the risk of preventable infections in individuals exposed to immunosuppressive and immunomodulatory agents.
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http://dx.doi.org/10.3899/jrheum.180784DOI Listing
July 2019
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