bluuebunny/crossref_metadata_2025_split huggingface dataset:
A40 INTESTINAL EPITHELIAL NCOR1 TARGETS TRYPTOPHAN METABOLISM AND PROTECTS AGAINST EXPERIMENTAL COLITIS
Authors: Lecours M , Di Castro A , Reyes-Nicolas V , St-Jean S , Loiselle A , Jones C , Perreault N , Boudreau F 
Published: February 2020

Abstract

Background
The nuclear co-repressor NCOR1 is a central protein that orchestrates the assembly of a large transcriptional repression complex. NCOR1 controls activation of macrophages by repressing a large variety of pro-inflammatory genes.

Aims
We aimed to investigate the role of intestinal epithelial NCOR1 during experimental colitis.

Methods
Conditional deletion of Ncor1 in the whole intestinal epithelium was achieved by crossing Villin-Cre and Ncor1loxP/loxP C57BL/6 mouse models. A gene profiling analysis in the colon of non-diseased NCOR1ΔIEC and control mice was performed. NCOR1ΔIEC and control littermate mice were treated with dextran sulfate sodium (DSS) in drinking water.

Results
DSS-induced colitis in NCOR1ΔIEC mice was more severe than control mice according to survival as well as clinical observations. A statistical analysis predicted 85 unique and mapped transcripts being significantly modulated between NCOR1ΔIEC and control mice. An Ingenuity Pathway Analysis from these predicted target genes identified gastrointestinal disease (79 transcripts) as top disease and biofunction. Analysis of enriched targets in specific canonical pathways predicted an increase in the tryptophan degradation pathway (P = 3.2E-02), a pathway recently demonstrated to be strongly relevant to inflammatory bowel disease severity. Indoleamine-pyrrole 2,3-dioxygenase (IDO1), that catalyzes the first and rate-limiting step of tryptophan oxidation, was induced more than 7 times in the colon of NCOR1ΔIEC mice. Induction of Ido1 was also confirmed in cultured ex vivo colon organoids deleted for Ncor1.

Conclusions
Our results highlight the critical role of NCOR1 to maintain intestinal inflammatory homeostasis during experimental colitis and uncover a novel function for NCOR1 in the regulation of Ido1 expression and potentially tryptophan metabolism.

Funding Agencies
CIHR
A61 FOCUSING ON THE FUTURE: REDUCING BARRIERS AND IMPROVING ACCESS TO IBD SPECIALTY CARE ACROSS CANADA
Authors: Heisler C , Mirza R , Kits O , Zelinsky S , Veldhuyzen van Zanten S , Nguyen G C , MacMillan M A , Lakatos P L , Targownik L , Fowler S , Rioux K P , Jones J 
Published: February 2020

Abstract

Background
Canada has the highest global age-adjusted incidence and prevalence rates of Inflammatory Bowel Disease (IBD). Resulting from compounding prevalence and limited resources, timely access to specialty care is a challenge faced by patients and healthcare providers. Despite this issue, there has been no published research elucidating the patient perspective using qualitative approaches to compare and contrast the patient experience across Canada.

Aims
To elicit a qualitative data stream to better understand phenomena related to access to healthcare for Canadians living with IBD from a patient-centered perspective.

Methods
Patients diagnosed with IBD (≥18 years of age) were recruited from gastroenterology clinics and communities through IBD specialists and Crohn’s & Colitis Canada. To ensure geographic diversity and representation, patients were recruited from urban and rural regions. In order to acquire multiple access perspectives, patients were invited to bring a family member who was involved in their care to the focus groups. Co-facilitated by a researcher and a patient research partner, the focus groups were held in Nova Scotia, New Brunswick, Quebec, Ontario, Manitoba, Saskatchewan, and British Columbia. All focus groups were audio recorded, transcribed, and coded for themes. Themes were distilled through qualitative thematic analysis using Atlas.ti software to ascertain congruence or discordance of IBD specialty care access experiences.

Results
A total of 63 participants were recruited in fourteen focus groups across seven provinces. The majority of participants were female (41/63, 65%) and from urban/suburban regions (34/63, 54%). The mean age of participants was 48 years (SD=16 years, range=16 to 77 years). Preliminary analyses illustrated three patient-identified access barrier themes: 1) Lack of multidisciplinary care (psycho-social and nutrition support), 2) Diagnostic delay, and 3) Inability to effectively receive and provide communication with healthcare providers. In response, four solutions were proposed: 1) Integration of holistic care into the clinical practice, 2) Readily accessible psycho-social and nutritional support, 3) Increased patient advocacy, and 4) Continuity and liaison through provision of a healthcare navigator resource.

Conclusions
The complexity of specialty care access for IBD patients in Canada cannot be underestimated. It is vital to possess a robust understanding of healthcare system structures, processes, and the significant impact these factors have on patients and the care received. Through the use of patient-centered exploration of barriers and facilitators, access to IBD specialty care in Canada can be better understood and improved on both a provincial and national scale.

Funding Agencies
CIHRNova Scotia Health Authority Research Fund
A63 HOSPITALIZATION RATES FOR INFLAMMATORY BOWEL DISEASE VARY GEOGRAPHICALLY IN SOUTHERN ALBERTA: A POPULATION-BASED COHORT STUDY
Authors: Stach J , Coward S , Charette J H , Jelinski S , van Zanten S , Morrin L , Kroeker K , Baumgart D , Seow C , Panaccione R , Novak K L , Kaplan G G 
Published: February 2020

Abstract

Background
Hospitalization rates for patients with inflammatory bowel disease (IBD) are decreasing throughout Canada; however, this may vary across Canadian jurisdictions. Access to gastroenterologists is limited in many parts of Canada, resulting in care by non-gastroenterologists, and variation in outcomes.

Aims
To assess trends of hospitalization rates in three regions in Southern Alberta: Calgary zone, a metropolitan city; Chinook region: local gastroenterologists; and Palliser region: no local gastroenterologists.

Methods
The Alberta IBD Surveillance Cohort is a population-based database consisting of an algorithmically defined prevalent IBD population for Alberta. IBD patients in Southern Alberta were identified by 3-digit postal code and their hospitalizations from the Discharge Administrative Database were extracted (2002 to 2015). IBD patients were stratified by the number of IBD prevalent patients: Calgary Zone (n=9625 in 2015), Palliser region (n=1419), and Chinook region (n=727). Age- and sex- standardized hospitalization rates, per 100 prevalent IBD patients, were calculated for each year. Average Annual Percentage Change (AAPC with associated 95% confidence intervals (CI)) were calculated using the log-linear regression. Rate ratios of standardized hospitalization rates between Calgary, Chinook, and Palliser were calculated.

Results
From 2002 to 2015 the average hospitalization rate (per 100 prevalent population) was: 27.6 in Calgary, 30.2 in Chinook, and 37.4 in Palliser (Table 1). The AAPCs across these regions were significantly decreasing (Figure 1). By 2011–2015 hospitalization rates fell to 23, 26.3, and 30.2 in Calgary, Chinook, and Palliser, respectively (Table 1). Calgary and Chinook had significantly lower hospitalization rates compared to Palliser (Calgary: 0.72, 95% CI: 0.70, 0.75; Chinook: 0.80, 95% CI: 0.76, 0.84) (Table 1).

Conclusions
Hospitalization rates for patients with IBD are decreasing, which may be explained by advances in therapeutic modalities and increased expertise of gastroenterologists. The lack of access to a local gastroenterologist in Palliser may account for higher hospitalization rates for patients with IBD. Future studies are needed.

Funding Agencies
CIHRDHSCN (Digestive Health Strategic Clinical Network), AHS (Alberta Health Services)
A68 CLOSTRIDIOIDES DIFFICILE INFECTION IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE
Authors: Zohni H , Chandrakumar A , El-Matary W 
Published: February 2020

Abstract

Background
Toxigenic Clostridioides difficile (C. difficile), previously known as Clostridium difficile, is an anaerobic gram-positive spore-forming opportunistic pathogen associated with profuse diarrhea and gastroenteritis associated mortality and morbidity especially in patients with inflammatory bowel disease (IBD).

Aims
To investigate the incidence and risk factors associated with clostridioides difficile infection (CDI) in children with IBD in the province of Manitoba.

Methods
Our longitudinal population-based cohort comprised of all children and young adults &lt; 17y diagnosed with IBD in the Canadian province of Manitoba between 2011 and 2019. The diagnosis of CDI was confirmed based on the Triage C. difficile immunoassay and polymerase chain reaction assay to detect the presence of toxigenic C. difficile. Fisher’s exact test was used to examine the relationship between categorical variables. Cox-regression model was used to estimate the risk of CDI development in IBD patients.

Results
Among the 261 children with IBD, 20 (7.7%) developed CDI with an incidence rate of 5.04 cases per 1000 person-years and the median age at diagnosis of 12.96 years (IQR: 9.33–15.81). The incidence rate of CDI among UC and CD patients were 4.16 cases per 1000 person-years and 5.88 cases per 1000 person-years, respectively (p=0.46). Compared to children without CDI, those who had CDI were at increased risk of future exposure to systemic corticosteroids (hazard ratio (HR)=4.30; 95% CI: 1.44–12.87) and anti-tumor necrosis factor (TNF) biologics (HR=3.37; 95% CI: 1.13–10.09). Recurrence rate of CDI in our pediatric IBD population was 25%.

Conclusions
Our findings confirm that children with IBD are at a high risk of developing CDI, which may predict future escalation of IBD therapy.

Funding Agencies
The Children’s Hospital Research Institute of Manitoba
A74 HELMINTH ANTIGENS OR REGULATORY MACROPHAGES REDUCE THE SEVERITY OF COLORECTAL CANCER
Authors: Callejas Pina B E , Wang A , Mendoza M , Terrazas L , McKay D M 
Published: February 2020

Abstract

Background
Infection with helminth parasites is a potent stimulus of immunity, and murine model systems reveal that a bystander benefit of this response to helminths is suppression of colitis. Unraveling the mechanism of this inhibition of colitis, the regulatory macrophage has emerged as a cell of interest in ‘helminth therapy’. Given the relationship between inflammation and cancer – patients with inflammatory bowel disease (IBD) have a higher risk of colorectal cancer (CRC).

Aims
To test the hypothesis that intraperitoneal administration of excretory/secretory products from the tapeworm Taenia crassiceps (TcES) or IL-4-treated macrophages (M(IL-4)) (characteristic of the immune response to helminths) would affect the outcome of CRC.

Methods
CRC was induced in female BALB/c and male C57Bl/6 mice using azoxymethane (AOM) (10 mg, ip) and three cycles of Dextran sulfate sodium (DSS: 7 days, 1–2% wt./vol.) separated by 2 weeks of normal tap water. Following initiation of CRC, mice received TcES (200 μg, ip.) - or M(IL-4) (106, ip). On necropsy, CRC incidence, number, and size of the tumour were recorded and tumors assessed histologically.

Results
Mice receiving TcES or M(IL-4)s were substantially protected from AOM-DSS induced CRC, as shown by statistically significant reductions in tumor number and size, although the number of mice developing tumors was unchanged (n=4–8 mice). The suppression of CRC in TcES-treated mice correlated with reduced mobilization of STAT3 and NF-κB signaling cascades in the as determined by immunostaining and immunoblot of whole tissue extracts.

Conclusions
With the speculation that helminth-derived molecules or transfer of in vitro educated macrophages could be used to treat IBD comes the specter of the putative oncogenic effects of regulatory macrophages. Contrary to this, the data herein show that the TcES reduced CRC; and, that murine macrophages (M(IL4)) also actually limit the severity of inflammation-driven CRC by directly targeting the cancer cells or reducing the inflammatory stimulus. These findings add emphasis to the consideration of autologous regulatory macrophage transfer to treat IBD and CRC

Funding Agencies
CCCCONACYT (Mexico)
A78 COMPARISON OF THE NICE, SANO, AND WASP CLASSIFICATIONS FOR OPTICAL DIAGNOSIS OF SMALL COLORECTAL POLYPS
Authors: Djinbachian R , Pohl H , Marchand E , Marques P , Bouin M , Deslandres E , Weber A , Bouchard S , Leduc R , Von Renteln D 
Published: February 2020

Abstract

Background
Optical diagnosis can be used as an alternative to pathology for the evaluation of colorectal polyps. There exist multiple classification systems that can be used to assist in performing optical diagnosis.

Aims
The aim of this study was to compare three different optical diagnosis classifications (NICE, SANO and WASP) when using Optivista and iScan image enhanced endoscopy (IEE).

Methods
The study included subjects between 45–80 years undergoing an elective screening, surveillance, or diagnostic colonoscopy with optical diagnosis using Optivista or iScan IEE. Three validated IEE scales (NICE, SANO and WASP classifications) were used for all optical diagnoses. Primary outcome was the agreement with pathology for surveillance intervals determined when using NICE, SANO and WASP for polyps 1-10mm. Secondary outcomes for polyps 1-10mm included accuracy of polyp diagnosis and negative predictive value (NPV) for rectosigmoid adenomas.

Results
A total of 399 patients were prospectively enrolled in the trial. The polyp detection and adenoma detection rates were 58.6% and 38.8% respectively. The proportion of correct surveillance interval assignment when at least one optical diagnosis was made was 92.9% when using NICE, 92.3% when using SANO, 89.5% when using WASP (p=0.656). Correct diagnosis was made for 74.2% of polyps when using NICE, 74.2% when using SANO, 65.6% when using WASP (p=0.012). The NPV for rectosigmoid adenomas was 91.2% when using NICE, 90.5% when using SANO, 87.5% when using WASP.

Conclusions
For optical diagnosis using Optivista and iScan IEE, all studied classifications performed equally for surveillance interval assignment. WASP had lower proportion of correct diagnoses on a polyp level and lower NPV for rectosigmoid adenomas.

Funding Agencies
None
A90 A UTILITY-BASED BAYESIAN OPTIMAL INTERVAL (U-BOIN) PHASE I/II DESIGN TO IDENTIFY THE OPTIMAL BIOLOGICAL DOSE FOR TARGETED AND IMMUNE THERAPIES
Authors: Zhou Y , Lee J , Yuan Y 
Published: February 2020

Abstract

Background
In the era of targeted therapy and immunotherapy, the objective of dose finding is often to identify the optimal biological dose (OBD), rather than the maximum tolerated dose (MTD).

Aims
To develop a utility-based Bayesian optimal interval (U-BOIN) phase I/II design to find the OBD.

Methods
We jointly model toxicity and efficacy using a multinomial-Dirichlet model, and employ a utility function to measure dose risk-benefit trade-off. The U-BOIN design consists of two seamlessly connected stages. In stage I, the Bayesian optimal interval (BOIN) design is used to quickly explore the dose space and collect preliminary toxicity and efficacy data. In stage II, in light of accumulating efficacy and toxicity from both stages I and II, we continuously update the posterior estimate of the utility for each dose after each cohort, and use this information to direct the dose assignment and selection. Compared to existing phase I/II designs, one prominent advantage of the U-BOIN design is its simplicity for implementation. Once the trial is designed, it can be easily applied using predetermined decision tables, without complex model fitting and estimation.

Results
Our simulation study shows that, despite its simplicity, the U-BOIN design is robust and has high accuracy to identify the OBD.

Conclusions
The U-BOIN design provide a practical, easy-to-implement method to identify the OBD for phase I-II clinical trials. It has great potential to accelate the drug development for GI diseases.

Funding Agencies
NIH
A93 HEPATOCELLULAR CARCINOMA SCREENING IN PATIENTS WITH CIRRHOSIS FOLLOWED BY A GASTROENTEROLOGIST- A RETROSPECTIVE STUDY OF HEALTHCARE QUALITY
Authors: Bourassa L , Décarie V , Beaudoin A 
Published: February 2020

Abstract

Background
The American Association for the Study of Liver Diseases (AASLD) guidelines recommend screening for hepatocellular carcinoma (HCC) in adults with cirrhosis every six months by abdominal ultrasound. This recommendation stands for patients with Child-Pugh A / B cirrhosis or Child-Pugh C who are on the transplant waiting list. The rationale behind this guideline is that surveillance for HCC has been shown to improve overall survival. However, in previous studies, rate of adherence to screening was suboptimal.

Aims
The goal of this study was to define the screening rate in our medical center while collecting demographic and descriptive data (Table 1).

Methods
We performed a monocentric retrospective study of healthcare quality. Adult patients who had a diagnosis of HCC between July 2010 and February 2018 and who were previously followed in gastroenterology for cirrhosis were included. The delay between the last abdominal imaging available and the first imaging that raised suspicion for or made the HCC diagnosis possible was calculated for each patient. Screening was considered appropriate if it was less than 8 months.

Results
102 of the 170 patients had to be excluded from the study because their cirrhosis wasn’t clearly documented before the HCC diagnosis (Figure 1). Amongst included patients, 52% (95% confidence interval 0,39-1,00) had received an appropriate screening for HCC.The average size of HCC at diagnosis was 37 mm and 53% had multicentric distribution. 56% of patients received treatment, with chemoembolization being the most frequently used in our population. 49% and 80% of patients had passed away at 1 and 3 years post-diagnosis, respectively. 52% of patients had normal alpha-feto-protein (AFP) initially.

Conclusions
Although limited in statistical power by the size of its sample, our study still sheds an interesting light on the reality of HCC screening in a Canadian hospital. The rate of appropriate screening, although suboptimal, is comparable to those reported in the literature elsewhere in the world. The dark prognosis associated with this disease is also illustrated. The proportion of patients who were excluded from the study due to occult cirrhosis highlights the importance of establishing this diagnosis so that screening recommendations can be put into practice. Further studies of larger scale would be needed to assess the causes of screening issues.

Funding Agencies
None
A102 MONOSODIUM GLUTAMATE INCREASES VISCERAL SENSITIVITY IN A MURINE MODEL OF IRRITABLE BOWEL SYNDROME
Authors: Brant B J , Yu Y , Lomax A E , Vanner S , Tuck C J 
Published: February 2020

Abstract

Background
Over 70% of patients suffering from symptoms of the irritable bowel syndrome (IBS) report that food is the most common trigger. Patients have identified that monosodium glutamate (MSG) is one food component that they suspect can trigger symptoms, but this remains unproven. As a first step towards establishing a potential role, we sought to examine whether there was a plausible mechanism of how MSG ingestion could underlie exaggerated pain signaling in IBS.

Aims
To examine the effects of MSG on visceral sensitivity in a murine model of IBS.

Methods
Balb/c mice were subjected to 6-days of water-avoidance stress (WAS) to create a pre-clinical model for IBS. To assess changes in visceral afferent nerve sensitivity in control and WAS mice, responses to ramp distension (0–60 mmHg), in the absence and presence 10 μM MSG perfused into the intestinal lumen (concentration based on diet analysis of MSG human ingestion), were recorded from afferent nerves innervating the jejunum ex vivo. To quantify these responses, the baseline firing frequency (spikes/second) was subtracted from the maximum response at each distending pressure. The relative distension response was calculated as a percentage of the control distension response (absence of MSG) (Figure 1). Jejunal preparations from the same WAS-treated mice were also used to measure ex vivo changes in mucosal permeability to MSG using Ussing chambers. We also ran the same distension protocol; however, we applied 10 μM MSG directly to the organ bath outside intestine obtained from control mice. This direct application would allow the MSG to have direct access to the nerve terminals without having to traverse the mucosa.

Results
The intraluminal administration of 10 μM MSG significantly increased afferent nerve sensitivity in WAS-treated jejunum but not controls. This response was significantly greater (23%) at pressures between 40 and 60 mmHg (p&lt;0.01) (Figure 1). WAS-treated mouse jejunum was also significantly more permeable to MSG (p&lt;0.05). Furthermore, the application of 10 μM MSG directly to the bath containing healthy jejunum significantly increased by 25% the sensitivity of afferent nerves specifically at 60 mmHg (p&lt;0.01).

Conclusions
Our findings demonstrate that MSG increases visceral sensitivity to distension in our pre-clinical model of IBS. The increased permeability to MSG in WAS tissue and increased distension response in healthy control tissue when MSG is applied directly to the bath rather than intraluminally, suggests that MSG signals to the immune compartment or directly to the afferent nerve terminals. These findings support the rationale for future in vivo studies with this model to further clarify the mechanism.

Funding Agencies
CCC, CIHR