bluuebunny/crossref_metadata_2025_split huggingface dataset:
A12 SKIN EXPOSURE TO NARROW BAND UVB LIGHT MODULATES THE HUMAN INTESTINAL MICROBIOME
Authors: Bosman E S , Albert A Y , Dutz J P , Vallance B 
Published: February 2020

Abstract

Background
The recent worldwide rise in idiopathic immune and inflammatory diseases such as multiple sclerosis and inflammatory bowel diseases has been linked to Western society-based changes in lifestyle and environment. These include decreased exposure to sunlight/UVB light and subsequent impairment in the production of vitamin D, as well as dysbiotic changes in the makeup of the gut microbiome. Despite their association, it is unclear if there are any direct links between UVB light and the gut microbiome.

Aims
In this study we investigated whether exposing the skin to Narrow Band Ultraviolet B (NB-UVB) light to increase serum vitamin D levels would also modulate the makeup of the human intestinal microbiota.

Methods
The effects of NB-UVB light were studied in a clinical pilot study using a healthy human female cohort (n=21). Participants were divided into those that took vitamin D supplements throughout the winter prior to the start of the study (VDS+) and those who did not (VDS-).

Results
After three full-body NB-UVB light exposures within the same week, the serum 25(OH)D levels of participants increased on average 7.3 nmol/L. The serum response was negatively correlated to the starting 25-hydroxy vitamin D (25(OH)D) serum concentration. Fecal microbiota composition analysis using 16S rRNA sequencing showed that exposure to NB-UVB significantly increased alpha and beta diversity in the VDS- group whereas there were no changes in the VDS+ group. Bacteria from several families were enriched in the VDS- group after the UVB exposures according to a Linear Discriminant Analysis (LDA) prediction, including Lachnospiracheae, Rikenellaceae, Desulfobacteraceae, Clostridiales vadinBB60 group, Clostridia Family XIII, Coriobacteriaceae, Marinifilaceae, and Ruminococcus. The serum 25(OH)D concentrations showed a positive correlation with the relative abundance of the Lachnospiraceae, specifically members of the Lachnopsira and Fusicatenibacter genera.

Conclusions
This is the first study to show that humans with low 25(OH)D serum levels display overt changes in their intestinal microbiome in response to NB-UVB skin exposure and increases in 25(OH)D levels, suggesting the existence of a novel skin-gut axis that could be used to promote intestinal homeostasis and health.

Funding Agencies
NRCBC Childrens Hospital Research Institute
A42 MICROBIAL METABOLISM OF DIETARY TRYPTOPHAN ENHANCES ARYL HYDROCARBON RECEPTOR ACTIVATION: IMPLICATIONS FOR IBD
Authors: Rondeau L , Clarizio A V , Jury J , Gibson D L , Bercik P , Sokol H , Caminero Fernandez A 
Published: February 2020

Abstract

Background
Intestinal immune homeostasis is maintained by the interplay between microbiota and the mucosal immune system. Changes in gut microbiota have been associated with chronic intestinal conditions, such as inflammatory bowel disease (IBD). The aryl hydrocarbon receptor (AhR) is a transcription factor that is activated by dietary and environmental stimuli to control immune responses in the gut and homeostatic mechanisms at mucosal surfaces. In IBD, AhR expression is downregulated. Major agonists of AhR in the gut include microbial tryptophan metabolites such as indole derivatives, which are decreased in IBD patients. The mechanisms involved in tryptophan metabolism by bacteria and their implications in AhR activation and thus IBD pathogenesis are not well understood.

Aims
To investigate whether tryptophan metabolism by intestinal bacteria participates in AhR activation and IBD pathogenesis.

Methods
Microbiota profiles (16S rRNA Illumina) and activation of AhR (luciferase reporter assay) were determined in fecal samples from IBD patients (n=10) and healthy volunteers (n=10). Germ-free C57BL/6 mice were colonized with fecal slurries of 2 healthy subjects and 4 IBD patients (n=4 mice/donor) by oral gavage (humanized-mice). All mice were fed irradiated tryptophan diets with 0.1% or 1% tryptophan content for 14 days. Simultaneously, SPF Mucin 2 (Muc2) deficient mice (C57BL/6 background), which develop colitis spontaneously, were fed tryptophan diets (0.1%, 0.3% and 1% content). Activation of AhR was measured in feces using an AhR luciferase reporter assay. Inflammation was determined by immunohistochemistry and the characterization of immune infiltrate in colon cross-sections. Bacteria from human and mouse fecal samples were isolated and screened for their ability to produce indoles using biochemical reagents. Positive bacteria were identified by colony PCR and 16S rRNA Sanger sequencing.

Results
IBD patients had an altered fecal microbiota with a lower capacity to activate AhR compared to healthy subjects. Colonization of mice with microbiota from healthy subjects induced greater activation of AhR compared to mice colonized with microbiota from patients with IBD. Furthermore, increasing dietary tryptophan composition rescued the capacity to activate AhR. In Muc2 deficient mice, dietary tryptophan treatment enhanced AhR activation capacity and reduced infiltration of innate immune cells before the onset of colitis. Several AhR agonist producing bacterial species were identified and will be used in future experiments.

Conclusions
Activation of AhR is dependent on the gut microbiota and disease status of the donor. Dietary intervention with tryptophan enhances AhR activation capacity and may be a potential therapeutic avenue in IBD individuals with intestinal dysbiosis.

Funding Agencies
Farncombe Family Digestive Health Research Institute, Biocodex Microbiota Foundation
A59 DECREASING HOSPITALIZATIONS AND SURGERIES IN CHILDREN WITH INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED COHORT STUDY
Authors: Dheri A , Kuenzig E , Mack D , Murthy S , Kaplan G G , Benchimol E I 
Published: February 2020

Abstract

Background
Health services use in inflammatory bowel disease (IBD) patients cost the Canadian healthcare system $1.3 billion per year, but recent changes to care in children with IBD may have altered trends in health services use. Characterization of these trends would aid health policy makers plan for the healthcare needs of IBD children.

Aims
To quantify time trends in IBD health services use in children and all-cause health services use in children with and without IBD using a population-based cohort.

Methods
Using the Ontario Crohn’s and Colitis Cohort, children &lt;18y with IBD diagnosed between 1994–2012 in Ontario were identified using validated algorithms from health administrative data, and matched on age, sex, rurality, and income to children without IBD. We evaluated trends in the number of IBD-specific and all-cause outpatient visits, emergency department (ED) visits, and hospitalizations using negative binomial regression. Cox proportional hazards regression models were used to describe changes in the hazard of intestinal resection (Crohn’s disease; CD) and colectomy (ulcerative colitis; UC) over time. Results are reported as annual percentage change (with 95%CI) for events within 5 years from the diagnosis/index date.

Results
IBD-specific hospitalization rates decreased by 2.5% (95%CI 1.8–3.2%) per year, but all-cause hospitalization rates in children without IBD decreased faster (APC, 95%CI: 4.3%, 3.5–5.1%, difference in rates p-value=0.0028). The hazard of intestinal resection for CD decreased by 6.0% (95%CI 4.6–7.3%) per year and the hazard of colectomy for UC decreased by 3.0% (95%CI 0.7–5.2%) per year. IBD-specific outpatient visit rates increased after 2005 by 4.0% (95%CI 3.1–4.9%) per year. Similar trends were not observed in children without IBD.

Conclusions
Decreasing hazards of intestinal resection and colectomy in children with IBD suggest changes in disease management, including more care being provided on an outpatient basis. Decreased hospitalization rates in IBD were mirrored by similar decreases in non-IBD children, indicating universal care changes. Understanding why these trends are occurring may help us better understand how to provide optimal care to children with IBD.

Funding Agencies
CIHRCanGIEC
A62 CANADIAN POPULATION-BASED EVALUATION OF THE NATURAL HISTORY OF PRIMARY BILIARY CHOLANGITIS OVER THE LAST DECADE
Authors: Azhari H , Swain M , Shaheen A M 
Published: February 2020

Abstract

Background
Few studies have evaluated the epidemiology of primary biliary cirrhosis (PBC) in North America. Ursodeoxycholic acid (URSO) improves outcomes amongst PBC patients.

Aims
Therefore, we undertook this study to determine the epidemiology of PBC in Canada, and impact of URSO on clinical outcomes, two decades after URSO approval in North America.

Methods
We used our previously validated coding algorithm to identify PBC patients in population based administrative databases in the Calgary Health Zone (population ~1.5 million) from 2005–2015. Multiple sources of data including inpatient, ambulatory, physician billing, laboratory, and pharmaceutical were linked. Annual prevalence and incidence were estimated using Poisson regression. Age/sex adjusted rate ratios were calculated. We used Cox regression models to estimate: all-cause mortality, liver transplant and decompensated cirrhosis free survival. In our models, we adjusted for demographic and clinical variables including response to URSO.

Results
During the study period over 11 years, the overall annual age/sex adjusted PBC incidence was 29.5 cases per million (48.3 and 9.9 per million for women and men, respectively). The highest incidence rate was observed among women aged 60–79 (90.9 per million) with an incidence rate ratio of 10.4 (95%: 6.83–15.9) compared to those aged 20–39. While incidence rate remained stable, prevalence rate increased significantly from 242 to 343 cases/ million, between 2005 and 2015 (P&lt;0.01). Prevalence rate was highest at 965 cases/ million amongst women aged 60–79. We identified 299 incident PBC cases with a median follow up of 5.1 years (IQR 2.9–8.3). 87 (29.1%) of these incident cases developed decompensated cirrhosis or HCC, 10 patients (3.4%) underwent liver transplantation, and 44 (14.7%) patients died. The annual mortality rate was 2.9% (95%CI: 2.1- 3.8) compared to 3.4% (2.3–4.9%) a decade ago (P=0.04). The estimated 5-year survival rate was 87.6% (82.6- 91.3). Standardized mortality rate was 3.2 (95%CI: 2.2–4.1). Overall, 25% of our incident cohort were not prescribed URSO. Patients not prescribed URSO were more likely to be male, older age, have normal ALP and had decompensated cirrhosis at diagnosis (P&lt;0.01 for all). Among those who used URSO, response rate was 86%. Response to URSO was an independent predictor of reduced risk of decompensated cirrhosis and liver transplant, and higher survival (aHR: 0.46, 0.29–0.74).

Conclusions
PBC prevalence is increasing in this North American population. While mortality rate decreases in our PBC cohort, survival was suboptimal compared to the general population, mainly due to late presentation at diagnosis. Therefore, better surveillance and early detection of possible PBC patients in the primary care setting are essential to improve PBC outcomes.

Funding Agencies
None
A71 MESOCAVAL SHUNT EMBOLIZATION AS A TREATMENT FOR MEDICALLY REFRACTORY HEPATIC ENCEPHALOPATHY IN A PATIENT WITH NON-DECOMPENSATED CIRRHOSIS
Authors: Gupta S , Wong F , Sniderman K , Ryan S , Tsien C 
Published: February 2020

Abstract

Background
Hepatic encephalopathy (HE) is a common complication of cirrhosis with a spectrum of neuropsychiatric manifestations. In patients with medically refractory HE (i.e. after a trial of Lactulose with or without Rifaximin), it is warranted to investigate and manage underlying spontaneous portosystemic shunts (SPS) as a cause of chronic or recurrent HE in the absence of precipitants.

Aims
Here we present a case report of a patient with non-decompensated cirrhosis who underwent mesocaval shunt embolization as a treatment for medically refractory HE (grade III) in the absence of underlying precipitants.

Methods
The patient’s chart was reviewed and radiological images pre- and post- shunt embolization were obtained. A literature review was performed on the treatment of SPS for HE in cirrhosis.

Results
Mr. H is a 56-year-old man with alcohol-related cirrhosis who was admitted to the hospital with a reduced level of consciousness. On examination he was arousable but nonverbal. Asterixis was observed with no focal neurologic findings. Laboratory, infectious and toxicology results were negative. His MELD-Na score was 11. Computed tomography (CT) of his head and ultrasound of his abdomen were normal. The patient did not improve with lactulose and rifaximin. A CT of his abdomen/pelvis revealed a large SPS arising from the superior mesenteric vein (SMV) to the infrarenal inferior vena cava (IVC). A decision was made to attempt partial occlusion of the shunt. A 22-mm Amplatzer™ Vascular Plug II and two 8mm x 59mm Atrium balloon expandable covered stents were deployed in the right gonadal vein. Partial occlusion was subsequently demonstrated with contrast injection. The patient had gradual improvement of his HE and became independent for his ADLs six months post-procedure.

Conclusions
Between 45–70% of patients with cirrhosis and medically refractory HE have SPS as a result of chronic liver injury and increased portal venous pressures. AASLD guidelines recommend screening for SPS in cirrhotic patients with medically refractory HE or in HE with compensated liver disease. Shunt embolization in patients with MELD &lt; 11 has been shown to reverse chronic or recurrent HE as well as improve hepatic outcomes for at least a two-year follow-up, as shown by a recent multicentre survey done by Laleman et al. Further studies have shown that portosystemic shunt embolization can result in reversal of HE in over 75% of cases. The most frequently encountered shunt in these studies is the splenorenal shunt. Our case, however, offers insight into the less commonly experienced mesocaval shunt, which accounts for only 5% of large SPS. We have shown that mesocaval shunts, when discovered, have the potential for successful treatment with embolization that can lead to reversal and long-term clinical remission of HE.

Funding Agencies
None
A88 EARLY-ONSET GASTRIC POLYPS IN CHILDREN WITH FAMILIAL ADENOMATOUS POLYPOSIS: A CASE SERIES
Authors: Stone J , El-Matary W 
Published: February 2020

Abstract

Background
Familial adenomatous polyposis (FAP) syndrome is a familial inherited autosomal dominant polyposis syndrome which predisposes affected individuals to a significantly increasing risk of colorectal cancer before the age of 30 years. Studies examining the rates of duodenal and gastric neoplasia in patients with FAP are scarce. Recent reports have shown a concerning rise in gastric cancer in Western FAP patients with certain endoscopic features. Current guidelines suggest screening with gastroscopy beginning at the age of 20 to 25 years.

Aims
We report a case series of seven pediatric patients with evidence of early-onset upper gastrointestinal adenomatous polyps.

Methods
A retrospective chart review was performed for all patients diagnosed with FAP between January 2012 and December 2016 in Winnipeg Children’s Hospital which is the only pediatric tertiary-care hospital in Manitoba. A total of seven pediatric patients from 3 different families were enrolled in our case series. The following data were collected: age of diagnosis, gene mutation, time of first screening endoscopy and total number of endoscopies, number of gastric and colonic polyps, pathology results, surgeries and further routine investigations. Descriptive data were then reported on each patient.

Results
Five of seven patients (71.4%) exhibited maternal inheritance of the APC gene mutation. The mean age of diagnosis was 5.3 years (SE 2.4, range 2–9 years) with male predominance (n=5, 71.4%). Mean age at first colonoscopy was 9.8 years (SE 2.05; range 6.6–11.9) and 9.9 years (SE 1.88; range 6.6–11.9 years) at first gastroscopy. Five (71.4%) patients had evidence of gastric polyps and three (43%) had evidence of duodenal polyps before the age of 14 years. All patients showed an increasing burden of gastric polyposis with age. Tubular adenomas were seen in all patients who developed &gt;50 gastric polyps (n=5), two with low-grade dysplasia diagnosed at the ages of 11 and 15 year. One patient with duodenal polyps showed tubular adenomatous changes at the age of 13.6 years. Capsule endoscopy was performed in all patients and none showed any small bowel polyposis beyond the duodenum. All seven patients had colonic tubular adenomas, two with low-grade dysplasia (at ages of 14 and 15 years) and only one without polyps at the initiation of endoscopic screening. No patients underwent surgery prior to age 15 years.

Conclusions
The presence of gastric and duodenal polyps in pediatric patients with FAP is not uncommon and may be underestimated. Early screening gastroscopy with gastric and duodenal biopsies should be considered at a younger age than what has currently been recommended.

Funding Agencies
None
A89 IMPLEMENTING ENDOSCOPIC SUBMUCOSAL DISSECTION IN A WESTERN CANADIAN SETTING: OUTCOMES, LEARNING CURVE AND LOGISTICAL CONSIDERATIONS
Authors: Trasolini R , Zhao B , Chahal D , Lam E 
Published: February 2020

Abstract

Background
Endoscopic submucosal dissection (ESD) is an advanced resection technique for large gastrointestinal lesions. ESD was developed in Japan and is popular in countries with gastric cancer screening and a high incidence of gastric cancer. ESD has benefits over endoscopic mucosal resection (EMR) such as increased complete resection, en bloc resection and lower recurrence. However, ESD is a longer procedure and is difficult to master in countries with low incidence of early gastric neoplasia which is the ideal anatomic location for learning. There is increasing interest in using ESD techniques including hybrid ESD/EMR in western centers. Barriers include procedure time, perforation risk and challenges accumulating sufficient experience.

Aims
To present our experience implementing an ESD program in British Columbia including outcomes and logistical considerations of interest.

Methods
All ESD procedures since implementation of the program in May 2015 to July 2019 were included. Descriptive statistics and performance indicators over time are reported. All procedures were performed by a staff endoscopist after specialized training. Procedures were performed at two hospitals in British Columbia. Cases were referred from endoscopists and were assessed with dedicated endoscopy with or without endoscopic ultrasound prior to booking ESD.

Results
40 procedures were performed, though only one procedure was performed in the first year (Mean age 70, 67.5% male). ASA class ranged from 1–4 (mean 2.08). 22 lesions were gastric, 13 were rectal, with the remainder throughout the colon. Mean lesion size was 25mm in maximum dimension (interquartile range 15-30mm). 18 procedures were performed under general anesthesia and the remainder using procedural sedation. Total surgical time ranged from 22 to 398 minutes. Mean surgical time was 104 minutes, or 126 minutes including anesthesia. 50% of procedures were performed using hybrid ESD/EMR technique. R0 resection rate across all cases was 68% (60% for hybrid procedures, 80% for strict ESD). En bloc resection rate was 60%. Recurrence rate was 10%. Complication rate was 7.5% all were post-procedure bleeds requiring hospitalization. No perforations occurred. 3 patients required surgery for incomplete resection or invasive cancer on pathology, 3 required repeat endoscopic resection. Surgical time per cm of lesion improved significantly from the first 10 cases to the last 10 (time per cm resected 75 min to 32 min p&lt;0.006).

Conclusions
ESD is an effective therapy for GI neoplasia. ESD is feasible in a Canadian setting. Hybrid techniques tend to be faster though at the expense of R0 resection. Patient centered outcomes in this sample are favorable and comparable to large ESD series. Monitoring of ESD quality is critical for comparison with standard of care as experience with ESD in Canada grows.

Funding Agencies
None
A92 DOSE ESCALATION STUDY OF CYBERKNIFE® BOOST IN UNRESECTABLE LOCALLY ADVANCED PANCREATIC CANCER
Authors: Quinlan J , Pantarotto J , Dennis K , Chatterjee A 
Published: February 2020

Abstract

Background
Pancreatic cancer is the 4th deadliest cancer in Canada, with an overall 5-year survival of only 6%. Every year, approximately 4000 Canadians are diagnosed with pancreatic cancer, and only 10–15% of these patients have surgically resectable disease. No satisfactory treatment exists for patients with inoperable locally advanced pancreatic carcinoma. The best survival has been achieved using a combination of chemotherapy and radiotherapy. Conventional radiotherapy has inadequate local disease control as the therapeutic radiation dose to the tumour is limited by the sensitivities of surrounding tissues. Stereotactic body radiotherapy (SBRT) is a minimally invasive treatment technique that allows for ultra-high doses of radiation to be delivered to small areas. The CyberKnife® Robotic Radiosurgery System is a radiation unit designed to deliver SBRT. Fiducial markers placed by endoscopic ultrasound help direct the radiotherapy. It is hypothesized that a higher overall dose of radiation will result in higher rates of local control, and potentially improved survival.

Aims
The goal of this study is to establish the safety and feasibility of using stereotactic body radiotherapy boost technique via CyberKnife in treating unresectable locally advanced pancreatic cancer, as well as to determine the maximal tolerable radiation dose (MTD) of the SBRT boost that can be safely delivered.

Methods
This is a prospective single-arm, single-institution phase I Time-to-event Continual Reassessment Methodology (TITE-CRM) radiation dose escalation trial. This study enrolled patients aged 18–84 with pathologically confirmed pancreatic cancer who were determined to have surgically unresectable disease, with an ECOG ≤2. These patients were treated with SBRT prior to starting conventional radiotherapy, which consisted of a total dose of 45 Gy in 25 fractions over 5 weeks.

Results
Between 2012 and 2018, a total of 11 patients met the eligibility criteria of this study. Their ages ranged from 61 to 84 with a mean of 71.5 years, and they were 64% (7/11) male. At the time of this analysis, 10 of the 11 patients had passed away. The mean and median survival times were 413 days and 313 days, respectively. Three of the patients had significant complications attributed to the radiotherapy, 2 gastric outlet obstructions and 1 deep duodenal ulcer. The doses used ranged from 21 Gy in 3 fractions to 50 Gy in 5 fractions.

Conclusions
This phase 1, single arm study demonstrates that stereotactic body radiotherapy in the treatment of locally advanced, unresectable pancreatic cancer is technically feasible. When combined with conventional radiotherapy, this therapy is generally well tolerated, and can effectively deliver higher doses of radiation to pancreatic malignancies. Doses up to 50 Gy in 5 fractions were tolerated, with the most common dose being 21 Gy in 3 fractions.

Funding Agencies
National Pancreatic Cancer Canada Foundation