bluuebunny/crossref_metadata_2025_split huggingface dataset:
A192 CONSUMPTION OF FOOD LOWER IN TRYPTOPHAN IS ASSOCIATED WITH SIGNIFICANT ANXIETY IN PATIENTS WITH CELIAC DISEASE
Authors: Gupta V , Jivraj A , Armstrong D , Verdu E , Pinto-Sanchez M I 
Published: February 2022

Abstract

Background
Tryptophan, an essential amino acid found in many protein-based foods, has been involved in the pathogenesis of mood disorders and celiac disease (CeD). However, dietary tryptophan consumption has not been investigated in CeD.

Aims
To estimate 1) differences in tryptophan content in food consumed in CeD patients compared to matched healthy controls (HC), and 2) whether consumption of tryptophan is associated with the presence of anxiety and depression in patients with CeD.

Methods
This prospective observational study examined adult patients with a diagnosis of CeD, based on positive specific serology and confirmed by duodenal biopsies, enrolled in the Celiac Registry at McMaster University. A group of sex matched HC were recruited from within the community. Participants completed several questionnaires to evaluate, gastrointestinal symptoms (GSRS), Anxiety and Depression (HADS), and dietary intake of tryptophan (Modified Food Frequency Questionnaire). In addition, CeD patients were assessed for celiac disease activity (CSI), gluten-free diet (GFD) adherence (CDAT) and nutritional status. HADs &gt;11 denoted significant anxiety or depression. Cut-off for low vs high amount of tryptophan content in food was established based on the median tryptophan food content in the HC population.

Results
A total of 443 participants were enrolled in the study; 222 with CeD and 221 controls. The majority of participants were female (74.3%) and the adherence to the GFD was very good (Median CDAT=13; IQR 11–15). The CeD patients were older than HC (Median age, yrs. CD= 40 vs HC= 35; p&lt;0.01). Patients with CeD consumed higher amount of tryptophan compared with HC (Median tryptophan g/day CeD=4.41 vs HC=3.31; p&lt;0.01). There were 157 active CeD patients (CSI ≧ 30). There was no difference in tryptophan consumption between patients with and without active CeD (OR=1.021; 95%CI 0.86–1.21; p=0.88). There was no association between tryptophan consumption and gastrointestinal symptoms or depression scores. Fifteen % of the overall population and 18% of the CeD population had anxiety. There was an increased risk of anxiety in the overall population that consumed low amount of tryptophan (OR=1.87; 95%CI 1.01–3.11; p=0.04), and the risk was greater in the CeD population (OR=4.57; 95%CI 1.26–16.41; p&lt;0.01).

Conclusions
Consumption of food with lower amounts of tryptophan in patients with CeD is associated with significant anxiety, which may influence disease management. Future studies should evaluate whether increasing tryptophan in the diet compared to supplements improves outcomes in CeD population, especially in those with anxiety.

Funding Agencies
None
A193 PERCEIVED BARRIERS TO GLUTEN-FREE FOOD ACCESS ON-CAMPUS EXPERIENCED BY STUDENTS FROM DIFFERENT CANADIAN UNIVERSITIES AND COLLEGES
Authors: Mistry J , Khaouli M , Weiten D , Case S , Gidrewicz D , Turner J , Duerksen D , Pinto-Sanchez M I 
Published: February 2022

Abstract

Background
Students with gluten-related disorders (GRD), a spectrum of conditions including celiac disease (CeD) and non-celiac wheat sensitivity (NCWS), often experience challenges when accessing gluten-free (GF) foods.

Aims
To identify barriers perceived by students with GRD to access GF products on-campus of universities and colleges across Canada.

Methods
We conducted a cross sectional survey using the RedCap platform and distributed it to the Canadian Celiac Association community. We included students who reported adopting a GFD for various reasons including CeD and other GRD. We collected data on adherence to the GFD using a validated questionnaire (CDAT), presence of perceived barriers to follow a GFD while dining on campus, persistent symptoms, and altered quality of life. Continuous data are expressed as median (IQR), and categorical data as proportions of patients. Mann-Whitney U and Chi2 with Fisher correction were used to assess differences between groups.

Results
Seventy nine students responded to the survey (5% male and median age = 25 yrs) and 78 had complete data for analysis. Of the 78 students, 52 (66.6%) reported a diagnosis of CeD, while 26 were adopting a GFD for other reasons (non-CeD). The majority were enrolled in university programs (72/78) and 18% were living on-campus. Almost 90% reported difficulties maintaining a GFD while dining on-campus. Similar proportion of CeD and non-CeD reported eating gluten accidentally (75% vs 80%), while 15% reported eating gluten intentionally on-campus at least a few times per week. This was observed more frequently in non-CeD compared with students with CeD (61% vs 17%; p=0.04). Barriers identified in CeD versus non-CeD groups were related to a reduced GF-food variety (48% vs 69%), lack of availability of GF food (21% vs 46%) and increased cost (46% vs 81%) compared with gluten-containing counterparts. The majority of participants were concerned whether the food available on-campus was truly GF (80% vs 54%) as they reported foods not properly labelled. The majority of participants considered their overall health (79%) and quality of life (65%) was fair to terrible while dining on campus. During the pandemic, 76% of them perceived that it was easier to stick to a GF diet.

Conclusions
Students from various universities and colleges across Canada experience barriers to access GF food on-campus. This has a significant impact on their overall health and quality of life. Proper food labeling, GF certification and improving the variety of GF food on-campus are options for improvement.

Funding Agencies
None
A194 THE ADDITION OF DEAMIDATED GLIADIN PEPTIDE TO TISSUE TRANSGLUTAMINASE ANTIBODIES DOES NOT INCREASE THE ODDS OF CELIAC DISEASE DIAGNOSIS IN AN IGA SUFFICIENT POPULATION
Authors: Moss K , Russell L , Mehta K , Faisal M , Armstrong D , Verdu E , Dowhaniuk J , Pinto-Sanchez M I 
Published: February 2022

Abstract

Background
Previous studies proposed that the combination of IgA anti-tissue transglutaminase 2 IgA (TTG) and IgG deamidated gliadin peptide IgG (DGP) antibodies increases celiac disease (CeD) detection rates. However, this remains controversial.

Aims
To evaluate the performance of adding DGP to TTG antibodies, for the diagnosis of celiac disease (CeD) in the immunoglobulin A (IgA)-sufficient population.

Methods
We included consecutive patients with suspected CeD who had both TTG and DGP serology performed simultaneously from 2017–2020 in Hamilton, Canada. Chart review was performed by 3 reviewers to extract data on biopsies, diagnosis of CeD and genetic HLA-DQ2/DQ8. CeD was defined as positive serology (either TTG and/or DGP) and villous atrophy in duodenal biopsies (≥Marsh-3a). A case was defined as an instance of TTG and DGP performed at a single timepoint. A single patient could have represented multiple cases if TTG and DGP were measured at multiple time points. Sensitivity, specificity, negative and positive predictive values were calculated, and ROC curves were generated. Diagnostic odds ratios (DOR) assessed the performance of each serological strategy compared to duodenal biopsies.

Results
There were 580 patients constituting 823 cases that met inclusion criteria, of whom 441 had CeD. IgA-deficient patients (n=100) were excluded. Of the 723 cases remaining, 337 (214 adult;123 pediatric) had serology performed at the time of CeD diagnosis. TTG increased the odds of CeD diagnosis compared with DGP, Diagnostic Odds Ratio (DOR)=53.22 (95% CI 22.63–119.80) vs DOR=21.28 (95% CI 10.67–42.46). The addition of DGP to TTG did not increase the odds of CeD diagnosis [DGP+TTG DOR=51.39 (95% CI 19.36–135.61) vs TTG alone DOR=53.22 (95% CI 22.63–119.80)]. There were 37 discordant cases where only one of either TTG or DGP was positive. HLA-DQ2/DQ8 were absent in 2/9 cases with isolated increased DGP. Among the discordant cases, TTG outperformed DGP (DOR TTG= 4.29; 95% CI 1.09–16.83 vs DOR DGP=0.23; 95% CI 0.06–0.92).

Conclusions
In the IgA-sufficient population, the addition of DGP to TTG testing does not increase the diagnostic accuracy of CeD serologic screening. This has implications in health-care costs as false positive results prompt further investigations. Given these findings, larger prospective studies should be completed prior to adding DGP antibodies to routine TTG serology.

Funding Agencies
None
A218 THE RISK OF RECURRENT HEPATOCELLULAR CARDINOMA IN POST-LIVER TRANSPLANT PATIENTS RECEIVING CAPECITABINE TREATMENT
Authors: Alsager M , Chaitanya V , Gandhi R , Puka K , Tang E , Teriaky A , Qumosani K , Skaro A , Parfitt J , Brahmania M 
Published: February 2022

Abstract

Background
Little is known on how to reduce the risk of hepatocellular carcinoma (HCC) recurrence post liver transplantation (LT). We examined if adjuvant oral Capecitabine reduces the risk of recurrent HCC in a high-risk group post-LT.

Aims
To examine if adjuvant oral Capecitabine reduces the risk of recurrent HCC in a high-risk group post-LT.

Methods
A retrospective study was performed from a pre-existing liver transplant database from the Liver Transplant Unit at London Health Sciences Center, London; Canada. This database contains demographic, clinical parameters and follow-up of all patients transplanted for HCC. Data was extracted for patients who underwent LT between January 2000 – April 2018 and included follow up until May 31st, 2020. High-risk of tumor recurrence was defined as a RETREAT score ≥5 or PARFITT score ≥10.5. Log rank test compared the recurrence of HCC or death among patients who were and were not prescribed Capecitabine.

Results
Out of 168 LT for HCC, 25 patients were identified as high-risk group for recurrence. The median age was 63 years (IQR=60–65). 19 (76%) patients had viral hepatitis including Hepatitis B and Hepatitis C as their primary disease while 4 (16%) patients had NASH. The remaining 2 (8%) patients had Autoimmune Hepatitis. 7 (28%) patients received Capecitabine while 18 (72%) did not. All patients were followed for a median of 22 months (IQR=8.9–57.5). No statistical significance difference was found between the two groups with respect to HCC recurrence or death (p=0.56).

Conclusions
Among patients with high risk features for recurrence of HCC, adding Capecitabine therapy added to conventional immunosuppression had no overall effect on reducing overall tumor recurrence or survival.

Funding Agencies
None
A219 AMINOTRANSFERASE IMPROVEMENTS IN PATIENTS WITH NON-ALCOHOLIC STEATOHEPATITIS ARE ASSOCIATED WITH FIBROSIS REGRESSION IN THE REGENERATE STUDY
Authors: Ramji A , Rinella M , Dufour J , Anstee Q M , Younossi Z , Loomba R , Sanyal A J , Capozza T , Trylesinki A , Ratziu V 
Published: February 2022

Abstract

Background
The interim analysis of the REGENERATE study showed obeticholic acid (OCA) 25 mg treatment significantly improved liver histology in patients with nonalcoholic steatohepatitis (NASH) and fibrosis. Elevations in aminotransferases are associated with adverse liver-related outcomes in NASH.

Aims
Here, we evaluate the utility of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) as markers of treatment response to OCA in patients with NASH.

Methods
Changes in ALT (upper limit of normal [ULN] = 55 U/L) and AST (ULN = 34 U/L) were assessed systematically at 1, 3, 6, 12, and 18 months in 931 NASH patients with stage 2 or 3 fibrosis randomized 1:1:1 to placebo (PBO), OCA 10 mg, or OCA 25 mg in REGENERATE (intent-to-treat population). Least-square mean (LSM) and 95% confidence intervals (CIs) of percentage change from baseline in ALT and AST were analyzed using a mixed-effect repeated-measures model.

Results
Baseline characteristics were well-balanced across treatment arms: ALT 79±53 U/L; AST 58±36 U/L; 44% F2, 56% F3. Aminotransferase values were &gt; ULN for ALT in 60% (7% &gt; 3xULN), and for AST in 74% (9% &gt; 3xULN) of patients. Rapid, progressive, and dose-dependent improvement in ALT and AST was seen across PBO, OCA 10 mg, and OCA 25 mg arms, which at Month 18 was: ALT LSM change (95% CI), respectively, -4.9% (-10.7–0.9), -23.2% (-28.9– -17.4) and -31.9% (-37.7– -26.1) and in AST, -8.7% (-12.1– -5.2), -13.4% (-16.8– -9.9), and -19.4 (-22.8– -15.9). ALT and AST LSM reductions in OCA arms vs PBO were seen regardless of patient ULN status at baseline. In all patients, ALT/AST reduction was associated with probability of fibrosis regression at Month 18, ranging from approximately 20%, 95% CI (14–27) to 45% (37–54) with any reduction in ALT (&gt; 0%–100%) and between approximately 20%, 95% CI (25–38) to 43% (35–57) with any reduction in AST (&gt; 0%–100%). Interestingly, even with increases of ≤ 40% in AST or ALT there was still a small probability of fibrosis regression (&lt; 20%). Analysis of changes in ALT and AST in individual patients showed that more patients had improvements on OCA than PBO at Month 18 (FIG 1).

Conclusions
OCA resulted in consistent dose-dependent improvement of ALT and AST. Patients with reductions in ALT or AST were up to twice as likely to have fibrosis improvement than those whose ALT or AST increased. The REGENERATE study is ongoing and will continue through clinical outcomes for verification and description of clinical benefits of OCA in treatment of NASH.

Funding Agencies
None
A239 COMBINED CANNABINOID RECEPTOR 1 AND MU-OPIOID RECEPTOR AGONISTS SYNERGISTICALLY INHIBIT VISCERAL PAIN IN VIVO WITHOUT ADVERSE SIDE EFFECTS OR TOLERANCE
Authors: Tsang Q K , Yu Y , Lomax A E , Vanner S , Reed D E 
Published: February 2022

Abstract

Background
Previously we have shown that both cannabinoid 1 receptor (CB1R) and mu-opioid receptor (MOR) agonists inhibit mechanosensitivity of colonic nociceptive nerves. However, it is unknown whether agonists of cannabinoid and opioid receptors have a synergistic interaction, such that very low doses of these agonists can be employed to reduce visceral pain and side effects.

Aims
To determine the effects of combined cannabinoid and opioid receptor agonists on visceral pain and its side effects.

Methods
Telemetric transmitters were surgically implanted into the abdominal cavity of C57/BL6 mice, with electrodes sutured to the external oblique muscle to measure the visceromotor response (VMR) to colorectal distention using a 4F arterial embolectomy catheter (volume range 20–80 µL). Mice were injected intraperitoneally with vehicle, arachidonyl-2’-chloroethylamide (ACEA), a selective CB1R agonist (0.3, 1, 3 mg/kg), HU-308, a selective CB2R agonist (0.3, 1, 3mg/kg), morphine, a MOR agonist (0.3, 3 mg/kg), or a combination, 30-minutes prior to distention. To assess side effects, pulse oximetry, heart rate, fecal pelleting, and locomotion (via an open-field maze) were measured. Data was analyzed with one or two-way ANOVA with post-hoc Bonferroni multiple comparisons test.

Results
ACEA dose-dependently reduced VMR (P&lt;0.01 vs. vehicle, N=5); at the 80 µL distention, reductions of 35% (P&lt;0.01) and 62% (P&lt;0.01) were observed for 1 mg/kg and 3 mg/kg respectively. In contrast, HU-308 did not reduce VMR at any dose (P=0.17, N=8). Morphine (0.3 mg/kg) did not reduce VMR (P&gt;0.99), while a higher dose (3 mg/kg) attenuated VMR (P&lt;0.01 vs. vehicle, N=5); reductions of 32% (P&lt;0.01) and 61% (P&lt;0.01) at 60 and 80 µL distentions respectively. Interestingly, a combination of sub-analgesic doses of ACEA (0.3 mg/kg) and morphine (0.3 mg/kg) significantly reduced VMR (P&lt;0.01 vs vehicle, N=5); compared to vehicle, VMR was reduced by 21% at 40 µL (P&lt;0.05), 27% at 60 µL (P&lt;0.01) and 60% at 80 µL (P&lt;0.01). Chronic administration (2x/day for 6 days) of this combination did not alter the magnitude of its inhibitory effect (P=0.67, N=5), suggesting tolerance did not develop. While analgesic doses of morphine (3mg/kg) decreased oxygen saturation (P&lt;0.01), heart rate (P&lt;0.01) and fecal pelleting (i.e., GI motility; P&lt;0.05), the sub-analgesic combination of ACEA and morphine had no effect (P&gt;0.99 for all, N=5). Locomotion was unchanged by the agonists alone or combined (P=0.17).

Conclusions
A combination of sub-analgesic doses of CB1R and MOR agonists significantly inhibits visceral pain in vivo, without development of sides effects or tolerance with chronic use. Thus, combining low doses of CB1R and MOR agonists may be an effective visceral pain management strategy.

Funding Agencies
NSERC
A244 PROVIDING THE FODMAP DIET THROUGH AN ONLINE PLATFORM: IMPACT ON THE QUALITY OF LIFE AND THE PHYSICAL AND PSYCHOLOGICAL SYMPTOMS IN IRRITABLE BOWEL SYNDROME
Authors: Laforce S , Mukaneza Y , Tremblay M , Lamarche B , Delawarde-Saïas C , Bouin M , Bemeur C 
Published: February 2022

Abstract

Background
Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder that affects approximately 15 % of the worldwide population. It is characterized by recurring abdominal pain and changes in bowel habits. This population is more at risk of suffering from chronic fatigue and psychological distress. Moreover, IBS significantly reduces the quality of life of patients and increases the economic burden on the health system. Many therapies have been developed to try to alleviate the symptoms and improve the lives of people with IBS. Among these is the FODMAP ( Fermentable Oligosaccharides Disaccharides Monosaccharides and Polyols) diet which aims to establish a personal tolerance to these nutrients (carbohydrates) that accentuate the symptoms related to IBS. This diet, lasting on average twelve weeks, is separated into three steps: elimination, reintroduction, and personalization. An innovative approach has been developed by the online platform SOSCuisine.com® to allow people with IBS to safely follow the FODMAP diet in a ‘self-service’ way. It consists of using an online service of personalized weekly menus low in FODMAP with tips and instructions for each step of the diet in combination with access to a peer support group, moderated by a specialized registered dietician.

Aims
The aim of this project is to evaluate the impact of this new online service on the quality of life and the control of the physiological and psychological symptoms of people living with IBS. We hypothesized that this online service improve the quality of life and the control of the symptoms.

Methods
The participant has to be at least 18 years old, understand French, have access to Internet and a Facebook account (sufficient familiarity to use them) and have an IBS diagnosis (Rome IV criteria) validated or re-validated by a gastroenterologist within three months. People with eating disorders, mental health problems, other chronic gastrointestinal illnesses (except gastroesophageal reflux disease), diabetes and with a pregnancy are excluded. Validated questionnaires are used to assess the quality of life ( IBS-Quality Of Life), physical symptoms ( IBS-Severity Scoring System), state and trait ( State-Trait Anxiety Inventory, Form Y) whereas food intake is assessed with a online 24-hour dietary recall.

Results
So far, 35 participants have been included in the study (83% female, 45,3±12,8 years old). After the intervention, the severity of symptoms significantly decreased (p&lt;0.001), and quality of life (p=0.041) and state anxiety (p=0.034) significantly improved.

Conclusions
This study should allow the identification of facilitating elements to adhere to the FODMAP diet and possibly improve the quality of life of this population.

Funding Agencies
None
A246 GASTROINTESTINAL ADVERSE EVENTS OF CANNABINOIDS IN PEDIATRIC POPULATIONS: A SYSTEMATIC REVIEW AND META-ANALYSIS
Authors: Ratcliffe E , Karimi P , Sunil M , Leong R , Ramirez-GarciaLuna J , Zuniga-Villanueva G 
Published: February 2022

Abstract

Background
Use of therapeutic cannabinoids in the pediatric population has increased in recent years within areas of epilepsy, palliative care, and cancer. Given the endocannabinoid system plays a crucial role in gastrointestinal (GI) homeostasis, exogenous cannabinoids have the potential to develop GI related side effects. While some GI adverse events have been reported with the use of therapeutic cannabinoids, the full profile of GI adverse events in the pediatric population is still unknown.

Aims
To understand the impact of therapeutic cannabinoids on the GI system of pediatric patients, we performed a systematic review and meta-analysis to assess the prevalence of various GI-related adverse events arising from cannabinoid usage within pediatric populations.

Methods
Searches were conducted from OVID MEDLINE, EMBASE, CINAHL, Web of Science, and The Cochrane Library for study screening. The included studies were quantitatively assessed for GI adverse events including nausea, diarrhea, increased appetite, decreased appetite, weight gain, weight loss, constipation, abdominal pain, and unspecified events. The prevalence along with their relation towards diagnosis, type of cannabinoid, dosage, duration of treatment, and study type were also assessed.

Results
Among a total of 1201 patients across 25 included studies, an overall prevalence of 33.91% GI adverse events was observed in patients. The statistical analysis of the pediatric population displayed no relation between therapeutic cannabinoid usage and GI adverse events, bearing a large heterogeneity (I2 = 91%, P &lt; 0.01). Upon analysis based on study type, a significant difference was observed between prospective and retrospective studies in categories of all GI adverse events, diarrhea, and decreased appetite, with prospective studies displaying a higher prevalence in all three categories. Nausea symptoms showed a significant negative correlation with maximum dosage of cannabinoid used. In addition, diarrhea was found to have a higher prevalence in Dravet syndrome related to an ion channel gene mutation (SCN1A) compared to other epilepsy patients.

Conclusions
While the meta-analysis did not identify any significant associations between therapeutic cannabinoid usage and GI adverse events, there remains the potential for interactions of cannabinoids on GI symptoms depending on dosage and underlying patient factors.

Funding Agencies
Farncombe Family Digestive Health Research Institute