bluuebunny/crossref_metadata_2025_split huggingface dataset:
A31 COMPLEX ROLE OF DIETARY FIBERS IN IBD: MICROBES MEDIATE FIBER-INDUCED INFLAMMATION
Authors: Armstrong H , Valcheva R , Santer D , Zhang Z , Rieger A , Dijk S I , Dickner R , Jerasi J , Mander I K , Moreau F , Gorman H , Lafleur D , Jovel J , Petrova A , Chadee K , Carroll M W , Huynh H Q , Madsen K , Dieleman L A , Wine E 
Published: March 2021

Abstract

Background
Dietary fibers pass through the bowel undigested and are fermented within the intestine by microbes, typically promoting gut health. However, many IBD patients describe experiencing sensitivity to fibers. β-glucan, found on the surface of fungal cells during fungal infection, has been shown to bind to fiber receptors, such as Dectin-1, on host immune cells, resulting in a pro-inflammatory response. These fungal fibres share properties with dietary fibers.

Aims
As an altered gut microbial composition has been associated with IBD, we hypothesized that the loss of fiber-fermenting microbes populating the gut in IBD could lead to dietary fibers not being efficiently broken down into their beneficial biproducts (e.g. short chain fatty acids; SCFA), resulting in binding of intact fibers to pro-inflammatory host cell receptors.

Methods
Immune and epithelial cell lines and colonic biopsies cultured ex vivo were incubated with oligofructose or inulin (5g/L), or pre-fermented fibers (24hr anaerobic fermentation). Immune responses were measured by cytokine secretion (ELISA), and expression (qPCR). Barrier integrity was measured by transepithelial resistance (TEER). Food frequency questionnaire (FFQ) data of patient fiber consumption were correlated with gut microbes (shotgun sequencing) and immune responses to fiber in patient biopsies.

Results
Unfermented oligofructose induced IL-1β secretion in leukocytes (macrophage, T cell, neutrophil) and in colon biopsies from pediatric Crohn disease (CD; n=38) and ulcerative colitis (UC; n=20) patients cultured ex vivo, but not in non-IBD patients (n=21). IL-1β secretion was greater in patients with more severe disease. Pre-fermentation of oligofructose by whole-microbe intestinal washes from non-IBD patients or remission patients reduced secretion of IL-1β, while whole microbe intestinal washes from severe IBD patients were unable to ferment oligofructose or reduce cytokine secretion. Fiber effects on IL-1β secretion in biopsies positively correlated with effects on barrier integrity in T84 cells. Fiber-associated immune responses in patient biopsies cultured ex vivo (ELISA) correlated with fiber avoidance (FFQ) and gut microbiome (sequencing) in matching patient samples.

Conclusions
Our findings demonstrate that intolerance and avoidance of prebiotic fibers in select IBD patients is associated with the inability to ferment these fibers, leading to pro-inflammatory immune responses and intestinal barrier disruption. This highlights select disease state scenarios, in which administration of fermentable fibers should be avoided and tailored dietary interventions should be considered in IBD patients.

Funding Agencies
CIHRWeston Foundation
A33 MEALTIME SUPPORT: A PILOT COHORT STUDY OF AN EFFECTIVE, COST-SAVING OUTPATIENT HUNGER-BASED FEEDING PROGRAM FOR TUBE DEPENDENCY
Authors: Huynh G , Vishram A , Graham-Parker C , Blatz D , Carroll M W , Turner J 
Published: March 2021

Abstract

Background
Tube dependency is an under recognized complication of long-term enteral feeding in young children. Many children struggle to progress to full oral feeds even with sufficient oral motor skills and swallowing ability. Tube dependency greatly impacts the quality of life of children and families and is a significant burden to the health care system. Economic challenges, increased burden of care and psychosocial issues all reinforce the need for timely tube removal.

Aims
We aimed to examine the efficacy of a multidisciplinary child-led, hunger-based approach called “Mealtime Support” at the Stollery Children’s Hospital in Edmonton. Nutritional outcomes, parental satisfaction and cost implications were evaluated. As a secondary aim we sought to determine the rates of gastrostomy tube insertions in the pediatric age range across Canada as a potential indicator of increasing need for long term tube feeding, hence the need for cost effective tube weaning programs to be developed in Canada.

Methods
The ambulatory program was delivered 2–3 times a day, for 2 weeks, by an occupational therapist and dietitian, under medical supervision. Hunger was promoted by reducing tube fed calories by 80% prior to commencement. Top-up tube feeds were given immediately after feeding sessions if needed. Caregivers completed 12-question subjective surveys pre and post intervention. Micro-costing methods compared costs between the program and ongoing tube feeding. The number of pediatric hospital admissions and gastrostomy tube insertions from 2008–2019, per province, was collected from the Canadian Institute for Health Information (CIHI).

Results
From 2016 - 2017, 6 children who had been tube fed from 7 to 21 months in total were enrolled and 5 completed the program. At 1-month post intervention, 4/5 of the children were 100% orally fed. Parents reported improvement in mealtime struggles (p-value = 0.005), reduction in worry about their child’s eating (p-value = 0.005) and improvement in their child’s appetite/variety foods eaten (p-value = 0.004). Over a year the potential cost savings were estimated at $42,471.24. By 6-months, all feeding tubes were removed. Based on the CIHI data, the number of gastrostomy tubes inserted per 100,000 children varied significantly between provinces, but highest in Nova Scotia, Saskatchewan and Alberta with increases seen from 2008–2018.

Conclusions
The transition from tube feeding to oral feeding is difficult for children who are tube dependent and poses several economic and psychosocial challenges. Mealtime Support was safe and successful in reducing tube dependency and cost-effective compared to no intervention or hospital based programs. There is a need to develop and fund Canadian outpatient feeding programs.

Funding Agencies
The Stollery Children’s Foundation
A39 CULTURE-ENRICHED METAGENOMICS REVEALED MICROBIAL ENGRAFTMENT FOLLOWING FMT IN PATIENTS WITH ULCERATIVE COLITIS
Authors: Shekarriz S , Whelan F , Lau J , Libertucci J , Moayyedi P , Surette M 
Published: March 2021

Abstract
NOT PUBLISHED AT AUTHOR’S REQUEST
Funding Agencies: CIHRImagine SPOR
A46 LOSS OF BMP-SIGNALING IN MESENCHYMAL TELOCYTES TRIGGERS MODIFICATION OF THE GLYCOSYLATION PROFILE OF COLONIC MUCINS.
Authors: Reyes-Nicolas V , Pomerleau V , Gómez D Pupo , Cofino G Marrero , Menendez A , Perreault N 
Published: March 2021

Abstract
NOT PUBLISHED AT AUTHOR’S REQUEST
Funding Agencies: CIHR
A54 THE CIRCADIAN CLOCK INFLUENCES JAK/STAT SIGNALING AND GUT PERMEABILITY
Authors: Parasram K , Bachetti D , Karpowicz P 
Published: March 2021

Abstract

Background
The circadian clock is a 24-hour feedback loop that drives rhythms in behaviours and physiological processes. This molecular timekeeper consists of the transcription factors, Clock-Cycle, that drive expression of thousands of clock-controlled genes, with two of these, Period and Timeless, acting as negative regulators of Clock-Cycle. This fundamental mechanism was initially characterized in the fruit fly, Drosophila melanogaster (Nobel Prize in Physiology & Medicine, 2017), and is highly conserved in humans. The intestine, or midgut, of Drosophila, is also similar to the human small intestine consisting of similar cellular lineage, signaling pathways, and physiological functions. The lineage of the Drosophila intestine contains the same four cell types as humans: intestinal stem cells (ISCs), progenitors called enteroblasts, enterocytes and enteroendocrine cells. This simplified lineage as well as the genetic tools available, make Drosophila an ideal model for intestinal regeneration in health and disease. We have previously shown that the circadian clock is active in ISCs, EBs and ECs during both homeostatic and regenerating conditions. Furthermore, the circadian clock regulates the mitosis of ISCs under regenerating conditions.

Aims
We sought to uncover if Jak/STAT signaling, one of the key pathways involved in ISC proliferation in the Drosophila intestine, shows a circadian rhythm and if there is a time-of-day difference in the regenerative response.

Methods
To test whether the clock regulates Jak/STAT during acute injury, we developed an irradiation assay that does not affect survival but acutely disrupts intestinal barrier function.

Results
Using a dynamic reporter of Jak/STAT activity we show that Period circadian clock mutants have low Jak/STAT signaling and a leaky gut phenotype. Wildtype controls show time-dependent gut leakiness upon irradiation, which is higher and time-independent in Period mutants. The level of Jak/STAT response differs depending on the time of irradiation in the controls, but is higher at all times in the mutants.

Conclusions
The Jak/Stat pathway regulates intestinal immunity and epithelial cell proliferation in humans, thus playing a role in colorectal cancer and inflammatory bowel disease. Our results suggest Jak/Stat is controlled by the circadian clock, which has implications for intestinal recovery following medical treatments, including radiation therapy.

Funding Agencies
NRC
A56 CLINICAL AND BIOCHEMICAL EFFICACY ARE NOT AFFECTED BY SWITCH FROM INFLIXIMAB ORIGINATOR TO RENFLEXIS IN PEDIATRIC INFLAMMATORY BOWEL DISEASE PATIENTS.
Authors: Rosborough K , Yu G , Barker C , Jacobson K , Lawrence S 
Published: March 2021

Abstract

Background
Increased infliximab (IFX) utilization has generated higher drug expenditures and cost burden to the healthcare system. The expiration of the IFX originator Remicade patent led to the addition of biosimilar agents to the drug market that may reduce drug expenditures. In British Columbia, Pharmacare’s 2019 biosimilar initiative mandated all pediatric inflammatory bowel disease (IBD) patients on Remicade to switch to the biosimilar Renflexis. To date, there is limited pediatric IBD data demonstrating that switching from IFX originator to IFX biosimilar CT-P13 is safe and effective, and no data on switching to Renflexis.

Aims
To determine the proportion of patients remaining on Renflexis 6 months after switch from originator IFX. The secondary aims are to determine the proportion of patients remaining in clinical and biochemical remission after switch.

Methods
In this prospective, longitudinal observation single-center study, all children with Crohn’s disease and ulcerative colitis receiving maintenance IFX originator therapy were switched to Renflexis by May 15th 2020. Baseline demographics, concomitant therapy, clinical disease indices (wPCDAI, PUCAI), growth data, blood work, fecal calprotectin and IFX drug levels were collected at baseline and prospectively from 6 months after the switch. All data are presented as median and interquartile range.

Results
A total of 139 children (110 CD, 25 UC and 4 IBDU; Median age 16.2 (3.7) years) with a median IFX originator duration of 42.7 (35.1) months before switching to Renflexis were included. 137/139 (99%) of patients remained on Renflexis at study end. The proportion of children in clinical remission from baseline to 6 months post switch was unchanged (133/139 (95.7%) vs. 130/132 (98.5%), p=0.17). There was no significant change pre and post switch in median CRP (&lt;5 (0) mg/L vs &lt;5 (0) mg/L, p=0.26) or fecal calprotectin (72.5 (144.2) ug/g vs. 65.5 (140.0) ug/g, p=0.87). There was no significant change pre and post switch in the proportion of patients with normal CRP (&lt;5 mg/L) (89/103 (86.4%) vs 89/98 (90.8%), p=0.33) or normal fecal calprotectin (&lt;250 ug/g)(91/112 (81.2%) vs 51/63 (80.9%), p=0.60). There was no significant change pre and post switch in IFX trough level (15.5 (12.3) ug/mL vs 17.5 (12.9) ug/mL, p=0.42). 2 patients had antibodies to IFX after switching. Safety profile is improved with adverse events in 38/139 (27.3%) children on IFX originator vs. 11/139 (7.91%) children on Renflexis for 6 months.

Conclusions
Pediatric IBD patients can be successfully switched from IFX originator to biosimilar Renflexis during maintenance without affecting efficacy, immunogenicity or safety in the short term.

Funding Agencies
None
A59 SEVERE CHEMOTHERAPY-INDUCED SECRETORY DIARRHEA
Authors: Emmerick M , Eindor A , Jacobson K , Schreiber R 
Published: March 2021

Abstract

Background
Diarrhea is one of the most common side effects of chemotherapy, estimated to occur in up to 40% of all patients undergoing cancer therapy. Non-complicated chemotherapy-induced diarrhea (CID) can be managed with loperamide, whereas complicated CID should be treated with continuous infusion of octreotide. Octreotide is usually effective within 48hs of administration. Options for patients that do not respond to loperamide or octreotide include atropine, oral budesonide and cholestyramine.

Aims
To describe the case of an 18 yo girl with acute myeloid leukemia (AML) who developed severe secretory diarrhea during her treatment course.

Methods
Retrospective case report.

Results
The patient was initially treated with Cytarabine, Daunorubicin and Etoposide, and on her third cycle, Gemtuzumab was added. Four weeks later she presented with watery diarrhea up to 6 L/day. She continued with high output despite no oral intake, which was consistent with secretory diarrhea. Infectious workup was negative, and she received Loperamide. Her output decreased to 1 L for 2 days but then increased again to 6 L. She deteriorated and loperamide was switched to octreotide 0.8mcg/Kg/h. The dose was increased to 1.2mcg/Kg/h and she presented blood in the stools. Her stool output was still 4 L/day and octreotide was stopped after one week. Flex sigmoidoscopy showed proctocolitis with friability. Biopsy showed architectural distortion with loss of the superficial epithelium. She was emotionally distressed due to many days of no oral intake, hence Pediasure peptide was introduced, with no changes in the output. Rice was introduced but her diarrhea worsened, and oral intake was stopped again. Four weeks after the onset of diarrhea, her stool output was still above 2 L/day, and cholestyramine 4g once daily was started. Four days later her output decreased and diet was slowly introduced. Two weeks later she had a normal stool output. Cholestyramine was stopped and she was discharged home.
Finding the culprit for this case is a challenge, but important to avoid this drug in the future as prior history of CID is a risk factor for a new-onset. Gemtuzumab is a relatively new anti-CD33 antibody used in AML, and results from a meta-analysis showed that adding it to induction chemotherapy may increase the incidence of diarrhea. Her diarrhea started four weeks after the dose of Gemtuzumab, and we believe this new agent might have played an important role in her case. To our knowledge, there are no cases in the literature associating Gemtzumab with such prolonged and severe diarrhea.

Conclusions
This was a challenging case of CID that did not respond to Loperamide or octreotide and caused a lot of emotional distress for the patient and her providers. Since she responded well to cholestyramine, we recommend its use when the loperamide and octreotide have failed, or in addition to octreotide in severe cases.

Funding Agencies
None
A64 REVIEW OF PATIENTS REFERRED TO THE DIVISION OF DIGESTIVE CARE AND ENDOSCOPY AT DALHOUSIE UNIVERSITY FOR COLORECTAL CANCER SCREENING BASED ON A FAMILY HISTORY OF COLORECTAL CANCER: HOW MANY UNDERWENT COLONOSCOPY?
Authors: Miles M 
Published: March 2021

Abstract

Background
Nova Scotia has provincial colorectal cancer (CRC) screening for asymptomatic, average risk individuals age 50–74 using fecal immunochemical testing (FIT) every 2 years. However, individuals with 1 or more first degree relatives (FDR) diagnosed with CRC by age 60 have a 2–4 fold increased risk for developing CRC. For these high risk individuals, current guidelines recommend CRC screening with colonoscopy rather than FIT testing. Annually, the Division of Digestive Care & Endoscopy (DCE) at Dalhousie University receives many referrals for patients with a family history of CRC but the percentage of patients who require this procedure is unclear.

Aims
The objectives of this quality assessment study were to review patients referred to DCE for a family history of CRC to (1) better understand the indication for referral; and (2) determine the percentage of patients undergoing colonoscopy

Methods
This was a retrospective cross sectional review of a prospectively updated database. The study population was patients referred to DCE from 2012–2019 based on a family history of CRC, as indicated on the referral. Family history of CRC was defined as 1 or more FDRs diagnosed with CRC. High risk patients were those with 2 or more FDRs with CRC or 1 FDR diagnosed by age 60. All patients were reviewed by a single gastroenterologist in clinic.

Results
A total of 107 referrals from 2012–2019 were reviewed. Of patients age 50 or older, 51/78 (65.4%) had performed at least 1 FIT. The indications for referral were 2 or more FDR diagnosed with CRC for 6/107 (5.6%) patients, 1 FDR diagnosed with CRC by age 60 for 37/107 patients (34.6%) and 1 FDR diagnosed with CRC over age 60 for 33/107 patients (30.8%). The remaining 31/107 patients (29.0%) had no FDR with CRC. Of the 43/107 patients (40.2%) considered high risk based on family history alone, 34/43 (79.1%) underwent colonoscopy and 8/43 (18.6%) opted for FIT testing. Of the 64/107 patients (59.8%) considered average risk based on family history alone, 26/64 (40.6%) had another indication for colonoscopy and 35/64 (54.7%) resumed FIT testing.

Conclusions
The majority of patients (71.0%) referred to the DCE for a family history of CRC had at least 1 FDR with CRC. Just over half of patients (55.1%) referred to the DCE for a family history of CRC underwent colonoscopy. Strategies to improve the referral process by better capturing high risk individuals are needed.

Funding Agencies
None
A71 RECOMMENDATION REVERSALS IN GASTROENTEROLOGY CLINICAL PRACTICE GUIDELINES
Authors: Gholami R , Gimpaya N , Khan R , Scaffidi M A , Bansal R , Ramkissoon A , Alabdulqader A , Grover S C 
Published: March 2021

Abstract

Background
Clinical practice guidelines are evidence-based resources designed to inform clinical decision making. Often, superior evidence will support the inclusion of novel procedures and practices to replace older recommendations. Recommendation reversals occur when (a) superior quality evidence emerges to suggest the harm or non-beneficence of prior recommendations, and (b) that recommendation is not supplanted by a newer one.

Aims
The primary objective of this study was to describe the content, frequency and rationale for recommendation reversals in CPGs published by gastroenterological societies.

Methods
For this meta-epidemiologic study, we considered two criteria to define a recommendation reversal: (a) the more recent CPG makes a recommendation that contradicts a previously accepted practice; and (b) the prior recommendation is not replaced by any novel intervention. We searched CPGs published by 20 major GI societies from 1991- 2019. Guidelines were included if had at least two iterations with the same title and used a valid evidence rating system (such as GRADE). Explicit recommendations which reported definite levels of evidence and strength of recommendation were extracted.

Results
We identified 1022 clinical guidelines from GI societies over 28 years. 292 CPGs were included for data synthesis. 5985 explicit statements were extracted. 12 reversals were confirmed and are summarized in the Table. Six reversals (50.0%) occurred due to studies reporting non-beneficence and 3 (25.0%) occrred due to studies reporting harm. Three recommendations (25.0%) were reversed due to new clinical trials; 3 (25.0%) due to systematic reviews or meta-analyses; and 2 to conform with CPGs of other societies (16.7%).

Conclusions
We describe recommendation reversals made in gastroenterology CPGs, and the reasons thereof. Investigation of recommendation reversals allows for the identification of low-value medical practices. This reinforces the need for GI CPG committees to (1) iteratively review guidelines to re-evaluate recommendations made on low-quality evidence and; (2) refrain from making recommendations when evidence for the same is weak.

Funding Agencies
None
A73 PERFORMANCE OF ASGE AND ESGE CRITERIA FOR RISK STRATIFICATION FOR CHOLEDOCHOLITHIASIS IN A REAL-WORLD SETTING
Authors: Lei Y , Wishart E , Mohamed R , Forbes N 
Published: March 2021

Abstract

Background
Choledocholithiasis (CDL) is a common clinical entity and can lead to serious complications, such as pancreatitis or ascending cholangitis. Endoscopic retrograde cholangio-pancreatography (ERCP) is generally the first-line procedure for definitive management of CDL. ERCP has well-established adverse events. Given the risks, patients can be stratified by likelihood of finding CDL on ERCP, thus potentially avoiding an unnecessary procedure in low probability patients. There are three commonly used criteria for this – the American Society for Gastrointestinal Endoscopy (ASGE) 2010 criteria, the ASGE 2019 criteria, and the European Society of Gastrointestinal Endoscopy (ESGE) 2019 criteria. These criteria use a mixture of biliary imaging, clinical condition, and liver biochemistry to stratify patients into low, intermediate, and high probability for CDL.

Aims
To test the performance characteristics of the ASGE 2010, ASGE 2019, and ESGE 2019 criteria for probability of CDL on a real-world sample.

Methods
We identified all adult patients who had ERCP done at our local centre for suspected CDL between 2012/01/01 and 2018/10/07. A sample of 1000 cases were chosen. We obtained the patients’ pre-procedural liver biochemistries, pre-procedural imaging in the preceding 6 months, and their ERCP reports. We used a semi-automated algorithm to determine confirmation of CDL. We inferred clinical gallstone pancreatitis using the surrogate of serum lipase at or greater than three times upper limit of normal. We could not capture clinical ascending cholangitis from the collected data. We stratified each patient according to the three guidelines and calculated their performance characteristics.

Results
After manually reviewing visits with incomplete ERCP or repeat ERCP, we analyzed 879 ERCP visits. There were 622 with stone or sludge found on ERCP. The performance characteristics of the high-probability and intermediate-probability criteria of the three guidelines are listed in the table below.

Conclusions
Our results for the 2010 ASGE guidelines high probability patients are in keeping with previous validation studies. There have been only one validation study each of the 2019 ASGE guidelines and the 2019 ESGE guidelines, and our results are different in sensitivity and negative predictive value. Future directions in refining these risk stratification tools are needed, and our project in ongoing in assessing the additional value of trends in liver biochemistry.

Funding Agencies
None