bluuebunny/crossref_metadata_2025_split huggingface dataset:
A103 PROBIOTIC FORMULATIONS DIFFERENTIALLY AFFECT DISEASE OUTCOME IN A MOUSE MODEL OF NECROTIZING ENTEROCOLITIS
Authors: Robinson S , Zhu H , Zhang Z , Li B , Pierro A , Sherman P M 
Published: February 2020

Abstract

Background
Necrotizing enterocolitis (NEC) causes severe gastrointestinal disease in premature infants. A precise etiology is not yet known, but it is generally agreed that intestinal immaturity & alterations in the gut microbiota play key roles in NEC progression. There is growing interest in the clinical use of probiotics for the prevention of NEC in at-risk infants. Some probiotics, which are defined as beneficial bioactive microbes that provide a health benefit when administered in sufficient amounts, may influence disease outcome in premature infants with NEC.

Aims
To investigate the efficacy of two commercially available probiotic formulations, Lacidofil® and ProBiokid®, in the prevention of experimentally-induced NEC.

Methods
At gestational day 12.5, treated dams were administered probiotics (109 cfu/mL) in drinking water (Table 1). NEC was induced at postnatal day 5 or when pups were ≥ 3.0 g by the administration of hyperosmolar formula, hypoxia, and lipopolysaccharide (4 mg/kg). NEC pups receiving probiotics were administered 108cfu in hyperosmolar formula once daily during the morning feeding. Body weight, survival and disease severity were scored.

Results
Neither probiotic intervention affected overall survival of NEC-induced pups. Control dam-fed pups (NN) continued to gain weight as expected over time, while untreated NEC pups (NNNEC) exhibited a significant delay in weight gain. LLNEC pups exhibited the greatest percent body weight increase over time, possibly due to a lower birth weight. Lacidofil administration did not improve NEC-induced tissue damage irrespective of the timing of intervention. In contrast, Probiokid provided to both dam and pups (PPNEC) resulted in less severe tissue damage compared to their control counterparts.

Conclusions
These finding demonstrate strain-specific differences in two different commercial probiotic formulations in the prevention of NEC in newborn mice. Future studies seek to provide insight into how Lacidofil and Probiokid engage intestinal stem cells (Lgr5-GFP mice), cell proliferation (Ki67 positivity) and differentiation (MUC2 & Chromogranin A positivity) in the NEC-damaged intestine.

Funding Agencies
CIHRMITACS Accelerate Postdoctoral Award
A104 A STUDY OF POST-INDUCTION INFLIXIMAB TROUGH LEVELS DEMONSTRATES MOST PEDIATRIC IBD PATIENTS ARE BEING UNDERDOSED
Authors: Faytrouni F , Harris R , Lawrence S , Russel R 
Published: February 2020

Abstract

Background
Infliximab (IFX) is widely used for induction and maintenance of remission in pediatric inflammatory bowel disease (PIBD). Post induction IFX trough levels are a predictor of clinical and biochemical remission at week 52.

Aims
- evaluate the effectiveness of infliximab (IFX) induction regimens in attaining therapeutic post induction IFX trough levels in 2 PIBD cohorts.
- investigate baseline laboratory values and patient factors as predictors of post-induction levels.

Methods
78 patients from Vancouver, Canada [Cohort 1 (C1) originator IFX; variable dose induction regimen] and 62 patients from Glasgow, Scotland [Cohort 2 (C2) replication cohort - biosimilar IFX; standard induction of 5mg/kg at 0, 2 and 6 weeks, with 8 weekly maintenance] were included in the study. Baseline characteristics and laboratory values from time of IFX initiation were recorded. Mann-Whitney U Testing was utilized to analyse the relationship between IFX trough levels and lab parameters.

Results
The median pre-dose 4 trough in C1 & C2 was 4.25mg/L (IQR 7.8) and 1.85mg/L (IQR 3.38) respectively. In C1 patients who had a trough level &lt;3mg/L pre-dose 4, 62% (20/32) had already had a dose adjustment documented. The IFX dose of 50% (39/78) of C1 patients and 65% (40/62) of C2 patients was escalated following the pre-dose 4 IFX level.
TABLE 1
Baseline median albumin (Alb) was significantly lower and replicated in both cohorts in those with low pre-dose 4 IFX levels:
IFX trough &lt;0.8mg/L
C1: Alb 30g/L vs 37.5g/L in IFX ≥0.8mg/L, p=0.002
C2: Alb 34.5g/L vs 37g/L in IFX ≥0.8mg/L, p=0.02
IFX trough &lt;3.0mg/L
C1:Alb 34.5g/L vs 38g/L in IFX ≥3.0mg/L, p= 0.05
C2:Alb 35g/L vs 37g/L in IFX ≥3.0mg/L, p=0.04
IFX trough &lt;5.0mg/L
C1:Alb 35g/L vs 39g/L in IFX ≥5.0mg/L, p=0.006
C2:Alb 35g/L vs 37g/L in IFX ≥5.0mg/L, p=0.45
In the combined cohort (C1 + 2), patients with baseline albumin ≤30g/L had significantly lower IFX levels pre-dose 4 than those with albumin &gt;30g/L (1.4mg/L vs 3.55mg/L, p=0.0003). In patients with an albumin ≤30g/L, 23% (6/26) achieved a dose 4 trough level of ≥3.0mg/L, however only 1/6 patients received a standard induction regime meaning only 4% (1/26) of patients had a trough ≥3.0mg/L on standard treatment.

Conclusions
Standard IFX induction regimen is ineffective in achieving relevant post-induction trough levels (&gt;5 mg/L) in the majority of PIBD patients regardless of IFX type. We suggest that optimization of initial IFX prescribing based on baseline albumin (i.e. a higher dose given to patients with albumin &lt; 30g/L) and subsequent levels will improve post-induction trough levels and consequently clinical outcomes for a greater proportion of patients.

Funding Agencies
None
A106 TTC7A MUTATION AND CHRONIC PRURITUS, A CASE REPORT
Authors: Hensen M , Decaluwe H , Haddad E , Marchand V 
Published: February 2020

Abstract

Background
TTC7A mutation is a rare autosomal recessive disease that can present with various phenotypes including multiple intestinal atresia (MIA), very early onset inflammatory bowel disease (VEOIBD), and profound combined immunodeficiency with hypoplastic thymus, altered T- and B-cell maturation, lymphopenia, monocytosis and agammaglobulinemia. Although TTC7A mutation mostly affects immune and gut function, it is a multisystemic disease. Chronic pruritus has not been described yet.

Aims
To describe the case of a child with TTC7A mutation with chronic pruritus and the potential treatment options.

Methods
Case report and review of literature

Results
We report a child with TTC7A mutation who developed severe chronic pruritus. The child presented ileal atresia and pyloric stenosis and underwent ileo-caecal resection and pyloroplasty at birth. She required a latero-lateral anastomosis between the stomach and the duodenum because of recurring pyloric stenosis and several dilatations of her ileo-colic anastomosis. She remained dependant on parenteral nutrition for most of her caloric needs. Her immune deficiency manifested with a very low lymphocyte count and low immunoglobulins. She had pneumocystis Carinii infection at 3 months of age and was put on gammaglobulin injections and pentamidine prophylaxis. At 3 years of age, she developed severe pruritus that led to skin infection and recurrent Staphylococcus Aureus sepsis. A skin biopsy revealed eczematous dermatitis with eosinophilic infiltration.
Various treatments were attempted. Replacing lipid fat emulsion by fish oil emulsion in her parenteral nutrition did not improve her symptoms. Amitryptiline, gabapentine, hydroxyzine hydrochloride and levofloxacine also failed. Corticosteroids seemed to have a mild effect. A trial of Mepolizumab (anti-IL 5) was unsuccessful.
At age of 4, after a sepsis treated by vancomycin, she presented with severe bullous skin disease. Skin biopsy was compatible with linear IgA bullous dermatosis. She was put on dupilumab and systemic corticosteroids. Dupilumab inhibits signaling of both IL-4 and IL-13, two cytokines involved in inflammation that contribute to atopic dermatitis. With this combination of IV steroids and dupilumab, pruritus has improved significantly.

Conclusions
Our patient’s evolution suggests that some TTC7A mutation can be complicated with severe pruritus and IgA linear bullosis. Skin disease, combined with immunodeficiency and the presence of a central line can lead to life threatening sepsis. Pruritus did not respond to usual treatments but improved the combination of intravenous steroids and dupilumab suggesting a role of IL-4 and IL-13 in the pathophysiology of the pruritus associated with this disease. Hematopoietic stem cell transplantation, may be an alternative solution.

Funding Agencies
None
A108 PROBIOTICS FOR CELIAC DISEASE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS
Authors: Seiler C , Kiflen M , Stefanolo J P , Bai J , Bercik P , Kelly C , Verdu E , Moayyedi P , Pinto-Sanchez M I 
Published: February 2020

Abstract

Background
Celiac disease is a chronic autoimmune disorder triggered by dietary gluten. The only available treatment for celiac disease is strict compliance to the gluten-free diet. Despite adherence to a gluten-free diet, many celiac patients still experience symptoms which may be mediated by the gut microbiota. Different studies have assessed the use of probiotics as an adjuvant treatment for celiac disease.

Aims
We performed a systematic review and meta-analysis to evaluate the efficacy of probiotics in improving gastrointestinal symptoms and quality of life in patients with celiac disease.

Methods
We searched MEDLINE (1966 to February 2019), EMBASE (1974 to February 2019), CINAHL, Web of Science, CENTRAL, DARE, and Sigle up to February 2019 for randomized controlled trials (RCTs) assessing the effects of probiotics on celiac disease. We collected data on gastrointestinal symptoms, quality of life, adverse events, serum tumor necrosis factor α (TNF-α), intestinal permeability, and microbiota composition.

Results
Out of 2831 records screened, 7 articles from 6 RCTs with a total of 279 participants were eligible for quantitative analysis. Probiotic supplementation for a minimum of 2 weeks improved gastrointestinal symptoms when assessed by the Gastrointestinal Symptoms Rating Scale (GSRS) (2 studies; 131 participants; mean difference (MD) symptom reduction: -28.7%; 95% CI -43.96 to -13.52; P=0.0002). No differences in gastrointestinal symptoms after probiotics were observed when pooling data from the GSRS, Celiac Symptoms Index (CSI), and the Celiac Disease Questionnaire (CDQ) (4 studies; 197 participants; standardized mean difference (SMD) symptom reduction: -0.48; 95% CI -1.21 to +0.25; P=0.20). TNF-α levels did not change after probiotics (SMD: -0.52; 95% CI -1.08 to +0.04; P=0.07). Levels of Bifidobacteria species increased (MD: increase by 0.85 log CFU/g; 95% CI +0.38 to +1.32 log CFU/g; P=0.0003) but there was no difference in Lactobacilli species (MD: change of 1.13 log CFU/g; 95% CI -0.67 to +2.93 log CFU/g; P=0.22) after probiotic supplementation. No difference in quality of life or adverse events was observed after probiotics. There was insufficient evidence to assess the effects of probiotics on intestinal permeability. The overall quality of the evidence ranged from very low to low.

Conclusions
Probiotics may improve gastrointestinal symptoms in patients with celiac disease; however, our confidence in these results is limited by the low quality of the evidence. Further large clinical trials with a more rigorous design are needed to improve the quality of the evidence.

Funding Agencies
None
A118 GUT MICROBIOTA TRANSPLANTATION FROM A PATIENT WITH SEVERE CONSTIPATION INDUCED CHANGES IN COLONIC FUNCTION AND STRUCTUR OF GNOTOBIOTIC MICE
Authors: Bai X , De Palma G , Lu J , Collins S M , Bercik P 
Published: February 2020

Abstract

Background
Increasing evidence suggests that gut microbiota play a key role in gastrointestinal (GI) tract function. We have previously shown that fecal microbiota transplantation diarrhea predominant IBS patients into germ-free mice induces faster GI transit, increased permeability and innate immune activation. However, it is unknown whether gut dysfunction is induced by microbiota from patients with chronic constipation.

Aims
Here, we investigated the role of the intestinal microbiota in the expression of severe slow transit constipation in a patient with previous C difficile infection and extensive antibiotic exposure.

Methods
Germ-free (GF) mice (14 weeks old) were gavaged with diluted fecal content from the patient with constipation (PA) or a sex and age-matched healthy control (HC). 12 weeks later, we assessed gut motility and GI transit using videofluoroscopy and a bead expulsion test.. We then investigated intestinal and colonic smooth muscle isometric contraction in vitro using electric field stimulation (EFS), and acetylcholine (Ach) release was assessed by superfusion using [3H] choline. Histological changes were evaluated by H&E and immunohistochemistry.

Results
Mice with PA microbiota had faster whole GI transit (score 18.9 ± 0.9 (N=9) than mice with HC microbiota (15.4 ± 1.0, N=10, p=0.032), with markers located mainly in the distal small bowel and cecum. However, bead expulsion from the colon was significantly longer in PA mice (420.8 s ± 124.6 s, N=9) than in HC mice (82.6 s ± 20.0 s, N=10, p=0.026). This delayed colonic transit was likely due to colonic retroperistalsis visualized videofluoroscopically by retrograde flow of barium in the right colon of PA mice. There was no difference between the two groups in small intestinal or colonic tissues in Ach release or contractility induced by carbachol or KCl,. EFS caused transient biphasic relaxation and contraction in small intestine and colon, with the colonic contraction being stronger in the PA group. Microscopic tissue analysis showed disruption of the interstitial cells of Cajal (ICC) network and increased lymphocyte infiltration in colonic mucosa and submucosa in PA mice.

Conclusions
These results indicate that the microbiota is a driver of delayed colonic transit in a patient whose constipation started following extensive antibiotic exposure for C. difficile infection. The observed dysmotility pattern was not due to lower muscle contractility but likely caused by immune mediated changes in the ICC network.

Funding Agencies
CIHR
A135 HEPATOLITHIASIS AND CHOLANGIOPATHY IN PEDIATRIC CYSTIC FIBROSIS: A CASE REPORT
Authors: Kortbeek S , Bhandal S , Machida H , Martin S R , Galante G J 
Published: February 2020

Abstract

Background
Liver disease has emerged as an important cause of cystic fibrosis (CF)-associated morbidity due to recent advancements in management and a resultant increase in life expectancy. Although focal biliary cirrhosis remains the pathognomonic finding in CF, other hepatic manifestations exist but are not as well described, particularly in the pediatric population.

Aims
Present two rare manifestations of pediatric CF-associated liver disease.

Methods
In this report, we present a pediatric CF patient with chronic abdominal pain who was found to have hepatolithiasis, cholangitis and secondary sclerosing cholangitis.

Results
A 12-year-old boy with CF was seen for abdominal pain with functional impairment. He had prior evidence of calculi in the common bile duct (CBD) and right intrahepatic (IH) duct, and had undergone endoscopic retrograde cholangiopancreatography (ERCP) twice with sphincterotomy once. Magnetic resonance cholangiopancreatography (MRCP) at presentation showed dilated CBD and bilateral IH ducts with calculi, evidence of acute cholecystitis and early cholangitis. He subsequently underwent a third ERCP with stone retrieval, stent placement and a laparoscopic cholecystectomy. Ursodiol dose was optimized and antibiotics were initiated.
Follow-up MRCP showed improvement in CBD and IH duct dilation; the stent was removed. One month later, a fifth ERCP was performed for worsening symptoms associated with a distal filling defect in the left IH duct. Sludge was removed from the CBD and another stent was placed. A sixth ERCP with stent removal showed no stones.
Interval MRCP showed resolution of IH calculi, a CBD filling defect suggestive of sludge, and thickening and enhancement of IH bile ducts with focal areas of alternating narrowing and dilation. He was maintained on antibiotics, and his symptoms persisted over the following months despite resolution of sludge, peri-portal edema and duct-wall enhancement. There was a background of increased IH ductal dilation with “beaded appearance”. Interval imaging has demonstrated persistence of these findings with recurrence of hepatolithiasis in both IH ducts, despite improved symptoms.

Conclusions
This case describes two rare manifestations of pediatric CF-associated liver disease: hepatolithiasis and secondary sclerosing cholangitis. While CFTR dysfunction alone predisposes to gallstone formation, the patient’s clinical course supports a theory for the development of hepatolithiasis resembling that of recurrent pyogenic cholangitis, whereby bacteriobilia from chronic or recurrent infection may promote lithogenesis in the presence of inflammatory bile duct damage. In this patient, secondary sclerosing cholangitis may have resulted from cycles of cholangitis and hepatolithiasis; alternatively, it may represent under-recognized cholangiopathy in the pediatric CF population.

Funding Agencies
None
A167 MANAGEMENT OF LARGE COLORECTAL POLYPS IN NOVA SCOTIA
Authors: Petropolis H , Farina D , Kohansal A R 
Published: February 2020

Abstract

Background
Colorectal cancer (CRC) has the third highest cancer incidence for males and females in Canada1. CRC rates are decreasing, likely due to implementation of CRC screening programs and removal of precancerous polyps. In Nova Scotia, management of large (&gt; 2 cm) polyps is varied. Some patients are referred for endoscopic mucosal resection (EMR), while others referred for surgical resection. EMR is effective2 and associated with less morbidity and mortality compared to surgery3. Furthermore, EMR is less expensive than surgery and requires less resources when performed as a day procedure. Management of these polyps are unknown in Canada and are potentially changing with gathering evidence on the safety and effectiveness of EMR. North American and European guidelines recommend EMR for non-invasive colonic polyps as first line management.

Aims
This projects aim is to determine how large polyps are being treated in a group of FIT positive patients from Nova Scotia.

Methods
This is a retrospective observational study. The Nova Scotia Colon Cancer screening database was searched for FIT positive patients in 2017. Patients found to have &gt; 2 cm colonic polyps were included. Malignant polyps were excluded. Electronic charts were reviewed to determine method of polyp removal. Endoscopic and histologic polyp information was obtained.

Results
196 patients had at least one polyp &gt; 2 cm. Within the central health zone where pathology results were available 78 patients had &gt; 2cm polyps. 13 were excluded for malignancy, one lost to follow up and one patient was miscoded. In total 63 patients were included, 8 of which underwent a surgical resection.
Of these surgically resected polyps the average size was 4 cm and 3 cm for the EMR group. The average time to removal was 3 months in the surgical group and one month in the EMR group. The average age was 68 years in the surgical group and 67 years in the EMR group. The endoscopists referring for surgery were 75% surgeon and 25% GI and the endoscopists performing EMR were 45% surgeon and 55% GI. 1 of 8 (12.5%) patients experienced complications (anastomotic leak) in the surgical group and 2 of 56 (3.6%) patients experienced post polypectomy bleeding in the EMR group.

Conclusions
In this study 12.5% of large nonmalignant polyps found in a group of FIT positive patients from Nova Scotia were removed surgically via resection. Polyps were on average larger by 1 cm in the surgical group and patients experienced a higher rate of complication. This study highlights the need for a structured system of referral and assessment for endoscopic removal of advanced polyps by expert endoscopists, to reduce the number of surgical resections.
Additional investigation of additional years, and health zones outside the tertiary central health zone is ongoing. This will help provide more validity to our current data, and allow comparison of academic vs community management of large polyps.

Funding Agencies
None
A216 EXAMINING THE EFFECTS OF GLYPHOSATE EXPOSURE ON THE GUT BACTERIOME AND INFLAMMATION IN A MURINE MODEL OF COLITIS
Authors: Barnett J A , Haskey N , Quin C S , Bonnie R , La Berge A , Alejandra Verdugo Meza A , Hart M , Gibson D L 
Published: February 2020

Abstract

Background
Canada has the highest incidence of inflammatory bowel disease in the world, which is expected to rise unabated for the next 30 years. Coincidently, Canada is one of the most prolific users of the herbicide glyphosate (tradename Roundup®), with over 25 million kilograms purchased annually. Previous studies examining the effects of glyphosate on the gut bacteriome have used high levels of glyphosate (ranging from 2.5mg – 25mg/kg bw/day) and have yielded conflicting results. Our goal is to examine the effects of dietary levels of glyphosate on the gut microbiome and inflammation in an animal model of colitis. Two environmentally relevant doses were explored: (1) the acceptable daily intake currently set by the Environmental Protection Agency (EPA) (1.75mg/kg bw/day) and (2) North American dose, calculated by a registered dietician using literature values of glyphosate found within food products (0.1mg/kg bw/day.)

Aims
1) To determine if glyphosate exposure influences intestinal permeability 2) To determine if glyphosate exposure influences intestinal inflammation 3) To determine if glyphosate exposure influences colitis onset and severity. We hypothesized that exposure to glyphosate leads to bacterial dysbiosis, increased intestinal permeability and increased severity of colitis in Mucin 2 deficient mice (Muc2-/-mice).

Methods
Upon weaning, Muc2-/- mice were exposed to glyphosate through their drinking water. Animals were monitored weekly for clinical signs of colitis, including rectal prolapse. Following 12-week glyphosate exposure, intestinal permeability was measured using the FITC-dextran permeability assay. Intestinal inflammation was measured using qPCR and markers relevant to our animal model including REGIIIγ, RELM-β and CLEC-2.

Results
Exposure to glyphosate at physiologically relevant levels does not increase intestinal permeability in Muc2-/-mice, with all groups showing equal levels of FITC-dextran present within their serum. Animals exposed to the EPA dose of glyphosate exhibited earlier onset of colitis symptoms with animals receiving higher clinical scores and displaying an increased rate of rectal prolapse. Animals exposed to the EPA dose also showed a significant increase in CLEC-2 expression. CLEC-2 is a C-type lectin-like receptor expressed by immune cells and platelets and has been implicated in tumor metastasis. Additionally, overexpression of CLEC-2 has been shown to promote pathogen adherence to mammalian cells.

Conclusions
Exposure to glyphosate at levels deemed safe by the EPA increases colitis onset and severity in Muc2-/- deficient animals. Additionally, EPA level glyphosate exposure upregulates CLEC-2 expression which may have implications for tumor development and increased enteropathogenic infections.

Funding Agencies
CCCCrowdfunding, NSERC