bluuebunny/crossref_metadata_2025 huggingface dataset:
Constitutional democracy in the time of elected authoritarians
Authors: Sadurski Wojciech
Published: February 2020

In this paper, colored as it is by my knowledge and experience of democratic backsliding in Central and Eastern Europe (CEE), I reflect upon the rise of autocracies characterized by electoral pedigree and consider some consequences of these developments. I focus in particular upon its relative invisibility, which is due, among other things, to the fact that autocratic changes proceed incrementally, that their truly invidious effects are triggered by mutual interactions between various discrete changes, that institutions are not formally dismantled but hollowed out of their original meanings, and that assaults upon various pillars of democracy do not proceed at the same pace. To conclude, I draw two lessons from the authoritarian turn in CEE: the first concerns the relative insignificance of formal constitutional design, and the second considers the end of the “transition paradigm.”
Types of Articles
Authors: Fontanarosa Phil B.
Published: February 2020

The Types of Articles chapter of the 11th edition of the AMA Manual of Style considers the different types and formats of articles that scientific journals may use to present their content: research reports, reviews (systematic and narrative), other substantive articles (nonresearch, nonreview), opinion (viewpoints or commentaries, editorials, personal vignettes and reflections), and correspondence (including research letters). Guidance is directed to authors for use in preparation of articles, as well as to journal editors in providing clear instruction to the journal’s authors.
Grammar
Authors: Christiansen Stacy
Published: February 2020

The Grammar chapter of the 11th edition of the AMA Manual of Style focuses on how to avoid common grammatical and writing errors. Topics include often-encountered dilemmas: who vs whom, that vs which, the number vs a number, a vs an. Guidance on frequent stumbling blocks such as double negatives, subject-verb agreement, false singulars and false plurals, collective nouns, compound subjects, misplaced modifiers, verbal phrase danglers, and parallel construction is illustrated with updated examples. The discussion of verbs considers voice, mood, and tense. Avoidance of idioms, colloquialisms, and slang, as well as euphemisms and clichés, is advised in material intended for an academic audience. A subsection on grammar considerations in social media has been added, as well as inclusion of they as a singular pronoun. A list of additional readings and general references concludes the chapter.
Abbreviations
Authors: Gregoline Brenda
Published: February 2020

The Abbreviations chapter of the 11th edition of the AMA Manual of Style begins by distinguishing between abbreviations, acronyms, and initialisms and cautions against overuse of abbreviations. Lists of abbreviations and their expansions are provided for academic degrees and honors; US military services and titles; days of the week, months, eras; local addresses; cities, states, counties, territories, possessions, provinces, countries; names and titles of persons; commercial firms; agencies, organizations, foundations, funding bodies; collaborative groups; names of journals; clinical, technical, and other common terms; units of measure; elements and chemicals; and radioactive isotopes. Several new policies: CI no longer requires expansion.In bylines, academic degrees should be reported; fellowship designations (eg, FRCP, FRCPC) and honorary degrees will no longer be included.
Mathematical Composition
Authors: Fischer Lauren , Frank Paul
Published: February 2020

The Mathematical Composition chapter of the 11th edition of the AMA Manual of Style addresses conventions used to display mathematical formulas and other expressions involving special symbols, character positions, and relationships, both in print and online. Topics include displayed vs run-in equations, stacked vs unstacked fractions or formulas, exponents, fractional exponents vs radicals, negative exponents, logarithmic expressions, long formulas, expression of multiplication and division, typography and capitalization, punctuation, and spacing with mathematical symbols. A list of commonly used symbols is also included, as well as more examples of complicated “fences” in equations.
A20 VITAMIN D SUPPLEMENTATION REDUCES THE OCCURRENCE OF COLORECTAL POLYPS IN HIGH-LATITUDE LOCATIONS
Authors: Sutherland R L , Ormsbee J , Pader J , Forbes N , Hilsden R J , Brenner D R
Published: February 2020

Background

There is suggestive evidence for the role of vitamin D in the development of colorectal cancer (CRC). Furthermore, previous studies have observed associations with vitamin D supplementation and lower incidence of CRC. Due to high latitudes in Canada, many Canadians are vitamin D deficient throughout winter

Aims

In this analysis, we aimed to examine the association between either vitamin D supplement use or meeting the reccommended daily intake of vitamin D, and either any colorectal polyp, or a known precursor of CRC: high-risk adenomatous polyps (HRAPs).

Methods

The study population was drawn from the biorepository at the Forzani & MacPhail Colon Cancer Screening Centre (CCSC) in Calgary. Data were obtained from the Diet History Questionnaire (DHQ) I or II, the Health and Lifestyle Questionnaire (HLQ), and through post-colonoscopy reports completed by the endoscopist. Multivariable logistic regression models were used to examine the association between intake of supplemental vitamin D and presence of HRAPs. Models were adjusted for age, sex, BMI, fiber intake, alcohol consumption, and smoking status.

Results

Individuals between the age of 50 and 74 years (n= 1,409) were included. When examining the association between any supplemental vitamin D use and HRAPs, a protective effect was observed with an ORadj of 0.57 (95% CI: 0.33–0.96). Similarly, meeting the recommended daily intake (RDI) of vitamin D (600 IU) was protective against HRAPs with an ORadj of 0.78 (95% CI: 0.62–0.99).

Conclusions

This study suggests that adequate vitamin D supplementation can reduce the risk of HRAPs. These results could be used to inform public health recommendations for vitamin D intake with hopes of reducing the risk of HRAPs.

Funding Agencies

None
A25 THE “UPSIDE-DOWN OR OUTSIDE-IN”: UNDERSTANDING HOW FOXL1+ TELOCYTES GOVERN THE EPITHELIAL-MESENCHYMAL CROSSTALK IMPACTING CELL BEHAVIOR BY USING PROTEOMICS STRATEGIES
Authors: Pomerleau V , Reyes-Nicolas V , Boisvert F , Perreault N
Published: February 2020

Background

The mechanical information contained in the basement membrane (BM) is translated into intracellular signals via a process called mechanotransduction. The integrin-mediated cellular adhesions are found at the center of this outside-in mechanism connecting specific extracellular matrix (ECM) proteins with intracellular adaptors proteins that relay the signal via F-actin cytoskeleton turnover, Rho GTPase activity and eventually down to the nucleus. Dysregulation in any step of this tightly controlled process is a major contributor of disease development. Mesenchymal Foxl1+-telocytes (TCs) are known as a communication hub between stromal and epithelial cells from their proximity to the BM and from their potential roles in epithelial mechanical support and cell signaling. We have shown that BMPR1A signaling deletion in TCs (TCΔBmpr1a) induces stem cell niche defects, stromagenesis and colonic dysplasia in mouse model of GI diseases. Thus far, no study explored TCs relevance in microenvironment biomechanics and its subsequent impact in epithelial mechanotransduction.

Aims

Understand how TCΔBmpr1a can modulate mechanotransduction to induce early dysplastic changes in mouse colon.

Methods

Matrisomics was performed to determine the inventory of ECM proteins expressed solely in the GI stromal compartment following tissue deconstruction of control and TCΔBmpr1a mice colons. Collagen fibers analysis, histological and biochemical methods were used to further characterize the matrix biodynamics. Proteomics of the associated epithelial compartment was also done to expose mechanosensors and signaling cascades affecting cell behaviour.

Results

Matrisomics indicate modulations in fiber assembly proteins (collagens (CL), Decorin, Biglycan), ECM remodelling enzymes (LOXL1, TGM2), growth factors (LTBP1, WNT2B) and cell adhesion mediators (Periostin). This is associated with a reorganization in CL fiber alignment, cellular delocalization of TGM2 and increased unfolded CL content. TCΔBmpr1a leads to shortcomings in matrix assembly, hence variations in the ECM architecture and a novel epithelial mechanotransduction potential. Deregulations in matrix-to-cell communication were shown by proteomic analysis of the epithelial-enriched compartment of colonic dysplastic areas, with modulations of mechanosensors such as focal adhesion components (integrins, paxillin), F-actin cytoskeleton (gelsolin, RhoA) and nuclear lamina (Prelamin A/C, nesprin).

Conclusions

Taken together, these results suggest that TCΔBmpr1a can reprogram epithelial cells by impacting on matrix biodynamics and epithelial mechanotransduction. Modulation in this fine regulated sequence of communication from TCs to the epithelial nucleus via ECM could lead to the etiology of GI pathologies.

Funding Agencies

CIHR
A34 EOSINOPHILS ALTER STEADY-STATE SMALL INTESTINAL IL-1α AND IL-1β LEVELS BUT ARE NOT REQUIRED FOR THE MAINTENANCE OF IGA-SECRETING LAMINA PROPRIA-RESIDENT PLASMA CELLS, SECRETORY IGA OR SERUM IGA LEVELS
Authors: FitzPatrick R D , Kennedy M H , Lawrence K M , Moeller B , Gauthier C M , Brosschot T P , Reynolds L A
Published: February 2020

Background

During homeostasis eosinophils are highly abundant in the lamina propria of the small intestine. Eosinophils have been reported to play a role in promoting barrier function in the steady state intestinal tract, and in the control of intestinal colonization by harmless or symbiotic members of the bacterial microbiota. However, the role eosinophils play during enteric infection with a bacterial pathogen is unknown.

Aims

Our study aims to confirm the previously reported role of eosinophils in supporting intestinal barrier function and to investigate how the absence of eosinophils affects intestinal colonization by an enteric bacterial pathogen.

Methods

We used wildtype BALB/c and eosinophil-deficient (dblGATA knockout) BALB/c mice that had been cohoused, or bred as littermate controls, to normalize bacterial microbiota populations between mice used for experiments. To investigate steady state barrier function in these mice we used naïve mice to quantify levels of small intestinal IL-1α and IL-1β by cytometric bead arrays, and we used ELISAs to measure levels of immunoglobulin A (sIgA) and serum IgA. Levels of lamina propria-resident B220-IgA+ plasma cells were quantified using flow cytometry. To investigate the contributions of eosinophils to enteric bacterial infection, mice were orally infected with Salmonella enterica serovar Typhimurium. Salmonella burdens along the intestinal tract as well as in the liver and spleen were quantified.

Results

We found that levels of IL-1α and IL-1β were significantly decreased in the small intestine of naive eosinophil-deficient mice, compared to wildtype mice. In naïve wildtype and eosinophil-deficient littermate control mice, we did not detect any differences in sIgA or serum IgA levels. Additionally, levels of IgA producing plasma cells were similar in the small intestinal lamina propria between wildtype and eosinophil-deficient mice. Following oral Salmonella infection, Salmonella burdens were similar between wildtype and eosinophil-deficient mice both 24 hours and three days post-infection.

Conclusions

Our data supports a role for eosinophils in modifying steady-state cytokine levels in the intestinal tract. For the first time we report data on IgA levels from littermate controls of wildtype and eosinophil-deficient mice, and contrary to previously published reports, we found that eosinophils are not critical for the maintenance of intestinal sIgA, serum IgA or lamina propria resident IgA producing plasma cells. Our data further concluded that an absence of eosinophils did not impact control of Salmonella infection.

Funding Agencies

CIHR
A51 UTILIZING MUCIN-DERIVED SUGARS CONFERS A FITNESS ADVANTAGE TO THE ENTERIC PATHOGEN CITROBACTER RODENTIUM THAT PROMOTES INTESTINAL COLONIZATION
Authors: Mslati M , Liang Q , Yu H , Ma C , Vallance B
Published: February 2020

Background

Citrobacter rodentium is an enteric murine pathogen used to model the human diarrheal pathogens. Following inoculation, C. rodentium colonizes the mouse cecum where it expands and ultimately spreads to the distal colon. During this process, C. rodentium has to compete with commensal microbes for available nutrients. Moreover, to spread throughout the gut, and infect the intestinal epithelium, C. rodentium has to cross through, and or dwell within the intestinal mucus layer which is composed of the heavily glycosylated protein Muc2. Muc-2 is glycosylated and coated by 5 distinct terminal sugar residues: galactose, N-acetylgalactosamine, N-acetylglucosamine, fucose, and sialic acid. Many commensal microbes have the ability to cleave and free these sugars from the Muc2 protein, releasing them for their own consumption, however pathogens appear to exploit this process. While studies have indicated that C. rodentium uses these terminal sugar residues as a nutritional source, their relative importance in the pathogenic strategy of C. rodentium (and other gut pathogens) remains unclear

Aims

Investigate the role played by mucin sugar residues in controlling C. rodentium pathogenesis

Methods

Deletions of agaW, nagE, mglB, galP, fucK, and nanT were generated on the chromosome of C. rodentium (Strepr) by overlap extension PCR. Growth assays were performed to examine the growth kinetics of mutants C. rodentium in minimal (M9) media supplemented with one of the 5 mucin sugars or M9 with whole mucin as control. Specific pathogen free (SPF) C57BL/6 mice, or germfree C57BL/6 mice were orally gavaged with wildtype C. rodentium (Strepr) or one of ΔagaW, ΔnagE, ΔmglB, ΔgalP, ΔfucK, or ΔnanT strains. Mice were euthanized at 6 days post-infection, and the cecum, colon, and spleen were collected and histologically scored for pathology and intestinal and systemic bacterial burden. Stool samples were collected throughout the 6 days to quantify C. rodentium burdens

Results

Growth assays confirmed that the specific sugar transporter/kinase mutant C. rodentium strains grew normally when placed in media supplemented with whole mucin, or with most sugars, only showing overt defects in growth when solely supplemented with the sugar for which they were impaired. Several of the C. rodentium mutants including ΔnanT showed overt defects in colonization/infection of SPF C57BL/6 mice, but their pathogenesis was normalized in germfree mice, or in mice treated with the antibiotic streptomycin at each day post-infection. These findings indicate that the impact of mucin sugar utilization on C. rodentium virulence is microbiota-dependent

Conclusions

C. rodentium uses mucin sugars as nutrient source in the mouse gut, and an inability to use these sugars impairs their ability to infect their hosts in a microbiota dependent manner

Funding Agencies

CAG, CCC, CIHR, NRC
A53 SACCHAROMYCES BOULARDII CNCM I-745 IMPROVES ANXIETY-LIKE BEHAVIOR AND RESCUES DYSMOTILITY IN A HUMANIZED MOUSE MODEL OF IRRITABLE BOWEL SYNDROME WITH CO-MORBID ANXIETY
Authors: Constante M , De Palma G , Lu J , Jury J , Collins S M , Bercik P , Verdu E
Published: February 2020

Background

Irritable bowel syndrome (IBS) is one of the most common conditions seen by gastroenterologists for which there is no effective cure. The pathophysiology of IBS is multifactorial and poorly understood, but the condition is characterized by chronic abdominal pain accompanied by altered bowel habits in the absence of an underlying structural abnormality. IBS is frequently associated with psychiatric co-morbidities such as anxiety and depression and has been considered a disorder of gut-brain communication. We previously developed a humanized mouse model of IBS with co-morbid anxiety (IBS+A) by colonizing germ-free mice with fecal microbiota of IBS+A patients.

Aims

To test the therapeutic potential of the probiotic yeast Saccharomyces boulardii CNCM I-745 (S. bou) in preventing the transfer of the IBS+A phenotype and investigated underlying mechanisms.

Methods

Germ-free Swiss-Webster mice were colonized with fecal microbiota from an IBS+A patient or from a healthy subject (controls) and after three weeks they were gavaged daily for two weeks with 3g/kg/day of the probiotic S. bou (Biocodex–France) or water. Behavior, intestinal motility and permeability were assessed at sacrifice. Potential mechanisms were assessed by microbiota 16S rRNA gene sequencing, gene expression by Nanostring Counter Gene Expression and indole quantification by absorption using Kovak’s reagent.

Results

IBS+A colonized mice developed 25% faster gastrointestinal transit (P<0.05) and had a 3-fold longer latency time in the step-down test (P<0.001), indicative of anxiety-like behaviour compared with controls. S. bou normalized gastrointestinal transit (P<0.05) and shortened by 50% the step-down latency (P<0.01), compared to water-treated mice. Microbiota of IBS+A colonized mice had higher abundance of Unc. Erysipelotrichaceae and Unc. Coriobacteriaceae, and lower abundance of Oscillospira, Weissela, and Fructubacillus. S. bou treatment prevented these changes and the microbiota was similar to controls. Predicted function analysis in S. bou treated mice suggested higher number of genes implicated in indole biosynthesis (P<0.05) and S. bou increased indole levels by 20% in vitro. Finally, Trpv1, a gene implicated in visceral hypersensitivity and anxiety, was increased by 2-fold in IBS+A colonized mice compared with controls (P<0.001), and this was reverted by 20% (P<0.05) by S. bou treatment.

Conclusions

Our data indicate that Saccharomyces boulardii CNCM I-745 supplementation improves the intestinal and behavioral phonotype that is induced by IBS+A microbiota in mice. Putative mechanisms include regulation of indole production by bacteria and regulation of host Trpv1 gene expression. The results prompt investigation of S. bou in IBS patients with co-morbid anxiety.

Funding Agencies

Biocodex – Gentilly – France
A64 HOSPITALIZATION IN INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED COMPARISON OF DEFINITIONS
Authors: Coward S , Benchimol E I , Bernstein C N , Bitton A , Carroll M W , Jelinski S , Jones J , Kuenzig E , Leddin D , Murthy S , Nguyen G C , Otley A , Rezaie A , Peña-Sánchez J , Singh H , Stach J , Targownik L , Windsor J W , Kaplan G G
Published: February 2020

Background

Most administrative studies of hospitalization in inflammatory bowel disease (IBD) use two definitions: IBD in any diagnostic position (IBD-ANY), and IBD as the most responsible diagnostic (IBD-MRD). There is a third less commonly used definition: total hospitalization; this definition captures all hospitalizations of prevalent IBD patients and therefore it can give a more realistic picture of the burden of IBD.

Aims

To compare differing definitions (total, IBD-ANY, and IBD-MRD) of hospitalizations.

Methods

A previously defined population-based IBD prevalent cohort for Alberta (n=30,698) was used to pull all hospital admissions from the Discharge Administrative Database (DAD; 2002–2015). Three hospitalization definitions were used: i. Total (all hospitalizations of prevalent cohort independent of presence of code for IBD); ii. IBD-ANY (code for IBD [K50.x; K51.x] contained in any diagnosis field); and, iii. IBD-MRD (most responsible diagnosis was IBD). Age- and sex- standardized rates (2015 Canadian population) were calculated using the prevalent population. Log-linear regression was performed to calculate Average Annual Percentage Change (AAPC) with associated 95% confidence intervals (CI) of each type of hospitalization. We assessed the top five most common most-responsible diagnosis codes for hospitalizations that were contained in the total hospitalizations but not an IBD-ANY hospitalization.

Results

From 2002 to 2015, 63.5% of IBD prevalent patients in AB had ≥1 hospitalization; 44.2% had ≥1 IBD-ANY hospitalization; 28.6% had ≥1 IBD-MRD hospitalization; and, 40.6% had a hospitalization that did not contain a code for IBD. All hospitalization rates decreased significantly over time. Of the top five most common most responsible diagnosis, contained in admissions that were not IBD-ANY, three were gastroenterological: i. K52.9 (non-infective gastroenteritis); ii. A09.9 (diarrhea and gastroenteritis of presumed infectious origin); and, iii. Z43.2 (attention to ileostomy).

Conclusions

Total hospitalizations is an important measure to report since accounting for all hospitalizations of IBD patients is necessary in order to allocate healthcare resources appropriately. To be able to ensure these patients receive the care they need we need to be able to accurately assess the true burden of IBD.

Funding Agencies

CIHR
A73 PHARYNGEAL VARICES AS A COMPLICATION OF PORTAL HYPERTENSION: A CASE SERIES
Authors: Ghaith J , James P , Wong F
Published: February 2020

Background

One of the complications of portal hypertension, with or without the presence of cirrhosis, is the development of varices along the length of the gastrointestinal tract. The commonest sites are along the esophagus or in the stomach. Ectopic varices in the small and large bowels can also be observed, but ectopic varices in the pharynx are extremely uncommon.

Aims

To present a case series and review the literature regarding pharyngeal varcies.

Methods

-

Results

Three elderly female patients presented for esophagogastric varices surveillance gastroscopy were diagnosed with pharyngeal varices. One patient has hepatitis C cirrhosis, while the other two non-cirrhotic patients have myeloproliferative neoplasm (MPN). None of the patients had thromboses of the portal vein or its tributaries. All three patient have concomitant esophageal varices, but only one required band ligation of her esophageal varices. All patients are asymptotic except for mild dysphagia. No patient has bled from their pharyngeal varices to date. Two patients have had prophylactic treatment of their portal hypertension with non-selective beta blocker (NSBB), while the third one has not received NSBB prophylaxis because of her age.

Conclusions

Pharyngeal varices are extremely rare. To date, there are three case reports in the literature, however, we have been able to identify three cases in our practice. The previous two cases reported possible left-sided portal hypertension with splenic vein thrombosis, leading to the development of collateral vessels including a gastrocaval shunt, which by some contiguous route connects to the brachiocephalic vein; and a third case was a complication of neck dissection surgery. In our case series, none of our patients had splenic vein thrombosis. However, none of them has had a careful CT angiogram to delineate the portal vein tributaries and the collateral vessels, which may further help to define their pathogenesis. It is unclear whether NSBB would be effective as primary prophylaxis against their bleeding, The plan is to continue to monitor these patients to learn about the natural history of these pharyngeal varices.

Funding Agencies

None
A82 SUCCESSFUL RESECTION OF GRADE 1 DUODENAL NEUROENDOCRINE TUMOURS USING ENDOSCOPIC TECHNIQUES IN TWO CANADIAN HOSPITALS
Authors: Klemm N K , Lu-Cleary D , Chahal D , Trasolini R , Lam E , Donnellan F
Published: February 2020

Background

Given the rarity of duodenal neuroendocrine tumours (dNETs), limited guidelines exist for resection of well-differentiated, ≤10 mm dNETS. As incidence rises, alternatives to surgery are valuable. We present 9 cases of endoscopic dNET resections and a literature review.

Aims

To demonstrate efficacy and safety of endoscopic resection for dNETs ≤10 mm at 2 Canadian hospitals.

Methods

We retrospectively analyzed data on 7 patients that had endoscopic dNET resection from 2013–2018. Endoscopic resection occurred if dNETs were ≤10 mm in diameter, did not extend to the muscularis propria and lymphovascular invasion was absent. WHO 2017 classification was used.

Results

All patients had biopsies and 5 (71%) had EUS prior to resection; 4 females and 3 males underwent resection of 9 dNETs; 2 via cap-assisted snare polypectomy; 4 with cap-assisted band mucosectomy; and 2 over-the-scope clip-assisted resection. The median size was 10 mm (4–11); 6 (67%) dNETS were found in the duodenal bulb, 2 at the D1/D2 junction and 1 in D2 alone. The median age was 68.5 (50–79) years.

All dNETs were submucosal and well-differentiated. The dNETs were resected en bloc, but 3 did not have clear margins. Two procedures were complicated by duodenal perforation; 1 requiring surgery and 18 days in hospital. One case was complicated by bleeding with successful endoscopic hemostasis. The majority (75%) of resections were day procedures.

Patients were followed for 6–12 months with an EGD or chromogrannin A. None of the patients had endoscopic residual disease, but 1 patient required a second procedure to remove a dNET left in situ following the initial resection of 2 dNETs 12 months earlier.

In our literature review of 178 patients, the majority of dNETs were resected by EMR 81% (150/185) versus ESD, similar to our experience. Patients were slightly younger with a mean age of 63.28, and most dNETs (46%) were found in the duodenal bulb. Complications included intraoperative bleeding, perforation and death in 17 (9.55%), 9 (5.06%) and 1 (0.06%) patient(s) respectively. The rate of recurrence was 4/178 (2.25%) and patients had a mean follow up of 26.1 months.

Conclusions

Well-differentiated dNETs ≤10 mm in diameter can be successfully resected endoscopically. Complications can be managed intraoperatively and hospital stay remains minimal.

Funding Agencies

None
A86 SUBMUCOSAL INJECTION FOR POLYPECTOMY AND INTERVENTIONAL ENDOSCOPY: AN INTERNATIONAL SURVEY
Authors: Alaoui A , Marques P , Djinbachian R , Pohl H , Libanio D , Barkun A N , von Renteln D
Published: February 2020

Background

Submucosal injection (SI) is used for standard polypectomies or during complex endoscopic interventions. SI helps to facilitate endoscopic resection and to prevent complications such as bleeding or perforation.

Aims

We were interested to evaluate endoscopists practice patterns of using SI during routine standard polypectomy and complex endotherapeutic procedures.

Methods

An online survey using the Google Form application was distributed through medical societies. Survey domains included training and practice characteristics of participating endoscopists as well as questions regarding the use of SI products for endoscopy procedures.

Results

A total of 236 endoscopists (mainly from the US, Canada, and Europe) participated in the survey. About half (48%) of endoscopists start using SI for routine polypectomies when polyps are larger than 10 mm, while 37% of endoscopist report having a size threshold larger than 15mm for using SI (22% report using SI starting at >15 mm, and 15% report using SI starting at >20 mm). Only a minority (11%) of endoscopists report using SI for polyps <10 mm and starting SI at 6 mm. However, 30,3% of endoscopists reported that their size threshold for using SI during polypectomies has decreased in recent years. 83% reported that using SI is beneficial for en-bloc resection, avoiding perforation (91,5%), avoiding thermic lesions (80%) and identifying dysplastic tissue (54,5%). Normal saline is the submucosal agent most commonly available for endoscopists (86,4%), followed by Eleview (66,8%), and ORISE Gel (20%). “Short lasting lift” and “cost” are reported concerns when opting for a specific SI solution. Methylene blue is the coloring agent that is most commonly used (68,9%). Excellent submucosal elevation, availability, and length of action are the most important features an SI should have according to endoscopists’ responses.

Conclusions

The use of SI is common during endoscopy procedures. For standard colorectal polypectomy procedures, most endoscopists start using SI only for polyps larger than 10mm. SI is used by endoscopists to prevent complications, improve endoscopic resection and to identify dysplastic tissue.

Funding Agencies

None
A96 PERIOPERATIVE RATE OF CHANGE IN SODIUM CONCENTRATION AND ITS IMPACT ON LENGTH OF STAY IN CRITICAL CARE UNIT POST LIVER TRANSPLANTATION: BENCHMARKING FOR QUALITY MANAGEMENT PROGRAM
Authors: James L J , Allen S E , Peltekian K M
Published: February 2020

Aims

The aim of this quality improvement project was to benchmark the rate of change in serum sodium (delta-Na) in the perioperative period for liver transplantation (OLT) to correlate it with neurological complications as well as length of stay in critical care unit.

Methods

Data for total of 46 patients who underwent liver transplantation in Halifax between January 2015 and December 2016 were extracted from Atlantic Multi-Organ Transplant Program and QEII-HSC Information Systems. Pre-operative, immediate post-operative and 24–48 hours post-operative serum sodium concentrations were entered into EXCEL worksheet. In addition post-transplant neurological complications were identified in addition to length of stay in critical care unit.

Results

During the review period, 23 males and 23 females underwent OLT. Their mean age was 56 yrs (ranging from 23 - 70 yrs). The primary indication for transplantation was cirrhosis (57%) and hepatocellular carcinoma (35%). Fatty liver disease was most common etiology for cirrhosis (46%), followed by PBC (27%), Alcohol-related (15%). Average natural MELD-Na score was 20 (with a range from 7 – 41). Average OR time was 7hr 23min (range 4hr 15min – 15hr).

In 22% of patients, the rate of delta-Na levels were rapid (more than 8 mEq/L) between the pre-operative and immediate post-operative period. Only 2% of patients had more than 8 mEq/L change in their serum sodium levels between the first and second post-operative days. Prior to OLT 21 (46%) patients had hepatic encephalopathy but this was mild or controlled in the majority of patients. In 8 (17%) patients there was multiple-etiology encephalopathy/delirium in the post-operative period. None of these patients developed neurological deficits. Only in 3 patients, tremors were documented (probably multifactorial including calcineurin-inhibitor toxicity). In this project, none of these findings correlated with a high rate of delta-Na.

The average number of days in critical care unit was 6 (range 1 – 62 days). There was no clear correlation between length of stay (surrogate marker for neurologic complications) and rate of delta-Na.

Conclusions

In this benchmarking project, we were unable to identify a specific cut-off rate for delta-Na to correlate with either neurologic complication or length of stay in critical care unit. Rapid correction of serum sodium is often associated with various neurologic complications including central pontine myelinosis. Larger data-base with more numbers of liver transplant patients are needed to show any significant relationship and optimize the electrolyte and volume management. Rapid change in serum sodium could not help with our attempt to classify this benchmarking metric into one of four categories: productivity, quality, time and cost-related.

Funding Agencies

NoneKEVORK M PELTEKIAN
A97 TACROLIMUS-ASSOCIATED HEMOLYTIC UREMIC SYNDROME IN A PEDIATRIC LIVER TRANSPLANT RECIPIENT
Authors: Wong K W , Gilmour S
Published: February 2020

Background

Tacrolimus associated hemolytic uremic syndrome (HUS) has been reported in renal and pediatric cardiac transplantation. Furthermore, in adults receiving liver transplant, there are reports of multiorgan failure, death, and end stage renal failure secondary to tacrolimus induced HUS [J NEPHROL 2003; 16: 580–585]. Although tacrolimus is commonly used in pediatric liver transplantation, there are no reports of the same entity.

Aims

To describe a case of tacrolimus induced HUS in a pediatric liver transplant patient and subsequent re-initiation of tacrolimus.

Methods

The patient was followed during his hospital admission and after discharge.

Results

An 8-year-old male with Progressive Familial Intrahepatic Cholestasis (PFIC) Type III, diagnosed at age 2, presents for living unrelated donor liver transplantation. He was previously well compensated but began to deteriorate in the months leading up to transplant with rising liver enzymes, ascites, and mild encephalopathy after presumed viral gastroenteritis.

He receives a left lateral segment liver transplantation and is started on tacrolimus immunosuppression post liver transplant as per protocol.

On initiation of tacrolimus, the patient’s hemoglobin trends downward to a trough of 59 g/L four days post transplantation. Concurrently, his haptoglobin is <0.10g/L, total bilirubin peaks at 708 umol/L, creatinine rises to a peak of 71 umol/L, urea peaks at 23.0 mmol/L. Platelets reach a nadir at 27x10^9/L, seven days post transplantation. Direct antibody test was negative, and blood cultures remained negative. Given the constellation of hemolytic anemia, thrombocytopenia, and acute kidney injury following initiation of tacrolimus, a diagnosis of atypical HUS is made.

Tacrolimus is discontinued, intravenous methylprednisolone is started and the patient is switched to cyclosporine immunosuppression. Both the hemolysis and kidney injury resolve gradually.

The patient develops side effects from cyclosporine including hypertension and excessive hair growth. One month post discontinuation of tacrolimus, he is started on sirolimus, while weaning steroids and cyclosporine.

Seven weeks post discontinuation of tacrolimus, he is restarted on tacrolimus and is currently tolerating dual immunosuppression with no signs of HUS recurrence.

Conclusions

Atypical HUS secondary to tacrolimus post liver transplant in children is a rare entity.

In the acute period, discontinuation of tacrolimus is essential to preserve renal function given potentially devastating outcomes seen in adults. Cyclosporine is an alternative immunosuppressive agent used in pediatric solid organ transplantation, although it has also been implicated in causing HUS.

Funding Agencies

None
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

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

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 <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 <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 <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 <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 >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 (>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 < 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

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

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

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