bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

Abstract

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

Abstract

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&lt;0.05) and had a 3-fold longer latency time in the step-down test (P&lt;0.001), indicative of anxiety-like behaviour compared with controls. S. bou normalized gastrointestinal transit (P&lt;0.05) and shortened by 50% the step-down latency (P&lt;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&lt;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&lt;0.001), and this was reverted by 20% (P&lt;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

Abstract

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

Abstract

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

Abstract

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

Abstract

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 &gt;15 mm, and 15% report using SI starting at &gt;20 mm). Only a minority (11%) of endoscopists report using SI for polyps &lt;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

Abstract

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

Abstract

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 &lt;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