bluuebunny/crossref_metadata_2025_split huggingface dataset:
A178 DIAGNOSIS OF A MYCOTIC AORTIC ANEURYSM USING ENDOSCOPIC ULTRASOUND: A CASE REPORT
Authors: Reise-Filteau M , Toliopoulos P , Desilets E 
Published: February 2020

Abstract

Background
The role of endoscopic ultrasound (EUS) has expanded over the last decade. It is a well-established imaging modality in the diagnosis of gastrointestinal and pancreatic lesions as well as in mediastinal lesions. To date, EUS has not been reported in the literature for the diagnosis of mycotic aortic aneurysm after intravesical bacille Calmette-Guérin (BCG) therapy.

Aims
This case report describes the presentation and diagnosis of a mycotic aneurysm in the context of disseminated Mycobacterium bovis infection.

Methods
An 86-year-old man with previous intravesical BCG immunotherapy for the treatment of bladder carcinoma presented with weight loss and deconditioning at admission. Based on the patient’s past medical history and age, malignancy was suspected. An endoscopic ultrasound (EUS) revealed a mass at the lymph node station 9 masquerading as a lymphadenopathy. Multiple investigations were completed. Following the second EUS, the diagnosis of mycotic aneurysm was raised. The smear collected with EUS guided fine needle aspiration (FNA) was positive after Ziehl-Neelsen staining. The diagnosis of mycotic aneurysm to Mycobacterium bovis was confirmed.

Results
Treatment was initiated with rifampin, isoniazid and ethambutol. Despite optimal medical management, the patient presented with new onset fever, and a clinical deterioration with positive mycobacterial blood cultures. Within two months of admission, the treatment was discontinued and the patient died in palliative care.

Conclusions
Recognition of mycotic aneurysms is critical for institution of appropriate therapy and averting more severe complications, as they are associated with significant morbidity. This case aims to raise awareness to this rare disease after BCG treatment. It also highlights the novel role of EUSin the challenging diagnosis of mycotic aneurysm.

Funding Agencies
None
A191 EFFICIENCY OF TAILORED ERADICATION REGIMEN BASED ON ANTIBIOTIC SUSCEPTIBILITY AND CYP2C19 GENOTYPE TESTING IN CHILDREN WITH REFRACTORY HELICOBACTER PYLORI INFECTION
Authors: Ding Z , Pai N 
Published: February 2020

Abstract

Background
Refractory helicobacter pylori (Hp) is a challenging problem for pediatric population. Whether Hp culture and CYP2C19 genotype need to be done together still remains contraversial.

Aims
To explore the efficiency of tailored eradication therapy based on helicobacter pylori culture, susceptibility and CYP2C19 genotype in children who failed to empirical Hp eradication strategy in Baoding region(China).

Methods
This study is an observational cohort study. A total of 156 children with Hp infection who failed to amoxicillin + clarithromycin +omeprazole triple regimen in Baoding Children’s Hospital were selected as study subjects, and 92 of them underwent Hp culture and CYP2C19 genetic testing. 75 cases with successful Hp culture were defined as successful culture group and were treated according to antibiotics sensitivity and genotype results. 17 cases with failed culture were defined as culture failure group and were treated only based on the results of CYP2C19 genotype. 64 children who did not agree to perform Hp culture and CYP2C19 gene testing were defined as the empirical eradication therapy group and were treated with quadruple therapy (amoxicillin + metronidazole + omeprazole + bismuth). Antibiotics resistance, CYP2C19 gene polymorphism and therapeutic efficiency between the three groups were compared and analyzed.

Results
Results of Hp culture and antibiotics susceptibility: among the 75 children with successful culture, 72 (96%) were resistant to clarithromycin, 3 (4%) were resistant to metronidazole, 5 (7%) were resistant to levofloxacin, 5 (7%) were resistant to rifampicin, 1 (1%) was resistant to tetracycline, and there was no resistance to amoxicillin and furazolidone.
Results of CYP2C19 genotype test: among the 92 patients who underwent genotype test, 43 were Extensive Metabolizer (EM) (47%), 9 were Poor Metabolizer (PM) (10%), and 40 were Intermediate Metabolizer (IM) (44%).
Efficiency results: eradication rate in the successful culture group, culture failure group and empirical eradication therapy group was 99% (74/75),88%(15/17) and 72%(46/64), respectively. The eradication rate of children in the culture failure group and the empirical eradication therapy group were both lower than that in the successful culture group,and there were no difference between empirical eradication therapy group and culture failure group(p=0.283).

Conclusions
Tailored treatment based on Hp culture + antibiotics susceptibility and CYP2C19 genotype detection should be performed in children with refractory Hp infection. Hp culture + antibiotics susceptibility plays a more important role than CYP2C19 genotype.

Funding Agencies
None
A205 NON-POLAR HELMINTH-DERIVED METABOLITES MODULATES INNATE IMMUNE CELL RESPONSE AND PROTECTS MICE FROM EXPERIMENTAL COLITIS
Authors: Arai T , Siciliani E A , Jardim A , Lopes F 
Published: February 2020

Abstract

Background
The hygiene hypothesis postulates that the lack of exposure to helminth parasites would contribute to the development of the auto-inflammatory disease. There has been a significant increase in patients with inflammatory bowel disease (IBD) in North America. The previous study showed that infection with gastrointestinal helminth parasitedownregulated inflammatory pathways in several gut inflammation models. Given the known risks of live helminth infection, the therapy should direct towards helminth-derived properties.

Aims
To determine if helminth-derived metabolites treated mice are protected from DSS-induced colitis.

Methods
Preliminary, our screening reveled that non-polar fractions of 4 distinct helminth modulate LPS-induced inflammatory cytokines in vitro. 3% DSS or water was given to C57BL/6 mice for 5 days, followed by 4 days of a recovery period. The mice were treated intraperitoneal injection with non-polar helminth-derived metabolites (NPHM) on days 5, 6, and 7. Inflammation was assessed by disease activity,histopathology and cytokine mRNA expression in colons. The effect of NPHM on neutrophil chemotaxis was assess inin vitroand in vivo.

Results
The disease activity and histopathology score were significantly lower in DSS treated mice received NPHM. Also, NPHM treatment resulted in a decrease of an inflammatory cytokine such as TNF-α mRNA expression in the colon of mice with DSS-induced colitis. Mechanistically, NPHM reduced neutrophil chemotaxis.

Conclusions
NPHM treatment protects against DSS-induced colitis and modulate neutrophil response, which supports helminth therapy for IBD.

Funding Agencies
Supported by Hashimoto Municipal Hospital scholarship to TA and an NSERC Discovery grant to Fernando Lopes.
A211 ANTIFIBROTIC ACTIVITY OF NOVEL TYROSINE KINASE INHIBITORS IN VITRO
Authors: Kataria J , Lourenssen S , Blennerhassett M G 
Published: February 2020

Abstract

Background
Chronic inflammation in inflammatory bowel disease (IBD) causes structural alterations of the intestine. In Crohn’s disease, this can lead to stricture formation, arising from unclear interactions among local inflammatory cells, cytokines, and mesenchymal intestinal cells. Specifically, proliferation of smooth muscle and increased deposition of collagen-rich extracellular matrix leads to fibrosis and obstructive wall thickening. Since there are minimal treatment options, we explored the effects of two multimodal tyrosine kinase inhibitors, nintedanib and pirfenidone, which were recently approved for idiopathic pulmonary fibrosis (IPF), a chronic lung condition resembling Crohn’s disease.

Aims
To understand the basic pharmacology of two novel anti-fibrotic tyrosine kinase inhibitors and their effects on cell proliferation and collagen deposition.

Methods
In vitro model systems of adult rat colonic circular smooth muscle cells (CSMS), rat IEC-18 intestinal epithelial cells or mouse 3T3 were assessed for response to serum or the mesenchymal growth factor PDGF-BB, evaluating growth responses by proliferation assay, and type I collagen expression by immunocytochemistry and western blotting. Programmed cell death was detected by ICC and western blotting for caspase-dependent apoptotic markers.

Results
Both 3T3 fibroblasts and rat ISMC showed concentration-dependent proliferation in response to serum or PDGF application. Nintedanib reduced this response to baseline at EC100 of 2.3 ± 0.7 (n=5) µM, and EC50 of 0.3 ± 0.1 (n=6) µM without cytotoxicity, while pirfenidone was ineffective at levels ≤ 5mM. Nintedanib (10 µM) was ineffective against serum-induced growth of rat IEC-18 cells while blocking growth of rat CSMC or mouse 3T3 fibroblasts in parallel assays, suggesting a selective effect on mesenchymal cell types. In nintedanib-treated cultures, nuclear staining showed concentration-dependent reduction of mitotic figures with proportional appearance of nuclear fragmentation, typical of apoptosis. Western blotting for collagen I identified at 125kD band for both CSMC and 3T3 cells and suggested down-regulation with both nintedanib and pirfenidone.

Conclusions
Novel anti-fibrotic therapies for chronic idiopathic pulmonary disease display distinctive effects on ISMC proliferation and extracellular matrix production. These address molecular mechanisms of fibrosis that are in common with IBD, and so the translation of therapeutic approaches may be a promising treatment option. Detecting specific mechanisms of action of nintedanib, such as apoptosis, leads to better targets for therapeutic options.

Funding Agencies
NSERC
A213 A NOVEL PH-SENSITIVE OPIOID ANALGESIC THAT IS SELECTIVELY ACTIVATED IN ACIDIC INFLAMMATORY ENVIRONMENTS
Authors: Yu Y , Jiménez-Vargas N N , Lopez Lopez C D , Jaramillo Polanco J O , Bunnett N W , Vanner S 
Published: February 2020

Abstract

Background
Opioids drugs are effective analgesics for inflammatory disorders such as inflammatory bowel disease (IBD) but their effects at non-inflammed sites can cause serious morbidity and even death. Exploiting the knowledge that tissue pH in inflamed tissues is acidic (e.g. 6.5–7.0), a novel opioid analgesic, ±)-N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenylpropionamide (NFEPP), with a low acid dissociation constant, was developed that selectively activates peripheral µ-opioid receptor (MOPr) at acidic pH. Thus, pH-sensitive binding of NFEPP could selectively inhibit nociceptive nerves in the inflamed colon and have no effect on non-inflamed tissues outside the GI tract.

Aims
Evaluate whether NFEPP causes inhibition of colonic nociceptors at acidic pH’s, which mimic the inflamed colon.

Methods
To evaluate pH sensitive property of NFEPP to activate MOPr, dorsal root ganglia (DRG) neurons from C57BL/6 mice were exposed to the MOPr agonists NFEPP (300nM, 15 min) or DAMGO (100nM, 15 min) or vehicle at pH 6.5 or 6.8 or 7.4. Neuronal excitability was measured by recording the rheobase (minimum current to fire an action potential) using patch clamp recordings of isolated dorsal root ganglia neurons. In parallel ex vivo studies of mouse colon, extracellular recordings were obtained from afferent nerves innervating the distal colon. Afferent responses to probing with von Frey hair (1 gm) were examined before and after exposure to NFEPP (300nM, 5 min superfusion) at pH 6.5 and 7.4 respectively. Oneway ANOVA and post hoc Dunnett and Bonferroni tests were used to analyze the data.

Results
In patch clamp studies, NFEPP caused a decrease in DRG excitability at pH 6.5 and 6.8 (increased rheobase 21.3%, p&lt;0.05 and 28.9%, p&lt;0.05 respectively compared to vehicle) but had no effect at physiological pH 7.4. DAMGO, a MOPr agonist, caused inhibition of nociceptor excitability at pH 7.4 (increased rheobase 25.2%, p&lt;0.05 compared to vehicle) as shown in previous experiments, but had no effect at pH 6.5 and 6.8. Vehicle had no effect at the different pH’s. In colonic afferent nerve recordings, NFEPP significantly attenuated afferent response (28.9% P&lt;0.01) to probing at pH 6.5 and this effect was reversed after a 15 min washout. At pH 7.4 NFEPP had no effect on afferent nerve firing.

Conclusions
NFEPP activated MOPr at acidic pH causing inhibition of colonic nociceptors. This pH-selective agonist provides a new strategy to relieve pain at the site of inflammation while being devoid of any of unwanted activity in non-inflamed organs.

Funding Agencies
CCC
A214 GENETIC VARIATION IN THE FARNESOID X RECEPTOR PREDICTS CROHN’S DISEASE SEVERITY IN FEMALE PATIENTS
Authors: Wilson A , Wang Q , Almousa A , Jansen L , Choi Y , Schwarz U I , Kim R 
Published: February 2020

Abstract

Background
Crohn’s disease (CD) is an immune-mediated inflammatory bowel disease defined by episodes of intestinal inflammation. There is now an increasing appreciation of the bile acid-sensing nuclear receptor, FXR, as an important regulator of intestinal inflammation, intestinal permeability and response to bacterial overgrowth. Many of these processes are dysregulated in CD. It is unclear how genetic variation in FXR impacts on CD severity. FXR deficiency is rare. Loss of function mutations in FXR as contributors to CD are unlikely; however, partial loss of function of FXR may contribute to CD progression or severity. Our group demonstrated that FXR-1G&gt;T, a SNV adjacent to the ATG start codon, is linked to reduced transactivation of FXR gene targets. We hypothesized that changes in the intestinal barrier as a result of reduced FXR expression among those who harbor the FXR-1T allele are more likely to exhibit a severe CD phenotype compared to G (reference) allele carriers, and thereby experience a more rapid progression to surgery. Alterations in FXR activity may in part be secondary to genetic variation in the FXR gene.

Aims
To evaluate FXR-1G&gt;T as a genomic biomarker of severity in CD and propose a plausible molecular mechanism.

Methods
A retrospective study (n=542) was conducted in a Canadian cohort of CD patients. Blood samples were obtained for genotypic analysis (FXR-1G&gt;T), as well as determination of the FXR downstream product, fibroblast growth factor (FGF) 19. Primary outcomes included risk and time to first CD-related surgery. To better elucidate a potential molecular basis for the observed effect of FXR-1G&gt;T genotype on CD prognosis (more frequent and early surgery) in female CD patients, we explored a connection between the estrogen receptor (ER)-mediated pathway and genetic variation in FXR using a cell-based model. .

Results
The FXR-1GT genotype was associated with the risk of (odds ratio, OR=3.34, 95%CI=1.58–7.05, p=0.002) and early progression to surgery (hazard ratio, HR=3.00, 95%CI=1.86–4.83, p&lt;0.0001) in CD. Female carriers of the FXR-1GT genotype had the greatest risk of surgery (OR=14.87 95%CI=4.22–52.38, p&lt;0.0001) and early progression to surgery (HR=6.28, 95%CI=3.62–10.90, p&lt;0.0001). Furthermore, women carriers of FXR-1GT polymorphism had a nearly three-fold lower FGF19 plasma concentration compared to women with wildtype FXR-1GG genotype (p&lt;0.0001). In HepG2 cells cotransfected with estrogen receptors (ERα and β) and FXR, presence of estradiol further attenuated variant FXR activity.

Conclusions
FXR-1GT is deleterious to women with CD through ER-mediated attenuation of FXR activation. Female CD FXR-1GT carriers should be considered for more aggressive medical management.

Funding Agencies
CAG, CCC, CIHR
A223 THE GEM PROJECT: ASSOCIATIONS OF DIETARY PATTERNS WITH MICROBIOME AND FECAL CALPROTECTIN IN HEALTHY FIRST-DEGREE RELATIVES OF CROHN’S DISEASE PATIENTS
Authors: Sasson G , Raygoza Garay J , Turpin W , Power N , Smith M , Guttman D S , Research Consortium T , Croitoru K 
Published: February 2020

Abstract

Background
Crohn’s disease (CD) is thought to be due to an interaction between environmental factors and the gut microbiome that activates an immune response in genetically susceptible hosts. Epidemiologic studies suggest diet is an important variable in CD development; however, little is known about the mechanism by which diet contributes to pathogenesis. It has recently been shown that diet plays a substantial role in shaping microbiome composition (MC). We hypothesize that specific diet patterns are associated with differences in MC that may be related to CD risk.

Aims
To characterize associations between diet patterns with MC and fecal calprotectin (FC) in healthy first-degree relatives (FDR’s) of CD patients in the Genetic, Environmental, Microbial (GEM) Project.

Methods
A validated food frequency questionnaire (FFQ) was used to assess diet for North American FDR’s at recruitment. Each question was summarized as a score based on weekly consumption frequency. The Dirichlet method of unsupervised clustering was used to generate dominant diet clusters. Diet-microbiome associations were assessed using the two-part microbiome model. Stool microbiota at recruitment was characterized by 16s RNA sequencing of V4 region using MiSeq platform. Baseline FC was measured by BUHLMANN ELISA test.

Results
2766 FDR’s had FFQ’s at recruitment; mean age 18.52 years, 53% female. The Dirichlet method identified 4 clusters, some of which resembled known diet patterns: Superbowl (mainly organ meats, non-red meat, beer, spirits), High Carbohydrate (HC), Mediterranean (MD) and Western (WD) diets. HC was associated with increased relative abundance of V. veillonella (P=2.68E-4). Both HC and MD were associated with decreased abundance of E. klebsiella (P=2.64E-5 and P=1.02E-5 respectively). WD was associated with decreased abundance of L. dorea (P=5.74E-5), a genus considered high risk for CD. A per question analysis demonstrated significant associations between several taxa and individual foods. Diet clusters were then correlated with FC, and a decrease in FC was observed with MD (estimate -16.96, P=0.012). There were no associations with FC in a per question analysis.

Conclusions
Dominant dietary patterns and certain individual foods are associated with specific gut MC. As well, MD is inversely associated with FC and therefore has potential use as an intervention for lowering inflammation. Understanding relationships between diet, MC and FC in individuals at high risk for CD would be beneficial in defining new dietary strategies in predictably modulating future risk of CD.

Funding Agencies
CCCHelmsley Charitable Trust
A224 THE MANITOBA LIVING WITH IBD STUDY: MEDICATION ADHERENCE AND MARS-5 VALIDATION
Authors: Stone J , Witges K , Shafer L , Targownik L E , Lix L M , Haviva C , Walker J , Graff L A , Vagianos K , Sargent M , Bernstein C N 
Published: February 2020

Abstract

Background
Medication non-adherence in IBD has previously been reported to be quite variable, ranging from 7 to 73%, and is considered to be an important contributor to disease flares. While there is currently no gold standard for medication adherence reporting in IBD, the Medication Adherence Reporting Scale 5 (MARS-5) has frequently been used in this population, but never validated.

Aims
This study aimed to analyze medication adherence rates in a cohort of persons with IBD in Manitoba, report predictors of medication non-adherence on self-reported symptoms, and validate the MARS-5 as a medication adherence tool.

Methods
55 subjects were prospectively followed with biweekly online surveys in the Manitoba Living with IBD Study. Subjects not taking any medications for IBD or only taking as needed, missing adherence data and those lost to follow-up were excluded, leaving 112 subjects. Descriptive data on demographics, surgeries, IBD medications, medication adherence, and measures of disease activity utilizing IBDSI-SF scores were collected. Mean annual medication adherence percentage, IBDSI-SF(&gt;14=active for Crohn’s,&gt;13=active for UC) and MARS-5 scores were calculated. Logistic regression analysis was performed to determine variables associated with medication adherence and to validate the MARS-5.

Results
Mean age was 42.9 years (SD 12.8), with 71.4% being female. Crohn’s disease (CD) was diagnosed in 67.9%, with 37.5% having undergone at least one abdominal surgery. 70.5% of patients were on 2 or more IBD medications. Mean IBDSI score was 15.5 and mean MARS-5 score was 22.5. 20 (17.9%) patients reported a mean adherence of &lt;90% across all medications- 18 were oral medication users, 1 was on an infusion biologic and 1 on subcutaneous adalimumab. 10 (9.8%) had adherence &lt;80%, all of which were to oral medications. Multivariate regression analysis revealed only a diagnosis of Crohn’s disease (OR 4.62; 95% CI 1.37–15.7; p=0.014) to be a predictor of adherence. Disease activity as defined by IBDSI (OR 0.43, 95% CI 0.13–1.45; p=0.139) and fecal calprotectin &gt;250ug/L (OR 1.04, 95% CI 0.35–3.11; p=0.724), age &gt;55 (OR 2.37, 95% CI 0.65–8.65; p=0.476), female sex (OR 0.38, 95% CI 0.097–1.52; p=0.150) and stress (OR 0.67, 95% CI 0.19–2.32; p=0.498) were not shown to be predictors. MARS-5 was compared to percentage adherence, showing moderate correlation (Pearson r=0.46). Logistic regression analysis showed each additional MARS-5 point was associated with a 1.7 times greater odds of &gt;90% adherence.

Conclusions
We report a highly adherent Manitoba IBD cohort. A diagnosis of CD was the only predicitor of adherence. MARS-5 showed moderate correlation with mean percentage adherence values, suggesting it is a valid assessment tool for determining medication adherence in an IBD population.

Funding Agencies
None