bluuebunny/crossref_metadata_2025_split huggingface dataset:
A122 THE INFLUENCE OF SEX AND THE GUT MICROBIOTA ON VISCERAL PAIN SENSITIVITY IN MICE
Authors: Pujo J , De Palma G , Lu J , Collins S M , Bercik P 
Published: February 2020

Abstract

Background
Abdominal pain is a common complaint in patients with chronic gastrointestinal disorders. Its treatment is of limited efficacy as the pathophysiology is largely unknown. Accumulating evidence suggests that gut microbiota is an important determinant of gut function, including visceral sensitivity. Germ-free (GF) mice have been shown to have altered pain signaling, which normalizes after colonization. Sex also appears to play a key role in visceral sensitivity, as abdominal pain is diagnosed predominantly in female patients. Thus, both gut bacteria and sex are important in the regulation of gut nociception, but the underlying mechanisms remain poorly understood.

Aims
To investigate the role of gut microbiota and sex in abdominal pain.

Methods
We used primary cultures of sensory neurons from dorsal root ganglia (DRG) of female and male conventional mice (SPF) or germ-free (GF) mice, age 7–18 weeks. To study the visceral afferent activity in vitro, calcium mobilization in DRG sensory neurons was measured by inverted fluorescence microscope using a fluorescent calcium probe Fluo-4 (1mM). Two parameters were considered: i) percentage of responding neurons and ii) intensity of neuronal response. First, DRG sensory neurons were stimulated by a TRPV1 agonist capsaicin (12.5nM, 125nM and 1.25µM) or by an agonist mix of G-protein coupled receptors (GPCR: bradykinin, histamine and serotonin; 1µM, 10µM and 100µM). We next cultured Escherichia coli JM83 (E. coli) and Enterobacter aerogenes (E. aer) overnight in LB and LDMIIG medium, respectively. Bacterial supernatant of 1010 CFU/mL was diluted to 1% in Krebs Ringer solution to treat DRG neurons from GF/SPF mice and calcium mobilization was measured.

Results
The percentage of neurons responding to capsaicin and GPCR agonist was similar in SPF male and SPF female. In contrast, the intensity of the neuronal response was higher in SPF male compared to SPF female mice in response to capsaicin (125nM p&lt;0.035 and 1.25µM p&lt;0.038) but not in response to GPCR. The same trend was observed in GF mice. Neuronal activation induced by capsaicin or GPCR agonist was similar in SPF and GF mice. While bacterial supernatant from E. coli did not affect the activity of sensory neurons, the bacterial supernatant from E. aer induced changes in calcium mobilization in DRG neurons.

Conclusions
Our data suggest that at the level of DRG neurons from healthy mice, female sex and the absence of gut microbiota do not predispose to visceral hypersensitivity. In fact, the intensity of neuronal responses to capsaicin appear to be higher in DRGs from male mice. Furthermore, we show that metabolites from certain bacteria can activate sensory neurons. Thus, further studies are needed to investigate the role of gut microbiota and sex in visceral sensitivity

Funding Agencies
CIHR
A124 SYNERGISTIC INTERACTION OF CANNABINOIDS AND OPIOIDS REDUCES PAIN SIGNALING IN COLONIC NOCICEPTIVE NERVES
Authors: Tsang Q , Yu Y , Lomax A E , Vanner S , Reed D E 
Published: February 2020

Abstract

Background
With the recent legalization of recreational marijuana in Canada, increasing numbers of patients with gastrointestinal (GI) disorders are using cannabis to treat their pain, either alone or together with opioids. However, little is known about potential benefits of cannabinoids for treating visceral pain originating within the GI tract and whether the combined use of cannabinoids and opioids could enable the reduction or even discontinuation of opioids.

Aims
To investigate the effects of cannabinoids alone or in combination with opioids on colonic nociceptive nerves.

Methods
Extracellular afferent nerve recordings were obtained from ex vivo flat sheet preparations of male C57BL/6 mouse distal colons. Single unit analysis discriminated individual afferent neuron responses to mechanical probing of the colon with a 1g von Frey hair before and after superfusion of HU-210, a selective CB1 receptor agonist, HU-308, a selective CB2 receptor agonist, DAMGO, a selective mu-opioid receptor (MOR) agonist, or a combination. In parallel studies, perforated patch clamp techniques were employed to assess the rheobase as a measure of neuronal excitability in acutely dissociated dorsal root ganglia (DRG) neurons in the presence of one or more of these agonists. Data were analyzed using a one-way ANOVA with Bonferroni multiple comparisons test.

Results
Superfusion of HU-210 (1 μM), caused significant inhibition in afferent nerve mechanosensitivity compared to control (6.2±1.1 vs. 13.7±2.5 Hz, p=0.005, n=10); lower concentrations (10 nM and 100 nM) had no effect (p&gt;0.99, n=11; p=0.600, n=10 respectively). Conversely, the CB2 agonist HU-308 (1 μM and 10 μM), did not alter mechanosensitivity (p&gt;0.9, n=8 for both concentrations). Superfusion of HU-210 alone (100 nM) or DAMGO (1 nM) alone in the same recording had no effect, but when both agonists were superfused together, there was a significant reduction in mechanosensitivity (8.1±1.7 vs. 14.8±2.3 Hz, p&lt;0.01, n=10). In patch clamp recordings of DRG neurons, HU-210 (1 μM) decreased excitability (i.e. increased rheobase, 94.4±9.4 vs. 62.7±6.4 pA; p=0.031, n=9), whereas a lower concentration (100 nM) had no effect. Similar to afferent nerve recordings, when applied alone, DAMGO (1 nM) and HU-210 (100 nM) did not affect rheobase (DAMGO: p&gt;0.99, n=9; HU-210: p&gt;0.99, n=10), whereas the combination of both agonists significantly decreased excitability (123.0±13.4 vs. 62.7±6.4 pA, p&lt;0.01, n=10).

Conclusions
Activation of CB1 receptors inhibits mechanosensitivity of colonic afferent nerves while a CB2 agonist had no effect. Interestingly, combination of sub-threshold concentrations of CB1 and MOR agonists inhibited colonic afferent nerves and thus, may suggest that cannabinoids could enable opioid dose reduction or discontinuation.

Funding Agencies
None
A125 ABNORMAL REFLUX IS UNCOMMON IN PATIENTS PRESENTING WITH ISOLATED OROPHARYNGEAL SYMPTOMS
Authors: Fruitman J , Parker C H , Liu L W 
Published: February 2020

Abstract

Background
Gastroesophageal reflux disease (GERD) is often implicated as a potential etiology for various oropharyngeal (OP) symptoms. Although ambulatory reflux monitoring has been recommended by professional societies for the assessment of OP symptoms, it is unclear if objective measures of acid exposure in the esophagus correlate with the presence of these OP symptoms.

Aims
The aim of this study is to determine the prevalence of abnormal 24-hour pH monitoring in patients presenting with various OP symptoms in our motility unit.

Methods
A retrospective chart review was performed on all patients referred for 24-hour pH monitoring for the evaluation of OP symptoms to the open-access Clinical Motility Unit at the University Health Network between January 1, 2008 and June 1, 2019. Seven symptom categories were examined including cough, globus, throat discomfort, voice change, dental erosion, altered taste, and sensation of phlegm in the throat. The results of the 24-hour pH monitoring were collected. A test was considered abnormal if while off anti-secretory therapy the overall acid exposure (pH &lt; 4) in the distal esophagus was greater than 4.2% of the total time or if while on anti-secretory therapy the overall acid exposure in the esophagus was greater than 1.2% of the time. Descriptive statistics were performed to analyze the data.

Results
384 patients were included in the final analysis. 167 patients (43.5%) presented with cough, 63 (16.4%) with globus, 86 (22.4%) with throat discomfort, 19 (5.9%) with voice changes, 13 (3.4%) with dental erosion, 17 (4.4%) with altered taste and 19 (4.9%) with sensation of phlegm in the throat. Overall, 19.5% of patients presenting with oropharyngeal symptoms had abnormal 24-hour pH monitoring. Abnormal 24-hr pH monitoring was present in 24.6% of those with cough, 15.9% of those with globus, 16.3% of those with throat discomfort, 21.1% of those with voice changes, 23.1% of those with dental erosion, 5.9% of those with altered taste and 10.5% of those with sensation of phlegm in the throat.

Conclusions
This study demonstrates that only a small proportion of patients with OP symptoms have abnormal gastroesophageal acid reflux based on objective 24-hour pH monitoring. Given these findings, future studies to examine the factors that predict having abnormal 24-hour pH monitoring in patients presenting with OP symptoms will help guide resource management of motility testing to determine which patients would benefit most from this type of evaluation.

Funding Agencies
None
A136 PREDICTIVE FACTORS OF CIRRHOSIS IN HCV PATIENTS WITH LOW PRE-TREATMENT APRI AND/OR FIB-4 SCORES
Authors: Pi S , Mitchell R A , Mohajerani A , Farivar J , Ko H , Ramji A 
Published: February 2020

Abstract

Background
It is essential to evaluate the stage of hepatic fibrosis prior to the initiation of HCV therapy. In addition to being a major prognostic factor, the presence of cirrhosis requires monitoring for hepatocellular carcinoma (HCC), esophageal varices, and decompensated liver disease. In some cases the presence of cirrhosis may affect the choice of therapy. In tertiary hepatology clinics, transient elastography (TE) is routinely used to assess fibrosis; however access to TE is limited. Fibrosis-4 (FIB4) and AST-to-platelet ratio index (APRI) are simple, easily available non-invasive methods of fibrosis measurement based on routine serum biomarkers. Studies evaluating HCV treatment pathways have reported that the use of FIB4 and APRI are cost-effective strategies for excluding cirrhosis thereby reducing the need for TE prior to treatment. Although the NPV of these tests are well described, a minority of patients will have advanced fibrosis despite low APRI and/or FIB4 scores.

Aims
To investigate predictive factors of cirrhosis in HCV patients with low pre-treatment APRI and/or FIB-4 scores.

Methods
Retrospective observational study with data obtained from the Pacific Gastroenterology Associates (PGA), a tertiary care outpatient Gastroenterology clinic located in Vancouver, British Columbia. Inclusions: Chronic HCV patients treated between Jan 2015 to 2019, pre-treatment TE values ≥12.5 kPa, FIB-4 &lt;1.45 and/or APRI &lt;0.7. Exclusions: those without cirrhosis, or incomplete evaluation prior to HCV treatment. Cirrhosis was defined as those with TE ≥12.5 kPa with clinical, radiographic, or pathologic features of cirrhosis.

Results
52 patients were identified. 11 patients did not have clinical, radiographic, or pathologic features of cirrhosis and 3 patients were excluded for insufficient data. Thus, 39 patients were included in multivariate analysis. The mean age was 59 years and 66% (25/38) were male gender. 10% (4/38) were Genotype 3 (G3). Presence of G3 was not included in the multivariate analysis due to low number of observations.

Conclusions
Generally, an APRI &lt;0.7 and FIB-4 &lt;1.45 have good test characteristics for excluding fibrosis. Our study demonstrates that patients with obesity, dyslipidemia, excessive alcohol use, or known steatosis on ultrasound may have cirrhosis despite low serum biomarker scores. Co-existence of other liver diseases such as alcohol related or non-alcoholic fatty liver disease (NAFLD) should prompt further evaluation for fibrosis assessment beyond biomarkers as these persons may have more advanced liver disease.

Funding Agencies
None
A151 ASSESSMENT OF CAPSULE ENDOSCOPY UTILIZING CAPSOCAM PLUS® IN PATIENTS WITH SUSPECTED SMALL BOWEL DISEASE INCLUDING PILOT STUDY WITH REMOTE ACCESS PATIENTS
Authors: Enns C , Galorport C , Enns R A 
Published: February 2020

Abstract

Background
Capsule endoscopy (CE) has been widely utilized for the assessment of patients with known/suspected small bowel disease. The CapsoCam Plus® capsule is unique in that it utilizes four cameras at sequential 90 degree intervals in its mid-section permitting a 360-degree panoramic perspective with a 15+ hour battery life. A panoramic view has been suggested to improve overall visualization of the small bowel (SB) therefore potentially improving diagnostic yield. Unlike other small bowel capsules, it must be retrieved upon excretion (utilizing a magnetic kit) since the images are stored on the device.

Aims
To assess the use of CapsoCam Plus in patients referred for suspected small bowel disease, including pilot assessments for patients in remote locations.

Methods
A retrospective chart review (01/16 – 09/19) assessing consecutive capsule procedures utilizing this device was performed. Information acquired included basic demographics, indication, extent of examination, gastric transit time, small bowel transit time, yield, adverse events, capsule retention, recovery rates and recommendations for follow up. A pilot study was also initiated for patients in rural centers to access capsule testing remotely through mail courier without attendance/travel to the primary dispensing site.

Results
Acquired data included 63 patients receiving CapsoCam Plus®. Indications: 32% obscure gastrointestinal bleeding, 52% iron deficiency anemia, 2% abdominal pain and 6% for IBD. 92% of studies were completed to cecal visualization. Mean gastric and small bowel transit time were 0:48:17 and 3:54:29. 94% were retrieved using retrieval kits provided to patients. 2% retrieved endoscopically from the stomach (retained due to pyloric stenosis), 2% retained in terminal ileum (previously undiagnosed stricture) and 2% not retrieved due to failure of patient to use retrieval kit. 73% of studies were normal SB, 13% contained SB ulceration/erosive disease and 8% did not demonstrate the entire small bowel. Recommendations for follow up included supportive therapy (47%), more aggressive iron supplementation (1%), repeat capsules (19%) and 14% for routine office follow up and discussion. All three capsules mailed to patients in remote communities were completed successfully.

Conclusions
CapsoCam Plus® had a high retrieval rate of 97% demonstrating that with appropriate patient selection, recovery rates are very high. Only 3% of patients had retained capsules. Most patients in this study had a normal small bowel, however; images and completion rates were adequate to assess small bowel in the vast majority of patients. Success was obtained with mailing this capsule to remote sites sparing the patient travel to the dispensing site.

Funding Agencies
None
A155 VIDEO INTERVENTIONS TO IMPROVE SELF-ASSESSMENT ACCURACY IN GASTROINTESTINAL ENDOSCOPY: A SYSTEMATIC REVIEW
Authors: Pattni C , Scaffidi M A , Gimpaya N , Grover S C 
Published: February 2020

Abstract

Background
Physicians generally have inaccurate self-assessment of their performance. One type of proposed intervention to improve this inaccuracy is the use of video-based feedback. The overall impact of this intervention on self-assessment accuracy in gastrointestinal endoscopy is unclear.

Aims
To systematically review current literature to determine if video-based interventions can effectively improve self-assessment accuracy in endoscopy.

Methods
We searched the following electronic databases from inception to 2019: Ovid MEDLINE; Ovid EMBASE, the Cochrane Register of Controlled Trials (CENTRAL); Education Resources Information Center (ERIC); Education Source on EBSCO; and Canadian Business Current Affairs EBM Reviews. Specifically, we searched for terms related to self-assessment, self-report, self-efficacy, video recording, and physician. Studies were included if they met the following criteria: physicians at any level of training and/or practice; studies that used an experimental design; compared self-rated assessments with external assessments of procedural skills in endoscopy; and at least one arm of the study involved a video-based intervention.

Results
Our search yielded 755 articles, of which 2 met all inclusion criteria. One study explored the use of three feedback interventions (practice only with no video; observation of their own video performance; observation of expert video performance) among general surgery residents performing flexible endoscopy, which found that only participants who watched expert video performances had improved accuracy of self-assessments. The other study investigated the use of three video interventions (video of own performance; video of expert performance; video of both own and expert performances) among novice endoscopists performing esophagoduodenoscopy (EGD), which found that the video of expert performance significantly improved self-assessment accuracy compared to the group with both videos.

Conclusions
The current data tentatively support the use of video review of expert performance to improve self-assessment accuracy in gastrointestinal endoscopy. A meta-analysis is planned to quantitatively assess the overall impact.

Funding Agencies
None
A181 ENDOSCOPIC BALLOON DILATION IS EFFECTIVE AND SAFE IN THE MANAGEMENT OF NSAID-INDUCED NON-ULCERATIVE GASTRIC OUTLET OBSTRUCTION
Authors: Lim D R , Farina D , Huang W , Zhu J 
Published: February 2020

Abstract

Background
We describe an unusual case of NSAID-induced gastric outlet obstruction (GOO) in the absence of malignancy or ulcers. This was successfully managed conservatively with drug withdrawal and serial endoscopic balloon dilation (EBD).

Aims
Case Report

Methods
Case Report and Literature Review

Results
A 58-year-old woman with 20-year history of daily Ketorolac use for osteoarthritis presented with iron deficiency anemia (IDA) of 58 g/L and post-prandial emesis for 2 months. There was no overt GI bleeding. Gastroscopy revealed severe erosive esophagitis and GOO with no ulcers. After a negative CT imaging ruled out extrinsic malignant compression, GOO was managed with EBD. Examination of the duodenum post-EBD revealed complete atrophy and scalloping. Focused biopsies reveal chronic gastritis, complete villous atrophy in the duodenum; ruled out H. Pylori, celiac disease, amyloidosis and dysplasia. EUS negative for infiltrative disease or regional adenopathy. Vitamin B12, anti-TTG I IgA, HLA DQ2/8 were normal. These findings made drug-induced enteropathy the top contender.
PPI therapy was initiated and NSAID discontinued. Five serial EBD were performed over 4 months to 18mm. A pureed diet was tolerated after 2 dilations. Follow-up at 3 months showed partial recovery of enteropathy and pyloric stenosis. No adverse events were seen.
The severe esophagitis was likely an erosive process secondary to reflux from GOO. Her IDA is likely multifactorial: Severe enteropathy and GOO may have led to chronic malabsorption; occult GI bleeding from erosions or ulcers that have healed may further contribute. Ketorolac could explain the enteropathy. COX-1 inhibition leads to decreased gastric cytoprotection. In rat models, COX-2 inhibition has been suggested to delay gastric healing and dysregulated immune response to food antigens in the small bowel [4–6].
NSAID-induced GOO almost always occur in the context of peptic ulcer disease [1,2]. A similar case [3] found pyloric stenosis in a 75-year old woman with esophagitis and ulcer-induced pyloric stenosis. They postulate that post ulcerative healing led to benign pyloric stenosis and explained the absence of ulcers.
Historically, surgical intervention and stent placement have played a major role in the management of benign mechanical GOO. EBD has replaced surgical intervention as first line therapy [7] showing promising results beyond 3 months post EBD[8], sparing patients from surgery related morbidity. An algorithm has been suggested by us [Img 1] for the management of benign GOO.

Conclusions
We present an unusual case of NSAID-induced mechanical GOO and enteropathy. This case highlights these entities as rare but serious complications of chronic NSAID use. Management of benign mechanical GOO should be individualized. Prudence with prescribing NSAIDs to at risk populations is recommended.

Funding Agencies
None
A225 AGE OF DIAGNOSIS DOES NOT IMPACT LIKELIHOOD OF EXPERIENCING POOR IBD-RELATED OUTCOMES
Authors: Piracha Y , Reza S , Fadida M , Chattha R , Moradshahi M , Dezfooli N , Chattha Z , Sambhi G , Chauhan U , Halder S L , Marshall J , Narula N 
Published: February 2020

Abstract

Aims
The relationship between the age of diagnosis of inflammatory bowel disease (IBD) and adverse disease outcomes has not been well defined. This study aims to determine whether an early age of diagnosis is associated with worse disease outcomes.

Methods
This was a retrospective study of IBD patients seen at McMaster University Medical Centre, in Hamilton, ON, Canada from 2012 to 2018. Patients were classified as having poor outcomes if they had any of the following: (1) two or more bowel resections since diagnosis; (2) two or more hospitalizations for disease exacerbation since diagnosis; or (3) more than three months of corticosteroid use within 24 months of diagnosis. Prior knowledge in combination with forward selection was used to develop a multivariate logistic regression model and identify predictors of poor IBD outcomes. The variables used in the forward selection model included age at diagnosis (less than vs. greater than 25), smoking status, sex, disease duration, and type of IBD.

Results
A total of 617 IBD patients were included in the analysis, of which 356 (57.7%) had Crohn’s disease, 234 (37.9%) had ulcerative colitis, and 27 (4.4%) had IBD-U. The median age at diagnosis was 25 (interquartile range (IQR) 17–37). Median disease duration was 16 years (IQR 11–24). A univariate regression analysis indicated that the odds ratio (OR) of poor outcomes was found to be 0.55 (0.38 - 0.79) for those ≥25 years of age compared to to those &lt;25. In the multivariate regression analysis (Table 1), all of disease duration, smoking status, and IBD type were found to have a significant association with having poor outcomes. Each year of disease duration was associated with an increase in odds of poor outcomes (OR 1.06, 95% CI 1.03–1.09). Active smokers had increased odds of poor outcomes compared to past or never smokers (OR 5.01, 95% CI 1.71–14.68). Patients with ulcerative colitis were less likely to experience poor outcomes compared to Crohn’s disease patients (OR 0.38, 95% CI 0.24–0.57). Age of diagnosis was no longer found to have a significant association with poor outcomes, once adjusted for other co-variates (OR 0.74, 95% CI 0.47–1.15).

Conclusions
Age of diagnosis was not found to have a relationship with occurrence of poor IBD outcomes, after adjustment for co-variates. However, patients with increased disease duration, active smoking status, and Crohn’s disease (compared to UC) were found to have increased odds of poor IBD-related outcomes.

Funding Agencies
None