bluuebunny/crossref_metadata_2025 huggingface dataset:
A119 AN EX VIVO MODEL TO STUDY THE GUT SEROTONERGIC SYSTEM RESPONSE TO LIVE AND HEAT-KILLED LACTOBACILLUS RHAMNOSUS STRAIN JB-1
Authors: Javkar T , Paul M , Stanisz A , Forsythe P
Published: February 2020

Background

Enterochromaffin (EC) cells are one of the most abundant enteroendocrine cells in the intestinal epithelium, responsible for producing and storing the largest pool of serotonin or 5-hydroxytryptamine (5-HT) in the body. 5-HT has been shown to be important for modulating a large number of gastrointestinal reflexes in health and disease. 5-HT can stimulate extrinsic (vagal and spinal afferents) or intrinsic primary afferent neurons (IPANs) which are involved in motility, secretion and vasodilation within the intestines. Where EC cell localized enzyme tryptophan hydroxylase (TpH) isoform 1 is responsible for 5-HT synthesis, serotonin reuptake transporter (Sert) and monoamine oxidase A (Mao A) are responsible for termination by uptake and metabolism of 5-HT respectively. Our previous research has demonstrated the effects Lactobacillus rhamnosus (JB-1) on the firing frequency of spinal nerve fibres and motility. Increasing interest is being focused on potential health benefits of heat-inactivated microbes and purified bacterial components. However, the effect of these heat-killed bacteria on the intestinal epithelium cells, particularly on EC cells, is unknown.

Aims

Small intestinal organoids are shown to recapitulate in vivo characteristics of the small intestine epithelium. The present study aims to assess the suitability of intestinal organoids to study bacterial effects on the serotonergic system in the gut. Here we determined changes in the gene expression of key mediators in the serotonergic system [serotonin reuptake transporter (Sert), tryptophan hydroxylase-1 (Tph-1) and monoamine oxidase A (Mao A)] in response to live and heat-killed JB-1.

Methods

Male C57bl/6 mice aged 6–8 weeks were used for both ex vivo and in vivo experiments. Jejunal organoids were grown from whole crypts isolated using DTT-EDTA solution. Live and heat-killed JB-1 bacteria were used as treatments. Gene expression analysis was performed on jejunal organoids and jejunum tissue using qRT-PCR.

Results

JB-1 induced a significant increase in gene expression of Sert, Mao A and Tph-1. No significant difference was observed between the effects of live and heat-killed bacteria. In contrast the JB-1 increased expression of the peptide hormone CCK. Effects of JB-1 on gene expression in organoid culture were reflective of changes observed in in vivo experiments involving feeding of the bacteria.

Conclusions

Ex vivo organoid culture could be a useful tool in studying mechanisms underlying bacterial effects on serotonergic signalling. The observation that heat-killed bacteria produced comparable effects to the live organism suggests the possibility of isolating active 5-HT modulating components from these strains. Future research will focus on identifying such bacterial components and how their effects on gene expression influence serotonin availability

Funding Agencies

None
A120 INFLUENCE OF THE MICROBIOTA ON THE POSTNATAL DEVELOPMENT OF THE ENTERIC NERVOUS SYSTEM IS DEPENDENT ON MOUSE STRAIN
Authors: Huang J , Popov J , Markovic F , Ratcliffe E
Published: February 2020

Background

Gastrointestinal function depends on the normal formation of the enteric nervous system (ENS) during fetal and postnatal development. Prior research in an outbred strain of mice (NIH Swiss) has shown that the absence of the gut microbiome in germ-free (GF) mice results in morphological and functional abnormalities of the ENS compared to specific pathogen free (SPF) mice, including an alteration in proportion of nitrergic neurons. Increasing research has been suggesting that the genetic background of the host can impact the host response to the GF state.

Aims

We tested the hypothesis that the absence of the microbiome in an inbred mouse strain (C57BL/6) could influence the development of the ENS during early postnatal life.

Methods

C57BL/6 GF and SPF mice were sacrificed at postnatal day 3 (P3) and P28 (n=4–5 per group). Ileum and colon were collected at P3 and P28 and processed for whole mount preparations. The neuronal network in the myenteric plexus was visualized by immunohistochemistry using antibodies against the pan-neuronal marker PGP9.5. Neuronal cell bodies and nitrergic neurons were identified by immunolabeling with antibodies to the neuronal marker HuC/D and to neuronal nitric oxide (nNOS). Nerve fibre density was quantified by measuring the percentage of PGP9.5-positive pixels (μm2) compared to the whole field using an image analysis program (Volocity; reported as %). Proportions of nitrergic to myenteric neurons were determined by manually counting (blinded) the number of nNOS-positive neurons and dividing by the total number of HuC/D-positive cells per field (reported as %).

Results

We found a significant increase in nerve density at P3 in the GF compared to SPF mice in both ileum (43% vs. 37%; p=0.03) and colon (45% vs. 39%; p=0.03). No significant differences, however, were identified between GF and SPF mice at P28 in either ileum (27% vs. 25%; n.s.) or colon (31% vs. 32%; n.s.). At P3, no significant differences in proportion of nitrergic neurons were seen in the GF compared to SPF ileum (27% vs. 27%; n.s.).

Conclusions

In contrast to earlier observations in the NIH Swiss mice, in which GF mice had decreased nerve density and an increase in nitrergic neurons at P3, our findings reveal an opposite response in nerve density in the C57BL/6 mice and no change in nitrergic neurons. These results suggest that the genetic strain of the mouse model can influence the host response to changes in the microbiome. Further studies are needed to further elucidate potential underlying mechanisms.

Funding Agencies

NSERC
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

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<0.035 and 1.25µM p<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

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>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>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<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>0.99, n=9; HU-210: p>0.99, n=10), whereas the combination of both agonists significantly decreased excitability (123.0±13.4 vs. 62.7±6.4 pA, p<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

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 < 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

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 <1.45 and/or APRI <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 <0.7 and FIB-4 <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

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

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

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

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 <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
A260 THE LACK OF CHROMOGRANIN-A MODIFIES THE GUT MICROBIOTA COMPOSITION AND REGULATES EXPERIMENTAL COLONIC INFLAMMATION
Authors: Eissa N , Diarra A , Hussein H , Bernstein C N , Ghia J
Published: February 2020

Background

Ulcerative colitis (UC)is characterized by distinct changes in the gut microbiome and elevated chromogranin-A (CHGA) level, which seem to be a relevant pathogenetic mechanism.CHGA, a prohormone produced by enterochromaffin (EC) cells and cleaved into several bioactive peptides, regulates experimental colonic inflammation. In the rodent, intra-rectal infusion of catestatin, a Chga-derived peptide, alters the distal colonic microbial composition. However, the interplay between CHGA, as a pro-hormone, and the gut microbiome remains elusive.

Aims

in homoeostatic and pathophysiologic conditions, we investigated the functional consequences of the lack of Chgaon the distal colonic microbiota.

Methods

Acute colitis (5 % dextran sulfate sodium [DSS], 5 days) was induced in Chga-C57BL/6-deficient (Chga-/-) and wild-type (Chga+/+)mice. Feces and mucosa-associated microbiota (MAM) samples were collected and the V4 region of 16s rRNA was subjected to Miseq Illumina sequencing. Alpha diversity was calculated using Shannon’s diversity index. OTU abundances were summarized using the Bray-Curtis index and non-metric multidimensional scaling (NMDS) analysis to visualize microbiome similarities and a permutational analysis of variance (PERMANOVA) to test the significance of groups were performed respectively.

Results

In non-colitic homoeostatic condition, the absence of Chga (Chga-/) significantly increased the bacterial richness and modified the bacterial community composition at the genera level between the groups, represented by increased abundance of Lactobacillus species and reduced abundance of Helicobacter& Oscillospira species compared to Chga+/+mice in fecal and colonic MAM. Moreover, the absence of Chga (Chga-/-) resulted in a significant change in the alpha-diversity of fecal and colonic MAM compared to Chga+/+mice. DSS induced-colitis resulted in a significant microbial dysbiosis in Chga+/+mice, however, deletion of Chgaprotected against DSS-induced colitis and reduced the microbial dysbiosis, reduced the family of Rikenellaceaeand maintained the abundance of Bacteroides species, compared to wild-type (Chga+/+).

Conclusions

The lack of CHGA regulates the biodiversity and the composition of the colonic gut microbiota suggesting a cross-talk between the EC cell and the microbiome. Therefore, targeting CHGA could provide a novel therapeutic strategy by regulating the gut microbiome in physiological and pathophysiological conditions.

Funding Agencies

CIHR
A278 TB OR NOT TB OF THE PANCREAS
Authors: Chis R , Tartaro P
Published: February 2020

Background

Pancreatic TB is a rare clinical presentation which has proved difficult to diagnose. Its symptomatology and imaging characteristics mimic neoplastic findings.

Aims

We present the case of a previously healthy 58-year-old man, from an endemic area who presented with epigastric pain caused by pancreatic TB.

Methods

Case report and review of literature

Results

A previously well 58-year-old male presented to the emergency room with severe epigastric pain, without fevers or significant weight loss. He had immigrated to Canada from the Philippines in 2001. He denied a personal history of TB, however, he did report that his father had received treatment for active TB. An abdominal CT revealed intrahepatic and extrahepatic bile tree dilation with an abrupt transition in the pancreatic head, possible stricture, as well as mucosal thickening of the duodenum at the level of the abrupt narrowing of the dilated common bile duct, concerning for malignancy. Initial laboratory investigations revealed WBC 6.1 x10E9 cells/L, amylase 114 U/L and lipase 59 U/L. Malignancy work up revealed a normal Ca 19-9 at 29.6 kU/L. HIV testing was negative. CT chest revealed bilateral apical fibrotic lesions and smaller lesions throughout the upper and mid-zones bilaterally, suggestive of progressive massive fibrosis. This was in keeping with the patient’s former occupation as a miner. There was no evidence of granulomatous disease.

EUS was undertaken and this revealed a mass in the head of the pancreas measuring 29 x 29 mm. The mass was invading into the common bile duct. The pancreatic head mass appeared to be invading into the duodenum, as a necrotic ulcerating lesion was also identified in the second part of the duodenum and this was biopsied. The surgical pathology returned as necrotizing granuloma, however, the tissue could not be tested for TB. The patient underwent a repeat endoscopy which again revealed a fungating and friable mass in the second part of the duodenum with biopsies taken. Pathology revealed mild chronic inflammation. Staining for Acid Fast Bacilli was negative, however, Mycobacterium Tuberculosis Complex was isolated on tissue culture. The patient was diagnosed with pancreatic TB and initiated on pyrazinamide, ethambutol, isoniazid and rifampin.

Conclusions

Pancreatic involvement by TB is very rare but it has been increasingly reported in both immunocompromised and immunocompetent populations. Symptomatically, pancreatic TB can present with a multitude of non-specific symptoms, including epigastric pain, fever, anorexia, weight loss, or jaundice. In addition, imaging findings of pancreatic TB may mimic malignancy. Our patient, from an endemic area, presented with epigastric pain consistent with the existing literature on pancreatic TB. Isolated pancreatic TB is a rare clinical entity but should be in the list of differential diagnoses in a patient with pancreatic mass especially in the setting of risk factors of TB.

Funding Agencies

None
Trap-Based Economic Injury Levels and Thresholds for Euschistus servus (Hemiptera: Pentatomidae) in Florida Peach Orchards
Authors: Penca Cory , Hodges Amanda C , Leppla Norman C , Cottrell Ted E
Published: February 2020

Populations of the brown stink bug, Euschistus servus (Say), in Florida peach orchards were monitored during the 2017 and 2018 growing seasons using yellow pheromone-baited pyramid traps. Peaches were evaluated at harvest for the presence of stink bug injury. A relationship between E. servus trap capture and fruit injury was used to estimate the economic injury level (EIL) for varying scenarios of crop price, per-hectare yield, and control costs. Economic thresholds were then set based on observed E. servus population trends and expected rates of increase. Thresholds were lowest in the period immediately following shuck split due to the rapid increase in E. servus populations during this period. Euschistus servus trap capture trended downward at the time of harvest. Therefore, increased E. servus management early in the Florida peach season provides the greatest overall benefit, whereas late season populations decline independent of management actions. The proposed EIL for Florida peaches determined by this study is 5.53 E. servus per trap over a 14-d trapping period, which was surpassed in only 16 of the 60 recorded trapping periods. This suggests that the current recommended spray frequency may not be economically justified.
Lethal and Sublethal Effects of Ingested Hydroprene and Methoprene on Development and Fecundity of the Common Bed Bug (Hemiptera: Cimicidae)
Authors: Sierras Angela , Schal Coby
Published: February 2020

In the last two decades, bed bugs (Cimex lectularius L. and Cimex hemipterus F.) have become perennial and difficult to control indoor pests. Current pest control options are severely constrained by high prevalence of insecticide resistance and availability and relatively high costs of alternative interventions. Among various measures to counter the drawbacks of insecticide resistance include efforts to diversify the modes of action of insecticides with residual applications of combinations of insecticides, which include a juvenile hormone analog (JHA). JHAs, such as hydroprene and methoprene, have a desirable safety profile and are effective against a variety of indoor pests. We evaluated the potential of hydroprene and methoprene to be incorporated into an ingestible bait, with dose–response studies on fifth-instar male and female bed bugs. Females were more susceptible than males to both JHAs, and methoprene was more effective by ingestion than hydroprene at inducing both lethal and sublethal effects. Ingestion of ≥10 µg/ml blood of either JHA by last instar nymphs reduced oviposition; untreated females that mated with males exposed to high concentrations of either JHA also exhibited lower oviposition. We suggest that methoprene could be incorporated into integrated pest management programs in liquid baits and residual sprays in combination with other active ingredients.
Area Deprivation Index and Rurality in Relation to Lung Cancer Prevalence and Mortality in a Rural State
Authors: Fairfield Kathleen M , Black Adam W , Ziller Erika C , Murray Kimberly , Lucas F Lee , Waterston Leo B , Korsen Neil , Ineza Darlene , Han Paul K J
Published: February 2020

Background

We sought to describe lung cancer prevalence and mortality in relation to socioeconomic deprivation and rurality.

Methods

We conducted a population-based cross-sectional analysis of prevalent lung cancers from a statewide all-payer claims dataset from 2012 to 2016, lung cancer deaths in Maine from the state death registry from 2012 to 2016, rurality, and area deprivation index (ADI), a geographic area-based measure of socioeconomic deprivation. Analyses examined rate ratios for lung cancer prevalence and mortality according to rurality (small and isolated rural, large rural, or urban) and ADI (quintiles, with highest reflecting the most deprivation) and after adjusting for age, sex, and area-level smoking rates as determined by the Behavioral Risk Factor Surveillance System.

Results

Among 1 223 006 adults aged 20 years and older during the 5-year observation period, 8297 received lung cancer care, and 4616 died. Lung cancer prevalence and mortality were positively associated with increasing rurality, but these associations did not persist after adjusting for age, sex, and smoking rates. Lung cancer prevalence and mortality were positively associated with increasing ADI in models adjusted for age, sex, and smoking rates (prevalence rate ratio for ADI quintile 5 compared with quintile 1 = 1.41, 95% confidence interval [CI] =1.30 to 1.54) and mortality rate ratio = 1.59, 95% CI = 1.41 to 1.79).

Conclusion

Socioeconomic deprivation, but not rurality, was associated with higher lung cancer prevalence and mortality. Interventions should target populations with socioeconomic deprivation, rather than rurality per se, and aim to reduce lung cancer risk via tobacco treatment and control interventions and to improve patient access to lung cancer prevention, screening, and treatment services.
Urinary Estrogen Metabolites and Long-Term Mortality Following Breast Cancer
Authors: Wang Tengteng , Nichols Hazel B , Nyante Sarah J , Bradshaw Patrick T , Moorman Patricia G , Kabat Geoffrey C , Parada Humberto , Khankari Nikhil K , Teitelbaum Susan L , Terry Mary Beth , Santella Regina M , Neugut Alfred I , Gammon Marilie D
Published: February 2020

Background

Estrogen metabolite concentrations of 2-hydroxyestrone (2-OHE1) and 16-hydroxyestrone (16-OHE1) may be associated with breast carcinogenesis. However, no study has investigated their possible impact on mortality after breast cancer.

Methods

This population-based study was initiated in 1996–1997 with spot urine samples obtained shortly after diagnosis (mean = 96 days) from 683 women newly diagnosed with first primary breast cancer and 434 age-matched women without breast cancer. We measured urinary concentrations of 2-OHE1 and 16-OHE1 using an enzyme-linked immunoassay. Vital status was determined via the National Death Index (n = 244 deaths after a median of 17.7 years of follow-up). We used multivariable-adjusted Cox proportional hazards to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the estrogen metabolites-mortality association. We evaluated effect modification using likelihood ratio tests. All statistical tests were two-sided.

Results

Urinary concentrations of the 2-OHE1 to 16-OHE1 ratio (>median of 1.8 vs ≤median) were inversely associated with all-cause mortality (HR = 0.74, 95% CI = 0.56 to 0.98) among women with breast cancer. Reduced hazard was also observed for breast cancer mortality (HR = 0.73, 95% CI = 0.45 to 1.17) and cardiovascular diseases mortality (HR = 0.76, 95% CI = 0.47 to 1.23), although the 95% confidence intervals included the null. Similar findings were also observed for women without breast cancer. The association with all-cause mortality was more pronounced among breast cancer participants who began chemotherapy before urine collection (n = 118, HR = 0.42, 95% CI = 0.22 to 0.81) than among those who had not (n = 559, HR = 0.98, 95% CI = 0.72 to 1.34; Pinteraction = .008).

Conclusions

The urinary 2-OHE1 to 16-OHE1 ratio may be inversely associated with long-term all-cause mortality, which may depend on cancer treatment status at the time of urine collection.
A comparison of exoplanet spectroscopic retrieval tools
Authors: Barstow Joanna K , Changeat Quentin , Garland Ryan , Line Michael R , Rocchetto Marco , Waldmann Ingo P
Published: February 2020

Over the last several years, spectroscopic observations of transiting exoplanets have begun to uncover information about their atmospheres, including atmospheric composition and indications of the presence of clouds and hazes. Spectral retrieval is the leading technique for interpretation of transmission spectra and is employed by several teams using a variety of forward models and parameter estimation algorithms. However, different model suites have mostly been used in isolation and so it is unknown whether the results from each are comparable. As we approach the launch of the James Webb Space Telescope, we anticipate advances in wavelength coverage, precision, and resolution of transit spectroscopic data, so it is important that the tools that will be used to interpret these information-rich spectra are validated. To this end, we present an intermodel comparison of three retrieval suites: TauREx, nemesis, and chimera. We demonstrate that the forward model spectra are in good agreement (residual deviations on the order of 20–40 ppm), and discuss the results of cross-retrievals among the three tools. Generally, the constraints from the cross-retrievals are consistent with each other and with input values to within 1σ. However, for high precision scenarios with error envelopes of order 30 ppm, subtle differences in the simulated spectra result in discrepancies between the different retrieval suites, and inaccuracies in retrieved values of several σ. This can be considered analogous to substantial systematic/astrophysical noise in a real observation, or errors/omissions in a forward model such as molecular line list incompleteness or missing absorbers.
Switches between accretion structures during flares in 4U 1901+03
Authors: Ji L , Ducci L , Santangelo A , Zhang S , Suleimanov V , Tsygankov S , Doroshenko V , Nabizadeh A , Zhang S N , Ge M Y , Tao L , Bu Q C , Qu J L , Lu F J , Chen L , Song L M , Li T P , Xu Y P , Cao X L , Chen Y , Liu C Z , Cai C , Chang Z , Chen G , Chen T X , Chen Y B , Chen Y P , Cui W , Cui W W , Deng J K , Dong Y W , Du Y Y , Fu M X , Gao G H , Gao H , Gao M , Gu Y D , Guan J , Guo C C , Han D W , Huang Y , Huo J , Jia S M , Jiang L H , Jiang W C , Jin J , Jin Y J , Kong L D , Li B , Li C K , Li G , Li M S , Li W , Li X , Li X B , Li X F , Li Y G , Li Z W , Liang X H , Liao J Y , Liu B S , Liu G Q , Liu H X , Liu H W , Liu X J , Liu Y N , Lu B , Lu X F , Luo Q , Luo T , Ma X , Meng B , Nang Y , Nie J Y , Ou G , Sai N , Shang R C , Song X Y , Sun L , Tan Y , Tuo Y L , Wang C , Wang G F , Wang J , Wang P J , Wang W S , Wang Y S , Wen X Y , Wu B Y , Wu B B , Wu M , Xiao G C , Xiao S , Xiong S L , Xu H , Yang J W , Yang S , Yang Yan-Ji , Yang Yi-Jung , Yi Q B , Yin Q Q , You Y , Zhang A M , Zhang C M , Zhang F , Zhang H M , Zhang J , Zhang P , Zhang T , Zhang W , Zhang W C , Zhang W Z , Zhang Yi , Zhang Y F , Zhang Y J , Zhang Y H , Zhang Yue , Zhang Zhao , Zhang Zhi , Zhang Z L , Zhao H S , Zhao X F , Zheng S J , Zhou D K , Zhou J F , Zhu Y X , Zhu Y , Zhuang R L
Published: February 2020

We report on our analysis of the 2019 outburst of the X-ray accreting pulsar 4U 1901+03 observed with Insight-HXMT and NICER. Both spectra and pulse profiles evolve significantly in the decaying phase of the outburst. Dozens of flares are observed throughout the outburst. They are more frequent and brighter at the outburst peak. We find that the flares, which have a duration from tens to hundreds of seconds, are generally brighter than the persistent emission by a factor of ∼1.5. The pulse-profile shape during the flares can be significantly different from that of the persistent emission. In particular, a phase shift is clearly observed in many cases. We interpret these findings as direct evidence of changes of the pulsed beam pattern, due to transitions between the sub- and supercritical accretion regimes on a short time-scale. We also observe that at comparable luminosities the flares’ pulse profiles are rather similar to those of the persistent emission. This indicates that the accretion on the polar cap of the neutron star is mainly determined by the luminosity, i.e. the mass accretion rate.
Chemical evolution of ultrafaint dwarf galaxies: testing the IGIMF
Authors: Lacchin E , Matteucci F , Vincenzo F , Palla M
Published: February 2020

We test the integrated galactic initial mass function (IGIMF) on the chemical evolution of 16 ultrafaint dwarf (UFD) galaxies discussing in detail the results obtained for three of them: Boötes I, Boötes II, and Canes Venatici I, taken as prototypes of the smallest and the largest UFDs. These objects have very small stellar masses (∼103–104 M⊙) and quite low metallicities ([Fe/H] < −1.0 dex). We consider four observational constraints: the present-day stellar mass, the [α/Fe] versus [Fe/H] relation, the stellar metallicity distribution function and the cumulative star formation history. Our model follows in detail the evolution of several chemical species (H, He, α-elements, and Fe). We take into account detailed nucleosynthesis and gas flows (in and out). Our results show that the IGIMF, coupled with the very low star formation rate predicted by the model for these galaxies (∼10−4–10−6 M⊙yr−1), cannot reproduce the main chemical properties, because it implies a negligible number of core-collapse SNe and even Type Ia SNe, the most important polluters of galaxies. On the other hand, a constant classical Salpeter IMF gives the best agreement with data, but we cannot exclude that other formulations of the IGIMF could reproduce the properties of these galaxies. Comparing with Galaxy data, we suggest that UFDs could not be the building blocks of the entire Galactic halo, although more data are necessary to draw firmer conclusions.