A Preclinical Blinded Randomized-Controlled Trial Evaluating the Clinical Relevance of Polyp Size Measurement Using a Virtual Scale Endoscope.

Background: The virtual scale endoscope (VSE) helps endoscopists measure colorectal polyp size more accurately compared to visual assessment (VA). However, previous studies were not adequately powered to evaluate the sizing of polyps at clinically relevant size thresholds and relative accuracy for size subgroups. Methods: We created 64 artificial polyps of varied sizes and Paris class morphology, randomly assigned 1:1 to be measured (383 total measurement datapoints with VSE and VA by 6 endoscopists blinded to true size) in a colon model. We added data from two previous trials (480 measurement datapoints). We evaluated for correct classification of polyps into size groups at 3 mm, 5 mm, 10 mm, and 20 mm size thresholds and the relative size measurement accuracy for diminutive polyps (≤5 mm), small polyps (5-9 mm), large polyps at 10-19 mm, and polyps (≥20). Results: VSE had significantly less size group misclassifications at the 5 mm, and 10 mm thresholds (28 percent vs. 45 percent, P = 0.0159 and 26 percent vs. 44 percent, P = 0.0135, respectively). For the 3 mm and 20 mm thresholds, VSE had lower misclassifications; however, this was not statistically significant (36 percent vs. 46 percent, P = 0.3853 and 38 percent vs. 41 percent, P = 0.2705, respectively). The relative size measurement accuracy was significantly higher for VSE compared to VA for all size subgroups (diminutive (P < 0.01), small polyps (P < 0.01), 10-19 mm (P < 0.01), and ≥20 mm (P < 0.01)). Conclusion: VSE outperforms VA in categorizing polyps into size groups at the clinically relevant size thresholds of 5 mm and 10 mm. Using VSE resulted in significantly higher relative measurement accuracy for all size subgroups.

Crohn's Disease Phenotypes and Associations With Comorbidities, Surgery Risk, Medications and Nonmedication Approaches: The MAGIC in IMAGINE Study.

BACKGROUND: We aimed to establish a cohort of persons with Crohn's disease (CD) enrolled from 14 Canadian centers to describe the contemporary presentation of CD in Canada. METHODS: All enrollees were at least 18 years old and underwent chart review for phenotype documentation by Montreal Classification at time of enrollment, comorbidities, inflammatory bowel disease (IBD) and other surgeries, and use IBD and other therapies. RESULTS: Of 2112 adults, 59% were female, and the mean age was 44.1 (+/-14.9SD) years. The phenotype distribution was B1 = 50.4%, B2 = 22.4%, B3 = 17.3%, and missing information = 9.9%. Perineal disease was present in 14.2%. Pertaining to disease location, 35.2% of patients had disease in L1, 16.8% in L2, 48% in L3, and 0.4% in L4. There was no difference in phenotype by gender, anxiety score, depression score. Disease duration was significantly different depending on disease behavior type (B1 = 12.2 ±â€…10.1; B2 = 19.4 ±â€…12.9; B3 = 18.9 ±â€…11.8, P < .0001). Isolated colonic disease was much less likely to be fibrostenotic or penetrating than inflammatory disease. Penetrating disease was more likely to be associated with ileocolonic location than other locations. Perineal disease was most commonly seen in persons with B3 disease behavior (24%) than other behaviors (11% B1; 20% B2 disease, P < .0001) and more likely to be seen in ileocolonic disease (L3;19%) vs L2 (17%) and L1 (11%; P < .0001). Surgery related to IBD occurred across each behavior types at the following rates: B1 = 23%, B2 = 64%, and B3 = 74%. Inflammatory bowel disease-related surgery rates by location of disease were L1 = 48%, L2 = 21%, and L3 = 51%. CONCLUSIONS: In exploring this large contemporary CD cohort we have determined that inflammatory disease is the main CD phenotype in Canada and that CD-related surgery remains very common.

Autonomous Artificial Intelligence vs Artificial Intelligence-Assisted Human Optical Diagnosis of Colorectal Polyps: A Randomized Controlled Trial.

BACKGROUND & AIMS: Artificial intelligence (AI)-based optical diagnosis systems (CADx) have been developed to allow pathology prediction of colorectal polyps during colonoscopies. However, CADx systems have not yet been validated for autonomous performance. Therefore, we conducted a trial comparing autonomous AI to AI-assisted human (AI-H) optical diagnosis. METHODS: We performed a randomized noninferiority trial of patients undergoing elective colonoscopies at 1 academic institution. Patients were randomized into (1) autonomous AI-based CADx optical diagnosis of diminutive polyps without human input or (2) diagnosis by endoscopists who performed optical diagnosis of diminutive polyps after seeing the real-time CADx diagnosis. The primary outcome was accuracy in optical diagnosis in both arms using pathology as the gold standard. Secondary outcomes included agreement with pathology for surveillance intervals. RESULTS: A total of 467 patients were randomized (238 patients/158 polyps in the autonomous AI group and 229 patients/179 polyps in the AI-H group). Accuracy for optical diagnosis was 77.2% (95% confidence interval [CI], 69.7-84.7) in the autonomous AI group and 72.1% (95% CI, 65.5-78.6) in the AI-H group (P = .86). For high-confidence diagnoses, accuracy for optical diagnosis was 77.2% (95% CI, 69.7-84.7) in the autonomous AI group and 75.5% (95% CI, 67.9-82.0) in the AI-H group. Autonomous AI had statistically significantly higher agreement with pathology-based surveillance intervals compared to AI-H (91.5% [95% CI, 86.9-96.1] vs 82.1% [95% CI, 76.5-87.7]; P = .016). CONCLUSIONS: Autonomous AI-based optical diagnosis exhibits noninferior accuracy to endoscopist-based diagnosis. Both autonomous AI and AI-H exhibited relatively low accuracy for optical diagnosis; however, autonomous AI achieved higher agreement with pathology-based surveillance intervals. (ClinicalTrials.gov, Number NCT05236790).

Vasoactive Intestinal Polypeptide Plays a Key Role in the Microbial-Neuroimmune Control of Intestinal Motility.

BACKGROUND & AIMS: Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract. METHODS: Gastric emptying, intestinal transit, muscle contractility, acetylcholine release, gene expression, and vasoactive intestinal polypeptide (VIP) immunoreactivity were assessed in wild-type and Myd88-/-Trif-/- mice in germ-free, gnotobiotic, and specific pathogen-free conditions. Effects of transient colonization and antimicrobials as well as immune cell blockade were investigated. VIP levels were assessed in human full-thickness biopsies by Western blot. RESULTS: Germ-free mice had similar gastric emptying but slower intestinal transit compared with specific pathogen-free mice or mice monocolonized with Lactobacillus rhamnosus or Escherichia coli, the latter having stronger effects. Although muscle contractility was unaffected, its neural control was modulated by microbiota by up-regulating jejunal VIP, which co-localized with and controlled cholinergic nerve function. This process was responsive to changes in the microbial composition and load and mediated through toll-like receptor signaling, with enteric glia cells playing a key role. Jejunal VIP was lower in patients with chronic intestinal pseudo-obstruction compared with control subjects. CONCLUSIONS: Microbial control of gastrointestinal motility is both region- and bacteria-specific; it reacts to environmental changes and is mediated by innate immunity-neural system interactions. By regulating cholinergic nerves, small intestinal VIP plays a key role in this process, thus providing a new therapeutic target for patients with motility disorders.

Measuring Size of Colorectal Polyps Using a Virtual Scale Endoscope or Visual Assessment: A Randomized Controlled Trial.

INTRODUCTION: This study aimed to compare the accuracy of polyp size measurements using a virtual scale endoscope (VSE) with an integrated laser-based adaptive scale function and visual assessment (VA) during colonoscopies. METHODS: We conducted a single-blinded, prospective randomized controlled trial. Eligible patients (aged 45-80 years) undergoing screening, surveillance, or diagnostic colonoscopies were randomly assigned (1:1) into 2 groups. In the intervention group, all detected polyps were measured for size using VSE; in the control group, all polyps were measured using VA. Size measurements were compared with a reference standard of digital caliper measurement immediately post polypectomy. The primary outcome was the relative accuracy of real-time VSE measurement compared with VA. Secondary outcomes included the mean differences and the correlations between VSE or VA sizes and the reference standard of measurement. RESULTS: Overall, 230 patients were enrolled and randomized. The relative size measurement accuracy of VSE was 84% in 118 polyps, which was significantly higher than that of VA (105 polyps; 68.4%, P < 0.001). VSE resulted in a significantly higher percentage of size measurements within 25% of true size compared with VA (81.4% vs 41%, P < 0.001). VSE had a significantly lower percentage for >5-mm polyps incorrectly sized as 1-5 mm compared with VA (13.5% vs 57.1%; P < 0.001) and a significantly lower percentage for >3-mm polyps incorrectly sized as 1-3 mm compared with VA (11.3% vs 56.5%; P < 0.001). DISCUSSION: VSE significantly improves the size measurement accuracy of colorectal polyps during colonoscopies compared with VA and results in fewer misclassifications at relevant decision-making size thresholds.

Measuring the observer (Hawthorne) effect on adenoma detection rates.

Background and study aims An independent observer can improve procedural quality. We evaluated the impact of the observer (Hawthorne effect) on important quality metrics during colonoscopies. Patients and Methods In a single-center comparative study, consecutive patients undergoing routine screening or diagnostic colonoscopy were prospectively enrolled. In the index group, all procedural steps and quality metrics were observed and documented, and the procedure was video recorded by an independent research assistant. In the reference group, colonoscopies were performed without independent observation. Colonoscopy quality metrics such as polyp, adenoma, serrated lesions, and advanced adenoma detection rates (PDR, ADR, SLDR, AADR) were compared. The probabilities of increased quality metrics were evaluated through regression analyses weighted by the inversed probability of observation during the procedure. Results We included 327 index individuals and 360 referents in the final analyses. The index group had significantly higher PDRs (62.4% vs. 53.1%, P =0.02) and ADRs (39.4% vs. 28.3%, P =0.002) compared with the reference group. The SLDR and AADR were not significantly increased. After adjusting for potential confounders, the ADR and SLDR were 50% (relative risk [RR] 1.51; 95%, CI 1.05-2.17) and more than twofold (RR 2.17; 95%, CI 1.05-4.47) more likely to be higher in the index group than in the reference group. Conclusions The presence of an independent observer documenting colonoscopy quality metrics and video recording the colonoscopy resulted in a significant increase in ADR and other quality metrics. The Hawthorne effect should be considered an alternative strategy to advanced devices to improve colonoscopy quality in practice.

Automated Detection of Anatomical Landmarks During Colonoscopy Using a Deep Learning Model.

Background and aims: Identification and photo-documentation of the ileocecal valve (ICV) and appendiceal orifice (AO) confirm completeness of colonoscopy examinations. We aimed to develop and test a deep convolutional neural network (DCNN) model that can automatically identify ICV and AO, and differentiate these landmarks from normal mucosa and colorectal polyps. Methods: We prospectively collected annotated full-length colonoscopy videos of 318 patients undergoing outpatient colonoscopies. We created three nonoverlapping training, validation, and test data sets with 25,444 unaltered frames extracted from the colonoscopy videos showing four landmarks/image classes (AO, ICV, normal mucosa, and polyps). A DCNN classification model was developed, validated, and tested in separate data sets of images containing the four different landmarks. Results: After training and validation, the DCNN model could identify both AO and ICV in 18 out of 21 patients (85.7%). The accuracy of the model for differentiating AO from normal mucosa, and ICV from normal mucosa were 86.4% (95% CI 84.1% to 88.5%), and 86.4% (95% CI 84.1% to 88.6%), respectively. Furthermore, the accuracy of the model for differentiating polyps from normal mucosa was 88.6% (95% CI 86.6% to 90.3%). Conclusion: This model offers a novel tool to assist endoscopists with automated identification of AO and ICV during colonoscopy. The model can reliably distinguish these anatomical landmarks from normal mucosa and colorectal polyps. It can be implemented into automated colonoscopy report generation, photo-documentation, and quality auditing solutions to improve colonoscopy reporting quality.

Incomplete resection rates of 4- to 20-mm non-pedunculated colorectal polyps when using wide-field cold snare resection with routine submucosal injection.

Background and study aims Incomplete resection of 4- to 20-mm colorectal polyps occur frequently (> 10 %), putting patients at risk for post-colonoscopy colorectal cancer. We hypothesized that routine use of wide-field cold snare resection with submucosal injection (CSP-SI) might reduce incomplete resection rates (IRRs). Patients and methods Patients aged 45 to 80 years undergoing elective colonoscopies were enrolled in a prospective clinical study. All 4- to 20-mm non-pedunculated polyps were resected using CSP-SI. Post-polypectomy margin biopsies were obtained to determine IRRs through histopathology assessment. The primary outcome was IRR, defined as remnant polyp tissue found on margin biopsies. Secondary outcomes included technical success and complication rates. Results A total of 429 patients (median age 65 years, 47.1 % female, adenoma detection rate 40 %) with 204 non-pedunculated colorectal polyps 4 to 20 mm removed using CSP-SI were included in the final analysis. CSP-SI was technical successful in 97.5 % (199/204) of cases (5 conversion to hot snare polypectomy). IRR for CSP-SI was 3.8 % (7/183) (95 % confidence interval [CI] 2.7 %-5.5 %). IRR was 1.6 % (2/129), 16 % (4/25), and 3.4 % (1/29) for adenomas, serrated lesions, and hyperplastic polyps respectively. IRR was 2.3 % (2/87), 6.3 % (4/64), 4.0 % (6/151), and 3.1 % (1/32) for polyps 4 to 5 mm, 6 to 9 mm, < 10 mm, and 10 to 20 mm, respectively. There were no CSP-SI-related serious adverse events. Conclusions Use of CSP-SI results in lower IRRs compared to what has previously been reported in the literature for hot or cold snare polypectomy when not using wide-field cold snare resection with submucosal injection. CSP-SI showed an excellent safety and efficacy profile, however comparative studies to CSP without SI are required to confirm these results.

Comparing size measurement of colorectal polyps using a novel virtual scale endoscope, endoscopic ruler or forceps: A preclinical randomized trial.

Background and study aims Accurate polyp size measurement is important for guideline conforming choice of polypectomy techniques and subsequent surveillance interval assignments. Some endoscopic tools (biopsy forceps [BF] or endoscopic rulers [ER]) exist to help with visual size estimation. A virtual scale endoscope (VSE) has been developed that allows superimposing a virtual measurement scale during live endoscopies. Our aim was to evaluate the performance of VSE when compared to ER and BF-based measurement. Methods We conducted a preclinical randomized trial to evaluate the relative accuracy of size measurement of simulated colorectal polyps when using: VSE, ER, and BF. Six endoscopists performed 60 measurements randomized at a 1:1:1 ratio using each method. Primary outcome was relative accuracy in polyp size measurement. Secondary outcomes included misclassification of sizes at the 5-, 10-, and 20-mm thresholds. Results A total of 360 measurements were performed. The relative accuracy of BF, ER, and VSE was 78.9 % (95 %CI = 76.2-81.5), 78.4 % (95 %CI = 76.0-80.8), and 82.7 % (95 %CI = 80.8-84.8). VSE had significantly higher accuracy compared to BF ( P  = 0.02) and ER ( P  = 0.006). VSE misclassified a lower percentage of polyps > 5 mm as ≤ 5 mm (9.4 %) compared to BF (15.7 %) and ER (20.9 %). VSE misclassified a lower percentage of ≥ 20 mm polyps as < 20 mm (8.3 %) compared with BF (66.7 %) and ER (75.0 %). Of polyps ≥10mm, 25.6 %, 25.5 %, and 22.5 % were misclassified as <10 mm with ER, BF, and VSE, respectively. Conclusions VSE had significantly higher relative accuracy in measuring polyps compared to ER or BF assisted measurement. VSE improves correct classification of polyps at clinically important size thresholds.

Comparing size measurements of simulated colorectal polyp size and morphology groups when using a virtual scale endoscope or visual size estimation: Blinded randomized controlled trial.

OBJECTIVES: The virtual scale endoscope (VSE) allows projection of a virtual scale onto colorectal polyps allowing real-time size measurements. We studied the relative accuracy of VSE compared to visual assessment (VA) for the measuring simulated polyps of different size and morphology groups. METHODS: We conducted a blinded randomized controlled trial using simulated polyps within a colon model. Sixty simulated polyps were evenly distributed across four size groups (1-5, >5-9.9, 10-19.9, and ≥20 mm) and three Paris morphology groups (flat, sessile, and pedunculated). Six endoscopists performed polyp size measurements using random allocation of either VA or VSE. RESULTS: A total of 359 measurements were completed. The relative accuracy of VSE was significantly higher when compared to VA for all size groups >5 mm (P = 0.004, P < 0.001, P < 0.001). For polyps ≤5 mm, the relative accuracy of VSE compared to VA was not significantly higher (P = 0.186). The relative accuracy of VSE was significantly higher when compared to VA for all morphology groups. VSE misclassified a lower percentage of >5 mm polyps as ≤5 mm (2.9%), ≥10 mm polyps as <10 mm (5.5%), and ≥20 mm polyps as <20 mm (21.7%) compared to VA (11.2%, 24.7%, and 52.3% respectively; P = 0.008, P < 0.001, and P = 0.003). CONCLUSION: Virtual scale endoscope had significantly higher relative accuracies for every polyp size group or morphology type aside from diminutive. VSE enables the endoscopist to better classify polyps into correct size categories at clinically relevant size thresholds of 5, 10, and 20 mm.

Incomplete resection of colorectal polyps of 4-20 mm in size when using a cold snare, and its associated factors.

BACKGROUND : Cold snare polypectomy (CSP) is increasingly used for polypectomy and is recommended as the first-line modality for small (< 10 mm) polyps. This study aimed to evaluate incomplete resection rates (IRRs) when using CSP for colorectal polyps of 4-20 mm. METHODS : Adults (45-80 years) undergoing screening, surveillance, or diagnostic colonoscopy and CSP by one of nine endoscopists were included. The primary outcome was the IRR for colorectal polyps of 4-20 mm, defined as the presence of polyp tissue in marginal biopsies after resection of serrated polyps or adenomas. Secondary outcomes included the IRR for serrated polyps, ease of resection, and complications. RESULTS: 413 patients were included (mean age 63; 48 % women) and 182 polyps sized 4-20 mm were detected and removed by CSP. CSP required conversion to hot snare resection in < 1 % of polyps of < 10 mm and 44 % of polyps sized 10-20 mm. The IRRs for polyps < 10 mm and ≥ 10 mm were 18 % and 21 %. The IRR was higher for serrated polyps (26 %) compared with adenomas (16 %). The IRR was higher for flat (IIa) polyps (odds ratio [OR] 2.9, 95 %CI 1.1-7.4); and when resection was judged as difficult (OR 4.2, 95 %CI 1.5-12.1), piecemeal resection was performed (OR 6.6, 95 %CI 2.0-22.0), or visible residual polyp was present after the initial resection (OR 5.4, 95 %CI 2.0-14.9). Polyp location, use of a dedicated cold snare, and submucosal injection were not associated with incomplete resection. Intraprocedural bleeding requiring endoscopic intervention occurred in 4.7 %. CONCLUSIONS : CSP for polyps of 4-9 mm is safe and feasible; however, for lesions ≥ 10 mm, CSP failure occurs frequently, and the IRR remains high even after technical success. Incomplete resection was associated with flat polyps, visual residual polyp, piecemeal resection, and difficult polypectomies.

Clinical Management of the Microbiome in Irritable Bowel Syndrome.

BACKGROUND: A growing body of evidence suggests that dysbiosis contributes to the onset and symptomatology of irritable bowel syndrome (IBS) and other functional bowel disorders. Changes to the gastrointestinal microbiome may contribute to the underlying pathophysiology of IBS. METHODS: The present review summarizes the potential effects of microbiome changes on GI transit, intestinal barrier function, immune dysregulation and inflammation, gut-brain interactions and neuropsychiatric function. RESULTS: A multimodal approach to IBS management is recommended in accordance with current Canadian guidelines. Pharmacologic treatments are advised to target the presumed underlying pathophysiological mechanism, such as dysregulation of GI transit, peristalsis, intestinal barrier function and pain signalling. The management plan for IBS may also include treatments directed at dysbiosis, including dietary modification and use of probiotics, which may promote the growth of beneficial bacteria, affect intestinal gas production and modulate the immune response; and the administration of periodic short courses of a nonsystemic antibiotic such as rifaximin, which may re-establish microbiota diversity and improve IBS symptoms. CONCLUSION: Dysregulated host-microbiome interactions are complex and the use of microbiome-directed therapies will necessarily be empiric in individual patients. A management algorithm comprising microbiome- and nonmicrobiome-directed therapies is proposed.

The Prevalence of Helicobacter pylori Infection in a Quaternary Hospital in Canada.

BACKGROUND: Helicobacter pylori (H. pylori) prevalence in Canada has been estimated to be around 20% to 30%. However, H. pylori prevalence is declining in industrialized countries. We conducted a retrospective study on a population of patients referred for esophagogastroduodenoscopy (EGD) in a Canadian quaternary hospital to see the current prevalence of H. pylori infection and identify its main risk factors. METHODS: We performed a retrospective cross-sectional study from the Electronic Medical Records of 500 patients who visited our endoscopy clinic and who had biopsies to search for H. pylori infection. In addition to the outcome of the biopsies, we collected demographic characteristics of patients, EGD indication and endoscopic findings. RESULTS: The overall prevalence of H. pylori was 13.0% (65/500) among our population. We found no association with age, sex, tobacco or alcohol consumption. However, we noticed a significantly higher prevalence of H. pylori among African (25.0%; 8/32), Asian (30.8%; 4/13) and South American (34.9%; 15/43) born subjects when compared to the Caucasian group (8.0%; 28/350) (all P < 0.05). CONCLUSIONS: The prevalence of H. pylori in Canada is declining, particularly among its Caucasian population. The race seems to be the strongest risk factor associated with this infection.

Predictors of Small Intestinal Bacterial Overgrowth in Symptomatic Patients Referred for Breath Testing.

BACKGROUND: Indications for a breath test (BT) are well established in the symptomatic patient with risk factors predisposing them to small intestinal bacterial overgrowth (SIBO). Characteristics and the profile of this population are not well known. Our objective was to study the characteristics of patients undergoing a BT for SIBO and to identify factors associated with a positive BT. METHODS: Retrospective study was conducted from 2012 to 2016 at the neurogastroenterology unit of the Centre Hospitalier de l'Universite de Montreal (CHUM). All patients who completed a BT (lactulose and/or glucose) were included. Demographics and clinical factors were analyzed to identify predictors of positive BT. Type of antibiotic treatment and clinical response were compiled. Groups of patients with (SIBO+) and without SIBO (SIBO-) were also compared. RESULTS: A total of 136 patients were included in the study (mean age 51.2, range 20 - 80 years; 63% women), and SIBO was detected in 33.8% (n = 46). Both groups were similar in terms of age, body mass index, and gender. SIBO was significantly associated with the presence of abdominal pain (odds ratio (OR) = 4.78; P < 0.05), bloating (OR = 5.39; P < 0.05), smoking (OR = 6.66; P < 0.05), and anemia (OR = 4.08; P < 0.05). No association was identified with gender, age, obesity, and risk factors for SIBO. Antibiotics were used in 43% of patients with a positive BT, but clinical response was not significantly different in the subgroup that received antibiotics versus the subgroup that did not. CONCLUSIONS: The prevalence of SIBO is high in symptomatic patients who underwent breath testing. Abdominal pain, bloating, smoking, and anemia are strongly associated with SIBO. Treatment of SIBO with antibiotics needs to be further investigated to better determine its efficacy on gastrointestinal symptoms.

High occurrence of small intestinal bacterial overgrowth in primary biliary cholangitis.

BACKGROUND: Primary biliary cholangitis (PBC) is a chronic autoimmune liver disease affecting mainly middle-aged women. An alteration in intestinal motility has been well documented in cirrhosis predisposing to small intestinal bacterial overgrowth (SIBO). Patients with PBC frequently complain of various gastrointestinal symptoms compatible with SIBO. No study has specifically been published to this day to determine the occurrence of SIBO in PBC. Our objective was to determine the prevalence of SIBO in patients with PBC. METHODS: Retrospective study from 2010 to 2018. All patients diagnosed with PBC during this period had a systematic screening for SIBO in their diagnostic workup. The diagnosis of SIBO was made by a carbohydrate breath test (lactulose and/or glucose). Clinical and paraclinical factors of patients were compared with a control group of healthy subjects. KEY RESULTS: Ninety-eight subjects were included in the study (mean age 49, range 21-88 years) including 58 patients with PBC and 40 healthy subjects. The PBC group was older than the control group (mean age 56, range 31-88 vs 39, range 21-62 years; P < .001), but identical for gender and body mass index. The prevalence of SIBO was higher in PBC versus controls (32.8% vs 2.5%; P < .001). The PBC group with SIBO had significantly more diarrhea (78.9% vs 35.9%; P < .05) than the PBC group without SIBO, but the prevalence of abdominal pain and bloating was similar. CONCLUSIONS & INFERENCES: The high occurrence of SIBO in PBC may explain some of the frequently reported gastrointestinal symptoms. This study justifies the systematic screening for SIBO in PBC.

Patient Engagement and Multidisciplinary Involvement Has an Impact on Clinical Guideline Development and Decisions: A Comparison of Two Irritable Bowel Syndrome Guidelines Using the Same Data.

BACKGROUND AND AIM: The value of a multidisciplinary group and patient engagement in guideline groups is uncertain. We compared the recommendations of two guidelines that used the same data during the same time frame but with different participants to obtain a "real world" perspective on influence of the composition of guideline groups. METHODS: The Canadian Association of Gastroenterology (CAG) and the American College of Gastroenterology (ACG) recently updated their clinical practice guidelines for the management of Irritable Bowel Syndrome (IBS). Both the CAG and ACG used the same methodology and methodologist and were presented with the same data for interpretation. The ACG group consisted of predominantly academic gastroenterologists, while the CAG group also included general practitioners, a psychiatrist, a psychologist and a patient representative. The CAG group were also asked what components of the group were valuable. RESULTS: There were 14 statements with the same or similar recommendations. There were 10 statements in the CAG guideline not addressed by the ACG guideline and five recommendations where the opposite was the case. There was one statement that the two groups both addressed, but each group came to different conclusions. CAG members were in 100% agreement that involving a patient and having a multidisciplinary team was valuable and may have played a role in these differing interpretations of the same data in an IBS guideline. CONCLUSIONS: There has been little uptake of patient involvement and multidisciplinary teams in guideline groups. However, this study provides a unique example of added benefit through broader group representation.

Canadian Association of Gastroenterology Clinical Practice Guideline for the Management of Irritable Bowel Syndrome (IBS).

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is one of the most common gastrointestinal (GI) disorders, affecting about 10% of the general population globally. The aim of this consensus was to develop guidelines for the management of IBS. METHODS: A systematic literature search identified studies on the management of IBS. The quality of evidence and strength of recommendations were rated according to the Grading of Recommendation Assessment, Development and Evaluation (GRADE) approach. Statements were developed through an iterative online platform and then finalized and voted on by a multidisciplinary group of clinicians and a patient. RESULTS: Consensus was reached on 28 of 31 statements. Irritable bowel syndrome is diagnosed based on symptoms; serological testing is suggested to exclude celiac disease, but routine testing for C-reactive protein (CRP), fecal calprotectin or food allergies is not recommended. A trial of a low fermentable oligosaccharides, disaccharides, monosaccharides, polyols (FODMAP) diet is suggested, while a gluten-free diet is not. Psyllium, but not wheat bran, supplementation may help reduce symptoms. Alternative therapies such as peppermint oil and probiotics are suggested, while herbal therapies and acupuncture are not. Cognitive behavioural therapy and hypnotherapy are suggested psychological therapies. Among the suggested or recommended pharmacological therapies are antispasmodics, certain antidepressants, eluxadoline, lubiprostone, and linaclotide. Loperamide, cholestyramine and osmotic laxatives are not recommended for overall IBS symptoms. The nature of the IBS symptoms (diarrhea-predominant or constipation-predominant) should be considered in the choice of pharmacological treatments. CONCLUSIONS: Patients with IBS may benefit from a multipronged, individualized approach to treatment, including dietary modifications, psychological and pharmacological therapies.

Transplantation of fecal microbiota from patients with irritable bowel syndrome alters gut function and behavior in recipient mice.

Irritable bowel syndrome (IBS) is a common disorder characterized by altered gut function and often is accompanied by comorbid anxiety. Although changes in the gut microbiota have been documented, their relevance to the clinical expression of IBS is unknown. To evaluate a functional role for commensal gut bacteria in IBS, we colonized germ-free mice with the fecal microbiota from healthy control individuals or IBS patients with diarrhea (IBS-D), with or without anxiety, and monitored gut function and behavior in the transplanted mice. Microbiota profiles in recipient mice clustered according to the microbiota profiles of the human donors. Mice receiving the IBS-D fecal microbiota showed a taxonomically similar microbial composition to that of mice receiving the healthy control fecal microbiota. However, IBS-D mice showed different serum metabolomic profiles. Mice receiving the IBS-D fecal microbiota, but not the healthy control fecal microbiota, exhibited faster gastrointestinal transit, intestinal barrier dysfunction, innate immune activation, and anxiety-like behavior. These results indicate the potential of the gut microbiota to contribute to both intestinal and behavioral manifestations of IBS-D and suggest the potential value of microbiota-directed therapies in IBS patients.

Prevalence of Small Intestinal Bacterial Overgrowth among Chronic Pancreatitis Patients: A Case-Control Study.

Background. Patients with chronic pancreatitis (CP) exhibit numerous risk factors for the development of small intestinal bacterial overgrowth (SIBO). Objective. To determine the prevalence of SIBO in patients with CP. Methods. Prospective, single-centre case-control study conducted between January and September 2013. Inclusion criteria were age 18 to 75 years and clinical and radiological diagnosis of CP. Exclusion criteria included history of gastric, pancreatic, or intestinal surgery or significant clinical gastroparesis. SIBO was detected using a standard lactulose breath test (LBT). A healthy control group also underwent LBT. Results. Thirty-one patients and 40 controls were included. The patient group was significantly older (53.8 versus 38.7 years; P < 0.01). The proportion of positive LBTs was significantly higher in CP patients (38.7 versus 2.5%: P < 0.01). A trend toward a higher proportion of positive LBTs in women compared with men was observed (66.6 versus 27.3%; P = 0.056). The subgroups with positive and negative LBTs were comparable in demographic and clinical characteristics, use of opiates, pancreatic enzymes replacement therapy (PERT), and severity of symptoms. Conclusion. The prevalence of SIBO detected using LBT was high among patients with CP. There was no association between clinical features and the risk for SIBO.

A reassessment of the response of the bacterial ribosome to the frameshift stimulatory signal of the human immunodeficiency virus type 1.

HIV-1 uses a programmed -1 ribosomal frameshift to produce the precursor of its enzymes. This frameshift occurs at a specific slippery sequence followed by a stimulatory signal, which was recently shown to be a two-stem helix, for which a three-purine bulge separates the upper and lower stems. In the present study, we investigated the response of the bacterial ribosome to this signal, using a translation system specialized for the expression of a firefly luciferase reporter. The HIV-1 frameshift region was inserted at the beginning of the coding sequence of the luciferase gene, such that its expression requires a -1 frameshift. Mutations that disrupt the upper or the lower stem of the frameshift stimulatory signal or replace the purine bulge with pyrimidines decreased the frameshift efficiency, whereas compensatory mutations that re-form both stems restored the frame-shift efficiency to near wild-type level. These mutations had the same effect in a eukaryotic translation system, which shows that the bacterial ribosome responds like the eukaryote ribosome to the HIV-1 frameshift stimulatory signal. Also, we observed, in contrast to a previous report, that a stop codon immediately 3' to the slippery sequence does not decrease the frameshift efficiency, ruling out a proposal that the frameshift involves the deacylated-tRNA and the peptidyl-tRNA in the E and P sites of the ribosome, rather than the peptidyl-tRNA and the aminoacyl-tRNA in the P and A sites, as commonly assumed. Finally, mutations in 16S ribosomal RNA that facilitate the accommodation of the incoming aminoacyl-tRNA in the A site decreased the frameshift efficiency, which supports a previous suggestion that the frameshift occurs when the aminoacyl-tRNA occupies the A/T entry site.