Benefits of Prokinetics, Gastroparesis Diet, or Neuromodulators Alone or in Combination for Symptoms of Gastroparesis.

BACKGROUND & AIMS: Prokinetics have limited effectiveness for treating symptoms of gastroparesis. Thus, alternative or adjunct therapies, such as gastroparesis diets or neuromodulators, are often prescribed. Their therapeutic benefits alone or in combination remain unclear. METHODS: One hundred and twenty-nine patients with symptoms of gastroparesis underwent wireless motility capsule gastric emptying time and gastric emptying scintigraphy. Based on test results, changes in therapy were recommended. Changes in Gastroparesis Cardinal Symptom Index (GCSI) and individual symptom scores over 6 months were related to recommendations for prokinetics, gastroparesis diet, or neuromodulators given as solo new therapies or in dual combinations. Multivariate analyses were performed to adjust for gastric emptying and other variables. RESULTS: In the whole group regardless of therapy, GCSI scores decreased by 0.53 points (interquartile range, -1.25 to 0.05; P < .0001) over 6 months. GCSI did not decrease for prokinetics as solo new therapy (P = .95). Conversely, neuromodulators as solo therapy decreased GCSI scores (P = .04) and all individual symptoms except nausea/vomiting (P = .86). Prokinetics combined with gastroparesis diets or neuromodulators improved GCSI scores (P ≤ .04) and most individual symptoms. Adjusting for gastric emptying time on multivariate analyses showed greater GCSI decreases for nondelayed emptying for neuromodulators as solo new therapy (P = .01). Gastric emptying scintigraphy, gender, diabetes, and functional dyspepsia did not influence responses to any treatment. CONCLUSIONS: Initiating prokinetics as solo new therapy had little benefit for patients with symptoms of gastroparesis. Neuromodulators as the only new therapy decreased symptoms other than nausea and vomiting, especially with nondelayed gastric emptying. Adding gastroparesis diets or neuromodulators to prokinetics offered relief, suggesting that combination therapies may be more useful in managing these patients. (ClinicalTrials.gov NCT02022826.).

Clinical Presentation of Small Intestinal Bacterial Overgrowth from Aerodigestive Tract Bacteria Versus Colonic-Type Bacteria: A Comparison Study.

BACKGROUND: Small Intestinal Bacterial Overgrowth (SIBO) is a heterogenous syndrome from excessive bacteria in the small intestine lumen. It is unknown if differences in type of bacterial overgrowth lead to differences in symptoms. METHODS: Patients with suspected SIBO were recruited prospectively. Exclusion criteria were probiotics, antibiotics, or bowel prep in preceding 30 days. Clinical characteristics, risk factors, and labs were collected. Proximal jejunal aspiration via upper enteroscopy was performed. Aerodigestive tract (ADT) SIBO was defined as > 105 CFU/mL of oropharyngeal and respiratory bacteria. Colonic-type SIBO was defined as > 104 CFU/mL of distal small bowel and colon bacteria. Aims were to compare symptom profiles, clinical complications, labs, and underlying risk factors between ADT and colonic-type SIBO. KEY RESULTS: We consented 166 subjects. Aspiration was not obtained in 22 and SIBO was found in 69 (49%) of 144 subjects. Daily abdominal distention trended towards more prevalent in ADT SIBO versus colonic-type SIBO (65.2% vs 39.1%, p = 0.09). Patient symptom scores were similar. Iron deficiency was more prevalent in ADT SIBO (33.3% vs 10.3%, p = 0.04). Subjects with colonic-type SIBO were more likely to have a risk factor for colonic bacteria colonization (60.9% vs 17.4%, p = 0.0006). Subjects with ADT SIBO were more likely to have a risk factor for diminished gastric acid (91.3% vs 67.4%, p = 0.02). CONCLUSIONS & INFERENCES: We found differences in iron deficiency and underlying risk factors between ADT and colonic-type SIBO. However, distinct clinical profiles remained elusive. Future research is needed to develop validated symptom assessment tools and distinguish cause from correlation.

Safety of same-day discharge after peroral endoscopic myotomy.

There are limited data on the safety of same-day discharge (SDD) after peroral endoscopic myotomy (POEM). The aim of our study is to assess the frequency and relationship to POEM for emergency department (ED) visits and hospitalizations after SDD in these patients. We retrospectively identified consecutive patients between November 2019 and August 2021 who underwent POEM with SDD and at least 6 months follow-up. Criteria for SDD includes: (1) no serious procedure-related adverse event; (2) post-POEM esophagram without leak; (3) stable vital signs; (4) ability to take liquids orally; (5) pain controlled without IV analgesia; (6) adequate social support; (7) American Society of Anesthesiologists (ASA) class I-III. A causative relationship between POEM and ED visits and hospitalizations was assigned by consensus. Out of 185 POEMs performed, 78 (41.7%, 42M, mean 51±16 years) had SDD. Within 30 days of POEM, 8 ED visits occurred in 7/78 (9%) patients and 2 (25%) were considered related to POEM; hospitalization was required in 3 (38%). After 30 days, 11 ED visits occurred in 10/78 (12.8%) patients and 1 (9%) was considered related to POEM; hospitalization was required in 5 (45%). In this study of consecutive SDD patients after POEM, 3/19 (16%) ED visits and 2/8 (25%) hospitalizations within 6 months were considered related to the procedure. Therefore, eligible patients who follow and fulfill a strict protocol after POEM may be safely discharged the same day.

Baseline Predictors of Longitudinal Changes in Symptom Severity and Quality of Life in Patients With Suspected Gastroparesis.

BACKGROUND & AIMS: Whether gastric emptying tests predict longitudinal outcomes in patients with symptoms of gastroparesis is unclear. We aimed to determine whether baseline gastric emptying tests and gut motility parameters could impact longitudinal symptom(s) and quality of life (QOL) in a prospective, observational cohort study of patients with symptoms of gastroparesis. METHODS: One hundred fifty patients with gastroparesis symptoms underwent simultaneous scintigraphy (GES) and wireless motility capsule (WMC) measurement of gastric emptying and other motility parameters. Patient Assessment of Upper Gastrointestinal Symptoms and Quality of Life were administered at baseline, and 3 and 6 months after testing. Multivariable generalized linear marginal models were fit to determine which baseline parameters predict longitudinal changes in symptoms and QOL. RESULTS: Overall upper GI symptoms and QOL scores were moderate in severity at baseline and significantly improved over 6 months. Clinical variables, including female gender, harder stools by Bristol stool form score, and presence of functional dyspepsia (FD) by Rome III criteria, were predictive of more severe upper GI symptoms. Even after controlling for these clinical factors, delayed gastric emptying by GES or WMC was associated with worse symptom severity and QOL scores. Low gastric and elevated small bowel contractile parameters by WMC were also independently associated with more severe upper GI symptoms and worse QOL scores. CONCLUSIONS: Baseline features, including demographic and clinical variables, delayed gastric emptying and abnormal gastrointestinal contractility, were independent predictors of more severe longitudinal symptoms and worse quality of life outcomes. These factors may help to risk stratify patients and guide treatment decisions. ClinicalTrials.gov no: NCT02022826.

Symptom Association for Gastroesophageal Reflux Disease by pH Monitoring After Peroral Endoscopic Myotomy.

INTRODUCTION: There are limited data correlating symptoms with reflux episodes during pH studies after peroral endoscopic myotomy. METHODS: Consecutive patients who underwent POEM followed up ≥6 months later by 48-hour ambulatory wireless pH testing off antisecretory therapy were identified. Reflux symptom association was defined as symptom association probability >95%. RESULTS: The most frequent symptoms of heartburn (47.2%), cough (45.1%), and chest pain (39.6%) were associated with a positive reflux symptom association (symptom association probability >95%) in 20.9%, 17.1%, and 19.4%, respectively. DISCUSSION: There is poor correlation between reported symptoms and esophageal acid exposure during pH testing after POEM.

Comparison of functional lumen imaging probe and high-resolution manometry to assess response after peroral endoscopic myotomy.

BACKGROUND AND AIMS: Outcomes after peroral endoscopic myotomy (POEM) are assessed clinically by the Eckardt score (ES) or objectively by high-resolution manometry (HRM) and functional lumen imaging probe (FLIP). This study compared HRM and FLIP to evaluate clinical response after POEM. METHODS: This was a single tertiary center retrospective study of consecutive patients who underwent POEM for treatment-naive achalasia and with ≥6 months of follow-up. Baseline and follow-up testing in all patients included ES, HRM, and FLIP of the esophagogastric junction (EGJ). A normal post-POEM (or normalized) EGJ distensibility index (EGJ-DI) >2.8 mm2/mm Hg, maximum EGJ diameter (MxEGJD) ≥14 mm, and integrated relaxation pressure (IRP) <15 mm Hg were compared with a clinical response, defined as ES ≤3. RESULTS: Eighty-seven patients (58% men, mean age 51 ± 17 years) were included. Overall clinical response by ES, IRP, MxEGJD, and EGJ-DI were 97.7%, 86.2%, 75.9%, and 92.0%, respectively. The sensitivity of a normal IRP (87.1% [95% confidence interval {CI}, 78.0-93.4]) was similar to the sensitivity of a normal MxEGJD (75.3% [95% CI, 64.7-84.0], P = .053) and normal EGJ-DI (91.8% [95% CI, 83.8%-96.6%], P = .39) after POEM to predict clinical response. However, the sensitivity of a normal post-POEM EGJ-DI was superior to a normal post-POEM MxEGJD (P = .001) to predict clinical response. There was no difference in the area under the curve of a normal MxEGJD or EGJ-DI to predict a normal IRP (P = .956) after POEM. CONCLUSIONS: Normal FLIP metrics ≥6 months after POEM for achalasia show good to excellent sensitivity but are equivalent to a normalized IRP by HRM to predict clinical response by ESs. FLIP may be used as an alternative to HRM to assess lower esophageal sphincter response to POEM in these patients. (Clinical trial registration number: NCT02770859.).

Associations of Habitual Dietary Intake With Fecal Short-Chain Fatty Acids and Bowel Functions in Irritable Bowel Syndrome.

BACKGROUND GOALS: Diet may contribute to symptoms of irritable bowel syndrome (IBS) and luminal production of putative IBS biomarkers including short-chain fatty acids (SCFAs). Study aims were to to assess relationships of habitual fiber or starch intake with fecal SCFAs in patients with IBS and healthy volunteers (HVs). STUDY: In 18 HVs and 30 patients with IBS (13 constipation-predominant [IBS-C] and 17 diarrhea-predominant [IBS-D]), habitual diet using a food frequency questionnaire; bowel functions using a validated bowel diary; and fecal SCFAs by HPLC-mass spectrometry were assessed. Associations of fiber and starch with SCFAs were analyzed using Spearman (rs) and Pearson (R) correlations. Relationships between other dietary endpoints, SCFAs, and bowel functions were explored. RESULTS: Habitual fiber or starch intakes were not significantly correlated with SCFAs or bowel functions in all participants or HVs nor with SCFAs in IBS. Starch was negatively correlated (R=-0.53; P=0.04) with complete evacuation in IBS-D. Fiber (rs=0.65; P=0.02) and starch (rs=0.56; P=0.05) were correlated with ease of passage in IBS-C. Stool form, frequency, and ease of passage were positively correlated with total SCFAs (all P<0.05), acetate (all P<0.01), propionate (all P<0.05), and butyrate (form P=0.01; ease of passage P=0.05) among all participants, but not in IBS. Complete evacuation was negatively correlated with propionate (R=-0.34; P=0.04) in all participants. Total (P=0.04) and individual SCFAs (all P<0.05) were positively correlated with stool form in HVs. CONCLUSIONS: Habitual fiber and starch intake does not influence fecal SCFAs but may influence bowel functions in IBS. Fecal SCFAs correlate with bowel functions among all participants including HVs.

Relationships of Intestinal Lactase and the Small Intestinal Microbiome with Symptoms of Lactose Intolerance and Intake in Adults.

BACKGROUND: Approximately two-thirds of adults are genetically predisposed to decreased lactase activity after weaning, putting them at risk of lactose intolerance. However, symptoms are a poor marker of lactose maldigestion. AIMS: We assessed association between self-reported lactose intolerance and intestinal lactase, lactose intake, and the small intestinal microbiome. METHODS: Patients 18-75 years presenting for upper endoscopy were recruited prospectively. Observational study participants completed a lactose intolerance symptom questionnaire and reported lactose intake. Post-bulbar biopsies were obtained to measure lactase activity and assess the small intestinal mucosal microbiome. We compared intestinal lactase between patients with and without lactose intolerance. We assessed associations between lactose intolerance symptoms and lactase and lactose intake. We examined associations of small bowel microbial composition with self-reported lactose intolerance and symptoms. RESULTS: Among 34 patients, 23 (68%) reported lactose intolerance. Those with lactose intolerance had higher total symptom scores, more frequent bowel urgency, and more bowel movements after consuming dairy. The proportion of individuals with abnormal lactase activity did not differ by lactose intolerance status. Median lactase levels were correlated with total lactose intolerance symptom scores (p = 0.038) and frequency of bowel urgency (p = 0.012). Daily lactose intake did not differ between groups. In 19 patients, we observed significant associations of small intestinal microbiome beta diversity with stool consistency after consuming dairy (p = 0.03). CONCLUSIONS: Intestinal lactase is associated with lactose intolerance symptoms and bowel urgency in adults but does not distinguish the clinical phenotype entirely. Studying other contributing factors (microbiota, diet) may further clarify the pathophysiology of lactose intolerance.

Gastric peroral endoscopic myotomy for the treatment of refractory gastroparesis: a prospective single-center experience with mid-term follow-up (with video).

BACKGROUND AND AIMS: Gastroparesis (GP) is a multifactorial disease associated with a large burden on the health care systems. Pyloric-directed therapies including gastric peroral endoscopic myotomy (G-POEM) can be effective in improving patient quality of life and symptom severity. We report on the safety and efficacy of G-POEM and its impact on the quality of life of patients managed at a large referral center. METHODS: Consecutive patients with confirmed GP referred for G-POEM due to failure of medical therapy were included. All patients were assessed at baseline and then at 1, 3, 6, and 12 and 24 months after G-POEM using validated symptom and quality of life instruments, including the Gastroparesis Cardinal Symptom Index (GCSI), Patient Assessment of Gastrointestinal Disorders Symptom Severity Index (PAGI-SYM), and 36-Item Short Form Survey (SF-36). Patients were evaluated before and 6 months after the procedure with EGD, 4-hour scintigraphy, and pyloric EndoFLIP. Technical success was defined as the ability to perform full-thickness pyloromyotomy. Clinical response was defined as an improvement of ≥1 point on GCSI. RESULTS: Fifty-two patients (median age, 48 years; range, 25-80 years, 88% female) underwent G-POEM between February 2018 and September 2020 for the following phenotypes: vomiting-predominant (n=30), dyspepsia-predominant (n=16), and regurgitation-predominant (n=6) GP. The technical success rate was 100%. Adverse events were noted in 3 of 52 patients (5.77%), and were all managed successfully endoscopically. Clinical response was achieved in 68%, 58%, and 48% of patients at 1-month, 6-month, and 12-month follow-up (P < .001, P < .001, and P < .01, respectively). When classified by the cause of GP, the clinical response rates were diabetic GP 64% (11 of 17), postsurgical GP 67% (6 of 9), and idiopathic GP 72% (13 of 18). A statistically significant improvement in PAGI-SYM scores was observed at 1, 3, 6, 12, and 24 months, in addition to significant improvement in several domains of SF-36. Mean 4-hour gastric emptying was reduced 6 months after G-POEM (10.2%) compared with baseline (36.5%, P < .001). We report a significant reduction in the number of emergency department visits and days spent in the hospital up to 24 months after G-POEM. CONCLUSIONS: G-POEM appears to be a safe and feasible treatment alternative for refractory GP with significant short-term and mid-term improvements in overall symptoms, quality of life scores, and health care utilization.

Delayed Gastric Emptying Is Not Associated with a Microbiological Diagnosis of Small Intestinal Bacterial Overgrowth.

BACKGROUND: Clinical symptoms of patients with small intestinal bacterial overgrowth (SIBO) may overlap with symptoms of gastroparesis. Prior studies suggest delayed small intestinal transit is associated with SIBO, but have not shown an association between delayed gastric emptying and SIBO. However, these studies have generally relied on the indirect method of breath testing to diagnose SIBO. AIMS: The aim of this study was to examine the association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. METHODS: In a single-center retrospective study of previous research participants who presented for small bowel enteroscopy for diagnostic evaluation of SIBO, we identified 73 participants who underwent gastric emptying study by scintigraphy. A microbiological diagnosis of SIBO was made in patients based on culture results of jejunal aspirates. Clinical symptoms were assessed using the total gastroparesis cardinal symptom index (GCSI) score. We compared delayed gastric emptying, 2- and 4-h gastric retention, and gastroparesis symptoms between patients with and without a microbiological diagnosis of SIBO. KEY RESULTS: Among 29 participants with SIBO and 44 without SIBO, 33 (45%) had evidence of delayed gastric emptying. There was no significant association between a microbiological diagnosis of SIBO and delayed gastric emptying by scintigraphy. Percent retained at 2 and 4 h, and total GCSI scores did not differ significantly between those with and without SIBO. CONCLUSIONS: Although delayed gastric emptying is common in patients with suspected SIBO, gastric emptying is not associated with a microbiological diagnosis of SIBO.

Impact of a ring-fitted cap on insertion time and adenoma detection: a randomized controlled trial.

BACKGROUND AND AIMS: Devices for flattening colon folds can improve polyp detection at colonoscopy. However, there are few data on the endoscopic ring-fitted cap (EndoRings; EndoAid, Caesarea, Israel). We sought to compare adenoma detection with EndoRings with that of standard high-definition colonoscopy. METHODS: This was a single-center, randomized controlled trial of 562 patients (284 randomized to EndoRings and 278 to standard colonoscopy) at 2 outpatient endoscopy units in the Indiana University Hospital system. Adenoma detection was the primary outcome measured as adenoma detection rate (ADR) and adenomas per colonoscopy (APC). We also compared sessile serrated polyp detection rate, insertion times, withdrawal times, and ease of passage through the sigmoid colon. RESULTS: EndoRings was superior to standard colonoscopy in terms of APC (1.46 vs 1.06, P = .025), but there were no statistically significant differences in ADR or sessile serrated polyp detection rate. Mean withdrawal time (in patients with no polyps) was shorter and insertion time (all patients) was longer in the EndoRings arm by 1.8 minutes and 0.75 minutes, respectively. One provider had significantly higher detection with Endo-Rings and contributed substantially to the overall results. CONCLUSIONS: EndoRings can increase adenoma detection without a significant increase in procedure time, but the effect varies between operators. The use of EndoRings slows colonoscope insertion. (Clinical trial registration number: NCT03418662.).

Risk Factors Associated With Upper Aerodigestive Tract or Coliform Bacterial Overgrowth of the Small Intestine in Symptomatic Patients.

INTRODUCTION: The clinical relevance of bacterial types identified in small bowel aspirate cultures during diagnostic evaluation of small intestinal bacterial overgrowth (SIBO) is unclear. AIM: The main purpose of this study was to assess associations between risk factors for upper aerodigestive tract (UAT) or coliform SIBO and SIBO diagnosis by culture. MATERIALS AND METHODS: Small bowel aspirates were cultured in patients with suspected SIBO, defined as ≥10 colony-forming units/mL coliform or ≥10 colony-forming units/mL UAT bacteria. History was reviewed for risk factors and potential SIBO complications. Symptoms, quality of life, psychological traits, and laboratory values were assessed. We compared groups by 2-sample t test, Wilcoxon rank sum test, and the Fisher exact test. Overall associations of primary and secondary endpoints with type of bacterial overgrowth were assessed by analysis of variance F-test, Kruskal-Wallis test, and the Fisher exact tests. Associations of risk factors with type of overgrowth were explored using multinomial logistic regression. RESULTS: Among 76 patients, 37 had SIBO (68% coliform, 33% UAT) and 39 did not. Conditions (P=0.02) and surgery (P<0.01) associated with decreased gastric acid were associated with SIBO. In multinomial logistic regression, conditions of decreased acid was associated with UAT SIBO [odds ratio (OR), 5.8; 95% confidence interval, 1.4-33.3]. Surgery causing decreased acid was associated with UAT [OR, 9.5 (1.4-106)] and coliform SIBO [OR, 8.4 (1.6-86.4)]. Three patients with discontinuous small bowel had coliform SIBO [OR, 17.4 (1.2-2515)]. There were no differences in complications, overall symptoms, quality of life, or psychological traits. CONCLUSIONS: Conditions or surgeries associated with decreased gastric acid are associated with SIBO diagnosis by culture.

Validation of Diagnostic and Performance Characteristics of the Wireless Motility Capsule in Patients With Suspected Gastroparesis.

BACKGROUND & AIMS: It is a challenge to make a diagnosis of gastroparesis. There is good agreement in results from wireless motility capsule (WMC) analysis and gastric emptying scintigraphy (GES), but the diagnostic yield of WMC is unclear and the accuracy of this method has not been validated. We compared the performance characteristics of WMC vs GES in assessing gastric emptying in patients with suspected gastroparesis. METHODS: We performed a prospective study of 167 subjects with gastroparesis (53 with diabetes and 114 without) at 10 centers, from 2013 through 2016. Subjects were assessed simultaneously by GES and with a WMC to measure gastric emptying and regional transit. Delayed gastric emptying by GES was defined as more than 10% meal retention at 4 hrs whereas delayed gastric emptying by WMC was defined as more than 5 hrs for passage of the capsule into the duodenum; a severe delay in gastric emptying was defined as a gastric emptying time of more than 12 hrs by WMC or more than 35% retention at 4 hrs by GES. Rapid gastric emptying was defined as less than 38% meal retention at 1 hr based on by GES or gastric emptying times less than 1:45 hrs by WMC. We compared diagnostic and performance characteristics of GES vs WMC. RESULTS: Delayed gastric emptying was detected in a higher proportion of subjects by WMC (34.6%) than by GES (24.5%) (P=.009). Overall agreement in results between methods was 75.7% (kappa=0.42). In subjects without diabetes, the WMC detected a higher proportion of subjects with delayed gastric emptying (33.3%) than GES (17.1%) (P < .001). A higher proportion of subjects with diabetes had delayed gastric emptying detected by GES (41.7%) compared with non-diabetic subjects (17.1%) (P=.002). Severe delays in gastric emptying were observed in a higher proportion of subjects by WMC (13.8%) than by GES (6.9%) (P = .02). Rapid gastric emptying was detected in a higher proportion of subjects by GES (13.8%) than by WMC (3.3%) (P < .001). Regional and generalized transit abnormalities were observed in 61.8% subjects and only detected by WMC. CONCLUSION: Although there is agreement in analysis of gastric emptying by GES vs WMC, WMC provides higher diagnostic yield than GES. WMC detects delayed gastric emptying more frequently than GES and identifies extra-gastric transit abnormalities. Diabetic vs non-diabetic subjects have different results from GES vs WMC. These findings could affect management of patients with suspected gastroparesis. ClinicalTrials.gov no: NCT02022826.

Assessment of Small Intestinal Transit Times in Ulcerative Colitis and Crohn's Disease Patients with Different Disease Activity Using Video Capsule Endoscopy.

Small intestinal transit times (SITT) influence drug bioavailability. This study aimed to compare SITT in Crohn's disease and ulcerative colitis patients with non-inflammatory bowel disease (IBD) and to determine influence of disease activity on transit times, and in addition, to establish the utility of small bowel video capsule endoscopy (SB-VCE) in investigation of SITT in IBD patients. A retrospective review was performed on consecutive patients who had undergone SB-VCE at a university hospital out-patient clinic. In total, 125 non-IBD patients, 55 Crohn's disease patients, and 23 ulcerative colitis patients were included. SITT were calculated from the first duodenal image to the first cecal image. Disease activity was assessed based on endoscopy results and inflammatory markers (calprotectin, C-reactive protein, erythrocyte sedimentation rate). SITT were longer in ulcerative colitis patients compared to non-IBD patients (median 264 min vs. 216 min, p = 0.010). Patients with active Crohn's disease (n = 33) also displayed prolonged SITT compared to non-IBD patients (median 253 min vs 216 min, p = 0.017) and patients with quiescent Crohn's disease (n = 22) (p = 0.005). SITT can be prolonged in IBD patients depending on disease activity which may alter the drug release profiles and clinical response to colonic drug delivery systems. SB-VCE is a simple, non-invasive tool that can be utilized in pharmacokinetic studies to understand drug bioavailability in different patient groups. Moreover, this variability in transit times needs to be simulated in dissolution testing for in vitro in vivo correlations.

Narrow-band imaging versus white light for the detection of proximal colon serrated lesions: a randomized, controlled trial.

BACKGROUND: The value of narrow-band imaging (NBI) for detecting serrated lesions is unknown. OBJECTIVE: To assess NBI for the detection of proximal colon serrated lesions. DESIGN: Randomized, controlled trial. SETTING: Two academic hospital outpatient units. PATIENTS: Eight hundred outpatients 50 years of age and older with intact colons undergoing routine screening, surveillance, or diagnostic examinations. INTERVENTIONS: Randomization to colon inspection in NBI versus white-light colonoscopy. MAIN OUTCOME MEASUREMENTS: The number of serrated lesions (sessile serrated polyps plus hyperplastic polyps) proximal to the sigmoid colon. RESULTS: The mean inspection times for the whole colon and proximal colon were the same for the NBI and white-light groups. There were 204 proximal colon lesions in the NBI group and 158 in the white light group (P = .085). Detection of conventional adenomas was comparable in the 2 groups. LIMITATIONS: Lack of blinding, endoscopic estimation of polyp location. CONCLUSION: NBI may increase the detection of proximal colon serrated lesions, but the result in this trial did not reach significance. Additional study of this issue is warranted. ( CLINICAL TRIAL REGISTRATION NUMBER: NCT01572428.).

Therapeutic applications of ghrelin agonists in the treatment of gastroparesis.

There remains an unmet need for effective pharmacologic treatments for gastroparesis. Ghrelin is the endogenous ligand for the growth hormone secretagogue receptor and has been shown to regulate energy homeostasis and exert prokinetic effects on gastrointestinal motility. In recent years, several ghrelin receptor agonists have been studied in clinical trials of patients with diabetic gastroparesis. The intravenous macrocyclic peptidomimetic, TZP-101, initially suggested improvement in gastroparesis symptoms with intravenous administration when compared to placebo. However, in subsequent studies of oral preparations, TZP-102 failed to confirm these results. Another ghrelin receptor agonist, RM-131, was recently shown to significantly accelerate gastric emptying (GE) in patients with type 1 and type 2 diabetes and delayed GE. RM-131 reduced total Gastroparesis Cardinal Symptom Index-Daily Diary (GCSI-DD) and composite scores among type 1 diabetics. Continued development of ghrelin agonists should be explored in attempts to expand therapeutic options for the treatment of gastroparesis.

Balloon expulsion testing for the diagnosis of dyssynergic defecation in women with chronic constipation.

INTRODUCTION AND HYPOTHESIS: Dyssynergic defecation can be difficult to diagnose. Anorectal manometry and defecography are often used to make this diagnosis. However, these tests are expensive and require expertise. Balloon expulsion testing may be a simple alternative. We compared balloon expulsion to anorectal manometry and defecography for diagnosing dyssynergia in women with chronic constipation. METHODS: We conducted a retrospective review. All women presenting for evaluation of chronic constipation who underwent concurrent balloon testing, manometry, and defecography were included. A diagnosis of dyssynergic defecation was established by either defecography revealing prolonged/incomplete rectal evacuation and/or by manometry revealing paradoxical contraction/inadequate relaxation of the pelvic floor. Inability to expel a 50-ml balloon defined dyssynergic defecation by balloon testing. Sensitivity, specificity, and predictive values were calculated. RESULTS: A total of 61 women met inclusion criteria. Mean age was 50 years. There were 36 women (59 %) who met Rome III criteria for dyssynergic defecation on defecography and/or manometry. Only 12 of these 36 (33 %) were similarly diagnosed by balloon testing. The sensitivity and positive predictive value of balloon testing for dyssynergia were 33 and 71 %, respectively. Of the 25 (41 %) women who did not meet Rome III criteria for dyssynergia on defecography and/or manometry, 20 (80 %) also had negative balloon testing. Thus, the specificity and negative predictive value of balloon testing for diagnosing dyssynergia were 80 and 50 %, respectively. CONCLUSIONS: In our population, balloon expulsion was not an ideal screening test for dyssynergic defecation in women with constipation. Multimodal testing is necessary for more accurate diagnosis.

Predicting Response to Neuromodulators or Prokinetics in Patients With Suspected Gastroparesis Using Machine Learning: The "BMI, Infectious Prodrome, Delayed GES, and No Diabetes" Model.

INTRODUCTION: Pharmacologic therapies for symptoms of gastroparesis (GP) have limited efficacy, and it is difficult to predict which patients will respond. In this study, we implemented a machine learning model to predict the response to prokinetics and/or neuromodulators in patients with GP-like symptoms. METHODS: Subjects with suspected GP underwent simultaneous gastric emptying scintigraphy (GES) and wireless motility capsule and were followed for 6 months. Subjects were included if they were started on neuromodulators and/or prokinetics. Subjects were considered responders if their GP Cardinal Symptom Index at 6 months decreased by ≥1 from baseline. A machine learning model was trained using lasso regression, ridge regression, or random forest. Five-fold cross-validation was used to train the models, and the area under the receiver operator characteristic curve (AUC-ROC) was calculated using the test set. RESULTS: Of the 150 patients enrolled, 123 patients received either a prokinetic and/or a neuromodulator. Of the 123, 45 were considered responders and 78 were nonresponders. A ridge regression model with the variables, such as body mass index, infectious prodrome, delayed gastric emptying scintigraphy, no diabetes, had the highest AUC-ROC of 0.72. The model performed well for subjects on prokinetics without neuromodulators (AUC-ROC of 0.83) but poorly for those on neuromodulators without prokinetics. A separate model with gastric emptying time, duodenal motility index, no diabetes, and functional dyspepsia performed better (AUC-ROC of 0.75). DISCUSSION: This machine learning model has an acceptable accuracy in predicting those who will respond to neuromodulators and/or prokinetics. If validated, our model provides valuable data in predicting treatment outcomes in patients with GP-like symptoms.

Microbiota-Short Chain Fatty Acid Relationships Underlie Clinical Heterogeneity and Identify Key Microbial Targets in Irritable Bowel Syndrome (IBS).

Background: Identifying microbial targets in irritable bowel syndrome (IBS) and other disorders of gut-brain interaction (DGBI) is challenging due to the dynamic nature of microbiota-metabolite-host interactions. SCFA are key microbial metabolites that modulate intestinal homeostasis and may influence IBS pathophysiology. We aimed to assess microbial features associated with short chain fatty acids (SCFA) and determine if features varied across IBS subtypes and endophenotypes. Among 96 participants who were screened, 71 completed the study. We conducted in-depth investigations of stool microbial metagenomes, stool SCFA, and measurable IBS traits (stool bile acids, colonic transit, stool form) in 41 patients with IBS (IBS with constipation [IBS-C] IBS with diarrhea [IBS-D]) and 17 healthy controls. We used partial canonical correspondence analyses (pCCA), conditioned on transit, to quantify microbe-SCFA associations across clinical groups. To explore relationships between microbially-derived SCFA and IBS traits, we compared gut microbiome-encoded potential for substrate utilization across groups and within a subset of participants selected by their stool characteristics as well as stool microbiomes of patients with and without clinical bile acid malabsorption. Results: Overall stool microbiome composition and individual taxa abundances differed between clinical groups. Microbes-SCFA associations differed across groups and revealed key taxa including Dorea sp. CAG:317 and Bifidobacterium pseudocatenulatum in IBS-D and Akkermansia muciniphila and Prevotella copri in IBS-C that that may drive subtype-specific microbially-mediated mechanisms. Strongest microbe-SCFA associations were observed in IBS-D and several SCFA-producing species surprisingly demonstrated inverse correlations with SCFA. Fewer bacterial taxa were associated with acetate to butyrate ratios in IBS compared to health. In participants selected by stool form, we demonstrated differential abundances of microbial genes/pathways for SCFA metabolism and degradation of carbohydrates and mucin across groups. SCFA-producing taxa were reduced in IBS-D patients with BAM. Conclusion: Keystone taxa responsible for SCFA production differ according to IBS subtype and traits and the IBS microbiome is characterized by reduced functional redundancy. Differences in microbial substrate preferences are also linked to bowel functions. Focusing on taxa that drive SCFA profiles and stool form may be a rational strategy for identifying relevant microbial targets in IBS and other DGBI.

Predicting Response to Neuromodulators or Prokinetics in Patients with Suspected Gastroparesis Using Machine Learning: the "BIDnD" Model.

INTRODUCTION: Pharmacologic therapies for symptoms of gastroparesis have limited efficacy and it is difficult to predict which patients will respond. In this study, we implemented a machine-learning model to predict the response to prokinetics and/or neuromodulators in patients with gastroparesis-like symptoms. METHODS: Subjects with suspected gastroparesis underwent simultaneous gastric emptying scintigraphy (GES) and wireless motility capsule (WMC) and were followed for 6 months. Subjects were included if they were started on neuromodulators and/or prokinetics. Subjects were considered responders if their Gastroparesis Cardinal Symptom Index (GCSI) at 6 months decreased by ≥1 from baseline. A machine-learning model was trained using lasso regression, ridge regression or random forest. Five-fold cross-validation was used to train the models and the area under the receiver operator characteristic curve (AUC-ROC) was calculated using the test set. RESULTS: Of the 150 patients enrolled, 123 patients received either a prokinetic and/or a neuromodulator. Of the 123, 45 were considered responders and 78 were non-responders. A ridge regression model with the variables: BMI, Infectious prodrome, delayed GES, no diabetes (BIDnD), had the highest AUC-ROC of 0.72. The model performed well for subjects on prokinetics without neuromodulators (AUC-ROC of 0.83) but poorly for those on neuromodulators without prokinetics. A separate model with GET, duodenal MI, no diabetes, and functional dyspepsia performed better (AUC-ROC of 0.75). DISCUSSION: This machine learning model has an acceptable accuracy in predicting those who will respond to neuromodulators and/or prokinetics. If validated, our model provides valuable data in predicting treatment outcomes in patients with gastroparesis-like symptoms.