Reduced Stool Frequency Research Articles

103-OR: The Glucagon-Like Peptide-1 Analog, Liraglutide Is a Safe and Effective Treatment of Bile Acid Malabsorption: A Proof of Concept Study

Bile acid malabsorption (BAM) is caused by excessive spill-over of bile acids to the colon and is estimated to affect ∼1% of the general population. It is a socially debilitating disease with watery diarrhea and high stool frequency as main symptoms. BAM is diagnosed by the 75selenium homotaurocholic acid test (SeHCAT) measuring the retention of bile acids. Bile acid sequestrant (BAS) treatment, which is the only recommended treatment of BAM, is associated with poor effect and low compliance. Case reports suggest that the glucagon-like peptide 1 receptor analog (GLP-1RA) liraglutide may be an effective treatment of BAM. In this double-blind, double-dummy, non-inferiority study, nondiabetic individuals with SeHCAT-verified BAM, age 18-75 years and BMI 18.5-40 kg/m2 were randomized to receive the GLP-1RA liraglutide (uptitrated to 1.8 mg per day) or the BAS colesevelam (1.875 mg × 2 per day) for 6 weeks prior to a 7-day run-in period without treatment. SeHCAT was made at baseline, week 3 and week 6. The primary outcome was the proportion of patients experiencing a reduction in stool frequency of ≥25% per day. Of 52 randomized subjects (18 males, 34 females, mean age 50.2 years and BMI 29.9 kg/m2), one patient from each group dropped out due to gastrointestinal side effects. At end-of-treatment, 20 (77%) individuals on liraglutide had experienced a reduction in stool frequency of ≥25% per day vs. 13 (50%) on colesevelam treatment, corresponding to a statistically superior risk difference of -0.27 (one-sided 95% CI: -1; -0.06). In contrast to the colesevelam-treated group, the liraglutide-treated group exhibited a significant increase in SeHCAT values resulting in significantly higher values at end-of-treatment (mean (SD) 8.9 (7.3) vs. 0.9 (2.0) %, P<0.0001). In conclusion, we show that liraglutide enhances the reabsorption of bile acids and constitutes a safe and effective treatment of BAM which is superior compared to current standard of care (colesevelam). Disclosure M. L. Kårhus: None. A. Brønden: None. J. Forman: None. A. Haaber: None. E. Langholz: None. T. Vilsbøll: Consultant; Self; Amgen Inc., AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Gilead Sciences, Inc., Lilly Diabetes, Merck Sharp & Dohme Corp., Mundipharma International, Novo Nordisk, Sanofi, Sun Pharmaceutical Industries Ltd. D. P. Sonne: None. F. K. Knop: Advisory Panel; Self; MSD Corporation, Novo Nordisk A/S, Sanofi, Consultant; Self; AstraZeneca, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, Novo Nordisk A/S, Pharmacosmos, Zealand Pharma A/S, Research Support; Self; Novo Nordisk A/S, Zealand Pharma A/S, Speaker’s Bureau; Self; AstraZeneca, Bayer AG, Boehringer Ingelheim Pharmaceuticals, Inc., Eli Lilly and Company, MSD Corporation, Novo Nordisk A/S. Funding Novo Nordisk Foundation (NNF17OC0029710); A.P. Møller and Chastine Mc-Kinney Møller Foundation (19-L-0002)

IN-VIVO ANTI-DIARRHOEAL ACTIVITY AND PHYTOCHEMICAL SCREENING OF ETHANOL STEM BARK EXTRACT OF VITELLARIA PARADOXA GAERTN F. (SAPOTACEAE)

Different parts of Vitellaria paradoxa plant have many applications in ethno-medicine. Some of the uses of this plant include treatment of diarrhoea and other GIT disorders. In this study the antidiarrhoeal activity of the ethanol extract of Vitellaria paradoxa was evaluated using three experimental models: Castor oil-induced diarrhoea; small intestinal motility and intestinal fluid accumulation (enteropooling) models in mice. Five groups of five mice were used for each model. Group one mice received 10 ml/kg of distilled water, while groups 2, 3, and 4 received 125, 250 and 500 mg/kg of the extract orally respectively. Group 5 mice received Loperamide 5 mg/kg orally. Oral median lethal dose (LD50) of the extract was determined using OECD (2008) Guideline 425. Phytochemical studies were conducted using standard procedures. The LD50 was estimated to be greater than 5000 mg/kg body weight and there were no signs of mortality or visible signs of toxicity in all the mice treated. Phytochemical screening revealed the presence of carbohydrates, alkaloids, flavonoids, saponins, tannins, triterpenes, steroids, cardiac glycosides and anthraquinones glycosides. Extract showed a dose-dependent anti-diarrhoeal activity by reducing stool frequency and consistency. The extract at the higher doses significantly (p < 0.05) inhibited GIT motility and castor oil-induced enteropooling, comparable to that of the reference control drug Loperamide. The study showed that ethanol stem bark extract of Vitellaria paradoxa possess anti-diarrhoeal activity and thus justifies its ethno-medicinal use in the treatment of diarrhoea.

A short course of oral ranitidine as a novel treatment for toddler\u2019s diarrhea: a parallel-group randomized controlled trial

BackgroundThe current paradigm for treating toddler’s diarrhea comprises dietary modification and fluid restriction. Previous studies show that probiotics and proton-pump inhibitors (PPIs) or H2 blockers could control diarrhea associated with functional gastrointestinal disorders (FGIDs). This study aims to determine and compare the efficacy of a short course of oral ranitidine and a probiotic in the treatment of toddler’s diarrhea.MethodsThis study was a parallel-group randomized controlled trial (RCT). We sequentially enrolled 40 patients who met the eligibility criteria. We randomly assigned 20 patients to the oral ranitidine group, ten patients to the probiotic group, and ten patients to the placebo group. In the oral ranitidine group, patients received oral ranitidine (3 mg/kg/day) once daily for 10 days; in the probiotic and placebo groups, they were administered 5 to 10 billion colony-forming units (CFUs) per day of lyophilized Lactobacillus rhamnosus and 50 mg of once-daily oral vitamin C tablet respectively for 10 days. Stool frequency and consistency on the 10th day of the interventions were recorded as the primary outcomes. We used the Student’s t-test to determine if there were significant differences in the mean daily stool frequencies in the three intervention groups. A p-value < 0.05 was adopted as the level of statistical significance.ResultsIn the ranitidine group, stool frequency decreased significantly from an average of five per day on the first day to an average of approximately one per day on the 10th day of intervention (t = 10.462, p < 0.001). Additionally, stool consistency normalized on the 10th day of intervention. In the probiotic group, there was a significant reduction in stool frequency from an average of five per day on the first day to four per day on the 10th day (t = 2.586, p = 0.041), although stool consistency remained loose. However, stool consistency and frequency were not significantly affected in the placebo group (t = 1.964, p = 0.072).ConclusionOral ranitidine is more effective than probiotics in reducing stool frequency and normalizing stool consistency in toddler’s diarrhea. We recommend multi-center trials with appropriate study designs to confirm and validate this finding.Trial registrationISRCTN, ISRCTN10783996. Registered 8 April 2016-Registered retrospectively.

P687 Early and sustained improvement in stool frequency and rectal bleeding following 52 weeks of mirikizumab treatment

Abstract Background Interleukin (IL)-23 is a key cytokine in inflammatory bowel disease pathogenesis. Mirikizumab (miri), a p19-directed IL-23 antibody, demonstrated efficacy and was well-tolerated in patients with moderate-to-severely active ulcerative colitis (UC) during 52 weeks of a Phase 2 randomised clinical trial (AMAC, NCT02589665). The effects of miri on stool frequency (SF) and rectal bleeding (RB) through Week 52 are reported. Methods Patients (Mayo score 6–12 with endoscopic subscore [ES] ≥2) were randomised 1:1:1:1 to receive intravenous (IV) placebo (n = 63), miri 50 mg (n = 63) or 200 mg (n = 62) with possibility of exposure-based (EB) dose increases, or fixed miri 600 mg (n = 61) every 4 weeks (Q4W). Responders to miri at Week 12 (9-point Mayo score decrease ≥2 points and ≥35% change from baseline, with RB=0 or 1 or decrease ≥1) were re-randomised 1:1 into a double-blind maintenance period to receive miri 200 mg subcutaneously (SC) Q4W (n = 47) or every 12 weeks (Q12W; n = 46), and were treated through Week 52. Patients reported UC symptoms, including SF and RB, via a daily diary. Changes from baseline in average Mayo SF and RB subscores at Weeks 2, 4, and 12 were analysed using a mixed model repeated-measures method to account for missingness and baseline characteristics. Results Significant improvement in SF was observed as early as Week 2 in the miri 600 mg Q4W group and as early as Week 4 in the miri 200 mg Q4W group (Figure). Similarly, significant improvement in RB was observed as early as Week 2 in both the miri 200 mg Q4W and 600 mg Q4W groups. Patients who received miri 200 mg Q4W or 600 mg Q4W had a significantly greater reduction in both SF and RB compared with placebo at Week 12 (all p &amp;lt; 0.001) (Figure). Patients who achieved clinical response at Week 12 and were treated with miri 200 mg SC Q4W or SC Q12W maintained a low average SF and RB score at Week 52. Conclusion Significant improvements in SF and RB occurred as early as Week 2 of induction treatment and continued to improve during maintenance treatment with mirikizumab. These data demonstrate the early efficacy and longer-term effects of an IL-23p19 antibody on these patient-reported outcomes.

Surgical treatment of low anterior resection syndrome

Objective To compare functional outcomes of various rectal reconstruction after total mesorectal excision. Material and methods A prospective randomized trial included 90 patients with mid-to-low rectal carcinoma who underwent total mesorectal excision. Results There were 22 patients after J-pouch surgery, 30 patients with side-to-end anastomoses and 38 patients with end-to-end anastomoses. Eight patients (26.6%) required conversion of J-P to E-E (7 patients) and S-E (1) anastomosis for technical reasons. Postoperative morbidity was similar (13.6, 16.7 and 34.2% in J-P, S-E and E-E groups, respectively, p=0.705). Sensory threshold, earliest and constant defecation urge and maximal tolerable volume were higher for J-P surgery within 3-6-12 months after surgery. Stool frequency was significantly lower after J-P surgery compared to S-E and E-E anastomoses within 3-6-12 months. Wexner scores were 3, 5, 6 after 6 months (p 0.05). Evacuation dysfunction was observed in 59.1% with J-P, 33.3% with S-E and 21.1% with E-E anastomoses in 6 months after stoma closure. Conclusion J-pouch reconstruction demonstrates higher neorectal volume that ensures reduced stool frequency up to 12 months after stoma closure. However, technical challenges of J-pouch surgery and evacuation dysfunction restrain application of this procedure in clinical practice.

Clinical effects and safety of Compound Glutamine Entersoluble Capsules for diarrhea-predominant irritable bowel syndrome: A systematic review and meta-analysis

IntroductionDiarrhea-predominant irritable bowel syndrome (IBS-D) is a gastrointestinal disease with a high incidence and no effective drugs available. Compound Glutamine Entersoluble Capsules (CGEC) is a compound preparation integrating Sijunzi Decoction and L-Glutamine. The aim of this systematic review was to evaluate the clinical effects and safety of CGEC for IBS-D. MethodsPubMed, Web of Science, the Cochrane library, CNKI, VIP and Wanfang Databases were searched from inception to June 30, 2019. Randomized controlled trials (RCTs) assessing the clinical effects and safety of CGEC for IBS-D were included. Global improvement of IBS-D symptoms was used as the primary outcome. The data were analyzed by RevMan5.3 software. Risk ratio (RR) calculations and 95% confidence intervals (CI) were used for dichotomous outcomes, and mean difference (MD) with 95% CI were used for continuous outcomes. ResultsTwelve RCTs involving 1232 participants were included. Compared with western conventional medicine (WCM) alone (i.e. gastrointestinal spasmodic and probiotics), CGEC demonstrated no significant differences in global improvement of IBS-D symptoms (RR 1.09, 95% CI [0.97, 1.23]), reduction in stool frequency (MD 0.14, 95% CI [−0.18, 0.46]) and relief of abdominal pain (MD 0.12, 95% CI [−0.27, 0.52]). The combination of CGEC and WCM had advantages over WCM alone in terms of global improvement of IBS-D symptoms (RR 1.37, 95% CI [1.25, 1.49]). Regarding the recurrence rate, both the CGEC group and the combined drug group were lower than the WCM group. In terms of safety, there is currently no evidence to suggest that CGEC can cause adverse reactions/events in patients with IBS-D. ConclusionsLow or very low certainty evidence indicated that there was no difference between CGEC and WCM for the treatment of IBS-D. The combination of CGEC and WCM had a better therapeutic effect than WCM alone for the treatment of IBS-D.

2881 Can Eluxadoline Be Useful in Managing Patients With Functional Diarrhea?

INTRODUCTION: Eluxadoline is an FDA approved medication for use in patients with irritable bowel syndrome with diarrhea (IBS-d). It is a peripheral mu-opioid receptor agonist resulting in a reduction in colonic motility while antagonizing central delta receptors that modify pain and thus targets the two key components of IBS-d. Functional diarrhea (FD) is similar to IBS-d, but there is no pain with FD and there are currently no FDA approved medications for its treatment. This caseseries examines the efficacy of eluxadoline in managing FD. METHODS: Electronic medical records at a private gastroenterology clinic were reviewed from May 2015-present. Patients must have undergone diagnostic evaluation including stool elastase, lactoferrin, breath testing, celiac serology, and both upper and lower endoscopy with biopsies. Detailed clinical histories and medication reconciliation were also performed to exclude other causes for diarrhea. Patients found to have other FGIDs, IBD, bowel obstruction, malabsorption, or cholecystectomy were excluded. Patients must also have failed or demonstrated intolerance to OTC anti-diarrheals, dietary changes and supplemental fiber, and anticholinergics or tricyclics. Eligible patients were treated for 6 months with open label eluxadoline and clinical follow up was required. All patients began 100 mg bid, but were allowed to reduce the dose to 75 mg bid if constipation or abdominal discomfort occurred. There were 2 primary endpoints: Improvement in Bristol Stool Scale (BSS) and decrease in daily stool frequency by 30%. RESULTS: Eleven patients with FD were identified by Rome IV criteria and were included in the series. All completed 6 months of therapy with eluxadoline. Patients had a mean BSS of 6.2 (range 6-7) and mean daily stool frequency of 4.8 (range 3-10) at baseline. Eight patients (73%) satisfied both clinical endpoints with an average reduction in stool frequency to 2.8 (range: every other day to 4 per day). The mean BSS decreased from 6.2 to 4.2, with a range of 2-5. 2 patients developed constipation but responded to the lower dose. The remaining 3 patients (27%) showed moderate clinical improvement but did not meet one or both of the primary endpoints. CONCLUSION: 1. Eluxadoline may be an effective tool in managing FD where conventional therapy has failed. 2. The length of the trial demonstrated durability. 3. This open label case series should stimulate interest into funding a blinded placebo controlled trial.

2079 Coexistence of Lymphocytic Colitis in a Patient With Ulcerative Colitis

INTRODUCTION: Microscopic colitis (MC) is an inflammatory condition of the colon that is histologically divided into two different conditions, lymphocytic colitis (LC) and collagenous colitis. Initially suspected to be unrelated to inflammatory bowel disease, a growing body of evidence now suggests a common pathophysiology between MC and IBD. We describe a case report of a patient presenting with both LC and UC. CASE DESCRIPTION/METHODS: A 59-year-old Caucasian, nonsmoking female with a history of diabetes underwent a colonoscopy for evaluation of constipation which demonstrated significant colitis, consistent with UC. Her disease was managed with mesalamine however due to social restrictions, clinical follow up and management of her disease was limited. As part of age appropriate management, patient underwent routine screening colonoscopy 15 years after her initial diagnosis as an open access procedure. During the procedure patient was noted to have terminal ileum apthae with Mayo score 2 pancolitis. Random biopsies taken during the procedure demonstrated focal acute inflammation. In follow up clinic visit, patient endorsed having 3-4 non-bloody, loose bowel movements daily but was otherwise asymptomatic. She was started on balsalazide capsules with improvement in stool consistency and reduction in frequency of bowel movements. Shortly after starting balsalazide patient lost insurance access and was unable to follow up as directed. Patient returned to gastroenterology clinic two years later endorsing 4-5 non-bloody, loose bowel movements every day. Fecal calprotectin at this time was noted to be 26.7 mg/kg (normal &lt; 50 mg/kg) however due to ongoing symptoms balsalazide was restarted. Repeat colonoscopy was performed to evaluate for dysplasia and ongoing symptoms which demonstrated Mayo score 1 pancolitis. Random biopsies taken during the procedure demonstrated chronic active colitis with superimposed lymphocytic colitis. Patient was started on budesonide in addition to balsalazide with reduction in stool frequency and improvement in consistency. DISCUSSION: In literature, coexistence of UC and LC is described in 12 cases, typically in patients with complete remission of UC. Here we describe a case of active UC further complicated by lymphocytic colitis which was successfully managed with a combination of a 5-aminosalicyclic-acid derivative and glucocorticoids. This case emphasizes the importance of looking for alternative causes of symptoms in patients with mild colonoscopic findings.

The Clinical Efficacy of Multi-strain Probiotics in the Management of Acute Watery Diarrhoea of Children aged 2 Months to 5 Years-a Randomized Controlled Trial

Background: Acute gastroenteritis is considered as one of the most common causes of under-five morbidity and mortality worldwide. Standard treatment is the use of oral rehydration solution (ORS), intravenous fluid if indicated, and zinc supplement. Recently, the use of probiotics has been introduced as an adjunct to the treatment of acute gastroenteritis. The aim of this study is to determine the clinical efficacy of multi-strain probiotics as adjunct treatment of acute gastroenteritis.&#x0D; Methodology: A randomized controlled trial was done in 250 bed district Sadar Hospital, Brahmanbaria, Bangladesh from January 2016 to June 2017. After fulfilling the inclusion criteria, 507 children aged 2 months to 5 years were enrolled in this study. Those with dysentery, chronic diarrhea, diarrhea due to known genetic disorder, chronic illness, malnutrition, systemic infection, CNS disorder and congenital malformation were excluded. Children were divided into two groups randomly. One group was With Probiotic, zinc and standard WHO (ORS) as case and other group was Without Probiotic, zinc and standard WHO ORS as control.&#x0D; Results: Among 507 children, 257 were without probiotic while 250 were with probiotic. The mean difference in stool frequency between the two groups were 3.3 after 24 hours, 3.5 after 48 hours and 1.6 after 72 hours after hospitalization which was statistically significant (p=0.000). Reduction of stool frequency was highest after 48 hours of admission. Mean duration of hospital stay was 4.40±1.22 days in control and 4.03±.89 days in case group. Probiotic group children with exclusive breastfeeding had mean recovery time of 3.95±0.85 days and those who were not exclusively breastfeed had recovery time of 4.2±0.95 days (p=0.025).&#x0D; Conclusion: Probiotic is efficacious in reducing purging duration and frequency of acute watery diarrhea in children.&#x0D; Bangladesh J Child Health 2019; VOL 43 (2) :97-101

Effects of Conventional Milk Versus Milk Containing Only A2 β-Casein on Digestion in Chinese Children: A Randomized Study.

ABSTRACTObjectives:In this study, we hypothesized that replacing conventional milk, which contains A1 and A2 β-casein proteins, with milk that contains only A2 β-casein in the diet of dairy or milk-intolerant preschoolers (age 5 to 6 years) would result in reduced gastrointestinal symptoms associated with milk intolerance, and that this would correspond with cognitive improvements.Methods:This randomized, double-blind, crossover study aimed to compare the effects of 5 days’ consumption of conventional milk versus milk containing only A2 β-casein on gastrointestinal symptoms, as assessed via visual analog scales, average stool frequency and consistency, and serum inflammatory and immune biomarkers in healthy preschoolers with mild-to-moderate milk intolerance. The study also aimed to compare changes in the cognitive behavior of preschoolers, based on Subtle Cognitive Impairment Test scores.Results:Subjects who consumed milk containing only A2 β-casein had significantly less severe gastrointestinal symptoms as measured by visual analog scales, reduced stool frequency, and improvements in stool consistency, compared with subjects consuming conventional milk. There were significant increases from baseline in serum interleukin-4, immunoglobulins G, E, and G1, and beta-casomorphin-7 coupled to lower glutathione levels, in subjects consuming conventional milk compared with milk containing only A2 β-casein. Subtle Cognitive Impairment Test analysis showed significant improvements in test accuracy after consumption of milk containing only A2 β-casein. There were no severe adverse events related to consumption of either milk product.Conclusions:Replacing conventional milk with milk containing only A2 β-casein reduced gastrointestinal symptoms associated with milk intolerance in Chinese preschool children, with corresponding improvements in aspects of cognitive performance.

A cross-sectional study of stool form (using Bristol stool chart) in an urban South Indian population.

BackgroundThere is paucity of data on Bristol stool form (BSF) in healthy South Indian residents.AimTo determine the BSF types and associated factors in an urban bowel health noncomplainant population.MethodsThis cross‐sectional study, performed using a self‐administered questionnaire among adult Chennai residents, compared BSF types by gender for various factors (age, occupation, bowel frequency, and defecation‐related abdominal pain). BSF types 1/2 and 6/7 were grouped as hard and loose stools, respectively. The statistical tests used were proportion test, χ 2, and Kruskal–Wallis tests (P < 0.05 deemed significant).ResultsThe study cohort of 1402 subjects included 748 (53.3%) men and a third each of professionals, semiprofessionals, and “non‐office goers” (homemakers, retirees, students, and unemployed). A total of 97% had daily bowel movement, and 8.5% reported defecation associated abdominal pain. The BSF types in decreasing prevalence were: Type 3 (35.6%), Type 4 (32.5%), Types 1 or 2 (20.5%), Type 5 (6.9%), and Types 6 or 7 (4.5%). On gender comparison, significantly more men passed hard (P = 0.03) or loose stools (P = 0.001), while more women passed Type 3 (P = 0.0002). Loose stools in men were associated with abdominal pain (P = 0.0035). Women passing hard or loose stool types were slightly older (median age in 30s vs. 20s in Types 3–5) and had reduced stool frequency (P = 0.026: hard; P = 0.006: loose).ConclusionsThis South Indian noncomplainant cohort's most common stool types were BSF Types 3 and 4, with few gender variations in extreme stool types.

Bovine colostrum and product intervention associated with relief of childhood infectious diarrhea

This meta-analysis aimed to investigate the protective effects of bovine colostrum against childhood infectious diarrhea. A systematic search was conducted using PubMed, Cochrane Library databases and clinicaltrial.gov. Among 166 research articles, only five RCTs were included into final analysis. Review manager (version 5.2) was used to pool the effect-size across studies. Sensitivity and risk of bias were estimated accordingly. Under a pooled analysis, bovine colostrum consumption correlated with a significant reduction in stool frequency of infectious diarrhea, by 1.42 times per day (95% CI: −2.70, −0.14). Bovine colostrum intervention also reduced occurrence of diarrhea by 71% (pooled OR = 0.29, 95%CI 0.16, 0.52). The OR of positive detection of pathogen in the stool was 0.29 (95%CI 0.08, 0.71) in bovine colostrum treated group, compared with placebo group. In the sensitivity analysis of studies with low risk of biases, bovine colostrum significantly reduced stool frequency, occurrence of diarrhea and pathogen detection. BC and related products have a significant benefit in reducing the frequency and relieving the symptoms of childhood infectious diarrhea.

Acetarsol in the management of mesalazine-refractory ulcerative proctitis: a tertiary-level care experience.

Mesalazine-refractory ulcerative proctitis is common, with a significant proportion of the patients requiring escalation to immunomodulators or biological therapy. Three small preliminary cohort studies suggested good clinical efficacy for the organic arsenic derivative acetarsol in the management of proctitis. Our aim was to describe our experience on the use of acetarsol in proctitis and to review all existing evidence on its safety and efficacy. We retrospectively reviewed clinical records of all ulcerative colitis patients exposed to acetarsol at Nottingham University Hospitals since 2012. Clinical response was determined basing on physicians' global assessments and patients' improvement over the baseline (reduction in stool frequency and rectal bleeding). Clinical remission was defined as total resolution of symptoms including bleeding cessation. Serum arsenic, C-reactive protein and faecal calprotectin levels reviewed when available. Nonparametric analysis performed. Twenty-eight (16 males) patients with median (range) age 39 (35) and 9 (19) years disease duration received acetarsol suppositories for proctitis. All had failed mesalazine or corticosteroid topical therapy, with 50% having additionally failed immunomodulators. Median treatment duration was 70 (64) days. 16/28 were prescribed acetarsol more than once. 67.9% achieved clinical response and 46.4% clinical remission. 32.1% required treatment escalation to steroids, thiopurines or antitumour necrosis factor agents. 6/28 patients stopped acetarsol due to side effects. Acetarsol could be an effective and safe option in the management of refractory proctitis. A definitive trial with long-term safety follow-up is required to investigate the efficacy and safety of this promising drug.

Efficacy of gelatin tannate for acute diarrhea in children: a systematic review and meta-analysis.

To investigate by meta-analysis the efficacy of gelatin tannate (GT), a mucosal barrier protector, in children with acute gastroenteritis. A comprehensive literature search was conducted. Studies were selected according to PICO: Participants: children aged 0-12 years with acute diarrhea; Intervention: GT; Comparison: oral rehydration solution and/or placebo; Outcomes: diarrhea-related outcomes. Three published randomized controlled trials were identified of pediatric diarrhea treated with GT (n=203) or control (n=204). GT significantly (p<0.01) reduced stool frequency at 12 h in two randomized controlled trials. A significant treatment effect (risk ratio=0.74; p<0.01) in favor of GT was found for the exploratory composite outcome of 'diarrhea or liquid stools at 24h' in three studies. Risk ratios in a single study which reported the percentage of patients with liquid stools at 12, 24 and 48 h favored GT at all time points. No significant differences were found between GT and control for patients with diarrhea at 12 or 24h or for duration of diarrhea. GT improved stool frequency and stool consistency in children with acute diarrhea, although further well-controlled studies would be useful to confirm a beneficial treatment effect.

Serum-derived bovine immunoglobulin for children with diarrhea-predominant irritable bowel syndrome.

BackgroundOral serum-derived bovine immunoglobulin (SBI)/protein isolate is a medical food intended to manage chronic diarrhea. It has been shown to improve pain and diarrhea in adults with diarrhea-predominant irritable bowel syndrome (d-IBS).AimTo determine if SBI can improve symptoms in children with d-IBS.MethodsWe performed a randomized, double-blind, placebo-controlled, pilot study (NCT02609529) to evaluate the effectiveness of SBI in children 8–18 years with d-IBS. We recorded stool number, abdominal pain, and stool form in all patients for 1 week and then assigned the patients at a ratio of 2:1 to treatment with SBI 5 g BID or placebo for 3 weeks. The patients and their parents completed the Pediatric Quality of Life Inventory™ for Gastrointestinal Symptoms (PedsQOL) and the Pediatric Functional Disability Index (FDI). In addition, complete blood counts and serum chemistries were recorded at the start and end of treatment to evaluate safety.ResultsFifteen patients (nine SBI, six placebo) completed the study. Both SBI and placebo groups reported nonstatistical reductions in stool frequency per week. The SBI group showed a significant reduction in stool frequency at weeks 1 and 2 but not at the end of treatment. The SBI group also demonstrated statistical improvements in abdominal pain and stool form by 3 weeks. The placebo group did not achieve similar improvements. The overall FDI and PedsQOL scores, as well as PedsQOL subscale scores for pain, discomfort when eating, diarrhea, worry about stomach aches, and communication, improved significantly in the SBI group, but not in the placebo group. No serious adverse events occurred. Serum chemistries and hemograms were normal at baseline and at the end of study in all patients.ConclusionIn this single-center, exploratory pilot study, we demonstrated that 10 g SBI per day was safe in children with d-IBS and improved symptoms. Larger studies, with longer treatment duration, seem warranted based on these initial positive results.

Asymptomatic Gastric Heterotopia in the Rectum? A Rare Finding with Unclear Malignant Risk

Introduction Gastric heterotopia (GHT) is the presence of normal gastric mucosa in extra-gastric regions in the gastrointestinal tract (GIT). The most common locations are the esophagus, duodenum, and Meckel's diverticulum, but rarely it may occur in the rectum resulting in symptoms and unclear long-term risk. Detailed Case Description We describe a case of a 27 year old, healthy woman, with a long-standing history of loose stools, up to 8 bowel movements per day, and bloating. After diagnostic workup including lactose-breath test, celiac screen, microbiologic, and endocrinologic work up as well as colonoscopy for microscopic colitis; the presumptive diagnosis was irritable bowel syndrome (IBS) - diarrhea subtype. Her colonoscopy revealed normal biopsies of the cecum, transverse colon; however, the rectum contained a well demarcated, erythematous region of approximately 1 inch diameter, adjacent to a prominent fold and resembling a flat polyp. Pathologic biopsy of the folds identified benign gastric mucosa and benign large intestinal mucosa respectively. The diagnosis of rectal GHT was made based on the presence of gastric oxyntic mucosa with chief, parietal, and foveolar cells. Hpylori was not seen. The patient's IBS was treated with diet and lifestyle intervention. Loperamide was used to reduce stool frequency. Repeat sigmoidoscopy 2 years later confirmed stable GHT in rectum. The patient responded well to a reduced gluten diet, and had resolution of her longstanding IBS. She remains stable 8 years after diagnosis with no active IBS symptoms, and no clinical concerns about her GHT. Discussion GHT distal to the foregut is believed to be caused by pluripotent stem cells abnormally differentiating into gastric mucosa. Common symptoms of GHT include abdominal pain and gastrointestinal bleeding but many cases are asymptomatic. A literature review demonstrates higher prevalence in males with a younger median age at diagnosis. Complications are more common in the pediatric population, while risk of malignant transformation is higher in adults. Treatment is with H2-receptor antagonists or proton-pump inhibitors for bleeding, or complete excision for refractory symptoms. Few cases of neoplastic changes are reported in the literature but further observation is needed to appreciate the risk and benefit of pre-emptive excision by surgery or endoscopic submucosal dissection.1614 Figure 1. Heterotopic gastric tissue in rectum

Characterization of ulcerative colitis-associated constipation syndrome (proximal constipation).

BackgroundThe syndrome of constipation with other abdominal symptoms (“proximal constipation”) in ulcerative colitis (UC) is commonly recognized by practitioners but is poorly described, with no recognized definition and little understanding with regard to prevalence and effect of therapies on disease outcomes. This study aimed to address these issues in a cross‐sectional, consecutive series of patients with UC.MethodsA working definition of proximal constipation was established. Consecutive patients were recruited, and their disease activity, recent medications, and investigations plus abdominal symptoms were assessed at a study visit. Relevant clinical data were also extracted from medical records.ResultsOf 125 patients with UC, (mean age 47, range 14–84 years, 61 male), 58 (46%) fulfilled the definition of proximal constipation. The main symptoms were reduced stool frequency (69%), hard stools (43%), abdominal pain (40%), excessive flatus (29%), straining (24%), and sensation of incomplete emptying (14%). Proximal constipation was associated with female gender (OR 3.45 [1.45–8.24]), left‐sided (OR 2.84 [1.14–7.11]) and concurrently active disease (OR 5.56 [1.96–16.67]), but not age, disease duration or therapy. A total of 88% had an increase in anti‐inflammatory therapy, with the use of laxatives or fiber supplements in 63% compared with 1.4% of those without proximal constipation.ConclusionsProximal constipation is common, and its risk increases in active and distal disease, especially in women. Validation of its definition and evaluation of therapeutic strategies are needed. A new term “ulcerative colitis‐associated constipation syndrome” is proposed to more accurately depict its nature.

The Role of Bile Acid Sequestrant in Diarrhea Management: Too Good to Be True?

Background: diarrhea can be caused by a wide range of conditions including malabsorption (e.g. Bile acid malabsorption (BAM)), infection (eg. Clostridium difficile (C. difficile)), other gastrointestinal diseases (e.g. ileal resection, bile acid overproduction, pancreatic insufficiency, bacterial overgrowth, cholecystectomy and malignancy), and even stress and anxiety. BAM is a condition associated with inability to effectively absorb bile in the small intestine which results in chronic diarrhea. is a bile acid sequestrant (BAS) with the potential to control chronic diarrhea induced by BAM and C. difficile infection. Objective: To explore the role of BAS in the management of chronic diarrhea and assess how the theoretical knowledge is supported by practical evidence. Methods: Ovid (MEDLINE, PsychInfo, Embase) was searched for Cholestyramine Resin” AND Chronic Diarrhea with limits on the years 1946 – present. 8 studies which were deemed to be relevant to the objective at hand were summarized. Additional sources from Grey literature search were added using the same research strategies. Results: The results showed positive therapeutic impact of BAS, particularly cholestyramine in reducing stool frequency regardless of type and severity of BAM-induced diarrhea. However, low tolerability of BAS due to adverse effects can limit its use in some patients. Conclusion: BAS was more likely to be a good option as a short-term medication to better control symptoms and prevent illness. Therapeutic effect of BAS in the management of chronic diarrhea can be considered in palliative care to benefit patients who can tolerate this medication although not without the existent controversies.

Post-operative outcome following ileal pouch-anal anastomosis (IPAA)

Background IPAA procedure is the surgery of choice in severe ulcerative colitis (UC) and familial adenomatous polyposis (FAP). The objectives of the study were to assess symptomatic improvement, complications, effect on sexual function and quality of life (QOL) following IPAA procedure. Methods Twenty one patients who underwent IPAA procedure at a tertiary care unit with a minimum of one year follow-up from 2009, were included. QOL was assessed retrospectively prior to surgery and one year after surgery using Cleveland Global Quality of Life Score (CGQLS). Details of pre and post-op symptoms, complications and sexual function were obtained using clinical records, operative notes and interviewer administered questionnaire. Results Male: female ratio was 1.33:1. Fourteen (66.7%) were sexually active and seven (33.3%) were not. Mean age was 40.48(range, 17-69) years. 13(61.9%) had UC and 8(38.1%) had FAP. Mean pre-op CGQL scores for UC and FAP were 0.5754 and 0.7537 respectively. Post-op CGQLS for UC and FAP were 0.7532 and 0.7070. There was no statistically significant difference between CGQL scores against the indication for surgery (P=0.779). Stool frequency was significantly reduced in UC (pre-op=12.4, post-op=5.2 per day, p=0.004) but no difference in FAP (pre-op=2.6, postop= 3.5 per day, p=0.292). Post-operatively, one patient developed erectile dysfunction and another patient developed dyspareunia. Conclusion There is no significant difference of CGQL scores following IPAA procedure in relation to the surgical indication. IPAA significantly reduced stool frequency per day in UC but not in FAP. Erectile dysfunction and dyspareunia are possible sexual dysfunctions following IPAA procedure.

Outcomes of Bismuth Subsalicylate Treatment in Patients With Microscopic Colitis

Introduction: Bismuth subsalicylate (BSS) is commonly used to treat microscopic colitis (MC) with limited data on response and recurrence rates from small clinical trials. We aimed to evaluate clinical response and recurrence to BSS for MC. Methods: Patients with collagenous colitis (CC) or lymphocytic colitis (LC) treated with BSS at a single tertiary care institution from 12/31/2001 to 12/31/2016 were included. MC was defined by presence of diarrhea with normal endoscopy and compatible histopathology. Complete response to BSS was defined as normalization of stool frequency and partial response was defined as at least 50% reduction in stool frequency from baseline at 8±2 weeks. Recurrence was defined by return of increased stool frequency with no alternative etiology after complete resolution. Results: Overall, 94 patients (91.4% female, median age 69.4 years; 49 (52%) had LC and 45 (48%) had CC) were treated with BSS with a median duration of follow-up of 2 years (range, 0.1-11 years). Fifty four (57.4%) had complete response, 20 (21.2%) had partial response, and 20 (21.2%) had no response. Of the 54 patients with complete response, 28 (51.8 %) had recurrence. The median time to recurrence was 12.5 weeks after stopping BSS. Of the patients with recurrence, 23 (82.1%) were retreated successfully with BSS, 3 (10.7%) with loperamide and 2 (7.1%) were treated with budesonide. There were no serious adverse events reported with BSS.On univariate analysis, there was evidence for a dose response, with a higher dose being associated with a higher rate of complete response (P=0.0025, Table 1). Moreover, response rates varied by MC subtype (with LC more likely to have a complete response than CC (67.3% vs 48.8%, P=0.003)), but not by age or diarrhea severity.On multivariate analysis after adjusting for age and gender, both a higher dose (P=0.0044) and presence of LC (P=0.03) were associated with a higher response to BSS. Recurrence rates were not dependent on dose (Table 1), number of baseline bowel movements per day or type of MC.Table: Table. Dose response and recurrence for BSS for MCConclusion: Patients with microscopic colitis treated with BSS have a high clinical response rate but also have a high risk of recurrence. A higher dose is associated with a higher response rate and patients with LC are more likely to respond compared to CC. A large prospective clinical trial is needed to evaluate the efficacy of BSS for MC patients.