Treatment of non-constipated irritable bowel syndrome with the histamine 1 receptor antagonist ebastine: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: We evaluated the histamine 1 receptor antagonist ebastine as a potential treatment for patients with non-constipated irritable bowel syndrome (IBS) in a randomised, placebo-controlled phase 2 study. METHODS: Non-constipated patients with IBS fulfilling the Rome III criteria were randomly assigned to 20 mg ebastine or placebo for 12 weeks. Subjects scored global relief of symptoms (GRS) and abdominal pain intensity (API). A subject was considered a weekly responder for GRS if total or obvious relief was reported and a responder for API if the weekly average pain score was reduced by at least 30% vs baseline. The primary endpoints were the proportion of subjects who were weekly responders for at least 6 out of the 12 treatment weeks for both GRS and API ('GRS+API', composite endpoint) and for GRS and API separately. RESULTS: 202 participants (32±11 years, 68% female) were randomly allocated to receive ebastine (n=101) or placebo (n=101). Treatment with ebastine resulted in significantly more responders (12%, 12/92) for GRS+API compared with placebo (4%, 4/87, p=0.047) while the proportion of responders for GRS and API separately was higher for ebastine compared with placebo, although not statistically significant (placebo vs ebastine, GRS: 7% (6/87) vs 15% (14/91), p=0.072; API: 25% (20/85) vs 37% (34/92), p=0.081). CONCLUSIONS: Our study shows that ebastine is superior to placebo and should be further evaluated as novel treatment for patients with non-constipated IBS. TRIAL REGISTRATION NUMBER: The study protocol was approved by the local ethics committee of each study site (EudraCT number: 2013-001199-39; ClinicalTrials.gov identifier: NCT01908465).

Fecal Microbiota Transplantation Reduces Symptoms in Some Patients With Irritable Bowel Syndrome With Predominant Abdominal Bloating: Short- and Long-term Results From a Placebo-Controlled Randomized Trial.

BACKGROUND & AIMS: Irritable bowel syndrome (IBS) is a functional gastrointestinal disorder associated with intestinal dysbiosis. Given the reported promising results of open-label fecal microbiota transplantation (FMT) therapy in patients with predominant abdominal bloating, we studied efficacy of this treatment in a randomized, placebo-controlled trial. METHODS: Patients with refractory IBS, defined as failure of ≥3 conventional therapies, were randomly assigned to single-dose nasojejunal administration of donor stools (n = 43) or autologous stools (n = 19) in a double-blind study, performed from December 2015 through October 2017, and were followed up for 1 year. IBS-related symptoms were assessed by using a daily symptom diary to determine general abdominal discomfort, abdominal bloating, abdominal pain, and flatulence on a scale of 1-6. Number of daily bowel movements, consistency of the stools, and abdominal circumference were also recorded. Patients completed the IBS-specific quality of life questionnaire. Primary endpoints were improvement of IBS symptoms and bloating at 12 weeks (response). Secondary endpoints were changes in IBS symptom scores and quality of life. Stool samples were collected for microbiota amplicon sequencing. Open-label retransplantation was offered after the trial. RESULTS: At week 12, 56% of patients given donor stool reported improvement in both primary endpoints compared with 26% of patients given placebo (P = .03). Patients given donor stool had significant improvements in level of discomfort (mean reduction, 19%; median score before FMT, 3.98; range, 2.13-6.00; median score after FMT, 3.1; range, 951.29-5.90), stool frequency (mean reduction, 13%; median score before FMT, 2.10; range, 0.57-14.29; median score after FMT 1.7; range, 0.71-4.29), urgency (mean reduction, 38%; median score before FMT, 0.61; range, 0.00-1.00; median score after FMT, 0.37; range, 0.00-1.00), abdominal pain (mean reduction, 26%; median score before FMT, 3.88; range, 1.57-5.17; median score after FMT, 2.80; range, 1.14-4.94), flatulence (mean reduction, 10%; median score before FMT, 3.42; range, 0.71-6.00; median score after FMT, 3.07; range, 0.79-4.23), and quality of life (mean increase, 16%; median score before FMT 32.6; range, 11-119; median score after FMT, 43.1; range, 32.25-99). A significantly higher proportion of women given donor stool (69%) had a response than men (29%) (P = .01). Fecal samples from responders had higher diversity of microbiomes before administration of donor material than fecal samples from nonresponders (P = .04) and distinct baseline composition (P = .04), but no specific marker taxa were associated with response. After single FMT, 21% of patients given donor stool reported effects that lasted for longer than 1 year compared with 5% of patients given placebo stool. A second FMT reduced symptoms in 67% of patients with an initial response to donor stool but not in patients with a prior nonresponse. CONCLUSIONS: In a randomized trial of patients with treatment-refractory IBS with predominant bloating, FMT relieved symptoms compared with placebo (autologous transplant), although the effects decreased over 1 year. A second FMT restored the response patients with a prior response. Response was associated with composition of the fecal microbiomes before FMT; this might be used to as a biomarker to select patients for this treatment. ClinicalTrials.gov, Number: NCT02299973.

Efficacy and safety of radiofrequency ablation of Barrett's esophagus in the absence of reimbursement: a multicenter prospective Belgian registry.

BACKGROUND: Radiofrequency ablation (RFA), combined with endoscopic resection, can be used as a primary treatment for low grade dysplasia, high grade dysplasia, and early esophageal adenocarcinoma (EAC) in Barrett's esophagus (BE). The aim of the Belgian RFA registry is to capture the real-life outcome of endoscopic therapy for BE with RFA and to assess efficacy and safety outside study protocols, in the absence of reimbursement. PATIENTS AND METHODS: Between February 2008 and January 2017, data from 7 different expert centers were prospectively collected in the registry. Efficacy outcomes included complete remission of intestinal metaplasia (CR-IM), complete remission of dysplasia (CR-D), and durability of remission. Safety outcomes included immediate and late adverse events. RESULTS: 684 RFA procedures in 342 different patients were registered. Of these, 295 patients were included in the efficacy analysis, with CR-IM achieved in 88 % and CR-D in 93 %, in per-protocol analysis; corresponding rates in intention-to-treat analysis were 82 % and 87 %, respectively. Sustained remission was seen in 65 % with a median (interquartile range) follow-up of 25 (12 - 47) months. No risk factors for recurrent disease were identified. Immediate complications occurred in 4 % of all procedures and 6 % of all patients, whereas late complications occurred in 9 % of all procedures and in 20 % of all patients. CONCLUSIONS: Data from the Belgian registry confirm that RFA in combination with endoscopic resection is an efficient treatment for BE with dysplasia or early EAC. In the absence of reimbursement, more rescue treatments are used, not compromising outcome. Since there is recurrent disease after CR-IM in 35 %, surveillance endoscopy remains necessary.

High post-operative pain scores despite multimodal analgesia in ambulatory anorectal surgery: a prospective cohort study.

Background: Ambulatory surgery for anorectal procedures has become widely accepted. Recent reviews recommend a multimodal approach to pain management. However, these recommendations are largely based on single intervention studies. Our goal was to evaluate post-operative pain in patients receiving a multimodal analgesic regimen. Methods: All patients undergoing an ambulatory anorectal procedure between December 2015 and September 2016 received a pain diary. Mean pain throughout the day and pain during defecation where recorded on day 0-14 and day 21 postoperatively using a numeric rating scale-11. Use of oral analgesics was also recorded. Results: Forty-two patients completed the pain diary. The use of local anesthetic infiltration did not result in a significant difference in pain scores in this study. Patients who received written information on postoperative pain management and hygienic measures had higher intake of oral analgesics. Despite receiving multimodal analgesic treatment, patients undergoing surgery for hemorrhoids or anal fissures reported pain scores ≥4 and used analgesics longer. Conclusion: A multimodal analgesic approach consisting of local anesthetic infiltration, multiple oral analgesics and written information seems to be insufficient for certain patient groups after ambulatory anorectal surgery. Especially patients undergoing surgery for hemorrhoids or an anal fissure should receive adequate analgesia. Pain during defecation is problematic and finding a solution for this problem remains challenging. Further research into the combined use of different analgesic modalities is recommended.

Bleeding Lesion of the Small Bowel: an Extensive Update Leaving No Stone Unturned.

PURPOSE OF REVIEW: Gastrointestinal bleeding originating from the small bowel (SB) poses a challenge to the treating gastroenterologist. Once diagnosed, management is not a walk in the park either. This review intends to summarize the current state-of-the-art evidence in a complete way with special attention for vascular and ulcerative lesions, to provide the reader with a clinical guide and flow chart towards SB bleeding. RECENT FINDINGS: Absence of SB bleeding lesions on CE does not directly yield better prognosis; although having a lower rebleeding rate the first 2 years, rebleeding in the long term is high. Push enteroscopy can play an early role in patients with SB bleeding if suspicion of angioectasia is high, since these lesions tend to be located in the proximal SB. Endoscopic management of angioectasia is, however, difficult and shows poor results. Capsule endoscopy (CE) or device-assisted enteroscopy (DAE) remain the diagnostic mainstay in SB bleeding, choosing one over the other based upon patient characteristics and expected lesions.

Safety and efficacy of faecal microbiota transplantation in patients with mild to moderate Parkinson's disease (GUT-PARFECT): a double-blind, placebo-controlled, randomised, phase 2 trial.

Background: Dysregulation of the gut microbiome has been implicated in Parkinson's disease (PD). This study aimed to evaluate the clinical effects and safety of a single faecal microbiota transplantation (FMT) in patients with early-stage PD. Methods: The GUT-PARFECT trial, a single-centre randomised, double-blind, placebo-controlled trial was conducted at Ghent University Hospital between December 01, 2020 and December 12, 2022. Participants (aged 50-65 years, Hoehn and Yahr stage 2) were randomly assigned to receive nasojejunal FMT with either healthy donor stool or their own stool. Computer-generated randomisation was done in a 1:1 ratio through permutated-block scheduling. Treatment allocation was concealed for participants and investigators. The primary outcome measure at 12 months was the change in the Movement Disorders Society-Unified Parkinson's Disease Rating Scale (MDS-UPDRS) motor score obtained during off-medication evaluations. Intention-to-treat analysis was performed using a mixed model for repeated measures analysis. This completed trial is registered on ClinicalTrials.gov (NCT03808389). Findings: Between December 2020 and December 2021, FMT procedures were conducted on 46 patients with PD: 22 in the healthy donor group and 24 in the placebo group. Clinical evaluations were performed at baseline, 3, 6, and 12 months post-FMT. Full data analysis was possible for 21 participants in the healthy donor group and 22 in the placebo group. After 12 months, the MDS-UPDRS motor score significantly improved by a mean of 5.8 points (95% CI -11.4 to -0.2) in the healthy donor group and by 2.7 points (-8.3 to 2.9) in the placebo group (p = 0.0235). Adverse events were limited to temporary abdominal discomfort. Interpretation: Our findings suggested a single FMT induced mild, but long-lasting beneficial effects on motor symptoms in patients with early-stage PD. These findings highlight the potential of modulating the gut microbiome as a therapeutic approach and warrant a further exploration of FMT in larger cohorts of patients with PD in various disease stages. Funding: Flemish PD patient organizations (VPL and Parkili), Research Foundation Flanders (FWO), Biocodex Microbiota Foundation.

Comprehensive RNA dataset of tissue and plasma from patients with esophageal cancer or precursor lesions.

In the past decades, the incidence of esophageal adenocarcinoma has increased dramatically in Western populations. Better understanding of disease etiology along with the identification of novel prognostic and predictive biomarkers are urgently needed to improve the dismal survival probabilities. Here, we performed comprehensive RNA (coding and non-coding) profiling in various samples from 17 patients diagnosed with esophageal adenocarcinoma, high-grade dysplastic or non-dysplastic Barrett's esophagus. Per patient, a blood plasma sample, and a healthy and disease esophageal tissue sample were included. In total, this comprehensive dataset consists of 102 sequenced libraries from 51 samples. Based on this data, 119 expression profiles are available for three biotypes, including miRNA (51), mRNA (51) and circRNA (17). This unique resource allows for discovery of novel biomarkers and disease mechanisms, comparison of tissue and liquid biopsy profiles, integration of coding and non-coding RNA patterns, and can serve as a validation dataset in other RNA landscaping studies. Moreover, structural RNA differences can be identified in this dataset, including protein coding mutations, fusion genes, and circular RNAs.

Classifying perianal fistulising Crohn's disease: an expert consensus to guide decision-making in daily practice and clinical trials.

Perianal fistulising Crohn's disease is an aggressive disease phenotype that can have a substantial detrimental impact on patients' quality of life. Current biological understanding of perianal fistulising Crohn's disease remains inadequate and previous classification systems have not provided clear guidance on therapy in clinical practice nor on defining patient cohorts within clinical trials. We propose a new classification system for perianal fistulising Crohn's disease that was developed through a modified nominal group technique expert consensus process. The classification identifies four groups of patients. Key elements include stratification according to disease severity as well as disease outcome; synchronisation of patient and clinician goals in decision making, with a proactive, combined medical and surgical approach, on a treat to patient goal basis; and identification of indications for curative fistula treatment, diverting ostomy, and proctectomy. The new classification retains an element of flexibility, in which patients can cycle through different classes over time. Furthermore, with each specific class comes a paired treatment strategy suggestion and description of clinical trial suitability. The proposed classification system is the first of its kind and is an important step towards tailored standardisation of clinical practice and research in patients with perianal fistulising Crohn's disease.

Health Literacy and Quality of Life in Young Adults From The Belgian Crohn's Disease Registry Compared to Type 1 Diabetes Mellitus.

Background and Aims: The management of chronic inflammatory bowel diseases in youth is challenging. We aimed to determine health literacy (HL), quality of life (QoL) and clinical outcomes in young adults from the BELgian CROhn's disease registry (BELCRO) in comparison to type 1 diabetes mellitus (DM) as a control. Methods: In this prospective and observational study, young adults with Crohn's disease (CD) diagnosed < 18 years and with > 5 years disease duration and a comparable group of patients with DM completed validated HL, QoL and work productivity and activity impairment questionnaires (HLS-EU-Q16, EQ-5D-5L and WPAI). HL was scored as sufficient (13-16), problematic (9-12) or inadequate (0-8). QoL was dichotomized into "no problems" (EQ-5D level 1) or "problems" (EQ-5D levels 2 to 5). Non-parametric (Mann-Whitney U) analyses and Spearman correlations were performed. Results: A total of 52 CD (median [IQR] age of 25.0 [23.8-27.0], 64% male) and 50 DM (age 20.0 [19.0-22.0], 50% male) patients were included. HL was 14.0 [11.0-16.0] for CD and 14.0 [11.3-14.8] for DM (p = 0.6) with similar proportions of sufficient (60 vs. 68%, p = 0.4), problematic (34 vs. 26%, p = 0.3) and inadequate HL (both 6%, p = 1). Although QoL was comparable for CD and DM (77.0 [68.8-82.0] vs. 75.0 [65.0-80.0] %, p =0.4), CD had a trend for higher pain/discomfort (50 vs. 32%, p = 0.06). HL and QoL correlated in CD (r = 0.6, p < 0.001) and DM patients (r = 0.6, p < 0.001). Fewer CD patients with recent hospitalization/surgery had sufficient HL (31 vs. 69%, p = 0.01) and had lower QoL (70.0 [60.0-77.0] vs. 80.0 [70.0-85.0], p = 0.04) compared to those without. Conclusions: Selected young Belgian adults suffering from CD for >5 years have similar and sufficient HL compared to DM patients. However, CD patients requiring hospitalization/surgery have lower HL, which indicates the need for targeted educational programs.

The use of Faecal Microbiota Transplantation (FMT) in Europe: A Europe-wide survey.

BACKGROUND: Faecal microbiota transplantation (FMT) is an emerging treatment modality, but its current clinical use and organisation are unknown. We aimed to describe the clinical use, conduct, and potential for FMT in Europe. METHODS: We invited all hospital-based FMT centres within the European Council member states to answer a web-based questionnaire covering their clinical activities, organisation, and regulation of FMT in 2019. Responders were identified from trials registered at clinicaltrials.gov and from the United European Gastroenterology (UEG) working group for stool banking and FMT. FINDINGS: In 2019, 31 FMT centres from 17 countries reported a total of 1,874 (median 25, quartile 10-64) FMT procedures; 1,077 (57%) with Clostridioides difficile infection (CDI) as indication, 791 (42%) with experimental indications, and 6 (0•3%) unaccounted for. Adjusted to population size, 0•257 per 100,000 population received FMT for CDI and 0•189 per 100,000 population for experimental indications. With estimated 12,400 (6,100-28,500) annual cases of multiple, recurrent CDI and indication for FMT in Europe, the current European FMT activity covers approximately 10% of the patients with indication. The participating centres demonstrated high safety standards and adherence to international consensus guidelines. Formal or informal regulation from health authorities was present at 21 (68%) centres. INTERPRETATION: FMT is a widespread routine treatment for multiple, recurrent CDI and an experimental treatment. Embedded within hospital settings, FMT centres operate with high standards across Europe to provide safe FMT. A significant gap in FMT coverage suggests the need to raise clinical awareness and increase the FMT activity in Europe by at least 10-fold to meet the true, indicated need. FUNDING: NordForsk under the Nordic Council and Innovation Fund Denmark (j.no. 8056-00006B).

Colonic transit time in mentally retarded persons.

INTRODUCTION: Constipation is frequently seen in patients with mental retardation (MR). Its pathophysiology is poorly understood. Measurement of colon transit time (CTT) differentiates between retentive and non-retentive constipation. AIM: To determine total and segmental CTT in MR patients compared to healthy controls. METHOD: Of 250 residents, 60 patients older then 16, without swallowing disorder or scoliosis, are randomly chosen, 58 participated (intelligence quotient < 50, median age 35.5 year, 29 male). Constipation was defined as less than three defecations a week. Controls are 32 non-constipated age-matched healthy volunteers (median age 29 year, 19 male). CTT is measured by daily administration of ten radio-opaque markers during 6 days and abdominal X-ray on day 7. CTT is calculated using Bouchoucha's [7] method. RESULTS: Compared to controls, total CTT is significantly (P < 0.001) longer in MR (median 22.8 h vs. 57.6 h, respectively). Of the MR patients, 21/58 (36%) are constipated. The mental retardated and constipated (MRC) have a significant prolonged CTT in all segments (P < 0.01; median right CTT 19.2 h vs. 4.8 h; left CTT 14.4 h vs. 4.8 h; rectosigmoidal CTT 42 h vs. 9.6 h), whereas in mental retarded non-constipated (MRNC) persons, the rectosigmoidal CTT is prolonged (median 21.6 h vs. 9.6 h). CONCLUSION: Patients with moderate to deep MR have a significantly prolonged total CTT. In MRNC persons, rectosigmoidal CTT prolongation suggests a defecation problem. In MRC, CTT is prolonged in all segments, suggesting diffuse colonic inertia problem.

Clinical implications of decision making in colorectal polypectomy: an international survey of Western endoscopists suggests priorities for change.

Introduction Colonoscopy prevents colorectal cancer via the detection and resection of premalignant polyps. This effect may be attenuated by variations in polypectomy, with multiple techniques available and a wide range of experience amongst endoscopists. We assessed current practice against the best available contemporary evidence. Methods An online survey was distributed to members of the gastroenterological and surgical societies of seven countries during July 2017. Images of colorectal polyps were presented and respondents requested to provide the polypectomy technique they would employ in their daily practice. Responses were compared to the evidence-based techniques in the 2017 ESGE Colorectal Polypectomy Guideline. Results In total, 707 endoscopists (627 physicians, 71 surgeons, 9 nurse endoscopists, median practice duration 18 years) completed the survey. Of these, 3.1 % selected hot biopsy forceps and 5.2 % hot snare polypectomy (without submucosal lifting) to remove a 3 mm ascending colon polyp. Only 43.3 % selected cold snare polypectomy (CSP) to remove an 8 mm ascending colon polyp. Surgical referral was selected by 16.7 % of respondents for a 45 mm transverse colon polyp without endoscopic evidence of submucosal invasive cancer (SMIC). Endoscopic resection was selected by 12.0 % for an 80 mm sigmoid polyp with imaging consistent with deep SMIC, and a further 26.4 % selected tertiary endoscopist referral, suggesting they had not appreciated that it was endoscopically unresectable. Conclusion CSP is underutilized for small polyp resection despite its favorable safety and efficacy. Benign polyps are commonly referred for surgery and overt SMIC is underappreciated using endoscopic imaging. Addressing these issues may reduce diathermy-related adverse events, surgery, and unnecessary colonoscopic procedures for patients and reduce rates of post-colonoscopy colorectal cancer.

Self-medication of upper gastrointestinal symptoms: a community pharmacy study.

BACKGROUND: Upper gastrointestinal (GI) symptoms are a common reason for self-treatment with over-the-counter (OTC) medication. However, data are scarce on the typology of GI complaints for which individuals seek self-medication and, more importantly, on the prevalence of alarm symptoms in this population. OBJECTIVE: To investigate: (1) the nature of GI symptoms that people intend to self-medicate, (2) prevalence of alarm symptoms, (3) adherence to referral advice given by the pharmacist, and (4) self-reported efficacy and frequency of use of OTC medication for minor complaints. METHODS: This descriptive study was performed in 63 community pharmacies. Participants (N = 592, aged 18-82 y) completed a questionnaire to assess symptom characteristics and previous medical consulting. Based on this information, the pharmacist referred subjects to a physician or advised self-treatment. Four weeks later, participants were presented a follow-up questionnaire evaluating their adherence to referral advice or efficacy of self-treatment. RESULTS: The most frequently reported GI symptoms were burning retrosternal discomfort (49.2%), acid regurgitation (53.2%), and bothersome postprandial fullness (51.2%). At least one alarm symptom was present in 22.4% of the individuals, with difficulty in swallowing being the most prevalent (15.4%). Although 21% of the customers were referred, only 51.7% of these contacted a physician. Almost all (95.1%) of the remaining customers who were advised self-treatment reported symptom relief with the OTC drug obtained. CONCLUSIONS: Mild GI symptoms will mostly resolve with self-treatment. Yet, the value of pharmacist counseling on OTC treatment should be recognized, as community pharmacists can play an important role in distinguishing symptoms that warrant further medical examination.