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BACKGROUND: Bile acid diarrhoea is a common but overlooked cause of chronic watery diarrhoea. Plasma 7α-hydroxy-4-cholesten-3-one (C4) is an alternative to the gold standard tauroselcholic [75Se] acid (SeHCAT) test. Low-certainty evidence supports sequestrant treatment, including colesevelam. We aimed to determine the efficacy and safety of colesevelam in bile acid diarrhoea.METHODS: In this randomised, double-blind, placebo-controlled, investigator-initiated phase 4 trial of the sequestrant colesevelam in bile acid diarrhoea (SINBAD), we enrolled consecutive patients aged 18-79 years without inflammatory bowel disease attending SeHCAT testing for suspected bile acid diarrhoea at four Danish secondary care centres. Participants were randomly allocated 1:1 to receive 12 days of treatment with colesevelam (overencapsulated tablets of 625 mg) or placebo, with the starting dose of two capsules twice daily and titrated to effect during the first 5 days of treatment. A pharmacist independent of the clinical investigators generated a randomisation list on the web page randomization.com using block randomisation (randomisation was not stratified). C4 and SeHCAT diagnostic results were blinded during treatment. We treated all patients with diarrhoea, with a daily mean of 3·0 or more bowel movements or 1·0 or more watery bowel movements (Bristol stool scale type 6 and 7). Remission was defined as the absence of both these criteria during treatment days 6-12. The primary outcome was the intention-to-treat remission rate in bile acid diarrhoea diagnosed by C4 concentration greater than 46 ng/mL. A secondary outcome was the intention-to-treat remission rate in bile acid diarrhoea diagnosed by SeHCAT retention of 10% or less. This trial is registered with ClinicalTrials.gov, NCT03876717.FINDINGS: Between Oct 25, 2018, and July 1, 2021, 168 patients were randomly assigned to receive colesevelam (n=84) or placebo (n=84). 41 patients had C4 concentration greater than 46 ng/mL (22 assigned to the colesevelam group and 19 to the placebo group). For the C4-defined primary outcome, 14 (64%) of 22 participants receiving colesevelam versus three (16%) of 19 participants receiving placebo achieved remission (adjusted odds ratio 9·1, 95% CI 1·9-62·8; p=0·011). For the SeHCAT-defined secondary outcome, 75 of the 168 participants had retention of less than 10% (37 assigned to the colesevelam group and 38 assigned to the placebo group); 22 (59%) of 37 participants receiving colesevelam achieved remission versus five (13%) of 38 participants receiving placebo (adjusted odds ratio 11·1, 95% CI 3·4-45·6; p=0·00020). There were no serious adverse events. Common adverse events were transient. For patients receiving colesevelam within the primary outcome population, five had abdominal pain, nine had bloating, and four had nausea. For patients receiving placebo, four had abdominal pain, four had bloating, and one had nausea. No participants with bile acid diarrhoea withdrew due to adverse events.INTERPRETATION: Colesevelam was superior to placebo at inducing remission of bile acid diarrhoea diagnosed with C4 concentration greater than 46 ng/mL. Secondary outcome data suggest similar efficacy treating SeHCAT-defined bile acid diarrhoea. Colesevelam was safe during the treatment.FUNDING: Fabrikant Vilhelm Pedersen og hustrus mindelegat; recommended by the Novo Nordisk Foundation.

Background and aims: Incomplete microscopic colitis (MCi) is a subtype of microscopic colitis (MC). Budesonide is recommended as a first-line treatment for MC. However, randomised trials on efficacy of treatment in MCi are missing. We therefore performed a randomised, placebo-controlled trial to evaluate budesonide as induction therapy for MCi. Methods: Patients with active MCi were randomly assigned to either budesonide 9 mg once daily or placebo for 8 weeks in a double-blind, double-dummy design. The primary endpoint was clinical remission, defined as a mean of

Introduction Microscopic colitis is a chronic inflammatory bowel disease characterised by normal or almost normal endoscopic appearance of the colon, chronic watery, non-bloody diarrhoea and distinct histological abnormalities, which identify three histological subtypes, the collagenous colitis, the lymphocytic colitis and the incomplete microscopic colitis. With ongoing uncertainties and new developments in the clinical management of microscopic colitis, there is a need for evidence-based guidelines to improve the medical care of patients suffering from this disorder. Methods Guidelines were developed by members from the European Microscopic Colitis Group and United European Gastroenterology in accordance with the Appraisal of Guidelines for Research and Evaluation II instrument. Following a systematic literature review, the Grading of Recommendations Assessment, Development and Evaluation methodology was used to assess the certainty of the evidence. Statements and recommendations were developed by working groups consisting of gastroenterologists, pathologists and basic scientists, and voted upon using the Delphi method. Results These guidelines provide information on epidemiology and risk factors of microscopic colitis, as well as evidence-based statements and recommendations on diagnostic criteria and treatment options, including oral budesonide, bile acid binders, immunomodulators and biologics. Recommendations on the clinical management of microscopic colitis are provided based on evidence, expert opinion and best clinical practice. Conclusion These guidelines may support clinicians worldwide to improve the clinical management of patients with microscopic colitis. Funding Agencies|UEG Activity Grant

Anne-Marie Kanstrup Fiehn,1,2 Martin Kristensson,3 Ulla Engel,4 Lars Kristian Munck,5,6 Susanne Holck,4 Peter Johan Heiberg Engel1,6 1Department of Pathology, Roskilde Hospital, Roskilde, 2Department of Pathology, Copenhagen University Hospital, Rigshospitalet, Copenhagen, 3Digital Pathology, Visiopharm, Hørsholm, 4Department of Pathology, Copenhagen University Hospital, Hvidovre, 5Department of Gastroenterology, Koege Hospital, Koege, 6Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark Purpose: The aim of this study was to develop an automated image analysis software to measure the thickness of the subepithelial collagenous band in colon biopsies with collagenous colitis (CC) and incomplete CC (CCi). The software measures the thickness of the collagenous band on microscopic slides stained with Van Gieson (VG). Patients and methods: A training set consisting of ten biopsies diagnosed as CC, CCi, and normal colon mucosa was used to develop the automated image analysis (VG app) to match the assessment by a pathologist. The study set consisted of biopsies from 75 patients. Twenty-five cases were primarily diagnosed as CC, 25 as CCi, and 25 as normal or near-normal colonic mucosa. Four pathologists individually reassessed the biopsies and categorized all into one of the abovementioned three categories. The result of the VG app was correlated with the diagnosis provided by the four pathologists. Results: The interobserver agreement for each pair of pathologists ranged from Κ-values of 0.56–0.81, while theΚ-value for the VG app vs each of the pathologists varied from 0.63 to 0.79. The overall agreement between the four pathologists wasΚ=0.69, while the overall agreement between the four pathologists and the VG app wasΚ=0.71. Conclusion: In conclusion, the Visiopharm VG app is able to measure the thickness of a subepithelial collagenous band in colon biopsies with an accuracy comparable to the performance of a pathologist and thereby provides a promising supplementary tool for the diagnosis of CC and CCi and in particular for research. Keywords: microscopic colitis, collagenous colitis, incomplete collagenous colitis, automated image analysis

We explored the effects of fractioning heterogeneous bulk wheat by fast unsupervised single-kernel near-infrared (SKNIR) sorting according to an internal complex NIR functionality trait using a fast prototype kernel sorter designed for postharvest bulk sorting. Sorting into three functionality fractions was performed on low quality lots from an organic field experiment from two growth years and two locations. Sorted lots were mixtures originally diversified by three different preceding catch crops. The resulting 12 fractions, as well as the 12 original wheat lots were characterized by 20 standard quality variables of grains and flours. The data was analyzed by principal component analysis (PCA) and analysis of variance (ANOVA). Within each year and location/cultivar, the SKNIR fractionation had significant positive effect on bulk grain density, protein, wet gluten content, Zeleny sedimentation volume, farinograph water absorption, farinograph softening, falling number, gelatinization temperature,...

Transport of glycine, lysine and beta-alanine in rabbit, guinea pig and rat small intestine has been examined by measurements of the unidirectional influx across the brush border membrane of the intact epithelium. In rabbit distal ileum the chloride-dependent fraction of glycine transport, and all sodium- and chloride-dependent lysine transport is carried on the beta-alanine carrier. Lysine eliminates all saturable, sodium-independent transport of glycine. The saturable, sodium-dependent, and lysine resistant influx of glycine is characterized by a K1/2Gly of 60 mM. Glycine transport in the mid intestine of the guinea pig is chloride-independent and in the rat only a minute fraction may be chloride-dependent. These species do not possess an equivalent of the rabbit beta-alanine carrier. In conclusion, glycine transport in rabbit distal ileum is by the sodium-dependent carrier of neutral amino acids, by the sodium-independent lysine carrier, and by the sodium- and chloride-dependent beta-alanine carrier which closely resembles the B0,+ carrier described in mouse blastocysts. All sodium dependent lysine transport in rabbit distal ileum is by the chloride- and sodium-dependent beta-alanine carrier. It is proposed that the beta-alanine carrier in rabbit distal ileum be renamed the B0,+ carrier.