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BACKGROUND: Diabetes type 1 and type 2 may develop gastrointestinal complications e.g., gastroparesis and gastroenteropathy. Concomitant celiac disease and pancreatic exocrine insufficiency occur with high prevalence in diabetes and with symptomatic overlap. Consequently, it is a challenge to disentangle symptoms of these conditions and separate them from functional dyspepsia. We aim to develop a clinical decision-support tool to differentiate the underlying disease in a plethora of gastrointestinal symptoms.METHODS: An internet-based computerized survey will collect basic characteristics (diabetes type, age, gender, duration, HbA1c, treatment) and patient reported outcomes by validated questionnaires focusing on (1) gastroparesis using Gastroparesis Cardinal Symptom Index; (2) gastroenteropathy using Gastrointestinal Symptom Rating Scale; (3) celiac disease using Celiac Symptom Index and (4) pancreatic exocrine insufficiency with Pancreatic Exocrine Insufficiency Questionnaire. Logistic regression and multiple regression analyses will identify risk factors and gastrointestinal complications. Cluster analyses and machine learning will classify different symptoms and co-existing presentations, into a likely diagnosis. We seek biomarkers for autonomic neuropathy by characterizing development of retinopathy using the Visual Function Questionnaire-25 and peripheral neuropathy by the Michigan neuropathy questionnaire. Participants are re-examined yearly for disease progression over time.RESULTS: From focus group studies gastrointestinal symptoms are of major concern in diabetes. Potentially, estimates of symptom prevalence, risk factor identification and classifications of gastrointestinal complications can be unraveled for feedback to health care providers.CONCLUSION: The web-based DICODI project will open up possibilities to detect gastrointestinal complications of diabetes in a societal setting, benefitting people living with diabetes, health care professionals, and society.

Background and AimsGhrelin is an endogenous appetite-stimulating peptide hormone with potential cardiovascular benefits. Effects of acylated (activated) ghrelin were assessed in patients with heart failure and reduced ejection fraction (HFrEF) and in ex vivo mouse cardiomyocytes.Methods and resultsIn a randomized placebo-controlled double-blind trial, 31 patients with chronic HFrEF were randomized to synthetic human acyl ghrelin (0.1 µg/kg/min) or placebo intravenously over 120 min. The primary outcome was change in cardiac output (CO). Isolated mouse cardiomyocytes were treated with acyl ghrelin and fractional shortening and calcium transients were assessed. Acyl ghrelin but not placebo increased cardiac output (acyl ghrelin: 4.08 ± 1.15 to 5.23 ± 1.98 L/min; placebo: 4.26 ± 1.23 to 4.11 ± 1.99 L/min, P < 0.001). Acyl ghrelin caused a significant increase in stroke volume and nominal increases in left ventricular ejection fraction and segmental longitudinal strain and tricuspid annular plane systolic excursion. There were no effects on blood pressure, arrhythmias, or ischaemia. Heart rate decreased nominally (acyl ghrelin: 71 ± 11 to 67 ± 11 b.p.m.; placebo 69 ± 8 to 68 ± 10 b.p.m.). In cardiomyocytes, acyl ghrelin increased fractional shortening, did not affect cellular Ca2+ transients, and reduced troponin I phosphorylation. The increase in fractional shortening and reduction in troponin I phosphorylation was blocked by the acyl ghrelin antagonist D-Lys 3.ConclusionIn patients with HFrEF, acyl ghrelin increased cardiac output without causing hypotension, tachycardia, arrhythmia, or ischaemia. In isolated cardiomyocytes, acyl ghrelin increased contractility independently of preload and afterload and without Ca2+ mobilization, which may explain the lack of clinical side effects. Ghrelin treatment should be explored in additional randomized trials.Clinical Trial RegistrationClinicalTrials.gov Identifier: NCT05277415

Background: Electronic medical records (EMRs) are adopted for storing patient-related healthcare information. Using data mining techniques, it is possible to make use of and derive benefit from this massive amount of data effectively. We aimed to evaluate validity of data extracted by the Customized eXtraction Program (CXP). Methods: The CXP extracts and structures data in rapid standardised processes. The CXP was programmed to extract TNFα-native active ulcerative colitis (UC) patients from EMRs using defined International Classification of Disease-10 (ICD-10) codes. Extracted data were read in parallel with manual assessment of the EMR to compare with CXP-extracted data. Results: From the complete EMR set, 2,802 patients with code K51 (UC) were extracted. Then, CXP extracted 332 patients according to inclusion and exclusion criteria. Of these, 97.5% were correctly identified, resulting in a final set of 320 cases eligible for the study. When comparing CXP-extracted data against manually assessed EMRs, the recovery rate was 95.6–101.1% over the years with 96.1% weighted average sensitivity. Conclusion: Utilisation of the CXP software can be considered as an effective way to extract relevant EMR data without significant errors. Hence, by extracting from EMRs, CXP accurately identifies patients and has the capacity to facilitate research studies and clinical trials by finding patients with the requested code as well as funnel down itemised individuals according to specified inclusion and exclusion criteria. Beyond this, medical procedures and laboratory data can rapidly be retrieved from the EMRs to create tailored databases of extracted material for immediate use in clinical trials.

Background Irritable bowel syndrome (IBS) has been associated with diets rich in fermentable oligo-, di-, monosaccharides and polyols (FODMAPs), and gluten. Most previous studies have been single-blind and have focused on elimination of FODMAPs or provocation with single FODMAPs. The effect of gluten is unclear, large trials isolating the effect of gluten from that of FODMAPs are needed. Objective The aims of this study were to ensure high intakes of a wide range of FODMAPs, gluten, or placebo, and to evaluate the effects on IBS symptoms using the IBS severity scoring system (IBS-SSS). Methods The study was carried out with a double-blind, placebo-controlled, randomized three-way crossover design in a clinical facility in Uppsala in September 2018-June 2019. In all, 110 participants fulfilling the IBS Rome IV criteria, with moderate to severe IBS, were randomized; 103 (90 female, 13 male) completed the trial. Throughout, IBS participants maintained a diet with minimal FODMAP content and no gluten. Participants were block-randomized to one-week interventions with FODMAPs (50 g/day), gluten (17.3 g/day), or placebo, separated by one week washout. All participants who completed at least one intervention were included in the intention-to-treat analysis. Results In participants with IBS (n = 103), FODMAPs caused higher IBS-SSS scores (mean 240 [95% CI 222, 257]) than placebo (198 [180, 215]; 0.00056) or gluten (208 [190, 226]; P = 0.013); no differences were found between the placebo and gluten groups (P = 1.0). There were large inter-individual differences in IBS-SSS scores associated with treatment. No adverse events were reported. Conclusion In participants with IBS, FODMAPs had a modest effect on typical IBS symptoms, whereas gluten had no effect. The large inter-individual differences in responses to the interventions warrant further detailed studies to identify possible underlying causes and enable individual prediction of responses. Trial registration www.ClinicalTrials.gov (NCT03653689).

Objective: Determine diagnostic accuracy of a quantitative faecal immunochemical haemoglobin test (QuikRead go (R) FIT, Orion Diagnostica Oy) in symptomatic patients referred for colonoscopy, at various cut-offs and for one or two tests. Methods: Patients referred to four endoscopy units in mid-Sweden between 2013 and 2017 provided information on lower abdominal symptoms and faecal samples from two separate days prior to colonoscopy. Results: In all, 5.4% (13/242) patients had colorectal cancer (CRC). For one FIT at cut-off 10 mu g Hb/g faeces, sensitivity for CRC was 92% (95% CI 78-100%) and specificity 77% (95% CI 72-83%); equal to 74%; 95% CI 68-80 (178/242) colonoscopies potentially avoidable and one CRC missed. Based on the maximal outcome of two FITs, sensitivity was 100%, specificity 71% (66-77%) and 68%; 95% CI 62-74 (160/237) colonoscopies potentially avoidable. Among 17% (42/242) patients with one FIT of >200 mu g Hb/g faeces, 85% (11/13) had CRC. Positive predictive values of FIT varied 16.9-26.2% depending on cut-off and one or two FITs, whereas NPVs were 99% and above in all scenarios. In 60 patients reporting rectal bleeding, one FIT at cut-off 10 mu g Hb/g discriminated well between CRC and other conditions (p = .001). In regression models, FIT was more important than age, sex and all symptoms. Conclusion: One or two FITs in symptomatic patients referred for colonoscopy imply powerful risk stratification abilities for CRC, even among patients reporting rectal bleeding. Larger studies in various settings will clarify how to make the best use of this opportunity.

Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms. Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE >= 1 cm, The Prague C/M-classification with a minimum length of 1 cm. Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE >= 1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49-8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85-5.00), or CLE >= 1 cm (OR: 1.64, CI: 0.77-3.49). Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).

Background: Fecal calprotectin (FC) and serum C-reactive protein (CRP) are biomarkers of disease activity in Crohn's disease (CD) and ulcerative colitis (UC). We assessed FC, CRP, Harvey-Bradshaw index (HBi), partial Mayo Clinic Scoring (pMCS) and a cytokine panel during infliximab induction to predict therapy outcome. Methods: FC, CRP and clinical indices were evaluated in 123 (76 CD, 47 UC) patients before infliximab induction and after 12 weeks. Responders were monitored 48 weeks for an 'incident' (dosage increase, shortened dosage interval, surgery). Cutoff values for FC and CRP were obtained using receiver-operating characteristics (ROC). Disease progression was analyzed with Kaplan-Meier survivals, log-rank test and logistic regression for combined biomarkers. Cytokines were analyzed with Luminex multiplexing system. Results: Following infliximab, FC and CRP declined (p < .0001) along with HBi for CD and pMCS for UC. Simultaneously, IL-6 and TNF-alpha decreased, while IL-10 increased. Optimal FC ROC cutoff was 221 mu g/g (sensitivity 66%, specificity 67%, AUC 0.71) and CRP ROC cutoff 2.1 mg/L (sensitivity 54%, specificity 60%, AUC 0.58). In CD, FC > 221 mu g/g (p < .0001), but not CRP > 2.1 mg/L predicted an 'incident'. However, combined FC and CRP also predicted an 'incident' (p < .042). In UC, both FC > 221 mu g/g (p < .0005) and CRP > 2.1 mg/L (p = .0334) predicted 'incident', as did combined biomarkers (p < .005). Conclusions: Clinical disease activity is reduced by treatment with infliximab. In CD, persistently high FC, but not CRP, predict a treatment 'incident', whereas in UC both high FC and high CRP predict 'incident'. Combined FC and CRP values also predict an 'incident'.

Background: Delayed gastric emptying may impairʟ-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption ofʟ-dopa and symptoms of PD. Methods: Phase II, double‐blind, placebo‐controlled trial. Participants were randomized to receive camicinal 50 mg once‐daily (n = 38) or placebo (n = 20) for 7 to 9 days. Results:ʟ-dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximumʟ-dopa concentration was reduced, indicating more rapid absorption ofʟ-dopa. Camicinal resulted in significant reduction in OFF time (–2.31 hours; 95% confidence interval: –3.71, –0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS‐UPDRS score (–12.5; 95% confidence interval: –19.67, ‐5.29). Camicinal treatment was generally well tolerated. Conclusions: PD symptom improvement with camicinal occurred in parallel with more rapid absorption ofʟ-dopa. This study provides evidence of an improvement of the motor response toʟ-dopa in people with PD treated with camicinal 50 mg once‐daily compared with placebo, which will require further evaluation.

Objectives: The clinical relevance of small to moderate sliding hiatal hernias is controversial. The aims of the present study were to (1) investigate which symptoms are associated with sliding hiatal hernias and (2) define the length of a sliding hiatal hernia at which gastrointestinal symptoms occur. Methods: A study population representative of the general Swedish population answered a questionnaire regarding gastrointestinal symptoms and was investigated with an upper endoscopy. The length of any sliding hiatal hernia was measured. Results: Only reflux-related symptoms were associated with length of the hiatal hernia (acid regurgitation OR 1.46, CI 1.19–1.79, heartburn OR 1.27, CI 1.05–1.54), and the association did not become significant until an axial hiatal hernia length of 2 cm. Conclusions: Only reflux symptoms could be attributed to sliding hiatal hernias. Hiatal hernias less than 2 cm should be considered clinically insignificant.

Introduction: Helicobacter-induced atrophic gastritis with a hypochlorhydric milieu is a risk factor for gastric cancer. Microbes colonising acid-free stomach oxidise ethanol to acetaldehyde, a recognised group 1 carcinogen. Objective: To assess gastric production of acetaldehyde and its inert condensation product, non-toxic 2-methyl-1,3-thiazolidine-4-carboxylic acid (MTCA), after alcohol intake under treatment with slow-release L-cysteine or placebo. Methods: Seven patients with biopsy-confirmed atrophic gastritis, low serum pepsinogen and high gastrin-17 were studied in a cross-over single-blinded design. On separate days, patients randomly received 200 mg slow-release L-cysteine or placebo with intragastric instillation of 15% (0.3 g/kg) ethanol. After intake, gastric concentrations of ethanol, acetaldehyde, L-cysteine and MTCA were analysed. Results: Administration of L-cysteine increased MTCA (p

OBJECTIVE: This 1-year study aimed to assess low-dose budesonide therapy for maintenance of clinical remission in patients with collagenous colitis.DESIGN: A prospective, randomised, placebo-controlled study beginning with an 8-week open-label induction phase in which patients with histologically confirmed active collagenous colitis received budesonide (Budenofalk, 9 mg/day initially, tapered to 4.5 mg/day), after which 92 patients in clinical remission were randomised to budesonide (mean dose 4.5 mg/day; Budenofalk 3 mg capsules, two or one capsule on alternate days) or placebo in a 12-month double-blind phase with 6 months treatment-free follow-up. Primary endpoint was clinical remission throughout the double-blind phase.RESULTS: Clinical remission during open-label treatment was achieved by 84.5% (93/110 patients). The median time to remission was 10.5 days (95% CI (9.0 to 14.0 days)). The maintenance of clinical remission at 1 year was achieved by 61.4% (27/44 patients) in the budesonide group versus 16.7% (8/48 patients) receiving placebo (treatment difference 44.5% in favour of budesonide; 95% CI (26.9% to 62.7%), pCONCLUSIONS: Budesonide at a mean dose of 4.5 mg/day maintained clinical remission for at least 1 year in the majority of patients with collagenous colitis and preserved health-related quality of life without safety concerns. Treatment extension with low-dose budesonide beyond 1 year may be beneficial given the high relapse rate after budesonide discontinuation.TRIAL REGISTRATION NUMBERS: http://www.clinicaltrials.gov (NCT01278082) and http://www.clinicaltrialsregister.eu (EudraCT: 2007-001315-31).

Whole-grain rye foods reduce appetite, insulin and sometimes glucose responses. Increased gut fermentation and plant protein may mediate the effect. The aims of the present study were to investigate whether the appetite-suppressing effects of whole-grain rye porridge could be enhanced by replacing part of the rye with fermented dietary fibre and plant protein, and to explore the role of gut fermentation on appetite and metabolic responses over 8 h. We conducted a randomised, cross-over study using two rye porridges (40 and 55 g), three 40-g rye porridges with addition of inulin:gluten (9:3; 6:6; 3:9 g) and a refined wheat bread control (55 g), served as part of complete breakfasts. A standardised lunch and anad libitumdinner were served 4 and 8 h later, respectively. Appetite, breath hydrogen and methane, glucose, insulin and glucagon-like peptide-1 (GLP-1) responses were measured over 8 h. Twenty-one healthy men and women, aged 23–60 years, with BMI of 21–33 kg/m2participated in this study. Before lunch, the 55-g rye porridges lowered hunger by 20 % and desire to eat by 22 % and increased fullness by 29 % compared with wheat bread (PPPPad libitumfood intake, insulin or GLP-1. We conclude that no further increase in satiety was observed when replacing part of the rye with inulin and gluten compared with plain rye porridges.

Irritable bowel syndrome is a chronic gastrointestinal disorder characterized by abdominal pain and altered bowel habits in the absence of organic disease. We present 2 cases where diarrhea-predominant irritable bowel syndrome occurred in association with earlier intestinal infection or antibiotic treatment. Both were successfully treated with instillation of an anaerobic cultivated human intestinal microbiota. Thereafter, they were symptom free for at least 12 months. We now introduce the term dysbiotic bowel syndrome covering cases where a disturbed intestinal microbiota is assumed to be present. We recommend that restoration of the dysbiotic gut microbiota should be first-line treatment in these conditions.

BACKGROUND: Although organoboronic acids are efficient high-throughput sugar sensors, they have not been pursued for gut permeability studies. A modification of the lactulose/mannitol assay is described by which small intestinal permeability is assessed at the time of urine collection using a lactulose/riboflavin ratio. METHODS: Volunteers ingested 50mg riboflavin and either 5g mannitol or 10g lactulose. Urine was collected for 6hrs. Riboflavin was assayed by autofluorescence. Riboflavin was removed by C18 solid phase extraction. Lactulose and mannitol were then assayed using 1,1'-bis(2-boronobenzyl)-4,4'-bipyridinium (4,4'oBBV) coupled to the fluorophore HPTS. RESULTS: The temporal profile over 6hrs for riboflavin paralleled mannitol. Riboflavin recovery in urine was 11.1±1.9 % (mean±SEM, n=7), similar to mannitol. There was selective binding of 4,4'oBBV to lactulose, likely involving cooperativity between the fructose and galactose moieties. Lower limits of detection and quantification were 90 and 364μM. The lactulose assay was insensitive to other permeability probes (e.g., sucrose, sucralose) while tolerating glucose or lactose. This assay can be adapted to automated systems. Stability of 4,4'oBBV exceeds 4years. CONCLUSIONS: Riboflavin measured by autofluorescence combined with lactulose measured with 4,4'oBBV represents a useful new chemistry for rapid measurement of intestinal permeability with excellent stability, cost and throughput benefits. De två första författarna delar första författarskapet.

Background Eating disorders during pregnancy can affect fetal growth and the child’s early development, but the underlying mechanisms have not been elucidated. The aim of the present study was to investigate serum biomarkers of nutrition and stress in pregnant women with previous eating disorders compared to controls and in relation to head circumference and early neurocognitive development of the offspring. Methods In a longitudinal cohort study, pregnant nulliparous non-smoking women with a history of anorexia nervosa (n = 20), bulimia nervosa (n = 17) and controls (n = 59) were followed during pregnancy and their children’s growth and neurocognitive development were followed up to five years of age. We investigated maternal serum biomarkers of nutrition and stress (ferritin, cortisol, thyroid-stimulating hormone, free thyroxine, insulin, insulin-like growth factor I (IGF-I) and IGF binding protein 1) in blood samples collected during early pregnancy and compared between groups (ANOVA, LSD post-hoc test). The results were related to previous data on head circumference at birth and neurocognitive development at five years of age of the offspring (Spearman rank correlation or Pearson correlation test). Results Serum levels of ferritin in the women with previous anorexia nervosa, but not in those with a history of bulimia nervosa, were significantly lower than in the controls (p < 0.01), and correlated strongly to impaired memory function in their children (rs = −0.70, p < 0.001). Maternal serum levels of free thyroxine were similar between groups but correlated positively to reduced head circumference at birth of the children in the bulimia nervosa group (r = 0.48, p < 0.05), and with the same tendency in the anorexia nervosa group (r = 0.42, p = 0.07), but not in the controls (r = 0.006). There were no significant differences in cortisol or the other biomarkers between groups. Conclusions Low maternal serum ferritin in women with previous anorexia nervosa may be of importance for impaired memory capacity in the offspring at five years of age. Our results also indicate that thyroxin levels in pregnant women with previous eating disorders are positively associated with fetal head growth. Electronic supplementary material The online version of this article (doi:10.1186/s12884-015-0741-7) contains supplementary material, which is available to authorized users.