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Objectives The use of biologic therapy in inflammatory bowel disease (IBD) is likely to increase with lower costs and more biologics and biosimilars becoming available. Our aim was to estimate the trends in use of first-line biologics during the first year after diagnosis in a Norwegian IBD population from 2010 to 2016. Methods Data were collected from the Norwegian National Patient Registry and Norwegian Prescription Database. Patients defined as incident IBD cases between 2010 and 2016 were included and followed for 12 months. Patients were stratified by year of diagnosis to examine change over time. Chi-square test was used for calculations on proportions. Time from diagnosis to first biologic was calculated by Kaplan-Meier failure estimates. Results 14,645 patients were included, 5283 (36%) with Crohn’s disease (CD) and 9362 (64%) with ulcerative colitis (UC). In the 2010 and 2016 cohort, the proportion initiating biologics increased from 17% to 33% (p

Background Human immunodeficiency virus (HIV)–infected immunological nonresponders (INRs) fail to reconstitute their CD4+ T-cell pool after initiation of antiretroviral therapy, and their prognosis is inferior to that of immunological responders (IRs). A prevailing hypothesis is that the INR phenotype is caused by a persistently disrupted mucosal barrier, but assessments of gut mucosal immunology in different anatomical compartments are scarce. Methods We investigated circulating markers of mucosal dysfunction, immune activation, mucosal Th17 and Th22 cells, and mucosa-adherent microbiota signatures in gut mucosal specimens from sigmoid colon and terminal ileum of 19 INRs and 20 IRs in addition to 20 HIV-negative individuals. Results INRs had higher blood levels of the enterocyte damage marker intestinal fatty acid–binding protein than IRs. In gut mucosal biopsies, INRs had lower fractions of CD4+ T cells, higher fractions of interleukin 22, and a tendency to higher fractions of interleukin 17–producing CD4+ T cells. These findings were all restricted to the colon and correlated to circulating markers of enterocyte damage. There were no observed differences in gut microbial composition between INRs and IRs. Conclusions Restricted to the colon, enterocyte damage and mucosal immune dysfunction play a role for insufficient immune reconstitution in HIV infection independent of the gut microbiota.

Type 2 diabetes (T2DM) is associated with gastroesophageal reflux disease (GERD) in the general population, but the relationship between these conditions in candidates for bariatric surgery is uncertain. We compared the prevalence of GERD and the association between GERD symptoms and esophagitis among bariatric candidates with and without T2DM. Cross-sectional study of baseline data from the Oseberg study in Norway. Both groups underwent gastroduodenoscopy and completed validated questionnaires: Gastrointestinal Symptom Rating Scale and Gastroesophageal Reflux Disease Questionnaire. Participants with T2DM underwent 24-h pH-metry. A total of 124 patients with T2DM, 81 women, mean (SD) age 48.6 (9.4) years and BMI 42.3 (5.5) kg/m2, and 64 patients without T2DM, 46 women, age 43.0 (11.0) years and BMI 43.0 (5.0) kg/m2, were included. The proportions of patients reporting GERD-symptoms were low (

HIV-infected immunological nonresponders (INRs) have increased risk of non-AIDS morbidity and compromised gut barrier immunity. Probiotics are widely used to improve health. We assessed the effects of probiotics in INRs with a comprehensive analysis of gut immunity and microbiome in terminal ileum and sigmoid colon.The study involved clinical intervention with five-strain probiotic capsules (1.2 × 1010 CFUs/d) for 8 weeks in 20 INRs with CD4+ T-cell counts400 cells/µL and plasma HIV RNA50 copies/mL for more than 3.5 years. Colonoscopy with sampling of gut biopsies from terminal ileum and sigmoid colon and fecal and blood sampling were performed before and after the intervention. Flow cytometry (cytokine production, immune activation, and exhaustion), ELISA (inflammation, microbial translocation, and enterocyte damage), and 16S rRNA sequencing analyses were applied.In the terminal ileum, increased alpha diversity, increased abundance of Bifidobacterium sp., and decreased frequencies of IL-22+ CD4+ T cells were observed. The increased abundance of Bifidobacterium sp. in the terminal ileum correlated with increased fraction of CD4+ T cells in the same compartment (r = 0.54, P = 0.05) and increased CD4/CD8 ratio in peripheral blood (r = 0.49, P = 0.05). There were no corresponding changes in the sigmoid colon and no changes in fecal microbiome. Probiotic intervention did not affect peripheral blood CD4 count, viral load, or soluble markers of inflammation and microbial translocation.Probiotics induced segment-specific changes in the terminal ileum but did not affect systemic CD4 counts in INRs. Further clinical studies are warranted to recommend probiotics to INRs.

The efficacy of vedolizumab (VDZ) has been demonstrated in clinical trials. The aim of this report is to evaluate the long-term effectiveness and safety of VDZ in a real-world cohort and to explore possible associations between concentration measurements of VDZ and treatment effectiveness.This is a prospective clinical follow-up including all adult patients with ulcerative colitis (UC) and Crohn's disease (CD) treated with VDZ from October 2014 until September 2017 at a single center in Norway. The patients were followed for at least 14 weeks or until termination of treatment. Clinical and biochemical activity were obtained at every infusion throughout follow-up. Plasma measurements of VDZ (p-VDZ) were performed before every infusion during maintenance therapy.In total, 71 patients received VDZ. Improvement of CRP and hemoglobin was observed in CD but not in UC, whereas Partial Mayo Score improved in UC while no change in Harvey Bradshaw Index was revealed in CD. Furthermore, CRP at baseline was negatively correlated with p-VDZ at week 14 in CD but not in UC patients.Improvement of biochemical markers of inflammation was observed in CD while clinical activity scores improved in UC patients. For CD, baseline CRP was correlated with lower concentrations of p-VDZ at week 14.

Background and aim: Modern treatment strategies for inflammatory bowel disease (IBD) are postulated to change the natural disease course. Inception cohort studies are the gold standard for investigating such changes. We have initiated a new population-based inception cohort study; Inflammatory bowel disease in South Eastern Norway III (IBSEN III). In this article, we describe the study protocol and baseline characteristics of the cohort. Methods: IBSEN III is an ongoing, population-based observational inception cohort study with prospective follow-up. Adult and pediatric patients with suspected IBD in the South-Eastern Health Region of Norway (catchment area of 2.95 million inhabitants in 2017), during the 3-year period from 2017 to 2019, were eligible for inclusion. Comprehensive clinical, biochemical, endoscopic, demographic, and patient-reported data were collected at the time of diagnosis and throughout standardized follow-up. For a portion of the patients, extensive biological material was biobanked. Results: The study included 2168 patients, of whom 1779 were diagnosed with IBD (Crohn's disease: 626, ulcerative colitis: 1082, IBD unclassified: 71). In 124 patients, there were subtle findings indicative of, but not diagnostic for, IBD. The remaining 265 patients were classified as symptomatic non-IBD controls. Conclusion: We have included patients in a comprehensive population-based IBD cohort from a catchment population of 2.95 million, and a unique biobank with materials from newly diagnosed and treatment-naïve IBD patients and symptomatic non-IBD controls. We believe this cohort will add important knowledge about IBD in the years to come.

Background and aims Peroral endoscopic myotomy (POEM) is an established therapy for achalasia, but outcome evaluation has often been limited to Eckardt score (ES). The present study was aimed to improve knowledge about outcome evaluation and predictive outcome factors by performing a comprehensive objective evaluation of achalasia patients treated by POEM. Methods This single centre prospective study reports outcome data 12 months after POEM in treatment-naive achalasia patients. A predefined follow-up protocol included ES, high resolution manometry, 24-h pH measurement, upper endoscopy and timed barium esophagogram (TBE). Univariate and multivariate regression analyses were performed to analyze association between post-POEM variables and identify predictive factors for objective outcome. Results Fifty patients were included with a drop-out rate of 3 cm after POEM was associated with treatment failure assessed by ES (p = .04) and TBE (p = .03). Advanced achalasia stage (p = .02) and long symptom duration (p = .04) were identified as independent predictive factors for poor outcome assessed by TBE. Conclusions The present study confirms that POEM is an efficient therapy for achalasia. The comprehensive objective evaluation after POEM demonstrates that long symptom duration and major changes in oesophageal anatomy at diagnosis imply poor treatment outcome, and a post-POEM dilated oesophagus is associated with treatment failure.Key messagesPeroral endoscopic myotomy (POEM) is established as a safe and effective therapy for achalasia.Timed barium esophagogram offers objective variables that are valuable in treatment response evaluation.Advanced achalasia stage and long symptom duration are predictive factors for poor objective treatment response after POEM.

Background and aims: Obesity with type-2 diabetes is a global challenge. Lifestyle interventions have limited effect for most patients. Bariatric surgery is highly effective, but resource-demanding, invasive and associated with serious complications. Recently, a new intragastric balloon was introduced, not requiring endoscopy for placement or removal (Elipse™, Allurion Inc., Natick, MA). The balloon is swallowed in a capsule and filled with water once in the stomach. The balloon self-deflates after 4 months and is naturally excreted. The present trial investigated balloon feasibility, safety and efficacy in patients with obesity and type-2 diabetes. Patients and methods: We treated 19 patients, with type-2 diabetes and body mass index (BMI) of 30.0-39.9 kg/m2 at two Norwegian centers with the Elipse balloon. Patient follow-up during balloon treatment mimicked real-world clinical practice, including dietary plan and outpatient visits. The primary efficacy endpoints were total body weight loss (TBWL) and HbA1c at weeks 16 and 52. Results: All patients underwent balloon insertion uneventfully as out-patients. Mean TBWL and HbA1c reduction after 16 and 52 weeks of balloon insertion was 3.9% (95%CI 2.1-5.7) and 0.8% (95%CI 1.9-3.5); and 7 (95%CI 4-10), and 1 (95%CI -6 to 9) mmol/mol, respectively. Adverse events occurred in two patients (10.5%): one developed gastric outlet obstruction, managed by endoscopic balloon removal; the other excessive vomiting and dehydration, managed conservatively. Conclusions: This first Scandinavian real-world clinical trial with a new minimally invasive intragastric balloon system demonstrated good feasibility, but did not confirm expected efficacy for weight loss and diabetes control.

Background Systematic training in colonoscopy is highly recommended; however, we have limited knowledge of the effects of “training-the-colonoscopy-trainer” (TCT) courses. Using a national quality register on colonoscopy performance, we aimed to evaluate the effects of TCT participation on defined quality indicators. Methods This observational study compared quality indicators (pain, cecal intubation, and polyp detection) between centers participating versus not participating in a TCT course. Nonparticipating centers were assigned a pseudoparticipating year to match their participating counterparts. Results were compared between first year after and the year before TCT (pseudo)participation. Time trends up to 5 years after TCT (pseudo)participation were also compared. Generalized estimating equation models, adjusted for age, sex, and bowel cleansing, were used. Results 11 participating and 11 nonparticipating centers contributed 18 555 and 10 730 colonoscopies, respectively. In participating centers, there was a significant increase in detection of polyps ≥ 5 mm, from 26.4 % to 29.2 % (P = 0.035), and reduction in moderate/severe pain experienced by women, from 38.2 % to 33.6 % (P = 0.043); no significant changes were found in nonparticipating centers. Over 5 years, 20 participating and 18 nonparticipating centers contributed 85 691 and 41 569 colonoscopies, respectively. In participating centers, polyp detection rate increased linearly (P = 0.003), and pain decreased linearly in women (P = 0.004). Nonparticipating centers did not show any significant time trend during the study period. Conclusions Participation in a TCT course improved polyp detection rates and reduced pain experienced by women. These effects were maintained during a 5-year follow-up.

Simen Tveten Berge,1 Nathkai Safi,2 Asle W Medhus,3 Jon O Sundhagen,1 Jonny Hisdal,1,2 Syed SH Kazmi1,2 1Department of Vascular Surgery, Oslo University Hospital HF, Oslo, Norway; 2Faculty of Medicine, University in Oslo, Oslo, Norway; 3Department of Gastroenterology, Oslo University Hospital HF, Oslo, NorwayCorrespondence: Simen Tveten BergeDepartment of Vascular Surgery, Oslo University Hospital HF, Aker, Mail box: 4959 Nydalen, Oslo 0424, NorwayTel +47 97 72 32 20Email simen_berge@outlook.comSyed SH KazmiDepartment of Vascular Surgery, Oslo University Hospital HF, Oslo 0586, NorwayTel +47 92468309Email sshkazmi@gmail.comPurpose: Physiological tests may aid in diagnosing median arcuate ligament syndrome (MALS). MALS is a symptomatic compression of the celiac artery causing symptoms similar to chronic mesenteric ischemia (CMI) of atherosclerotic etiology. Simultaneous use of visible light spectroscopy (VLS) and laser doppler flowmetry (LDF) during upper endoscopy may detect microcirculatory changes in these patients.Patients and Methods: In a single-center, prospective comparative cohort, 25 patients were evaluated for MALS. Patients with a consensus diagnosis of MALS (n=15) underwent a gastroscopy assisted, transmucosal microcirculatory assessment with LDF and VLS. Results were compared to individuals with normal intestinal circulation (n=38) evaluated with duplex ultrasonography, and to patients with chronic mesenteric ischemia (n=32). Treatment response was evaluated clinically at 1, 3, 6, and 12 months, and with ultrasound, VLS and LDF at three months. Health-related quality of life (QoL) was assessed with Euroqol (EQ-5D-5L), preoperatively, and 12 months postoperatively.Results: Preoperative mean transmucosal oxygen saturation was significantly lower in patients with MALS (SO2 76± 6), as compared to healthy individuals (SO2 81± 4), p=0.02. An overall significant improvement in SO2 after surgical decompression of the celiac artery was found (SO2 81± 3.7, p=0.05). Eleven (92%) patients with clinical improvement after laparoscopic decompression had a definitive diagnosis of MALS. Median follow-up was 18 months (4– 24 months). Four of the five dimensions investigated with EQ-5D-5L improved.Conclusion: VLS detected a significantly lower baseline transmucosal SO2 in patients with MALS as compared to control subjects with normal intestinal circulation. An improvement in SO2 after laparoscopic decompression was found, supporting a possible ischemic etiology in our patient population.Keywords: mesenteric ischemia, functional test, endoscopy, vascular surgery, abdominal pain

Long-term data regarding switching from originator infliximab to biosimilar CT-P13 are sparse. Concerns about increased immunogenicity after switching have been raised. We aimed to study the effectiveness, safety and immunogenicity after switching from originator infliximab to CT-P13 in a real-world IBD population with 18 months prospective follow-up.All adult IBD patients treated with originator infliximab at the Department of Gastroenterology, Oslo University Hospital, were switched to CT-P13 and followed prospectively for 18 months. The primary endpoints were (i) the proportion of patients remaining on CT-P13 18 months after switching and (ii) immunogenicity during 18 months after switching. The secondary endpoints included (i) adverse events, (ii) changes in disease activity, C-reactive protein, anaemia, faecal calprotectin, infliximab dose and interval and p-infliximab.In total, 143 IBD patients were switched, 99 with Crohn's disease and 44 with ulcerative colitis. Altogether, 130 (91%) remained on CT-P13 throughout 18 months. Two patients developed ADAs at moderate level and discontinued CT-P13. Another 10 patients discontinued CT-P13 (two due to loss of response without ADAs, four due to adverse events, and four in remission and a personal wish to stop). There was no overall change in disease activity scores or in the other studied variables except for p-infliximab, which increased significantly.The present study provides valuable evidence for the safety and effectiveness of switching from originator to biosimilar infliximab over a prolonged period of 18 months and demonstrates that switching was well tolerated and did not affect the long term clinical outcome.

Aim of the study Preoperative gastric emptying (GE) rate in patients with gastrointestinal reflux disease (GERD) was evaluated as a predictor of outcome after antireflux surgery. Methods and patients GE was assessed using radionuclide scintigraphy and a standardized meal with cow's milk. GE half time (T1/2), patient demographics and GERD symptoms including vomiting (>4days/week), retching (>4days/week), prolonged feeding time (>3h/day), and discomfort after meals were recorded pre- and postoperatively. A standardized follow-up included a 24-h pH-monitoring and an upper gastrointestinal contrast study. Of 74 patients undergoing Nissen fundoplication between 2003 and 2009, 35 underwent a preoperative GE study. The remaining 39 patients were not examined owing to volume intolerance, cow's milk intolerance or allergy, inability to lie still, or parents refusing participation. Main results Median age at fundoplication was 4.9 [range 1.1–15.4] years, and follow-up time was median 4.3 [1.9–8.9] years. GERD recurred in 7 (20%) patients. Preoperative T1/2 in the seven patients with recurrent GERD was median 45 [21–87] min compared to 44 [16–121] min in the 28 patients without recurrent GERD (p=0.92). There was no significant difference between the one third of patients with the slowest GE [T1/2 54–121min] and the remaining patients [T1/2 16–49min] regarding GERD recurrence or postoperative vomiting, retching, prolonged feeding time, or discomfort after meals. Conclusion Preoperative GE rate did not predict outcome after antireflux surgery, as slow GE was not associated with recurrent GERD or postoperative troublesome symptoms such as vomiting, retching, or meal discomfort.

Mucosal pathology due to chronic mesenteric ischemia (CMI) is rarely seen during upper endoscopy. Combining Laser Doppler Flowmetry (LDF) and Visible Light Spectroscopy (VLS) may aid in detection of CMI at an early stage. We aimed to investigate the utility of LDF and VLS in detecting microcirculatory changes in patients with CMI during upper endoscopy. In a single center, prospective study, 104 patients were evaluated for mesenteric ischemia during a 24 months period. Patients with a consensus diagnosis of CMI (n = 40) were examined with LDF and VLS. Thirty-two were successfully treated and had a definitive diagnosis of CMI. Results were compared with controls (n = 38) with normal intestinal circulation evaluated with duplex ultrasonography (DUS). Treatment response was evaluated clinically and with DUS at 1 month and with VLS and LDF at 3 months. A significant reduction in mucosal capillary hemoglobin oxygen saturation (SO2) was found in CMI patients compared to controls before treatment: mean ± SD: 67 ± 9%, 81 ± 4%, respectively (p

Background Alcohol-related morbidity may involve changes in the gut microbiota and immune dysregulation. We have previously demonstrated alterations in gut microbiota composition and functions in patients with alcohol overconsumption, and now aimed to investigate possible associations between cytokine levels, gut microbiota, and clinical symptoms. Methods We included hospital inpatients with a history of chronic alcohol overconsumption. For comparison, we included control patients with a low alcohol intake. Cytokine levels (TGF-β1, TNF-α, IL-10, IL-8, IL-6, IFN-γ, MCP-1, IL-1RA, IL-1β, and IL-17) were determined using a customized V-plex assay. We then examined associations of cytokine levels with the abundance of Proteobacteria and Faecalibacterium, percentage of the short-chain fatty acid butyrate, psychiatric symptoms (Hospital Anxiety and Depression Scale), and biochemical liver variables. Results We included 28 patients with alcohol overconsumption (79% men), and 25 control patients (72% men). Patients with alcohol overconsumption had higher levels of IL-6 (p = 0.002), IFN-γ (p = 0.018), and MCP-1 (p = 0.006), and lower levels of TGF-β1 (p = 0.017) compared with control patients. Inverse correlations were found between Proteobacteria abundance and TNF-α (Rs = −0.55, p = 0.02) and IL-8 (Rs = −0.58, p = 0.014), and between Faecalibacterium and MCP-1 levels (Rs = −0.56, p = 0.02) in the control patients, but not in patients with alcohol overconsumption. Patients with alcohol overconsumption reported more psychiatric symptoms, and these symptoms were inversely correlated with IL-10 levels. There were positive correlations between several of the assessed cytokines and biochemical liver variables, and negative correlations between cytokine levels and albumin. Conclusion Patients with alcohol overconsumption had a cytokine profile suggestive of increased systemic inflammatory activity, with higher levels of pro-inflammatory cytokines (IL-6, IFN-γ, and MCP-1) and lower levels of anti-inflammatory cytokines (TGF-β1). The findings may represent a link between alcohol use and alcohol-related morbidity.

We would like to thank for the interest and comments on our review [1] by Tan et al. They express some concerns regarding the studies included in the review and the review process. We will respond ...

Objectives: Achalasia is a primary motility disorder of the esophagus characterized by aperistalsis and failure of lower esophageal sphincter (LES) relaxation. Treatment of achalasia aims at reducing LES pressure. The common treatment modalities are laparoscopic Heller myotomy and pneumatic dilatation, but during the last decade, a promising treatment, per oral endoscopic myotomy (POEM), has been introduced. The aim of the present study was to perform a systematic review of the literature to assess the outcome of POEM in treatment-naive patients. Materials and methods: A systematic literature search in PubMed, Embase and Cochrane databases was performed using the terms ‘Achalasia AND (POEM OR peroral endoscopic myotomy OR per-oral endoscopic myotomy)’. Inclusion criteria were: original article; English language; n ≥ 20 with ≥90% treatment-naive patients; follow-up ≥3 months; and outcome evaluation of POEM including symptom score and objective tests. Exclusion criteria were: reviews and meta-analyses; pediatric data; duplicates; and articles with overlapping data material. Results: Of the 1641 articles identified, seven were included. The included studies all reported a short-term clinical success of >90%. Clinical success including post-POEM reflux was mainly estimated by symptom scorings. There were few procedure-related complications. Conclusions: The studies of treatment-naive patients indicate a high rate of clinical success. Nevertheless, a more systematic and standardized evaluation is recommended to improve the reports on outcome of POEM. The follow-up rate should be high and the evaluation protocol should include both symptom scoring and objective testing with predefined treatment goals.

Excessive alcohol intake can alter the gut microbiota, which may underlie the pathophysiology of alcohol-related diseases. We examined gut microbiota composition and functions in patients with alcohol overconsumption for >10 years, compared to a control group of patients with a history of no or low alcohol intake. Faecal microbiota composition was assessed by 16S rRNA sequencing. Gut microbiota functions were evaluated by quantification of short-chain fatty acids (SCFAs) and predictive metagenome profiling (PICRUSt). Twenty-four patients, mean age 64.8 years (19 males), with alcohol overconsumption, and 18 control patients, mean age 58.2 years (14 males) were included. The two groups were comparable regarding basic clinical variables. Nutritional assessment revealed lower total score on the screening tool Mini Nutritional Assessment, lower muscle mass as assessed by handgrip strength, and lower plasma vitamin C levels in the alcohol overconsumption group. Bacteria from phylum Proteobacteria were found in higher relative abundance, while bacteria from genus Faecalibacterium were found in lower relative abundance in the group of alcohol overconsumers. The group also had higher levels of the genera Sutterella, Holdemania and Clostridium, and lower concentration and percentage of butyric acid. When applying PICRUSt to predict the metagenomic composition, we found that genes related to invasion of epithelial cells were more common in the group of alcohol overconsumers. We conclude that gut microbiota composition and functions in patients with alcohol overconsumption differ from patients with low consumption of alcohol, and seem to be skewed into a putative pro-inflammatory direction. © 2019 The Author(s). Published with license by Taylor & Francis Group, LLC. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivatives License (http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited, and is not altered, transformed, or built upon in any way.

Background Colonoscopy performance varies between endoscopists, but little is known about the impact of endoscopy assistants on key performance indicators. We used a large prospective colonoscopy quality database to perform an exploratory study to evaluate differences in selected quality indicators between endoscopy assistants. Methods All colonoscopies reported to the Norwegian colonoscopy quality assurance register Gastronet can be used to trace individual endoscopy assistants. We analyzed key quality indicators (cecum intubation rate, polyp detection rate, colonoscopies rated as severely painful, colonoscopies with sedation or analgesia, and satisfaction with information) for colonoscopies performed between 1 January 2013 and 31 December 2014. Differences between individual assistants were analyzed by fitting multivariable logistic regression models, with the best performing assistant at each participating hospital as reference. All models were adjusted for the endoscopist. Results 63 endoscopy assistants from 12 hospitals assisted in 15 365 colonoscopies. Compared with their top performing peers from the same hospital, one assistant was associated with cecum intubation failure, four with poor polyp detection, nine with painful colonoscopy, 16 with administration of sedation or analgesics during colonoscopy, and three with patient dissatisfaction about information given relating to the colonoscopy. The number of procedures during the study period or lifetime experience as an endoscopy assistant were not associated with any quality indicator. Conclusion In this exploratory study, there was little variation on important colonoscopy quality indicators between endoscopy assistants. However, there were differences among assistants that may be clinically important. Endoscopy assistants should be subject to quality surveillance similarly to endoscopists.

Background Anti-tumor necrosis factor α (anti-TNF-α) is important in the treatment of inflammatory bowel disease, but some patients experience only a partial response. In these patients, a combination of anti-TNF-α and vedolizumab (VDZ) may act as a bridge until the full VDZ effect occurs. At present, clinical data on combination treatment with anti-TNF-α and VDZ are not available. The aim of this case series was to evaluate the safety and clinical response of combination therapy with anti-TNF-α and VDZ in clinical practice. Methods All patients started on combination treatment with anti-TNF-α and VDZ from November 2015 to July 2016 were prospectively followed for at least 12 months. Results Six patients with ulcerative colitis and four patients with Crohn's disease received combination treatment. These patients were followed for a median of 1712-20 months. No more adverse events than expected with anti-TNF-α alone were observed during combination treatment. At the end of follow-up, all patients were in clinical remission, and 8 patients could discontinue anti-TNF-α treatment and receive VDZ monotherapy. Two of the patients with Crohn's disease required combination treatment throughout follow-up to obtain sustained remission. Conclusion Our findings suggest that combination treatment with anti TNF-α and VDZ is safe and might represent a long-term treatment option in selected patients.

Background: Biological agents, mainly tumor necrosis factor-α inhibitors, play an important role in the treatment of inflammatory bowel disease (IBD). These drugs are expensive and constitute a major cost in the IBD care. In 2013, the first biosimilar monoclonal antibody, infliximab (IFX), was approved in the EU. Key Messages: There has been considerable skepticism regarding the use of biosimilars. Both clinicians and patients have questioned the safety and efficacy of these new drugs. In particular, the extrapolation of treatment effects between patients with different diagnoses has been debated. Due to national negotiations, the price reductions vary considerably between countries. In Norway, the biosimilars Remsima® and Inflectra® come at a very favourable price, and have supplanted the originator Remicade® almost completely. The total sale of IFX has also increased, indicating that extended indications and increased doses are being implemented in clinical use. Conclusions: The introduction of biosimilars has raised questions not only about the efficacy and safety but also about health politics. There is reason to believe that the introduction of cheaper biosimilars will change the clinical use of biologics.

Purpose The aim of this report is to examine whether children with gastroesophageal reflux (GER) have delayed gastric emptying compared to healthy children. Methods All patients had GER verified by 24-hour pH monitoring. Gastric emptying of cow’s milk was examined by radionuclide scintigraphy in 51 patients with GER and in 24 controls. Gastric emptying rate was expressed as exponential half time (T1/2). Results Median age was 4.4 years [range 0.1–15.4] in patients and 6.1 years [range 2.5–10.0] in controls (p = .10). A wide range of gastric emptying rates was observed both in GER patients [range 16–121] and controls [range 29–94]. One GER patient (2%) had slower gastric emptying (T1/2 = 121 min) than the healthy child with the longest T1/2 (94 min). Mean T1/2 was 49 minutes (SD 20.1) and 46 minutes (SD 14.2) in GER patients and controls, respectively (p = .51). Conclusions Gastric emptying rate of milk was not significantly different between children with GER and healthy children. A wide range of gastric emptying rates was observed in both groups.

Summary Background & aims The aim was to study the influence of Nissen fundoplication on rate of gastric emptying and postprandial symptoms in relation to protein source in liquid meals in children with cerebral palsy. Methods Ten children with cerebral palsy and Nissen fundoplication and ten with cerebral palsy without Nissen fundoplication were studied. Patients had gastrostomy and received two meals, double-blinded, in random order, on separate days. Meals contained a standardised carbohydrate and fat base plus one of two protein modules (Meal A: 100% casein; Meal B: 40% casein/60% whey). The 13 C octanoic acid breath test was used to assess gastric emptying. Postprandial symptoms were recorded. Results are given as median. Results For meal A and B, respectively, time until 50% of the meal had emptied ( T 1/2 ) was 110 in the Nissen fundoplication- and 181 min in the non-Nissen fundoplication group, ( p = 0.35) and 50 and 85 min ( p = 0.25). Seven in the Nissen fundoplication group reported postprandial symptoms to meal B, none in the non-Nissen fundoplication group ( p Conclusions Compared with cerebral palsy-children without Nissen fundoplication, those with Nissen fundoplication have postprandial symptoms more frequently after receiving a rapid emptying meal. Gastric emptying alone, however, does not seem to explain the symptom occurrence. ClinicalTrials.gov: UUSKBK 28200706.

Background The clinical effect of stent treatment has been evaluated by mainly physicians; only a limited number of prospective studies have used patient-reported outcomes for this purpose. The aim of this work was to study the clinical effect of self-expanding metal stents in treatment of malignant gastrointestinal obstructions, as evaluated by patient-reported outcomes, and compare the rating of the treatment effect by patients and physicians. Methods Between November 2006 and April 2008, 273 patients treated with SEMS for malignant GI and biliary obstructions were recruited from nine Norwegian hospitals. Patients and physicians assessed symptoms independently at the time of treatment and after 2 weeks using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 questionnaire supplemented with specific questions related to obstruction. Results A total of 162 patients (99 males; median age = 72 years) completed both assessments and were included in the study. A significant improvement in the mean global health score was observed after 2 weeks (from 9 to 18 on a 0–100 scale, P\0.03) for all stent locations. Both patients and physicians reported a significant reduction in all obstruction-related symptoms ([20 on the 0–100 scale, P\0.006) after SEMS treatment. The physicians reported a larger mean improvement in symptoms than did the patients, mainly because they reported more severe symptoms before treatment. Conclusion SEMS treatment is effective in relieving symptoms of malignant GI and biliary obstruction, as reported by patients and physicians. The physicians, however, reported a larger reduction in obstructive symptoms than did the patients. A prospective assessment of patientreported outcomes is important in evaluating SEMS treatment. publishedVersion

Dysmotility of the upper gastrointestinal tract has been reported in children with Hirschsprung's disease. In the present study, gastric emptying was studied in adult patients with Hirschsprung's disease to elucidate whether there is a persisting involvement of the upper gastrointestinal tract in this group of patients.Gastric emptying of caloric liquids and solids was studied in 16 adult patients with surgically treated Hirschsprung's disease during early childhood and in age-matched controls. To examine liquid emptying, the paracetamol absorption test was applied using a meal containing glucose, lactose, maize oil, water (2020 kJ) and paracetamol. To examine solid emptying, the 13C gastric emptying breath test was applied using a meal containing white bread, margarine, a one-egg omelette (1050 kJ) and [13C]-octanoic acid. Gastrointestinal symptoms were recorded according to a standardized questionnaire.For liquid meal emptying, the time until emptying commenced was 8.1+/-1.9 and 2.9+/-0.9 min (mean+/-SE) in patients and controls, respectively (p=0.02). Thereafter, the first 25% of the meal emptied in 6.8+/-0.8 and 12.1+/-1.1 min in patients and controls, respectively (p=0.0005). The overall emptying rate tended to be delayed in patients compared with controls (p=0.06). For the solid meal, a delay in emptying was evident (p=0.02). The patients reported more symptoms from the upper gastrointestinal tract than the controls, but the symptoms were not significantly related to the emptying pathology demonstrated.The present study demonstrates that adult patients with Hirschsprung's disease have an abnormal pattern of gastric emptying, indicating persisting involvement of the upper gastrointestinal tract.

Background More than 20% of the hip fracture patients die within the first year after the incident. Few data are available on the trends in mortality following a hip fracture. The present aim was to study changes in excess mortality after hip fracture from 1978/79 up to 1996/97. Methods Data on 5180 hip fracture patients aged ≥ 50 years, identified in three earlier, well validated, incidence studies from Oslo were used. The studies took place in the two years periods 1978–79 and 1989–89 and in a one year period from 1st of May 1996 to 30th of April 1997. The study was designed as a historic cohort study. Exposure was sustaining a hip fracture in the registration periods. Outcome was death of all causes. Age- and sex-specific one year-mortality rates were provided by Statistics Norway. Standardized mortality ratios (SMR) were calculated for the three cohorts for each sex and age-group, for the 0–6 months, 6–12 months, 0–1 year, 1–5 years and 5–10 years intervals after fracture. To assess the duration of the excess mortality in hip fracture patients, time-framed Kaplan-Meier curves for consecutive 5-years intervals were conducted for the hip fracture patients and the corresponding background population. Only patients still alive at the start of the time interval were included. One sample log rank tests were used to test for statistical significance. Results The one-year SMR ranged from 3.64 (2.82 – 4.61) to 4.53 (3.67 – 5.54) in men and from 2.78 (2.39 – 3.19) to 3.60 (3.19 – 4.05) in women. In the 0–6 months interval a reduction in SMR from 1978/79 to 1996/97 was observed in women aged ≥85 years. The duration of excess mortality ranged from two years in men ≥85 years to more than ten years in men and women aged 65–84 years. Conclusion Excess mortality among hip fracture patients remains high. Over the decades, a reduced excess mortality was mainly seen in the oldest patients, suggesting that specific efforts intending to improve prevention and treatment of osteoporosis and osteoporotic fractures in the youngest elderly are required.

Self-expanding metal stents (SEMS) are commonly used in the palliative treatment of malignant gastrointestinal (GI) obstructions with favorable short-term outcome. Data on long-term outcome are scarce, however.To evaluate long-term outcome after palliative stent treatment of malignant GI obstruction.Between October 2006 and April 2008, nine Norwegian hospitals included patients treated with SEMS for malignant esophageal, gastroduodenal, biliary, and colonic obstructions. Patients were followed for at least 6 months with respect to stent patency, reinterventions, and readmissions.Stent placement was technically successful in 229 of 231 (99%) and clinically successful after 1 week in 220 of 229 (96%) patients. Long-term follow-up was available for 219 patients. Of those, 72 (33%) needed reinterventions. Stent occlusions or migrations (92%) were the most common reasons. Esophageal stents required reinterventions most frequently (41%), and had a significantly (p = 0.02) shorter patency (median 152 days) compared to other locations (gastroduodenal, 256 days; colon, 276 days; biliary, 460 days). Eighty percent of reinterventions were repeated endoscopic procedures that successfully restored patency. Readmissions were required for 156 (72%) patients. Progression of the underlying cancer was the most common reason, whereas 24% were readmitted due to stent complications.Long-term outcome after palliative treatment with SEMS for malignant GI and biliary obstruction shows that 70% had a patent stent until death, and that most reobstructions could be solved endoscopically. Hospital readmissions were mainly related to progression of the underlying cancer disease.

Background and aims: A biosimilar version of infliximab (CT-P13/Remsima®) recently entered the European market. The clinical data on its use in inflammatory bowel disease are sparse, especially on switching from the originator Remicade®. In this study, we aimed to prospectively investigate the feasibility, safety and immunogenicity of switching from Remicade® to Remsima® in a real-life IBD population. Methods: All adult patients who were treated with Remicade® in the Department of Gastroenterology at Oslo University Hospital were switched to Remsima®. The follow-up lasted for 6 months. In addition, a retrospective registration was performed with a start time of 6 months before switching drugs. The primary endpoints were i) the proportion of patients remaining on medication 6 months after switching and ii) adverse events during the 6 months after switching. The secondary endpoints included i) disease activity scores (Harvey-Bradshaw Index and Partial Mayo Score), C-reactive protein, haemoglobin, faecal calprotectin, Infliximab dose and interval, p-infliximab and ii) the development of antidrug antibodies. Results: In total, 143 IBD patients were switched, 99 with Crohn’s disease and 44 with ulcerative colitis. The large majority (97%) remained on the medication throughout follow-up. A low number of adverse events were observed. No change in disease activity, C-reactive protein, haemoglobin, faecal calprotectin, Infliximab dose and interval or p-Infliximab was detected. Three patients developed new detectable antidrug antibodies. Conclusions: Our study demonstrated that switching from Remicade® to Remsima® was feasible and with few adverse events, including very limited antidrug antibody formation and loss of response.

Advanced pancreatic cancer and other malignancies located proximal to the small bowel might cause gastric outlet obstruction (GOO) resulting in nausea, vomiting, dehydration, and malnutrition. Self-expandable metal stents (SEMS) to a large extent have replaced surgical treatment, with gastro-entero-anastomosis as palliative treatment for GOO. The aim of the present study was to evaluate the effect of duodenal stenting on the rate of gastric emptying, symptoms, and survival. Patients with endoscopically verified malignant obstruction of the proximal duodenum were included. Gastric emptying rate was measured prior to and within 1 week after stent placement using a meal containing 13C-octanoic acid as a marker. Symptoms related to GOO were assessed by the patients before and 2 weeks after stent treatment and during the gastric emptying tests. All patients were followed up until death. In the patients included (n = 17), all studied variables of gastric emptying improved significantly following treatment, and a reduction in self-reported obstructive symptoms was observed. There was no correlation between survival and the rate of gastric emptying before or after, or the change in the rate of emptying. The present study demonstrated that treatment with SEMS results in improved gastric emptying in most patients with GOO and a corresponding reduction in self-reported obstruction symptoms. However, survival and emptying were not related. The present findings provide further evidence that treatment with stents is an effective palliative treatment in patients with GOO.

Dysmotility, nausea and vomiting are common among children with cerebral palsy. This study aimed to evaluate influence of protein composition on rate of gastric emptying and study the relation between gastric emptying and postprandial gastrointestinal symptoms.15 children with cerebral palsy, using gastrostomy, received four liquid test meals on separate days in random order. The meals contained a standard carbohydrate and fat base plus one of four protein modules (100% casein (A), hydrolysed whey (B), amino acids (C) and 40% casein/60% whey (D)) with a total energy of 1 kcal/ml. The (13)C octanoic acid breath test was applied to assess gastric emptying.When comparing half emptying time (T(1/2)) of the fast emptying meals (meal B, C and D) with the slowest emptying meal (meal A), more rapid emptying was demonstrated for meal D (p 0.001). For meal D, emptying was significantly faster in children with postprandial symptoms than in those without (p 0.01).In children with cerebral palsy using gastrostomy, gastric emptying is influenced by type of protein in the meal. The present results also suggest that there is a relation between rapid gastric emptying and postprandial gastrointestinal symptoms. CLINICALTRIALS.GOV: UUSKBK 28200706.

Objective The aim of the present study was to examine the validity of local and national electronic databases using medical records as gold Standard. Study design and setting All hospital admissions with ICD 9-code 820.X (hip fracture) in a 1-year period were identified in the electronic discharge registers of the hospitals in Oslo and in the national electronic database (The Norwegian Patient Register). Medical records for all patients identified by the discharge registers and the logbooks of the operating theater of the hospitals were retrieved, and the diagnosis was verified. Results Compared with the total number of fractures confirmed in medical records, the electronic discharge register of one of the hospitals underestimated the number of fractures by 46%, whereas the two other overestimated the number by 17% and 19%. For the national electronic database, an overall overestimation of 19% was found. Conclusion The present findings question the validity of electronic databases and thus have implications for epidemiologic studies.

Hirschsprung's disease (HD) is considered a focal disease usually confined to the distal colon and rectum. However, autonomic dysfunction and dysmotility in the upper gastrointestinal tract have been reported, suggesting that this disease is not only confined to the distal gastrointestinal tract. This study examines the fasting and postprandial levels of glucose and insulin in adult patients with HD to elucidate whether there might also be an endocrine involvement in this disease. Sixteen patients with surgically treated HD during early childhood and 17 healthy subjects were studied. All subjects ingested a caloric liquid meal containing glucose, lactose, maize oil, and water (2,020 kJ) after an overnight fast. Blood samples were collected at regular intervals for insulin and glucose analyses. Fasting levels of both glucose (P

An algorithm for the paracetamol absorption test for gastric emptying, adjusting for individual pharmacokinetics, was recently developed. The aim of the present study was to validate the use of this algorithm. Furthermore, the algorithm was applied to elucidate whether a gastric tube interferes with the rate of gastric emptying. A caloric liquid meal with paracetamol was administered orally to nine healthy volunteers on two separate days. On one occasion, the subjects were intubated with a nasogastric tube and the meal was aspirated from the stomach 45 min after meal intake. The percentage of the meal retained in the stomach at the time of aspiration was determined by analyses of paracetamol in the aspirate and compared with calculations by the algorithm. On the other examination day, the same meal was ingested without tube and aspiration. The median percentage of the meal retained in the stomach at aspiration was 47% (range 33-70%) calculated by the algorithm and 48% (range 23-61%) based on the aspiration data. The correlation between the emptying parameters was r=0.97 (P < 0.001). The median of gastric emptying parameters was similar when the number of samples included in the calculation by the algorithm was reduced, but the range tended to increase. The gastric tube moderately inhibited gastric emptying during the period 20-40 min after meal intake (P < 0.05), but for the period from meal intake until start of aspiration, no inhibition was found. The present study demonstrates that the novel algorithm for the paracetamol absorption test provides valid estimates for gastric emptying.

The relationship between the preceding phase of the migrating motor complex (MMC) and postprandial motility in the small intestine was studied.In eight healthy subjects small-bowel manometry was performed, and a 55-ml caloric liquid bolus (280 kJ) containing paracetamol and 14C-D-xylose was instilled into the duodenum during phase I and late phase II of the intestinal MMC, respectively, in randomized order. Blood samples were drawn at regular intervals and analysed for insulin, gastrin, glucose, paracetamol, and 14C-D-xylose.After bolus administration during late phase II a phase-III-like activity succeeded by quiescence occurred in the duodenum in seven of eight subjects, whereas administration during phase I initiated irregular contractions in seven of eight subjects (P0.05). The caloric bolus induced a significant increase in serum insulin and gastrin. Areas under the curves for serum insulin, gastrin, glucose, paracetamol, and 14C-D-xylose were not modulated by the preceding phase of the MMC.The present study shows that a nutrient bolus instilled into the intestinal lumen induces MMC-like activity when administered during late phase II. These findings provide further evidence of interference between MMC and postprandial motility.

The phase of the migrating motor complex (MMC) in the proximal small intestine at meal intake modulates gastric emptying, which is accelerated after intake during phase II. In the present study the relationship between phase of the MMC at meal intake and the postprandial endocrine response was studied.Eight healthy subjects ingested a caloric liquid meal of 2020 kJ during phase I and late phase II of the intestinal MMC, respectively, in a randomized order. Blood samples were drawn at regular intervals after meal intake and analysed for insulin, gastrin, neurotensin, cholecystokinin, motilin, and somatostatin by radioimmunoassays.The area under the curve (AUC) until 15 min for serum insulin (P0.05) and plasma neurotensin (P0.02) and AUC until 120 min for serum gastrin (P0.05) were higher after intake during late phase II than after phase I. Plasma cholecystokinin increased earlier (P0.05) after intake during late phase II than after phase I. Plasma motilin and somatostatin were not influenced by preceding phase of the MMC.This study shows that the phase of intestinal MMC at meal intake modulates the postprandial endocrine response, which may be explained by the prior entry of nutrients to the small intestine after intake during phase II.

The present study elucidates whether the phase of the migrating motor complex (MMC) present at the moment of food intake modulates postprandial motor response and rate of gastric emptying of caloric meals. Eight healthy male volunteers with a mean age of 26 years were examined twice. During water-perfused gastroduodenal manometry, a liquid meal with paracetamol added as a marker was orally administered during phase I and late phase II. Paracetamol appeared in serum 14.1 +/- 3.8 min and 9.1 +/- 4.0 (mean +/- SD) min, respectively, after intake of the meal (P < 0.02). The area under the curve of s-paracetamol until 25 min after intake was 232 +/- 169 mumol l-1 min and 362 +/- 130 (P < 0.05), respectively. When taken during late phase II, a phase III-like activity occurred within 2.1 +/- 1.3 min in the duodenum, and was succeeded by quiescence. During phase I, the meal invariably initiated irregular contractions within 4 min. The phase of MMC during which a caloric meal is ingested modulates duodenal motor response and rate of gastric emptying during the initial postprandial period. Initial postprandial motor activity thus represents the combined effect of nutrient stimulation and the underlying enteric biorhythm as reflected by phase of MMC.

Background Dysmotility of the upper gastrointestinal (GI) tract has been reported in children with Hirschsprung’s disease (HD). In the present study, motility of the oesophagus and the small bowel was studied in adults treated for HD during early childhood to elucidate whether there are alterations in motility of the upper GI tract in this patient group. [Correction added after online publication 15 Sep: The preceding sentence has been rephrased for better clarity.] Methods Ambulatory small bowel manometry with recording sites in duodenum/jejunum was performed in 16 adult patients with surgically treated HD and 17 healthy controls. In addition, oesophageal manometry was performed with station pull-through technique. Key Results The essential patterns of small bowel motility were recognized in all patients and controls. During fasting, phase III of the migrating motor complex (MMC) was more prominent in patients with HD than in controls when accounting for duration and propagation velocity (P = 0.006). Phase I of the MMC was of shorter duration (P = 0.008), and phase II tended to be of longer duration (P = 0.05) in the patients. During daytime fasting, propagated clustered contractions (PCCs) were more frequent in the patients (P = 0.01). Postprandially, the patients demonstrated a higher contractile frequency (P = 0.02), a shorter duration of contractions (P = 0.008) and more frequent PCCs (P