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Immune responses following SARS-CoV-2 vaccination in patients with inflammatory bowel disease (IBD) are not well characterized. The aims of this study were to explore the serological response associated with IBD, and immunosuppressive medications including serum concentrations of biologics and thiopurine metabolites. This prospective, observational study included adult patients with ulcerative colitis (UC) and Crohn’s disease (CD), and healthy controls. Antibodies to the receptor-binding domain of SARS-CoV-2 spike proteins, and serum concentrations of ongoing biologic and immunomodulatory medications were assessed prior to, and 2-5 weeks after the second vaccine dose. Serologic response was defined as anti-Spike antibodies ≥70 AU/ml. In 958 IBD patients (380 UC, 578 CD) and 323 healthy controls, the median (Q1; Q3) anti-Spike antibody level (AU/ml) was lower in patients (618 (192; 4370)) compared to controls (3355 (896; 7849)) (p < 0.001). The antibody levels were lower in CD (439 (174; 3304)) compared to UC (1088 (251; 5975)) (p < 0.001). No associations were demonstrated between antibody levels and serum drug concentrations for TNF inhibitor (TNFi), vedolizumab and ustekinumab. Patients receiving TNFi + thiopurines with a subtherapeutic 6-thioguanine nucleotide (6-TGN) level had higher response rate (93%) compared to patients with 6-TGN within the therapeutic range (53%) (p = 0.003). A diagnosis of UC, mRNA-1273 vaccine, and other treatments than TNFi + thiopurines were associated with humoral response. Patients with CD had an attenuated humoral response to SARS-COV-2 vaccination as compared to patients with UC. The lack of association between serum levels of biologics and serologic response indicates vaccination regardless of proximity to drug administration.

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

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.

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.

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 ...

Objective. Alterations of the small intestinal absorptive surface are a probable cause of d-xylose malabsorption in chronic alcoholism. Delayed gastric emptying, however, may influence the 13C-d-xylose breath test, which is used to study intestinal function in alcoholics. The aim of this study was to measure gastric emptying in alcoholics to elucidate whether retention of the test meal could explain the malabsorptive pattern of the 13C-d-xylose breath test observed in alcoholics. Material and methods. Fifteen alcoholics performed the 13C-octanoic acid and the 13C-d-xylose breath tests on consecutive days in a random order. The 13CO2 expired was measured every 30 or 15 min for 4 h in the 13C-d-xylose and the 13C-octanoic acid breath tests, respectively, using a mass spectrometer equipped with a gas chromatograph. Test meals consisted of 100 mg of 13C-d-xylose and 5 g of unmarked d-xylose dissolved in 250 ml water and 91 mg 13C-octanoic acid embedded in a one-egg omelette served with white bread wi...

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.

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.

Objective. The 14C-d-xylose breath test was used at Ulleval University Hospital in the period from 1986 TO 1995 for malabsorption testing. The objective of this retrospective study was to reveal whether patients with chronic alcoholism may have intestinal malabsorption. Materials and methods. The consecutive 14C-d-xylose breath test database was reviewed and patients with the diagnosis of chronic alcoholism were identified. 14C-d-xylose breath test results of the alcoholic patients were compared with the results of untreated celiac patients and patient and healthy controls. In the 14C-d-xylose breath test, 14C-d-xylose was dissolved in water and given orally after overnight fast. Breath samples were taken at 30-min intervals for 210 min, and 14CO2 : 12CO2 ratios were calculated for each time point, presenting a time curve for 14C-d-xylose absorption. Urine was collected after 210 min and the fraction of the total d-xylose passed was calculated (U%). 14CO2 in breath and 14C-d-xylose in urine were ...

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.