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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.

Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 serum samples. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

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.

Introduction Ischemia is considered as the main reason for thoracic gastroesophageal anastomotic leaks after esophagectomy. Microcirculatory monitoring with laser Doppler flowmetry and visible light spectroscopy may provide valuable intraoperative real-time information about the gastric tube's tissue perfusion and circulation. Patients and methods Ten patients with esophageal cancer operated with minimally invasive esophagectomy participated in this single-center, prospective, observational pilot study. A single probe with laser Doppler flowmetry and visible light spectroscopy was used to perform transserosal microcirculation assessment of the gastric tube at predefined anatomical sites during different operation phases. Group comparison and changes were evaluated using the paired sample t-test. Results A reduction in StO2 was found at all measuring sites after the gastric tube formation compared with the baseline measurements. The mean StO2 reduction from baseline to gastric tube formation and after anastomosis was 16% (range 4%-28%) and 42% (range, 35%-52%), respectively. A statistically significant increase in the rHb concentration, representing venous congestion, was detected at the most cranial part of the gastric tube (P = 0.04). Three patients developed anastomotic leaks. Conclusion Intraoperative real-time laser Doppler flowmetry and visible light spectroscopy are feasible and may provide insight to microcirculatory changes in the gastric tube and at the anastomotic site. Patients with anastomotic leaks seem to have critical local tissue StO2 reduction and venous congestion that should be further evaluated in studies with larger sample sizes.

Diagnostic assays currently used to monitor the efficacy of COVID-19 vaccines measure levels of antibodies to the receptor-binding domain of ancestral SARS-CoV-2 (RBDwt). However, the predictive value for protection against new variants of concern (VOCs) has not been firmly established. Here, we used bead-based arrays and flow cytometry to measure binding of antibodies to spike proteins and receptor-binding domains (RBDs) from VOCs in 12,000 sera. Effects of sera on RBD-ACE2 interactions were measured as a proxy for neutralizing antibodies. The samples were obtained from healthy individuals or patients on immunosuppressive therapy who had received two to four doses of COVID-19 vaccines and from COVID-19 convalescents. The results show that anti-RBDwt titers correlate with the levels of binding- and neutralizing antibodies against the Alpha, Beta, Gamma, Delta, Epsilon and Omicron variants. The benefit of multiplexed analysis lies in the ability to measure a wide range of anti-RBD titers using a single dilution of serum for each assay. The reactivity patterns also yield an internal reference for neutralizing activity and binding antibody units per milliliter (BAU/ml). Results obtained with sera from vaccinated healthy individuals and patients confirmed and extended results from previous studies on time-dependent waning of antibody levels and effects of immunosuppressive agents. We conclude that anti-RBDwt titers correlate with levels of neutralizing antibodies against VOCs and propose that our method may be implemented to enhance the precision and throughput of immunomonitoring.

Background and study aims Knowledge on self-reported quality of life (QoL) in achalasia and QoL improvements after peroral endoscopic myotomy (POEM) is limited. Furthermore, the clinical role of QoL in achalasia follow-up has not been evaluated. The present study aimed to examine QoL in achalasia patients before and after POEM and assess associations between QoL, Eckardt score (ES) and objective results. Patients and methods This was a single-center prospective study of treatment-naïve achalasia patients with 12-month follow-up after POEM including manometry, upper endoscopy, 24-hour pH registration, and timed barium esophagogram. QoL data were registered using European Organisation for Research and Treatment of Cancer core questionnaire (QLQ-C30) and esophageal module (QLQ-OES18). Comparison with a reference population was performed to assess impact of achalasia on QoL and effect of therapy. Mixed models for repeated measures were applied. Results Fifty patients (26 females) with a median age of 47 years (18–76) were included. Before treatment, all QoL domains were significantly impaired compared with an age- and gender-adjusted reference population (P Conclusions Achalasia is associated with severe QoL impairment. Following POEM, a significant and clinically relevant QoL improvement is observed. QoL is associated with ES, but not with objective results after POEM.

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 (

Background Laparoscopic aortomesenteric bypass may be performed to treat the chronic mesenteric ischemia patients who are not suitable for endovascular treatment. This study presents an initial experience with a limited series of laparoscopic mesenteric artery revascularization for the treatment of mesenteric ischemia. Methods Chronic mesenteric ischemia (CMI) patients with previous unsuccessful endovascular treatment or with arterial occlusion and extensive calcification precluding safe endovascular treatment were offered laparoscopic mesenteric revascularization. From October 2015 until November 2018, nine patients with CMI underwent laparoscopic revascularization. In addition to demographic data and perioperative results of the treatment, graft patency was assessed with Duplex ultrasound at 1, 3, 6 and 12 months, and annually thereafter. A descriptive analysis of the data was performed. Results All bypasses were constructed with an 8 mm ring enforced expanded polytetrafluoroethylene graft in a retrograde fashion (from infrarenal aorta or iliac artery) to either superior mesenteric artery or splenic artery (2 cases). Median operation time was 356 mins (range 247-492 mins). Five patients had a history of unsuccessful endovascular treatment. Laparoscopic technical success was 78%, and the primary open conversion rate was 22%. All laparoscopic revascularization procedures remained patent after discharge during a median follow-up time of 26 months (range 18-49 months). The primary graft patency at 30 days was 78%. Primary assisted, and secondary graft patency was 78% and 100%, respectively. Median weight gain was 2 kg (range 2-18 kg), and all patients achieved relief from postprandial pain and nausea. No mortality was observed during the follow-up period. Conclusion Laparoscopic aortomesenteric revascularization procedures for chronic mesenteric ischemia are feasible but require careful patient selection. These procedures should only be performed at referral centers by vascular surgeons with prior experience in laparoscopic vascular surgery.

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 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 The efficacy and safety of anti-TNF treatment for ulcerative colitis (UC) have been well documented in clinical trials. More data are required to increase knowledge on treatment success in a real world setting. This study reports real world data on treatment success, drug persistence and safety of anti-TNF treatment in patients with UC. Methods Patients with UC starting anti-TNF treatment with infliximab (IFX) or adalimumab (ADA) between January 2014 and December 2019 at Oslo University Hospital in Norway were included in a retrospective review of medical records. Eligible patients were biologically naïve adults (≥18 years) with no history of UC-related surgery. Follow-up was 12 months. Drug persistence was defined as the proportion of patients still receiving first-line anti-TNF treatment without addition of a second biologic agent. Remission was defined as i) clinical remission (six-point Mayo Score Results In total, 116 patients were included (mean age 35.5 ±13.9 years (SD), 58% male), of which 95 received IFX treatment and 21 ADA. Drug persistence was 74%. Treatment success by different definitions of remission and remission rates for drug persistent patients according to these definitions are reported in the table. SAEs were recorded on 18 occasions (four immediate infusion reactions, two colectomies, five infections and seven other events). Conclusion Treatment success by the strictest definition of remission was 40%. Of drug persistent patients, 44% were not in remission when applying the same definition. Whether these results reflect inadequacies in definitions of remission, a tendency for clinicians to let other variables guide treatment or a delay in drug switching warrants further investigation.

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.

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

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.

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 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 ...

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.