Frailty risk and treatment strategy in elderly-onset inflammatory bowel disease. A Norwegian nationwide population-based registry study.

BACKGROUND/AIMS: To determine real-world medical and surgical treatment patterns in elderly-onset inflammatory bowel disease in a nationwide cohort, and to investigate associations between frailty and treatment choices. METHODS: Norwegian health registries were used to identify adult-onset (born 1950-1989) and elderly-onset (born 1910-1949) patients with Crohn's disease (CD) and ulcerative colitis (UC) diagnosed 2010-2017 (n = 13,006). Patients were classified as no, low and intermediate/high frailty risk after the Hospital Frailty Risk Score. Outcomes included use of medical and surgical treatment. RESULTS: Within five years, elderly-onset patients received less biologics (13% [CD], 7% [UC]) and immunomodulators (24% [CD], 11% [UC]), and major surgery was more frequent (22% [CD], 9% [UC]) than in adult-onset. Respective log rank tests were significant (p < 0.01). Compared to no frailty risk groups, elderly-onset UC with intermediate/high frailty risk had lower probability of starting biologics (4% versus 9%), immunomodulators (7% versus 13%) and 5-aminosalisylic acids (66% versus 84%), and elderly-onset CD with intermediate/high frailty risk had higher probability of starting prednisolone (67% versus 49%). Respective log rank tests were significant (p < 0.05). CONCLUSIONS: Elderly-onset patients received less biologics and immunomodulators and a larger proportion underwent major surgery. Frailty risk in elderly-onset patients was associated with increased use of prednisolone, and less use of 5-aminosalisylic acids, immunomodulators and biologics.

Intraoperative distensibility measurement in POEM for achalasia: impact on patient outcome and associations with other outcome variables at 1-year follow-up.

BACKGROUND AND AIMS: The functional luminal imaging probe (FLIP) can provide measurements of lower esophageal sphincter (LES) distensibility. Studies report that use of intraoperative FLIP examination during peroral endoscopic myotomy (POEM) for achalasia is associated with treatment success, but evidence is limited and inconsistent. The main aim of the present study was to assess associations between intraoperative FLIP values and 1-year outcomes. Additionally, associations between 1-year FLIP measurements and other 1-year outcome variables were studied. METHODS: We performed a single-center prospective study of consecutive achalasia patients treated with POEM with a standardized 1-year follow-up. The inclusion period was from June 2017 to January 2020. We compared 1-year outcomes (FLIP measurement values, Eckardt score (ES), reflux esophagitis, timed barium esophagogram (TBE), and lower esophageal sphincter resting pressure (LES-rp)) in patients with and without intraoperative FLIP examination. We also assessed associations between intraoperative FLIP values, 1-year FLIP values, and other 1-year outcomes. Results are given as median (IQR), and non-parametrical statistical analyses were applied. RESULTS: Sixty-two patients (27 females) with median age 45 years (35-54) were included. Baseline characteristics were similar in patients with (n = 32) and without (n = 30) intraoperative FLIP examination. In patients with intraoperative FLIP, ES was 2 (1-3) and LES distensibility index (DI) 3.7 (2.6-5.4) after 1 year, compared with ES 2 (1-3) and DI 4.0 (3.1-6.8)) in patients without intraoperative FLIP (ns). Intraoperative DI was not correlated with 1-year ES or DI. One-year DI correlated significantly with 1-year ES (rs - 0.42), TBE (rs - 0.34), and LES-rp (rs - 0.29). CONCLUSIONS: Use of intraoperative FLIP measurements in POEM for achalasia is not associated with improved 1-year outcome, and the clinical value of intraoperative FLIP in POEM for achalasia is questioned. Follow-up FLIP measurements are moderately associated with symptomatic outcome, and may serve as an additional diagnostic modality in post-treatment evaluation.

Patient-reported outcomes, weight loss, and remission of type 2 diabetes 3 years after gastric bypass and sleeve gastrectomy (Oseberg); a single-centre, randomised controlled trial.

BACKGROUND: Little is known about the comparative effects of various bariatric procedures on patient-reported outcomes. We aimed to compare 3-year effects of gastric bypass and sleeve gastrectomy on patient-reported outcome measures in patients with obesity and type 2 diabetes. METHODS: The Oseberg trial was a single-centre, parallel-group, randomised trial at Vestfold Hospital Trust, a public tertiary obesity centre in Tønsberg, Norway. Eligible patients were aged 18 years or older with previously verified BMI 35·0 kg/m2 or greater. Diabetes was diagnosed if glycated haemoglobin was at least 6·5% (48 mmol/mol) or by their use of anti-diabetic medications with glycated haemoglobin at least 6·1% (43 mmol/mol). Eligible patients were randomly assigned (1:1) to gastric bypass or sleeve gastrectomy. All patients received identical preoperative and postoperative treatment. Randomisation was done with a computerised random number generator and a block size of ten. Study personnel, patients, and the primary outcome assessor were blinded to allocations for 1 year. The prespecified secondary outcomes reported here were 3-year changes in several clinically important patient-reported outcomes, weight loss, and diabetes remission. Analyses were done in the intention to treat population. This trial is ongoing, closed to recruitment and is registered with ClinicalTrials.gov, NCT01778738. FINDINGS: Between Oct 15, 2012 and Sept 1, 2017, 319 consecutive patients with type 2 diabetes scheduled for bariatric surgery were assessed for eligibility. 101 patients were not eligible (29 did not have type 2 diabetes according to inclusion criteria and 72 other exclusion criteria) and 93 declined to participate. 109 patients were enrolled and randomly assigned to sleeve gastrectomy (n=55) or gastric bypass (n=54). 72 (66%) of 109 patients were female and 37 (34%) were male. 104 (95%) of patients were White. 16 patients were lost to follow up and 93 (85%) patients completed the 3-year follow-up. Three additional patients were contacted by phone for registration of comorbidities Compared with sleeve gastrectomy, gastric bypass was associated with a greater improvement in weight-related quality of life (between group difference 9·4, 95% CI 3·3 to 15·5), less reflux symptoms (0·54, 0·17 to -0·90), greater total bodyweight loss (8% difference, 25% vs 17%), and a higher probability of diabetes remission (67% vs 33%, risk ratio 2·00; 95% CI 1·27 to 3·14). Five patients reported postprandial hypoglycaemia in the third year after gastric bypass versus none after sleeve-gastrectomy (p=0·059). Symptoms of abdominal pain, indigestion, diarrhoea, dumping syndrome, depression, binge eating, and appetitive drive did not differ between groups. INTERPRETATION: At 3 years, gastric bypass was superior to sleeve gastrectomy in patients with type 2 diabetes and obesity regarding weight related quality of life, reflux symptoms, weight loss, and remission of diabetes, while symptoms of abdominal pain, indigestion, diarrhoea, dumping, depression and binge eating did not differ between groups. This new patient-reported knowledge can be used in the shared decision-making process to inform patients about similarities and differences between expected outcomes after the two surgical procedures. FUNDING: Morbid Obesity Centre, Vestfold Hospital Trust. TRANSLATION: For the Norwegian translation of the abstract see Supplementary Materials section.

Fatigue in Patients with Newly Diagnosed Inflammatory Bowel Disease: Results from a Prospective Inception Cohort, the IBSEN III Study.

BACKGROUND AND AIMS: Although fatigue is common in inflammatory bowel disease [IBD], its pathogenesis remains unclear. This study aimed to determine the prevalence of fatigue and its associated factors in a cohort of patients newly diagnosed with IBD. METHODS: Patients ≥18 years old were recruited from the Inflammatory Bowel Disease South-Eastern Norway [IBSEN III] study, a population-based, observational inception cohort. Fatigue was assessed using the Fatigue Questionnaire and compared with data from a Norwegian general population. Univariate and multivariate linear and logistic regression analyses were performed to evaluate the associations of total fatigue [TF; continuous score] and substantial fatigue [SF; dichotomized score ≥4] with sociodemographic, clinical, endoscopic, laboratory, and other relevant patient data. RESULTS: In total, 983/1509 [65.1%] patients with complete fatigue data were included (ulcerative colitis [UC], 68.2%; Crohn's disease [CD], 31.8%). The prevalence of SF was higher in CD [69.6%] compared with UC [60.2%] [p < 0.01], and in both diagnoses when compared to the general population [p < 0.001]. In multivariate analyses, depressive symptoms, pain intensity, and sleep disturbances were associated with increased TF for both diagnoses. In addition, increased clinical disease activity and Mayo endoscopic score were significantly associated with TF in UC, whereas all disease-related variables were insignificant in CD. Similar findings were observed for SF, except regarding the Mayo endoscopic score. CONCLUSIONS: SF affects approximately two-thirds of patients newly diagnosed with IBD. Fatigue was associated with depressive symptoms, sleep disturbances, and increased pain intensity in both diagnoses, while clinical and endoscopic activity were associated factors only in UC.

Humoral immune response to SARS-CoV-2 vaccination in patients with inflammatory bowel disease on immunosuppressive medication: association to serum drug levels and disease type.

OBJECTIVES: 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. MATERIALS AND METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Quality of life in patients with achalasia: Associations with Eckardt score and objective treatment outcomes after peroral endoscopic myotomy.

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  < 0.05). No significant QoL-differences were found after POEM, except for fatigue and nausea/vomiting. Clinically relevant QoL improvement was observed in ≥ 50 % of the patients in all QoL domains, except for physical and role functioning. QoL was significantly associated with ES ( P  < 0.05) but not with objective results. 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.

A novel intragastric balloon for treatment of obesity and type 2 diabetes. A two-center pilot trial.

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.

Probiotics to HIV-Infected Immunological Nonresponders: Altered Mucosal Immunity and Microbial Diversity Restricted to Ileum.

BACKGROUND: 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. METHODS: 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 counts <400 cells/µL and plasma HIV RNA <50 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. RESULTS: 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. CONCLUSIONS: 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.

One year comprehensive prospective follow-up of achalasia patients after peroral endoscopic myotomy.

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 <5%. ES, lower oesophageal sphincter pressures, TBE heights and maximal oesophageal diameter were all reduced after POEM (p < .001), and 28% (13/47) of the patients had a positive 24-h pH registration. An oesophageal diameter >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.

First-line biologic treatment of inflammatory bowel disease during the first 12 months after diagnosis from 2010 to 2016: a Norwegian nationwide registry study.

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 < .001) for CD and 7% to 13% (p < .001) for UC. The most frequently used first-line biologics were infliximab (CD: 64% and UC: 82%) and adalimumab (CD: 36% and UC: 15%). The highest registered use of adalimumab was in the 2012 cohort (CD: 56% and UC: 39%). In the 2014-2016 cohorts, infliximab was the most used first-line biologic for both CD and UC. CONCLUSIONS: The proportion of IBD patients initiating biologics within 12 months after diagnosis increased between 2010 and 2016. The use of infliximab as first-line biologic increased after the approval of biosimilar infliximab in 2013.

The effect of train-the-colonoscopy-trainer course on colonoscopy quality indicators.

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.

Perioperative Microcirculatory Changes Detected with Gastroscopy Assisted Laser Doppler Flowmetry and Visible Light Spectroscopy in Patients with Median Arcuate Ligament Syndrome.

PURPOSE: 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.

Erosive Esophagitis and Symptoms of Gastroesophageal Reflux Disease in Patients with Morbid Obesity with and without Type 2 Diabetes: a Cross-sectional Study.

BACKGROUND: 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. METHODS: 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. RESULTS: 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 (< 29%) and did not differ significantly between groups, while the proportions of patients with esophagitis were high both in the T2DM and non-T2DM group, 58% versus 47%, p = 0.16. The majority of patients with esophagitis did not have GERD-symptoms (68-80%). Further, 55% of the patients with T2DM had pathologic acid reflux. Among these, 71% also had erosive esophagitis, whereof 67% were asymptomatic. CONCLUSIONS: The prevalence of GERD was similar in bariatric patients with or without T2DM, and the proportion of patients with asymptomatic GERD was high independent of the presence or absence of T2DM. Accordingly, GERD may be underdiagnosed in patients not undergoing a preoperative endoscopy or acid reflux assessment. TRIAL REGISTRATION: Clinical Trials.gov number NCT01778738.

Plasma cytokine levels in patients with chronic alcohol overconsumption: Relations to gut microbiota markers and clinical correlates.

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-ß1, TNF-α, IL-10, IL-8, IL-6, IFN-γ, MCP-1, IL-1RA, IL-1ß, 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-ß1 (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-ß1). The findings may represent a link between alcohol use and alcohol-related morbidity.

Gastroscopy assisted laser Doppler flowmetry and visible light spectroscopy in patients with chronic mesenteric ischemia.

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 < .001). A significant reduction was also seen for the relative hemoglobin (rHb) amount, flow and velocity (p < .001). The sensitivity of SO2 measured by VLS for diagnosing CMI was 94% and the specificity 72% (cut-off 78%), calculated with ROC curve analysis. A combination of SO2 and rHb increased the test sensitivity and specificity to 97% and 79%, respectively. Conclusion: CMI patients have significantly reduced microcirculation in the stomach and duodenum compared to controls. The results suggest that VLS should be included when performing an upper endoscopy in patients with suspected CMI.

Real world data on effectiveness, safety and therapeutic drug monitoring of vedolizumab in patients with inflammatory bowel disease. A single center cohort.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Outcome of peroral endoscopic myotomy (POEM) in treatment-naive patients. A systematic review.

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.

Combining Anti-TNF-α and Vedolizumab in the Treatment of Inflammatory Bowel Disease: A Case Series.

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.

Endoscopy assistants influence the quality of colonoscopy.

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.