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1.
  • Abdalla, Maie, et al. (author)
  • Anorectal Function After Ileo-Rectal Anastomosis Is Better than Pelvic Pouch in Selected Ulcerative Colitis Patients
  • 2020
  • In: Digestive Diseases and Sciences. - : Springer-Verlag New York. - 0163-2116 .- 1573-2568. ; , s. 250-259
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: With a lifelong perspective, 12% of ulcerative colitis patients will need a colectomy. Further reconstruction via ileo-rectal anastomosis or pouch can be affected by patients' perspective of their quality of life after surgery.AIM: To assess the function and quality of life after restorative procedures with either ileo-rectal anastomosis or ileal pouch-anal anastomosis in relation to the inflammatory activity on endoscopy and in biopsies.METHOD: A total of 143 UC patients operated with subtotal colectomy and ileo-rectal anastomosis or pouches between 1992 and 2006 at Linköping University Hospital were invited to participate. Those who completed the validated questionnaires (Öresland score, SF-36, Short Health Scale) were offered an endoscopic evaluation including multiple biopsies. Associations between anorectal function and quality of life with type of restorative procedure and severity of endoscopic and histopathologic grading of inflammation were evaluated.RESULTS: Some 77 (53.9%) eligible patients completed questionnaires, of these 68 (88.3%) underwent endoscopic evaluation after a median follow-up of 12.5 (range 3.5-19.4) years after restorative procedure. Patients with ileo-rectal anastomosis reported better overall Öresland score: median = 3 (IQR 2-5) for ileo-rectal anastomosis (n = 38) and 10 (IQR 5-15) for pouch patients (n = 39) (p < 0.001). Anorectal function (Öresland score) and endoscopic findings (Baron-Ginsberg score) were positively correlated in pouch patients (tau: 0.28, p = 0.006).CONCLUSION: Patients operated with ileo-rectal anastomosis reported better continence compared to pouches. Minor differences were noted regarding the quality of life. Ileo-rectal anastomosis is a valid option for properly selected ulcerative colitis patients if strict postoperative endoscopic surveillance is carried out.
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  • Bodecker-Zingmark, L., et al. (author)
  • Anti-Saccharomyces Cerevisiae antibodies are only modestly more common in subjects later developing Crohn's disease
  • 2023
  • In: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 68, s. 608-615
  • Journal article (peer-reviewed)abstract
    • Background: The pathogenic processes in the preclinical phase of inflammatory bowel disease (IBD) are mainly unknown.Aims: To study typical antibodies for IBD in the preclinical phase in a cohort of Northern Sweden.Methods: Antibodies typical for IBD (ASCA, pANCA, lactoferrin-ANCA, antibodies to goblet cells, and pancreas antigen) were analyzed in 123 subjects with preclinical ulcerative colitis (UC), 54 subjects with preclinical Crohn's disease (CD) and in 390 sex- and age-matched controls. In addition, in a subset of subjects, inflammatory markers (CRP, albumin, calprotectin and ferritin) were measured in plasma.Results: The mean years between blood samples and IBD diagnosis were for UC 5.1 (SD 3.5) years and CD 5.6 (SD 3.5) years. There was no difference in the proportion of overall positive antibodies between subjects who later developed IBD compared to controls (16.9% vs. 12.3%; p = 0.137). The subjects who later developed CD had a significantly higher proportion of positive ASCA compared to controls (9.3% vs 2.8%; p = 0.034), but for all other antibodies, there were no differences compared to control subjects. Subjects with preclinical IBD and elevated antibodies showed significantly higher plasma calprotectin levels compared to subjects without antibodies (980 μg/L vs 756 μg/L; p = 0.042), but there was no difference in the levels of CRP, albumin and ferritin.Conclusions: We found no significant increase in antibodies typical for IBD years before diagnosis except for ASCA, which was slightly more common in subjects who later developed CD. Very few subjects had detectable antibodies to goblet cells and pancreas antigen.
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  • Clevers, Egbert, et al. (author)
  • Coffee, Alcohol, and Artificial Sweeteners Have Temporal Associations with Gastrointestinal Symptoms
  • 2024
  • In: DIGESTIVE DISEASES AND SCIENCES. - 0163-2116 .- 1573-2568. ; 69, s. 2522-2529
  • Journal article (peer-reviewed)abstract
    • BackgroundVarious dietary strategies for managing irritable bowel syndrome (IBS) target mechanisms such as brain-gut interactions, osmotic actions, microbial gas production, and local immune activity. These pathophysiological mechanisms are diverse, making it unclear which foods trigger IBS symptoms for a substantial proportion of patients.AimTo identify associations between foods and gastrointestinal symptoms.MethodsFrom the mySymptoms smartphone app, we collected anonymized diaries of food intake and symptoms (abdominal pain, diarrhea, bloating, and gas). We selected diaries that were at least 3 weeks long. The diaries were analyzed for food-symptom associations using a proprietary algorithm. As the participants were anonymous, we conducted an app-wide user survey to identify IBS diagnoses according to Rome IV criteria.ResultsA total of 9,710 food symptom diaries that met the quality criteria were collected. Of the survey respondents, 70% had IBS according to Rome IV criteria. Generally, strong associations existed for caffeinated coffee (diarrhea, 1-2 h postprandial), alcoholic beverages (multiple symptoms, 4-72 h postprandial), and artificial sweeteners (multiple symptoms, 24-72 h postprandial). Histamine-rich food intake was associated with abdominal pain and diarrhea. Some associations are in line with existing literature, whilst the absence of an enriched FODMAP-symptom association contrasts with current knowledge.ConclusionsCoffee, alcohol, and artificial sweeteners were associated with GI symptoms in this large IBS-predominant sample. Symptom onset is often within 2 h postprandial, but some foods were associated with a delayed response, possibly an important consideration in implementing dietary recommendations. Clinical trials must test the causality of the demonstrated food-symptom associations.
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  • Dahlgren, David, et al. (author)
  • Hypotonicity-Induced Increase in Duodenal Mucosal Permeability Is Regulated by Cholinergic Receptors in Rats
  • 2023
  • In: Digestive Diseases and Sciences. - : Springer. - 0163-2116 .- 1573-2568. ; 68:5, s. 1815-1823
  • Journal article (peer-reviewed)abstract
    • BackgroundThe role of cholinergic receptors in the regulation of duodenal mucosal permeability in vivo is currently not fully described.AimsTo elucidate the impact of nicotinic and muscarinic acetylcholine receptor signaling in response to luminal hypotonicity (50 mM NaCl) in the proximal small intestine of rat.MethodsThe effect on duodenal blood-to-lumen clearance of 51Cr-EDTA (i.e., mucosal permeability) and motility was studied in the absence and presence of nicotinic and muscarinic receptor agonists and antagonists, a sodium channel blocker (tetrodotoxin), and after bilateral cervical vagotomy.ResultsRats with duodenal contractions responded to luminal hypotonicity by substantial increase in intestinal permeability. This response was absent in animals given a non-selective nicotinic receptor antagonist (mecamylamine) or agonist (epibatidine). Pretreatment with tetrodotoxin reduced the increase in mucosal permeability in response to luminal hypotonicity. Further, the non-selective muscarinic receptor antagonist (atropine) and agonist (bethanechol) reduced the hypotonicity-induced increase in mucosal permeability, while vagotomy was without an effect, suggesting that local enteric reflexes dominate. Finally, neither stimulating nor blocking the α7-nicotinic receptor had any significant effects on duodenal permeability in response to luminal hypotonicity, suggesting that this receptor is not involved in regulation of duodenal permeability. The effect of the different drugs on mucosal permeability was similar to the effect observed for duodenal motility.ConclusionsA complex enteric intramural excitatory neural reflex involving both nicotinic and muscarinic receptor subtypes mediates an increase in mucosal permeability induced by luminal hypotonicity.
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  • Engstrand, L, et al. (author)
  • Microbiome and Gastric Cancer
  • 2020
  • In: Digestive diseases and sciences. - : Springer Science and Business Media LLC. - 1573-2568 .- 0163-2116. ; 65:3, s. 865-873
  • Journal article (peer-reviewed)
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  • Eriksson, Carl, 1981-, et al. (author)
  • Ustekinumab Versus Anti-tumour Necrosis Factor Alpha Agents as Second-Line Biologics in Crohn's Disease
  • 2023
  • In: Digestive Diseases and Sciences. - : Springer-Verlag New York. - 0163-2116 .- 1573-2568. ; 68:7, s. 3119-3128
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: There are little data on positioning biologics in Crohn's disease (CD). AIMS: We aimed to assess the comparative effectiveness and safety of ustekinumab vs tumour necrosis factor-alpha (anti-TNF) agents after first-line treatment with anti-TNF in CD.METHODS: We used Swedish nationwide registers to identify patients with CD, exposed to anti-TNF who initiated second-line biologic treatment with ustekinumab or second-line anti-TNF therapy. Nearest neighbour 1:1 propensity score matching (PSM) was used to balance the groups. The primary outcome was 3-year drug survival used as a proxy for effectiveness. Secondary outcomes included drug survival without hospital admission, CD-related surgery, antibiotics, hospitalization due to infection and exposure to corticosteroids.RESULTS: Some 312 patients remained after PSM. Drug survival at 3 years was 35% (95% CI 26-44%) in ustekinumab compared to 36% (95% CI 28-44%) in anti-TNF-treated patients (p = 0.72). No statistically significant differences were observed between the groups in 3-year survival without hospital admission (72% vs 70%, p = 0.99), surgery (87% vs 92%, p = 0.17), hospital admission due to infection (92% vs 92%, p = 0.31) or prescription of antibiotics (49% vs 50%, p = 0.56). The proportion of patients continuing second-line biologic therapy did not differ by reason for ending first-line anti-TNF (lack of response vs intolerance) or by type of first-line anti-TNF (adalimumab vs infliximab).CONCLUSION: Based on data from Swedish routine care, no clinically relevant differences in effectiveness or safety of second-line ustekinumab vs anti-TNF treatment were observed in patients with CD with prior exposure to anti-TNF.
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8.
  • Forss, Anders, et al. (author)
  • Ustekinumab Is Associated with Real-World Long-Term Effectiveness and Improved Health-Related Quality of Life in Crohn's Disease
  • 2023
  • In: Digestive Diseases and Sciences. - : Kluwer Academic Publishers. - 0163-2116 .- 1573-2568. ; 68:1, s. 65-76
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Prospectively and systematically collected long-term real-world clinical data on ustekinumab (anti-interleukin-12/23) are still scarce.AIMS: To assess the long-term effectiveness of ustekinumab in patients with active Crohn's disease (CD).METHODS: This is a prospective multicenter study of adult patients with CD initiating ustekinumab according to recommended doses at 20 Swedish hospitals. The primary outcome was clinical remission (Harvey-Bradshaw Index (HBI) ≤ 4 points) at weeks 52 and 104. Secondary outcomes included clinical response (≥ 3-point-decrease in HBI among patients with initial HBI ≥ 5 points), treatment retention, and biomarkers (C-reactive protein (CRP), hemoglobin, fecal-calprotectin) at weeks 52 and 104 compared to baseline. We also reported Health-related Quality of Life (HRQoL) measures.RESULTS: Of 114 included patients, 107 (94%) had previously failed ≥ 1 and 58 (51%) ≥ 2 anti-tumor necrosis factor agents. Forty (35%) had failed anti-integrin agents. Ustekinumab retention rates at weeks 52 and 104 were 70% (n = 80/114) and 61% (n = 69/114), respectively. Clinical response was seen in 36% (n = 25/69) and 29% (n = 20/69) of the patients, and remission was achieved in 32% (n = 31/96) and 29% (n = 28/96) at weeks 52 and 104, respectively. Median HBI and CRP levels decreased significantly at both timepoints as compared to baseline. Significant improvements were also observed in HRQoL. Adverse events were reported in 11% (n = 13/114) of the patients, including five cases of severe adverse events. No malignancies were observed.CONCLUSIONS: In this nationwide prospective real-world 104-week-follow-up study of adult patients with active CD, ustekinumab was associated with long-term clinical effectiveness and improvement in HRQoL measures when used in routine clinical care.
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9.
  • Han, Hedong, et al. (author)
  • Temporary Trend, Characteristics and Clinical Outcomes of Acute Pancreatitis Patients Infected with Human Immunodeficiency Virus
  • 2021
  • In: Digestive Diseases and Sciences. - : Kluwer Academic/Plenum Publishers. - 0163-2116 .- 1573-2568. ; 66, s. 1683-1692
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Compared to general population, human immunodeficiency virus (HIV) infection may increase frequency of acute pancreatitis (AP); however, evidence regarding effects of HIV infection on AP-related outcomes is limited and controversial.AIMS: We aim to investigate the temporary trend, characteristics and clinical outcomes of AP infected with HIV.METHODS: We reviewed data from the 2003-2014 National Inpatient Sample to identify patients with a primary diagnosis of AP. The primary outcomes (in-hospital mortality, acute respiratory failure, acute kidney injury, and prolonged length of stay [LOS]) and secondary outcomes (gastrointestinal hemorrhage, sepsis and total cost) were compared between patients with and without HIV infection using univariate, multivariable and propensity score matching analyses.RESULTS: Of 594,106 patients diagnosed with AP, 6775 (1.14%) had HIV infection. Patients with HIV were more likely to be younger, black, male, less likely to be gallstone-related and had lower rate of interventions. Multivariable analyses based on multiple imputation revealed that HIV infection was associated with higher risk of mortality (odds ratio [OR]: 1.74; 95% confidence interval [CI] 1.34-2.25), acute kidney injury (OR: 1.13; 95% CI 1.19-1.44), prolonged LOS (OR: 1.26; 95% CI 1.15-1.37) and 6% higher cost. There were no differences in sepsis, gastrointestinal bleeding, and respiratory failure between groups.CONCLUSIONS: HIV infection is associated with adverse outcomes including increased mortality, acute kidney injury and more healthcare utilization in AP patients. More assertive management strategies like early intravenous fluid resuscitation in HIV patients hospitalized with AP to prevent acute kidney injury may be helpful to improve clinical outcomes.
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  • Lamichhane, N., et al. (author)
  • Real-World Outcomes of Patients Starting Intravenous and Transitioning to Subcutaneous Vedolizumab in Inflammatory Bowel Disease
  • 2024
  • In: Digestive Diseases and Sciences. - : Kluwer Academic Publishers. - 0163-2116 .- 1573-2568. ; 69:6, s. 2175-2183
  • Journal article (peer-reviewed)abstract
    • BACKGROUND: Real-world data on starting intravenous (IV) vedolizumab (VDZ) and transitioning to subcutaneous (SC) treatment in inflammatory bowel disease (IBD) are scarce. AIMS: To assess treatment outcomes of patients with IBD starting IV VDZ and switching to SC VDZ in routine clinical care.METHODS: Adult patients with IBD switching from IV to SC VDZ treatment between 1 March 2020 and 31 December 2021 were identified from the Swedish IBD quality register. The primary outcome was SC VDZ persistence. Secondary outcomes included clinical remission, changes in quality of life (QoL) according to EuroQual 5-Dimensions 5-Levels (EQ-5D-5L) and the Short-Health Scale (SHS) and inflammatory markers, including faecal Calprotectin (FCP).RESULTS: Altogether, 406 patients with IBD (Crohn's disease, n = 181; ulcerative colitis, n = 225) were identified. After a median follow-up of 30 months from starting IV VDZ treatment, the persistence rates were 98%(178/181) in Crohn's disease and 94% (211/225) in ulcerative colitis. Most patients (84%) transitioned during maintenance therapy, and the median follow-up from switch to SC VDZ was 10 months. Compared to baseline, statistically significant improvements were observed in all domains of the SHS, EQ-5D index value and visual analogue scale. Median (interquartile range) FCP concentrations (μg/g) decreased from 459 (185-1001) to 65 (26-227) in Crohn's disease (n = 45; p < 0.001) and from 646 (152-1450) to 49 (20-275) in ulcerative colitis (n = 58; p < 0.001).CONCLUSION: Initiating IV VDZ and switching to SC treatment was associated with high persistence rates and improvements in measures of QoL and FCP. These findings are reassuring for patients who start IV VDZ and switch to SC VDZ.
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13.
  • Lingblom, Christine, 1984, et al. (author)
  • Patient-Reported Outcomes and Blood-Based Parameters Identify Response to Treatment in Eosinophilic Esophagitis
  • 2021
  • In: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 66, s. 1556-1564
  • Journal article (peer-reviewed)abstract
    • Background Noninvasive methods to assess treatment response in eosinophilic esophagitis are needed. Aims Our aim was to determine whether a blood-based biomarker panel centered on immune parameters could identify histologic response to treatment in eosinophilic esophagitis patients. Methods A pilot study involving adult patients with active eosinophilic esophagitis recruited at two Ear, Nose, Throat clinics in Sweden was designed. The patients (n = 20) donated blood and esophageal biopsies and filled in three questionnaires before and after a 2-month course of topical corticosteroids. Blood samples were analyzed for absolute levels of granulocytes and T cells and the fractions of eosinophils expressing 10 different surface markers by flow cytometry. All data were analyzed by multivariate methods of pattern recognition. Results Multivariate modeling revealed that a combination of 13 immune parameters and 10 patient-reported outcome scores were required to create a model capable of separating responders (n = 15) from non-responders (n = 5). Questions regarding symptoms of esophageal dysfunction and capacity to eat certain foods from two of the questionnaires were discriminatory in the multivariate model, as were absolute counts of T cells, eosinophils, and eosinophil expression of activation markers and cell adhesion molecules. Conclusions A combination of blood-based immune parameters and directed questions may prove helpful to monitor response to treatment, perhaps reducing the need for repeat endoscopies in eosinophilic esophagitis patients in the future.
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14.
  • Malmquist, Marianne, 1961, et al. (author)
  • Frequent Occurrence of Perianal Disease and Granuloma Formation in Patients with Crohn's Disease and Coexistent Orofacial Granulomatosis
  • 2023
  • In: Digestive Diseases and Sciences. - : Springer Science and Business Media LLC. - 0163-2116 .- 1573-2568. ; 68:7, s. 3129-3138
  • Journal article (peer-reviewed)abstract
    • BackgroundOrofacial granulomatosis (OFG) is an inflammatory disorder of the perioral region and oral cavity. Crohn's disease (CD) in conjunction with OFG (CD-OFG), has been suggested to constitute a phenotype of CD with distinct features at diagnosis.AimsThe aim of this project was to investigate whether the distinct phenotypic features of CD-OFG persist in the years following the initial diagnosis of CD.MethodsClinical data were extracted from medical records covering the first 5 years post-diagnosis for a cohort of patients with CD-OFG, and were compared to those of references with CD without OFG.ResultsThe clinical characteristics of our cohort of patients with CD-OFG (N = 25) were evaluated in comparison to references with CD without OFG (ratio 1:2). Five years post-diagnosis, more patients with CD-OFG had a phenotype with perianal disease (cumulative incidence: 16/25, 64% vs 13/50, 26%, P = 0.002) and intestinal granulomas (cumulative incidence: 22/25, 88% vs 24/50, 48%, P = 0.0009) than patients in the CD reference group. The patients with CD-OFG were also more likely to have undergone perianal surgery (12/25, 48% vs 4/50, 8%, P = 0.0002). At the end of the observation period, more of the patients with CD-OFG were receiving combination therapy, i.e., immunomodulators and tumor necrosis factor antagonists, than those in the CD reference group (9/25, 36% vs 5/50, 10%, P = 0.01).ConclusionThe results support the notion that CD in conjunction with OFG represents a specific phenotype of CD that is characterized by frequent perianal disease, pronounced intestinal granuloma formation and a need for extensive therapy.
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  • Zuzek, Rachael, et al. (author)
  • Prevalence of Histological Gastritis in a Community Population and Association with Epigastric Pain
  • 2024
  • In: Digestive Diseases and Sciences. - 0163-2116 .- 1573-2568. ; 69, s. 528-537
  • Journal article (peer-reviewed)abstract
    • Background and Aims Gastritis is a common histological diagnosis, although the prevalence is decreasing in developed populations, alongside decreasing prevalence of H. pylori infection. We sought to determine the prevalence of the etiology of gastritis in a Swedish population sample and to analyze any associations with symptoms, an area of clinical uncertainty. Methods Longitudinal population-based study based in osthammar, Sweden. A randomly sampled adult population completed a validated gastrointestinal symptom questionnaire (Abdominal Symptom Questionnaire, ASQ) in 2011 (N = 1175). Participants < 80 years of age and who were eligible were invited to undergo esophagogastroduodenoscopy (EGD) (N = 947); 402 accepted and 368 underwent EGD with antral and body biopsies (average 54.1 years, range 20-79 years; 47.8% male) with H. pylori serology. Results Gastritis was found in 40.2% (148/368; 95% CI 35.2-45.2%). By rank, the most common histological subtype was reactive (68/148; 45.9%), then H. pylori (44/148; 29.7%), chronic non-H. pylori (29/148; 19.6%), and autoimmune (4/148; 2.7%). Gastritis was significantly associated with older age and H. pylori status (p < 0.01). Gastritis subjects were divided into three histological categories: chronic inactive inflammation, autoimmune gastritis, and active inflammation; there was no difference in the presence of upper gastrointestinal symptoms when categories were compared to cases with no pathological changes. Functional dyspepsia or gastroesophageal reflux were reported in 25.7% (38/148) of those with gastritis (any type or location) versus 34.1% (75/220) with no pathological changes (p = 0.32). Epigastric pain was more common in chronic H. pylori negative gastritis in the gastric body (OR = 3.22, 95% CI 1.08-9.62). Conclusion Gastritis is common in the population with a prevalence of 40% and is usually asymptomatic. Chronic body gastritis may be associated with epigastric pain, but independent validation is required to confirm these findings. Clinicians should not generally ascribe symptoms to histological gastritis.
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