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Engström, J., Lönnkvist, M., Befrits, R., Ljung, T., Diaz, H., Holst, M. & Hellström, P. M. (2019). Comparison of fecal calprotectin and serum C-reactive protein in early prediction of outcome to infliximab induction therapy. Scandinavian Journal of Gastroenterology, 54(9), 1081-1088
Open this publication in new window or tab >>Comparison of fecal calprotectin and serum C-reactive protein in early prediction of outcome to infliximab induction therapy
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 9, p. 1081-1088Article in journal (Refereed) Published
Abstract [en]

Background: Fecal calprotectin (FC) and serum C-reactive protein (CRP) are biomarkers of disease activity in Crohn's disease (CD) and ulcerative colitis (UC). We assessed FC, CRP, Harvey-Bradshaw index (HBi), partial Mayo Clinic Scoring (pMCS) and a cytokine panel during infliximab induction to predict therapy outcome.

Methods: FC, CRP and clinical indices were evaluated in 123 (76 CD, 47 UC) patients before infliximab induction and after 12 weeks. Responders were monitored 48 weeks for an 'incident' (dosage increase, shortened dosage interval, surgery). Cutoff values for FC and CRP were obtained using receiver-operating characteristics (ROC). Disease progression was analyzed with Kaplan-Meier survivals, log-rank test and logistic regression for combined biomarkers. Cytokines were analyzed with Luminex multiplexing system.

Results: Following infliximab, FC and CRP declined (p < .0001) along with HBi for CD and pMCS for UC. Simultaneously, IL-6 and TNF-alpha decreased, while IL-10 increased. Optimal FC ROC cutoff was 221 mu g/g (sensitivity 66%, specificity 67%, AUC 0.71) and CRP ROC cutoff 2.1 mg/L (sensitivity 54%, specificity 60%, AUC 0.58). In CD, FC > 221 mu g/g (p < .0001), but not CRP > 2.1 mg/L predicted an 'incident'. However, combined FC and CRP also predicted an 'incident' (p < .042). In UC, both FC > 221 mu g/g (p < .0005) and CRP > 2.1 mg/L (p = .0334) predicted 'incident', as did combined biomarkers (p < .005).

Conclusions: Clinical disease activity is reduced by treatment with infliximab. In CD, persistently high FC, but not CRP, predict a treatment 'incident', whereas in UC both high FC and high CRP predict 'incident'. Combined FC and CRP values also predict an 'incident'.

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Biomarker, cytokines, IBD clinical, induction therapy, outcome
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-396104 (URN)10.1080/00365521.2019.1660402 (DOI)000485990200001 ()31499013 (PubMedID)
Funder
Swedish Research Council, 2017-02243Swedish Society for Medical Research (SSMF)
Available from: 2019-11-01 Created: 2019-11-01 Last updated: 2019-11-01Bibliographically approved
Hellström, P. M. (2019). GLP-1 analogue liraglutide as adjunct treatment in diabetes type 2 after failed bariatric/metabolic surgery. Annals of Translational Medicine, 7, Article ID S240.
Open this publication in new window or tab >>GLP-1 analogue liraglutide as adjunct treatment in diabetes type 2 after failed bariatric/metabolic surgery
2019 (English)In: Annals of Translational Medicine, ISSN 2305-5839, E-ISSN 2305-5847, Vol. 7, article id S240Article in journal, Editorial material (Other academic) Published
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:uu:diva-395750 (URN)10.21037/atm.2019.08.94 (DOI)000487291000067 ()
Note

Comment on: Miras AD, Pérez-Pevida B, Aldhwayan M, et al. Adjunctive liraglutide treatment in patients with persistent or recurrent type 2 diabetes after metabolic surgery (GRAVITAS): a randomised, double-blind, placebo-controlled trial. Lancet Diabetes Endocrinol 2019;7:549-59.

Available from: 2019-10-24 Created: 2019-10-24 Last updated: 2019-10-24Bibliographically approved
Sima, E., Webb, D.-L., Hellström, P. M. & Sundbom, M. (2019). Non-responders After Gastric Bypass Surgery for Morbid Obesity: Peptide Hormones and Glucose Homeostasis. Obesity Surgery, 29(12), 4008-4017
Open this publication in new window or tab >>Non-responders After Gastric Bypass Surgery for Morbid Obesity: Peptide Hormones and Glucose Homeostasis
2019 (English)In: Obesity Surgery, ISSN 0960-8923, E-ISSN 1708-0428, Vol. 29, no 12, p. 4008-4017Article in journal (Refereed) Published
Abstract [en]

INTRODUCTION: About 20% of patients operated with Roux-en-Y gastric bypass (RYGBP) experience poor long-term weight result. This study compared levels of leptin and gut hormones in long-term weight responders with non-responders after RYGBP. In a subgroup analysis, hormone levels were assessed in T2DM (type 2 diabetes mellitus) and normoglycemic participants.

METHODS: Insulin, glucose, leptin, acyl-ghrelin, total PYY, active GLP-1, and GIP were measured during an oral glucose tolerance test (OGTT) in post-RYGBP subjects: 22 non-responders (BMI 40.6 ± 6.0 kg/m2 after an excess BMI loss [EBMIL] of 26.0 ± 15.9%) and 18 responders (BMI 29.5 ± 3.5 kg/m2 after an EBMIL of 74.9 ± 18.2%). Subjects were matched for preoperative age, BMI, and years of follow-up. Measures of glucose homeostasis were calculated, and body composition was measured.

RESULTS: Fat mass-adjusted fasting leptin correlated negatively with %EBMIL (r = - 0.57, p < 0.01). Non-responders presented higher levels of leptin during the OGTT. Leptin decreased and ghrelin returned to baseline levels earlier in non-responders. Despite having higher insulin resistance than responders, non-responders demonstrated similar OGTT responses of GLP-1, GIP, and PYY. T2DM participants demonstrated lower GLP-1 levels than normoglycemic participants of similar weight.

CONCLUSION: Fasting leptin is associated with weight result after RYGBP, and hormonal responses to a glucose oral load might work towards promoting obesity in long-term non-responders after RYGBP. Poor long-term weight result and glycemic status after RYGBP are each associated with differences in peptide hormone levels.

Keywords
Gastric bypass, Incretins, Leptin, Long-term results, Weight loss
National Category
Gastroenterology and Hepatology
Research subject
Medical Science
Identifiers
urn:nbn:se:uu:diva-400343 (URN)10.1007/s11695-019-04089-8 (DOI)000504613300014 ()31338735 (PubMedID)
Funder
The Swedish Medical Association
Available from: 2019-12-19 Created: 2019-12-19 Last updated: 2020-01-09Bibliographically approved
Hellström, P. M. (2019). Pathophysiology of the irritable bowel syndrome - Reflections of today. Baillière's Best Practice & Research: Clinical Gastroenterology, 40-41, Article ID 101620.
Open this publication in new window or tab >>Pathophysiology of the irritable bowel syndrome - Reflections of today
2019 (English)In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 40-41, article id 101620Article, review/survey (Refereed) Published
Abstract [en]

Irritable bowel syndrome (IBS) is a chronic gastrointestinal symptom complex defined by abdominal pain and disturbed bowel habits over 3 months within a period of 6 months, in absence of any identifiable organic pathology. Over the years, speculations of the pathophysiology of IBS has moved from elusive central nervous symptoms impinging on psychosomatic disease, to objective signs of intestinal fermentation with abdominal bloating and intestinal dysmotility. The specific subgroup of post infectious IBS is of special interest since it opens the possibility of dysbiosis as the pivotal point for development of IBS in association with traveler's diarrhea or antibiotic treatment with ensuing dysbiosis and abdominal symptoms that may resolve over decades. The undefined disease mechanisms that take place within the gut seem responsible for the gut-brain signaling leading to activation of brain centers that drive the clinical picture of IBS, further modulated by the patient's social background and previous lifetime events. (C) 2019 Published by Elsevier Ltd.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Dysbiosis, Irritable bowel syndrome, Motility, Rectal distension, Serotonin
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-408002 (URN)10.1016/j.bpg.2019.05.007 (DOI)000517974000002 ()31594651 (PubMedID)
Funder
Swedish Research Council, 2017-02243
Available from: 2020-04-02 Created: 2020-04-02 Last updated: 2020-04-02Bibliographically approved
Hellström, P. M. (2019). Preface - Functional gastrointestinal disorders. Baillière's Best Practice & Research: Clinical Gastroenterology, 40-41, Article ID 101605.
Open this publication in new window or tab >>Preface - Functional gastrointestinal disorders
2019 (English)In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 40-41, article id 101605Article in journal, Editorial material (Other academic) Published
Place, publisher, year, edition, pages
Elsevier, 2019
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-407998 (URN)10.1016/j.bpg.2019.03.001 (DOI)000517974000003 ()31594652 (PubMedID)
Available from: 2020-04-03 Created: 2020-04-03 Last updated: 2020-04-03Bibliographically approved
Söderquist, F., Sundberg, I., Ramklint, M., Widerström, R., Hellström, P. M. & Cunningham, J. (2019). The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care. Psychosomatic Medicine, 81(1), 51-56
Open this publication in new window or tab >>The Relationship Between Daytime Salivary Melatonin and Gastrointestinal Symptoms in Young Adults Seeking Psychiatric Care
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2019 (English)In: Psychosomatic Medicine, ISSN 0033-3174, E-ISSN 1534-7796, Vol. 81, no 1, p. 51-56Article in journal (Refereed) Published
Abstract [en]

Objective: The pathophysiology of irritable bowel syndrome (IBS) is not completely understood, although we do know that patients with IBS have a high prevalence of psychiatric comorbidity (mainly depression and anxiety disorders). Melatonin, produced in the gastrointestinal tract, influences gutmotility. Psychiatric conditions are associated with circadian disturbances in peripheral melatonin levels. This study aimed to investigate associations between daytime salivary melatonin and gastrointestinal symptoms in young adult psychiatric patients.

Methods: Ninety-six patients (86% women), aged 18-25 years (M (SD) = 21 (2)), seeking psychiatric care with primarily anxiety disorders, affective disorders, or both were included in the study. Total scores from the Gastrointestinal Symptoms Rating Scale -IBS were compared with salivary melatonin measured at three time points (30 minutes after waking up, at 11: 00 hours and 30 minutes after lunch) during the waking hours of 1 day.

Results: After adjustment for potential confounders, melatonin levels in saliva 30 minutes after lunch remained significantly correlated to the total Gastrointestinal Symptoms Rating Scale -IBS score after correction for multiple testing (B = 0.016, SE = 0.006, p =.015, q = 0.045). In a post hoc analysis, symptoms of gastrointestinal pain and bloating contributed most to this association.

Conclusions: In young adult psychiatric patients, salivary melatonin levels after lunch are associated with gastrointestinal symptoms, which is consistent with the proposed effect of elevated levels of gastrointestinal melatonin on gut motility. This result suggests a link between IBS symptoms and regulation of melatonin in patients with psychiatric disorders.

Place, publisher, year, edition, pages
LIPPINCOTT WILLIAMS & WILKINS, 2019
Keywords
depression, human, irritable bowel syndrome, melatonin, mental health
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-375232 (URN)10.1097/PSY.0000000000000644 (DOI)000455260000007 ()30299401 (PubMedID)
Funder
Erik, Karin och Gösta Selanders FoundationStiftelsen Söderström - Königska sjukhemmet
Available from: 2019-01-29 Created: 2019-01-29 Last updated: 2019-01-29Bibliographically approved
Hellström, P. M. & Benno, P. (2019). The Rome IV: Irritable bowel syndrome - A functional disorder. Baillière's Best Practice & Research: Clinical Gastroenterology, 40-41, Article ID 101634.
Open this publication in new window or tab >>The Rome IV: Irritable bowel syndrome - A functional disorder
2019 (English)In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 40-41, article id 101634Article, review/survey (Refereed) Published
Abstract [en]

Functional gastrointestinal disorders are the most common disorders encountered in the clinical gastroenterology setting. Over the years the Rome process has generated consensus definitions of functional gastrointestinal disorders, and given diagnostic criteria, based on various symptom patterns, that have evolved over the years. The latest Rome IV consensus was presented in May 2016. This summary points out some of the important changes made from the Rome III 2006 consensus including evaluation of symptoms from the stand-point of basal normative values and disorders of gut-brain interaction, as well as additions of the importance of the microflora. However, we are all aware of the fact that there are limitations, and the Rome consensus does not pick up all patients with functional gastrointestinal disorders. Out of those that seek medical help for their functional gastrointestinal symptoms additional outlines of disease have to be considered and judgements made on the patients' actual symptoms, or rather presentation of their symptoms. The Rome IV consensus is a robust standard for a clinical and research approach to functional gastrointestinal disorders, but might be improved by use of exclusion criteria and additional biochemical biomarkers in order to accurately diagnose those patients who may achieve relief by an extended treatment approach in the clinical setting of gastroenterology. A biopsychosocial approach to the patient is recommended to improve compliance and optimize treatment and outcomes. (C) 2019 Published by Elsevier Ltd.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Constipation, Defecation, Diarrhoea, Bloating, Abdominal pain, Stool
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-407999 (URN)10.1016/j.bpg.2019.101634 (DOI)000517974000010 ()31594650 (PubMedID)
Available from: 2020-04-03 Created: 2020-04-03 Last updated: 2020-04-03Bibliographically approved
Benno, P., Norin, E., Midtvedt, T. & Hellström, P. M. (2019). Therapeutic potential of an anaerobic cultured human intestinal microbiota, ACHIM, for treatment of IBS. Baillière's Best Practice & Research: Clinical Gastroenterology, 40-41, Article ID 101607.
Open this publication in new window or tab >>Therapeutic potential of an anaerobic cultured human intestinal microbiota, ACHIM, for treatment of IBS
2019 (English)In: Baillière's Best Practice & Research: Clinical Gastroenterology, ISSN 1521-6918, E-ISSN 1532-1916, Vol. 40-41, article id 101607Article, review/survey (Refereed) Published
Abstract [en]

By administering an anaerobic cultivated human intestinal microbiota (ACHIM) via upper gastrointestinal route using endoscopy we aimed to rectify intestinal dysbiosis and simultaneously achieve a treatment response in IBS patients. The study population fulfilled the Rome III IBS criteria and comprised 50 patients. During 10 days, patients recorded the irritable bowel syndrome symptom severity scale (IBS-SSS) along with the Bristol stool scale and number of stools/day. The enrolled patients were categorized as follows: 37 with diarrhea, 5 with constipation and 8 with mixed symptoms. The treatment response showed reduction in a majority of patients, 32 of which with 50-point reduction of IBS-SSS and 21 with a 100-point IBS-SSS reduction. The percentage improvement was 36 (23-49) and 28 (18-38) for women and men respectively. Short-chain fatty acids were not changed. We consider fecal microbiota transplantation in the form of ACHIM as an option for the future therapeutic armamentarium in IBS. (C) 2019 Published by Elsevier Ltd.

Place, publisher, year, edition, pages
Elsevier, 2019
Keywords
Anaerobic cultivated human intestinal microbiota, Irritable bowel syndrome, Microbiota transplant
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-408000 (URN)10.1016/j.bpg.2019.03.003 (DOI)000517974000009 ()31594647 (PubMedID)
Funder
Swedish Society of Medicine
Available from: 2020-04-02 Created: 2020-04-02 Last updated: 2020-04-02Bibliographically approved
Wallner, B., Björ, O., Andreasson, A., Vieth, M., Schmidt, P. T., Hellström, P. M., . . . Agreus, L. (2019). Z-line alterations and gastroesophageal reflux: an endoscopic population-based prospective cohort study. Scandinavian Journal of Gastroenterology, 54(9), 1065-1069
Open this publication in new window or tab >>Z-line alterations and gastroesophageal reflux: an endoscopic population-based prospective cohort study
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2019 (English)In: Scandinavian Journal of Gastroenterology, ISSN 0036-5521, E-ISSN 1502-7708, Vol. 54, no 9, p. 1065-1069Article in journal (Refereed) Published
Abstract [en]

Background and study aims: Barrett's esophagus is a premalignant condition in the distal esophagus associated with esophageal adenocarcinoma. Since gastroesophageal reflux is known to be of etiological importance in both Barrett's esophagus and esophageal adenocarcinoma, we aimed to study which endoscopic alterations at the Z-line can be attributed to a previous history of reflux symptoms.

Patients and methods: From 1988, a population cohort in Sweden has been prospectively studied regarding gastrointestinal symptoms, using a validated questionnaire. In 2012, the population was invited to undergo a gastroscopy and participate in the present study. In order to determine which endoscopic alterations that can be attributed to a previous history of gastroesophageal reflux, three different endoscopic definitions of columnar-lined esophagus (CLE) were used: (1) ZAP I, An irregular Z-line with a suspicion of tongue-like protrusions; (2) ZAP II/III, Distinct, obvious tongues of metaplastic columnar epithelium; (3) CLE >= 1 cm, The Prague C/M-classification with a minimum length of 1 cm.

Results: A total of 165 community subjects were included in the study. Of these, 40 had CLE >= 1 cm, 99 had ZAP I, and 26 had ZAP II/III. ZAP II/III was associated with an over threefold risk of previous GER symptoms (OR: 3.60, CI: 1.49-8.70). No association was found between gastroesophageal reflux and ZAP I (OR: 2.06, CI: 0.85-5.00), or CLE >= 1 cm (OR: 1.64, CI: 0.77-3.49).

Conclusions: In a general community, the only endoscopic alteration to the Z-line definitely linked to longstanding GER symptoms was the presence of obvious tongues of metaplastic columnar epithelium (ZAP II/III).

Place, publisher, year, edition, pages
TAYLOR & FRANCIS LTD, 2019
Keywords
Barrett's esophagus, endoscopy, gastroesophageal reflux
National Category
Gastroenterology and Hepatology
Identifiers
urn:nbn:se:uu:diva-396106 (URN)10.1080/00365521.2019.1656775 (DOI)000484019100001 ()31453726 (PubMedID)
Available from: 2019-11-01 Created: 2019-11-01 Last updated: 2019-11-01Bibliographically approved
Marrinan, S. L., Otiker, T., Vasist, L. S., Gibson, R. A., Sarai, B. K., Barton, M. E., . . . Burn, D. J. (2018). A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.. Movement Disorders, 33(2), 329-332
Open this publication in new window or tab >>A randomized, double-blind, placebo-controlled trial of camicinal in Parkinson's disease.
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2018 (English)In: Movement Disorders, ISSN 0885-3185, E-ISSN 1531-8257, Vol. 33, no 2, p. 329-332Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Delayed gastric emptying may impair l-dopa absorption, contributing to motor fluctuations. We evaluated the effect of camicinal (GSK962040), a gastroprokinetic, on the absorption of l-dopa and symptoms of PD.

METHODS: Phase II, double-blind, placebo-controlled trial. Participants were randomized to receive camicinal 50 mg once-daily (n = 38) or placebo (n = 20) for 7 to 9 days.

RESULTS: l-dopa exposure was similar with coadministration of camicinal compared to placebo. Median time to maximum l-dopa concentration was reduced, indicating more rapid absorption of l-dopa. Camicinal resulted in significant reduction in OFF time (-2.31 hours; 95% confidence interval: -3.71, -0.90), significant increase in ON time (+1.88 hours; 95% confidence interval: 0.28, 3.48) per day, and significant decrease in mean total MDS-UPDRS score (-12.5; 95% confidence interval: -19.67, -5.29). Camicinal treatment was generally well tolerated.

CONCLUSIONS: PD symptom improvement with camicinal occurred in parallel with more rapid absorption of l-dopa. This study provides evidence of an improvement of the motor response to l-dopa in people with PD treated with camicinal 50 mg once-daily compared with placebo, which will require further evaluation.

Keywords
Clinical trials Randomized controlled (CONSORT agreement), Parkinson's disease/parkinsonism
National Category
Neurology
Identifiers
urn:nbn:se:uu:diva-343107 (URN)10.1002/mds.27259 (DOI)000424815100022 ()29278279 (PubMedID)
Funder
GlaxoSmithKline (GSK)
Available from: 2018-02-25 Created: 2018-02-25 Last updated: 2018-03-26Bibliographically approved
Organisations
Identifiers
ORCID iD: ORCID iD iconorcid.org/0000-0001-8428-0772

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