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  1. Article ; Online: Proteomic analyses do not reveal subclinical inflammation in fatigued patients with clinically quiescent inflammatory bowel disease

    Arno R. Bourgonje / Sietse J. Wichers / Shixian Hu / Hendrik M. van Dullemen / Marijn C. Visschedijk / Klaas Nico Faber / Eleonora A. M. Festen / Gerard Dijkstra / Janneke N. Samsom / Rinse K. Weersma / Lieke M. Spekhorst

    Scientific Reports, Vol 12, Iss 1, Pp 1-

    2022  Volume 11

    Abstract: Abstract Fatigue is a common and clinically challenging symptom in patients with inflammatory bowel diseases (IBD), occurring in ~ 50% of patients with quiescent disease. In this study, we aimed to investigate whether fatigue in patients with clinically ... ...

    Abstract Abstract Fatigue is a common and clinically challenging symptom in patients with inflammatory bowel diseases (IBD), occurring in ~ 50% of patients with quiescent disease. In this study, we aimed to investigate whether fatigue in patients with clinically quiescent IBD is reflected by circulating inflammatory proteins, which might reflect ongoing subclinical inflammation. Ninety-two (92) different inflammation-related proteins were measured in plasma of 350 patients with clinically quiescent IBD. Quiescent IBD was defined as clinical (Harvey-Bradshaw Index < 5 or Simple Clinical Colitis Activity Index < 2.5) and biochemical remission (C-reactive protein < 5 mg/L and absence of anemia) at time of fatigue assessment. Leukemia inhibitory factor receptor (LIF-R) concentrations were inversely associated with severe fatigue, also after adjustment for confounding factors (nominal P < 0.05). Although solely LIF-R showed weak ability to discriminate between mild and severe fatigue (area under the curve [AUC] = 0.61, 95%CI: 0.53–0.69, P < 0.05), a combined set of the top seven (7) fatigue-associated proteins (all P < 0.10) was observed to have reasonable discriminative performance (AUC = 0.82 [95%CI: 0.74–0.91], P < 0.01). Fatigue in patients with IBD is not clearly reflected by distinct protein signatures, suggesting there is no subclinical inflammation defined by the studied inflammatory proteins. Future studies are warranted to investigate other proteomic markers that may reflect fatigue in clinically quiescent IBD.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610
    Language English
    Publishing date 2022-08-01T00:00:00Z
    Publisher Nature Portfolio
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Serological Biomarkers of Extracellular Matrix Turnover and Neutrophil Activity Are Associated with Long-Term Use of Vedolizumab in Patients with Crohn’s Disease

    Marta S. Alexdottir / Arno R. Bourgonje / Morten A. Karsdal / Martin Pehrsson / Roberta Loveikyte / Hendrik M. van Dullemen / Marijn C. Visschedijk / Eleonora A. M. Festen / Rinse K. Weersma / Klaas Nico Faber / Gerard Dijkstra / Joachim H. Mortensen

    International Journal of Molecular Sciences, Vol 23, Iss 15, p

    2022  Volume 8137

    Abstract: Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by increased extracellular matrix (ECM) remodeling. The introduction of the α4β7-integrin inhibitor vedolizumab (VEDO) has improved ... ...

    Abstract Crohn’s disease (CD) is a relapsing-remitting inflammatory disease of the gastrointestinal (GI) tract characterized by increased extracellular matrix (ECM) remodeling. The introduction of the α4β7-integrin inhibitor vedolizumab (VEDO) has improved disease management, although there is a high rate of primary non-response in patients with CD. We studied whether ECM biomarkers of neutrophil activity and mucosal damage could predict long-term response to VEDO in patients with CD. Serum levels of human neutrophil elastase (HNE)-derived fragments of calprotectin (CPa9-HNE), and matrix metalloproteinase (MMP)-derived fragments of type I (C1M), III (C3M), IV (C4M), and VI (C6Ma3) collagen, type III collagen formation (PRO-C3), basement membrane turnover (PRO-C4) and T-cell activity (C4G), were measured using protein fingerprint assays in patients with CD ( n = 32) before VEDO therapy. Long-term response was defined as VEDO treatment of at least 12 months. CPa9-HNE was significantly increased at baseline in non-responders compared with responders ( p < 0.05). C1M, C3M, C4M, C6Ma3, and PRO-C4 were also significantly increased at baseline in non-responders compared with responders (all p < 0.05). All biomarkers were associated with response to VEDO (all p < 0.05). To conclude, baseline levels of serum biomarkers for neutrophil activity and mucosal damage are linked to the pathology of CD, and are associated with long-term use of VEDO in patients with CD. Therefore, these biomarkers warrant further validation and could aid in therapeutic decision-making concerning vedolizumab therapy.
    Keywords inflammatory bowel disease ; biomarkers ; extracellular matrix ; neutrophils ; vedolizumab ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 610
    Language English
    Publishing date 2022-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Polygenetic risk scores do not add predictive power to clinical models for response to anti-TNFα therapy in inflammatory bowel disease.

    Naomi Karmi / Amber Bangma / Lieke M Spekhorst / Hendrik M van Dullemen / Marijn C Visschedijk / Gerard Dijkstra / Rinse K Weersma / Michiel D Voskuil / Eleonora A M Festen

    PLoS ONE, Vol 16, Iss 9, p e

    2021  Volume 0256860

    Abstract: Background Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn's disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose ... ...

    Abstract Background Anti-tumour necrosis factor alpha (TNFα) therapy is widely used in the management of Crohn's disease (CD) and ulcerative colitis (UC). However, up to a third of patients do not respond to induction therapy and another third of patients lose response over time. To aid patient stratification, polygenetic risk scores have been identified as predictors of response to anti-TNFα therapy. We aimed to replicate the association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients, to establish its clinical validity. Materials and methods Primary non-response, primary response, durable response and loss of response to anti-TNFα therapy was retrospectively assessed for each patient using stringent definitions. Genome wide genotyping was performed and previously described polygenetic risk scores for primary non-response and durable response were calculated. We compared polygenetic risk scores between patients with primary response and primary non-response, and between patients with durable response and loss of response, using separate analyses for CD and UC. Results Out of 334 patients with CD, 15 (4%) patients met criteria for primary non-response, 221 (66%) for primary response, 115 (34%) for durable response and 35 (10%) for loss of response. Out of 112 patients with UC, 12 (11%) met criteria for primary non-response, 68 (61%) for primary response, 19 (17%) for durable response and 20 (18%) for loss of response. No significant differences in polygenetic risk scores were found between primary non-responders and primary responders, and between durable responders and loss of responders. Conclusions We could not replicate the previously reported association between polygenetic risk scores and response to anti-TNFα therapy in an independent cohort of patients with CD or UC. Currently, there is insufficient evidence to use polygenetic risk scores to predict response to anti-TNFα therapy in patients with IBD.
    Keywords Medicine ; R ; Science ; Q
    Subject code 610 ; 310
    Language English
    Publishing date 2021-01-01T00:00:00Z
    Publisher Public Library of Science (PLoS)
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Endoscopic ultrasonography-guided gastroenterostomy versus surgical gastrojejunostomy for palliation of malignant gastric outlet obstruction (ENDURO)

    Janine B. Kastelijn / Yorick L. van de Pavert / Marc G. Besselink / Paul Fockens / Rogier P. Voermans / Roy L. J. van Wanrooij / Thomas R. de Wijkerslooth / Wouter L. Curvers / Ignace H. J. T. de Hingh / Marco J. Bruno / Bas Groot Koerkamp / Gijs A. Patijn / Alexander C. Poen / Jeanin E. van Hooft / Akin Inderson / J. Sven D. Mieog / Jan-Werner Poley / Alderina Bijlsma / Daan J. Lips /
    Niels G. Venneman / Robert C. Verdonk / Hendrik M. van Dullemen / Frederik J. H. Hoogwater / Geert W. J. Frederix / I. Quintus Molenaar / Paco M. J. Welsing / Leon M. G. Moons / Hjalmar C. van Santvoort / Frank P. Vleggaar / for the Dutch Pancreatic Cancer Group

    Trials, Vol 24, Iss 1, Pp 1-

    study protocol for a randomized controlled trial

    2023  Volume 14

    Abstract: Abstract Background Malignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a ... ...

    Abstract Abstract Background Malignant gastric outlet obstruction (GOO) is a debilitating condition that frequently occurs in patients with malignancies of the distal stomach and (peri)ampullary region. The standard palliative treatment for patients with a reasonable life expectancy and adequate performance status is a laparoscopic surgical gastrojejunostomy (SGJ). Recently, endoscopic ultrasound-guided gastroenterostomy (EUS-GE) emerged as a promising alternative to the surgical approach. The present study aims to compare these treatment modalities in terms of efficacy, safety, and costs. Methods The ENDURO-study is a multicentre, open-label, parallel-group randomized controlled trial. In total, ninety-six patients with gastric outlet obstruction caused by an irresectable or metastasized malignancy will be 1:1 randomized to either SGJ or EUS-GE. The primary endpoint is time to tolerate at least soft solids. The co-primary endpoint is the proportion of patients with persisting or recurring symptoms of gastric outlet obstruction for which a reintervention is required. Secondary endpoints are technical and clinical success, quality of life, gastroenterostomy dysfunction, reinterventions, time to reintervention, adverse events, quality of life, time to start chemotherapy, length of hospital stay, readmissions, weight, survival, and costs. Discussion The ENDURO-study assesses whether EUS-GE, as compared to SGJ, results in a faster resumption of solid oral intake and is non-inferior regarding reinterventions for persistent or recurrent obstructive symptoms in patients with malignant GOO. This trial aims to guide future treatment strategies and to improve quality of life in a palliative setting. Trial registration International Clinical Trials Registry Platform (ICTRP): NL9592. Registered on 07 July 2021.
    Keywords Gastric outlet obstruction ; Malignancy ; Gastroenterostomy ; Gastrojejunostomy ; Endoscopic ultrasonography ; Surgery ; Medicine (General) ; R5-920
    Subject code 610
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher BMC
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: A Combined Set of Four Serum Inflammatory Biomarkers Reliably Predicts Endoscopic Disease Activity in Inflammatory Bowel Disease

    Arno R. Bourgonje / Julius Z. H. von Martels / Ruben Y. Gabriëls / Tjasso Blokzijl / Manon Buist-Homan / Janette Heegsma / Bernadien H. Jansen / Hendrik M. van Dullemen / Eleonora A. M. Festen / Rinze W. F. ter Steege / Marijn C. Visschedijk / Rinse K. Weersma / Paul de Vos / Klaas Nico Faber / Gerard Dijkstra

    Frontiers in Medicine, Vol

    2019  Volume 6

    Abstract: Introduction: Blood C-reactive protein (CRP) and fecal calprotectin levels are routinely measured as surrogate markers of disease activity in Inflammatory Bowel Disease (IBD), but often do not correlate well with the degree of mucosal inflammation in the ...

    Abstract Introduction: Blood C-reactive protein (CRP) and fecal calprotectin levels are routinely measured as surrogate markers of disease activity in Inflammatory Bowel Disease (IBD), but often do not correlate well with the degree of mucosal inflammation in the intestine as established by endoscopy. Therefore, novel predictive biomarkers are urgently needed that better reflect mucosal disease activity in IBD. The aim of this study was to identify a combination of serum inflammatory biomarkers predictive for endoscopic disease activity.Methods: Serum concentrations of 10 inflammatory biomarkers were analyzed in 118 IBD patients [64 Crohn's disease (CD), 54 ulcerative colitis (UC)] and 20 healthy controls. In a subset of 71 IBD patients, endoscopic disease activity was established. Non-parametric ROC estimation with bootstrap inference was used to establish the best combination of inflammatory biomarkers predicting endoscopic disease activity.Results: Six (6) inflammatory biomarkers (serum amyloid A (SAA), Eotaxin-1, IL-6, IL-8, IL-17A, and TNF-α) showed better prediction of IBD disease activity than routine measures (CRP, fecal calprotectin and HBI/SCCAI scores). The best combination of predictive inflammatory biomarkers consisted of serum SAA, IL-6, IL-8, and Eotaxin-1, showing an optimism-adjusted area under the ROC (AuROC) curve of 0.84 (95% CI: 0.73–0.94, P < 0.0001), which predicted significantly better (P = 0.002) than serum CRP levels with an AuROC of 0.57 (95% CI: 0.43–0.72, P = 0.32).Conclusion: The combination of SAA, IL-6, IL-8, and Eotaxin-1 reliably predicts endoscopic disease activity in IBD and might be valuable for monitoring disease activity and management of the disease.
    Keywords Inflammatory Bowel Disease (IBD) ; inflammatory biomarkers ; endoscopy ; inflammation ; disease activity ; Medicine (General) ; R5-920
    Subject code 610 ; 630
    Language English
    Publishing date 2019-11-01T00:00:00Z
    Publisher Frontiers Media S.A.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Are Pancreatic Autoantibodies Associated with Azathioprine-Induced Pancreatitis in Crohns Disease?

    Rinse K Weersma / Manou R Batstra / Jan H Kleibeuker / Hendrik M van Dullemen

    JOP Journal of the Pancreas, Vol 9, Iss 3, Pp 283-

    2008  Volume 289

    Abstract: Context Azathioprine is frequently used in the treatment of Crohn’s disease. A severe side effect is acute pancreatitis, which is specific for Crohn’s disease. Autoantibodies against exocrine pancreas occur in about 30% of Crohn’s disease cases but not ... ...

    Abstract Context Azathioprine is frequently used in the treatment of Crohn’s disease. A severe side effect is acute pancreatitis, which is specific for Crohn’s disease. Autoantibodies against exocrine pancreas occur in about 30% of Crohn’s disease cases but not in other inflammatory diseases. Pancreatic autoantibody positive Crohn’s disease patients might have a low grade inflammation of the pancreas which may be aggravated by the introduction of azathioprine, resulting in clinically overt acute pancreatitis. Objective We hypothesized that the presence of pancreatic autoantibodies in Crohn’s disease patients is associated with the development of azathioprine-induced pancreatitis. Participants Eight patients with Crohn’s disease and azathioprine-induced pancreatitis and 26 patients with Crohn’s disease not using azathioprine. Main outcome measure Pancreatic autoantibodies were determined by a standardized immunofluorescence method. Results Two out of 8 patients with azathioprine-induced pancreatitis were positive for pancreatic autoantibodies (25.0%), detectable in serum dilutions of 1:40 and 1:160, respectively. In the control group of Crohn’s disease patients, two (7.7%) were positive in serum dilutions of 1:2. All positive samples had an extracellular fluorescence pattern. The difference in the prevalence of pancreatic autoantibodies was not statistically significant (P=0.229). Conclusions We could not confirm our hypothesis that most or all patients with azathioprine-induced pancreatitis were pancreatic autoantibody positive. The prevalence of pancreatic autoantibodies in the Crohn’s disease patients in our group was lower than in previous reports.This study does not support an association between pancreatic autoantibodies and azathioprine-induced pancreatitis in Crohn’s disease. However, this association should not be definitively excluded and larger, preferably prospective, studies are needed.
    Keywords Antibodies ; Azathioprine ; Crohn Disease ; Inflammatory Bowel Diseases ; Pancreas ; Pancreatitis ; Serology ; Medicine ; R ; Internal medicine ; RC31-1245 ; Specialties of internal medicine ; RC581-951 ; Diseases of the digestive system. Gastroenterology ; RC799-869
    Subject code 610
    Publishing date 2008-05-01T00:00:00Z
    Publisher E S Burioni Ricerche Bibliografiche
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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