References of "Rutgeerts, P"
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See detailIntestinal mucosal expression of matrix metalloproteinase and ADAM genes in patients with inflammatory bowel disease and the impact of infliximab therapy
Arijs, Ingrid; Quintens, R.; Lemaire, K. et al

in Gastroenterology (2010), 138(5), 677

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See detailImmortal time bias and infliximab-related mortality and malignancy incidence
Fidder, H.; Van Steen, Kristel ULg; Van Assche, G. et al

in Gut (2010), 59

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See detailColonic mucosal expression of barrier genes in patients with inflammatory bowel disease before and after first infliximab treatmen
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Acta Gastro-Enterologica Belgica (2009)

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See detailCluster analysis of genetic variants enables reclassification of Crohn’s disease at the molecular level
Cleynen, I.; Van Moerkercke, W.; Mahachie John, Jestinah ULg et al

in Gut (2009)

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See detailMucosal gene signatures to predict response to infliximab in patients with ulcerative colitis
Arijs, I.; Li, K.; Toedter, G. et al

in Gut (2009), 58(12), 1612-9

BACKGROUND AND AIMS: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti ... [more ▼]

BACKGROUND AND AIMS: Infliximab is an effective treatment for ulcerative colitis with over 60% of patients responding to treatment and up to 30% reaching remission. The mechanism of resistance to anti-tumour necrosis factor alpha (anti-TNFalpha) is unknown. This study used colonic mucosal gene expression to provide a predictive response signature for infliximab treatment in ulcerative colitis. METHODS: Two cohorts of patients who received their first treatment with infliximab for refractory ulcerative colitis were studied. Response to infliximab was defined as endoscopic and histological healing. Total RNA from pre-treatment colonic mucosal biopsies was analysed with Affymetrix Human Genome U133 Plus 2.0 Arrays. Quantitative RT-PCR was used to confirm microarray data. RESULTS: For predicting response to infliximab treatment, pre-treatment colonic mucosal expression profiles were compared for responders and non-responders. Comparative analysis identified 179 differentially expressed probe sets in cohort A and 361 in cohort B with an overlap of 74 probe sets, representing 53 known genes, between both analyses. Comparative analysis of both cohorts combined, yielded 212 differentially expressed probe sets. The top five differentially expressed genes in a combined analysis of both cohorts were osteoprotegerin, stanniocalcin-1, prostaglandin-endoperoxide synthase 2, interleukin 13 receptor alpha 2 and interleukin 11. All proteins encoded by these genes are involved in the adaptive immune response. These markers separated responders from non-responders with 95% sensitivity and 85% specificity. CONCLUSION: Gene array studies of ulcerative colitis mucosal biopsies identified predictive panels of genes for (non-)response to infliximab. Further study of the pathways involved should allow a better understanding of the mechanisms of resistance to infliximab therapy in ulcerative colitis. ClinicalTrials.gov number, NCT00639821. [less ▲]

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See detailPredictive Value of C-Reactive Protein Level Changes On the Long Term Outcome of Infliximab in Crohn's Disease
Jürgens, M.; Schnitzler, F.; Van Steen, Kristel ULg et al

in Gastroenterology (2009), 136(5), 171

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See detailThe impact of infliximab therapy on colonic mucosal expression of barrier genes in patients with inflammatory bowel disease
Arijs, I.; Quintens, R.; Van Lommel, L. et al

in Gastroenterology (2009), 136

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See detailLong-term outcome of treatment with infliximab in 614 patients with Crohn's disease: results from a single-centre cohort
Schnitzler, F.; Fidder, H.; Ferrante, M. et al

in Gut (2009), 58(4), 492-500

BACKGROUND AND AIMS: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD) from a single centre during a median follow ... [more ▼]

BACKGROUND AND AIMS: This observational study assessed the long-term clinical benefit of infliximab (IFX) in 614 consecutive patients with Crohn's disease (CD) from a single centre during a median follow-up of 55 months (interquartile range (IQR) 27-83). METHODS: The primary analysis looked at the proportion of patients with initial response to IFX who had sustained clinical benefit at the end of follow-up. The long-term effects of IFX on the course of CD as reflected by the rate of surgery and hospitalisations and need for corticosteroids were also analysed. RESULTS: 10.9% of patients were primary non-responders to IFX. Sustained benefit was observed in 347 of the 547 patients (63.4%) receiving long-term treatment. In 68.3% of these, treatment with IFX was ongoing and in 31.7% IFX was stopped, with the patient being in remission. Seventy patients (12.8%) had to stop IFX due to side effects and 118 (21.6%) due to loss of response. Although the yearly drop-out rates of IFX in patients with episodic (10.7%) and scheduled treatment (7.1%) were similar, the need for hospitalisations and surgery decreased less in the episodic than in the scheduled group. Steroid discontinuation also occurred in a higher proportion of patients in the scheduled group than in the episodic group. CONCLUSIONS: In this large real-life cohort of patients with CD, long-term treatment with IFX was very efficacious to maintain improvement during a median follow-up of almost 5 years and changed disease outcome by decreasing the rate of hospitalisations and surgery. [less ▲]

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See detailColonic mucosal expression of barrier genes in patients with inflammatory bowel disease before and after first infliximab treatment.
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Journal of Crohn’s and Colitis [=JCC] (2009), 3(1), 3

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See detailPredictive Value of C-Reactive Protein Level Changes On the Long Term Outcome of Infliximab in Crohn's Disease
Jürgens, M.; Schnitzler, F.; Van Steen, Kristel ULg et al

in Acta Gastro-Enterologica Belgica (2009)

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See detailTECK and MADCAM-1 mucosal expression in active IBD: the effect of infliximab therapy
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Gastroenterology (2009), 136

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See detailPolymorphisms in innate immunity genes predispose to bacteremia and death in the medical intensive care unit
Henckaerts, L.; Nielsen, K. R.; Steffensen, R. et al

in Critical Care Medicine (2009), 37(1), 192-2011-3

OBJECTIVE: Critically ill patients are at risk of sepsis, organ failure, and death. Studying the impact of genetic determinants may improve our understanding of the pathophysiology and allow ... [more ▼]

OBJECTIVE: Critically ill patients are at risk of sepsis, organ failure, and death. Studying the impact of genetic determinants may improve our understanding of the pathophysiology and allow identification of patients who would benefit from specific treatments. Our aim was to study the influence of single nucleotide polymorphisms in selected genes involved in innate immunity on the development of bacteremia or risk of death in patients admitted to a medical intensive care unit. DESIGN, SETTING, AND PATIENTS: DNA was available from 774 medical intensive care unit patients. We selected 31 single nucleotide polymorphisms in 14 genes involved in host innate immune defense. Serum levels of MASP2 and chemotactic capacity, phagocytosis, and killing capacity of monocytes at admission were quantified. Univariate Kaplan-Meier estimates with log-rank analysis and multivariate logistic regression were performed. Bootstrap resampling technique and ten-fold cross-validation were used to assess replication stability, prognostic importance of the variables, and repeatability of the final regression model. MAIN RESULTS: Patients with at least one NOD2 variant were shown to have a reduced phagocytosis by monocytes (p = 0.03) and a higher risk of bacteremia than wild-type patients (p = 0.02). The NOD2/TLR4 combination was associated with bacteremia using survival analyses (time to bacteremia development, log-rank p < 0.0001), univariate regression (p = 0.0003), and multivariate regression analysis (odds ratio [OR] 4.26, 95% confidence interval [CI] 1.85-9.81; p = 0.0006). Similarly, the same combination was associated with hospital mortality using survival analysis (log-rank p = 0.03), univariate regression (p = 0.02), and multivariate regression analysis (OR 2.27, 95% CI 1.09-4.74; p = 0.03). Also variants in the MASP2 gene were significantly associated with hospital mortality (survival analysis log-rank-p = 0.003; univariate regression p = 0.02; multivariate regression analysis OR 2.35, 95% CI 1.38-3.99; p = 0.002). CONCLUSIONS: Functional polymorphisms in genes involved in innate immunity predispose to severe infections and death, and may become part of a risk model, allowing identification of patients at risk, who could benefit from early introduction of specific preventive or therapeutic interventions. [less ▲]

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See detailThe impact of infliximab therapy on colonic mucosal expression of barrier genes in patients with inflammatory bowel disease.
Arijs, I.; Quintens, R.; Van Lommel, L. et al

in Acta Gastro-Enterologica Belgica (2009)

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See detailMucosal Healing Predicts Long-term Outcome of Maintenance Therapy with Infliximab in Crohn's Disease
Schnitzler, F.; Fidder, H.; Ferrante, M. et al

in Inflammatory Bowel Diseases (2009), 15(9), 1295-1301

Background: Infliximab (IFX) treatment induces mucosal healing (MH) in patients with Crohn's disease (CD) but the impact of MH oil the long-term outcome of IFX treatment in CID is still debated. Methods ... [more ▼]

Background: Infliximab (IFX) treatment induces mucosal healing (MH) in patients with Crohn's disease (CD) but the impact of MH oil the long-term outcome of IFX treatment in CID is still debated. Methods: We studied MH during long-term treatment with IFX in 214 CID patients. A total of 193 patients (85.5%) responded to induction therapy and 31 patients (14.5%) were primary nonresponders. They underwent lower gastrointestinal (GI) endoscopy within a median of 0.7 months (interquartile range [IQR] 0.1-6.9) prior to first IFX and after a median of 6.7 months (IQR 1.4-24.6) after start of IFX and were further analyzed. The relationship between the outcome of IFX treatment long-term and MH was studied. Results: MH was observed in 67.8% of the 183 initial responders (n = 124), with 83 patients having complete healing (45.4%) and 41 having partial healing (22.4%). Scheduled IFX treatment from the start resulted in MH more frequently (76.9% MH rate) than episodic treatment (61.0% MH rate; P = 0.0222, odds ratio [OR] 2.14, 95% confidence interval [CI] 1.11-4.12). Concomitant treatment with corticosteroids (CS) had a negative impact on MH (37.9% in patients with CS versus 63.2% in patients without CS; P = 0.021, OR 0.36, 95% CI 0.16-0.80). MH was associated with a significantly lower need for major abdominal surgery (MAS) during long-term follow-up (14.1% of patients with MH needed MAS versus 38.4% of patients Without MH: P < 0.0001). Conclusions: MH induced by long-term maintenance IFX treatment is associated with an improved long-term outcome of the I disease especially with a lower need for major abdominal surgeries. [less ▲]

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See detailMucosal Gene Expression of Antimicrobial Peptides in Inflammatory Bowel Disease Before and After First Infliximab Treatment
Arijs, I.; De Hertogh, G.; Lemaire, K. et al

in PLoS ONE (2009), 4(11), 7984

Background: Antimicrobial peptides (AMPs) protect the host intestinal mucosa against microorganisms. Abnormal expression of defensins was shown in inflammatory bowel disease (IBD), but it is not clear ... [more ▼]

Background: Antimicrobial peptides (AMPs) protect the host intestinal mucosa against microorganisms. Abnormal expression of defensins was shown in inflammatory bowel disease (IBD), but it is not clear whether this is a primary defect. We investigated the impact of anti-inflammatory therapy with infliximab on the mucosal gene expression of AMPs in IBD. Methodology/Principal Findings: Mucosal gene expression of 81 AMPs was assessed in 61 IBD patients before and 4-6 weeks after their first infliximab infusion and in 12 control patients, using Affymetrix arrays. Quantitative real-time reverse-transcription PCR and immunohistochemistry were used to confirm microarray data. The dysregulation of many AMPs in colonic IBD in comparison with control colons was widely restored by infliximab therapy, and only DEFB1 expression remained significantly decreased after therapy in the colonic mucosa of IBD responders to infliximab. In ileal Crohn's disease (CD), expression of two neuropeptides with antimicrobial activity, PYY and CHGB, was significantly decreased before therapy compared to control ileums, and ileal PYY expression remained significantly decreased after therapy in CD responders. Expression of the downregulated AMPs before and after treatment (DEFB1 and PYY) correlated with villin 1 expression, a gut epithelial cell marker, indicating that the decrease is a consequence of epithelial damage. Conclusions/Significance: Our study shows that the dysregulation of AMPs in IBD mucosa is the consequence of inflammation, but may be responsible for perpetuation of inflammation due to ineffective clearance of microorganisms. [less ▲]

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See detailMolecular Reclassification of Crohn’s Disease by cluster analysis of genetic variants
Cleynen, I.; Mahachie John, Jestinah ULg; Henkaerts, L. et al

in Gut (2009)

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See detailMucosal gene signatures to predict response to infliximab in patients with inflammatory bowel disease
Arijs, I.; Van Lommel, L.; Van Steen, Kristel ULg et al

in Acta Gastro-Enterologica Belgica (2008)

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See detailGene expression of antimicrobial peptides in colonic mucosa of patients with inflammatory bowel disease before and after first infliximab treatment.
Arijs, I.; Lemaire, K.; Quintens, R. et al

in Gut (2008), 57(Suppl II), 102-103

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