Journal of Crohn s and Colitis (J CROHNS COLITIS )

Publisher: Elsevier


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Publications in this journal

  • [Show abstract] [Hide abstract]
    ABSTRACT: Background and Aims: Azathioprine (AZA) is an established treatment for ulcerative colitis (UC). However, controversy exists regarding its efficacy in inducing and maintaining clinical remission, and long-term data are lacking. We studied the effectiveness of AZA in a large cohort of UC patients treated in a single centre. Methods: All UC patients treated with AZA were identified from a prospective electronic database. We assessed response to therapy at 4 months and sustained clinical benefit at last point of follow-up. We also examined predictors of response and sustained clinical benefit, as well as outcomes in those treated with AZA for >5 years. Results: 255 patients were included. At 4 months, 207 (81.2%) of 255 patients were still on AZA, and 163 (63.9%) had responded to therapy. There were 164 (64.3%) patients still receiving AZA at last point of follow-up, of whom 154 (60.4%) achieved sustained clinical benefit. This effect was durable among 71 patients who received AZA for >5 years, with 61 (85.9%) considered to have achieved sustained clinical benefit. Twenty-six patients required admission to hospital for an exacerbation during AZA treatment, 20 patients ultimately required biologic therapy, and 21 underwent colectomy. Only two (2.8%) of 71 patients receiving AZA for >5 years needed to escalate to a biological therapy, and only one (1.4%) required a colectomy. Conclusion: AZA is a safe and effective therapy in UC patients who fail 5-aminosalisylates both in the short and long-term. Escalation to a biological therapy or colectomy was unlikely among patients who were able to continue AZA therapy beyond 5 years.
    Journal of Crohn s and Colitis 12/2014;
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    ABSTRACT: Ulcerative colitis can develop during the reproductive years, and there are limited data about perinatal care for patients with ulcerative colitis. In this study, we analyzed perinatal follow-up, complications, and maternal and fetal outcomes in pregnant patients undergoing surgery for ulcerative colitis. Between January 1998 and July 2013, female patients who underwent surgery during pregnancy for abdominal complications of ulcerative colitis and followed up during their pregnancy in our institution were included in our study. Patient characteristics, complications, operations performed, maternal and fetal morbidity and mortality during the perinatal period, and type of delivery were analyzed. There were nine female patients with a median (range) age of 30 (21-33) years. Indications for surgery were fulminant/refractory colitis (n = 6) and bowel obstruction (n = 3). Operations performed were subtotal colectomy with an end ileostomy (n = 3), Turnbull blowhole procedure (n = 3), adhesiolysis with small bowel resection (n = 1), detorsion and decompression of bowel (n = 1) and adhesolysis (n = 1). Median (range) postoperative length of stay was 11 (5-28) days and median (range) duration of pregnancy was 36 (32-40) weeks. There were only two patients who had a transvaginal delivery, while a cesarean section was performed in seven patients. Indications for cesarean section were as follows: physician's preference (n = 4), planned small bowel surgery with cesarean section (n = 2), and metabolic disorders (n = 1). There were no perinatal maternal or fetal deaths. Surgery for ulcerative colitis complications can be performed safely if indicated during pregnancy under the care of a multidisciplinary team that includes gastroenterologists, obstetricians, and colorectal surgeons. Copyright © 2014 European Crohn’s and Colitis Organisation (ECCO). Published by Oxford University Press. All rights reserved. For permissions, please email:
    Journal of Crohn s and Colitis 11/2014;
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    ABSTRACT: Background and aims Vitamin D deficiency has been observed in a wide range of medical conditions including Crohn's disease (CD). We aimed to assess whether CD patients have lower vitamin D levels than healthy controls, and to determine risk factors for vitamin D deficiency. Methods 25(OH)D was measured by chemiluminescent immunoassay in serum obtained from 101 CD patients and 41 controls. Demographics, sunlight exposure, dietary vitamin D intake, comorbidities and medication were recorded using validated questionnaires. In CD patients the Harvey–Bradshaw index, Montreal classification and surgical resections were also evaluated. 25(OH)D levels of > 75 nmol/L, between 50 and 75 nmol/L and < 50 nmol/L were considered as normal, suboptimal and deficient, respectively. Results Vitamin D levels were rather low but comparable among CD patients and controls (mean 25(OH)D 51.6 nmol/L(± 26.6) in CD, and 60.8 nmol/L(± 27.6) in controls. Multivariate regression analysis revealed BMI, sun protection behaviour, non-Caucasian ethnicity, no use of tanning beds, and no holidays in the last year as significantly associated with serum 25(OH)D levels in CD patients (R = 0.62). In the control group no statistically significant factors were identified that had an impact on 25(OH)D serum levels. Conclusions Vitamin D deficiency is common in CD patients, but also in healthy controls. Appropriate vitamin D screening should be advised in patients with CD. Moreover, the positive effect of sunlight on the vitamin D status should be discussed with CD patients, but this should be balanced against the potential risk of developing melanomas, especially in patients using thiopurines.
    Journal of Crohn s and Colitis 10/2014;
  • Journal of Crohn s and Colitis 10/2014;
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    ABSTRACT: Background and aim The adhesion molecule expression and matrix metalloproteinases (MMPs) are proposed to be major factors for intestinal injury mediated by T cells in (IBD) and are up-regulated in intestinal mucosa of IBD patients. To investigate the effect of vitamin D derivatives on adhesion molecules and MMPs in colonic biopsies of IBD patients. Methods Biopsies from inflamed and non-inflamed tract of terminal ileum and colon and PBMC from the same IBD patients were cultured with or without vitamin D derivatives. MMP activity and adhesion molecule levels were determined. Results 1,25(OH)2D3 and ZK 191784 significantly decrease ICAM-1 protein levels in the biopsies obtained only from the inflamed region of intestine of UC patients, while MAdCAM-1 levels decrease in the presence of 1,25(OH)2D3 in the non-inflamed region, and, in the presence of ZK, in the inflamed one. In CD patients 1,25(OH)2D3 and ZK decrease ICAM-1 and MAdCAM-1 in the biopsies obtained from the non-inflamed and inflamed regions, with the exception of ICAM-1 in the inflamed region in the presence of 1,25(OH)2D3. The expression of MMP-9, MMP-2, and MMP-3 decreases in the presence of vitamin D derivatives in UC and CD with the exception of 1,25(OH)2D3 that does not affect the levels of MMP-9 and MMP-2 in CD. Vitamin D derivatives always affect MMP-9, MMP-2 and ICAM-1 in PBMC of UC and CD patients. Conclusions Based on the increased expression of ICAM-1, MAdCAM-1 and MMP-2,-9,-3 in IBD, our study suggests that vitamin D derivatives may be effective in the management of these diseases.
    Journal of Crohn s and Colitis 09/2014;
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    ABSTRACT: Background & aims To improve the clinical course of ulcerative colitis (UC), more accurate serum diagnostic and assessment methods are required. We used serum metabolomics to develop diagnostic and assessment methods for UC. Methods Sera from UC patients, Crohn's disease (CD) patients, and healthy volunteers (HV) were collected at multiple institutions. The UC and HV were randomly allocated to the training or validation set, and their serum metabolites were analyzed by gas chromatography mass spectrometry (GC/MS). Using the training set, diagnostic and assessment models for UC were established by multiple logistic regression analysis. Then, the models were assessed using the validation set. Additionally, to establish a diagnostic model for discriminating UC from CD, the CD patients' data were used. Results The diagnostic model for discriminating UC from HV demonstrated an AUC of 0.988, 93.33% sensitivity, and 95.00% specificity in the training set and 95.00% sensitivity and 98.33% specificity in the validation set. Another model for discriminating UC from CD exhibited an AUC of 0.965, 85.00% sensitivity, and 97.44% specificity in the training set and 83.33% sensitivity in the validation set. The model for assessing UC showed an AUC of 0.967, 84.62% sensitivity, and 88.23% specificity in the training set and 84.62% sensitivity, 91.18% specificity, and a significant correlation with the clinical activity index (rs = 0.7371, P < 0.0001) in the validation set. Conclusions Our models demonstrated high performance and might lead to the development of a novel treatment selection method based on UC condition.
    Journal of Crohn s and Colitis 09/2014;
  • Journal of Crohn s and Colitis 09/2014;
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    ABSTRACT: Background and Aims Psychological interventions are used in patients with inflammatory bowel disease (IBD) but there is uncertainty about who the optimal target population is. Multi-convergent therapy (MCT) is a form of psychotherapy that combines mindfulness meditation with aspects of cognitive behavioural therapy and has been used in the management of irritable bowel syndrome (IBS). This study aimed to assess the feasibility and efficacy of MCT in the management of IBD patients with either functional abdominal symptoms or high perceived stress levels. Methods Sixty-six IBD patients in clinical remission with either IBS-type symptoms or high perceived stress levels were randomly allocated to a 16-week MCT course or waiting list control group. Patients were followed-up for one year with the Inflammatory Bowel Disease Questionnaire (IBDQ) as the primary outcome measurement. Results A higher mean IBDQ score was observed in the active group compared to controls at the 4-month assessment (167 vs. 156, p = 0.081), but this was not statistically significant nor did it reached the predefined clinically significant difference of 20. In patients with IBS-type symptoms at baseline there was a significantly higher mean IBDQ score in the active group compared to controls (161 vs. 145, p = 0.021). There was no difference between groups in relapse rate based on faecal calprotectin measurement. Conclusions IBS-type symptoms in patients with IBD represent a potential therapeutic target to improve quality of life. This study suggests that MCT may be useful in the management of these symptoms but larger studies are required to confirm this. Clinical Trial Registration Number NCT01426568.
    Journal of Crohn s and Colitis 09/2014;
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    ABSTRACT: Background and aims Adalimumab is an effective therapy for induction and maintenance of Crohn's disease. However, results in clinical trials don't necessarily reflect daily clinical practice. Therefore, we assessed real-life long-term clinical response to adalimumab in a large population-based cohort and identified clinical parameters affecting response Methods All consecutive patients in North-Holland that started adalimumab between 2003 and 2011 were included, of which medical charts were reviewed. Response to induction therapy was assessed after 3 months. Sustained benefit of maintenance therapy was calculated from Kaplan–Meier survival tables depicting ongoing adalimumab treatment. Regression analyses were performed to identify factors predicting response to adalimumab therapy. Results In total 438 Crohn's patients started adalimumab with 92.5% response to the induction phase. After 1 year 83.3% showed sustained benefit of maintenance treatment, followed by 74.0% after 2 years. Nevertheless, one third of patients were in steroid-free remission at the end of their follow-up. Response to induction was negatively affected by longer disease duration (OR 1.05; p < 0.01) and strictures (OR 3.73; p = 0.04). Increased CRP levels predicted higher rates of initial response (OR 0.31; p < 0.01). Concomitant thiopurines in the first 6 months of adalimumab treatment decreased the risk to fail maintenance therapy (HR 0.69, p = 0.05). Previous infliximab therapy did not affect response to adalimumab, however dose escalation was more often deemed necessary (p < 0.01). Conclusion Adalimumab was successful in the majority of patients, with 10% loss of response per subsequent year. Concomitant thiopurines might improve adalimumab maintenance treatment.
    Journal of Crohn s and Colitis 08/2014;
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    ABSTRACT: Anemia is a frequent complication of inflammatory bowel disease (IBD). Hepcidin, a key mediator in this anemia, is up-regulated by high iron levels and inflammation, and serum levels are elevated in IBD. However, the extent of inflammatory activity and iron deficiency for the regulation of hepcidin is not known. This study aimed to evaluate serum hepcidin levels in anemic and non-anemic IBD patients, with iron or non-iron deficiency, and active or inactive disease. This retrospective, observational study analyzed serum hepcidin levels from 247 patients with IBD (130 Crohn's patients and 117 with ulcerative colitis) recruited at Swiss Inflammatory Bowel Disease Cohort Study centers. Patients were divided into 5 different groups using criteria of active and inactive diseases (C-reactive protein, and CDAI/MTWAI=disease activity-index), anemia (hemoglobin) and iron deficiency (ferritin) and compared to healthy controls with no signs of anemia and normal ferritin levels. Hepcidin was measured using enzyme-linked immunosorbent assay. Independent of inflammatory activity, all patients with decreased ferritin (<30μg/L) had significantly lower hepcidin levels when compared to patients and healthy controls having normal ferritin (>30μg/L). A significant correlation between serum ferritin levels and serum hepcidin was found (Spearman's Rho=0.491; p<0.001). A backward multi-linear stepwise regression analysis showed that only ferritin, and none of the inflammatory markers or age and sex correlated significantly (p=0.005) with hepcidin. This retrospective analysis suggests that iron deficiency is the key trigger for hepcidin regulation in IBD patients with anemia.
    Journal of Crohn s and Colitis 05/2014;
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    ABSTRACT: Background and aims: Defects in the interleukin 10 (IL-10) signalling pathway have been shown to cause very early onset inflammatory bowel disease (IBD). We report a patient with severe infantile-onset IBD with a compound heterozygous IL-10 receptor alpha subunit (IL-10RA) mutation, one of which was paternally-inherited and the other occurring de novo. Methods: Deep sequencing of IL-10, IL-10RA and IL-10 receptor beta subunit (IL-10RB) were performed. Peripheral blood mononuclear cell (PBMC) surface expression of IL-10RA was analysed by flow cytometry. IL-10 signalling pathway was examined by measuring phosphorylated STAT3 in PBMC cultured in the presence of IL-6 or IL-10. Result: We identified a missense mutation in exon 4 of IL-10RA (c.583T>C) in one allele and a nonsense mutation in exon 7 of IL-10RA (c.1368G>T) in the other allele. Neither mutation has been reported previously. The patient has functional IL-10RA deficiency despite normal IL-10RA expression. Conclusion: This represents the first case report of a de novo mutation of IL-10RA that is associated with very early onset severe IBD. Therefore, IL-10 pathway defect should be considered in patients with infantile-onset IBD even if the parents are non-consanguineous.
    Journal of Crohn s and Colitis 05/2014;
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    Journal of Crohn s and Colitis 05/2014;
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    ABSTRACT: Primary sclerosing cholangitis (PSC) is typically associated with inflammatory bowel disease (IBD), particularly ulcerative colitis (UC). PSC-IBD patients are at an increased risk for colorectal neoplasia. The ileal pouch-anal anastomosis (IPAA) is a treatment option for patients with medically refractory UC or neoplasia. However, little is known about the development of pouch neoplasia in PSC-UC patients following an IPAA. We aim to describe the incidence of pouch neoplasia in PSC-UC patients after an IPAA. We conducted a retrospective chart review of patients with a confirmed diagnosis of PSC and IBD who underwent colectomy with IPAA followed by pouch surveillance between 1995 and 2012. Sixty-five patients were included in the cohort and were followed up from the time of colectomy/IPAA for a median of 6years. The most common indications for surgery were low-grade dysplasia (LGD) and refractory colitis. Only 3 patients developed evidence of neoplasia (LGD n=1, high-grade dysplasia n=1, adenocarcinoma n=1). The cumulative 5-year incidence of pouch neoplasia was 5.6% (95% confidence intervals [CI], 1.8%-16.1%). Based on our short-term follow-up, surveying the pouch frequently appears to be an unnecessary practice in PSC-IBD patients. Longer follow-up will be needed to develop an optimal surveillance strategy for the development of dysplasia and cancer in such patients.
    Journal of Crohn s and Colitis 04/2014;