Relapse Of Colitis Research Articles

P169 Usability of a home-based test for the measurement of fecal calprotectin in IBD patients

Background: Fecal calprotectin (FC) correlates well with mucosal healing and risk of relapse in inflammatory Bowel Disease (IBD). An obstacle for a broader use of FC measurement in routine practice is the need to bring stool samples at the hospital or the send them by mail. The aim of our work was to test the usability of a home-based test for the measurement of FC in IBD patients. Methods: IBD patients in clinical remission or mild disease activity and declaring motivation to perform home-based FC measurements were prospectively recruited in three IBD centres in Oslo, Barcelona and Liège. They received a standardized training. They were instructed to collect and extract stools and to measure FC with a dedicated tool and smartphone application, 5 times at two weeks intervals over a 8 weeks period. The included patients had to fill in a usability questionnaire made of simple questions and Linkert scales at the first and the last FC measurement. Two global scores were calculated integrating the different aspects of usability: the System Usability Scale (SUS: 0–100) and the Global Usability Score (GUS: 0–85). FC was also centrally measured by ELISA. Results: 58 patients were recruited, including 18 ulcerative colitis (UC) and 40 Crohn's disease (CD), 30 females. Median (IQR) age was 35 yrs (27–40), median (IQR) HBI in CD was 0 (0–4), median (IQR) Clinical Mayo in UC was 0 (0–1). Over the 58 included patients, 42 performed at least one FC measurement and 27 performed all the FC requested measurements. The median (IQR) GUS (0–85) at the first and last use were 74 (69–80) and 77 (68–83), respectively; the median (IQR) SUS (0–100) at the first and last use were 85 (78–90) and 81 (70–88), respectively. Adherence to the planned measurements and usability of the tool were higher in females and in less severe disease. The inter-class correlation coefficient between home-based and centrally measured FC was 0.85. Conclusions: Around three quarters of the patients who declared themselves motivated to use home-based test of FC measurement actually did it, but only half of them fully adhered to the planned measurements. Usability scores for the home-based test were high. There was a very good correlation with the centrally measured FC by ELISA.

Comparison of Fecal Calprotectin Methods for Predicting Relapse of Pediatric Inflammatory Bowel Disease.

Background. Pediatric inflammatory bowel disease (IBD) is on the rise worldwide. Endoscopies are necessary for IBD assessment but are invasive, expensive, and inconvenient. Recently, fecal calprotectin (FCal) was proposed as a noninvasive and specific marker of gut inflammation. We evaluated the analytical performance of three FCal assays and their clinical performance in predicting relapse in pediatric IBD. Methods. This study used 40 pediatric IBD and 40 random non-IBD patients' fecal samples. Two automated ELISAs (Bühlmann and PhiCal® Calprotectin-EIA) and an EliA (Phadia 250 EliA-Calprotectin) were used to evaluate the analytical performance. The clinical performance was assessed by PhiCal Calprotectin-EIA, EliA-Calprotectin, and Bühlmann immunochromatographic point-of-care test (POCT). Results. All assays displayed acceptable analytical performance below and above the medical decision cut-off [imprecision (CV < 10% intra-assay; <15% interassay); linearity (overall mean % deviation < 16.5%)]. The agreement with PhiCal Calprotectin-EIA was 100% and 78.6% for Bühlmann (95% CI, 87.5–100; Kappa: 1) and EliA-Calprotectin (95% CI, 60.5–89.8; Kappa: 0.32), respectively, and 63.6% between Bühlmann and EliA-Calprotectin (95% CI, 46.6–77.8; Kappa: 0.16). All assays evaluated had similar clinical performance [AUC: 0.84 (EliA-Calprotectin); 0.83 (POCT and PhiCal Calprotectin-EIA)]. Conclusion. FCal levels determined using the same method and assay together with clinical history would be a noninvasive and useful tool in monitoring pediatric IBD.

Irritable bowel syndrome-like symptoms associated with endoscopic activity predict ulcerative colitis relapse in patients with clinical remission.

Irritable bowel syndrome-like symptoms associated with endoscopic activity predict ulcerative colitis relapse in patients with clinical remission.

Evolution After Anti-TNF Discontinuation in Patients With Inflammatory Bowel Disease: A Multicenter Long-Term Follow-Up Study.

The aims of this study were to assess the risk of relapse after discontinuation of anti-tumor necrosis factor (anti-TNF) drugs in patients with inflammatory bowel disease (IBD), to identify the factors associated with relapse, and to evaluate the overcome after retreatment with the same anti-TNF in those who relapsed. This was a retrospective, observational, multicenter study. IBD patients who had been treated with anti-TNFs and in whom these drugs were discontinued after clinical remission was achieved were included. A total of 1,055 patients were included. The incidence rate of relapse was 19% and 17% per patient-year in Crohn's disease and ulcerative colitis patients, respectively. In both Crohn's disease and ulcerative colitis patients in deep remission, the incidence rate of relapse was 19% per patient-year. The treatment with adalimumab vs. infliximab (hazard ratio (HR)=1.29; 95% confidence interval (CI)=1.01-1.66), elective discontinuation of anti-TNFs (HR=1.90; 95% CI=1.07-3.37) or discontinuation because of adverse events (HR=2.33; 95% CI=1.27-2.02) vs. a top-down strategy, colonic localization (HR=1.51; 95% CI=1.13-2.02) vs. ileal, and stricturing behavior (HR=1.5; 95% CI=1.09-2.05) vs. inflammatory were associated with a higher risk of relapse in Crohn's disease patients, whereas treatment with immunomodulators after discontinuation (HR=0.67; 95% CI=0.51-0.87) and age (HR=0.98; 95% CI=0.97-0.99) were protective factors. None of the factors were predictive in ulcerative colitis patients. Retreatment of relapse with the same anti-TNF was effective (80% responded) and safe. The incidence rate of inflammatory bowel disease relapse after anti-TNF discontinuation is relevant. Some predictive factors of relapse after anti-TNF withdrawal have been identified. Retreatment with the same anti-TNF drug was effective and safe.

Microbial, metabolomic, and immunologic dynamics in a relapsing genetic mouse model of colitis induced by T-synthase deficiency

ABSTRACTIntestinal dysbiosis is thought to confer susceptibility to inflammatory bowel disease (IBD), but it is unknown whether dynamic changes in the microbiome contribute to fluctuations in disease activity. We explored this question using mice with intestine-specific deletion of C1galt1 (also known as T-synthase) (Tsyn mice). These mice develop spontaneous microbiota-dependent colitis with a remitting/relapsing course due to loss of mucin core-1 derived O-glycans. 16S rRNA sequencing and untargeted metabolomics demonstrated age-specific perturbations in the intestinal microbiome and metabolome of Tsyn mice compare with littermate controls at weeks 3 (disease onset), 5 (during remission), and 9 (after relapse). Colitis remission corresponded to increased levels of FoxP3+RORγt+CD4+ T cells in the colonic lamina propria that were positively correlated with operational taxonomic units (OTUs) in the S24–7 family and negatively correlated with OTUs in the Clostridiales order. Relapse was characterized by marked expansion of FoxP3-RORγt+CD4+ T cells expressing IFNγ and IL17A, which were associated with Clostridiales OTUs distinct from those negatively correlated with FoxP3+RORγt+CD4+ T cells. Our findings suggest that colitis remission and relapse in the Tsyn model may reflect alterations in the microbiome due to reduced core-1 O-glycosylation that shift the balance of regulatory and pro-inflammatory T cell subsets. We investigated whether genetic variation in C1galt1 correlated with the microbiome in a cohort of 78 Crohn's disease patients and 101 healthy controls. Polymorphisms near C1galt1 (rs10486157) and its molecular chaperone, Cosmc (rs4825729), were associated with altered composition of the colonic mucosal microbiota, supporting the relevance of core-1 O-glycosylation to host regulation of the microbiome.

Clinical Significance of Serum Cytokine Levels in Patients Hospitalized for Active Inflammatory Bowel Diseases

Introduction: Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory bowel diseases (IBD) of unknown cause. We aimed to investigate the clinical significance of serum cytokine levels in patients hospitalized for active CD or UC. Methods: Serum cytokine levels were measured in 13 CD patients and 19 UC patients before and after corticosteroids or anti TNF-α therapy during hospitalization. Thirty-two subjects were enrolled as a healthy control (HC) for comparison. Pre-treatment blood samples were collected on the day of hospitalization before the initiation of corticosteroids or anti TNF-α therapy. Post-treatment blood samples were collected on the 7th day after beginning corticosteroids or anti TNF-α therapy. Serum cytokine levels were compared between IBD patients and HC. Comparison was also performed between pre- and post-treatment phase. Results: Relapse of IBD within 1 year was observed in 27.3% of CD and 31.6% of UC patients. Interleukin-6 (IL-6) and TNF-α levels were significantly elevated in CD patients during pre-treatment active (P< 0.001, both) and post-treatment phase (P< 0.001, P=0.001) compared with HC. Similar results were observed in UC patients during pre-treatment active (P< 0.001, both) and post-treatment phase (P< 0.001, both) compared with HC. IL-6 and TNF-α levels significantly decreased in post-treatment CD patients compared with pre-treatment active phase (P=0.001, P=0.009). Similar results were found in post-treatment UC patients compared with pre-treatment active phase (P=0.001, P=0.022). Among preand post-treatment serum cytokine levels, only post-treatment serum IL-6 level was significantly associated with relapse of UC within 1 year (P=0.012). Conclusion: Elevated post-treatment serum IL-6 level was significantly associated with relapse of UC within 1 year. IL-6 and TNF-α levels were significantly elevated in pre- and post-treatment IBD patients compared with HC. Post-treatment IL-6 and TNF-α levels significantly decreased compared with pretreatment levels. IL-6 and TNF-α may act as a potential biomarker of diagnosing active disease, assessing therapeutic response, and predicting relapse in IBD patients.

Systematic Review: Adverse Events of Fecal Microbiota Transplantation.

BackgroundFecal microbiota transplantation (FMT) is a microbiota-based therapy that shows therapeutic potential in recurrent or refractory Clostridium difficile infections and other intestinal or extra-intestinal disorders. Nonetheless, adverse events (AEs) remain a major challenge in the application of FMT.AimTo review the AEs of FMT and to address the concerns of safety during the procedure.MethodsPublications were retrieved in the databases of Medline, Embase and Cochrane Library. AEs were classified according to their causality with FMT or their severity.ResultsA total of 7562 original articles about FMT were identified in this study, 50 of them fulfilled the inclusion criteria. Totally 78 kinds of AEs were revealed enrolled in these 50 selected publications. The total incidence rate of AEs was 28.5%. Among the 42 publications, 5 kinds were definitely and 38 kinds were probably related to FMT. The commonest FMT-attributable AE was abdominal discomfort, which was reported in 19 publications. For upper gastrointestinal routes of FMT, 43.6% (89/204) patients were compromised by FMT-attributable AE, while the incidence dropped to 17.7% (76/430) for lower gastrointestinal routes. In contrast, the incidences of serious adverse events (SAEs) were 2.0% (4/196) and 6.1% (40/659) for upper and lower gastrointestinal routes, respectively. A total of 44 kinds of SAEs occurred in 9.2% patients, including death (3.5%, 38/1089), infection (2.5%, 27/1089), relapse of inflammatory bowel diseases (0.6%, 7/1089) and Clostridium difficile infection (0.9%, 10/1089).ConclusionConsequently, both AEs and SAEs are not rare and should be carefully monitored throughout FMT. However, high quality randomized controlled trials are still needed for the more definite incidence of AEs of FMT.

The prognostic significance of faecal calprotectin in patients with inactive inflammatory bowel disease.

Faecal calprotectin, an established biomarker used to assess mucosal inflammation, has been shown to correlate with endoscopic activity in inflammatory bowel disease (IBD). Longitudinal monitoring of faecal calprotectin, however, has rarely been employed beyond assessment of therapy response and post hoc analyses of clinical trials. To study whether consecutive measurements of faecal calprotectin every third month are useful for monitoring patients with IBD in clinical remission. Patients aged 18 years or older, with a known diagnosis of IBD in clinical remission, were prospectively studied. Patients provided faecal samples every third month and were prospectively followed until the first clinical relapse or the end of the 2-year follow-up period. Measurements (EK-CAL, Bühlmann Lab. AG, Switzerland) were done at the end of the study. A Cox model with time-dependent covariates was used for analysis. Among 104 patients, Crohn's disease (n = 49) and ulcerative colitis (n = 55), 37 had a relapse. A doubling of faecal calprotectin level between two consecutively collected samples was associated with a 101% increased risk of relapse (HR: 2.01; 95% CI: 1.53-2.65; P < 0.001). The relative risk of relapse attenuated with time (HR: 0.80; 95% CI: 0.75-0.86; P < 0.001), by a 20% decrease in risk of relapse per 3-month period since the sample was obtained. By consecutively measuring faecal calprotectin every third month, we quantified the risk of relapse related to faecal calprotectin change and observed attenuation of the risk across time. Our data suggest that longitudinal monitoring of faecal calprotectin is informative in predicting relapse in IBD.

PTU-012 Faecal Calprotectin as Predictor of Small-Bowel Crohn’s Disease in Capsule Endoscopy – A Systematic Review and Meta-Analysis

Introduction Faecal calprotectin (FC) is a well-established marker of gut inflammation. While the correlation of elevated FC levels with colonic inflammation has been confirmed in several studies,1,2 data regarding the correlation of FC with small-bowel inflammation is either scarce or conflicting.3 Capsule endoscopy (CE) is the modality of choice for detection of small-bowel inflammation and/or small-bowel Crohn’s disease (CD).4 Therefore, we aimed to systematically review and meta-analyse the evidence for the diagnostic accuracy of FC as a predictor of small-bowel CD. Methods A comprehensive literature search of the databases PubMed and Embase was performed, using the search string: “capsule endoscopy” + calprotectin. Studies including patients with suspected and/or established CD evaluated by both FC and CE were retrieved. Corresponding authors were contacted for any missing data. The following FC cut-offs were evaluated: >50, 100 and 200 μg/g, as available in each included study. A diagnostic meta-analysis was performed; pooled diagnostic sensitivity (Se), specificity (Sp) and diagnostic odds ratio (DOR) with 95% confidence intervals (95% CI) were obtained for each of the cut-offs. Bias was evaluated using the quality assessment of studies of diagnostic accuracy in systematic reviews (QUADAS) 2 tool. A minimum of 4 studies was required for each analysis. Results A total of 135 studies were identified; seven (3 prospective, 4 retrospective) studies, including 463 patients, entered the final analysis. Overall, the methodological quality of the studies was high, with 6/7 studies showing low risk of bias. For studies including only patients with suspected CD, the diagnostic accuracy of FC for the cut-off of 50 μg/g was as follows: 5 studies, 305 patients; Se 89% (CI 68%;97%), Sp 55% (CI 36%;73%), DOR 10.3 (CI 3.7;28.6) . For all included studies (suspected and established CD), the DOR was significant for all the evaluated FC cut-offs. FC > 50μg/g: 7 studies, 463 patients; Se 83% (CI 73%;90%), Sp 53% (CI 36%;71%), DOR 5.64 (CI 3.2;10.1). FC > 100μg/g: 5 studies, 379 patients; Se 68% (CI 56%;76%), Sp 71% (CI 46%;88%), DOR 5.01 (CI 2.03;12.07). FC > 200μg/g: 4 studies, 309 patients; Se 42% (CI 26%;64%), Sp 94% (CI 64%;99%), DOR 13.64 (CI 2.01;88.6). Sensitivity analysis based on methodological quality did not change those results significantly. Conclusion This meta-analysis confirms that FC, when used as a predictor of small-bowel CD prior to CE, has high diagnostic accuracy. For patients with suspected CD, a FC cut-off level of 50 μg/g provided high sensitivity and DOR, while for the entire patient cohort (suspected and established CD) FC > 200 μg/g provided the best overall DOR. The likelihood of diagnosing small-bowel CD is extremely low in suspected CD patients with FC References 1 D’Haens G, et al. Faecal calprotectin is a surrogate marker for endoscopic lesions in inflammatory bowel disease. Inflamm Bowel Dis 2012;18:2218–2224. 2 Van Rheenen PF, et al. Faecal calprotectin for screening of patients with suspected inflammatory bowel disease: diagnostic meta-analysis. BMJ 2010;341:c3369. 3 Mao R, et al. Faecal calprotectin in predicting relapse of inflammatory bowel diseases: A meta‐analysis of prospective studies. Inflamm Bowel Dis 2012;18:1894–1899. 4 Annese V, et al. European evidence based consensus for endoscopy in inflammatory bowel disease. J Crohns Colitis 2013;7:982–1018. Disclosure of Interest None Declared

Incidence of Ulcerative Colitis Relapse: A Prospective Cohort Study in Southern Iran

Background The epidemiology of inflammatory bowel disease (IBD) is changing globally and there is disagreement between studies about the prevalence of relapse of ulcerative colitis (UC) as a type of IBD. Objectives The current study aimed to find out the incidence of relapses in patients with UC in Southern Iran. Patients and Methods In a prospective cohort study in a period of one year (from October 2012 to October 2013) 157 patients with UC who were in clinical remission for at least three months and were registered in the IBD registry of Shiraz University of Medical Sciences, Shiraz, Iran were enrolled. The sample size was calculated according to the formula to determine a ratio. Clinical relapse was described as deterioration of bowel movements, lower intestinal bleeding or worsening of abdominal pain and diarrhea leading to changes in previous treatment. Age and gender distribution and the frequency of relapse in a one-year follow-up were recorded. Results Among the 1273 registered patients with UC, 157 patients were enrolled in the survey by systematic sampling. Among patients, 48.7% were female and no significant difference was observed between the mean age of two gender groups (P = 0.70). Seventy-four patients, 48.1% (33 males and 41 females), relapsed during the 12-month follow-up period and the main medication of the 64 non-relapsing (80%) and 62 relapsing (83.8%) patients was mesalazin (P = 0.65). Conclusions Although, the reported incidence was almost equal to previous reports from other regions of the world, relapsed and non-relapsed UC patients received mesalazin as treatment without any significant differences.

Preconception Care Reduces Relapse of Inflammatory Bowel Disease During Pregnancy.

Women with inflammatory bowel disease (IBD) may have incorrect beliefs about their disease and its medication in relation to pregnancy. We studied the effects of preconception care (PCC) on patients' behavior during pregnancy, disease relapse during pregnancy, and birth outcomes. In a prospective study, we followed up all women with IBD seen at the preconception outpatient clinic at Erasmus MC-University Medical Center in Rotterdam, The Netherlands (from 2008 through 2014). We compared patients who received PCC before they became pregnant (PCC group; n= 155) with patients who visited the clinic after they already were pregnant (no-PCC group; n= 162). We collected data on lifestyle, medication adherence, planning of conception, disease activity, and birth outcomes. We compared adherence to medical advice, rates of disease relapse during pregnancy, and birth outcomes. The PCC group was on average younger than the no-PCC group (29.7 vs 31.4 y; P= .001), and a greater proportion were nulliparous (76.1% vs 51.2%; P= .0001). PCC was associated with adherence to IBD medication during pregnancy (adjusted odds ratio [aOR],5.69; 95% confidence interval [CI], 1.88-17.27), adequate folic acid intake (aOR, 5.26; 95% CI, 2.70-10.26), and smoking cessation (aOR, 4.63; 95% CI, 1.22-17.55). PCC reduced disease relapse during pregnancy independent of parity, disease duration, or disease activity before conception (aOR, 0.51; 95% CI, 0.28-0.95). The PCC group was less likely to deliver babies of low birth weight (aOR, 0.08; 95% CI, 0.01-0.48). In a prospective study, we found that preconception care reduces IBD relapse during pregnancy by promoting adherence to medication and smoking cessation. Preconception also reduces risk for babies of low birth weight.

Utility of surrogate markers for the prediction of relapses in inflammatory bowel diseases

Patients with diagnosed inflammatory bowel disease (IBD) will commonly experience a clinical relapse in spite of a prolonged therapy-induced period of clinical remission. The current methods of assessing subclinical levels of low-grade inflammation which predispose patients to relapse are not optimal when considering both cost and patient comfort. Over the past few decades, much investigation has discovered that proteins such as calprotectin that are released from inflammatory cells are capable of indicating disease activity. Along with C-reactive protein and erythrocyte sedimentation rate, calprotectin has now become part of the current methodology for assessing IBD activity. More recently, research has identified that other fecal and serum biomarkers such as lactoferrin, S100A12, GM-CSF autoantibodies, α1-antitrypsin, eosinophil-derived proteins, and cytokine concentrations have variable degrees of utility in monitoring gastrointestinal tract inflammation. In order to provide direction toward novel methods of predicting relapse in IBD, we provide an up-to-date review of these biomarkers and their potential utility in the prediction of clinical relapse, given their observed activities during various stages of clinical remission.

Berberine ameliorates chronic relapsing dextran sulfate sodium-induced colitis in C57BL/6 mice by suppressing Th17 responses

Ulcerative colitis (UC) is an increasingly common condition particularly in developed countries. The lack of satisfactory treatment has fueled the search for alternative therapeutic strategies. In recent studies, berberine, a plant alkaloid with a long history of medicinal use in Chinese medicine, has shown beneficial effects against animal models of acute UC. However, UC usually presents as a chronic condition with frequent relapse in patients. How berberine will act on chronic UC remains unclear. In the present study, we adopted dextran sulfate sodium (DSS)-induced chronic relapsing colitis model to assess the ameliorating activity of berberine. Colitis was induced by two cycles of 2.0% DSS for five days followed by 14days of drinking water plus a third cycle consisting of DSS only for five days. The colitis mice were orally administered 20mg/kg berberine from day 13 onward for 30days and monitored daily. The body weight, stool consistency, and stool bleeding were recorded for determination of the disease activity index (DAI). At the end of treatment, animals were sacrificed and samples were collected and subjected to histological, RT-qPCR, Western blot, and LC–MS analyses. Lymphocytes were isolated from spleens and mesenteric lymph nodes (MLN) and cultured for flow cytometry analysis of IL-17 secretion from CD4+ cells and the Th17 cell differentiation. Results showed that berberine significantly ameliorated the DAI, colon shortening, colon tissue injury, and reduction of colonic expression of tight junction (TJ) protein ZO-1 and occludin of colitis mice. Notably, berberine treatment pronouncedly reduced DSS-upregulated Th17-related cytokine (IL-17 and ROR-γt) mRNAs in the colon. Furthermore, the mRNA expression of IL-6 and IL-23, and the phosphorylation of STAT3 in colon tissues from DSS-treated mice were pronouncedly inhibited by berberine. Moreover, the up-regulation of IL-17 secretion from CD4+ cells of spleens and MLNs caused by DSS were significantly reversed by berberine treatment. Furthermore, Th17 cell differentiation from naive CD4+ cells isolated from above DSS colitis mice were suppressed by berberine in a concentration-dependent manner. In summary, we demonstrated for the first time that berberine reduced the severity of chronic relapsing DSS-induced colitis by suppressing Th17 responses. The demonstration of activity in this mouse model supports the possibility of clinical efficacy of berberine in treating chronic UC.

Confocal laser endomicroscopy in ulcerative colitis: a longitudinal study of endomicroscopic changes and response to medical therapy (with videos)

Confocal laser endomicroscopy enables real-time invivo microscopy during endoscopy and can predict relapse in patients with inflammatory bowel disease in remission. However, little is known about how endomicroscopic features change with time. The aim of this longitudinal study was to correlate colonic confocal laser endomicroscopy (CLE) in ulcerative colitis with histopathology and macroscopic appearance before and after intensification of medical treatment. Twenty-two patients with ulcerative colitis in clinical relapse and 7 control subjects referred for colonoscopy were enrolled. The colonic mucosa was examined with high-definition colonoscopy, histopathology, and CLE at 4 colonic sites. Subsequently, patients requiring medical treatment escalation were referred for repeat endoscopy with CLE after 6 to 8 weeks. The baseline frequency of fluorescein leakage (P< .001), microerosions (P< .001), tortuosity of thecrypts (P= .001), distortion of the crypts openings (P= .001), presence of inflammatory infiltrates (P<.001), and decreased crypt density (P< .001) were significantly higher in active ulcerative colitis compared with inactive ulcerative colitis and control subjects. A decrease in histopathologic score after medical treatment escalation was correlated with improvement in crypt tortuosity (rs= .35, P= .016), distortion of crypt openings (rs= .30, P= .045), and decreased crypt density (rs= .33, P= .026) but not in other features. CLE is an emerging endoscopic technique that reproducibly identifies mucosal changes in ulcerative colitis. With the exception of crypt changes, endomicroscopic features appear to improve slowly with time after medical treatment. ( NCT01684514.).

O-019 Anxiety in Pediatric IBD

The impact of anxiety on disease relapse and health care use for pediatric patients diagnosed with inflammatory bowel disease (IBD) still requires further inquiry. Anxiety can influence health care utilization through multiple avenues, including manipulation of inflammatory processes central to IBD, and via somatic manifestation of psychological stress that may be misinterpreted as disease symptoms or medication side effects. The aim of this study was to examine the association between anxiety and risk for disease relapse, and test whether anxiety predicted greater gastrointestinal (GI) health care utilization over a 12-month period. Families were asked to complete Child and Parent versions of an anxiety questionnaire (Screen for Child Anxiety Related Emotional Disorders; SCARED) at their GI visit check-in, as part of a larger study (Reigada et al, in press). To be included in this study, children had to return a completed questionnaire, receive their primary IBD care at the medical practice, and remain a patient for ≥1 year. The final sample included 86 children ages 11 to 18 (M = 15.0, SD = 2.0) and their caregivers (n = 77). The number of disease relapses and GI health care utilization frequencies (i.e., GI office encounters, outpatient procedures, and hospital-based interventions) were extracted from medical records during the 12 months following completion of the anxiety questionnaire (i.e., baseline). Physicians also used documentation from patient charts to complete measures of disease activity at baseline and 12 months later. Analysis of variance was used to compare anxiety levels between those who experienced 2 or more disease relapses, and those who experienced 0 to 1. Poisson regressions were used to model relationships between child- and caregiver-reported anxiety symptoms and GI health care utilization. IBD relapses (0, 1, ≥2) and change in disease activity were also entered into the models. The sample was predominantly white (81%) and the majority was male (56%). Children who experienced 2 or more disease relapses over 12 months (n = 14) had a mean baseline SCARED score of 19.6 (SD = 13.7), compared to a mean score of 12.6 (SD = 10.3) reported by children who had 0 to 1 IBD relapses (P < 0.05). Caregiver-reported anxiety symptoms did not differ between groups. Higher anxiety at baseline, irrespective of reporter, predicted greater total GI health care use (Ps < 0.01). Examination of individual GI visit types showed that child and caregiver-proxy reports predicted hospital-based interventions (P < 0.001), but not office encounters or outpatient procedures. Findings remained significant after controlling for disease severity (Ps < 0.05). Results suggest that elevated self-reported anxiety may signal those children at risk for repeated disease relapses. Findings also show that child anxiety predicts the use of pediatric IBD health care over the subsequent year, especially hospital-based interventions such as emergency room visits and surgery. The influences of anxiety on health care utilization remained after accounting for disease severity, suggesting that health-seeking behavior may be influenced by emotional factors in addition to disease processes. Future studies should incorporate biological markers of disease and measures of somatic symptoms, as well as test the health and cost benefits of treating anxiety in pediatric IBD.

Fecal Calprotectin as Predictor of Relapse in Patients With Inflammatory Bowel Disease Under Maintenance Infliximab Therapy.

Predicting relapse in Inflammatory Bowel Disease (IBD) could allow for early changes of treatment. Close monitoring of fecal calprotectin (FC) could be useful to predict relapse in IBD. Aim of the study was to evaluate the predictive value of a rapid FC test to predict flares in patients with IBD under maintenance therapy with Infliximab. A prospective observational cohort study was designed. IBD patients in clinical remission under maintenance Infliximab therapy were included. FC was measured using a rapid test on a stool sample obtained within 24 hours before Infliximab infusion. Clinical examination was performed 2 months after that infusion. Fifty-three patients were included (52.8% female). Thirty-three patients (62.3%) had Crohn's disease and 20 (37.7%) had ulcerative colitis. All patients were in remission at inclusion. After 2 months, 41 patients (77.4%) remained in clinical remission and 12 (22.6%) presented a relapse. FC (mean±SD) in relapsing and not-relapsing disease was 332±168 and 110±163 µg/g, respectively (P<0.005). A FC concentration>160 µg/g had a sensitivity of 91.7%, and specificity of 82.9% to predict relapse. In IBD patients under Infliximab maintenance therapy, high FC levels allow predicting relapse within the following 2 months. Long-term remission is associated with low calprotectin levels. Further studies are required to confirm these results.

Importance of Patients’ Knowledge of Their Prescribed Medication in Improving Treatment Adherence in Inflammatory Bowel Disease

To investigate the association between treatment nonadherence and patients' knowledge of the prescribed medication among individuals with inflammatory bowel disease (IBD), and evaluate the impact of nonadherence on relapse. The patient's knowledge of the prescribed medication has been identified as an important predictor of treatment adherence in chronic diseases. However, this association has not been examined in IBD. In this prospective study, at baseline, 138 patients with IBD completed a self-reported survey on demographic data, knowledge of the prescribed medication, and candidate factors related to the degree of treatment adherence. To investigate the impact of nonadherence among patients in remission, relapse was analyzed for 18 months after enrollment. Nonadherence was observed in 50 (36.2%) of the 138 subjects. In multivariate analysis, nonadherence was significantly associated with younger age (less than 30 y) at participation [odds ratio (OR), 5.88; 95% confidence interval (CI), 1.51-22.94; P=0.011], longer intervals between outpatient clinic visits (≥3 mo) (OR, 30.31; 95% CI, 3.06-300.17; P=0.004), and limited knowledge of the prescribed medication (OR, 5.61; 95% CI, 1.60-19.67; P=0.038). Nonadherent patients had a significantly greater risk of relapse of IBD than adherent patients (relative risk, 2.9; 95% CI, 2.25-3.79; P=0.045). Younger age, longer intervals between outpatient clinic visits, and limited knowledge of the prescribed medication tended to be associated with nonadherence to treatment, which consequently also affects the risk of relapse.

Intestinal Microbiota Signatures Associated with Inflammation History in Mice Experiencing Recurring Colitis.

Acute colitis causes alterations in the intestinal microbiota, but the microbiota is thought to recover after such events. Extreme microbiota alterations are characteristic of human chronic inflammatory bowel diseases, although alterations reported in different studies are divergent and sometimes even contradictory. To better understand the impact of periodic disturbances on the intestinal microbiota and its compositional difference between acute and relapsing colitis, we investigated the beginnings of recurrent inflammation using the dextran sodium sulfate (DSS) mouse model of chemically induced colitis. Using bacterial 16S rRNA gene-targeted pyrosequencing as well as quantitative fluorescence in situ hybridization, we profiled the intestinal and stool microbiota of mice over the course of three rounds of DSS-induced colitis and recovery. We found that characteristic inflammation-associated microbiota could be detected in recovery-phase mice. Successive inflammation episodes further drove the microbiota into an increasingly altered composition post-inflammation, and signatures of colitis history were detectable in the microbiota more sensitively than by pathology analysis. Bacterial indicators of murine colitis history were identified in intestinal and stool samples, with a high degree of consistency between both sample types. Stool may therefore be a promising non-invasive source of bacterial biomarkers that are highly sensitive to inflammation state and history.

Inflammatory Bowel Disease Patients' Willingness to Accept Medication Risk to Avoid Future Disease Relapse.

Biomarkers, endoscopy and imaging tests can identify patients at increased risk for early recurrence of symptomatic inflammatory bowel disease (IBD). However, patients may be unwilling to accept additional medical therapy risks related to therapy escalation to avoid a future disease relapse. We sought to quantify IBD patients' willingness to accept medication risk to avoid future disease relapse. We conducted a discrete-choice experiment among 202 patients with IBD who were offered choices of therapies with varying risks of lymphoma and infection, and varying time to next IBD relapse. Random parameters logit was used to estimate patients' willingness to accept tradeoffs among treatment features in selecting medication therapy to avoid future disease relapse. To avoid a disease relapse over the next 5 years, IBD patients were willing to accept an average of a 28% chance of a serious infection; and an average of 1.8% chance of developing lymphoma. These results did not significantly change when patients were offered 10 years until their next disease relapse, but were lower (11 and 0.7%, respectively) when offered 1.5 years until the next disease relapse. Patients with active disease symptoms were significantly less willing to accept medication risk for time in remission. IBD patients are willing to accept high levels of lymphoma and serious infection risk to maintain disease remission. These preferences are congruent with the treatment paradigms emphasizing mucosal healing and early aggressive therapy and highlight patients' strong preferences for therapies resulting in durable remission of at least 5 years.

Effect of Chondroitin Sulphate on Pro-Inflammatory Mediators and Disease Activity in Patients with Inflammatory Bowel Disease

Background/Aims: To evaluate the incidence rate of relapse in patients with inflammatory bowel disease (IBD) undergoing chondroitin sulphate (CS) treatment and its effect on the concentrations of several pro-inflammatory proteins. Methods: Prospective, observational, 12-month follow-up study in patients with IBD in remission, starting CS (Condrosan®, Bioiberica S.A.) treatment for osteoarthritis (OA). Crohn's Disease Activity Index and modified Truelove-Witts severity index were calculated for Crohn's disease and ulcerative colitis (UC) respectively. Levels of vascular endothelial growth factor (VEGFA), -C, fibroblast growth factor 2, hepatocyte growth factor, angiopoietin (Ang)-1, Ang-2, transforming growth factor beta, tumour necrosis factor alpha, interleukin (IL)-1β, IL-6, IL-12, IL-17, IL-23, intracellular adhesion molecule-1, vascular adhesion molecule-1, matrix metalloproteinase-3 and PGE2 were quantified by ELISA. OA joint pain was evaluated using a visual analogue scale. Results: A total of 37 patients (19 UC and 18 Crohn's disease) were included. The mean values for OA joint pain decreased after 12 months from 5.9 ± 2.8 to 3.0 ± 2.3 (p < 0.05). Only 1 patient (with UC) flared during follow-up. The incidence rate of relapse was 3.4% per patient-year of follow-up. Mean serum VEGFA levels increased between baseline (492 pg/ml) and 12-month treatment (799 pg/ml; p < 0.05). Conclusion: The incidence of IBD relapse in patients under CS treatment was lower than that generally reported. This treatment might modulate VEGFA. CS decreases OA-related pain in patients with IBD.