Serum Dipeptidyl Peptidase 4: A Predictor of Disease Activity and Prognosis in Inflammatory Bowel Disease.

BACKGROUND: Serum dipeptidyl peptidase 4 (DPP-4) has drawn particular interest as a biomarker in inflammatory bowel disease (IBD), as this protease inactivates several peptides that participate in the inflammatory cascade. METHODS: Two prospectively recruited cohorts consisting of 195 patients (101 had Crohn's disease [CD] and 94 had ulcerative colitis [UC]) were evaluated using clinical indexes and followed up to assess for treatment escalation. Sixty-eight patients underwent endoscopic evaluation at baseline. In the second cohort of 46 biologically treated patients, treatment response was assessed. Serum DPP-4, C-reactive protein (CRP), and fecal calprotectin levels were quantified at baseline and during follow-up. RESULTS: Median DPP-4 levels were significantly lower in active IBD patients when compared with remitters (CD: 1043 [831-1412] vs 1589 [1255-1956] ng/mL; P < 0.001; UC: 1317 [1058-1718] vs 1798 [1329-2305] ng/mL; P = 0.001) and healthy controls (2175 [1875-3371] ng/mL). In fact, DPP-4 was able to distinguish clinical and endoscopic activity from remission, with areas under the curve (AUC) of 0.81/0.93 (CD) and 0.71/0.79 (UC), along with the need for treatment escalation, with comparable AUCs of 0.79 (CD) and 0.77 (UC). Furthermore, DPP-4 levels were higher in responders to treatment and more pronounced among UC (1467 [1301-1641] vs 1211 [1011-1448] ng/mL; P < 0.001) than CD patients (1385 [1185-1592] vs 1134 [975-1469] ng/mL; P = 0.015). CONCLUSIONS: Our results suggest that serum DPP-4 can be used as a noninvasive biomarker of IBD activity and biological treatment response and a predictor of treatment escalation, particularly when combined with other biomarkers.

Cutaneous Morbidity Among Inflammatory Bowel Disease Patients: A Cohort Study.

BACKGROUND AND AIMS: Patients with inflammatory bowel diseases are prone to cutaneous manifestations. The aim of this study was to investigate their prevalence, type and association to demographic and clinical factors. METHODS: This was a cross-sectional study. Information relative to patients of a central Portuguese hospital with a definitive diagnosis of an inflammatory bowel disease, who were prospectively recruited, was collected. RESULTS: The final cohort included 342 patients, 62% of whom had Crohn's disease and 38% had ulcerative colitis. Cutaneous extraintestinal manifestations were present in 44.4% of all patients; this prevalence was lower [14.9%] when excluding cutaneous manifestations secondary to nutrition deficiency or drugs. These skin lesions were classified as granulomatous [0.3%], reactive [4.4%], immunologically associated [10.5%] and secondary to nutritional deficiencies [6.4%] or to bowel-related therapy [29.5%]. Excluding those secondary to nutrition or drugs, cutaneous manifestations were significantly associated with females (odds ratio [OR] 3.210 [1.625-6.340], p = 0.001) and younger patients (OR 0.954 [0.924-0.985], p = 0.004). Additionally, their occurrence was related to patients up to 16 years (OR 13.875 [1.332-144.484], p = 0.028) among the Crohn's disease sub-cohort, whereas in the ulcerative colitis sub-cohort they were more likely to occur in patients with extensive colitis (OR 5.317 [1.552-18.214], p = 0.008). CONCLUSIONS: Nearly half of the patients analysed had at least one cutaneous extraintestinal manifestation. The fact that certain lesions tend to be more common among patients with defined characteristics should alert the physicians and allow an early diagnosis and, when pertinent, a reference to dermatology.

Serial Tuberculosis Screening in Inflammatory Bowel Disease Patients Receiving Anti-TNFα Therapy.

BACKGROUND AND AIMS: One of the adverse effects of the tumour necrosis factor alpha [[TNFα] monoclonal antibodies for the treatment of immune-mediated inflammatory diseases is a higher propensity for tuberculosis development. The aim of this study was to explore the utility and sensitivity of serial tuberculosis screening during anti-TNFα treatment. METHODS: A cohort of 46 inflammatory bowel disease patients receiving infliximab was prospectively recruited and followed for 26 months. During this period of time, a tuberculosis skin test and two different interferon ϒ release assays [QFT-GIT and T-SPOT.TB] were applied at 4-6-month intervals. RESULTS: Overall, 16 patients were diagnosed with latent tuberculosis infection after having at least one test conversion: 12 patients had a positive tuberculosis skin test, seven patients had a positive T-SPOT.TB, and two patients had a positive QFT-GIT. Active tuberculosis was excluded in all; 15 were treated with isoniazid. A comparison between tests showed a moderate accuracy [72% to 85%] but low kappa values [0.063 to 0.377]. Concerning association with demographic and clinical characteristics, test conversion was more common among the male gender and those with a longer disease duration. CONCLUSIONS: Tuberculosis tests conversions were common in inflammatory bowel disease patients treated with infliximab alone or in association with immunomodulators. In these immunosuppressed individuals, the classical tuberculosis skin test seems to have a higher sensitivity than the modern tests based on the release of interferonϒ.

Portuguese Version of the Pain Beliefs and Perceptions Inventory: A Multicenter Validation Study.

BACKGROUND: We aimed to perform the translation, cultural adaptation, and validation of the Pain Beliefs and Perceptions Inventory (PBPI) for the European Portuguese language and chronic pain population. METHODS: This is a longitudinal multicenter validation study. A Portuguese version of the PBPI (PBPI-P) was created through a process of translation, back translation, and expert panel evaluation. The PBPI-P was administered to a total of 122 patients from 13 chronic pain clinics in Portugal, at baseline and after 7 days. Internal consistency and test-retest reliability were assessed by Cronbach's alpha (α) and intraclass correlation coefficient (ICC). Construct (convergent and discriminant) validity was assessed based on a set of previously developed theoretical hypotheses about interrelations between the PBPI-P and other measures. Exploratory and confirmatory factor analyses were performed to test the theoretical structure of the PBPI-P. RESULTS: The internal consistency and test-retest reliability coefficients for each respective subscale were α = 0.620 and ICC = 0.801 for mystery; α = 0.744 and ICC = 0.841 for permanence; α = 0.778 and ICC = 0.791 for constancy; and α = 0.764 and ICC = 0.881 for self-blame. Exploratory and confirmatory factor analysis revealed a four-factor structure (performance, constancy, self-blame, and mystery) that explained 63% of the variance. The construct validity of the PBPI-P was shown to be adequate, with more than 90% of the previously defined hypotheses regarding interrelations with other measures confirmed. CONCLUSION: The PBPI-P has been shown to be adequate and to have excellent reliability, internal consistency, and validity. It may contribute to a better pain assessment and is suitable for research and clinical use.

Predictive factors of small bowel patency in Crohn’s disease patients

Background: Patency capsule was developed to avoid small bowel video capsule endoscopy retention, namely in patients with Crohn’s disease. Aims: To evaluate the predictive factors of small bowel patency in Crohn’s disease patients. Patients and methods: Retrospective analysis including 151 Crohn’s disease patients submitted to patency capsule (Agile® Patency Capsule) from 2011 to 2012. Patients that excreted the intact patency capsule were classified as having a patent small bowel (without patency capsule retention), other patients were considered to have negative patency of the small bowel (patency capsule retention). Results: Patients had a mean age of 41±14 years, 54% were female and 25% had been previously submitted to surgery. Stricturing disease was seen in 20% of cases and penetrating disease in 16% of cases. Left-sided colonic lesions and ileal strictures were observed at colonoscopy in 13% and 9% of patients, respectively. In our sample, 28% of patients had negative patency of the small bowel (patency capsule retention). In multivariate analysis, independent factors that were associated with negative patency of the small bowel in Crohn’s disease patients were structuring (OR 10.16, p < 0.001) and penetrating phenotypes (OR 11.73, p = 0.001), left-sided colonic lesions (OR 3.77, p = 0.038), ileal stricture (OR 9.76, p = 0.003); previous intestinal surgery was found to be protective (OR 0.16, p = 0.006). Conclusions: Stricturing or penetrating disease, ileal strictures, no previous surgery and left-sided colonic lesions were the factors associated with negative small bowel patency in Crohn’s disease patients (AU)

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Assessing overall patient satisfaction in inflammatory bowel disease using structural equation modeling.

BACKGROUND/AIMS: Structural equation modeling (SEM) is a very popular data-analytic technique for the evaluation of customer satisfaction. We aimed to measure the overall satisfaction of inflammatory bowel disease (IBD) patients with healthcare in Portugal and to define its main determinants using SEM. PATIENTS AND METHODS: The study included three steps: (i) specification of a patient satisfaction model that included the following dimensions: Image, Expectations, Facilities, Admission process, Assistant staff, Nursing staff, Medical staff, Treatment, Inpatient care, Outpatient care, Overall quality, Overall satisfaction, and Loyalty; (ii) sample survey from 2000 patients, members of the Portuguese Association of the IBD; and (iii) estimation of the satisfaction model using partial least squares (XLSTAT-PLSPM). RESULTS: We received 498 (25%) valid questionnaires from 324 (66%) patients with Crohn's disease and 162 (33%) patients with ulcerative colitis. Our model provided a substantial explanation for Overall satisfaction (R=0.82). The mean index of overall satisfaction was 74.4 (0-100 scale). The main determinants of Overall satisfaction were the Image (ß=0.26), Outpatient care (ß=0.23), and Overall quality (ß=0.21), whose mean indices were 83, 75, and 81, respectively. Facilities and Inpatient care were the variables with a significant impact on Overall satisfaction and the worst mean indices. CONCLUSION: SEM is useful for the evaluation of IBD patient satisfaction. The Overall satisfaction of IBD patients with healthcare in Portugal is good, but to increase it, IBD services need to focus on the improvement of Outpatient care, Facilities, and Inpatient care. Our model could be a matrix for a global model of IBD patient satisfaction.

Is it possible to change phenotype progression in Crohn's disease in the era of immunomodulators? Predictive factors of phenotype progression.

OBJECTIVES: Crohn's disease (CD) induces cumulative structural damage, initially characterized by a non-stenosing non-penetrating behavior (B1) with progression over time to a fibro-stenosing (B2) and/or penetrating phenotype (B3). Our aim was to assess the long-term evolution of disease behavior of CD and determine what factors predict phenotype progression. METHODS: This was a study based on prospectively collected data from a CD database in an inflammatory bowel disease outpatient clinic. B1 corresponds to a non-stenosing non-penetrating disease, B2 to a stenosing behavior, and B3 to a penetrating one. RESULTS: Seven hundred and thirty-six patients with CD (368 female) were followed up for 12.3 years (± 8.4), with 87.0% of them exhibiting B1 phenotype at diagnosis. Of these patients, 28.5% progressed to B2 phenotype and 23.5% to B3. Fifty percent of the patients started azathioprine treatment before phenotype change and 13.9% started anti-tumor necrosis factor-α (anti-TNFα) treatment before phenotype change. Monotherapy with azathioprine before phenotype change as well as combination therapy with azathioprine/anti-TNFα before phenotype change delayed disease progression (B1-B2 or B3) in comparison with patients who did not receive treatment (P<0.001). The hazard ratio (HR) for disease progression was lower for both monotherapy with azathioprine (HR: 0.15, P<0.001) or combination therapy with anti-TNFα (HR: 0.33, P<0.001). Upper gastrointestinal tract involvement, male gender, and steroid use were associated with an early progression of phenotype from B1 to B2 or B3 (P<0.001). The HR for disease progression was higher in patients who used steroids without criteria of dependence or resistance (HR: 2.67, P<0.001) and was even higher in patients with criteria of dependence or resistance (HR: 6.44, P<0.001). Longer delays between CD diagnosis and beginning of therapy with azathioprine and/or anti-TNFα were associated with disease progression. The longer the duration of treatment, the less likely the disease progression. CONCLUSIONS: Monotherapy with azathioprine before behavior change as well as combination therapy with azathioprine and anti-TNFα before behavior change delays phenotype progression of CD, whereas upper gastrointestinal tract involvement, male gender, and steroid use with or without criteria of steroid dependence are associated with a higher risk for disease progression.

High C-reactive protein in Crohn's disease patients predicts nonresponse to infliximab treatment.

BACKGROUND: Infliximab (IFX) is effective in treating Crohn's disease (CD) and C-reactive protein (CRP) is a useful biomarker in assessing inflammatory activity. AIM: Correlate CRP levels before beginning of IFX, at week 14 and CRP delta within the first year of IFX treatment. METHODS: Retrospective study of CD patients undergoing treatment with IFX. Primary nonresponse (PNR) was defined as no symptomatic improvement and CRP persistently elevated; sustained response (SR) as symptomatic improvement for at least 1 year without therapeutic adjustment; response after therapeutic adjustment (RTA) as analytic and clinical response but requiring IFX dose/frequency adjustment or association with another drug. RESULTS: Baseline CRP levels were higher in PNR compared with SR (26.2mg/L vs 9.6 mg/L, p=0.015) and RTA (26.2mg/L vs 7.6 mg/L, p=0.007). CRP levels greater than 15 mg/L at baseline predict PNR with 67% sensitivity and 65% specificity. Lower CRP levels at week 14 were more likely to predict SR relative to RTA (3.1mg/L vs 7.6 mg/L p=0.019) and PNR (3.1mg/L vs 9.1mg/L; p=0.013). CRP levels greater than 4.6 mg/L at week 14 predict PNR with 67% sensitivity and 62% specificity. A higher CRP delta between beginning of treatment and week 14 is more likely to predict SR relative to RTA (5.2mg/L vs 0.6 mg/L p=0.027). CONCLUSION: CRP levels at week 14 were associated with SR in patients treated with IFX, independently of baseline CRP serum levels. High inflammatory burden at beginning of IFX treatment was correlated with a worse response.