Maria Esteve

Early Azathioprine Therapy Is No More Effective Than Placebo for Newly Diagnosed Crohn's Disease

BACKGROUND & AIMS A small placebo-controlled trial reported the efficacy of mercaptopurine therapy for children newly diagnosed with Crohns disease, yet little is known about the efficacy of early thiopurine therapy in adults. METHODS We performed a prospective double-blind trial of adult patients with a recent (<8 weeks) diagnosis of Crohns disease. Patients were randomly assigned to groups given azathioprine (2.5 mg · kg(-1) · day(-1), n = 68) or placebo (n = 63) at 31 hospitals from February 2006 to September 2009. Corticosteroids but no other concomitant medications were allowed for control of disease activity. The primary measure of efficacy was sustained corticosteroid-free remission. RESULTS After 76 weeks of treatment, 30 patients treated with azathioprine (44.1%) and 23 given placebo (36.5%) were in sustained corticosteroid-free remission (difference of 7.6%; 95% confidence interval, -9.2 to 24.4%; P = .48). The rates of relapse (defined as Crohns Disease Activity Index score >175) and corticosteroid requirements were similar between groups. A post hoc analysis of relapse, defined as a Crohns Disease Activity Index score >220, showed lower relapse rates in the azathioprine group than in the placebo group (11.8% vs 30.2%; P = .01). Serious adverse events occurred in 14 patients in the azathioprine group (20.6%) and 7 in the placebo group (11.1%) (P = .16). A larger percentage of patients in the azathioprine group had adverse events that led to study drug discontinuation (20.6%) than in the placebo group (6.35%) (P = .02). CONCLUSIONS In a study of adults with Crohns disease, early azathioprine therapy was no more effective than placebo to achieve sustained corticosteroid-free remission but was more effective in preventing moderate to severe relapse in a post hoc analysis. EudraCT 2005-001186-34.

Addition of metronidazole to azathioprine for the prevention of postoperative recurrence of Crohn's disease: a randomized, double-blind, placebo-controlled trial.

Background:Endoscopic recurrence occurs in up to 80% of patients with Crohn’s disease 1 year after intestinal resection. Imidazole antibiotics, thiopurines, and particularly their combination have proven efficacy in preventing endoscopic recurrence. The aim of the study was to compare the efficacy of the addition of metronidazole (for 3 months after the surgical treatment) to azathioprine for the prevention of postsurgical endoscopic recurrence. Methods:A pilot study was made of 50 patients with Crohn’s disease undergoing intestinal resection with ileocolic anastomosis and treated with 2 to 2.5 mg/kg of azathioprine per day for 1 year. The patients were randomized to receive additional 15 to 20 mg/kg of metronidazole per day or placebo for the first 3 months (n = 25 per arm). Endoscopic assessment was performed 6 and 12 months after the surgical resection. The primary end point was the prevention of endoscopic recurrence as defined by a Rutgeerts score of <2 at 6 months. The initial sample size had an 80% statistical power in detecting an absolute risk reduction of ≥30%. Results:Endoscopic recurrence occurred in 28% and 44% of the patients at 6 months (P = 0.19) and in 36% and 56% (P = 0.15) at 12 months in the metronidazole and placebo groups, respectively. No statistically significant differences were found between the treatment groups regarding severe endoscopic recurrence (Rutgeerts score ≥ 3) at 6 and 12 months. Likewise, there were no differences in the rate of adverse events between the treatment groups. Conclusions:The addition of metronidazole to azathioprine did not significantly reduce the risk of endoscopic recurrence beyond azathioprine alone in this study but does not worsen its safety profile.

Evaluation of interferon-gamma release assays in the diagnosis of recent tuberculosis infection in health care workers.

Background Health care workers (HCWs) are a group at risk of latent tuberculosis infection (LTBI). The aims of this study were to determine IFN-γ response by QuantiFERON-TB GOLD In Tube (QFN-G-IT) and T-SPOT.TB in HCWs, comparing the results with tuberculin skin test (TST); and to analyze the capacity of IFN-γ tests to detect recent versus remote LTBI with a prolonged stimulation test (PST). Methodology/Principal Findings A total of 147 HCWs were enrolled; 23 of whom were BCG vaccinated. 95 HCWs (64.6%) had a previous positive TST and were not retested; and 52 HCWs had a previous negative TST or were tested for the first time. When we analysed individuals without previous positive TST, the number of positive results for T-SPOT.TB was 12/52 (23.1%); and for QFN-G-IT, 9/52 (17.3%). The global concordance (κ) between T-SPOT.TB and QFN-G-IT with TST was 0.754 and 0.929 respectively. Of individuals with previous positive TST, T-SPOT.TB and QFN-G-IT were negative in 51.6% (49/95) and 62.1% (59/95) respectively, decreasing the concordance to 0.321 and 0.288, respectively. In non-BCG vaccinated HCWs with previous positive TST a positive IFN-γ test was associated with degree of exposure and diameter of TST. PST was performed in 24 HCW with previous positive TST and negative IFN-γ tests. PST was developed in 3 cell cultures stimulated with medium alone, ESAT-6 and CFP-10, respectively. In the third and sixth day of incubation period, part of the supernatants were replaced with complete medium supplemented with (rIL)-2. On day 9, ELISPOT assay was performed. In 14 samples PST was not valid due to not having enough cells. In 8 cases, the response was negative, and in 2 cases positive, suggesting that these patients were infected with Mycobacterium tuberculosis in some point in the past. Conclusions Both IFN-γ tests showed a similar number of positive results, and concordance between the tests was excellent. None of the tests was affected by prior BCG vaccination. IFN-γ tests are a useful tool for detecting recent infection in HCW population.

Recomendaciones GETECCU-2005 para el uso de infliximab (Remicade®) en la enfermedad inflamatoria intestinal

Servicio de Aparato Digestivo. Hospital Germans Trias i Pujol. Badalona. Barcelona. Servicio de Aparato Digestivo. Hospital Mútua de Terrassa. Barcelona. España. Servicio de Aparato Digestivo. Hospital Clínico de Zaragoza. Zaragoza. España. Servicio de Aparato Digestivo. Hospital de Sagunto. Valencia. España. Servicio de Gastroenterología. Hospital Clínico. Barcelona. España. Servicio de Aparato Digestivo. Hospital Son Dureta. Palma de Mallorca. España.

Decision tree for early introduction of rescue therapy in active ulcerative colitis treated with steroids

Background: Corticosteroids are the treatment of choice for moderate‐to‐severe active ulcerative colitis (UC) but up to 30%–40% of patients fail to respond. It has been reported that early clinical‐biological parameters may identify those patients at high risk of colectomy. The aim was to identify predictors of rapid response to systemic steroids in moderate‐to‐severe attacks of UC. Methods: Consecutive patients treated with prednisone 1 mg/kg/day for moderate‐to‐severe attacks of UC were prospectively included. Clinical and biological parameters at 3 and 7 days after starting steroids were recorded. Response was defined as mild or inactive UC activity at day 7 (as assessed by the Montreal Classification of severity) together with no need for rescue therapies (cyclosporin, infliximab, or colectomy). A logistic regression analysis was performed to identify those independent predictors of response. In addition, a decision‐tree analysis was also performed. Results: Sixty‐eight percent of patients (64 out of 94) responded to steroids. In the univariate analysis the number of bowel movements, rectal bleeding, platelet count, and C‐reactive protein (CRP) levels at day 3 were associated with response at day 7, but only rectal bleeding was found to be an independent predictor in the logistic regression analysis. Conversely, the classification and regression tree (CART) model included these four variables. The decision‐tree model showed a higher sensitivity in predicting a rapid response to steroids than the logistic regression one. Conclusions: Rapid response to steroids in active UC attacks can be predicted after 3 days of treatment by simple clinical and biological parameters. A decision‐tree model for early introduction of rescue therapies is provided.

Thiopurine Therapy Reduces the Incidence of Colorectal Neoplasia in Patients with Ulcerative Colitis. Data from the ENEIDA Registry

BACKGROUND AND AIMS Patients with ulcerative colitis (UC) are at increased risk of developing colorectal cancer (CRC), but recent studies suggest a lower risk than previously reported. The aim was to evaluate the incidence of dysplasia, CRC and related risk factors in UC patients from a Spanish nationwide database. METHODS All UC patients were identified and retrospectively reviewed. Clinical-epidemiological data and the finding of dysplasia and/or CRC were collected. RESULTS A total of 831 UC patients were included. Twenty-six cases of CRC in 26 patients and 29 cases of high-grade dysplasia (HGD) in 24 patients were found, accounting for 55 diagnoses of advanced neoplasia (AN = CRC and/or HGD) in 45 patients (33% of them within the first 8 years after UC diagnosis). The cumulative risk of AN was 2, 5.3 and 14.7% at 10, 20 and 30 years, respectively. Concomitant primary sclerosing cholangitis (odds ratio [OR] 10.90; 95% confidence interval [CI] 3.75-31.76, p < 0.001), extensive UC (OR 2.10, 95% CI 1.01-4.38, p = 0.048), UC diagnosis at an older age (OR 2.23, 95% CI 1.03-4.83, p = 0.043) and appendectomy prior to UC diagnosis (OR 2.66, 95% CI 1.06-6.71, p = 0.038) were independent risk factors for AN. Use of thiopurines (OR 0.21, 95% CI 0.06-0.74, p = 0.015) and being in a surveillance colonoscopy programme (OR 0.33; 95% CI 0.16-0.67; p = 0.002) were independent protective factors for AN. CONCLUSIONS The risk of AN among UC patients is lower than previously reported but steadily increases from the time of UC diagnosis. The widespread use of thiopurines may have influenced this reduced incidence of UC-related neoplasias.

Tuberculosis en personal sanitario de un hospital general

BACKGROUND AND OBJECTIVE: Tuberculosis is an occupational disease in health care workers. The objective of our study was to review tuberculosis cases in health care professionals from a general hospital and to determine their incidence in relation to the general population. PATIENTS AND METHOD: This was a retrospective study of tuberculosis cases among health care workers in a university hospital from 1988 to 2002, evaluating the annual cumulative incidence. RESULTS: 21 tuberculosis cases were found in health care workers. Pulmonary disease was the most frequent type (62%) followed by pleural effusion (28%). The most affected professional category were medical residents (38%) with the emergency service (48%) being the work place with the highest risk. The cumulative incidence in our hospital was higher in relation to the general population although there was a variability between both populations. CONCLUSIONS: There is risk of tuberculosis transmission among health care workers, principally in the emergency service and the pathology and microbiological departments. A concerted effort is needed to maintain prevention measures in the work place where there is a high risk of infection.

Intestinal Intraepithelial Lymphocyte Cytometric Pattern Is More Accurate than Subepithelial Deposits of Anti-Tissue Transglutaminase IgA for the Diagnosis of Celiac Disease in Lymphocytic Enteritis

Background & Aims An increase in CD3+TCRγδ+ and a decrease in CD3− intraepithelial lymphocytes (IEL) is a characteristic flow cytometric pattern of celiac disease (CD) with atrophy. The aim was to evaluate the usefulness of both CD IEL cytometric pattern and anti-TG2 IgA subepithelial deposit analysis (CD IF pattern) for diagnosing lymphocytic enteritis due to CD. Methods Two-hundred and five patients (144 females) who underwent duodenal biopsy for clinical suspicion of CD and positive celiac genetics were prospectively included. Fifty had villous atrophy, 70 lymphocytic enteritis, and 85 normal histology. Eight patients with non-celiac atrophy and 15 with lymphocytic enteritis secondary to Helicobacter pylori acted as control group. Duodenal biopsies were obtained to assess both CD IEL flow cytometric (complete or incomplete) and IF patterns. Results Sensitivity of IF, and complete and incomplete cytometric patterns for CD diagnosis in patients with positive serology (Marsh 1+3) was 92%, 85 and 97% respectively, but only the complete cytometric pattern had 100% specificity. Twelve seropositive and 8 seronegative Marsh 1 patients had a CD diagnosis at inclusion or after gluten free-diet, respectively. CD cytometric pattern showed a better diagnostic performance than both IF pattern and serology for CD diagnosis in lymphocytic enteritis at baseline (95% vs 60% vs 60%, p = 0.039). Conclusions Analysis of the IEL flow cytometric pattern is a fast, accurate method for identifying CD in the initial diagnostic biopsy of patients presenting with lymphocytic enteritis, even in seronegative patients, and seems to be better than anti-TG2 intestinal deposits.

Legionella pneumophila in cooling towers: fluctuations in counts, determination of genetic variability by pulsed-field gel electrophoresis (PFGE), and persistence of PFGE patterns.

ABSTRACT The concentrations of Legionella pneumophila in cooling towers may vary considerably over short periods of time, producing significant fluctuations throughout the year. Despite genetic variability, in small geographical areas the same indistinguishable pulsed-field gel electrophoresis patterns may be shared among different cooling towers and persist over time.

Lymphocytic enteropathy, HLA-DQ2/DQ8 genotype and wheat-dependent symptoms: non-celiac wheat sensitivity or Marsh I celiac disease?

Lymphocytic Enteropathy, HLA-DQ2/DQ8 Genotype and Wheat-Dependent Symptoms: Non-Celiac Wheat Sensitivity or Marsh I Celiac Disease?