Performance of Screening Strategies for Latent Tuberculosis Infection in Patients with Inflammatory Bowel Disease: Results from the ENEIDA Registry of GETECCU

Inflammatory bowel disease; Interferon gamma release assays; Latent tuberculosis infectionEnfermedad inflamatoria intestinal; Ensayos de liberación de interferón gamma; Infección tuberculosa latenteMalaltia inflamatòria intestinal; Assajos d'alliberament gamma d'interferó; Infecció tuberculosa latentAims: Patients receiving antitumor necrosis factor (anti-TNF) therapy are at risk of developing tuberculosis (TB), usually due to the reactivation of a latent TB infection (LTBI). LTBI screening and treatment decreases the risk of TB. This study evaluated the diagnostic performance of different LTBI screening strategies in patients with inflammatory bowel disease (IBD). Methods: Patients in the Spanish ENEIDA registry with IBD screened for LTBI between January 2003 and January 2018 were included. The diagnostic yield of different strategies (dual screening with tuberculin skin test [TST] and interferon-ץ-release assay [IGRA], two-step TST, and early screening performed at least 12 months before starting biological treatment) was analyzed. Results: Out of 7594 screened patients, 1445 (19%; 95% CI 18−20%) had LTBI. Immunomodulator (IMM) treatment at screening decreased the probability of detecting LTBI (20% vs. 17%, p = 0.001). Regarding screening strategies, LTBI was more frequently diagnosed by dual screening than by a single screening strategy (IGRA, OR 0.60; 95% CI 0.50−0.73, p < 0.001; TST, OR 0.76; 95% CI 0.66−0.88, p < 0.001). Two-step TST increased the diagnostic yield of a single TST by 24%. More cases of LTBI were diagnosed by early screening than by routine screening before starting anti-TNF agents (21% [95% CI 20−22%] vs. 14% [95% CI 13−16%], p < 0.001). The highest diagnostic performance for LTBI (29%) was obtained by combining early and TST/IGRA dual screening strategies in patients without IMM. Conclusions: Both early screening and TST/IGRA dual screening strategies significantly increased diagnostic performance for LTBI in patients with IBD, with optimal performance achieved when they are used together in the absence of IMM

Case-control study for colorectal cancer genetic susceptibility in EPICOLON: previously identified variants and mucins

<p>Abstract</p> <p>Background</p> <p>Colorectal cancer (CRC) is the second leading cause of cancer death in developed countries. Familial aggregation in CRC is also important outside syndromic forms and, in this case, a polygenic model with several common low-penetrance alleles contributing to CRC genetic predisposition could be hypothesized. Mucins and GALNTs (N-acetylgalactosaminyltransferase) are interesting candidates for CRC genetic susceptibility and have not been previously evaluated. We present results for ten genetic variants linked to CRC risk in previous studies (previously identified category) and 18 selected variants from the mucin gene family in a case-control association study from the Spanish EPICOLON consortium.</p> <p>Methods</p> <p>CRC cases and matched controls were from EPICOLON, a prospective, multicenter, nationwide Spanish initiative, comprised of two independent stages. Stage 1 corresponded to 515 CRC cases and 515 controls, whereas stage 2 consisted of 901 CRC cases and 909 controls. Also, an independent cohort of 549 CRC cases and 599 controls outside EPICOLON was available for additional replication. Genotyping was performed for ten previously identified SNPs in <it>ADH1C</it>, <it>APC</it>, <it>CCDN1</it>, <it>IL6</it>, <it>IL8</it>, <it>IRS1</it>, <it>MTHFR</it>, <it>PPARG</it>, <it>VDR </it>and <it>ARL11</it>, and 18 selected variants in the mucin gene family.</p> <p>Results</p> <p>None of the 28 SNPs analyzed in our study was found to be associated with CRC risk. Although four SNPs were significant with a <it>P</it>-value < 0.05 in EPICOLON stage 1 [rs698 in <it>ADH1C </it>(OR = 1.63, 95% CI = 1.06-2.50, <it>P</it>-value = 0.02, recessive), rs1800795 in <it>IL6 </it>(OR = 1.62, 95% CI = 1.10-2.37, <it>P</it>-value = 0.01, recessive), rs3803185 in <it>ARL11 </it>(OR = 1.58, 95% CI = 1.17-2.15, <it>P</it>-value = 0.007, codominant), and rs2102302 in <it>GALNTL2 </it>(OR = 1.20, 95% CI = 1.00-1.44, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles], only rs3803185 achieved statistical significance in EPICOLON stage 2 (OR = 1.34, 95% CI = 1.06-1.69, <it>P</it>-value = 0.01, recessive). In the joint analysis for both stages, results were only significant for rs3803185 (OR = 1.12, 95% CI = 1.00-1.25, <it>P</it>-value = 0.04, log-additive 0, 1, 2 alleles) and borderline significant for rs698 and rs2102302. The rs3803185 variant was not significantly associated with CRC risk in an external cohort (MCC-Spain), but it still showed some borderline significance in the pooled analysis of both cohorts (OR = 1.08, 95% CI = 0.98-1.18, <it>P</it>-value = 0.09, log-additive 0, 1, 2 alleles).</p> <p>Conclusions</p> <p><it>ARL11</it>, <it>ADH1C</it>, <it>GALNTL2 </it>and <it>IL6 </it>genetic variants may have an effect on CRC risk. Further validation and meta-analyses should be undertaken in larger CRC studies.</p

Refractory iron-deficiency anemia and gluten intolerance: Response to gluten-free diet Anemia ferropénica refractaria e intolerancia al gluten: respuesta a la dieta sin gluten

Introduction: refractory iron-deficiency anemia has a multifactorial origin related to various gastrointestinal conditions, with celiac disease plus malabsorption and IBD together with isolated gluten intolerance being most common. Objectives: to determine the prevalence of serum, genetic, and histological markers for gluten intolerance, and to analyze the response to gluten withdrawal from the diet in these patients. Methods: a number of patients with refractory anemia were prospectively and consecutively enrolled. A protocol to measure serum (TGt-2), genetic (HLA-DQ2/DQ8), and histological markers for celiac disease was applied. All followed a gluten-free diet for a median 3.6 years. Sustained remission of anemia during follow-up was interpreted as positive response. Results: ninety-eight patients (84% females) with a mean age of 54 years were studied. Anti-TGt2 antibodies were positive in 5% of cases. A total of 67 cases (68%) were haplotype HLA-DQ2 or -DQ8 (+). We found villous atrophy (Marsh III) in 13% of patients, and an inflammatory pattern (Marsh I or II) in 13%. All remaining 72 patients (74%) had no histological duodenal changes. Age, anemia duration, number of transfusions, number of parenteral iron doses, and time on a gluten-free diet were all compared according to the presence or absence of villous atrophy and HLA-DQ2/8 positivity, and no significant differences were found for any of the analyzed variables. Response was positive in 92% of subjects. Conclusions: celiac disease with villous atrophy is rarely a cause of refractory anemia. Gluten intolerance with no histological lesions is seen in almost 75% of patients, and therefore plays a relevant role in its development.<br>Introducción: la anemia ferropénica refractaria presenta un origen multifactorial, relacionado con diversas enfermedades digestivas, siendo las más frecuentes la enfermedad celiaca con malabsorción y la EII junto con la intolerancia al gluten aislada. Objetivos: determinar la prevalencia de marcadores serológicos, genéticos e histológicos de intolerancia al gluten y analizar la respuesta a la retirada del gluten de la dieta en estos pacientes. Métodos: se incluyeron de forma prospectiva y consecutiva una serie de pacientes con anemia refractaria. Se les aplicó un protocolo consistente en determinación marcadores serológicos (TGt-2), genéticos (HLA-DQ2/DQ8) e histológicos de enfermedad celíaca. Todos siguieron una dieta sin gluten durante una mediana de 3,6 años. Se interpretó como respuesta positiva la desaparición mantenida de la anemia durante el seguimiento. Resultados: se estudiaron 98 pacientes (84% mujeres) con una edad media de 54 años. Los ac. anti-TGt2 fueron positivos en el 5% de los casos. Un total de 67 casos (68%) presentaban el haplotipo HLA-DQ2 o DQ8 (+). Encontramos atrofia vellositaria (Marsh III) en el 13% de los casos y patrón inflamatorio (Marsh I o II) en el 13%. Los 72 casos restantes (74%) no presentaban alteraciones histológicas duodenales. Se compararon la edad, el tiempo de evolución de la anemia, número de transfusiones, número de dosis de hierro parenteral y tiempo en dieta sin gluten, en función de la presencia o no de atrofia vellositaria y de la positividad para el HLA-DQ2/8, sin encontrar diferencias significativas en ninguna de las variables analizadas. La respuesta fue positiva en el 92% de los casos. Conclusiones: la enfermedad celiaca con atrofia vellositaria es causa poco frecuente de anemia refractaria. Las formas de intolerancia al gluten sin lesión histológica asociada, representan cerca del 75% de los casos y desempeñan, por lo tanto, un papel importante en su aparición