Gut bacterial DNA translocation is an independent risk factor of flare at short term in patients with crohn's disease

OBJECTIVES We aimed at evaluating bacterial DNA (bactDNA) presence in blood of Crohn's disease (CD) patients in remission as an independent risk factor of flare at 6 months. METHODS This is a prospective, multicenter study on CD patients with Crohn's disease activity index (CDAI)150 in the following 6 months. BactDNA in blood, the nucleotide-binding oligomerization domain containing 2 (NOD2) genotype, and serum cytokine levels were determined at baseline. RESULTS A total of 288 patients were included. BactDNA was detected in 98 patients (34.0%). A variant-NOD2 genotype was identified in 114 patients (39.6%). Forty patients (14%) relapsed during follow-up. Multivariate survival analysis identified bactDNA as an independent risk factor of flare (hazard ratio (HR) 8.75 (4.02-19.06) 95% confidence interval (CI)). Hospitalization, surgery, switch of treatment, initiation and escalation of anti-tumor necrosis factor (TNF) therapy, steroids initiation, and increased fecal calprotectin levels at 6 months were associated with bactDNA at baseline. A logistic regression analysis showed bactDNA as an independent and significant predictive factor of hospitalization (odds ratio (OR) 11.9 (3.4-42.3); P<0.001), steroids startup (OR 8.5 (2.7-27.1); P<0.001), and switch of treatment (OR 3.5 (1.6-7.7); P=0.002) at 6 months. No relationship was observed between bactDNA and mucosal lesions in patients with colonoscopy at admission. Serum pro-inflammatory cytokines were significantly increased in patients with bactDNA or a variant-NOD2 genotype. The combination of both factors induced decreased anti-TNF-α levels and a higher percentage of patients on intensified anti-TNF therapy. CONCLUSIONS BactDNA is an independent risk factor of relapse at 6 months in CD patients. BactDNA is also independently associated with an increased risk of hospitalization, switch of treatment, and steroids initiation

Consumo crónico de olmesartán como causa de enteropatía “sprue-like”

La diarrea es un efecto secundario habitual a la toma de fármacos, y en algunas ocasiones la enteropatía perdedora de proteínas tipo “sprue like” puede estar detrás de esta patología. El estudio de esta enfermedad puede suponer un desafío importante para el clínico, sobre todo en los casos que cursan con serología negativa para enfermedad celiaca.  La atrofia vellositaria duodenal secundaria a la ingesta de micofenolato-mofetil  y metotrexate es bien conocida y descrita desde hace tiempo, pero desde la inclusión en la posológica habitual de olmesartán como antihipertensivo de primera elección hemos objetivado un repunte importante de esta entidad. Debido al amplio uso de esta medicación, queremos poner de manifiesto esta enteropatía iatrogénica a través de dos casos clínicos ocurridos en nuestro hospital en 2014

Actual Anti-TNF Trough Levels Relate to Serum IL-10 in Drug-Responding Patients With Crohn's Disease

BACKGROUND Patients with Crohn's disease (CD) responding to anti-tumor necrosis factor (anti-TNF) show great variability in serum drug levels, even within the therapeutic range. We aimed at exploring the role of inflammatory, genetic, and bacterial variables in relation to anti-TNF through levels in CD patients. METHODS Consecutive CD patients receiving stable doses of infliximab or adalimumab were included. Clinical and analytical parameters were recorded. Cytokine response, bacterial DNA translocation, and several immune-related genes' genotypes were evaluated, along with serum through anti-TNF drug levels. A linear regression analysis controlled by weight and drug regimen was performed. RESULTS One hundred nineteen patients were initially considered. Five patients on infliximab and 2 on adalimumab showed antidrug antibodies in serum and were excluded. One hundred twelve patients were finally included (62 on infliximab, 50 on adalimumab). Fourteen patients on infliximab and 15 on adalimumab (22.6% vs 30%, P = 0.37) were receiving an intensified drug regimen. C-reactive protein (CRP), fecal calprotectin, Crohn's Disease Activity Index, leukocyte count, and albumin levels in plasma were not significantly associated with infliximab or adalimumab levels in the multivariate analysis. Serum interleukin-10 (IL-10) levels were directly related to infliximab (Beta = 0.097, P < 0.0001) and adalimumab levels (Beta = 0.069, P = 0.0241). The best multivariate regression model explaining the variability of serum infliximab and adalimumab levels included IL-10. Predicted drug levels by this model robustly fitted with actual drug levels (R2 = 0.841 for infliximab, R2 = 0.733 for adalimumab). CONCLUSION Serum IL-10 is significantly related to serum anti-TNF levels in CD patients, showing how the disposition of anti-TNF drugs is significantly influenced by the degree of immunological activation

Evolución del impacto emocional en pacientes con enfermedad inflamatoria intestinal temprana durante y después del bloqueo de COVID-19

Background: Patients with inflammatory bowel disease (IBD) are vulnerable to some psychological disorders. Here we describe the psychological impact of a COVID-19 pandemic lockdown in patients with IBD. Methods: This multicenter prospective cohort study included 145 patients recently diagnosed with IBD. Data on clinical and demographic characteristics, anxiety and depression scales, and IBD activity were collected in two telephone surveys, during and after the first COVID-19 lockdown in Spain. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated. Results: During lockdown, 33.1% and 24.1% scored high on the anxiety and depression scales, respectively. Independent factors related to anxiety (all values ORs; 95% CIs) during lockdown were female sex (2; 1.2–5.4) and IBD activity (4.3; 1.8–10.4). Factors related to depression were comorbidity (3.3; 1.1–9.8), IBD activity (6; 1.9–18.1), use of biologics (2.9; 1.1–7.6), and living alone or with one person (3.1; 1.2–8.2). After lockdown, anxiety and depression symptoms showed significant improvement, with 24.8% and 15.2% having high scores for anxiety and depression, respectively. Factors related to post-lockdown anxiety were female sex (2.5; 1.01–6.3), Crohn’s disease (3.3; 1.3–8.5), and active IBD (4.1; 1.2–13.7). Factors associated with depression were previous history of mood and/or anxiety disorders (6.3; 1.6–24.9), active IBD (7.5; 2.1–26.8), and steroid use (6.4; 1.4–29). Conclusions: Lockdown during the COVID-19 pandemic had a significant psychological impact in patients with IBD. Disease activity was related to the presence of anxiety and depression symptoms during and after lockdown.Antecedentes: Los pacientes con enfermedad inflamatoria intestinal (EII) son vulnerables a sufrir trastornos psicológicos. En este estudio describimos el impacto psicológico que ha supuesto el confinamiento durante el COVID-19 en pacientes con EII. Métodos: Este estudio de cohorte prospectivo multicéntrico se incluyeron 145 pacientes con diagnóstico de EII reciente. Los datos sobre las características clínicas y demográficas, las escalas de ansiedad y depresión y la actividad de la EII se recogieron en dos encuestas telefónicas, durante y después del primer confinamiento por COVID-19 en España. Se calcularon las odds ratios (OR) y los intervalos de confianza (IC) al 95%. Resultados: Durante el confinamiento, el 33,1% y el 24,1% puntuaron alto en las escalas de ansiedad y depresión respectivamente. Los factores independientes relacionados con la ansiedad (todos los valores OR; IC del 95%) durante el confinamiento fueron el sexo femenino (2; 1,2-5,4) y la actividad de la EII (4,3; 1,8-10,4). Los factores relacionados con la depresión fueron la comorbilidad (3,3; 1,1-9,8), la actividad de la EII (6; 1,9-18,1), el uso de biológicos (2,9; 1,1-7,6) y el vivir solo o con una persona (3,1; 1,2-8,2). Tras el confinamiento, los síntomas de ansiedad y depresión mostraron una mejoría significativa, ya que el 24,8% y el 15,2% tenían puntuaciones altas en ansiedad y depresión, respectivamente. Los factores relacionados con la ansiedad tras el confinamiento fueron el sexo femenino (2,5; 1,01-6,3), enfermedad de Crohn (3,3; 1,3-8,5) y EII activa (4,1; 1,2-13,7). Los factores asociados con la depresión fueron los antecedentes de trastornos del estado de ánimo y/o de ansiedad (6,3; 1,6-24,9), EII activa (7,5; 2,1-26,8), y el uso de esteroides (6,4; 1,4-29). Conclusiones: El confinamiento durante la pandemia de COVID-19 tuvo un impacto psicológico significativo en los pacientes con EII. La actividad de la enfermedad se relacionó con la presencia de síntomas de ansiedad y depresión durante y después del confinamiento.This work was supported by Instituto de Salud Carlos III (PI 18/01547) and the SVPD-Sociedad Valenciana de Patología Digestiva (Becas-2019)