Mitochondrial Stress Links Environmental Triggers with Pro-Inflammatory Signaling in Crohn's Disease.

Inflammatory Bowel Diseases (IBD) are a group of chronic, inflammatory disorders of the gut. The incidence and activity of IBD are determined by both genetic and environmental factors. Among these factors, polymorphisms in genes related to autophagy and the consumption of non-steroidal anti-inflammatory drugs (NSAIDs) have been consistently associated with IBD. We show that NSAIDs induce mitochondrial stress and mitophagy in intestinal epithelial cells. In an altered mitophagy context simulating that observed in IBD patients, NSAID-induced mitochondrial stress leads to the release of mitochondrial components, which act as Danger Associated Molecular Patterns with pro-inflammatory potential. Furthermore, colonic organoids from Crohn's disease patients and healthy donors show activation of the mitochondrial Unfolded Protein Response (UPRmt) upon treatment with ibuprofen. Finally, colon biopsies from Crohn's disease patients in remission or with low-to-moderate activity also show expression of genes involved in UPRmt, while patients with severe activity show no increase compared to healthy donors. Our results suggest the involvement of mitochondria in the mechanisms triggering inflammation in IBD after NSAID use. Moreover, our results highlight the clinical relevance of mitochondrial stress and activation of the UPRmt pathway in the pathophysiology of Crohn's disease.

Epidemiología de la enfermedad inflamatoria intestinal en Málaga: incidencia y seguimiento a la cohorte diagnosticada en 2007-2008 / Epidemiology of inflammatory bowel disease in Málaga: incidence rate and follow-up of a cohort diagnosed between 2007-2008

Introducción y objetivos: la incidencia de enfermedad inflamatoria intestinal (EII) en España ha sido clásicamente inferior a la incidencia de los países del norte de Europa. Estudios epidemiológicos recientes muestran que la brecha está disminuyendo. Este estudio estima la incidencia de EII en Málaga, una ciudad en el sur de España, y relaciona dichas cifras con los datos de nuestro entorno. Material y métodos: este es un estudio prospectivo que fue diseñado para recoger los nuevos casos diagnosticados durante los años 2007-2008, y para realizar el seguimiento de estos pacientes. La incidencia se expresa como el número de pacientes por cada 100.000 habitantes por año. La distribución de la población del estudio colaborativo europeo se utilizó para normalizar la tasa de incidencia. Resultados: la incidencia bruta de la EII en Málaga es 9/105, la incidencia estandarizada es de 12,3/105 (9,7-15,6). Conclusiones: estos datos son similares a los de nuestro medio ambiente, aunque se observa una mayor incidencia para la enfermedad de Crohn (EC) que para la colitis ulcerosa (CU). Las características clínicas y evolución de nuestro paciente no presentan grandes diferencias con respecto a lo descrito en otras poblaciones (AU)

Background and objectives: The incidence of inflammatory bowel disease (IBD) in Spain has been traditionally lower than in Northern European countries. Recent epidemiological studies have found that these differences are diminishing. This study estimates the incidence of IBD in Málaga (Spain), a city in Southern Spain and relates its results to those found in our neighboring countries. Material and methods: This was a prospective study designed to collect new cases diagnosed during the period from 2007-2008 and follow up these patients. Incidence is expressed as number of patients per 100,000 population per year. The population distribution found in the European Collaborative Study was used to standardize incidence rates. Results: The gross incidence rate of IBD in Málaga is 9/105, the standardized incidence rate is 12.3/105 (9.7-15.6). Conclusions: These data are similar to those found in our surroundings, although a higher incidence rate for Crohn's disease (CD) as compared to ulcerative colitis (UC) was found. The clinical characteristics and outcomes of our patients do not differ significantly from those described for other populations (AU)

Epidemiology of inflammatory bowel disease in Málaga: incidence rate and follow-up of a cohort diagnosed between 2007-2008.

BACKGROUND AND OBJECTIVES: The incidence of inflammatory bowel disease (IBD) in Spain has been traditionally lower than in Northern European countries. Recent epidemiological studies have found that these differences are diminishing. This study estimates the incidence of IBD in Málaga (Spain), a city in Southern Spain and relates its results to those found in our neighboring countries. MATERIAL AND METHODS: This was a prospective study designed to collect new cases diagnosed during the period from 2007-2008 and follow up these patients. Incidence is expressed as number of patients per 100,000 population per year. The population distribution found in the European Collaborative Study was used to standardize incidence rates. RESULTS: The gross incidence rate of IBD in Málaga is 9/105, the standardized incidence rate is 12.3/105 (9.7-15.6). CONCLUSIONS: These data are similar to those found in our surroundings, although a higher incidence rate for Crohn's disease (CD) as compared to ulcerative colitis (UC) was found. The clinical characteristics and outcomes of our patients do not differ significantly from those described for other populations.

Prognosis of Patients with Ulcerative Colitis in Sustained Remission After Thiopurines Withdrawal.

BACKGROUND: The ideal length of treatment with thiopurines in patients with ulcerative colitis (UC) in sustained remission remains unknown. It is widely accepted that the drug withdrawal is associated with a worse outcome. The aim of this study was to analyze the outcome after this withdrawal and to identify predictors of relapse. METHODS: A multicenter and retrospective study was designed. A total of 102 patients with UC who discontinued thiopurines in a situation of sustained remission were included. All the patients were followed up until last revision or until relapse (understood as the occurrence of signs and symptoms of UC that required a rescue treatment). RESULTS: After thiopurines withdrawal, overall relapse was recorded in 32.35% of the patients: 18.88% in the first year, 36.48% in the third, and 43.04% in the fifth year after withdrawal. On multivariate analysis, predictors of relapse were the time from diagnosis of UC until the starting of thiopurines (hazard ratio [HR], 1.01; 95% confidence interval [CI], 1.01-1.02; P = 0.039), the number of relapses before the withdrawal (HR, 1.3; 95% CI, 1.01-1.66; P = 0.029), pancolitis (HR, 5.01; 95% CI, 1.95-26.43; P = 0.028), the duration of treatment with thiopurines (HR, 0.15; 95% CI, 0.03-0.66; P = 0.013) and the situation of biological remission at withdrawal (HR, 0.004; 95% CI, 0.0001-0.14; P = 0.002). CONCLUSIONS: The withdrawal of thiopurines in patients with UC, although in sustained remission, is related to a high relapse rate. Clinical variables such as the extent of the disease, the duration of treatment or time from diagnosis to the start of thiopurines should be considered before stopping these drugs.