Differential effects of FXR or TGR5 activation in cholangiocarcinoma progression.

BACKGROUND AND AIMS: Cholangiocarcinoma (CCA) is an aggressive tumor type affecting cholangiocytes. CCAs frequently arise under certain cholestatic liver conditions. Intrahepatic accumulation of bile acids may facilitate cocarcinogenic effects by triggering an inflammatory response and cholangiocyte proliferation. Here, the role of bile acid receptors FXR and TGR5 in CCA progression was evaluated. METHODS: FXR and TGR5 expression was determined in human CCA tissues and cell lines. An orthotopic model of CCA was established in immunodeficient mice and tumor volume was monitored by magnetic resonance imaging under chronic administration of the specific FXR or TGR5 agonists, obeticholic acid (OCA) or INT-777 (0,03% in chow; Intercept Pharmaceuticals), respectively. Functional effects of FXR or TGR5 activation were evaluated on CCA cells in vitro. RESULTS: FXR was downregulated whereas TGR5 was upregulated in human CCA tissues compared to surrounding normal liver tissue. FXR expression correlated with tumor differentiation and TGR5 correlated with perineural invasion. TGR5 expression was higher in perihilar than in intrahepatic CCAs. In vitro, FXR was downregulated and TGR5 was upregulated in human CCA cells compared to normal human cholangiocytes. OCA halted CCA growth in vivo, whereas INT-777 showed no effect. In vitro, OCA inhibited CCA cell proliferation and migration which was associated with decreased mitochondrial energy metabolism. INT-777, by contrast, stimulated CCA cell proliferation and migration, linked to increased mitochondrial energy metabolism. CONCLUSION: Activation of FXR inhibits, whereas TGR5 activation may promote, CCA progression by regulating proliferation, migration and mitochondrial energy metabolism. Modulation of FXR or TGR5 activities may represent potential therapeutic strategies for CCA.

Prevalencia del síndrome del burnout y factores asociados a dicho síndrome en los profesionales sanitarios de Atención Primaria / Prevalence of burnout syndrome and its associated factors in Primary Care staff

Introducción: El agotamiento profesional es una afección emergente entre los profesionales sanitarios. El objetivo del estudio es determinar la prevalencia del síndrome de burnout entre los trabajadores de Atención Primaria, determinar las diferencias de prevalencia entre médicos, pediatras, ATS-DUE, administrativos y trabajadores sociales, y evaluar las variables asociadas. Materiales y métodos: Estudio descriptivo transversal en 54 centros de salud de Navarra desde septiembre a diciembre de 2010, con 178 profesionales pertenecientes a los 5 grupos de estudio. Cuestionario anónimo autoadministrado que incluye: el Maslach Burnout Inventory y una encuesta sobre variables sociodemográficas y laborales. Resultados: La prevalencia de burnout en los profesionales de Atención Primaria fue del 39,3%. Presentaron mayores niveles los administrativos y los médicos de familia, con una OR frente a ATS-DUE de 4,58 y 5,37, respectivamente, en la dimensión de cansancio emocional, 4,98 y 2,87 en despersonalización, y 8,37 para los administrativos en realización personal. Encontramos asociación del burnout con los siguientes factores: ser varón (para las dimensiones de cansancio emocional y despersonalización, cifras de 25,5 y 31,9%, respectivamente), trabajar en un área urbana (para cansancio emocional y despersonalización, 20 y 27,8%, respectivamente), consumo de psicofármacos (para cansancio emocional, 30%), tamaño del cupo (para despersonalización, con una media de 1.565 pacientes), y presión asistencial (para cansancio emocional y despersonalización, medias de 170,35 y 153,54 pacientes/semana, respectivamente). Conclusiones: Aproximadamente un tercio de los profesionales de Atención Primaria presentaron niveles altos de burnout, asociado principalmente con el área de trabajo, el tamaño del cupo y el grupo profesional, con mayor prevalencia en administrativos y médicos de familia (AU)

Introduction: Burnout syndrome is an emerging disease among health professionals. The aim of this study is to determine the prevalence of occupational burnout among Primary Care staff, as well as to determine the differences in prevalence between family doctors, paediatricians, nurses, administrative-officers, and social-workers, and to evaluate the different related factors. Materials and methods: A cross-sectional, descriptive study was conducted on 178 professionals from 5 different occupational groups in 54 Primary Care centres in Navarre from September to December 2010. An anonymous, self-administered questionnaire that included: the Maslach Burnout Inventory and a questionnaire on socio-demographic and work-related factors. Results: Burnout was detected in 39.3% of staff. Those with higher levels are administrative-officers and family doctors, with an OR compared to nurses of 4.58 and 5.37, respectively in the dimension of emotional exhaustion, 4.98 and 2.87 in depersonalization, and 8.37 for administrative-officers in personal accomplishment. An association was found between burnout and the following factors: to be a male (for the dimensions of emotional exhaustion and depersonalization, 25.5 and 31.9%, respectively), to be employed in an urban area (for emotional exhaustion and depersonalization, 20 and 27.8%, respectively), use of psychiatric medication (for emotional exhaustion, 30%), size of patient-quota (for depersonalization, with an average of 1,565 patients), and welfare pressure (for emotional exhaustion and depersonalization, averages of 170.35 and 153.54 patients/week, respectively). Conclusions: About one-third of Primary Care professionals have a high level of burnout, which is mainly associated with the working area, the size of the quota, and professional group, with higher prevalence in administrative-officers and family doctors (AU)

[Prevalence of burnout syndrome and its associated factors in Primary Care staff]. / Prevalencia del síndrome del burnout y factores asociados a dicho síndrome en los profesionales sanitarios de Atención Primaria.

INTRODUCTION: Burnout syndrome is an emerging disease among health professionals. The aim of this study is to determine the prevalence of occupational burnout among Primary Care staff, as well as to determine the differences in prevalence between family doctors, paediatricians, nurses, administrative-officers, and social-workers, and to evaluate the different related factors. MATERIALS AND METHODS: A cross-sectional, descriptive study was conducted on 178 professionals from 5 different occupational groups in 54 Primary Care centres in Navarre from September to December 2010. An anonymous, self-administered questionnaire that included: the Maslach Burnout Inventory and a questionnaire on socio-demographic and work-related factors. RESULTS: Burnout was detected in 39.3% of staff. Those with higher levels are administrative-officers and family doctors, with an OR compared to nurses of 4.58 and 5.37, respectively in the dimension of emotional exhaustion, 4.98 and 2.87 in depersonalization, and 8.37 for administrative-officers in personal accomplishment. An association was found between burnout and the following factors: to be a male (for the dimensions of emotional exhaustion and depersonalization, 25.5 and 31.9%, respectively), to be employed in an urban area (for emotional exhaustion and depersonalization, 20 and 27.8%, respectively), use of psychiatric medication (for emotional exhaustion, 30%), size of patient-quota (for depersonalization, with an average of 1,565 patients), and welfare pressure (for emotional exhaustion and depersonalization, averages of 170.35 and 153.54 patients/week, respectively). CONCLUSIONS: About one-third of Primary Care professionals have a high level of burnout, which is mainly associated with the working area, the size of the quota, and professional group, with higher prevalence in administrative-officers and family doctors.

Role of the new azoles in the treatment of fungal osteoarticular infections.

OBJECTIVES: To analyze the usefulness of the new azoles for the treatment of fungal osteoarticular infections, and to report three cases of fungal knee arthritis treated with fluconazole in our unit. METHODS: The medical literature was reviewed for all cases of osteoarticular infection caused by fungi and treated with fluconazole or itraconazole registered in the MedLine Silver Platter database from 1972 to 1997. RESULTS: The total number of patients included in this review was 56; 19 were treated with fluconazole and 37 with itraconazole. The most frequent causative agents implicated were fungi of the genuses Candida and Aspergillus. There were eight therapeutic failures, and there were no statistically different findings among the patients in terms of their health status. Adverse effects were unusual. CONCLUSIONS: Controlled studies are necessary to establish the true role of the new azole drugs in the treatment of fungal osteoarticular infections, but they seem to be a promising therapeutic option.