Chronic melatonin treatment improves obesity by inducing uncoupling of skeletal muscle SERCA-SLN mediated by CaMKII/AMPK/PGC1α pathway and mitochondrial biogenesis in female and male Zücker diabetic fatty rats.

Melatonin acute treatment limits obesity of young Zücker diabetic fatty (ZDF) rats by non-shivering thermogenesis (NST). We recently showed melatonin chronically increases the oxidative status of vastus lateralis (VL) in both obese and lean adult male animals. The identification of VL skeletal muscle-based NST by uncoupling of sarcoendoplasmic reticulum Ca2+-ATPase (SERCA)- sarcolipin (SLN) prompted us to investigate whether melatonin is a SERCA-SLN calcium futile cycle uncoupling and mitochondrial biogenesis enhancer. Obese ZDF rats and lean littermates (ZL) of both sexes were subdivided into two subgroups: control (C) and 12 weeks orally melatonin treated (M) (10 mg/kg/day). Compared to the control groups, melatonin decreased the body weight gain and visceral fat in ZDF rats of both sexes. Melatonin treatment in both sex obese rats restored the VL muscle skin temperature and sensitized the thermogenic effect of acute cold exposure. Moreover, melatonin not only raised SLN protein levels in the VL of obese and lean rats of both sexes; also, the SERCA activity. Melatonin treatment increased the SERCA2 expression in obese and lean rats (both sexes), with no effects on SERCA1 expression. Melatonin increased the expression of thermogenic genes and proteins (PGC1-α, PPARγ, and NRF1). Furthermore, melatonin treatment enhanced the expression ratio of P-CaMKII/CaMKII and P-AMPK/AMPK. In addition, it rose mitochondrial biogenesis. These results provided the initial evidence that chronic oral melatonin treatment triggers the CaMKII/AMPK/PGC1α axis by upregulating SERCA2-SLN-mediated NST in ZDF diabetic rats of both sexes. This may further contribute to the body weight control and metabolic benefits of melatonin.

Correction to: Cost-effectiveness analysis of umeclidinium bromide/vilanterol 62.5/25 mcg versus tiotropium/olodaterol 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease: a Spanish National Healthcare System perspective.

Following publication of the original article [1], we have been notified of the below corrections to the 5th paragraph in the Discussion section.

Cost-effectiveness analysis of umeclidinium bromide/vilanterol 62.5/25 mcg versus tiotropium/olodaterol 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease: a Spanish National Healthcare System perspective.

BACKGROUND: A head-to-head study demonstrated the superiority of once-daily umeclidinium bromide/vilanterol (UMEC/VI) 62.5/25 mcg on trough forced expiratory volume in 1 s (FEV1) versus once-daily tiotropium/olodaterol (TIO/OLO) 5/5 mcg in symptomatic patients with chronic obstructive pulmonary disease (COPD). This analysis evaluated the cost effectiveness of UMEC/VI versus TIO/OLO from a Spanish National Healthcare System perspective, using data from this study and Spanish literature. METHODS: This analysis was conducted from the perspective of the Spanish National Healthcare System with a 3-year horizon as base case. A disease progression model using a linked risk equation approach was used to estimate disease progression and associated healthcare costs, and quality-adjusted life years (QALYs). The Evaluation of COPD Longitudinally to Identify Predictive Surrogate Endpoints (ECLIPSE) study was used to develop the statistical risk equations for clinical endpoints, and costs were calculated using a health state approach (by dyspnea severity). Utilities for QALY calculation were estimated using patient baseline characteristics within a regression fit to Spanish observational data. Treatment effect, expressed as change from baseline in FEV1 was obtained from the head-to-head study and used in the model (UMEC/VI minus TIO/OLO difference: + 52 mL [95% confidence interval: 28, 77]). Baseline patient characteristics were sourced from Spanish literature or the head-to-head study if unavailable. A scenario analysis using only the intent-to-treat (ITT) population from the head-to-head study, and sensitivity analyses (including probabilistic sensitivity analyses), were conducted. Direct healthcare costs (2017 Euro) were obtained from Spanish sources and costs and benefits were discounted at 3% per annum. RESULTS: UMEC/VI was associated with small improvements in QALYs (+ 0.029) over a 3-year time horizon, compared with TIO/OLO, alongside cost savings of €393/patient. The ITT scenario analysis and sensitivity analyses had similar results. All probabilistic simulations resulted in UMEC/VI being less costly and more effective than TIO/OLO. CONCLUSION: UMEC/VI dominated TIO/OLO (more effective and less expensive). These results may aid payers and decision-makers in Spain when making judgements on which long-acting muscarinic antagonist/long-acting ß2-agonist (LAMA/LABA) treatments can be considered cost effective in Spain.

Seguridad y tolerancia de la prueba de provocación bronquial con manitol inhalado en la EPOC leve- moderada / Safety and tolerance of the inhaled mannitol bronchial provocation test in mild-moderate COPD

INTRODUCCIÓN: la prueba de provocación bronquial con manitol inhalado (Osmohale(R)) es un test indirecto de medición de la hiperrespuesta bronquial. Se desconoce su utilidad clínica en pacientes con EPOC y su perfil de seguridad en pacientes con EPOC leve-moderado. MATERIAL Y MÉTODOS: estudio observacional prospectivo en el que participaron pacientes con EPOC leve-moderado, atendidos ambulatoriamente durante la fase de estabilidad de su enfermedad. Para todos los pacientes se recogieron los datos de función pulmonar y puntuación del cuestionario CAT. Se sometió a los pacientes a un test de provocación bronquial comercializado (Osmohale(R)). RESULTADOS: participaron en el estudio 72 pacientes con EPOC leve-moderado. En un 26% de los participantes se demostró la existencia de HRB. No hubo ningún abandono de la prueba por efectos adversos. La prueba fue bien tolerada por los pacientes, con la tos como efecto secundario más frecuentemente comunicado. La prueba fue segura, con una caída media del FEV1 del 10% y un tiempo medio de realización de la misma de 27 minutos. CONCLUSIONES: la prueba de provocación bronquial con manitol inhalado es un procedimiento seguro y bien tolerado en pacientes con EPOC leve-moderado

INTRODUCTION: bronchial provocation test with inhaled mannitol (Osmohale(R)) is and indirect approach to the measurement of bronchial hyperresponsiveness (BHR). Neither its clinical utility in COPD nor the secutiry profile en mild to moderate COPD patients is well kwon. MATERIAL AND METHODS: this was an observational prospective study enrrolling mild to moderate COPD patients in an outpatient setting during stability period. Data about lung fuction and CAT questionaire were collected from all patients. Aproved bronchial provocation test (Osmohale (R)) was performed. RESULTS: 72 mild to moderate COPD patients were included. BHR could be assesed in 26% of the sample. There was no drop out due to adverse events. The test was well tolerated, with cough being the most reported adverse event. The test was safe, with a mean FEV1 drop of 10% and a mean performance time of 27 minutes. CONCLUSIONS: bronchial provocation test with inhaled manitol is a safe and well tolerated procedure in mild to moderate COPD patients

Diagnostic performance of the measurement of nitric oxide in exhaled air in the diagnosis of COPD phenotypes.

INTRODUCTION: COPD is a highly heterogeneous disease that has a serious impact on affected populations. Patients share some of the features of bronchial asthma, often summarized under the term ACOS (asthma-COPD overlap syndrome). The objective of this study is to evaluate the utility of the measurement of nitric oxide in exhaled air (FENO50) in the diagnosis of COPD phenotypes. MATERIAL AND METHODS: The study comprised cross-sectional observation of patients receiving assistance during a respiratory outpatient visit. Patient data was collected on lung function, FENO, questionnaires scoring CAT®(COPD Assessment Test), and COPD clinical phenotype. RESULTS: 192 patients were studied: 103 with COPD; 16 healthy non-smokers; 30 healthy smokers; and 43 asthmatics. COPD patients were grouped by phenotype: 34 non exacerbators (33.0%); 22 ACOS (21.3%); 13 frequent exacerbators with emphysema (12.6%); and 34 frequent exacerbators with chronic bronchitis (33.0%). ACOS patients showed significantly higher FENO50 values compared to the others after adjustments for confounding factors. FENO50 demonstrated greater diagnostic accuracy than the bronchodilator test (BT) in the diagnosis of ACOS and COPD phenotypes (AUC 0.79 vs 0.74), with an optimal cut-off value of 19 ppb (sensitivity 0.68, specificity 0.75). CONCLUSIONS: Patients with COPD have different levels of FENO50 depending on the COPD phenotype. FENO50 measurement provides better diagnostic accuracy than BT, with an optimal cut-off value of 19 ppb.

Hallazgos radiológicos y correlación con la evolución clínica en pacientes ingresados con infección por gripe A (H1N1) / Radiological findings and correlation with the clinical development in patients who were hospitalized due to an H1N1 flu infection

OBJETIVO: analizar si distintas variables radiológicas y de presentación clínica de los pacientes hospitalizados por infección por Influenza H1N1 se asocian con la gravedad del cuadro y ayudan a predecir su pronóstico. MATERIAL Y MÉTODOS: estudio observacional retrospectivo, en el que se incluyeron pacientes hospitalizados por infección confirmada por Influenza AH1N1 durante las epidemias de los años 2009-2010 y 2010-2011. Para cada paciente se recogieron variables sociodemográficas, de presentación clínica y características radiológicas. Las variables continuas se presentan como media ± DE y las variables dicotómicas se presentan como frecuencias. Para la comparativa de variables continuas hemos utilizado la prueba de la T de Student y para las variables dicotómicas la χ2, considerando un nivel de significación estadísticas para p < 0,05. Se realizó un análisis multivariante para obtener las variables que predecían el resultado principal (ingreso en UCI y/o muerte durante el ingreso), mostrando los resultados de los intervalos de confianza al 95% para la OR. RESULTADOS: durante los períodos de estudio ingresaron en nuestro centro 98 pacientes con infección confirmada por Influenza AH1N1, con una edad media (± DE) de 42,45 (± 16,35), siendo un 53,1% de los mismos varones, de los que un 16,3% precisó ingreso en UCI, con una mortalidad durante el mismo del 6,1%. La comorbilidad más frecuente fue el asma bronquial (28,6%), seguida de la EPOC (11,2%) y con sólo un 3,1% del total con embarazo. En cuanto a las características radiológicas al ingreso, un 26,8% presentaba un estudio normal, un 38,8% un infiltrado bilateral y un 24,5% un infiltrado unilateral. Los pacientes que sufrieron el resultado principal se diferenciaban por un mayor porcentaje de varones, de embarazadas, infiltrados bilaterales al ingreso, peor SpO2 y un mayor porcentaje de pacientes con enfermedad complicada. El análisis multivariante demostró que la única variable que se asociaba de forma significativa a la evolución favorable fue la SpO2 (OR por cada -1% de SpO2 1,521, p < 0,001), con una tendencia a la significación estadística para la presencia de infiltrados unilaterales (OR 8,243, p = 0,134). CONCLUSIONES: la evolución desfavorable de la infección por Influenza AH1N1 que precisa ingreso hospitalario puede ser determinada por el grado de insuficiencia respiratoria presente al ingreso

OBJECTIVE: to examine whether different radiological and clini cal variables of patients hospitalized with H1N1 influenza in fection are associated with disease severity and help predicting prognosis. MATERIAL AND METHODS: a retrospective observational study, which included patients hospitalized for influenza AH1N1 confirmed infection during 2009 - 2010 and 2010 -2011 epidemics. For each patient, sociodemographic, clinical, and radiographic features were registered. Continuous variables are presented as mean ± SD, and dichotomous variables are presented as frequencies. For the comparison of continuous variables we used the T-Student test, and 2 for dichotomous variables, considering a statistical significance level of p < 0.05. Multivariate analysis was performed looking for variables that predicted the primary outcome (ICU admission and/or death during hospitalization), showing the results of the confidence intervals at 95% for the OR. RESULTS: during the study periods 98 patients with confirmed Influenza AH1N1 infection were admitted to our hospital, with a mean age (± SD) of 42,45 (± 16,35) years, 53,1% male, 16,3% requiring ICU admission and total hospital mortality of 6,1%. The most frequent comorbidity was bronchial asthma (28,6%) followed by COPD (11,2%), and pregnancy (3,1%). Regarding the radiological characteristics at admission, 26,8% had a normal study, 38,8% bilateral infiltrates and 24,5% unilateral infiltrates. Patients who met the primary outcome differed by a higher percentage of males, pregnant, bilateral infiltrates on admission, worse SpO2 and a higher percentage of complicated disease. Multivariate analysis showed that the only variable that was significantly associated with the outcome was the SpO2 (OR for every -1% SpO2 1,521, p < 0,001), with a trend toward statistical significance for unilateral infiltrates (OR 8,243, p = 0,134). CONCLUSIONS: influenza AH1N1 infection associated with ICU admission and/ or mortality during hospital admission may be determined by the degree of respiratory failure present at the ED

Prevalencia de comorbilidades en pacientes con EPOC / Prevalence of comorbidity in patients with COPD

Objetivo: Estudiar la prevalencia de comorbilidades en pacientes con EPOC estables, en Andalucía y Extremadura, y analizar su relación con el consumo de recursos sanitarios, grado de obstrucción al flujo aéreo y calidad de vida. Material y métodos: Estudio con dos fases, una primera prospectiva transversal multicéntrica concurrente de pacientes con EPOC estables, reclutados en seis hospitales de Andalucía y Extremadura. Se recogieron datos demográficos, funcionales respiratorios, índice de comorbilidad de Charlson, índice BODE, escala hospitalaria de ansiedad y depresión y cuestionario específico de calidad de vida (SGRQ). Se recogió la existencia de comorbilidad a través de la historia clínica del paciente y entrevista detallada. Una segunda fase prospectiva longitudinal de un año para estudiar el consumo de recursos sanitarios. Resultados: Se incluyeron 164 pacientes, el 83,5% varones, con edad media de 65,7 años, y FEV1 medio de 48,1%. Las prevalencias de comorbilidades mas frecuentes en nuestros pacientes fueron de cardiopatía isquémica 9,8%, insuficiencia cardiaca 6,1%, enfermedad vascular periférica 6,1%, enfermedad cerebrovascular 4,9%, diabetes mellitus 12,8%, neoplasias 10,9%, hepatopatía 10,4%, ansiedad 15,2% y depresión 14%. No se observó asociación significativa entre la prevalencia de comorbilidades o el índice de comorbilidad de Charlson y la necesidad de asistencia sanitaria, calidad de vida o función pulmonar. Conclusiones: la prevalencia de comorbilidades en pacientes con EPOC estable en Andalucía y Extremadura es elevada. La existencia de comorbilidad fue independiente del deterioro de la función pulmonar, de la necesidad de asistencia a urgencias o ingresos hospitalarios y del deterioro de la calidad de vida (AU)

Objective: To Study the prevalence of comorbidity in patients with stable COPD, in Andalusia and Extremadura and to analyze its relationship with the consumption of healthcare resources, degree of airway obstruction and quality of life. Material and methods: Two phase study: the first was a transversal, multi-center, prospective study, concurrent with stable COPD patients, recruited from six hospitals in the regions of Andalusia and Extremadura (Spain). Demographic data was collected, as well as respiratory function, Charlson comorbidity index, BODE index, hospital scale for anxiety and depression and specific quality of life questionnaire). The existence of comorbidity was assessed through patient clinical history and detailed interview. The second phase was a longitudinal, one year prospective study to review the use of healthcare resources. Results: 164 patients were included, of which 83.5% were males with an average age of 65.7 years, and an average FEV1 of 48.1%. The most frequent prevalence of comorbidity in our patients was ischemic heart disease 9.8%, cardiac insufficiency 6.1%, peripheral vascular disease 6.1%, cerebrovascular disease 4.9%, diabetes mellitus 12.8%, neoplasm 10.9%, hepatopathy 10.4%, anxiety 15.2% and depression 14%. No significant association was observed between the prevalence of comorbidities or Charlson comorbidity Index and the need for healthcare, the quality of living or pulmonary function. Conclusions: the prevalence of comorbidities in patients with stable COPD in the regions of Andalusia and Extremadura is high. The existence of comorbidity was independent on the deterioration of pulmonary function, the need for emergency healthcare or admittance to hospital and deterioration of living quality (AU)

Tratamiento antimicrobiano en las agudizaciones de la Enfermedad Pulmonar Obstructiva Crónica / No disponible

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El futuro de la EPOC: De la afectación pulmonar a la enfermedad cardiovascular / No disponible

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Mujer de 67 años con síndrome constitucional e infiltrados cavitados en lóbulos superiores / No disponible

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Pruebas funcionales respiratorias (II): test de esfuerzo cardiopulmonar / No disponible

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Características de las neumonías adquiridas en la comunidad que requieren ingreso en una planta de neumología / No disponible

Objetivo. Conocer las características clínicas de los pacientes ingresados en un Servicio de neumología de un Hospital de tercer nivel con el diagnóstico de Neumonía Adquirida en la Comunidad (NAC) en el año 2004. Metodología: Se estudiaron de forma retrospectiva los pacientes no inmunodeprimidos ingresados en nuestra planta con el diagnóstico de NAC según criterios clínicos y radiológicos. Resultados: Durante el año de estudio ingresaron 180 pacientes con NAC, de los cuales 69,4% eran varones y con edad media (DE) 66 (1.25) años. La mortalidad global fue del 7.22%. Dentro de las variables estudiadas, la gravedad inicial en la escala de Fine, edad > 74 años y presencia de Diabetes mellitas (DM), se asociaban a una mayor mortalidad (p<0.05). Dentro de las variables estudiadas, encontramos una estancia media mayor (p<0.05) en los casos de (Enfermedad Obstructiva Crónica) EPOC, DM, gravedad inicial alta, y en aquellos con necesidad de cambio de tratamiento, ingreso en la Unidad de Cuidados Intensivos (UCI) o realización de Tomografía axial computada (TAC). En el subgrupo dde pacientes con EPOC no encontramos diferencias en cuanto a mortalidad aunque ingresaban con una mayor gravedad inicial. Conclusiones: La comorbilidad y grado inicial de gravedad según escalas clínicas en pacientes con NAC aumenta la estancia media de hospitalización y en algunos caos aumenta también la mortalidad gravedad inicial, senilidad, DM). En camibo la EPOC no condiciona un aumento significativo de la mortalidad (AU)

Characteristics of community-acquired pneumonia requiring admission to a respiratory service

Objectives. To know the clinical characteristics of patients admitted to a Respiratory Service diagnosed as having Community- Acquired Pneumonia (CAP) in 2004. Methods. Non-immunodepressed patients admitted into the Service and diagnosed as having CAP were retrospectively studied according to clinical and radiological criteria. Results. During the year of the study, 180 patients with CAP were admitted to hospital. Among them, 69% were males and mean age was 66 years old 81.25 years). Total mortality was 7,22%. Among the variables studied, initial severity according to Fine´s prediction criteria, age> 74 years, and the presence of diabetes mellitus (DM) are related to a higher mortality (p<0.05). Among them, a longer mean stay (p<0.05) in the cases of Chronic Obstructive Pulmonary Disease (COPD), DM, and high initial severity were found. They were also found in those cases in which a treatment change, the admission to the Intensive Care Unit (ICU), or carrying out a computed axial tomography (CAT scanning) were required. In the subgroup of patients with COPD, we did not find any difference regarding mortality although patients showed a higher initial severity on admission. Conclusions. Comorbidity and initial severity level according to clinical scales in patients with CAP increase the mean stay in hospital and, in some cases, also increase mortality (initial severity, senility, DM). However, COPD does not determine a significant increase in mortality (AU)

Enferma con eosinofilia e infiltrados parcheados en lóbulos superiores pulmonares / Eosinophylia and patchy inflitrates in upper lung lobes

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[Bronchiectasis following colectomy in a patient with ulcerative colitis and factor V Leiden mutation]. / Bronquiectasias tras colectomía en paciente con colitis ulcerosa y mutación del factor V Leiden.

For some years it has been known that lung disease may be present in patients with inflammatory bowel disease (IBD). Diseases of the central airway, bronchi, and lung parenchyma are among the most common forms of lung involvement in IBD patients. Bronchiectasis is frequent and almost always appears after the onset of disease and in close association with inflammatory activity. However, reports of the appearance of bronchiectasis following colectomy for an exacerbation of IBD have been rare. We present the case of a 36-year-old man with severe ulcerative colitis who, following a total colectomy, developed bilateral bronchiectasis 12 months after surgery and for whom both preoperative and postoperative computed tomography scans were available.

Bronquiectasias tras colectomía en paciente con colitis ulcerosa y mutación del factor V Leiden / Bronchiectasis following colectomy in a patient with ulcerative colitis and factor V Leiden mutation

Desde hace años se sabe que los pacientes con enfermedad inflamatoria intestinal (EII) pueden presentar afectación pulmonar. De entre las formas de aparición, las más frecuentes incluyen la afectación de la vía aérea central, la afectación bronquial y la afectación del parénquima pulmonar. Las bronquiectasias son frecuentes en los pacientes con EII, casi siempre después del inicio de ésta y en muy íntima relación con la actividad inflamatoria de la EII. Sin embargo, los casos publicados sobre la aparición de bronquiectasias tras una colectomía por un brote de EII son excepcionales. Nosotros presentamos el caso de un varón de 36 años con una colitis ulcerosa grave que, tras una colectomía total, desarrolló un cuadro de bronquiectasias bilaterales a los 12 meses de la intervención, y en el que se dispone de tomografía axial computarizada antes y después de éstas

For some years it has been known that lung disease may be present in patients with inflammatory bowel disease (IBD). Diseases of the central airway, bronchi, and lung parenchyma are among the most common forms of lung involvement in IBD patients. Bronchiectasis is frequent and almost always appears after the onset of disease and in close association with inflammatory activity. However, reports of the appearance of bronchiectasis following colectomy for an exacerbation of IBD have been rare. We present the case of a 36-year-old man with severe ulcerative colitis who, following a total colectomy, developed bilateral bronchiectasis 12 months after surgery and for whom both preoperative and postoperative computed tomography scans were available

[Chronic thromboembolic pulmonary hypertension associated with endomyocardial fibrosis of the right ventricle]. / Hipertensión pulmonar tromboembólica crónica asociada a fribrosis endomiocárdica del ventrículo derecho.

Chronic thromboembolic pulmonary hypertension is a rare sequela to an acute untreated or recurrent pulmonary embolism. The mechanisms that underlie the failure to resolve the thrombus are still uncertain. As most patients are not diagnosed until a relatively late stage, little is known about the course of their illness. We report the case of a 51-year-old woman who had previously been diagnosed with and operated on for endomyocardial fibrosis of the right ventricle and who developed chronic thromboembolic pulmonary hypertension several years later.

Hipertensión pulmonar tromboembólica crónica asociada a fibrosis endomiocárdica del ventrículo derecho / Chronic thromboembolic pulmonary hypertension associated with endomyocardial fibrosis of the right ventricle

La hipertensión pulmonar tromboembólica crónica es una secuela infrecuente de la embolia pulmonar aguda no tratada o recurrente. Los mecanismos subyacentes para el fallo de resolución del trombo son todavía inciertos. La mayoría de los pacientes se diagnostican en un estadio tardío de la enfermedad, por lo que su historia natural no es completamente conocida. Presentamos el caso de una paciente de 51 años diagnosticada e intervenida de fibrosis endomiocárdica del ventrículo derecho que, tras varios años de evolución, desarrolló hipertensión pulmonar tromboembólica crónica (AU)