Expresión de los factores de transcripción sensibles a la hipoxia, de la respuesta inflamatoria y del estrés oxidativo a nivel muscular en tres modelos clínicos de hipoxemia / Expression of transcription factors sensitive to hypoxia, of the inflammatory response and oxidative stress to muscle level in three clinical models of hypoxemia

OBJETIVO: Comparar la expresión de marcadores de respuesta a hipoxia, inflamatorios y de estrés oxidativo en biopsia muscular de grupos de pacientes con hipoxia crónica continua, crónica intermitente y ambas combinadas. Evaluar el estado de la musculatura periférica y compararla entre grupos. METODOLOGÍA: Incluimos varones mayores de 18 años, diagnosticados de EPOC, Apnea Obstructiva del Sueño (AOS) o AOS-EPOC, a los que se realizó biopsia muscular del cuádriceps. Los biomarcadores seleccionados para su estudio en músculo fueron factores de transcripción asociados a la hipoxia, como el factor inducible por hipoxia HIF-1, HIF-2 y el factor nuclear. También biomarcadores inflamatorios como factor de necrosis tumoral-α, interkeukina 6 y 8, factor de crecimiento endotelial vascular y proteína de adhesión celular vascular 1 (VCAM-1), así como biomarcadores de estrés oxidativo, como superóxidodismutasa (SOD) y actividad catalasa. Además se realizó evaluación de la función muscular en los tres grupos. RESULTADOS: Reclutamos 29 sujetos: 4 con EPOC, 12 con AOS y 13 EPOC-AOS. En el músculo, encontramos diferencias entre los grupos de estudio en VCAM-1 (casos de EPOC que expresan 2,1 veces más que AOS y 1,16 veces más que EPOC-AOS) y SOD (EPOC-AOS que expresan 3,48 veces más que EPOC, y AOS 3,02 veces más que EPOC). CONCLUSIONES: La expresión de biomarcadores estudiados es de intensidad similar en los tres grupos de pacientes referidos, con pocas excepciones.La fuerza muscular periférica y el porcentaje de masa libre de grasa es significativamente menor en los pacientes con EPOC que en los pacientes con AOS. (AU)

OBJECTIVE: Compare the expression of markers of response to hypoxia, inflammation and oxidative stress in biopsy muscle of groups of patients with continuous chronic hypoxia, intermittent chronic and both combined. Evaluate the state of the peripheral musculature and compare it between groups. METHODOLOGY: We included males older than 18 years, diagnosed of COPD, Obstructive Sleep Apnea (OSA) or OSA-COPD, to quadriceps muscle biopsy was performed. biomarkers selected for study in muscle were factors of transcription associated with hypoxia, such as the factor inducible by hypoxia HIF-1, HIF-2 and nuclear factor. Also biomarkers Inflammatory agents such as tumor necrosis factor-α, interkeukin 6, and 8, vascular endothelial growth factor and adhesion protein vascular cell 1 (VCAM-1), as well as stress biomarkers oxidative, such as superoxide dismutase (SOD) and catalase activity. In addition, evaluation of muscle function was performed in the three groups. RESULTS: We recruited 29 subjects: 4 with COPD, 12 with OSA and 13 COPD-OSA. In muscle, we found differences between the study groups in VCAM-1 (COPD cases expressing 2.1-fold more than OSA and 1.16 times more than COPD-OSA) and SOD (COPD-OSA than express 3.48 times more than COPD, and OSA 3.02 times more than COPD). CONCLUSIONS: The expression of studied biomarkers is of similar intensity in the three groups of referred patients, with few exceptions. Peripheral muscle strength and percentage of fat-free mass is significantly lower in patients with COPD than in patients with OSA. (AU)

Recursos y propuestas de mejora en el manejo de la Apnea Obstructiva del Sueño en Andalucía / Resources and proposals for improvement in the management of obstructive sleep apnea in Andalusia

Título abreviado: Se exponen los recursos asistenciales del Sistema Sanitario Público de Andalucía relacionados con el diagnóstico, tratamiento y seguimiento de los pacientes con apnea obstructiva del sueño. Igualmente se describen propuestas para una optimización en el manejo de esta entidad enfatizando la necesidad de recursos y colaboración entre diferentes niveles asistenciales. Objetivo: Determinar en el Sistema Sanitario Público de Andalucía (SSPA) los recursos actuales en la apnea obstructiva del sueño (AOS) e identificar propuestas de mejora. Método: Estudio transversal, basado en encuestas realizadas en 49 hospitales del SSPA. Se registraron variables relacionadas al diagnóstico, tratamiento y seguimiento de la AOS, distinguiendo entre centros que realizaban polisomnografía y los que no. Incluimos un apartado sobre propuestas de mejora. Resultados: Un 97% de los centros realizan poligrafía y un 29% polisomnografía, y sólo el 39,5% disponen de consulta específica. La demora diagnóstica para la poligrafía es de 169 ± 163,4 días y para la polisomnografía de 173 ± 152,5 días. Se realizan un total de 1.113 ± 1.004,6 pruebas por 100.000 habitantes y año, de ellas 235 ± 166,2 son poligrafías diagnósticas. La presión eficaz se titula en un 49% con auto-CPAP y el control terapéutico lo realiza frecuentemente la empresa suministradora (77%). Entre las propuestas de mejora, destacan la falta de un protocolo de derivación y coordinación entre diferentes niveles asistenciales (90% de los encuestados), y la demora diagnóstica, atribuible en un 63% de los casos al déficit de recursos físicos y de personal. Conclusión: El número de pruebas diagnósticas aún son insuficientes y la demora diagnóstica es excesiva. Sobre todo, en el control terapéutico la empresa suministradora tiene un papel relevante. Se propone la realización de protocolos entre diferentes unidades asistenciales y aumentar los recursos actuales. (AU)

Short title: The healthcare resources of the Andalusian Public Health System related to the diagnosis, treatment and follow-up of patients with obstructive sleep apnea are presented. Proposals for optimizing the management of this entity are also described, emphasizing the need for resources and collaboration between different levels of care. Objective: Determine the current resources in the Public Health System of Andalusia (SSPA) in obstructive sleep apnea (OSA) and identify proposals for improvement. Method: Cross-sectional study, based on surveys conducted in 49 SSPA hospitals. Variables related to the diagnosis, treatment, and follow-up of OSA were recorded, distinguishing between centers that performed polysomnography and those that did not. We include a section on proposals for improvement. Results: 97% of the centers perform polygraphy and 29% polysomnography, and only 39.5% have a specific consultation. The diagnostic delay for polygraphy is 169 ± 163.4 days and for polysomnography 173 ± 152.5 days. A total of 1,113 ± 1,004.6 tests are performed per 100,000 inhabitants per year, of which 235 ± 166.2 are diagnostic polygraphs. The effective pressure is titrated in 49% with auto-CPAP and therapeutic control is frequently carried out by the supplying company (77%). Among the proposals for improvement, the lack of a protocol for referral and coordination between different levels of care (90% of those surveyed), and the diagnostic delay, attributable in 63% of cases to the lack of physical and personnel resources, stand out. Conclusion: The number of diagnostic tests are still insufficient and the diagnostic delay is excessive. Above all, in therapeutic control, the supplier company has a relevant role. It is proposed to carry out protocols between different care units and increase current resources

Differential biomarker profiles between unprovoked venous thromboembolism and cancer.

BACKGROUND: The relationship between cancer and venous thromboembolic disease (VTD) are complex because the activated coagulation factors are not only involved in thrombosis but also in malignant processes, such as angiogenesis and metastasis. OBJECTIVE: To compare phenotypes of extracellular vesicles (EVs), and levels of D-dimer, soluble P-selectin (sP-selectin) and antigenic tissue factor (TF) between unprovoked VTD patients, who did not develop cancer during one-year follow-up, and those with advanced stage of cancer but not associated with VTD. METHODS: A prospective study in which we included 138 unprovoked VTD patients and 67 advanced cancer patients, who did not develop thrombosis. Levels of EVs of different cellular origin (platelet, endothelium and leukocyte), EVs positive for tissue factor (TF) and P-selectin glycoprotein ligand 1 were quantified by flow cytometry. D-dimer, soluble P-selectin (sP-selectin) and antigenic TF were determined by ELISA. RESULTS: TF-positive EVs, D-dimer, and sP-selectin were markedly elevated in unprovoked VTD patients compared to cancer patients without association with thrombosis. CONCLUSIONS: Levels of TF-positive EVs, D-dimer and sP-selectin are able to discriminate between unprovoked VTD patients not related to cancer and cancer patients not associated with VTD. These results could lead to the application of EVs as biomarkers of both diseases. Key messages: Circulating EVs, specifically TF-positive EVs, in combination with plasmatic markers of hypercoagulable states, such as D-dimer, sP-selectin and antigen TF, are able to discriminate between cancer patients without thrombosis and patients with unprovoked VTD. Research fields could be opened. Future studies will assess if these biomarkers together serve as predicting thrombotic events in cancer populations.

Primary Care Physicians Can Comprehensively Manage Patients with Sleep Apnea. A Noninferiority Randomized Controlled Trial.

Rationale: General practitioners play a passive role in obstructive sleep apnea (OSA) management. Simplification of the diagnosis and use of a semiautomatic algorithm for treatment can facilitate the integration of general practitioners, which has cost advantages.Objectives: To determine differences in effectiveness between primary health care area (PHA) and in-laboratory specialized management protocols during 6 months of follow-up.Methods: A multicenter, noninferiority, randomized, controlled trial with two open parallel arms and a cost-effectiveness analysis was performed in six tertiary hospitals in Spain. Sequentially screened patients with an intermediate to high OSA probability were randomized to PHA or in-laboratory management. The PHA arm involved a portable monitor with automatic scoring and semiautomatic therapeutic decision-making. The in-laboratory arm included polysomnography and specialized therapeutic decision-making. Patients in both arms received continuous positive airway pressure treatment or sleep hygiene and dietary treatment alone. The primary outcome measure was the Epworth Sleepiness Scale. Secondary outcomes were health-related quality of life, blood pressure, incidence of cardiovascular events, hospital resource utilization, continuous positive airway pressure adherence, and within-trial costs.Measurements and Main Results: In total, 307 patients were randomized and 303 were included in the intention-to-treat analysis. Based on the Epworth Sleepiness Scale, the PHA protocol was noninferior to the in-laboratory protocol. Secondary outcome variables were similar between the protocols. The cost-effectiveness relationship favored the PHA arm, with a cost difference of €537.8 per patient.Conclusions: PHA management may be an alternative to in-laboratory management for patients with an intermediate to high OSA probability. Given the clear economic advantage of outpatient management, this finding could change established clinical practice.Clinical trial registered with www.clinicaltrials.gov (NCT02141165).

Gamma glutamyl transferase and oxidative stress in obstructive sleep apnea: a study in 1744 patients.

OBJECTIVE: We analyze a large population of patients to determine whether gamma glutamyl transferase (GGT) levels are increased in sleep apnea-hypopnea syndrome (OSA) and whether these levels are related to clinical characteristics or polygraphic indexes. METHODS: A cross-sectional study in a population of 1744 patients referred for OSA suspicion was conducted. The following variables were determined: glucose, cholesterol, triglycerides, aspartate aminotransferase (GOT), alanine aminotransferase (GPT), GGT, body mass index, waist-hip ratio (WHR), and overnight sleep study. RESULTS: The 483 patients with GGT ≥40 IU/l were younger and more obese, and had a pattern of more centrally distributed fat than the 1261 with GGT <40 IU/l. Patients with high levels of GGT also consumed more alcohol, had a poorer biochemical profile, and had more respiratory and oximetric alterations during sleep. GGT levels were significantly correlated with AHI, DI, and CT90. In the binary regression test, WHR, glucose, cholesterol, triglycerides, and grams of alcohol consumed per day predicted GGT levels ≥40 IU/l, while none of the polygraphic variables had predictive value. CONCLUSIONS: High GGT levels were associated with the severity of OSA. However, this relationship seems to be due to the coexistence of other associated factors, mainly central obesity, rather than to the respiratory disorders found in this disease.

Results from an audit feedback strategy for chronic obstructive pulmonary disease in-hospital care: a joint analysis from the AUDIPOC and European COPD audit studies.

BACKGROUND: Clinical audits have emerged as a potential tool to summarize the clinical performance of healthcare over a specified period of time. However, the effectiveness of audit and feedback has shown inconsistent results and the impact of audit and feedback on clinical performance has not been evaluated for COPD exacerbations. In the present study, we analyzed the results of two consecutive nationwide clinical audits performed in Spain to evaluate both the in-hospital clinical care provided and the feedback strategy. METHODS: The present study is an analysis of two clinical audits performed in Spain that evaluated the clinical care provided to COPD patients who were admitted to the hospital for a COPD exacerbation. The first audit was performed from November-December 2008. The feedback strategy consisted of personalized reports for each participant center, the presentation and discussion of the results at regional, national and international meetings and the creation of health-care quality standards for COPD. The second audit was part of a European study during January and February 2011. The impact of the feedback strategy was evaluated in term of clinical care provided and in-hospital survival. RESULTS: A total of 94 centers participated in the two audits, recruiting 8,143 admissions (audit 1∶3,493 and audit 2∶4,650). The initially provided clinical care was reasonably acceptable even though there was considerable variability. Several diagnostic and therapeutic procedures improved in the second audit. Although the differences were significant, the degree of improvement was small to moderate. We found no impact on in-hospital mortality. CONCLUSIONS: The present study describes COPD hospital care in Spanish hospitals and evaluates the impact of peer-benchmarked, individually written and group-oral feedback strategy on the clinical outcomes for treating COPD exacerbations. It describes small to moderate improvements in the clinical care provided to COPD patients with no impact on in-hospital mortality.

Niveles séricos de mesotelina. Valor pronóstico en mesotelioma pleural maligno / Serum levels of mesothelin. Prognosis value in malignant pleural mesothelioma

El mesotelioma pleural maligno (MPM) es un tumor agresivo que surge del epitelio pleural. Se han detectado concentraciones aumentadas de proteínas solubles relacionadas con la mesotelina (SMRP) en suero de pacientes con MPM (..) (AU)

Malignant pleural mesothelioma (MPM) is an aggressive tumour that arises from pleural epithelium. Increased concentrations of soluble mesothelin related proteins (SMRP)