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.

Calidad de vida relacionada con la salud en pacientes oncológicos con enfermedad tromboembólica venosa aguda sintomática. Diseño del estudio qca (quality of life in cancer). Estudio de casos y controles / Health-related quality of life in cancer patients with acute symptomatic venous thromboembolic disease. Design of the QCa (quality of life in cancer) study. Case-control study

La asociación entre cáncer y enfermedad tromboembólica (ETV) se encuentra bien establecida. La ETV presenta una elevada morbimortalidad, objetivándose un incremento del riesgo de ETV hasta 4 veces mayor en aquellos pacientes con cáncer respecto a la población general. Sin embargo, existe poca evidencia científica sobre la CVRS (calidad de vida relacionada con la salud) en pacientes oncológicos con ETV, cuando es presumible que esta patología suponga un agravante sobre la percepción del estado de salud de los pacientes oncológicos. Nuestro objetivo es presentar el estudio "QCa Study", el cual pretende evaluar la CVRS de los pacientes oncológicos con ETV aguda sintomática en comparación con pacientes oncológicos sin ETV. "QCa study" es un estudio nacional de cohortes, prospectivo, de casos y controles en pacientes con cáncer activo. Definimos "caso" como aquel paciente oncológico con ETV aguda sintomática, y "control" aquel paciente oncológico sin ETV aguda sintomática. Los criterios de inclusión son: para los casos: presentar cáncer activo al momento de la inclusión. Tener más de 18 años, pacientes diagnosticados de trombosis venosa profunda (TVP) en miembros inferiores aguda sintomática o de embolia de pulmón (EP) confirmado de forma objetiva mediante pruebas de imagen y firma del consentimiento informado. Para los controles; presentar cáncer activo. Tener más de 18 años. Firma del consentimiento informado. Dado los escasos datos publicados respecto a la CVRS en pacientes con ETV, hemos diseñado el estudio Qca, para poder determinar el impacto que genera la ETV en la calidad de vida de los pacientes con cáncer

The association between cancer and venous thromboembolic disease (VTD) is well established. VTD presents a high rate of morbidity and mortality, with patients with cancer showing an increased risk of VTD that is up to 4 times greater than the general population. However, there is little scientific evidence on HRQoL (health-related quality of life) in cancer patients with VTD when this disease is likely to be an aggravating factor in perceived state of health among cancer patients. Our objective is to present the QCa study, which aims to evaluate the HRQoL of cancer patients with acute symptomatic VTD in comparison with cancer patients without VTD. The QCa study is a prospective, case-control national cohort study in patients with active cancer. We define "case" as a cancer patient with acute symptomatic VTD and "control" as a cancer patient without acute symptomatic VTD. Inclusion criteria for cases were: having active cancer at the time of inclusion, being over the age of 18, patients diagnosed with acute symptomatic deep vein thrombosis (DVT) in the lower extremities or pulmonary embolism (EP) that was objectively confirmed through imaging tests, and having signed the informed consent. For the controls: having active cancer, being over the age of 18, and having signed the informed consent. Given the scarce data published with regard to HRQoL in patients with VTD, we designed the QCa study to determine the impact VTD has on the quality of life of patients with cancer

Incidencia de enfermedad pulmonar obstructiva crónica en pacientes con el virus de la inmunodeficiencia humana. Análisis post-hoc del estudio viva / Incidence of chronic obstructive pulmonary disease in patients with human immunodeficiency virus. Post-hoc analysis of the viva study

Introducción: desde la aparición de la terapia antiretroviral la supervivencia de los pacientes infectados por el virus de la inmunodeficiencia humana (VIH) ha aumentado considerablemente tomando importancia la aparición de otras patologías crónicas en estos pacientes como puede ser la enfermedad pulmonar obstructiva crónica (EPOC). Nuestro objetivo fue conocer la incidencia de EPOC en una cohorte de pacientes VIH derivados en un programa de detección de hipertensión pulmonar (HTP). Material y Métodos: análisis post-hoc, de un prospectivo, pseudo-experimental de pacientes con infección del VIH a los que se les preguntaba por disnea y en caso afirmativo eran derivados a consultas de neumología para despistaje de HTP. Resultado: desde 2014 hasta 2016, reclutamos un total de 32 pacientes, con un predominio de varones (75%). La disnea según la mMRC (Medical Reserach Council) fue grado 1, 2 y 3 en el 37,5%, 43,8% y 18,8%, respectivamente. La prevalencia de tabaquismo fue del 87,1% (intervalo de confianza [IC] 95%: 71- 96,4%), y 18 pacientes fueron catalogados de EPOC (62%; IC95%: 42,2 - 79,3%). Conclusión: la incidencia de EPOC en nuestra serie fue muy superior a la de la población general. Es necesario plantear estrategias de búsqueda activa de EPOC en estos pacientes para un diagnóstico y tratamiento precoz

Introduction: Since the advent of antiretroviral therapy, the survival of patients infected with the human immunodeficiency virus (HIV) has considerably increased, with the occurrence of other chronic diseases such as chronic obstructive pulmonary disease (COPD) gaining importance in these patients. Our objective was to find out the incidence of COPD in a cohort of HIV patients that were referred to a program to detect pulmonary hypertension (PH). Materials and Methods: Post hoc analysis of a prospective, quasi-experimental study on HIV-infected patients who were asked whether they had dyspnea. If this was the case, they were referred to a pulmonologist for PH screening. Results: From 2014 to 2016, we recruited a total of 32 patients, with a predominance of male recruits (75%). According to the mMRC (Modified Medical Research Council) Dyspnea Scale, 37.5%, 43.8% and 18.8% were classified as Grade 1, 2 and 3, respectively. The prevalence of smoking was 87.1% (95% confidence interval [CI]: 71 - 96.4%), and 18 patients were classified with COPD (62%; 95% CI: 42.2 - 79.3%). Conclusion: The incidence of COPD in our sample was much higher than that of the general population. It is necessary to plan active search strategies for COPD in these patients for early diagnosis and treatment

Origen celular de micropartículas circulantes en pacientes con enfermedad tromboembólica venosa y cáncer / Celular origin of circulating microparticles in patients with venous thromboembolism and cancer

Las micropartículas (MPs) son unas vesículas extracelulares consideradas potentes efectores celulares. Están presentes en individuos sanos y se encuentran elevadas en estados patológicos como enfermedades inflamatorias, neoplásicas y trombosis. La relación entre enfermedad tromboembólica venosa (ETV) y cáncer está bien establecida. Se piensa que las MPs serían una conexión patogénica entre ambas entidades. De confirmarse, podrían utilizarse como biomarcadores. Nuestro objetivo fue caracterizar las MPs en ambas patologías atendiendo a su origen celular (celular, endotelial, plaquetar, leucocitario y las que exhibían en su superficie mucina 1). También se estudiaron parámetros funcionales como el dímero D (DD) y la P-selectina soluble (sPS). Se consideraron 96 pacientes con ETV idiopática y 85 con neoplasias avanzadas de pulmón, gástrico o páncreas. A todos ellos se les realizó un seguimiento clínico de dos años en el que se excluyeron del estudio aquellos que fueron diagnosticados de cáncer en el grupo de ETV o que desarrollaron trombosis en el grupo de pacientes neoplásicos. Finalmente, se analizaron 82 pacientes con ETV y 68 con cáncer. En nuestros resultados encontramos que las MPs totales y las MPs de origen plaquetar diferenciaban ambos grupos de pacientes. Además, se determinaron cifras significativamente mayores de DD y sPS (p <0,001) en el grupo de ETV. Las diferencias encontradas entre ambos grupos, teniendo en cuenta el origen de las MPs, podrían estar causadas por las características protrombóticas del grupo neoplásico y por el secuestro de las mismas dentro de los coágulos activos en el grupo de ETV

Microparticles (MPs) are extracellular vesicles considered to be powerful cellular effectors. They are present in healthy individuals and are elevated in pathological conditions such as inflammatory and neoplastic diseases, and thrombosis. The relationship between venous thromboembolism (VTE) and cancer has been well established. MPs are thought to be a pathogenic connection between the two entities. If confirmed, they could be used as biomarkers. Our aim was to characterize the MPs in both diseases according to their cellular origin (cellular, endothelial, platelet, leukocyte and those that exhibited mucin 1 on their surface). Functional parameters such as D-dimer (DD) and soluble P-selectin (sPsel) were also studied. 96 patients with idiopathic VTE and 85 with advanced lung, stomach or pancreatic neoplasia were considered. All of them were followed clinically for two years and those who were diagnosed with cancer in the VTE group or those who developed thrombosis in the group of neoplastic patients were excluded from the study. Finally, 82 VTE patients and 68 cancer patients were analyzed. In our results, we found that total MPs and platelet-derived MPs differentiated both patient groups. Additionally, significantly greater numbers of DD and sPsel (p <0.001) were determined in the VTE group. The differences found between both groups, taking into account the origin of the MPs, could be caused by the prothrombotic characteristics of the neoplastic group and their sequestration within active clots in the VTE group

La ecografía en el diagnóstico de la enfermedad tromboembólica venosa / No disponible

La trombosis venosa profunda (TVP) y el tromboembolismo pulmonar (TEP) son manifestaciones clínicas distintas de una misma enfermedad, la enfermedad tromboembólica venosa (ETV). La ecografía de miembros inferiores es la técnica de imagen de elección para el diagnóstico de la TVP. Para el neumólogo, cuyo objetivo sería el diagnóstico de la TVP, no es necesario realizar una ecografía doppler, ya que se puede hacer el diagnóstico mediante ecografía compresiva bidimensional en escala de grises. El signo ecográfico más sensible (S) y específico (E) para el diagnóstico de TVP de miembros inferiores es la falta de compresibilidad de la vena (S 91% y E 99%). Además, nos puede dar un diagnóstico alternativo distinto a la TVP. Tanto la ecografía compresiva en dos puntos, realizada de forma seriada, como la ecografía compresiva completa única, son técnicas ecográficas que han demostrado ser seguras para descartar TVP, con una baja incidencia de ETV a los 3 meses de seguimiento. La ecografía torácica es útil clínicamente para el diagnóstico del TEP y puede ser una alternativa al angioTAC de tórax en grupos especiales de pacientes, como enfermos renales o embarazadas. El hallazgo ecográfico más característico es la existencia de una zona hipoecoica de base pleural y morfología triangular, localizada en la zona donde el paciente ha tenido dolor pleurítico. Además de hallazgos parenquimatosos, podemos encontrar hallazgos vasculares y pleurales. La sensibilidad de la ecografía para el diagnóstico de TEP es del 74% y la especificidad del 95%. Su principal limitación es que sólo permite detectar lesiones tromboembólicas que afecten a la periferia. La ecografía multiórgano (miembros inferiores, corazón y tórax) ha demostrado mejores resultados que la ecografía de cada órgano por separado en la sospecha de TEP y podría ser útil para seleccionar a aquellos pacientes a los que no habría que realizar angioTAC de tórax

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Management and outcomes in chronic thromboembolic pulmonary hypertension: From expert centers to a nationwide perspective.

BACKGROUND: The Spanish "Registry of Pulmonary Arterial Hypertension" (REHAP), started in 2007, includes chronic thromboembolic hypertension (CTEPH) patients. Based on data provided by this registry and retrospective data from patients diagnosed during 2006 (≤ 12 months since the registry was created), clinical management and long-term outcomes of CTEPH patients are analyzed nationwide for the first time in a scenario of a decentralized organization model of CTEPH management. METHODS AND RESULTS: A total of 391 patients (median [Q1:Q3] age 63.7 [48.0;73.3] years, 58% females) with CTEPH included during the period January 1, 2006-December 31, 2013 in the REHAP registry were analyzed. Rate of pulmonary endarterectomy (PEA) was 31.2%, and highly asymmetric among centers: rate was 47.9% at two centers designated as CTEPH expert centers, while it was 4.6% in other centers. Among patients not undergoing PEA, 82% were treated with therapies licensed for pulmonary arterial hypertension (PAH). Five-year survival rate was 86.3% for PEA patients, and 64.9% for non-PEA patients. Among non-PEA patients, presenting proximal lesions (42% of non-referred patients) was associated with a 3-fold increase in mortality. PEA patients achieved significantly better hemodynamic and clinical outcomes at one-year follow-up compared to non-PEA patients. Patients not being referred for PEA assessment were older and had a worse functional capacity. Older age was the most deterrent factor for non-operability. CONCLUSION: Despite the increase in diagnosis and expertise in PEA-specialized centers, an important percentage of patients do not benefit of PEA in a decentralized organization model of CTEPH management.

Marcadores inflamatorios de disfunción endotelial en la enfermedad tromboembólica venosa / Inflammatory markers of endothelial dysfunction in venous thromboembolic disease

OBJETIVO: investigar si los pacientes con ETV presentan diferencias en la cuantificación de marcadores inflamatorios de disfunción endotelial (IL-6 y IL8) en fase estable. MATERIAL Y MÉTODOS: pacientes con ETV aguda sintomática de cualquier causa en los que, a los 3 meses de seguimiento, se les realizó una determinación de IL-6 e IL-8. Los pacien tes con ETV los dividimos en 3 grupos según la etiología del evento: 1) ETV idiopático. 2) ETV 2º a cáncer. 3) ETV 2º a otra causa. RESULTADOS: la muestra fue de 77 pacientes. La distribución de los pacientes según la etiología de la ETV fue la siguiente: ETV idiopático (n=40). ETV 2º a cáncer (n=26). ETV 2º a otra etiología (n=11). La mediana de IL-6 para cada uno de los grupos fue: ETV idiopática 2,96 pg/ml, ETV secundaria a cáncer 3,87 pg/ml y ETV secundaria a otra etiología 2,30 pg/ml. La mediana de IL-8 para cada uno de los grupos fue de 0,00 pg/ml. Cuando comparamos las dos determinaciones en los 3 grupos según la etiología del evento: 1) ETV idiopático. 2) ETV 2º a cáncer. 3) ETV 2º a otra causa. RESULTADOS: la muestra fue de 77 pacientes. La distribución de los pacientes según la etiología de la ETV fue la siguiente: ETV idiopático (n=40). ETV 2º a cáncer (n=26). ETV 2º a otra etiología (n=11). La mediana de IL-6 para cada uno de los grupos fue: ETV idiopática 2,96 pg/ml, ETV secundaria a cáncer 3,87 pg/ml y ETV secundaria a otra etiología 2,30 pg/ml. La mediana de IL-8 para cada uno de los grupos fue de 0,00 pg/ml. Cuando comparamos las dos determinaciones en los 3 grupos obser-vamos como no hay diferencias significativas entre ellos, aun-que existía cierta tendencia a la significación estadística en la determinación de IL-6 (p = 0,054). CONCLUSIONES: los marcadores inflamatorios de disfunción endotelial (IL-6 y IL8) no mostraron diferencias significativas en los tres grupos, aunque un incremento de la muestra podría evidenciar diferencias de la IL-6 entre los tres grupos. A los tres meses de tratamiento los niveles medios de IL-8 son inde-tectables en los 3 grupos

OBJECTIVE: to investigate whether patients with VTD present differences in the quantification of endothelial dys-function inflammatory markers (IL-6 and IL8) during the stable phase. MATERIAL AND METHODS: patients with symptomatic acute VTD of any cause and who, at the 3 months follow-up, had determina-tion for IL-6 and IL-8 performed. The patients with VTD were divided into three groups according to the etiology of the event: 1) idiopathic VTD, 2) VTD secondary to cancer, 3) VTD secondary to another cause. RESULTS: there were 77 patients in the sample. The distribution of the patients according to the etiology of the VTD was as fo-llowing: idiopathic VTD (n=40). VTD secondary to cancer (n=26). VTD secondary to another cause (n=11). The median of IL-6 for each one of the groups was: idiopathic VTD 2.96 pg/ml. VTD secondary to cancer 3.87 pg/ml. VTD secondary to another cause 2.30 pg/ml. The median of IL-8 for each one of the groups at three months was 0.00 pg/ml. When we compared the two determinations in the three groups, we observed that there were no significant differences between them, although there was a certain tenden-cy towards statistical significance in the determination of IL-6 (p = 0.054). CONCLUSIONS: the endothelial dysfunction inflammatory markers (IL-6 and IL8) did not show significant differences in the three groups, although an increase in the size of the sample could lead to differences being found in the IL-6 between the three groups. After three months of treatment, the median levels of IL-8 are indetectables in the three groups

Seguimiento del paciente con embolismo pulmonar: complicaciones y evolución / Follow-up of patients with pulmonary embolism: Complications and developments

Objetivo: Analizar la supervivencia a 2 años de pacientes consecutivos diagnosticados de EP, las recidivas trombóticas y los eventos hemorrágicos. Pacientes y Método: Estudio de cohorte de pacientes diagnosticados de forma consecutiva de EP seguidos durante dos años, analizando la supervivencia y las complicaciones a largo plazo (recidivas y hemorragia).Resultados: 165 pacientes diagnosticados de forma consecutiva de EP, 17 fallecieron durante el evento agudo. Se incluyeron en el estudio 148 pacientes, 50% varones, con una edad de 64.17 +/- 17.23 años. Durante el seguimiento fallecieron 34 pacientes (23%), se perdieron 5 (3.4%), recidivaron 13 (8.8%) y 16 (10.8%) presentaron sangrado. Las recidivas se presentaron como EP (n=6), trombosis venosa profunda (TVP) (n=6) o EP con TVP (n=1). Seis de los pacientes con recidiva se presentaron inicialmente como EP idiopático, y 7 de ellos como EP secundario. De los 13 pacientes que presentaron recidiva, 2 fallecieron a los 2 años de seguimiento, y ninguno como consecuencia de la recidiva. En cuanto al sangrado, éste se produjo a los 3.23 meses (rango 28.17 meses) del evento agudo; el 37.5% fueron sangrados mayores. La causa de muerte más frecuente fue el cáncer. La incidencia acumulada de mortalidad fue del 19.2% al año y del 29.6% a los dos años. Las variables asociadas a una menor supervivencia fueron una creatinina mayor de 2 mg/dl, la existencia de neoplasia previa, la demencia y la dislipemia. Conclusiones: el seguimiento de los pacientes con EP debe ser más estrecho en los primeros meses, ya que en este periodo de tiempo se producen las complicaciones de la enfermedad (muerte, recidivas y hemorragias) (AU)

Objective: To analyze the survival after two years in consecutive patients diagnosed of pulmonary embolism (PE), thrombotic relapse and episodes of bleeding. Patients and Method: Cohort study of patients diagnosed consecutively of PE, with a two-year follow-up, analyzing survival and long-term complications (relapse and bleeding). Results: 165 consecutive patients diagnosed of PE were initially included in the study., Seventeen died during an acute event, .and 148 patients were finally included in the study, of which 50% were males, with mean age = 64.17 + 17.23 years. During follow-up, 34 patients died (23%), 5 were lost (3.4%), 13 relapsed (8.8%) and 16 (10.8%) suffered bleeding. Relapse appeared as PE (n=6), deep vein thrombosis (DVT) (n=6) or PE with DVT (n=1). Six of the patients with relapse initially appeared as idiopathic PE and seven of them as secondary PE. Of the 13 patients with relapse, 2 died after the two-year follow-up and none as a consequence of the relapse. In terms of bleeding, this event appeared 3.23 month (average, extreme range= 28.17 months) after an acute event; 37.5% were major bleeding events. The most frequent cause of death was cancer. The accumulated mortality incidence was 19.2% after one year and 29.6% after two years. The variables associated with less survival were serum creatinine greater than 2 mg/dl, the existence of prior neoplasm, dementia and dyslipidemia. Conclusions: Follow-up of PE patients must be strict during the first few months, as this is when the complications appear (death, relapse and hemorrhaging) (AU)

Enfermedad tromboembólica indicental y cáncer / No disponible

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Análisis de 3 métodos para determinar el dímero D en pacientes con sospecha de trombosis venosa profunda / Clinical usefulness of three quantitative D-dimers tests in outpatients with suspected deep vein thrombosis

Antecedentes y objetivo. En los algoritmos diagnósticos de pacientes ambulatorios con sospecha de trombosis venosa profunda (TVP), se incluye la determinación del dímero D (DD). Un valor elevado del DD no es diagnóstico de TVP, pero una cifra normal contribuye a excluir una TVP. Desconocemos el mejor método para determinar el DD. Hemos analizado la utilidad clínica de 3 métodos cuantitativos para determinar el DD en pacientes ambulatorios con sospecha de TVP. Pacientes y métodos. Incluimos a pacientes consecutivos, ambulatorios, con sospecha de TVP que fueron remitidos a la consulta de enfermedad tromboembólica venosa. Aplicamos un algoritmo diagnóstico que incluía la determinación de la probabilidad clínica de padecer una TVP (escala de Wells) y la determinación del DD mediante 3 métodos cuantitativos (ELISA mini-VIDAS®, Acute-care DDMR y DD-Plus). El diagnóstico de TVP se confirmó mediante ecografía compresiva seriada de miembros inferiores. Analizamos la concordancia entre los 3 métodos analíticos para cuantificar el DD, así como sus características. Resultados. Incluimos 306 pacientes (edad media: 60 años; mujeres: 62%) con sospecha de TVP. La ecografía compresiva confirmó el diagnóstico de TVP en el 23,8% de los casos. Los pacientes en los que se descartó TVP no fueron anticoagulados y no se produjo ningún evento tromboembólico en 3 meses de seguimiento. Los métodos de determinación de DD que mejor se correlacionaron fueron el ELISA mini-VIDAS® y el Acute-care DDMR. Ambos métodos mostraron una elevada sensibilidad y un valor predictivo negativo. El mejor método analítico para el subgrupo de pacientes con probabilidad clínica baja de TVP fue el ELISA mini-VIDAS®. Conclusiones. El método ELISA mini-VIDAS® para la determinación del DD descarta con seguridad una TVP en pacientes con baja probabilidad clínica(AU)

Background and objective. The diagnostic approach in outpatients with suspected deep vein thrombosis (DVT) of the lower limbs includes D-dimer measurement (DD). Elevated DD is not a diagnostic value for DVT. However, a normal value contributes to ruling out DVT. We do not know the best method to determine DD. Therefore, we have analyzed the clinical utility of three quantitative assays to determine DD in outpatients with suspected DVT. Patients and methods. Consecutive outpatients with suspected DVT of the lower limbs who were referred to the DVT medical consultation were enrolled in the study. We used a diagnostic algorithm that included determining the pretest clinical probability (PCP) (Wells scale), DD level using three different quantitative methods (ELISA mini-VIDAS®, Acure-care DDMR and DD-Plus). The DVT diagnosis was confirmed by seriated compression ultrasonography of the lower limbs. We analyzed the concordance between the three analytic methods to quantify DD and the characteristics. Results. A total of 306 patients (mean age 60 years, 62% women) with suspected DVT of the lower limbs were included. The compression ultrasonography confirmed the diagnosis of DVT in 23.8% of the patients. Anticoagulation treatment was not performed in patients in whom DVT was ruled out, and no thromboembolic event occurred during the 3 months of follow-up. The best concordance test results were between ELISA mini-VIDAS® and Acure-care DDMR assays. Both assays demonstrated elevated sensibility and a negative predictive value. ELISA mini-VIDAS® was the best analytic method for the subgroup of patients with low clinical probability. Conclusions. The ELISA mini-VIDAS® method to determine DD rules out DVT in patients with low clinical probability(AU)

[Clinical usefulness of three quantitative D-dimers tests in outpatients with suspected deep vein thrombosis]. / Análisis de 3 métodos para determinar el dímero D en pacientes con sospecha de trombosis venosa profunda.

BACKGROUND AND OBJECTIVE: The diagnostic approach in outpatients with suspected deep vein thrombosis (DVT) of the lower limbs includes D-dimer measurement (DD). Elevated DD is not a diagnostic value for DVT. However, a normal value contributes to ruling out DVT. We do not know the best method to determine DD. Therefore, we have analyzed the clinical utility of three quantitative assays to determine DD in outpatients with suspected DVT. PATIENTS AND METHODS: Consecutive outpatients with suspected DVT of the lower limbs who were referred to the DVT medical consultation were enrolled in the study. We used a diagnostic algorithm that included determining the pretest clinical probability (PCP) (Wells scale), DD level using three different quantitative methods (ELISA mini-VIDAS(®), Acure-care DDMR and DD-Plus). The DVT diagnosis was confirmed by seriated compression ultrasonography of the lower limbs. We analyzed the concordance between the three analytic methods to quantify DD and the characteristics. RESULTS: A total of 306 patients (mean age 60 years, 62% women) with suspected DVT of the lower limbs were included. The compression ultrasonography confirmed the diagnosis of DVT in 23.8% of the patients. Anticoagulation treatment was not performed in patients in whom DVT was ruled out, and no thromboembolic event occurred during the 3 months of follow-up. The best concordance test results were between ELISA mini-VIDAS(®) and Acure-care DDMR assays. Both assays demonstrated elevated sensibility and a negative predictive value. ELISA mini-VIDAS(®) was the best analytic method for the subgroup of patients with low clinical probability. CONCLUSIONS: The ELISA mini-VIDAS(®) method to determine DD rules out DVT in patients with low clinical probability.

Dyslipidemia as a long-term marker for survival in pulmonary embolism.

OBJECTIVES: To analyse survival rate after 24 months in consecutive patients with a diagnosis of PE as well as associated factors. METHODS: Prospective cohort study during a follow-up period of two years in a series of consecutive patients with PE. RESULTS: During the follow-up period, 34 out of 148 patients died (23%). Factors independently associated with reduced survival rate were: creatinine levels > 2 (OR, 8.8; 95% CI, 1.1 - 70.87), previous neoplasm (OR, 8.8; 95% CI, 3.69 - 20.98), dementia (OR, 6.85; 95% CI, 2.1 - 22.33) and dyslipidemia (OR, 5.07; 95% CI, 1.92 - 13.44). Forty four percent of the patients with dyslipidemia died vs. 20.8% of patients without this condition. CONCLUSIONS: In our study dyslipidemia shows as a long-term negative prognostic marker for survival in patients with EP.

Análisis clínico-epidemiológico de pacientes consecutivos con tromboembolismo pulmonar / Clinical-epidemiological analysis of consecutive patients with pulmonary thromboembolism

INTRODUCCIÓN: El tromboembolismo pulmonar (TEP) constituye un problema sanitario de gran trascendencia debido a su elevada morbimortalidad. La enfermedad tromboembólica venosa (ETV) ocasiona unas 300.000 hospitalizaciones al año, con una incidencia del 0,5 al 2,5% entre los pacientes ingresados por patología médica y del 0,1 al 0,6% de los ingresados por causa quirúrgica. La prevalencia entre los ingresados es aproximadamente del 1%.OBJETIVO: Estudiar las características de los pacientes ingresados por TEP en nuestro medio hospitalario a fin de poder valorar la epidemiología, los factores de riesgo y la evolución durante el periodo agudo. PACIENTES Y MÉTODO: Se estudiaron a todos los pacientes ingresados y diagnosticados de TEP en los Hospitales Universitarios Virgen del Rocío de Sevilla en el periodo comprendido desde febrero de 2003 hasta septiembre del 2004. Se realizó una sistemática recogida de datos clínicos, diagnósticos, y evolutivos hasta el alta hospitalaria. RESULTADOS: Durante 19 meses consecutivos un total de456 pacientes ingresaron en nuestra área hospitalaria por sospecha de TEP. De estos sólo en 165 casos (36%) se confirmó dicho diagnóstico. Ochenta y dos (49.7%) eran mujeres y ochenta y tres hombres (50.3%). La edad media de fue de 64.47±16.77. El factor de riesgo para la ETV presente con más frecuencia fue la inmovilización secundaria. Los síntomas de presentación más frecuente fueron la disnea y el dolor torácico. El electrocardiograma fue normal en la mayoría de los pacientes [N=61(37%)] El derrame pleural fue el hallazgo radiológico más frecuente (37.6%). El signo más prevalente en la ecocardiografía fue la presencia de insuficiencia tricuspíde a (50.3%). La mortalidad en nuestra serie fue del 10.3%. CONCLUSIONES: El incremento en la edad de nuestros pacientes, los factores de riesgo asociados a la enfermedad tromboembólica, y las nuevas herramientas pronosticas, pueden facilitarnos el manejo de esta enfermedad que escasamente ha variado su morbimortalidad a pesar de los avances médicos

INTRODUCTION: Pulmonary thromboembolism (PTE) constitutes a health problem of great importance due to its high morbimortality. Venous thromboembolic disease (VTE) causes 300,000 hospitalizations a year, with an incidence from 0.5 to 2.5%among the patients admitted for medical pathology and from 0.1 to0.6% of those admitted for surgical causes. The prevalence among admissions is approximately 1%.OBJECTIVE: To study the characteristics of the patients admitted for PTE in our hospital area in order to be able to evaluate the epidemiology, the risk factors and the evolution during the acute period. PATIENTS AND METHOD: We studied all patients who were admitted to the University Hospitals Virgen del Rocio of Seville in the period included from February 2003 to September 2004 and diagnosed with PTE. Clinical data, diagnoses, and evolutions were systematically collected until the hospital discharge. Troponin and BNP (brain natriuretic peptide) levels in blood were determined, and echocardiography was performed, in the first 48 h after admission. RESULTS: During 19 consecutive months a total of 456patients entered our hospital area with suspicion of PTE. Of these, this diagnosis was confirmed in only 165 cases (36%). Eighty two(49.7%) were women and eighty three (50.3%) were men. The average age was 64.47±16.77. The risk factor for VTE presented with more frequency was immobilisation secondary to admission. The symptoms presented more frequently were dyspnoea and thoracic pain. The electrocardiogram was normal in most of the patients [N=61 (37%). Pleural effusion was the more frequent radiological finding (37.6%). The more prevalent sign in the echocardiography was the presence of tricuspid insufficiency (50.3%). Mortality in our series was 10.3%.CONCLUSIONS: The increase in the age of our patients, the risk factors associated to thromboembolic disease mainly in hospitalized patients, and the new prognostic tools, can facilitate our handling of this disease that has barely varied its morbimortality in spite of the technological advances

[Community acquired pneumonia in patients older than 60 years. Incidence of atypical agents and clinical-radiological progression]. / Neumonías adquiridas en la comunidad en pacientes mayores de 60 años. Incidencia de gérmenes atípicos y evolución clinicorradiológica.

BACKGROUND: Seventy five patients older than 60 years with a community acquired pneumonia followed up in an outpatient clinic, were prospectively studied in order to determine the incidence of atypical agents, clinical-radiological characteristics, progression and the differences with pneumonia in younger patients. METHOD: Clinical-radiological evaluation protocols were activated in the first visit and in two subsequent controls. Etiological diagnosis was made by means of serology (in the first visit and three weeks later). RESULTS: Initially, 85 patients older than 60 years were included of which 75 non hospitalized were fully followed up. Also, in the comparative study, 216 outpatient clinic patients 60 years old or younger were followed up during the same period. In the first group the frequency of atypical agents was 33.3%. The most frequently isolated bacteria was Coxiella burnetii (13.3%)followed by virus and Legionella pneumophila. No case of Mycoplasma pneumoniae was diagnosed. The most frequent radiological onset was alveolar infiltrate (85%). The comparative study between the two populations (older or younger than 60 years), found few clinical differences (dyspnea more frequent in older,feverish chill in younger) and auscultation (crackles more frequent in older). We did not find differences remaining clinical-radiological or laboratory data. Most patients presented a favourable clinical and radiological progression. Only 2 patients needed hospital admission (2.7%). CONCLUSIONS: In outpatient clinic patients older than 60 years with community acquired pneumonia a high number of atypical agents have been found. The clinical-radiological evolution was satisfactory for most of them. Age was not a decisive element in determining hospital admissions.

Inspiratory muscle training in patients with COPD: effect on dyspnea, exercise performance, and quality of life.

OBJECTIVE: The aim of the study was to assess the effect of target-flow inspiratory muscle training (IMT) on respiratory muscle function, exercise performance, dyspnea, and health-related quality of life (HRQL) in patients with COPD. PATIENTS AND METHODS: Twenty patients with severe COPD were randomly assigned to a training group (group T) or to a control group (group C) following a double-blind procedure. Patients in group T (n = 10) trained with 60 to 70% maximal sustained inspiratory pressure (SIPmax) as a training load, and those in group C (n = 10) received no training. Group T trained at home for 30 min daily, 6 days a week for 6 months. MEASUREMENTS: The measurements performed included spirometry, SIPmax, inspiratory muscle strength, and exercise capacity, which included maximal oxygen uptake (VO(2)), and minute ventilation (VE). Exercise performance was evaluated by the distance walked in the shuttle walking test (SWT). Changes in dyspnea and HRQL also were measured. RESULTS: Results showed significant increases in SIPmax, maximal inspiratory pressure, and SWT only in group T (p < 0.003, p < 0.003, and p < 0.001, respectively), with significant differences after 6 months between the two groups (p < 0.003, p < 0.003, and p < 0.05, respectively). The levels of VO(2) and VE did not change in either group. The values for transitional dyspnea index and HRQL improved in group T at 6 months in comparison with group C (p < 0.003 and p < 0.003, respectively). CONCLUSIONS: We conclude that targeted IMT relieves dyspnea, increases the capacity to walk, and improves HRQL in COPD patients.

[Results of a psychotherapeutic program for smoking after 12 months of follow-up]. / Resultados de un programa psicoterapéutico de deshabituación tabáquica tras 12 meses de seguimiento.

OBJECTIVE: To compare the efficacy of psychological counseling for smokers in a cessation program in comparison with treatment based only on providing information about damage caused by tobacco and advice for quitting, and to determine the reasons patients started to smoke. PATIENTS AND METHODS: We studied 249 patients who came to a preliminary interview; 226 began treatment for smoking cessation. The average level of dependence, quantified the Fagerstrom test was 7.26 +/- 1.85 points. Two treatment groups were formed: the first patients seen made up the control group (n = 37), which received information about the dangers of tobacco and strategies for quitting, and the psychological counseling group (n = 189). Follow-up examinations were performed three, six and twelve months after treatment, with abstinence checked by measurement of CO in exhaled air. Only patients with CO levels less than 5 ppm (particles per million) in exhaled air were considered non-smokers. RESULTS: Most patients of both sexes named social pressure as the reason for starting to smoke. The rate of abstinence in the information and strategies group was 8.1% at all three follow-up visits, whereas the rate was 37%, 25.4% and 24.3% at three, six and twelve months, respectively, in the group receiving counseling. The differences between the two groups were significant at all visits. CONCLUSIONS: Social pressure is the main reason for starting to smoke. We observed a success rate of 24.3% after one year of follow-up after psychological treatment only, a rate that was significantly higher than that of the group that received only information. We believe that psychological counseling is an effective alternative for smokers who want to quit.

Resultados de un programa psicoterapéutico de deshabituación tabáquica tras 12 meses de seguimiento / Psychological cunseling for smoking cessation: results after twelve months

Objetivo: El objetivo de nuestro estudio ha sido conocer la efectividad de un programa psicoterapéutico de deshabituación tabáquica en relación con una intervención basada en información sobre el daño del tabaco y consejos para su abandono, así como los motivos de inicio del tabaquismo. Pacientes y métodos: Estudiamos a un total de 249 pacientes que acudieron a una entrevista preliminar, de los cuales 226 comenzaron un tratamiento para la deshabituación tabáquica. El nivel medio de dependencia, cuantificado por el test de Fagerström, fue de 7,26 ñ 1,85 puntos. Se formaron dos grupos de estudio: un grupo control de información sobre los peligros del tabaco y diversas estrategias de abandono (n = 37) con los primeros pacientes, y un grupo de intervención psicoterapéutica (n = 189) en el que se incluyeron de forma consecutiva el resto. Se efectuaron revisiones a los 3, 6 y 12 meses una vez finalizado el tratamiento, objetivándose mediante cooximetría la situación de abstinencia. Fueron considerados como no fumadores exclusivamente aquellos individuos en que se pudieron objetivar valores iguales o menores a 5 ppm (partículas por millón) de CO en aire espirado. Resultados: La mayoría de los pacientes en ambos sexos indicaron como motivo de inicio del tabaquismo la presión social. El porcentaje de abstinencia en el grupo de información y estrategias de abandono fue del 8,1 por ciento en las tres revisiones efectuadas, mientras que en el grupo de intervención psicoterapéutica fue del 37, 25,4 y 24,3 por ciento, respectivamente, a los 3, 6 y 12 meses, existiendo diferencias significativas respecto al primer grupo en todas las revisiones. Conclusiones: Los factores de presión social son fundamentales en el inicio del tabaquismo. Hemos objetivado un 24,3 por ciento de éxitos en la abstinencia al año de seguimiento exclusivamente con tratamiento psicológico, existiendo diferencias significativas en relación con el grupo que sólo recibió información. Creemos que la terapia psicológica se presenta como alternativa eficaz en el abandono del tabaquismo. (AU)

[Comparative study of the efficacy of 2 respiratory physiotherapy protocols for patients with cystic fibrosis]. / Estudio comparativo de la eficacia de dos protocolos de fisioterapia respiratoria en pacientes con fibrosis quística.

OBJECTIVE: To compare the short-term efficacy of two respiratory physiotherapy protocols on sputum clearance, lung function and symptoms in patients with cystic fibrosis. Treatment A consisted of diaphragm breathing with incentive spirometry and postural drainage. Treatment B consisted of diaphragm breathing with positive expiratory pressure (PEP-mask) and postural drainage. METHODS: Twenty-seven cystic fibrosis patients in stable condition followed both protocols (A and B) in random order on different days separated by at least 48 hours. After each treatment session the amount of sputum removed was weighed. Lung function variables (FVC, FEV1, FEV1%, MMEFwt-75, MVV and PEF) were measured pre- and posttreatment. PEF was measured with a peak flow meter. The patients later recorded PEF every hour at home and filled in a questionnaire on frequency and intensity of coughing, sputum characteristics, chest discomfort and dyspnea. RESULTS: During treatment A with incentive spirometry, 14.6 +/- 13.7 g of sputum was removed, whereas 9.8 +/- 10.2 g was eliminated during treatment B (p < 0.05). The differences in PEF after treatments A and B in comparison with baseline values were +19.3 l/min and -0.2 l/min, respectively (p < 0.01). PEF stayed high during the afternoon, in comparison with baseline, with treatment A (p < 0.02). After treatment B, no changes in PEF in comparison with baseline were observed (p = 0.49). Neither treatment led to significant differences in symptoms reported on the clinical questionnaire. CONCLUSIONS: Respiratory physiotherapy with incentive spirometry significantly increases sputum clearance in cystic fibrosis patients, with no immediate repercussions on lung function or symptoms.

[Abdominal respiratory muscle activity in patients with stable chronic obstructive pulmonary disease]. / Actividad de la musculatura espiratoria abdominal en pacientes con enfermedad pulmonar obstructiva crónica estable.

With the purpose of defining the pattern of abdominal respiratory muscle activity in patients with chronic obstructive pulmonary disease (COPD), we studied the electromyogram of the rectus abdominis (RA), the external oblique (EO) and transversus (TM) muscles in 14 patients with different degrees of airways obstruction (FEV1: 41 +/- 12%; FEV1/FVC: 45 +/- 10%; RV: 198 +/- 38%; PaO2: 75.8 +/- 12 y PaCO2: 41.4 +/- 5.7 mmHg). The EMG was obtained by insertion of bipolar electrodes guided by an ultrasound image of the abdominal wall to locate the position of the muscles. The measurements were recorded in supine decubitus position in 5 situations: a) breathing at tidal volume; b) slow expiration until RV; c) with inspiratory load; d) with expiratory load, and e) during relaxed breathing with the arms raised. Recordings were also made in the same situations with 10 patients sitting. Eight patients presented phasic expiratory activity during relaxed breathing (TM activity alone or accompanied by EO). We found no significant differences in degree of hyperinflation or in arterial gases between patients with phasic expiratory activity and those without. There were significant differences between these 2 groups, however, as to degree of airways obstruction, for absolute values of FEV1 (p < 0.02) and in raw values (p < 0.04). Slow breathing until RV recruited muscular activity in 13 patients; the muscles did not operate in unison, however, with TM acting first. Recruitment was also observed when inspiratory and expiratory loads were placed, although in this case the 3 muscles acted simultaneously. Phasic activity was observed in only 2 patients for recordings made with arms raised, at which time there was greater tonic muscle activity. The phasic activity pattern recorded when patients were sitting was very similar to that obtained in supine position. In summary, some patients with stable COPD have phasic expiratory activity of the abdominal muscles when resting. These muscles do not appear to act as a unit and this phasic expiratory activity is related to severity of upper airways obstruction.