RESUMEN
INTRODUCTION AND OBJECTIVES: Surgical aortic valve replacement (SAVR) can modify the natural history of severe aortic stenosis (SAS). However, compared with the general population, these patients have a loss of life expectancy. The life expectancy of patients who undergo SAVR due to low-gradient SAS with preserved left ventricular ejection fraction (LVEF) is unknown. METHODS: We included all patients between 50 and 65 years who underwent isolated SAVR in 27 Spanish centers during an 18-year period. We analyzed observed and expected survival at 18 years in patients with low-gradient SAS with preserved LVEF and all other types of SAS. We used propensity score matching to compare the life expectancy of patients with low-gradient SAS with preserved LVEF vs those with high-gradient SAS with preserved LVEF. RESULTS: We analyzed 5084 patients, of whom 413 had low-gradient SAS with preserved LVEF. For these patients, observed survival at 10, 15 and 18 years was 86.6% (95%CI, 85.3-87.8), 75% (95%CI, 72.7-77.2), and 63.5% (95%CI, 58.8-67.8). Expected survival at 10, 15 and 18 years was 90.2%, 82.1%, and 75.7%. In the matched sample, survival of patients with low-gradient SAS with preserved LVEF was similar to that of patients with high-gradient with preserved LVEF, log-rank test, P=.95; HR=1 (95%CI, 0.7-1.4; P=.95). CONCLUSIONS: There is a loss of life expectancy in patients with all types of SAS undergoing SAVR. This loss is higher in patients with left ventricular dysfunction and lower in patients with low-gradient or high-gradient aortic stenosis with preserved LVEF. The benefit of surgery is similar between these last 2 groups.
Asunto(s)
Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Humanos , Válvula Aórtica/diagnóstico por imagen , Válvula Aórtica/cirugía , Volumen Sistólico , Función Ventricular Izquierda , Resultado del Tratamiento , Pronóstico , Estenosis de la Válvula Aórtica/diagnóstico , Estenosis de la Válvula Aórtica/cirugía , Esperanza de Vida , Índice de Severidad de la Enfermedad , Estudios RetrospectivosRESUMEN
INTRODUCTION AND OBJECTIVES: In young patients with severe aortic stenosis, it is unknown whether their life expectancy restored after aortic valve replacement (AVR) is unknown. METHODS: We analyzed all patients aged between 50 and 65 years who underwent isolated AVR in 27 Spanish centers during an 18-year period. We compared observed and expected survival at 15 years of follow-up. We repeated all analyses for patients without complications in the postoperative period. RESULTS: A total of 5084 patients were analyzed. For the overall sample, observed survival at 10 and 15 years was 85.3% (95%CI, 84.1%-86.4%) and 73.7% (95%CI, 71.6%-75.6%), respectively. Expected survival was 90.1% and 82.1%. Cumulative relative survival for 1, 5, 10 and 15 years of follow-up was 97.4% (95%CI, 96.9%-97.9%), 96.5% (95%CI, 95.7%-97.3%), 94.7% (95%CI, 93.3%-95.9%), and 89.8% (95%CI, 87.3%-92.1%). For patients without complications, cumulative relative survival for 1, 5, 10 and 15 years was 100.3% (95%CI, 99.8%-100.5%), 98.9% (95%CI 97.6% -99.9%), 97.3% (95%CI, 94.9%-99.4%), and 91.9% (95%CI, 86.5%-96.8%). CONCLUSIONS: Life expectancy in young patients who have severe aortic stenosis and undergo AVR is lower than that of the general population. Life expectancy of individuals without complications during the postoperative period is also reduced. Therefore, baseline characteristics are likely the main factors that explain the reduction in life expectancy.
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Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Anciano , Válvula Aórtica/cirugía , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Esperanza de Vida , Persona de Mediana Edad , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
OBJECTIVES: Some researchers have observed an increased number of deaths during the follow-up of young patients who undergo aortic valve replacement due to severe aortic stenosis, suggesting that this procedure does not restore their life expectancy. Our goal was to confirm these findings and explore sex-based differences. METHODS: All patients between 50 and 65 years of age who underwent isolated aortic valve replacement in 27 Spanish centres during an 18-year period were included. We compared observed and expected survival at 15 years of follow-up and estimated the cumulative incidence of death from a competing risks point of view. We stratified by sex and analysed if being a woman was an independent risk factor for death. RESULTS: For men, the observed survival at 10 and 15 years of follow-up was 85% [95% confidence interval (CI) 83.6%-86.4%] and 72.3% (95% CI 69.7%-74.7%), respectively whereas the expected survival was 88.1% and 78.8%. For women, the observed survival at 10 and 15 years was 85% (95% CI 82.8%-86.9%) and 73% (95% CI 69.1%-76.4%), whereas the expected survival was 94.6% and 89.4%. At 15 years of follow-up, the cumulative incidence of death due to the disease in men and women was 8.2% and 16.7%, respectively. In addition, being a woman was an independent risk factor for death (hazard ratio = 1.23 (95% CI 1.02-1.48; P = 0.03). CONCLUSIONS: After the aortic valve replacement, men and women do not have their life expectancy restored, but this loss is much higher in women than in men. In addition, being a woman is a risk factor for long-term death. Reasons for these findings are unknown and must be investigated.
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Estenosis de la Válvula Aórtica , Implantación de Prótesis de Válvulas Cardíacas , Prótesis Valvulares Cardíacas , Reemplazo de la Válvula Aórtica Transcatéter , Válvula Aórtica/cirugía , Estenosis de la Válvula Aórtica/cirugía , Femenino , Implantación de Prótesis de Válvulas Cardíacas/efectos adversos , Humanos , Esperanza de Vida , Masculino , Factores de Riesgo , Reemplazo de la Válvula Aórtica Transcatéter/efectos adversos , Resultado del TratamientoRESUMEN
We present the clinical case of a 60-year-old woman complained of dyspnea on exertion. Echocardiogram showed a giant mass in the right ventricle (RV) with obstruction to the outflow tract. Thorax computed tomography confirmed a mass of greater than 60 mm infiltrating RV and causing severe stenosis in the pulmonary artery, with severe pericardial effusion. Cardiac surgery was performed for tumor resection and pulmonary root replacement with a biological valved conduit. Histological analysis diagnosed a poorly differentiated large-cell neuroendocrine carcinoma. The patient had no immediate postoperative complications and has completed radiotherapy at a 9-month follow-up.
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Carcinoma Neuroendocrino/diagnóstico por imagen , Carcinoma Neuroendocrino/cirugía , Procedimientos Quirúrgicos Cardíacos/métodos , Ecocardiografía , Neoplasias Cardíacas/diagnóstico por imagen , Neoplasias Cardíacas/cirugía , Ventrículos Cardíacos/diagnóstico por imagen , Ventrículos Cardíacos/cirugía , Arteria Pulmonar/diagnóstico por imagen , Arteria Pulmonar/cirugía , Tomografía Computarizada por Rayos X , Implantación de Prótesis Vascular/métodos , Carcinoma Neuroendocrino/complicaciones , Carcinoma Neuroendocrino/patología , Constricción Patológica/diagnóstico por imagen , Constricción Patológica/etiología , Constricción Patológica/cirugía , Femenino , Neoplasias Cardíacas/complicaciones , Neoplasias Cardíacas/patología , Ventrículos Cardíacos/patología , Humanos , Persona de Mediana Edad , Derrame Pericárdico/diagnóstico por imagen , Derrame Pericárdico/etiología , Arteria Pulmonar/patología , Índice de Severidad de la Enfermedad , Resultado del TratamientoRESUMEN
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Humanos , Femenino , Persona de Mediana Edad , Dolor en el Pecho/etiología , Disnea/complicaciones , Bloqueo de Rama/diagnóstico por imagen , Pericardio/patología , Electrocardiografía/métodos , Radiografía Torácica , Bloqueo de Rama/tratamiento farmacológico , Pericardio/cirugíaAsunto(s)
Bloqueo de Rama/etiología , Dolor en el Pecho/etiología , Disnea/etiología , Quiste Mediastínico/complicaciones , Femenino , Humanos , Quiste Mediastínico/diagnóstico por imagen , Quiste Mediastínico/cirugía , Persona de Mediana Edad , Pericardio/diagnóstico por imagen , Radiografía TorácicaRESUMEN
Toxoplasma gondii pathogenesis includes the invasion of host cells by extracellular parasites, replication of intracellular tachyzoites, and differentiation to a latent bradyzoite stage. We present the analysis of seven novel T. gondii insertional mutants that do not undergo normal differentiation to bradyzoites. Microarray quantification of the variation in genome-wide RNA levels for each parasite line and times after induction allowed us to describe states in the normal differentiation process, to analyze mutant lines in the context of these states, and to identify genes that may have roles in initiating the transition from tachyzoite to bradyzoite. Gene expression patterns in wild-type parasites undergoing differentiation suggest a novel extracellular state within the tachyzoite stage. All mutant lines exhibit aberrant regulation of bradyzoite gene expression and notably some of the mutant lines appear to exhibit high proportions of the intracellular tachyzoite state regardless of whether they are intracellular or extracellular. In addition to the genes identified by the insertional mutagenesis screen, mixture model analysis allowed us to identify a small number of genes, in mutants, for which expression patterns could not be accounted for using the three parasite states--genes that may play a mechanistic role in switching from the tachyzoite to bradyzoite stage.
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Mutación , Toxoplasma/genética , Toxoplasma/metabolismo , Análisis por Conglomerados , Perfilación de la Expresión Génica , Genes Protozoarios/genética , Modelos Genéticos , Modelos Estadísticos , Análisis de Secuencia por Matrices de Oligonucleótidos , Fenotipo , Reacción en Cadena de la Polimerasa/métodos , Factores de Tiempo , Toxoplasma/fisiología , Transcripción Genética , Regulación hacia ArribaRESUMEN
Signaling via the NF-kappaB cascade is critical for innate recognition of microbial products and immunity to infection. As a consequence, this pathway represents a strong selective pressure on infectious agents and many parasitic, bacterial and viral pathogens have evolved ways to subvert NF-kappaB signaling to promote their survival. Although the mechanisms utilized by microorganisms to modulate NF-kappaB signaling are diverse, a common theme is targeting of the steps that lead to IkappaB degradation, a major regulatory checkpoint of this pathway. The data presented here demonstrate that infection of mammalian cells with Toxoplasma gondii results in the activation of IKK and degradation of IkappaB. However, despite initiation of these hallmarks of NF-kappaB signaling, neither nuclear accumulation of NF-kappaB nor NF-kappaB-driven gene expression is observed in infected cells. However, this defect was not due to a parasite-mediated block in nuclear import, as general nuclear import and constitutive nuclear-cytoplasmic shuttling of NF-kappaB remain intact in infected cells. Rather, in T. gondii-infected cells, the termination of NF-kappaB signaling is associated with reduced phosphorylation of p65/RelA, an event involved in the ability of NF-kappaB to translocate to the nucleus and bind DNA. Thus, these studies demonstrate for the first time that the phosphorylation of p65/RelA represents an event downstream of IkappaB degradation that may be targeted by pathogens to subvert NF-kappaB signaling.