[Acute aortic regurgitation due to infective endocarditis]. / Insuficiencia aórtica aguda por endocarditis infecciosa.

Acute aortic regurgitation (AAR) due to infective endocarditis (IE) is a serious disease and usually requires surgical treatment. Our study aims to compare the clinical, echocardiographic, and microbiological characteristics as well as in-hospital outcome of patients with AAR according to the severity of heart failure (HF) and to evaluate predictors of in-hospital mortality in a tertiary centre. In a prospective analysis, we compared patients with NYHA functional class I-II HF (G1) vs. functional class III-IV HF (G2). From 06/92 to 07/16, 439 patients with IE were hospitalized; 86 presented AAR: (G1, 39: 45.4% y G2, 47: 54.7%). The G1 had higher prosthetic IE (43.6% vs. 17%, p 0.01). All G2 patients had dyspnoea vs. 30.8% of the G1 (p < 0.0001). There were no differences in clinical, echocardiographic and microbiological characteristics. Surgical treatment was indicated mainly due to infection extension or valvular dysfunction in G1 and HF in G2. In-hospital mortality was 15.4% vs. 27.7% (G1 and G2 respectively p NS). In multivariate analysis, health care-associated acquisition (p 0.001), negative blood cultures (p 0.004), and functional class III-IV HF (p 0.039) were in-hospital mortality predictors. One-fifth of the patients with EI had AAR. Half of them had severe HF which needed emergency surgery and the remaining needed surgery for extension of the infection and / or valvular dysfunction. Both groups remain to have high surgical and in-hospital mortality. Health care-associated acquisition, negative blood cultures and advanced HF were predictors of in-hospital mortality.

Insuficiencia aórtica aguda por endocarditis infecciosa / Acute aortic regurgitation due to infective endocarditis

La insuficiencia aórtica aguda (IAOA) por endocarditis infecciosa (EI) es grave y generalmente requiere tratamiento quirúrgico. Se compararon los pacientes con IAOA grave por EI e insuficiencia cardíaca (IC) en clase funcional I-II NYHA (G1) con los pacientes en clase funcional III-IV (G2) en relación a características clínicas, ecocardiográficas, microbiológicas y evolución hospitalaria y se evaluaron los predictores de mortalidad, en un centro de alta complejidad. Desde 06/92 a 07/16, de 439 pacientes con EI, 86 presentaron IAOA: (G1, 39: 45.4% y G2, 47: 54.7%). El G1 presentó mayor EI protésica (43.6% vs. 17.0%; p < 0.01). Los 47 casos G2 presentaban disnea vs. 12 (30.8%) G1 (p < 0.0001). No hubo diferencias en cuanto a las características clínicas, ecocardiográficas y microbiológicas. El tratamiento quirúrgico fue principalmente por extensión de la infección y/disfunción valvular en el G1 y por IC en el G2. La mortalidad hospitalaria fue del 15.4% vs. 27.7% (G1 y G2 respectivamente, p NS). Fueron predictores en el análisis multivariado: la infección intrahospitalaria (p 0.001), los hemocultivos negativos (p 0.004) y la presencia de IC clase funcional III-IV (p 0.039).Una quinta parte de los pacientes con EI presentaron IAOA. Aquellos con IC grave requirieron tratamiento quirúrgico de emergencia y con IC con clase funcional I-II requirieron cirugía por extensión de la infección y/o disfunción valvular. La mortalidad quirúrgica y hospitalaria continúan siendo elevadas en ambos grupos y fueron predictores de mortalidad hospitalaria: la infección intrahospitalaria, los hemocultivos negativos y la IC avanzada.

Acute aortic regurgitation (AAR) due to infective endocarditis (IE) is a serious disease and usually requires surgical treatment. Our study aims to compare the clinical, echocardiographic, and microbiological characteristics as well as in-hospital outcome of patients with AAR according to the severity of heart failure (HF) and to evaluate predictors of in-hospital mortality in a tertiary centre. In a prospective analysis, we compared patients with NYHA functional class I-II HF (G1) vs. functional class III-IV HF (G2). From 06/92 to 07/16, 439 patients with IE were hospitalized; 86 presented AAR: (G1, 39: 45.4% y G2, 47: 54.7%). The G1 had higher prosthetic IE (43.6% vs. 17%, p 0.01). All G2 patients had dyspnoea vs. 30.8% of the G1 (p < 0.0001). There were no differences in clinical, echocardiographic and microbiological characteristics. Surgical treatment was indicated mainly due to infection extension or valvular dysfunction in G1 and HF in G2. In-hospital mortality was 15.4% vs. 27.7% (G1 and G2 respectively p NS). In multivariate analysis, health care-associated acquisition (p 0.001), negative blood cultures (p 0.004), and functional class III-IV HF (p 0.039) were in-hospital mortality predictors. One-fifth of the patients with EI had AAR. Half of them had severe HF which needed emergency surgery and the remaining needed surgery for extension of the infection and / or valvular dysfunction. Both groups remain to have high surgical and in-hospital mortality. Health care-associated acquisition, negative blood cultures and advanced HF were predictors of in-hospital mortality.

Gestational hypothyroidism increases the severity of experimental autoimmune encephalomyelitis in adult offspring.

BACKGROUND: Maternal thyroid hormones play a fundamental role in appropriate fetal development during gestation. Offspring that have been gestated under maternal hypothyroidism suffer cognitive impairment. Thyroid hormone deficiency during gestation can significantly impact the central nervous system by altering the migration, differentiation, and function of neurons, oligodendrocytes, and astrocytes. Given that gestational hypothyroidism alters the immune cell ratio in offspring, it is possible that this condition could result in higher sensitivity for the development of autoimmune diseases. METHODS: Adult mice gestated under hypothyroidism were induced with experimental autoimmune encephalomyelitis (EAE). Twenty-one days after EAE induction, the disease score, myelin content, immune cell infiltration, and oligodendrocyte death were evaluated. RESULTS: We observed that mice gestated under hypothyroidism showed higher EAE scores after disease induction during adulthood compared to mice gestated in euthyroidism. In addition, spinal cord sections of mice gestated under hypothyroidism that suffered EAE in adulthood showed higher demyelination, CD4(+) and CD8(+) infiltration, and increased oligodendrocyte death. CONCLUSIONS: These results show for the first time that a deficiency in maternal thyroid hormones during gestation can influence the outcome of a central nervous system inflammatory disease, such as EAE, in their offspring. These data strongly support evaluating thyroid hormones in pregnant women and treating hypothyroidism during pregnancy to prevent increased susceptibility to inflammatory diseases in the central nervous system of offspring.

Impaired learning resulting from respiratory syncytial virus infection.

Respiratory syncytial virus (RSV) is the major cause of respiratory illness in infants worldwide. Neurologic alterations, such as seizures and ataxia, have been associated with RSV infection. We demonstrate the presence of RSV proteins and RNA in zones of the brain--such as the hippocampus, ventromedial hypothalamic nucleus, and brainstem--of infected mice. One month after disease resolution, rodents showed behavioral and cognitive impairment in marble burying (MB) and Morris water maze (MWM) tests. Our data indicate that the learning impairment caused by RSV is a result of a deficient induction of long-term potentiation in the hippocampus of infected animals. In addition, immunization with recombinant bacillus Calmette-Guérin (BCG) expressing RSV nucleoprotein prevented behavioral disorders, corroborating the specific effect of RSV infection over the central nervous system. Our findings provide evidence that RSV can spread from the airways to the central nervous system and cause functional alterations to the brain, both of which can be prevented by proper immunization against RSV.

Efficient lung recruitment of respiratory syncytial virus-specific Th1 cells induced by recombinant bacillus Calmette-Guérin promotes virus clearance and protects from infection.

Infection by the respiratory syncytial virus (RSV) can cause extensive inflammation and lung damage in susceptible hosts due to a Th2-biased immune response. Such a deleterious inflammatory response can be enhanced by immunization with formalin- or UV-inactivated RSV, as well as with vaccinia virus expressing the RSV-G protein. Recently, we have shown that vaccination with rBCG-expressing RSV Ags can prevent the disease in the mouse. To further understand the immunological mechanisms responsible for protection against RSV, we have characterized the T cell populations contributing to virus clearance in mice immunized with this BCG-based vaccine. We found that both CD4(+) and CD8(+) T cells were recruited significantly earlier to the lungs of infected mice that were previously vaccinated. Furthermore, we observed that simultaneous adoptive transfer of CD8(+) and CD4(+) RSV-specific T cells from vaccinated mice was required to confer protection against virus infection in naive recipients. In addition, CD4(+) T cells induced by vaccination released IFN-γ after RSV challenge, indicating that protection is mediated by a Th1 immune response. These data suggest that vaccination with rBCG-expressing RSV Ags can induce a specific effector/memory Th1 immune response consisting on CD4(+) and CD8(+) T cells, both necessary for a fully protective response against RSV. These results support the notion that an effective induction of Th1 T cell immunity against RSV during childhood could counteract the unbalanced Th2-like immune response triggered by the natural RSV infection.

Aldosterone promotes autoimmune damage by enhancing Th17-mediated immunity.

Excessive production of aldosterone leads to the development of hypertension and cardiovascular disease by generating an inflammatory state that can be promoted by T cell immunity. Because nature and intensity of T cell responses is controlled by dendritic cells (DCs), it is important to evaluate whether the function of these cells can be modulated by aldosterone. In this study we show that aldosterone augmented the activation of CD8(+) T cells in a DC-dependent fashion. Consistently, the mineralocorticoid receptor was expressed by DCs, which showed activation of MAPK pathway and secreted IL-6 and TGF-beta in response to aldosterone. In addition, DCs stimulated with aldosterone impose a Th17 phenotype to CD4(+) T cells, which have recently been associated with the promotion of inflammatory and autoimmune diseases. Accordingly, we observed that aldosterone enhances the progression of experimental autoimmune encephalomyelitis, an autoimmune disease promoted by Th17 cells. In addition, blockade of the mineralocorticoid receptor prevented all aldosterone effects on DCs and attenuated experimental autoimmune encephalomyelitis development in aldosterone-treated mice. Our data suggest that modulation of DC function by aldosterone enhances CD8(+) T cell activation and promotes Th17-polarized immune responses, which might contribute to the inflammatory damage leading to hypertension and cardiovascular disease.