Role of age and comorbidities in mortality of patients with infective endocarditis.

PURPOSE: The aim of this study was to analyse the characteristics of patients with IE in three groups of age and to assess the ability of age and the Charlson Comorbidity Index (CCI) to predict mortality. METHODS: Prospective cohort study of all patients with IE included in the GAMES Spanish database between 2008 and 2015.Patients were stratified into three age groups:<65 years,65 to 80 years,and ≥ 80 years.The area under the receiver-operating characteristic (AUROC) curve was calculated to quantify the diagnostic accuracy of the CCI to predict mortality risk. RESULTS: A total of 3120 patients with IE (1327 < 65 years;1291 65-80 years;502 ≥ 80 years) were enrolled.Fever and heart failure were the most common presentations of IE, with no differences among age groups.Patients ≥80 years who underwent surgery were significantly lower compared with other age groups (14.3%,65 years; 20.5%,65-79 years; 31.3%,≥80 years). In-hospital mortality was lower in the <65-year group (20.3%,<65 years;30.1%,65-79 years;34.7%,≥80 years;p < 0.001) as well as 1-year mortality (3.2%, <65 years; 5.5%, 65-80 years;7.6%,≥80 years; p = 0.003).Independent predictors of mortality were age ≥ 80 years (hazard ratio [HR]:2.78;95% confidence interval [CI]:2.32-3.34), CCI ≥ 3 (HR:1.62; 95% CI:1.39-1.88),and non-performed surgery (HR:1.64;95% CI:11.16-1.58).When the three age groups were compared,the AUROC curve for CCI was significantly larger for patients aged <65 years(p < 0.001) for both in-hospital and 1-year mortality. CONCLUSION: There were no differences in the clinical presentation of IE between the groups. Age ≥ 80 years, high comorbidity (measured by CCI),and non-performance of surgery were independent predictors of mortality in patients with IE.CCI could help to identify those patients with IE and surgical indication who present a lower risk of in-hospital and 1-year mortality after surgery, especially in the <65-year group.

A549 cells as a model to study endogenous LPA1 receptor signaling and regulation.

Lysophosphatidic acid (LPA) modulates the function of many organs, including the lung. A549 is a lung carcinoma-derived cell line, frequently used as a model for type II pneumocytes. Here we show that these cells expressed messenger RNA coding for LPA1-3 receptors with the following order of abundance: LPA1 > LPA2 > LPA3 and that LPA was able to increase intracellular calcium, extracellular signal-regulated kinases 1/2 phosphorylation, and cell contraction. These effects were blocked by Ki16425, an antagonist selective for LPA1 and LPA3 receptors, and by the LPA1-selective antagonist, AM095. Activation of protein kinase C inhibited LPA-induced intracellular calcium increase. This action was blocked by protein kinase C inhibitors and enzyme down-regulation. Phorbol myristate acetate and AM095, but not Ki16425, decreased the baseline intracellular calcium concentration. Ki16425 blocked the effect of AM095 but not that of phorbol myristate acetate. The data indicate that LPA1 receptors exhibit constitutive activity and that AM095 behaves as an inverse agonist, whereas Ki16425 appears to be a classic antagonist. Furthermore, the LPA agonist, 1-oleoyl-2-O-methyl-rac-glycerophosphothionate, OMPT, induced a weak increase in intracellular calcium, but was able to induce full ERK 1/2 phosphorylation and cell contraction. These effects were blocked by AM095. These data suggest that OMPT is a biased LPA1 agonist. A549 cells express functional LPA1 receptors and seem to be a suitable model to study their signaling and regulation.

Cardiomiopatia de Takotsubo: Um diagnóstico diferencial da síndrome coronariana aguda: revisão de literatura / Takotsubo cardiomyopathy: a differential diagnosis of the acute coronary syndrome: review of the literature

A cardiomiopatia de Takotsubo, também conhecida como síndrome do balonamento apical transitório do ventrículo esquerdo, foi recentemente descrita no Japão, frequentemente desencadeada por intenso estresse, que apresenta características clínicas, eletrocardiográficas e laboratoriais semelhantes à síndrome coronariana aguda. A realização de um estudo hemodinâmico é, portanto, crucial para sua confirmação diagnóstica, desde que a abordagem terapêutica do infarto agudo do miocárdio é diferente da cardiomiopatia de Takotsubo. O objetivo deste artigo é esclarecer a fisiopatologia, diagnóstico e tratamento dessa entidade nosológica. Presume-se que 1 a 2% dos diagnósticos iniciais de síndrome coronariana aguda sejam cardiomiopatia de Takotsubo, que só é confirmada após a realização de cineangiocoronariografia e ventriculografia. A sua fisiopatologia permanece indefinida, mas sabe-se que deve ser tratada diferentemente do infarto agudo do miocárdio e seu prognóstico é mais favorável.

Takotsubo cardiomyopathy, also known as transient apical ballooning syndrome of the left ventricle, was recently described in Japan, often triggered by intense stress, which presents clinical, electrocardiographic and laboratory findings similar to acute coronary syndrome. The realization of a hemodynamic study is therefore crucial for diagnostic confirmation, since the therapeutic approaches to acute myocardial infarction is different from Takotsubo cardiomyopathy.The aim of this paper is to clarify the pathophysiology, diagnosis and treatment of this illness. It is assumed that 1-2% of the initial diagnosis of acute coronary syndrome are Takotsubo cardiomyopathy, which is confirmed only after coronary angiography and ventriculography are performed. Its pathophysiology remains unclear, but it is known it must to be treated differently from acute myocardial infarction and its prognosis is more favorable.