Prognostic Trends and Current Challenges in Candidemia: A Comparative Analysis of Two Multicenter Cohorts within the Past Decade.

Candidemia remains a major public health challenge due to its high mortality rates, especially in developing countries. Monitoring epidemiological trends may provide insights for better clinical outcomes. This study aimed to describe trends in the epidemiology, therapeutic practices, and mortality in candidemia through a retrospective comparative analysis between two surveillance cohorts of all candidemic adults at eleven tertiary hospitals in Brazil, from 2010-2011 (Period I) versus 2017-2018 (Period II). A total of 616 cases were diagnosed, with 247 being from Period II. These patients were more likely to have three or more coexisting comorbidities [72 (29.1%) vs. 60 (16.3%), p < 0.001], had a prior history of in-hospital admissions more often [102 (40.3%) vs. 79 (21.4%), p = 0.001], and presented with candidemia earlier after admission, within 15 days (0-328) vs. 19 (0-188), p = 0.01. Echinocandins were more frequently prescribed [102 (41.3%) vs. 50 (13.6%), p = 0.001], but time to antifungal initiation [2 days (0-14) vs. 2 (0-13), p = 0.369] and CVC removal within 48 h [90/185 (48.6%) vs. 148/319 (46.4%), p = 0.644] remained unchanged. Additionally, many patients went untreated in both periods I and II [87 (23.6%) vs. 43 (17.4%), p = 0.07], respectively. Unfortunately, no improvements in mortality rates at 14 days [123 (33.6%) vs. 93 (37.7%), p = 0.343] or at 30 days [188 (51.4%) vs. 120 (48.6%), p = 0.511] were observed. In conclusion, mortality rates remain exceedingly high despite therapeutic advances, probably associated with an increase in patients' complexity and suboptimal therapeutic interventions. Management strategies should be tailored to suit epidemiological changes, expedite diagnosis to reduce the number of untreated eligible patients and guarantee early antifungal initiation and source control.

Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe.

BACKGROUND: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. OBJECTIVE: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. METHODS: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. RESULTS: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. CONCLUSION: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Endothelial Effect of Statin Therapy at a High Dose Versus Low Dose Associated with Ezetimibe / Efeito Endotelial da Terapia com Estatina em Alta Dose versus Baixa Dose Associada à Ezetimiba

Abstract Background: The effect of statins on the endothelial function in humans remains under discussion. Particularly, it is still unclear if the improvement in endothelial function is due to a reduction in LDL-cholesterol or to an arterial pleiotropic effect. Objective: To test the hypothesis that modulation of the endothelial function promoted by statins is primarily mediated by the degree of reduction in LDL-cholesterol, independent of the dose of statin administered. Methods: Randomized clinical trial with two groups of lipid-lowering treatment (16 patients/each) and one placebo group (14 patients). The two active groups were designed to promote a similar degree of reduction in LDL-cholesterol: the first used statin at a high dose (80 mg, simvastatin 80 group) and the second used statin at a low dose (10 mg) associated with ezetimibe (10 mg, simvastatin 10/ezetimibe group) to optimize the hypolipidemic effect. The endothelial function was assessed by flow-mediated vasodilation (FMV) before and 8 weeks after treatment. Results: The decrease in LDL-cholesterol was similar between the groups simvastatin 80 and simvastatin 10/ezetimibe (27% ± 31% and 30% ± 29%, respectively, p = 0.75). The simvastatin 80 group presented an increase in FMV from 8.4% ± 4.3% at baseline to 11% ± 4.2% after 8 weeks (p = 0.02). Similarly, the group simvastatin 10/ezetimibe showed improvement in FMV from 7.3% ± 3.9% to 12% ± 4.4% (p = 0.001). The placebo group showed no variation in LDL-cholesterol level or endothelial function. Conclusion: The improvement in endothelial function with statin seems to depend more on a reduction in LDL-cholesterol levels, independent of the dose of statin administered, than on pleiotropic mechanisms.

Resumo Fundamento: O efeito das estatinas na função endotelial em seres humanos permanece em discussão. Particularmente, ainda carece resposta se a melhora na função endotelial deve-se à redução do LDL-colesterol ou a um efeito pleiotrópico arterial. Objetivo: Testar a hipótese de que a modulação da função endotelial promovida por estatinas é prioritariamente mediada pelo grau de redução do LDL-colesterol, independente da dose de estatina utilizada. Métodos: Ensaio clínico randomizado com dois grupos de tratamento hipolipemiante (16 pacientes/cada) e um grupo placebo (14 pacientes). Os dois grupos ativos foram desenhados para promover graus semelhantes de redução de LDL-colesterol: o primeiro utilizou estatina em alta dose (80 mg, grupo sinvastatina 80) e o segundo em baixa dose (10 mg) associada a ezetimiba (10 mg, grupo sinvastatina 10/ezetimiba) para otimizar o efeito hipolipemiante. A função endotelial foi analisada pela vasodilatação mediada por fluxo (VMF) antes e após 8 semanas de tratamento. Resultados: A redução no LDL-colesterol foi semelhante entre os grupos sinvastatina 80 e sinvastatina 10/ezetimiba (27% ± 31% e 30% ± 29%, respectivamente, p = 0,75). O grupo sinvastatina 80 apresentou incremento da VMF de 8,4% ± 4,3% no basal para 11% ± 4,2% após 8 semanas (p = 0,02). Da mesma forma, o grupo sinvastatina 10/ezetimiba apresentou melhora da VMF de 7,3% ± 3,9% para 12% ± 4,4% (p = 0,001). O grupo placebo não apresentou variação no nível de LDL-colesterol ou da função endotelial. Conclusão: A melhora da função endotelial com uso de estatina parece depender mais da redução do LDL-colesterol, independente da dose de estatina utilizada, do que de mecanismos pleiotrópicos.

Prognostic value of endothelial function in patients with atherosclerosis: systematic review.

Analysis of flow-mediated vasodilation (FMV) of the brachial artery by use of ultrasound allows assessing endothelial function, and provides pathophysiological, diagnostic and prognostic information. This systematic review was aimed at assessing the literature level of evidence of the predictive capacity of endothelial function, measured through brachial artery FMV by use of ultrasound, regarding cardiovascular events in individuals with atherosclerosis. The MEDLINE, SCIELO and LILACS databases were searched, and prospective cohort studies on human beings about the prognostic value of endothelial function, measured by use of brachial artery FMV in individuals with peripheral or coronary atherosclerosis, were selected. Studies with clear methodological biases were excluded. The final selection consisted of 15 studies. Of the 13 studies that on univariate analysis showed statistical significance of the FMV method to predict cardiovascular events, 12 showed independent predictive capacity on multivariate analysis. None of the studies reviewed described the incremental predictive value of FMV to the traditional predictive models, such as the Framingham score. Results of three studies have suggested that the method adds prognostic value to isolated markers such as ankle-brachial index (ABI), diabetes, and high-sensitivity C-reactive protein (hsCRP). In conclusion, brachial artery FMV predicts cardiovascular risk, but its incremental predictive value to clinical prognostic models has not been established. In addition, solid evidence supporting its use in routine clinical practice to predict cardiovascular risk still lacks.

Valor prognóstico da função endotelial em portadores de aterosclerose: revisão sistemática / Prognostic value of endothelial function in patients with atherosclerosis: systematic review

A Vasodilatação Mediada por Fluxo (VMF) da artéria braquial, por meio da ultrassonografia, é um método de avaliação da função endotelial que pode oferecer informações fisiopatológicas, diagnósticas e prognósticas. A realização dessa revisão sistemática objetivou avaliar o nível de evidência na literatura a respeito da capacidade preditora da função endotelial, medida pela VMF da artéria braquial, por meio da ultrassonografia, quanto a eventos cardiovasculares, em indivíduos portadores de aterosclerose. Foram realizadas buscas nas bases de dados MEDLINE, SCIELO e LILACS e selecionados estudos de coorte prospectivos, em seres humanos, que analisaram o valor prognóstico da função endotelial medida pela VMF da artéria braquial, em populações portadoras de doença aterosclerótica, periférica ou coronariana. Trabalhos com evidentes vieses metodológicos foram excluídos. A seleção final constituiu-se de 15 estudos. Dos 13 estudos que, na análise univariada, mostraram significância estatística do método da VMF na predição de eventos cardiovasculares, 12 deles demonstraram sua capacidade preditora independente, em análise multivariada. Em nenhum dos trabalhos foi descrito valor prognóstico incremental em relação a modelos preditores tradicionais, como escore de Framingham. Resultados de três trabalhos sugerem que o método agrega valor prognóstico a marcadores isolados como: Índice Tornozelo-Braquial (ITB), diabetes e Proteína C Reativa (PCR) de alta sensibilidade. Em conclusão, a VMF da artéria braquial prediz risco cardiovascular, porém não é estabelecido seu valor preditor incremental a modelos prognósticos clínicos, não havendo, até o momento, evidências sólidas que amparem seu uso na rotina clínica para predição de risco cardiovascular.

Analysis of flow-mediated vasodilation (FMV) of the brachial artery by use of ultrasound allows assessing endothelial function, and provides pathophysiological, diagnostic and prognostic information. This systematic review was aimed at assessing the literature level of evidence of the predictive capacity of endothelial function, measured through brachial artery FMV by use of ultrasound, regarding cardiovascular events in individuals with atherosclerosis. The MEDLINE, SCIELO and LILACS databases were searched, and prospective cohort studies on human beings about the prognostic value of endothelial function, measured by use of brachial artery FMV in individuals with peripheral or coronary atherosclerosis, were selected. Studies with clear methodological biases were excluded. The final selection consisted of 15 studies. Of the 13 studies that on univariate analysis showed statistical significance of the FMV method to predict cardiovascular events, 12 showed independent predictive capacity on multivariate analysis. None of the studies reviewed described the incremental predictive value of FMV to the traditional predictive models, such as the Framingham score. Results of three studies have suggested that the method adds prognostic value to isolated markers such as ankle-brachial index (ABI), diabetes, and high-sensitivity C-reactive protein (hsCRP). In conclusion, brachial artery FMV predicts cardiovascular risk, but its incremental predictive value to clinical prognostic models has not been established. In addition, solid evidence supporting its use in routine clinical practice to predict cardiovascular risk still lacks.