Níveis Elevados de Netrina-1 e IL-1β em Mulheres Idosas com SCA: Pior Prognóstico no Acompanhamento de Dois Anos / High Serum Netrin-1 and IL-1β in Elderly Females with ACS: Worse Prognosis in 2-years Follow-up

Resumo Fundamento Vários marcadores têm sido avaliados quanto a um potencial impacto nas decisões clínicas ou na predição de mortalidade na síndrome coronariana aguda (SCA), incluindo Netrina-1 e IL-1β. Objetivo Examinamos o valor prognóstico de Netrina-1 e IL-1β em pacientes com SCA (2 anos de acompanhamento). Métodos Avaliamos Netrina-1, IL-1β e outros fatores de risco em amostras de soro de 803 pacientes. Curvas de Kaplan-Meier e regressão de Cox foram usadas para análise de óbito por todas as causas, óbito por doenças cardiovasculares (DCV) e desfecho combinado de infarto agudo do miocárdio (IAM) fatal ou novo IAM não fatal, considerando p < 0,05. Resultados Houve 115 óbitos por todas as causas, 78 óbitos por DCV e 67 eventos no desfecho combinado. Níveis de Netrina-1 acima da mediana (> 44,8 pg/mL) foram associados a pior prognóstico (óbito por todas as causas e por DCV) em mulheres idosas, mesmo após o ajuste do modelo (HR: 2,08, p = 0,038 e HR: 2,68, p = 0,036). Níveis de IL-1β acima da mediana (> 13,4 pg/mL) em mulheres idosas foram associados a risco aumentado para todos os desfechos após o ajuste (todas as causas - HR: 2,03, p = 0,031; DCV - HR: 3,01, p = 0,013; desfecho combinado - HR: 3,05, p = 0,029). Para homens, não foram observadas associações entre Netrina-1 ou IL-1β e os desfechos. Conclusão Níveis séricos elevados de Netrina-1 e IL-1β mostraram associação significativa com pior prognóstico em idosas do sexo feminino. Eles podem ser úteis como indicadores prognósticos em SCA. (Arq Bras Cardiol. 2020; 114(3):507-514)

Abstract Background Several markers have been evaluated for a potential impact on clinical decisions or mortality prediction in acute coronary syndrome (ACS), including Netrin-1 and IL-1β that have been associated with cardiovascular disease. Objective Our study examined the prognostic value of Netrin-1 and IL-1β in patients with ACS (2-year follow-up). Methods We evaluate Netrin-1, IL-1β and other risk factors in the serum sample of 803 patients. Kaplan-Meier curves and Cox regression were used for the analysis of all-cause mortality, cardiovascular mortality, and a combined outcome of fatal myocardial infarction (MI) or new non-fatal MI, considering p-value < 0.05. Results There were 115 deaths from all causes, 78 deaths due to cardiovascular causes and 67 events in combined outcomes. Netrin-1 levels above the median (>44.8 pg/mL) were associated with a worse prognosis (all-cause mortality and cardiovascular mortality) in elderly females, even after model adjustment (HR: 2.08, p = 0.038 and HR: 2.68, p = 0.036). IL-1β levels above the median (>13.4 pg/mL) in elderly females were associated with increased risk of all outcomes after adjustment (all-cause mortality - HR: 2.03, p = 0.031; cardiovascular mortality - HR: 3.01, p = 0.013; fatal MI or new non-fatal MI - HR: 3.05, p = 0.029). For males, no associations were observed between Netrin-1 or IL-1β and outcomes. Conclusion High serum levels of Netrin-1 and IL-1β showed significant association with worse prognosis in elderly females. They may be useful as prognostic indicators in ACS. (Arq Bras Cardiol. 2020; 114(3):507-514)

Netrin 1 and Alpha-Methyl Acylcoenzim-A Racemase in diagnosis of prostate cancer / Netrina 1 y Alfa Metil-Acil coenzima-A Racemasa para el diagnóstico de cáncer de próstata

Abstract Objectives: To investigate serum and urine levels of Alpha-methylacyl-CoA-racemase (AMACR) and Netrin 1 in patients with and without prostate cancer and to determine whether these markers could be used as alternatives in diagnosis of prostate cancer instead of serum prostate specific antigen (PSA) levels. Methods: One hundred and seventy five patients between 45-75 years to whom transrectal ultrasound guided biopsies were performed for abnormal serum PSA levels or digital rectal examinations were included. The levels of AMACR and Netrin 1 levels of blood and urine samples of 5 mL those were taken prior to biopsies were measured. . Results: The mean age of the patients was 62.7 ±6.4 years. Prostate cancer was detected in 40 patients (22.8%) while 135 of them (77.2%) were diagnosed as benign prostate hyperplasia (BPH). In BPH group, serum and urine levels of AMACR and Netrin 1 were 13.4 ±16.9 ng/mL; 7.1 ±3.4 ng/mL; 164.1±46 pg/mL and 19.5 ±5.0 pg/mL respectively. The levels of serum and urine levels of AMACR and Netrin 1 were 10.2 ±9.8 ng/mL; 6.8 ±2.5 ng/mL; 159.1 ±44.1 pg/mL and 20.1 ±5.3 pg/mL respectively in prostate cancer group. There was no statistically significant difference or correlation between these two groups serum and urine AMACR and Netrin 1 results Conclusions: Serum and urine levels of AMACR and Netrin 1 were not found to be alternatives for serum PSA levels in the diagnosis of prostate cancer in this study.

Resumen Objetivos: Investigar los niveles de alfa-metil acilcoenzima-A y Netrina 1 en pacientes con y sin cáncer de próstata y determinar si estos marcadores pueden ser usados como una alternativa en el diagnóstico de cáncer de próstata en lugar del antígeno prostático específico en suero (PSA). Métodos: Fueron incluidos 175 pacientes entre 45-75 años, a quienes se les realizó una biopsia de próstata guiada por ultrasonido por presentar un nivel anormal de PSA en el suero o un tacto rectal. Se tomó una muestra de 5 mL de sangre y orina para medir los niveles de alfa-metil acilcoenzima-A y Netrina 1. Estos niveles se midieron antes del análisis de la biopsia. Resultados: La edad media de los pacientes fue de 62.7±6.4 años. Se detectó cander en 40 pacientes (22.8%), mientras que a 135 de ellos (77.2%) se les diagnóstico una hiperplasia benigna de próstata (HBP). En el grupo HBP los niveles en suero y orina de alfa-metil acilcoenzima-A y Netrina 1 fueron 13.4 ±16.9 ng/mL; 7.1 ±3.4 ng/mL; 164.1 ±46 pg/mL y 19.5 ±5.0 pg/mL respectivamente. En el grupo con cáncer de próstata los niveles en suero y orina de alfa-metil acilcoenzima-A y Netrina 1 fueron 10.2 ±9.8 ng/mL; 6.8 ±2.5 ng/mL; 159.1 ±44.1 pg/mL y 20.1 ±5.3 pg/mL respectivamente. No hubo una diferencia significativa o una correlación entre los niveles de alfa-metil acilcoenzima-A y Netrina 1 en suero y orina al comparar estos dos grupos de pacientes. Conclusiones: Los niveles de alfa-metil acilcoenzima-A y Netrina 1 en suero y orina no son una alternativa para reemplazar el PSA en suero para el diagnóstico de cáncer de próstata.