Association of LVV-Hemorphin-7 with Sepsis and Shock: Roles of Cathepsin D and G in Hemoglobin Metabolism in a Prospective ICU Cohort Study

LVV-血吗啡肽-7 与脓毒症和休克的关系:前瞻性 ICU 队列研究中组织蛋白酶 D 和 G 在血红蛋白代谢中的作用

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作者:Yao-Kuang Wu, Hsueh-Wen Chung, Yi-Ting Chen, Hsing-Chun Chen, I-Hung Chen, Wen-Lin Su

Background

Sepsis is a leading cause of mortality in intensive care units (ICUs). Cell-free hemoglobin (CFH) released during sepsis interacts with lysosomal enzymes from neutrophils and macrophages. This study aims to examine the association of LVV-hemorphin-7 (LVV-H7), cathepsin D, and cathepsin G with sepsis and shock in ICU patients.

Conclusions

LVV-H7, cathepsin D, and cathepsin G are associated with the classification of sepsis and shock episodes in critically ill patients with elevated SOFA scores.

Methods

A prospective observational cohort study was conducted in the medical ICU of a tertiary referral hospital in Taiwan. The patients with an acute increasing sequential organ failure assessment (SOFA) score ≥ 2 between 2022 and 2023. Blood samples from 40 healthy controls were obtained from the hospital biobank. CFH metabolites, including LVV-H7 and lysosomal enzyme cathepsin D and cathepsin G, were compared between the sepsis (definite and probable) and non-sepsis (possible sepsis) groups. Multivariate logistic regression analyzed factors associated with sepsis and shock.

Results

Among 120 patients, 75 were classified as septic and 45 as non-septic. Significant differences were observed in CFH, cathepsin D, cathepsin G, and LVV-H7 levels between sepsis and non-sepsis groups. LVV-H7 was a significant predictor for sepsis (adjusted OR [aOR] 1.009, 95% CI 1.005-1.013; p < 0.001) and shock (aOR 1.005, 95% CI 1.002-1.008; p < 0.05). Cathepsin G predicted non-shock (aOR 0.917, 95% CI 0.848-0.991; p < 0.05), while cathepsin D predicted septic shock (aOR 1.001, 95% CI 1.000-1.002; p < 0.05). Conclusions: LVV-H7, cathepsin D, and cathepsin G are associated with the classification of sepsis and shock episodes in critically ill patients with elevated SOFA scores.

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