Plasma Vanin-1 as a Novel Biomarker of Sepsis for Trauma Patients: A Prospective Multicenter Cohort Study

血浆Vanin-1作为创伤患者脓毒症的新型生物标志物:一项前瞻性多中心队列研究

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Abstract

INTRODUCTION: Vanin-1 plays a pivotal role in oxidative stress and the inflammatory response. However, its relationship with traumatic sepsis remains unknown. The aim of our study was to evaluate whether plasma vanin-1 could be used for the early prediction of traumatic sepsis. METHODS: In this three-stage prospective cohort study, severe trauma patients admitted from January 2015 to October 2018 at two hospitals were enrolled. Plasma vanin-1 levels were measured by enzyme-linked immunosorbent assay (ELISA). The associations among variables and traumatic sepsis were identified by logistic regression models and the receiver operating characteristic (ROC) curve was analyzed to evaluate the diagnostic efficiency. RESULTS: A total of 426 trauma patients (22 in the discovery cohort, 283 in the internal test cohort, and 121 in the external validation cohort) and 16 healthy volunteers were recruited. The plasma vanin-1 of trauma patients was significantly higher than that of healthy volunteers (P < 0.05). Patients with sepsis had higher plasma vanin-1 than patients without sepsis in the discovery trauma cohort (P < 0.05). In the internal test cohort, plasma vanin-1 at day 1 after trauma was significantly associated with the incidence of sepsis (OR = 3.92, 95% CI 2.68-5.72, P = 1.62 × 10(-12)). As a predictive biomarker, vanin-1 afforded a better area under the curve (AUC) (0.82, 95% CI 0.77-0.87) than C-reaction protein (CRP) (0.62, 95% CI 0.56-0.68, P < 0.0001), procalcitonin (PCT) (0.66, 95% CI 0.60-0.71, P < 0.0001), and Acute Physiology and Chronic Health Evaluation II (APACHE II) (0.71, 95% CI 0.65-0.76, P = 6.70 × 10(-3)). The relevance was further validated in the external validation cohort (OR = 4.26, 95% CI 2.22-8.17, P = 1.28 × 10(-5)), with an AUC of 0.83 (95% CI 0.75-0.89). Vanin-1 could also improve the diagnostic efficiency of APACHE II (AUC = 0.85). CONCLUSIONS: Our study demonstrated that plasma vanin-1 increased among trauma patients and was independently associated with the risk of sepsis. Vanin-1 might be a potential biomarker for the early prediction of traumatic sepsis. TRIAL REGISTRATION: Clinicaltrials.gov Identifier, NCT01713205.

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