Serum NOX4 as a Promising Prognostic Biomarker in Association with 90-Day Outcome of Severe Traumatic Brain Injury

Abstract

Purpose Nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) is related to brain oxidative stress. We attempted to examine the association between serum NOX4 levels, severity and prognosis of severe traumatic brain injury (sTBI). Methods We measured serum NOX4 levels in 105 patients with sTBI. Trauma severity was assessed using Glasgow coma scale (GCS) and Rotterdam computed tomography (CT) classification. Study outcome data on death and worst outcome (Glasgow outcome scale score of 1–3) were collected at 90 days after trauma. Multivariate analyses were performed to determine independent factors for overall survival and worst outcome. Area under receiver operating characteristic curve (AUC) was estimated to assess prognostic predictive ability. Results Serum NOX4 levels were tightly correlated with GCS score (t=−5.843, P < 0.001) and Rotterdam CT score (t = 4.231, P < 0.001). During 90 days of follow-up, 50 participants (47.6%) experienced a worse outcome, 28 (26.7%) died and the mean overall survival time was 71.9 days (95% confidence interval (CI), 65.7–78.1 days). Serum NOX4 was independently associated with an increased risk of short overall survival (hazard ratio, 1.129; 95% CI, 1.039–1.228) or worse outcome (odds ratio, 1.053; 95% CI, 1.014–1.095). Serum NOX4 levels had a certain predictive value for the patient’s risk of mortality (AUC, 0.803; 95% CI, 0.714–0.874) or worse outcome (AUC, 0.780; 95% CI, 0.689–0.855). Moreover, its AUC was in the range of GCS score and Rotterdam CT score (both P > 0.05) and it significantly improved their AUCs (both P < 0.05). Conclusion Serum NOX4 levels in the acute phase of sTBI were associated with trauma severity, an increased risk of mortality and worse outcome, suggesting that serum NOX4 could be an important prognostic factor for sTBI.

Utility of serum chemokine–like factor 1 as a biomarker of severity and prognosis after severe traumatic brain injury: A prospective observational study

“…We investigated the associations of serum CKLF1 levels with trauma severity and prognosis through a linear regression model, a binary logistic regression model, and a Cox proportional hazard model and found that serum CKLF1 levels were independently correlated with GCS scores and Rotterdam CT classification and were independently associated with 180‐day mortality and poor prognosis in sTBI patients. In current clinical studies, GCS scores and Rotterdam CT classification are often used to assess trauma severity and predict the prognosis of patients (Jiang et al., 2022 ; Yang et al., 2021 ; Zhang et al., 2023 ). We therefore hypothesized that serum CKLF1 levels may be strongly associated with trauma severity, 180‐day mortality, and the long‐term function prognosis of sTBI.…”