Yidong Jin,1 Han Zhang,2 Min Zhou,1 Shaojun Zhang,1 Mi Guo1 

1Emergency Department, Shengzhou People’s Hospital (Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, The Shengzhou Hospital of Shaoxing University), Shengzhou, Zhejiang, People’s Republic of China; 2Department of Neurosurgery, Shengzhou People’s Hospital (Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, The Shengzhou Hospital of Shaoxing University), Shengzhou, Zhejiang, People’s Republic of China

Correspondence: Mi Guo, Emergency Department, Shengzhou People’s Hospital (Shengzhou Branch of the First Affiliated Hospital of Zhejiang University School of Medicine, The Shengzhou Hospital of Shaoxing University), Shengzhou, Zhejiang, People’s Republic of China, Email szguomi123@126.com

Background: Mixed lineage kinase domain-like protein (MLKL), which modulates necroptosis, has been implicated in pathophysiological processes following acute brain injury. Here, serum MLKL was quantified to determine its prognostic significance in severe traumatic brain injury (sTBI).
Methods: This prospective cohort study enrolled 155 patients with sTBI and 155 healthy volunteers. The severity metrics included the Glasgow Coma Scale (GCS) score and Rotterdam computed tomography (CT) classification. The extended Glasgow outcome scale (GOSE) at posttraumatic 180 days was considered as a prognostic parameter, with a score of 1– 4 as indicating poor prognosis. Univariate and subsequent multivariate analyses were used for independent factorial investigation.
Results: Compared to controls, patients displayed profoundly elevated serum MLKL levels. In the framework of restricted cubic spline analysis, serum MLKL levels were linearly correlated with the likelihood of mortality, overall survival, and poor prognosis. Serum MLKL levels were not only independently correlated with GCS, Rotterdam CT scores and GOSE scores, but were also independently predictive of death, overall survival, and poor prognosis. Subgroup analysis showed that serum MLKL levels exhibited negligible interactions with age, sex, hypertension, diabetes, smoking habits, and alcohol consumption to distinguish the possibility of death, overall survival, and poor prognosis. Within the context of receiver operating characteristic curve analysis, serum MLKL levels had strong discrimination effectiveness for death and poor prognosis and, in contrast to GCS and Rotterdam CT scores, were considered to have equivalent predictive ability.
Conclusion: Extreme elevation of serum MLKL levels is intimately related to trauma severity, death, and neurological outcomes, suggesting that serum MLKL may act as a potential predictor for facilitating severity stratification and prognosis prediction of sTBI.

Keywords: traumatic brain injury, mixed lineage kinase domain-like protein, severity, outcome, death, overall survival, biomarkers