Alteration of Serum MLKL Levels and Their Association with Severity and Clinical Outcomes in Human Severe Traumatic Brain Injury: A Prospective Cohort Study

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 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.