Utility of Serum Occludin as a Prognostic Biomarker of Severe Traumatic Brain Injury and Mediation Role of Acute Lung Injury: A Two-Center Prospective Cohort Study

Shaojun Zhang,1 Xiufeng Ye,2 Mi Guo,1 Yidong Jin,1 Xuebo Zhang,1 Jiehao Tu,1 Jing Huang,2 Zhiqiang Lian,2 Fangfang You,2 Han Zhang1 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, Longquan People’s Hospital, Longquan, Zhejiang, People’s Republic of ChinaCorrespondence: Han Zhang, 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 [email protected]: Occludin is a crucial biomarker of blood-brain barrier disruption. Here, we investigated the association between serum occludin levels and poor neurological outcomes after severe traumatic brain injury (sTBI) and the mediating effect of acute lung injury (ALI).Methods: In this two-center prospective cohort study of 246 patients with sTBI and 100 controls, the serum occludin levels were measured. In-hospital ALI and six-month post-sTBI Glasgow Outcome Scale (GOS) scores were documented. Independent factorial relationships between severity and prognosis were determined.Results: Patients showed notably enhanced serum occludin levels compared to controls. Serum occludin levels were independently associated with Glasgow coma scale (GCS) scores, and Rotterdam computed tomography (CT) scores were linearly related to the likelihood of ALI and poor prognosis (GOS scores of 1– 3), as well as independently associated with ALI, poor prognosis, ordinal GOS scores, and continuous GOS scores. The association of serum occludin levels with ALI and poor prognosis was not moderated by age, sex, hypertension, diabetes, alcohol consumption, or tobacco smoking. ALI partially mediates the relationship between serum occludin level and poor prognosis. As confirmed via a series of statistical approaches, prediction models of poor prognosis and ALI incorporating serum occludin levels and their respective independent predictors performed satisfactorily.Conclusion: A significant increase in serum occludin levels following sTBI is closely correlated with trauma severity, ALI, and poor prognosis. This may partially elucidate the link between serum occludin levels and poor prognosis, thereby strengthening serum occludin as an acceptable prognostic biomarker of sTBI.Keywords: traumatic brain injury, occludin, severity, prognosis, acute lung injury, mediation role, biomarkers