Low Serum Calcium Levels Upon Admission as a Novel Predictor of Long-Term Unfavorable Outcomes after Traumatic Brain Injury

Background: Risk factors associated with long-term prognosis of traumatic brain injury (TBI) have been widely reported, but among them serological biomarkers are remain lacking. This study aims to explore the potential of serum calcium for predicting long-term prognosis in TBI patientsMethods: 1255 and 719 patients from multicenter were included into development and validation cohorts, respectively. The 6-month prognoses and in-hospital death incidence were recorded. Serum calcium levels of the patients were measured through routine blood tests within 24 h of admission. The least absolute shrinkage and selection operator regression analysis was used to select risk factors for unfavorable outcomes. The receiver operating characteristic curves, calibration curves, and decision curves were analyzed to estimate the performance of predictive models for unfavorable outcomes.Findings: In the development cohort, 264 (21.04%) patients with hypocalcemia at admission had a higher frequency of 6-month unfavorable outcomes than those without. Serum calcium levels were independent risk factors for 6-month unfavorable outcomes after adjusted by other risk factors. Low serum calcium level was nonlinearly positively associated with unfavorable outcomes (odds ratio, 0.43) and in-hospital deaths (odds ratio, 0.51). Serum calcium substantially improved the discrimination, calibration, and clinical net benefit of the multivariate model for predicting 6-month unfavorable outcomes. Serum calcium level maintained its excellent performance in the external validation cohort.Interpretation: Low serum calcium level upon admission is an independent risk factor for 6-month unfavorable outcomes and in-hospital deaths in patients with TBI, an easy-to-use calcium nomogram was established for clinical applications.Funding Information: This study was funded through China Postdoctoral Science Foundation (2018M633091); the Natural Science Foundation of Guangdong Province (2019A1515010649, 2022A1515012144); Medical Scientific Research Foundation of Guangdong Province, China (A2017168) and High-level talent introduction research start-up fee of Shantou University Medical College (510858047).Declaration of Interests: The authors declare that they have no competing interests.Ethics Approval Statement: This study was approved by the ethics committees of the First Affiliated Hospital of Shantou University Medical College, the Second Affiliated Hospital of Shantou University Medical College, the affiliated Jieyang Hospital of Sun Yat-sen University, and the Affiliated East Hospital of Xiamen University Medical College. The ethical approval number (No. 2020-042) was available for all of the ethics committees. All the data from the retrospective cohorts are anonymous; hence, the requirement for informed consent was waived. All procedures in this study were performed in accordance with the ethical standards and regulations in the appropriate version of the Declaration of Helsinki (Revised, Brazil, 2013).