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Background: Severe traumatic brain injury (sTBI) is extremely disabling and associated with high mortality. Early detection of patients at risk of short-term (≤14 days after injury) death and provision of timely treatment is critical. This study aimed to establish and independently validate a nomogram to estimate individualised short-term mortality for sTBI based on large-scale data from China. Methods: The data were from the Collaborative European NeuroTrauma Effectiveness Research in TBI (CENTER-TBI) China registry (between Dec 22, 2014, and Aug 1, 2017; registered at ClinicalTrials.gov, NCT02210221). This analysis included information of eligible patients with diagnosed sTBI from 52 centres (2631 cases). 1808 cases from 36 centres were enrolled in the training group (used to construct the nomogram) and 823 cases from 16 centres were enrolled in the validation group. Multivariate logistic regression was used to identify independent predictors of short-term mortality and establish the nomogram. The discrimination of the nomogram was evaluated using area under the receiver operating characteristic curves (AUC) and concordance indexes (C-index), the calibration was evaluated using calibration curves and Hosmer-Lemeshow tests (H-L tests). Decision curve analysis (DCA) was used to evaluate the net benefit of the model for patients. Findings: In the training group, multivariate logistic regression demonstrated that age (odds ratio [OR] 1.013, 95% confidence interval [CI] 1.003-1.022), Glasgow Coma Scale score (OR 33.997, 95% CI 14.657-78.856), Injury Severity Score (OR 1.020, 95% CI 1.009-1.032), abnormal pupil status (OR 1.738, 95% CI 1.178-2.565), midline shift (OR 2.266, 95% CI 1.378-3.727), and pre-hospital intubation (OR 2.059, 95% CI 1.472-2.879) were independent predictors for short-term death in patients with sTBI. A nomogram was built using the logistic regression prediction model. The AUC and C-index were 0.859 (95% CI 0.837-0.880). The calibration curve of the nomogram was close to the ideal reference line, and the H-L test p value was 0.504. DCA curve demonstrated significantly better net benefit with the model. Application of the nomogram in external validation group still showed good discrimination (AUC and C-index were 0.856, 95% CI 0.827-0.886), calibration, and clinical usefulness. Interpretation: A nomogram was developed for predicting the occurrence of short-term (≤14 days after injury) death in patients with sTBI. This can provide clinicians with an effective and accurate tool for the early prediction and timely management of sTBI, as well as support clinical decision-making around the withdrawal of life-sustaining therapy. This nomogram is based on Chinese large-scale data and is especially relevant to low- and middle-income countries. Funding: Shanghai Academic Research Leader (21XD1422400), Shanghai Medical and Health Development Foundation (20224Z0012).
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BACKGROUND: After a traumatic brain injury (TBI), the cell environment is dramatically changed, which has various influences on grafted neural stem cells (NSCs). At present, these influences on NSCs have not been fully elucidated, which hinders the finding of an optimal timepoint for NSC transplantation. METHODS: Brain extracts of TBI mice were used in vitro to simulate the different phase TBI influences on the differentiation of human NSCs. Protein profiles of brain extracts were analyzed. Neuronal differentiation and the activation of autophagy and the WNT/CTNNB pathway were detected after brain extract treatment. RESULTS: Under subacute TBI brain extract conditions, the neuronal differentiation of hNSCs was significantly higher than that under acute brain extract conditions. The autophagy flux and WNT/CTNNB pathway were activated more highly within the subacute brain extract than in the acute brain extract. Autophagy activation by rapamycin could rescue the neuronal differentiation of hNSCs within acute TBI brain extract. CONCLUSIONS: The subacute phase around 7 days after TBI in mice could be a candidate timepoint to encourage more neuronal differentiation after transplantation. The autophagy flux played a critical role in regulating neuronal differentiation of hNSCs and could serve as a potential target to improve the efficacy of transplantation in the early phase.
RESUMEN
Increasing traumatic brain injury (TBI) among older adults constitutes a substantial socioeconomic burden, in step with the growing aging global population. Here, we aimed to investigate the profile of geriatric TBI in the CENTER-TBI China registry, a prospective observational study conducted in 56 centers of 22 provinces across China. Patients admitted to the hospital with a clinical diagnosis of TBI were enrolled in the study. Data on demographic characteristics, injury, clinical features, treatments, and survival at discharge were collected and assessed. The primary end point was survival state at discharge. We analyzed a total of 2415 patients aged ≥65 years, accounting for 18.34% of the overall population. The median age was 72 years (interquartile range [IQR]: 68-78), and 1588 (65.76%) were men. Incidental falls (n = 1044, 43.23%) were the leading cause of TBI, followed by road traffic injuries (n = 1034, 42.82%). Roads and homes were the main sites of injury. The median Glasgow Coma Scale (GCS) score was 13 (IQR: 9-15); 1397 (57.85%) patients had mild TBI (GCS 13-15), while 530 (21.95%) and 488 (20.21%) presented with moderate (GCS 9-12) and severe TBI (sTBI; GCS 3-8), respectively. A total of 546 (22.61%) patients underwent intracranial surgery. The overall in-hospital mortality rate was 8.24% (n = 199), and most survivors were transferred home. This study revealed that the demographic patterns and injury mechanisms are changing among elderly patients with TBI in China. More attention should be given to the high incidence of geriatric TBI to improve prevention and management strategies.
