Severe traumatic brain injury (TBI) activates a robust systemic response that involves inflammatory and other factors, including estradiol (E2), associated with increased deaths. Tumor necrosis factor-alpha (TNFα) is a significant mediator of systemic shock, and it is an extra-gonadal transcription factor for E2 production. The study objectives were to test the hypotheses: (1) a positive feedback relationship exists between acute serum TNFα and E2; and (2) acute concentrations of E2 and TNFα are prognostic indicators of death after severe TBI. This prospective cohort study included N = 157 adults with severe TBI. Serum samples were collected for the first five days post-injury. The TNFα and E2 levels were averaged into two time epochs: first 72 h (T1) and second 72 h post-injury (T2). A cross-lag panel analysis conducted between T1 and T2 TNFα and E2 levels showed significant cross-lag effects: T1 TNFα and T1 E2 were related to T2 E2 and T2 TNFα, respectively. Cox proportional hazards multi variable regression models determined that increases in T1 E2 (hazard ratio [HR] = 1.79, 95% confidence interval [CI]: 1.15, 2.81), but not T2 E2 (HR = 0.91, 95% CI: 0.56, 1.47), were associated with increased risk of death. Increased T2 TNFα (HR = 2.47, 95% CI: 1.35, 4.53), and T1 TNFα (HR = 1.47, 95% CI: 0.99, 2.19), to a lesser degree, were associated with increased risk of death. Relationships of death with T2 TNFα and T1 E2 were mediated partially by cardiovascular, hepatic, and renal dysfunction. Both E2 and TNFα are systemic, reciprocally related biomarkers that may be indicative of systemic compromise and increased risk of death after severe TBI.

中文翻译：

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严重创伤性脑损伤后时间急性血清雌二醇和肿瘤坏死因子-α 关联和死亡风险。

严重的创伤性脑损伤 (TBI) 会激活强大的全身反应，涉及炎症和其他因素，包括与死亡增加相关的雌二醇 (E2)。肿瘤坏死因子-α (TNFα) 是全身性休克的重要介质，它是 E2 产生的性腺外转录因子。研究目的是检验以下假设：（1）急性血清TNFα与E2之间存在正反馈关系；(2) E2 和 TNFα 的急性浓度是严重 TBI 后死亡的预后指标。这项前瞻性队列研究包括 N = 157 名患有严重 TBI 的成人。在受伤后的前五天收集血清样品。TNFα 和 E2 水平平均分为两个时间段：第一个 72 小时（T1）和第二个受伤后 72 小时（T2）。在 T1 和 T2 TNFα 和 E2 水平之间进行的交叉滞后面板分析显示出显着的交叉滞后效应：T1 TNFα 和 T1 E2 分别与 T2 E2 和 T2 TNFα 相关。Cox 比例风险多变量回归模型确定 T1 E2 增加（风险比 [HR] = 1.79，95% 置信区间 [CI]：1.15、2.81），而不是 T2 E2（HR = 0.91，95% CI：0.56， 1.47)，与死亡风险增加有关。T2 TNFα (HR = 2.47, 95% CI: 1.35, 4.53) 和 T1 TNFα (HR = 1.47, 95% CI: 0.99, 2.19) 在较小程度上与死亡风险增加相关。死亡与 T2 TNFα 和 T1 E2 的关系部分由心血管、肝和肾功能障碍介导。E2 和 TNFα 都是全身性的，