Cai Liang, Dou Xianghong, Dong Wensheng, Zou Kangqin, Zhang Lixin, Hong Huayong, Zhang Xiaole, Liu Jin, Tian Da, Wu Xiaoyu, Zhang Jianhua
Department of Neurosurgery, The second People's Hospital of Lianyungang Affiliated to Kangda College of Nanjing Medical University, Lianyungang, Jiangsu, 222000, People's Republic of China.
Department of Neurology, Donghai County People's Hospital, Lianyungang, Jiangsu, 222300, People's Republic of China.
Ther Clin Risk Manag. 2025 Mar 20;21:385-405. doi: 10.2147/TCRM.S502775. eCollection 2025.
Receptor-interacting protein kinase-1 (RIPK1), a regulator of necroptosis, is involved in acute brain injury and acute lung injury (ALI). Here, serum RIPK1 levels were measured after severe traumatic brain injury (sTBI), with an endeavor to unveil its prognostic implications and mediation effects of ALI.
In this multicenter prospective study, serum RIPK1 levels were gauged in 100 healthy individuals and 158 sTBI patients in need of decompressive craniectomy for brain herniation. The collected materials encompassed the Glasgow Coma Scale (GCS), pupil enlargement status, basal cisternal shapes, ALI, etc. The extended Glasgow outcome scale (GOSE) was employed for estimating neurological impairments at posttraumatic 180-day mark. Multifactorial analytical methods were applied to assess relevancies.
Patients, as opposed to controls, had markedly raised serum RIPK1 levels, with the even substantially higher levels in those with lower GCS scores, bilateral pupil enlargement or obliterated basal cisterns. Using restricted cubic spline, RIPK1 levels were linearly related to occurrent risks of the four outcome variables of interest, that is 180-day death, overall survival, poor prognosis (GOSE scores 1-4) and ALI. RIPK1 levels independently predicted these outcome variables. RIPK1 levels had noninteractional effects with age, sex, hypertension, diabetes, smoking and alcohol habits in terms of its association with these outcome variables. RIPK1 levels exhibited high discriminatory efficiency for these outcome variables under the receiver operating characteristic curve. RIPK1 levels, via partial mediation by ALI, were associated with death and poor prognosis of patients.
Elevated serum RIPK1 levels of patients with sTBI may be highly related to trauma severity, and risks of poor outcomes and ALI; and ALI partially explains the links between serum RIPK1 levels, death and poor prognosis, substantializing serum RIPK1 as a serological prognostic predictor of good prospect in sTBI.
受体相互作用蛋白激酶1(RIPK1)是坏死性凋亡的调节因子,参与急性脑损伤和急性肺损伤(ALI)。在此,我们检测了重度创伤性脑损伤(sTBI)后血清RIPK1水平,以揭示其预后意义及对ALI的介导作用。
在这项多中心前瞻性研究中,我们检测了100名健康个体和158例因脑疝需要去骨瓣减压术的sTBI患者的血清RIPK1水平。收集的资料包括格拉斯哥昏迷量表(GCS)、瞳孔散大状态、基底池形态、ALI等。采用扩展格拉斯哥预后量表(GOSE)评估伤后180天时的神经功能障碍。应用多因素分析方法评估相关性。
与对照组相比,患者血清RIPK1水平显著升高,在GCS评分较低、双侧瞳孔散大或基底池闭塞的患者中水平甚至更高。使用受限立方样条,RIPK1水平与180天死亡、总生存、预后不良(GOSE评分1 - 4)和ALI这四个感兴趣的结局变量的发生风险呈线性相关。RIPK1水平可独立预测这些结局变量。就其与这些结局变量的关联而言,RIPK1水平与年龄、性别、高血压、糖尿病、吸烟和饮酒习惯无交互作用。在受试者工作特征曲线下,RIPK1水平对这些结局变量具有较高的鉴别效率。RIPK1水平通过ALI的部分介导作用,与患者的死亡和预后不良相关。
sTBI患者血清RIPK1水平升高可能与创伤严重程度、不良结局和ALI风险高度相关;并且ALI部分解释了血清RIPK1水平、死亡和预后不良之间的联系,使血清RIPK1成为sTBI中具有良好前景的血清学预后预测指标。