用于创伤性脑损伤诊断和预后的神经炎症生物标志物：TRACK-TBI试点研究
Neuroinflammatory Biomarkers for Traumatic Brain Injury Diagnosis and Prognosis: A TRACK-TBI Pilot Study.
作者信息
Yue John K, Kobeissy Firas H, Jain Sonia, Sun Xiaoying, Phelps Ryan R L, Korley Frederick K, Gardner Raquel C, Ferguson Adam R, Huie J Russell, Schneider Andrea L C, Yang Zhihui, Xu Haiyan, Lynch Cillian E, Deng Hansen, Rabinowitz Miri, Vassar Mary J, Taylor Sabrina R, Mukherjee Pratik, Yuh Esther L, Markowitz Amy J, Puccio Ava M, Okonkwo David O, Diaz-Arrastia Ramon, Manley Geoffrey T, Wang Kevin K W
机构信息
Department of Neurosurgery, University of California, San Francisco, San Francisco, California, USA.
Brain and Spinal Injury Center, Zuckerberg San Francisco General Hospital, San Francisco, California, USA.
出版信息
Neurotrauma Rep. 2023 Mar 24;4(1):171-183. doi: 10.1089/neur.2022.0060. eCollection 2023.
The relationship between systemic inflammation and secondary injury in traumatic brain injury (TBI) is complex. We investigated associations between inflammatory markers and clinical confirmation of TBI diagnosis and prognosis. The prospective TRACK-TBI Pilot (Transforming Research and Clinical Knowledge in Traumatic Brain Injury Pilot) study enrolled TBI patients triaged to head computed tomography (CT) and received blood draw within 24 h of injury. Healthy controls (HCs) and orthopedic controls (OCs) were included. Thirty-one inflammatory markers were analyzed from plasma. Area under the receiver operating characteristic curve (AUC) was used to evaluate discriminatory ability. AUC >0.7 was considered acceptable. Criteria included: TBI diagnosis (vs. OC/HC); moderate/severe vs. mild TBI (Glasgow Coma Scale; GCS); radiographic TBI (CT positive vs. CT negative); 3- and 6-month Glasgow Outcome Scale-Extended (GOSE) dichotomized to death/greater relative disability versus less relative disability (GOSE 1-4/5-8); and incomplete versus full recovery (GOSE <8/ = 8). One-hundred sixty TBI subjects, 28 OCs, and 18 HCs were included. Markers discriminating TBI/OC: HMGB-1 (AUC = 0.835), IL-1b (0.795), IL-16 (0.784), IL-7 (0.742), and TARC (0.731). Markers discriminating GCS 3-12/13-15: IL-6 (AUC = 0.747), CRP (0.726), IL-15 (0.720), and SAA (0.716). Markers discriminating CT positive/CT negative: SAA (AUC = 0.767), IL-6 (0.757), CRP (0.733), and IL-15 (0.724). At 3 months, IL-15 (AUC = 0.738) and IL-2 (0.705) discriminated GOSE 5-8/1-4. At 6 months, IL-15 discriminated GOSE 1-4/5-8 (AUC = 0.704) and GOSE <8/ = 8 (0.711); SAA discriminated GOSE 1-4/5-8 (0.704). We identified a profile of acute circulating inflammatory proteins with potential relevance for TBI diagnosis, severity differentiation, and prognosis. IL-15 and serum amyloid A are priority markers with acceptable discrimination across multiple diagnostic and outcome categories. Validation in larger prospective cohorts is needed. ClinicalTrials.gov Registration: NCT01565551.
创伤性脑损伤（TBI）中全身炎症与继发性损伤之间的关系很复杂。我们研究了炎症标志物与TBI诊断及预后的临床确认之间的关联。前瞻性TRACK-TBI试点研究（创伤性脑损伤转化研究与临床知识试点研究）纳入了经分诊接受头部计算机断层扫描（CT）且在受伤后24小时内接受抽血的TBI患者。纳入了健康对照（HC）和骨科对照（OC）。对血浆中的31种炎症标志物进行了分析。采用受试者操作特征曲线下面积（AUC）来评估鉴别能力。AUC>0.7被认为是可接受的。标准包括：TBI诊断（与OC/HC相比）；中度/重度与轻度TBI（格拉斯哥昏迷量表；GCS）；影像学TBI（CT阳性与CT阴性）；3个月和6个月时格拉斯哥扩展预后量表（GOSE）分为死亡/更大相对残疾与较小相对残疾（GOSE 1-4/5-8）；以及不完全恢复与完全恢复（GOSE<8/=8）。纳入了160名TBI受试者、28名OC和18名HC。鉴别TBI/OC的标志物：高迁移率族蛋白B1（HMGB-1，AUC=0.835）、白细胞介素-1β（IL-1b，0.795）、IL-16（0.784）、IL-7（0.742）和胸腺活化调节趋化因子（TARC，0.731）。鉴别GCS 3-12/13-15的标志物：IL-6（AUC=0.747）、C反应蛋白（CRP，0.726）、IL-15（0.720）和血清淀粉样蛋白A（SAA，0.716）。鉴别CT阳性/CT阴性的标志物：SAA（AUC=0.767）、IL-6（0.757）、CRP（0.733）和IL-15（0.724）。在3个月时，IL-15（AUC=0.738）和IL-2（0.705）鉴别GOSE 5-8/1-4。在6个月时，IL-15鉴别GOSE 1-4/5-8（AUC=0.704）和GOSE<8/=8（0.711）；SAA鉴别GOSE 1-4/5-8（0.704）。我们确定了一组急性循环炎症蛋白，它们可能与TBI诊断、严重程度区分和预后相关。IL-15和血清淀粉样蛋白A是在多个诊断和结局类别中具有可接受鉴别的优先标志物。需要在更大的前瞻性队列中进行验证。ClinicalTrials.gov注册号：NCT01565551。
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