Serial Measurements of Serum Glial Fibrillary Acidic Protein in Moderate-Severe Traumatic Brain Injury: Potential Utility in Providing Insights into Secondary Insults and Long-Term Outcome.
Serial Measurements of Serum Glial Fibrillary Acidic Protein in Moderate-Severe Traumatic Brain Injury: Potential Utility in Providing Insights into Secondary Insults and Long-Term Outcome.
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中度至重度创伤性脑损伤中血清胶质纤维酸性蛋白的系列测量：在提供对继发性损伤和长期结果的见解方面的潜在效用。
DOI：
10.1089/neu.2023.0111
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发表时间：
2024
影响因子：
4.2
通讯作者：
Wagner,AmyK
中科院分区：
文献类型：
--
作者：
Robertson,ClaudiaS;Martinez,FelipeSalinas;McQuillan,LeahE;Williamson,John;Lamb,DamonG;Wang,KevinKW;Rubenstein,Richard;Wagner,AmyK
在创伤性脑损伤(TBI)患者中，血清生物标记物可能有助于评估继发性脑损伤的演变。对100例中重度颅脑损伤患者伤后10天以上的血清样本中的9个脑损伤相关生物标志物进行了检测。在被评估的生物标志物中，血清胶质纤维酸性蛋白(GFAP)与急性病理生理综合指标的相关性最强，包括颅内压(ICP)、脑灌注压(CPP)和脑组织氧分压(PbtO2)。使用基于组的轨迹(TRAJ)分析来识别三个不同的GFAP亚组。低TRAJ组(n=23)峰值为9.4±1.2 ng/ml，并迅速下降。中度TRAJ组(n=48)峰值较高(31.5±5.0 ng/ml)，随时间延长下降较慢。高TRAJ组(n=26)有很高的持续峰值(59.6±12.5 ng/ml)，有些患者甚至在10天后升高。高TRAJ组的死亡率显著高于低/中TRAJ组(26.9%vs.7.0%，P=0.028)。高TRAJ组、中TRAJ组和低TRAJ组神经预后不良的发生率分别为88.5%、54.2%和30.4%(P<；0.001)。高TRAJ组的颅内压最高(中位数17.6 mm Hg)，而低TRAJ组和中等TRAJ组的颅内压分别为14.4 mm Hg和15.9 mm Hg(p=0.002)。高TRAJ组持续时间最长，为25毫米汞柱，中位数为23小时，中低组分别为2小时和6小时(P=0.006)，中位数为5小时，最长为30毫米汞，中低组分别为0小时和1小时(P=0.013)。高TRAJ组患者更多地需要二级或三级治疗来控制颅内压。高TRAJ组持续时间最长，CPP为±50 mm Hg(P=0.007)，PbtO2为±10 mm Hg(P=0.002)。用Logistic回归分析血清GFAP分型与6个月GOS-E评分的关系。这里，低TRAJ组和中TRAJ组合并为低风险组，高TRAJ组被指定为高危组。高TRAJ组患者6个月GOS-E差的机会更大(p<；0.0001)。在调整基线损伤特征后，GFAP-TRAJ组成员仍然与GOS-E相关(p=0.003)。当将用于量化生理紊乱的ICU损伤负担评分添加到模型中时，GFAPTRAJ组成员资格仍然与GOS-E相关(p=0.014)。中介分析显示，ICU负荷评分在TRAJ组与6个月死亡率或GOS-E之间存在因果关系。我们的结果提示GFAP对中重度脑外伤患者的连续监测可能是有用的。未来需要在更大的队列中进行研究来证实这些结果。
In patients with traumatic brain injury (TBI), serum biomarkers may have utility in assessing the evolution of secondary brain injury. A panel of nine brain-injury associated biomarkers were measured in archived serum samples over 10 days post-injury from 100 patients with moderate-severe TBI. Among the biomarkers evaluated, serum glial fibrillary acidic protein (GFAP) had the strongest associations with summary measures of acute pathophysiology, including intracranial pressure (ICP), cerebral perfusion pressure (CPP), and brain tissue pO2 (PbtO2). Group based trajectory (TRAJ) analysis was used to identify three distinct GFAP subgroups. The low TRAJ group (n= 23) had peak levels of 9.4+ 1.2 ng/ml that declined rapidly. The middle TRAJ group (n= 48) had higher peak values (31.5+ 5.0 ng/ml) and a slower decline over time. The high TRAJ group (n= 26) had very high, sustained peak values (59.6+ 12.5 ng/ml) that even rose among some patients over 10 days. Patients in the high TRAJ group had significantly higher mortality rate than patients in low/middle TRAJ groups (26.9% vs. 7.0%, p= 0.028). The frequency of poor neurological outcome (Glasgow Outcome Score Extended [GOS-E] 1-4) was 88.5% in the high TRAJ group, 54.2% in the middle TRAJ group, and 30.4% in the low TRAJ group (p< 0.001). ICP was highest in the high TRAJ group (median 17.6 mmHg), compared to 14.4 mmHg in low and 15.9 mmHg in middle TRAJ groups (p= 0.002). High TRAJ patients spent the longest time with ICP> 25 mmHg, median 23 hrs compared to 2 and 6 hrs in low and middle TRAJ groups (p= 0.006), and the longest time with ICP> 30 mmHg, median 5 hrs, compared to 0 and 1 hr in low and middle TRAJ groups, respectively (p= 0.013). High TRAJ group patients more commonly required tier 2 or 3 treatment to control ICP. The high TRAJ group had the longest duration where CPP was< 50 mmHg (P= 0.007), and where PbtO2 was< 10 mmHg (p= 0.002). Logistic regression was used to study the relationship between temporal serum GFAP patterns and 6-month GOS-E. Here, the low and middle TRAJ groups were combined to form a low-risk group, and the high TRAJ group was designated the high-risk group. High TRAJ group patients had a greater chance of a poor 6-month GOS-E (p< 0.0001). When adjusting for baseline injury characteristics, GFAP TRAJ group membership remained associated with GOS-E (p= 0.003). When an ICU injury burden score, developed to quantify physiological derangements, was added to the model, GFAP TRAJ group membership remained associated with GOS-E (p= 0.014). Mediation analysis suggested that ICU burden scores were in the causal pathway between TRAJ group and 6-month mortality or GOS-E. Our results suggest that GFAP may be useful to monitor serially in moderate-severe TBI patients. Future studies in larger cohorts are needed to confirm these results.