Elevated plasma levels of TIMP-3 are associated with a higher risk of acute respiratory distress syndrome and death following severe isolated traumatic brain injury.
Elevated plasma levels of TIMP-3 are associated with a higher risk of acute respiratory distress syndrome and death following severe isolated traumatic brain injury.
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DOI：
10.1136/tsaco-2018-000171
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发表时间：
2018
影响因子：
2
通讯作者：
Cohen MJ
中科院分区：
文献类型：
--
作者：
Hendrickson CM;Gibb SL;Miyazawa BY;Keating SM;Ross E;Conroy AS;Calfee CS;Pati S;Cohen MJ
创伤后的并发症，如急性呼吸窘迫综合征(ARDS)，在创伤性脑损伤(TBI)后很常见，并与不良的临床结果相关。导致脑外伤后非神经器官功能障碍的机制尚不清楚。基质金属蛋白酶组织抑制因子-3(TIMP-3)是基质金属蛋白酶活性、炎症和血管通透性的调节因子，因此有望作为全身创伤反应的生物标志物。在对182例严重孤立性脑损伤患者的回顾性研究中，我们测定了急诊科到达时获取的血浆中TIMP-3的含量。我们使用非参数检验和Logistic回归分析来检验TIMP-3与入院8天内ARDS的发生率和住院死亡率之间的关系。在发生急性呼吸窘迫综合征的患者中，TIMP-3的水平显著高于未发生急性呼吸窘迫综合征的患者(中位数为2810 pg/mL)，与未发生急性呼吸窘迫综合征的患者相比，TIMP-3的中位数为(2260 pg/mL，p=0.008)；在死亡的患者中，TIMP-3的水平显著高于存活至出院的患者(中位数为2960 pg/mL，与未发生急性呼吸窘迫综合征的患者相比，中位数为2080 pg/mL，p<；0.001)。在未调整的Logistic回归模型中，血浆TIMP-3每增加一次，ARDS的发生几率显著增加，OR 1.5(95%可信区间为1.1至2.1)。这种关联仅在多变量模型中减弱，OR为1.4(95%可信区间为1.0至2.0)。在未调整的Logistic回归模型中，血浆TIMP-3每增加一次SD，死亡的风险显著增加，OR为1.7(95%CI为1.2至2.3)。在根据损伤严重程度的标志进行调整的多变量模型中，这种关联的程度更大，OR为1.9(95%可信区间为1.2至2.8)。TIMP-3可能在人类脑损伤全身反应的生物学中发挥重要作用。结合临床和人口学数据，对TIMP-3等血浆生物标志物的早期测量可能有助于识别严重孤立性脑损伤后ARDS和死亡风险较高的患者。三.
Complications after injury, such as acute respiratory distress syndrome (ARDS), are common after traumatic brain injury (TBI) and associated with poor clinical outcomes. The mechanisms driving non-neurologic organ dysfunction after TBI are not well understood. Tissue inhibitor of matrix metalloproteinase-3 (TIMP-3) is a regulator of matrix metalloproteinase activity, inflammation, and vascular permeability, and hence has plausibility as a biomarker for the systemic response to TBI. In a retrospective study of 182 patients with severe isolated TBI, we measured TIMP-3 in plasma obtained on emergency department arrival. We used non-parametric tests and logistic regression analyses to test the association of TIMP-3 with the incidence of ARDS within 8 days of admission and in-hospital mortality. TIMP-3 was significantly higher among subjects who developed ARDS compared with those who did not (median 2810 pg/mL vs. 2260 pg/mL, p=0.008), and significantly higher among subjects who died than among those who survived to discharge (median 2960 pg/mL vs. 2080 pg/mL, p<0.001). In an unadjusted logistic regression model, for each SD increase in plasma TIMP-3, the odds of ARDS increased significantly, OR 1.5 (95% CI 1.1 to 2.1). This association was only attenuated in multivariate models, OR 1.4 (95% CI 1.0 to 2.0). In an unadjusted logistic regression model, for each SD increase in plasma TIMP-3, the odds of death increased significantly, OR 1.7 (95% CI 1.2 to 2.3). The magnitude of this association was greater in a multivariate model adjusted for markers of injury severity, OR 1.9 (95% CI 1.2 to 2.8). TIMP-3 may play an important role in the biology of the systemic response to brain injury in humans. Along with clinical and demographic data, early measurements of plasma biomarkers such as TIMP-3 may help identify patients at higher risk of ARDS and death after severe isolated TBI. III.