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重度创伤性脑损伤后的慢性炎症:损伤后6个月和12个月的特征及与预后的关联

Chronic Inflammation After Severe Traumatic Brain Injury: Characterization and Associations With Outcome at 6 and 12 Months Postinjury.

作者信息

Kumar Raj G, Boles Jennifer A, Wagner Amy K

机构信息

Department of Physical Medicine and Rehabilitation (Mr Kumar, Ms Boles, and Dr Wagner), Center for Neuroscience (Dr Wagner), and Safar Center for Resuscitation Research (Dr Wagner), University of Pittsburgh, Pittsburgh, Pennsylvania.

出版信息

J Head Trauma Rehabil. 2015 Nov-Dec;30(6):369-81. doi: 10.1097/HTR.0000000000000067.

Abstract

OBJECTIVE

Examine associations between chronic inflammatory profiles and outcome 6 to 12 months following severe traumatic brain injury (TBI).

SETTING

University-affiliated level 1 trauma center and community.

PARTICIPANTS

Adults with severe TBI (n = 87); healthy controls (n = 7).

DESIGN

Prospective cohort study.

MAIN MEASURES

Glasgow Outcome Scale; serum cytokines (interleukin [IL]-1β, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, tumor necrosis factor α), 2 weeks to 3 months, 4- to 6-month averages, 6- and 12-month levels.

RESULTS

Serum levels of IL-1β, IL-6, IL-8, IL-10, and tumor necrosis factor α were elevated over 3 months following TBI. Multivariate analysis showed that increased cytokine load score was associated with a 1.21 (95% confidence interval, 1.06-1.38) and 1.18 (95% confidence interval, 1.02-1.37) increase in odds of unfavorable Glasgow Outcome Scale score at 6 and 12 months, respectively. Also, elevated IL-6/IL-10 ratios were associated with increased odds of unfavorable outcomes at 6 months (adjusted odds ratio = 1.76; 95% confidence interval, 1.08-2.88).

CONCLUSIONS

Chronic inflammation has not been well characterized following TBI. Our subacute cytokine load score classifies individuals at risk for unfavorable outcomes following injury. Higher proinflammatory burden with IL-6, relative to the anti-inflammatory marker IL-10, is significantly associated with outcome. Further research should examine whether inflammatory genes and other inflammatory biomarkers affect risk for unfavorable outcomes and TBI complications.

摘要

目的

研究重度创伤性脑损伤(TBI)后6至12个月慢性炎症指标与预后之间的关联。

设置

大学附属一级创伤中心及社区。

参与者

重度TBI成人患者(n = 87);健康对照者(n = 7)。

设计

前瞻性队列研究。

主要测量指标

格拉斯哥预后量表;血清细胞因子(白细胞介素[IL]-1β、IL-4、IL-5、IL-6、IL-7、IL-8、IL-10、IL-12、肿瘤坏死因子α),分别于伤后2周、3个月、4至6个月平均水平、6个月及12个月时检测。

结果

TBI后3个月内,血清IL-1β、IL-6、IL-8、IL-10及肿瘤坏死因子α水平升高。多因素分析显示,细胞因子负荷评分增加分别与伤后6个月及12个月时格拉斯哥预后量表评分不良的比值比增加1.21(95%置信区间,1.06 - 1.38)及1.18(95%置信区间,1.02 - 1.37)相关。此外,IL-6/IL-10比值升高与6个月时不良预后的比值比增加相关(校正比值比 = 1.76;95%置信区间,1.08 - 2.88)。

结论

TBI后的慢性炎症尚未得到充分表征。我们的亚急性细胞因子负荷评分可对伤后预后不良风险个体进行分类。相对于抗炎标志物IL-10,IL-6的促炎负担较高与预后显著相关。进一步研究应探讨炎症基因及其他炎症生物标志物是否影响不良预后及TBI并发症的风险。

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