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中重度创伤性脑损伤患儿的炎症细胞因子血浆谱:一项前瞻性队列研究。

Plasma profiles of inflammatory cytokines in children with moderate to severe traumatic brain injury: a prospective cohort study.

机构信息

Department of Critical Care Medicine, Children's Hospital of Chongqing Medical University, Chongqing, 400014, China.

National Clinical Research Center for Child Health and Disorders, Chongqing, 400014, China.

出版信息

Eur J Pediatr. 2024 Aug;183(8):3359-3368. doi: 10.1007/s00431-024-05604-5. Epub 2024 May 15.

Abstract

UNLABELLED

The role of inflammatory cytokines in children with moderate to severe TBI (m-sTBI) is still incompletely understood. We aimed to investigate the associations between early plasma expression profiles of inflammatory cytokines and clinical outcomes in children with m-sTBI. We prospectively recruited children admitted to the intensive care unit (ICU) of a tertiary pediatric hospital due to m-sTBI from November 2022 to May 2023. Plasma interleukin (IL)-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10, IL-12p70, IL-17A, interferon (IFN)-α, IFN-γ and tumor necrosis factor (TNF)-α concentrations were detected by flow cytometry on admission and on days 5 to 7. The primary outcome was in-hospital mortality. The secondary outcome was the 6-month functional outcome assessed by the Glasgow Outcome Scale Extended-Pediatrics (GOS-E Peds) score, dichotomized as favorable (1-4) or unfavorable (5-8). Fifty patients and 20 healthy controls were enrolled. Baseline IL-6, IL-8 and IL-10 levels were significantly higher in TBI patients than in healthy controls. Twelve patients died in the hospital. Compared with survivors, nonsurvivors had significantly increased baseline IL-6 and IL-8 levels. Baseline IL-5, IL-6 and IL-8 levels were also significantly greater in children with unfavorable versus favorable outcomes. The area under the receiver operating characteristic curve (AUC) of the IL-6 and IL-8 levels and motor Glasgow Coma Scale (GCS) score for predicting in-hospital mortality was 0.706, 0.754, and 0.776, respectively. Baseline IL-1β, IL-2, IL-4, IL-10, IL-12p70, IL-17A, IFN-γ, IFN-α and TNF-α levels were not associated with in-hospital mortality or an unfavorable 6-month outcome. On days 5 to 7, the IL-6 and IL-8 levels were significantly decreased in survivors but increased in nonsurvivors compared to their respective baselines.

CONCLUSION

After m-sTBI, the plasma profiles of inflammatory cytokines are markedly altered in children. The trends of IL-6 and IL-8 expression vary among m-sTBI children with different outcomes. Elevated plasma IL-6 and IL-8 levels are related to in-hospital mortality and unfavorable 6-month outcomes.

TRIAL REGISTRATION

This trial was registered in the Chinese Clinical Trial Registry (Registration number: ChiCTR2200065505). Registered November 7, 2022.

WHAT IS KNOWN

• Inflammation is an important secondary physiological response to TBI.

WHAT IS NEW

• The plasma profiles of inflammatory cytokines are markedly altered in children with m-sTBI. Elevated IL-6 and IL-8 levels are related to mortality and unfavorable outcomes.

摘要

目的

本研究旨在探讨中度至重度创伤性脑损伤(m-sTBI)患儿早期血浆炎症细胞因子表达谱与临床结局的相关性。

方法

前瞻性纳入 2022 年 11 月至 2023 年 5 月因 m-sTBI 入住我院重症监护病房(ICU)的患儿。入院和入院后第 5-7 天通过流式细胞术检测血浆白细胞介素(IL)-1β、IL-2、IL-4、IL-5、IL-6、IL-8、IL-10、IL-12p70、IL-17A、干扰素(IFN)-α、IFN-γ和肿瘤坏死因子(TNF)-α浓度。主要结局为院内死亡率。次要结局为 6 个月时采用格拉斯哥结局量表扩展儿科版(GOS-E Peds)评估的功能结局,分为有利(1-4 分)或不利(5-8 分)。

结果

共纳入 50 例患儿和 20 例健康对照者。与健康对照组相比,TBI 患儿的基线 IL-6、IL-8 和 IL-10 水平显著升高。12 例患儿在院死亡。与幸存者相比,非幸存者的基线 IL-6 和 IL-8 水平显著升高。与预后良好的患儿相比,预后不良的患儿的基线 IL-5、IL-6 和 IL-8 水平也显著升高。IL-6 和 IL-8 水平以及运动性格拉斯哥昏迷量表(GCS)评分预测院内死亡率的受试者工作特征曲线(AUC)分别为 0.706、0.754 和 0.776。基线 IL-1β、IL-2、IL-4、IL-10、IL-12p70、IL-17A、IFN-γ、IFN-α和 TNF-α水平与院内死亡率或 6 个月不良结局无关。与幸存者相比,非幸存者在第 5-7 天的 IL-6 和 IL-8 水平与各自的基线相比显著升高。

结论

m-sTBI 后,儿童的血浆炎症细胞因子谱发生明显改变。不同结局 m-sTBI 患儿的 IL-6 和 IL-8 表达趋势不同。血浆 IL-6 和 IL-8 水平升高与院内死亡率和 6 个月不良结局相关。

临床试验注册号

ChiCTR2200065505,于 2022 年 11 月 7 日在国家临床试验注册中心登记。

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