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细胞因子生物标志物表型用于钝器创伤患者脓毒症的早期预测和分诊。

Cytokine Biomarker Phenotype for Early Prediction and Triage of Sepsis in Blunt Trauma Patients.

机构信息

Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China; Department of Emergency Surgery, The Affiliated Hospital, Guizhou Medical University, Guiyang, Guizhou, China.

Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China.

出版信息

J Surg Res. 2023 Mar;283:824-832. doi: 10.1016/j.jss.2022.10.059. Epub 2022 Dec 5.

DOI:10.1016/j.jss.2022.10.059
PMID:36915009
Abstract

BACKGROUND

Altered levels of inflammatory markers secondary to severe trauma present a major problem to physicians and are prone to interfering with the clinical identification of sepsis events. This study aimed to establish the profiles of cytokines in trauma patients to characterize the nature of immune responses to sepsis, which might enable early prediction and individualized treatments to be developed for targeted intervention.

METHODS

A 15-plex human cytokine magnetic bead assay system was used to measure analytes in citrated plasma samples. Analysis of the kinetics of these cytokines was performed in 40 patients with severe blunt trauma admitted to our trauma center between March 2016 and February 2017, with an Injury Severity Score (ISS) greater than 20 with regard to sepsis (Sepsis-3) over a 14-d time course.

RESULTS

In total, the levels of six cytokines were altered in trauma patients across the 1-, 3-, 5-, 7-, and 14-d time points. Additionally, IL-6, IL-10, IL-15, macrophage derived chemokine (MDC), GRO, sCD40 L, granulocyte colony-stimulating factor (G-CSF), and fibroblast growth factor (FGF)-2 levels could be used to provide a significant discrimination between sepsis and nonsepsis patients at day 3 and afterward, with an area under the curve (AUC) of up to 0.90 through a combined analysis of the eight biomarkers (P < 0.001). Event-related analysis demonstrated 1.5- to 4-fold serum level changes for these cytokines within 72 h before clinically apparent sepsis.

CONCLUSIONS

Cytokine profiles demonstrate a high discriminatory ability enabling the timely identification of evolving sepsis in trauma patients. These abrupt changes enable sepsis to be detected up to 72 h before clinically overt deterioration. Defining cytokine release patterns that distinguish sepsis risk from trauma patients might enable physicians to initiate timely treatment and reduce mortality. Large prospective studies are needed to validate and operationalize the findings.

TRIAL REGISTRATION

Clinicaltrials, NCT01713205. Registered October 22, 2012, https://register.

CLINICALTRIALS

gov/NCT01713205.

摘要

背景

严重创伤导致的炎症标志物水平改变给医生带来了重大问题,并容易干扰脓毒症事件的临床识别。本研究旨在建立创伤患者细胞因子谱,以描述对脓毒症的免疫反应性质,这可能使我们能够开发针对早期预测和个体化治疗的靶向干预措施。

方法

使用 15 聚体人细胞因子磁珠分析系统测量柠檬酸血浆样本中的分析物。对 2016 年 3 月至 2017 年 2 月期间我院创伤中心收治的 40 例严重钝器伤患者的这些细胞因子的动力学进行分析,这些患者的损伤严重度评分(ISS)均大于 20,并且在 14 天的时间内发生了脓毒症(Sepsis-3)。

结果

总的来说,创伤患者在 1、3、5、7 和 14 天时间点有六种细胞因子水平发生改变。此外,在第 3 天及之后,IL-6、IL-10、IL-15、巨噬细胞来源趋化因子(MDC)、GRO、sCD40L、粒细胞集落刺激因子(G-CSF)和成纤维细胞生长因子(FGF)-2 水平可用于对脓毒症和非脓毒症患者进行显著区分,联合分析这 8 种生物标志物的曲线下面积(AUC)可达 0.90(P<0.001)。事件相关分析显示,在临床明显脓毒症前 72 小时内,这些细胞因子的血清水平变化了 1.5 至 4 倍。

结论

细胞因子谱显示出较高的鉴别能力,使我们能够及时识别创伤患者中发生的进展性脓毒症。这些急剧变化使脓毒症能够在临床恶化前 72 小时被检测到。确定区分脓毒症风险与创伤患者的细胞因子释放模式,可能使医生能够及时进行治疗并降低死亡率。需要开展大型前瞻性研究来验证和实施这些发现。

临床试验注册

ClinicalTrials.gov,NCT01713205。注册于 2012 年 10 月 22 日,https://register.clinicaltrials.gov/NCT01713205。

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