TLR/NF-κB信号轴预测开放性骨折患者骨感染的价值

Value of TLR/NF-κB signaling axis in predicting bone infection in patients with open fractures

  • 摘要:
    目的 分析开放性骨折患者围术期Toll样受体(TLR)/核转录因子-κB(NF-κB)信号轴关键因子动态变化对骨感染的预测价值。
    方法 选取在围术期发生骨感染的开放性骨折患者55例为骨感染组,另选取同期在围术期未发生感染的开放性骨折患者110例为未感染组。比较2组临床资料、手术前后血清常规炎症因子C反应蛋白(CRP)、白细胞介素-6(IL-6)、降钙素原(PCT)、TLR/NF-κB信号轴关键因子(TLR4、NF-κB)水平。采用多因素Logistic回归分析筛选开放性骨折患者围术期发生骨感染的影响因素。绘制受试者工作特征(ROC)曲线分析手术前后血清TLR/NF-κB信号轴关键因子变化值(变化值的绝对值以△表示)预测发生骨感染的价值,并与血清常规炎症因子进行比较。根据筛选出的影响因素构建列线图预测模型,分析该模型预测围术期发生骨感染的价值。
    结果 骨感染组骨折至手术时间、手术时间长于未感染组, Gustilo类型Ⅲ型、伤口深度≥2 cm占比高于未感染组,差异均有统计学意义(P < 0.05);术后24 h, 2组血清CRP、IL-6、PCT、TLR4、NF-κB水平均高于术前,且骨感染组血清CRP、IL-6、PCT、TLR4、NF-κB水平及变化值高于未感染组,差异均有统计学意义(P < 0.05)。Logistic回归分析显示,骨折至手术时间、手术时间、Gustilo类型Ⅲ型、伤口深度≥2 cm以及△CRP、△IL-6、△PCT、△TLR4和△NF-κB为开放性骨折患者围术期发生骨感染的影响因素(P < 0.05)。ROC曲线分析结果显示, △CRP、△IL-6、△PCT、△TLR4、△NF-κB预测骨感染的曲线下面积(AUC)分别为0.786、0.833、0.772、0.826、0.736。ROC曲线分析曲线显示,列线图预测模型预测围术期发生骨感染的AUC为0.893(95%CI: 0.834~0.952), 预测效能较高。决策曲线显示,列线图预测模型具有明显的正向净收益,其在预测骨感染发生风险方面拥有良好临床效用。
    结论 开放性骨折患者围术期的TLR/NF-κB信号轴关键因子动态变化对术后发生骨感染具有一定的预测价值。基于影响因素构建的列线图预测模型具有良好的预测价值及临床正向净收益。

     

    Abstract:
    Objective To analyze the predictive value of dynamic changes in key factors of the toll-like receptor (TLR)/nuclear factor-κB (NF-κB) signaling axis during the perioperative period for bone infection inpatients with open fractures.
    Methods A total of 55 patients with open fractures who developed bone infections during the perioperative period were selected as infection group, and 110 patients with open fractures who did not develop infections during the same period were selected as non-infection group. Clinical data, pre-and post-operative serum levels of routine inflammatory markers C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) and key factors of the TLR/NF-κB signaling axis (TLR4, NF-κB) were compared between the two groups. Logistic multivariate regression analysis was used to identify risk factors for bone infection during the perioperative period in patients with open fractures. Receiver operating characteristic (ROC) curves were plotted to evaluate the predictive value of the absolute change (the absolute value of the changes was expressed as △) in the levels of key factors of the TLR/NF-κB signaling axis before and after surgery for bone infection, and these results were compared with the predictive value of routine inflammatory markers. A nomogram prediction model was developed based on the identified risk factors, and its value in predicting perioperative bone infection was analyzed.
    Results The time from fracture to surgery and the duration of surgery were significantly longer, and the proportion of Gustilo type Ⅲ fractures and wounds with a depth ≥2 cm was significantly higher in the infection group compared to the non-infection group (P < 0.05). At 24 h after surgery, serum CRP, IL-6, PCT, TLR4 and NF-κB levels in two groups were significantly higher than before surgery, and serum CRP, IL-6, PCT, TLR4 as well as NF-κB levels and their changes in bone infection group were significantly higher than those in the non-infection group (P < 0.05). Logistic regression analysis indicated that time from fracture to surgery, surgical duration, Gustilo type Ⅲ and wound depth ≥2 cm, and △CRP, △IL-6, △PCT, △TLR4 as well as △NF-κB were risk factors for perioperative bone infection in patients with open fractures (P < 0.05). ROC results showed that the area under the curve (AUC) of △CRP, △IL-6, △PCT, △TLR4 and △NF-κB for predicting bone infection were 0.786, 0.833, 0.772, 0.826 and 0.736, respectively. ROC curve showed that the AUC of the nomogram prediction model for perioperative bone infection was 0.893(95%CI, 0.834 to 0.952), indicating high predictive efficacy. The decision curve showed that the nomogram prediction model had a significant positive net benefit, and it had good clinical utility in predicting the risk of bone infection.
    Conclusion The dynamic changes of key factors of TLR/NF-κB signal axis in perioperative period of patients with open fracture have certain predictive value for postoperative bone infection. The nomogram prediction model based on the above influencing factors has good predictive value and positive clinical net benefit.

     

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