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中华实验和临床感染病杂志(电子版)

中华实验和临床感染病杂志(电子版) ›› 2023, Vol. 17 ›› Issue (03) : 187 -193. doi: 10.3877/cma.j.issn.1674-1358.2023.03.007

论著

血清乳酸脱氢酶、白细胞介素6、降钙素原和超敏C反应蛋白水平变化在多发性骨髓瘤合并细菌感染者预后中的评估价值
路炳通†(), 侯英荣, 胡永强, 齐雅欣   
  1. 061000　沧州市，河北省沧州中西医结合医院体检中心
  • 收稿日期:2022-11-08 出版日期:2023-06-15
  • 通信作者: 路炳通
  • 基金资助:
    河北省人才工程培养资助项目(No. A201901110); 河北省卫健委重点科技研究计划(No. 20191283); 沧州市重点研发计划指导项目(No. 213106073); 沧州市科学技术研究与发展指导计划项目(No. 172302167)

Clinical analysis of serum lactate dehydrogenase, interleukin-6, procalcitonin and high-sensitivity C-reactive protein levels in evaluating the prognosis of multiple myeloma patients with bacterial infection

Bingtong Lu†(), Yingrong Hou, Yongqiang Hu, Yaxin Qi   

  1. Physical Examination Center, Hebei Cangzhou Integrated Traditional Chinese and Western Medicine Hospital, Cangzhou 061000, China
  • Received:2022-11-08 Published:2023-06-15
  • Corresponding author: Bingtong Lu
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引用本文：

路炳通, 侯英荣, 胡永强, 齐雅欣. 血清乳酸脱氢酶、白细胞介素6、降钙素原和超敏C反应蛋白水平变化在多发性骨髓瘤合并细菌感染者预后中的评估价值[J/OL]. 中华实验和临床感染病杂志(电子版), 2023, 17(03): 187-193.

Bingtong Lu, Yingrong Hou, Yongqiang Hu, Yaxin Qi. Clinical analysis of serum lactate dehydrogenase, interleukin-6, procalcitonin and high-sensitivity C-reactive protein levels in evaluating the prognosis of multiple myeloma patients with bacterial infection[J/OL]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2023, 17(03): 187-193.

目的

评估血清乳酸脱氢酶（LDH）、白细胞介素6（IL-6）、降钙素原（PCT）、超敏C-反应蛋白（hs-CRP）水平变化与多发性骨髓瘤合并感染者预后的临床价值。

方法

回顾性分析2019年6月至2022年6月沧州中西医结合医院收治的141例多发性骨髓瘤患者的临床资料，根据是否发生感染将其分为感染组（84例）和对照组（57例）。比较两组患者血清LDH、IL-6、PCT和hs-CRP水平差异，并比较感染组患者治疗前后LDH、IL-6、PCT和hs-CRP水平变化，比较感染组不同临床预后（恢复、持续感染、感染性休克和感染性死亡）患者IL-6、PCT、LDH和hs-CRP水平。多因素Logistics回归分析LDH、IL-6、PCT和hs-CRP水平对多发性骨髓瘤合并细菌感染预后的影响，并应用受试者工作特征曲线（ROC）评估血清LDH、IL-6、PCT和hs-CRP水平对多发性骨髓瘤合并细菌感染者预后的预测价值。

结果

感染组患者血清LDH、IL-6、PCT和hs-CRP水平显著高于对照组（U = 67.491、38.425、53.597、29.617，P均< 0.001）。较治疗前，感染组患者治疗后LDH、IL-6、PCT和hs-CRP水平均显著降低（t = 10.150、15.012、12.062、16.756，P均< 0.001）。感染组不同预后患者治疗前血清LDH、IL-6、PCT和hs-CRP水平差异均有统计学意义（P均< 0.001）；持续性感染、感染性休克、感染性死亡患者治疗前血清LDH、IL-6、PCT和hs-CRP水平显著高于恢复期患者，感染性死亡患者显著高于持续感染及感染性休克患者（P均< 0.05）。多因素Logistic回归分析显示，LDH（OR = 5.436、95%CI：1.864~15.850、P = 0.002）、IL-6（OR = 4.572、95%CI：1.470~14.223、P = 0.009）、PCT（OR = 4.797，95%CI：1.738~13.240、P = 0.002）和hs-CRP（OR = 5.089、95%CI：1.794~14.436、P = 0.002）水平升高均为多发性骨髓瘤合并细菌感染预后的独立危险因素。ROC曲线显示，血清LDH（最佳阈值：853.00 U/L）（灵敏度和特异度分别为73.41%和61.78%）、IL-6（最佳阈值：21.50 pg/ml）（灵敏度和特异度分别为65.24%和52.31%）、PCT（最佳阈值：9.90 pg/ml）（灵敏度和特异度分别为68.98%和46.37%）和hs-CRP（最佳阈值：35.3 mg/L）（灵敏度和特异度分别为59.49%和45.34%）诊断多发性骨髓瘤合并细菌感染者预后的ROC曲线下面积（AUC）分别为0.813、0.849、0.858和0.805，四者联合诊断的AUC为0.884（灵敏度和特异度分别为91.32%和94.16%），均显著高于4个指标单独诊断的AUC值（P均< 0.05）。

结论

血清LDH、IL-6、PCT和hs-CRP联合诊断多发性骨髓瘤合并细菌感染者预后效能较高，可作为监测临床疗效、评估临床预后的指标。

关键词: 多发性骨髓瘤, 乳酸脱氢酶, 白细胞介素6, 降钙素原, 超敏C-反应蛋白, 预后
Objective

To evaluate the clinical value of serum levels of lactate dehydrogenase (LDH), interleukin-6 (IL-6), procalcitonin (PCT) and high-sensitivity C-reactive protein (hs-CRP) on the prognosis of patients with multiple myeloma (MM) complicated with infection.

Methods

The clinical data of 141 patients with MM admitted to Cangzhou Integrated Traditional Chinese and Western Medicine Hospital from June 2019 to June 2022 were analyzed, retrospectively. According to the incidence of infection, patients with MM were divided into infection group (84 cases) and control group (57 cases). Differences of serum LDH, IL-6, PCT and hs-CRP levels between the two groups, and the changes of LDH, IL-6, PCT and hs-CRP levels before and after treatment in infection group were compared, respectively. Also, the levels of IL-6, PCT, LDH and hs-CRP of patients with different clinical outcomes (recovery, persistent infection, septic shock and septic death) in infection group were compared. The influence of LDH, IL-6, PCT and hs-CRP levels on the prognosis of MM patients with infection were analyzed by Multivariate Logistic regression analysis, and the predictive value of serum LDH, IL-6, PCT and hs-CRP levels on the prognosis of MM patients with infection were evaluated by the receiver operating characteristic curve (ROC).

Results

The serum levels of LDH, IL-6, PCT and hs-CRP in infection group were significantly higher than those of the control group (U = 67.491, 38.425, 53.597, 29.617, all P < 0.001). Compared with before treatment, the levels of LDH, IL-6, PCT and hs-CRP of patients in infection group reduced significantly after treatment (t = 10.150, 15.012, 12.062, 16.756, all P < 0.001). There were statistically significant differences in serum LDH, IL-6, PCT and hs-CRP levels before treatment among patients with different prognosis in infection group (all P < 0.001); the levels of serum LDH, IL-6, PCT and hs-CRP of patients with persistent infection, septic shock, and septic death before treatment were significantly higher than those in the recovery period, which were significantly higher in patients with septic death than those with persistent infection and septic shock (all P < 0.05). Multivariate Logistic regression analysis showed that the increase of LDH (OR = 5.436, 95%CI: 1.864-15.850, P = 0.002), IL-6 (OR = 4.572, 95%CI: 1.470-14.223, P = 0.009), PCT (OR = 4.797, 95%CI: 1.738-13.240, P = 0.002), hs-CRP (OR = 5.089, 95%CI: 1.794-14.436, P = 0.002) were independent risk factors for the prognosis of MM with bacterial infection. The ROC analysis showed that the areas under ROC (AUCs) of serum LDH (the best threshold: 853.00 U/L) (sensitivity and specificity were 73.41% and 61.78%), IL-6 (the best threshold: 21.50 pg/ml) (sensitivity and specificity were 65.24% and 52.31%), PCT (the best threshold: 9.90 pg/ml) (sensitivity and specificity were 68.98% and 46.37%) and hs-CRP (the best threshold: 35.3 mg/L) (sensitivity and specificity were 59.49% and 45.34%) in the diagnosis of MM with bacterial infection were 0.813, 0.849, 0.858 and 0.805, the AUC of combined diagnosis of the four indexes was 0.884 (sensitivity and specificity were 91.32% and 94.16%), which were significantly higher than the AUCs of the four single indexes, respectively (all P < 0.001).

Conclusions

Combination of serum LDH, IL-6, PCT and hs-CRP levels for the diagnosis of MM with bacterial infection has a high prognosis value, which can be used as an indicator for monitoring clinical efficacy and evaluating clinical prognosis.

Key words: Multiple myeloma, Lactate dehydrogenase, Interleukin-6, Procalcitonin, Hypersensitive C-reactive protein, Prognosis
表1 感染组和对照组患者的基线资料
组别 例数 男/女 年龄（ ± s，岁） DS分期（Ⅰ/Ⅱ/Ⅲ，例） 免疫分型（IgG/IgA/IgD/轻链型，例）
感染组 84 49/35 60.80 ± 12.43 20/24/40 46/26/3/9
对照组 57 36/21 62.40 ± 14.32 13/16/28 29/20/2/6
统计量   χ2 = 0.330 t = 0.705 χ2 = 0.034 χ2 = 0.287
P值   0.566 0.482 0.983 0.601
表2 感染组和对照组患者血清LDH、IL-6、PCT和hs-CRP水平[M（P25，P75）]
组别 例数 LDH（U/L） IL-6（pg/ml） PCT（pg/ml） hs-CRP（mg/L）
感染组 84 743.18（652.31，801.92） 26.45（17.42，35.21） 14.6（8.91，27.49） 42.52（27.19，63.24）
对照组 57 287.41（253.15，318.94） 4.12（2.91，6.15） 0.18（0.09，0.27） 6.18（5.47，9.28）
U值   67.491 38.425 53.597 29.617
P值   < 0.001 < 0.001 < 0.001 < 0.001
表3 感染组患者治疗前后血清LDH、IL-6、PCT和hs-CRP水平（ ± s）
时间 例数 LDH（U/L） IL-6（pg/ml） PCT（pg/ml） hs-CRP（mg/L）
治疗前 84 761.21 ± 154.01 27.82 ± 6.60 15.53 ± 3.24 46.60 ± 8.56
治疗后 84 536.57 ± 132.02 14.90 ± 4.32 10.27 ± 2.34 26.67 ± 6.75
t值   10.150 15.012 12.062 16.756
P值   < 0.001 < 0.001 < 0.001 < 0.001
表5 多因素Logistics回归分析LDH、IL-6、PCT和hs-CRP水平对MM合并细菌感染预后的影响
影响因素 β值 S.E值 Wald χ2值 OR值 95%CI P值
LDH 1.693 0.546 9.615 5.436 1.864~15.850 0.002
IL-6 1.520 0.579 6.892 4.572 1.470~14.223 0.009
PCT 1.568 0.518 9.163 4.797 1.738~13.240 0.002
hs-CRP 1.627 0.532 9.353 5.089 1.794~14.436 0.002
图1 血清LDH、IL-6、PCT和hs-CRP水平与MM合并细菌感染预后的ROC曲线
表4 感染组不同预后患者血清LDH、IL-6、PCT和hs-CRP水平（ ± s）
预后 例数 LDH（U/L） IL-6（pg/ml） PCT（pg/ml） hs-CRP（mg/L）
恢复 64 703.28 ± 170.70 21.30 ± 4.52 10.24 ± 2.38 39.86 ± 7.55
持续感染 13 868.62 ± 171.50 39.92 ± 6.94 24.82 ± 5.77 53.89 ± 8.76
感染性休克 4 883.75 ± 84.89 41.00 ± 8.31 22.70 ± 6.93 54.28 ± 9.48
感染性死亡 3 1368.33 ± 130.52 91.67 ± 10.55 88.30 ± 8.73 135.00 ± 12.00
F值   18.259 23.241 45.253 24.921
P值   < 0.001 < 0.001 < 0.001 < 0.001
t1值   3.182 12.274 15.092 5.946
P1值   < 0.002 < 0.001 < 0.001 < 0.001
t2值   2.087 8.033 8.775 3.658
P2值   0.041 < 0.001 < 0.001 0.001
t3值   6.638 24.718 47.208 20.848
P3值   < 0.001 < 0.001 < 0.001 < 0.001
t4值   0.168 0.261 0.616 0.077
P4值   0.869 0.798 0.547 0.940
t5值   4.692 10.684 15.784 13.628
P5值   < 0.001 < 0.001 < 0.001 < 0.001
t6值   6.012 7.156 11.154 10.008
P6值   < 0.001 < 0.001 < 0.001 < 0.001
表6 血清LDH、IL-6、PCT和hs-CRP水平预测MM合并细菌感染预后的ROC曲线
指标 AUC 最佳阈值 敏感性（%） 特异性（%） 95%CI
LDH 0.813 853.00 U/L 73.41 61.78 0.697~0.930
IL-6 0.849 21.50 pg/ml 65.24 52.31 0.761~0.937
PCT 0.858 9.90 pg/ml 68.98 46.37 0.780~0.936
hs-CRP 0.805 35.3 mg/L 59.49 45.34 0.711~0.899
联合检测 0.884 — 91.32 94.16 0.808~0.959
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