论著 · 临床研究

骨折后手术患者异位骨化风险的nomogram临床评分系统的建立

  • 王晔恺 ,
  • 陈位 ,
  • 杨颍辉 ,
  • 吴静泽 ,
  • 王和平 ,
  • 姚燕珍 ,
  • 鲍舟君
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  • 1.浙江省舟山医院检验中心,舟山 316021
    2.浙江省舟山医院骨科,舟山 316021
    3.浙江省舟山医院放射诊断中心,舟山 316021
王晔恺(1982—),男,副主任技师,学士;电子信箱:wangyekai@163.com
王晔恺,电子信箱:wangyekai@163.com

收稿日期: 2021-08-04

  网络出版日期: 2022-01-24

基金资助

浙江省卫生健康委员会医药科技计划面上项目(2020KY340)

Establishment of a nomogram clinical scoring system for the risk of heterotopic ossification in patients undergoing surgery after fracture

  • Yekai WANG ,
  • Wei CHEN ,
  • Yinghui YANG ,
  • Jingze WU ,
  • Heping WANG ,
  • Yanzhen YAO ,
  • Zhoujun BAO
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  • 1.Clinical Lab, Zhoushan Hospital, Zhejiang Province, Zhoushan 316021, China
    2.Department of Orthopaedics, Zhoushan Hospital, Zhejiang Province, Zhoushan 316021, China
    3.Radiology Diagnostic Center, Zhoushan Hospital, Zhejiang Province, Zhoushan 316021, China
WANG Yekai, E-mail: wangyekai@163.com.

Received date: 2021-08-04

  Online published: 2022-01-24

Supported by

General Project of Medical Science and Technology Plan of Health Commission of Zhejiang Province(2020KY340)

摘要

目的·建立预测骨折后接受手术治疗患者发生异位骨化(heterotopic ossification,HO)风险的nomogram临床评分系统。方法·选取2018年8月至2020年10月在浙江省舟山医院骨科或脑外科住院的骨折并接受手术的患者共124例,其中男性81例,女性43例,年龄25~91岁[平均年龄(56.48±15.45)岁]。收集患者入院临床资料,包括性别、年龄、是否合并脑外伤、麻醉方式、手术持续时间、术中出血量等。采集患者骨折后1 d、7 d、15 d共3个时间点的外周血,ELISA法检测血清骨成形蛋白2(bone morphogenetic protein 2,BMP-2)、BMP-4、BMP-5、BMP-7及细胞因子白介素-4(interleukin 4,IL-4)、IL-6、IL-10、γ干扰素(interferon γ, IFN-γ)、转化生长因子-β(transforming growth factor-β,TGF-β)的浓度。按随访结果将患者分为可见HO组和未见HO组,以α=0.15从临床和实验室指征中挑选2组间差异具有统计学意义的变量纳入单变量Cox回归模型;再以α=0.05从单变量Cox回归模型中挑选变量纳入多变量Cox回归模型来筛选患者发生异位骨化的独立风险因子,并计算风险率(HR);最后通过R语言中的rms包进行nomogram可视化输出。结果·随访共发现13例异位骨化患者,随访发现时间中位数为71(38,292)d。通过组间比较、单变量Cox回归分析、多变量Cox回归分析得到合并脑外伤(HR=2.932,P=0.038),手术持续时间(HR=1.005,P=0.007),术中出血量(HR=1.004,P=0.022),15 d时的BMP-2(HR=1.009,P=0.044)、BMP-4(HR=1.004,P=0.011)、TGF-β(HR=1.011,P=0.046),以及7 d时的BMP-7(HR=1.004,P=0.008)共7个对异位骨化结局有显著影响的独立因子并输出得到骨折后90 d、180 d、360 d患者异位骨化发生概率预测的nomogram评分系统。结论·预测骨折后手术患者异位骨化风险的nomogram评分系统的7个评分指标分别为是否合并脑外伤,手术持续时间,术中出血量,骨折后15 d外周血BMP-2、BMP-4、TGF-β水平,以及骨折后7 d外周血BMP-7水平。

本文引用格式

王晔恺 , 陈位 , 杨颍辉 , 吴静泽 , 王和平 , 姚燕珍 , 鲍舟君 . 骨折后手术患者异位骨化风险的nomogram临床评分系统的建立[J]. 上海交通大学学报(医学版), 2022 , 42(2) : 166 -172 . DOI: 10.3969/j.issn.1674-8115.2022.02.005

Abstract

Objective

·To establish a nomogram scoring system to predict morbidity of heterotopic ossification (HO) in the patients undergoing surgery after fracture.

Methods

·From August 2018 to October 2020, 124 patients with fractures from department of orthopaedics or brain surgery, including 81 males and 43 females with an average age of (56.48±15.45) years old (ranging from 25?91 years old), were enrolled in the study. Clinical features including gender, age, with brain trauma or not, anesthetic mode, operation duration time, and blood loss during operation were collected. Peripheral blood samples were collected at three time points, i.e. 1 d, 7 d and 15 d after fracture, and the sera levels of bone morphogenetic protein 2 (BMP-2), BMP-4, BMP-5, BMP-7, interleukin 4 (IL-4), IL-6, IL-10, interferon γ (IFN-γ), and transforming growth factor-β (TGF-β) were detected by ELISA. All the patients were divided into HO group and non-HO group according to follow-up outcomes. The variables with statistically significant differences (α=0.15) between the two groups selected from clinical and laboratory indications were included in the univariate Cox regression model. Then the variables selected from univariate Cox regression model (α=0.05) were incorporated into multivariate Cox regression model to screen the independent risk factors of HO and calculate the risk ratios (HR). Finally, the nomogram scoring system was output through rms package in R language.

Results

·The follow-up observation found 13 HO cases after a median time of 71 (38, 292) d. Seven independent risk factors for HO, i.e. brain trauma (HR=2.932, P=0.038), operation duration time (HR=1.005, P=0.007), blood loss during operation (HR=1.004, P=0.022), BMP-2 (15d) (HR=1.009, P=0.044), BMP-4 (15 d) (HR=1.004, P=0.011), TGF-β (15 d) (HR=1.011, P=0.046), and BMP-7 (7 d) (HR=1.004, P=0.008), were selected by comparison between groups, univariate COX regression and multivariate COX regression sequentially. The nomogram to predict morbidity of HO after 90 d, 180 d, and 360 d was generated.

Conclusion

·The seven scoring indexes of nomogram scoring system for predicting the risk of HO in the patients undergoing surgery after fracture are with brain trauma or not, operation duration time, blood loss during operation, levels of BMP-2, BMP-4 and TGF-β in peripheral blood 15 d after fracture and BMP-7 7 d after fracture.

参考文献

1 KUSANO T, NAKATANI M, ISHIGURO N, et al. Desloratadine inhibits heterotopic ossification by suppression of BMP2-Smad1/5/8 signaling[J]. J Orthop Res, 2021, 39(6): 1297-1304.
2 PARK J O, LEE B H, KANG Y M, et al. Inflammatory cytokines induce fibrosis and ossification of human ligamentum flavum cells[J]. J Spinal Disord Tech, 2013, 26(1): E6-12.
3 WANG X, LI F F, XIE L, et al. Inhibition of overactive TGF-β attenuates progression of heterotopic ossification in mice[J]. Nat Commun, 2018, 9: 551.
4 RANGANATHAN K, LODER S, AGARWAL S, et al. Heterotopic ossification: basic-science principles and clinical correlates[J]. J Bone Joint Surg Am, 2015, 97(13): 1101-1111.
5 ?EGOSZ P, OTWOROWSKI M, SIBILSKA A, et al. Heterotopic ossification: a challenging complication of total hip arthroplasty: risk factors, diagnosis, prophylaxis, and treatment[J]. Biomed Res Int, 2019, 2019: 3860142.
6 高悠水, 孙玉强, 张长青. 获得性异位骨化预防和治疗策略的研究进展[J]. 上海交通大学学报(医学版), 2014, 34(6): 934-938.
7 THILAK J, PANAKKAL J J, KIM T Y, et al. Risk factors of heterotopic ossification following total hip arthroplasty in patients with ankylosing spondylitis[J]. J Arthroplasty, 2015, 30(12): 2304-2307.
8 赵萌. 全髋关节置换术5年随访研究[J]. 现代预防医学, 2014, 41(14): 2686-2688.
9 SUNG HSIEH H H, CHUNG M T, ALLEN R M, et al. Evaluation of salivary cytokines for diagnosis of both trauma-induced and genetic heterotopic ossification[J]. Front Endocrinol (Lausanne), 2017, 8: 74.
10 HAYASHI D, GOULD E S, HO C, et al. Severity of heterotopic ossification in patients following surgery for hip fracture: a retrospective observational study[J]. BMC Musculoskelet Disord, 2019, 20(1): 348.
11 LI L, JIANG Y, LIN H, et al. Muscle injury promotes heterotopic ossification by stimulating local bone morphogenetic protein-7 production[J]. J Orthop Translat, 2019, 18: 142-153.
12 LIU T, LI B, ZHENG X F, et al. Chordin-like 1 improves osteogenesis of bone marrow mesenchymal stem cells through enhancing BMP4-SMAD pathway[J]. Front Endocrinol (Lausanne), 2019, 10: 360.
13 SUUTRE S, TOOM A, AREND A, et al. Bone tissue content of TGF-β2 changes with time in human heterotopic ossification after total hip arthroplasty[J]. Growth Factors, 2009, 27(2): 114-120.
14 WANG L, WAN G, SHEN Y, et al. A nomogram to predict mortality in patients with severe fever with thrombocytopenia syndrome at the early stage: a multicenter study in China[J]. PLoS Negl Trop Dis, 2019, 13(11): e0007829.
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