Volume 38 Issue 3
Mar.  2022
Turn off MathJax
Article Contents
Chen XR,Jiang DW,Tang YH,et al.Predictive values of serum 8-hydroxydeoxyguanosine on disease progression and prognosis of patients with sepsis[J].Chin J Burns Wounds,2022,38(3):207-214.DOI: 10.3760/cma.j.cn501120-20210910-00311.
Citation: Chen XR,Jiang DW,Tang YH,et al.Predictive values of serum 8-hydroxydeoxyguanosine on disease progression and prognosis of patients with sepsis[J].Chin J Burns Wounds,2022,38(3):207-214.DOI: 10.3760/cma.j.cn501120-20210910-00311.

Predictive values of serum 8-hydroxydeoxyguanosine on disease progression and prognosis of patients with sepsis

doi: 10.3760/cma.j.cn501120-20210910-00311
Funds:

General Program of National Natural Science Foundation of China 81871583, 81772112

Key Research and Development Planning Project of Zhejiang Province of China 2021C03072

Wenzhou Municipal Science and Technology Project Y20190086

More Information
  • Corresponding author: Zhao Guangju, Email: zgj_0523@126.com
  • Received Date: 2021-09-10
  •     Objective   To investigate the values of serum 8-hydroxydeoxyguanosine (8-OHdG) in predicting disease progression and prognosis of patients with sepsis.    Methods   The prospective observational research methods were used. A total of 124 patients with sepsis who met the inclusion criteria were admitted to the Department of Emergency of the First Affiliated Hospital of Wenzhou Medical University from April 2015 to July 2016, including 79 males and 45 females, aged (62±15) years. The sepsis-related organ failure assessment (SOFA) scores of all patients on admission and on the second day of admission and their difference (ΔSOFA) were calculated. The patients were divided into non-progression group with ΔSOFA score<2 (n=101) and progression group with ΔSOFA score ≥2 (n=23), and according to the survival during hospitalization, the patients were divided into survival group (n=85) and death group (n=39). Data of patients between non-progression group and progression group, survival group and death group were compared, including the gender, age, days in emergency intensive care unit (ICU), smoking, hypertension, diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission, and serum 8-OHdG within 24 h of admission. The multivariate logistic regression analysis was used to screen the independent risk factors of disease progression and death during hospitalization in 124 patients with sepsis, the receiver's operating characteristic (ROC) curves were drawn according to the independent risk factors, and the area under the curve (AUC), the best threshold, and the sensitivity and specificity under the best threshold were calculated. The patients were divided into high 8-OHdG group (n=35) and low 8-OHdG group (n=89) according to the best threshold in ROC curve of death during hospitalization. The data including the gender, age, SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in the two groups were compared. The survival rates of patients within 90 d of admission in the two groups were compared by the Kaplan-Meier method. Data were statistically analyzed with independent sample t test, Mann-Whitney U test, chi-square test, and Log-rank test.    Results   The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in non-progression group and progression group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in progression group was significantly higher than that in non-progression group (Z=-2.31, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for disease progression of 124 patients with sepsis (odds ratio=1.06, with 95% confidence interval of 1.01-1.11, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict disease progression of 124 patients with sepsis was 0.65 (with 95% confidence interval of 0.52-0.79, P<0.05), the optimal threshold was 32.88 ng/mL, and the sensitivity and specificity under the optimal threshold was 52.2% and 79.2%, respectively. The gender, age, days in emergency ICU, smoking, complicated with hypertension, complicated with diabetes mellitus, and serum white blood cell count, serum C-reactive protein, and serum procalcitonin on admission of patients in survival group and death group were similar (P>0.05). The serum 8-OHdG within 24 h of admission of patients in death group was significantly higher than that in survival group (Z=-2.37, P<0.05). Multivariate logistic regression analysis showed that the serum 8-OHdG within 24 h of admission was the independent risk factor for death of 124 patients with sepsis (odd ratio=1.04, with 95% confidence interval of 1.00-1.09, P<0.05). The AUC under the ROC curve of serum 8-OHdG within 24 h of admission to predict death of patients during hospitalization was 0.63 (with 95% confidence interval of 0.52-0.75, P<0.05), the optimal threshold was 32.43 ng/mL, the sensitivity and specificity under the optimal threshold was 51.3% and 84.7%, respectively. The gender and age of patients in high 8-OHdG group and low 8-OHdG group were similar (P>0.05). The SOFA score on admission, SOFA score on the second day of admission, and ΔSOFA score of patients in high 8-OHdG group were significantly higher than those in low 8-OHdG group (with Z values of -2.49, -3.01, and -2.64, respectively, P<0.05 or P<0.01). The survival rate within 90 d of admission of patients in low 8-OHdG group was significantly higher than that in high 8-OHdG group (χ2=14.57, P<0.01).    Conclusions   Serum 8-OHdG level is an independent risk factor for disease progression and death in sepsis patients with limited ability for predicting disease progression and prognosis of sepsis of patients. The patients with higher serum 8-OHdG level have higher death risk within 90 d of admission.

     

  • loading
  • [1]
    RhodesA, EvansLE, AlhazzaniW, et al. Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016[J]. Crit Care Med, 2017,45(3):486-552. DOI: 10.1097/CCM.0000000000002255.
    [2]
    FleischmannC,ScheragA,AdhikariNK,et al.Assessment of global incidence and mortality of hospital-treated sepsis. Current estimates and limitations[J].Am J Respir Crit Care Med,2016,193(3):259-272.DOI: 10.1164/rccm.201504-0781OC.
    [3]
    姚咏明,张卉,童亚林.深化对烧伤脓毒症诊断体系与治疗策略的认识[J].中华烧伤杂志,2021,37(5):404-409.DOI: 10.3760/cma.j.cn501120-20200703-00337.
    [4]
    徐志宏,施小燕.氧化应激参与脓毒症过程的研究进展及其对治疗的启发[J].中华急诊医学杂志,2008,17(2):221-223.DOI: 10.3760/j.issn:1671-0282.2008.02.029.
    [5]
    JoffreJ,HellmanJ.Oxidative stress and endothelial dysfunction in sepsis and acute inflammation[J].Antioxid Redox Signal,2021,35(15):1291-1307.DOI: 10.1089/ars.2021.0027.
    [6]
    WeissSL,ZhangD,BushJ,et al.Mitochondrial dysfunction is associated with an immune paralysis phenotype in pediatric sepsis[J].Shock,2020,54(3):285-293.DOI: 10.1097/SHK.0000000000001486.
    [7]
    宋文亮,吴健锋.氢化可的松、维生素C、硫胺素联合方案在脓毒症治疗中的争议与价值[J].中华医学杂志,2021,101(17):1206-1209.DOI: 10.3760/cma.j.cn112137-20210107-00045.
    [8]
    KasaiH.Analysis of a form of oxidative DNA damage, 8-hydroxy-2'-deoxyguanosine, as a marker of cellular oxidative stress during carcinogenesis[J].Mutat Res,1997,387(3):147-163.DOI: 10.1016/s1383-5742(97)00035-5.
    [9]
    KawanishiS,HirakuY,OikawaS.Mechanism of guanine-specific DNA damage by oxidative stress and its role in carcinogenesis and aging[J].Mutat Res,2001,488(1):65-76.DOI: 10.1016/s1383-5742(00)00059-4.
    [10]
    AuWW,OberheitmannB,HarmsC.Assessing DNA damage and health risk using biomarkers[J].Mutat Res,2002,509(1/2):153-163.DOI: 10.1016/s0027-5107(02)00226-9.
    [11]
    Comparison of different methods of measuring 8-oxoguanine as a marker of oxidative DNA damage. ESCODD (European Standards Committee on Oxidative DNA Damage)[J].Free Radic Res,2000,32(4):333-341.DOI: 10.1080/10715760000300331.
    [12]
    GrailleM,WildP,SauvainJJ,et al.Urinary 8-OHdG as a biomarker for oxidative stress: a systematic literature review and meta-analysis[J].Int J Mol Sci,2020,21(11):3743.DOI: 10.3390/ijms21113743.
    [13]
    KroeseLJ,SchefferPG.8-hydroxy-2'-deoxyguanosine and cardiovascular disease: a systematic review[J].Curr Atheroscler Rep,2014,16(11):452.DOI: 10.1007/s11883-014-0452-y.
    [14]
    MoslemnezhadA,MahjoubS,MoghadasiM.Altered plasma marker of oxidative DNA damage and total antioxidant capacity in patients with Alzheimer's disease[J].Caspian J Intern Med,2016,7(2):88-92.
    [15]
    LiJ,ZhangD,RamosKS,et al.Blood-based 8-hydroxy-2'- deoxyguanosine level: a potential diagnostic biomarker for atrial fibrillation[J].Heart Rhythm,2021,18(2):271-277.DOI: 10.1016/j.hrthm.2020.09.017.
    [16]
    SingerM,DeutschmanCS,SeymourCW,et al.The third international consensus definitions for sepsis and septic shock (Sepsis-3)[J].JAMA,2016,315(8):801-810.DOI: 10.1001/jama.2016.0287.
    [17]
    ValavanidisA,VlachogianniT,FiotakisC.8-hydroxy-2'- deoxyguanosine (8-OHdG): a critical biomarker of oxidative stress and carcinogenesis[J].J Environ Sci Health C Environ Carcinog Ecotoxicol Rev,2009,27(2):120-139.DOI: 10.1080/10590500902885684.
    [18]
    DaiL,WatanabeM,QureshiAR,et al.Serum 8-hydroxydeoxyguanosine, a marker of oxidative DNA damage, is associated with mortality independent of inflammation in chronic kidney disease[J].Eur J Intern Med,2019,68:60-65.DOI: 10.1016/j.ejim.2019.07.035.
    [19]
    FerreiraFL,BotaDP,BrossA,et al.Serial evaluation of the SOFA score to predict outcome in critically ill patients[J].JAMA,2001,286(14):1754-1758.DOI: 10.1001/jama.286.14.1754.
    [20]
    RonfléR,LefebvreL,DuclosG,et al.Venous-to-arterial carbon dioxide partial pressure difference: predictor of septic patient prognosis depending on central venous oxygen saturation[J].Shock,2020,53(6):710-716.DOI: 10.1097/SHK.0000000000001442.
    [21]
    BriegerK,SchiavoneS,MillerFJ,et al.Reactive oxygen species: from health to disease[J].Swiss Med Wkly,2012,142:w13659.DOI: 10.4414/smw.2012.13659.
    [22]
    王兴程,杨磊,温霄雄,等.氧化应激在脓毒症器官功能损伤中的作用[J].中国急救医学,2019,39(4):388-392.DOI: 10.3969/j.issn.1002-1949.2019.04.019.
    [23]
    KozlovAV,BahramiS,CalziaE,et al.Mitochondrial dysfunction and biogenesis: do ICU patients die from mitochondrial failure?[J].Ann Intensive Care,2011,1(1):41.DOI: 10.1186/2110-5820-1-41.
    [24]
    KarapetsaM,PitsikaM,GoutzourelasN,et al.Oxidative status in ICU patients with septic shock[J].Food Chem Toxicol,2013,61:106-111.DOI: 10.1016/j.fct.2013.03.026.
    [25]
    RogobeteAF,SandescD,PapuricaM,et al.The influence of metabolic imbalances and oxidative stress on the outcome of critically ill polytrauma patients: a review[J/OL].Burns Trauma,2017,5:8[2021-09-10]. https://pubmed.ncbi.nlm.nih.gov/28286784/. DOI: 10.1186/s41038-017-0073-0.
    [26]
    邱春芳,吴健锋,裴飞,等.血浆氧化应激因子水平与脓毒症患者预后的相关性研究[J].中华危重病急救医学,2019,31(7):847-851.DOI: 10.3760/cma.j.issn.2095-4352.2019.07.010.
    [27]
    AydınS,ŞahinTT,BacanlıM,et al.Resveratrol protects sepsis-induced oxidative DNA damage in liver and kidney of rats[J].Balkan Med J,2016,33(6):594-601.DOI: 10.5152/balkanmedj.2016.15516.
    [28]
    PrauchnerCA.Oxidative stress in sepsis: pathophysiological implications justifying antioxidant co-therapy[J].Burns,2017,43(3):471-485.DOI: 10.1016/j.burns.2016.09.023.
    [29]
    KashiourisMG, L'HeureuxM, CableCA,et al.The emerging role of vitamin C as a treatment for sepsis[J].Nutrients,2020,12(2):292. DOI: 10.3390/nu12020292.
    [30]
    YaoR,ZhuY,YuY,et al.Combination therapy of thiamine, vitamin C and hydrocortisone in treating patients with sepsis and septic shock: a meta-analysis and trial sequential analysis[J/OL].Burns Trauma,2021,9:tkab040[2021-09-10]. https://pubmed.ncbi.nlm.nih.gov/34901285/. DOI: 10.1093/burnst/tkab040.
    [31]
    JarugaP,DizdarogluM.Repair of products of oxidative DNA base damage in human cells[J].Nucleic Acids Res,1996,24(8):1389-1394.DOI: 10.1093/nar/24.8.1389.
    [32]
    GotoM,UedaK,HashimotoT,et al.A formation mechanism for 8-hydroxy-2'-deoxyguanosine mediated by peroxidized 2'- deoxythymidine[J].Free Radic Biol Med,2008,45(9):1318-1325.DOI: 10.1016/j.freeradbiomed.2008.08.003.
    [33]
    贾艳慧,刘佳琦,王耘川,等.白细胞介素17的信号转导调控及白细胞介素17在脓毒症中作用的研究进展[J].中华烧伤杂志,2021,37(7):675-680.DOI: 10.3760/cma.j.cn501120-20200515-00266.
    [34]
    KumarP,SwainMM,PalA.Hyperglycemia-induced inflammation caused down-regulation of 8-oxoG-DNA glycosylase levels in murine macrophages is mediated by oxidative-nitrosative stress-dependent pathways[J].Int J Biochem Cell Biol,2016,73:82-98.DOI: 10.1016/j.biocel.2016.02.006.
    [35]
    BaharI,ElayG,BaşkolG,et al.Increased DNA damage and increased apoptosis and necrosis in patients with severe sepsis and septic shock[J].J Crit Care,2018,43:271-275.DOI: 10.1016/j.jcrc.2017.09.035.
    [36]
    Di MinnoA,TurnuL,PorroB,et al.8-Hydroxy-2-deoxyguanosine levels and heart failure: a systematic review and meta-analysis of the literature[J].Nutr Metab Cardiovasc Dis,2017,27(3):201-208.DOI: 10.1016/j.numecd.2016.10.009.
    [37]
    CaoP,ZhangC,HuaDX,et al.Serum 8-hydroxy-2'- deoxyguanosine predicts severity and prognosis of patients with acute exacerbation of chronic obstructive pulmonary disease[J].Lung,2022,200(1):31-39.DOI: 10.1007/s00408-021-00507-w.
    [38]
    CaoLF,ChengJY,XuZ,et al.Serum 8-hydroxydeoxyguanosine is a potential indicator for the severity and prognosis in patients with community-acquired pneumonia: a prospective cohort study[J].J Immunol,2022,208(2):321-327.DOI: 10.4049/jimmunol.2100711.
    [39]
    LorenteL,MartínMM,González-RiveroAF,et al.Association between DNA and RNA oxidative damage and mortality in septic patients[J].J Crit Care,2019,54:94-98.DOI: 10.1016/j.jcrc.2019.08.008.
  • 加载中

Catalog

    通讯作者: 陈斌, bchen63@163.com
    • 1. 

      沈阳化工大学材料科学与工程学院 沈阳 110142

    1. 本站搜索
    2. 百度学术搜索
    3. 万方数据库搜索
    4. CNKI搜索

    Figures(3)  / Tables(4)

    Article Metrics

    Article views (1288) PDF downloads(32) Cited by()
    Proportional views
    Related

    /

    DownLoad:  Full-Size Img  PowerPoint
    Return
    Return