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

  • Author Footnotes
    1 Equal contributors.
    Jun Wang
    Footnotes
    1 Equal contributors.
    Affiliations
    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
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  • Author Footnotes
    1 Equal contributors.
    Dalin Wen
    Footnotes
    1 Equal contributors.
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Shi Zeng
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Juan Du
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Li Cui
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Jianhui Sun
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Guosheng Chen
    Affiliations
    Department of Emergency Surgery, The Affiliated Hospital, Guizhou Medical University, Guiyang, Guizhou, China
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  • Ling Zeng
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Dingyuan Du
    Affiliations
    Department of Cardiothoracic Surgery, The Affiliated Central Hospital of Chongqing University, Chongqing Emergency Medical Center, Chongqing, China
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  • Lianyang Zhang
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Jin Deng
    Correspondence
    Corresponding author. Department of Emergency Surgery, The Affiliated Hospital, Guizhou Medical University, Guiyi Street 28, Yunyang District, Guiyang City, Guizhou Province, China. Tel.: +86 13 608510419.
    Affiliations
    Department of Emergency Surgery, The Affiliated Hospital, Guizhou Medical University, Guiyang, Guizhou, China
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  • Jianxin Jiang
    Correspondence
    Corresponding author. Wound Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University, Changjiang Branch Road 10, Daping Street, Yuzhong District, Chongqing City, China. Tel.: +86 23 68757777.
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Anqiang Zhang
    Correspondence
    Corresponding author. Wound Trauma Medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Research Institute of Surgery, Daping Hospital, Army Medical University. Changjiang Branch Road 10, Daping Street, Yuzhong District, Chongqing 400042, China. Tel.: +86 23 68757512.
    Affiliations
    Wound trauma medical Center, State Key Laboratory of Trauma, Burns and Combined Injury, Institute of Surgery Research, Daping Hospital, Army Medical University, Chongqing, China
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  • Author Footnotes
    1 Equal contributors.
Published:December 05, 2022DOI:https://doi.org/10.1016/j.jss.2022.10.059

      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.

      Keywords

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      References

        • Rhodes A.
        • Evans L.E.
        • Alhazzani W.
        • et al.
        Surviving sepsis campaign: international guidelines for management of sepsis and septic shock: 2016.
        Intensive Care Med. 2017; 43: 304-377
        • Singer M.
        • Deutschman C.S.
        • Seymour C.W.
        • et al.
        The Third International Consensus Definitions for sepsis and septic shock (Sepsis-3).
        JAMA. 2016; 315: 801-810
        • Kim M.H.
        • Choi J.H.
        An update on sepsis biomarkers.
        Infect Chemother. 2020; 52: 1-18
        • Stanski N.L.
        • Wong H.R.
        Prognostic and predictive enrichment in sepsis.
        Nat Rev Nephrol. 2020; 16: 20-31
        • Delano M.J.
        • Ward P.A.
        The immune system's role in sepsis progression, resolution, and long-term outcome.
        Immunol Rev. 2016; 274: 330-353
        • D'Elia R.V.
        • Harrison K.
        • Oyston P.C.
        • Lukaszewski R.A.
        • Clark G.C.
        Targeting the "cytokine storm" for therapeutic benefit.
        Clin Vaccin Immunol. 2013; 20: 319-327
        • Trzeciak A.
        • Pietropaoli A.P.
        • Kim M.
        Biomarkers and associated immune mechanisms for early detection and therapeutic management of sepsis.
        Immune Netw. 2020; 20: e23
        • Muñoz B.
        • Suárez-Sánchez R.
        • Hernández-Hernández O.
        • Franco-Cendejas R.
        • Cortés H.
        • Magaña J.J.
        From traditional biochemical signals to molecular markers for detection of sepsis after burn injuries.
        Burns. 2019; 45: 16-31
        • Cahill L.A.
        • Joughin B.A.
        • Kwon W.Y.
        • et al.
        Multiplexed plasma immune mediator signatures can differentiate sepsis from NonInfective SIRS: American surgical association 2020 annual meeting paper.
        Ann Surg. 2020; 272: 604-610
        • Rangel-Frausto M.S.
        • Pittet D.
        • Costigan M.
        • Hwang T.
        • Davis C.S.
        • Wenzel R.P.
        The natural history of the systemic inflammatory response syndrome (SIRS). A prospective study.
        JAMA. 1995; 273: 117-123
        • Subbe C.P.
        • Slater A.
        • Menon D.
        • Gemmell L.
        Validation of physiological scoring systems in the accident and emergency department.
        Emerg Med J. 2006; 23: 841-845
        • Vincent J.L.
        • Moreno R.
        • Takala J.
        • et al.
        The SOFA (Sepsis-related Organ Failure Assessment) score to describe organ dysfunction/failure.
        Intensive Care Med. 1996; 22: 707-710
      1. Gennarelli T.A. Wodzin E. The Abbreviated Injury Scale. Association for the Advancement of Automotive Medicine, Barrington, lL2005
        • Zhang A.Q.
        • Gu W.
        • Zeng L.
        • et al.
        Genetic variants of microRNA sequences and susceptibility to sepsis in patients with major blunt trauma.
        Ann Surg. 2015; 261: 189-196
        • Wang H.E.
        • Donnelly J.P.
        • Yende S.
        • et al.
        Validation of the REGARDS severe sepsis risk score.
        J Clin Med. 2018; 7: 536
        • Shankar-Hari M.
        • Datta D.
        • Wilson J.
        • et al.
        Early PREdiction of sepsis using leukocyte surface biomarkers: the ExPRES-sepsis cohort study.
        Intensive Care Med. 2018; 44: 1836-1848
        • Lippi G.
        Sepsis biomarkers: past, present and future.
        Clin Chem Lab Med. 2019; 57: 1281-1283
        • Peters van Ton A.M.
        • Kox M.
        • Abdo W.F.
        • Pickkers P.
        Precision immunotherapy for sepsis.
        Front Immunol. 2018; 9: 1926