ArticleAnnals of surgery2020
Multiplexed Plasma Immune Mediator Signatures Can Differentiate Sepsis From NonInfective SIRS: American Surgical Association 2020 Annual Meeting Paper.
Article in Annals of surgery, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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10 citing papers in PubMed, 14 citations in OpenAlex.
- Endothelial-Derived CCL7 Promotes Macrophage Polarization and Aggravates Septic Acute Lung Injury via CCR1-Mediated STAT1 Succinylation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Sepsis in liver failure patients: Diagnostic challenges and recent advancements.World journal of critical care medicine · 2025Review
- Heme-Inducing Endothelial Pyroptosis Plays a Key Role in Radiofrequency Ablation of Hepatic Hemangioma Leading to Systemic Inflammatory Response Syndrome.Journal of inflammation research · 2024Article
- Herbal formula BaWeiBaiDuSan alleviates polymicrobial sepsis-induced liver injuryActa pharmaceutica Sinica. B · 2023Article
- Identifying biomarkers deciphering sepsis from trauma-induced sterile inflammation and trauma-induced sepsis.Frontiers in immunology · 2023Article
- Sepsis biomarkers and diagnostic tools with a focus on machine learning.EBioMedicine · 2022Review
- Management algorithm of external fixation in lower leg arterial injury for limb salvages.BMC surgery · 2022Article
- Translational and Clinical Significance of DAMPs, PAMPs, and PRRs in Trauma-induced Inflammation.Archives of clinical and biomedical research · 2022Article
- Article
- Profiling the Expression of Circulating Acute-Phase Proteins, Cytokines, and Checkpoint Proteins in Patients with Severe Trauma: A Pilot Study.Journal of inflammation research · 2021Article
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10 authors at 4 institutions in 2 countries.
Funding
Abstract
objectivesSepsis and sterile both release "danger signals' that induce the systemic inflammatory response syndrome (SIRS). So differentiating infection from SIRS can be challenging. Precision diagnostic assays could limit unnecessary antibiotic use, improving outcomes.
methodsAfter surveying human leukocyte cytokine production responses to sterile damage-associated molecular patterns (DAMPs), bacterial pathogen-associated molecular patterns, and bacteria we created a multiplex assay for 31 cytokines. We then studied plasma from patients with bacteremia, septic shock, "severe sepsis," or trauma (ISS ≥15 with circulating DAMPs) as well as controls. Infections were adjudicated based on post-hospitalization review. Plasma was studied in infection and injury using univariate and multivariate means to determine how such multiplex assays could best distinguish infective from noninfective SIRS.
resultsInfected patients had high plasma interleukin (IL)-6, IL-1α, and triggering receptor expressed on myeloid cells-1 (TREM-1) compared to controls [false discovery rates (FDR) <0.01, <0.01, <0.0001]. Conversely, injury suppressed many mediators including MDC (FDR <0.0001), TREM-1 (FDR <0.001), IP-10 (FDR <0.01), MCP-3 (FDR <0.05), FLT3L (FDR <0.05), Tweak, (FDR <0.05), GRO-α (FDR <0.05), and ENA-78 (FDR <0.05). In univariate studies, analyte overlap between clinical groups prevented clinical relevance. Multivariate models discriminated injury and infection much better, with the 2-group random-forest model classifying 11/11 injury and 28/29 infection patients correctly in out-of-bag validation.
conclusionsCirculating cytokines in traumatic SIRS differ markedly from those in health or sepsis. Variability limits the accuracy of single-mediator assays but machine learning based on multiplexed plasma assays revealed distinct patterns in sepsis- and injury-related SIRS. Defining biomarker release patterns that distinguish specific SIRS populations might allow decreased antibiotic use in those clinical situations. Large prospective studies are needed to validate and operationalize this approach.
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