Young and Aged Blunt Trauma Patients Display Major Differences in Circulating Inflammatory Mediator Profiles after Severe Injury Ashley J. Lamparello,

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Young and Aged Blunt Trauma Patients Display Major Differences in Circulating Inflammatory Mediator Profiles after Severe Injury Ashley J. Lamparello, MD, Rami A. Namas, MD, Othman Abdul-Malak, MD, Yoram Vodovotz, PhD, Timothy R. Billiar, MD, FACS Journal of the American College of Surgeons Volume 228, Issue 2, Pages 148-160.e7 (February 2019) DOI: 10.1016/j.jamcollsurg.2018.10.019 Copyright © 2018 American College of Surgeons Terms and Conditions

Figure 1 Dynamic Bayesian Network (DyBN) suggests differential expression of dynamic networks among the (A) young group matched for Injury Severity Score and (B) aged group matched for Injury Severity Score. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

Figure 2 (A) Dynamic Network Analysis (DyNA) of inflammatory mediators among the groups matched for Injury Severity Score suggests a differential inflammation profile from 0 to 24 hours. (B) DyNA network complexity and (C) Dynamic Robustness Index differs between the young and aged patients. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

eFigure 1 Abbreviated Injury Scale analysis of injury patterns in the (A) overall cohorts and (B) groups matched for Injury Severity Score. ∗p < 0.05 by Mann-Whitney U test. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

eFigure 2 Time course analysis from time of injury up to day (D) 7 of interleukin (IL)-1β, IL-1 receptor antagonist (IL-1RA), IL-2, soluble IL-2 receptor-α (sIL-2Rα), IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-15, IL-17A, IL-21, IL-23, interferon (IFN)-α, granulocyte-macrophage colony-stimulating factor (GM-CSF), macrophage inflammatory protein (MIP)-1β, MIP-1α, monocyte chemoattractant protein (MCP)-1, tumor necrosis factor (TNF)-α, eotaxin, interferon gamma-induced protein 10 (IP-10), and monokine induced by gamma interferon (MIG) among the overall cohorts of young vs aged. Data presented as mean ± SEM. Statistical significance set at p < 0.05 by 2-way ANOVA. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

eFigure 3 Time course analysis from time of injury up to day (D) 7 of interleukin (IL)-5, IL-6, IL-7, macrophage inflammatory protein (MIP)-1β, interferon gamma-induced protein 10 (IP-10), and monokine induced by gamma interferon (MIG) among the groups matched for ISS. Data presented as mean ± SEM. Statistical significance set at p < 0.05 by 2-way ANOVA. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

eFigure 4 Injury Severity Score vs area under the curve (AUC) of interleukin (IL)-5, IL-6, IL-7, macrophage inflammatory protein (MIP)-1β, interferon gamma-induced protein 10 (IP-10), and monokine induced by gamma interferon (MIG) in (A) the first 24 hours post-injury and (B) day 1 to day 7 among the overall cohorts of young vs aged. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

eFigure 5 Time course analysis from time of injury up to day (D) 7 of interleukin (IL)-5, IL-6, IL-7, macrophage inflammatory protein (MIP)-1β, interferon gamma-induced protein 10 (IP-10), and monokine induced by gamma interferon (MIG) among patients 65 to 75 years old vs 80 to 90 years old. Data presented as mean ± SEM. Statistical significance set at p < 0.05 by 2-way ANOVA. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

eFigure 6 Time course analysis from time of injury up to day (D) 7 of interleukin (IL)-5, IL-6, and IL-7 for the aged without comorbidities subgroup vs aged with cardiovascular (CV) disease subgroup. Data presented as mean ± SEM. Statistical significance set at p < 0.05 by 2-way ANOVA.fx Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

eFigure 7 Time course analysis from time of injury up to day (D) 7. (A) Interleukin (IL)-5, IL-6, IL-7, macrophage inflammatory protein (MIP)-1β, interferon gamma-induced protein 10 (IP-10), and monokine induced by gamma interferon (MIG) for the young vs aged subgroups without nosocomial infection, and (B) IL-6 and IL-7 for the young vs aged subgroups with nosocomial infection. Data presented as mean ± SEM. Statistical significance set at p < 0.05 by 2-way ANOVA. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions

eFigure 8 Time course analysis from time of injury up to day (D) 7. (A) Interferon gamma-induced protein 10 (IP-10), monokine induced by gamma interferon (MIG), and macrophage inflammatory protein (MIP)-1β for the young vs aged subgroups with ICU length of stay (LOS) ≤5 days, and (B) interleukin (IL)-5, IL-6, and MIP-1β for the young vs aged subgroups with ICU LOS >5 days. Data presented as mean ± SEM. Statistical significance set at p < 0.05 by 2-way ANOVA. Journal of the American College of Surgeons 2019 228, 148-160.e7DOI: (10.1016/j.jamcollsurg.2018.10.019) Copyright © 2018 American College of Surgeons Terms and Conditions