Tjitske van Engelen

125 Host response in patients with ICU-acquired pneumonia p1 = 0.0005 p2 = 0.002 101.5 102 102.5 103 2 5 10 20 30 Time to ICU-A Pneumonia IL-6 (pg/mL) Baseline IL-6 p1 = 0.0066 p2 = 0.0113 101.4 101.6 101.8 2 5 10 20 30 Time to ICU-A Pneumonia IL-8 (pg/mL) Baseline IL-8 p1 = 0.0201 p2 = 0.0157 101 101.1 101.2 101.3 101.4 2 5 10 20 30 Time to ICU-A Pneumonia IL-10 (pg/mL) Baseline IL-10 p1 = 0.0003 p2 = 0.0375 103.2 103.4 103.6 103.8 104 104.2 104.4 2 5 10 20 30 Time to ICU-A Pneumonia IL-1RA (pg/mL) Baseline IL-1RA p1 = 0.0033 p2 = 0.6143 103 103.5 104 104.5 2 5 10 20 30 Time to ICU-A Pneumonia Procalcitonin (pg/mL) Baseline Procalcitonin p1 = 0.016 p2 = 0.4509 104 104.5 105 2 5 10 20 30 Time to ICU-A Pneumonia MMP-8 (pg/mL) Baseline MMP-8 p1 = 0.0005 p2 = 0.0111 102.5 102.6 102.7 102.8 102.9 103 103.1 2 5 10 20 30 Time to ICU-A Pneumonia sTREM-1 (pg/mL) Baseline sTREM-1 p1 = 0.0001 p2 = 0.0003 103.4 103.6 103.8 104 2 5 10 20 30 Time to ICU-A Pneumonia sRAGE (pg/mL) Baseline sRAGE p1 = 0.0033 p2 = 0.0826 104.2 104.3 104.4 104.5 2 5 10 20 30 Time to ICU-A Pneumonia Tenascin-C (pg/mL) Baseline Tenascin-C p1 = 0.6513 p2 = 0.9165 105.7 105.8 105.9 106 106.1 106.2 106.3 2 5 10 20 30 Time to ICU-A Pneumonia sCD163 (pg/mL) Baseline sCD163 Figure S7. Baseline cytokine release and systemic inflammatory responses in Intensive Care Unit (ICU) patients who developed ICU-acquired pneumonia. Baseline value plotted against the time of onset of the event in the ICU with 95% confidence intervals. Adjusted regression analysis for the following clinical baseline characteristics: site of enrolment, age, gender, body mass index, Charlson comorbidity index, reason for admission (medical, surgery, trauma), S. aureus colonization status, Acute Physiology And Chronic Health Evaluation (APACHE)-IV score, and immunosuppressed status. P value <0.05 of p1 indicates that the time of onset of pneumonia was significantly associated with the biomarker level at ICU admission. P value of p2 indicates nonlinearity (P <0.05) of the association of p1, assessed with the Wald statistic using restricted cubic splines. Definition of abbreviations: CD = cluster of differentiation; ICU-A = Intensive Care Unit acquired; IL = interleukin; MMP = matrix metalloproteinase; RA = receptor antagonist; RAGE = receptor for advanced glycation endproducts; s = soluble; TREM = triggering receptor expressed on myeloid cells. 5

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