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Here, we investigated a panel of serum biomarkers with the aim of identifying biomarkers for major events and mechanisms that contribute to disease progression in established SLI. A panel of biomarkers including GRO\u03b1, HGF, SCF, SCGF\u03b2, SDF1\u03b1, TRAIL, IL-6, IL-8, FGF\u03b2, GCSF, GMCSF, IP10, MCP1, PDGFbb, RANTES, TNF\u03b1, VEGF, sICAM, sVCAM, TM, and E-selectin was measured in serum samples from a subset (n\u2009=\u2009108) of the JUVENTAS cohort. The primary outcome was major events, defined as major amputation or death. The inflammatory biomarkers IL-6, IL-8, GRO\u03b1 and IP-10 were significantly elevated in patients who reached a major endpoint. Results were validated in a secondary cohort (n\u2009=\u2009146). Cox regression showed that adjusted hazard ratios were 1.40 (95% CI: 1.15\u20131.70, p\u2009=\u20090.0007) and 1.48 (95% CI 1.16\u20131.87, p\u2009=\u20090.001) for IL-6 and IP-10 in a fully adjusted model containing both biomarkers. A prediction model using IL-6 and IP-10 showed predictive accuracy with an AUC of ~ 78% in both discovery and validation cohorts, which is higher than previously published models. We conclude that inflammatory biomarkers predict major events in patients with SLI and allow the creation of biomarker-based risk-prediction models.<\/jats:p>","DOI":"10.1038\/s41598-019-47217-1","type":"journal-article","created":{"date-parts":[[2019,7,24]],"date-time":"2019-07-24T09:07:35Z","timestamp":1563959255000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["A Pro-Inflammatory Biomarker-Profile Predicts Amputation-Free Survival in Patients with Severe Limb Ischemia"],"prefix":"10.1038","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7818-620X","authenticated-orcid":false,"given":"Hendrik","family":"Gremmels","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6751-6752","authenticated-orcid":false,"given":"Martin","family":"Teraa","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Saskia C. 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