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dc.contributor.authorMeertens JH
dc.contributor.authorNienhuis HL
dc.contributor.authorLefrandt JD
dc.contributor.authorSchalkwijk CG
dc.contributor.authorNyyssönen K
dc.contributor.authorLigtenberg JJ
dc.contributor.authorSmit AJ
dc.contributor.authorZijlstra JG
dc.contributor.authorMulder DJ
dc.date.accessioned2018-02-26T09:29:09Z
dc.date.available2018-02-26T09:29:09Z
dc.date.issued2016
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/6160
dc.description.abstractBackground Advanced glycation end products (AGEs) have been implicated in multiple organ failure, predominantly via their cellular receptor (RAGE) in preclinical studies. Little is known about the time course and prognostic relevance of AGEs in critically ill human patients, including those with severe sepsis. Objective 1) To explore the reliability of Skin Autofluorescence (AF) as an index of tissue AGEs in ICU patients, 2) to compare its levels to healthy controls, 3) to describe the time course of AGEs and influencing factors during ICU admission, and 4) to explore their association with disease severity, outcome, and markers of oxidative stress and inflammation. Methods Skin AF, serum N"-(carboxyethyl)lysine (CEL), N"-(carboxymethyl)lysine (CML), and soluble RAGE (sRAGE) were serially measured for a maximum of 7 days in critically ill ICU patients with multiple organ failure and compared to age-matched healthy controls. Correlations with (changes in) clinical parameters of disease severity, LDL dienes, and CRP were studied and survival analysis for in-hospital mortality was performed. Results Forty-five ICU patients (age: 59±15 years; 60% male), and 37 healthy controls (59±14; 68%) were included. Skin AF measurements in ICU patients were reproducible (CV right-left arm: 13%, day-to-day: 10%), with confounding effects of skin reflectance and plasma bilirubin levels. Skin AF was higher in ICU patients vs healthy controls (2.7±0.7 vs 1.8±0.3 au; p<0.001). Serum CEL (23±10 vs, 16±3 nmol/gr protein; p<0.001), LDL dienes (19 (15–23) vs. 9 (8–11) μmol/mmol cholesterol; <0.001), and sRAGE (1547 (998–2496) vs. 1042 (824–1388) pg/ml; p = 0.003) were significantly higher in ICU patients compared to healthy controls, while CML was not different (27 (20–39) vs 29 (25–33) nmol/gr protein). While CRP and LDL dienes decreased significantly, Skin AF and serum AGEs and sRAGE did not change significantly during the first 7 days of ICU admission. CML and CEL were strongly correlated with SOFA scores and CML above the median at baseline was associated with increased risk for mortality (Hazard ratio 3.3 (1.3–8.3); p = 0.01). All other markers did not correlate with disease severity and did not predict mortality. Conclusions This study demonstrates that markers for the AGE-RAGE axis are elevated in critically ill patients compared to healthy controls but remain stable for at least 7 days despite clearly fading inflammation and oxidative stress. Circulating AGEs may be associated with disease severity and outcome. Further research should be conducted to elucidate the role of the AGE-RAGE axis in the exaggerated inflammatory response leading to multiple organ failure and death, and whether or not this may be a target for treatment.en
dc.language.isoENen
dc.publisherPublic Library of Science (PLoS)en
dc.relation.ispartofseriesPLOS ONEen
dc.relation.urihttp://dx.doi.org/10.1371/journal.pone.0160893en
dc.rightsCC BY http://creativecommons.org/licenses/by/4.0/en
dc.titleThe Course of Skin and Serum Biomarkers of Advanced Glycation Endproducts and Its Association with Oxidative Stress, Inflammation, Disease Severity, and Mortality during ICU Admission in Critically Ill Patients: Results from a Prospective Pilot Studyen
dc.description.versionpublished versionen
dc.contributor.departmentSchool of Medicine / Public Healthen
uef.solecris.id44076666en
dc.type.publicationinfo:eu-repo/semantics/articleen
dc.rights.accessrights© Authorsen
dc.relation.doi10.1371/journal.pone.0160893en
dc.description.reviewstatuspeerRevieweden
dc.relation.articlenumbere0160893en
dc.relation.issn1932-6203en
dc.relation.issue8en
dc.relation.volume11en
dc.rights.accesslevelopenAccessen
dc.type.okmA1en
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
uef.solecris.openaccessOpen access -julkaisukanavassa ilmestynyt julkaisu


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