title: Methylglyoxal as a new biomarker in patients with septic shock: an observational clinical study.
abstract: BACKGROUND
  The role of reactive carbonyl species, such as methylglyoxal (MG), has been overlooked within the context of the sepsis syndrome. The aims of this study were to assess the impact of MG formation in different inflammatory settings and to evaluate its use for early diagnosis as well as prognosis of the sepsis syndrome.
  
  
  METHODS
  In total, 120 patients in three groups were enrolled in this observational clinical pilot study. The three groups included patients with septic shock (n = 60), postoperative controls (n = 30), and healthy volunteers (n = 30). Plasma samples from patients with septic shock were collected at sepsis onset and after 24 hours and 4, 7, 14, and 28 days. Plasma samples from postoperative controls were collected prior to surgery, immediately following the end of the surgical procedure as well as 24 hours later and from healthy volunteers once. Plasma levels of MG were determined by high-performance liquid chromatography. Additionally, plasma levels of procalcitonin, C-reactive protein, soluble CD14 subtype, and interleukin-6 were determined.
  
  
  RESULTS
  Patients with septic shock showed significantly higher plasma levels of MG at all measured times, compared with postoperative controls. MG was found to identify patients with septic shock more effectively-area under the curve (AUC): 0.993-than procalcitonin (AUC: 0.844), C-reactive protein (AUC: 0.791), soluble CD14 subtype (AUC: 0.832), and interleukin-6 (AUC: 0.898) as assessed by receiver operating characteristic (ROC) analysis. Moreover, plasma levels of MG in non-survivors were significantly higher than in survivors (sepsis onset: *P = 0.018 for 90-day survival; **P = 0.008 for 28-day survival). Plasma levels of MG proved to be an early predictor for survival in patients with septic shock (sepsis onset: ROC-AUC 0.710 for 28-day survival; ROC-AUC 0.686 for 90-day survival).
  
  
  CONCLUSIONS
  MG was identified as a marker for monitoring the onset, development, and remission of sepsis and was found to be more useful than routine diagnostic markers. Further studies are required to determine the extent of MG modification in sepsis and whether targeting this pathway could be therapeutically beneficial to the patient.
  
  
  BACKGROUND
  German Clinical Trials Register DRKS00000505. Registered 8 November 2010.
authors.affiliation: Department of Anesthesiology, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. thorsten.brenner@med.uni-heidelberg.de.
authors.forename: Thorsten
authors.initials: T
authors.lastname: Brenner
authors.affiliation: Department of Medicine I and Clinical Chemistry, University of Heidelberg, 410, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. thomas.fleming@med.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Fleming
authors.affiliation: Department of Anesthesiology, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. florian.uhle@med.uni-heidelberg.de.
authors.forename: Florian
authors.initials: F
authors.lastname: Uhle
authors.affiliation: Department of Anesthesiology, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. silaff@web.de.
authors.forename: Stephan
authors.initials: S
authors.lastname: Silaff
authors.affiliation: Department of Anesthesiology, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. felix.schmitt@med.uni-heidelberg.de.
authors.forename: Felix
authors.initials: F
authors.lastname: Schmitt
authors.affiliation: Department of Anesthesiology, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. eduardo.salgado@med.uni-heidelberg.de.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Salgado
authors.affiliation: Department of General and Transplant Surgery, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. alexis.ulrich@med.uni-heidelberg.de.
authors.forename: Alexis
authors.initials: A
authors.lastname: Ulrich
authors.affiliation: Department of Infectious Diseases, University of Heidelberg, 324, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. stefan.zimmermann@med.uni-heidelberg.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zimmermann
authors.affiliation: Institute of Medical Biometry and Informatics, University of Heidelberg, 305, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. bruckner@imbi.uni-heidelberg.de.
authors.forename: Thomas
authors.initials: T
authors.lastname: Bruckner
authors.affiliation: Department of Anesthesiology, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. eike.martin@med.uni-heidelberg.de.
authors.forename: Eike
authors.initials: E
authors.lastname: Martin
authors.affiliation: Department of Medicine I and Clinical Chemistry, University of Heidelberg, 410, Im Neuenheimer Feld, D-69120, Heidelberg, Germany.
authors.forename: Angelika
authors.initials: A
authors.lastname: Bierhaus
authors.affiliation: Department of Medicine I and Clinical Chemistry, University of Heidelberg, 410, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. peter.nawroth@med.uni-heidelberg.de.
authors.forename: Peter P
authors.initials: PP
authors.lastname: Nawroth
authors.affiliation: Department of Anesthesiology, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. markus.weigand@med.uni-heidelberg.de.
authors.forename: Markus A
authors.initials: MA
authors.lastname: Weigand
authors.affiliation: Department of Anesthesiology, University of Heidelberg, 110, Im Neuenheimer Feld, D-69120, Heidelberg, Germany. stefan.hofer@med.uni-heidelberg.de.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hofer
mesh_terms: D000368:Aged; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D015415:Biomarkers / Q000097:blood; D010865:Pilot Projects; D011765:Pyruvaldehyde / Q000097:blood; D012772:Shock, Septic / Q000097:blood / Q000175:diagnosis
chemical_list: D015415:Biomarkers; D011765:Pyruvaldehyde