title: Higher serum caspase-cleaved cytokeratin-18 levels during the first week of sepsis diagnosis in non-survivor patients.
abstract: BACKGROUND
  Caspase-cleaved cytokeratin (CCCK)-18 is a protein released into the blood during apoptosis. Higher circulating CCCK-18 concentrations have been found in non-survivor than in survivor septic patients at moment of sepsis diagnosis. The following questions arise now: (1) How are serum CCCK-18 levels during the first week of sepsis? (2) Is there an association between sepsis severity and mortality and serum CCCK-18 levels during the first week? The aims of this study were to answer these questions.
  
  
  METHODS
  Multicenter study with 321 severe septic patients from eight Spanish intensive care units. We determined serum concentration of CCCK-18, tumor necrosis factor (TNF)-α, and interleukin (IL)-10 during the first week. Our end-point study was 30-day mortality.
  
  
  RESULTS
  Non-survivor (n=108) compared to survivor patients (n=213) showed higher serum CCCK-18 levels at days 1, 4 and 8 (p<0.001). ROC curve analyses showed that serum CCCK-18 levels at days 1 (AUC=0.77; 95% CI=0.72-0.82), 4 (AUC=0.81; 95% CI=0.76-0.85) and 8 (AUC=0.83; 95% CI=0.78-0.88) could predict mortality at 30 days (p<0.001). Logistic regression analyses showed that serum CCCK-18 levels at days 1 (OR=4.367; 95% CI=2.491-7.659), 4 (OR=10.137; 95% CI=4.741-21.678) and 8 (OR=8.781; 95% CI=3.626-21.268) were associated with 30-day mortality (p<0.001). We found a positive correlation between CCCK-18, SOFA, and lactic acid at days 1, 4 and 8.
  
  
  CONCLUSIONS
  Non-survivor septic patients showed persistently during the first week higher serum CCCK-18 levels than survivor patients, and there is an association between sepsis severity and mortality and serum CCCK-18 levels during the first week.
authors.affiliation: .
authors.forename: Leonardo
authors.initials: L
authors.lastname: Lorente
authors.affiliation: .
authors.forename: María M
authors.initials: MM
authors.lastname: Martín
authors.affiliation: .
authors.forename: Antonia
authors.initials: A
authors.lastname: Pérez-Cejas
authors.affiliation: .
authors.forename: Raquel Ortiz
authors.initials: RO
authors.lastname: López
authors.affiliation: .
authors.forename: José
authors.initials: J
authors.lastname: Ferreres
authors.affiliation: .
authors.forename: Jordi
authors.initials: J
authors.lastname: Solé-Violán
authors.affiliation: .
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Labarta
authors.affiliation: .
authors.forename: César
authors.initials: C
authors.lastname: Díaz
authors.affiliation: .
authors.forename: Salomé
authors.initials: S
authors.lastname: Palmero
authors.affiliation: .
authors.forename: Manuel
authors.initials: M
authors.lastname: Buitrago
authors.affiliation: .
authors.forename: Alejandro
authors.initials: A
authors.lastname: Jiménez
authors.affiliation: .
authors.forename: Juan M
authors.initials: JM
authors.lastname: Borreguero-León
mesh_terms: D000328:Adult; D000368:Aged; D019540:Area Under Curve; D020169:Caspases / Q000378:metabolism*; D005260:Female; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D053208:Kaplan-Meier Estimate; D053538:Keratin-18 / Q000097:blood* / Q000378:metabolism; D019344:Lactic Acid / Q000097:blood; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012372:ROC Curve; D018805:Sepsis / Q000175:diagnosis* / Q000401:mortality; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D053538:Keratin-18; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D019344:Lactic Acid; D020169:Caspases
keywords: caspase-cleaved cytokeratin (CCCK)-18; mortality; outcome; sepsis