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Higher serum caspase-cleaved cytokeratin-18 levels during the first week of sepsis diagnosis in non-survivor patients

  • Leonardo Lorente EMAIL logo , María M. Martín , Antonia Pérez-Cejas , Raquel Ortiz López , José Ferreres , Jordi Solé-Violán , Lorenzo Labarta , César Díaz , Salomé Palmero , Manuel Buitrago , Alejandro Jiménez and Juan M. Borreguero-León
Published/Copyright: March 7, 2017
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Clinical Chemistry and Laboratory Medicine (CCLM)
From the journal Clinical Chemistry and Laboratory Medicine (CCLM) Volume 55 Issue 10

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.

Keywords: caspase-cleaved cytokeratin (CCCK)-18; mortality; outcome; sepsis

  1. Author contributions: L.Lo. conceived, designed and coordinated the study, participated in acquisition and interpretation of data, and drafted the manuscript. M.M.M., R.O.L., J.F., J.S.V., L.La., C.D., S.P., M.B. participated in acquisition of data. APC and JMBL participated in blood determination levels. A.J. participated in the interpretation of data. All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

  2. Research funding: This study was supported by grants from Instituto de Salud Carlos III (PI14/00220 and INT16/00165) (Madrid, Spain) and co-financed by Fondo Europeo de Desarrollo Regional (FEDER). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

  3. Employment or leadership: None declared.

  4. Honorarium: None declared.

  5. Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

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Received: 2016-11-10
Accepted: 2017-1-26
Published Online: 2017-3-7
Published in Print: 2017-8-28

©2017 Walter de Gruyter GmbH, Berlin/Boston

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https://doi.org/10.1515/cclm-2016-1034
Keywords for this article
caspase-cleaved cytokeratin (CCCK)-18; mortality; outcome; sepsis

Articles in the same Issue

  1. Frontmatter
  2. Editorials
  3. Reporting LDL-cholesterol levels in the era of intensive lipid management: a clarion call
  4. The challenges of genetic risk scores for the prediction of coronary heart disease
  5. Reviews
  6. Advanced lipoprotein testing for cardiovascular diseases risk assessment: a review of the novel approaches in lipoprotein profiling
  7. A review of the challenge in measuring and standardizing BCR-ABL1
  8. Mini Review
  9. Challenges in the analysis of epigenetic biomarkers in clinical samples
  10. Opinion Paper
  11. Defining a roadmap for harmonizing quality indicators in Laboratory Medicine: a consensus statement on behalf of the IFCC Working Group “Laboratory Error and Patient Safety” and EFLM Task and Finish Group “Performance specifications for the extra-analytical phases”
  12. Genetics and Molecular Diagnostics
  13. Assessment of EGFR mutation status using cell-free DNA from bronchoalveolar lavage fluid
  14. General Clinical Chemistry and Laboratory Medicine
  15. A survey of patients’ views from eight European countries of interpretive support from Specialists in Laboratory Medicine
  16. Verification of examination procedures in clinical laboratory for imprecision, trueness and diagnostic accuracy according to ISO 15189:2012: a pragmatic approach
  17. Expressing analytical performance from multi-sample evaluation in laboratory EQA
  18. A candidate reference method for serum potassium measurement by inductively coupled plasma mass spectrometry
  19. Practical motives are prominent in test-ordering in the Emergency Department
  20. Technical and clinical validation of the Greiner FC-Mix glycaemia tube
  21. Comparison of pneumatic tube system with manual transport for routine chemistry, hematology, coagulation and blood gas tests
  22. Accuracy of cerebrospinal fluid Aβ1-42 measurements: evaluation of pre-analytical factors using a novel Elecsys immunosassay
  23. Evaluation of cannabinoids concentration and stability in standardized preparations of cannabis tea and cannabis oil by ultra-high performance liquid chromatography tandem mass spectrometry
  24. Analytical performance and diagnostic accuracy of six different faecal calprotectin assays in inflammatory bowel disease
  25. Novel immunoassays for detection of CUZD1 autoantibodies in serum of patients with inflammatory bowel diseases
  26. Hematology and Coagulation
  27. Critical appraisal of discriminant formulas for distinguishing thalassemia from iron deficiency in patients with microcytic anemia
  28. Reference Values and Biological Variations
  29. Reference ranges of thromboelastometry in healthy full-term and pre-term neonates
  30. Cancer Diagnostics
  31. Immunoparesis in IgM gammopathies as a useful biomarker to predict disease progression
  32. Cardiovascular Diseases
  33. Assessment of the clinical utility of adding common single nucleotide polymorphism genetic scores to classical risk factor algorithms in coronary heart disease risk prediction in UK men
  34. Time and age dependent decrease of NT-proBNP after septal myectomy in hypertrophic obstructive cardiomyopathy
  35. Infectious Diseases
  36. Higher serum caspase-cleaved cytokeratin-18 levels during the first week of sepsis diagnosis in non-survivor patients
  37. Letters to the Editor
  38. Data mining for age-related TSH reference intervals in adulthood
  39. Intra-laboratory variation and its effect on gestational diabetes diagnosis
  40. Evaluation of long-term imprecision of automated complete blood cell count on the Sysmex XN-9000 system
  41. Sensitivity of the Sysmex XN9000 WPC-channel for detection of monoclonal B-cell populations
  42. Evaluation of biotin interference on immunoassays: new data for troponin I, digoxin, NT-Pro-BNP, and progesterone
  43. Stability of procalcitonin in cerebrospinal fluid
  44. Between-laboratory analysis of IgG antibodies against Aspergillus fumigatus in paired quality control samples
  45. Mass spectrometry vs. immunoassay in clinical and forensic toxicology: qui modus in rebus est?
  46. Great need for changes in higher education in Greece
  47. A note from the Editor in Chief regarding the Letter to the Editor “Great need for changes in higher education in Greece”
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