Observational studyPloS one2014
Serum levels of caspase-cleaved cytokeratin-18 and mortality are associated in severe septic patients: pilot study.
Observational study in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
17 citing papers in PubMed, 32 citations in OpenAlex.
- Search for novel biomarkers of febrile neutropenia in hematological patients: an overview.Clinical and experimental medicine · 2025Review
- Hierarchical Capability in Distinguishing Severities of Sepsis via Serum Lactate: A Network Meta-Analysis.Biomedicines · 2024Review
- Early alveolar epithelial cell necrosis is a potential driver of COVID-19-induced acute respiratory distress syndrome.iScience · 2023Article
- Serum reactive oxygen species and apoptosis markers in septic patients.Anaesthesiology intensive therapy · 2021Article
- High Serum Caspase-Cleaved Cytokeratin-18 Levels and Mortality of Traumatic Brain Injury Patients.Brain sciences · 2019Article
- Article
- New prognostic biomarkers of mortality in patients undergoing liver transplantation for hepatocellular carcinoma.World journal of gastroenterology · 2018Review
- Serum Caspase-Cleaved Cytokeratin (M30) Indicates Severity of Liver Dysfunction and Predicts Liver Outcome.Annals of transplantation · 2018Article
- Observational
- Association between serum levels of caspase-cleaved cytokeratin-18 and early mortality in patients with severe spontaneous intracerebral hemorrhage.BMC neuroscience · 2018Article
- High serum levels of caspase-cleaved cytokeratin-18 are associated with malignant middle cerebral artery infarction patient mortality.BMC neurology · 2018Observational
- High Circulating Caspase-Cleaved Keratin 18 Fragments (M30) Indicate Short-Term Mortality in Critically Ill Patients.Disease markers · 2018Observational
- Liver - guardian, modifier and target of sepsis.Nature reviews. Gastroenterology & hepatology · 2017Review
- Association between Interleukin-6 Promoter Polymorphism (-174 G/C), Serum Interleukin-6 Levels and Mortality in Severe Septic Patients.International journal of molecular sciences · 2016Observational
- Prognostic Value of Serum Caspase-Cleaved Cytokeratin-18 Levels before Liver Transplantation for One-Year Survival of Patients with Hepatocellular Carcinoma.International journal of molecular sciences · 2016Article
- New Prognostic Biomarkers in Patients With Traumatic Brain Injury.Archives of trauma research · 2015Review
- Propofol or sevoflurane anaesthesia does not affect hepatic integrity as assessed by the M30 & M65 cell death markers & liver enzymes.The Indian journal of medical research · 2014Article
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveApoptosis is increased in sepsis. Cytokeratin 18 (CK-18), a protein of the intermediate filament group present in most epithelial and parenchymal cells, is cleaved by the action of caspases and released into the blood as caspase-cleaved CK (CCCK)-18 during apoptosis. Circulating levels of CCCK-18 have scarcely been explored in septic patients. In one study with 101 severe septic patients, the authors reported higher serum CCCK-18 levels in non-survivors than in survivors; however, the sample size was too small to demonstrate an association between serum CCCK-18 levels and early mortality and whether they could be used as a biomarker to predict outcomes in septic patients. Thus, these were the objectives of this study with a large series of patients.
methodsWe performed a prospective, multicenter, observational study in six Spanish Intensive Care Units with 224 severe septic patients. Blood samples were collected at the time that severe sepsis was diagnosed to determine serum levels of CCCK-18, tumor necrosis factor (TNF)-alpha, interleukin (IL)-6 and IL-10. The end point was 30-day mortality.
resultsNon-surviving patients (n = 80) showed higher serum CCCK-18 levels (P<0.001) than survivors (n = 144). Multiple logistic regression analysis showed that serum CCCK-18 levels>391 u/L were associated with 30-day survival (Odds ratio = 2.687; 95% confidence interval = 1.449-4.983; P = 0.002), controlling for SOFA score, serum lactic acid levels and age. Kaplan-Meier survival analysis showed that the risk of death in septic patients with serum CCCK-18 levels >391 u/L was higher than in patients with lower values (Hazard Ratio = 3.1; 95% CI = 1.96-4.84; P<0.001). Serum CCCK-18 levels were positively associated with serum levels of IL-6 and lactic acid, and with SOFA and APACHE scores.
conclusionsThe major novel finding of our study, the largest cohort of septic patients providing data on circulating CCCK-18 levels, was that serum CCCK-18 levels are associated with mortality in severe septic patients.
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