Subacute Elevation of Plasma Level of Caspase-Cleaved Cytokeratin-18 is Associated with Hemorrhagic Transformation and Functional Outcome in Ischemic Stroke

Tihamer Molnar, Kata Borocz, Timea Berki, Laszlo Szapary, Alex Szolics, Jozsef Janszky, Zsolt Illes, Peter Csecsei*

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

BACKGROUND: Caspase-cleaved cytokeratin-18 (CCCK-18) is an apoptosis marker. Here, we analyzed the relationship between plasma level of CCCK-18 in the acute and subacute stage of ischemic stroke and early and late functional outcome. Besides, correlation among CCCK-18 and complications, such as hemorrhagic transformation (HT) were also explored.

METHODS: Plasma concentration of CCCK-18 was investigated in 54 patients at admission and poststroke 72 hours. HT was evaluated by CT scans on 24 poststroke hours. Outcome measures were assessed by modified Rankin scale at hospital discharge and 6-month later. Receiver operating characteristics (ROC) analysis was used to determine the best cut-off values of CCCK-18 as a predictor of unfavorable functional outcome.

RESULTS: Significantly elevated CCCK-18 level was observed at 72 hours after onset of stroke, in nonsurviving compared to surviving patients (331 ± 191 ng/L versus 251 ± 164 ng/L, P = .01). Based on ROC analysis, the cut-off value of plasma CCCK-18 levels >223 ng/L at 72 poststroke hours predicted 6-month unfavorable stroke outcome with a sensitivity of 84.4% and a specificity of 77.3% (area under the curve: .851, 95% confidence interval = .745-.955, P < .001). The rate of complications such as HT and in-hospital infection was significantly higher in patients presented with a plasma CCCK-18 level above the cut-off value.

CONCLUSIONS: The association between high serum CCCK-18 levels and unfavorable early and late stroke outcome in an unselected study population was first described here. Besides, the apoptosis marker CCCK-18 might be a predictor of further complication such as HT and in-hospital infection.

Original languageEnglish
JournalJournal of Stroke and Cerebrovascular Diseases
Volume28
Issue number3
Pages (from-to)719-727
ISSN1052-3057
DOIs
Publication statusPublished - 1. Mar 2019

Fingerprint

Keratin-18
ROC Curve
Apoptosis
Patient Admission
Area Under Curve
Outcome Assessment (Health Care)
Confidence Intervals

Keywords

  • Caspase-cleaved cytokeratin-18
  • hemorrhagic transformation
  • ischemic stroke
  • outcome
  • Up-Regulation
  • Cross Infection/etiology
  • Prognosis
  • Prospective Studies
  • Humans
  • Middle Aged
  • Patient Admission
  • Male
  • Recovery of Function
  • Time Factors
  • Aged, 80 and over
  • Biomarkers/blood
  • Female
  • Intracranial Hemorrhages/blood
  • Stroke/blood
  • Disability Evaluation
  • Multidetector Computed Tomography
  • Risk Factors
  • Caspases/metabolism
  • Keratin-18/blood
  • Brain Ischemia/blood
  • Aged
  • Peptide Fragments/blood

Cite this

Molnar, Tihamer ; Borocz, Kata ; Berki, Timea ; Szapary, Laszlo ; Szolics, Alex ; Janszky, Jozsef ; Illes, Zsolt ; Csecsei, Peter. / Subacute Elevation of Plasma Level of Caspase-Cleaved Cytokeratin-18 is Associated with Hemorrhagic Transformation and Functional Outcome in Ischemic Stroke. In: Journal of Stroke and Cerebrovascular Diseases. 2019 ; Vol. 28, No. 3. pp. 719-727.
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title = "Subacute Elevation of Plasma Level of Caspase-Cleaved Cytokeratin-18 is Associated with Hemorrhagic Transformation and Functional Outcome in Ischemic Stroke",
abstract = "BACKGROUND: Caspase-cleaved cytokeratin-18 (CCCK-18) is an apoptosis marker. Here, we analyzed the relationship between plasma level of CCCK-18 in the acute and subacute stage of ischemic stroke and early and late functional outcome. Besides, correlation among CCCK-18 and complications, such as hemorrhagic transformation (HT) were also explored.METHODS: Plasma concentration of CCCK-18 was investigated in 54 patients at admission and poststroke 72 hours. HT was evaluated by CT scans on 24 poststroke hours. Outcome measures were assessed by modified Rankin scale at hospital discharge and 6-month later. Receiver operating characteristics (ROC) analysis was used to determine the best cut-off values of CCCK-18 as a predictor of unfavorable functional outcome.RESULTS: Significantly elevated CCCK-18 level was observed at 72 hours after onset of stroke, in nonsurviving compared to surviving patients (331 ± 191 ng/L versus 251 ± 164 ng/L, P = .01). Based on ROC analysis, the cut-off value of plasma CCCK-18 levels >223 ng/L at 72 poststroke hours predicted 6-month unfavorable stroke outcome with a sensitivity of 84.4{\%} and a specificity of 77.3{\%} (area under the curve: .851, 95{\%} confidence interval = .745-.955, P < .001). The rate of complications such as HT and in-hospital infection was significantly higher in patients presented with a plasma CCCK-18 level above the cut-off value.CONCLUSIONS: The association between high serum CCCK-18 levels and unfavorable early and late stroke outcome in an unselected study population was first described here. Besides, the apoptosis marker CCCK-18 might be a predictor of further complication such as HT and in-hospital infection.",
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author = "Tihamer Molnar and Kata Borocz and Timea Berki and Laszlo Szapary and Alex Szolics and Jozsef Janszky and Zsolt Illes and Peter Csecsei",
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Subacute Elevation of Plasma Level of Caspase-Cleaved Cytokeratin-18 is Associated with Hemorrhagic Transformation and Functional Outcome in Ischemic Stroke. / Molnar, Tihamer; Borocz, Kata; Berki, Timea; Szapary, Laszlo; Szolics, Alex; Janszky, Jozsef; Illes, Zsolt; Csecsei, Peter.

In: Journal of Stroke and Cerebrovascular Diseases, Vol. 28, No. 3, 01.03.2019, p. 719-727.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Subacute Elevation of Plasma Level of Caspase-Cleaved Cytokeratin-18 is Associated with Hemorrhagic Transformation and Functional Outcome in Ischemic Stroke

AU - Molnar, Tihamer

AU - Borocz, Kata

AU - Berki, Timea

AU - Szapary, Laszlo

AU - Szolics, Alex

AU - Janszky, Jozsef

AU - Illes, Zsolt

AU - Csecsei, Peter

PY - 2019/3/1

Y1 - 2019/3/1

N2 - BACKGROUND: Caspase-cleaved cytokeratin-18 (CCCK-18) is an apoptosis marker. Here, we analyzed the relationship between plasma level of CCCK-18 in the acute and subacute stage of ischemic stroke and early and late functional outcome. Besides, correlation among CCCK-18 and complications, such as hemorrhagic transformation (HT) were also explored.METHODS: Plasma concentration of CCCK-18 was investigated in 54 patients at admission and poststroke 72 hours. HT was evaluated by CT scans on 24 poststroke hours. Outcome measures were assessed by modified Rankin scale at hospital discharge and 6-month later. Receiver operating characteristics (ROC) analysis was used to determine the best cut-off values of CCCK-18 as a predictor of unfavorable functional outcome.RESULTS: Significantly elevated CCCK-18 level was observed at 72 hours after onset of stroke, in nonsurviving compared to surviving patients (331 ± 191 ng/L versus 251 ± 164 ng/L, P = .01). Based on ROC analysis, the cut-off value of plasma CCCK-18 levels >223 ng/L at 72 poststroke hours predicted 6-month unfavorable stroke outcome with a sensitivity of 84.4% and a specificity of 77.3% (area under the curve: .851, 95% confidence interval = .745-.955, P < .001). The rate of complications such as HT and in-hospital infection was significantly higher in patients presented with a plasma CCCK-18 level above the cut-off value.CONCLUSIONS: The association between high serum CCCK-18 levels and unfavorable early and late stroke outcome in an unselected study population was first described here. Besides, the apoptosis marker CCCK-18 might be a predictor of further complication such as HT and in-hospital infection.

AB - BACKGROUND: Caspase-cleaved cytokeratin-18 (CCCK-18) is an apoptosis marker. Here, we analyzed the relationship between plasma level of CCCK-18 in the acute and subacute stage of ischemic stroke and early and late functional outcome. Besides, correlation among CCCK-18 and complications, such as hemorrhagic transformation (HT) were also explored.METHODS: Plasma concentration of CCCK-18 was investigated in 54 patients at admission and poststroke 72 hours. HT was evaluated by CT scans on 24 poststroke hours. Outcome measures were assessed by modified Rankin scale at hospital discharge and 6-month later. Receiver operating characteristics (ROC) analysis was used to determine the best cut-off values of CCCK-18 as a predictor of unfavorable functional outcome.RESULTS: Significantly elevated CCCK-18 level was observed at 72 hours after onset of stroke, in nonsurviving compared to surviving patients (331 ± 191 ng/L versus 251 ± 164 ng/L, P = .01). Based on ROC analysis, the cut-off value of plasma CCCK-18 levels >223 ng/L at 72 poststroke hours predicted 6-month unfavorable stroke outcome with a sensitivity of 84.4% and a specificity of 77.3% (area under the curve: .851, 95% confidence interval = .745-.955, P < .001). The rate of complications such as HT and in-hospital infection was significantly higher in patients presented with a plasma CCCK-18 level above the cut-off value.CONCLUSIONS: The association between high serum CCCK-18 levels and unfavorable early and late stroke outcome in an unselected study population was first described here. Besides, the apoptosis marker CCCK-18 might be a predictor of further complication such as HT and in-hospital infection.

KW - Caspase-cleaved cytokeratin-18

KW - hemorrhagic transformation

KW - ischemic stroke

KW - outcome

KW - Up-Regulation

KW - Cross Infection/etiology

KW - Prognosis

KW - Prospective Studies

KW - Humans

KW - Middle Aged

KW - Patient Admission

KW - Male

KW - Recovery of Function

KW - Time Factors

KW - Aged, 80 and over

KW - Biomarkers/blood

KW - Female

KW - Intracranial Hemorrhages/blood

KW - Stroke/blood

KW - Disability Evaluation

KW - Multidetector Computed Tomography

KW - Risk Factors

KW - Caspases/metabolism

KW - Keratin-18/blood

KW - Brain Ischemia/blood

KW - Aged

KW - Peptide Fragments/blood

U2 - 10.1016/j.jstrokecerebrovasdis.2018.11.015

DO - 10.1016/j.jstrokecerebrovasdis.2018.11.015

M3 - Journal article

C2 - 30528602

AN - SCOPUS:85057827243

VL - 28

SP - 719

EP - 727

JO - Journal of Stroke & Cerebrovascular Diseases

JF - Journal of Stroke & Cerebrovascular Diseases

SN - 1052-3057

IS - 3

ER -