重度创伤性脑损伤患者血清中半胱天冬酶切割的细胞角蛋白-18水平与死亡率相关：一项初步研究。
Serum levels of caspase-cleaved cytokeratin-18 in patients with severe traumatic brain injury are associated with mortality: a pilot study.
作者信息
Lorente Leonardo, Martín María M, González-Rivero Agustín F, Argueso Mónica, Ramos Luis, Solé-Violán Jordi, Cáceres Juan J, Jiménez Alejandro, Borreguero-León Juan M
机构信息
Intensive Care Unit, Hospital Universitario de Canarias, La Laguna, Tenerife, Spain.
Intensive Care Unit, Hospital Universitario Nuestra Señora de Candelaria, Santa Cruz de Tenerife, Spain.
出版信息
PLoS One. 2015 Mar 30;10(3):e0121739. doi: 10.1371/journal.pone.0121739. eCollection 2015.
OBJECTIVE
There have been found apoptotic changes in brain tissue samples from animals and humans after a traumatic brain injury (TBI). The protein cytokeratin 18 (CK-18), present in epithelial cells, is cleaved by the action of caspases during apoptosis, and the resulting fragments are released into the blood as caspase-cleaved CK (CCCK)-18. Circulating levels of CCCK-18, as biomarker of apoptosis, have been determined in patients with different processes; however, it has not been explored in TBI patients. Thus, the objective of this study was to determine whether there is an association between serum CCCK-18 levels and mortality and whether such levels could be used as a biomarker to predict outcomes in TBI patients.
METHODS
A prospective, observational, multicenter study carried out in six Spanish Intensive Care Units. We included patients with severe TBI defined as Glasgow Coma Scale (GCS) lower than 9; and were excluded those patients with Injury Severity Score (ISS) in non-cranial aspects higher than 9. We measured serum CCCK-18 levels at admission. The end-point of the study was 30-day mortality.
RESULTS
Surviving patients (n = 73) showed lower serum CCCK-18 levels (P = 0.003) than non-survivors (n = 27). On ROC analysis, the area under the curve (AUC) for serum CCCK-18 levels as predictor of 30-day mortality was 0.69 (95% CI = 0.59-0.78; P = 0.006). We found in survival analysis that patients with serum CCCK-18 higher than 201 u/L had higher 30-day mortality than patients with lower levels (Hazard ratio = 3.9; 95% CI = 1.81-8.34; P<0.001). Regression analyses showed that serum CCCK-18 levels higher than 201 u/L were associated with 30-day mortality (OR = 8.476; 95% CI = 2.087-34.434; P = 0.003) after controlling for age and GCS.
CONCLUSIONS
The novel finding of our study was that serum CCCK-18 levels are associated with 30-day mortality and could be used as a prognostic biomarker in patients with severe TBI.
目的
在动物和人类创伤性脑损伤（TBI）后的脑组织样本中发现了凋亡变化。存在于上皮细胞中的细胞角蛋白18（CK-18）在凋亡过程中被半胱天冬酶作用裂解，产生的片段作为半胱天冬酶裂解的CK（CCCK）-18释放到血液中。已在患有不同病症的患者中测定了作为凋亡生物标志物的循环CCCK-18水平；然而，尚未在TBI患者中进行探索。因此，本研究的目的是确定血清CCCK-18水平与死亡率之间是否存在关联，以及这些水平是否可作为预测TBI患者预后的生物标志物。
方法
在西班牙六个重症监护病房进行的一项前瞻性、观察性、多中心研究。我们纳入了格拉斯哥昏迷量表（GCS）低于9分的重度TBI患者；排除了非颅脑方面损伤严重程度评分（ISS）高于9分的患者。我们在入院时测量血清CCCK-18水平。研究的终点是30天死亡率。
结果
存活患者（n = 73）的血清CCCK-18水平低于非存活患者（n = 27）（P = 0.003）。在ROC分析中，血清CCCK-18水平作为30天死亡率预测指标的曲线下面积（AUC）为0.69（95%CI = 0.59 - 0.78；P = 0.006）。我们在生存分析中发现，血清CCCK-18高于201 u/L的患者30天死亡率高于水平较低的患者（风险比 = 3.9；95%CI = 1.81 - 8.34；P<0.001）。回归分析显示，在控制年龄和GCS后，血清CCCK-18水平高于201 u/L与30天死亡率相关（OR = 8.476；95%CI = 2.087 - 34.434；P = 0.003）。
结论
我们研究的新发现是血清CCCK-18水平与30天死亡率相关，可作为重度TBI患者的预后生物标志物。
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