Cell death serum biomarkers are early predictors for survival in severe septic patients with hepatic dysfunction.
Cell death serum biomarkers are early predictors for survival in severe septic patients with hepatic dysfunction.
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细胞死亡血清生物标志物是肝功能障碍的严重化粪池患者生存的早期预测因子。
DOI：
10.1186/cc7923
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发表时间：
2009
期刊：
影响因子：
--
通讯作者：
Weigand MA
中科院分区：
文献类型：
--
作者：
Hofer S;Brenner T;Bopp C;Steppan J;Lichtenstern C;Weitz J;Bruckner T;Martin E;Hoffmann U;Weigand MA
严重脓毒症、脓毒性休克和由此导致的器官衰竭是重症监护医学中最常见的死亡原因，死亡率为40%至70%。目前尚不清楚坏死或凋亡在严重脓毒症中起主导作用。确定细胞死亡的普遍模式将是有价值的，因为新的治疗药物（例如，抗凋亡药物，如半胱天冬酶抑制剂）可能会改善严重脓毒症患者的不良结局。此外，新开发的细胞死亡血清生物标志物的预后价值是非常感兴趣的。共入组147例患者（101例严重脓毒症患者，28例腹部大手术后患者，18例健康志愿者）。评估基线和临床数据。在脓毒症诊断时以及48和120小时后采集严重脓毒症患者的血液样本;健康志愿者采集一次样本，术后患者术后立即采集一次样本。我们测量了半胱天冬酶切割和未切割的细胞角蛋白-18（CK-18，中间丝蛋白）作为细胞死亡的标志物，分离的CK-18片段作为细胞凋亡的标志物，以及IL-6，可溶性血管细胞粘附分子和可溶性细胞间粘附分子。严重脓毒症患者和术后患者的年龄和性别相当，而健康志愿者明显年轻。在健康志愿者中，细胞更新的模式主要是凋亡性细胞死亡。术后患者表现出相当水平的凋亡活性，但坏死细胞死亡明显增加，可能是由于手术组织损伤。相比之下，严重脓毒症患者，尤其是脓毒症组的非幸存者，表现出细胞凋亡和坏死细胞死亡的标志物水平增加。在伴有肝功能障碍的严重脓毒症患者中，坏死相对于肝功能完整的严重脓毒症患者增加。对于伴有肝功能障碍的严重脓毒症患者，可以计算半胱天冬酶切割和未切割的细胞角蛋白-18的截止值，以识别因严重脓毒症而死亡的高风险患者。半胱天冬酶切割和未切割的细胞角蛋白-18的测量似乎是严重脓毒症伴肝功能障碍患者生存的早期预测因子。此外，由于坏死导致的实质细胞损失可能是这些患者中细胞死亡的主要模式。这可能会限制可能的治疗选择。
Severe sepsis, septic shock, and resulting organ failure represent the most common cause of death in intensive care medicine, with mortality ranging from 40% to 70%. It is still unclear whether necrosis or apoptosis plays the predominant role in severe sepsis. Determining the prevalent mode of cell death would be valuable, as new therapeutic agents (eg, antiapoptotic drugs such as caspase inhibitors) may improve unsatisfactory outcomes in patients with severe sepsis. Furthermore, the prognostic value of newly developed cell death serum biomarkers is of great interest. In total, 147 patients (101 patients with severe sepsis, 28 postoperative patients after major abdominal surgery, 18 healthy volunteers) were enrolled. Baseline and clinical data were evaluated. Blood samples from patients with severe sepsis were collected at the time of sepsis diagnosis, and 48 and 120 hours later; samples from healthy volunteers were collected once, and from postoperative patients, once immediately after surgery. We measured caspase-cleaved and uncleaved cytokeratin-18 (CK-18, intermediate filament protein) as a marker of cell death, isolated CK-18 fragments as a marker of apoptosis, as well as IL-6, soluble vascular cell adhesion molecule, and soluble intercellular adhesion molecule. Age and sex of patients with severe sepsis and postoperative patients were comparable, whereas healthy volunteers were significantly younger. In healthy volunteers, the mode of cellular turnover was primarily apoptotic cell death. Postoperative patients showed comparable levels of apoptotic activity, but necrotic cell death was markedly increased, probably due to surgical tissue injury. In contrast, patients with severe sepsis, and especially non-survivors of the septic group showed increased levels of markers for both apoptotic and necrotic cell death. In severe septic patients with liver dysfunction, necrosis is increased relative to severe septic patients with intact hepatic function. For severe septic patients with liver dysfunction, a cut-off value for caspase-cleaved and uncleaved cytokeratin-18 could be calculated, in order to identify patients at high risk for death due to severe sepsis. The measurement of caspase-cleaved and uncleaved cytokeratin-18 appears to be an early predictor for survival in severe septic patients with hepatic dysfunction. Furthermore, the loss of parenchymal cells due to necrosis may be the primary mode of cell death in these patients. This may limit possible therapeutic options.
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影响因子：
168.9
作者：
Bernal, W;Donaldson, N;Wendon, J
通讯作者：
Wendon, J
DOI：
10.1164/rccm.200208-785oc
发表时间：
2003-07-01
影响因子：
24.7
作者：
Alberti, C;Brun-Buisson, C;Le Gall, JR
通讯作者：
Le Gall, JR
影响因子：
120.7
作者：
BRUNBUISSON, C;DOYON, F;REGNIER, B
通讯作者：
REGNIER, B
影响因子：
3.8
作者：
Jaeschke, H;Gores, GJ;Lemasters, JJ
通讯作者：
Lemasters, JJ
DOI：
10.1073/pnas.90.9.4261
发表时间：
1993-05-01
影响因子：
11.1
作者：
CHU, YW;RUNYAN, RB;HENDRIX, MJC
通讯作者：
HENDRIX, MJC