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Preoperative protein profiles in cerebrospinal fluid in elderly hip fracture patients at risk for delirium: A proteomics and validation study

机译:老年hip骨骨折高龄患者发生sp妄的脑脊液中蛋白质的蛋白质组学和验证研究

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Background A neuroinflammatory response is suggested to play an important role in delirium, a common complication in older hospitalized patients. We examined whether hip fracture patients who develop postoperative delirium have a different proteome in cerebrospinal fluid (CSF) prior to surgery. Methods Patients (≥ 75 years) were admitted for hip fracture surgery. CSF was collected during spinal anaesthesia; proteins were separated using gel electrophoresis and identified with mass spectrometry. We compared the proteome of patients with and without postoperative delirium. Findings were validated in an independent, comparable cohort using immuno-assays. Results In the derivation cohort 53 patients were included, 35.8% developed postoperative delirium. We identified differences in levels of eight CSF proteins between patients with and without subsequent delirium: complement factor C3, contactin-1, fibulin-1 and I-beta-1,3-N-acetylglucosaminyltransferase were significantly lower in patients with postoperative delirium, while neural cell adhesion molecule-2, fibrinogen, zinc-α-2-glycoprotein and haptoglobin levels were significantly higher. In the validation cohort 21.2% of 52 patients developed postoperative delirium. Immuno-assays confirmed contactin-1 results although not statistically significant. Complement factor C3 was significantly higher in patients with postoperative delirium. Conclusion Our results show the complexity of pathophysiological mechanisms involved in delirium and emphasizes the need of independent validation of findings. General significance This study highlights the challenges and inconsistent findings in studies of delirium, a serious complication in older patients. We analysed proteins in CSF, the most proximal fluid to the brain. All patients were free from delirium at the time of sampling.
机译:背景技术提示神经炎症反应在del妄中起重要作用,ir妄是老年住院患者的常见并发症。我们检查了发生ir妄的髋部骨折患者在手术前脑脊液(CSF)的蛋白质组是否不同。方法对≥75岁的患者进行髋部骨折手术。脊髓麻醉期间收集脑脊液;使用凝胶电泳分离蛋白质并通过质谱鉴定。我们比较了有或没有术后ir妄的患者的蛋白质组。在独立的,可比较的队列中使用免疫测定法对发现进行了验证。结果在衍生队列中包括53例患者,其中35.8%发生了术后del妄。我们确定了有和没有随后patients妄的患者之间八种脑脊液蛋白水平的差异:术后del妄患者补体因子C3,contactin-1,fibulin-1和I-β-1,3-N-乙酰氨基葡萄糖氨基转移酶明显降低,而神经细胞粘附分子2,纤维蛋白原,锌-α-2-糖蛋白和触珠蛋白水平显着升高。在验证队列中,52例患者中有21.2%发生了del妄。免疫测定证实了contactin-1的结果,尽管没有统计学意义。术后del妄患者的补体因子C3明显更高。结论我们的结果显示了del妄中涉及的病理生理机制的复杂性,并强调需要对结果进行独立验证。一般意义本研究突出了ir妄研究的挑战和不一致的发现,ir妄是老年患者的严重并发症。我们分析了脑脊液中最接近大脑的液体中的蛋白质。采样时所有患者均未出现ir妄。

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