研究动态
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一项前瞻性可行性试验,探索孤立肢体灌注后神经毒性的新型生物标志物。

A prospective feasibility trial exploring novel biomarkers for neurotoxicity after isolated limb perfusion.

发表日期:2023 Nov 07
作者: Anna Corderfeldt Keiller, Markus Axelsson, Gudrun Bragadottir, Kaj Blennow, Henrik Zetterberg, Roger Olofsson Bagge
来源: Alzheimers & Dementia

摘要:

离体肢体灌注(ILP)是一种局部癌症治疗方法,其中在离体肢体中进行高剂量化疗。主要副作用是局部毒性,偶尔会导致神经损伤。测量神经轴突生物标志物可能是预测此类并发症的一种方法。因此,本研究的主要目的是调查神经元生物标志物在 ILP 期间是否可测量并在孤立的肢体中发生变化。其次,术后局部毒性、敏感性变化和/或肌肉力量是否与生物标志物水平相关。该研究包括 18 名预定的 ILP 患者。使用超灵敏单分子阵列 (Simoa) 技术,在术前、ILP 开始和结束时、第 3 天和第 30 天采集的血浆样本中测量胶质纤维酸性蛋白 (GFAP)、神经丝光 (NfL) 和 tau 蛋白浓度。物理治疗师在术前和术后对患者进行评估。ILP 结束时,四肢测得的 NfL 和 tau 水平显着高于相应的体循环(NfL;17 vs 6 ng/L,p < .01,tau; 1.8 vs 0.6 ng/L,p < .01),并且 ILP 结束时四肢水平显着升高(NfL;66 ± 37%,p < .001,tau;75 ± 45%,p = .001)。第 3 天和第 30 天,系统性测量 NfL 和 GFAP 水平显着升高(NfL 第 3 天:69 ± 30%,p < .001;第 30 天:76 ± 26%,p < .001;GFAP 第 3 天:33 ± 22 %,p < .002;第 30 天:33 ± 23%,p ≤ .004)。最后,区域毒性之间或术后肌肉或敏感性降低与生物标志物释放之间没有发现显着相关性。在 ILP 期间,NfL 和 tau 水平显着增加。尽管需要进行大规模研究,但在生物标志物释放与区域毒性或肌肉力量或敏感性下降之间没有观察到明显的相关性。
Isolated limb perfusion (ILP) is a regional cancer treatment in which high-dose chemotherapy is administered in an isolated extremity. The main side effect is regional toxicity, which occasionally leads to nerve damage. Measuring neuroaxonal biomarkers, might be a method predicting such complications. Therefore, the primary aim of the study is to investigate if neuronal biomarkers are measurable and alters in an isolated extremity during ILP. Secondly, if postoperative regional toxicity, alterations in sensitivity, and/or muscle strength are correlated to the biomarker levels.Eighteen scheduled ILP-patients were included in the study. Glial fibrillary acidic protein (GFAP), neurofilament light (NfL), and tau concentrations were measured in plasma sampled preoperatively, at the start and end of the ILP, on days 3 and 30, using ultrasensitive Single molecule array (Simoa) technology. The patients were assessed by a physiotherapist pre- and postoperatively.At ILP end, significantly higher NfL and tau levels were measured in the extremity than in the corresponding systemic circulation (NfL; 17 vs 6 ng/L, p < .01, tau; 1.8 vs 0.6 ng/L, p < .01), and the extremity levels were significantly increased at ILP end (NfL; 66 ± 37%, p < .001, tau; 75 ± 45%, p = .001). On days 3 and 30, significantly increased NfL and GFAP levels were measured systemically (NfL day 3: 69 ± 30%, p < .001; day 30: 76 ± 26%, p < .001; GFAP day 3: 33 ± 22%, p < .002; day 30: 33 ± 23%, p ≤ .004). Finally, no significant correlations were found between regional toxicity or between postoperative muscle or sensitivity decrease and biomarker release.During ILP, NfL and tau levels increased significantly. No obvious correlations were observed between biomarker release and regional toxicity or decreased muscle strength or sensitivity, although large-scale studies are warranted.