Biomakers
2021-10-13 22:05:29 0 举报
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Biomarkers of Unfavorable Outcome in Acute Ischemic Stroke Patients with Successful Recanalization by Endovascular Thrombectomy
作者其他创作
大纲/内容
Results
Clinical Characteristics
共纳入61例,34例患者无效再通,21例患者出现整体早期并发症,其中END患者20例,MBE患者15例,脑疝患者15例,9例合并sHT
Table 1——有效再通与无效再通的基线比较
Table 2——有无早期并发症的患者基线比较
Table 3——血浆生物标志物与成功EVT再通AIS患者不良预后(无效再通及早期并发症)的单变量和多变量逻辑回归
Table 4——将血浆生物标志物加入BCM模型预测EVT成功再通的AIS患者不良结局的ROC曲线分析:输出AUC值及其95%CI
Conclusion
血浆生物标志物提高鉴别EVT不良预后及90天无效再通的能力
分别概述了这几类有意义的biomaker的生物学意义
目前为止,关于上述血浆生物标志物在AIS患者EVT后的预测价值的研究较少
优点
首次探索了上述血浆生物标志物与无效再通的关系的重要性
缺点
纳入标准严格,患者数量相对较少,如取栓后血管再通不成功的患者(mTICI <2b)未纳入本研究。目的是作为AIS患者EVT后的结局生物标志物,以确保入组患者的同质性。
可能有潜在的采血和并发症的发生重叠,因为我们不能排除一些患者在采血时已经发生了早期并发症,而没有经典的临床表现的可能性。因此,我们不能得出结论,EVT后18 - 24小时测定的血浆生物标志物是早期并发症的预测因素。所以就是为什么在采血前排除并发症患者?非常严谨?但是你也没法预测你的标志物是不是在采血前就升高了。
第三,检测的血浆生物标志物是在EVT后单一时间点进行的,没有调查EVT后的动态演变。
ABSRTACT
Aims
Identify plasma markers of unfavorable outcomes for AIS after recanalization by EVT
Methods
Time
2017.11-2019.05
Patiens
Anterior large vessel occlusion
Achieved recanalization by EVT
Plasma Sample
- 18-24h after recanalization
Unfavorable outcomes
1)Futile recanalization at 90-day 2)Overall early complications within 7 days after EVT
Result
MMP-9, tenascin-C, thioredoxin, ADAMTS13, and gelsolin & futile recanalization and overall early complications (P<0.05)
CRP & overall early complications (P=0.031);CRP & futile recanalization (P=0.051)
To predict futile recanalization: 1) Age+NIHSS(AUC=0.807)2)BCM+MMP-9+thioredoxin (AUC=0.98)(improved)
To predict overall early complications
Age+NIHSS(AUC=0.749)
BCM+MMP-9+tenascin-C(AUC=0.868)⬆
BCM+MMP-9+CRP,(AUC=0.882)⬆
BCM+MMP-9ADAMTS13(AUC=0.886)⬆
BCM+tenascin-C+ADAMTS13(AUC=0.880)⬆
BCM+CRP+ADAMTS13(AUC=0.863)⬆
Conclusions
Independent predictors of futile recanalization
Increased:MMP-9, tenascinC, CRP, thioredoxin
Decreased:ADAMTS13 and gelsolin
Introduction
Defenition of Futile Recanalization
mRS 3-6 at 90-d after successful recanalization
Early Complications after recanalization
Early neurological deterioration (END)
Symptomatic hemorrhagic transformation (sHT)
Brain herniation 脑疝
Malignant brain edema (MBE)恶性脑水肿
Identifing Futile recanalization can help target patients to have close attention and timely treatments
Blood biomakers
MMP-9 and CRP are associated with functional outcomes of AIS
Undetermined
Blood biomakers AND Futile recanalization
METHODS
Study Design
single-center observational study
2017.11-2019.05
Patient Selection
AIS due to anterior circulation LVO前循环闭塞
Successful recanalization by EVT using stent retrievers取栓支架成功再通
Inclusion criteria
AIS patients who underwent EVT for anterior circulation LVO
aged ≥18 years
initial NIHSS on admission ≥6
ASPECTS based on DWI ≥6
Anterior circulation LVO confirmed by DSA;Occlusion site——ICA+MCA M1+MCA M2
EVT was performed within 6h from onset, 6-16h was eligible according Defuse-3
mTICI<2b before EVT but mTICI≥2b after EVT
Exclusion criteria
Unfavorable outcomes occurred before sampling
Pre-stroke mRS ≥2
颅内出血、蛛网膜下腔出血、动静脉畸形、动脉瘤或颅内肿瘤
Preexisting neurological or psychiatric disease confounding neurological evaluation
Hemorrhage of trauma or surgery within 2 months
Concurrent infection
风湿性免疫疾病、严重的肝肾疾病、血液病或恶性肿瘤
怀疑感染性栓子或细菌性心内膜炎
EVT history
Baseline platelet count <50,000/μL
Pregnant/lactating women
Missing clinical/imaging/follow-up data
Blood sample sshowed poor quality??不懂
Clinical Information
Clinical characteristics and information 基本信息和取栓信息
Complications during hospitalization
ASPECTS,NIHSS score
CT was conducted at 24h after EVT or when patient's status got deteriorated
Bp was measured every 60 min at the first 24h after EVT; Recording the mean and maximal SBP values
Outcome Definitions
The primary outcome
Futile recanalization——mTICI 2b-3
mRS 3-6 at 90-d
The secondary outcome
END
sHT
brain herniation
MBE
Plasma Collection and Biomarker Analysis
18-24 h after EVT
6 biomarkers were found related to unfavorable outcomes in 35 kinds of proteins 用质谱分析分析出来的35种蛋白只有6种与AIS不良预后有关
MMP-9 (a marker of BBB disruption)
Tenascin-C (involved in neuronal apoptosis and BBB disruption
CRP(an inflammatory marker)
Thioredoxin (an indicator of oxidative stress)
ADAMTS13 (related to microcirculatory disturbances)
Gelsolin (implicated in microcirculatory disturbances)
Statistical Analysis
采用多元回归分析中与不良结局独立相关的临床变量建立基线临床模型(baseline clinical model, BCM)
然后将单个或联合血浆生物标志物加入到BCM中,研究这些生物标志物是否能提高不良结局的识别能力。
采用受试者工作特征曲线分析和综合鉴别改进(IDI)方法评价患者的鉴别能力
NRI对模型准确性进行比较
若NRI<0,则为负改善,新模型预测能力下降
若NRI>0,则为正改善,新模型预测能力提高
<0.20 (low risk)
0.20–0.50 (intermediate-low risk)
0.50–0.80 (intermediate-high risk)
>0.80 (high risk)
若NRI=0,则认为新模型没有改善
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