Association of NETs Markers with Clinical and Radiological Outcomes in Patients with Acute Ischemic Stroke Undergoing Thrombectomy: Does Heparin Treatment Modify This?

急性缺血性卒中接受取栓治疗患者中性粒细胞胞外诱捕网标志物与临床和影像学结局的关联：肝素治疗会改变这种关联吗？

The aim of this study is to investigate the association of neutrophil extracellular traps (NETs) markers with clinical and radiological outcomes in acute ischemic stroke (AIS) patients undergoing endovascular thrombectomy (EVT) and assess the effect of periprocedural heparin during EVT on NETs markers and their association with outcomes. From 198 AIS patients included in the MRCLEAN-MED trial, randomized to receive EVT with (N = 104) or without (N = 94) low-dose unfractionated heparin (5000 IU bolus followed by 500 IU/h for 6 h, n = 104), blood samples were collected at baseline, 1 h, and 24 h post-reperfusion. NETs markers (MPO-DNA, histone-DNA, citrullinated histone H3 [CitH3]) were measured in blood samples, and their associations with stroke severity (National Institutes of Health Stroke Scale [NIHSS] score at 24 h post-reperfusion), long-term functional outcome (modified Rankin Scale [mRS] score at 90-day), and final infarct size (5-7 days) were assessed in EVT and heparin + EVT-treated patients using logistic regression, linear regression, and Pearson's correlation. Histone-DNA levels at 1 h post-heparin + EVT, but not EVT alone, were positively associated with final infarct size. Histone-DNA levels at 24 h post-heparin + EVT were negatively associated with infarct size mRS and NIHSS, while baseline CitH3 was positively correlated with NIHSS at 24 h post-EVT. Interaction analysis showed that the association between histone-DNA levels at 24 h and NIHSS at 24 h was different in the two treatment groups. No further associations were observed. At 1 h post-heparin + EVT, the histone-DNA levels were independently associated with larger infarct size, while at 24 h, histone-DNA linked to improved outcomes post-heparin + EVT and baseline-CitH3 to worse outcomes post-EVT, suggesting heparin may attenuate histone-DNA's effect on outcome.

本研究旨在探讨中性粒细胞胞外诱捕网（NETs）标志物与接受血管内血栓切除术（EVT）的急性缺血性卒中（AIS）患者的临床和影像学结局之间的关联，并评估EVT围手术期使用肝素对NETs标志物的影响及其与结局的关联。从纳入MRCLEAN - MED试验的198例AIS患者中，随机分为接受EVT联合低剂量普通肝素治疗组（N = 104）和单纯EVT治疗组（N = 94）（低剂量普通肝素治疗方案为静脉推注5000 IU，随后以500 IU/h的速度持续输注6小时，n = 104），在基线、再灌注后1小时和24小时采集血样。检测血样中的NETs标志物（髓过氧化物酶 - DNA、组蛋白 - DNA、瓜氨酸化组蛋白H3 [CitH3]），并使用逻辑回归、线性回归和皮尔逊相关性分析评估这些标志物与EVT治疗患者和肝素 + EVT治疗患者的卒中严重程度（再灌注后24小时美国国立卫生研究院卒中量表 [NIHSS]评分）、长期功能结局（90天改良Rankin量表 [mRS]评分）以及最终梗死灶大小（5 - 7天）之间的关联。肝素 + EVT治疗后1小时的组蛋白 - DNA水平（而非单纯EVT治疗后）与最终梗死灶大小呈正相关。肝素 + EVT治疗后24小时的组蛋白 - DNA水平与梗死灶大小、mRS评分和NIHSS评分呈负相关，而基线CitH3水平与EVT治疗后24小时的NIHSS评分呈正相关。交互作用分析显示，两个治疗组中治疗后24小时组蛋白 - DNA水平与治疗后24小时NIHSS评分之间的关联存在差异。未观察到其他关联。肝素 + EVT治疗后1小时，组蛋白 - DNA水平与更大的梗死灶大小独立相关，而治疗后24小时，组蛋白 - DNA与肝素 + EVT治疗后更好的结局相关，基线CitH3与EVT治疗后更差的结局相关，这表明肝素可能会减弱组蛋白 - DNA对结局的影响。

REF: Barakzie A, van der Steen W, Jansen AJG, et al. Association of NETs Markers with Clinical and Radiological Outcomes in Patients with Acute Ischemic Stroke Undergoing Thrombectomy: Does Heparin Treatment Modify This?. Transl Stroke Res. Published online June 26, 2025. doi:10.1007/s12975-025-01362-0 PMID: 40571868

Gut Microbiota Improve the Prediction of Stroke-Associated Pneumonia Risk and Outcomes in Acute Ischemic Stroke

肠道微生物群可改善急性缺血性卒中患者卒中相关性肺炎风险及预后的预测

Stroke-associated pneumonia (SAP) is the most significant acute ischemic stroke (AIS) comorbidity. This investigation aimed to explore the relationship between gut microbiome composition and SAP risk in patients with moderate-to-severe AIS and to develop a robust and accessible SAP risk-prediction model for this population. This prospective study included AIS patients with an NIHSS score ≥ 9 within 48 h of onset who were admitted to the First Affiliated Hospital of Wenzhou Medical University. Our findings suggest that combining clinical indicators, gut microbiota, and blood metabolites enhances SAP prediction. Furthermore, microorganisms can potentially serve as prognostic markers and therapeutic targets for SAP in the future.

卒中相关性肺炎（SAP）是急性缺血性卒中（AIS）最严重的合并症。本研究旨在探讨中重度AIS患者肠道微生物群组成与SAP风险之间的关系，并为该人群建立一个可靠且实用的SAP风险预测模型。这项前瞻性研究纳入了发病48小时内美国国立卫生研究院卒中量表（NIHSS）评分≥9分、入住温州医科大学附属第一医院的AIS患者。我们的研究结果表明，结合临床指标、肠道微生物群和血液代谢物可提高对SAP的预测能力。此外，微生物有望在未来成为SAP的预后标志物和治疗靶点。

REF: Lin YS, Chen JH, Zhuang WH, et al. Gut Microbiota Improve the Prediction of Stroke-Associated Pneumonia Risk and Outcomes in Acute Ischemic Stroke. Transl Stroke Res. Published online June 12, 2025. doi:10.1007/s12975-025-01363-z PMID: 40500582

SMART-M24: A Prognostic Nomogram for Long-Term Mortality in Acute Ischemic Stroke Beyond 24 H from Symptom Onset

SMART - M24：用于症状发作超24小时急性缺血性脑卒中患者长期死亡率的预后列线图

Prognostication after acute ischemic stroke is crucial for long-term care plans. Although hyperacute management significantly affects outcomes, prognostic factors for patients receiving delayed care remain unknown. This study aimed to evaluate predictors and develop a method for estimating long-term mortality in patients with delayed hospital arrival 24 h after stroke symptom onset. The SMART-M24 nomogram provides a prognostic tool for estimating long-term mortality in ischemic stroke patients with delayed hospital arrival 24 h after symptom onset. This model can assist clinical decision-making and long-term care planning for patients who have not undergone hyperacute treatment.

急性缺血性卒中后的预后评估对于长期护理计划至关重要。尽管超急性期治疗会显著影响预后，但接受延迟治疗的患者的预后因素仍不清楚。本研究旨在评估预测因素，并建立一种方法来估算卒中症状发作24小时后才入院的患者的长期死亡率。SMART - M24列线图为估算症状发作24小时后才入院的缺血性卒中患者的长期死亡率提供了一种预后工具。该模型可辅助未接受超急性期治疗患者的临床决策和长期护理计划制定。

REF: Park SH, Lee JS, Kim TJ, et al. SMART-M24: A Prognostic Nomogram for Long-Term Mortality in Acute Ischemic Stroke Beyond 24 H from Symptom Onset. Transl Stroke Res. Published online June 9, 2025. doi:10.1007/s12975-025-01361-1 PMID: 40488807

Clinical Significance of Somatic PIK3CA and MAP3K3 Mutations in Cerebral and Spinal Cavernous Malformations

脑和脊髓海绵状血管畸形中体细胞PIK3CA和MAP3K3突变的临床意义

Somatic PIK3CA and MAP3K3 mutations in cerebral and spinal cavernous malformations (CMs) have been identified in recent studies. However, their significance in the clinical presentation and risk of hemorrhage in CMs remains poorly understood. We aimed to analyze the association between these mutations and the clinical characteristics of CMs. Among patients with CMs who underwent surgical resection of lesions between July 2002 and March 2022, those with complete clinical and radiological data at the time of initial surgery were included. The results suggest that PIK3CA and MAP3K3 mutations are associated with clinical and radiological characteristics in patients with CMs and that the presence of a somatic PIK3CA mutation increases susceptibility to hemorrhage. These findings may help guide future therapeutic strategies.

近期研究已在脑和脊髓海绵状血管畸形（CMs）中发现了体细胞PIK3CA和MAP3K3突变。然而，这些突变在CMs临床表现和出血风险方面的意义仍知之甚少。我们旨在分析这些突变与CMs临床特征之间的关联。纳入了2002年7月至2022年3月期间接受病变手术切除的CMs患者，且这些患者在初次手术时有完整的临床和影像学资料。结果表明，PIK3CA和MAP3K3突变与CMs患者的临床和影像学特征相关，并且体细胞PIK3CA突变的存在会增加出血易感性。这些发现可能有助于指导未来的治疗策略。

REF: Hongo H, Miyawaki S, Takai K, et al. Clinical Significance of Somatic PIK3CA and MAP3K3 Mutations in Cerebral and Spinal Cavernous Malformations. Transl Stroke Res. Published online June 6, 2025. doi:10.1007/s12975-025-01360-2 PMID: 40478424