Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial

在缺血性卒中 (TASTE) 发作后4·5小时内使用灌注成像选择的患者中，替奈普酶与阿替普酶溶栓的比较: 一项多中心，随机，对照，3期非劣效性试验

Intravenous tenecteplase increases reperfusion in patients with salvageable brain tissue on perfusion imaging and might have advantages over alteplase as a thrombolytic for ischaemic stroke. We aimed to assess the non-inferiority of tenecteplase versus alteplase on clinical outcomes in patients selected by use of perfusion imaging. The findings in our study provide further evidence to strengthen the assertion of the non-inferiority of tenecteplase to alteplase, specifically when perfusion imaging has been used to identify reperfusion-eligible stroke patients. Although non-inferiority was achieved in the per-protocol population, it was not reached in the intention-to-treat analysis, possibly due to sample size limtations. Nonetheless, large-scale implementation of perfusion CT to assist in patient selection for intravenous thrombolysis in the early time window was shown to be feasible.

在灌注成像中，静脉替奈普酶可增加具有可挽救脑组织的患者的再灌注，并且在缺血性卒中的溶栓治疗中可能比阿替普酶更具优势。我们旨在评估替奈普酶与阿替普酶对通过灌注成像选择的患者的临床结局的非劣效性。我们研究中的发现提供了进一步的证据，以加强对阿替普酶替奈普酶的非劣效性的断言，特别是当灌注成像已用于识别符合再灌注条件的卒中患者时。尽管在符合方案人群中实现了非劣效性，但在意向治疗分析中未达到非劣效性，这可能是由于样本量的限制。尽管如此，在早期时间窗口内大规模实施灌注CT以帮助患者选择进行静脉溶栓是可行的。

REF: Parsons MW, Yogendrakumar V, Churilov L, et al. Tenecteplase versus alteplase for thrombolysis in patients selected by use of perfusion imaging within 4·5 h of onset of ischaemic stroke (TASTE): a multicentre, randomised, controlled, phase 3 non-inferiority trial. Lancet Neurol. 2024;23(8):775-786. doi:10.1016/S1474-4422(24)00206-0 PMID: 38880118

Optimal drainage time after evacuation of chronic subdural haematoma (DRAIN TIME 2): a multicentre, randomised, multiarm and multistage non-inferiority trial in Denmark

慢性硬膜下血肿排空后的最佳引流时间 (引流时间2): 丹麦的多中心，随机，多臂和多阶段非劣效性试验

Postoperative drainage after surgical evacuation of chronic subdural haematoma reduces the risk of recurrence, but the optimum drainage time is uncertain. We aimed to investigate the shortest possible drainage time without increasing the haematoma recurrence rate. Patients surgically treated for symptomatic chronic subdural haematoma and postoperatively drained for 6 h or 12 h had higher rates of haematoma recurrence than did patients drained for 24 h. The findings from this non-inferiority trial provide evidence to support 24 h of postoperative drainage as the standard drain time when a fixed drain time approach is used. To provide solid evidence of generalisability of the results to countries other than Denmark, a multinational randomised controlled trial will be needed.

手术清除慢性硬膜下血肿后的术后引流可降低复发的风险，但最佳引流时间尚不确定。我们旨在研究在不增加血肿复发率的情况下尽可能短的引流时间。手术治疗有症状的慢性硬膜下血肿并术后引流6小时或12小时的患者血肿复发率高于引流24小时的患者。这项非劣效性试验的结果提供了证据，支持使用固定引流时间方法将术后24小时引流作为标准引流时间。为了提供可靠的证据证明结果在丹麦以外的国家/地区具有普遍性，需要进行跨国随机对照试验。

REF: Hjortdal Grønhøj M, Jensen TSR, Miscov R, et al. Optimal drainage time after evacuation of chronic subdural haematoma (DRAIN TIME 2): a multicentre, randomised, multiarm and multistage non-inferiority trial in Denmark. Lancet Neurol. 2024;23(8):787-796. doi:10.1016/S1474-4422(24)00175-3 PMID: 38878790

Bailout intracranial angioplasty or stenting following thrombectomy for acute large vessel occlusion in China (ANGEL-REBOOT): a multicentre, open-label, blinded-endpoint, randomised controlled trial

中国急性大血管闭塞血栓切除术后的救助颅内血管成形术或支架置入术 (ANGEL-REBOOT): 一项多中心、开放标签、盲法终点、随机对照试验

Unsuccessful recanalisation or reocclusion after thrombectomy is associated with poor outcomes in patients with large vessel occlusion (LVO) acute ischaemic stroke (LVO-AIS). Bailout angioplasty or stenting (BAOS) could represent a promising treatment for these patients. We conducted a randomised controlled trial with the aim to investigate the safety and efficacy of BAOS following thrombectomy in patients with LVO. From Dec 19, 2021, to March 17, 2023, 706 patients were screened, and 348 were enrolled, with 176 assigned to the intervention group and 172 to the control group. No patients withdrew from the trial or were lost to follow-up for the primary outcome. The median age of patients was 63 years (IQR 55-69), 258 patients (74%) were male, and 90 patients (26%) were female; all participants were Chinese. After random allocation, tirofiban was administered either intra-arterially, intravenously, or both in 334 [96%] of 348 participants. No between-group differences were observed in the primary outcome (common odds ratio 0·86 [95% CI 0·59-1·24], p=0·41). Mortality was similar between the two groups (19 [11%] of 176 vs 17 [10%] of 172), but the intervention group showed a higher risk of symptomatic intracranial haemorrhage (eight [5%] of 175 vs one [1%] of 169), parenchymal haemorrhage type 2 (six [3%] of 175 vs none in the control group), and procedure-related arterial dissection (24 [14%] of 176 vs five [3%] of 172).

血栓切除术后不成功的再通或再闭塞与大血管闭塞 (LVO) 急性缺血性卒中 (LVO) 患者的不良预后有关。Bailout血管成形术或支架置入术 (BAOS) 可能代表这些患者的有希望的治疗方法。我们进行了一项随机对照试验，旨在研究LVO患者血栓切除术后BAOS的安全性和有效性。从2021年12月19日至2023 3月17日，筛选了706例患者，并纳入了348例患者，其中176分配到干预组，172分配到对照组。没有患者退出试验或失去主要结局的随访.患者的中位年龄为63岁 (IQR 55-69)，258例患者 (74%) 为男性，90例患者 (26%) 为女性; 所有参与者均为中国人。随机分配后，替罗非班在348名参与者的334 [96%] 中进行了动脉内，静脉内或同时进行。在主要结局中没有观察到组间差异 (共同优势比0·86 [95% CI 0·59-1·24]，p = 0·41)。两组之间的死亡率相似 (19 [11%] 176 vs 17 [10%] 172)，但干预组显示出更高的症状性颅内出血风险 (8 [5%] 175 vs 1 [1%] 169)，2型脑实质出血 (6 [3%]对照组为175例，对照组为无例)，与手术相关的动脉夹层 (176例为24 [14%]，172例为5 [3%])。

REF: Gao F, Tong X, Jia B, et al. Bailout intracranial angioplasty or stenting following thrombectomy for acute large vessel occlusion in China (ANGEL-REBOOT): a multicentre, open-label, blinded-endpoint, randomised controlled trial. Lancet Neurol. 2024;23(8):797-806. doi:10.1016/S1474-4422(24)00186-8 PMID: 38914085

Safety and efficacy of active blood-pressure reduction to the recommended thresholds for intravenous thrombolysis in patients with acute ischaemic stroke in the Netherlands (TRUTH): a prospective, observational, cluster-based, parallel-group study

荷兰急性缺血性卒中患者主动降压至静脉溶栓推荐阈值的安全性和有效性 (TRUTH): 一项前瞻性、观察性、基于聚类的平行组研究

Intravenous thrombolysis is contraindicated in patients with ischaemic stroke with blood pressure higher than 185/110 mm Hg. Prevailing guidelines recommend to actively lower blood pressure with intravenous antihypertensive agents to allow for thrombolysis; however, there is no robust evidence for this strategy. Because rapid declines in blood pressure can also adversely affect clinical outcomes, several Dutch stroke centres use a conservative strategy that does not involve the reduction of blood pressure. We aimed to compare the clinical outcomes of both strategies. Insufficient evidence was available to establish a difference between an active blood-pressure-lowering strategy-in which antihypertensive agents were administered to reduce blood pressure below 185/110 mm Hg-and a non-lowering strategy for the functional outcomes of patients with ischaemic stroke, despite higher intravenous thrombolysis rates and shorter door-to-needle times among those in the active blood-pressure-lowering group. Randomised controlled trials are needed to inform the use of an active blood-pressure-lowering strategy.

血压高于185/110mm Hg的缺血性卒中患者禁用静脉溶栓。现行指南建议使用静脉内降压药积极降低血压，以进行溶栓治疗; 然而，没有强有力的证据支持这种策略。由于血压的快速下降也会对临床结果产生不利影响，一些荷兰卒中中心使用不涉及降低血压的保守策略。我们旨在比较两种策略的临床结果。对于缺血性卒中患者的功能结局，没有足够的证据来确定主动降血压策略与非降血压策略之间的差异，在主动降血压策略中，使用降压药将血压降至185/110mm Hg以下。尽管在主动降血压组中，静脉溶栓率较高，门到针时间较短。需要进行随机对照试验，以告知主动降血压策略的使用。

REF: Zonneveld TP, Vermeer SE, van Zwet EW, et al. Safety and efficacy of active blood-pressure reduction to the recommended thresholds for intravenous thrombolysis in patients with acute ischaemic stroke in the Netherlands (TRUTH): a prospective, observational, cluster-based, parallel-group study [published correction appears in Lancet Neurol. 2024 Aug;23(8):e12. doi: 10.1016/S1474-4422(24)00286-2]. Lancet Neurol. 2024;23(8):807-815. doi:10.1016/S1474-4422(24)00177-7 PMID: 38763149

Prognostic value of tissue bridges in cervical spinal cord injury: a longitudinal, multicentre, retrospective cohort study

组织间桥在颈部脊髓损伤中的预后价值: 一项纵向、多中心、回顾性队列研究

The accuracy of prognostication in patients with cervical spinal cord injury (SCI) needs to be improved. We aimed to explore the prognostic value of preserved spinal tissue bridges-injury-spared neural tissue adjacent to the lesion-for prediction of sensorimotor recovery in a large, multicentre cohort of people with SCI. The cohort included 227 patients: 93 patients from Murnau (22 [24%] female); 43 patients from Zurich (four [9%] female); and 91 patients from Denver (14 [15%] female). 136 of these participants (from Murnau and Zurich) were followed up for up to 12 months. At 3 months, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 9·3% (SD 0·9) of maximal total motor score (95% CI 7·5-11.2), 8·6% (0·8) of maximal pinprick score (7·0-10·1), and 10·9% (0·8) of maximal light touch score (9·4-12·5). At 12 months post SCI, per preserved 1 mm of tissue bridge at baseline, patients recovered a mean of 10·9% (1·3) of maximal total motor score (8·4-13·4), 5·7% (1·3) of maximal pinprick score (3·3-8·2), and 6·9% (1·4) of maximal light touch score (4·1-9·7). Partitioning models identified a tissue bridge cutoff width of 2·0 mm to be indicative of higher or lower 3-month total motor, pinprick, and light touch scores, and a cutoff of 4·0 mm to be indicative of higher and lower 12-month scores. Compared with models that contained clinical predictors only, models additionally including tissue bridges had significantly improved prediction accuracy across all three centres.

颈部脊髓损伤 (SCI) 患者预后的准确性有待提高。我们的目的是探讨保留脊髓组织桥的预后价值-损伤-邻近病变的神经组织-在大型多中心SCI患者队列中预测感觉运动恢复。该队列包括227名患者: 93名来自Murnau的患者 (22 [24%] 名女性); 43名来自苏黎世的患者 (4 [9%] 名女性); 91名来自丹佛的患者 (14 [15%] 名女性)。对其中136名参与者 (来自Murnau和苏黎世) 进行了长达12个月的随访。在3个月时，在基线时每保留组织间桥的1毫米，患者恢复平均9·3% (SD 0·9) 的最大总运动评分 (95% CI 7·5-11.2)，8·6% (0·8) 最大针刺得分 (7·0-10·1) 和最大轻触得分 (9·4-12·5) 的10·9% (0·8)。在SCI后12个月，在基线时每保留组织桥的1毫米，患者平均恢复10·9% (1·3) 的最大总运动评分 (8·4-13·4)，5·7% (1·3) 最大针刺得分 (3·3-8·2) 和最大轻触得分 (4·1-9·7) 的6·9% (1·4)。分区模型确定了组织桥的截止宽度为2·0毫米，表明3个月的总运动，针刺和轻触得分较高或较低，而截止宽度为4·0毫米，表明12个月的评分较高和较低。与仅包含临床预测因素的模型相比，另外包括组织间桥的模型在所有三个中心的预测准确性均显着提高。

REF: Pfyffer D, Smith AC, Weber KA 2nd, et al. Prognostic value of tissue bridges in cervical spinal cord injury: a longitudinal, multicentre, retrospective cohort study. Lancet Neurol. 2024;23(8):816-825. doi:10.1016/S1474-4422(24)00173-X PMID: 38945142

Effects of spaceflight on the brain

航天飞行对大脑的影响

The number of long duration human spaceflights has increased substantially over the past 15 years, leading to the discovery of numerous effects on the CNS. Microgravity results in headward fluid shifts, ventricular expansion, an upward shift of the brain within the skull, and remodelling of grey and white matter. The fluid changes are correlated with changes to perivascular space and spaceflight associated neuro-ocular syndrome. Microgravity alters the vestibular processing of head tilt and results in reduced tactile and proprioceptive inputs during spaceflight. Sensory adaptation is reflected in postflight effects, evident as transient sensorimotor impairment. Another major concern is that galactic cosmic radiation, which spacefarers will be exposed to when going beyond the magnetosphere around Earth, might have a negative effect on CNS function. Research with rodents points to the potential disruptive effects of space radiation on blood-brain barrier integrity and brain structures. More work is needed to understand and mitigate these effects on the CNS before humans travel to Mars, as the flight durations will be longer than anyone has previously experienced.

在过去的15年中，长时间的人类太空飞行的数量已大大增加，从而发现了对CNS的许多影响。微重力会导致液体向头部移动，心室扩张，颅骨内大脑的向上移动以及灰质和白质的重塑。液体变化与血管周围空间和航天相关的神经眼综合征的变化相关。微重力改变了头部倾斜的前庭处理，并导致太空飞行期间触觉和本体感受输入减少。感觉适应反映在飞行后效应中，表现为短暂的感觉运动障碍。另一个主要问题是，太空飞行人员在超出地球周围的磁层时将暴露于银河宇宙辐射，这可能会对CNS功能产生负面影响。对啮齿动物的研究指出了空间辐射对血脑屏障完整性和大脑结构的潜在破坏性影响。在人类前往火星之前，需要做更多的工作来理解和减轻这些对中枢神经系统的影响，因为飞行时间将比任何人以前经历的都长。

REF: Seidler RD, Mao XW, Tays GD, Wang T, Zu Eulenburg P. Effects of spaceflight on the brain. Lancet Neurol. 2024;23(8):826-835. doi:10.1016/S1474-4422(24)00224-2 PMID: 38945144