Zhongming Qiu

Background and ObjectivesThe impact of ischemic extent on the efficacy and safety of intravenous thrombolysis before thrombectomy remains uncertain. The aim of this study was to evaluate whether th...

BACKGROUND: Although the neuroprotective potential of remote ischemic postconditioning (RIPC) has been reported, the efficacy and safety of ultra-early RIPC administered after endovascular treatment (EVT) in patients with acute ischemic stroke remain unclear. This study evaluated the efficacy and safety of ultra-early RIPC in patients with acute ischemic stroke undergoing EVT. METHODS: The EnTRIPS trial (Endovascular Treatment Combined with Remote Ischemic Postconditioning in Patients with Acute Ischemic Stroke) was a multicenter, randomized, controlled, outcome assessor-blinded, prospective clinical trial. The trial was conducted at 8 hospitals in China between April 12, 2021, and March 26, 2025. Eligible patients were adults with acute ischemic stroke due to large vessel occlusion who presented within 24 hours of symptom onset, underwent EVT, and achieved successful recanalization. A total of 270 eligible patients were randomized within 6 hours after EVT to receive either RIPC plus guideline-based therapy (n=135) or guideline-based therapy alone (n=135). RIPC was administered for 7 days using pneumatic devices consisting of 5 cycles of bilateral upper-arm cuff inflation (5 minutes at 180 mm Hg) followed by deflation (3 minutes). The primary outcome was functional independence at 90 days, defined as a modified Rankin Scale score of 0 to 2 (range, 0 [no symptoms] to 6 [death]). Safety outcomes included the incidence of RIPC-related adverse events within 7 days. RESULTS: Among 270 randomized patients, a total of 268 (99.3%) participants completed the trial, including 133 in the RIPC group and 135 in the control group (mean [SD] age, 65.5 [16.8] years; 171 [63.8%] men). At 90 days, functional independence was achieved in 81 (60.9%) patients in the RIPC group and 78 (57.8%) patients in the control group (adjusted risk ratio, 1.07 [95% CI, 0.89–1.30]; P =0.46). RIPC-related adverse events occurred in 10 of 133 (7.5%) patients, and no intervention-related adverse events occurred in the control group. CONCLUSIONS: Ultra-early RIPC is safe for patients with acute ischemic stroke treated with EVT, but it does not significantly improve the 90-day functional outcomes. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT04581759.

BACKGROUND: The disruption of the blood–brain barrier (BBB) is a central pathogenic event in many central nervous system disorders. However, the mechanisms regulating BBB function remain incompletely understood, and effective treatments are lacking. Brain mural cells differ significantly from their peripheral counterparts, a distinction likely critical for maintaining BBB integrity. METHODS: We combined proteomic profiling of human brain vs peripheral mural cells with multiple ischemic stroke models (global apolipoprotein D [ApoD] knockout, mural cell–specific ApoD knockout, and adeno-associated virus–mediated ApoD overexpression) to evaluate the role of ApoD in BBB integrity. Mechanistic studies (co-immunoprecipitation, binding assays, including surface plasmon resonance, bio-layer interferometry, cross-linking mass spectrometry, and CD36 loss-of-function approaches, both in vitro and in vivo) were performed to determine how ApoD interacts with CD36 and inhibits its signaling. Finally, we assessed the effect of ApoD glycosylation on CD36 binding and tested therapeutic delivery of hypoglycosylated ApoD in stroke. RESULTS: Our study has shown an increased expression of ApoD in mural cells after ischemic stroke. We found that mural cell–derived ApoD functions as an inhibitory ligand of endothelial CD36, suppressing pathological endothelial proliferation, preserving BBB integrity, and promoting neurological recovery. Additionally, overexpression of ApoD in mural cells improved BBB integrity and enhanced functional recovery in ApoD -null mice. Mechanistically, ApoD competes with long-chain fatty acids for CD36 binding and directly attenuates downstream CD36 signaling. Furthermore, we reveal that peripheral hyperglycosylated ApoD (hyperglyco-ApoD) showed minimal effect on BBB integrity maintenance, whereas hypoglycosylation of ApoD enhances its binding affinity to CD36, amplifying its therapeutic efficacy. Exogenous administration of hypoglyco-ApoD via vein injection profoundly inhibited BBB disruption and improved neural function, especially in aging stroke. CONCLUSIONS: Our work identifies a previously unrecognized paracrine mechanism in which mural cell–derived ApoD directly engages endothelial CD36 to restrain pathological endothelial proliferation, thereby preserving BBB integrity and promoting neurological recovery after stroke. These findings further suggest that hypoglycosylated ApoD, with its higher CD36-binding affinity, merits investigation as a potential strategy to enhance BBB repair in central nervous system disorders.

Background: Intravenous thrombolysis followed by endovascular thrombectomy (EVT) is a first‐line recommended strategy for thrombolysis‐eligible patients with stroke due to acute large‐vessel occlusion. Tirofiban, one of the most used glycoprotein IIb/IIIa receptor inhibitors, has been increasingly advocated to counteract different stages of thrombosis mediated by activated platelets. It is unclear whether tirofiban could be used as an alternative to thrombolysis as adjuvant medicine for EVT. This trial aims to assess whether intravenous tirofiban plus EVT is noninferior to intravenous thrombolysis bridging with EVT in patients with acute ischemic stroke due to large‐vessel occlusion who are eligible for thrombolysis. Methods: ADJUVANT (Intravenous Tirofiban Versus Thrombolysis Before Endovascular Stroke Thrombectomy) is an investigator‐initiated, multicenter, randomized, open‐label, noninferiority trial with blinded end point assessment conducted at 42 thrombectomy‐capable centers in China. This trial will randomize 976 thrombolysis‐eligible stroke patients with confirmed occlusion of the internal carotid artery, M1/M2 segments of the middle cerebral artery, or basilar artery in a 2:1 ratio to receive intravenous tirofiban plus EVT or intravenous thrombolysis bridging with EVT. Results: The primary efficacy outcome is functional independence, defined as a score of 0 to 2 on the modified Rankin scale, at 90 days. Safety outcomes are symptomatic intracranial hemorrhage within 48 hours and death within 90 days. Conclusions: ADJUVANT will provide unique information about the efficacy and safety of adjuvant intravenous tirofiban before EVT in thrombolysis‐eligible patients with stroke due to acute large‐vessel occlusion. Registration: URL: https://clinicaltrials.gov . Unique Identifier: NCT05728333.

BACKGROUND: Current evidence on differential outcomes of endovascular therapy for the different pathological subtypes of vertebrobasilar artery occlusion is still limited. The study aimed to compare characteristics and clinical outcomes among distinct pathological subtypes of vertebrobasilar artery occlusion undergoing endovascular therapy. METHODS: This was a posthoc pooled analysis of 1320 patients from the BASILAR (Endovascular Treatment for Acute Basilar Artery Occlusion Study; 2014–2019) and the PERSIST (Posterior Circulation Ischemic Stroke Registries; 2015–2018) registries. This analysis included adults (≥18 years) with moderate to severe vertebrobasilar artery occlusion who underwent endovascular therapy within 24 hours of their last known well. Patients were stratified by stroke mechanism: group 1 (embolism without vertebral stenosis), group 2 (tandem embolism from vertebral stenosis/occlusion), and group 3 (in situ atherosclerotic thrombosis). Baseline characteristics, procedural details, and clinical outcomes were compared across these 3 groups. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale score of 0 to 3 at 90 days. Baseline characteristics, procedural details, and clinical outcomes were compared across these 3 groups. Because the primary independent variable was categorical with no single referent category, all comparisons among the 3 groups were conducted as exploratory analyses. RESULTS: A total of 1067 patients were included (group 1, n=257 [24.08%]; group 2, n=176 [16.49%]; group 3, n=634 [59.42%]). The overall successful recanalization rate was 84.72% (904/1067), and the favorable functional outcome (90-day modified Rankin Scale score of 0–3) rate was 33.40% (275/1063). The procedure time in group 1 was significantly shorter than that in groups 2 and 3 (median time, 90 versus 135 and 110 minutes, P <0.001). There was no significant difference in the primary outcome of a favorable functional outcome among the 3 groups. After adjusting for potential confounders, group 1 exhibited a significantly higher proportion of patients achieving excellent outcomes at 90 days (modified Rankin Scale score, 0–1) compared with groups 2 and 3 (21.9% versu 17.1%, adjusted odds ratio, 0.57 [95% CI, 0.32–0.99]; 21.9% versus 16.5%, adjusted odds ratio, 0.59 [95% CI, 0.37–0.95]). No significant differences were observed in recanalization rates, favorable functional outcome, symptomatic intracranial hemorrhage, or mortality among the 3 groups. CONCLUSIONS: The outcome of endovascular therapy for vertebrobasilar artery occlusion may vary based on the stroke mechanism; patients with embolism without vertebral artery steno-occlusion may achieve excellent outcomes compared with other causes. REGISTRATION: URL: http://www.chictr.org.cn ; Unique identifier: CTR1800014759 and CTR2000033211.

Background Despite successful endovascular thrombectomy (EVT) for acute ischemic stroke (AIS) with a large infarct core, patient disability and mortality remain high. Aim The MIRACLE trial aims to evaluate the efficacy and safety of administering adjunct intravenous methylprednisolone in AIS patients with a large infarct core. Design Methylprednisolone as Adjunct to Endovascular Thrombectomy for patients with Acute Large Ischemic Stroke (MIRACLE) is a multicenter, prospective, randomized, double-blind, placebo-controlled phase 3 trial conducted across 99 stroke centers in China. A total of 902 patients with anterior circulation large vessel occlusion and large infarct core (Alberta Stroke Program Early CT Score [ASPECTS] Study outcomes The primary efficacy outcome is all-cause mortality at 90 days. Key secondary outcomes include functional status assessed by the modified Rankin Scale (mRS), neurological status assessed by National Institutes of Health Stroke Scale (NIHSS), quantitative cerebral edema markers (midline shift, relative hemispheric volume, and water uptake), and decompressive craniectomy rates. The primary safety outcome is symptomatic intracranial hemorrhage (SICH) within 48 hours post-EVT. Analyses will follow the intention-to-treat principle. Recruitment began in August 2024 and is expected to conclude by October 2025. Conclusion The MIRACLE trial will provide evidence of the efficacy and safety of adjunctive methylprednisolone in AIS patients with a large core undergoing EVT within 12 hours of last known well. Trial Registration ClinicalTrials.gov NCT06360458 What Is New?The MARVEL trial (Methylprednisolone as Adjunct to Endovascular Thrombectomy for Large Vessel Occlusion Stroke) [1] demonstrated a potential safety benefit and reduced mortality with adjunctive methylprednisolone in patients with anterior circulation large vessel occlusion stroke undergoing endovascular thrombectomy (EVT), but it excluded patients with very large infarct core (Alberta Stroke Program Early CT Score [ASPECTS] 50-70 mL), leaving its efficacy in this high-risk population unknown. This study aims to investigate whether adjunctive methylprednisolone improves survival in acute ischemic stroke (AIS) patients with large infarct core undergoing EVT (ASPECTS < 6 and/or core infarct volume > 50 ml). What Aare the Clinical Implications?If positive, MIRACLE will provide robust evidence for a simple, accessible, and inexpensive adjunctive therapy to EVT that could improve outcomes for AIS patients with large infarct core.

Hemorrhagic transformation is a prevalent and serious complication that frequently occurs after endovascular recanalization in acute large vessel occlusion stroke. The impact of asymptomatic intracranial hemorrhage (aICH) on outcomes after endovascular thrombectomy (EVT) remains to be elucidated. This was a pooled analysis of individual patient data of 2 randomized trials in China, the RESCUE BT trial from October 2018 to October 2021 and the Direct Endovascular Treatment for Large Vessel Occlusion Stroke trial from May 2018 to May 2020. Patients with acute anterior circulation large vessel occlusion were categorized into 3 groups based on CT or MRI examination within 48 hours after thrombectomy: no intracranial hemorrhage (no-ICH), aICH, and symptomatic ICH (sICH). The primary outcome was functional independence (defined as modified Rankin Scale score of 0-2) at 90 days. Secondary outcomes were the change in NIH Stroke Scale score from baseline to 5-7 days and 3-month mortality. A total of 1,177 patients (median age, 68 years; 58.4% male) were included in this study, comprising 818 patients without ICH, 268 patients with aICH, and 91 patients with sICH. The proportion of functional independence was 57.3% in the no-ICH group, 34.7% in the aICH group, and 3.3% in the sICH group. Compared with the no-ICH group, there was a lower proportion of functional independence in the aICH group (adjusted odds ratio [aOR], 0.40; 95% CI 0.29-0.55; p < 0.001) and the sICH group (aOR, 0.02; 95% CI 0.01-0.07; p < 0.001). Both aICH and sICH were associated with less improvement of neurologic disability at 5-7 days from baseline and higher mortality at 90 days. Among patients with large vessel occlusion stroke who underwent EVT, the presence of aICH was associated with less early neurologic improvement and greater disability at 90 days. Asymptomatic ICH should be assessed in EVT trials, and strategies to reduce asymptomatic hemorrhage should be investigated.

Background and objectives: Intra-arterial thrombolysis (IAT) after mechanical thrombectomy (MT) may improve microvascular reperfusion and reduce disability in patients with ischemic stroke. We conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) and observational cohort studies to investigate the efficacy and safety of MT combined with IAT for the treatment of acute ischemic stroke. Methods: We searched Pubmed, Embase, Cochrane Library, and Web of Science databases in all languages published from inception to May 30th, 2025, using the search terms “stroke”, “thrombectomy”, “intra-arterial thrombolysis”. The primary efficacy outcome was excellent functional outcome (modified Rankin scale 0-1) at 90 days and the key safety outcomes were death and symptomatic intracerebral hemorrhage. Effect sizes were computed as risk ratio (RR) with random-effect or fixed-effect models. Results: Seven RCTs and 9 cohort studies with a total of 6258 patients met the inclusion criteria. The results of the RCTs indicated that for patients with large vessel occlusion stroke who were treated with MT and achieved successful recanalization, the subsequent administration of IAT significantly increased the chances of excellent functional outcome (mRS 0-1, RR: 1.24, 95% CI 1.12-1.37, P<0.0001) without increasing the risk of sICH or death. While cohort studies lacked excellent functional outcome rates, other endpoints were consistent with RCTs. The results of subgroup analysis suggested that, in patients who did not receive IVT before MT, the combination of MT and IAT significantly improved the likelihood of achieving excellent functional outcomes (RR: 1.17, 95% CI 1.04-1.32). Conclusion: This systematic review and meta-analysis indicated that MT combined with IAT could lead to a higher opportunity of excellent functional outcome (mRS 0-1) than MT alone in acute stroke. Importantly, adding IAT was safe and did not increase the risk of symptomatic intracranial hemorrhage and death.

Background Malignant cerebral edema (MCE) following basilar artery occlusion (BAO) thrombectomy is a critical, yet understudied, complication. Objective To investigate the incidence, predictors, and clinical impact of MCE in patients with BAO after endovascular thrombectomy (EVT). Methods In this retrospective analysis of the national multicenter PERSIST Registry (2422 patients with BAO treated with EVT recruited from 65 Chinese centers, 2015–2022), MCE was defined as Jauss score ≥4 on follow-up imaging. Multivariable logistic regression identified predictors of MCE and its association with 90-day outcomes. A favorable outcome was defined as achieving a modified Rankin Scale score of 0–3 at 90 days. Results A total of 1883 patients who met the eligibility requirements were included. MCE occurred in 39.6% (746/1883) of patients. Independent predictors included admission systolic blood pressure ≥160 mm Hg (aOR=1.26, 95% CI 1.02 to 1.54), prolonged procedure time (aOR=1.01, 95% CI 1.01 to 1.01), BATMAN score ≥7 (aOR=0.68, 95% CI 0.55 to 0.84), and vertebral V4 occlusion (vs proximal BA: aOR=0.68, 95% CI 0.52 to 0.89). Successful reperfusion reduced MCE risk (aOR=0.57, 95% CI 0.42 to 0.75). Diabetes mellitus exhibited an inverse association (aOR=0.78, 95% CI 0.61 to 0.99). MCE predicted lower odds of favorable outcome (aOR=2.41, 95% CI 1.94 to 3.01; PConclusions MCE complicates 39.6% of patients with BAO after EVT and portends catastrophic outcomes despite successful recanalization. Shortening the procedure time, increasing the likelihood of first-pass success, and optimal admission blood pressure management might be targets to decrease MCE for patients with BAO undergoing EVT.

The safety and efficacy of treatment with intravenous tenecteplase before endovascular thrombectomy in patients with acute ischemic stroke due to large-vessel occlusion remain uncertain. In this open-label trial conducted in China, we randomly assigned patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset and were eligible for thrombolysis to receive either intravenous tenecteplase followed by endovascular thrombectomy or endovascular thrombectomy alone. The primary outcome was functional independence (a score of 0 to 2 on the modified Rankin scale; range, 0 to 6, with higher scores indicating more severe disability) at 90 days. Secondary outcomes included successful reperfusion before and after thrombectomy. Safety outcomes included symptomatic intracranial hemorrhage within 48 hours and death within 90 days. A total of 278 patients were randomly assigned to the tenecteplase-thrombectomy group and 272 to the thrombectomy-alone group. Functional independence at 90 days was observed in 147 patients (52.9%) in the tenecteplase-thrombectomy group and in 120 patients (44.1%) in the thrombectomy-alone group (unadjusted risk ratio, 1.20; 95% confidence interval, 1.01 to 1.43; P = 0.04). A total of 6.1% of the patients in the tenecteplase-thrombectomy group and 1.1% of those in the thrombectomy-alone group had successful reperfusion before thrombectomy, and 91.4% and 94.1%, respectively, had successful reperfusion after thrombectomy. Symptomatic intracranial hemorrhage within 48 hours occurred in 8.5% of the patients in the tenecteplase-thrombectomy group and in 6.7% of those in the thrombectomy-alone group; mortality at 90 days was 22.3% and 19.9%, respectively. Among patients with acute ischemic stroke due to large-vessel occlusion who had presented within 4.5 hours after onset, the percentage of patients with functional independence at 90 days was higher with intravenous tenecteplase plus endovascular thrombectomy than with endovascular thrombectomy alone. (Funded by the Chongqing Science and Health Joint Medical Research Project and others; BRIDGE-TNK ClinicalTrials.gov number, NCT04733742.).