Reperfusion Injury Is Associated With Poor Outcome in Patients With Recanalization After Thrombectomy.

BACKGROUND: The existence of cerebral reperfusion injury in human beings remains controversial. Thus, we aimed to explore the presence of reperfusion injury in acute ischemic stroke patients with recanalization after mechanical thrombectomy and analyzed its impact on neurological outcome. METHODS: We reviewed our prospectively collected database CIPPIS (Comparison Influence to Prognosis of CTP and MRP in AIS Patients, NCT03367286), and enrolled anterior circulation large artery occlusion patients with recanalization after mechanical thrombectomy who underwent (1) computed tomography (CT) perfusion on admission and immediately after recanalization to determine reperfusion region, and (2) CT and/or magnetic resonance imaging (MRI) immediately and 24 hours after recanalization to determine lesion areas. The expansion of lesion between recanalization and 24 hours within reperfusion region was potentially caused by reperfusion, thus termed as radiological observed reperfusion injury (RORI). Based on the imaging modality immediately after recanalization, RORI was further divided into RORICT and RORIMRI. We first included a small cohort who had performed both CT and MRI immediately after recanalization to validate the consistency between RORICT and RORIMRI (Study 1). Then the association with RORICT and poor outcome, defined as 3-month modified Rankin Scale score of 3 to 6, was explored in a larger cohort (Study 2). RESULTS: Study 1 included 23 patients and good consistency was found between RORICT and RORIMRI (intraclass correlation=0.97, P<0.001). Among 226 patients included in Study 2, a total of 106 (46.9%) were identified with RORI. The ratio of RORI to reperfusion region was 30.1 (16.2, 51.0)% and was independently associated with poor outcome (odds ratio=1.55 per 10% [95% CI' 1.30-1.84]; P<0.001). CONCLUSIONS: Our findings suggested that RORI was relatively frequent in stroke patients with recanalization after mechanical thrombectomy and associated with poor outcome despite successful recanalization. REGISTRATION: URL: https://www. CLINICALTRIALS: gov; Unique identifier: NCT03367286.

Early Fibrinogen Depletion and Symptomatic Intracranial Hemorrhage After Reperfusion Therapy.

Background and Purpose- We aimed to thoroughly investigate the relationship between early fibrinogen depletion and symptomatic intracranial hemorrhage (sICH) in patients receiving reperfusion therapy including intravenous thrombolysis (IVT) with or without endovascular thrombectomy (EVT). Methods- This study included 1135 stroke patients with baseline and follow-up fibrinogen levels at 2 hours after the beginning of alteplase infusion for those with IVT only or immediately after the end of EVT for those with combined IVT and EVT. Patients received alteplase up to 9 hours after the onset or on awakening based on automated perfusion imaging. sICH was ascertained using ECASS II (The Second European-Australasian Acute Stroke Study) criteria. Δfibrinogen was calculated as follow-up fibrinogen minus baseline fibrinogen. Results- In patients with IVT only, baseline fibrinogen level was 3.36±0.94 g/L and decreased to 2.47±0.80 g/L at 2 hours after the beginning of alteplase infusion. In patients with IVT followed by EVT, baseline fibrinogen level was 3.35±0.82 g/L and decreased to 2.52±0.83 g/L immediately after the end of EVT. sICH was observed in 44 (3.9%) patients. The extent of Δfibrinogen was associated with sICH in patients with IVT only (odds ratio, 1.929; 95% CI, 1.402-2.654; P<0.001) and in those with IVT followed by EVT (odds ratio, 1.765; 95% CI, 1.135-2.743; P=0.012). Conclusions- An early decrease in fibrinogen levels was related to sICH after reperfusion therapy with alteplase. More fibrin-specific thrombolytic agents are warranted to be tested in acute ischemic stroke patients. Clinical Trial Registration- URL: https://www.clinicaltrials.gov. Unique identifier: NCT03367286.

Application of postoperative autotransfusion in total joint arthroplasty reduces allogeneic blood requirements: a meta-analysis of randomized controlled trials.

BACKGROUND: Total joint arthroplasty is associated with significant blood loss and often requires blood transfusion. However, allogeneic blood transfusion (ABT) may lead to severe problems, such as immunoreaction and infection. Postoperative autotransfusion, an alternative to ABT, is controversial. We conducted a meta-analysis to evaluate the ability of postoperative autotransfusion to reduce the need for ABT following total knee arthroplasty (TKA) and total hip arthroplasty (THA). METHODS: Systematic literature searches for randomized controlled trials were performed using PubMed, Embase, and the Cochrane Library until February 2016. Relative risks (RRs) and weighted mean differences with 95% confidence intervals (CIs) were calculated using fixed-effect or random-effect models; we also evaluated publication bias and heterogeneity. RESULTS: Seventeen trials with a total of 2314 patients were included in the meta-analysis. The pooled RRs of ABT rate between autotransfusion and the regular drainage/no drainage groups for TKA and THA were 0.446 (95% CI = 0.287, 0.693; p < 0.001) and 0.757 (95% CI = 0.599, 0.958; p = 0.020), respectively. In the subgroup analysis performed in TKA patients according to control interventions, the pooled RRs were 0.377 (95% CI = 0.224, 0.634; p < 0.001) (compared with regular drainage) and 0.804 (95% CI = 0.453, 1.426, p = 0.456) (compared with no drainage). In the subgroup analysis performed for THA, the pooled RRs were 0.536 (95% CI = 0.379, 0.757, p < 0.001) (compared with regular drainage) and 1.020 (95% CI = 0.740, 1.405, p = 0.904) (compared with no drainage). CONCLUSIONS: Compared to regular drainage, autotransfusion reduces the need for ABT following TKA and THA. This reduction is not present when comparing autotransfusion to no drainage. However, the reliability of the meta-analytic results concerning TKA was limited by significant heterogeneity in methods among the included studies.

Impaired Meningeal Lymphatics and Glymphatic Pathway in Patients with White Matter Hyperintensity.

White matter hyperintensity (WMH) represents a critical global medical concern linked to cognitive decline and dementia, yet its underlying mechanisms remain poorly understood. Here, humans are directly demonstrated that high WMH burden correlates with delayed drainage of meningeal lymphatic vessels (mLVs) and glymphatic pathway. Additionally, a longitudinal cohort study reveals that glymphatic dysfunction predicts WMH progression. Next, in a rat model of WMH, the presence of impaired lymphangiogenesis and glymphatic drainage is confirmed, followed by elevated microglial activation and white matter demyelination. Notably, enhancing meningeal lymphangiogenesis through adeno-associated virus delivery of vascular endothelial growth factor-C (VEGF-C) mitigates microglial gliosis and white matter demyelination. Conversely, blocking the growth of mLVs with a VEGF-C trap strategy exacerbates these changes. The findings highlight the role of mLVs and glymphatic pathway dysfunction in aggravating brain white matter injury, providing a potential novel strategy for WMH prevention and treatment.

Impaired intracranial venous outflow profiles are associated with poor outcome in stroke after reperfusion therapy: A hypoperfusion-matched intracranial venous scale.

PURPOSE: Arterial blood flow provided prognostic information in acute ischemic stroke (AIS). However, part of the patients with favorable arterial blood flow still suffered from poor outcomes after reperfusion therapy. We aimed to verify the hypothesis that intracranial venous outflow profiles (both cortical and deep) within the hypoperfusion area were associated with clinical outcome in AIS patients who received reperfusion therapy. METHOD: We performed a retrospective analysis of prospectively collected data from anterior circulation AIS patients. All patients underwent pretreatment CTP and received reperfusion therapy. We constructed a 5-point hypoperfusion-matched Intracranial Venous Scale (hypo-IVS) from the sum of the contrast enhancement degree (1, attenuated contrast enhancement; 0, complete contrast enhancement) of 4 typical veins (superficial middle cerebral vein, vein of Labbé, vein of Trolard, and internal cerebral vein) whose outflow territories had matched hypoperfusion. Logistic and ordinal regression were used to analyze the association between hypo-IVS and clinical outcome. RESULTS: A total of 751 patients were included. Higher Hypo-IVS was significantly associated with poor outcome (3-month mRS of >2; OR = 1.194; 95 % CI: 1.014-1.407; p = 0.033). The adjusted ORs for poor outcome and high 24-hour NIHSS were 1.172 (95 %CI: 1.035-1.328; p = 0.012) and 1.176 (95 %CI: 1.030-1.330; p = 0.010) in ordinal regression, respectively. Hypo-IVS > 2 was an independent risk factor of poor outcome (75.2 % vs 40.8 %; OR = 1.932; 95 %CI: 1.158-3.224; p = 0.012). CONCLUSIONS: Intracranial venous outflow profiles deliver prognostic information in AIS and the hypo-IVS is a helpful tool to predict clinical outcomes after reperfusion therapy.

Higher Functional Connectivity of Ventral Attention and Visual Network to Maintain Cognitive Performance in White Matter Hyperintensity.

Ventral attention network (VAN), associated with cognitive performance, is one of the functional networks that are most vulnerable in white matter hyperintensity (WMH). Considering the global interaction of networks for cognitive performance, we hypothesized that VAN-related between-network connectivity might play a role in maintaining cognition in patients with WMH. We included 139 participants for both cross-sectional and longitudinal analysis from CIRCLE study (ClinicalTrials.gov ID: NCT03542734) between January 2014 and January 2021. Differences of VAN-related between-network connectivity were compared between normal-cognition (NC) and cognitive-impairment (CI) groups cross-sectionally, and between cognitive-decline (CD) and cognitive non-decline (CND) groups longitudinally by using t-test. False Discovery Rate was used for multiple comparison correction. The relationship between the network connectivity and WMH was tested on linear and quadratic models. Subgroup analysis of different WMH burdens were performed to test the difference of network connectivity between NC and CI groups. Among VAN-related between-network connectivity, only VAN-Visual Network (VN) connectivity was higher both in NC (n = 106) and CND (n = 113) groups versus CI (n = 33) and CD groups (n = 26), respectively. There was an inverted U-shaped relation between periventricular WMH (PWMH) burden and VAN-VN connectivity. Normal-cognition participants had higher VAN-VN connectivity among high, but not low PWMH burden subgroups. These findings suggest that the VAN-VN connectivity plays an important role in maintaining cognitive performance in WMH patients. It may serve as a unique marker for cognitive prediction and a potential target for intervention to prevent cognitive decline in WMH patients.

Multi-Mode Imaging Scale for Endovascular Therapy in Patients with Acute Ischemic Stroke (META).

Background: With the guidance of multi-mode imaging, the time window for endovascular thrombectomy (EVT) has been expanded to 24 h. However, poor clinical outcomes are still not uncommon. We aimed to develop a multi-mode imaging scale for endovascular therapy in patients with acute ischemic stroke (META) to predict the neurological outcome in patients receiving endovascular thrombectomy (EVT). Methods: We included consecutive acute ischemic stroke patients with occlusion of middle cerebral artery and/or internal carotid artery who underwent EVT. Poor outcome was defined as modified Rankin Scale (mRS) score of 3−6 at 3 months. A five-point META score was constructed based on clot burden score, multi-segment clot, the Alberta Stroke Program early computed tomography score of cerebral blood volume (CBV-ASPECTS), and collateral status. We evaluated the META score performance using area under the curve (AUC) calculations. Results: A total of 259 patients were included. A higher META score was independently correlated with poor outcomes at 3 months (odds ratio, 1.690, 95% CI, 1.340 to 2.132, p < 0.001) after adjusting for age, hypertension, baseline National Institutes of Health Stroke Scale (NIHSS) score, and baseline blood glucose. Patients with a META score ≥ 2 were less likely to benefit from EVT (mRS 3−6: 60.8% vs. 29.2%, p < 0.001). The META score predicted poor outcomes with an AUC of 0.714, higher than the Pittsburgh Response to Endovascular therapy (PRE) score, the totaled health risks in vascular events (THRIVE) score (AUC: 0.566, 0.706), and the single imaging marker in the scale. Conclusions: The novel META score could refine the predictive accuracy of prognosis after EVT, which might provide a promising avenue for future automatic imaging analysis to help decision making.