Comparing Outcomes of Thrombectomy Versus Intravenous Thrombolysis Based on Middle Cerebral Artery M2 Occlusion Features.

BACKGROUND: Current evidence provides limited support for the superiority of endovascular thrombectomy (EVT) in patients with M2 segment middle cerebral artery occlusion. We aim to investigate whether imaging features of M2 segment occlusion impact the effectiveness of EVT. METHODS: We conducted a retrospective cohort study from January 2017 to January 2022, drawing data from the CASE II registry (Computer-Based Online Database of Acute Stroke Patients for Stroke Management Quality Evaluation), which specifically documented patients with acute ischemic stroke presenting with M2 segment occlusion undergoing reperfusion therapy. Patients were stratified into the intravenous thrombolysis (IVT) group (IVT alone) and EVT group (IVT plus EVT or EVT alone). The primary outcome was a modified Rankin Scale score 0 to 2 at 90 days. Secondary outcomes included additional thresholds and distribution of modified Rankin Scale scores, 24-hour recanalization, early neurological deterioration, and relevant complications during hospitalization. Safety outcomes encompassed intracranial hemorrhagic events at 24 hours and mortality at 90 days. Binary logistic regression analyses with propensity score matching were used. Subgroup analyses were performed based on the anatomic site of occlusion, including right versus left, proximal versus distal, dominant/co-dominant versus nondominant, single versus double/triple branch(es), and anterior versus central/posterior branch. RESULTS: Among 734 patients (43.3% were females; median age, 73 years) with M2 segment occlusion, 342 (46.6%) were in the EVT group. Propensity score matching analysis revealed no statistical difference in the primary outcome (odds ratio, 0.860 [95% CI, 0.611-1.209]; P=0.385) between the EVT group and IVT group. However, EVT was associated with a higher incidence of subarachnoid hemorrhage (odds ratio, 6.655 [95% CI, 1.487-29.788]; P=0.004) and pneumonia (odds ratio, 2.015 [95% CI, 1.364-2.977]; P<0.001). Subgroup analyses indicated that patients in the IVT group achieved better outcomes when presenting with right, distal, or nondominant branch occlusion (Pall interaction<0.05). CONCLUSIONS: Our study showed similar efficiency of EVT versus IVT alone in acute M2 segment middle cerebral artery occlusion. This suggested that only specific patient subpopulations might have a potentially higher benefit of EVT over IVT alone. REGISTRATION: URL: https://clinicaltrials.gov; Unique identifier: NCT04487340.

Choroid Plexus Enlargement Exacerbates White Matter Hyperintensity Growth through Glymphatic Impairment.

OBJECTIVE: Choroid plexus (CP) is a key regulator in cerebrospinal fluid production, but its contribution to glymphatic clearance function and association with white matter hyperintensity (WMH) remains unclear. METHODS: This retrospective study included 2 prospective 3.0-T magnetic resonance imaging (MRI) cohorts. In cohort 1, patients with indications for lumbar puncture underwent 3-dimensional T1-weighted sequence (3D-T1) before and at 39 hours after intrathecal administration of contrast agent (glymphatic MRI). In cohort 2, patients with WMH were enrolled from the CIRCLE study and had a median follow-up time of 1.4 years. WMH and CP of the lateral ventricles were automatically segmented on T2 fluid-attenuated inversion recovery (FLAIR) and 3D-T1, respectively. CP volume was expressed as a ratio to intracranial volume. Glymphatic clearance was measured as signal percentage change from baseline to 39 hours at 8 brain locations based on glymphatic MRI in the first cohort, or as noninvasive diffusion tensor image analysis along the perivascular space (DTI-ALPS) index based on DTI in the second cohort. RESULTS: In cohort 1, a total of 52 patients were included. Higher CP volume was correlated with slower glymphatic clearance rate in all brain locations. In cohort 2, a total of 197 patients were included. Baseline CP volume was positively associated with WMH volume and its growth. Furthermore, DTI-ALPS index partially mediated the association of CP with both WMH load and growth. INTERPRETATIONS: Enlarged CP volume could be an indicator for larger growth of WMH, potentially involving impaired glymphatic clearance function. The exploration of CP may provide a novel perspective to clarify the mechanism of WMH pathogenesis, as well as other glymphatic-related disorders. ANN NEUROL 2023;94:182-195.

Effect of computed tomography vs. computed tomography perfusion on mechanical thrombectomy outcomes within 6 hours.

OBJECTIVES: It is unclear which selection strategy, plain CT vs. CT perfusion (CTP), is more powerful in predicting outcome after mechanical thrombectomy (MT). We aimed to compare the effect of plain CT and CTP in predicting outcome after MT within 6 h. METHODS: We conducted a prospective analysis of a retrospective cohort from our single-center study, which had occlusion of the internal carotid artery and middle cerebral artery up to the proximal M2 segment and received MT within 6 h. According to the Alberta Stroke Program Early CT Score (ASPECTS), patients were divided into a high-ASPECTS group (≥ 6) and a low ASPECTS group (< 6). Similarly, patients were divided into mismatch and no-mismatch groups according to the DEFUSE3 criteria for CTP. A good outcome was defined as a 90-day modified Rankin Scale (mRS) score of ≤ 3. Univariate and binary logistic regression analyses were used to investigate the association between different imaging modality and 90-day mRS score, and mortalities, respectively. RESULTS: The high ASPECTS group included 307 patients (89.2%). The mismatch group included 189 (54.9%) patients meeting the DEFUSE3 criterion. Compared to the low ASPECTS group, the high ASPECTS group had a good outcome (odds ratio (OR), 2.285; [95% confidence interval (CI) (1.106, 4.723)], p = 0.026) and lower mortality (OR, 0.350; [95% CI (0.163, 0.752)], p = 0.007). However, there were no significant differences in good outcomes and mortality between the mismatch and no-mismatch groups. CONCLUSIONS: Compared with plain CT, CTP does not provide additional benefits in the selection of patients suitable for MT within 6 h. CLINICAL RELEVANCE STATEMENT: CT perfusion is not superior to plain CT for the prediction of clinical outcomes when selecting patients for mechanical thrombectomy in the first 6 h. In that clinical setting, plain CT may be safe in the absence of perfusion data. KEY POINTS: • The advantage of CT perfusion (CTP) over CT in pre-mechanical thrombectomy (MT) screening has not been proven for patients with a large infarct core. • CTP is not better than plain CT in predicting good outcome following MT within 6 h. • Plain CT is sufficient for selecting patients suitable for MT within 6 h of large artery occlusion.

Influencing factors of futile recanalization after endovascular intervention in patients with acute basilar artery occlusion. / æ€¥æ€§åŸºåº•åŠ¨è„‰é—­å¡žæ‚£è€ è¡€ç®¡å† æ²»ç–—åŽå‘ç”Ÿæ— æ•ˆå†é€šçš„å½±å“å› ç´ .

OBJECTIVES: To explore the influence factors for futile recanalization following endovascular treatment (EVT) in patients with acute basilar artery occlusion (BAO). METHODS: Clinical data of patients with acute BAO, who underwent endovascular treatment within 24 h of onset from January 2017 to November 2022, were retrospectively analyzed. The futile recanalization was defined as modified thrombolysis in cerebral infarction (mTICI) grade ≥2b or 3 after successful reperfusion, but the modified Rankin Scale score >2 at 3 months after EVT. Binary logistic regression model was used to analyze the influencing factors of futile recanalization. RESULTS: A total of 471 patients with a median age of 68 (57, 74) years were included and 68.9% were males, among whom 298 (63.27%) experienced futile recanalization. Multivariate analysis revealed that concomitant atrial fibrillation (OR=0.456, 95%CI: 0.282-0.737, P<0.01), bridging thrombolysis (OR=0.640, 95%CI: 0.416-0.985, P<0.05), achieving mTICI grade 3 (OR=0.554, 95%CI: 0.334-0.918, P<0.05), arterial occlusive lesion (AOL) grade 3 (OR=0.521, 95%CI: 0.326-0.834, P<0.01), and early postoperative statin therapy (OR=0.509, 95%CI: 0.273-0.948, P<0.05) were protective factors for futile recanalization after EVT in acute BAO patients. High baseline National Institutes of Health Stroke Scale (NIHSS) score (OR=1.068, 95%CI: 1.049-1.087, P<0.01), coexisting hypertension (OR=1.571, 95%CI: 1.017-2.427, P<0.05), multiple retrieval attempts (OR=1.237, 95%CI: 1.029-1.488, P<0.05) and postoperative hemorrhagic transformation (OR=8.497, 95%CI: 2.879-25.076, P<0.01) were risk factors. For trial of ORG 10172 in acute stroke treatment (TOAST) classification, cardiogenic embolism (OR=0.321, 95%CI: 0.193-0.534, P<0.01) and other types (OR=0.499, 95%CI: 0.260-0.961, P<0.05) were related to lower incidence of futile recanalization. CONCLUSIONS: The incidence of futile recanalization after EVT in patients with acute BAO is high. Bridging venous thrombolysis before operation and an early postoperative statin therapy may reduce the incidence of futile recanalization.

Association between baseline hemoglobin level and early neurological deterioration after intravenous thrombolysis in patients with acute ischemic stroke. / åŸºçº¿è¡€çº¢è›‹ç™½æ°´å¹³å¯¹æ€¥æ€§ç¼ºè¡€æ€§è„‘å’ä¸­æ‚£è€ é™è„‰æº¶æ “åŽæ—©æœŸç¥žç»åŠŸèƒ½æ¶åŒ–çš„å½±å“.

OBJECTIVES: To investigate the association between baseline hemoglobin level and early neurologic deterioration (END) after intravenous thrombolysis in patients with acute ischemic stroke (AIS). METHODS: Data of AIS patients who received intravenous thrombolytic therapy at multiple hospitals across the country between January 2017 and July 2020 were collected from the online database Acute Stroke Patients for Stroke Management Quality Evaluation (CASE-Ⅱ, NCT04487340). Binary logistic regression analysis was used to study the factors affecting the occurrence of END after intravenous thrombolytic therapy, and the correlation between baseline hemoglobin level and END was investigated by limiting cubic spline curve analysis. RESULTS: A total of 8162 patients were included. Patients with END had lower baseline hemoglobin levels (136 and 140 g/L, P<0.01) and higher rates of anemia (24.2% and 16.9%, P<0.01) compared with non-END patients. Binary logistic regression analysis showed that baseline hemoglobin level (OR=0.995, 95%CI: 0.991-0.999, P<0.05) and anemia (OR=1.238, 95%CI: 1.055-1.454, P<0.01) were independently correlated with the occurrence of END after intravenous thrombolysis in AIS patients. Restricted cubic spline regression showed that there was a U-shaped relationship between hemoglobin level and the risk of END after intravenous thrombolysis in AIS patients (P<0.01), although this relationship was only significant in male patients (P<0.05) and not in female patients (P>0.05). CONCLUSIONS: There is a correlation between baseline hemoglobin level and the risk of END in AIS patients after intravenous thrombolysis, especially in male patients, in whom both lower and higher hemoglobin level may increase the risk of END.

Effect of anesthesia mode during endovascular treatment on neurological functional outcomes in patients with acute posterior circulation stroke. / éº»é†‰æ–¹å¼å¯¹æ€¥æ€§åŽå¾ªçŽ¯è„‘å’ä¸­è¡€ç®¡å† æ²»ç–—æ‚£è€ ç¥žç»åŠŸèƒ½ç»“å±€çš„å½±å“.

OBJECTIVES: To compare the effect of anesthesia mode on the neurological functional outcomes in patients undergoing endovascular treatment for acute posterior circulation ischemic stroke. METHODS: Clinical data of 656 patients undergoing intravascular therapy for acute posterior circulation ischemic stroke registered in online Acute Stroke Patients for Stroke Management Quality Evaluation Database from January 2017 to December 2022 were retrospectively analyzed. The data included 163 cases with conscious sedation and 493 cases with general anesthesia during the procedure. After propensity score matching, 428 patients were included in the analysis, including 155 cases in the conscious sedation group and 273 cases in the general anesthesia group. The differences of operation mode, etiology type, vascular recanalization, hemorrhagic transformation at 24 h, modified Rankin Scale (mRS) score at 3 months and mortality within 3 months were compared between the two groups. Binary logistic regression was used to explore the effect of different anesthesia mode on neurological functional outcomes. RESULTS: There was a significant difference in operation mode between the two groups (P<0.01), while there were no significant differences in etiology type, vascular recanalization, hemorrhagic transformation at 24 h, mRS score at 3 months or mortality within 3 months (all P>0.05). Binary logistic regression analysis revealed that anesthesia modes were not significantly associated with functional outcomes of patients (OR=1.151, 95%CI: 0.751-1.765, P>0.05). CONCLUSIONS: Anesthesia mode (conscious sedation or general anesthesia) will not affect the neurological functional outcomes in patients with acute posterior circulation ischemic stroke undergoing endovascular treatment.

Effect of Imaging Markers on Reperfusion Therapy in Basilar Artery Occlusion.

OBJECTIVE: We aimed to investigate the effectiveness of endovascular therapy (EVT) versus intravenous thrombolysis (IVT) in patients with basilar artery occlusion (BAO), based on the information of advanced imaging. METHODS: We analyzed data of stroke patients with radiologically confirmed BAO within 24 hours. BAO subjects were categorized into "top-of-the-basilar" syndrome (TOBS) and other types. An initial infarct size of <70ml and a ratio of ischemic tissue to infarct volume of ≥1.8 was defined as "target mismatch." The primary outcome was a good outcome, defined as a modified Rankin Scale score of 0 to 3 at 3 months. Propensity score adjustment and inverse probability of treatment weighting (IPTW) propensity score methods were used. RESULTS: Among 474 BAO patients, 93 (19.6%) were treated with IVT prior to EVT, 91 (19.2%) were treated with IVT alone, 95 (20.0%) were treated with EVT alone, and 195 (41.1%) were treated with antithrombotic therapy. In IPTW analyses, we found no benefit of EVT over IVT for good outcome in either TOBS patients (odds ratio = 1.08, 95% confidence interval [CI] = 0.88-1.31) or those with other types (odds ratio = 1.13, 95% CI = 0.94-1.36). However, in patients with other types, if there existed a target mismatch, EVT was independently related to good outcome (odds ratio = 1.46, 95% CI = 1.17-1.81). INTERPRETATION: The "target mismatch profile" seems to be a possible candidate selection standard of EVT for those with other types of BAO. Future studies should separate TOBS from other types of BAO, and try to use advanced imaging. ANN NEUROL 2022;92:97-106.

Glymphatic function plays a protective role in ageing-related cognitive decline.

OBJECTIVE: The glymphatic pathway, characterised as a cerebral drainage system, influences cognitive function in neurodegenerative diseases; however, evidence is limited in a normal ageing population. The aim of this study was to investigate the effect of glymphatic function on ageing-related cognitive decline. METHODS: We retrospectively reviewed the Cognitive Impairment, Retinopathy, and Cerebrovascular Lesions in the Elderly (CIRCLE) study, and participants with multi-model magnetic resonance imaging (MRI) scans and Mini-Mental State Examinations (MMSE) were enrolled. Glymphatic function was evaluated via the diffusion tensor imaging along the perivascular space (DTI-ALPS) index. Regression models were used to estimate the impact of the DTI-ALPS index on cognitive decline cross-sectionally and longitudinally. We further analysed the mediation effect of the DTI-ALPS on age and cognitive function. RESULTS: A total of 633 participants were included in this study (48.2% female; mean age, 62.8 ± 8.9 years). The DTI-ALPS index was positively associated with cognitive function cross-sectionally (ß = 0.108, P = 0.003), and was an independent protective factor for cognitive decline longitudinally (odds ratio (OR) = 0.029, P = 0.007). The DTI-ALPS index declined progressively with ageing (r = -0.319, P <0.001), and the decrease was more pronounced after 65 years of age. Furthermore, the DTI-ALPS index mediated the relationship between age and MMSE score (ß = -0.016, P <0.001). The mediation effect accounted for 21.3%, which was higher in subjects aged over 65 years (25.3%) compared with those aged under 65 years (5.3%). CONCLUSION: Glymphatic function played a protective role in normal ageing-related cognitive decline, which may serve as a potential therapeutic target against cognitive decline in future.

Prevalent stroke, age of its onset, and post-stroke lifestyle in relation to dementia: A prospective cohort study.

INTRODUCTION: The association of age at stroke onset with dementia and the role of post-stroke lifestyle on dementia risk remains unclear. METHODS: We leveraged data of 496,251 dementia-free participants from UK Biobank and explored the relationship between age at stroke onset and incident dementia. Among 8328 participants with stroke history, we further investigated the association of a healthy lifestyle with risk of dementia. RESULTS: Participants with stroke history had a higher risk of dementia (hazard ratio [HR], 2.02). The association was stronger among participants with stroke onset at a younger age (≤50: HR, 2.63) compared with those at the age > 50 years (50-60: HR, 2.17; ≥60: HR, 1.58). Among participants with stroke history, a favorable lifestyle was associated with a lower risk of incident dementia. DISCUSSION: Stroke onset in earlier life stage predicted a higher risk for dementia, but a favorable post-stroke lifestyle may protect against dementia.

Evaluation of a multicomponent intervention to shorten thrombolytic door-to-needle time in stroke patients in China (MISSION): A cluster-randomized controlled trial.

BACKGROUND: Rapid intravenous thrombolysis (IVT) for acute ischemic stroke (AIS) is crucial for improving outcomes. However, few randomized trials of interventions aimed at reducing in-hospital delay have been carried out in China. We aimed to evaluate the effect of a multicomponent intervention on thrombolytic door-to-needle time (DNT) of AIS patients via video teleconference based on the Behavior Change Wheel (BCW) method. METHODS AND FINDINGS: This cluster-randomized trial, conducted between January 1, 2019 and December 31, 2019, randomly allocated 22 hospitals equally to PEITEM (Persuasion Environment reconstruction Incentivization Training Education Modeling) intervention or routine care plus stroke registry and subsequently enrolled 1,634 AIS patients receiving IVT within 4.5 hours upon stroke onset from participant hospitals. The PEITEM group received a 1-year PEITEM 6-component intervention based on the behavioral theory monthly via video teleconference. The primary outcome was the proportion of patients with a DNT of 60 minutes or less. A total of 987 patients participated in the PEITEM group (mean age, 69 years; female, 411 [41.6%]) and 647 patients in the control group (mean age, 70 years; female, 238 [36.8%]). Of all participants, the proportion of DNT ≤60 minutes in the PEITEM group was higher than in the control group (82.0% versus 73.3%; adjusted odds ratio, 1.77; 95% confidence interval (CI), 1.17 to 2.70; ICC, 0.04; P = 0.007). Among secondary outcomes, the average DNT was 43 minutes in the PEITEM group and 50 minutes in the control group (adjusted mean difference: -8.83; 95% CI, -14.03 to -3.64; ICC, 0.12; P = 0.001). Favorable functional outcome (score of 0 to 1 on the modified Rankin scale (mRS)) was achieved in 55.6% patients of the PEITEM group and 50.4% of the control group (adjusted odds ratio, 1.38; 95% CI, 1.00 to 1.90; ICC, 0.01; P = 0.049). Main study limitations include non-blinding of clinicians, and that specific interventions component responsible for the observed changes could not be determined. CONCLUSIONS: The teleconference-delivered PEITEM intervention resulted in a moderate but clinically relevant shorter DNT and better functional outcome in AIS patients receiving IVT. TRIAL REGISTRATION: Clinicaltrials.gov NCT03317639.

Stroke outcome of early antiplatelet in post-thrombolysis haemorrhagic infarction.

BACKGROUND AND PURPOSE: Initiation of early antiplatelet (EA) therapy after acute ischaemic stroke (AIS) is essential. We aimed to investigate the safety and effectiveness of EA therapy in patients who had an AIS with haemorrhagic infarction (HI) after intravenous thrombolysis (IVT). METHODS: Based on a multicentre stroke registry database, patients who had an AIS with post-thrombolysis HI at 24 hours were identified. EA users and non-EA users were defined as patients with HI who received or did not receive antiplatelet therapy between 24 and 48 hours after IVT. Primary outcome was favourable outcome defined as modified Rankin Scale scores 0-2 at 3 months. Secondary outcomes were early neurological deterioration (END) and haemorrhagic transformation expansion. RESULTS: A total of 842 patients with HI were identified from 24 061 thrombolytic patients within 4.5 hours, and 341 (40.5%) received EA therapy. EA users were more likely to have a favourable outcome (55.7% vs 39.5%, OR 1.565; 95% CI 1.122 to 2.182; p=0.008) and lower rate of END (12.6% vs 21.4%, OR 0.585; 95% CI 0.391 to 0.875; p=0.009) compared with non-EA users. EA therapy was not associated with haemorrhagic transformation expansion (p=0.125). After propensity score matching, EA therapy was still independently associated with favourable outcome (54.3% vs 46.3%, OR 1.495; 95% CI 1.031 to 2.167; p=0.038) and lower risk of END (13.5% vs 21.2%, OR 0.544; 95% CI 0.350 to 0.845; p=0.007). CONCLUSIONS: Antiplatelet therapy can be safely used between 24 and 48 hours when HI occurs after IVT, and such therapy is associated with reduced risk of END and improved neurological outcome in patients who had an AIS.

Early NT-ProBNP (N-Terminal Probrain Natriuretic Peptide) Elevation Predicts Malignant Edema and Death After Reperfusion Therapy in Acute Ischemic Stroke Patients.

BACKGROUND AND PURPOSE: We aimed to investigate the relationship between early NT-proBNP (N-terminal probrain natriuretic peptide) and all-cause death in patients receiving reperfusion therapy, including intravenous thrombolysis and endovascular thrombectomy (EVT). METHODS: This study included 1039 acute ischemic stroke patients with early NT-proBNP data at 2 hours after the beginning of alteplase infusion for those with intravenous thrombolysis only or immediately at the end of EVT for those with EVT. We performed natural log transformation for NT-proBNP (Ln(NT-proBNP)). Malignant brain edema was ascertained by using the SITS-MOST (Safe Implementation of Thrombolysis in Stroke-Monitoring Study) criteria. RESULTS: Median serum NT-proBNP level was 349 pg/mL (interquartile range, 89-1250 pg/mL). One hundred twenty-one (11.6%) patients died. Malignant edema was observed in 78 (7.5%) patients. Ln(NT-proBNP) was independently associated with 3-month mortality in patients with intravenous thrombolysis only (odds ratio, 1.465 [95% CI, 1.169-1.836]; P=0.001) and in those receiving EVT (odds ratio, 1.563 [95% CI, 1.139-2.145]; P=0.006). The elevation of Ln(NT-proBNP) was also independently associated with malignant edema in patients with intravenous thrombolysis only (odds ratio, 1.334 [95% CI, 1.020-1.745]; P=0.036), and in those with EVT (odds ratio, 1.455 [95% CI, 1.057-2.003]; P=0.022). CONCLUSIONS: An early increase in NT-proBNP levels was related to malignant edema and stroke mortality after reperfusion therapy.

miR-33 and RIP140 participate in LPS-induced acute lung injury

Background/aim: Pulmonary microvascular endothelial cells (PMVECs) play a pivotal role in the process of acute lung injury (ALI), which can be induced by lipopolysaccharide (LPS). Numerous reports have indicated that both miR-33 and RIP140 are involved in the inflammatory response in macrophages. In this study, we sought to investigate whether miR-33 and RIP140 participate in ALI induced by LPS. Materials and methods: First, we isolated and identified PMVECs from BALB/c mice. Subsequently, both PMVECs and BALB/c mice were treated with PBS, LPS, or pyrrolidine dithiocarbamate (PDTC) plus LPS and divided into three groups: control (PBS), LPS (LPS), and L+P (LPS plus PDTC) groups. We assessed pathology by hematoxylin and eosin staining, and miR-33 and RIP140 expression levels were examined using quantitative PCR and Western blot analyses. Results: Our results demonstrated that LPS can induce PMVEC injury and ALI and that LPS treatment significantly decreased miR-33 expression compared with controls (P < 0.001, n = 5). On the contrary, RIP140 was markedly overexpressed by LPS treatment (P < 0.001, n = 5). However, this alteration can be inhibited by pretreatment with PDTC before LPS (P < 0.05, n = 5). Conclusion: This study is the first to confirm that both miR-33 and RIP140 participate in LPS-induced PMVEC injury and ALI, which may help uncover the mechanism of ALI

[Effects of emergency medical service on prognosis of ischemic stroke patients treated with intravenous thrombolysis].

OBJECTIVE: To investigate the effect of emergency medical service (EMS) on the prognosis of ischemic stroke patients treated with intravenous thrombolysis. METHODS: Clinical data of 2123 ischemic stroke patients treated with intravenous thrombolysis in 70 hospitals in Zhejiang province were retrospectively analyzed. There were 808 patients sent to the hospital by ambulance (EMS group) and 1315 patients by other transportations (non-EMS group). Good outcome was defined as modified Rankin Scale (mRS) ≤ 2 at 3-month. The onset to needle time (ONT), onset to door time (ODT), door to needle time (DNT) and outcome were compared between EMS group and non-EMS group. Binary logistic regression was used to explore the influencing factors for the outcome at 3-month. RESULTS: Compared with the non-EMS group, patients in the EMS group were older, with higher baseline National Institute of Health Sroke Scale (NIHSS) score, and had a higher proportion of atrial fibrillation (all P<0.05), but there were no significant differences in ONT, ODT and DNT between two groups (all P>0.05). Binary logistic regression showed that EMS was not independently associated with good outcome (OR=0.856, 95%CI:0.664-1.103, P>0.05). CONCLUSIONS: EMS had not improve the outcome of patients receiving intravenous thrombolysis in Zhejiang province.

Association of Atrial Fibrillation with Remote Intracerebral Hemorrhage After Intravenous Thrombolysis: Results from a Multicenter Study in China.

INTRODUCTION: This study aimed to investigate the association between atrial fibrillation (AF), particularly newly diagnosed AF, and remote intracerebral hemorrhage (rICH) in patients with ischemic stroke who were treated with intravenous thrombolysis (IVT). METHODS: This observational study was conducted on patients with ischemic stroke who received IVT with recombinant tissue-type plasminogen activator. The data were taken from a multicenter prospective registry of a Chinese population. rICH was defined as any extraischemic hemorrhage detected on computerized tomography (CT) 24 h after intravenous thrombolysis. We collected and compared the demographic data and clinical characteristics of all the patients with rICH to those of patients without any type of hemorrhagic transformation. The association between AF and rICH was analyzed using univariate analysis and binary logistic regression. RESULTS: A total of 20,697 patients were included in the study, with 1566 (7.6%) experiencing intracerebral hemorrhage (ICH), 586 (2.8%) experiencing rICH, and 19,131 (92.4%) not experiencing any form of hemorrhagic transformation. Univariate analysis revealed significant differences in age, pre-thrombolysis systolic blood pressure, baseline National Institute of Health Stroke Scale score, previously known AF, newly diagnosed AF, coronary heart disease, congestive heart failure, hyperhomocysteinemia, and history of thrombolysis between the rICH and control groups (P < 0.05). Further multivariate logistic regression analysis indicated that total AF (OR 1.821, 95% CI 1.082-3.065, P < 0.05), previously known AF (OR 1.470, 95% CI 1.170-1.847), and newly diagnosed AF (OR 1.920, 95% CI 1.304-2.825) were independently associated with rICH. CONCLUSIONS: This study suggests that AF, regardless of whether it is newly diagnosed or previously known, may be associated with the occurrence of rICH following intravenous thrombolysis. Interestingly, our findings suggest that newly diagnosed AF may have a stronger impact on rICH than previously known AF, although confirmation from more studies is needed.

The Association of Allergy-Related and Non-Allergy-Related Olfactory Impairment with Cognitive Function in Older Adults: Two Cross- Sectional Studies.

BACKGROUND: Evidence on the association of Olfactory Impairment (OI) with age-related cognitive decline is inconclusive, and the potential influence of allergy remains unclear. OBJECTIVE: We aimed to evaluate the cross-sectional associations of allergy-related and non-allergy- related OI to cognitive function. METHODS: We included 2,499 participants from the Health and Retirement Study (HRS)-Harmonized Cognitive Assessment Protocol (HCAP) sub-study and 1,086 participants from the English Longitudinal Study of Ageing (ELSA)-HCAP. The Olfactory Function Field Exam (OFFE) using Sniffin' Stick odor pens was used to objectively assess olfactory function and an olfactory score <6/11 indicated OI. Mini-Mental Status Examination (MMSE) was used to assess global cognitive function and define cognitive impairment (<24/30). A neuropsychologic battery was used to assess five cognitive domains. RESULTS: Compared to non-OI participants, individuals with OI had lower MMSE z-score [ßHRS = -0.33, 95% Confidence Interval (CI): -0.41 to -0.24; ßELSA = -0.31, -0.43 to -0.18] and higher prevalence of cognitive impairment (Prevalence Ratio (PR)HRS = 1.46, 1.06 to 2.01; PRELSA = 1.63, 1.26 to 2.11). The associations were stronger for non-allergy-related OI (ßHRS = -0.36; ßELSA = -0.34) than for allergy-related OI (ßHRS = -0.26; ßELSA = 0.13). Similar associations were observed with domain- specific cognitive function measures. CONCLUSION: OI, particularly non-allergy-related OI, was related to poorer cognitive function in older adults. Although the current cross-sectional study is subject to several limitations, such as reverse causality and residual confounding, the findings will provide insights into the OI-cognition association and enlighten future attention to non-allergy-related OI for the prevention of potential cognitive impairment.

Safety of Antiplatelet Therapy in Noncardioembolic Ischemic Stroke With Thrombocytopenia: The CASE II Study.

BACKGROUND: There is scant evidence regarding the safety of antiplatelet therapy in acute ischemic stroke (AIS) patients with thrombocytopenia. Our study aims to address this concern by examining AIS patients with thrombocytopenia from a large database in real-world settings. METHODS AND RESULTS: We included patients with AIS with a platelet count <100×109/L who had complete records of antiplatelet drug use. Those requiring anticoagulation or having contraindications to antiplatelet therapy were excluded. Short-term safety outcomes were in-hospital bleeding events, while the long-term safety outcome was 1-year all-cause mortality. A good clinical outcome was defined as functional independence, indicated by a modified Rankin Scale score of 0 to 2 at discharge. Propensity score matched analyses were used. We screened 169 423 patients with AIS from 90 stroke centers in the CASE II register, ultimately enrolling 2808 noncardioembolic patients with thrombocytopenia. In the propensity score matched analyses, no significant difference was observed between the antiplatelet and nonantiplatelet groups in terms of intracranial hemorrhage (odds ratio=0.855 [95% CI, 0.284-5.478]; P=0.160) or gastrointestinal bleeding (odds ratio=2.034 [95% CI, 0.755-5.478]; P=0.160). Antiplatelet therapy was associated with improved functional outcomes at discharge (odds ratio=1.405 [95% CI, 1.028-1.920]; P=0.033), and showed a trend towards reducing 1-year mortality (odds ratio=0.395 [95% CI, 0.152-1.031]; P=0.058). CONCLUSIONS: The use of antiplatelet therapy lessened as platelet count decreased in patients with AIS with thrombocytopenia. However, our findings suggest that antiplatelet medications remain safe and effective for this population.

Efficacy and safety of Ginkgolide with intravenous alteplase thrombolysis in acute ischemic stroke with large vessel occlusion: a subgroup analysis of GIANT.

Aim: This study aims to explore the effectiveness and safety of Ginkgolide® in acute ischemic stroke (AIS) patients with large vessel occlusion (LVO) and moderate-to-severe stroke receiving intravenous alteplase thrombolysis (IVT). Methods: Ginkgolide with Intravenous Alteplase Thrombolysis in Acute Ischemic Stroke Improving Neurological Function (GIANT) was an open-label, prospective, multicenter, cluster-randomized clinical trial and included AIS patients in 24 centers randomized to the intervention of intravenous Ginkgolide® or control group within the first 24 h after IVT. LVO was defined as any occlusion of the internal carotid artery, M1 or M2 of the middle cerebral artery, A1 or A2 of the anterior cerebral artery, P1 of the posterior cerebral artery, and V4 of the vertebral artery or the basilar artery. Stroke severity was assessed with the National Institutes of Health Stroke Scale (minor ≤5; moderate-to-severe >5). The primary outcome was a good outcome, defined as a modified Rankin Scale (mRS) score of 0-2 at 90 days. Secondary outcomes were early neurological improvement (ENI), defined as ≥18% increase in the National Institutes of Health Stroke Scale (NIHSS) score at 7 days compared to baseline and distribution of mRS at 3 months. Results: A total of 1,113 patients were included, with 268/913 (29.4%) presenting LVO and 508 (45.6%) presenting moderate-to-severe stroke. In patients with LVO, Ginkgolide® usage was independently associated with ENI (P = 0.001) but not with a good outcome (P = 0.154). In the moderate-to-severe stroke subgroup, Ginkgolide® was independently associated with both a good outcome (P = 0.009) and ENI (P = 0.028). Ginkgolide® did not increase the risk of hemorrhagic transformation (all P > 0.05). Conclusion: Using Ginkgolide® within 24-h after intravenous rt-PA is effective and safe in LVO and moderate-to-severe stroke patients.

Argatroban in Patients With Acute Ischemic Stroke With Early Neurological Deterioration: A Randomized Clinical Trial.

Importance: The effect of argatroban in patients with acute ischemic stroke (AIS) and early neurological deterioration (END) is unknown. Objective: To assess the efficacy of argatroban for END in AIS. Design, Setting, and Participants: This open-label, blinded-end point, randomized clinical trial was conducted from April 4, 2020, through July 31, 2022. The date of final follow-up was October 31, 2022. This was a multicenter trial. Eligible patients were adults with AIS who experienced END, which was defined as an increase of 2 or more points on the National Institutes of Health Stroke Scale within 48 hours from symptom onset. Patients who withdrew consent, experienced duplicate randomization, or were lost to follow-up were excluded from the study. Interventions: Patients were randomly assigned to the argatroban group and control group within 48 hours of symptom onset. Both groups received standard therapy based on guidelines, including oral mono or dual antiplatelet therapy. The argatroban group received intravenous argatroban for 7 days (continuous infusion at a dose of 60 mg per day for 2 days, followed by 20 mg per day for 5 days) in addition to standard therapy. Main Outcome and Measure: The primary end point was good functional outcome at 90 days, defined as a modified Rankin Scale score of 0 to 3. Results: A total of 628 patients (mean [SD] age, 65 [11.9] years; 400 male [63.7%]) were included in this study (argatroban group, 314 [50%] and control group, 314 [50%]). Of these, 18 withdrew consent, 1 had duplicate randomization, and 8 were lost to follow-up. A total of 601 patients with stroke were included in the intention-to-treat analysis. Finally, 564 patients were included in the per-protocol analysis as 6 participants in the argatroban group and 31 participants in the control group did not follow the complete protocol. The number of patients with good functional outcome at 90 days was 240 (80.5%) in the argatroban group and 222 (73.3%) in the control group (risk difference, 7.2%; 95% CI, 0.6%-14.0%; risk ratio, 1.10; 95% CI, 1.01-1.20; P = .04). The proportion of symptomatic intracranial hemorrhage was 3 of 317 (0.9%) in the argatroban group and 2 of 272 (0.7%) in the control group (P = .78). Conclusions and Relevance: Among patients with AIS with END, treatment with argatroban and antiplatelet therapy resulted in a better functional outcome at 90 days. This trial provided evidence to support the use of argatroban in reducing disability for patients with END. Trial Registration: ClinicalTrials.gov Identifier: NCT04275180.

Multiple Sensory Impairments in Relation to Cognitive Function: Two Nationwide Cross-sectional Studies.

INTRODUCTION: Sensory impairments (SIs, including visual, hearing, olfactory, and taste impairments) have been individually associated with age-related cognitive function. Little is known regarding their combined associations with cognitive function. METHODS: We included 2,931 participants (mean age of 69.1 years) from the National Health and Nutrition Examination Survey (NHANES, 2011-2014) and 10,785 participants (mean age of 70.2 years) from the National Health Interview Survey (NHIS, 2021). Status of visual, hearing, olfactory, and taste functions were self-reported in structured questionnaires. In NHANES, cognitive function was objectively measured by a battery of tests, including memory, verbal fluency, and processing speed. NHIS participants answered a single question about subjective cognitive complaints (SCC). We used regression models to assess the relation of the total number and the individual sensory impairments to z-scores of cognitive domains (linear regression) in NHANES and to SCC (logistic regression) in NHIS. RESULTS: A larger number of SI was related to poorer domain-specific cognitive function (all Ptrend <0.05), including memory (beta each additional SI = -0.12, 95% confidence interval: -0.17 to -0.08), verbal fluency (-0.05, -0.10 to -0.01), and processing speed (-0.13, -0.16 to -0.09). In NHIS, each additional SI was related to 96% higher odds of SCC. We also observed independent associations of sensory impairments (except olfactory impairment) with specific cognitive domains. In addition, each individual SI was associated with higher odds of SCC (the odds ratios ranged from 1.30 to 1.78). CONCLUSION: A larger number of SI was related to worse cognitive function and higher odds of SCC.