Extended Time Window Research Articles

Dynamical arrest transition of a bidisperse two-patchy colloidal dispersion: A dynamic Monte Carlo study.

During the last few years, patchy colloidal dispersions have emerged as ideal candidates of glass-formers of systems composed of particles that interact with non-isotropic potentials. However, from the computational point of view, the characterization of their dynamical properties close to the glass transition via any kind of molecular dynamics simulation technique can be very difficult due to the slowing down of both the rotational and translational dynamics. Although a plethora of dynamical techniques have been developed to account for the dynamics of patchy colloids, new and complementary simulation techniques are required to explore, much faster and more efficiently, the dynamical arrest transition of patchy colloidal dispersions when computer simulation consists of a large number of particles and, due to the slow particle dynamics at the glass transition, an extended time window is explicitly required. Then, in this contribution, by means of the so-called dynamic-Monte Carlo method, we report on the dynamical arrest transition, both rotational and translational, of a bidisperse patchy colloidal dispersion, following three different paths along the density-temperature plane, including high densities and low temperatures. Although this method has not been extensively tested at extreme thermodynamic conditions, we show that even at the dynamical arrest transition, it allows us to extract good dynamical data from a complex system. Therefore, it turns out to be a promising technique to explore the onset of vitrification of anisotropic colloidal particles.

Abstract WP26: Effectiveness of Tenecteplase versus Alteplase in Acute Ischemic Stroke Selected Subgroups of a Real-World-Data Set

Introduction: Tenecteplase is increasingly utilized as an alternative acute ischemic stroke (AIS) thrombolytic to Alteplase (tPA). Although many larger AIS trials have demonstrated the non-inferiority of TNK, Real World Data in many specific subgroups continue to be lacking. We studied the comparative effectiveness of AIS thrombolysis with TNK to tPA at our institution, focusing on currently understudied cohorts. Methods: We conducted a retrospective cohort analysis of AIS patients treated with thrombolysis within our health system. We utilized the Get With the Guidelines (GWTG) database to obtain basic demographic data. Additional variables and key outcomes (functional and radiographic) were abstracted independently by two authors from the electronic record. Disagreements were resolved by mutual consensus or a third investigator. An ordinal logistic regression model was used to assess the interventions' effectiveness, with the outcome being the modified Rankin Scale (mRS) score 90 days post-stroke. Subgroups included Age (<60, 61-80, >80), location of vessel occlusion (Large or Medium vessel), thrombolysis in the extended time window (beyond 4.5 hours), treatment via telestroke, and thrombectomy. Results: There were 500 consecutive AIS patients with complete outcome data. The mean age of the participants was 70.1 years, with 52.7% of patients being male. In the adjusted ordinal logistic regression analysis, the TNK group presented with 1.00 odds of a worse mRS score than the tPA group (95% CI 0.57-1.74). Subgroup regression analysis demonstrated no heterogeneity in effect size. Figure 1 is a Forest Plot demonstrating the Odds Ratio for each subgroup. Conclusions: It’s well-published that TNK is a comparable treatment for AIS and has demonstrated advantages. This analysis compared specific subgroups of real-world patients and showed no heterogeneity. This real-world subgroup analysis adds to the literature supporting the use of TNK for the treatment of AIS.

CHinese Acute Tissue-Based Imaging Selection for Lysis In Stroke Tenecteplase II (CHABLIS-T II): rationale and design

Background and purposeTenecteplase (TNK) has demonstrated non-inferiority to alteplase in patients who had an acute ischaemic stroke presenting within 4.5 hours from symptom onset. The trial is aimed to explore...

Abstract 86: Outcomes of Endovascular Therapy for Late Large Vessel Occlusion in Patients With Pre-Stroke Disability

Background: There is a paucity of research to develop evidence-based recommendations for endovascular management in the extended time window (>6 hours after time last seen well [TLSW]) for large vessel occlusion (LVO) patients with pre-stroke disability. Methods: We analyzed data from a multinational cohort (66 sites, 10 countries from 2014 to 2022) of acute ischemic stroke patients with pre-stroke modified Rankin Scale (mRS) 0-4 and anterior or posterior circulation LVO who received endovascular therapy 6-24 hours after TLSW. The primary outcome was the composite of functional independence (FI, mRS 0-2) or return to pre-stroke mRS (return of Rankin, RoR) at 90 days. Outcomes were compared between patients with pre-stroke disability (pre-stroke mRS 2-4) vs those without (mRS 0-1). Results: There were 2231 patients (median age 77 years; median NIH Stroke Scale 16) included in the present study, of whom 564 (25.3%) had pre-stroke disability. The primary outcome (FI or ROR) was seen in 30.7% of patients with pre-stroke disability (FI, 16.5%; RoR 30.7%), compared with 44.1% of those without (FI, 44.1%; RoR 13.0%) ( P <0.0001, Figure 1 ). In both multivariable logistic regression and inverse probability of treatment weighting analysis, pre-stroke disability was not associated with a lower odds of achieving FI or RoR (adjusted odds ratio [aOR] 0.76, 95% confidence interval [CI] 0.50-1.15 and aOR 0.73, 95% CI 0.43-1.25, respectively). FI or ROR was achieved at a higher percentage with reperfusion with mTICI ≥2b than with mTICI 0-2a, both in patients with pre-stroke disability (34.8% vs 10.8%, P <0.0001) and in those without (49.2% vs 12.1%, P <0.0001). Symptomatic intracranial hemorrhage occurred in 6.3% in both groups ( P =0.995). Conclusions: A substantial proportion of late LVO patients with pre-stroke disability regained pre-stroke mRS after EVT and did not have a worse functional prognosis than patients without pre-stroke disability when their pre-stroke mRS was considered.

Tenecteplase thrombolysis for stroke up to 24 hours after onset with perfusion imaging selection: the umbrella phase IIa CHABLIS-T randomised clinical trial

BackgroundThe performance of intravenous tenecteplase in patients who had an acute ischaemic stroke with large/medium vessel occlusion or severe stenosis in an extended time window remains unknown. We investigated the...

The effect of auditory training on listening effort in hearing-aid users: insights from a pupillometry study

Objective The study investigated how auditory training affects effort exerted by hearing-impaired listeners in speech-in-noise task. Design Pupillometry was used to characterise listening effort during a hearing in noise test (HINT) before and after phoneme-in-noise identification training. Half of the study participants completed the training, while the other half formed an active control group. Study sample Twenty 63-to-79 years old experienced hearing-aid users. Results Higher peak pupil dilations (PPDs) were obtained at the end of the study compared to the beginning in both groups of the participants. The analysis of pupil dilation in an extended time window revealed, however, that the magnitude of pupillary response increased more in the training than in the control group. The effect of training on effort was observed in pupil responses even when no improvement in HINT was found. Conclusion The results demonstrate that using a listening effort metric adds additional insights into the effectiveness of auditory training compared to the situation when only speech-in-noise performance is considered. Trends observed in pupil responses suggested increased effort—both after the training and the placebo intervention—most likely reflecting the effect of the individual’s motivation.

Tenecteplase for the treatment of acute ischemic stroke in the extended time window: a systematic review and meta-analysis.

Outcome data regarding the administration of tenecteplase (TNK) to acute ischemic stroke (AIS) patients presenting in the extended time window are limited. We aimed to assess the current evidence regarding the efficacy and safety of TNK at a dose of 0.25 mg/kg for AIS treatment in the extended time window. A systematic review and meta-analysis was conducted including all available randomized-controlled clinical trials (RCTs) that compared TNK 0.25 mg/kg versus no thrombolysis in AIS patients presenting in the extended time window (>4.5 h after last-seen-well or witnessed onset). Eligible studies were identified by searching Medline, Scopus, and international conference abstracts. The predefined efficacy outcomes of interest were 3-month excellent functional outcome [defined as the modified Rankin Scale (mRS) score ⩽1; primary outcome], 3-month good functional outcome (mRS ⩽ 2), 3-month reduced disability (⩾1-point reduction across all mRS scores). We determined symptomatic intracranial hemorrhage (sICH), any ICH and 3-month mortality as safety endpoints. A random-effects model was used to calculate risk ratios (RRs) and common odds ratios (cORs) with corresponding 95% confidence intervals (CIs). Three RCTs were included comprising 556 patients treated with TNK versus 560 controls. TNK 0.25 mg/kg was associated with a higher likelihood of 3-month excellent functional outcome compared to controls (RR = 1.17; 95% CI = 1.01-1.36; I2 = 0%), whereas there was no difference regarding good functional outcome (RR = 1.05; 95% CI = 0.94-1.17; I2 = 0%) and reduced disability (adjusted cOR = 1.14; 95% CI = 0.92-1.40; I2 = 0%) at 3 months. The risks of sICH (RR = 1.67; 95% CI = 0.70-4.00; I2 = 0%), any ICH (RR = 1.08; 95% CI = 0.90-1.29; I2 = 0%) and 3-month mortality (RR = 1.10; 95% CI = 0.81-1.49; I2 = 0%) were similar between the groups. Based on data from three RCTs showing increased efficacy and a favorable safety profile of TNK in the treatment of AIS in the extended time window, continuing efforts of ongoing RCTs in the field are clearly supported. PROSPERO registration ID: CRD42023448707.

Extended Time Window (>6 Hour) Mechanical Thrombectomy; Good Clinical Outcome in the Younger Age Population in Thrombectomy Cases: Relationship between Age and Prognosis.

Mechanical thrombectomy (MT) has become increasingly common in recent years, as studies have shown that it can be an effective treatment for acute ischemic stroke (AIS) caused by large vessel occlusion (LVO). However, the efficacy of MT in the extended time window (6 to 24 h) is still uncertain. Our study aims to evaluate the outcomes of MT in the extended time window for AIS patients. We reviewed data on AIS patients who received MT beyond six hours of stroke onset from 2015 to 2022. The patients' occlusions were in the internal carotid artery (ICA), middle cerebral artery (MCA), or posterior circulation. Our evaluation included the modified Rankin scale (mRS) and 90-day mortality rates, as well as complications, such as symptomatic intracranial hemorrhage (sICH). Thirty-one patients were included in this study, with a mean age of 75.6 ± 15.1 years, of whom 54.8% were male. The median NIHSS score at presentation was 17. Successful recanalization (TICI 2b to 3) was achieved in 90.3% of patients and the rate of sICH was 6.4%. No difference was observed between the two age groups. The younger age group (<80 years old) showed a better clinical outcome (mRS 0-2; p < 0.05, Fisher's exact test) compared with the older age group. The overall mortality rate was 6.4%. Our study shows that (MT) can be performed effectively and safely within an extended time window, resulting in satisfactory functional outcomes, particularly in the younger age group.

Efficacy of Urinary Kallidinogenase Plus Intravenous Recombinant Tissue Plasminogen Activator for Stroke Patients With Extended Window: A Retrospective Analysis.

To assess the outcome of human urinary kallidinogenase (HUK) plus recombinant tissue plasminogen activator (rT-PA) intravenous thrombolysis for stroke patients with an extended time window(4.5 to 9 h). A total of 92 acute ischemic stroke patients who fulfilled the criteria were included in this study. All patients received basic treatment and intravenous rT-PA, and 49 patients received additional injections of HUK (HUK group) once a day for 14 consecutive days. Outcomes were indicated by the thrombolysis in cerebral infarction score as the primary endpoint and the National Institute of Health Stroke Scale, modified Rankin Scale, and Barthel Index as the secondary endpoints. The safety outcomes were the rate of symptomatic intracranial hemorrhage, bleeding, angioedema, and mortality. The National Institute of Health Stroke Scale scores were significantly lower in the HUK group at hospital discharge (4.55 ± 3.78 vs 7.88 ± 7.31, P = 0.009) and day 90 (4.04 ± 3.51 vs 8.12 ± 9.53, P = 0.011). The improvements in the Barthel Index scores were more obvious in the HUK group. Patients in the HUK group achieved favorable functional independence (67.35% vs 46.51%; odds ratio: 2.37; 95% CI: 1.01-5.53) at 90 days. The recanalization rate of the HUK group was 64.10%, whereas that was 41.48% in the control group (P = 0.050). The complete reperfusion rates were 42.9% and 23.3% in the HUK group and the control group, respectively. No significant differences were observed for adverse events between the two groups. Combination therapy of HUK plus rT-PA in patients with acute ischemic stroke with an extended time window can safely improve their functional outcomes.

Abstract 232: Endovascular Thrombectomy for Distal Vessel Occlusions in Early vs Extended Time Window

Introduction There has been a growing body of literature in recent years suggesting the safety and efficacy of endovascular thrombectomy (EVT) in patients with acute ischemic stroke (AIS) from distal vessel occlusion (DVO). Limited data is available regarding the risks and benefits of EVT in this patient population, especially when comparing the early window (6 hours from LKW) to the extended window (6‐24 hours from LKW). We aim to study this further. Methods We queried our stroke registry, a prospectively maintained database of AIS patients who presented from December 2014 to July 2023, and isolated patients with DVO who underwent EVT. DVO was defined as M2, M3, M4 occlusion, ACA occlusion, and/or PCA occlusion. We then further subdivided this into two groups, patients within the early window, and patients within the extended window. We compared characteristics between these groups using univariate analysis. We additionally performed a multivariable logistic regression analysis adjusted for Alberta Stroke Program Early CT Score (ASPECTS), National Institutes of Health Stroke Scale (NIHSS) score, age, sex, and use of intravenous (IV) thrombolysis to investigate whether or not extended window thrombectomy was associated with worse outcome. Our primary outcomes were modified Rankin Score (mRS) at discharge and at 90 days. Results Total of 290 patients had DVO and underwent EVT. Of these, 214 had all relevant data. 147 (68.7%) underwent EVT in the early window and 67 (31.3%) received EVT in the extended window. Mean age was 72.3 (±14.4). There were more women in the extended window 51.5% vs 44.8% (χ² = 20.57, p‐value &lt; 0.001). No significant difference was observed in the average NIHSS between early (13.7) and extended (13.9) windows (t=‐0.44, p=0.66). Similarly, the median ASPECTS score was comparable between early (9.3) and extended (9.0) windows (t=1.41, p=0.16). As expected, there was a striking difference seen in patients receiving IV thrombolysis between early (54.5%) and extended (4.5%) windows (χ²=48.48, p&lt;0.001). Post‐operative hematoma also was not different between the early (23.8%) and extended (14.9%) windows (χ² = 0.69, p‐value = 0.40). Symptomatic intracerebral hemorrhage (SICH) was only seen in 3.4% of patient in the early window and 2.9% of patients in extended window. No significant difference was found in the mRS at discharge (early: 3.1, extended: 3.4, t=‐0.90, p=0.37) or at 90 days (early: 3.1, extended: 3.5, t=‐1.08, p=0.29). Additionally, in our multivariable logistic regression model, receiving EVT in the extended window didn't significantly affect the discharge mRS (β=0.10, p=0.27) or the 90 day mRS (β=‐0.15, p=0.38). In this model, increasing age, lower ASPECTS score, and higher admission NIHSS predicted a higher discharge mRS, while IV thrombolysis was linked to a lower discharge mRS. Higher admission NIHSS was associated with a higher mRS at both discharge and 90 days. Conclusion In our study, outcome of EVT in the extended time window in patients with DVO was comparable to EVT outcome in early window, with no increased hemorrhagic complications. More studies are required to further understand the risks and benefits of EVT in patients with DVO stroke

Noncontrast versus perfusion CT to select endovascular therapy in an extended time window: Systematic review/meta-analysis.

The effect of noncontrast CT (NCCT) on the eligibility for endovascular therapy (EVT) in an extended time window remains to be elucidated. We sought to assess the efficacy and safety of NCCT in comparison with CT perfusion (CTP) in selecting patients with acute ischemic stroke (AIS) for EVT 6-24hours after onset. PubMed, Embase, and Cochrane libraries were searched from inception to August 31, 2022, to identify all studies reporting 90-day outcomes of EVT in patients with AIS in an extended time window. A meta-analysis was performed for the pooled risk ratio (RR) with 95% confidence interval (CI) using a random-effects model. The primary outcome used to assess efficacy was good functional independence, defined as a modified Rankin Scale score of 0-2 at 90days. Secondary outcomes included successful reperfusion, symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We included four nonrandomized studies with a total of 2685 patients. The outcomes of good functional independence at 90days (RR=0.98; 95% CI: 0.88-1.07; I2 =0%; p=.62), successful reperfusion (RR=0.98; 95% CI: 0.93-1.03; I2 =50.5%; p=.11), sICH (RR=1.11; 95% CI: 0.55-2.21; I2 =49.4%; p=.12), or mortality at 90days (RR=1.18; 95% CI: 0.99-1.40; I2 =0%; p=.42) did not differ significantly between the two groups. These findings suggest that NCCT is as effective as CTP in selecting patients for EVT in an extended time window.

ASPECTS evolution after endovascular successful reperfusion in the early and extended time window.

The Alberta Stroke Program Early CT scan Score (ASPECTS) is a reliable imaging biomarker of infarct extent on admission but the value of 24-hour ASPECTS evolution in day-to-day practice is not well studied, especially after successful reperfusion. We aimed to assess the association between ASPECTS evolution after successful reperfusion with functional and safety outcomes, as well as to identify the predictors of ASPECTS evolution. We used data from an ongoing prospective multicenter registry. Stroke patients with anterior circulation large vessel occlusion treated with endovascular therapy (EVT) and achieved successful reperfusion (modified thrombolysis in cerebral ischemia (mTICI) 2b-3) were included. ASPECTS evolution was defined as one or more point decrease in ASPECTS at 24 hours. A total of 2366 patients were enrolled. In a fully adjusted model, ASPECTS evolution was associated with lower odds of favorable outcome (modified Rankin Scale (mRS) score 0-2) at 90 days (adjusted odds ratio (aOR) = 0.46; 95% confidence interval (CI) = 0.37-0.57). In addition, ASPECTS evolution was a predictor of excellent outcome (90-day mRS 0-1) (aOR = 0.52; 95% CI = 0.49-0.57), early neurological improvement (aOR = 0.42; 95% CI = 0.35-0.51), and parenchymal hemorrhage (aOR = 2.64; 95% CI, 2.03-3.44). Stroke severity, admission ASPECTS, total number of passes, complete reperfusion (mTICI 3 vs. mTICI 2b-2c) and good collaterals emerged as predictors of ASPECTS evolution. ASPECTS evolution is a strong predictor of functional and safety outcomes after successful endovascular therapy. Higher number of EVT attempts and incomplete reperfusion are associated with ASPECTS evolution at day 1.

Investigating Neurologic Improvement After IV Thrombolysis: The Effect of Time From Stroke Onset vs Imaging-Based Tissue Clock.

Time from stroke onset is associated with clinical response to intravenous thrombolysis (IVT) with alteplase and is therefore used to select patients for treatment. Alternatively, neuroimaging may be used for treatment in the uncertain or extended time window. We hypothesized that the patient-specific imaging indicator of ischemic lesion progression ("tissue clock") using CT perfusion (CTP) or quantitative net water uptake (NWU) is a predictor of early neurologic improvement (ENI) independent of time. Observational study of anterior circulation ischemic stroke patients with proximal vessel occlusion and known time from symptom onset triaged by multimodal CT undergoing endovascular treatment. Quantitative NWU using an established threshold (11.5%) or CTP lesion core mismatch (EXTEND criteria) was used to estimate ischemic lesion progression. The treatment effect of IVT depending on lesion progression defined by tissue clock vs time clock was assessed by inverse probability weighting (IPW). End points were binarized ENI and functional independence at day 90. Four hundred nine patients were included, of which 223 (54.5%) received IVT. The proportion of patients within an early time window (<4.5hours), low NWU, and CTP mismatch were 45.0%, 86.5%, and 80.3%. In IPW, IVT was associated with higher rates of ENI (%-difference: 7.3%, p = 0.02). For patients with CTP mismatch or low NWU, IVT was associated with a 9.6% or 7.2% higher rate of ENI, which was different than the effect of IVT in patients without CTP mismatch or high NWU (-9.3%/-7.3%; p = 0.004/p = 0.03), whereas early treatment window did not modify the effect of IVT. CT-based measures of the "tissue clock" might identify patients who benefit from IVT more accurately than conventional time windows. Considering the high number of patients with early "tissue clock" (low NWU/CTP mismatch) within an extended time window, considerable benefit from IVT using imaging indicators of the "tissue clock" may be achieved.

Update on Neurointerventional Therapy for the Treatment of Acute Cerebral Ischemia.

Mechanical thrombectomy (MT) is a minimally invasive, fluoroscopically guided procedure to remove clots from the arteries in the head and neck. The procedure can be performed very quickly and effectively, with low complication rates, as techniques and technology have advanced in recent years. MT is among the most efficacious procedures performed today, with a very low number needed to treat (NNT) to impact outcomes. Expanded indications for MT include patients with large core infarcts, extended time windows from stroke onset, more distal occlusions, and milder symptoms. Trials have shown a significant benefit of MT in terms of reduced disability in nearly every patient population studied.

Glutamate-releasing BEST1 channel is a new target for neuroprotection against ischemic stroke with wide time window.

Many efforts have been made to understand excitotoxicity and develop neuroprotectants for the therapy of ischemic stroke. The narrow treatment time window is still to be solved. Given that the ischemic core expanded over days, treatment with an extended time window is anticipated. Bestrophin 1 (BEST1) belongs to a bestrophin family of calcium-activated chloride channels. We revealed an increase in neuronal BEST1 expression and function within the peri-infarct from 8 to 48h after ischemic stroke in mice. Interfering the protein expression or inhibiting the channel function of BEST1 by genetic manipulation displayed neuroprotective effects and improved motor functional deficits. Using electrophysiological recordings, we demonstrated that extrasynaptic glutamate release through BEST1 channel resulted in delayed excitotoxicity. Finally, we confirmed the therapeutic efficacy of pharmacological inhibition of BEST1 during 6-72h post-ischemia in rodents. This delayed treatment prevented the expansion of infarct volume and the exacerbation of neurological functions. Our study identifies the glutamate-releasing BEST1 channel as a potential therapeutic target against ischemic stroke with a wide time window.

Tissue Outcome Prediction in Patients with Proximal Vessel Occlusion and Mechanical Thrombectomy Using Logistic Models

Perfusion CT is established to aid selection of patients with proximal intracranial vessel occlusion for thrombectomy in the extended time window. Selection is mostly based on simple thresholding of perfusion parameter maps, which, however, does not exploit the full information hidden in the high-dimensional perfusion data. We implemented a multiparametric mass-univariate logistic model to predict tissue outcome based on data from 405 stroke patients with acute proximal vessel occlusion in the anterior circulation who underwent mechanical thrombectomy. Input parameters were acute multimodal CT imaging (perfusion, angiography, and non-contrast) as well as basic demographic and clinical parameters. The model was trained with the knowledge of recanalization status and final infarct localization. We found that perfusion parameter maps (CBF, CBV, and Tmax) were sufficient for tissue outcome prediction. Compared with single-parameter thresholding-based models, our logistic model had comparable volumetric accuracy, but was superior with respect to topographical accuracy (AUC of receiver operating characteristic). We also found higher spatial accuracy (Dice index) in an independent internal but not external cross-validation. Our results highlight the value of perfusion data compared with non-contrast CT, CT angiography and clinical information for tissue outcome-prediction. Multiparametric logistic prediction has high potential to outperform the single-parameter thresholding-based approach. In the future, the combination of tissue and functional outcome prediction might provide an individual biomarker for the benefit from mechanical thrombectomy in acute stroke care.

Imaging Caveats to Consider When Screening for Thrombolysis in the Extended Time Window.

HomeStrokeAhead of PrintImaging Caveats to Consider When Screening for Thrombolysis in the Extended Time Window No AccessCase ReportRequest AccessAboutView PDFSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toNo AccessCase ReportRequest AccessImaging Caveats to Consider When Screening for Thrombolysis in the Extended Time Window Dennys Reyes, Sabrena M. Ahmadi, Stuart Kieran, Nils H. Mueller-Kronast, Scott E. Blumenthal, Shlee S. Song and Alexis N. Simpkins Dennys ReyesDennys Reyes Delray Medical Center, Delray Beach, FL (D.R., S.K., N.H.M.-K., S.E.B.). Search for more papers by this author , Sabrena M. AhmadiSabrena M. Ahmadi Department of Vascular Neurology, Cedars Sinai Medical Center, Los Angeles, CA (S.M.A., S.S.S., A.N.S.). Search for more papers by this author , Stuart KieranStuart Kieran https://orcid.org/0009-0006-8083-8584 Delray Medical Center, Delray Beach, FL (D.R., S.K., N.H.M.-K., S.E.B.). Search for more papers by this author , Nils H. Mueller-KronastNils H. Mueller-Kronast Delray Medical Center, Delray Beach, FL (D.R., S.K., N.H.M.-K., S.E.B.). Search for more papers by this author , Scott E. BlumenthalScott E. Blumenthal Delray Medical Center, Delray Beach, FL (D.R., S.K., N.H.M.-K., S.E.B.). Search for more papers by this author , Shlee S. SongShlee S. Song https://orcid.org/0000-0002-7838-0205 Department of Vascular Neurology, Cedars Sinai Medical Center, Los Angeles, CA (S.M.A., S.S.S., A.N.S.). Search for more papers by this author and Alexis N. SimpkinsAlexis N. Simpkins Correspondence to: Alexis N. Simpkins, MD, PhD, MSCR, Director of Vascular Neurology Research and the SkRIPT Research Program, Department Neurology, 127 S San Vicente Blvd, Los Angeles, CA 90048. Email E-mail Address: [email protected] https://orcid.org/0000-0001-7529-4267 Department of Vascular Neurology, Cedars Sinai Medical Center, Los Angeles, CA (S.M.A., S.S.S., A.N.S.). Department of Neurology, University of Florida College of Medicine, Gainesville (A.N.S.). Search for more papers by this author Originally published15 May 2023https://doi.org/10.1161/STROKEAHA.122.042019Stroke. 2023;0FootnotesFor Sources of Funding and Disclosures, see page xxx.Correspondence to: Alexis N. Simpkins, MD, PhD, MSCR, Director of Vascular Neurology Research and the SkRIPT Research Program, Department Neurology, 127 S San Vicente Blvd, Los Angeles, CA 90048. Email alexis.[email protected]org Previous Back to top Next FiguresReferencesRelatedDetails Advertisement Article InformationMetrics © 2023 American Heart Association, Inc.https://doi.org/10.1161/STROKEAHA.122.042019PMID: 37183685 Originally publishedMay 15, 2023 Keywordsbrain imagingthrombolytic therapyischemic strokemagnetic resonancePDF download Advertisement SubjectsCerebrovascular Disease/StrokeIschemic Stroke

Low-dose vs. standard-dose intravenous alteplase for acute ischemic stroke with unknown time of onset.

Standard-dose intravenous alteplase for acute ischemic stroke (AIS) in the unknown or extended time window beyond 4.5 h after symptom onset is both effective and safe for certain patients who were selected based on multimodal neuroimaging. However, uncertainty exists regarding the potential benefit of using low-dose alteplase among the Asian population outside the 4.5-h time window. Consecutive AIS patients who received intravenous alteplase between 4.5 and 9 h after symptom onset or with an unknown time of onset guided by multimodal computed tomography (CT) imaging were identified from our prospectively maintained database. The primary outcome was excellent functional recovery, defined as having a modified Rankin scale (mRS) score of 0-1 at 90 days. Secondary outcomes included functional independence (an mRS score of 0-2 at 90 days), early major neurologic improvement (ENI), early neurologic deterioration (END), any intracranial hemorrhage (ICH), symptomatic ICH (sICH), and 90-day mortality. Propensity score matching (PSM) and multivariable logistic regression models were used to adjust for confounding factors and compare the clinical outcomes between the low- and standard-dose groups. From June 2019 to June 2022, a total of 206 patients were included in the final analysis, of which 143 were treated with low-dose alteplase and 63 were treated with standard-dose alteplase. After accounting for confounding factors, we observed that there were no statistically significant differences between the standard- and low-dose groups with respect to excellent functional recovery [adjusted odds ratio = 1.22 (aOR), 95% confidence interval (CI): 0.62-2.39; adjusted rate difference (aRD) = 4.6%, and 95% CI: -11.2 to 20.3%]. Patients of both groups had similar rates of functional independence, ENI, END, any ICH, sICH, and 90-day mortality. In the subgroup analysis, patients aged ≥70 years were more likely to achieve excellent functional recovery when receiving standard-dose rather than low-dose alteplase. The effectiveness of low-dose alteplase might be comparable to that of standard-dose alteplase in AIS patients aged <70 years with favorable perfusion-imaging profiles in the unknown or extended time window but not in those aged ≥70 years. Furthermore, low-dose alteplase did not significantly reduce the risk of sICH compared to standard-dose alteplase.

Cultural Differences and Bilateral Trade: An Empirical Study Based on Industrial Data from OECD and BRIICS Countries

ABSTRACT This study extends the cross-sectional gravity function in the Eaton and Kortum model to a panel-data model based on 36 OECD and six BRIICS countries from 2010 to 2018 and introduce heterogeneous technology to measure the competitiveness of each country by interaction fixed effects. The results illustrate that the total cultural distance between countries significantly impedes bilateral trade, as it increases trade costs. The conclusions are robust with instrumental variables, alternative measurement of cultural differences, and extended time window estimation. And the effects present heterogeneity in sub-dimensions of cultural distance and sub-industries.

Does MRI add value in selecting patients for thrombectomy beyond the 6 h window? A matched-control analysis.

Controversy exists regarding the need of advanced imaging for patient selection in the extended window. To analyze the effect of initial imaging modalities on clinical outcomes of patients underwent MT in the extended window. This was a retrospective analysis of a prospective registry, the Endovascular Treatment Key Technique and Emergency Workflow Improvement of Acute Ischemic Stroke (ANGEL-ACT) registry which was conducted at 111 hospitals between November 2017 and March 2019 in China. Primary study cohort and Guideline like cohort were identified, in each cohort, two imaging modalities for patient selection in 6 to 24 h window were defined: (1) NCCT ± CTA, (2) MRI. Guideline-like cohort were further screened based on key features of the DAWN and DEFUSE 3 trials. The primary outcome was 90 day mRS. The safety outcomes were sICH, any ICH and 90-day mortality. After adjusting for covariates, there were no significant differences in 90 day mRS or any safety outcomes between two imaging modalities groups in both cohorts. All outcome measures of mixed-effects logistic regression model were consistent with propensity score matching model. Our results indicate that patients presented with anterior large vessel occlusion in the extended time window can potentially benefit from MT even in the absence of MRI selection. This conclusion needs to be verified by the prospective randomized clinical trials.