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Background: Hematoma enlargement (HE) after intracerebral hemorrhage (ICH) is a therapeutic target for improving outcomes. Hemostatic therapies to prevent HE may be more effective the earlier they are attempted. An understanding of HE in first 1 to 2 hours specifically in the prehospital setting would help guide future treatment interventions in this time frame and setting. Methods: Patients with spontaneous ICH within 4 hours of symptom onset were prospectively evaluated between May 2014 and April 2020 as a prespecified substudy within a multicenter trial of prehospital mobile stroke unit versus standard management. Baseline computed tomography scans obtained 6 mL if baseline ICH volume was < 20 mL and 33% increase if baseline volume >20 mL. The association between time from symptom onset to baseline computed tomography (hours) and HE was investigated using Wilcoxon rank-sum test when time was treated as a continuous variable and using Fisher exact test when time was categorized. Kruskal-Wallis and Wilcoxon rank-sum tests evaluated differences in baseline volumes and HE. Univariable and multivariable logistic regression analyses were conducted to identify factors associated with HE and variable selection was performed using cross-validated L1-regularized (Lasso regression). This study adhered to STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology) for cohort studies. Results: One hundred thirty-nine patients were included. There was no difference between baseline ICH volumes obtained 2 hours (n=45) from symptom onset (median [interquartile range], 13 mL [6–24] versus 14 mL [6–30] versus 12 mL [4–19]; P =0.65). However, within the same 3 time epochs, initial hematoma growth (volume/time from onset) was greater with earlier baseline scanning (median [interquartile range], 17 mL/hour [9–35] versus 9 mL/hour [5–23]) versus 4 mL/hour [2–7]; P 2 hours; P =0.02). HE did not occur between the scans repeated at 1 hour and 24 hours. No association between baseline variables and HE was detected in multivariable analyses. Conclusions: HE in the next hour occurs in 28% of ICH patients with baseline imaging within the first hour after symptom onset, and in 17% of those with baseline imaging between 1 and 2 hours. These patients would be a target for ultraearly hemostatic intervention.

Several approaches have been developed to optimize prehospital systems for acute stroke given poor access and significant delays to timely treatment. Specially equipped ambulances that directly initiate treatment, known as Mobile Stroke Units (MSUs), have rapidly proliferated across the world. This review provides a comprehensive summary on the efficacy of MSUs in acute stroke, its various applications beyond thrombolysis, as well as the establishment, optimal setting and cost-effectiveness of incorporating an MSU into healthcare systems.MSUs speed stroke treatment into the first "golden hour" when better outcomes from thrombolysis are achieved. While evidence for the positive impact of MSUs on outcomes was previously unavailable, two recent landmark controlled trials, B_PROUD and BEST-MSU, show that MSUs result in significantly lesser disability compared to conventional ambulance care. Emerging literature prove the significant impact of MSUs. Adaptability however remains limited by significant upfront financial investment, challenges with reimbursements and pending evidence on their cost-effectiveness.

Purpose of the ReviewThis article reviews common imaging modalities used in diagnosis and management of acute stroke. Each modality is discussed individually and clinical scenarios are presented to demonstrate how to apply these modalities in decision-making.Recent FindingsAdvances in neuroimaging provide unprecedented accuracy in determining tissue viability as well as tissue fate in acute stroke. In addition, advances in machine learning have led to the creation of decision support tools to improve the interpretability of these studies.SummaryNoncontrast head computed tomography (CT) remains the most commonly used initial imaging tool to evaluate stroke. Its exquisite sensitivity for hemorrhage, rapid acquisition, and widespread availability make it the ideal first study. CT angiography (CTA), the most common follow-up study after noncontrast head CT, is used primarily to identify intracranial large vessel occlusions and cervical carotid or vertebral artery disease. CTA is highly sensitive and can improve accuracy of patient selection for endovascular therapy through delineations of ischemic core. CT perfusion is widely used in endovascular therapy trials and benefits from multiple commercially available machine-learning packages that perform automated postprocessing and interpretation. Magnetic resonance imaging (MRI) and magnetic resonance angiography (MRA) can provide valuable insights for outcomes prognostication as well as stroke etiology. Optical coherence tomography (OCT), positron emission tomography (PET), single-photon emission computerized tomography (SPECT) offer similar insights. In the clinical scenarios presented, we demonstrate how multimodal imaging approaches can be tailored to gain mechanistic insights for a range of cerebrovascular pathologies.

INTRODUCTION: We have demonstrated in a multicenter cohort that the COVID-19 pandemic has led to a delay in intravenous thrombolysis (IVT) among stroke patients. Whether this delay contributes to meaningful short-term outcome differences in these patients warranted further exploration. METHODS: We conducted a nested observational cohort study of adult acute ischemic stroke patients receiving IVT from 9 comprehensive stroke centers across 7 U.S states. Patients admitted prior to the COVID-19 pandemic (1/1/2019-02/29/2020) were compared to patients admitted during the early pandemic (3/1/2020-7/31/2020). Multivariable logistic regression was used to estimate the effect of IVT delay on discharge to hospice or death, with treatment delay on admission during COVID-19 included as an interaction term. RESULTS: Of the 676 thrombolysed patients, the median age was 70 (IQR 58-81) years, 313 were female (46.3%), and the median NIHSS was 8 (IQR 4-16). Longer treatment delays were observed during COVID-19 (median 46 vs 38 min, p = 0.01) and were associated with higher in-hospital death/hospice discharge irrespective of admission period (OR per hour 1.08, 95% CI 1.01-1.17, p = 0.03). This effect was strengthened after multivariable adjustment (aOR 1.15, 95% CI 1.07-1.24, p < 0.001). There was no interaction of treatment delay on admission during COVID-19 (pinteraction = 0.65). Every one-hour delay in IVT was also associated with 7% lower odds of being discharged to home or acute inpatient rehabilitation facility (aOR 0.93, 95% CI 0.89-0.97, p < 0.001). CONCLUSION: Treatment delays observed during the COVID-19 pandemic led to greater early mortality and hospice care, with a lower probability of discharge to home/rehabilitation facility. There was no effect modification of treatment delay on admission during the pandemic, indicating that treatment delay at any time contributes similarly to these short-term outcomes.

Background and Purpose: The optimal endovascular stroke therapy (EVT) care delivery structure is unknown. Here, we present our experience in creating an integrated stroke system (ISS) to expand EVT availability throughout our region while maintaining hospital and physician quality standards. Methods: We identified all consecutive patients with large vessel occlusion acute ischemic stroke treated with EVT from January 2014 to February 2019 in our health care system. In October 2017, we implemented the ISS, in which 3 additional hospitals (4 total) became EVT-performing hospitals (EPHs) and physicians were rotated between all centers. The cohort was divided by time into pre-ISS and post-ISS, and the primary outcome was time from stroke onset to EPH arrival. Secondary outcomes included hospital and procedural quality metrics. We performed an external validation using data from the Southeast Texas Regional Advisory Council. Results: Among 513 patients with large vessel occlusion acute ischemic stroke treated with EVT, 58% were treated pre-ISS and 43% post-ISS. Over the study period, EVT procedural volume increased overall but remained relatively low at the 3 new EPHs (P P P Conclusions: In our system, increasing EVT availability decreased time from stroke onset to EPH arrival. The ISS provides a framework to maintain quality in lower volume hospitals.

Supplemental Digital Content is available in the text., Background and Purpose: The pandemic caused by the novel coronavirus disease 2019 (COVID-19) has led to an unprecedented paradigm shift in medical care. We sought to evaluate whether the COVID-19 pandemic may have contributed to delays in acute stroke management at comprehensive stroke centers. Methods: Pooled clinical data of consecutive adult stroke patients from 14 US comprehensive stroke centers (January 1, 2019, to July 31, 2020) were queried. The rate of thrombolysis for nontransferred patients within the Target: Stroke goal of 60 minutes was compared between patients admitted from March 1, 2019, and July 31, 2019 (pre–COVID-19), and March 1, 2020, to July 31, 2020 (COVID-19). The time from arrival to imaging and treatment with thrombolysis or thrombectomy, as continuous variables, were also assessed. Results: Of the 2955 patients who met inclusion criteria, 1491 were admitted during the pre–COVID-19 period and 1464 were admitted during COVID-19, 15% of whom underwent intravenous thrombolysis. Patients treated during COVID-19 were at lower odds of receiving thrombolysis within 60 minutes of arrival (odds ratio, 0.61 [95% CI, 0.38–0.98]; P=0.04), with a median delay in door-to-needle time of 4 minutes (P=0.03). The lower odds of achieving treatment in the Target: Stroke goal persisted after adjustment for all variables associated with earlier treatment (adjusted odds ratio, 0.55 [95% CI, 0.35–0.85]; P

Tissue plasminogen activator (tPA) requires a one-hour infusion after the bolus. The frequency of delay or interruption of the tPA infusion may be useful in weighing the advantages of Tenecteplase (TNKase, TNK) which does not require an infusion.Utilizing the Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services study database, we calculated the frequency and magnitude of tPA infusion delay or interruption.Of 497 patients treated with tPA on the Houston Mobile Stroke Unit (MSU), 41 (8.3%) had delay or interruption of the infusion for reasons that did not reflect a side effect of, or contraindication to, tPA. Nine received less than 90% of their calculated dose (median 62%, range 28-88%), and eleven had more than a 10% prolongation of their infusion (median 19 min, range 7-210 min). Six patients (1.2%) had infusion stopped for a valid concern for tPA side effect or contraindication.Interruption or discontinuation of the tPA infusion occurs in 8% of patients treated on a MSU providing an opportunity for more complete and faster treatment with TNK.

Background: Prehospital automated large vessel occlusion (LVO) detection in Mobile Stroke Units (MSUs) could accelerate identification and treatment of patients with LVO acute ischemic stroke. Here, we evaluate the performance of a machine learning (ML) model on CT angiograms (CTAs) obtained from 2 MSUs to detect LVO. Methods: Patients evaluated on MSUs in Houston and Los Angeles with out-of-hospital CTAs were identified. Anterior circulation LVO was defined as an occlusion of the intracranial internal carotid artery, middle cerebral artery (M1 or M2), or anterior cerebral artery vessels and determined by an expert human reader. A ML model to detect LVO was trained and tested on independent data sets consisting of in-hospital CTAs and then tested on MSU CTA images. Model performance was determined using area under the receiver-operator curve statistics. Results: Among 68 patients with out-of-hospital MSU CTAs, 40% had an LVO. The most common occlusion location was the middle cerebral artery M1 segment (59%), followed by the internal carotid artery (30%), and middle cerebral artery M2 (11%). Median time from last known well to CTA imaging was 88.0 (interquartile range, 59.5–196.0) minutes. After training on 870 in-hospital CTAs, the ML model performed well in identifying LVO in a separate in-hospital data set of 441 images with area under receiver-operator curve of 0.84 (95% CI, 0.80–0.87). ML algorithm analysis time was under 1 minute. The performance of the ML model on the MSU CTA images was comparable with area under receiver-operator curve 0.80 (95% CI, 0.71–0.89). There was no significant difference in performance between the Houston and Los Angeles MSU CTA cohorts. Conclusions: In this study of patients evaluated on MSUs in 2 cities, a ML algorithm was able to accurately and rapidly detect LVO using prehospital CTA acquisitions.

© 2021 American Academy of Neurology, Objective: To measure the global impact of COVID-19 pandemic on volumes of IV thrombolysis (IVT), IVT transfers, and stroke hospitalizations over 4 months at the height of the pandemic (March 1 to June 30, 2020) compared with 2 control 4-month periods. Methods: We conducted a cross-sectional, observational, retrospective study across 6 continents, 70 countries, and 457 stroke centers. Diagnoses were identified by their ICD-10 codes or classifications in stroke databases. Results: There were 91,373 stroke admissions in the 4 months immediately before compared to 80,894 admissions during the pandemic months, representing an 11.5% (95% confidence interval [CI] -11.7 to -11.3, p < 0.0001) decline. There were 13,334 IVT therapies in the 4 months preceding compared to 11,570 procedures during the pandemic, representing a 13.2% (95% CI -13.8 to -12.7, p < 0.0001) drop. Interfacility IVT transfers decreased from 1,337 to 1,178, or an 11.9% decrease (95% CI -13.7 to -10.3, p = 0.001). Recovery of stroke hospitalization volume (9.5%, 95% CI 9.2-9.8, p < 0.0001) was noted over the 2 later (May, June) vs the 2 earlier (March, April) pandemic months. There was a 1.48% stroke rate across 119,967 COVID-19 hospitalizations. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection was noted in 3.3% (1,722/52,026) of all stroke admissions. Conclusions: The COVID-19 pandemic was associated with a global decline in the volume of stroke hospitalizations, IVT, and interfacility IVT transfers. Primary stroke centers and centers with higher COVID-19 inpatient volumes experienced steeper declines. Recovery of stroke hospitalization was noted in the later pandemic months.

Arterial and venous thromboses are common in glioma patients, both in the perioperative period and throughout the course of the disease. High-grade glioma patients harbor underlying hypercoagulability, which predisposes these high-risk patients with prolonged immobility and neurologic deficits to thrombotic events. Despite the high incidence and recurrent nature of these complications, there is no standardized approach to the management of glioma patients, and many challenges remain. Historically, the perceived risk of intracranial and intratumoral hemorrhage limited the use of anticoagulation, favoring nonpharmacological prophylaxis and treatment. Multiple studies have demonstrated the safety and efficacy of anticoagulation when indicated, with low molecular weight heparin as the preferred short- or long-term treatment. This review will discuss the epidemiology, risk factors, and therapeutic management of both venous and arterial thrombotic complications in glioma.

Background: Recent clinical trials have established the efficacy of endovascular stroke therapy and intravenous thrombolysis using advanced imaging, particularly computed tomography perfusion (CTP). The availability and utilization of CTP for patients and hospitals that treat acute ischemic stroke (AIS), however, is uncertain. Methods: We performed a retrospective cross-sectional analysis using 2 complementary Medicare datasets, full sample Texas and 5% national fee-for-service data from 2014 to 2017. AIS cases were identified using International Classification of Diseases , Ninth Revision and International Classification of Diseases , Tenth Revision coding criteria. Imaging utilization performed in the initial evaluation of patients with AIS was derived using Current Procedural Terminology codes from professional claims. Primary outcomes were utilization of imaging in AIS cases and the change in utilization over time. Hospitals were defined as imaging modality–performing if they submitted at least 1 claim for that modality per calendar year. The National Medicare dataset was used to validate state-level findings, and a local hospital-level cohort was used to validate the claims-based approach. Results: Among 50 797 AIS cases in the Texas Medicare fee-for-service cohort, 64% were evaluated with noncontrast head CT, 17% with CT angiography, 3% with CTP, and 33% with magnetic resonance imaging. CTP utilization was greater in patients treated with endovascular stroke therapy (17%) and intravenous thrombolysis (9%). CT angiography (4%/y) and CTP (1%/y) utilization increased over the study period. These findings were validated in the National dataset. Among hospitals in the Texas cohort, 100% were noncontrast head CT–performing, 77% CT angiography–performing, and 14% CTP-performing in 2017. Most AIS cases (69%) were evaluated at non-CTP–performing hospitals. CTP-performing hospitals were clustered in urban areas, whereas large regions of the state lacked immediate access. Conclusions: In state-wide and national Medicare fee-for-service cohorts, CTP utilization in patients with AIS was low, and most patients were evaluated at non-CTP–performing hospitals. These findings support the need for alternative means of screening for AIS recanalization therapies.

Highlights • Multicenter study evaluating the impact of COVID-19 pandemic on ischemic stroke volumes, subtypes, and clinical presentation in US. • Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes, LVOs, and IV-tPA administration. • Patients admitted to the hospital had severe disease (NIHSS>14) and were more likely to discharge home., Background To evaluate overall ischemic stroke volumes and rates, specific subtypes, and clinical presentation during the COVID-19 pandemic in a multicenter observational study from eight states across US. Methods We compared all ischemic strokes admitted between January 2019 and May 2020, grouped as; March-May 2020 (COVID-19 period) and March-May 2019 (seasonal pre-COVID-19 period). Primary outcome was stroke severity at admission measured by NIHSS stratified as mild (0−7), moderate [[8], [9], [10], [11], [12], [13], [14]], and severe (>14). Secondary outcomes were volume of large vessel occlusions (LVOs), stroke etiology, IV-tPA rates, and discharge disposition. Results Of the 7969 patients diagnosed with acute ischemic stroke during the study period, 933 (12 %) presented in the COVID-19 period while 1319 (17 %) presented in the seasonal pre-COVID-19 period. Significant decline was observed in the mean weekly volumes of newly diagnosed ischemic strokes (98 ± 3 vs 50 ± 20,p = 0.003), LVOs (16.5 ± 3.8 vs 8.3 ± 5.9,p = 0.008), and IV-tPA (10.9 ± 3.4 vs 5.3 ± 2.9,p = 0.0047), whereas the mean weekly proportion of LVOs (18 % ±5 vs 16 % ±7,p = 0.24) and IV-tPA (10.4 % ±4.5 vs. 9.9 % ±2.4,p = 0.66) remained the same, when compared to the seasonal pre-COVID-19 period. Additionally, an increased proportion of patients presented with a severe disease (NIHSS > 14) during the COVID-19 period (29.7 % vs 24.5 %,p < 0.025). The odds of being discharged to home were 26 % greater in the COVID-19 period when compared to seasonal pre-COVID-19 period (OR:1.26, 95 % CI:1.07–1.49,p = 0.016). Conclusions During COVID-19 period there was a decrease in volume of newly diagnosed ischemic stroke cases and IV-tPA administration. Patients admitted to the hospital had severe neurological clinical presentation and were more likely to discharge home.

Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM, Background: The COVID-19 pandemic led to profound changes in the organization of health care systems worldwide. Aims: We sought to measure the global impact of the COVID-19 pandemic on the volumes for mechanical thrombectomy, stroke, and intracranial hemorrhage hospitalizations over a three-month period at the height of the pandemic (1 March–31 May 2020) compared with two control three-month periods (immediately preceding and one year prior). Methods: Retrospective, observational, international study, across 6 continents, 40 countries, and 187 comprehensive stroke centers. The diagnoses were identified by their ICD-10 codes and/or classifications in stroke databases at participating centers. Results: The hospitalization volumes for any stroke, intracranial hemorrhage, and mechanical thrombectomy were 26,699, 4002, and 5191 in the three months immediately before versus 21,576, 3540, and 4533 during the first three pandemic months, representing declines of 19.2% (95%CI, −19.7 to −18.7), 11.5% (95%CI, −12.6 to −10.6), and 12.7% (95%CI, −13.6 to −11.8), respectively. The decreases were noted across centers with high, mid, and low COVID-19 hospitalization burden, and also across high, mid, and low volume stroke/mechanical thrombectomy centers. High-volume COVID-19 centers (−20.5%) had greater declines in mechanical thrombectomy volumes than mid- (−10.1%) and low-volume (−8.7%) centers (p < 0.0001). There was a 1.5% stroke rate across 54,366 COVID-19 hospitalizations. SARS-CoV-2 infection was noted in 3.9% (784/20,250) of all stroke admissions. Conclusion: The COVID-19 pandemic was associated with a global decline in the volume of overall stroke hospitalizations, mechanical thrombectomy procedures, and intracranial hemorrhage admission volumes. Despite geographic variations, these volume reductions were observed regardless of COVID-19 hospitalization burden and pre-pandemic stroke/mechanical thrombectomy volumes

© 2020 World Stroke Organization., [Background]: Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) has been associated with a significant risk of thrombotic events in critically ill patients. [Aim]: To summarize the findings of a multinational observational cohort of patients with SARS-CoV-2 and cerebrovascular disease. [Methods]: Retrospective observational cohort of consecutive adults evaluated in the emergency department and/or admitted with coronavirus disease 2019 (COVID-19) across 31 hospitals in four countries (1 February 2020–16 June 2020). The primary outcome was the incidence rate of cerebrovascular events, inclusive of acute ischemic stroke, intracranial hemorrhages (ICH), and cortical vein and/or sinus thrombosis (CVST). [Results]: Of the 14,483 patients with laboratory-confirmed SARS-CoV-2, 172 were diagnosed with an acute cerebrovascular event (1.13% of cohort; 1130/100,000 patients, 95%CI 970–1320/100,000), 68/171 (40.5%) were female and 96/172 (55.8%) were between the ages 60 and 79 years. Of these, 156 had acute ischemic stroke (1.08%; 1080/100,000 95%CI 920–1260/100,000), 28 ICH (0.19%; 190/100,000 95%CI 130–280/100,000), and 3 with CVST (0.02%; 20/100,000, 95%CI 4–60/100,000). The in-hospital mortality rate for SARS-CoV-2-associated stroke was 38.1% and for ICH 58.3%. After adjusting for clustering by site and age, baseline stroke severity, and all predictors of in-hospital mortality found in univariate regression (p < 0.1: male sex, tobacco use, arrival by emergency medical services, lower platelet and lymphocyte counts, and intracranial occlusion), cryptogenic stroke mechanism (aOR 5.01, 95%CI 1.63–15.44, p < 0.01), older age (aOR 1.78, 95%CI 1.07–2.94, p ¼ 0.03), and lower lymphocyte count on admission (aOR 0.58, 95%CI 0.34–0.98, p ¼ 0.04) were the only independent predictors of mortality among patients with stroke and COVID-19. [Conclusions]: COVID-19 is associated with a small but significant risk of clinically relevant cerebrovascular events, particularly ischemic stroke. The mortality rate is high for COVID-19-associated cerebrovascular complications; therefore, aggressive monitoring and early intervention should be pursued to mitigate poor outcomes.

Objectives Studies face challenges with missing 5-level EQ-5D (EQ-5D-5L) data, often because of the need for longitudinal EQ-5D-5L data collection. There is a dearth of validated methodologies for dealing with missing EQ-5D-5L data in the literature. This study, for the first time, examined the possibility of using retrospectively collected EQ-5D-5L data as proxies for the missing data. Methods Participants who had prospectively completed a 3rd month postdischarge EQ-5D-5L instrument (in-the-moment collection) were randomly interviewed to respond to a 2nd “retrospective collection” of their 3rd month EQ-5D-5L at 6th, 9th, or 12th month after hospital discharge. A longitudinal single imputation was also used to assess the relative performance of retrospective collection compared with the longitudinal single imputation. Concordances between the in-the-moment, retrospective, and imputed measures were assessed using intraclass correlation coefficients and weighted kappa statistics. Results Considerable agreement was observed on the basis of weighted kappa (range 0.72-0.95) between the mobility, self-care, and usual activities dimensions of EQ-5D-5L collected in-the-moment and retrospectively. Concordance based on intraclass correlation coefficients was good to excellent (range 0.79-0.81) for utility indices computed, and excellent (range 0.93-0.96) for quality-adjusted life-years computed using in-the-moment compared with retrospective EQ-5D-5L. The longitudinal single imputation did not perform as well as the retrospective collection method. Conclusions This study demonstrates that retrospective collection of EQ-5D-5L has high concordance with “in-the-moment” EQ-5D-5L and could be a valid and attractive alternative for data imputation when longitudinally collected EQ-5D-5L data are missing. Future studies examining this method for other disease areas and populations are required to provide more generalizable evidence.

Background and Purpose: Noncontrast head CT and CT perfusion (CTP) are both used to screen for endovascular stroke therapy (EST), but the impact of imaging strategy on likelihood of EST is undetermined. Here, we examine the influence of CTP utilization on likelihood of EST in patients with large vessel occlusion (LVO). Methods: We identified patients with acute ischemic stroke at 4 comprehensive stroke centers. All 4 hospitals had 24/7 CTP and EST capability and were covered by a single physician group (Neurology, NeuroIntervention, NeuroICU). All centers performed noncontrast head CT and CT angiography in the initial evaluation. One center also performed CTP routinely with high CTP utilization (CTP-H), and the others performed CTP optionally with lower utilization (CTP-L). Primary outcome was likelihood of EST. Multivariable logistic regression was used to determine whether facility type (CTP-H versus CTP-L) was associated with EST adjusting for age, prestroke mRS, National Institutes of Health Stroke Scale, Alberta Stroke Program Early CT Score, LVO location, time window, and intravenous tPA (tissue-type plasminogen activator). Results: Among 3107 patients with acute ischemic stroke, 715 had LVO, of which 403 (56%) presented to CTP-H and 312 (44%) presented to CTP-L. CTP utilization among LVO patients was greater at CTP-H centers (72% versus 18%, CTP-H versus CTP-L, P Conclusions: We identified an increased likelihood for undergoing EST in centers with lower CTP utilization, which was not associated with worse clinical outcomes or increased hemorrhage. These findings suggest under-treatment bias with routine CTP.

Background and Purpose— Endovascular thrombectomy (ET) door-to-puncture time (DTPT) is a modifiable metric. One of the most important, yet time-consuming steps, is documentation of large vessel occlusion by computed tomography angiography (CTA). We hypothesized that obtaining CTA on board a Mobile Stroke Unit and direct alert of the ET team shortens DTPT by over 30 minutes. Methods— We compared DTPT between patients having CTA onboard the Mobile Stroke Unit then subsequent ET from September 2018 to November 2019 and patients in Mobile Stroke Unit from August 2014 to August 2018, when onboard CTA was not yet being used. We also correlated DTPT with change in National Institutes of Health Stroke Scale between baseline and 24 hours. Results— Median DTPT was 53.5 (95% CI, 35–67) minutes shorter with onboard CTA and direct ET team notification: 41 minutes (interquartile range, 30.0–63.5) versus 94.5 minutes (interquartile range, 69.8–117.3; P P P =0.07). Conclusions— Prehospital Mobile Stroke Unit management including on-board CTA and ET team alert substantially shortens DTPT. Registration— URL: https://clinicaltrials.gov ; Unique identifier: NCT02190500.

Background and Purpose- The impact of a mobile stroke unit (MSU) on access to intraarterial thrombectomy (IAT) is a prespecified BEST-MSU substudy (Benefits of Stroke Treatment Delivered Using a Mobile Stroke Unit Compared to Standard Management by Emergency Medical Services). On the MSU, IAT decision-making steps, such as computed tomography, neurological exam, and tPA (tissue-type plasminogen activator) treatment are completed before emergency department arrival. We hypothesized that such pre-ED assessment of potential IAT patients on an MSU improves the time from ED arrival to skin puncture time (door-to-puncture-time, DTPT). Methods- BEST-MSU is a prospective comparative effectiveness study of MSU versus standard management by emergency medical services (EMS). We compared ED DTPT among the following groups of MSU and EMS patients: all IAT patients, IAT patients post-tPA, and IAT patients post-tPA meeting thrombolytic adjudication criteria over the first 4 years of the study. Results- From August 2014 to July 2018, a total of 161 patients underwent IAT. Ninety-four patients presented to the ED via the MSU and 67 by EMS. One hundred forty patients received tPA before IAT, 85 in the MSU arm, and 55 in the EMS arm. One hundred twenty-six patients received tPA within thrombolytic adjudication criteria: 76 MSU and 50 EMS. DTPT in minutes was shorter for MSU patients (all IAT MSU versus EMS 89 versus 99, P=0.01; IAT post-tPA MSU versus EMS 93 versus 100, P=0.03; and IAT post-tPA within adjudicated criteria MSU versus EMS 93 versus 99.5, P=0.03). From 2014 to 2018, DTPT decreased at a faster rate for EMS compared with MSU-managed patients, improving by about an hour. Conclusions- Pre-ED IAT evaluation on an MSU results in faster DTPT compared with arrival by EMS. Since 2014, dramatic improvement in ED IAT metrics has attenuated this difference. However, DTPT in all groups indicates substantial room for improvement.

BackgroundUnprecedented workflow shifts during the coronavirus disease 2019 (COVID-19) pandemic have contributed to delays in acute care delivery, but whether it adversely affected endovascular thrombectomy metrics in acute large vessel occlusion (LVO) is unknown.MethodsWe performed a retrospective review of observational data from 14 comprehensive stroke centers in nine US states with acute LVO. EVT metrics were compared between March to July 2019 against March to July 2020 (primary analysis), and between state-specific pre-peak and peak COVID-19 months (secondary analysis), with multivariable adjustment.ResultsOf the 1364 patients included in the primary analysis (51% female, median NIHSS 14 [IQR 7–21], and 74% of whom underwent EVT), there was no difference in the primary outcome of door-to-puncture (DTP) time between the 2019 control period and the COVID-19 period (median 71 vs 67 min, P=0.10). After adjustment for variables associated with faster DTP, and clustering by site, there remained a trend toward shorter DTP during the pandemic (βadj=-73.2, 95% CI −153.8–7.4, Pp=0.07). There was no difference in DTP times according to local COVID-19 peaks vs pre-peak months in unadjusted or adjusted multivariable regression (βadj=-3.85, 95% CI −36.9–29.2, P=0.80). In this final multivariable model (secondary analysis), faster DTP times were significantly associated with transfer from an outside institution (βadj=-46.44, 95% CI −62.8 to – -30.0, Padj=-2.15, 95% CI −4.2to – -0.1, P=0.05).ConclusionsIn this multi-center study, there was no delay in EVT among patients treated for intracranial occlusion during the COVID-19 era compared with the pre-COVID era.

Despite the high mortality, there is currently no specific treatment for intracerebral hemorrhage (ICH). Research investigating optimum degree of blood pressure control in patients presenting with ICH and hypertension is ongoing. However, there is limited understanding of the potential benefits of specific classes of antihypertensive therapy. β-Adrenergic antagonists may provide neuroprotection from inflammation-induced injury by inhibiting sympathetic nervous system mediated immune activation. We examined mortality in ICH patients receiving β-adrenergic antagonists to determine whether this class of antihypertensive therapy was associated with improved survival.A retrospective analysis of a large, prospectively collected database of patients presenting with acute ICH was performed. Patients were grouped by inpatient β-blocker treatment to determine an effect on mortality during the inpatient stay and at 3 months of follow-up. Additional analysis was conducted comparing β-blocker therapy to any other antihypertensive treatment to determine a class-specific association of β-blocker treatment with mortality.The study population included 426 patients with acute, spontaneous ICH. Inpatient β-blocker use was independently associated with decreased rates of inpatient death and mortality at 3 months of follow-up. However, univariate and multivariable analyses comparing β-blocker use to other antihypertensives failed to show any class-specific reduction in mortality at either time point.Our study demonstrates that the improvement seen in patients treated with β-adrenergic antagonists is not an effect unique to this class. This supports ongoing trials to determine optimum levels of blood pressure control using multiple classes of antihypertensives.

Background Intracerebral hemorrhage (ICH) is a severe type of stroke for which there is currently no specific medical therapy. We hypothesized that statins reduce immediate inflammatory injury and improve long-term recovery from increased neurogenesis and angiogenesis. We conducted a large retrospective cohort study to assess the influence of statin therapy on patient death and disability at 12 months after ICH. Methods This was a retrospective analysis of a prospectively collected database at a tertiary care medical center. Patients were grouped based on statin use, and poor outcome was assessed as dead or alive with dependency (modified Barthel Index ≤14). Results We compared outcomes in 190 patients exposed to statins to 236 patients who were not exposed to statins. Univariate analysis found that statin use was associated with decreased mortality in-hospital and at 12 months ( P = .001). Multivariable analysis found that statin use was associated with a decreased odds of death or disability at 12 months after ICH (odds ratio 0.44; 95% confidence interval 0.21-0.95). Conclusions Statin use is associated with improved long-term outcome at 12 months after ICH. This finding supports previous clinical studies that have shown the short-term benefits of statin therapy. In addition, this study correlates with animal studies supporting the possible long-term recovery benefits of statins.

RasGRP3, an activator for H-Ras, R-Ras and Ras-associated protein-1/2, has emerged as an important mediator of signaling downstream from receptor coupled phosphoinositide turnover in B and T cells. Here, we report that RasGRP3 showed a high level of expression in multiple human melanoma cell lines as well as in a subset of human melanoma tissue samples. Suppression of endogenous RasGRP3 expression in these melanoma cell lines reduced Ras-GTP formation as well as c-Met expression and Akt phosphorylation downstream from hepatocyte growth factor (HGF) or epidermal growth factor (EGF) stimulation. RasGRP3 suppression also inhibited cell proliferation and reduced both colony formation in soft agar and xenograft tumor growth in immunodeficient mice, demonstrating the importance of RasGRP3 for the transformed phenotype of the melanoma cells. Reciprocally, overexpression of RasGRP3 in human primary melanocytes altered cellular morphology, markedly enhanced cell proliferation and rendered the cells tumorigenic in a mouse xenograft model. Suppression of RasGRP3 expression in these cells inhibited downstream RasGRP3 responses and suppressed cell growth, confirming the functional role of RasGRP3 in the altered behavior of these cells. The identification of the role of RasGRP3 in melanoma highlights its importance, as a Ras activator, in the phosphoinositide signaling pathway in human melanoma and provides a new potential therapeutic target.

Patients with acute ischemic stroke have improved outcomes when cared for in designated stroke centers (SC), in part due to enhanced thrombolytic use. Whether patients with intracerebral hemorrhage (ICH) also benefit from SC care is unknown. In this study, we compared the clinical characteristics and outcomes of ICH patients who underwent interhospital transfer (IHT) to a Joint Commission (JC) designated SC, to ICH patients who presented directly to the SC's emergency department (ED).Patients with ICH admitted between 2006 and 2013 were evaluated. The primary outcome measure was in-hospital death or hospice.Among 760 consecutive admissions for ICH, 321 (42.2%) were IHTs. There has been a 30% annual increase in IHT of ICH patients since 2006. The IHT group was younger (70.26 vs 72.28; P =.055), had lower ICH scores (P = .007), a higher Glasgow Coma Scale (GCS) (P = .037), and lower systolic blood pressure (SBP) (P = .003) than those arriving directly to the ED. Female sex was a predictor of in-hospital mortality (OR = 2.26).IHT is increasingly common for patients with ICH. The benefit of transfer remains unclear, as younger, healthier patients were the most likely to be transferred. Comprehensive stroke registries are needed to determine if outcomes differ for ICH patients based on transfer or SC care.

Background Hypothyroidism is associated with increased ischemic stroke risk but paradoxically results in more favorable outcomes once a stroke occurs. Whether a similar pattern emerges in patients with primary intracerebral hemorrhage (ICH) is unknown. Methods A retrospective analysis of a prospective stroke center database was performed to analyze the clinical presentation and outcomes of hypothyroid patients with spontaneous ICH. Patients were classified into groups with no history of thyroid disease (n = 491) versus those with hypothyroidism (n = 72). Hypothyroid patients were further classified into patients receiving thyroid replacement on admission or those without replacement. The Glasgow Coma Scale, ICH score, and the National Institutes of Health Stroke Scale (NIHSS) were used to assess the initial severity. Outcome was assessed by admission to discharge change in the NIHSS and modified Barthel Index (mBI), in-hospital mortality, discharge disposition and mortality, and the mBI at 3 and 12 months. Results There were 563 patients in the analysis. Seventy-two patients had a history of hypothyroidism, and of these, 63% received thyroid hormone replacement. Patients receiving replacement had significantly lower NIHSS at presentation (median 4 [IQR 1, 11]) compared with either the control group (median 8 [IQR 3, 16]) or hypothyroid patients without replacement (median 9 [IQR 3.8, 15.5]; P = .004). There was no difference in in-hospital and 3-month mortality or functional outcomes at 3 and 12 months among the groups. Conclusions This study suggests that the history of hypothyroidism does not affect clinical severity or outcome after ICH.

Background Intracerebral hemorrhage (ICH) is a devastating disease that carries a 30 day mortality of approximately 45%. Only 20% of survivors return to independent function at 6 months. The role of inflammation in the pathophysiology of ICH is increasingly recognized. Several clinical studies have demonstrated an association between inflammatory markers and outcomes after ICH; however the relationship between serum biomarkers and functional outcomes amongst survivors has not been previously evaluated. Activation of the inflammatory response as measured by change in peripheral leukocyte count was examined and assessment of mortality and functional outcomes after ICH was determined. Findings Patients with spontaneous ICH admitted to a tertiary care center between January 2005 and April 2010 were included. The change in leukocyte count was measured as the difference between the maximum leukocyte count in the first 72 hours and the leukocyte count on admission. Mortality was the primary outcome. Secondary outcomes were mortality at 1 year, discharge disposition and the modified Barthel index (MBI) at 3 months compared to pre-admission MBI. 423 cases were included. The in-hospital mortality was 30.4%. The change in leukocyte count predicted worse discharge disposition (OR = 1.258, p = 0.009). The change in leukocyte count was also significantly correlated with a decline in the MBI at 3 months. These relationships remained even after removal of all patients with evidence of infection. Conclusions Greater changes in leukocyte count over the first 72 hours after admission predicted both worse short term and long term functional outcomes after ICH.

Bryostatin 1 has attracted considerable attention both as a cancer chemotherapeutic agent and for its unique activity. Although it functions, like phorbol esters, as a potent protein kinase C (PKC) activator, it paradoxically antagonizes many phorbol ester responses in cells. Because of its complex structure, little is known of its structure-function relations. Merle 23 is a synthetic derivative, differing from bryostatin 1 at only four positions. However, in U-937 human leukemia cells, Merle 23 behaves like a phorbol ester and not like bryostatin 1. Here, we characterize the behavior of Merle 23 in the human prostate cancer cell line LNCaP. In this system, bryostatin 1 and phorbol ester have contrasting activities, with the phorbol ester but not bryostatin 1 blocking cell proliferation or tumor necrosis factor alpha secretion, among other responses. We show that Merle 23 displays a highly complex pattern of activity in this system. Depending on the specific biological response or mechanistic change, it was bryostatin-like, phorbol ester-like, intermediate in its behavior, or more effective than either. The pattern of response, moreover, varied depending on the conditions. We conclude that the newly emerging bryostatin derivatives such as Merle 23 provide powerful tools to dissect subsets of bryostatin mechanism and response.

Environmental and patient-care control measures were initiated in response to an outbreak of legionellosis in an intensive care unit in 1992. The measures included maintaining elevated potable hot-water temperatures following superheating and using sterile water for administrations through nasogastric tubes.Legionellaspecies remained below detectable levels in the potable hot-water system upon reevaluation in 1999. Nosocomial cases of legionellosis have not been reported since the outbreak.

We report a case of a boy with a long-standing foreign body aspiration in the left main bronchus causing severe pneumonia of the left lung. During intravenous therapy with antibiotics there was a life-threatening event with acute dislocation of the foreign body into the right main bronchus, leading to acute respiratory insufficiency. We conclude that in chronic foreign body aspiration antibiotic therapy preceding bronchoscopy should only be performed in in-patients and with strict monitoring.