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Introduction: While the goal of IV tissue plasminogen activator (TPA) is to prevent infarction, few data exist on averted stroke. Methods: Secondary analysis of a multicenter trial from 2014-2020 comparing outcomes between patients treated for stroke by mobile stroke unit (MSU) vs standard care (SC). The analytical cohort were patients with suspected stroke treated with IV TPA. The primary outcome was a time-defined averted stroke diagnosis, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours. The secondary outcome was a tissue-defined averted stroke diagnosis, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours and no acute infarction/hemorrhage on imaging. We used multivariable logistic regression to evaluate associations between study exposures (demographics, comorbidities, stroke characteristics) and outcomes. Results: Among 1009 patients with a median last known well-to-TPA time of 87 minutes, 276 patients (27%) had a time-defined averted stroke (31% MSU, 21% SC) and 159 patients (16%) had a tissue-defined averted stroke (18% MSU, 11% SC). Factors independently associated with time-defined averted stroke were younger age (OR, 0.98; 95% CI, 0.96-0.99), female sex (0R, 0.51; 95% CI, 0.36-0.74), hyperlipidemia (OR, 1.81, 95% CI, 1.24-2.64), normal premorbid function (0R, 2.22; 95% CI, 1.37-3.67), lower glucose (OR, 0.996; 95% CI, 0.993-0.999), lower MAP (OR, 0.991; 95% CI, 0.983-0.998), MSU care (OR, 1.77; 95% CI, 1.21-2.62), lower NIH stroke scale (OR, 0.89; 95% CI, 0.86-0.93), and no large vessel occlusion (LVO) (OR, 0.52; 95% CI, 0.32-0.83). For tissue-based averted stroke, younger age, female sex, hyperlipidemia, lower MAP, MSU treatment, lower NIH stroke scale, and no LVO were significantly associated. Conclusion: In a modern acute stroke trial, one-in-four patients treated with TPA for stroke recovered within 24 hours and one-in-six had no demonstrable brain injury on imaging. Younger age, female sex, hyperlipidemia, lower MAP, MSU care, lower stroke severity, and no LVO may increase the odds of averting stroke.

Background Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard m...

Cerebrovascular complications among critically ill patients with COVID-19 have yet to be fully characterized. In this retrospective case series from a single academic tertiary care referral center in New York City, we present 12 patients with ischemic or hemorrhagic strokes that were found on imaging after a period of prolonged sedation in the setting of COVID-19 pneumonia. This series demonstrates a pattern of cerebrovascular events clinically masked by deep sedation required for management of COVID-19 related acute respiratory distress syndrome (ARDS). Of the 12 patients included, 10 had ischemic stroke, 4 of which had hemorrhagic conversion, and 2 had primary intracerebral hemorrhage. Ten patients were on therapeutic anticoagulation prior to discovery of their stroke, and the remainder received intermediate dose anticoagulation (in a range between prophylactic and therapeutic levels). Additional studies are needed to further characterize the counterbalancing risks of ischemic and hemorrhagic stroke, as well as the optimal management of this patient population.

To derive models that identify patients with COVID-19 at high risk for stroke.We used data from the AHA's Get With The Guidelines® COVID-19 Cardiovascular Disease Registry to generate models for predicting stroke risk among adults hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our models, we used data on demographics, comorbidities, medications, and vital sign and laboratory values at admission. The outcome was a cerebrovascular event (stroke, TIA, or cerebral vein thrombosis). First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable and multivariable analyses. Then, we assigned points for each variable based on corresponding coefficients to create a prediction score. Second, we used machine learning techniques to create risk estimators using all available covariates.Among 21,420 patients hospitalized with COVID-19, 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created/validated a COVID-19 stroke risk score with a C-statistic of 0.66 (95% CI, 0.60-0.72). The CANDLE score assigns 1 point each for prior cerebrovascular disease, afebrile temperature, no prior pulmonary disease, history of hypertension, leukocytosis, and elevated systolic blood pressure. CANDLE stratified risk of an acute cerebrovascular event according to low- (0-1: 0.2% risk), medium- (2-3: 1.1% risk), and high-risk (4-6: 2.1-3.0% risk) groups. Machine learning estimators had similar discriminatory performance as CANDLE: C-statistics, 0.63-0.69.We developed a practical clinical score, with similar performance to machine learning estimators, to help stratify stroke risk among patients hospitalized with COVID-19.

Background: Access to mechanical thrombectomy in the US remains limited, in part due to a relative lack of trained interventionalists. Given potential staffing challenges, we hypothesized that access to thrombectomy would be worse on nights and weekends. Methods: We used 2016-2018 all-payer claims data from all nonfederal emergency departments and acute care hospitals across 11 US states encompassing 80 million residents. Using recorded arrival times, hospital presentation was classified as on-hours if it fell between 8:00 a.m. and 6:00 p.m. on weekdays and as off-hours otherwise. For patients who underwent interhospital transfer, we used the arrival time at the initial hospital. We examined the association between off-hours arrival and mechanical thrombectomy using multiple logistic regression adjusted for age, sex, race/ethnicity, insurance type, socioeconomic status, urban-rural location of residence, the Charlson comorbidity index, initial presentation to a thrombectomy hub, and treatment with intravenous thrombolysis. We performed a sensitivity analysis limited to patients who presented with a probable large-vessel occlusion, defined as a documented NIHSS score ≥12, to a thrombectomy hub and underwent intravenous thrombolysis. Results: Among 169,199 patients with ischemic strokes, the 82,784 (48.9%) who presented during off-hours had higher NIHSS scores (4 [IQR, 2-10] vs 2 [IQR, 1-9], P P P = 0.25). In adjusted models, off-hours presentation was not significantly associated with lower odds of mechanical thrombectomy (OR, 0.94; 95% CI, 0.85-1.03). Our findings were similar in a sensitivity analysis limited to patients with a probable large-vessel occlusion who initially presented to a thrombectomy hub and underwent intravenous thrombolysis (OR, 0.87; 0.69-1.09). Conclusions: In a large population-based sample of ischemic stroke patients across the US, the odds of mechanical thrombectomy did not vary by time of presentation.

Introduction: Coronavirus Disease 2019 (COVID-19) is associated with an increased risk of stroke and worse stroke outcomes. A clinical score that can identify high-risk patients could enable closer monitoring and targeted preventative strategies. Methods: We used data from the AHA’s COVID-19 CVD Registry to create a clinical score to predict the risk of stroke among patients hospitalized with COVID-19. We included patients aged >18 years who were hospitalized with COVID-19 at 122 centers from March 2020-March 2021. To build our score, we used demographics, preexisting comorbidities, home medications, and vital sign and lab values at admission. The outcome was a cerebrovascular event, defined as any ischemic or hemorrhagic stroke, TIA, or cerebral vein thrombosis. We used two separate analytical approaches to build the score. First, we used Cox regression with cross validation techniques to identify factors associated with the outcome in both univariable (p Results: Among 21,420 patients hospitalized with COVID-19 (mean age 61 years, 54% men), 312 (1.5%) had a cerebrovascular event. Using traditional Cox regression, we created and internally validated a risk stratification score (CANDLE) (Fig) with a C-statistic of 0.66 (95% CI, 0.60-0.72). The machine learning estimator had similar discriminatory performance, with a C-statistic of 0.69 (95% CI, 0.65-0.72). For ischemic stroke or TIA, CANDLE’s C-statistic was 0.67 (95% 0.59-0.76). Conclusion: We developed an easy-to-use clinical score, with similar performance to a machine learning estimator, to help stratify stroke risk among patients hospitalized with COVID-19.

Introduction. Transient headache and neurologic deficits with cerebrospinal fluid lymphocytosis (HaNDL) is defined as a secondary, nonvascular headache disorder characterized by the findings described in its name. Patients with HaNDL syndrome typically present with gradual onset migrainous headaches of moderate to severe intensity with transient neurological symptoms. Case Report. We discuss a patient who presented with thunderclap headache, recent transient neurologic deficits, and was ultimately diagnosed with HaNDL after an extensive neurologic evaluation. Conclusion. Thunderclap headache has very rarely been described in patients with HaNDL. After excluding emergent and secondary causes, HaNDL should be considered in patients with thunderclap-quality headaches, particularly when there is a history of transient neurological symptoms.

Introduction: Black Americans face a higher risk of recurrent stroke than White Americans, and the reasons are unclear. Smoking after stroke is associated with a higher risk of recurrence. We investigated whether there are racial disparities in smoking cessation among stroke survivors in the United States. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention Behavioral Risk Factor Surveillance System, an annual, nationally representative health survey. Respondents are asked about medical conditions and health-related behaviors. We pooled data from 2013-2018, during which race and ethnicity were uniformly reported. We included respondents with prior stroke and any smoking history. The exposure was self-reported race, and the outcome was smoking cessation. We calculated the quit ratio, defined as the proportion of former smokers among ever smokers; this is a standard measure in population-based studies of smoking cessation. Survey procedures were used to estimate frequencies and summarize quit ratios by race. Multiple logistic regression was used to assess the association of Black race with smoking cessation, as compared to White race, while adjusting for age, gender, Hispanic ethnicity, education, income, health insurance, and the number of smoking-related health conditions (heart disease, lung disease, cancer) that may prompt cessation. Results: Among 4,374,011 Americans with a history of stroke and any smoking, the median age was 67 years (IQR, 58-76), and 45.7% were women; 15.4% were Black, 74.8% were White, and 9.8% reported other race. The crude quit ratio was 51.4% (95% CI, 49.0-53.7) in Black and 63.2% (95% CI, 62.4-64.1) in White stroke survivors. In unadjusted analyses, Black stroke survivors were less likely to have quit smoking than White stroke survivors (OR, 0.61; 95% CI, 0.55-0.68). This remained the case after accounting for differences in demographics and smoking-related comorbidities (OR, 0.85; 95% CI, 0.74-0.98). Conclusion: In this nationwide study, Black stroke survivors had lower smoking quit rates than White stroke survivors, even after accounting for group differences. Expanding access to smoking-cessation interventions may reduce disparities in recurrent stroke.

Introduction: Patients with acute ischemic stroke (AIS) are generally vulnerable to subsequent infection, but there are few population-based data on the risk of herpes zoster infection after AIS. We tested the hypothesis that AIS is associated with an increased risk of zoster. Methods: We performed a retrospective cohort study using statewide administrative claims data from all emergency department (ED) visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. These Healthcare Cost and Utilization Project data are well suited for longitudinal analyses of acute care utilization. The primary exposure was AIS, and the outcome was subsequent zoster; diagnoses were ascertained using validated ICD-9-CM codes. We excluded people with zoster before AIS. Survival statistics were used to calculate incidence rates, and Cox proportional hazards analysis was used to determine the association between AIS and subsequent ED visit or admission with zoster. In addition to demographics and comorbidities, models were adjusted for conditions associated with zoster (cancer and HIV/AIDS). In a secondary analysis, we limited the population to people under 50 years old, because current guidelines recommend zoster vaccination for only those at least 50 years old. Results: Among 19,675,854 beneficiaries, 421,940 (2.1%) had AIS; their mean age was 70.8 (SD, 14.5) years. Follow-up duration was a mean of 4.1 (SD, 3.0) years. The incidence of zoster was 4.1 per 1000 patient-years in those with AIS and 2.1 per 1000 patient-years in those without. After AIS, the median time to zoster was 1.7 years (IQR, 0.4-4.1). In unadjusted models, patients with AIS had a two-fold higher risk of zoster (HR, 2.1; 95% CI, 2.0-2.1). AIS remained associated with zoster after adjusting for cardiopulmonary comorbidities and risk factors, medical comorbidities, tobacco and alcohol use, cancer, and HIV/AIDS (HR, 1.34; 95% CI, 1.30-1.39). This association was also observed in people under 50 years old (HR, 1.55; 95% CI, 1.31-1.84). Conclusions: AIS is associated with an increased risk of subsequent ED and inpatient visit with zoster infection. Preventive strategies, including with currently available vaccinations, should be investigated.

Introduction: Patients with stroke face an increased risk of contracting influenza and herpes zoster. We compared vaccination rates in stroke survivors versus the general United States population. Methods: We performed a cross-sectional analysis of data from the Centers for Disease Control and Prevention (CDC) Behavioral Risk Factor Surveillance System, which is an annual, nationally representative, health survey. Respondents are asked about medical conditions and care. We used the most recent years with complete data for influenza (2018) and zoster (2017). We utilized survey procedures to estimate CDC-recommended vaccination rates for influenza (annual vaccination for all) and zoster (one-time vaccination for those at least 50 years old). Multiple logistic regression was used to compare the odds of vaccination in those with and without prior stroke, while adjusting for demographics (including income and health insurance) and comorbidities that may influence vaccination rates (obesity, diabetes, heart disease, cancer, pulmonary disease, and smoking). Results: In 2018, 8,254,136 (3.4%; 95% CI, 3.3-3.5) Americans were stroke survivors. The influenza vaccination rate was 44.4% (95% CI, 42.8-46.2) in stroke survivors and 32.8% (95% CI, 32.5-33.1) otherwise. In unadjusted models, stroke survivors were more likely to have had an influenza vaccination in the past year than those without stroke (OR, 1.6; 95% CI, 1.5-1.8). In 2017, 5,839,186 (5.7%; 95% CI, 5.5-5.9) Americans over 50 years old (i.e., eligible for zoster vaccination) were stroke survivors. The zoster vaccination rate was 30.3% (95% CI, 28.8-32.0) in stroke survivors and 27.6% (95% CI, 27.3-28.0) in those without prior stroke. Stroke survivors were more likely to have had zoster vaccination than those without stroke (OR, 1.14; 95% CI, 1.06-1.23). However, after accounting for demographics and comorbidities, stroke survivors were not more likely to be vaccinated for influenza (OR, 1.01; 95% CI, 0.93-1.10) or zoster (OR, 1.00; 95% CI, 0.90-1.12). Conclusion: Stroke survivors were not vaccinated at higher rates than expected based on demographics and comorbidities, and absolute vaccination rates were low, especially for zoster. Efforts to increase vaccination after stroke may be needed.

Background: Cervical artery dissection (CAD) often affects young, otherwise healthy people. Few data exist on whether patients with CAD face an increased vulnerability to aortic dissection. Herein we tested the hypothesis that CAD is associated with an increased risk of aortic dissection. Methods: We performed a retrospective cohort study using statewide administrative claims data from all Emergency Department visits and admissions at nonfederal hospitals in Florida from 2005 to 2015 and New York from 2006 to 2015. We used previously validated International Classification of Disease, Ninth Revision, Clinical Modification codes (ICD-9-CM) to identify patients with CAD and aortic dissection. Patients with prevalent aortic dissection were excluded. Our exposure variable was CAD and the outcome was incident aortic dissection after discharge from CAD hospitalization. Survival statistics were used to calculate incidence rates and Cox proportional hazards analysis was used to determine the association between CAD and aortic dissection while adjusting for demographics and vascular risk factors. In a secondary analysis, we excluded patients who had a traumatic CAD, defined as having concomitant ICD-9-CM codes for head or neck trauma at the time of CAD. Results: Among 19,715,114 patients, 4,537 (0.02%) had a CAD. The mean age of patients with CAD was 52.3±16.4 years. During 4.2±3.1 years of follow up, 16,571 patients were diagnosed with an aortic dissection (0.08%). The incidence of aortic dissection was 2.5 (95% CI, 1.7-3.7) per 1,000 patients per year in those with CAD versus 0.2 (95% CI, 0.2-0.2) per 1,000 patients per year in those without CAD. After adjustment for demographics and vascular risk factors, we found that CAD was associated with subsequent aortic dissection (HR 3.0, 95% CI, 2.1-4.5). Our results were similar in a secondary analysis excluding patients with traumatic CAD (HR 3.3, 95% CI, 2.2-4.8). Conclusions: In a large population-based cohort, we found that CAD was associated with a 3-fold increased risk of aortic dissection. Future studies should evaluate the utility of performing screening aortic imaging in patients with CAD.

Importance It is uncertain whether coronavirus disease 2019 (COVID-19) is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection. Objective To compare the rate of ischemic stroke between patients with COVID-19 and patients with influenza, a respiratory viral illness previously associated with stroke. Design, Setting, and Participants This retrospective cohort study was conducted at 2 academic hospitals in New York City, New York, and included adult patients with emergency department visits or hospitalizations with COVID-19 from March 4, 2020, through May 2, 2020. The comparison cohort included adults with emergency department visits or hospitalizations with influenza A/B from January 1, 2016, through May 31, 2018 (spanning moderate and severe influenza seasons). Exposures COVID-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 in the nasopharynx by polymerase chain reaction and laboratory-confirmed influenza A/B. Main Outcomes and Measures A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, mechanisms, and outcomes. We used logistic regression to compare the proportion of patients with COVID-19 with ischemic stroke vs the proportion among patients with influenza. Results Among 1916 patients with emergency department visits or hospitalizations with COVID-19, 31 (1.6%; 95% CI, 1.1%-2.3%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78 years); 18 (58%) were men. Stroke was the reason for hospital presentation in 8 cases (26%). In comparison, 3 of 1486 patients with influenza (0.2%; 95% CI, 0.0%-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was higher with COVID-19 infection than with influenza infection (odds ratio, 7.6; 95% CI, 2.3-25.2). The association persisted across sensitivity analyses adjusting for vascular risk factors, viral symptomatology, and intensive care unit admission. Conclusions and Relevance In this retrospective cohort study from 2 New York City academic hospitals, approximately 1.6% of adults with COVID-19 who visited the emergency department or were hospitalized experienced ischemic stroke, a higher rate of stroke compared with a cohort of patients with influenza. Additional studies are needed to confirm these findings and to investigate possible thrombotic mechanisms associated with COVID-19.

Key Points Question How does the risk of acute ischemic stroke compare between patients with Covid-19 and patients with influenza (a respiratory virus previously linked to stroke)? Findings In this large retrospective cohort study conducted at two academic hospitals in New York City, patients with emergency department visits and hospitalizations with Covid-19 were approximately seven times as likely to have an acute ischemic stroke as compared to patients with emergency department visits or hospitalizations with influenza. Meaning Patients with Covid-19 are at heightened risk for acute ischemic stroke as compared to patients with influenza. Importance Case series without control groups suggest that Covid-19 may cause ischemic stroke, but whether Covid-19 is associated with a higher risk of ischemic stroke than would be expected from a viral respiratory infection is uncertain. Objective To compare the rate of ischemic stroke between patients with Covid-19 and patients with influenza, a respiratory viral illness previously linked to stroke. Design A retrospective cohort study. Setting Two academic hospitals in New York City. Participants We included adult patients with emergency department visits or hospitalizations with Covid-19 from March 4, 2020 through May 2, 2020. Our comparison cohort included adult patients with emergency department visits or hospitalizations with influenza A or B from January 1, 2016 through May 31, 2018 (calendar years spanning moderate and severe influenza seasons). Exposures Covid-19 infection confirmed by evidence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the nasopharynx by polymerase chain reaction, and laboratory-confirmed influenza A or B. Main Outcomes and Measures A panel of neurologists adjudicated the primary outcome of acute ischemic stroke and its clinical characteristics, etiological mechanisms, and outcomes. We used logistic regression to compare the proportion of Covid-19 patients with ischemic stroke versus the proportion among patients with influenza. Results Among 2,132 patients with emergency department visits or hospitalizations with Covid-19, 31 patients (1.5%; 95% confidence interval [CI], 1.0%-2.1%) had an acute ischemic stroke. The median age of patients with stroke was 69 years (interquartile range, 66-78) and 58% were men. Stroke was the reason for hospital presentation in 8 (26%) cases. For our comparison cohort, we identified 1,516 patients with influenza, of whom 0.2% (95% CI, 0.0-0.6%) had an acute ischemic stroke. After adjustment for age, sex, and race, the likelihood of stroke was significantly higher with Covid-19 than with influenza infection (odds ratio, 7.5; 95% CI, 2.3-24.9). Conclusions and Relevance Approximately 1.5% of patients with emergency department visits or hospitalizations with Covid-19 experienced ischemic stroke, a rate 7.5-fold higher than in patients with influenza. Future studies should investigate the thrombotic mechanisms in Covid-19 in order to determine optimal strategies to prevent disabling complications like ischemic stroke.

Mobile stroke units (MSUs) have revolutionized emergency stroke care by delivering pre-hospital thrombolysis faster than conventional ambulance transport and in-hospital treatment. This review discusses the history of MSUs technological development, current operations and research, cost-effectiveness, and future directions. Multiple prospective and retrospective studies have shown that MSUs deliver acute ischemic stroke treatment with intravenous recombinant tissue plasminogen activator (IV r-tPA) approximately 30 min faster than conventional care. The 90-day modified Rankin Scores for patients who received IV r-tPA on the MSU compared to conventional care were not statistically different in the PHANTOM-S study. Two German studies suggest that the MSU model is cost-effective by reducing disability and improving adjusted quality-life years post-stroke. The ongoing BEST-MSU trial will be the first multicenter, randomized controlled study that will shed light on MSUs’ impact on long-term neurologic outcomes and cost-effectiveness. MSUs are effective in reducing treatment times in acute ischemic stroke without increasing adverse events. MSUs could potentially improve treatment times in large vessel occlusion and intracranial hemorrhage. Further studies are needed to assess functional outcomes and cost-effectiveness. Clinical trials are ongoing internationally.

Background Mobile stroke units ( MSU s) reduce time to intravenous thrombolysis in acute ischemic stroke. Whether this advantage exists in densely populated urban areas with many proximate hospitals is unclear. Methods and Results We evaluated patients from the METRONOME (Metropolitan New York Mobile Stroke) registry with suspected acute ischemic stroke who were transported by a bi‐institutional MSU operating in Manhattan, New York, from October 2016 to September 2017. The comparison group included patients transported to our hospitals via conventional ambulance for acute ischemic stroke during the same hours of MSU operation (Monday to Friday, 9 am to 5 pm) . Our exposure was MSU care, and our primary outcome was dispatch‐to‐thrombolysis time. We estimated mean differences in the primary outcome between both groups, adjusting for clinical, demographic, and geographic factors, including numbers of nearby designated stroke centers and population density. We identified 66 patients treated or transported by MSU and 19 patients transported by conventional ambulance. Patients receiving MSU care had significantly shorter dispatch‐to‐thrombolysis time than patients receiving conventional care (mean: 61.2 versus 91.6 minutes; P =0.001). Compared with patients receiving conventional care, patients receiving MSU care were significantly more likely to be picked up closer to a higher mean number of designated stroke centers in a 2.0‐mile radius (4.8 versus 2.7, P =0.002). In multivariable analysis, MSU care was associated with a mean decrease in dispatch‐to‐thrombolysis time of 29.7 minutes (95% CI , 6.9–52.5) compared with conventional care. Conclusions In a densely populated urban area with a high number of intermediary stroke centers, MSU care was associated with substantially quicker time to thrombolysis compared with conventional ambulance care.

Background and Purpose— We sought to model the effects of interhospital transfer network design on endovascular therapy eligibility and clinical outcomes of stroke because of large-vessel occlusion for the residents of a large city. Methods— We modeled 3 transfer network designs for New York City. In model A, patients were transferred from spoke hospitals to the closest hub hospitals with endovascular capabilities irrespective of hospital affiliation. In model B, which was considered the base case, patients were transferred to the closest affiliated hub hospitals. In model C, patients were transferred to the closest affiliated hospitals, and transfer times were adjusted to reflect full implementation of streamlined transfer protocols. Using Monte Carlo methods, we simulated the distributions of endovascular therapy eligibility and good functional outcomes (modified Rankin Scale score, 0–2) in these models. Results— In our models, 200 patients (interquartile range [IQR], 168–227) with a stroke amenable to endovascular therapy present to New York City spoke hospitals each year. Transferring patients to the closest hub hospital irrespective of affiliation (model A) resulted in 4 (IQR, 1–9) additional patients being eligible for endovascular therapy and an additional 1 (IQR, 0–2) patient achieving functional independence. Transferring patients only to affiliated hospitals while simulating full implementation of streamlined transfer protocols (model C) resulted in 17 (IQR, 3–41) additional patients being eligible for endovascular therapy and 3 (IQR, 1–8) additional patients achieving functional independence. Conclusions— Optimizing acute stroke transfer networks resulted in clinically small changes in population-level stroke outcomes in a dense, urban area.

Background: Mobile stroke units (MSUs) reduce time to thrombolytic treatment in acute ischemic stroke. It is unclear whether this time advantage persists in densely-populated urban areas with many readily-accessible hospitals. Methods: We collected clinical data, treatment times, numbers of nearby designated stroke centers (DSC), and distances traveled from suspected stroke patients transported by a single-institution MSU operating in Manhattan, New York from October 2016-September 2017. For comparison, we collected information on patients transported to our institution via conventional ambulance for acute stroke during the same hours of MSU operation (Monday-Friday, 9AM-5PM). Our exposure was MSU care, and our coprimary outcomes were dispatch-to-scene arrival and scene arrival-to-thrombolysis times. We estimated mean differences in each primary outcome between both groups, adjusting for clinical, demographic, and geographic factors. Results: We identified 66 patients transported by MSU, of whom 29 (44%) were treated with IV thrombolysis, and 19 patients transported by conventional ambulance, of whom 9 (48%) were treated with IV thrombolysis. Patients treated in the MSU traveled longer to accepting hospitals and were picked up closer to a greater number of DSCs in a 1 mile radius than non-MSU patients (Table). Despite longer median dispatch-to-ambulance arrival and ambulance arrival-to-hospital arrival times than non-MSU patients, MSU patients had shorter mean dispatch-to-thrombolysis and ambulance arrival-to-thrombolysis times. In multivariable analysis, MSU care was associated with a mean increase in dispatch-to-ambulance arrival time of 6.5 minutes (95% CI, 2.3-10.6) that was offset by a mean decrease in ambulance arrival-to-thrombolysis time of 42.2 minutes (95% CI, 31.1-53.4). Conclusions: In a densely populated urban area, MSU care was associated with substantially quicker time-to-thrombolysis when compared to conventional care.

Introduction: It is unknown how the clinical characteristics of stroke mimics treated on Mobile Stroke Units (MSUs) compare to confirmed acute strokes treated on these units. Methods: We retrospectively analyzed all patients transported by the NewYork-Presbyterian MSU in New York City from October 2016-May 2018. A vascular neurologist assigned a final diagnosis after comprehensive medical record review. Clinical data were abstracted, including comorbidities, presenting symptoms, stroke severity, acute treatments, and short-term outcomes. We compared characteristics of patients with a stroke mimic diagnosis versus those with acute ischemic or hemorrhagic stroke using targeted minimum loss-based estimation to adjust for demographics, comorbidities, NIH Stroke Scale (NIHSS) score, and intravenous tPA administration. Results: Among 92 suspected stroke patients transported by MSU, 56 (61%) had confirmed acute stroke (77% ischemic, 23% hemorrhagic) and 36 (39%) had a stroke mimic. Mimics consisted of seizure (n=8), metabolic encephalopathy (n=6), somatoform disorders (n=4), and others (n=18). The mean NIHSS score was 8 (SD 7) among mimics versus 11 (SD 8) among confirmed strokes (p=0.14). The top presenting symptoms among mimics were unilateral weakness (n=8), aphasia (n=6), confusion (n=6), and decreased consciousness (n=6). Nine mimics (25%) received tPA and none had hemorrhagic conversion; while 30 (53%) confirmed strokes received tPA and 2 (7%) had hemorrhagic conversion. There was no difference in MSU arrival-to-tPA time between groups (46 vs. 44 minutes, p=0.70). In multivariable analyses, compared to patients with confirmed stroke, mimics had significantly lower NIHSS scores, higher initial blood pressures, and shorter lengths-of-stay. Rates of death and discharge disposition were similar between groups. Conclusions: Among patients transported by a MSU for suspected stroke, two-fifths were stroke mimics. Seizure, metabolic encephalopathy, and somatoform disorders were the most common mimic diagnoses. Patients with stroke mimics had lower NIHSS scores and less often were treated with tPA.

Introduction: Stroke is a frequent complication of infective endocarditis, but there are few data and guidelines to inform appropriate neurological evaluation and imaging in this setting. We sought to determine how often patients with endocarditis undergo neuroimaging and evaluation by a neurologist. Methods: Using claims between 2009-2015 from a 5% sample of Medicare beneficiaries, we identified all patients ≥66 years of age who were hospitalized with infective endocarditis, as defined by previously validated ICD-9-CM codes. Using CPT codes and Medicare provider specialty codes from claims submitted during the hospitalization, we ascertained our outcomes of brain imaging (CT or MRI), intracranial vessel imaging (CTA, MRA, or catheter angiography), and evaluation by a neurologist. We first assessed these outcomes in all patients hospitalized with infective endocarditis, and then in the subset of patients who had a concurrent diagnosis of stroke. Stroke was ascertained using a validated ICD-9-CM code algorithm and defined as the composite of ischemic stroke, intracerebral hemorrhage, and subarachnoid hemorrhage. We used descriptive statistics with Wald confidence intervals (CI) to report crude rates. Results: Among 3,200 patients with infective endocarditis, brain imaging was performed in 34.5% (95% CI, 32.8-36.1%) of patients, intracranial vessel imaging in 4.7% (95% CI, 4.0-5.5%), and evaluation by a neurologist in 18.1% (95% CI, 16.8-19.5%). In this overall cohort, 343 (10.7%) patients had a concurrent diagnosis of stroke, 292 (85.1%) of which were ischemic. Among the 343 patients with both endocarditis and stroke, brain imaging was performed in 89.5% (95% CI, 86.3-92.7%) of cases, intracranial vessel imaging in 35.0% (95% CI, 30.0-40.0%), and neurologist evaluation in 74.6% (95% CI, 69.7-79.2%). Conclusions: In a nationally representative cohort of Medicare beneficiaries, we found that approximately one-third of patients with infective endocarditis underwent brain imaging and few were evaluated by a neurologist or received intracranial vessel imaging. Most patients with endocarditis complicated by stroke underwent head imaging and were seen by a neurologist, but a minority received intracranial vessel imaging.

A primitive neoplasm composed predominantly of nonhost cells was detected in the thoracic spinal cord and thecal sac of a 66-year-old man who had received experimental stem-cell treatment from commercial clinics.

Introduction: The effect of mechanical thrombectomy (MT) on functional outcomes after acute ischemic stroke is time-dependent. Interhospital transfer (IHT) introduces delays between stroke onset and MT. Methods: We created models of two IHT network designs in New York City involving 26 Department of Health designated stroke centers without MT capabilities (spokes) and 14 hospitals able to perform MT (hubs). In Model A, all patients were transferred from the initial hospital without MT capabilities to the closest hub irrespective of hospital affiliation. In Model B, all patients were transferred to the closest affiliated hub. We calculated the number of patients eligible for MT presenting to each spoke annually using publicly available data. With Google Traffic API software, we estimated travel times between spoke and hub hospitals under constant conditions that approximated ambulance travel. We determined the effect of transfer time on MT eligibility based on a reported 2.5% reduction in odds of MT per minute of travel delay beyond a minimum threshold. Rates of a good functional outcome (modified Rankin Scale score 0-2) were predicted based on MT trial data. Last, we calculated the efficiency advantage needed among affiliated hospitals (Model B) to offset increased travel times. Results: In our models, 371 patients (interquartile range [IQR], 229-628) with a stroke amenable to MT present to New York City spoke hospitals without MT capability each year. The mean travel time to the closest hub was 15.9 (±5.7) minutes in Model A versus 23.0 (±9.5) minutes to the closest affiliated hub in Model B. Transferring patients to the closest hub irrespective of affiliation (Model A) resulted in 71 (IQR, 44-120) additional patients being eligible for MT upon arrival and thereby an additional 14 (IQR, 8-23) patients achieving functional independence per year. To attenuate the differences in outcomes between Model A and Model B, a 10.9-minute decrease was required in the combined door-in to door-out time at the spoke plus the door-in to MT-start time at the affiliated hub. Conclusions: Optimizing IHT networks requires balancing the efficiency gains of transferring to affiliated hospitals with the travel delays resulting from bypassing nearby MT-capable centers.

Background and Purpose: We assessed whether sinus bradycardia is an early sign of atrial dysfunction that might predispose to atrial thrombogenesis and therefore be associated with stroke risk. Methods: We retrospectively used inpatient and outpatient claims data from a 5% sample of Medicare beneficiaries ≥ 66 years old from 2008-2014. Our predictor variable was sinus bradycardia, defined as ICD-9-CM code 427.8x. Our primary outcome was ischemic stroke, ascertained using a previously validated diagnosis code algorithm. Patients with ischemic stroke or atrial fibrillation/flutter prior to or at the time of a bradycardia diagnosis were excluded. We used Cox regression analysis adjusted for demographics and vascular risk factors to evaluate the association between sinus bradycardia and the risk of stroke. Patients were censored at the time of a diagnosis of atrial fibrillation/flutter. In a confirmatory analysis, we assessed whether sinus bradycardia was more common in patients with cryptogenic stroke compared to stroke due to large-artery atherosclerosis or small-vessel disease using data from the Cornell AcutE Stroke Academic Registry (CAESAR), which comprises all adults with acute stroke at New York-Presbyterian Hospital/Weill Cornell Medical Center from 2011 to 2014. Results: Among 1,417,069 Medicare beneficiaries (mean age 73.4 +/- 7.6 years) who were followed for a mean of 4.36 (+/- 1.8) years, 63,385 patients received a diagnosis of sinus bradycardia. Bradycardia was significantly associated with stroke in unadjusted analysis (hazard ratio [HR], 1.7; 95% confidence interval [CI], 1.6-1.8) but not after adjustment for demographics and vascular risk factors (HR, 0.9; 95% CI, 0.8-0.9). Among 608 patients with cryptogenic or non-cardioembolic stroke in CAESAR, 93 (15.3%) had sinus bradycardia. We did not find an association between sinus bradycardia and cryptogenic stroke after adjustment for demographics, stroke severity, insular infarction, and vascular comorbidities (OR 0.9, 95% CI 0.4-1.9). Conclusion: We found no association between sinus bradycardia and future stroke risk in stroke-free patients nor an over-representation of sinus bradycardia among cryptogenic strokes versus non-cardioembolic strokes.

Introduction: Spinal cord infarction (SCI) is a rare ischemic event comprising 1% of all strokes. In many cases of SCI, the cause remains undetermined. Case reports have suggested a relationship between cardiac embolism and SCI, but the association between the most common cause of cardiac embolism, atrial fibrillation (AF), and SCI has not been evaluated. Hypothesis: AF is associated with SCI. Methods: We performed a retrospective cohort study using inpatient and outpatient claims data from 2008-2014 on a 5% sample of Medicare beneficiaries. Our predictor variable was AF, ascertained by previously validated ICD-9-CM codes. The primary outcome was SCI, defined as ICD-9-CM diagnosis code 336.1 (vascular myelopathy) among patients who underwent spinal magnetic resonance imaging to rule out a compressive lesion and who did not have a concomitant diagnosis of degenerate joint disease, the most common cause of non-traumatic compressive myelopathy. In sensitivity analyses, we also excluded SCI cases accompanied by codes for traumatic spinal cord injury, spinal cord abscess, or spinal or aortic surgery. Cox proportional hazards analysis was used to assess the relationship between AF and SCI while adjusting for demographic characteristics and vascular risk factors. Results: Among 1,638,461 patients with a mean 3.9 years of follow-up, 423,856 had AF and 22 developed SCI. The annual incidence of SCI was 8.2 (95% confidence interval [CI], 4.4-15.4) per million in patients with AF compared to 2.3 (95% CI, 1.3-4.0) per million per year in those without AF. After adjustment for demographic characteristics and vascular risk factors, AF was associated with a higher risk of SCI (hazard ratio [HR], 4.8; 95% CI, 1.7-13.6). The association between AF and SCI persisted or grew stronger after excluding those with concomitant diagnoses of spinal cord injury, spinal abscess, and spinal or aortic surgery. Conclusions: In Medicare beneficiaries, AF was associated with increased risk of subsequent SCI. These results suggest the need for a thorough evaluation of potential underlying cardioembolic sources in patients with otherwise unexplained SCI.

A previously healthy 4-year-old girl presented with a 2-day history of severe nausea, vomiting, and diarrhea. Her symptoms began with diffuse abdominal pain followed by alternating episodes of vomiting and nonbloody diarrhea. There were no reports of sick contacts, recent travel, camping, or unusual food or water consumption. On the first day of symptoms, her primary care physician diagnosed viral gastroenteritis and stool cultures were sent to an outside laboratory. The following day, her vomiting increased in frequency and the diarrhea became streaked with blood and mucus. The patient was taken to a regional hospital where a complete blood count revealed a white blood cell count of 22 500/mL (reference interval, 5.5–15.5 × 1000/mL) with 89% neutrophils and 7% bands. A urinalysis revealed positive ketones of 150 mg/dL (reference value, negative) and a specific gravity of 1.030 (reference interval, 1.005–1.030). She was then transferred to our hospital for management of neutrophilia and dehydration. On admission, her temperature was 38.7 °C, but other vital signs and physical exam results were unremarkable. She was treated with intravenous fluids. Stool cultures for bacteria, shiga toxin, ova, and parasites were obtained. Urinalysis showed positive protein of 300 mg/dL protein (reference value, negative) and 4 red blood cells per high-power field (reference value, negative). On day 2 of admission, the patient passed cranberry-colored urine. Repeat laboratory test results at this time revealed creatinine of 1.10 mg/dL (97.2 μmol/L) (reference interval, 0.03–0.7 mg/dL), a blood urea nitrogen (BUN)4 of 26 mg/dL (9.3 mmol/L) (reference interval, 6–20 mg/dL), a hematocrit of 30.7% (reference interval, 34.0%–40.0%), and a platelet count of …

Acute myelogenous leukemias (AMLs) and endothelial cells depend on each other for survival and proliferation. Monotherapy antivascular strategies such as targeting vascular endothelial growth factor (VEGF) has limited efficacy in treating AML. Thus, in search of a multitarget antivascular treatment strategy for AML, we tested a novel vascular disrupting agent, OXi4503, alone and in combination with the anti-VEGF antibody, bevacizumab. Using xenotransplant animal models, OXi4503 treatment of human AML chloromas led to vascular disruption in leukemia cores that displayed increased leukemia cell apoptosis. However, viable rims of leukemia cells remained and were richly vascular with increased VEGF-A expression. To target this peripheral reactive angiogenesis, bevacizumab was combined with OXi4503 and abrogated viable vascular rims, thereby leading to enhanced leukemia regression. In a systemic model of primary human AML, OXi4503 regressed leukemia engraftment alone and in combination with bevacizumab. Differences in blood vessel density alone could not account for the observed regression, suggesting that OXi4503 also exhibited direct cytotoxic effects on leukemia cells. In vitro analyses confirmed this targeted effect, which was mediated by the production of reactive oxygen species and resulted in apoptosis. Together, these data show that OXi4503 alone is capable of regressing AML by a multitargeted mechanism and that the addition of bevacizumab mitigates reactive angiogenesis.

a Medicine, b Surgery, c Abstract: Background: Although innate immunity is crucial to host defense against pathogens, the extent to which innate immune mechanisms participate in the rejection of allogenic tissues in humans is unknown. We hypothesize that activation of innate immunity through Toll-like receptors (TLRs) critically regulates the development of renal allograft rejection. We have recently demonstrated decreased acute rejection in lung transplant recipients heterozygous for either of two functional polymorphisms in TLR4 associated with endotoxin hyporesponsiveness. In the present investigation, we sought to evaluate the role of innate immune activation through TLR4, in either donor or recipient, upon the development of renal allograft rejection. Methods: Patients and donors were screened for the TLR4 functional polymorphisms (Asp299Gly and Thr399Ile) by polymerase chain reaction (PCR) using sequence-specific primers. Results: The incidence of biopsy-proven acute renal allograft rejection was significantly reduced in patients receiving donor grafts heterozygous for the Asp299Gly or Thr399Ile alleles, when compared with wild type (22% vs. 0%, respectively, p 5 0.02). There was no association with recipient TLR4 allele and rejection. Conclusions: The results suggest activation of innate immunity through TLR4 in the donor kidney contributes to the development of acute rejection after renal transplantation.