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Devin M Howell,1,2 Timmy Li,1 Elizabeth Quellhorst,2 Jeffrey M Katz,3 Rohan Arora,3 Jonathan Berkowitz2 1Department of Emergency Medicine, Northwell Health, Manhasset, NY, USA; 2Center for Emergency Medical Services, Northwell Health, Syosset, NY, USA; 3Department of Neurology, Northwell Health, Manhasset, NY, USACorrespondence: Devin M Howell, Department of Emergency Medicine, Northwell Health, 300 Community Drive, Manhasset, NY, 11030, USA, Email dhowell6@northwell.eduBackground: Door-in to door-out (DIDO) time for large vessel occlusion (LVO) stroke is an emerging stroke performance measure. Initial presentation at a non-Comprehensive Stroke Center (CSC) requires a transfer process that minimizes delays. Our objective was to assess whether DIDO time for stroke patients was reduced after implementation of an AutoLaunch protocol for interfacility transfers.Methods: This was a pre-post analysis of an AutoLaunch protocol for all acute stroke patients transferred to a CSC for mechanical thrombectomy. The distribution of DIDO times between patients transferred via the AutoLaunch and traditional dispatch protocols were compared.Results: We evaluated 92 interfacility transfers, with 22 utilizing the AutoLaunch protocol and 70 utilizing traditional dispatch. Among AutoLaunch transfers, the median DIDO time was 85 minutes (IQR: 71, 133), while the median DIDO time among the traditional transfers was 109 minutes (IQR, 84, 144) (p=0.044).Conclusion: Implementation of an AutoLaunch protocol for patients with suspected LVO was associated with a reduction in DIDO time to CSCs. Further studies should evaluate patient outcomes based on transfer strategies.Keywords: AutoLaunch, interfacility, transfer, EMS, stroke

Seroprevalence of antibodies to influenza A(H1N1)pdm09 virus among 193 emergency department health care personnel was similar among 147 non-health care personnel (odds ratio 1.4, 95% CI 0.8-2.4). Working in an acute care setting did not substantially increase risk for virus infection above risk conferred by community-based exposures. [ABSTRACT FROM AUTHOR]

Host innate immunity is the first line of defense against invading pathogens, including influenza viruses. Ferrets are well recognized as the best model of influenza virus pathogenesis and transmission, but little is known about the innate immune response of ferrets after infection with this virus. The goal of this study was to investigate the contribution of localized host responses to influenza virus pathogenicity and transmissibility in this model by measuring the level of messenger RNA expression of 12 cytokines and chemokines in the upper and lower respiratory tracts of ferrets infected with H5N1, H1N1, or H3N2 influenza viruses that exhibit diverse virulence and transmissibility in ferrets. We found a strong temporal correlation between inflammatory mediators and the kinetics and frequency of transmission, clinical signs associated with transmission, peak virus shedding, and virulence. Our findings point to a link between localized innate immunity and influenza virus transmission and disease progression. [ABSTRACT FROM AUTHOR]

Background. After identifying a student with triple-reassortant swine influenza virus (SIV) infection and pig exposure at a livestock event, we investigated whether others were infected and if human-to-human transmission occurred. Methods. We conducted a cohort study and serosurvey among persons exposed to (1) event pigs, (2) other pigs, (3) the index case, and (4) persons without pig or index case exposure. Confirmed cases had respiratory specimens positive for SIV within 2 weeks of the index case's illness. Probable and suspected cases had illness and (1) exposure to any pig or (2) contact with a confirmed case preceding illness. Probable cases were seropositive. Suspected cases did not give serum samples. Results. Of 99 event pig-exposed students, 72 (73%) participated in the investigation, and 42 (42%) provided serum samples, of whom 17 (40%) were seropositive and 5 (12%) met case criteria. Of 9 students exposed to other pigs, 2 (22%) were seropositive. Of 8 index case-exposed persons and 10 without exposures, none were seropositive. Pig-exposed persons were more likely to be seropositive than persons without pig exposure (37% vs 0%, P < .01). Conclusions. We identified an outbreak of human SIV infection likely associated with a livestock event; there was no evidence of human-to-human transmission. [ABSTRACT FROM AUTHOR]

Avian influenza A viruses of the H7 subtype have resulted in more than 100 cases of human infection since 2002. Highly pathogenic avian influenza (HPAI) H7 viruses have the capacity to cause severe respiratory disease and even death; however, the induction of the human innate immune response to H7 virus infection has not been well characterized. To better understand H7 virus pathogenesis in the human respiratory tract, we employed a polarized human bronchial epithelial cell model and primary human monocyte-derived macrophages. Here, we show that infection with HPAI H7 viruses resulted in a delayed and weakened production of cytokines, including the type I interferon response, compared with infections of other influenza A subtypes, including H7 viruses of low pathogenicity. These studies revealed that H7 viruses vary greatly in their ability to activate host innate responses and may contribute to the virulence of these viruses observed in humans. [ABSTRACT FROM AUTHOR]

BACKGROUND: We conducted investigations in 2 villages in Cambodia where outbreaks of influenza H5N1 occurred among humans and poultry to determine the frequency of and risk factors for H5N1 virus transmission. METHODS: During May 2006, approximately 7 weeks after outbreaks of influenza H5N1 among poultry occurred, villagers living near households of 2 patients with influenza H5N1 were interviewed about potential H5N1 exposures and had blood samples obtained for H5N1 serological testing by microneutralization assay. A seropositive result was defined as an influenza H5N1 neutralizing antibody titer of 1:80, with confirmation by Western blot assay. A case-control study was conducted to identify risk factors for influenza H5N1 virus infection. Control subjects, who had seronegative results of tests, were matched with H5N1-seropositive persons by village residence, households with an influenza H5N1-infected poultry flock, sex, and age. RESULTS: Seven (1.0%) of 674 villagers tested seropositive for influenza H5N1 antibodies and did not report severe illness; 6 (85.7%) were male. The 7 H5N1-seropositive persons, all of whom were aged

Increasing resistance to currently available influenza antivirals highlights the need to develop alternate approaches for the prevention and/or treatment of influenza. DAS181 (Fludase), a novel sialidase fusion protein that enzymatically removes sialic acids on respiratory epithelium, exhibits potent antiviral activity against influenza A and B viruses. Here, we use a mouse model to evaluate the efficacy of DAS181 treatment against a highly pathogenic avian influenza H5N1 virus. When used to treat mice daily beginning 1 day before infection with A/Vietnam/1203/2004(H5N1) virus, DAS181 treatment at 1 mg/kg/day protected 100% of mice from fatal disease, prevented viral dissemination to the brain, and effectively blocked infection in 70% of mice. DAS181 at 1 mg/kg/day was also effective therapeutically, conferring enhanced survival of H5N1 virus-challenged mice when treatment was begun 72 h after infection. This notable antiviral activity underscores the potential utility of DAS181 as a new class of drug that is effective against influenza viruses with pandemic potential. [ABSTRACT FROM AUTHOR]

Historically, theorists and clinicians from various schools of family therapy have discussed therapist self-disclosure in terms of either helping or inhibiting therapeutic progress. Although postmodern language-based theorists and therapists accept and encourage its use, few clinical examples of therapist self-disclosure exist in the family therapy literature. In this paper, a postmodern family therapist working within the language-based tradition describes the use of self-disclosures with a couple. The therapist then reviews the effects of those self-disclosures through the eyes of husband, wife, and therapist. [ABSTRACT FROM AUTHOR]

The first outbreak of avian influenza A (H5N1) occurred among humans in Hong Kong in 1997. To estimate the risk of person-to-person transmission, a retrospective cohort study was conducted to compare the prevalence of H5N1 antibody among health care workers (HCWs) exposed to H5N1 case-patients with the prevalence among nonexposed HCWs. Information on H5N1 case-patient and poultry exposures and blood samples for H5N1-specific antibody testing were collected. Eight (3.7%) of 217 exposed and 2 (0.7%) of 309 nonexposed HCWs were H5N1 seropositive (P=.01). The difference remained significant after controlling for poultry exposure (P=.01). This study presents the first epidemiologic evidence that H5N1 viruses were transmitted from patients to HCWs. Human-to-human transmission of avian influenza may increase the chances for the emergence of a novel influenza virus with pandemic potential. Copyright © 2000 The University of Chicago [ABSTRACT FROM AUTHOR]

Introduction: Avian H5N1 influenza viruses currently circulating in southeast Asia could potentially cause the next pandemic. However, currently licensed human vaccines are subtype-specific and do not protect against these H5N1 viruses. We aimed to develop an influenza vaccine and assessed its immunogenicity and efficacy to confer protection in BALB/c mice.Methods: We developed an egg-independent strategy to combat the avian influenza virus, because the virus is highly lethal to chickens and the maintenance of a constant supply of embryonated eggs would be difficult in a pandemic. We used a replication-incompetent, human adenoviral-vector-based, haemagglutinin subtype 5 influenza vaccine (HAd-H5HA), which induces both humoral and cell-mediated immune responses against avian H5N1 influenza viruses isolated from people.Findings: Immunisation of mice with HAd-H5HA provided effective protection from H5N1 disease, death, and primary viral replication (p<0.0001) against antigenically distinct strains of H5N1 influenza viruses. Unlike the recombinant H5HA vaccine, which is based on a traditional subunit vaccine approach, HAd-H5HA vaccine induced a three-fold to eight-fold increase in HA-518-epitope-specific interferon-gamma-secreting CD8 T cells (p=0.01).Interpretation: Our findings highlight the potential of an Ad-vector-based delivery system, which is both egg-independent and adjuvant-independent and offers stockpiling options for the development of a pandemic influenza vaccine. [ABSTRACT FROM AUTHOR]

Background: This report summarizes the discussions and conclusions from the "Correlates of Protection for Next Generation Influenza Vaccines: Lessons Learned from the COVID-19 Pandemic" meeting, which took place in Seattle, USA, from March 1, 2023, to March 3, 2023., Conclusions: Discussions around influenza virus correlates of protection and their use continued from where the discussion had been left off in 2019. While there was not much progress in the influenza field itself, many lessons learned during the coronavirus disease 2019 (COVID-19) pandemic, especially the importance of mucosal immunity, were discussed and can directly be applied to influenza correlates of protection., (© 2024 The Author(s). Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Objectives: As indications for acute ischemic stroke treatment expand, it is unclear whether disparities in treatment utilization and outcome still exist. The main objective of this study was to investigate disparities in acute ischemic stroke treatment and determine impact on outcome., Materials and Methods: Retrospective observational cohort study of consecutive ischemic stroke admissions to a comprehensive stroke center from 2012-2021 was performed. Primary exposure was intravenous thrombolysis and/or endovascular thrombectomy. Primary end points were discharge modified Rankin Scale, home disposition, and expired/hospice. Multivariable logistic regression analyses were conducted to elucidate disparities in treatment utilization and determine impact on outcome., Results: Of 517,615 inpatient visits, there were 7,540 (1.46 %) ischemic stroke admissions, increasing from 1.14 % to 1.79 % from 2012-2021. Intravenous thrombolysis significantly decreased from 14.4 % to 9.8 % while endovascular thrombectomy significantly increased from 0.8 % to 10.5 %. Both intravenous thrombolysis and endovascular thrombectomy increased odds of discharge home and modified Rankin Scale 0-2, and thrombectomy decreased odds of expired/hospice. After adjusting for covariates, decreased odds of thrombectomy was associated with Medicaid insurance (Odds Ratio [95 % Confidence Interval] 0.55 [0.32-0.93]), age 80+ (0.49 [0.35-0.69]), prior stroke (0.49 [0.31-0.77]), and diabetes mellitus (0.55 [0.39-0.79]), while low median household income (<$80,000/year) increased odds of no acute treatment (1.34 [1.16-1.56]). No sex or racial disparities were observed. Medicaid and low-income were not associated with worse clinical outcomes., Conclusions: Less endovascular thrombectomy occurred in Medicaid, older, prior stroke, and diabetic patients, while low-income was associated with no treatment. The observed socioeconomic disparities did not impact discharge outcome., Competing Interests: Declaration of competing interest Dr. Katz, Dr. Wang, and Dr. Sanmartin received grants from Siemens Healthineers during the conduct of the study. Dr. Katz is a paid consultant for Xcath, Inc., and speaker for Medtronic, Inc. Dr. Sanelli received research grants from the Harvey L. Neiman Health Policy Institute and Siemens Healthineers during the conduct of this study., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Importance: Recent large infarct thrombectomy trials used heterogeneous imaging modalities and time windows for patient selection. Noncontrast computed tomographic (CT) scan is the most common stroke imaging approach. It remains uncertain whether thrombectomy is effective for patients with large infarcts identified using noncontrast CT alone within 24 hours of stroke onset., Objective: To evaluate the effect of thrombectomy in patients with a large infarct on a noncontrast CT scan within 24 hours of onset., Design, Setting, and Participants: Open-label, blinded-end point, bayesian-adaptive randomized trial with interim analyses for early stopping (futility or success) or population enrichment, which was conducted at 47 US academic and community-based stroke thrombectomy centers. Three hundred patients presenting within 24 hours with anterior-circulation, large-vessel occlusion and large infarct on noncontrast CT scan, with Alberta Stroke Program Early CT Scores of 2 to 5, were randomized to undergo thrombectomy or usual care. Enrollment occurred July 16, 2019 to October 17, 2022; final follow-up, January 25, 2023., Intervention: The intervention patients (n = 152) underwent endovascular treatment using standard thrombectomy devices and usual medical care. Control patients (n = 148) underwent usual medical care alone., Main Outcomes and Measures: The primary efficacy end point was improvement in 90-day functional outcome measured using mean utility-weighted modified Rankin Scale (UW-mRS) scores (range, 0 [death or severe disability] to 10 [no symptoms]; minimum clinically important difference, 0.3). A bayesian model determined the posterior probability that the intervention would be superior to usual care; statistical significance was a 1-sided posterior probability of .975 or more. The primary adverse event end point was 90-day mortality; secondary adverse event end points included symptomatic intracranial hemorrhage and radiographic intracranial hemorrhage., Results: The trial enrolled 300 patients (152 intervention, 148 control; 138 females [46%]; median age, 67 years), without early stopping or enrichment; 297 patients completed the 90-day follow-up. The mean (SD) 90-day UW-mRS score was 2.93 (3.39) for the intervention group vs 2.27 (2.98) for the control group with an adjusted difference of 0.63 (95% credible interval [CrI], -0.09 to 1.34; posterior probability for superiority of thrombectomy, .96). The 90-day mortality was similar between groups: 35.3% (53 of 150) for the intervention group vs 33.3% (49 of 147) for the control group. Six of 151 patients (4.0%) in the intervention group and 2 of 149 (1.3%) in the control group experienced 24-hour symptomatic intracranial hemorrhage. Fourteen patients of 148 (9.5%) in the intervention group vs 4 of 146 (2.7%) in the control group experienced parenchymal hematoma type 1 hemorrhages; 14 (9.5%) in the intervention group vs 5 (3.4%) in the control group experienced parenchymal hematoma type 2 hemorrhages; and 24 (16.2%) in the intervention group vs 9 (6.2%) in the control group experienced subarachnoid hemorrhages., Conclusions and Relevance: Among patients with a large infarct on noncontrast CT within 24 hours, thrombectomy did not demonstrate improvement in functional outcomes. But the width of the credible interval around the effect estimate includes the possibility of both no important effect and a clinically relevant benefit, so the potential role of thrombectomy with this imaging approach and time window will likely require additional study., Trial Registration: ClinicalTrials.gov Identifier: NCT03805308.

Background and Objectives: Moyamoya disease (MMD) is a chronic steno-occlusive disease of the intracranial circulation that depends on neoangiogenesis of collateral vessels to maintain cerebral perfusion and is primarily managed with cerebral revascularization surgery. A quantitative assessment of preoperative and postoperative collateral flow using quantitative magnetic resonance angiography with noninvasive optimal vessel analysis (NOVA) was used to illustrate the impact of revascularization on cerebral flow distribution., Methods: A retrospective review of patients with unilateral MMD who underwent direct, indirect, or combined direct/indirect cerebral revascularization surgery was conducted between 2011 and 2020. Using NOVA, flow was measured at the anterior cerebral artery (ACA), ACA distal to the anterior communicating artery (A2), middle cerebral artery (MCA), posterior cerebral artery (PCA), and PCA distal to the posterior communicating artery (P2). Pial flow (A2 + P2) and collateral flow (ipsilateral [A2 + P2])-(contralateral [A2 + P2]) were measured and compared before and after revascularization surgery. Total hemispheric flow (MCA + A2 + P2) with the addition of the bypass graft flow postoperatively was likewise measured., Results: Thirty-four patients with unilateral MMD underwent cerebral revascularization. Median collateral flow significantly decreased from 68 to 39.5 mL/min ( P = .007) after bypass. Hemispheres with maintained measurable bypass signal on postoperative NOVA demonstrated significant reduction in median collateral flow after bypass ( P = .002). Median total hemispheric flow significantly increased from 227 mL/min to 247 mL/min ( P = .007) after bypass. Only one patient suffered an ipsilateral ischemic stroke, and no patients suffered a hemorrhage during follow-up., Conclusion: NOVA measurements demonstrate a reduction in pial collateral flow and an increase in total hemispheric flow after bypass for MMD, likely representing a decrease in leptomeningeal collateral stress on the distal ACA and PCA territories. Further studies with these measures in larger cohorts may elucidate a role for NOVA in predicting the risk of ischemic and hemorrhagic events in MMD., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

Background: Socioeconomically disadvantaged neighborhoods are particularly vulnerable to heat-related illnesses. We aim to investigate the association between the heat vulnerability index (HVI), an established neighborhood-level metric of heat-related mortality risk, and acute ischemic stroke (AIS) severity., Methods: We conducted a retrospective analysis of consecutive AIS admissions to a comprehensive stroke center between 2012 and 2021. Stroke severity was defined upon admission based on the National Institutes of Health Stroke Scale (NIHSS). Demographic, socioeconomic, and clinical characteristics were extracted from electronic health records. HVI status was assigned using residential ZIP codes. Multivariable logistic regression analyses were performed., Results: Of 3429 AIS admissions, 1123 (32.8%) were from high-HVI (scores 4-5) neighborhoods and 868 (25.3%) had severe stroke (NIHSS score ≥ 10). In the multivariable regression model with stepwise selection, a high HVI was independently associated with severe stroke (adjusted odds ratio: 1.40 [95% confidence interval 1.16-1.69])., Conclusions: The association between a high HVI and severe stroke underscores the importance of targeting policy interventions to mitigate heat-related illness in socioeconomically disadvantaged neighborhoods.

Objective: Our purpose was to synthesize evidence in the literature to determine the diagnostic accuracy of cone-beam CT (CBCT) for the detection of intracranial hemorrhage (ICH) and hemorrhage types, including intraparenchymal hemorrhage (IPH), subarachnoid hemorrhage (SAH), and intraventricular hemorrhage (IVH)., Methods: We performed a meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analyses guidelines. Our protocol was registered with International Prospective Register of Systematic Reviews (PROSPERO-CRD42021261915). Systematic searches were last performed on April 30, 2024, in EMBASE, PubMed, Web-of-Science, Scopus, and Cumulative Index to Nursing and Allied Health Literature databases. Inclusion criteria were (1) studies reporting diagnostic metrics of CBCT for ICH and (2) studies using a reference standard to determine ICH. Exclusion criteria were (1) case reports, abstracts, reviews and (2) studies without patient-level data. Pooled estimates and 95% confidence intervals (CIs) were calculated for diagnostic odds ratios (DORs), sensitivity, and specificity using random-effects and common-effects models. Mixed methods appraisal tool was used to evaluate risk of bias., Results: Seven studies were included in the meta-analysis yielding 466 patients. Mean or median age ranged from 54 to 75 years. Female patients represented 51.4% (222 of 432) in reported studies. Multidetector CT was the reference standard in all studies. DOR, pooled sensitivity, and pooled specificity for ICH were 5.28 (95% CI: 4.11-6.46), 0.88 (95% CI: 0.79-0.97), and 0.99 (95% CI: 0.98-1.0). Pooled sensitivity for IPH, SAH, and IVH was 0.98 (95% CI: 0.95-1.0), 0.82 (95% CI: 0.57-1.0), and 0.78 (95% CI: 0.55-1.0). Pooled specificity for IPH, SAH, and IVH was 0.99 (95% CI: 0.98-1.0), 0.99 (95% CI: 0.97-1.0), and 1.0 (95% CI: 0.98-1.0)., Discussion: CBCT had moderate DOR and high pooled specificity for ICH and hemorrhage types. However, pooled sensitivity varied by hemorrhage type, with the highest sensitivity for IPH, followed by SAH and IVH., (Copyright © 2024 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Background: Although patients with COVID-19 have a higher risk of acute ischemic stroke (AIS), the impact on stroke outcomes remains uncertain., Aims: To determine the clinical outcomes of patients with AIS and COVID-19 (AIS-COVID+)., Methods: We performed a systematic review and meta-analysis following the Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) guidelines. Our protocol was registered with the International Prospective Register of Systematic Reviews (CRD42020211977). Systematic searches were last performed on June 3, 2021 in EMBASE, PubMed, Web-of-Science, Scopus, and CINAHL Databases., Inclusion Criteria: (1) studies reporting outcomes on AIS-COVID+; (2) original articles published in 2020 or later; (3) study participants aged ≥18 years., Exclusion Criteria: (1) case reports with <5 patients, abstracts, review articles; (2) studies analyzing novel interventions. Risk of bias was assessed using the Mixed Methods Appraisal Tool. Random-effects models estimated the pooled OR and 95% confidence intervals (95% CI) for mortality, modified Rankin Scale (mRS) score, length of stay (LOS), and discharge disposition., Results: Of the 43 selected studies, 46.5% (20/43) reported patients with AIS without COVID-19 (AIS-COVID-) for comparison. Random-effects model included 7294 AIS-COVID+ and 158 401 AIS-COVID-. Compared with AIS-COVID-, AIS-COVID+ patients had higher in-hospital mortality (OR=3.87 (95% CI 2.75 to 5.45), P<0.001), less mRS scores 0-2 (OR=0.53 (95% CI 0.46 to 0.62), P<0.001), longer LOS (mean difference=4.21 days (95% CI 1.96 to 6.47), P<0.001), and less home discharge (OR=0.31 (95% CI 0.21 to 0.47), P<0.001)., Conclusions: Patients with AIS-COVID had worse outcomes, with almost fourfold increased mortality, half the odds of mRS scores 0-2, and one-third the odds of home discharge. These findings confirm the significant impact of COVID-19 on early stroke outcomes., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Direct-to-angiography (DTA) is a novel care pathway for endovascular treatment (EVT) of acute ischemic stroke (AIS) that has been shown to reduce time-to-treatment and improve clinical outcomes for EVT-eligible patients. The institutional costs of adopting the DTA pathway and the many factors affecting costs have not been studied. In this study, we assess the costs and main cost drivers associated with the DTA pathway compared to the conventional CT pathway for patients presenting with AIS and suspected LVO in the anterior circulation., Methods: Time driven activity based costing (TDABC) model was used to compare costs of DTA and conventional pathways from the healthcare institution perspective. Process mapping was used to outline all activities and resources (personnel, equipment, materials) needed for each step in both pathways. The cost model was developed using our institutional patient database and average New York state wages for personnel costs. Total, incremental and proportional costs were calculated based on institutional and patient factors affecting the pathways., Results: DTA pathway accrued additional $82,583.61 (9%) in total costs compared to the conventional approach for all AIS patients. For EVT-ineligible patients, the DTA pathway incurred additional $82,964.37 (76%) in total costs compared to the CT pathway. For EVT eligible patients, the total and per-patient costs were greater in the CT pathway by $380.76 (0.04%) and $5.60 (0.04%) respectively., Conclusion: As the DTA pathway incurred additional $82,964.37 for EVT-ineligible patients, appropriate patient selection criteria are needed to avoid transferring EVT-ineligible patients to the angiography suite., Competing Interests: Declaration of competing interest Kinpritma Sangha and Artem Boltyenkov are employees and shareholders of Siemens Medical Solutions USA, Inc. Jeffrey M. Katz, and Pina C. Sanelli receive research support from Siemens Medical Solutions USA, Inc., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background and Purpose: Tenecteplase is increasingly being used as a first-line treatment for acute ischemic stroke after several randomized studies demonstrated its safety and efficacy, resulting in a massive increase in the number of published studies on this topic. Our aim was to investigate the most impactful authors and relevant journals that have been instrumental in validating this treatment, in hopes of identifying objective research trends that may assist scientists, health organizations, and funding agencies to collaborate and plan future avenues of research., Methods: Using the search terms "Tenecteplase" and "Tenecteplase" AND "Stroke," 2683 and 1150 references were queried, respectively, using the abstract and citation database, Scopus. Scopus Citation Analysis was used to categorize the countries and authors who produced the most research. Metadata was retrieved and transferred to bibliographic visualization software, VOSviewer, for co-authorship and co-occurrence analyses to identify trends in tenecteplase research., Results: Data visualization software identified three tenecteplase research clusters - myocardial infarction, pulmonary embolism, and acute ischemic stroke. Our bibliographic analysis graphically identified that ischemic stroke currently leads both myocardial infarction and pulmonary embolism in annual publications pertaining to tenecteplase therapy, and further pinpointed perfusion imaging and wake-up strokes as the most relevant areas of study. The United States led all countries in tenecteplase publications, including exclusively stroke studies. The European Heart Journal led all journals in overall publications, while Stroke led all journals in stroke-related studies., Conclusions: Through the use of bibliographic analysis and data visualization, we identified major articles and journals that reflected and shaped the current landscape of tenecteplase; recognized authors who engaged in tenecteplase research as it progressed from cardiopulmonary disease to stroke; and postulated future avenues of research., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Introduction: Current methods for angioplasty and stenting of the intracranial vasculature for neurointervention are limited. The Wingspan Stent System is Food and Drug Administration (FDA) approved with human device exemption for a limited patient group and despite numerous prospective registries and trials demonstrating reasonable safety, still carries warnings from the FDA for its use. Given these limitations, we present the technical nuances and outcomes of the off-label use of the Resolute Onyx drug-eluting stent (DES) for neurointerventional purposes., Methods: Retrospective chart review of all patients undergoing a neurointerventional procedure with the Resolute Onyx DES was done from January 2017-2021. The Resolute Onyx is a coronary balloon-mounted drug-eluting (zotarolimus) single wire laser cut stent. Technical details and procedural outcomes were collected., Results: In total 40 patients had attempted placement of the Resolute Onyx DES with procedural success in 95% of patients. The most common vessel stented was the basilar artery, 30% (12/40). The most common indication was intracranial atherosclerotic disease in 62.5% (25/40) patients, followed by acute stroke in 17.5% (7/40) of patients. The technical and procedural outcomes were excellent with only one technical complication (2.5%)., Conclusions: This series describes the initial technical safety and utility of utilizing a new generation balloon-mounted drug-eluting stent for neurointerventional purposes. This stent offers the potential for improved navigability, delivery, and outcomes compared to current neurointerventional options and warrants further study., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Prior studies have revealed significant socio-economic disparities in neuro-imaging and treatment utilization for patients with acute ischemic stroke (AIS). In this study, we sought to evaluate whether a sex-based disparity exists in neuro-imaging and to determine its etiology and association with acute treatment and outcomes., Materials and Methods: This was a retrospective study of consecutive patients with AIS admitted to a comprehensive stroke center between 2012 and 2021. Patient demographic and clinical characteristics, neuro-imaging, acute treatment, and early clinical outcomes were extracted from the electronic medical records. Trend analysis, bivariate analysis of patient characteristics by sex, and multivariable logistic regression analyses were conducted., Results: Of the 7,540 AIS episodes registered from 2012 to 2021, 47.9% were female patients. After adjusting for demographic, clinical, and temporal factors, significantly higher utilization of CTA was found for male patients (odds ratio = 1.20 [95% confidence interval 1.07-1.34]), particularly from socio-economically advantaged groups, and in years 2015 and 2019, representing the years endovascular thrombectomy recommendations changed. Despite this, male patients had significantly lower intravenous thrombolysis utilization (odds ratio = 0.83 [95% confidence interval 0.71-0.96]) and similar endovascular thrombectomy rates as female patients. There were no significant sex differences in early clinical outcomes, and no relevant clinical or demographic factors explained the CT angiography utilization disparity., Conclusion: Despite higher CT angiography utilization in socio-economically advantaged male patients with AIS, likely overutilization due to implicit biases following guideline updates, the rates of acute treatment, and early clinical outcomes were unaffected., (Copyright © 2023 American College of Radiology. Published by Elsevier Inc. All rights reserved.)

Introduction: Flow augmentation is the mainstay treatment for moyamoya disease as hemodynamic failure is believed to be the dominant mechanism. We aimed to investigate the mechanisms of stroke in moyamoya disease by assessing the relationship between infarction patterns and quantitative magnetic resonance angiography flow state., Methods: A retrospective study of adult patients with suspected MMD who presented with MRI confirmed acute ischemic stroke predating or following QMRA by a maximum of six months between 2009 and 2021 was conducted. Of the 177 consecutive patients with MMD who received QMRA, 35 patients, consisting of 41 hemispheres, met inclusion criteria. Flow-status was dichotomized into low-flow and normal-flow state based on previously established criteria., Results: Mixed infarction pattern was the most frequent finding (70.7 %), followed by embolic (17.1 %), perforator (7.3 %), and internal borderzone (IBZ) (4.9 %). Infarction patterns were further dichotomized into IBZ+ (internal borderzone alone or mixed) and IBZ- (no internal borderzone constituent). Low-flow states were not significantly more frequent in the IBZ+ compared to IBZ- population (48.4 % vs. 20.0 %, p = 0.14). Ipsilateral posterior cerebral artery fractional flow was significantly higher with IBZ+ compared to IBZ- (345.0 % vs. 214.7 %, p = 0.04)., Conclusion: Mixed infarction pattern was the most common pattern of infarction in patients with moyamoya disease, implying hypoperfusion and thromboembolism are codominant stroke mechanisms. An association between ICA flow status and infarction pattern was not found, although QMRA evidence of more robust posterior cerebral artery leptomeningeal collaterals was found in patients with a hypoperfusion contribution to their stroke mechanism., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest.., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Importance: The STROKE AF study found that in patients with prior ischemic stroke attributed to large-artery atherosclerotic disease (LAD) or small-vessel occlusive disease (SVD), 12% developed AF over 1 year when monitored with an insertable cardiac monitor (ICM). The occurrence over subsequent years is unknown., Objectives: To compare the rates of AF detection through 3 years of follow-up between an ICM vs site-specific usual care in patients with prior ischemic stroke attributed to LAD or SVD., Design, Setting, and Participants: This multicenter, randomized (1:1) clinical trial took place at 33 sites in the US with enrollment between April 2016 and July 2019 and 3-year follow-up through July 2022. Eligible patients were aged 60 years or older, or aged 50 to 59 years with at least 1 additional stroke risk factor and had an index ischemic stroke attributed to LAD or SVD within 10 days prior to ICM insertion. Of the 496 patients enrolled, 492 were randomized and 4 were excluded., Interventions: ICM monitoring vs site-specific usual care., Main Outcomes and Measures: The prespecified long-term outcome of the trial was AF detection through study follow-up (up to 3 years). AF was defined as an episode lasting more than 30 seconds, adjudicated by an expert committee., Results: In total, 492 patients were randomized and included in the analyses (median [IQR] age, 66 [60-74] years; 307 men [62.4%] and 185 women [37.6%]), of whom 314 completed 3-year follow-up (63.8%). The incidence rate of AF at 3 years was 21.7% (46 patients) in the ICM group vs 2.4% (5 patients) in the control group (hazard ratio, 10.0; 95% CI, 4.0-25.2; P < .001)., Conclusions and Relevance: Patients with ischemic stroke attributed to LAD or SVD face an increasing risk of AF over time and most of the AF occurrences are not reliably detected by standard medical monitoring methods. One year of negative monitoring should not reassure clinicians that patients who have experienced stroke will not develop AF over the next 2 years., Trial Registration: ClinicalTrials.gov Identifier: NCT02700945.

Functional human brown and white adipose tissue (BAT and WAT) are vital for thermoregulation and nutritional homeostasis, while obesity and other stressors lead, respectively, to cold intolerance and metabolic disease. Understanding BAT and WAT physiology and dysfunction necessitates clinical trials complemented by mechanistic experiments at the cellular level. These require standardized in vitro models, currently lacking, that establish references for gene expression and function. We generated and characterized a pair of immortalized, clonal human brown (hBA) and white (hWA) preadipocytes derived from the perirenal and subcutaneous depots, respectively, of a 40-year-old male individual. Cells were immortalized with hTERT and confirmed to be of a mesenchymal, nonhematopoietic lineage based on fluorescence-activated cell sorting and DNA barcoding. Functional assessments showed that the hWA and hBA phenocopied primary adipocytes in terms of adrenergic signaling, lipolysis, and thermogenesis. Compared to hWA, hBA were metabolically distinct, with higher rates of glucose uptake and lactate metabolism, and greater basal, maximal, and nonmitochondrial respiration, providing a mechanistic explanation for the association between obesity and BAT dysfunction. The hBA also responded to the stress of maximal respiration by using both endogenous and exogenous fatty acids. In contrast to certain mouse models, hBA adrenergic thermogenesis was mediated by several mechanisms, not principally via uncoupling protein 1 (UCP1). Transcriptomics via RNA-seq were consistent with the functional studies and established a molecular signature for each cell type before and after differentiation. These standardized cells are anticipated to become a common resource for future physiological, pharmacological, and genetic studies of human adipocytes., (Published by Oxford University Press on behalf of the Endocrine Society 2023.)

Background: Evidence has shown that endovascular thrombectomy (EVT) treatment improves clinical outcomes. Yet, its benefit remains uncertain in patients with large established infarcts as defined by ASPECTS (Alberta Stroke Program Early CT Score) <6. This study evaluates the cost-effectiveness of EVT, compared with standard care (SC), in acute ischemic stroke (AIS) patients with ASPECTS 3-5., Methods: An economic evaluation study was performed combining a decision tree and Markov model to estimate lifetime costs (2021 US$) and quality-adjusted life years (QALYs) of AIS patients with ASPECTS 3-5. Incremental cost-effectiveness ratios (ICERs), net monetary benefits (NMBs), and deterministic one-way and two-way sensitivity analyses were performed. Probabilistic sensitivity analyses were also performed to evaluate the robustness of our model., Results: Compared with SC, the cost-effectiveness analyses revealed that EVT yields higher lifetime benefits (2.20 QALYs vs 1.41 QALYs) with higher lifetime healthcare cost per patient ($285 861 vs $272 954). The difference in health benefits between EVT and SC was 0.79 QALYs, equivalent to 288 additional days of healthy life per patient. Even though EVT is more costly than SC alone, it is still cost-effective given better outcomes with ICER of $16 239/QALY. The probabilistic sensitivity analyses indicated that EVT was the most cost-effective strategy in 98.8% (9882 of 10 000) of iterations at the willingness-to-pay threshold of $100 000 per QALY., Conclusions: The results of this study suggest that EVT is cost-effective in AIS patients with a large ischemic core (ASPECTS 3-5), compared with SC alone over the patient's lifetime., Competing Interests: Competing interests: MXS and KS hold a Visiting Scholar appointment at the Feinstein Institutes for Medical Research in the Center for Health Innovations and Outcomes Research and are employees of Siemens Medical Solutions USA Inc. MXS and KS are shareholders of Siemens Healthineers. JMK, JW and PCS receive research support from Siemens Healthineers., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Parent-centered emotion socialization beliefs that children should manage their emotions on their own without parent support may seem convenient for parents but may actually relate to greater parenting stress if this approach is incompatible with children's developmental needs. We explored relations between mothers' and fathers' parent-centered autonomy beliefs about children's emotions and their parenting stress, controlling for child behavior problems and parent education. We also examined whether these associations varied depending on child age. Participants included 142 mothers and 60 paired fathers with a 5- to 8-year-old child who completed survey measures on parenting and child behavior. The sample was primarily White (59%) or Hispanic (20%) and low (44%) to middle income (47%). Path analyses revealed significant actor effects, such that mothers and fathers who endorsed more parent-centered emotion socialization beliefs reported greater parenting stress. Partner effects showed that mothers also reported greater parenting stress when their partners endorsed more parent-centered emotion socialization beliefs. Child age did not moderate these associations. Findings are discussed in terms of developmentally appropriate parenting expectations, gender roles for family emotion work, and practical implications., (© 2023 Family Process Institute.)

Background and Objectives: Stroke is a major cause of morbidity and mortality worldwide, and intracranial stenoses increase the risk for stroke. Superficial temporal artery to middle cerebral artery bypass can be beneficial in selected patients with non-moyamoya steno-occlusive disease, however data is limited regarding the postoperative occurrence of hyperperfusion syndrome in this population. This case series describes the outcomes and complications, including hyperperfusion, in these patients who underwent bypass., Methods: This is a retrospective review of bypass procedures done for medically refractory intracranial stenosis at a single institution by a single surgeon between 2014 and 2021., Results: 30 patients underwent 33 bypass procedures for unequivocal non-moyamoya steno-occlusive disease. All patients had immediate bypass patency on post-operative day one. Major perioperative complications (9%) included one stroke and two cases of hyperperfusion syndrome. Minor perioperative complications (12%) included two seizures, one superficial wound infection and one deep vein thrombosis. Modified Rankin Score improved in 20 patients (74%), worsened in one patient (4%), and remained stable in seven patients (22%) at the last follow up. Twenty-three patients (85%) had scores ≤ 2. The recurrent stroke rate was 3% at 30 days and 7% at two years. The bypass patency rate at one year was 87.5%., Conclusion: In this series, bypass for patients with medically refractory non-moyamoya steno-occlusive disease was well tolerated and effective, with overall favorable outcomes. The occurrence of hyperperfusion syndrome is rare but significant and should be considered in post-operative management of this population., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Published by Elsevier Inc.)

Background and Purpose: We aimed to investigate the relationship between the degree and location of vertebrobasilar stenosis and quantitative magnetic resonance angiography (QMRA) distal flow., Methods: We retrospectively reviewed patients who presented with acute ischemic stroke with ≥50% stenosis of the extracranial or intracranial vertebral or basilar arteries, and QMRA performed within 1 year of stroke. Standardized techniques were used to measure stenosis and to dichotomize vertebrobasilar distal flow status. Patients were grouped based on the involved artery and the severity of disease. All p-values were calculated using chi-squared analysis and Fisher exact test with statistical significance defined as p < .05., Results: Sixty-nine patients met study inclusion, consisting of 31 with low distal flow and 38 with normal distal flow. The presence of severe stenosis or occlusion was 100% sensitive, but only 47% predictive and 26% specific of a low distal flow state. Bilateral vertebral disease was only 55% sensitive but was 71% predictive and 82% specific of a low-flow state and was five times and nearly three times more likely to result in a low-flow state compared to unilateral vertebral disease (14%) and isolated basilar disease (28%), respectively., Conclusions: Severe stenosis of ≥70% may mark the minimal threshold required to cause hemodynamic insufficiency in the posterior circulation, but nearly half of these patients may remain hemodynamically sufficient. Bilateral vertebral stenosis resulted in a fivefold increase in QMRA low distal flow status compared to unilateral vertebral disease. These results may have implications in the design of future treatment trials of intracranial atherosclerotic disease., (© 2023 American Society of Neuroimaging.)