A recombinant herpes virus expressing influenza hemagglutinin confers protection and induces antibody-dependent cellular cytotoxicity.

Despite widespread yearly vaccination, influenza leads to significant morbidity and mortality across the globe. To make a more broadly protective influenza vaccine, it may be necessary to elicit antibodies that can activate effector functions in immune cells, such as antibody-dependent cellular cytotoxicity (ADCC). There is growing evidence supporting the necessity for ADCC in protection against influenza and herpes simplex virus (HSV), among other infectious diseases. An HSV-2 strain lacking the essential glycoprotein D (gD), was used to create ΔgD-2, which is a highly protective vaccine against lethal HSV-1 and HSV-2 infection in mice. It also elicits high levels of IgG2c antibodies that bind FcγRIV, a receptor that activates ADCC. To make an ADCC-eliciting influenza vaccine, we cloned the hemagglutinin (HA) gene from an H1N1 influenza A strain into the ΔgD-2 HSV vector. Vaccination with ΔgD-2::HAPR8 was protective against homologous influenza challenge and elicited an antibody response against HA that inhibits hemagglutination (HAI+), is predominantly IgG2c, strongly activates FcγRIV, and protects against influenza challenge following passive immunization of naïve mice. Prior exposure of mice to HSV-1, HSV-2, or a replication-defective HSV-2 vaccine (dl5-29) does not reduce protection against influenza by ΔgD-2::HAPR8 This vaccine also continues to elicit protection against both HSV-1 and HSV-2, including high levels of IgG2c antibodies against HSV-2. Mice lacking the interferon-α/ß receptor and mice lacking the interferon-γ receptor were also protected against influenza challenge by ΔgD-2::HAPR8 Our results suggest that ΔgD-2 can be used as a vaccine vector against other pathogens, while also eliciting protective anti-HSV immunity.

Biomarkers of Coagulation and Inflammation in COVID-19-Associated Ischemic Stroke.

[Figure: see text].

A Predictive Model for Functional Outcome in Patients with Acute Ischemic Stroke Undergoing Endovascular Thrombectomy.

INTRODUCTION: Endovascular thrombectomy (EVT) is a well-established treatment of acute ischemic stroke. Variability in outcomes among thrombectomy patients results in a need for patient centered approaches to recovery. Identifying key factors that are associated with outcomes can help prognosticate and direct resources for continued improvement post-treatment. Thus, we developed a comprehensive predictive model of short-term outcomes post-thrombectomy. METHODS: This is a retrospective chart review of adult patients who underwent EVT at our institution over the last four years. Primary outcome was dichotomized 90-day mRS (mRS 0-2 v mRS 3-6). Bivariate analyses were conducted, followed by logistic regression modelling via a backward-elimination approach to identify the best fit predictive model. RESULTS: 326 thrombectomies were performed; 230 cases were included in the model. In the final predictive model, adjusting for age, gender, race, diabetes, and presenting NIHSS, pre-admission mRS = 0-2 (OR 18.1; 95% 3.44-95.48; p < 0.001) was the strongest predictor of a good outcome at 90-days. Other independent predictors of good outcomes included being a non-smoker (OR 5.4; 95% CI 1.53-19.00; p = 0.01) and having a post-thrombectomy NIHSS<10 (OR 9.7; 95% CI 3.90-24.27; p < 0.001). A decompressive hemicraniectomy (DHC) was predictive of a poor outcome at 90-days (OR 0.07; 95% CI 0.01-0.72; p = 0.03). This model had a Sensitivity of 79%, a Specificity of 89% and an AUC=0.89. CONCLUSION: Our model identified low pre-admission mRS score, low post-thrombectomy NIHSS, non-smoker status and not requiring a DHC as predictors of good functional outcomes at 90-days. Future works include developing a prognostic scoring system.

Impact of Antithrombotic Medications and Reversal Strategies on the Surgical Management and Outcomes of Traumatic Acute Subdural Hematoma.

OBJECTIVE: Careful hematologic management is required in surgical patients with traumatic acute subdural hematoma (aSDH) taking antithrombotic medications. We sought to compare outcomes between patients with aSDH taking antithrombotic medications at admission who received antithrombotic reversal with patients with aSDH not taking antithrombotics. METHODS: Retrospective review identified patients with traumatic aSDH requiring surgical evacuation. The cohort was divided based on antithrombotic use and whether pharmacologic reversal agents or platelet transfusions were administered. A 3-way comparison of outcomes was performed between patients taking anticoagulants who received pharmacologic reversal, patients taking antiplatelets who received platelet transfusion, and patients not taking antithrombotics. Multivariable regressions, adjusted for injury severity, further investigated associations with outcomes. RESULTS: Of 138 patients who met inclusion criteria, 13.0% (n = 18) reported taking anticoagulants, 16.7% (n = 23) reported taking antiplatelets, and 3.6% (n = 5) reported taking both. Patients taking antiplatelets who received platelet transfusion had longer intraoperative times (P = 0.040) and higher rates of palliative care consultations (P = 0.046) compared with patients taking anticoagulants who received pharmacologic reversal and patients not taking antithrombotics. Across groups, no significant differences were found in frequency of in-hospital intracranial hemorrhage and venous thromboembolism, length of hospital stay, rate of inpatient mortality, or follow-up health status. In multivariable analysis, intraoperative time remained longest for the antiplatelets with platelet transfusion group. Other outcomes were not associated with patient group. CONCLUSIONS: Among surgical patients with traumatic aSDH, those taking antiplatelet medications who receive platelet transfusions experience longer intraoperative procedure times and higher rates of palliative care consultation. Comparable outcomes were observed between patients receiving antithrombotic reversal and patients not taking antithrombotics.

Craniotomy versus craniectomy for traumatic acute subdural hematoma-coarsened exact matched analysis of outcomes.

BACKGROUND AND OBJECTIVES: Acute subdural hematoma (aSDH) after traumatic brain injury frequently requires emergent craniotomy (CO) or decompressive craniectomy (DC). We sought to determine the variables associated with either surgical approach and to compare outcomes between matched patients. METHODS: A multi-center retrospective review was used to identify traumatic aSDH patients who underwent CO or DC. Patient variables independently associated with surgical approach were used for coarsened exact matching.Multivariate logistic regression and multivariate Cox proportional-hazards regression wereconducted on matched patients to determine independent predictors of mortality. RESULTS: Seventy-six patients underwent CO and sixty-two underwent DC for aSDH evacuation. DC patients were21.4 years younger (P < 0.001), more likely to be male (80.6 % vs 60.5 %,P = 0.011), and present with GCS ≤ 8 (64.5 % vs 36.8 %,P = 0.001). Age (P < 0.001), epidural hematoma (P = 0.01), skull fracture (P = 0.001), and cisternal effacement (P = 0.02) were independently associated with surgical approach. After coarsened exact matching, DC (P = 0.008), older age (P = 0.007), male sex (P = 0.04), and intraventricular hemorrhage (P = 0.02), were independently associated with inpatient mortality. Multivariate Cox proportional-hazards regression demonstrated that DC was independently associated with mortality at 90-days (P = 0.001) and 1-year post-operation (P = 0.003). CONCLUSION: aSDH patients who receive surgical evacuation via DC as opposed to CO are younger, more likely to be male, and have worse clinical exam. After controlling for patient differences via coarsened exact matching, DC is independently associated with mortality.

Evaluation of the Glasgow Coma Scale-Pupils score for predicting inpatient mortality among patients with traumatic subdural hematoma at United States trauma centers.

OBJECTIVE: The Glasgow Coma Scale-Pupils (GCS-P) score has been suggested to better predict patient outcomes compared with GCS alone, while avoiding the need for more complex clinical models. This study aimed to compare the prognostic ability of GCS-P versus GCS in a national cohort of traumatic subdural hematoma (SDH) patients. METHODS: Patient data were obtained from the National Trauma Data Bank (2017-2019). Inclusion criteria were traumatic SDH diagnosis with available data on presenting GCS score, pupillary reactivity, and discharge disposition. Patients with severe polytrauma or nonsurvivable head injury at presentation were excluded. Sensitivity, specificity, and area under the receiver operating characteristic curve (AUC) of GCS-P versus GCS scores for inpatient mortality prediction were evaluated across the entire cohort, as well as in subgroups based on age and traumatic brain injury (TBI) type (blunt vs penetrating). Calibration curves were plotted based on predicted probabilities and actual outcomes. RESULTS: A total of 196,747 traumatic SDH patients met the study inclusion criteria. Sensitivity (0.707 vs 0.702), specificity (0.821 vs 0.823), and AUC (0.825 vs 0.814, p < 0.001) of GCS-P versus GCS scores for prediction of inpatient mortality were similar. Calibration curve analysis revealed that GCS scores slightly underestimated inpatient mortality risk, whereas GCS-P scores did not. In patients > 65 years of age with blunt TBI (51.9%, n = 102,148), both GCS-P and GCS scores underestimated inpatient mortality risk. In patients with penetrating TBI (2.4%, n = 4,710), the AUC of the GCS-P score was significantly higher (0.902 vs 0.851, p < 0.001). In this subgroup, both GCS-P and GCS scores underestimated inpatient mortality risk among patients with lower rates of observed mortality and overestimated risk among patients with higher rates of observed mortality. This effect was more pronounced in the GCS-P calibration curve. CONCLUSIONS: The GCS-P score provides better short-term prognostication compared with the GCS score alone among traumatic SDH patients with penetrating TBI. The GCS-P score overestimates inpatient mortality risk among penetrating TBI patients with higher rates of observed mortality. For penetrating TBI patients, which comprised 2.4% of our SDH cohort, a low GCS-P score should not justify clinical nihilism or forgoing aggressive treatment.

Predictors of Blunt Cerebrovascular Injury, Stroke, and Mortality in Patients with Cervical Spine Trauma.

BACKGROUND: Blunt cerebrovascular injury (BCVI), defined as blunt traumatic injury to the carotid or vertebral arteries, is associated with significant risk of stroke and mortality. Cervical spine trauma is a recognized risk factor for BCVI. OBJECTIVE: The objective of this study was to identify significant predictors of BCVI and its sequelae in patients with known cervical spine injury. METHODS: Patients from 2007 to 2018 with blunt cervical spine injury diagnoses were identified in the National Trauma Data Bank. Multivariable logistic regression models were used to identify patient baseline and injury characteristics associated with BCVI, stroke, and mortality. RESULTS: We identified 229,254 patients with cervical spine injury due to blunt trauma. The overall rate of BCVI was 1.6%. Factors associated with BCVI in patients with cervical spine injury included lower Glasgow Coma Scale, motor vehicle crash, higher Injury Severity Score, concomitant traumatic brain or spinal cord injury, and current smoking status. BCVI was a strong predictor of stroke (odds ratio, 8.2; 95% confidence interval, 5.7-12.0) and was associated with mortality (odds ratio, 1.7; 95% confidence interval, 1.3-2.2). Stroke occurred in 3.3% of patients with BCVI versus 0.02% for patients without BCVI. CONCLUSIONS: While BCVI is rare following cervical spine injury due to blunt trauma, it is a significant predictor of stroke and mortality. The risk factors associated with BCVI, stroke, and mortality identified here should be used in the development of more effective predictive tools to improve care.

Altered mental status in COVID-19.

BACKGROUND: Altered mental status (AMS) is a common neurological manifestation of COVID-19 infection in hospitalized patients. The principal causes of AMS have yet to be determined. We aimed to identify the common causes of AMS in patients with COVID-19 presenting to the emergency department with AMS on arrival. METHODS: We conducted a retrospective observational study of patients presenting with AMS to three New York hospitals, from March 1 to April 16, 2020. Underlying causes of AMS on arrival to the emergency department (ED) were categorized as (1) neurological causes (stroke, seizure, encephalitis); (2) metabolic encephalopathy; (3) indeterminant. Multivariable analysis was used to assess independent predictors. RESULTS: Overall, 166 patients presented to the ED with AMS. Metabolic encephalopathy was diagnosed as the cause in 154 (92.8%), with 118 (71.1%) categorized as multifactorial ME and 36 (21.7%) with single-cause ME. Hypoxia 103 (62.0%) and renal failure 75 (45.2%) were the most common underlying mechanisms. Neurological causes of AMS occurred in a total 20 patients (12%) and as the sole factor in 5 (3.0%); 10 (6.0%) cases were seizure related and 10 (6.0%) were cerebrovascular events. Of the 7 patients with indeterminant causes, only 1 was suspicious for encephalitis (0.6%). Age, pre-existing dementia and cerebrovascular disease, and impaired renal function were independent predictors of AMS. CONCLUSION: In patients with COVID-19, AMS on presentation to the ED is most frequently caused by metabolic encephalopathy (delirium). Seizures and cerebrovascular events contribute to a lesser degree; encephalitis appears rare.

Dataset on flow diversion procedures performed with the Pipeline Embolization Device, Pipeline Flex, and Surpass Streamline for intracranial aneurysms.

Flow diversion is an evolving endovascular modality for treating intracranial aneurysms. Although rare, serious adverse events following flow diversion may include ischemic stroke, intracranial hemorrhage, or delayed rupture of the treated aneurysm. This dataset describes 141 flow diversion procedures performed with the Pipeline Embolization Device, Pipeline Flex, or Surpass Streamline on 126 subjects with intracranial aneurysms [1]. The retrospective data were collected from electronic medical records at two large tertiary centers. Baseline patient data included age, sex, and medical comorbidities. The dataset also describes aneurysm characteristics including laterality, anatomic location, morphology, dome height, and neck width. In addition, digital subtraction images showing the internal carotid artery tortuosity were included for aneurysms in the anterior cerebral circulation [2]. Procedural data include case duration, radiation exposure, number of flow diverters deployed, and complications encountered during deployment. In addition, data related to the duration of hospitalization and postoperative adverse events are included. Finally, time to follow up and rates of total aneurysm obliteration at first and second postoperative visits are included. This data is propensity score matching are included. This data is presented as a starting point for future prospective comparisons in the safety and efficacy of flow diverters as more devices become approved and commercially available.

Predictors of Radiographic and Symptomatic Hemorrhagic Conversion Following Endovascular Thrombectomy for Acute Ischemic Stroke Due to Large Vessel Occlusion.

Background Endovascular therapy is known to achieve a high rate of recanalization in patients with acute ischemic stroke (AIS) due to large vessel occlusion (LVO) and is currently the standard of care. Hemorrhagic conversion is a severe complication that may occur following AIS in patients undergoing endovascular thrombectomy (EVT). There is a scarcity of data on the risk factors related to HV in post-EVT patients, especially those who develop symptomatic hemorrhagic conversion. The main objective of our study is to identify independent predictors of radiographic and symptomatic hemorrhagic conversion in our diverse patient population with multiple baseline comorbidities that presented with AIS and were treated with EVT as per the most updated guidelines and practices. Methodology This is a retrospective chart review in which we enrolled adult patients treated with EVT for AIS at a comprehensive stroke center in the Bronx, NY, over a four-year period. Bivariate analyses followed by multiple logistic regression modeling were performed to determine the independent predictors of all and symptomatic hemorrhagic conversion. Results A total of 326 patients who underwent EVT for AIS were enrolled. Of these, 74 (22.7%) had an HC, while 252 (77.3%) did not. In total, 25 out of the 74 (33.7%) patients were symptomatic. In the logistic regression model, a history of prior ischemic stroke (odds ratio (OR) = 2.197; 95% confidence interval (CI) = 1.062-4.545; p-value = 0.034), Alberta Stroke Program Early CT Score (ASPECTS) of <6 (OR = 2.207; 95% CI = 1.477-7.194; p-value = 0.019), and Thrombolysis in Cerebral Infarction (TICI) 2B-3 recanalization (OR = 2.551; 95% CI = 1.998-6.520; p-value=0.045) were found to be independent predictors of all types of hemorrhagic conversion. The only independent predictor of symptomatic hemorrhagic conversion on multiple logistic regression modeling was an elevated international normalized ratio (INR) (OR = 11.051; 95% CI = 1.866-65.440; p-value = 0.008). Conclusions History of prior ischemic stroke, low ASPECTS score, and TICI 2B-3 recanalization are independent predictors of hemorrhagic conversion while an elevated INR is the only independent predictor of symptomatic hemorrhagic conversion in post-thrombectomy patients.

Pipeline Embolization Device and Pipeline Flex Versus Surpass Streamline Flow Diversion in Intracranial Aneurysms: A Retrospective Propensity Score-Matched Study.

OBJECTIVE: To compare safety and efficacy profiles in aneurysms treated with Pipeline Embolization Device or Pipeline Flex versus Surpass Streamline flow diverters (FDs). METHODS: Patients who underwent flow diversion for aneurysm treatment at 2 centers were included. Covariates comprised patient demographics, comorbidities, and aneurysm characteristics. Metrics included number of devices, adjuvant device use, case duration, and radiation exposure. Outcomes included periprocedural complications and radiographic results at follow-up. Propensity score-matched pairs were generated using demographic and aneurysm characteristics to verify the outcomes in equally sized groups. RESULTS: The majority of 141 flow diversion procedures performed on 126 patients were in the anterior circulation (96%) and unruptured (93%). Operators experienced more complications placing Surpass FDs compared with Pipelines (18.2% vs. 3.1%, P = 0.005) but used fewer Surpass devices per case (1 device in all Surpass cases and range for Pipeline cases 1-7; P < 0.001). Ballooning was more frequent for Surpass (29.5% vs. 2.1%, P < 0.001). There were no differences in mortality (2.1% vs. 0, P = 1.00), intracranial hemorrhage (3.1% vs. 0, P = 0.551), or stroke (4.2% vs. 6.8%, P = 0.680). Rates of aneurysm obliteration at follow-up were similar. Propensity-matched pairs had no differences in FD deployment complications or perioperative events, yet the significant differences remained for adjuvant balloon use and number of FDs deployed. CONCLUSIONS: While the devices demonstrated similar safety and efficacy profiles, deployment of the Surpass Streamline was more technically challenging than Pipeline Embolization Device or Pipeline Flex. Prospective cohort studies are needed to corroborate these findings.

Associating cryptogenic ischemic stroke in the young with cardiovascular risk factor phenotypes.

Acute Ischemic Stroke (AIS) in the young is increasing in prevalence and the largest subtype within this cohort is cryptogenic. To curb this trend, new ways of defining cryptogenic stroke and associated risk factors are needed. We aimed to gain insights into the presence or absence of cardiovascular risk factors in cases of cryptogenic stroke. We conducted a retrospective cohort study of patients aged 18-49 who presented to an urban tertiary care center with AIS. We manually collected predefined demographic, clinical, laboratory and radiological variables. Clinical risk phenotypes were determined using these variables through multivariate analysis of patients with the small and large vessel disease subtypes (vascular phenotype) and cardioembolic subtype (cardiac phenotype). The resultant phenotype models were applied to cases deemed cryptogenic. Within the 449 patients who met criteria, patients with small and large vessel disease (vascular phenotype) had higher rates of hypertension, intracranial atherosclerosis, and diabetes mellitus, and higher admission glucose, HbA1c, admission blood pressure, and cholesterol compared to the patients with cardioembolic AIS. The cardioembolic subgroup (cardiac phenotype) had significantly higher rates of congestive heart failure (CHF), rheumatic heart disease, atrial fibrillation, clotting disorders, left ventricular hypertrophy, larger left atrial sizes, lower ejection fractions, and higher B-type natriuretic peptide and troponin levels. Adjusted multivariate analysis produced six variables independently associated with the vascular phenotype (age, male sex, hemoglobin A1c, ejection fraction (EF), low-density lipoprotein (LDL) cholesterol, and family history of AIS) and five independently associated with the cardiac phenotype (age, female sex, decreased EF, CHF, and absence of intracranial atherosclerosis). Applying these models to cryptogenic stroke cases yielded that 51.5% fit the vascular phenotype and 3.1% fit the cardiac phenotype. In our cohort, half of young patients with cryptogenic stroke fit the risk factor phenotype of small and large vessel strokes.

Re-Evaluating Stroke Systems of Care: Association of Transfer Status With Thrombectomy Outcomes at an Urban Comprehensive Stroke Center.

Introduction Given the efficacy of mechanical thrombectomies (MT) for large vessel occlusions (LVO), there is concern that the Hub and Spoke model of stroke care, which prioritizes initial assessment of the acute ischemic stroke (AIS) patient at a primary stroke center, would cause a delay in arterial reperfusion, thus leading to worse outcomes. In this study that occurred at our comprehensive stroke center in New York, we compared the clinical outcomes of patients that were either directly admitted for thrombectomy versus those who were transferred from another institution. Methods Retrospective review of the electronic medical record (EMR) was performed on all adult patients treated with endovascular therapy for ischemic stroke between January 2016 and February 2020. A bivariate analysis was performed to compare patients in the direct admit versus transfer group. A multivariable logistic regression model was developed to determine which factors affect 90-day modified Rankin score (mRS) and to evaluate if transfer status was an independent predictor in this model. Results Three hundred and twenty-five patients were included in this study; 127 patients belonged to the direct admit group while 198 were in the transfer group. Thirteen patients (20%) in the direct admit group had a 90-day mRS score of 0-2 and so did 29 patients (25.2%) in the transfer group; thus, no statistically significant difference found in clinical outcomes between both groups (p-value = 0.427). In a multivariable logistic regression model that accounts for age, gender, smoking status, baseline mRS, presenting National Institute of Health Stroke Scale (NIHSS), procedure duration, thrombolysis in cerebral infarction (TICI) score, post-NIHSS and decompressive hemicraniectomy, transfer status was not found to be predictive of clinical outcomes (OR 0.727 95% CI 0.349-1.516; p-value = 0.396).  Conclusion Transfer status is not significantly associated with 90-day outcome. Since Hub and Spoke is not associated with worse outcomes compared to direct admit, it remains a viable model for providing effective care to stroke patients in an urban setting.

Prevalence of Cervical Artery Dissection Among Hospitalized Patients With Stroke by Age in a Nationally Representative Sample From the United States.

OBJECTIVE: To test the hypothesis that the prevalence of cervical artery dissection remains constant across age groups, we evaluated the relationship between age and cervical artery dissection in patients with stroke using a nationally representative sample from the United States. METHODS: We used inpatient claims data included in the 2012-2015 releases of the National Inpatient Sample (NIS). We used validated ICD-9-CM codes to identify adults hospitalized with ischemic stroke and a concomitant diagnosis of carotid or vertebral artery dissection. Survey weights provided by the NIS and population estimates from the US census were used to calculate nationally representative estimates. The χ2 test for trend was used to compare the prevalence of concomitant dissection among stroke hospitalizations across patient subgroups defined by age. Poisson regression and the Wald test for trend were used to evaluate whether the prevalence of hospitalizations for stroke and concomitant dissection per million person-years varied by age groups. RESULTS: There were 17,320 (95% confidence interval [CI], 15,614-19,026) hospitalizations involving ischemic stroke and a concomitant dissection. The prevalence of dissection among stroke hospitalizations decreased across 10-year age groups from 7.2% (95% CI, 6.2%-8.1%) among persons younger than 30 years to 0.2% (95% CI, 0.1%-0.2%) among persons older than 80 years (p value for trend <0.001). However, the prevalence of hospitalizations for stroke and concomitant dissection increased from 5.4 (95% CI, 4.6-6.2) hospitalizations per million person-years among adults younger than 30 to 24.4 (95% CI, 21.0-27.9) hospitalizations per million person-years among adults older than age 80 (p value for trend <0.01). CONCLUSION: In a nationally representative sample, the prevalence of hospitalizations for dissection-related stroke increased with age.

Neurologic Syndromes Predict Higher In-Hospital Mortality in COVID-19.

OBJECTIVE: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is protean in its manifestations, affecting nearly every organ system. However, nervous system involvement and its effect on disease outcome are poorly characterized. The objective of this study was to determine whether neurologic syndromes are associated with increased risk of inpatient mortality. METHODS: A total of 581 hospitalized patients with confirmed SARS-CoV-2 infection, neurologic involvement, and brain imaging were compared to hospitalized non-neurologic patients with coronavirus disease 2019 (COVID-19). Four patterns of neurologic manifestations were identified: acute stroke, new or recrudescent seizures, altered mentation with normal imaging, and neuro-COVID-19 complex. Factors present on admission were analyzed as potential predictors of in-hospital mortality, including sociodemographic variables, preexisting comorbidities, vital signs, laboratory values, and pattern of neurologic manifestations. Significant predictors were incorporated into a disease severity score. Patients with neurologic manifestations were matched with patients of the same age and disease severity to assess the risk of death. RESULTS: A total of 4,711 patients with confirmed SARS-CoV-2 infection were admitted to one medical system in New York City during a 6-week period. Of these, 581 (12%) had neurologic issues of sufficient concern to warrant neuroimaging. These patients were compared to 1,743 non-neurologic patients with COVID-19 matched for age and disease severity admitted during the same period. Patients with altered mentation (n = 258, p = 0.04, odds ratio [OR] 1.39, confidence interval [CI] 1.04-1.86) or radiologically confirmed stroke (n = 55, p = 0.001, OR 3.1, CI 1.65-5.92) had a higher risk of mortality than age- and severity-matched controls. CONCLUSIONS: The incidence of altered mentation or stroke on admission predicts a modest but significantly higher risk of in-hospital mortality independent of disease severity. While other biomarker factors also predict mortality, measures to identify and treat such patients may be important in reducing overall mortality of COVID-19.

Predictors of mortality for patients with COVID-19 and large vessel occlusion.

BACKGROUND: This study evaluates the mortality risk of patients with emergent large vessel occlusion (ELVO) and COVID-19 during the pandemic. METHODS: We performed a retrospective cohort study of two cohorts of consecutive patients with ELVO admitted to a quaternary hospital from March 1 to April 17, 2020. We abstracted data from electronic health records on baseline, biomarker profiles, key time points, quality measures and radiographic data. RESULTS: Of 179 patients admitted with ischemic stroke, 36 had ELVO. Patients with COVID-19 and ELVO had a higher risk of mortality during the pandemic versus patients without COVID-19 (OR 16.63, p = 0.004). An age-based sub-analysis showed in-hospital mortality in 60% of COVID-19 positive patients between 61-70 years-old, 66.7% in between 51-60 years-old, 50% in between 41-50 years-old and 33.3% in between 31-40 years old. Patients that presented with pulmonary symptoms at time of stroke presentation had 71.4% mortality rate. 27.3% of COVID-19 patients presenting with ELVO had a good outcome at discharge (mRS 0-2). Patients with a history of cigarette smoking (p = 0.003), elevated d-dimer (p = 0.007), failure to recanalize (p = 0.007), and elevated ferritin levels (p = 0.006) had an increased risk of mortality. CONCLUSION: Patients with COVID-19 and ELVO had a significantly higher risk for mortality compared to COVID-19 negative patients with ELVO. A small percentage of COVID-19 ELVO patients had good outcomes. Age greater than 60 and pulmonary symptoms at presentation have higher risk for mortality. Other risk factors for mortality were a history of cigarette smoking, elevated, failure to recanalize, elevated d-dimer and ferritin levels.

Virtual reality simulation of neuroendovascular intervention improves procedure speed in a cohort of trainees.

BACKGROUND: Realistic virtual reality (VR) simulators have greatly expanded the tools available for training surgeons and interventionalists. While this technology is effective in improving performance in many fields, it has never been evaluated for neuroendovascular procedures. This study aims to determine whether VR is an effective tool for improving neuroendovascular skill among trainees. METHODS: Trainees performed two VR revascularizations of a right-sided middle cerebral artery (MCA) thrombosis and their times to procedural benchmarks (time to enter internal carotid artery [ICA], traverse clot, and complete procedure) were compared. To determine whether the improvement was case specific, trainees with less procedural exposure were timed during VR left-sided ICA (LICA) aneurysm coiling before or after performing MCA thrombectomy simulations. To determine the value of observing simulations, medical students were timed during the right MCA revascularization simulations after watching other VR procedures. RESULTS: Trainees significantly improved their time to every procedural benchmark during their second MCA revascularization (mean decrease = 1.08, 1.57, and 2.24 min; P = 0.0072, 0.0466, and 0.0230). In addition, time required to access the LICA during aneurysm coiling was shortened by 0.77 min for each previous VR right MCA revascularization performed (P = 0.0176; r 2 = 0.71). Finally, medical students' MCA revascularization simulation times improved by 0.87 min for each prior simulation viewed (P < 0.0221; r 2 = 0.96). CONCLUSION: Both performance and viewing of simulated procedures produced significant decreases in time to reach neuroendovascular procedural benchmarks. These data show that VR simulation is a valuable tool for improving trainee skill in neuroendovascular procedures.

Kinesin-6 KIF20B is required for efficient cytokinetic furrowing and timely abscission in human cells.

Cytokinesis requires the cooperation of many cytoskeletal and membrane regulators. Most of the major players required for cytokinesis are known, but the temporal regulation and adaptations for different cell types are less understood. KIF20B (previously called MPHOSPH1 or MPP1) is a member of the Kinesin-6 family, which also includes the better-known members KIF23/MKLP1 and KIF20A/MKLP2. Previously, we showed that mouse Kif20b is involved in cerebral cortex growth and midbody organization of neural stem cells. Here, using siRNA-mediated knockdown of KIF20B in a human cell line and fixed and live imaging, we show that KIF20B has a cell-autonomous role in cytokinesis. KIF20B depletion affects the speed of both furrow ingression and abscission. It localizes to microtubules of the central spindle and midbody throughout cytokinesis, at sites distinct from the other Kinesin-6 family members. KIF20B is not required for midbody assembly, but may accelerate or coordinate midbody maturation. In particular, KIF20B appears to regulate late steps of maturation including anillin dispersal, ESCRT-III recruitment, and the formation of microtubule constriction sites.