Autologous bone marrow mononuclear cells to treat severe traumatic brain injury in children.

Autologous bone marrow mononuclear cells (BMMNCs) infused after severe traumatic brain injury have shown promise for treating the injury. We evaluated their impact in children, particularly their hypothesized ability to preserve the blood-brain barrier and diminish neuroinflammation, leading to structural CNS preservation with improved outcomes. We performed a randomized, double-blind, placebo-sham-controlled Bayesian dose-escalation clinical trial at two children's hospitals in Houston, TX and Phoenix, AZ, USA (NCT01851083). Patients 5-17 years of age with severe traumatic brain injury (Glasgow Coma Scale score ≤ 8) were randomized to BMMNC or placebo (3:2). Bone marrow harvest, cell isolation and infusion were completed by 48 h post-injury. A Bayesian continuous reassessment method was used with cohorts of size 3 in the BMMNC group to choose the safest between two doses. Primary end points were quantitative brain volumes using MRI and microstructural integrity of the corpus callosum (diffusivity and oedema measurements) at 6 months and 12 months. Long-term functional outcomes and ventilator days, intracranial pressure monitoring days, intensive care unit days and therapeutic intensity measures were compared between groups. Forty-seven patients were randomized, with 37 completing 1-year follow-up (23 BMMNC, 14 placebo). BMMNC treatment was associated with an almost 3-day (23%) reduction in ventilator days, 1-day (16%) reduction in intracranial pressure monitoring days and 3-day (14%) reduction in intensive care unit (ICU) days. White matter volume at 1 year in the BMMNC group was significantly preserved compared to placebo [decrease of 19 891 versus 40 491, respectively; mean difference of -20 600, 95% confidence interval (CI): -35 868 to -5332; P = 0.01], and the number of corpus callosum streamlines was reduced more in placebo than BMMNC, supporting evidence of preserved corpus callosum connectivity in the treated groups (-431 streamlines placebo versus -37 streamlines BMMNC; mean difference of -394, 95% CI: -803 to 15; P = 0.055), but this did not reach statistical significance due to high variability. We conclude that autologous BMMNC infusion in children within 48 h after severe traumatic brain injury is safe and feasible. Our data show that BMMNC infusion led to: (i) shorter intensive care duration and decreased ICU intensity; (ii) white matter structural preservation; and (iii) enhanced corpus callosum connectivity and improved microstructural metrics.

Dynamic Imaging of Blood Coagulation Within the Hematoma of Patients With Acute Hemorrhagic Stroke.

BACKGROUND: The dynamics of blood clot (combination of Hb [hemoglobin], fibrin, and a higher concentration of aggregated red blood cells) formation within the hematoma of an intracerebral hemorrhage is not well understood. A quantitative neuroimaging method of localized coagulated blood volume/distribution within the hematoma might improve clinical decision-making. METHODS: The deoxyhemoglobin of aggregated red blood cells within extravasated blood exhibits a higher magnetic susceptibility due to unpaired heme iron electrons. We propose that coagulated blood, with higher aggregated red blood cell content, will exhibit (1) a higher positive susceptibility than noncoagulated blood and (2) increase in fibrin polymerization-restricted localized diffusion, which can be measured noninvasively using quantitative susceptibility mapping and diffusion tensor imaging. In this serial magnetic resonance imaging study, we enrolled 24 patients with acute intracerebral hemorrhage between October 2021 to May 2022 at a stroke center. Patients were 30 to 70 years of age and had a hematoma volume >15 cm3 and National Institutes of Health Stroke Scale score >1. The patients underwent imaging 3×: within 12 to 24 (T1), 36 to 48 (T2), and 60 to 72 (T3) hours of last seen well on a 3T magnetic resonance imaging system. Three-dimensional anatomic, multigradient echo and 2-dimensional diffusion tensor images were obtained. Hematoma and edema volumes were calculated, and the distribution of coagulation was measured by dynamic changes in the susceptibilities and fractional anisotropy within the hematoma. RESULTS: Using a coagulated blood phantom, we demonstrated a linear relationship between the percentage coagulation and susceptibility (R2=0.91) with a positive red blood cell stain of the clot. The quantitative susceptibility maps showed a significant increase in hematoma susceptibility (T1, 0.29±0.04 parts per millions; T2, 0.36±0.04 parts per millions; T3, 0.45±0.04 parts per millions; P<0.0001). A concomitant increase in fractional anisotropy was also observed with time (T1, 0.40±0.02; T2, 0.45±0.02; T3, 0.47±0.02; P<0.05). CONCLUSIONS: This quantitative neuroimaging study of coagulation within the hematoma has the potential to improve patient management, such as safe resumption of anticoagulants, the need for reversal agents, the administration of alteplase to resolve the clot, and the need for surgery.

Enhancing long-term survival prediction with two short-term events: Landmarking with a flexible varying coefficient model.

Patients with cardiovascular diseases who experience disease-related short-term events, such as hospitalizations, often exhibit diverse long-term survival outcomes compared to others. In this study, we aim to improve the prediction of long-term survival probability by incorporating two short-term events using a flexible varying coefficient landmark model. Our objective is to predict the long-term survival among patients who survived up to a pre-specified landmark time since the initial admission. Inverse probability weighting estimation equations are formed based on the information of the short-term outcomes before the landmark time. The kernel smoothing method with the use of cross-validation for bandwidth selection is employed to estimate the time-varying coefficients. The predictive performance of the proposed model is evaluated and compared using predictive measures: area under the receiver operating characteristic curve and Brier score. Simulation studies confirm that parameters under the landmark models can be estimated accurately and the predictive performance of the proposed method consistently outperforms existing methods that either do not incorporate or only partially incorporate information from two short-term events. We demonstrate the practical application of our model using a community-based cohort from the Atherosclerosis Risk in Communities (ARIC) study.

Comparing Stroke Risk Factors Among Sexual Minority Groups in Texas.

BACKGROUND: Knowledge gaps remain on stroke risk and disparities between sexual minority (SM) subgroups. In this study, stroke risk between SM subgroups, specifically gay/bisexual men and lesbian/bisexual women (G/BM and L/BW), was assessed. METHOD: Data were collected in June 2022 using a bilingual (English and Spanish) cross-sectional paper-and-pen survey distributed among 183 SM individuals attending the 2022 Houston Pride Parade and Festival, as well as across Texas via phone call or online format. Relevant sociodemographic and stroke risk factors were compared between G/BM and L/BW using chi-square (or Fisher's exact, when appropriate) and two-sample t-tests. Sexual orientation was used to predict stroke risk using multiple binomial logistic regression, adjusting for other sociodemographic determinants. RESULTS: While comparing the stroke risk factors between G/BW and L/BW, statistically significant differences were found in hypertension (p = 0.047), age (p < 0.001), smoking status (p = 0.043), cholesterol level (p < 0.001), and HIV (p = 0.038). G/BM were 2.79 times more likely to have a higher stroke risk compared to L/BW (aOR = 2.79; CI, 1.11-6.05, p = 0.032), after adjusting for other sociodemographic factors. CONCLUSION: This pilot study, conducted in Texas, adds to the existing scientific literature on stroke risk among the SM population and revealed that G/BM might have a higher stroke risk compared to L/BW. These findings can inform future research and intervention designs tailored to G/BM and L/BW communities and improve their overall health.

Serial Diffusion Tensor Imaging and Rate of Ventricular Blood Clearance in Patients with Intraventricular Hemorrhage.

BACKGROUND: We developed a noninvasive biomarker to quantify the rate of ventricular blood clearance in patients with intracerebral hemorrhage and extension to the ventricles-intraventricular hemorrhage. METHODS: We performed magnetic resonance imaging in 26 patients at 1, 14, 28, and 42 days of onset and measured their hematoma volume (HV), ventricular blood volume (VBV), and two diffusion metrics: fractional anisotropy (FA), and mean diffusivity (MD). The ipasilesional ventricular cerebral spinal fluid's FA and MD were associated with VBV and stroke severity scores (National Institute of Health Stroke Scale [NIHSS]). A subcohort of 14 patients were treated with external ventricular drain (EVD). A generalized linear mixed model was applied for statistical analysis. RESULTS: At day 1, the average HVs and NIHSS scores were 14.6 ± 16.7 cm3 and 16 ± 8, respectively. A daily rate of 2.1% and 1.3% blood clearance/resolution were recorded in HV and VBV, respectively. Ipsilesional ventricular FA (vFA) and ventricular MD (vMD) were simultaneously decreased (vFA = 1.3% per day, posterior probability [PP] > 99%) and increased (vMD = 1.5% per day, PP > 99%), respectively. Patients with EVD exhibited a faster decline in vFA (1.5% vs. 1.1% per day) and an increase in vMD (1.8% vs. 1.5% per day) as compared with patients without EVD. Temporal change in vMD was associated with VBV; a 1.00-cm3 increase in VBV resulted in a 5.2% decrease in vMD (PP < 99%). VBV was strongly associated with NIHSS score (PP = 97-99%). A larger cerebral spinal fluid drained volume was associated with a greater decrease (PP = 83.4%) in vFA, whereas a smaller volume exhibited a greater increase (PP = 94.8%) in vMD. CONCLUSIONS: In conclusion, vFA and vMD may serve as biomarkers for VBV status.

African American patients have a higher probability of cognitive impairment after incident stroke: An analysis of national electronic health record data.

BACKGROUND: Cognitive impairment (CI) and stroke are diseases with significant disparities in race and geography. Post stroke cognitive impairment (PSCI) can be as high as 15-70 % but few studies have utilized large administrative or electronic health records (EHR) to evaluate trends in PSCI. We utilized an EHR database to evaluate for disparities in PSCI in a large sample of patients after first recorded stroke to evaluate for disparities in race. METHODS: This is a retrospective cohort analysis of Cerner Health Facts® EHR database, which is comprised of EHR data from hundreds of hospitals/clinics in the US from 2009-2018. We evaluated patients ≥40 years of age with a first time ischemic stroke (IS) diagnosis for PSCI using ICD9/10 codes for both conditions. Patients with first stroke in the Cerner database and no pre-existing cognitive impairment were included, we compared hazard ratios for developing PSCI for patient characteristics RESULTS: A total of 150,142 IS patients with follow-up data and no pre-existing evidence of CI were evaluated. Traditional risk factors of age, female sex, kidney injury, hypertension, and hyperlipidemia were associated with PSCI. Only African American stroke survivors had a higher probability of developing PSCI compared to White survivors (HR 1.347, 95 % CI (1.270, 1.428)) and this difference was most prominent in the South. Among those to develop PSCI, median time to documentation was 1.8 years in African American survivors. CONCLUSION: In a large national database, African American stroke survivors had a higher probability of PSCI five years after stroke than White survivors.

Feasibility and user-experience of a virtual environment for social connection and education after stroke: A pilot study.

OBJECTIVES: To evaluate the feasibility and usability of stroke survivor participation in an 8-week virtual environment intervention that provides opportunities for social support exchanges, social network interactions, and recovery education. MATERIALS AND METHODS: A single-group, pre- and post-test measure design was used. Descriptive statistics were used to examine enrollment and retention rates, proportion of questionnaires completed, and virtual environment process data (e.g., number of log-ins) and usability scores. Changes in pre- and post-intervention questionnaire (e.g., usability, social support, depression, anxiety, loneliness, and self-efficacy) scores were explored using Wilcoxon signed-rank tests and paired t-test. RESULTS: Fifteen (65 %) of the eligible stroke survivors enrolled (60 % white, 27 % black), 12 (80 %) had an ischemic stroke, ages ranged from 33 to 74 years (mean 44 years), and mean months since stroke was 33 ± 23. Retention and questionnaire completion rates were both 93 % (n = 14). Survivors logged into the virtual environment a total of 122 times, logged an average of 49 min/log-in, and 12 (80 %) attended support groups and social activities. Median usability score indicated lower than average usability. Improvement trends in social support, loneliness, and depressive symptoms were found, but significant changes in mean questionnaire scores were not found. CONCLUSIONS: Overall, the results suggest that using a virtual environment to foster social support exchanges, social network interactions, and recovery education after stroke is feasible. Similar to other chronic disease populations, stroke survivor adoption of a virtual environment likely requires ongoing technical assistance, repetition of instructions, and opportunities for practice to reinforce engagement. TRIAL REGISTRATION: NCT05487144.

A qualitative study of barriers and facilitators to using tenecteplase to treat acute ischemic stroke.

BACKGROUND: Tenecteplase (TNK) is emerging as an alternative to alteplase (ALT) for thrombolytic treatment of acute ischemic stroke (AIS). Compared to ALT, TNK has a longer half-life, shorter administration time, lower cost, and similarly high efficacy in treating large vessel occlusion. Nevertheless, there are barriers to adopting TNK as a treatment for AIS. This study aimed to identify thematic barriers and facilitators to adopting TNK as an alternative to ALT as a thrombolytic for eligible AIS patients. METHODS: Qualitative research methodology using hermeneutic cycling and purposive sampling was used to interview four stroke clinicians in Texas. Interviews were recorded and transcribed verbatim. Enrollment was complete when saturation was reached. All members of the research team participated in content analysis during each cycle and in thematic analysis after saturation. RESULTS: Interviews were conducted between November 2022 and February 2023 with stroke center representatives from centers that either had successfully adopted TNK, or had not yet adopted TNK. Three themes and eight sub-themes were identified. The theme "Evidence" had three sub-themes: Pro-Con Balance, Fundamental Knowledge, and Pharmacotherapeutics. The theme "Process Flow" had four subthemes: Proactive, Reflective self-doubt, Change Process Barriers, and Parameter Barriers. The theme "Consensus" had one sub-theme: Getting Buy-In. CONCLUSION: Clinicians experience remarkably similar barriers and facilitators to adopting TNK. The results lead to a hypothesis that providing evidence to support a practice change, and identifying key change processes, will help clinicians achieve consensus across teams that need to 'buy in' to adopting TNK for AIS treatment.

Multicenter exploration of tenecteplase transition factors: A quantitative analysis.

BACKGROUND: Tenecteplase (TNK) is gaining recognition as a novel therapy for acute ischemic stroke (AIS). Despite TNK offering a longer half-life, time and cost saving benefits and comparable treatment and safety profiles to Alteplase (ALT), the adoption of TNK as a treatment for AIS presents challenges for hospital systems. OBJECTIVE: Identify barriers and facilitators of TNK implementation at acute care hospitals in Texas. METHODS: This prospective survey used open-ended questions and Likert statements generated from content experts and informed by qualitative research. Stroke clinicians and nurses working at 40 different hospitals in Texas were surveyed using a virtual platform. RESULTS: The 40 hospitals had a median of 34 (IQR 24.5-49) emergency department beds and 42.5 (IQR 23.5-64.5) inpatient stroke beds with 506.5 (IQR 350-797.5) annual stroke admissions. Fifty percent of the hospitals were Comprehensive Stroke Centers, and 18 (45 %) were solely using ALT for treatment of eligible AIS patients. Primary facilitators to TNK transition were team buy-in and a willingness of stroke physicians, nurses, and pharmacists to adopt TNK. Leading barriers were lack of clinical evidence supporting TNK safety profile inadequate evidence supporting TNK use and a lack of American Heart Association guidelines support for TNK administration in all AIS cases. CONCLUSION: Understanding common barriers and facilitators to TNK adoption can assist acute care hospitals deciding to implement TNK as a treatment for AIS. These findings will be used to design a TNK adoption Toolkit, utilizing implementation science techniques, to address identified obstacles and to leverage facilitators.

Door to needle time trends after transition to tenecteplase: A Multicenter Texas stroke registry.

BACKGROUND: Tenecteplase (TNK) is considered a promising option for the treatment of acute ischemic stroke (AIS) with the potential to decrease door-to-needle times (DTN). This study investigates DTN metrics and trends after transition to tenecteplase. METHODS: The Lone Star Stroke (LSS) Research Consortium TNK registry incorporated data from three Texas hospitals that transitioned to TNK. Subject data mapped to Get-With-the-Guidelines stroke variables from October 1, 2019 to March 31, 2023 were limited to patients who received either alteplase (ALT) or TNK within the 90 min DTN times. The dataset was stratified into ALT and TNK cohorts with univariate tables for each measured variable and further analyzed using descriptive statistics. Logistic regression models were constructed for both ALT and TNK to investigate trends in DTN times. RESULTS: In the overall cohort, the TNK cohort (n = 151) and ALT cohort (n = 161) exhibited comparable population demographics, differing only in a higher prevalence of White individuals in the TNK cohort. Both cohorts demonstrated similar clinical parameters, including mean NIHSS, blood glucose levels, and systolic blood pressure at admission. In the univariate analysis, no difference was observed in median DTN time within the 90 min time window compared to the ALT cohort [40 min (30-53) vs 45 min (35-55); P = .057]. In multivariable models, DTN times by thrombolytic did not significantly differ when adjusting for NIHSS, age (P = .133), or race and ethnicity (P = .092). Regression models for the overall cohort indicate no significant DTN temporal trends for TNK (P = .84) after transition; nonetheless, when stratified by hospital, a single subgroup demonstrated a significant DTN upward trend (P = 0.002). CONCLUSION: In the overall cohort, TNK and ALT exhibited comparable temporal trends and at least stable DTN times. This indicates that the shift to TNK did not have an adverse impact on the DTN stroke metrics. This seamless transition is likely attributed to the similarity of inclusion and exclusion criteria, as well as the administration processes for both medications. When stratified by hospital, the three subgroups demonstrated variable DTN time trends which highlight the potential for either fatigue or unpreparedness when switching to TNK. Because our study included a multi-ethnic cohort from multiple large Texas cities, the stable DTN times after transition to TNK is likely applicable to other healthcare systems.

Dietary Intake and Quality among Stroke Survivors: NHANES 1999-2018.

BACKGROUND: Nutrition is an important modifiable risk factor for prevention and treatment of stroke. However, examination of nutrient intake and diet quality in stroke survivors is limited. OBJECTIVES: The aim of the study was to estimate usual nutrient intake and diet quality in US adults with and without a history of self-reported stroke. METHODS: Using US National Health and Nutrition Examination Survey (NHANES) 1999-2018, we analyzed demographics, health history, and dietary intake data in 1626 individuals with a history of stroke matched for age, gender, and survey cycle to respective controls (n=1621) with no history of stroke. A minimum of one 24-h dietary recall was used to assess dietary intake. Diet quality was determined using Healthy Eating Index 2015 (HEI-2015) scores. Adult food security was assessed based on responses to the US Department of Agriculture Household Food Security Survey Module. Physical and mental limitations were assessed from responses to the NHANES Physical Functioning Questionnaire. Estimates were reported as mean (standard error). RESULTS: In comparison to controls, stroke survivors were more likely to be food insecure, experience poverty, and report physical and mental limitations (P < .001, all comparisons). Stroke survivors were more likely to report excessive (% > acceptable macronutrient distribution range) intake for total fat (50.9 [2.7]% vs. 40.4 [2.2]%, P < .001) and inadequate intake (% < estimated average requirement) for calcium (54.6 [1.8]% vs. 43.5 [2.4]%, P = .001) and magnesium (66 [1.8] vs. 53.6 [1.8]%, P < .001). In addition, stroke survivors reported lower HEI-2015 total scores than controls (49.8 vs. 51.9, P < .001). Finally, HEI-2015 total scores were lower in stroke survivors who were food insecure and those with a lower income-to-poverty ratio (< 185%) (P = .001). CONCLUSIONS: Dietary intake in stroke survivors was nutritionally poor, with suboptimal nutrient intake and lower overall diet quality compared with age- and gender-matched controls. Furthermore, poverty and food insecurity were more prevalent in stroke survivors and associated with worse diet quality.

Non-invasive arterial blood pressure measurement and SpO2 estimation using PPG signal: a deep learning framework.

BACKGROUND: Monitoring blood pressure and peripheral capillary oxygen saturation plays a crucial role in healthcare management for patients with chronic diseases, especially hypertension and vascular disease. However, current blood pressure measurement methods have intrinsic limitations; for instance, arterial blood pressure is measured by inserting a catheter in the artery causing discomfort and infection. METHOD: Photoplethysmogram (PPG) signals can be collected via non-invasive devices, and therefore have stimulated researchers' interest in exploring blood pressure estimation using machine learning and PPG signals as a non-invasive alternative. In this paper, we propose a Transformer-based deep learning architecture that utilizes PPG signals to conduct a personalized estimation of arterial systolic blood pressure, arterial diastolic blood pressure, and oxygen saturation. RESULTS: The proposed method was evaluated with a subset of 1,732 subjects from the publicly available ICU dataset MIMIC III. The mean absolute error is 2.52 ± 2.43 mmHg for systolic blood pressure, 1.37 ± 1.89 mmHg for diastolic blood pressure, and 0.58 ± 0.79% for oxygen saturation, which satisfies the requirements of the Association of Advancement of Medical Instrumentation standard and achieve grades A for the British Hypertension Society standard. CONCLUSIONS: The results indicate that our model meets clinical standards and could potentially boost the accuracy of blood pressure and oxygen saturation measurement to deliver high-quality healthcare.

A retrospective examination of pain in acute stroke at hospital discharge.

OBJECTIVES: Pain is an overlooked sequela of stroke. Persistent pain after stroke is an underrecognized experience and significantly impacts survivors' function, ability to participate in rehabilitation, and quality of life. The aim of this retrospective, observational study is to examine the incidence of pain at the acute hospitalization period immediately after stroke, to identify the characteristics of those reporting pain at discharge, and to compare pain reporting between stroke and non-stroke hospital controls. MATERIALS AND METHODS: Using discharge diagnosis, this retrospective review examined self- reports of pain during acute hospitalization for stroke compared to those with COPD (control group) admitted during the same time in the same facilities. Variables of interest included age, gender, body mass index (BMI), length of stay, pain assessment score (numeric rating scale [NRS], behavior pain scale [BPS], and medication administration record pain score total [MAR]), smoking history, prevalence of hypertension and race. 821 subjects were included from a total of three campuses from one large hospital system. 772 subjects were included in the comparative analysis with COPD patients from the same facilities during the same time. RESULTS: 43% of patients diagnosed with stroke reported pain at discharge. For stroke survivors reporting pain at discharge, the average BMI was higher (p=0.009), average arrival NIHSS was higher (p=0.044), and mean hospital length of stay was longer (p<0.001). CONCLUSIONS: The evidence demonstrated in this study highlights the critical need for the implementation of targeted objective pain assessment and effective pain interventions for stroke survivors beginning at initial hospitalization.

Personalizing repetitive transcranial magnetic stimulation for precision depression treatment based on functional brain network controllability and optimal control analysis.

Brain neuromodulation effectively treats neurological diseases and psychiatric disorders such as Depression. However, due to patient heterogeneity, neuromodulation treatment outcomes are often highly variable, requiring patient-specific stimulation protocols throughout the recovery stages to optimize treatment outcomes. Therefore, it is critical to personalize neuromodulation protocol to optimize the patient-specific stimulation targets and parameters by accommodating inherent interpatient variability and intersession alteration during treatments. The study aims to develop a personalized repetitive transcranial magnetic stimulation (rTMS) protocol and evaluate its feasibility in optimizing the treatment efficiency using an existing dataset from an antidepressant experimental imaging study in depression. The personalization of the rTMS treatment protocol was achieved by personalizing both stimulation targets and parameters via a novel approach integrating the functional brain network controllability analysis and optimal control analysis. First, the functional brain network controllability analysis was performed to identify the optimal rTMS stimulation target from the effective connectivity network constructed from patient-specific resting-state functional magnetic resonance imaging data. The optimal control algorithm was then applied to optimize the rTMS stimulation parameters based on the optimized target. The performance of the proposed personalized rTMS technique was evaluated using datasets collected from a longitudinal antidepressant experimental imaging study in depression (n = 20). Simulation models demonstrated that the proposed personalized rTMS protocol outperformed the standard rTMS treatment by efficiently steering a depressive resting brain state to a healthy resting brain state, indicated by the significantly less control energy needed and higher model fitting accuracy achieved. The node with the maximum average controllability of each patient was designated as the optimal target region for the personalized rTMS protocol. Our results also demonstrated the theoretical feasibility of achieving comparable neuromodulation efficacy by stimulating a single node compared to stimulating multiple driver nodes. The findings support the feasibility of developing personalized neuromodulation protocols to more efficiently treat depression and other neurological diseases.

Toward Generalizable Trajectory Planning for Human Intracerebral Trials and Therapy.

INTRODUCTION: Stereotactic neurosurgical techniques are increasingly used to deliver biologics, such as cells and viruses, although standardized procedures are necessary to ensure consistency and reproducibility. OBJECTIVE: We provide an instructional guide to help plan for complex image-guided trajectories; this may be of particular benefit to surgeons new to biologic trials and companies planning such trials. METHODS: We show how nuclei can be segmented and multiple trajectories with multiple injection points can be created through a single or multiple burr hole(s) based on preoperative images. Screenshots similar to those shown in this article can be used for planning purposes and for quality control in clinical trials. RESULTS: This method enables the precise definition of 3-D target structures, such as the putamen, and efficient planning trajectories for biologic injections. The technique is generalizable and largely independent of procedural format, and thus can be integrated with frame-based or frameless platforms to streamline reproducible therapeutic delivery. CONCLUSIONS: We describe an easy-to-use and generalizable protocol for intracerebral trajectory planning for stereotactic delivery of biologics. Although we highlight intracerebral stem cell delivery to the putamen using a frame-based stereotactic delivery system, similar strategies may be employed for different brain nuclei using different platforms. We anticipate this will inform future advanced and fully automated neurosurgical procedures to help unify the field and decrease inherent variability seen with manual trajectory planning.

Integrated Stroke System Model Expands Availability of Endovascular Therapy While Maintaining Quality Outcomes.

BACKGROUND AND PURPOSE: The optimal endovascular stroke therapy (EVT) care delivery structure is unknown. Here, we present our experience in creating an integrated stroke system (ISS) to expand EVT availability throughout our region while maintaining hospital and physician quality standards. METHODS: We identified all consecutive patients with large vessel occlusion acute ischemic stroke treated with EVT from January 2014 to February 2019 in our health care system. In October 2017, we implemented the ISS, in which 3 additional hospitals (4 total) became EVT-performing hospitals (EPHs) and physicians were rotated between all centers. The cohort was divided by time into pre-ISS and post-ISS, and the primary outcome was time from stroke onset to EPH arrival. Secondary outcomes included hospital and procedural quality metrics. We performed an external validation using data from the Southeast Texas Regional Advisory Council. RESULTS: Among 513 patients with large vessel occlusion acute ischemic stroke treated with EVT, 58% were treated pre-ISS and 43% post-ISS. Over the study period, EVT procedural volume increased overall but remained relatively low at the 3 new EPHs (<70 EVT/y). After ISS, the proportion of patients who underwent interhospital transfer decreased (46% versus 37%; P<0.05). In adjusted quantile regression, ISS implementation resulted in a reduction of time from stroke onset to EPH arrival by 40 minutes (P<0.01) and onset to groin puncture by 29 minutes (P<0.05). Rates of postprocedural hemorrhage, modified Thrombolysis in Cerebral Infarction (TICI) 2b/3, and 90-day modified Rankin Scale were comparable at the higher and lower volume EPHs. The improvement in onset-to-arrival time was not reflective of overall improvement in secular trends in regional prehospital care. CONCLUSIONS: In our system, increasing EVT availability decreased time from stroke onset to EPH arrival. The ISS provides a framework to maintain quality in lower volume hospitals.

Optimizing Patient Selection for Endovascular Treatment in Acute Ischemic Stroke (SELECT): A Prospective, Multicenter Cohort Study of Imaging Selection.

OBJECTIVE: The primary imaging modalities used to select patients for endovascular thrombectomy (EVT) are noncontrast computed tomography (CT) and CT perfusion (CTP). However, their relative utility is uncertain. We prospectively assessed CT and CTP concordance/discordance and correlated the imaging profiles on both with EVT treatment decisions and clinical outcomes. METHODS: A phase 2, multicenter, prospective cohort study of large-vessel occlusions presented up to 24 hours from last known well was conducted. Patients received a unified prespecified imaging evaluation (CT, CT angiography, and CTP with Rapid Processing of Perfusion and Diffusion software mismatch determination). The treatment decision, EVT versus medical management, was nonrandomized and at the treating physicians' discretion. An independent, blinded, neuroimaging core laboratory adjudicated favorable profiles based on predefined criteria (CT:Alberta Stroke Program Early CT Score ≥ 6, CTP:regional cerebral blood flow (<30%) < 70ml with mismatch ratio ≥ 1.2 and mismatch volume ≥ 10ml). RESULTS: Of 4,722 patients screened from January 2016 to February 2018, 361 patients were included. Two hundred eighty-five (79%) received EVT, of whom 87.0% had favorable CTs, 91% favorable CTPs, 81% both favorable profiles, 16% discordant, and 3% both unfavorable. Favorable profiles on the 2 modalities correlated similarly with 90-day functional independence rates (favorable CT = 56% vs favorable CTP = 57%, adjusted odds ratio [aOR] = 1.91, 95% confidence interval [CI] = 0.40-9.01, p = 0.41). Having a favorable profile on both modalities significantly increased the odds of receiving thrombectomy as compared to discordant profiles (aOR = 3.97, 95% CI = 1.97-8.01, p < 0.001). Fifty-eight percent of the patients with favorable profiles on both modalities achieved functional independence as compared to 38% in discordant profiles and 0% when both were unfavorable (p < 0.001 for trend). In favorable CT/unfavorable CTP profiles, EVT was associated with high symptomatic intracranial hemorrhage (sICH) (24%) and mortality (53%) rates. INTERPRETATION: Patients with favorable imaging profiles on both modalities had higher odds of receiving EVT and high functional independence rates. Patients with discordant profiles achieved reasonable functional independence rates, but those with an unfavorable CTP had higher adverse outcomes. Ann Neurol 2020;87:419-433.

Allogeneic Bone Marrow-Derived Mesenchymal Stem Cell Safety in Idiopathic Parkinson's Disease.

BACKGROUND: Neuroinflammation plays a key role in PD pathogenesis, and allogeneic bone marrow-derived mesenchymal stem cells can be used as an immunomodulatory therapy. OBJECTIVE: The objective of this study was to prove the safety and tolerability of intravenous allogeneic bone marrow-derived mesenchymal stem cells in PD patients. METHODS: This was a 12-month single-center open-label dose-escalation phase 1 study of 20 subjects with mild/moderate PD assigned to a single intravenous infusion of 1 of 4 doses: 1, 3, 6, or 10 × 106 allogeneic bone marrow-derived mesenchymal stem cells/kg, evaluated 3, 12, 24, and 52 weeks postinfusion. Primary outcome safety measures included transfusion reaction, study-related adverse events, and immunogenic responses. Secondary outcomes included impact on peripheral markers, PD progression, and changes in brain perfusion. RESULTS: There were no serious adverse reactions related to the infusion and no responses to donor-specific human leukocyte antigens. Most common treatment-emergent adverse events were dyskinesias (20%, n = 4) with 1 emergent and 3 exacerbations; and hypertension (20%, n = 4) with 3 transient episodes and 1 requiring medical intervention. One possibly related serious adverse event occurred in a patient with a 4-year history of lymphocytosis who developed asymptomatic chronic lymphocytic leukemia. Peripheral inflammation markers appear to be reduced at 52 weeks in the highest dose including, tumor necrosis factor-α (P < 0.05), chemokine (C-C motif) ligand 22 (P < 0.05), whereas brain-derived neurotrophic factor (P < 0.05) increased. The highest dose seems to have demonstrated the most significant effect at 52 weeks, reducing the OFF state UPDRS motor, -14.4 (P < 0.01), and total, -20.8 (P < 0.05), scores. CONCLUSION: A single intravenous infusion of allogeneic bone marrow-derived mesenchymal stem cells at doses of 1, 3, 6, or 10 × 106 allogeneic bone marrow-derived mesenchymal stem cells/kg is safe, well tolerated, and not immunogenic in mild/moderate PD patients. © 2021 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Routine surveillance of pelvic and lower extremity deep vein thrombosis in stroke patients with patent foramen ovale.

Patent foramen ovale (PFO) is a potential conduit for paradoxical embolization to the systemic atrial circulation of a thrombus originating in the venous system. In a selected group of subjects, the prevalence of deep vein thrombosis (DVT) was assessed. Subjects were identified if they underwent magnetic resonance venography (MRV) pelvis and lower extremity doppler (LE-VDU) for assessment of DVT with PFO. The primary outcome measure was to report the number of patients with paradoxical embolization as their suspected etiology of stroke due to the presence of DVT, which then will be considered as determined stroke. Others with determined stroke diagnosis were reported using Treatment of Acute Stroke Trial (TOAST) criteria. At discharge, those without etiology of their stroke were grouped under embolic stroke of undetermined source (ESUS). We further analyzed the prevalence of DVT by age group, ≤ 60 years vs > 60 years to describe if the prevalence is higher with younger age and to evaluate if higher Risk of Paradoxical Embolism (ROPE) score will have higher number of DVTs compared to lower ROPE scores. Of the 293, 19 (7%) were strokes due to paradoxical embolism. At discharge, determined stroke were 54% vs ESUS were 46%. The overall prevalence of DVT was 19 (7%); MRV-pelvis 13 (4%), and LE-VDU was 9 (3%). No significant difference was noted using both modalities. However, in multivariable regression analysis, a trend suggested an association between pelvic thrombi and high ROPE score as the etiology of stroke; OR 3.56 (0.98, 12.93); p = 0.054. Detection of DVT was not associated with PFO, high ROPE scores or young age. Our data indicate an over-reliance of testing for DVT, particularly MRV pelvis with contrast, in patients with PFO. Clinical studies are needed to identify other factors predictive of DVT in patients with ischemic stroke and PFO.

Leveraging Multimedia Patient Engagement to Address Minority Cerebrovascular Health Needs: Prospective Observational Study.

BACKGROUND: Social inequities affecting minority populations after Hurricane Katrina led to an expansion of environmental justice literature. In August 2017, Hurricane Harvey rainfall was estimated as a 3000- to 20,000-year flood event, further affecting minority populations with disproportionate stroke prevalence. The Stomp Out Stroke initiative leveraged multimedia engagement, creating a patient-centered cerebrovascular health intervention. OBJECTIVE: This study aims to address social inequities in cerebrovascular health through the identification of race- or ethnicity-specific health needs and the provision of in-person stroke prevention screening during two community events (May 2018 and May 2019). METHODS: Stomp Out Stroke recruitment took place through internet-based channels (websites and social networking). Exclusively through web registration, Stomp Out Stroke participants (aged >18 years) detailed sociodemographic characteristics, family history of stroke, and stroke survivorship. Participant health interests were compared by race or ethnicity using Kruskal-Wallis or chi-square test at an α=.05. A Bonferroni-corrected P value of .0083 was used for multiple comparisons. RESULTS: Stomp Out Stroke registrants (N=1401) were 70% (973/1390) female (median age 45 years) and largely self-identified as members of minority groups: 32.05% (449/1401) Hispanic, 25.62% (359/1401) African American, 13.63% (191/1401) Asian compared with 23.63% (331/1401) non-Hispanic White. Stroke survivors comprised 11.55% (155/1401) of our population. A total of 124 stroke caregivers participated. Approximately 36.81% (493/1339) of participants had a family history of stroke. African American participants were most likely to have Medicare or Medicaid insurance (84/341, 24.6%), whereas Hispanic participants were most likely to be uninsured (127/435, 29.2%). Hispanic participants were more likely than non-Hispanic White participants to obtain health screenings (282/449, 62.8% vs 175/331, 52.9%; P=.03). Asian (105/191, 54.9%) and African American (201/359, 55.9%) participants were more likely to request stroke education than non-Hispanic White (138/331, 41.6%) or Hispanic participants (193/449, 42.9%). African American participants were more likely to seek overall health education than non-Hispanic White participants (166/359, 46.2% vs 108/331, 32.6%; P=.002). Non-Hispanic White participants (48/331, 14.5%) were less likely to speak to health care providers than African American (91/359, 25.3%) or Asian participants (54/191, 28.3%). During the 2018 and 2019 events, 2774 health screenings were completed across 12 hours, averaging four health screenings per minute. These included blood pressure (1031/2774, 37.16%), stroke risk assessment (496/2774, 17.88%), bone density (426/2774, 15.35%), carotid ultrasound (380/2774, 13.69%), BMI (182/2774, 6.56%), serum lipids (157/2774, 5.65%), and hemoglobin A1c (102/2774, 3.67%). Twenty multimedia placements using the Stomp Out Stroke webpage, social media, #stompoutstroke, television, iQ radio, and web-based news reached approximately 849,731 people in the Houston area. CONCLUSIONS: Using a combination of internet-based recruitment, registration, and in-person assessments, Stomp Out Stroke identified race- or ethnicity-specific health care needs and provided appropriate screenings to minority populations at increased risk of urban flooding and stroke. This protocol can be replicated in Southern US Stroke Belt cities with similar flood risks.