Strokes Averted by Intravenous Thrombolysis: A Secondary Analysis of a Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

OBJECTIVE: This study was undertaken to examine averted stroke in optimized stroke systems. METHODS: This secondary analysis of a multicenter trial from 2014 to 2020 compared patients treated by mobile stroke unit (MSU) versus standard management. The analytical cohort consisted of participants with suspected stroke treated with intravenous thrombolysis. The main outcome was a tissue-defined averted stroke, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis and no acute infarction/hemorrhage on imaging. An additional outcome was stroke with early symptom resolution, defined as a final diagnosis of stroke with resolution of presenting symptoms/signs by 24 hours attributed to thrombolysis. RESULTS: Among 1,009 patients with a median last known well to thrombolysis time of 87 minutes, 159 (16%) had tissue-defined averted stroke and 276 (27%) had stroke with early symptom resolution. Compared with standard management, MSU care was associated with more tissue-defined averted stroke (18% vs 11%, adjusted odds ratio [aOR] = 1.82, 95% confidence interval [CI] = 1.13-2.98) and stroke with early symptom resolution (31% vs 21%, aOR = 1.74, 95% CI = 1.12-2.61). The relationships between thrombolysis treatment time and averted/early recovered stroke appeared nonlinear. Most models indicated increased odds for stroke with early symptom resolution but not tissue-defined averted stroke with earlier treatment. Additionally, younger age, female gender, hyperlipidemia, lower National Institutes of Health Stroke Scale, lower blood pressure, and no large vessel occlusion were associated with both tissue-defined averted stroke and stroke with early symptom resolution. INTERPRETATION: In optimized stroke systems, 1 in 4 patients treated with thrombolysis recovered within 24 hours and 1 in 6 had no demonstrable brain injury on imaging. ANN NEUROL 2024;95:347-361.

Prospective, Multicenter, Controlled Trial of Mobile Stroke Units.

BACKGROUND: Mobile stroke units (MSUs) are ambulances with staff and a computed tomographic scanner that may enable faster treatment with tissue plasminogen activator (t-PA) than standard management by emergency medical services (EMS). Whether and how much MSUs alter outcomes has not been extensively studied. METHODS: In an observational, prospective, multicenter, alternating-week trial, we assessed outcomes from MSU or EMS management within 4.5 hours after onset of acute stroke symptoms. The primary outcome was the score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes according to a patient value system, derived from scores on the modified Rankin scale of 0 to 6, with higher scores indicating more disability). The main analysis involved dichotomized scores on the utility-weighted modified Rankin scale (≥0.91 or <0.91, approximating scores on the modified Rankin scale of ≤1 or >1) at 90 days in patients eligible for t-PA. Analyses were also performed in all enrolled patients. RESULTS: We enrolled 1515 patients, of whom 1047 were eligible to receive t-PA; 617 received care by MSU and 430 by EMS. The median time from onset of stroke to administration of t-PA was 72 minutes in the MSU group and 108 minutes in the EMS group. Of patients eligible for t-PA, 97.1% in the MSU group received t-PA, as compared with 79.5% in the EMS group. The mean score on the utility-weighted modified Rankin scale at 90 days in patients eligible for t-PA was 0.72 in the MSU group and 0.66 in the EMS group (adjusted odds ratio for a score of ≥0.91, 2.43; 95% confidence interval [CI], 1.75 to 3.36; P<0.001). Among the patients eligible for t-PA, 55.0% in the MSU group and 44.4% in the EMS group had a score of 0 or 1 on the modified Rankin scale at 90 days. Among all enrolled patients, the mean score on the utility-weighted modified Rankin scale at discharge was 0.57 in the MSU group and 0.51 in the EMS group (adjusted odds ratio for a score of ≥0.91, 1.82; 95% CI, 1.39 to 2.37; P<0.001). Secondary clinical outcomes generally favored MSUs. Mortality at 90 days was 8.9% in the MSU group and 11.9% in the EMS group. CONCLUSIONS: In patients with acute stroke who were eligible for t-PA, utility-weighted disability outcomes at 90 days were better with MSUs than with EMS. (Funded by the Patient-Centered Outcomes Research Institute; BEST-MSU ClinicalTrials.gov number, NCT02190500.).

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.

Ideal Foundational Requirements for Stroke Program Development and Growth: A Scientific Statement From the American Heart Association.

Stroke center certification has evolved at a rapid pace and is now available at 4 different levels of service in the United States. Although certification standards provide guidance on stroke center process elements, lack of guidance on structural components such as workforce, staffing, and unit operations has resulted in heterogeneous services among hospitals credentialed at the same stroke center level. Such heterogeneity challenges public expectations and transparency about actual service capabilities within American stroke centers and in some cases may foster leniency in credentialing agency certification methods. Standards for other time-dependent diagnoses, including trauma, provide detailed guidance on structural elements that has improved patient triage and resuscitative care while enabling practitioners and administrators to more accurately gauge and plan service development to better support their communities. This scientific statement aims to provide similar structural guidance defined by each level of hospital stroke center services to reduce operational inconsistencies, to foster planning for service development, and to improve the interprofessional care of patients with acute stroke.

Examining the Potential of Vitamin C Supplementation in Tissue-Engineered Equine Superficial Digital Flexor Tendon Constructs.

Because equine tendinopathies are slow to heal and often recur, therapeutic strategies are being considered that aid tendon repair. Given the success of utilizing vitamin C to promote tenogenesis in other species, we hypothesized that vitamin C supplementation would produce dose-dependent improvements in the tenogenic properties of tendon proper (TP) and peritenon (PERI) cells of the equine superficial digital flexor tendon (SDFT). Equine TP- and PERI-progenitor-cell-seeded fibrin three-dimensional constructs were supplemented with four concentrations of vitamin C. The gene expression profiles of the constructs were assessed with 3'-Tag-Seq and real-time quantitative polymerase chain reaction (RT-qPCR); collagen content and fibril ultrastructure were also analyzed. Moreover, cells were challenged with dexamethasone to determine the levels of cytoprotection afforded by vitamin C. Expression profiling demonstrated that vitamin C had an anti-inflammatory effect on TP and PERI cell constructs. Moreover, vitamin C supplementation mitigated the degenerative pathways seen in tendinopathy and increased collagen content in tendon constructs. When challenged with dexamethasone in two-dimensional culture, vitamin C had a cytoprotective effect for TP cells but not necessarily for PERI cells. Future studies will explore the effects of vitamin C on these cells during inflammation and within the tendon niche in vivo.

Basic Structure, Physiology, and Biochemistry of Connective Tissues and Extracellular Matrix Collagens.

The physiology of connective tissues like tendons and ligaments is highly dependent upon the collagens and other such extracellular matrix molecules hierarchically organized within the tissues. By dry weight, connective tissues are mostly composed of fibrillar collagens. However, several other forms of collagens play essential roles in the regulation of fibrillar collagen organization and assembly, in the establishment of basement membrane networks that provide support for vasculature for connective tissues, and in the formation of extensive filamentous networks that allow for cell-extracellular matrix interactions as well as maintain connective tissue integrity. The structures and functions of these collagens are discussed in this chapter. Furthermore, collagen synthesis is a multi-step process that includes gene transcription, translation, post-translational modifications within the cell, triple helix formation, extracellular secretion, extracellular modifications, and then fibril assembly, fibril modifications, and fiber formation. Each step of collagen synthesis and fibril assembly is highly dependent upon the biochemical structure of the collagen molecules created and how they are modified in the cases of development and maturation. Likewise, when the biochemical structures of collagens or are compromised or these molecules are deficient in the tissues - in developmental diseases, degenerative conditions, or injuries - then the ultimate form and function of the connective tissues are impaired. In this chapter, we also review how biochemistry plays a role in each of the processes involved in collagen synthesis and assembly, and we describe differences seen by anatomical location and region within tendons. Moreover, we discuss how the structures of the molecules, fibrils, and fibers contribute to connective tissue physiology in health, and in pathology with injury and repair.

Sex-specific Association of Matrix Metalloproteinases with Secondary Injury and Outcomes after Intracerebral Hemorrhage.

OBJECTIVE: Intracerebral hemorrhage affects approximately 2 million individuals per year. While the incidence is roughly equal in men and women, few studies have examined the influence of sex on secondary injury and associated long-term functional outcomes. Matrix metalloproteinases (MMPs) promote vessel rupture and worsen outcomes by potentiating blood-brain barrier breakdown after injury. We hypothesized that different MMP isoform levels would be predictive of injury severity, secondary injury, and long-term functional outcomes in males and females, respectively. METHODS: We examined the levels of MMP isoforms in serum samples from a prospective patient biobank (n = 55). Baseline clinical, radiographic, and laboratory data were also analyzed. RESULTS: We found that MMP-1 (P = .036), MMP-2 (P = .014), MMP-3 (P < .001), and MMP-9 (P = .02) levels gradually increased over time in male patients until 10 DPI. In female patients, we found a different pattern of activation: MMP-8 (P = .02) was the only isoform that significantly changed with time, which reached a peak at 3-5 days postinjury. Several MMP isoforms correlated with markers of secondary injury in female patients (all P < .05). Additionally, serum levels of MMP-3 (P = .011) in males and MMP-10 (P = .044) in females were significantly associated with long-term functional outcomes in a sex-specific manner. CONCLUSIONS: This is the first sex-specific study to examine serum MMP levels and their correlation with clinicoradiologic measures after intracerebral hemorrhage, and identifies potential biomarkers of secondary injury and long-term outcomes in both sexes.

Hemicraniectomy for Supratentorial Primary Intracerebral Hemorrhage: A Retrospective, Propensity Score Matched Study.

BACKGROUND AND PURPOSE: Spontaneous supratentorial intracerebral hemorrhage (ICH) contributes disproportionately to stroke mortality, and randomized trials of surgical treatments for ICH have not shown benefit. Decompressive hemicraniectomy (DHC) improves functional outcome in patients with malignant middle cerebral artery ischemic stroke, but data in ICH patients is limited. We hypothesized that DHC would reduce in-hospital mortality and poor functional status (defined as modified Rankin scale ≥5) among survivors at 3 months, without increased complications. METHODS: We performed a retrospective, case-control, propensity score matched study to determine whether hemicraniectomy affected outcome in patients with spontaneous supratentorial ICH. The propensity score consisted of variables associated with outcome or predictors of hemicraniectomy. Forty-three surgical patients were matched to 43 medically managed patients on ICH location, sex, and nearest neighbor matching. Three-month functional outcomes, in-hospital mortality, and in-hospital complications were measured. RESULTS: In the medical management group, 72.1% of patients had poor outcome at 3 months compared with 37.2% who underwent hemicraniectomy (odds ratio 4.8, confidence interval 1.6-14). In-hospital mortality was 51.2% for medically managed patients and 16.3% for hemicraniectomy patients (odds ratio 8.5, confidence interval 2.0-36.8). There were no statistically significant differences in the occurrence of in-hospital complications. CONCLUSIONS: In our retrospective study of selected patients with spontaneous supratentorial ICH, DHC resulted in lower rate of in-hospital mortality and better 3-month functional status compared with medically managed patients. A randomized trial is necessary to evaluate DHC as a treatment for certain patients with spontaneous supratentorial ICH.

Treatment and Outcome of Hemorrhagic Transformation After Intravenous Alteplase in Acute Ischemic Stroke: A Scientific Statement for Healthcare Professionals From the American Heart Association/American Stroke Association.

PURPOSE: Symptomatic intracranial hemorrhage (sICH) is the most feared complication of intravenous thrombolytic therapy in acute ischemic stroke. Treatment of sICH is based on expert opinion and small case series, with the efficacy of such treatments not well established. This document aims to provide an overview of sICH with a focus on pathophysiology and treatment. METHODS: A literature review was performed for randomized trials, prospective and retrospective studies, opinion papers, case series, and case reports on the definitions, epidemiology, risk factors, pathophysiology, treatment, and outcome of sICH. The document sections were divided among writing group members who performed the literature review, summarized the literature, and provided suggestions on the diagnosis and treatment of patients with sICH caused by systemic thrombolysis with alteplase. Several drafts were circulated among writing group members until a consensus was achieved. RESULTS: sICH is an uncommon but severe complication of systemic thrombolysis in acute ischemic stroke. Prompt diagnosis and early correction of the coagulopathy after alteplase have remained the mainstay of treatment. Further research is required to establish treatments aimed at maintaining integrity of the blood-brain barrier in acute ischemic stroke based on inhibition of the underlying biochemical processes.

Variability in the Use of Platelet Transfusion in Patients with Intracerebral Hemorrhage: Observations from the Ethnic/Racial Variations of Intracerebral Hemorrhage Study.

BACKGROUND: We examined platelet transfusion (PTx) in the Ethnic/Racial Variations of Intracerebral Hemorrhage (ERICH) study, hypothesizing that rates of PTx would vary among hospitals and depend on whether patients were on an antiplatelet therapy or underwent intracerebral hemorrhage (ICH) surgical treatment. METHODS: The ERICH study is a prospective observational study evaluating risk factors for ICH among whites, blacks, and Hispanics. We identified factors associated with PTx, examined practice patterns of PTx across the United States, and explored the association of PTx with mortality and poor outcome (modified Rankin Scale score 4-6). RESULTS: Nineteen centers enrolled 2572 ICH cases; 11.7% received PTx. Factors significantly associated with PTx were antiplatelet use before onset (odds ratio [OR], 5.02; 95% confidence interval [CI], 3.81-6.61, P < .0001), thrombocytopenia (OR, 13.53; 95% CI, 8.43-21.72, P < .0001), and ventriculostomy placement (OR, 1.85; 95% CI, 1.36-2.52, P < .0001). Blacks were less likely (OR, .57; 95% CI, .41-0.80) to receive PTx. Among patients who received PTx, 42.4% were not on an antiplatelet therapy before onset. Twenty-three percent of patients on antiplatelet therapy received PTx, but percentages varied from 0% to 71% across centers. There was no difference in mortality or poor outcome at 3 months between patients receiving PTx and those who did not. CONCLUSIONS: The frequency of PTx for ICH varies across academic centers. Thrombocytopenia, antiplatelet use, vascular risk factors, and ventriculostomy placement were associated with PTx. PTx was not associated with improved outcomes. We anticipate reduced PTx use over time given recent clinical trial data suggesting its use could be harmful; however, the issue of whether surgical management warrants PTx remains.

Higher prehospital blood pressure prolongs door to needle thrombolysis times: a target for quality improvement?

BACKGROUND: Per the American Heart Association guidelines, blood pressure (BP) should be less than 185/110 to be eligible for stroke thrombolysis. No studies have focused on prehospital BP and its impact on door to needle (DTN) times. We hypothesized that DTN times would be longer for patients with higher prehospital BP. METHODS: We conducted a retrospective review of acute ischemic stroke patients who presented between January 2010 and December 2010 to our emergency department (ED) through emergency medical services within 3 hours of symptom onset. Patients were categorized into 2 groups: prehospital BP greater than or equal to 185/110 (group 1) and less than 185/110 (group 2). Blood pressure records were abstracted from emergency medical services run sheets. Primary outcome measure was DTN time, and secondary outcome measures were modified Rankin Score at discharge, symptomatic intracranial hemorrhage, length of stay in stroke unit, and discharge disposition. RESULTS: A total of 107 consecutive patients were identified. Of these, 75 patients (70%) were thrombolysed. Mean DTN times were significantly higher in group 1 (adjusted mean [95% confidence interval], 86minutes [76-97] vs 56minutes [45-68]; P<.0001). A greater number of patients required antihypertensive medications before thrombolysis in the ED in group 1 compared to group 2 (54% vs 27%; P=.02). CONCLUSION: Higher prehospital BP is associated with prolonged DTN times and DTN time remains prolonged if prehospital BP greater than or equal to 185/110 is untreated before ED arrival. Prehospital BP control could be a potential area for improvement to reduce DTN times in patients with acute ischemic stroke.

Dimethyl Fumarate Protects Brain From Damage Produced by Intracerebral Hemorrhage by Mechanism Involving Nrf2.

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) represents a devastating form of stroke for which there is no effective treatment. This preclinical study was designed to evaluate dimethyl fumarate (DMF), a substance recently approved for the treatment of multiple sclerosis, as therapy for ICH. We hypothesized that DMF through activating the master regulator of cellular self-defense responses, transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2), would act as effective treatment for ICH-mediated damage. METHODS: Male rats and mice, including Nrf2 knockouts, were subjected to intracerebral injection of blood (to mimic ICH) and then treated with DMF. Neurological deficit, brain edema, gene induction profile and hematoma resolution were evaluated. Phagocytic functions of primary microglia in culture were used to study hematoma resolution. RESULTS: Treatment with DMF induced Nrf2-target genes, improved hematoma resolution, reduced brain edema, and ultimately enhanced neurological recovery in rats and wild-type, but not Nrf2 knockout, mice. Most importantly, the treatment of ICH with DMF showed a 24 h window of therapeutic opportunity. CONCLUSIONS: A clinically relevant dose of DMF demonstrates potent therapeutic efficacy and impressive 24 h therapeutic window of opportunity. This study merits further evaluation of this compound as potential treatment for ICH in humans.

Time From Symptoms to Carotid Endarterectomy or Stenting and Perioperative Risk.

BACKGROUND AND PURPOSE: Prior meta-analysis showed that carotid endarterectomy benefits decline with increasing surgical delay following symptoms. For symptomatic patients in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST), we assessed if differences in time between symptoms and carotid endarterectomy or carotid artery stenting are associated with differences in risk of periprocedural stroke or death. METHODS: We analyzed the 1180 symptomatic patients in CREST who received their assigned procedure and had clearly defined timing of symptoms. Patients were classified into 3 groups based on time from symptoms to procedure: <15, 15 to 60, and >60 days. RESULTS: For carotid endarterectomy, risk of periprocedural stroke or death was not significantly different for the 2 later time periods relative to the earliest time period (hazard ratio, 0.74; 95% confidence interval, 0.22-2.49 for 15-60 days and hazard ratio, 0.91; 95% confidence interval, 0.25-3.33 for >60 days; P=0.89). For carotid artery stenting, risk of periprocedural stroke or death was also not significantly different for later time periods relative to the earliest time period (hazard ratio, 1.12; 95% confidence interval, 0.53-2.40 for 15-60 days and hazard ratio, 1.15; 95% confidence interval, 0.48-2.75 for >60 days; P=0.93). CONCLUSIONS: Time from symptoms to carotid endarterectomy or carotid artery stenting did not alter periprocedural safety, supporting early revascularization regardless of modality. CLINICAL TRIAL REGISTRATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Complication rates and center enrollment volume in the carotid revascularization endarterectomy versus stenting trial.

BACKGROUND AND PURPOSE: Evidence indicates that center volume of cases affects outcomes for both carotid endarterectomy and stenting. We evaluated the effect of enrollment volume by site on complication rates in the Carotid Revascularization Endarterectomy Versus Stenting Trial (CREST). METHODS: The primary composite end point was any stroke, myocardial infarction, or death within 30 days or ipsilateral stroke in follow-up. The 477 approved surgeons performed >12 procedures per year with complication rates <3% for asymptomatic patients and <5% for symptomatic patients; 224 interventionists were certified after a rigorous 2 step credentialing process. CREST centers were divided into tertiles based on the number of patients enrolled into the study, with Group 1 sites enrolling <25 patients, Group 2 sites enrolling 25 to 51 patients, and Group 3 sites enrolling >51 patients. Differences in periprocedural event rates for the primary composite end point and its components were compared using logistic regression adjusting for age, sex, and symptomatic status within site-volume level. RESULTS: The safety of carotid angioplasty and stenting and carotid endarterectomy did not vary by site-volume during the periprocedural period as indicated by occurrence of the primary end point (P=0.54) or by stroke and death (P=0.87). A trend toward an inverse relationship between center enrollment volume and complications was mitigated by adjustment for known risk factors. CONCLUSIONS: Complication rates were low in CREST and were not associated with center enrollment volume. The data are consistent with the value of rigorous training and credentialing in trials evaluating endovascular devices and surgical procedures. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00004732.

Racial and gender differences in stroke severity, outcomes, and treatment in patients with acute ischemic stroke.

BACKGROUND: Previous research has indicated that women and blacks have worse outcomes after acute ischemic stroke (AIS). Little research has been done to investigate the combined influence of race and gender in the presentation, treatment, and outcome of patients with AIS. We sought to determine the association of race and gender on initial stroke severity, thrombolysis, and functional outcome after AIS. METHODS: AIS patients who presented to 2 academic medical centers in the United States (2004-2011) were identified through prospective registries. In-hospital strokes were excluded. Stroke severity, measured by admission National Institutes of Health Stroke Scale (NIHSS) scores, treatment with tissue plasminogen activator (tPA), neurologic deterioration (defined by a ≥2-point increase in NIHSS score), and functional outcome at discharge, measured by the modified Rankin Scale, were investigated. These outcomes were compared across race/gender groups. A subanalysis was conducted to assess race/gender differences in exclusion criteria for tPA. RESULTS: Of the 4925 patients included in this study, 2346 (47.6%) were women and 2310 (46.9%) were black. White women had the highest median NIHSS score on admission (8), whereas white men had the lowest median NIHSS score on admission (6). There were no differences in outcomes between black men and white men. A smaller percentage of black women than white women were treated with tPA (27.6% versus 36.6%, P < .0001), partially because of a greater proportion of white women presenting within 3 hours (51% versus 45.5%, P = .0005). Black women had decreased odds of poor functional outcome relative to white women (odds ratio [OR] = .85, 95% confidence interval [CI] .72-1.00), but after adjustment for baseline differences in age, NIHSS, and tPA use, this association was no longer significant (OR = 1.2, 95% CI .92-1.46, P = .22). Black women with an NIHSS score less than 7 on admission were at lower odds of receiving tPA than the other race/gender groups, even after adjusting for arriving within 3 hours and admission glucose (OR = .66, 95% CI .44-.99, P = .0433). CONCLUSION: Race and gender were not significantly associated with short-term outcome, although black women were significantly less likely to be treated with tPA. Black women had more tPA exclusions than any other group. The primary reason for tPA exclusion in this study was not arriving within 3 hours of stroke symptom onset. Given the growth in incident strokes projected in minority groups in the next 4 decades, identifying factors that contribute to black women not arriving to the emergency department in time are of great importance.

How Do We Alleviate Long-Term Psychological Distress for Surrogate Decision Makers?

Our perspective as clinicians is focused on the patient; however, when patients present with severe stroke, we rely on family or surrogate decision-makers to assist with decisions regarding life-sustaining treatment. In this issue of Neurology®, Morgenstern et al.1 report on long-term psychological distress among surrogate decision-makers for patients with severe stroke. The authors used validated measures of post-traumatic stress, anxiety, and depression among family surrogate decision-makers and found between 17% and 28% of surrogates to have high scores on measures of psychological distress. One or more high levels of the psychological outcomes were found in 17%-43% of surrogates, 2 or more were found in 12%-27%, and all 3 were found in 5%-16% of surrogates. The study population included a biethnic community of predominantly nonimmigrant Mexican American (MA) and non-Hispanic White (NHW) persons, and outcomes were evaluated by ethnicity. Symptoms of post-traumatic stress remained worse among MA surrogates in the fully adjusted model; however, they were no longer significant for anxiety or depression after adjustment. The authors conclude that psychological distress is common among family surrogate decision-makers in the year after stroke and may be worse among MA surrogates. The authors propose that efforts are needed to support family members of all ethnic groups after severe stroke.

Auricular Chondrocytes as a Cell Source for Scaffold-Free Elastic Cartilage Tissue Engineering.

Current tissue engineering (TE) methods utilize chondrocytes primarily from costal or articular sources. Despite the robust mechanical properties of neocartilages sourced from these cells, the lack of elasticity and invasiveness of cell collection from these sources negatively impact clinical translation. These limitations invited the exploration of naturally elastic auricular cartilage as an alternative cell source. This study aimed to determine if auricular chondrocytes (AuCs) can be used for TE scaffold-free neocartilage constructs and assess their biomechanical properties. Neocartilages were successfully generated from a small quantity of primary neonatal AuCs of three minipig donors (n = 3). Neocartilage constructs had instantaneous moduli of 200.5 kPa ± 43.34 and 471.9 ± 92.8 kPa at 10% and 20% strain, respectively. TE constructs' relaxation moduli (Er) were 36.99 ± 6.47 kPa Er and 110.3 ± 16.99 kPa at 10% and 20% strain, respectively. The Young's modulus was 2.0 MPa ± 0.63, and the ultimate tensile strength was 0.619 ± 0.177 MPa. AuC-derived neocartilages contained 0.144 ± 0.011 µg collagen, 0.185 µg ± 0.002 glycosaminoglycans per µg dry weight, and 1.7e-3 µg elastin per µg dry weight. In conclusion, this study shows that AuCs can be used as a reliable and easily accessible cell source for TE of biomimetic and mechanically robust elastic neocartilage implants.

Addressing Disparities in Acute Stroke Management and Prognosis.

There are now abundant data demonstrating disparities in acute stroke management and prognosis; however, interventions to reduce these disparities remain limited. This special report aims to provide a critical review of the current landscape of disparities in acute stroke care and highlight opportunities to use implementation science to reduce disparities throughout the early care continuum. In the prehospital setting, stroke symptom recognition campaigns that have been successful in reducing prehospital delays used a multilevel approach to education, including mass media, culturally tailored community education, and professional education. The mobile stroke unit is an organizational intervention that has the potential to provide more equitable access to timely thrombolysis and thrombectomy treatments. In the hospital setting, interventions to address implicit biases among health care providers in acute stroke care decision-making are urgently needed as part of a multifaceted approach to advance stroke equity. Implementing stroke systems of care interventions, such as evidence-based stroke care protocols at designated stroke centers, can have a broader public health impact and may help reduce geographic, racial, and ethnic disparities in stroke care, although further research is needed. The long-term impact of disparities in acute stroke care cannot be underestimated. The consistent trend of longer time to treatment for Black and Hispanic people experiencing stroke has direct implications on long-term disability and independence after stroke. A learning health system model may help expedite the translation of evidence-based interventions into clinical practice to reduce disparities in stroke care.

Diversity, equity, and inclusion (DEI) in medical education: DEI at the bedside.

BACKGROUND: The ability to recognize and address bias is an important communication skill not typically addressed during training. We describe the design of an educational curriculum that aims to identify and change behavior related to diversity, equity, and inclusion (DEI). "DEI at the Bedside" uses the existing infrastructure of bedside teaching and provides a tool to normalize DEI discussions and develop skills to address bias during a neurology inpatient rotation. METHODS: As part of traditional clinical rounds, team members on an inpatient service shared experiences with DEI topics, including bias. The team developed potential responses should they encounter a similar situation in the future. We report the results of our needs assessment and curriculum development to evaluate the feasibility of incorporating a DEI educational curriculum in the neurology inpatient setting. RESULTS: Forty-two DEI experiences were recorded. Medical students were the most frequent discussants (44%). Direction of bias occurred between healthcare team members (33%), against patients (31%), and patients against healthcare team members (28%). Experiences ranged from microaggressions to explicit comments of racism, sexism, and homophobia. CONCLUSIONS: Based on needs assessment data, we developed a DEI educational curriculum for the inpatient neurology setting aimed to improve knowledge and skills related to DEI topics as well as to normalize conversation of DEI in the clinical setting. Additional study will demonstrate whether this initiative translates into measurable and sustained improvement in knowledge of how bias and disparity show up in the clinical setting and behavioral intent to discuss and address them.