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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.
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Importance: Cell therapy is a promising treatment approach for stroke and other diseases. However, it is unknown whether MultiStem (HLCM051), a bone marrow-derived, allogeneic, multipotent adult progenitor cell product, has the potential to treat ischemic stroke. Objective: To assess the efficacy and safety of MultiStem when administered within 18 to 36 hours of ischemic stroke onset. Design, Setting, and Participants: The Treatment Evaluation of Acute Stroke Using Regenerative Cells (TREASURE) multicenter, double-blind, parallel-group, placebo-controlled phase 2/3 randomized clinical trial was conducted at 44 academic and clinical centers in Japan between November 15, 2017, and March 29, 2022. Inclusion criteria were age 20 years or older, presence of acute ischemic stroke (National Institutes of Health Stroke Scale [NIHSS] score of 8-20 at baseline), confirmed acute infarction involving the cerebral cortex and measuring more than 2 cm on the major axis (determined with diffusion-weighted magnetic resonance imaging), and a modified Rankin Scale (mRS) score of 0 or 1 before stroke onset. Data analysis was performed between May 9 and August 15, 2022. Exposure: Patients were randomly assigned to either intravenous MultiStem in 1 single unit of 1.2 billion cells or intravenous placebo within 18 to 36 hours of ischemic stroke onset. Main Outcomes and Measures: The primary end points were safety and excellent outcome at day 90, measured as a composite of a modified Rankin Scale (mRS) score of 1 or less, a NIHSS score of 1 or less, and a Barthel index score of 95 or greater. The secondary end points were excellent outcome at day 365, mRS score distribution at days 90 and 365, and mRS score of 0 to 1 and 0 to 2 at day 90. Statistical analysis of efficacy was performed using the Cochran-Mantel-Haenszel test. Results: This study included 206 patients (104 received MultiStem and 102 received placebo). Their mean age was 76.5 (range, 35-95) years, and more than half of patients were men (112 [54.4%]). There were no between-group differences in primary and secondary end points. The proportion of excellent outcomes at day 90 did not differ significantly between the MultiStem and placebo groups (12 [11.5%] vs 10 [9.8%], P = .90; adjusted risk difference, 0.5% [95% CI, -7.3% to 8.3%]). The frequency of adverse events was similar between treatment groups. Conclusions and Relevance: In this randomized clinical trial, intravenous administration of allogeneic cell therapy within 18 to 36 hours of ischemic stroke onset was safe but did not improve short-term outcomes. Further research is needed to determine whether MultiStem therapy for ischemic stroke has a beneficial effect in patients who meet specific criteria, as indicated by the exploratory analyses in this study. Trial Registration: ClinicalTrials.gov Identifier: NCT02961504.
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Isquemia Encefálica , Trasplante de Células Madre Hematopoyéticas , Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Adulto , Masculino , Humanos , Anciano , Adulto Joven , Femenino , Accidente Cerebrovascular Isquémico/complicaciones , Isquemia Encefálica/complicaciones , Accidente Cerebrovascular/tratamiento farmacológico , Método Doble Ciego , Trasplante de Células Madre , Resultado del TratamientoRESUMEN
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.
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Accidente Cerebrovascular Hemorrágico , Accidente Cerebrovascular , Humanos , Accidente Cerebrovascular Hemorrágico/complicaciones , Imagen de Difusión Tensora , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/complicaciones , Hemorragia Cerebral/complicaciones , Imagen por Resonancia Magnética/métodos , Hematoma/complicaciones , Coagulación Sanguínea , Hemoglobinas , FibrinaRESUMEN
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 5-17â 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 6â months and 12â 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 1â 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.
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Trasplante de Médula Ósea , Lesiones Traumáticas del Encéfalo , Trasplante Autólogo , Humanos , Niño , Lesiones Traumáticas del Encéfalo/terapia , Masculino , Femenino , Adolescente , Método Doble Ciego , Preescolar , Trasplante de Médula Ósea/métodos , Trasplante Autólogo/métodos , Imagen por Resonancia Magnética , Resultado del Tratamiento , Leucocitos Mononucleares/trasplante , Teorema de BayesRESUMEN
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.
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Enfermedad Pulmonar Obstructiva Crónica , Rehabilitación de Accidente Cerebrovascular , Accidente Cerebrovascular , Humanos , Alta del Paciente , Estudios Retrospectivos , Calidad de Vida , Accidente Cerebrovascular/complicaciones , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , HospitalesRESUMEN
Stroke is a common cause of mortality and serious long-term disability worldwide. In the acute setting, current American Heart Association/American Stroke Association guidelines do not recommend routine anticoagulation for the management of acute ischemic strokes. However, short-term use of unfractionated heparin (UFH) in select subpopulations has demonstrated improved outcomes. While tools such as CHADSVASC and HASBLED scores are useful in stratifying risk of long-term anticoagulation in patients with nonvalvular atrial fibrillation and additional risk factors, the carefully selected patient populations for the design of these studies do not account for risk of hemorrhage from other preexisting conditions. Here, we present a patient with a posterior circulation intraluminal thrombus treated with UFH, who manifested with a near-fatal intra-abdominal hemorrhage from a previously undetected renal angiomyolipoma (AML).
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Ischemic stroke is a debilitating disease and one of the leading causes of long-term disability. During the early phase after ischemic stroke, the blood-brain barrier (BBB) exhibits increased permeability and disruption, leading to an influx of immune cells and inflammatory molecules that exacerbate the damage to the brain tissue. Mesenchymal stem cells have been investigated as a promising therapy to improve the recovery after ischemic stroke. The therapeutic effects imparted by MSCs are mostly paracrine. Recently, the role of extracellular vesicles released by these MSCs have been studied as possible carriers of information to the brain. This review focuses on the potential of MSC derived EVs to repair the components of the neurovascular unit (NVU) controlling the BBB, in order to promote overall recovery from stroke. Here, we review the techniques for increasing the effectiveness of MSC-based therapeutics, such as improved homing capabilities, bioengineering protein expression, modified culture conditions, and customizing the contents of EVs. Combining multiple techniques targeting NVU repair may provide the basis for improved future stroke treatment paradigms.
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Encéfalo/irrigación sanguínea , Vesículas Extracelulares/metabolismo , Accidente Cerebrovascular Isquémico/terapia , Células Madre Mesenquimatosas/metabolismo , Regeneración Nerviosa , Animales , Barrera Hematoencefálica/patología , HumanosRESUMEN
Bone marrow mononuclear cells (MNCs) attenuate secondary degeneration and enhance recovery in stroke animal models. In a nonrandomized clinical trial, we imaged 37 patients with stroke: 17 patients treated with MNCs (treated) and 20 patients who received standard of care (nontreated) at 1, 3, and 12 months onset of stroke on 3.0T MRI system. Three-dimensional anatomical and diffusion tensor images were obtained. The integrity of the corticospinal tract was assessed by measuring absolute and relative fractional anisotropy (FA) and mean diffusivity (MD) in the rostral pons (RP), posterior limb of the internal capsule, and corona radiata by drawing regions of interest. Infarct volume and stroke severity, which was assessed via the NIH Stroke Scale (NIHSS), were higher in the MNC group compared with the nontreated patients, which is a major limitation. Overall, the relative FA (rFA) of the nontreated patients exhibited continued reduction and an increase in relative MD (rMD) from 1 to 12 months, whereas despite larger infarcts and higher severity, treated patients displayed an increase in rFA from 3 to 12 months and no change in rMD. Contrary to the nontreated group, the treated patients' rFA was also significantly correlated (P < .05) with NIHSS score in the RP at all time points, whereas rMD at the last two.
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Trasplante de Médula Ósea , Neuroimagen , Tractos Piramidales , Accidente Cerebrovascular , Células de la Médula Ósea , Imagen de Difusión Tensora , Humanos , Tractos Piramidales/diagnóstico por imagen , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/terapiaRESUMEN
BACKGROUND: Prior studies on rupture risk of brain arteriovenous malformations (AVMs) in women undergoing pregnancy and delivery have reported conflicting findings, but also have not accounted for AVM morphology and heterogeneity. Here, we assess the association between pregnancy and the risk of intracranial hemorrhage (ICH) in women with AVMs using a cohort-crossover design in which each woman serves as her own control. METHODS: Women who underwent pregnancy and delivery were identified using DRG codes from the Healthcare Cost and Utilization Project State Inpatient Databases for California (2005-2011), Florida (2005-2014), and New York (2005-2014). The presence of AVM and ICH was determined using ICD 9 codes. Pregnancy was defined as the 40 weeks prior to delivery, and postpartum as 12 weeks after. We defined a non-exposure control period as a 52-week period prior to pregnancy. The relative risks of ICH during pregnancy were compared against the non-exposure period using conditional Poisson regression. RESULTS: Among 4 022 811 women identified with an eligible delivery hospitalization (median age, 28 years; 7.3% with gestational diabetes; 4.5% with preeclampsia/eclampsia), 568 (0.014%) had an AVM. The rates of ICH during pregnancy and puerperium were 6355.4 (95% CI 4279.4 to 8431.5) and 14.4 (95% CI 13.3 to 15.6) per 100 000 person-years for women with and without AVM, respectively. In cohort-crossover analysis, in women with AVMs the risk of ICH increased 3.27-fold (RR, 95% CI 1.67 to 6.43) during pregnancy and puerperium compared with a non-pregnant period. CONCLUSIONS: Among women with AVM, pregnancy and puerperium were associated with a greater than 3-fold risk of ICH.
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Malformaciones Arteriovenosas Intracraneales , Hemorragias Intracraneales , Complicaciones Cardiovasculares del Embarazo , Adulto , Estudios de Cohortes , Femenino , Humanos , Malformaciones Arteriovenosas Intracraneales/complicaciones , Malformaciones Arteriovenosas Intracraneales/diagnóstico , Malformaciones Arteriovenosas Intracraneales/epidemiología , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/epidemiología , Hemorragias Intracraneales/etiología , Embarazo , Complicaciones Cardiovasculares del Embarazo/diagnóstico , Complicaciones Cardiovasculares del Embarazo/epidemiología , Estudios Retrospectivos , Medición de Riesgo/métodos , Medición de Riesgo/estadística & datos numéricos , Estados Unidos/epidemiologíaRESUMEN
BACKGROUND: Although strokes are rare in trauma patients, they are associated with worse functional and cognitive outcomes and decreased mobility. Blunt cerebrovascular injury (BCVI)-related strokes and mortality have decreased, likely due to refined screening and treatment algorithms in trauma literature; however, there is a paucity of research addressing non-BCVI strokes in trauma. The purpose of this study is to evaluate the incidence, etiology, and risk factors of stroke in our trauma population in order to identify preventive strategies. METHODS: This study was a retrospective review of all adult trauma patients admitted to a level 1 trauma hospital who suffered a stroke during trauma admission from 2010 to 2017. Data were collected from the prospectively maintained trauma and stroke databases. Stroke etiology was determined by a vascular neurologist. RESULTS: Of the 43 674 adult trauma patients admitted during the study period, 99 (0.2%) were diagnosed with a stroke during the index admission. Twenty-one (21%) strokes were due to BCVI. Seventy-eight (79%) strokes were due to non-BCVI etiologies. Patients with non-BCVI strokes were older, less severely injured, and had more medical comorbidities compared with patients with a BCVI stroke. While patients with a BCVI stroke were more likely to suffer multiple traumatic injuries from MVC (76% vs 28%, p<0.001), non-BCVI strokes had more isolated extremity injuries from fall mechanism (55% vs 10%, p<0.001). Over the study period, the age and incidence of stroke and BCVI (p<0.001) increased. However, the rate of BCVI strokes decreased while the rate of non-BCVI strokes increased. DISCUSSION: The incidence of stroke has increased despite aggressive screening and treatment of BCVI. This increase is primarily due to non-BCVI strokes which are associated with advanced age and medical comorbidities after low mechanism traumatic injury. Medical optimization of comorbid conditions during trauma hospitalization will become increasingly important for stroke prevention as the population ages.Level of evidence: Level III.
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BACKGROUND AND PURPOSE: Recent studies show rising incidence of stroke in the young, for which risk factors are not well characterized. There is evidence of increased risk in certain racial and ethnic groups. We assessed racial differences in risk factors, stroke etiology, and outcomes among young stroke patients. METHODS: Using data from our inpatient registry for ischemic stroke, we reviewed patients aged 18-50 who were admitted 01/2013 to 04/2018. Race/ethnicity were characterized as non-Hispanic White (NHW), non-Hispanic Black (NHB), Hispanic (HIS). For univariate comparisons Chi-square and Kruskal-Wallis tests were performed as appropriate. Multivariable logistic regression was used to assess impact of race on day seven modified Rankin score (mRS). RESULTS: Among 810 patients with race and outcome data who were admitted in the study period, median age was 43, 57.1% were male, and 36.5% NHW, 43.2% NHB, 20.2% HIS. History of hypertension (HTN), type II diabetes (DM II), smoking, heart failure (CHF), prior stroke, and end-stage renal disease varied significantly by race. Compared to NHW, NHB had higher odds of HTN (OR 2.28, 1.65-3.15), CHF (OR 2.17, 1.06-4.46), and DM II 1.92 (1.25-2.94) while HIS had higher odds of DM II (OR 2.52, 1.55-4.10) and lower odds of smoking (OR 0.56, 0.35-0.90). Arrival NIHSS was higher in NHB, but etiology and rates of tpA treatment and thrombectomy did not vary by race. Compared to NHW patients, NHB (OR 0.50 CI (0.31-0.78)) and HIS (OR 0.37 CI (0.21-0.67)) were less likely to have good functional outcome (mRS <2) at day 7 in adjusted analyses. CONCLUSIONS: In this study, there was a higher prevalence of several modifiable risk factors in NHB and HIS young stroke patients and early functional outcome was worse in these groups. Our study suggests a need for targeted prevention efforts for younger populations at highest risk for stroke.
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Negro o Afroamericano , Isquemia Encefálica/etnología , Disparidades en el Estado de Salud , Hispánicos o Latinos , Accidente Cerebrovascular/etnología , Población Blanca , Adolescente , Adulto , Factores de Edad , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatología , Bases de Datos Factuales , Diabetes Mellitus/etnología , Evaluación de la Discapacidad , Femenino , Humanos , Hipertensión/etnología , Incidencia , Masculino , Persona de Mediana Edad , Prevalencia , Pronóstico , Factores Raciales , Recuperación de la Función , Sistema de Registros , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Fumar/efectos adversos , Fumar/etnología , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/fisiopatología , Texas/epidemiología , Factores de Tiempo , Adulto JovenRESUMEN
Importance: Intracerebral hemorrhage (ICH) during pregnancy and the postpartum period results in catastrophic maternal outcomes. There is a paucity of population-based estimates of pregnancy-related ICH risk, including risk during the extended postpartum period. Objective: To evaluate ICH risk during pregnancy and an extended 24-week postpartum period in a population-level cohort and to determine fetal and maternal outcomes as well as demographic and comorbidity factors associated with ICH during pregnancy and post partum. Design, Setting, and Participants: This study used a cohort-crossover design in which patients serve as their own controls when no longer exposed (pregnant or post partum). Administrative data were obtained from all hospital admissions for New York, California, and Florida for a 7- to 10-year period. Participants included all women admitted for labor and delivery who were older than 12 years and did not have a prior diagnosis of ICH. Conditional Poisson regression models were used to evaluate ICH risk, and data were reported as rate ratios and 95% CIs. Data analysis was performed from August 2018 to February 2020. Exposures: Women were tracked using hospitalization records for the duration of pregnancy (40 weeks), for 24 weeks post partum, and for an additional 64 weeks when no longer exposed. Main Outcomes and Measures: Diagnosis of ICH during both 64-week observation periods was determined using validated International Classification of Diseases, Ninth Revision codes. Results: A total of 3â¯314â¯945 pregnant women were included (mean [SD] age, 28.17 [6.47] years; 1â¯451â¯780 white [43.79%], 474â¯808 black [14.32%], 246â¯789 Asian [7.44%], and 835â¯917 Hispanic [25.22%]). The risk of ICH was significantly higher during the third trimester (2.9 vs 0.7 cases per 100â¯000 pregnancies; rate ratio, 4.16; 95% CI, 2.52-6.86) and remained elevated during the first 12 weeks post partum (4.4 vs 0.5 cases per 100â¯000 pregnancies; rate ratio, 9.15; 95% CI, 5.16-16.23). Advanced maternal age (adjusted odds ratio [OR], 1.08; 95% CI, 1.05-1.10), nonwhite race (adjusted ORs, 2.44 [95% CI, 1.73-3.44] for black patients, 2.12 [95% CI, 1.34-3.35] for Asian patients, and 1.59 [95% CI, 1.12-2.26] for Hispanic patients), hypertension (adjusted OR, 2.02; 95% CI, 1.19-3.42), coagulopathy (adjusted OR, 14.17; 95% CI, 9.17-21.89), preeclampsia or eclampsia (adjusted OR, 9.23; 95% CI, 6.99-12.19), and tobacco use (adjusted OR, 2.83; 95% CI, 1.53-5.23) were independently associated with ICH during pregnancy and the postpartum period. Pregnancy-related ICH was associated with a higher risk of maternal (relative risk difference, 792.6; absolute risk difference, 0.18) and fetal (relative risk difference, 5.3; absolute risk difference, 0.03) death, compared with pregnancies without ICH. Conclusions and Relevance: These findings suggest that the risk of ICH is significantly higher during the third trimester of pregnancy and the first 12 weeks post partum. There are age and race disparities in ICH risk that are associated with devastating maternal and fetal outcomes. These data illustrate the critical need for continuous monitoring and aggressive management of ICH-associated risk factors. These findings suggest that extended postpartum monitoring of high-risk women may be warranted.
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Hemorragia Cerebral/etiología , Hemorragia Cerebral/fisiopatología , Periodo Posparto , Complicaciones Cardiovasculares del Embarazo/fisiopatología , Adulto , Negro o Afroamericano/estadística & datos numéricos , Factores de Edad , Hemorragia Cerebral/epidemiología , Estudios de Cohortes , Femenino , Hispánicos o Latinos/estadística & datos numéricos , Humanos , Oportunidad Relativa , Embarazo , Complicaciones Cardiovasculares del Embarazo/epidemiología , Factores Raciales , Estudios Retrospectivos , Factores de Riesgo , Factores Socioeconómicos , Estados Unidos/epidemiología , Población Blanca/estadística & datos numéricos , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: Post-stroke anxiety (PSA) is common and disabling. PSA should be considered as an important outcome in stroke. However, there is a lack of understanding of factors that may be linked to PSA. The purpose of this study was to determine the frequency of PSA and sociodemographic and clinical factors associated with PSA in a cohort of racially and ethnically diverse stroke patients. METHODS: We conducted a retrospective study of ischemic and hemorrhagic stroke patients seen in a stroke outpatient clinic from August 1, 2017 to June 30, 2018. Patients were eligible if a Generalized Anxiety Disorder 7-Item (GAD-7) instrument was available. GAD-7 scores greater than or equal to 10 indicated the presence of moderate to severe PSA. Multivariable logistic regression was used to identify independent sociodemographic and clinical factors associated with PSA. RESULTS: Records from 289 stroke patients with a GAD-7 instrument were analyzed. PSA was common (21%; GAD-7 ≥ 10). Fifty-seven percent of females had a GAD-7 greater than or equal to 10 compared to 41% of females who had a GAD-7 less than 10 (Pâ¯=â¯.03). Multivariable analysis found that self-reported nonmarried status (odds ratio, 3.27; 95% confidence interval, 1.44-7.44), excessive fatigue (odds ratio, 4.46; 95% confidence interval, 1.87-10.63), and depression (odds ratio, 1.24; 95% confidence interval, 1.16-1.33) were independently associated with PSA. CONCLUSIONS: PSA may occur more frequently in those who report non-married, excessive fatigue, or depression. Trials of PSA interventions should consider the potential impact of social support, depression, and comorbid conditions contributing to post-stroke fatigue, including sleep apnea.
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Ansiedad/psicología , Isquemia Encefálica/psicología , Hemorragias Intracraneales/complicaciones , Ataque Isquémico Transitorio/psicología , Accidente Cerebrovascular/psicología , Adulto , Anciano , Ansiedad/diagnóstico , Ansiedad/epidemiología , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/epidemiología , Comorbilidad , Depresión/epidemiología , Depresión/psicología , Fatiga/epidemiología , Fatiga/psicología , Femenino , Humanos , Hemorragias Intracraneales/diagnóstico , Hemorragias Intracraneales/psicología , Ataque Isquémico Transitorio/diagnóstico , Ataque Isquémico Transitorio/epidemiología , Masculino , Salud Mental , Persona de Mediana Edad , Pronóstico , Estudios Retrospectivos , Medición de Riesgo , Factores de Riesgo , Persona Soltera/psicología , Aislamiento Social , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Texas/epidemiologíaRESUMEN
Cellular therapy is a promising investigational modality to enhance poststroke recovery. We conducted a single-arm, phase I clinical trial to determine the safety and feasibility of intravenous (IV) administration of autologous bone marrow mononuclear cells (MNCs) after acute ischemic stroke (AIS). Patients with moderate severity of AIS underwent bone marrow harvest followed by IV reinfusion of MNCs within 24-72 hours of onset. A target dose of 10 million cells per kilogram was chosen based on preclinical data. Patients were followed up daily during hospitalization and at 1, 3, 6, 12, and 24 months for incidence of adverse events using laboratory, clinical (12 months), and radiological (24 months) parameters. The trial was powered to detect severe adverse events (SAEs) with incidences of at least 10% and planned to enroll 30 patients. Primary outcomes were study-related SAEs and the proportion of patients successfully completing study intervention. A propensity score-based matched control group was used for the estimation of effect size (ES) for day-90 modified Rankin score (mRS). There were no study-related SAEs and, based on a futility analysis, enrolment was stopped after 25 patients. All patients successfully completed study intervention and most received the target dose. Secondary analysis estimated the ES to be a reduction of 1 point (95% confidence interval: 0.33-1.67) in median day-90 mRS for treated patients as compared with the matched control group. Bone marrow harvest and infusion of MNCs is safe and feasible in patients with AIS. The estimated ES is helpful in designing future randomized controlled trials. Stem Cells 2019;37:1481-1491.
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Células de la Médula Ósea/citología , Trasplante de Médula Ósea/efectos adversos , Isquemia Encefálica/terapia , Leucocitos Mononucleares/citología , Accidente Cerebrovascular/terapia , Administración Intravenosa , Anciano , Células de la Médula Ósea/fisiología , Trasplante de Médula Ósea/métodos , Isquemia Encefálica/diagnóstico por imagen , Imagen de Difusión Tensora , Estudios de Factibilidad , Femenino , Humanos , Leucocitos Mononucleares/fisiología , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/diagnóstico por imagen , Resultado del TratamientoRESUMEN
BACKGROUND AND OBJECTIVE: Most stroke patients are prescribed aspirin (ASA) to adjust blood coagulability. Marrow stromal cells (MSCs) are being tested in clinical trials for stroke patients who likely are prescribed aspirin. One of the principal mechanisms of action of MSCs and ASA is modulation of the inflammatory response, including those mediated by monocytes (Mo). Thus, here we tested if aspirin can modify anti-inflammatory properties of MSCs or Mo alone, and in combination. METHODS: Mo were isolated at 24â¯h of stroke onset from ischemic stroke patients with NIHSS ranging from 11 to 20 or from healthy controls. Human bone marrow-derived MSCs from healthy subjects were used at passage 3. Mo, MSCs, and MSCs-Mo co-cultures were exposed to ASA at clinically relevant doses. The secretome profile of inflammatory mediators was measured using Magpix multiplex cytokine array. Viability was measured using MTT assay. Linear mixed effect model was used for statistical analysis. RESULTS: Overall Mo from control subjects exposed to ASA showed increased secretion of IL-1RA, IL-8, MCP-1, and TNF-α and Mo from stroke patients showed greater release of IL-1RA and MCP-1. In MSCs-Mo co-cultures, ASA added to co-cultures of control Mo reduced fractalkine secretion while it increased the fractalkine secretion when added to Mo from stroke patients. In addition, in co-cultures independent of Mo origin, ASA reduced IL-6, IL-8, MCP-1, and TNF-α. CONCLUSIONS: Aspirin in acute stroke patients may modulate the secretome profile of Mo and MSCs, thus potentially modulating immune and inflammatory responses associated with stroke. Our results suggest that stroke trials involving the use of intravenous MSCs should consider the effect of aspirin as a confounding factor.
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Aspirina/uso terapéutico , Inmunomodulación/efectos de los fármacos , Accidente Cerebrovascular/tratamiento farmacológico , Anciano , Aspirina/metabolismo , Médula Ósea , Quimiocina CCL2 , Técnicas de Cocultivo , Citocinas , Femenino , Humanos , Proteína Antagonista del Receptor de Interleucina 1 , Masculino , Células Madre Mesenquimatosas/efectos de los fármacos , Células Madre Mesenquimatosas/metabolismo , Persona de Mediana Edad , Monocitos/efectos de los fármacos , Monocitos/metabolismo , Accidente Cerebrovascular/metabolismo , Células del Estroma/efectos de los fármacos , Células del Estroma/metabolismo , Factor de Necrosis Tumoral alfaRESUMEN
Purpose: Cell-based therapy offers new opportunities for the development of novel treatments to promote tissue repair, functional restoration, and cerebral metabolic balance. N-acetylasperate (NAA), Choline (Cho), and Creatine (Cr) are three major metabolites seen on proton magnetic resonance spectroscopy (MRS) that play a vital role in balancing the biochemical processes and are suggested as markers of recovery. In this preliminary study, we serially monitored changes in these metabolites in ischemic stroke patients who were treated with autologous bone marrow-derived mononuclear cells (MNCs) using non-invasive MRS. Materials and Methods: A sub-group of nine patients (3 male, 6 female) participated in a serial MRS study, as part of a clinical trial on autologous bone marrow cell therapy in acute ischemic stroke. Seven to ten million mononuclear cells were isolated from the patient's bone marrow and administered intravenously within 72 h of onset of injury. MRS data were obtained at 1, 3, and 6 months using a whole-body 3.0T MRI. Single voxel point-resolved spectroscopy (PRESS) was obtained within the lesion and contralesional gray matter. Spectral analysis was done using TARQUIN software and absolute concentration of NAA, Cho, and Cr was determined. National Institute of Health Stroke Scale (NIHSS) was serially recoreded. Two-way analysis of variance was performed and p < 0.05 considered statistically significant. Results: All metabolites showed statistically significant or clear trends toward lower ipsilesional concentrations compared to the contralesional side at all time points. Statistically significant reductions were found in ipsilesional NAA at 1M and 3M, Cho at 6M, and Cr at 1M and 6M (p < 0.03), compared to the contralesional side. Temporally, ipsilesional NAA increased between 3M and 6M (p < 0.01). On the other hand, ipsilesional Cho showed continued decline till 6M (p < 0.01). Ipsilesional Cr was stable over time. Contralesional metabolites were relatively stable over time, with only Cr showing a reduction 3M (p < 0.02). There was a significant (p < 0.03) correlation between ipsilesional NAA and NIHSS at 3M follow-up. Conclusion: Serial changes in metabolites suggest that MRS can be applied to monitor therapeutic changes. Post-treatment increasing trends of NAA concentration and significant correlation with NIHSS support a potential therapeutic effect.
RESUMEN
BACKGROUND: Ischemic stroke has no approved treatments to enhance recovery. ALD-401 is an enriched population of aldehyde dehydrogenase-bright stem cells, capable of reducing neurological deficits in animal models. The primary objective of this trial was to determine the safety of internal carotid artery, intra-arterially delivered autologous bone marrow-derived ALD-401 in patients with disabling middle cerebral artery stroke in comparison with sham harvest with sham infusion. Secondary objectives were to determine feasibility and efficacy. METHODS: This was a prospective phase 2, industry-funded, randomized, sham-controlled, parallel-group, multicenter study with blinded assessments. One hundred subjects were planned, aged 30 to 83 years, with confirmed first-time middle cerebral artery ischemic stroke with modified Rankin scale ≥3. Study patients were randomly assigned 3:2 to bone marrow harvest at 11 to 17 days after stroke followed 2 days later by intracarotid infusion of ALD-401 versus sham harvest and then sham infusion in the same timeframe. The primary study outcome was safety based on the incidence of a 4-point National Institutes of Health Stroke Scale worsening and the proportion of serious adverse events. Efficacy was based on modified Rankin scale change at 90 days. Other secondary outcomes were the proportions of patients experiencing adverse events, disability by Barthel Index, quality of life using EQ-5D, rehabilitation utilization, disability at 1 year, and MRI evidence of complications. RESULTS: There were no infusional or allergic reactions and no difference in treatment emergent adverse events. Four patients had small areas of asymptomatic restricted diffusion on MRI in the treatment group. There was no significant difference between the ALD-401 and placebo groups on the modified Rankin scale for the intent-to-treat population at day 90 (mean difference, 0.3; 95% CI, -0.3 to 0.8; P=0.330). There were no significant differences between the groups on any of the secondary efficacy measures. CONCLUSIONS: Intracarotid infusion of ALD-401 does not lead to clinical adverse events in patients with subacute ischemic stroke, although there was a higher incidence of small lesions on MRI in the treatment group. There was no difference in the primary efficacy end point between the groups. The study provides a framework for the design and conduct of future intra-arterial cell therapy trials in stroke. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT01273337.
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Aldehído Deshidrogenasa/metabolismo , Infarto de la Arteria Cerebral Media/cirugía , Trasplante de Células Madre/métodos , Células Madre/enzimología , Adulto , Anciano , Anciano de 80 o más Años , Arteria Carótida Interna , Evaluación de la Discapacidad , Método Doble Ciego , Estudios de Factibilidad , Femenino , Humanos , Infarto de la Arteria Cerebral Media/diagnóstico , Infarto de la Arteria Cerebral Media/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Calidad de Vida , Recuperación de la Función , Trasplante de Células Madre/efectos adversos , Encuestas y Cuestionarios , Factores de Tiempo , Resultado del Tratamiento , Estados UnidosRESUMEN
BACKGROUND: The likelihood of retreatment in patients undergoing procedures for cerebral aneurysms (CAs) has an important role in deciding the optimal treatment type. Existing determinations of retreatment rates, particularly for unruptured CAs, may not represent current clinical practice. OBJECTIVE: To use population-level data to examine a large cohort of patients with treated CAs over a 10-year period to estimate retreatment rates for both ruptured and unruptured CAs and explore the effect of changing treatment practices. METHODS: We used administrative data from all non-federal hospitalizations in California (2005-2011) and Florida (2005-2014) and identified patients with treated CAs. Surgical clipping (SC) and endovascular treatments (ETs) were defined by corresponding procedure codes and an accompanying code for ruptured or unruptured CA. Retreatment was defined as subsequent SC or ET. RESULTS: Among 19 482 patients with treated CAs, ET was performed in 12 007 (62%) patients and SC in 7475 (38%). 9279 (48%) patients underwent treatment for unruptured CAs and 10203 (52%) for ruptured. Retreatment after 90 days occurred in 1624 (8.3%) patients (11.2% vs 3.7%, ET vs SC). Retreatment rates for SC were greater in unruptured than in ruptured aneurysms (4.6% vs 3.1%), but the opposite was true for ET (10.6% vs 11.8%). 85% of retreatments were within 2 years of the index treatment. Retreatment was associated with age (OR=0.99, 95% CI 0.98 to 0.99), female sex (OR=1.5, 95% CI 1.3 to 1.7), Hispanic versus white race (OR=0.86, 95% CI 0.75 to 0.98), and ET versus SC (OR=3.25, 95% CI 2.85 to 3.71). The adjusted 2-year retreatment rate decreased from 2005 to 2012 for patients with unruptured CAs treated with ET (11% to 8%). CONCLUSIONS: Retreatment rates for CAs treated with ET were greater than those for SC. However, for patients with unruptured CAs treated with ET, we identify a continuous decline in retreatment rate over the past decade.
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Aneurisma Roto/terapia , Procedimientos Endovasculares/tendencias , Aneurisma Intracraneal/terapia , Vigilancia de la Población , Instrumentos Quirúrgicos/tendencias , Adulto , Anciano , Aneurisma Roto/diagnóstico por imagen , Aneurisma Roto/epidemiología , California/epidemiología , Estudios de Cohortes , Estudios Transversales , Embolización Terapéutica/métodos , Embolización Terapéutica/tendencias , Procedimientos Endovasculares/métodos , Femenino , Florida/epidemiología , Humanos , Aneurisma Intracraneal/diagnóstico por imagen , Aneurisma Intracraneal/epidemiología , Masculino , Persona de Mediana Edad , Vigilancia de la Población/métodos , Retratamiento/tendencias , Estudios Retrospectivos , Factores de TiempoRESUMEN
BACKGROUND AND PURPOSE: Women minorities have an overall increased lifetime incidence of cerebrovascular disease. The provision of risk factor modification in this group can prove difficult. In a population-based study, we used cluster enrollment to identify vascular risk factors in the female caregivers of stroke survivor study participants. METHODS: Obese women caregivers were identified as part of Swipe out Stroke, a Phase I PROBE study assessing the use of SmartPhone based intervention for dietary modification in minority stroke survivors. After written informed consent was obtained, both patients and caregivers were screened for vascular risk factors at study enrollment. Descriptive statistics were used to depict the study population. Continuous baseline variables were compared using 2 sample t-test or Wilcoxon rank-sum test by caregivers and patients. Categorical baseline variables were compared using Fisher's exact test. RESULTS: Thirty-six stroke patients (63.9% African-American, 36.1% Hispanic) and thirteen female caregivers (69.2% African-American, 30.8% Hispanic) were enrolled. Mean age, patients - 54.1 (SD 9.4), caregivers - 51.3 (SD 15.6) years, education, employment status and family history of stroke or obesity did not differ significantly. Compared to stroke patients, female caregivers were significantly less likely to self-report hypertension (69.2 versus 97.2%; P = 0.01) and hyperlipidemia (16.7 versus 60%; P = 0.02). Female caregivers were more likely to have elevated systolic blood pressure (147.6 vs 127.7 mmHg; P = 0.05), total cholesterol (207.5 versus 167 mg/dL; P = 0.01) and low density lipoprotein values (119.5 versus 88 mg/dL; P = 0.03) compared to stroke patients. CONCLUSIONS: Using cluster enrollment, we discovered minority female caregivers were more likely to have unknown or poorly controlled vascular risk factors compared to stroke patients. Innovative health screening tools may benefit the extended family of minority patients participating in clinical trials.