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1.
Neurology ; 102(12): e209442, 2024 Jun 25.
Artículo en Inglés | MEDLINE | ID: mdl-38771998

RESUMEN

BACKGROUND AND OBJECTIVES: Few population-based studies have assessed associations between the use of antithrombotic (platelet antiaggregant or anticoagulant) drugs and location-specific risks of spontaneous intracerebral hemorrhage (s-ICH). In this study, we estimated associations between antithrombotic drug use and the risk of lobar vs nonlobar incident s-ICH. METHODS: Using Danish nationwide registries, we identified cases in the Southern Denmark Region of first-ever s-ICH in patients aged 50 years or older between 2009 and 2018. Each verified case was classified as lobar or nonlobar s-ICH and matched to controls in the general population by age, sex, and calendar year. Prior antithrombotic use was ascertained from a nationwide prescription registry. We calculated odds ratios (aORs) for associations between the use of clopidogrel, aspirin, direct oral anticoagulants (DOACs) or vitamin K antagonists (VKA), and lobar and nonlobar ICH in conditional logistic regression analyses that were adjusted for potential confounders. RESULTS: A total of 1,040 cases of lobar (47.9% men, mean age [SD] 75.2 [10.7] years) and 1,263 cases of nonlobar s-ICH (54.2% men, mean age 73.6 [11.4] years) were matched to 41,651 and 50,574 controls, respectively. A stronger association with lobar s-ICH was found for clopidogrel (cases: 7.6%, controls: 3.5%; aOR 3.46 [95% CI 2.45-4.89]) vs aspirin (cases: 22.9%, controls: 20.4%; aOR 2.14 [1.74-2.63; p = 0.019). Corresponding estimates for nonlobar s-ICH were not different between clopidogrel (cases: 5.4%, controls: 3.4%; aOR 2.44 [1.71-3.49]) and aspirin (cases: 20.7%, controls: 19.2%; aOR 1.77 [1.47-2.15]; p = 0.12). VKA use was associated with higher odds of both lobar (cases: 14.3%, controls: 6.1%; aOR 3.66 [2.78-4.80]) and nonlobar (cases: 15.4%, controls: 5.5%; aOR 4.62 [3.67-5.82]) s-ICH. The association of DOAC use with lobar s-ICH (cases: 3.5%, controls: 2.7%; aOR 1.66 [1.02-2.70]) was weaker than that of VKA use (p = 0.006). Corresponding estimates for nonlobar s-ICH were not different between DOACs (cases: 5.1%, controls: 2.4%; aOR 3.44 [2.33-5.08]) and VKAs (p = 0.20). DISCUSSION: Antithrombotics were associated with higher risks of s-ICH, but the strength of the associations varied by s-ICH location and drug, which may reflect differences in the cerebral microangiopathies associated with lobar vs nonlobar hemorrhages and the mechanisms of drug action.


Asunto(s)
Hemorragia Cerebral , Fibrinolíticos , Sistema de Registros , Humanos , Masculino , Femenino , Anciano , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/inducido químicamente , Dinamarca/epidemiología , Persona de Mediana Edad , Fibrinolíticos/efectos adversos , Anciano de 80 o más Años , Inhibidores de Agregación Plaquetaria/efectos adversos , Anticoagulantes/efectos adversos , Clopidogrel/efectos adversos , Clopidogrel/uso terapéutico , Aspirina/efectos adversos , Incidencia
2.
Cereb Cortex ; 34(5)2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38715405

RESUMEN

OBJECTIVES: This retrospective study aimed to identify quantitative magnetic resonance imaging markers in the brainstem of preterm neonates with intraventricular hemorrhages. It delves into the intricate associations between quantitative brainstem magnetic resonance imaging metrics and neurodevelopmental outcomes in preterm infants with intraventricular hemorrhage, aiming to elucidate potential relationships and their clinical implications. MATERIALS AND METHODS: Neuroimaging was performed on preterm neonates with intraventricular hemorrhage using a multi-dynamic multi-echo sequence to determine T1 relaxation time, T2 relaxation time, and proton density in specific brainstem regions. Neonatal outcome scores were collected using the Bayley Scales of Infant and Toddler Development. Statistical analysis aimed to explore potential correlations between magnetic resonance imaging metrics and neurodevelopmental outcomes. RESULTS: Sixty preterm neonates (mean gestational age at birth 26.26 ± 2.69 wk; n = 24 [40%] females) were included. The T2 relaxation time of the midbrain exhibited significant positive correlations with cognitive (r = 0.538, P < 0.0001, Pearson's correlation), motor (r = 0.530, P < 0.0001), and language (r = 0.449, P = 0.0008) composite scores at 1 yr of age. CONCLUSION: Quantitative magnetic resonance imaging can provide valuable insights into neurodevelopmental outcomes after intraventricular hemorrhage, potentially aiding in identifying at-risk neonates. Multi-dynamic multi-echo sequence sequences hold promise as an adjunct to conventional sequences, enhancing the sensitivity of neonatal magnetic resonance neuroimaging and supporting clinical decision-making for these vulnerable patients.


Asunto(s)
Tronco Encefálico , Recien Nacido Prematuro , Imagen por Resonancia Magnética , Humanos , Masculino , Femenino , Imagen por Resonancia Magnética/métodos , Recién Nacido , Estudios Retrospectivos , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/crecimiento & desarrollo , Lactante , Hemorragia Cerebral Intraventricular/diagnóstico por imagen , Hemorragia Cerebral/diagnóstico por imagen , Trastornos del Neurodesarrollo/diagnóstico por imagen , Trastornos del Neurodesarrollo/etiología , Edad Gestacional
3.
Crit Care Explor ; 6(5): e1089, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38728059

RESUMEN

IMPORTANCE: Patients admitted with cerebral hemorrhage or cerebral edema often undergo external ventricular drain (EVD) placement to monitor and manage intracranial pressure (ICP). A strain gauge transducer accompanies the EVD to convert a pressure signal to an electrical waveform and assign a numeric value to the ICP. OBJECTIVES: This study explored ICP accuracy in the presence of blood and other viscous fluid contaminates in the transducer. DESIGN: Preclinical comparative design study. SETTING: Laboratory setting using two Natus EVDs, two strain gauge transducers, and a sealed pressure chamber. PARTICIPANTS: No human subjects or animal models were used. INTERVENTIONS: A control transducer primed with saline was compared with an investigational transducer primed with blood or with saline/glycerol mixtures in mass:mass ratios of 25%, 50%, 75%, and 100% glycerol. Volume in a sealed chamber was manipulated to reflect changes in ICP to explore the impact of contaminates on pressure measurement. MEASUREMENTS AND MAIN RESULTS: From 90 paired observations, ICP readings were statistically significantly different between the control (saline) and experimental (glycerol or blood) transducers. The time to a stable pressure reading was significantly different for saline vs. 25% glycerol (< 0.0005), 50% glycerol (< 0.005), 75% glycerol (< 0.0001), 100% glycerol (< 0.0005), and blood (< 0.0005). A difference in resting stable pressure was observed for saline vs. blood primed transducers (0.041). CONCLUSIONS AND RELEVANCE: There are statistically significant and clinically relevant differences in time to a stable pressure reading when contaminates are introduced into a closed drainage system. Changing a transducer based on the presence of blood contaminate should be considered to improve accuracy but must be weighed against the risk of introducing infection.


Asunto(s)
Presión Intracraneal , Transductores de Presión , Presión Intracraneal/fisiología , Humanos , Sangre/metabolismo , Glicerol , Monitoreo Fisiológico/instrumentación , Monitoreo Fisiológico/métodos , Drenaje/instrumentación , Hemorragia Cerebral/fisiopatología , Hemorragia Cerebral/diagnóstico
4.
Sci Rep ; 14(1): 10833, 2024 05 12.
Artículo en Inglés | MEDLINE | ID: mdl-38734835

RESUMEN

Our aim was to develop a machine learning-based predictor for early mortality and severe intraventricular hemorrhage (IVH) in very-low birth weight (VLBW) preterm infants in Taiwan. We collected retrospective data from VLBW infants, dividing them into two cohorts: one for model development and internal validation (Cohort 1, 2016-2021), and another for external validation (Cohort 2, 2022). Primary outcomes included early mortality, severe IVH, and early poor outcomes (a combination of both). Data preprocessing involved 23 variables, with the top four predictors identified as gestational age, birth body weight, 5-min Apgar score, and endotracheal tube ventilation. Six machine learning algorithms were employed. Among 7471 infants analyzed, the selected predictors consistently performed well across all outcomes. Logistic regression and neural network models showed the highest predictive performance (AUC 0.81-0.90 in both internal and external validation) and were well-calibrated, confirmed by calibration plots and the lowest two mean Brier scores (0.0685 and 0.0691). We developed a robust machine learning-based outcome predictor using only four accessible variables, offering valuable prognostic information for parents and aiding healthcare providers in decision-making.


Asunto(s)
Recien Nacido Prematuro , Recién Nacido de muy Bajo Peso , Aprendizaje Automático , Humanos , Recién Nacido , Femenino , Masculino , Estudios Retrospectivos , Taiwán/epidemiología , Lactante , Pronóstico , Hemorragia Cerebral/mortalidad , Edad Gestacional , Hemorragia Cerebral Intraventricular/mortalidad , Hemorragia Cerebral Intraventricular/epidemiología , Mortalidad Infantil , Peso al Nacer , Enfermedades del Prematuro/mortalidad
5.
Mikrochim Acta ; 191(6): 325, 2024 05 13.
Artículo en Inglés | MEDLINE | ID: mdl-38739279

RESUMEN

Glial fibrillary acidic protein (GFAP) in serum has been shown as a biomarker of traumatic brain injury (TBI) which is a significant global public health concern. Accurate and rapid detection of serum GFAP is critical for TBI diagnosis. In this study, a time-resolved fluorescence immunochromatographic test strip (TRFIS) was proposed for the quantitative detection of serum GFAP. This TRFIS possessed excellent linearity ranging from 0.05 to 2.5 ng/mL for the detection of serum GFAP and displayed good linearity (Y = 598723X + 797198, R2 = 0.99), with the lowest detection limit of 16 pg/mL. This TRFIS allowed for quantitative detection of serum GFAP within 15 min and showed high specificity. The intra-batch coefficient of variation (CV) and the inter-batch CV were both < 4.0%. Additionally, this TRFIS was applied to detect GFAP in the serum samples from healthy donors and patients with cerebral hemorrhage, and the results of TRFIS could efficiently discern the patients with cerebral hemorrhage from the healthy donors. Our developed TRFIS has the characteristics of high sensitivity, high accuracy, and a wide linear range and is suitable for rapid and quantitative determination of serum GFAP on-site.


Asunto(s)
Cromatografía de Afinidad , Proteína Ácida Fibrilar de la Glía , Límite de Detección , Proteína Ácida Fibrilar de la Glía/sangre , Humanos , Cromatografía de Afinidad/métodos , Tiras Reactivas , Hemorragia Cerebral/sangre , Hemorragia Cerebral/diagnóstico , Biomarcadores/sangre
7.
N Engl J Med ; 390(19): 1745-1755, 2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38749032

RESUMEN

BACKGROUND: Patients with acute intracerebral hemorrhage who are receiving factor Xa inhibitors have a risk of hematoma expansion. The effect of andexanet alfa, an agent that reverses the effects of factor Xa inhibitors, on hematoma volume expansion has not been well studied. METHODS: We randomly assigned, in a 1:1 ratio, patients who had taken factor Xa inhibitors within 15 hours before having an acute intracerebral hemorrhage to receive andexanet or usual care. The primary end point was hemostatic efficacy, defined by expansion of the hematoma volume by 35% or less at 12 hours after baseline, an increase in the score on the National Institutes of Health Stroke Scale of less than 7 points (scores range from 0 to 42, with higher scores indicating worse neurologic deficit) at 12 hours, and no receipt of rescue therapy between 3 hours and 12 hours. Safety end points were thrombotic events and death. RESULTS: A total of 263 patients were assigned to receive andexanet, and 267 to receive usual care. Efficacy was assessed in an interim analysis that included 452 patients, and safety was analyzed in all 530 enrolled patients. Atrial fibrillation was the most common indication for factor Xa inhibitors. Of the patients receiving usual care, 85.5% received prothrombin complex concentrate. Hemostatic efficacy was achieved in 150 of 224 patients (67.0%) receiving andexanet and in 121 of 228 (53.1%) receiving usual care (adjusted difference, 13.4 percentage points; 95% confidence interval [CI], 4.6 to 22.2; P = 0.003). The median reduction from baseline to the 1-to-2-hour nadir in anti-factor Xa activity was 94.5% with andexanet and 26.9% with usual care (P<0.001). Thrombotic events occurred in 27 of 263 patients (10.3%) receiving andexanet and in 15 of 267 (5.6%) receiving usual care (difference, 4.6 percentage points; 95% CI, 0.1 to 9.2; P = 0.048); ischemic stroke occurred in 17 patients (6.5%) and 4 patients (1.5%), respectively. There were no appreciable differences between the groups in the score on the modified Rankin scale or in death within 30 days. CONCLUSIONS: Among patients with intracerebral hemorrhage who were receiving factor Xa inhibitors, andexanet resulted in better control of hematoma expansion than usual care but was associated with thrombotic events, including ischemic stroke. (Funded by Alexion AstraZeneca Rare Disease and others; ANNEXA-I ClinicalTrials.gov number, NCT03661528.).


Asunto(s)
Hemorragia Cerebral , Inhibidores del Factor Xa , Factor Xa , Hematoma , Proteínas Recombinantes , Humanos , Inhibidores del Factor Xa/efectos adversos , Inhibidores del Factor Xa/uso terapéutico , Anciano , Masculino , Femenino , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/inducido químicamente , Persona de Mediana Edad , Proteínas Recombinantes/uso terapéutico , Proteínas Recombinantes/efectos adversos , Factor Xa/uso terapéutico , Factor Xa/efectos adversos , Hematoma/inducido químicamente , Hematoma/tratamiento farmacológico , Anciano de 80 o más Años , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Enfermedad Aguda
8.
Mo Med ; 121(2): 136-141, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38694609

RESUMEN

The landscape of the cranial neurosurgery has changed tremendously in past couple of decades. The main frontiers including introduction of neuro-endoscopy, minimally invasive skull base approaches, SRS, laser interstitial thermal therapy and use of tubular retractors have revolutionized the management of intracerebral hemorrhages, deep seated tumors other intracranial pathologies. Introduction of these novel techniques is based on smaller incisions with maximal operative corridors, decreased blood loss, shorter hospital stays, decreased post-operative pain and cosmetically appealing scars that improves patient satisfaction and clinical outcomes. The sophisticated tools like neuroendoscopy have improved light source, and better visualization around the corners. Advanced navigated tools and channel-based retractors help us to target deeply seated lesions with increased precision and minimal disruption of the surrounding neurovascular tissues. Advent of stereotactic radiosurgery has provided us alternative feasible, safe and effective options for treatment of patients who are otherwise not medically stable to undergo complex cranial surgical interventions. This paper review advances in treatment of intracranial pathologies, and how the neurosurgeons and other medical providers at the University of Missouri-Columbia (UMC) are optimizing these treatments for their patients.


Asunto(s)
Procedimientos Neuroquirúrgicos , Humanos , Procedimientos Neuroquirúrgicos/métodos , Procedimientos Neuroquirúrgicos/tendencias , Radiocirugia/métodos , Radiocirugia/tendencias , Hemorragia Cerebral/cirugía , Neoplasias Encefálicas/cirugía , Neuroendoscopía/métodos , Neuroendoscopía/tendencias
9.
Sci Rep ; 14(1): 10008, 2024 05 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693282

RESUMEN

Historically, investigators have not differentiated between patients with and without hemorrhagic transformation (HT) in large core ischemic stroke at risk for life-threatening mass effect (LTME) from cerebral edema. Our objective was to determine whether LTME occurs faster in those with HT compared to those without. We conducted a two-center retrospective study of patients with ≥ 1/2 MCA territory infarct between 2006 and 2021. We tested the association of time-to-LTME and HT subtype (parenchymal, petechial) using Cox regression, controlling for age, mean arterial pressure, glucose, tissue plasminogen activator, mechanical thrombectomy, National Institute of Health Stroke Scale, antiplatelets, anticoagulation, temperature, and stroke side. Secondary and exploratory outcomes included mass effect-related death, all-cause death, disposition, and decompressive hemicraniectomy. Of 840 patients, 358 (42.6%) had no HT, 403 (48.0%) patients had petechial HT, and 79 (9.4%) patients had parenchymal HT. LTME occurred in 317 (37.7%) and 100 (11.9%) had mass effect-related deaths. Parenchymal (HR 8.24, 95% CI 5.46-12.42, p < 0.01) and petechial HT (HR 2.47, 95% CI 1.92-3.17, p < 0.01) were significantly associated with time-to-LTME and mass effect-related death. Understanding different risk factors and sequelae of mass effect with and without HT is critical for informed clinical decisions.


Asunto(s)
Hospitalización , Infarto de la Arteria Cerebral Media , Humanos , Femenino , Masculino , Anciano , Estudios Retrospectivos , Persona de Mediana Edad , Infarto de la Arteria Cerebral Media/complicaciones , Hemorragia Cerebral/etiología , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/complicaciones , Edema Encefálico/etiología , Factores de Riesgo , Accidente Cerebrovascular Isquémico/mortalidad
10.
BMC Geriatr ; 24(1): 385, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693481

RESUMEN

BACKGROUND: The correlation between the triglyceride-glucose index (TyG) and the prognosis of ischemic stroke has been well established. This study aims to assess the influence of the TyG index on the clinical outcomes of critically ill individuals suffering from intracerebral hemorrhage (ICH). METHODS: Patients diagnosed with ICH were retrospectively retrieved from the Medical Information Mart for Intensive Care (MIMIC-IV) and the eICU Collaborative Research Database (eICU-CRD). Various statistical methods, including restricted cubic spline (RCS) regression, multivariable logistic regression, subgroup analysis, and sensitivity analysis, were employed to examine the relationship between the TyG index and the primary outcomes of ICH. RESULTS: A total of 791 patients from MIMIC-IV and 1,113 ones from eICU-CRD were analyzed. In MIMIC-IV, the in-hospital and ICU mortality rates were 14% and 10%, respectively, while in eICU-CRD, they were 16% and 8%. Results of the RCS regression revealed a consistent linear relationship between the TyG index and the risk of in-hospital and ICU mortality across the entire study population of both databases. Logistic regression analysis revealed a significant positive association between the TyG index and the likelihood of in-hospital and ICU death among ICH patients in both databases. Subgroup and sensitivity analysis further revealed an interaction between patients' age and the TyG index in relation to in-hospital and ICU mortality among ICH patients. Notably, for patients over 60 years old, the association between the TyG index and the risk of in-hospital and ICU mortality was more pronounced compared to the overall study population in both MIMIC-IV and eICU-CRD databases, suggesting a synergistic effect between old age (over 60 years) and the TyG index on the in-hospital and ICU mortality of patients with ICH. CONCLUSIONS: This study established a positive correlation between the TyG index and the risk of in-hospital and ICU mortality in patients over 60 years who diagnosed with ICH, suggesting that the TyG index holds promise as an indicator for risk stratification in this patient population.


Asunto(s)
Glucemia , Hemorragia Cerebral , Enfermedad Crítica , Mortalidad Hospitalaria , Triglicéridos , Humanos , Masculino , Femenino , Anciano , Enfermedad Crítica/mortalidad , Mortalidad Hospitalaria/tendencias , Hemorragia Cerebral/sangre , Hemorragia Cerebral/mortalidad , Hemorragia Cerebral/diagnóstico , Estudios Retrospectivos , Persona de Mediana Edad , Estudios de Casos y Controles , Triglicéridos/sangre , Glucemia/análisis , Glucemia/metabolismo , Unidades de Cuidados Intensivos/tendencias , Anciano de 80 o más Años , Pronóstico , Valor Predictivo de las Pruebas
11.
J Clin Neurosci ; 124: 144-149, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705027

RESUMEN

BACKGROUND: The effect of antithrombotic therapy on patients with atrial fibrillation who sustained previous intracerebral hemorrhage (ICH) remains uncertain. Data regarding antithrombotic therapy use in these patients are limited. This study aims to compare the clinical and overall outcomes of antithrombotic therapy and usual care in patients with atrial fibrillation who sustained ICH. METHODS: We assembled consecutive patients with atrial fibrillation sustaining an ICH from our institution. Multivariable regression analysis and propensity-matched analysis were applied to assess associations of different antithrombotic therapies and outcomes. The primary outcome was mortality within the longest follow-up. Kaplan-Meier curves and log-rank tests of the time-to-event data were used to assess differences in survival. RESULTS: In total, 296 consecutive patients with atrial fibrillation who survived an ICH were included in this study. Our analysis demonstrated that antithrombotic therapy was associated with reduced mortality up to a 4-year duration of follow-up (OR, 0.49, 95 % CI 0.30-0.81). Similar results were obtained from the propensity-matched analysis (OR, 0.58, 95 % CI 0.34-0.98). Subgroup analysis showed that compared with usual care, direct oral anticoagulant (DOAC) with or without antiplatelet was associated with a lower risk of long-term mortality (OR, 0.34, 95 % CI 0.17-0.69). In addition, our analysis observed a significant interaction between cardiac insufficiency and treatment effect (P = 0.04). CONCLUSIONS: In patients with atrial fibrillation who have a history of ICH, administration of antithrombotic therapy, especially DOAC, was associated with lower mortality. Future randomized trials are warranted to test the positive net clinical benefit of DOAC therapy.


Asunto(s)
Anticoagulantes , Fibrilación Atrial , Hemorragia Cerebral , Puntaje de Propensión , Humanos , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/complicaciones , Femenino , Masculino , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/mortalidad , Anciano , Anticoagulantes/uso terapéutico , Persona de Mediana Edad , Anciano de 80 o más Años , Resultado del Tratamiento , Estudios Retrospectivos , Estudios de Seguimiento
12.
Bioorg Chem ; 147: 107416, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705107

RESUMEN

BACKGROUND: Intracerebral hemorrhage (ICH) is a debilitating condition characterized by the rupture of cerebral blood vessels, resulting in profound neurological deficits. A significant challenge in the treatment of ICH lies in the brain's limited capacity to regenerate damaged blood vessels. This study explores the potential synergistic effects of Ginsenoside Rh2 and Chrysophanol in promoting angiogenesis following ICH in a rat model. METHODS: Network pharmacology was employed to predict the potential targets and pathways of Ginsenoside Rh2 and Chrysophanol for ICH treatment. Molecular docking was utilized to assess the binding affinity between these compounds and their respective targets. Experimental ICH was induced in male Sprague-Dawley rats through stereotactic injection of type VII collagenase into the right caudate putamen (CPu). The study encompassed various methodologies, including administration protocols, assessments of neurological function, magnetic resonance imaging, histological examination, observation of brain tissue ultrastructure, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), immunofluorescence staining, Western blot analysis, and statistical analyses. RESULTS: Network pharmacology analysis indicated that Ginsenoside Rh2 and Chrysophanol may exert their therapeutic effects in ICH by promoting angiogenesis. Results from animal experiments revealed that rats treated with Ginsenoside Rh2 and Chrysophanol exhibited significantly improved neurological function, reduced hematoma volume, and diminished pathological injury compared to the Model group. Immunofluorescence analysis demonstrated enhanced expression of vascular endothelial growth factor receptor 2 (VEGFR2) and CD31, signifying augmented angiogenesis in the peri-hematomal region following combination therapy. Importantly, the addition of a VEGFR2 inhibitor reversed the increased expression of VEGFR2 and CD31. Furthermore, Western blot analysis revealed upregulated expression of angiogenesis-related factors, including VEGFR2, SRC, AKT1, MAPK1, and MAPK14, in the combination therapy group, but this effect was abrogated upon VEGFR2 inhibitor administration. CONCLUSION: The synergistic effect of Ginsenoside Rh2 and Chrysophanol demonstrated a notable protective impact on ICH injury in rats, specifically attributed to their facilitation of angiogenesis. Consequently, this research offers a foundation for the utilization of Ginsenosides Rh2 and Chrysophanol in medical settings and offers direction for the advancement of novel pharmaceuticals for the clinical management of ICH.


Asunto(s)
Hemorragia Cerebral , Ginsenósidos , Ratas Sprague-Dawley , Animales , Ginsenósidos/farmacología , Ginsenósidos/química , Masculino , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/metabolismo , Ratas , Antraquinonas/farmacología , Antraquinonas/química , Simulación del Acoplamiento Molecular , Estructura Molecular , Relación Dosis-Respuesta a Droga , Sinergismo Farmacológico , Relación Estructura-Actividad , Angiogénesis
13.
N Engl J Med ; 390(18): 1677-1689, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38718358

RESUMEN

BACKGROUND: The use of thrombectomy in patients with acute stroke and a large infarct of unrestricted size has not been well studied. METHODS: We assigned, in a 1:1 ratio, patients with proximal cerebral vessel occlusion in the anterior circulation and a large infarct (as defined by an Alberta Stroke Program Early Computed Tomographic Score of ≤5; values range from 0 to 10) detected on magnetic resonance imaging or computed tomography within 6.5 hours after symptom onset to undergo endovascular thrombectomy and receive medical care (thrombectomy group) or to receive medical care alone (control group). The primary outcome was the score on the modified Rankin scale at 90 days (scores range from 0 to 6, with higher scores indicating greater disability). The primary safety outcome was death from any cause at 90 days, and an ancillary safety outcome was symptomatic intracerebral hemorrhage. RESULTS: A total of 333 patients were assigned to either the thrombectomy group (166 patients) or the control group (167 patients); 9 were excluded from the analysis because of consent withdrawal or legal reasons. The trial was stopped early because results of similar trials favored thrombectomy. Approximately 35% of the patients received thrombolysis therapy. The median modified Rankin scale score at 90 days was 4 in the thrombectomy group and 6 in the control group (generalized odds ratio, 1.63; 95% confidence interval [CI], 1.29 to 2.06; P<0.001). Death from any cause at 90 days occurred in 36.1% of the patients in the thrombectomy group and in 55.5% of those in the control group (adjusted relative risk, 0.65; 95% CI, 0.50 to 0.84), and the percentage of patients with symptomatic intracerebral hemorrhage was 9.6% and 5.7%, respectively (adjusted relative risk, 1.73; 95% CI, 0.78 to 4.68). Eleven procedure-related complications occurred in the thrombectomy group. CONCLUSIONS: In patients with acute stroke and a large infarct of unrestricted size, thrombectomy plus medical care resulted in better functional outcomes and lower mortality than medical care alone but led to a higher incidence of symptomatic intracerebral hemorrhage. (Funded by Montpellier University Hospital; LASTE ClinicalTrials.gov number, NCT03811769.).


Asunto(s)
Infarto de la Arteria Cerebral Anterior , Accidente Cerebrovascular , Trombectomía , Terapia Trombolítica , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Hemorragia Cerebral/etiología , Terapia Combinada , Procedimientos Endovasculares , Imagen por Resonancia Magnética , Accidente Cerebrovascular/diagnóstico por imagen , Accidente Cerebrovascular/etiología , Accidente Cerebrovascular/terapia , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Tomografía Computarizada por Rayos X , Infarto Encefálico/diagnóstico por imagen , Infarto Encefálico/etiología , Infarto Encefálico/terapia , Enfermedad Aguda , Arterias Cerebrales/diagnóstico por imagen , Arterias Cerebrales/cirugía , Enfermedades Arteriales Cerebrales/complicaciones , Enfermedades Arteriales Cerebrales/diagnóstico por imagen , Enfermedades Arteriales Cerebrales/patología , Enfermedades Arteriales Cerebrales/cirugía , Infarto de la Arteria Cerebral Anterior/diagnóstico por imagen , Infarto de la Arteria Cerebral Anterior/patología , Infarto de la Arteria Cerebral Anterior/cirugía
14.
Adv Emerg Nurs J ; 46(2): 101-107, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38736094

RESUMEN

Patients who develop an intracerebral hemorrhage (ICH) following thrombolysis in acute ischemic stroke (AIS) have a mortality rate as high as 50%. Treatment options include blood products, such as cryoprecipitate, or antifibrinolytics, such as tranexamic acid (TXA) or ε-aminocaproic acid (EACA). Current guidelines recommend cryoprecipitate first-line despite limited data to support one agent over another. In addition, compared to antifibrinolytics, cryoprecipitate is higher in cost and requires thawing before use. This case series seeks to characterize the management of thrombolytic reversal at a single institution as well as provide additional evidence for antifibrinolytics in this setting. Patients were included for a retrospective review if they met the following criteria: presented between January 2011-January 2017, were >18 years of age, were admitted for AIS, received a thrombolytic, and received TXA EACA, or cryoprecipitate. Twelve patients met the inclusion criteria. Ten (83.3%) developed an ICH, one (8.3%) experienced gastrointestinal bleeding, and one (8.3%) had bleeding at the site of knee arthroscopy. Eleven patients received cryoprecipitate (median dose: 10 units), three received TXA (median dose: 1,000 mg), and one patient received EACA (13 g). TXA was administered faster than the first blood product at a mean time of 19 min and 137 min, respectively. Hemorrhagic expansion (N = 8, 66.67%) and inhospital mortality (N = 7, 58.3%) were high. While limited by its small sample size, this case series demonstrates significant variability in reversal strategies for thrombolysis-associated bleeding. It also provides additional evidence for the role of antifibrinolytics in this setting.


Asunto(s)
Antifibrinolíticos , Fibrinógeno , Accidente Cerebrovascular Isquémico , Ácido Tranexámico , Humanos , Antifibrinolíticos/uso terapéutico , Antifibrinolíticos/administración & dosificación , Estudios Retrospectivos , Masculino , Femenino , Accidente Cerebrovascular Isquémico/tratamiento farmacológico , Fibrinógeno/uso terapéutico , Anciano , Ácido Tranexámico/uso terapéutico , Ácido Tranexámico/administración & dosificación , Terapia Trombolítica , Persona de Mediana Edad , Factor VIII/uso terapéutico , Ácido Aminocaproico/uso terapéutico , Anciano de 80 o más Años , Hemorragia Cerebral/tratamiento farmacológico
15.
Mol Genet Genomics ; 299(1): 50, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734849

RESUMEN

Intracerebral hemorrhage (ICH) is one of the major causes of death and disability, and hypertensive ICH (HICH) is the most common type of ICH. Currently, the outcomes of HICH patients remain poor after treatment, and early prognosis prediction of HICH is important. However, there are limited effective clinical treatments and biomarkers for HICH patients. Although circRNA has been widely studied in diseases, the role of plasma exosomal circRNAs in HICH remains unknown. The present study was conducted to investigate the characteristics and function of plasma exosomal circRNAs in six HICH patients using circRNA microarray and bioinformatics analysis. The results showed that there were 499 differentially expressed exosomal circRNAs between the HICH patients and control subjects. According to GO annotation and KEGG pathway analyses, the targets regulated by differentially expressed exosomal circRNAs were tightly related to the development of HICH via nerve/neuronal growth, neuroinflammation and endothelial homeostasis. And the differentially expressed exosomal circRNAs could mainly bind to four RNA-binding proteins (EIF4A3, FMRP, AGO2 and HUR). Moreover, of differentially expressed exosomal circRNAs, hsa_circ_00054843, hsa_circ_0010493 and hsa_circ_00090516 were significantly associated with bleeding volume and Glasgow Coma Scale score of the subjects. Our findings firstly revealed that the plasma exosomal circRNAs are significantly involved in the progression of HICH, and could be potent biomarkers for HICH. This provides the basis for further research to pinpoint the best biomarkers and illustrate the mechanism of exosomal circRNAs in HICH.


Asunto(s)
Exosomas , ARN Circular , Humanos , ARN Circular/genética , ARN Circular/sangre , Exosomas/genética , Exosomas/metabolismo , Masculino , Femenino , Persona de Mediana Edad , Anciano , Hemorragia Intracraneal Hipertensiva/genética , Hemorragia Intracraneal Hipertensiva/sangre , Biomarcadores/sangre , Biología Computacional/métodos , Perfilación de la Expresión Génica , Hemorragia Cerebral/genética , Hemorragia Cerebral/sangre , Redes Reguladoras de Genes
16.
Front Immunol ; 15: 1381472, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38726008

RESUMEN

X-linked lymphoproliferative disease (XLP) is a rare genetic disorder characterized by immune dysregulation. The three most common clinical phenotypes are EBV-associated infectious mononucleosis (FIM), abnormal gammaglobulinemia, and lymphoma. We present a rare case of XLP1 with neurovasculitis, which is non-EBV-related and involves multiple systems, a condition rarely seen in children. The patient initially presented with an unsteady gait, which progressively evolved into language and consciousness disorders. Additionally, CT scans revealed multiple nodules in the lungs. Subsequent genetic testing and brain tissue biopsy confirmed the diagnosis: XLP1-related cerebral vasculitis and cerebral hemorrhage. Tragically, during the diagnostic process, the child experienced a sudden cerebral hemorrhage and herniation, ultimately resulting in fatality. This case offers a comprehensive insight into XLP1-related cerebral vasculitis and cerebral hemorrhage, underscoring the significance of early diagnosis and prompt treatment, while also imparting valuable clinical experience and lessons to the medical community.


Asunto(s)
Hemorragia Cerebral , Trastornos Linfoproliferativos , Vasculitis del Sistema Nervioso Central , Humanos , Vasculitis del Sistema Nervioso Central/diagnóstico , Vasculitis del Sistema Nervioso Central/etiología , Masculino , Hemorragia Cerebral/etiología , Hemorragia Cerebral/diagnóstico , Trastornos Linfoproliferativos/diagnóstico , Trastornos Linfoproliferativos/complicaciones , Trastornos Linfoproliferativos/genética , Resultado Fatal
17.
PLoS One ; 19(5): e0303757, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38771834

RESUMEN

Whether 30-day modified Rankin Scale (mRS) scores can predict 90-day scores is unclear. This study derived and validated a model to predict ordinal 90-day mRS score in an intracerebral hemorrhage (ICH) population using 30-day mRS values and routinely available baseline variables. Adults enrolled in the Antihypertensive Treatment of Acute Cerebral Hemorrhage-2 (ATACH-2) trial between May 2011 and September 2015 with acute ICH, who were alive at 30 days and had mRS scores reported at both 30 and 90 days were included in this post-hoc analysis. A proportional odds regression model for predicting ordinal 90-day mRS scores was developed and internally validated using bootstrapping. Variables in the model included: mRS score at 30 days, age (years), hematoma volume (cm3), hematoma location (deep [basal ganglia, thalamus], lobar, or infratentorial), presence of intraventricular hemorrhage (IVH), baseline Glasgow Coma Scale (GCS) score, and National Institutes of Health Stroke Scale (NIHSS) score at randomization. We assessed model fit, calibration, discrimination, and agreement (ordinal, dichotomized functional independence), and EuroQol-5D ([EQ-5D] utility weighted) between predicted and observed 90-day mRS. A total of 898/1000 participants were included. Following bootstrap internal validation, our model (calibration slope = 0.967) had an optimism-corrected c-index of 0.884 (95% CI = 0.873-0.896) and R2 = 0.712 for 90-day mRS score. The weighted ĸ for agreement between observed and predicted ordinal 90-day mRS score was 0.811 (95% CI = 0.787-0.834). Agreement between observed and predicted functional independence (mRS score of 0-2) at 90 days was 74.3% (95% CI = 69.9-78.7%). The mean ± SD absolute difference between predicted and observed EQ-5D-weighted mRS score was negligible (0.005 ± 0.145). This tool allows practitioners and researchers to utilize clinically available information along with the mRS score 30 days after ICH to reliably predict the mRS score at 90 days.


Asunto(s)
Hemorragias Intracraneales , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Hemorragia Cerebral/complicaciones , Índice de Severidad de la Enfermedad , Escala de Coma de Glasgow , Pronóstico , Anciano de 80 o más Años
18.
Crit Pathw Cardiol ; 23(2): 58-72, 2024 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-38781079

RESUMEN

OBJECTIVE: To verify the incidence of bleeding events in patients on ongoing anticoagulant treatment in the real world and compare the results of different reversal or repletion strategies currently available for pharmacological treatment. METHODS: Patients managed in the emergency department (ED) with major bleeding events, on ongoing anticoagulation were stratified according to bleeding site and reversal or repletion therapy with andexanet alfa (ADX), idarucizumab (IDA), prothrombin complex concentrate (PCC), and vitamin K (Vit-K). ENDPOINT: Death at 30 days was compared in the subgroups with cerebral hemorrhage (CH) and gastrointestinal (GI) bleeding. RESULTS: Of the 809,397 visits in the years 2022-2023 at 6 EDs in the northwestern health district of Tuscany, 5372 patients with bleeding events were considered; 3740 were excluded due to minor bleeding or propensity score matching. Of the remaining 1632 patients with major bleeding, 548 on ongoing anticoagulation were enrolled; 334 received reversal or repletion agents. Patients with CH (n = 176) and GI bleeding (n = 108) represented the primary analysis cohorts in the study's strategic treatment assessment. Overall, 30-day survival of patients on ongoing aFXa treatment receiving on-label ADX versus off-label PCC showed a relative increase of 71%, while 30-day survival of patients on ongoing aFII receiving on-label IDA versus off-label PCC showed a relative increase of 30%; no substantial difference was found when comparing on-label PCC combined with Vit-K versus off-label Vit-K alone. Indeed, patients undergoing on-label ADX or IDA showed a statistically significant difference over off-label PCC (ADX vs. PCC: n = 15, events = 4, mean ± SD 82.50 ± 18.9, vs. 49, 13, 98.82 ± 27, respectively; analysis of variance [ANOVA] variance 8627; P < 0.001; posthoc test diff 32, 95% confidence interval: 28-35; P < 001; IDA vs. PCC: 20, 5, 32.29 ± 15.0 vs. 2, 1, 28.00 ± 0.0, respectively; ANOVA 1484; P < 0.001; posthoc test -29, -29 -29, respectively; P = n.d.). On-label PCC combined with Vit-K showed overall a slight statistically significant difference versus off-label Vit-K alone (52, 16, 100.58 ± 22.6 vs. 53, 11, 154.62 ± 29.8, respectively; ANOVA 310; P < 0.02; posthoc test 4, 0.7-7.2, respectively; P < 0.02). Data were confirmed in the group of patients with CH (ADX vs. PCC: n = 13, events = 3, mean ± SD 91.55 ± 18.6 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA variance 10,091, F = 261; P < 0.001; posthoc difference test 36, 95% confidence interval: 30-41; P < 0.001; IDA vs. PCC: 10, 2, 4.50 ± 2.5 vs. 78, 21, 108.91 ± 20.9, respectively; ANOVA 16,876,303, respectively; P < 0.001; posthoc test 41, 34-47, respectively; P < 0.001). On-label PCC combined with Vit-K showed an overall slight statistically significant difference compared with off-label Vit-K alone (P < 0.01 and P < 0.001 in the subgroups of CH and GI bleeding). CONCLUSIONS: Patients undergoing specific reversal therapy with on-label ADX or IDA, when treated with aFXa or aFII anticoagulants, respectively, showed statistically elevated differences in 30-day death compared with off-label repletion therapy with PCC. Overall, 30-day survival of patients on ongoing aFXa or aFII receiving on-label reversal therapy with ADX or IDA compared with off-label PCC repletion agents showed an increase of 71% and 30%, respectively.


Asunto(s)
Anticoagulantes , Factores de Coagulación Sanguínea , Servicio de Urgencia en Hospital , Humanos , Masculino , Femenino , Anciano , Italia/epidemiología , Factores de Coagulación Sanguínea/uso terapéutico , Anticoagulantes/uso terapéutico , Anticoagulantes/efectos adversos , Proteínas Recombinantes/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Vitamina K/antagonistas & inhibidores , Persona de Mediana Edad , Inhibidores del Factor Xa/uso terapéutico , Inhibidores del Factor Xa/efectos adversos , Anciano de 80 o más Años , Hemorragia/inducido químicamente , Hemorragia/epidemiología , Estudios Retrospectivos , Hemorragia Gastrointestinal/inducido químicamente , Hemorragia Gastrointestinal/epidemiología , Incidencia , Hemorragia Cerebral/inducido químicamente , Hemorragia Cerebral/epidemiología , Hemorragia Cerebral/tratamiento farmacológico , Hemorragia Cerebral/mortalidad , Resultado del Tratamiento , Factor Xa
19.
Sci Rep ; 14(1): 11818, 2024 05 23.
Artículo en Inglés | MEDLINE | ID: mdl-38782974

RESUMEN

This study aimed to evaluate the utility of an artificial intelligence (AI) algorithm in differentiating between cerebral cavernous malformation (CCM) and acute intraparenchymal hemorrhage (AIH) on brain computed tomography (CT). A retrospective, multireader, randomized study was conducted to validate the performance of an AI algorithm in differentiating AIH from CCM on brain CT. CT images of CM and AIH (< 3 cm) were identified from the database. Six blinded reviewers, including two neuroradiologists, two radiology residents, and two emergency department physicians, evaluated CT images from 288 patients (CCM, n = 173; AIH, n = 115) with and without AI assistance, comparing diagnostic performance. Brain CT interpretation with AI assistance resulted in significantly higher diagnostic accuracy than without (86.92% vs. 79.86%, p < 0.001). Radiology residents and emergency department physicians showed significantly improved accuracy of CT interpretation with AI assistance than without (84.21% vs. 75.35%, 80.73% vs. 72.57%; respectively, p < 0.05). Neuroradiologists showed a trend of higher accuracy with AI assistance in the interpretation but lacked statistical significance (95.83% vs. 91.67%, p = 0.56). The use of an AI algorithm can enhance the differentiation of AIH from CCM in brain CT interpretation, particularly for nonexperts in neuroradiology.


Asunto(s)
Algoritmos , Inteligencia Artificial , Hemorragia Cerebral , Hemangioma Cavernoso del Sistema Nervioso Central , Tomografía Computarizada por Rayos X , Humanos , Tomografía Computarizada por Rayos X/métodos , Masculino , Femenino , Persona de Mediana Edad , Adulto , Estudios Retrospectivos , Hemorragia Cerebral/diagnóstico por imagen , Hemangioma Cavernoso del Sistema Nervioso Central/diagnóstico por imagen , Diagnóstico Diferencial , Anciano , Adulto Joven , Adolescente , Encéfalo/diagnóstico por imagen , Encéfalo/patología
20.
Biosensors (Basel) ; 14(5)2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38785690

RESUMEN

Magnetic Induction Tomography (MIT) is a non-invasive imaging technique used for dynamic monitoring and early screening of cerebral hemorrhage. Currently, there is a significant challenge in cerebral hemorrhage MIT due to weak detection signals, which seriously affects the accuracy of the detection results. To address this issue, a dual-plane enhanced coil was proposed by combining the target field method with consideration of the spatial magnetic field attenuation pattern within the imaging target region. Simulated detection models were constructed using the proposed coil and cylindrical coil as excitation coils, respectively, and simulation imaging tests were conducted using the detection results. The simulation results indicate that compared to the cylindrical coil, the proposed coil enhances the linearity of the magnetic field within the imaging target region by 60.43%. Additionally, it effectively enhances the detection voltage and phase values. The simulation results of hemorrhage detection show that the proposed coil improves the accuracy of hemorrhage detection by 18.26%. It provides more precise detection results, offering a more reliable solution for cerebral hemorrhage localization and detection.


Asunto(s)
Hemorragia Cerebral , Hemorragia Cerebral/diagnóstico por imagen , Humanos , Tomografía , Simulación por Computador
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