The antioxidant effect of preischemic dexmedetomidine in a rat model: increased expression of Nrf2/HO-1 via the PKC pathway

Abstract Background The precise underlying mechanism of antioxidant effects of dexmedetomidine-induced neuroprotection against cerebral ischemia has not yet been fully elucidated. Activation of Nuclear factor erythroid 2-related factor (Nrf2) and Heme Oxygenase-1 (HO-1) represents a major antioxidant-defense mechanism. Therefore, we determined whether dexmedetomidine increases Nrf2/HO-1 expression after global transient cerebral ischemia and assessed the involvement of Protein Kinase C (PKC) in the dexmedetomidine-related antioxidant mechanism. Methods Thirty-eight rats were randomly assigned to five groups: sham (n = 6), ischemic (n = 8), chelerythrine (a PKC inhibitor; 5 mg.kg-1 IV administered 30 min before cerebral ischemia) (n = 8), dexmedetomidine (100 µg.kg-1 IP administered 30 min before cerebral ischemia (n = 8), and dexmedetomidine + chelerythrine (n = 8). Global transient cerebral ischemia (10 min) was applied in all groups, except the sham group; histopathologic changes and levels of nuclear Nrf2 and cytoplasmic HO-1 were examined 24 hours after ischemia insult. Results We found fewer necrotic and apoptotic cells in the dexmedetomidine group relative to the ischemic group (p< 0.01) and significantly higher Nrf2 and HO-1 levels in the dexmedetomidine group than in the ischemic group (p< 0.01). Additionally, chelerythrine co-administration with dexmedetomidine attenuated the dexmedetomidine-induced increases in Nrf2 and HO-1 levels (p< 0.05 and p< 0.01, respectively) and diminished its beneficial neuroprotective effects. Conclusion Preischemic dexmedetomidine administration elicited neuroprotection against global transient cerebral ischemia in rats by increasing Nrf2/HO-1 expression partly via PKC signaling, suggesting that this is the antioxidant mechanism underlying dexmedetomidine-mediated neuroprotection.

ABC-AF-Stroke score predicts thromboembolism in non-anticoagulated patients following successful atrial fibrillation ablation: a report from the Chinese Atrial Fibrillation Registry / 中华医学杂志(英文版)

BACKGROUND@#The age, biomarkers, and clinical history (ABC)-atrial fibrillation (AF)-Stroke score have been proposed to refine stroke risk stratification, beyond what clinical risk scores such as the CHA2DS2-VASc score can offer. This study aimed to identify risk factors associated with thromboembolism and evaluate the performance of the ABC-AF-Stroke score in predicting thromboembolism in non-anticoagulated AF patients following successful ablations.@*METHODS@#A total of 2692 patients who underwent successful ablations with discontinued anticoagulation after a 3-month blanking period in the Chinese Atrial Fibrillation Registry (CAFR) between 2013 and 2019 were included. Cox regression analysis was conducted to present the association of risk factors with thromboembolism risk. The ABC-AF-Stroke score was evaluated in terms of discrimination, including concordance index (C-index), net reclassification improvement (NRI) and integrated discrimination improvement (IDI), clinical utilization by decision curve analysis (DCA), and calibration by comparing the predicted risk with the observed annualized event rate.@*RESULTS@#After a median follow-up of 3.5 years, 64 patients experienced thromboembolism events. Age, prior history of stroke/transient ischemic attack (TIA), high-sensitivity cardiac troponin T (cTnT-hs), and N-terminal pro-B-type natriuretic peptide (NT-proBNP) were independently associated with thromboembolism risk. The ABC-AF-Stroke score performed statistically significantly better than the CHA2DS2-VASc score in terms of C-index (0.67, 95% confidence interval [CI]: 0.59-0.74 vs. 0.60, 95% CI: 0.52-0.67, P = 0.030) and reclassification capacity. The DCA implied that the ABC-AF-Stroke score could identify more thromboembolism events without increasing the false positive rate compared to the CHA2DS2-VASc score. The calibration curve showed that the ABC-AF-Stroke score was well calibrated in this population.@*CONCLUSIONS@#In this real-world study enrolling non-anticoagulated AF patients following successful ablations, age, prior history of stroke/TIA, level of NT-proBNP, and cTnT-hs were independently associated with an increased risk of thromboembolism. The ABC-AF-Stroke score was well-calibrated and statistically significantly outperformed the CHA2DS2-VASc score in predicting thromboembolism risk.

Multiple Mild Stimulations Reduce Membrane Distribution of CX3CR1 Promoted by Annexin a1 in Microglia to Attenuate Excessive Dendritic Spine Pruning and Cognitive Deficits Caused by a Transient Ischemic Attack in Mice / 神经科学通报·英文版

A transient ischemic attack (TIA) can cause reversible and delayed impairment of cognition, but the specific mechanisms are still unclear. Annexin a1 (ANXA1) is a phospholipid-binding protein. Here, we confirmed that cognition and hippocampal synapses were impaired in TIA-treated mice, and this could be rescued by multiple mild stimulations (MMS). TIA promoted the interaction of ANXA1 and CX3CR1, increased the membrane distribution of CX3CR1 in microglia, and thus enhanced the CX3CR1 and CX3CL1 interaction. These phenomena induced by TIA could be reversed by MMS. Meanwhile, the CX3CR1 membrane distribution and CX3CR1-CX3CL1 interaction were upregulated in primary cultured microglia overexpressing ANXA1, and the spine density was significantly reduced in co-cultured microglia overexpressing ANXA1 and neurons. Moreover, ANXA1 overexpression in microglia abolished the protection of MMS after TIA. Collectively, our study provides a potential strategy for treating the delayed synaptic injury caused by TIA.

Endarterectomía de carótida bilateral en un mismo tiempo quirúrgico / Bilateral carotid endarterectomy at the same surgical time

Los pacientes con estenosis bilateral presentan una elevada incidencia de clínica hemisférica e infartos cerebrales en relación con la primera carótida y en espera de una segunda cirugía de la carótida contralateral estenótica. La endarterectomía de carótida bilateral en un mismo tiempo quirúrgico representa todo un reto para el cirujano vascular por las complicaciones que puede conllevar. Pero puede realizarse una correcta selección del paciente con bajo riesgo quirúrgico, un análisis de la localización y las características de las placas que provocan la estenosis, y una técnica analgésica que permita monitorear constantemente la disfunción cerebral y siga los principios técnicos. Este estudio tuvo el objetivo de asociar los criterios anteriores a un caso de la endarterectomía de carótida bilateral en un mismo tiempo quirúrgico. Se seleccionó un paciente masculino de 72 años que había sufrido ataques transitorios de isquemia sin secuelas neurológicas. Se realizó el procedimiento sin complicaciones perioperatorias ni posoperatorias, por lo que se propone como una alternativa segura a llevar a cabo en pacientes con estenosis bilateral(AU)

Patients with bilateral stenosis have a high incidence of hemispheric clinical and cerebral infarctions in relation to the first carotid and waiting for a second surgery of the stenotic contralateral carotid. Bilateral carotid endarterectomy at the same surgical time represents a challenge for the vascular surgeon because of the complications it can entail. But a correct selection of the patient with low surgical risk can be made, an analysis of the location and characteristics of the plaques that cause stenosis, and also an analgesic technique that allows constant monitoring of brain dysfunction and follows technical principles. This study aimed to associate the above criteria with a case of bilateral carotid endarterectomy at the same surgical time. A 72-year-old male patient who had suffered transient ischemic attacks without neurological sequelae was selected. The procedure was performed without perioperative or postoperative complications, so it is proposed as a safe alternative to be carried out in patients with bilateral stenosis(AU)

Ataque isquémico transitorio por embolia aérea iatrogénica secundaria a inyecciones intracavernosas en procedimiento urológico / Transient ischemic attack due to iatrogenic air embolism secondary to intracavernous injections during an urologic procedure

RESUMEN Se presenta un caso de ataque isquémico transitorio con sintomatología compatible con lesión de la circulación cerebral posterior, secundario a embolia aérea iatrogénica. Se describe la evolución clínica y las consideraciones más relevantes de la atención y el diagnóstico del ataque cerebrovascular de la circulación posterior. En cuanto a la embolia gaseosa, se describen los métodos diagnósticos, las intervenciones clínicas y las opciones de tratamiento disponibles.

SUMMARY Here ia a case of transient ischemic attack with symptoms compatible with injury to the posterior cerebral circulation, secondary to iatrogenic air embolism. Clinical evolution and the most relevant aspects for the care and diagnosis of cerebrovascular stroke of the posterior circulation are described. Regarding air embolism, the diagnostic methods, clinical interventions, and available treatment options are described.

AISYF: first national, prospective, multicenter study of young patients with stroke in Argentina / AISYF: primer estudio nacional, prospectivo y multicéntrico de pacientes jóvenes con ataque cerebral en Argentina

Abstract Up to 15% of all strokes affect young patients and the incidence of ischemic stroke in this population is rising. Nevertheless, there is limited information of cerebrovascular events in this population both in our country and in Latin America. The aim of our study was to evaluate the clinical characteristics and risk factors of young adults with stroke in Argentina. This is a prospective, multicenter study of stroke in young adults (18 - 55 years) in Argentina. Patients presenting with a cerebrovascular event within 180 days were included. Stroke subtypes were classified according to TOAST criteria. A total number of 311 patients were enrolled (men 53.9%, mean age: 43.3 years). Ischemic strokes occurred in 91.8% (brain infarcts 82.6%, transient ischemic attack 9.2%) and hemorrhagic strokes in 8.2%. The most frequent vascular risk factors (including ischemic and hemorrhagic strokes) were: hypertension 120 (41%), smoking 92 (31.4%), dyslipidemia 81 (27.6%) and, over weight/obesity: 74 (25.3%). Stroke subtypes were: large artery disease 12.3%, cardioembolism 7.5, small artery occlusion 11.5%, other defined etiology 27.1%, and undetermined etiology 41.6%. Our study demonstrates that vascular risk factors are very frequent in young adults with stroke. Our findings underline that urgent strategies are required for primary and secondary stroke prevention in this group of patients.

Resumen Aproximadamente un 15% de todos los ataques cerebrovasculares afectan a pacientes jóvenes y su incidencia estaría en aumento. Existe escasa información sobre el ataque cerebral en esta población tanto en nuestro país como en Latinoamérica. El objetivo de nuestro estudio fue evaluar las características clínicas y los factores de riesgo de los adultos jóvenes con ictus en Argentina. Realizamos un estudio prospectivo y multicéntrico en adultos jóvenes (18-55 años) en Argentina, que presentaron un evento cerebrovascular dentro de los 180 días previos. Los subtipos de ictus se clasificaron según los criterios de TOAST. Se incluyeron un total de 311 pacientes (hombres 53.9%, edad media: 43,3 años). Los ataques cerebrovasculares isquémicos ocurrieron en el 91.8% (infartos cerebrales 82.6%, ataque isquémico transitorio 9.2%) y los eventos hemorrágicos correspondieron al 8.2%. Los factores de riesgo vascular más frecuentes (incluyendo los eventos isquémicos y hemorrágicos) fueron: hipertensión 120 (41%), tabaquismo 92 (31.4%), dislipidemia 81 (27.6%) y sobrepeso/obesidad: 74 (25.3%). Los subtipos de ictus isquémicos fueron: arteriopatía de gran vaso 12.3%, cardioembolismo 7.5%, oclusión de pequeña arteria 11.5%, otra etiología definida 27.1% y etiología indeterminada 41.6%. Los factores de riesgo vascular son muy frecuentes en los adultos jóvenes con ictus. Nuestros hallazgos subrayan que se requieren estrategias urgentes para la prevención primaria y secundaria del ictus en este grupo particular de pacientes en nuestro país.

Forma clínica indeterminada da doença de Chagas e o risco potencial de evento isquêmico / Indeterminate clinical form of Chagas disease and the potencial risk of ischemic event / Forma clínica indeterminada de la enfermedad de Chagas y potencial riesgo de evento isquémico

Acidentes vasculares cerebrais ou isquêmicos transitórios são eventos raros em pacientes jovens sem fatores de risco clássicos, correspondendo muitas vezes a eventos não definidos etiologicamente e caracterizados como fenômenos tromboembólicos criptogênicos. A doença de Chagas é um fator de risco que deve ser considerado como potencial causa etiológica quando especificamos áreas endêmicas, tanto pelo conhecido mecanismo cardioembólico de acometimento cardíaco como pelas demais formas sem acometimento cardíaco, uma vez que já é descrita como fator de risco independente para doenças cerebrovasculares. Este estudo demonstra, por meio de um relato de caso, o desfecho de uma paciente portadora da doença de Chagas crônica, na forma indeterminada, sem fatores de risco clássicos. A paciente foi acometida por um ataque isquêmico transitório, tendo como etiologia presumida a doença de Chagas, que pode determinar um perfil pró-inflamatório e pró-coagulante, de modo a corroborar a tese de que o prognóstico da forma indeterminada pode não ser benigno. A associação entre a forma indeterminada e as doenças cerebrovasculares incorre na necessidade de anexar ao protocolo de investigação de acidente vascular encefálico (AVE) criptogênicos da doença de Chagas, quando se refere a áreas endêmicas, bem como em alertar as áreas da saúde para essa forma da doença, como forma de ajudar em medidas de prevenção de fenômenos tromboembólicos encefálicos.

Transient strokes or ischemic attacks are rare events in young patients without classic risk factors, often corresponding to events not defined etiologically and characterized as cryptogenic thromboembolic phenomena. Chagas disease is a risk factor that should be considered as a potential etiological cause when specifying endemic areas, both for the cardioembolic mechanism and for other forms without cardiac involvement, since it is described as an independent risk factor for cerebrovascular diseases. This study shows, by means of a case report, the outcome of a patient with chronic indeterminate Chagas disease without classic risk factors. The patient was affected by a transient ischemic attack, with the presumed etiology being Chagas disease, which can determinate a pro-inflammatory and pro-coagulant profile, thus corroborating that the prognosis of the indeterminate form may not be benign. The association between the indeterminate form and stroke incurs in the need to attach to the investigation protocol for cryptogenic stroke of Chagas disease, when referring to endemic areas, as well as to take a better look at this form to help in prevention measures for encephalic thromboembolic phenomena.

Los accidentes cerebrovasculares o accidentes isquémicos transitorios son eventos raros en pacientes jóvenes sin factores de riesgo clásicos, que a menudo corresponden a eventos no definidos etiológicamente caracterizándose como fenómenos tromboembólicos criptogénicos. La enfermedad de Chagas es un factor de riesgo que debe ser considerado como una posible causa etiológica cuando especificamos áreas endémicas, tanto por el conocido mecanismo cardioembólico de afectación cardíaca como por otras formas sin afectación cardíaca, puesto que la enfermedad ya está descrita como factor de riesgo independiente de enfermedades cerebrovasculares. Este estudio demuestra, a partir de un reporte de caso, el desenlace de un paciente con enfermedad de Chagas crónica en forma indeterminada sin factores de riesgo clásicos. La paciente sufrió un ataque isquémico transitorio, con la enfermedad de Chagas como presunta etiología, lo que puede determinar un perfil proinflamatorio y procoagulante, por lo que corroboró con la tesis de que el pronóstico de la forma indeterminada puede no ser tan benigno. La asociación entre la forma indeterminada y las enfermedades cerebrovasculares incurre en la necesidad de adjuntar la enfermedad de Chagas al protocolo de investigación de accidente cerebrovascular (ACV) criptogénico cuando se habla de áreas endémicas, así como de incrementar la visión de las áreas de salud a esta forma de enfermedad, para así contribuir con las medidas preventivas de los fenómenos tromboembólicos cerebrales.

Estenosis bilateral de carótidas internas manifestado por síndrome de Limb-Shaking / Bilateral internal carotid artery stenosis presenting as Limb-Shaking syndrome

Introducción: El síndrome de limb-shaking o sacudida de extremidades como presentación de un ataque isquémico transitorio es raro y suele asociarse con estenosis de las arterias carótidas internas. El principal diagnóstico diferencial es con crisis convulsivas. Presentación del caso: presentamos el caso de un paciente con estenosis carotídea intracraneal bilateral que cursó con sacudidas en extremidades y tuvo mejoría clínica satisfactoria tras un procedimiento con stent.

Limb-shaking syndrome or involuntary shaking movements of the affected limbs as a manifestation of a transient ischemic attack is rare and often is associated with internal carotid artery stenosis. The main differential diagnosis is a convulsive seizure. We present the case of a patient with bilateral intracranial carotid artery stenosis presenting as limb shaking syndrome, showing satisfactory clinical improvement after undergoing stent revascularization.

The Role of Patent Foramen Ovale Closure in the Secondary Prevention of Cryptogenic Stroke: a Meta-Analysis Report

Abstract Background: Patent foramen ovale (PFO) closure has been compared to medical therapy for secondary prevention of recurrent cryptogenic stroke. Objectives: To produce an updated meta-analysis including only data from the primary analyses of clinical trials and to evaluate the role of PFO closure in the secondary prevention of recurrent stroke. Methods: Search in Medline (PubMed) and in ISI Web of Knowledge. Parameters under analysis and meta-analyses were: stroke, transient ischemic attack (TIA) and atrial fibrillation (AF). Comprehensive Meta-analysis Software V.2.0 (Biostat) was used. Random-effects analyses were carried out. A level of significance of 5% was used. Results: In this study six, randomized trials enrolling 3,750 patients were included. Unlike other published meta-analyses on the same topic, in this case, only clinical trial data, and not follow-up data, were used. PFO closure, as compared with medical therapy alone, demonstrated superiority in reducing the rate of recurrent stroke (risk ratio with PFO closure vs. medical therapy, 0.37; 95% confidence interval [CI], 0.17 to 0.78; p = 0.01). PFO closure did not offer a significant benefit in prevention of TIA (risk ratio with PFO closure vs. medical therapy, 0.96; 95% CI, 0.64 to 1.44; p = 0.85). Among patients assigned to closure group, an increased risk of atrial fibrillation was seen (risk ratio with PFO closure vs. medical therapy, 4.64; 95% CI, 2.38 to 9.01; p < 0.01). Conclusions: In patients with cryptogenic stroke who had a patent foramen ovale, a protective effect of closure was seen concerning the risk of recurrent stroke, but not regarding the prevention of TIA.

Cerebral Autoregulation in Patients with Unilateral Carotid Artery Stenosis / 中国医学科学院学报

To investigate cerebral autoregulation(CA)in patients with severe unilateral carotid artery stenosis by near infrared spectroscopy. Thirty patients who underwent general anesthesia in our hospital from January 2015 to February 2017 were enrolled in this study.The stenosis group included 15 patients with severe unilateral internal carotid artery stenosis,and the control group included 15 patients without carotid artery stenosis.Both groups were matched in sex and age.Cerebral tissue oxygenation index(TOI)and mean arterial pressure were recorded continuously under stable general anesthesia.The Pearson correlation coefficient()was calculated to judge the CA status. TOI was not significantly different between the stenosis side and the non-stenosis side in the stenosis group(66.52±6.50 65.23±4.50;=0.93, =0.368)or between the stenosis side in the stenosis group and the stenosis side in the control group(66.52±6.50 64.22±3.87;=1.18, =0.248).The values of stenosis side and non-stenosis side in the stenosis group were 0.36±0.12 and 0.17±0.11,respectively,and the values of the stenosis side in the stenosis group and the stenosis side of the control group were 0.36±0.12 and 0.13±0.08,respectively.In the stenosis group,5 patients had transient ischemic attack and 2 patients had a history of stroke within 3 months before operation.When an value of 0.342 was used as the judgment point of CA abnormality,the sensitivity and specificity were 0.625 and 0.909,respectively. Within the range of normal blood pressure fluctuation,cerebral blood flow is linked to blood pressure at the stenosis side in patients with severe unilateral carotid artery stenosis.

Doble terapia antiagregante en pacientes con accidente cerebrovascular isquémico agudo: Recomendación del grupo CIERTO / Dual antiplatelet therapy for secondary stroke prevention in patients with acute ischemic stroke. CIERTO group recommendation

El inicio precoz del tratamiento con antiagregantes plaquetarios es considerado el estándar de cuidado para pacientes con accidente cerebrovascular isquémico agudo. Distintos esquemas de antiagregación se han comparado con resultados que sugieren que la combinación de múltiples antiagregantes se asocian a menor riesgo de recurrencia de accidente cerebrovascular (ACV) pero a expensas de un aumento en el riesgo de sangrado, lo que a largo plazo termina opacando dichos beneficos. Sin embargo, considerando que el riesgo de recurrencia de ACV es mayor en el periodo inmediato al evento, la indicación de doble tratamiento antiagregante por tiempos limitados podría asociarse a beneficios relevantes. Con este concepto, se realizó una revisión sistemática rápida con el objetivo de evaluar el efecto del tratamiento con doble antiagregación por un periodo corto intentando maximizar el beneficio y reducir al mínimo el riesgo de sangrado. Se incluyeron todos los estudios primarios identificados en los que se comparó un esquema de doble antiagregación, iniciado en el periodo agudo del evento índice (ACV o accidente isquémico transitorio - AIT), contra un esquema de simple antiagregación. El cuerpo de la evidencia mostró que la intervención (doble antiagregación) reduce el riesgo de recurrencia de ACV y probablemente se asocie a un aumento marginal en el riesgo de sangrado mayor. Sugerimos indicar doble esquema antiplaquetario para el tratamiento inicial de pacientes con ACV isquémico menor (Score NIH < o igual a 3 o AIT).

One of the main pillars of acute ischemic stroke management is antiplatelet therapy. Different treatment schemes have been compared, suggesting that the combination of multiple antiplatelet drugs is associated with a reduced risk of stroke recurrence. However, it has also been associated with an increased risk of bleeding complications which, in the long term, surpass the mentioned benefits. However, considering that most stroke recurrences occur i n the short term, a time limited double antiplatelet scheme could result in significant benefits to patients with acute ischemic stroke. On this basis, we conducted a rapid systematic review of the literature in order to evaluate the effects of a short-term double antiplatelet therapy both on stroke recurrence and complications. All trials comparing double versus single antiplatelet therapy in patients with acute ischemic stroke were included. Results showed that double therapy reduces recurrence risk but probably marginally increases major bleeding complications. We suggest double antiplatelet therapy for the initial management of patients with minor (Score NIH < or equal to 3 or transient isquemic attack -TIA) acute ischemic stroke.

Stroke and transient ischemic attacks related to antiplatelet or warfarin interruption / Acidente vascular cerebral e ataques isquêmicos transitórios relacionados à interrupção de antiplaquetários ou varfarina

ABSTRACT Patients on anticoagulant or antiplatelet therapy are often required to discontinue these medications before and during surgical or invasive procedures. In some cases, the patient stops the treatment without medical supervision. These situations may increase stroke risk. Objective To identify the ischemic stroke and transient ischemic attack (TIA) prevalence related to length of time of discontinuation of antiplatelet or vitamin K antagonist therapy, in a group of inpatients from a specialized neurological hospital in Brazil. Methods Cross-sectional, retrospective and descriptive study of stroke inpatients for three years. Medical reports were reviewed to find study participants, stroke characteristics, risk factors, reasons and time of drug interruption. Results In three years, there were 360 stroke and TIA inpatients, of whom 27 (7.5%) had a history of antiplatelet or vitamin K antagonist interruption correlated with the time of the event (81% ischemic stroke, 19% TIA). The median time between antiplatelet interruption and an ischemic event was five days, and 62% of events occurred within seven days after drug suspension. For vitamin K antagonists, the average time to the ischemic event was 10.4 days (SD = 5.7), and in 67% of patients, the time between drug discontinuation and the event was 7-14 days. The most frequent reason for drug suspension was patient negligence (37%), followed by planned surgery or invasive examination (26%) and side effects, including hemorrhage (18.5%). Conclusion Antiplatelet or vitamin K antagonist suspension has a temporal relationship with the occurrence of stroke and TIA. Since these events are preventable, it is crucial that healthcare professionals convince their patients that drug withdrawal can cause serious consequences.

RESUMO Pacientes em terapia anticoagulante ou antiagregante plaquetária frequentemente são solicitados a descontinuar essas medicações antes e durante procedimentos cirúrgicos ou invasivos. Se o paciente interromper tratamento sem supervisão médica, poderá aumentar de risco de acidente vascular cerebral (AVC). Objetivo Identificar prevalência de AVC isquêmico e ataque isquêmico transitório (AIT) associados à descontinuação de terapia antiplaquetária ou coumarínicos em pacientes internados em hospital especializado em atendimento neurológico no Brasil. Métodos Estudo transversal, retrospectivo de três anos, descritivo dos pacientes hospitalizados por AVC. A revisão de relatórios médicos determinou características do AVC, fatores de risco, motivos e tempo de interrupção medicamentosa. Resultados Em três anos, foram internados 360 pacientes por AVC ou AIT; destes, 27 interromperam temporariamente terapia antiplaquetária ou coumarínicos relacionando ao evento (81% acidente vascular cerebral isquêmico, 19% AIT). A prevalência foi de 7,5%. O tempo médio entre interrupção antiplaquetária e evento foi cinco dias, com 62% deles ocorrendo até sete dias após suspensão medicamentosa. Para coumarínicos, o tempo médio foi 10,4 dias (d.p.= 5,7), em 67% dos casos o tempo entre a descontinuação medicamentosa e o evento foi 7-14 dias. O motivo mais frequente para suspensão do medicamento foi negligência do paciente (37%), seguido por cirurgia planejada ou exame invasivo (26%) e efeitos colaterais, incluindo hemorragia (18,5%). Conclusão Suspensão de terapia de antiplaquetários ou coumarínicos tem relação temporal com ocorrência de AVC e de AIT. Esses eventos são passíveis de serem evitados, sendo imprescindível que profissionais de saúde convençam seus pacientes das consequências graves da retirada do medicamento.

The cost of stroke in private hospitals in Brazil: a one-year prospective study / O custo do AVC em hospitais privados no Brasil: um estudo prospectivo

ABSTRACT Few studies from low- and middle-income countries have assessed stroke and cerebral reperfusion costs from the private sector. Objective To measure the in-hospital costs of ischemic stroke (IS), with and without cerebral reperfusion, primary intracerebral hemorrhage (PIH), subarachnoid hemorrhage (SAH) and transient ischemic attacks (TIA) in two private hospitals in Joinville, Brazil. Methods Prospective disease-cost study. All medical and nonmedical costs for patients admitted with any stroke type or TIA were consecutively determined in 2016-17. All costs were adjusted to the gross domestic product deflator index and purchasing power parity. Results We included 173 patients. The median cost per patient was US$3,827 (IQR: 2,800-8,664) for the 131 IS patients; US$2,315 (IQR: 1,692-2,959) for the 27 TIA patients; US$16,442 (IQR: 5,108-33,355) for the 11 PIH patients and US$28,928 (IQR: 12,424-48,037) for the four SAH patients (p < 0.00001). For the six IS patients who underwent intravenous thrombolysis, the median cost per patient was US$11,463 (IQR: 8,931-14,291), and for the four IS patients who underwent intra-arterial thrombectomy, the median cost per patient was US$35,092 (IQR: 31,833-37,626; p < 0.0001). A direct correlation was found between cost and length of stay (r = 0.67, p < 0.001). Conclusions Stroke is a costly disease. In the private sector, the costs of cerebral reperfusion for IS treatment were three-to-ten times higher than for usual treatments. Therefore, cost-effectiveness studies are urgently needed in low- and middle-income countries.

RESUMO Poucos estudos determinam o custo do AVC em países de baixa e média renda nos setores privados. Objetivos Mensurar o custo hospitalar do tratamento do(a): AVC isquêmico com e sem reperfusão cerebral, hemorragia intracerebral primária (HIP), hemorragia subaracnóidea e ataque isquêmico transitório (AIT) em hospitais privados de Joinville, Brasil. Métodos Estudo prospectivo de custo de doença. Os custos médicos e não médicos dos pacientes admitidos com qualquer tipo de AVC ou AIT foram consecutivamente verificados em 2016-17. Os valores foram ajustados ao índice do deflator do produto interno bruto e à paridade do poder de compra. Resultados Nós incluímos 173 pacientes. A mediana de custo por paciente foi de US$ 3.827 (IQR: 2.800-8.664) para os 131 pacientes com AVC isquêmico; US$ 2.315 (1.692-2.959) para os 27 pacientes com AIT; US$ 16.442 (5.108-33.355) para os 11 pacientes com HIP e US$ 28.928 (12.424-48.037) para os quatro pacientes com HSA (p < 0,00001). Para seis pacientes submetidos à trombólise intravenosa, a mediana do custo por paciente foi de US$ 11.463 (8.931-14.291) e, para quatro pacientes submetidos à trombectomia intra-arterial, a mediana de custo por paciente foi de US$ 35.092 (31.833-37.626; p < 0,0001). Uma correlação direta foi encontrada entre custo e tempo de permanência (r = 0,67, p < 0,001). Conclusão O AVC é uma doença cara. Em ambiente privado, os custos da reperfusão cerebral foram de três a dez vezes superiores aos tratamentos habituais do AVC isquêmico. Portanto, estudos de custo-efetividade são urgentemente necessários em países de baixa e média rendas.

The cost of stroke in a public hospital in Brazil: a one-year prospective study / Custo do AVC em um hospital público no Brasil: um estudo prospectivo de um ano

ABSTRACT Low- and middle-income countries face tight health care budgets, not only new resources, but also costly therapeutic resources for treatment of ischemic stroke (IS). However, few prospective data about stroke costs including cerebral reperfusion from low- and middle-income countries are available. Objective To measure the costs of stroke care in a public hospital in Joinville, Brazil. Methods We prospectively assessed all medical and nonmedical costs of inpatients admitted with a diagnosis of any stroke or transient ischemic attack over one year, analyzed costs per type of stroke and treatment, length of stay (LOS) and compared hospital costs with government reimbursement. Results We evaluated 274 patients. The total cost for the year was US$1,307,114; the government reimbursed the hospital US$1,095,118. We found a significant linear correlation between LOS and costs (r = 0.71). The median cost of 134 IS inpatients who did not undergo cerebral reperfusion (National Institutes of Health Stroke Scale [NIHSS] median = 3 ) was US$2,803; for IS patients who underwent intravenous (IV) alteplase (NIHSS 10), the median was US$5,099, and for IS patients who underwent IV plus an intra-arterial (IA) thrombectomy (NIHSS > 10), the median cost was US$10,997. The median costs of a primary intracerebral hemorrhage, subarachnoid hemorrhage, and transient ischemic attack were US$2,436, US$8,031 and US$2,677, respectively. Conclusions Reperfusion treatments were two-to-four times more expensive than conservative treatment. A cost-effectiveness study of the IS treatment option is necessary.

RESUMO Os países de baixa e media renda enfrentam orçamentos apertados na saúde, não somente devido aos novos recursos terapêuticos, mas relacionado ao custo oneroso do tratamento do acidente vascular cerebral. No entanto, poucos dados prospectivos sobre os custos do AVC, incluindo reperfusão cerebral de países de baixa e média renda estão disponíveis. Objetivo Mensurar os custos do atendimento ao AVC em um hospital público. Métodos Avaliamos prospectivamente todos os custos médicos e não médicos de pacientes internados com diagnóstico de acidente vascular cerebral ou AIT durante 1 ano, analisamos os custos por tipo de AVC e tratamento, tempo de permanência e comparamos os custos hospitalares com o reembolso governamental. Resultados Foram avaliados 274 pacientes. O custo total em um ano foi de US$ 1.307,114; o governo reembolsou o hospital no valor de US$ 1.095.118. Encontramos uma correlação linear significativa entre LOS e custos (r = 0,71). A mediana do custo do AVCI em 134 pacientes que não sofreram reperfusão cerebral (National Institutes of Health Stroke Scale [NIHSS] mediana = 3) foi de US$ 2.803; para pacientes submetidos a alteplase intravenosa (IV) (NIHSS 10), a mediana foi de US$ 5.099 e para os pacientes submetidos a trombectomia intra-arterial (IA) (NIHSS > 10), o custo mediano foi de US$ 10.997. A mediana do custo de uma hemorragia intracerebral primária, hemorragia subaracnóidea e AIT foram de US$ 2.436, US$ 8.031 e US$ 2.677, respectivamente. Conclusões Os tratamentos de reperfusão foram duas a quatro vezes mais caros do que o tratamento conservador. Estudo de custo-efetividade para o tratamento do AVC são necessários.

The relation between echocardiographic epicardial fat thickness and cha2ds2-vasc score in patients with sinus rhythm

Abstract Objective: To evaluate the predictive value of epicardial fat thickness (EFT) in CHA2DS2-VASc (congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, previous stroke or transient ischemic attack, vascular disease, age 65-74 years, sex category) score risk groups. Methods: A total of 158 consecutive patients (75 females, 83 males, mean age 70.8±6.3 years) admitted routinely for cardiologic control were divided into two groups according to their CHA2DS2-VASc scores (scores 0 and 1 were regarded as low risk, and score ≥2 as high risk). One hundred twenty-five of 158 patients had a high-risk score. Results: Mean EFT was significantly higher in the high-risk group than in the low-risk group (4.34±0.62 vs. 5.37±1.0; P<0.001). EFT was positively correlated with CHA2DS2-VASc score (r=0.577, P<0.001). According to receiver operating characteristics (ROC) analysis, EFT value of 4.4 mm was found to be predictive of high risk in CHA2DS2-VASc score with 80% of sensitivity and 79% of specificity (C-statistic = 0.875, P<0.001, 95% confidence interval [CI] = 0.76-0.90). And according to multivariate logistic regression analysis, EFT was an independent predictor of high thromboembolic risk in terms of CHA2DS2-VASc score. Conclusion: Our findings suggest that echocardiographic EFT measurement could provide additional information on assessing cardiovascular risks, such as thromboembolic events, and individuals with increased EFT should receive more attention to reduce unfavorable cardiovascular risk factors and the development of future cardiovascular events.

Meta Analysis of Risks of Cardiocerebral Vascular Events in Patients with Primary Biliary Cholangitis / 中国医学科学院学报

To systematically evaluate the risks of cardiocerebral vascular events in patients with primary biliary cholangitis(PBC). Methods We carried out a Meta analysis by RevMan 5.3 software to investigate literatureon the risk of cardiocerebral vascular events in patients with PBC and controls. Results Compared with non-PBC controls,PBC patients had significantly higher risk of coronary events(=1.56,=0.0002);however,the risk of cerebrovascular events showed no significant difference between these two groups(=1.01,=0.94).Subgroup analysis demonstrated a significantly lower risk of transient ischemic attack or carotid stenosis in PBC patients(=0.63,=0.03);however,there was no significant difference in the risk of stroke(=1.11,=0.40). Conclusion Patients with PBC have an increased risk of coronary events but may have a lower risk of transient ischemic attack or carotid stenosis.

Outcomes after Transverse-Incision 'Mini' Carotid Endarterectomy and Patch-Plasty

PURPOSE: Traditional longitudinal incision for carotid endarterectomy (CEA) can be painful, aesthetically displeasing, and associated with a high incidence of cranial nerve injury (CNI). This study describes the outcomes of CEA performed through small (<5 cm long), transversely oriented incisions located directly over the carotid bifurcation, as identified by color-enhanced duplex ultrasound. MATERIALS AND METHODS: Patient demographics and operative data were collected retrospectively from an in-house database of consecutive vascular patients undergoing CEA with a small transversely oriented incision for both symptomatic and asymptomatic carotid artery stenoses. RESULTS: A total of 52 consecutive patients underwent CEA between 2012 and 2016 (median age, 73.5 years; interquartile range, 67-80.3; male/female ratio, 40:12). CEA was performed under regional/local anesthesia (LA) in 48 (92.3%) patients, with 4 (7.7%) being performed under general anesthesia. One patient under LA experienced intraoperative neurological dysfunction intraoperatively (manifesting as an inability to count out loud) that resolved with insertion of shunt. One patient experienced a transient neurological event (expressive dysphasia) within the immediate postoperative period, which resolved within 6 hours. No in-hospital death or perioperative major adverse cardiovascular events were noted. Follow-up data were available for a median period of 3.1 years and for all patients. Three patients experienced strokes following discharge (2 strokes contralateral to the operated side and 1 transient ischemic attack ipsilateral to the operated side). No persistent CNIs nor bleeding complications necessitating re-exploration were reported. CONCLUSION: Small, transversely orientated incisions, hidden within a neck skin crease can be safely performed in the majority of patients undergoing CEA.

Regular transient limb ischemia prevents atherosclerosis progression in hypercholesterolemic rabbits / 中华医学杂志(英文版)

BACKGROUND@#Endothelial dysfunction, the initial pathogenic factor in atherosclerosis, can be alleviated via transient limb ischemia. We observed the effects of regular transient limb ischemia (RTLI) on atherosclerosis in hypercholesterolemic rabbits.@*METHODS@#Twenty-eight rabbits were randomized to control, cholesterol, sham, ischemia groups (n = 7 each) between October 2010 and March 2011. They were fed a normal diet in the control group and hypercholesterolemic diet in other groups for 12 weeks. Six cycles of RTLI were performed once per day on the ischemia group. Serum samples were prepared to measure the total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) before the experiment (W0), at the end of weeks 4, 8, 12 (W4, W8, W12). The whole aorta was harvested at W12 and stained using Sudan IV to identify the plaque. The plaque area was measured using Image J. Results were analyzed by analysis of variance or rank sum test.@*RESULTS@#Concentrations of TC in the cholesterol group were higher than those in the control group at W4 (29.60 [23.75, 39.30] vs. 1.00 [0.80, 1.55], Z = -2.745, P = 0.006), W8 (41.78 [28.08, 47.37] vs. 0.35 [0.10, 0.68], Z = -2.739, P = 0.006), W12 (48.32 [40.04, 48.95] vs. 0.61 [0.50, 0.86], Z = -2.739, P = 0.006). Similar results were obtained for HDL-C and LDL-C. Serum concentrations of TC, HDL-C, and LDL-C in the hypercholesterolemic groups had no differences (all P > 0.05). The percentage of plaque area in the cholesterol group was higher than that in the control group (47.22 ± 23.89% vs. 0, Z = -2.986, P = 0.003). Square root of the percentage of plaque area was smaller in the ischemia group than that in the cholesterol (0.44 ± 0.13 vs. 0.67 ± 0.18, P = 0.014) or sham groups (0.44 ± 0.13 vs. 0.61 ± 0.12, P = 0.049).@*CONCLUSION@#In hypercholesterolemic rabbits, RTLI might prevent atherosclerosis progression by reducing the percentage of plaque area.

Characteristics of Acute Cerebral Infarction in Patients with Familial Hypercholesterolemia

BACKGROUND: The patients with familial hypercholesterolemia (FH) suffer from early onset atherosclerotic vascular disease due to high level of cholesterol and subsequent vascular inflammation, especially in the form of coronary artery disease. We investigated the clinical characteristics of FH associated cerebral infarction and its possible mechanism. METHODS: Between January 2014 and May 2017, acute cerebral infarction patients who admitted to Chung-Ang University Hospital were reviewed from stroke registry and the diagnosis of FH was made based on the Dutch Lipid Clinic Network Diagnostic Criteria for FH. We reviewed their initial laboratory and brain imaging information, prescribed medication and followed lipid profile after discharge. Stroke mechanism was determined based on Trial of ORG 10172 in Acute Stroke Treatment classification. RESULTS: Among 1,401 acute cerebral infarction or transient ischemic attack patients, one probable and three possible FH stroke patients were detected. All the patients denied of previous coronary artery disease history and initial lipid panel revealed high levels of total cholesterol (378±75 mg/dL) and low-density lipoprotein-cholesterol (238±56 mg/dL). Stroke mechanisms were heterogeneous, including one atherosclerotic, two vertebral artery dissection cases and one coagulation disorder. All the patients were combined with noticeable degree of intracranial atherosclerosis and were maintained with statin treatment. CONCLUSIONS: This study illustrates diverse stroke mechanism among stroke patients with FH. Further research is required to disclose exact incidence of FH among stroke population and effective treatment strategy.