RESUMO
OBJECTIVES: Intracerebral hemorrhage (ICH) and cerebral microbleeds (CMB) in cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy are more common in East Asian populations than in people of white European ancestry. We hypothesized that the ethnic difference is explained by the East Asian-specific NOTCH3 p.R75P mutation. METHODS: This retrospective observational study included 118 patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in Japanese and Korean cohorts. We investigated whether the p.R75P mutation is associated with symptomatic ICH and multiple CMB (>5) using quasi-Poisson regression models. We predicted the NOTCH3 extracellular domain protein structures in silico and graded NOTCH3 extracellular domain immunostaining in skin vessels of some patients, with subsequent comparisons between p.R75P and other conventional mutations. RESULTS: Among 63 Japanese patients (median age 55 years; 56% men), 15 had a p.R75P mutation, significantly associated with symptomatic ICH (adjusted relative risk 9.56, 95% CI 2.45-37.31), multiple CMB (3.00, 1.34-6.71), and absence of temporopolar lesions (4.91, 2.29-10.52) after adjustment for age, sex, hypertension, and antithrombotics. In the Korean cohort (n = 55; median age 55 years; 51% men), the p.R75P mutation (n = 13) was also associated with symptomatic ICH (8.11, 1.83-35.89), multiple CMB (1.90, 1.01-3.56), and absence of temporopolar lesions (2.32, 1.08-4.97). Structural analysis revealed solvent-exposed free cysteine thiols in conventional mutations, directly causing aggregation, whereas a stereochemically incompatible proline residue structure in p.R75P lowers correct disulfide bond formation probability, indirectly causing aggregation. Pathologically, the p.R75P mutation resulted in less vascular NOTCH3 extracellular domain accumulation than the other conventional mutations. INTERPRETATION: NOTCH3 p.R75P mutation is associated with hemorrhagic presentations, milder temporopolar lesions, and distinct mutant protein structure properties. ANN NEUROL 2024;95:1040-1054.
Assuntos
CADASIL , Hemorragia Cerebral , Mutação , Receptor Notch3 , Humanos , Masculino , Feminino , Receptor Notch3/genética , Pessoa de Meia-Idade , CADASIL/genética , Estudos Retrospectivos , Hemorragia Cerebral/genética , Idoso , Mutação/genética , Adulto , Japão , República da Coreia , Povo Asiático/genéticaRESUMO
OBJECTIVE: We evaluated the efficacy of endovascular thrombectomy (EVT) on the functional outcome of patients with acute basilar artery occlusion and low posterior circulation acute stroke prognosis early computed tomography score (PC-ASPECTS). METHODS: We identified patients with acute ischemic stroke due to basilar artery occlusion and PC-ASPECTS of 6 or less, presenting within 24 h between August 2008 and April 2022. The primary outcome was a favorable functional outcome, defined as a modified Rankin Scale (mRS) score of 0-3 at 90 days. The secondary outcomes included an mRS score of 0-2, a favorable shift in the ordinal mRS scale, the occurrence of symptomatic intracranial hemorrhage (sICH), and mortality at 90 days. We compared the outcome of patients treated with EVT and those without EVT, using the inverse probability of treatment weighting methods. RESULTS: Out of 566 patients, 55.5% received EVT. In the EVT group, 106 (33.8%) achieved favorable outcomes, compared to 56 patients (22.2%) in the conservative group. EVT significantly increased the likelihood of achieving a favorable outcome compared to conservative treatment (relative risk [RR] 1.39, 95% confidence interval [CI], 1.11-1.74, p = 0.004). EVT was associated with a favorable shift in the mRS (RR 1.85, 95% CI, 1.49-2.29, p < 0.001) and reduced mortality without an increase in the risk of sICH. It did not have an impact on achieving an mRS score of 0-2. INTERPRETATION: Patients with acute basilar artery occlusion and a PC-ASPECTS of 6 or less might benefit from EVT without an increasing sICH. ANN NEUROL 2024;95:788-799.
Assuntos
Procedimentos Endovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Artéria Basilar , Resultado do Tratamento , AVC Isquêmico/etiologia , Acidente Vascular Cerebral/etiologia , Trombectomia/efeitos adversos , Hemorragias Intracranianas/etiologia , Sistema de Registros , Procedimentos Endovasculares/efeitos adversosRESUMO
BACKGROUND: Novel oral anticoagulants (NOACs) are currently recommended for the secondary prevention of stroke in patients with acute ischemic stroke (AIS) accompanied by atrial fibrillation (AF). However, the impact of NOACs on clinical outcomes in real-world practice remains ambiguous. This study analyzes the trend of clinical events in patients with AF-related AIS and determines how much the introduction of NOACs has mediated this trend. METHODS: We identified patients with AIS and AF between January 2011 and December 2019 using a multicenter stroke registry. Annual rates of NOAC prescriptions and clinical events within 1 year were evaluated. The primary outcome was a composite of recurrent stroke, myocardial infarction, and all-cause mortality. To assess the mediation effect of NOACs on the relationship between the calendar year and these outcomes, we used natural effect models and conducted exposure-mediator, exposure-outcome, and mediator-outcome analyses using multivariable regression models or accelerated failure time models, adjusting for potential confounders. RESULTS: Among the 12 977 patients with AF-related AIS, 12 500 (average age: 74.4 years; 51.3% male) were analyzed after excluding cases of valvular AF. Between 2011 and 2019, there was a significant decrease in the 1-year incidence of the primary composite outcome from 28.3% to 21.7%, while the NOAC prescription rate increased from 0% to 75.6%. A 1-year increase in the calendar year was independently associated with delayed occurrence of the primary outcome (adjusted time ratio, 1.10 [95% CI, 1.07-1.14]) and increased NOAC prescription (adjusted odds ratio, 2.20 [95% CI, 2.14-2.27]). Increased NOAC prescription was associated with delayed occurrence of the primary outcome (adjusted time ratio, 3.82 [95% CI, 3.17 to 4.61]). Upon controlling for NOAC prescription (mediator), the calendar year no longer influenced the primary outcome (adjusted time ratio, 0.97 [95% CI, 0.94-1.00]). This suggests that NOAC prescription mediates the association between the calendar year and the primary outcome. CONCLUSIONS: Our study highlights a temporal reduction in major clinical events or death in Korean patients with AF-related AIS, mediated by increased NOAC prescription, emphasizing NOAC use in this population.
Assuntos
Fibrilação Atrial , AVC Isquêmico , Idoso , Feminino , Humanos , Masculino , Administração Oral , Anticoagulantes/uso terapêutico , Fibrilação Atrial/complicações , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/epidemiologia , AVC Isquêmico/tratamento farmacológico , Estudos Multicêntricos como Assunto , Sistema de RegistrosRESUMO
OBJECTIVE: Heritability of stroke is assumed not to be low, especially in the young stroke population. However, most genetic studies have been performed in highly selected patients with typical clinical or neuroimaging characteristics. We investigated the prevalence of 15 Mendelian stroke genes and explored the relationships between variants and the clinical and neuroimaging characteristics in a large, unselected, young stroke population. METHODS: We enrolled patients aged ≤55 years with stroke or transient ischemic attack from a prospective, nationwide, multicenter stroke registry. We identified clinically relevant genetic variants (CRGVs) in 15 Mendelian stroke genes (GLA, NOTCH3, HTRA1, RNF213, ACVRL1, ENG, CBS, TREX1, ABCC6, COL4A1, FBN1, NF1, COL3A1, MT-TL1, and APP) using a customized, targeted next generation sequencing panel. RESULTS: Among 1,033 patients, 131 (12.7%) had 28 CRGVs, most frequently in RNF213 (n = 59), followed by ABCC6 (n = 53) and NOTCH3 (n = 15). The frequency of CRGVs differed by ischemic stroke subtypes (p < 0.01): the highest in other determined etiology (20.1%), followed by large artery atherosclerosis (13.6%). It also differed between patients aged ≤35 years and those aged 51 to 55 years (17.1% vs 9.3%, p = 0.02). Only 27.1% and 26.7% of patients with RNF213 and NOTCH3 variants had typical neuroimaging features of the corresponding disorders, respectively. Variants of uncertain significance (VUSs) were found in 15.4% patients. INTERPRETATION: CRGVs in 15 Mendelian stroke genes may not be uncommon in the young stroke population. The majority of patients with CRGVs did not have typical features of the corresponding monogenic disorders. Clinical implications of having CRGVs or VUSs should be explored. ANN NEUROL 2023;93:768-782.
Assuntos
Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Humanos , Estudos Prospectivos , Prevalência , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/genética , Mutação/genética , Serina Peptidase 1 de Requerimento de Alta Temperatura A/genética , Receptores de Activinas Tipo II/genética , Adenosina Trifosfatases/genética , Ubiquitina-Proteína Ligases/genéticaRESUMO
BACKGROUND: We aimed to evaluate covert brain infarction (CBI), frequently encountered during the diagnostic work-up of acute ischemic stroke, as a risk factor for stroke recurrence in patients with atrial fibrillation (AF). METHODS: For this prospective cohort study, from patients with acute ischemic stroke hospitalized at 14 centers between 2017 and 2019, we enrolled AF patients without history of stroke or transient ischemic attack and divided them into the CBI (+) and CBI (-) groups. The 2 groups were compared regarding the 1-year cumulative incidence of recurrent ischemic stroke and all-cause mortality using the Fine and Gray subdistribution hazard model with nonstroke death as a competing risk and the Cox frailty model, respectively. Each CBI lesion was also categorized into either embolic-appearing (EA) or non-EA pattern CBI. Adjusted hazard ratios and 95% CIs of any CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were estimated. RESULTS: Among 1383 first-ever stroke patients with AF, 578 patients (41.8%) had CBI. Of these 578 with CBI, EA pattern CBI only, non-EA pattern CBI only, and both CBIs were 61.8% (n=357), 21.8% (n=126), and 16.4% (n=95), respectively. The estimated 1-year cumulative incidence of recurrent ischemic stroke was 5.2% and 1.9% in the CBI (+) and CBI (-) groups, respectively (P=0.001 by Gray test). CBI increased the risk of recurrent ischemic stroke (adjusted hazard ratio [95% CI], 2.91 [1.44-5.88]) but did not the risk of all-cause mortality (1.32 [0.97-1.80]). The EA pattern CBI only and both CBIs elevated the risk of recurrent ischemic stroke (2.76 [1.32-5.77] and 5.39 [2.25-12.91], respectively), while the non-EA pattern only did not (1.44 [0.40-5.16]). CONCLUSIONS: Our study suggests that AF patients with CBI might have increased risk of recurrent stroke. CBI could be considered when estimating the stroke risk in patients with AF.
Assuntos
Fibrilação Atrial , Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Fibrilação Atrial/diagnóstico , Isquemia Encefálica/etiologia , Estudos Prospectivos , AVC Isquêmico/complicações , Infarto Encefálico/complicações , Fatores de Risco , RecidivaRESUMO
BACKGROUND: There is limited information on the delivery of acute stroke therapies and secondary preventive measures and clinical outcomes over time in young adults with acute ischemic stroke. This study investigated whether advances in these treatments improved outcomes in this population. METHODS: Using a prospective multicenter stroke registry in Korea, young adults (aged 18-50 years) with acute ischemic stroke hospitalized between 2008 and 2019 were identified. The observation period was divided into 4 epochs: 2008 to 2010, 2011 to 2013, 2014 to 2016, and 2017 to 2019. Secular trends for patient characteristics, treatments, and outcomes were analyzed. RESULTS: A total of 7050 eligible patients (mean age, 43.1; men, 71.9%) were registered. The mean age decreased from 43.6 to 42.9 years (Ptrend=0.01). Current smoking decreased, whereas obesity increased. Other risk factors remained unchanged. Intravenous thrombolysis and mechanical thrombectomy rates increased over time from 2008 to 2010 to 2017 to 2019 (9.5%-13.8% and 3.2%-9.2%, respectively; Ptrend<0.01). Door-to-needle time improved (Ptrend <.001), but onset-to-door and door-to-puncture times remained constant. Secondary prevention, including dual antiplatelets for noncardioembolic minor stroke (26.7%-47.0%), direct oral anticoagulants for atrial fibrillation (0.0%-56.2%), and statins for large artery atherosclerosis (76.1%-95.3%) increased (Ptrend<0.01). Outcome data were available from 2011. One-year mortality (2.5% in 2011-2013 and 2.3% in 2017-2019) and 3-month modified Rankin Scale scores 0 to 1 (68.3%-69.1%) and 0 to 2 (87.6%-86.2%) remained unchanged. The 1-year stroke recurrence rate increased (4.1%-5.5%; Ptrend=0.04), although the difference was not significant after adjusting for sex and age. CONCLUSIONS: Improvements in the delivery of acute stroke treatments did not necessarily lead to better outcomes in young adults with acute ischemic stroke over the past decade, indicating a need for further progress.
Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Masculino , Humanos , Adulto Jovem , Adulto , AVC Isquêmico/tratamento farmacológico , Isquemia Encefálica/epidemiologia , Isquemia Encefálica/terapia , Isquemia Encefálica/complicações , Estudos Prospectivos , Anticoagulantes/uso terapêutico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/complicações , Resultado do TratamentoRESUMO
OBJECTIVE: The frequency, management, and outcomes of early neurologic deterioration (END) after ischemic stroke specifically due to stroke progression or stroke recurrence have not been well delineated. MATERIALS AND METHODS: In a multicenter, nationwide registry, data on END due to stroke progression or recurrence confirmed by imaging were collected prospectively between January 2019 and July 2020. Patient characteristics, management strategies, and clinical outcomes were analyzed. RESULTS: Among 14,828 consecutive ischemic stroke patients, 1717 (11.6%) experienced END, including 1221 (8.2%) with END due to stroke progression (SP) or stroke recurrence (SR). Active management after END was implemented in 64.2% of patients. Active management strategies included volume expansion (29.2%), change in antithrombotic regimen (26.1%), induced hypertension (8.6%), rescue reperfusion therapy (6.8%), intracranial pressure lowering with hyperosmolar agents (1.5%), bypass surgery (0.6%), and hypothermia (0.1%). Active management strategies that varied with patient features included volume expansion and induced hypertension, used more often in large artery atherosclerosis and small vessel occlusion, and rescue endovascular thrombectomy, more common in other (dissection), cardioembolism, and large artery atherosclerosis. Active management was associated with higher rates of freedom from disability (modified Rankin Scale, mRS, 0-1; 24.3% vs. 16.6%) and functional independence (mRS, 0-2; 41.6% vs. 27.7%) at 3 months. CONCLUSION: END specifically due to stroke progression or recurrence occurs in 1 in 12 acute ischemic stroke patients. In this observational study, active management, undertaken in two-thirds of patients, was most often hemodynamic or antithrombotic and was associated with improved functional outcomes.
Assuntos
Aterosclerose , Isquemia Encefálica , Procedimentos Endovasculares , Hipertensão , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/terapia , Fibrinolíticos/efeitos adversos , AVC Isquêmico/tratamento farmacológico , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/terapia , Trombectomia/efeitos adversos , Trombectomia/métodos , Aterosclerose/complicações , Hipertensão/complicações , Procedimentos Endovasculares/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Stroke of other determined etiology (OE) includes patients with an uncommon cause of stroke. We described the general characteristics, management, and outcomes of stroke in OE and its subgroups. METHODS: This study is a retrospective analysis of a prospective, multicenter, nationwide registry, the Clinical Research Center for Stroke-Korea-National Institutes of Health registry. We classified OE strokes into 10 subgroups according to the literature and their properties. Each OE subgroup was compared according to clinical characteristics, sex, age strata, lesion locations, and management. Moreover, 1-year composites of stroke and all-cause mortality were investigated according to the OE subgroups. RESULTS: In total, 2119 patients with ischemic stroke with OE types (mean age, 55.6±16.2 years; male, 58%) were analyzed. In the Clinical Research Center for Stroke-Korea-National Institutes of Health registry, patients with OE accounted for 2.8% of all patients with stroke. The most common subtypes were arterial dissection (39.1%), cancer-related coagulopathy (17.3%), and intrinsic diseases of the arterial wall (16.7%). Overall, strokes of OE were more common in men than in women (58% versus 42%). Arterial dissection, intrinsic diseases of the arterial wall and stroke associated with migraine and drugs were more likely to occur at a young age, while disorders of platelets and the hemostatic system, cancer-related coagulopathy, infectious diseases, and hypoperfusion syndromes were more frequent at an old age. The composite of stroke and all-cause mortality within 1 year most frequently occurred in cancer-related coagulopathy, with an event rate of 71.8%, but least frequently occurred in stroke associated with migraine and drugs and arterial dissection, with event rates of 0% and 7.2%, respectively. CONCLUSIONS: This study presents the different characteristics, demographic findings, lesion locations, and outcomes of OE and its subtypes. It is characterized by a high proportion of arterial dissection, high mortality risk in cancer-related coagulopathy and an increasing annual frequency of cancer-related coagulopathy in patients with stroke of OE.
Assuntos
Dissecção Aórtica , Isquemia Encefálica , Transtornos de Enxaqueca , Neoplasias , Acidente Vascular Cerebral , Adulto , Idoso , Dissecção Aórtica/complicações , Isquemia Encefálica/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos de Enxaqueca/complicações , Neoplasias/complicações , Estudos Prospectivos , Sistema de Registros , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologiaRESUMO
Carotid artery thrombosis following carotidynia is an uncommon manifestation of systemic lupus erythematosus. We report the case of a woman without evidence of a lupus flare-up who presented with the unusual clinical course of ipsilateral carotidynia and recurrent ischemic stroke due to carotid thrombosis. To our knowledge, this is the first case of such an unusual manifestation in lupus and highlights distinctive challenges in the diagnosis and management of carotid artery thrombosis following carotidynia.
Assuntos
Doenças do Sistema Nervoso Autônomo , Doenças das Artérias Carótidas , Trombose das Artérias Carótidas , AVC Isquêmico , Lúpus Eritematoso Sistêmico , Acidente Vascular Cerebral , Feminino , Humanos , Trombose das Artérias Carótidas/diagnóstico por imagem , Trombose das Artérias Carótidas/etiologia , Lúpus Eritematoso Sistêmico/complicações , Lúpus Eritematoso Sistêmico/diagnóstico , Exacerbação dos Sintomas , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Dor , Acidente Vascular Cerebral/etiologiaRESUMO
This study aimed to present the prognosis after minor acute ischemic stroke (AIS) or transient ischemic attack (TIA), using a definition of subsequent stroke in accordance with recent clinical trials. In total, 9,506 patients with minor AIS (National Institutes of Health Stroke Scale ≤ 5) or high-risk TIA (acute lesions or ≥ 50% cerebral artery steno-occlusion) admitted between November 2010 and October 2013 were included. The primary outcome was the composite of stroke (progression of initial event or a subsequent event) and all-cause mortality. The cumulative incidence of stroke or death was 11.2% at 1 month, 13.3% at 3 months and 16.7% at 1 year. Incidence rate of stroke or death in the first month was 12.5 per 100 person-months: highest in patients with large artery atherosclerosis (17.0). The risk of subsequent events shortly after a minor AIS or high-risk TIA was substantial, particularly in patients with large artery atherosclerosis.
Assuntos
Aterosclerose , Ataque Isquêmico Transitório , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/epidemiologia , Recidiva , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/etiologiaRESUMO
BACKGROUND: There has been no comparison of the determinants of admission route between acute ischemic stroke (AIS) and acute myocardial infarction (AMI). We examined whether factors associated with direct versus transferred-in admission to regional cardiocerebrovascular centers (RCVCs) differed between AIS and AMI. METHODS: Using a nationwide RCVC registry, we identified consecutive patients presenting with AMI and AIS between July 2016 and December 2018. We explored factors associated with direct admission to RCVCs in patients with AIS and AMI and examined whether those associations differed between AIS and AMI, including interaction terms between each factor and disease type in multivariable models. To explore the influence of emergency medical service (EMS) paramedics on hospital selection, stratified analyses according to use of EMS were also performed. RESULTS: Among the 17,897 and 8,927 AIS and AMI patients, 66.6% and 48.2% were directly admitted to RCVCs, respectively. Multivariable analysis showed that previous coronary heart disease, prehospital awareness, higher education level, and EMS use increased the odds of direct admission to RCVCs, but the odds ratio (OR) was different between AIS and AMI (for the first 3 factors, AMI > AIS; for EMS use, AMI < AIS). EMS use was the single most important factor for both AIS and AMI (OR, 4.72 vs. 3.90). Hypertension and hyperlipidemia increased, while living alone decreased the odds of direct admission only in AMI; additionally, age (65-74 years), previous stroke, and presentation during non-working hours increased the odds only in AIS. EMS use weakened the associations between direct admission and most factors in both AIS and AMI. CONCLUSIONS: Various patient factors were differentially associated with direct admission to RCVCs between AIS and AMI. Public education for symptom awareness and use of EMS is essential in optimizing the transportation and hospitalization of patients with AMI and AIS.
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Serviços Médicos de Emergência , AVC Isquêmico , Infarto do Miocárdio , Acidente Vascular Cerebral , Humanos , Idoso , Infarto do Miocárdio/diagnóstico , Infarto do Miocárdio/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/complicações , Hospitalização , República da Coreia , GovernoRESUMO
Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is the most common genetic disorder among those responsible for hereditary strokes, and it is caused by a mutation in the NOTCH3 gene on chromosome 19. Blood biomarkers related to the Notch signaling pathway have not been investigated extensively in CADASIL. In this study, we measured the serum and plasma levels of NOTCH3 extracellular domain (N3ECD) and its ligand, Jagged-1, in 279 healthy subjects. The levels of N3ECD and Jagged-1 showed significant correlations in both serum (p < 0.0001, r = 0.2681) and plasma (p < 0.0001, r = 0.4065). The N3ECD levels were significantly higher in the serum than in plasma and tend to increase with age. In contrast, there was no significant difference between the serum and plasma levels of Jagged-1 levels. To summarize, we were able to measure N3ECD and Jagged-1 protein levels in healthy human serum and plasma. Taken together, our findings provide the basis for further studies investigating the clinical use of blood N3ECD and Jagged-1 levels for CADASIL and other Notch signaling-related diseases.
Assuntos
CADASIL , Biomarcadores , CADASIL/genética , Voluntários Saudáveis , Humanos , Proteína Jagged-1/genética , Ligantes , Mutação , Receptor Notch3/genética , Receptores Notch/genéticaRESUMO
BACKGROUND AND PURPOSE: The purpose of this study was to determine whether underweight is associated with poststroke cardiovascular events and whether such association is different according to the presence of atrial fibrillation (AF). METHODS: Patients with acute stroke or transient ischemic attack who were prospectively registered in a multicenter stroke database from April 2008 to July 2020 were analyzed, excluding those aged 75 or older and those who were overweight. We prospectively captured major adverse cardiovascular events (MACE) within one year after stroke. Cox-proportional hazard regression analysis was conducted for each subgroup with or without AF after adjusting for predetermined vascular risk factors and potential confounders. RESULTS: Among 30,912 patients, 1494 (4.8%) cases were underweight and 29,418 (95.2%) cases were normal weight. The cumulative event rate of 1-year MACE was higher in the underweight group (9.0%) than in the normal weight group (5.6%). In Cox-proportional regression, underweight was associated with significantly higher MACE (adjusted hazard ratio [HR]: 1.62, 95% confidence interval [CI]: 1.26-2.09) and recurrent stroke (adjusted HR: 1.42, 95% CI: 1.02-1.98) in all study patients. In patients with AF, the risk of MACE for the underweight group was not significantly increased. In contrast, in patients without AF, the underweight group had a consistently higher risk of MACE (adjusted HR: 1.66, 95% CI: 1.25-2.22) and recurrent stroke (adjusted HR: 1.50, 95% CI: 1.05-2.14). CONCLUSIONS: Underweight increased the risk of MACE and recurrent stroke within one year after acute stroke, especially in stroke without AF.
Assuntos
Fibrilação Atrial , Acidente Vascular Cerebral , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/epidemiologia , Humanos , Modelos de Riscos Proporcionais , Fatores de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Magreza/diagnóstico , Magreza/epidemiologiaRESUMO
Multinational enterprises (MNEs) have incentive to reduce tax payment through transfer pricing. The incentive is stronger when MNEs own intangibles, because it is easy to transfer them across countries. To mitigate such strategic tax planning, the OECD proposes the arm's length principle (ALP). This paper deals with technology patents as an example of intangibles and investigates how the ALP affects MNEs' licensing strategies and welfare in a model with a tax haven. The ALP may distort MNEs' licensing decisions, because providing a license to unrelated firms restricts MNEs' profit-shifting opportunities due to the emergence of comparable transaction. Interestingly, the termination of licensing in the presence of the ALP may worsen domestic welfare if the (potential) licensee and the MNE's subsidiary do not compete in the domestic market but may improve welfare if they compete. The results under ad valorem royalty are in distinct contrast with those under per-unit royalty.
RESUMO
Background and Purpose: Data on the effect on vascular outcomes of concomitant atherosclerotic vascular disease (ASVD) with atrial fibrillation (AF) after stroke are limited. This study evaluated the effect of ASVD with AF versus AF only on the risk of vascular events. Methods: We retrospectively analyzed a prospectively registered multicenter database involving 3213 stroke patients with AF. ASVD included extracranial atherosclerosis measured in the proximal portion of the internal carotid artery, intracranial atherosclerosis (all ≥50% stenosis), coronary artery disease, and peripheral artery disease and was categorized into 4 strata depending on the number of ASVDs (0, 1, 2, and 34). The independent associations of ASVD with major adverse cardiovascular events, stroke, and all-cause death were assessed. Results: A total of 2670 patients were included (mean age, 73.5±9.8 years; median CHA2DS2-VASc score, 5; interquartile range, 4−6). During the follow-up (mean, 1.7 years), a total of 672 (25.2%) major adverse cardiovascular events, 170 (6.4%) stroke events, and 501 (18.8%) all-cause deaths were noted. The adjusted hazard ratio for major adverse cardiovascular events versus no ASVD was 1.25 (95% CI, 1.001.56) for ASVD 1, 1.34 (95% CI, 1.021.76) for ASVD 2, and 1.93 (95% CI, 1.242.99) for ASVD 34. The adjusted hazard ratio for all-cause death versus no ASVD was 1.32 (1.011.74), 1.47 (1.062.03), and 2.39 (1.473.89), respectively. Among ASVD components, the presence of symptomatic or asymptomatic extracranial atherosclerosis was a more potent predictor of major adverse cardiovascular events (1.27 [1.051.54]) and all-cause death (1.45 [1.171.81]). Conclusions: ASVD burden with AF can be a cumulative marker of a high risk for untoward vascular outcomes. Among ASVD components, extracranial atherosclerosis seems to have a predominant effect.
Assuntos
Doença da Artéria Coronariana , Bases de Dados Factuais , Doença Arterial Periférica , Acidente Vascular Cerebral , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/mortalidade , Fibrilação Atrial/fisiopatologia , Doença da Artéria Coronariana/complicações , Doença da Artéria Coronariana/mortalidade , Doença da Artéria Coronariana/fisiopatologia , Feminino , Humanos , Arteriosclerose Intracraniana , Masculino , Pessoa de Meia-Idade , Doença Arterial Periférica/complicações , Doença Arterial Periférica/mortalidade , Doença Arterial Periférica/fisiopatologia , Estudos Retrospectivos , Fatores de Risco , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/fisiopatologiaRESUMO
BACKGROUND: Stroke risk scores (CHADS2 and CHA2DS2-VASc) not only predict the risk of stroke in atrial fibrillation (AF) patients, but have also been associated with prognosis after stroke. OBJECTIVE: The aim of this study was to evaluate the relationship between stroke risk scores and early neurological deterioration (END) in ischemic stroke patients with AF. METHODS: We included consecutive ischemic stroke patients with AF admitted between January 2013 and December 2015. CHADS2 and CHA2DS2-VASc scores were calculated using the established scoring system. END was defined as an increase ≥2 on the total National Institutes of Health Stroke Scale (NIHSS) score or ≥1 on the motor NIHSS score within the first 72 h of admission. RESULTS: A total of 2,099 ischemic stroke patients with AF were included. In multivariable analysis, CHA2DS2-VASc score (adjusted odds ratio [aOR] = 1.17, 95% confidence interval [CI] = 1.04-1.31) was significantly associated with END after adjusting for confounders. Initial NIHSS score, use of anticoagulants, and intracranial atherosclerosis (ICAS) were also found to be closely associated with END, independent of the CHA2DS2-VASc score. Multivariable analysis stratified by the presence of ICAS demonstrated that both CHA2DS2-VASc (aOR = 1.20, 95% CI = 1.04-1.38) and CHADS2 scores (aOR = 1.24, 95% CI = 1.01-1.52) were closely related to END in only patients with ICAS. In patients without ICAS, neither of the risk scores were associated with END. CONCLUSIONS: High CHA2DS2-VASc score was associated with END in ischemic stroke patients with AF. This close relationship is more pronounced in patients with ICAS.
Assuntos
Técnicas de Apoio para a Decisão , Avaliação da Deficiência , Serviços Médicos de Emergência , AVC Isquêmico/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Fibrilação Atrial/complicações , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/fisiopatologia , Progressão da Doença , Feminino , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico , Arteriosclerose Intracraniana/fisiopatologia , AVC Isquêmico/etiologia , AVC Isquêmico/fisiopatologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Sistema de Registros , República da Coreia , Estudos Retrospectivos , Medição de Risco , Fatores de RiscoRESUMO
BACKGROUND: We investigated the association between geographic proximity to hospitals and the administration rate of reperfusion therapy for acute ischemic stroke. METHODS: We identified patients with acute ischemic stroke who visited the hospital within 12 hours of symptom onset from a prospective nationwide multicenter stroke registry. Reperfusion therapy was classified as intravenous thrombolysis (IVT), endovascular therapy (EVT), or combined therapy. The association between the proportion of patients who were treated with reperfusion therapy and the ground transport time was evaluated using a spline regression analysis adjusted for patient-level characteristics. We also estimated the proportion of Korean population that lived within each 30-minute incremental service area from 67 stroke centers accredited by the Korean Stroke Society. RESULTS: Of 12,172 patients (mean age, 68 ± 13 years; men, 59.7%) who met the eligibility criteria, 96.5% lived within 90 minutes of ground transport time from the admitting hospital. The proportion of patients treated with IVT decreased significantly when stroke patients lived beyond 90 minutes of the transport time (P = 0.006). The proportion treated with EVT also showed a similar trend with the transport time. Based on the residential area, 98.4% of Korean population was accessible to 67 stroke centers within 90 minutes. CONCLUSION: The use of reperfusion therapy for acute stroke decreased when patients lived beyond 90 minutes of the ground transport time from the hospital. More than 95% of the South Korean population was accessible to 67 stroke centers within 90 minutes of the ground transport time.
Assuntos
Procedimentos Endovasculares , AVC Isquêmico/terapia , Terapia Trombolítica , Tempo para o Tratamento , Administração Intravenosa , Idoso , Idoso de 80 Anos ou mais , Terapia Combinada , Feminino , Fibrinolíticos/uso terapêutico , Humanos , AVC Isquêmico/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Sistema de Registros , República da Coreia , Fatores de TempoRESUMO
Background and Objectives: The relationship between depression in tinnitus patients without hearing loss remains elusive. This study aimed to investigate the association between tinnitus and normal hearing and depression. Materials and Methods: Participants aged ≥12 years with normal hearing levels were recruited from the Korea National Health and Nutrition Examination Survey (KNHANES), 2009-2012. Participants with normal hearing were divided into the tinnitus and non-tinnitus groups. The relationship between tinnitus with normal hearing and variables including age, sex, depression, ischemic heart diseases, stroke, diabetes, hypertension, dyslipidemia, chronic renal disease, noise exposure, and depression were analyzed. The odds of depression for tinnitus with normal hearing were estimated using multiple logistic regression tests with complex sampling. Results: The results showed that 4.9% (107/2221) and 2.8% (290/10,316) of participants in the tinnitus group and the non-tinnitus group, respectively, experienced depression (p < 0.001). Sex, ischemic heart disease, dyslipidemia, noise exposure, and depression were positively related to tinnitus with normal hearing. The odds ratio of depression for tinnitus with normal hearing were 1.89 (95% CI 1.37-2.60, p < 0.001). Conclusions: Tinnitus with normal hearing was related to the female sex, ischemic heart disease, dyslipidemia, noise exposure, and depression. Depression had the highest odds of tinnitus with normal hearing.
Assuntos
Zumbido , Idoso , Depressão/complicações , Depressão/epidemiologia , Feminino , Audição , Humanos , Inquéritos Nutricionais , República da Coreia/epidemiologia , Zumbido/complicações , Zumbido/epidemiologiaRESUMO
Background and Purpose- We evaluated whether hemoglobin concentration at admission was associated with stroke recurrence and composite vascular events (stroke, myocardial infarction, and vascular death) in acute ischemic stroke. Methods- We collected data from patients with acute ischemic stroke or transient ischemic attack from a multicenter stroke registry database in Korea. The association of hemoglobin concentration with 1-year stroke recurrence and composite vascular events was evaluated with respect to age, presence of cerebral artery stenosis, stroke severity, and stroke subtype. Results- Hemoglobin levels were inversely associated with stroke recurrence and composite vascular events. One-year rates of stroke recurrence and composite vascular events were significantly higher in patients with anemia or moderate anemia. In multivariable analyses, moderate anemia remained an independent predictor of stroke recurrence (adjusted hazard ratio, 1.43 [95% CI, 1.16-1.75]) and composite vascular events (adjusted hazard ratio, 1.26 [95% CI, 1.07-1.48]). Moderate anemia increased the risk of composite vascular events in patients with mild-to-moderate stroke severity (National Institutes of Health Stroke Scale score <16, P=0.01 for interaction). Conclusions- Hemoglobin concentration could be an independent predictor of stroke recurrence and composite vascular events.
Assuntos
Isquemia Encefálica/sangue , Isquemia Encefálica/diagnóstico , Hemoglobinas/metabolismo , Acidente Vascular Cerebral/sangue , Acidente Vascular Cerebral/diagnóstico , Idoso , Biomarcadores/sangue , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/diagnóstico , Estudos Prospectivos , RecidivaRESUMO
Background and Purpose- There is a paucity of information about the role of resting heart rate in the prediction of outcome events in patients with ischemic stroke with atrial fibrillation. We aimed to investigate the relationships between the level and variability of heart rate in the acute stroke period and stroke recurrence and mortality after acute ischemic stroke in patients with atrial fibrillation. Methods- Acute patients with ischemic stroke who had atrial fibrillation and were hospitalized within 48 hours of stroke onset were identified from a multicenter prospective stroke registry database. The acute stroke period was divided into early (within 24 hours of hospitalization) and late (72 hours to 7 days from onset) stages, and data on heart rate in both stages were collected. Moreover, the level and variability of heart rate were assessed using mean values and coefficients of variation. Outcome events were prospectively monitored up to 1 year after the index stroke. Results- Among 2046 patients eligible for the early acute stage analysis, 102 (5.0%) had a stroke recurrence, and 440 (21.5%) died during the first year after stroke. A statistically significant nonlinear J-shaped association was observed between mean heart rate and mortality (P<0.04 for quadratic and overall effect) but not between mean heart rate and stroke recurrence (P>0.1 for quadratic and overall effect). The nonlinear and overall effects of the coefficients of variation of heart rate were not significant for all outcome variables. The same results were observed in the late acute stage analysis (n=1576). Conclusions- In patients with atrial fibrillation hospitalized for acute ischemic stroke, the mean heart rate during the acute stroke period was not associated with stroke recurrence but was associated with mortality (nonlinear, J-shaped association). The relationships between heart rate and outcomes were not observed with respect to heart rate variability.