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1.
Neurosurg Rev ; 46(1): 72, 2023 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-36935466

RESUMO

For patients with unruptured intracranial arteriovenous malformations (AVMs), the risk of a hemorrhagic event is approximately 2% to 4% annually. These events have an associated 20-50% morbidity and 10% mortality rate. An understanding of risk factors that predispose these lesions to rupture is important for optimal management. We aimed to pool a large cohort of both ruptured and unruptured AVMs from the literature with the goal of identifying angiographic risk factors that contribute to rupture. A systematic review of the literature was conducted in accordance with the PRISMA guidelines using Pubmed, Embase, Scopus, and Web of Science databases. Studies that presented patient-level data from ruptured AVMs from January 1990 to January 2022 were considered for inclusion. The initial screening of 8,304 papers resulted in a quantitative analysis of 25 papers, which identified six angiographic risk factors for AVM rupture. Characteristics that significantly increase the odds of rupture include the presence of aneurysm (OR = 1.45 [1.19, 1.77], p < 0.001, deep location (OR = 3.08 [2.56, 3.70], p < 0.001), infratentorial location (OR = 2.79 [2.08, 3.75], p < 0.001), exclusive deep venous drainage (OR = 2.50 [1.73, 3.61], p < 0.001), single venous drainage (OR = 2.97 [1.93, 4.56], p < 0.001), and nidus size less than 3 cm (OR = 2.54 [1.41, 4.57], p = 0.002). Although previous literature has provided insight into AVM rupture risk factors, obscurity still exists regarding which risk factors pose the greatest risk. We have identified six major angiographic risk factors (presence of an aneurysm, deep location, infratentorial location, exclusive deep venous drainage, single venous drainage, and nidus size less than 3 cm) that, when identified by a clinician, may help to tailor patient-specific approaches and guide clinical decisions.


Assuntos
Hemorragia , Malformações Arteriovenosas Intracranianas , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/cirurgia , Fatores de Risco , Angiografia Cerebral , Estudos Retrospectivos
2.
JAMA ; 330(9): 821-831, 2023 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-37668620

RESUMO

Importance: The effects of moderate systolic blood pressure (SBP) lowering after successful recanalization with endovascular therapy for acute ischemic stroke are uncertain. Objective: To determine the futility of lower SBP targets after endovascular therapy (<140 mm Hg or 160 mm Hg) compared with a higher target (≤180 mm Hg). Design, Setting, and Participants: Randomized, open-label, blinded end point, phase 2, futility clinical trial that enrolled 120 patients with acute ischemic stroke who had undergone successful endovascular therapy at 3 US comprehensive stroke centers from January 2020 to March 2022 (final follow-up, June 2022). Intervention: After undergoing endovascular therapy, participants were randomized to 1 of 3 SBP targets: 40 to less than 140 mm Hg, 40 to less than 160 mm Hg, and 40 to 180 mm Hg or less (guideline recommended) group, initiated within 60 minutes of recanalization and maintained for 24 hours. Main Outcomes and Measures: Prespecified multiple primary outcomes for the primary futility analysis were follow-up infarct volume measured at 36 (±12) hours and utility-weighted modified Rankin Scale (mRS) score (range, 0 [worst] to 1 [best]) at 90 (±14) days. Linear regression models were used to test the harm-futility boundaries of a 10-mL increase (slope of 0.5) in the follow-up infarct volume or a 0.10 decrease (slope of -0.005) in the utility-weighted mRS score with each 20-mm Hg SBP target reduction after endovascular therapy (1-sided α = .05). Additional prespecified futility criterion was a less than 25% predicted probability of success for a future 2-group, superiority trial comparing SBP targets of the low- and mid-thresholds with the high-threshold (maximum sample size, 1500 with respect to the utility-weighted mRS score outcome). Results: Among 120 patients randomized (mean [SD] age, 69.6 [14.5] years; 69 females [58%]), 113 (94.2%) completed the trial. The mean follow-up infarct volume was 32.4 mL (95% CI, 18.0 to 46.7 mL) for the less than 140-mm Hg group, 50.7 mL (95% CI, 33.7 to 67.7 mL), for the less than 160-mm Hg group, and 46.4 mL (95% CI, 24.5 to 68.2 mL) for the 180-mm Hg or less group. The mean utility-weighted mRS score was 0.51 (95% CI, 0.38 to 0.63) for the less than 140-mm Hg group, 0.47 (95% CI, 0.35 to 0.60) for the less than 160-mm Hg group, and 0.58 (95% CI, 0.46 to 0.71) for the high-target group. The slope of the follow-up infarct volume for each mm Hg decrease in the SBP target, adjusted for the baseline Alberta Stroke Program Early CT score, was -0.29 (95% CI, -0.81 to ∞; futility P = .99). The slope of the utility-weighted mRS score for each mm Hg decrease in the SBP target after endovascular therapy, adjusted for baseline utility-weighted mRS score, was -0.0019 (95% CI, -∞ to 0.0017; futility P = .93). Comparing the high-target SBP group with the lower-target groups, the predicted probability of success for a future trial was 25% for the less than 140-mm Hg group and 14% for the 160-mm Hg group. Conclusions and Relevance: Among patients with acute ischemic stroke, lower SBP targets less than either 140 mm Hg or 160 mm Hg after successful endovascular therapy did not meet prespecified criteria for futility compared with an SBP target of 180 mm Hg or less. However, the findings suggested a low probability of benefit from lower SBP targets after endovascular therapy if tested in a future larger trial. Trial Registration: ClinicalTrials.gov Identifier: NCT04116112.


Assuntos
Anti-Hipertensivos , Pressão Sanguínea , Infarto Encefálico , Procedimentos Endovasculares , Hipertensão , AVC Isquêmico , Idoso , Feminino , Humanos , Pressão Sanguínea/efeitos dos fármacos , Hipotensão , Infarto , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/cirurgia , Acidente Vascular Cerebral/cirurgia , Doença Aguda , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Sístole , Anti-Hipertensivos/administração & dosagem , Anti-Hipertensivos/farmacologia , Anti-Hipertensivos/uso terapêutico , Infarto Encefálico/diagnóstico por imagem , Infarto Encefálico/tratamento farmacológico , Infarto Encefálico/cirurgia
3.
J Stroke Cerebrovasc Dis ; 32(8): 107216, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37392484

RESUMO

OBJECTIVES: Dual-energy CT allows differentiation between blood and iodinated contrast. This study aims to determine the predictive value of contrast density and volume on post-thrombectomy dual-energy CT for delayed hemorrhagic transformation and its impact on 90-day outcomes. MATERIALS AND METHODS: A retrospective analysis was performed on patients who underwent thrombectomy for anterior circulation large-vessel occlusion at a comprehensive stroke center from 2018-2021. Per institutional protocol, all patients underwent dual-energy CT immediately post-thrombectomy and MRI or CT 24 hours afterward. The presence of hemorrhage and contrast staining was evaluated by dual-energy CT. Delayed hemorrhagic transformation was determined by 24-hour imaging and classified into petechial hemorrhage or parenchymal hematoma using ECASS III criteria. Univariable and multivariable analyses were performed to determine predictors and outcomes of delayed hemorrhagic transformation. RESULTS: Of 97 patients with contrast staining and without hemorrhage on dual-energy CT, 30 and 18 patients developed delayed petechial hemorrhage and delayed parenchymal hematoma, respectively. On multivariable analysis, delayed petechial hemorrhage was predicted by anticoagulant use (OR,3.53;p=0.021;95%CI,1.19-10.48) and maximum contrast density (OR,1.21;p=0.004;95%CI,1.06-1.37;per 10 HU increase), while delayed parenchymal hematoma was predicted by contrast volume (OR,1.37;p=0.023;95%CI,1.04-1.82;per 10 mL increase) and low-density lipoprotein (OR,0.97;p=0.043;95%CI,0.94-1.00;per 1 mg/dL increase). After adjusting for potential confounders, delayed parenchymal hematoma was associated with worse functional outcomes (OR,0.07;p=0.013;95%CI,0.01-0.58) and mortality (OR,7.83;p=0.008;95%CI,1.66-37.07), while delayed petechial hemorrhage was associated with neither. CONCLUSION: Contrast volume predicted delayed parenchymal hematoma, which was associated with worse functional outcomes and mortality. Contrast volume can serve as a useful predictor of delayed parenchymal hematoma following thrombectomy and may have implications for patient management.

4.
J Stroke Cerebrovasc Dis ; 32(8): 107217, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37392485

RESUMO

OBJECTIVES: Dual-energy CT allows differentiation between blood and iodinated contrast. We aimed to determine predictors of subarachnoid and intraparenchymal hemorrhage on dual-energy CT performed immediately post-thrombectomy and the impact of these hemorrhages on 90-day outcomes. MATERIALS AND METHODS: A retrospective analysis was performed on patients who underwent thrombectomy for anterior circulation large-vessel occlusion and subsequent dual-energy CT at a comprehensive stroke center from 2018-2021. The presence of contrast, subarachnoid hemorrhage, or intraparenchymal hemorrhage immediately post-thrombectomy was assessed by dual-energy CT. Univariable and multivariable analyses were performed to identify predictors of post-thrombectomy hemorrhages and 90-day outcomes. Patients with unknown 90-day mRS were excluded. RESULTS: Of 196 patients, subarachnoid hemorrhage was seen in 17, and intraparenchymal hemorrhage in 23 on dual-energy CT performed immediately post-thrombectomy. On multivariable analysis, subarachnoid hemorrhage was predicted by stent retriever use in the M2 segment of MCA (OR,4.64;p=0.017;95%CI,1.49-14.35) and the number of thrombectomy passes (OR,1.79;p=0.019;95%CI,1.09-2.94;per an additional pass), while intraparenchymal hemorrhage was predicted by preprocedural non-contrast CT-based ASPECTS (OR,8.66;p=0.049;95%CI,0.92-81.55;per 1 score decrease) and preprocedural systolic blood pressure (OR,5.10;p=0.037;95%CI,1.04-24.93;per 10 mmHg increase). After adjusting for potential confounders, intraparenchymal hemorrhage was associated with worse functional outcomes (OR,0.25;p=0.021;95%CI,0.07-0.82) and mortality (OR,4.30;p=0.023,95%CI,1.20-15.36), while subarachnoid hemorrhage was associated with neither. CONCLUSIONS: Intraparenchymal hemorrhage immediately post-thrombectomy was associated with worse functional outcomes and mortality and can be predicted by low ASPECTS and elevated preprocedural systolic blood pressure. Future studies focusing on management strategies for patients presenting with low ASPECTS or elevated blood pressure to prevent post-thrombectomy intraparenchymal hemorrhage are warranted.


Assuntos
Isquemia Encefálica , Acidente Vascular Cerebral , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/etiologia , Hemorragia Subaracnóidea/cirurgia , Estudos Retrospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Acidente Vascular Cerebral/cirurgia , Trombectomia/efeitos adversos , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Isquemia Encefálica/complicações
5.
J Magn Reson Imaging ; 56(4): 983-994, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-35289460

RESUMO

BACKGROUND: Moyamoya is a progressive intracranial vasculopathy, primarily affecting distal segments of the internal carotid and middle cerebral arteries. Treatment may comprise angiogenesis-inducing surgical revascularization; however, lack of randomized trials often results in subjective treatment decisions. HYPOTHESIS: Compensatory presurgical posterior vertebrobasilar artery (VBA) flow-territory reactivity, including greater cerebrovascular reactivity (CVR) and reduced vascular delay time, portends greater neoangiogenic response verified on digital subtraction angiography (DSA) at 1-year follow-up. STUDY TYPE: Prospective intervention cohort. SUBJECTS: Thirty-one patients with moyamoya (26 females; age = 45 ± 13 years; 41 revascularized hemispheres). METHODS: Anatomical MRI, hypercapnic CVR MRI, and DSA acquired presurgically in adult moyamoya participants scheduled for clinically indicated surgical revascularization. One-year postsurgery, DSA was repeated to evaluate collateralization. FIELD STRENGTH: 3 T. SEQUENCE: Hypercapnic T 2 * -weighted gradient-echo blood-oxygenation-level-dependent, T2 -weighted turbo-spin-echo fluid-attenuated-inversion-recovery, T1 -weighted magnetization-prepared-rapid-gradient-echo, and T2 -weighted diffusion-weighted-imaging. ASSESSMENT: Presurgical maximum CVR and response times were evaluated in VBA flow-territories. Revascularization success was determined using an ordinal scoring system of neoangiogenic collateralization from postsurgical DSA by two cerebrovascular neurosurgeons (R.V.C. with 8 years of experience; M.R.F. with 9 years of experience) and one neuroradiologist (L.T.D. with 8 years of experience). Stroke risk factors (age, sex, race, vasculopathy, and diabetes) were recorded. STATISTICAL TESTS: Fisher's exact and Wilcoxon rank-sum tests were applied to compare presurgical variables between cohorts with angiographically confirmed good (>1/3 middle cerebral artery [MCA] territory revascularized) vs. poor (<1/3 MCA territory revascularized) outcomes. SIGNIFICANCE: two-sided P < 0.05. Normalized odds ratios (ORs) were calculated. RESULTS: Criteria for good collateralization were met in 25 of the 41 revascularized hemispheres. Presurgical normalized VBA flow-territory CVR was significantly higher in those with good (1.12 ± 0.13 unitless) vs. poor (1.04 ± 0.05 unitless) outcomes. Younger (OR = -0.60 ± 0.67) and White (OR = -1.81 ± 1.40) participants had highest revascularization success (good outcomes: age = 42 ± 14 years, race = 84% White; poor outcomes: age = 49 ± 11 years, race = 44% White). DATA CONCLUSION: Presurgical MRI-measures of VBA flow-territory CVR are highest in moyamoya participants with better angiographic responses to surgical revascularization. LEVEL OF EVIDENCE: 1 TECHNICAL EFFICACY STAGE: 4.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Adulto , Angiografia Digital , Revascularização Cerebral/métodos , Circulação Cerebrovascular/fisiologia , Feminino , Humanos , Imageamento por Ressonância Magnética/métodos , Pessoa de Meia-Idade , Artéria Cerebral Média/diagnóstico por imagem , Artéria Cerebral Média/cirurgia , Doença de Moyamoya/diagnóstico por imagem , Doença de Moyamoya/cirurgia , Estudos Prospectivos
6.
Neurocrit Care ; 37(1): 81-90, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35099712

RESUMO

BACKGROUND: Following aneurysmal subarachnoid hemorrhage (SAH), patients are monitored closely for vasospasm in the intensive care unit. Conditional vasospasm-free survival describes the risk of future vasospasm as a function of time elapsed without vasospasm. Conditional survival has not been applied to this clinical scenario but could improve patient counseling and intensive care unit use. The objective of this study was to characterize conditional vasospasm-free survival following SAH. METHODS: This was a single institution, retrospective cohort study of patients treated for aneurysmal SAH between 1/1/2000-6/1/2020. The primary outcome was the development of vasospasm defined by the first instance of either radiographic vasospasm on computed tomography angiography, Lindegaard Index > 3.0 by transcranial doppler ultrasonography, or vasospasm-specific intraarterial therapy. Multivariable Cox regression was performed, and conditional vasospasm-free survival curves were constructed. RESULTS: A total of 528 patients were treated for aneurysmal SAH and 309 (58.5%) developed vasospasm. Conditional survival curves suggest patients who survive to postbleed day 10 without vasospasm have a nearly 90% chance of being discharged without vasospasm. The median onset of vasospasm was postbleed day 6. Age more than 50 years was associated with a lower risk (hazard ratio [HR] = .76; 95% confidence interval [CI] 0.64-0.91; p < 0.001). Higher initial systolic blood pressure (HR = 1.18; 95% CI 1.046-1.350; p = .008), Hunt-Hess grades 4 or 5 (HR = 1.304; 95% CI 1.014-1.676), and modified Fisher scale score of 4 (HR = 1.808; 95% CI 1.198-2.728) were associated with higher vasospasm than the respective lower grades. CONCLUSION: Conditional survival provides a useful framework for counseling patients and making decisions around vasospasm risk for patients with aneurysmal SAH, while risk factor-stratified plots facilitate a patient-centric, evidence-based approach to these conversations and decisions.


Assuntos
Doenças do Sistema Nervoso Autônomo , Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Hemorragia Subaracnóidea/tratamento farmacológico , Hemorragia Subaracnóidea/terapia , Ultrassonografia Doppler Transcraniana , Vasoespasmo Intracraniano/tratamento farmacológico
7.
J Stroke Cerebrovasc Dis ; 30(4): 105658, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33588186

RESUMO

INTRODUCTION: The National Inpatient Sample (NIS) has led to several breakthroughs via large sample size. However, utility of NIS is limited by the lack of admission NIHSS and 90-day modified Rankin score (mRS). This study creates estimates for stroke severity at admission and 90-day mRS using NIS data for acute ischemic stroke (AIS) patients treated with mechanical thrombectomy (MT). METHODS: Three patient cohorts undergoing MT for AIS were utilized: Cohort 1 (N = 3729) and Cohort 3 (N = 1642) were derived from NIS data. Cohort 2 (N=293) was derived from a prospectively-maintained clinical registry. Using Cohort 1, Administrative Stroke Outcome Variable (ASOV) was created using disposition and mortality. Factors reflective of stroke severity were entered into a stepwise logistic regression predicting poor ASOV. Odds ratios were used to create the Administrative Data Stroke Scale (ADSS). Performances of ADSS and ASOV were tested using Cohort 2 and compared with admission NIHSS and 90-day mRS, respectively. ADSS performance was compared with All Patient Refined-Diagnosis Related Group (APR-DRG) severity score using Cohort 3. RESULTS: Agreement of ASOV with 90-day mRS > 2 was fair (κ = 0.473). Agreement with 90-day mRS > 3 was substantial (κ = 0.687). ADSS significantly correlated (p < 0.001) with clinically-significant admission NIHSS > 15. ADSS performed comparably (AUC = 0.749) to admission NIHSS (AUC = 0.697) in predicting 90-day mRS > 2 and mRS > 3 (AUC = 0.767, 0.685, respectively). ADSS outperformed APR-DRG severity score in predicting poor ASOV (AUC = 0.698, 0.682, respectively). CONCLUSION: We developed and validated measures of stroke severity at admission (ADSS) and outcome (ASOV, estimate for 90-day mRS > 3) to increase utility of NIS data in stroke research.


Assuntos
Demandas Administrativas em Assistência à Saúde , Avaliação da Deficiência , Pacientes Internados , AVC Isquêmico/diagnóstico , Idoso , Bases de Dados Factuais , Feminino , Humanos , AVC Isquêmico/tratamento farmacológico , AVC Isquêmico/epidemiologia , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Valor Preditivo dos Testes , Sistema de Registros , Reprodutibilidade dos Testes , Índice de Gravidade de Doença , Trombectomia , Fatores de Tempo , Resultado do Tratamento , Estados Unidos/epidemiologia
8.
J Stroke Cerebrovasc Dis ; 30(2): 105488, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33276300

RESUMO

BACKGROUND/PURPOSE: Our study aimed to assess the impacts of neighborhood socioeconomic status on mechanical thrombectomy (MT) outcomes for acute ischemic stroke (AIS). METHODS: We conducted a prospective observational study of consecutive adult AIS patients treated with MT at one US comprehensive stroke center from 2012 to 2018. A composite neighborhood socioeconomic score (nSES) was created using patient home address, median household income, percentage of households with interest, dividend, or rental income, median value of housing units, percentage of persons 25 or older with high school degrees, college degrees or holding executive, managerial or professional specialty occupations. Using this score, patients were divided into low, middle and high nSES tertiles. Outcomes included 90-day functional independence, in-hospital mortality, length of hospital stay, discharge location, time to recanalization, successful recanalization, and symptomatic intracranial hemorrhage (sICH). RESULTS: 328 patients were included. Between the three nSES groups, proportion of White patients, time-to-recanalization and admission NIH stroke scale differed significantly (p<0.05). Patients in the high nSES tertile were more likely to be functionally dependent at 90 days (unadjusted OR, 95% CI, 1.91 [1.10, 3.36]) and were less likely to die in the hospital (unadjusted OR, 95% CI, 0.46, [0.20, 0.98]). Further, patients in the high nSES tertile had decreased times to recanalization (median time in minutes, low=335, mid=368, high=297, p=0.04). However, after adjusting for variance in race and severity of stroke, the differences in clinical outcomes were not significant. CONCLUSION: This study highlights how unadjusted neighborhood socioeconomic status is significantly associated with functional outcome, mortality, and time-to-recanalization following MT for AIS. Since adjustment modifies the significant association, the socioeconomic differences may be influenced by differences in pre-hospital factors that drive severity of stroke and time to recanalization. Better understanding of the interplay of these factors may lead to timelier evaluation and improvement in patient outcomes.


Assuntos
Disparidades nos Níveis de Saúde , Disparidades em Assistência à Saúde , AVC Isquêmico/epidemiologia , AVC Isquêmico/terapia , Características de Residência , Classe Social , Determinantes Sociais da Saúde , Trombectomia , Idoso , Escolaridade , Feminino , Estado Funcional , Mortalidade Hospitalar , Humanos , Renda , AVC Isquêmico/diagnóstico , AVC Isquêmico/mortalidade , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Ocupações , Estudos Prospectivos , Fatores Raciais , Recuperação de Função Fisiológica , Fatores de Risco , Tennessee/epidemiologia , Trombectomia/efeitos adversos , Trombectomia/mortalidade , Fatores de Tempo , Tempo para o Tratamento , Resultado do Tratamento
9.
J Stroke Cerebrovasc Dis ; 30(2): 105464, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33246208

RESUMO

OBJECTIVES: Intracranial atherosclerotic disease (ICAD) is responsible for 8-10% of acute ischemic strokes, and resistance to antiplatelet therapy is prevalent. CYP2C19 gene loss-of-function (up to 45% of patients) causes clopidogrel resistance. For patients with asymptomatic ICAD and ICAD characterized by transient ischemic attack (TIA), this study measures the effect of CYP2C19 loss-of-function on ischemic stroke risk during clopidogrel therapy. MATERIALS AND METHODS: From a deidentified database of medical records, patients were selected with ICD-9/10 code for ICAD, availability of CYP2C19 genotype, clopidogrel exposure, and established patient care. Dual-antiplatelet therapy patients were included. Patients with prior ischemic stroke, other neurovascular condition, intracranial angioplasty/stenting, or observation time <1 month were excluded. Time-to-event analysis using Cox regression was conducted to model first-time ischemic stroke events based on CYP2C19 loss-of-function allele and adjusted for age, gender, race, length of aspirin, length of concurrent antiplatelet/anticoagulant treatment, diabetes, coagulopathy, hypertension, heart disease, atrial fibrillation, and lipid disorder. Subset analyses were performed for asymptomatic and post-TIA subtypes of ICAD. RESULTS: A total of 337 patients were included (median age 68, 58% male, 88% Caucasian, 26% CYP2C19 loss-of-function). A total of 161 (47.8%) patients had TIA at time of ICAD diagnosis, while 176 (52.2%) were asymptomatic. First-time ischemic stroke was observed among 20 (12.4%) post-TIA ICAD patients and 17 (9.7%) asymptomatic ICAD patients. Median observation time was 2.82 [IQR 1.13-5.17] years. CYP2C19 loss-of-function allele was associated with ischemic stroke event (HR 2.2, 95% CI 1.1-4.3, p=0.020) after adjustment. Post-TIA ICAD patients had a higher risk of ischemic stroke from CYP2C19 loss-of-function (HR 3.4, 95% CI 1.4-8.2, p=0.006). CONCLUSIONS: CYP2C19 loss-of-function was associated with 3-fold increased risk of first-time ischemic stroke for ICAD patients treated with clopidogrel after TIA. This effect was not observed for asymptomatic ICAD. CYP2C19-guided antiplatelet selection may improve stroke prevention in ICAD after TIA.


Assuntos
Clopidogrel/efeitos adversos , Citocromo P-450 CYP2C19/genética , Resistência a Medicamentos/genética , Arteriosclerose Intracraniana/tratamento farmacológico , Ataque Isquêmico Transitório/prevenção & controle , AVC Isquêmico/prevenção & controle , Variantes Farmacogenômicos , Inibidores da Agregação Plaquetária/efeitos adversos , Idoso , Clopidogrel/administração & dosagem , Bases de Dados Factuais , Feminino , Humanos , Arteriosclerose Intracraniana/complicações , Arteriosclerose Intracraniana/diagnóstico por imagem , Ataque Isquêmico Transitório/diagnóstico por imagem , Ataque Isquêmico Transitório/etiologia , AVC Isquêmico/diagnóstico por imagem , AVC Isquêmico/etiologia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento
10.
Stroke ; 51(2): 511-518, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31813361

RESUMO

Background and Purpose- Although higher blood pressure variability (BPV) is associated with worse functional outcome after stroke, this association is not as well established in large vessel occlusion strokes treated with endovascular treatment (EVT). Methods- In this post hoc analysis of BEST (Blood Pressure after Endovascular Therapy for Ischemic Stroke), a prospective, multicenter cohort study of anterior circulation acute ischemic stroke patients undergoing EVT, we determined the association of BPV with poor outcome or death (90-day modified Rankin Scale, 3-6). We calculated BPV during the first 24 hours after EVT for systolic and diastolic BP using 5 methodologies, then divided BPV into tertiles and compared the highest to lowest tertile using logistic regression. Results- Of the 443 patients included in our analysis, 259 (58.5%) had a poor outcome, and 79 (17.8%) died. All measures of BPV were significantly higher in patients with poor outcome or death, but the difference was more pronounced for systolic than diastolic BPV. In the logistic regression, the highest tertile of systolic BPV consistently predicted poor outcome (odds ratio, 1.8-3.5, all P<0.05). The rate of death within 90 days was 10.1% in the tertile with the lowest systolic BPV versus 25.2% in the tertile with the highest BPV (P<0.001). Conclusions- In EVT-treated stroke patients, higher BPV in the first 24 hours is associated with worse 90-day outcome. This association was more robust for systolic BPV. The mechanism by which BPV may exert a negative influence on neurological outcome remains unknown, but the consistency of this association warrants further investigation and potentially intervention.


Assuntos
Pressão Sanguínea/fisiologia , Isquemia Encefálica/terapia , Acidente Vascular Cerebral/terapia , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Determinação da Pressão Arterial/métodos , Isquemia Encefálica/fisiopatologia , Infarto Cerebral/complicações , Infarto Cerebral/terapia , Procedimentos Endovasculares/métodos , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/fisiopatologia , Trombectomia/métodos , Resultado do Tratamento
11.
Stroke ; 51(5): 1539-1545, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32268851

RESUMO

Background and Purpose- We aimed to compare functional and procedural outcomes of patients with acute ischemic stroke with none-to-minimal (modified Rankin Scale [mRS] score, 0-1) and moderate (mRS score, 2-3) prestroke disability treated with mechanical thrombectomy. Methods- Consecutive adult patients undergoing mechanical thrombectomy for an anterior circulation stroke were prospectively identified at 2 comprehensive stroke centers from 2012 to 2018. Procedural and 90-day functional outcomes were compared among patients with prestroke mRS scores 0 to 1 and 2 to 3 using χ2, logistic, and linear regression tests. Primary outcome and significant differences in secondary outcomes were adjusted for prespecified covariates. Results- Of 919 patients treated with mechanical thrombectomy, 761 were included and 259 (34%) patients had moderate prestroke disability. Ninety-day mRS score 0 to 1 or no worsening of prestroke mRS was observed in 36.7% and 26.7% of patients with no-to-minimal and moderate prestroke disability, respectively (odds ratio, 0.63 [0.45-0.88], P=0.008; adjusted odds ratio, 0.90 [0.60-1.35], P=0.6). No increase in the disability at 90 days was observed in 22.4% and 26.7%, respectively. Rate of symptomatic intracerebral hemorrhage (7.3% versus 6.2%, P=0.65), successful recanalization (86.7% versus 83.8%, P=0.33), and median length of hospital stay (5 versus 5 days, P=0.06) were not significantly different. Death by 90 days was higher in patients with moderate prestroke disability (14.3% versus 40.3%; odds ratio, 4.06 [2.82-5.86], P<0.001; adjusted odds ratio, 2.83 [1.84, 4.37], P<0.001). Conclusions- One-third of patients undergoing mechanical thrombectomy had a moderate prestroke disability. There was insufficient evidence that functional and procedural outcomes were different between patients with no-to-minimal and moderate prestroke disability. Patients with prestroke disability were more likely to die by 90 days.


Assuntos
Atividades Cotidianas , Doenças das Artérias Carótidas/cirurgia , Artéria Carótida Interna/cirurgia , Pessoas com Deficiência , Infarto da Artéria Cerebral Média/cirurgia , Trombectomia/métodos , Idoso , Idoso de 80 Anos ou mais , Hemorragia Cerebral , Comorbidade , Feminino , Humanos , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Mortalidade , Estudos Prospectivos , Acidente Vascular Cerebral/cirurgia , Terapia Trombolítica/métodos , Resultado do Tratamento
12.
J Stroke Cerebrovasc Dis ; 29(8): 104952, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32689611

RESUMO

Frequency and outcomes of mechanical thrombectomy (MT) in clinical practice for patients with severe pre-stroke disability are largely unknown. In this case series, we aim to describe the disability make-up and outcomes of 33 patients with severe pre-stroke disability undergoing MT. Patients with a permanent, severe, pre-stroke disability (modified Rankin Score, mRS, 4-5) were identified from a prospectively-maintained database of consecutive, MT-treated, anterior circulation acute ischemic stroke patients at two comprehensive stroke centers in the United States. We present details on the cause of disability and socio-demographic status as well as procedural and functional outcomes. This study, despite the lack of inferential testing due to limited sample size, provides insight into demographics and outcomes of MT-treated patients with severe pre-stroke disability. Rate of return to functional baseline as well as rates of procedural success and complications were comparable to that reported in the literature for patients without any pre-existing disability.


Assuntos
Isquemia Encefálica/terapia , Avaliação da Deficiência , Pessoas com Deficiência , Acidente Vascular Cerebral/terapia , Trombectomia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico , Isquemia Encefálica/fisiopatologia , Bases de Dados como Assunto , Feminino , Nível de Saúde , Humanos , Masculino , Valor Preditivo dos Testes , Recuperação de Função Fisiológica , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/fisiopatologia , Trombectomia/efeitos adversos , Fatores de Tempo , Resultado do Tratamento , Estados Unidos
13.
Stroke ; 50(12): 3449-3455, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31587660

RESUMO

Background and Purpose- To identify the specific post-endovascular stroke therapy (EVT) peak systolic blood pressure (SBP) threshold that best discriminates good from bad functional outcomes (a priori hypothesized to be 160 mm Hg), we conducted a prospective, multicenter, cohort study with a prespecified analysis plan. Methods- Consecutive adult patients treated with EVT for an anterior ischemic stroke were enrolled from November 2017 to July 2018 at 12 comprehensive stroke centers accross the United States. All SBP values within 24 hours post-EVT were recorded. Using Youden index, the threshold of peak SBP that best discriminated primary outcome of dichotomized 90-day modified Rankin Scale score (0-2 versus 3-6) was identified. Association of this SBP threshold with the outcomes was quantified using multiple logistic regression. Results- Among 485 enrolled patients (median age, 69 [interquartile range, 57-79] years; 51% females), a peak SBP of 158 mm Hg was associated with the largest difference in the dichotomous modified Rankin Scale score (absolute risk reduction of 19%). Having a peak SBP >158 mm Hg resulted in an increased likelihood of modified Rankin Scale score 3 to 6 (odds ratio, 2.24 [1.52-3.29], P<0.01; adjusted odds ratio, 1.29 [0.81-2.06], P=0.28, after adjustment for prespecified variables). Conclusions- A peak post-EVT SBP of 158 mm Hg was prospectively identified to best discriminate good from bad functional outcome. Those with a peak SBP >158 had an increased likelihood of having a bad outcome in unadjusted, but not in adjusted analysis. The observed effect size was similar to prior studies. This finding should undergo further testing in a future randomized trial of goal-targeted post-EVT antihypertensive treatment.


Assuntos
Pressão Sanguínea/fisiologia , Procedimentos Endovasculares/métodos , Acidente Vascular Cerebral/fisiopatologia , Acidente Vascular Cerebral/cirurgia , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/complicações , Isquemia Encefálica/fisiopatologia , Isquemia Encefálica/cirurgia , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Acidente Vascular Cerebral/etiologia , Resultado do Tratamento
14.
J Neurol Neurosurg Psychiatry ; 90(12): 1370-1374, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31427365

RESUMO

BACKGROUND: There is limited data on predictors of symptomatic intracranial haemorrhage (sICH) in patients who underwent mechanical thrombectomy. In this study, we aim to determine those predictors with external validation. METHODS: We evaluated mechanical thrombectomy in a derivation cohort of patients at a comprehensive stroke centre over a 30-month period. Clinical and radiographic data on these patients were obtained from the prospective quality improvement database. sICH was defined using the European Cooperative Acute Stroke Study III. We compared clinical and radiographic characteristics between patients with and without sICH using χ2 and t tests to identify independent predictors of sICH with p<0.1. Significant variables were then combined in a multivariate logistic regression model to derive an sICH prediction score. This score was then validated using data from the Blood Pressure After Endovascular Treatment multicentre prospective registry. RESULTS: We identified 578 patients with acute ischaemic stroke who received thrombectomy, 19 had sICH (3.3%). Predictive factors of sICH were: thrombolysis in cerebral ischaemia (TICI) score, Alberta stroke program early CT score (ASPECTS), and glucose level, and from these predictors, we derived the weighted TICI-ASPECTS-glucose (TAG) score, which was associated with sICH in the derivation (OR per unit increase 1.98, 95% CI 1.48 to 2.66, p<0.001, area under curve ((AUC)=0.79) and validation (OR per unit increase 1.48, 95% CI 1.22 to 1.79, p<0.001, AUC=0.69) cohorts. CONCLUSION: High TAG scores are associated with sICH in patients receiving mechanical thrombectomy. Larger studies are needed to validate this scoring system and test strategies to reduce sICH risk and make thrombectomy safer in patients with elevated TAG scores.


Assuntos
Hemorragias Intracranianas/etiologia , Hemorragias Intracranianas/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Trombectomia/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Glicemia , Pressão Sanguínea , Isquemia Encefálica/complicações , Isquemia Encefálica/terapia , Estudos de Coortes , Angiografia por Tomografia Computadorizada , Feminino , Humanos , Hemorragias Intracranianas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Medição de Risco , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
15.
J Endovasc Ther ; 25(5): 624-631, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30101624

RESUMO

PURPOSE: To determine through meta-analysis whether administration of statins before carotid artery stenting (CAS) is associated with fewer periprocedural adverse events. METHODS: All randomized and observational English-language studies of periprocedural statin administration prior to CAS that reported the outcomes of interest (stroke, transient ischemic attack, myocardial infarction, and death at 30 days) were included in a random-effects meta-analysis. The I2 statistic was used to assess heterogeneity. Meta-regression analysis was performed to determine whether an association of statin treatment with risk of outcome events was influenced by other trial-level baseline characteristics of statin-treated and untreated patients. RESULTS: Eleven studies comprising 4088 patients were included. Patients who received statins prior to CAS had a significantly lower risk of stroke (OR 0.39, 95% CI 0.27 to 0.58, p<0.01; I2=0%) and death (OR 0.30, 95% CI 0.10 to 0.96, p=0.042; I2=0%). Statin use was not associated with a reduced risk of transient ischemic attack or myocardial infarction. In meta-regression analysis, other trial-level baseline characteristics had no significant influence on the association of statin treatment with death or stroke. CONCLUSION: Statin therapy prior to CAS is associated with decreased risk of perioperative stroke and death without any effect on the rates of transient ischemic attack or myocardial infarction.


Assuntos
Doenças das Artérias Carótidas/terapia , Procedimentos Endovasculares/instrumentação , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Stents , Idoso , Doenças das Artérias Carótidas/mortalidade , Esquema de Medicação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Masculino , Fatores de Proteção , Fatores de Risco , Acidente Vascular Cerebral/mortalidade , Acidente Vascular Cerebral/prevenção & controle , Resultado do Tratamento
16.
Stroke ; 48(9): 2450-2456, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28747462

RESUMO

BACKGROUND AND PURPOSE: Whether prior intravenous thrombolysis provides any additional benefits to the patients undergoing mechanical thrombectomy for large vessel, acute ischemic stroke remains unclear. METHODS: We conducted a meta-analysis of 13 studies obtained through PubMed and EMBASE database searches to determine whether functional outcome (modified Rankin Scale) at 90 days, successful recanalization rate, and symptomatic intracerebral hemorrhage rate differed between patients who underwent mechanical thrombectomy with (MT+IVT) and without (MT-IVT) pre-treatment with intravenous thrombolysis. RESULTS: MT+IVT patients compared with MT-IVT patients had better functional outcomes (modified Rankin Scale score, 0-2; summary odds ratio [OR], 1.27 [95% confidence interval (CI), 1.05-1.55]; P=0.02; n=1769/1174), lower mortality (OR, 0.71 [95% CI, 0.55-0.91]; P=0.006; n=1774/1202), and higher rate of successful recanalization (OR, 1.46 [95% CI, 1.09-1.96]; P=0.01; n=1652/1216) without having increased odds of symptomatic intracerebral hemorrhage (OR, 1.11 [95% CI, 0.69-1.77]; P=0.67; n=1471/1143). A greater number of MT+IVT patients required ≤2 passes with a neurothrombectomy device to achieve successful recanalization (OR, 2.06 [95% CI, 1.37-3.10]; P=0.0005; n=316/231). CONCLUSIONS: Our results demonstrated that MT+IVT patients had better functional outcomes, lower mortality, higher rate of successful recanalization, requiring lower number of device passes, and equal odds of symptomatic intracerebral hemorrhage compared with MT-IVT patients. The results support the current guidelines of offering intravenous thrombolysis to eligible patients even if they are being considered for mechanical thrombectomy. Because the data are compiled from studies where the 2 groups differed based on eligibility for intravenous thrombolysis, randomized trials are necessary to accurately evaluate the added value of intravenous thrombolysis in patients treated with mechanical thrombectomy.


Assuntos
Fibrinolíticos/uso terapêutico , Acidente Vascular Cerebral/terapia , Trombectomia/métodos , Terapia Trombolítica/métodos , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa , Hemorragia Cerebral/induzido quimicamente , Hemorragia Cerebral/epidemiologia , Terapia Combinada , Humanos , Mortalidade , Razão de Chances , Complicações Pós-Operatórias/epidemiologia , Resultado do Tratamento
17.
Cerebrovasc Dis ; 42(3-4): 263-71, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27173669

RESUMO

BACKGROUND: Cerebral vasospasm and sodium and fluid imbalances are common sequelae of aneurysmal subarachnoid hemorrhage (SAH) and cause of significant morbidity and mortality. Studies have shown the benefit of corticosteroids in the management of these sequelae. We have reviewed the literature and analyzed the available data for corticosteroid use after SAH. METHODS: PubMed, EMBASE, and Cochrane electronic databases were searched without language restrictions, and 7 observational, controlled clinical studies of the effect of corticosteroids in the management of SAH patients were identified. Data on sodium and fluid balances, symptomatic vasospasm (SVS), and outcomes were pooled for meta-analyses using the Mantel-Haenszel random effects model. RESULTS: Corticosteroids, specifically hydrocortisone and fludrocortisone, decreased natriuretic diuresis and incidence of hypovolemia. Corticosteroid administration is associated with lower incidence of SVS in the absence of nimodipine, but does not alter the neurological outcome. CONCLUSIONS: Supplementation of corticosteroids with mineralocorticoid activity, such as hydrocortisone or fludrocortisone, helps in maintaining sodium and volume homeostasis in SAH patients. Larger trials are warranted to confirm the effects of corticosteroids on SVS and patient outcomes.


Assuntos
Corticosteroides/uso terapêutico , Hidrocortisona/uso terapêutico , Hiponatremia/tratamento farmacológico , Hipovolemia/tratamento farmacológico , Hemorragia Subaracnóidea/tratamento farmacológico , Vasoespasmo Intracraniano/tratamento farmacológico , Artérias Cerebrais/efeitos dos fármacos , Artérias Cerebrais/fisiopatologia , Distribuição de Qui-Quadrado , Fludrocortisona/uso terapêutico , Humanos , Hiponatremia/diagnóstico , Hiponatremia/fisiopatologia , Hipovolemia/diagnóstico , Hipovolemia/fisiopatologia , Natriurese/efeitos dos fármacos , Razão de Chances , Sódio/sangue , Hemorragia Subaracnóidea/diagnóstico , Hemorragia Subaracnóidea/fisiopatologia , Resultado do Tratamento , Vasoconstrição/efeitos dos fármacos , Vasoespasmo Intracraniano/diagnóstico , Vasoespasmo Intracraniano/fisiopatologia , Equilíbrio Hidroeletrolítico/efeitos dos fármacos
19.
J Spinal Disord Tech ; 28(4): 126-33, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-22960417

RESUMO

OF BACKGROUND DATA: A patient comorbidity score (RCS) was developed from a prospective study of complications occurring in spine surgery patients. OBJECTIVE: To validate the RCS, we present an International Classification of Disease Clinical Modification (ICD-CM)-9 model of the score and correlate the score with complication incidence in a group of patients from the Nationwide Inpatient Sample database. We compare the predictive value of the score with the Charlson index. STUDY DESIGN: We conducted a retrospective assessment of Nationwide Inpatient Sample patients undergoing cervical or thoracolumbar spine surgery for degenerative pathology from 2002 to 2009. METHODS: We generated an ICD-9-CM coding-based model of our prospectively derived RCS, categorizing diagnostic codes to represent relevant comorbidities. Multivariate models were constructed to eliminate the least significant variables. ICD-9-CM coding was also used to calculate a Charlson comorbidity score for each patient. The accuracy of the RCS was compared with the Charlson index through the use of a receiver-operating curve. RESULTS: A total of 352,535 patients undergoing 369,454 spine procedures for degenerative disease were gathered. Hypertension and hyperlipidemia were the most common comorbidities. Cervical procedures resulted in 8286 complications (4.50%), whereas thoracolumbar procedures produced 25,118 complications (13.55%). Increasing RCS correlated linearly with increasing complication incidence (odds ratio [OR] 1.11; 95% confidence interval [CI], 1.10-1.13; P<0.0001). Logistic regression revealed that neurological deficit, cardiac conditions, and drug or alcohol use had greatest association with complication occurrence. The Charlson index also correlated with complication occurrence in both cervical (OR 1.25; 95% CI, 1.23-1.27) and thoracolumbar (OR 1.11; 95% CI, 1.10-1.12) patient groups. Receiver-operating curve analysis allowed a comparison of accuracy of the indices by comparing predictive values. The RCS performed as well as the Charlson index in predicting complication occurrence in both cervical and thoracic spine patients. CONCLUSIONS: ICD-9-based modeling validated that RCS correlates with complication occurrence. The RCS performed as well as the Charlson index in predicting risk of complication in spine patients.


Assuntos
Complicações Intraoperatórias/epidemiologia , Procedimentos Ortopédicos/estatística & dados numéricos , Complicações Pós-Operatórias/epidemiologia , Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Comorbidade , Bases de Dados Factuais , Feminino , Humanos , Incidência , Classificação Internacional de Doenças , Vértebras Lombares/cirurgia , Masculino , Pessoa de Meia-Idade , Período Perioperatório , Estudos Prospectivos , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Vértebras Torácicas/cirurgia , Adulto Jovem
20.
ScientificWorldJournal ; 2014: 356042, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25401136

RESUMO

INTRODUCTION: The variables that predispose to postcranioplasty infections are poorly described in the literature. We formulated a multivariate model that predicts the risk of infection in patients undergoing cranioplasty. METHOD: Retrospective review of all patients who underwent cranioplasty following craniectomy from January, 2000, to December, 2011. Tested predictors were age, sex, diabetic status, hypertensive status, reason for craniectomy, urgency status of craniectomy, location of cranioplasty, reoperation for hematoma, hydrocephalus postcranioplasty, and material type. A multivariate logistic regression analysis was performed. RESULTS: Three hundred forty-eight patients met the study criteria. Infection rate was 26.43% (92/348). Of these cases with infection, 56.52% (52/92) were superficial (supragaleal), 43.48% (40/92) were deep (subgaleal), and 31.52% (29/92) were present in both the supragaleal and subgaleal spaces. The predominant pathogen was coagulase-negative staphylococcus (30.43%) followed by methicillin-resistant Staphylococcus aureus (22.83%) and methicillin-sensitive Staphylococcus aureus (15.22%). Approximately 15.22% of all cultures were polymicrobial. Multivariate analysis revealed convex craniectomy, hemorrhagic stroke, and hydrocephalus to be associated with an increased risk of infection (OR = 14.41; P < 0.05, OR = 4.33; P < 0.05, OR = 1.90; P = 0.054, resp.). CONCLUSION: Many of the risk factors for infection after cranioplasty are modifiable. Recognition and prevention of the risk factors would help decrease the infection's rate.


Assuntos
Craniotomia/efeitos adversos , Infecções Estafilocócicas/diagnóstico , Infecção da Ferida Cirúrgica/diagnóstico , Craniotomia/tendências , Humanos , Valor Preditivo dos Testes , Estudos Retrospectivos , Infecções Estafilocócicas/epidemiologia , Infecção da Ferida Cirúrgica/epidemiologia
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