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1.
Ann Neurol ; 96(2): 321-331, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38738750

RESUMO

OBJECTIVE: For stroke patients with unknown time of onset, mismatch between diffusion-weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) magnetic resonance imaging (MRI) can guide thrombolytic intervention. However, access to MRI for hyperacute stroke is limited. Here, we sought to evaluate whether a portable, low-field (LF)-MRI scanner can identify DWI-FLAIR mismatch in acute ischemic stroke. METHODS: Eligible patients with a diagnosis of acute ischemic stroke underwent LF-MRI acquisition on a 0.064-T scanner within 24 h of last known well. Qualitative and quantitative metrics were evaluated. Two trained assessors determined the visibility of stroke lesions on LF-FLAIR. An image coregistration pipeline was developed, and the LF-FLAIR signal intensity ratio (SIR) was derived. RESULTS: The study included 71 patients aged 71 ± 14 years and a National Institutes of Health Stroke Scale of 6 (interquartile range 3-14). The interobserver agreement for identifying visible FLAIR hyperintensities was high (κ = 0.85, 95% CI 0.70-0.99). Visual DWI-FLAIR mismatch had a 60% sensitivity and 82% specificity for stroke patients <4.5 h, with a negative predictive value of 93%. LF-FLAIR SIR had a mean value of 1.18 ± 0.18 <4.5 h, 1.24 ± 0.39 4.5-6 h, and 1.40 ± 0.23 >6 h of stroke onset. The optimal cut-point for LF-FLAIR SIR was 1.15, with 85% sensitivity and 70% specificity. A cut-point of 6.6 h was established for a FLAIR SIR <1.15, with an 89% sensitivity and 62% specificity. INTERPRETATION: A 0.064-T portable LF-MRI can identify DWI-FLAIR mismatch among patients with acute ischemic stroke. Future research is needed to prospectively validate thresholds and evaluate a role of LF-MRI in guiding thrombolysis among stroke patients with uncertain time of onset. ANN NEUROL 2024;96:321-331.


Assuntos
Imagem de Difusão por Ressonância Magnética , AVC Isquêmico , Humanos , Idoso , Masculino , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , AVC Isquêmico/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos
2.
Proc Natl Acad Sci U S A ; 119(21): e2202012119, 2022 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-35588457

RESUMO

Severe acute respiratory syndrome coronavirus 2 (SARS­CoV-2) is a worldwide health concern, and new treatment strategies are needed. Targeting inflammatory innate immunity pathways holds therapeutic promise, but effective molecular targets remain elusive. Here, we show that human caspase-4 (CASP4) and its mouse homolog, caspase-11 (CASP11), are up-regulated in SARS­CoV-2 infections and that CASP4 expression correlates with severity of SARS­CoV-2 infection in humans. SARS­CoV-2­infected Casp11−/− mice were protected from severe weight loss and lung pathology, including blood vessel damage, compared to wild-type (WT) mice and mice lacking the caspase downstream effector gasdermin-D (Gsdmd−/−). Notably, viral titers were similar regardless of CASP11 knockout. Global transcriptomics of SARS­CoV-2­infected WT, Casp11−/−, and Gsdmd−/− lungs identified restrained expression of inflammatory molecules and altered neutrophil gene signatures in Casp11−/− mice. We confirmed that protein levels of inflammatory mediators interleukin (IL)-1ß, IL-6, and CXCL1, as well as neutrophil functions, were reduced in Casp11−/− lungs. Additionally, Casp11−/− lungs accumulated less von Willebrand factor, a marker for endothelial damage, but expressed more Kruppel-Like Factor 2, a transcription factor that maintains vascular integrity. Overall, our results demonstrate that CASP4/11 promotes detrimental SARS­CoV-2­induced inflammation and coagulopathy, largely independently of GSDMD, identifying CASP4/11 as a promising drug target for treatment and prevention of severe COVID-19.


Assuntos
COVID-19 , Caspases Iniciadoras/metabolismo , SARS-CoV-2 , Tromboinflamação , Animais , COVID-19/enzimologia , COVID-19/patologia , Caspases Iniciadoras/genética , Progressão da Doença , Humanos , Pulmão/patologia , Camundongos , Camundongos Knockout , Índice de Gravidade de Doença , Tromboinflamação/enzimologia , Tromboinflamação/genética
3.
J Neurol Neurosurg Psychiatry ; 95(3): 256-263, 2024 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-37673641

RESUMO

BACKGROUND: Moyamoya is a chronic occlusive cerebrovascular disease of unknown etiology causing neovascularization of the lenticulostriate collaterals at the base of the brain. Although revascularization surgery is the most effective treatment for moyamoya, there is still no consensus on the best surgical treatment modality as different studies provide different outcomes. OBJECTIVE: In this large case series, we compare the outcomes of direct (DR) and indirect revascularisation (IR) and compare our results to the literature in order to reflect on the best revascularization modality for moyamoya. METHODS: We conducted a multicenter retrospective study in accordance with the Strengthening the Reporting of Observational studies in Epidemiology guidelines of moyamoya affected hemispheres treated with DR and IR surgeries across 13 academic institutions predominantly in North America. All patients who underwent surgical revascularization of their moyamoya-affected hemispheres were included in the study. The primary outcome of the study was the rate of symptomatic strokes. RESULTS: The rates of symptomatic strokes across 515 disease-affected hemispheres were comparable between the two cohorts (11.6% in the DR cohort vs 9.6% in the IR cohort, OR 1.238 (95% CI 0.651 to 2.354), p=0.514). The rate of total perioperative strokes was slightly higher in the DR cohort (6.1% for DR vs 2.0% for IR, OR 3.129 (95% CI 0.991 to 9.875), p=0.052). The rate of total follow-up strokes was slightly higher in the IR cohort (8.1% vs 6.6%, OR 0.799 (95% CI 0.374 to 1.709) p=0.563). CONCLUSION: Since both modalities showed comparable rates of overall total strokes, both modalities of revascularization can be performed depending on the patient's risk assessment.


Assuntos
Revascularização Cerebral , Doença de Moyamoya , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Revascularização Cerebral/efeitos adversos , Revascularização Cerebral/métodos , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Doença de Moyamoya/cirurgia
4.
Am J Emerg Med ; 82: 37-41, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38781784

RESUMO

BACKGROUND: Emergency Department (ED) Observation Units (OU) can provide safe, effective care for low risk patients with intracranial hemorrhages. We compared current ED OU use for patients with subdural hematomas (SDH) to the validated Brain Injury Guidelines (BIG) to evaluate the potential impact of implementing this risk stratification tool. METHODS: Retrospective cohort of patients ≥18 years old with SDH of any cause from 2014 to 2020 to evaluate for potential missed OU cases. Missed OU cases were defined as patients with an initial Glasgow Coma Score (GCS) of 15 with hospital length of stays (LOS) <2 days, who did not meet the composite outcome and were not cared for in the OU or discharged from the ED. Composite outcome included in-hospital death or transition to hospice care, neurosurgical intervention, GCS decline, and worsening SDH size. Secondary outcomes were whether application of BIG would increase ED OU use or reduce CT use. RESULTS: 264 patients met inclusion criteria over 5.3 year study timeframe. Mean age was 61 years (range 19-93) and 61.4% were male. SDH were traumatic in 76.9% and 60.2% of the cohort had additional injuries. The admission rate was 81.4% (n = 215). Fourteen (6.5%) missed OU cases were identified (2.6/year). Retrospective application of BIG resulted in 82.6% (n = 217) at BIG 3, 10.2% (n = 27) at BIG 2 and 7.6% (n = 20) at BIG 1. Application of BIG would not have decreased admission rates (82.6% BIG 3) and BIG 1 and 2 admissions were often for medical co-morbidities. The composite outcome was met in 50% of BIG 3, 22% of BIG 2, and no BIG 1 patients. CONCLUSION: In a level 1 trauma center with an established observation unit, current clinical care processes missed very few patients who could be discharged or placed in ED OU for SDH. Hospital admissions in BIG 1/2 were driven by co-morbidities and/or injuries, limiting applicability of BIG to this population.


Assuntos
Serviço Hospitalar de Emergência , Humanos , Estudos Retrospectivos , Masculino , Serviço Hospitalar de Emergência/estatística & dados numéricos , Feminino , Pessoa de Meia-Idade , Idoso , Adulto , Idoso de 80 Anos ou mais , Escala de Coma de Glasgow , Guias de Prática Clínica como Assunto , Hematoma Subdural/terapia , Hematoma Subdural/epidemiologia , Unidades de Observação Clínica/estatística & dados numéricos , Tempo de Internação/estatística & dados numéricos , Lesões Encefálicas/terapia , Lesões Encefálicas/epidemiologia , Admissão do Paciente/estatística & dados numéricos , Admissão do Paciente/normas , Adulto Jovem
5.
Acta Neurochir (Wien) ; 166(1): 366, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39269654

RESUMO

BACKGROUND: Moyamoya disease (MMD) is a rare cerebrovascular disorder characterized by progressive steno-occlusive changes in the internal carotid arteries, leading to an abnormal vascular network. Hypertension is prevalent among MMD patients, raising concerns about its impact on disease outcomes. This study aims to compare the clinical characteristics and outcomes of MMD patients with and without hypertension. METHODS: We conducted a multicenter, retrospective study involving 598 MMD patients who underwent surgical revascularization across 13 academic institutions in North America. Patients were categorized into hypertensive (n=292) and non-hypertensive (n=306) cohorts. Propensity score matching (PSM) was performed to adjust for baseline differences. RESULTS: The mean age was higher in the hypertension group (46 years vs. 36.8 years, p < 0.001). Hypertensive patients had higher rates of diabetes mellitus (45.2% vs. 10.7%, p < 0.001) and smoking (48.8% vs. 27.1%, p < 0.001). Symptomatic stroke rates were higher in the hypertension group (16% vs. 7.1%; OR: 2.48; 95% CI: 1.39-4.40, p = 0.002) before matching. After PSM, there were no significant differences in symptomatic stroke rates (11.1% vs. 7.7%; OR: 1.5; CI: 0.64-3.47, p = 0.34), perioperative strokes (6.2% vs. 2.1%; OR 3.13; 95% CI: 0.83-11.82, p = 0.09), or good functional outcomes at discharge (93% vs. 92.3%; OR 1.1; 95% CI: 0.45-2.69, p = 0.82). CONCLUSION: No significant differences in symptomatic stroke rates, perioperative strokes, or functional outcomes were observed between hypertensive and non-hypertensive Moyamoya patients. Appropriate management can lead to similar outcomes in both groups. Further prospective studies are required to validate these findings.


Assuntos
Hipertensão , Doença de Moyamoya , Pontuação de Propensão , Humanos , Doença de Moyamoya/cirurgia , Doença de Moyamoya/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Hipertensão/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Revascularização Cerebral/métodos
6.
J Stroke Cerebrovasc Dis ; 33(11): 107894, 2024 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-39106921

RESUMO

OBJECTIVES: SARS-CoV-2 (COVID) induces systemic thrombotic complications including acute ischemic stroke. In this case series, we report markers of inflammation, coagulation factors including von Willebrand factor antigen, and rotational thromboelastometry (ROTEM) data. MATERIALS AND METHODS: Retrospective case series of COVID patients seen at a single comprehensive stroke center between 2020-2022. For patients undergoing mechanical thrombectomy (MT), ROTEM data was collected during the procedure and analyzed on ROTEM delta system. RESULTS: Fifteen patients (33.3% female) median age 65-years-old presented with COVID and acute ischemic stroke. Thirteen had LVO. The mean NIHSS was 15 (range 0-35) on admission and 18 (0-42) at discharge. Most were cryptogenic (N=7, 46.7%), followed by cardioembolic (N=6, 40%) and large artery-to-artery embolization (N=2, 13.3%). mRS was < 3 in 8 (53%) patients at discharge. None of the patients were on anticoagulation, and five were on antiplatelet therapy pre-hospitalization. Seven received thrombolytics with alteplase (tPA), and 10 had MT. Baseline platelet count was 102 K/uL (range 102-291 K/uL). vWF was measured in 12 patients, all elevated, with seven having levels >400 (180%). ROTEM data was collected in six patients. Three who received tPA had abnormal EXTEM and FIBTEM data (CT extem > 85secs, A10 EXTEM < 45mm, and A10 FIBTEM < 10mm). Notably, INTEM (CT INTEM >208secs) was abnormal in five of the six patients, two of whom did not receive tPA. CONCLUSIONS: Elevated vWF antigen levels with abnormal ROTEM data suggests that COVID induces changes in the clotting cascade. More robust research is needed to investigate these findings. Thrombolytics, MT, and antiplatelet agents should be utilized to treat COVID-related ischemic stroke based on current clinical guidelines.


Assuntos
COVID-19 , AVC Isquêmico , Tromboelastografia , Fator de von Willebrand , Humanos , COVID-19/complicações , COVID-19/sangue , COVID-19/diagnóstico , COVID-19/terapia , Feminino , Fator de von Willebrand/metabolismo , Idoso , Masculino , Estudos Retrospectivos , AVC Isquêmico/diagnóstico , AVC Isquêmico/sangue , AVC Isquêmico/terapia , AVC Isquêmico/etiologia , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Valor Preditivo dos Testes , Trombectomia , Biomarcadores/sangue , Coagulação Sanguínea/efeitos dos fármacos , Resultado do Tratamento
7.
Brain ; 145(7): 2378-2393, 2022 07 29.
Artigo em Inglês | MEDLINE | ID: mdl-35905466

RESUMO

Stroke causes devastating sensory-motor deficits and long-term disability due to disruption of descending motor pathways. Restoration of these functions enables independent living and therefore represents a high priority for those afflicted by stroke. Here, we report that daily administration of gabapentin, a clinically approved drug already used to treat various neurological disorders, promotes structural and functional plasticity of the corticospinal pathway after photothrombotic cortical stroke in adult mice. We found that gabapentin administration had no effects on vascular occlusion, haemodynamic changes nor survival of corticospinal neurons within the ipsilateral sensory-motor cortex in the acute stages of stroke. Instead, using a combination of tract tracing, electrical stimulation and functional connectivity mapping, we demonstrated that corticospinal axons originating from the contralateral side of the brain in mice administered gabapentin extend numerous collaterals, form new synaptic contacts and better integrate within spinal circuits that control forelimb muscles. Not only does gabapentin daily administration promote neuroplasticity, but it also dampens maladaptive plasticity by reducing the excitability of spinal motor circuitry. In turn, mice administered gabapentin starting 1 h or 1 day after stroke recovered skilled upper extremity function. Functional recovery persists even after stopping the treatment at 6 weeks following a stroke. Finally, chemogenetic silencing of cortical projections originating from the contralateral side of the brain transiently abrogated recovery in mice administered gabapentin, further supporting the conclusion that gabapentin-dependent reorganization of spared cortical pathways drives functional recovery after stroke. These observations highlight the strong potential for repurposing gabapentinoids as a promising treatment strategy for stroke repair.


Assuntos
Acidente Vascular Cerebral , Animais , Axônios/fisiologia , Gabapentina , Camundongos , Plasticidade Neuronal/fisiologia , Tratos Piramidais , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/tratamento farmacológico
8.
Neurobiol Dis ; 165: 105647, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-35114362

RESUMO

Ischemic stroke is a devastating health problem, affecting approximately 800,000 patients in the US every year, making it the leading cause of combined death and disability in the country. Stroke has historically been thought of as predominantly impacting men, however it is becoming increasingly clear that stroke affects women to a greater degree than men. Indeed, women have worse outcomes compared to men following ischemic stroke. Recent clinical advances have shown great promise in acute stroke therapy, with the use of mechanical endovascular thrombectomy (with and without recombinant tissue plasminogen activator; rtPA) greatly improving outcomes. This observation makes it clear that removal of clots and reperfusion, either mechanically or pharmacologically, is critical for improving outcomes of patients following acute ischemic stroke. Despite these promising advances, long-term neurological sequelae persist in the post-stroke population. This review focuses on mechanisms of thrombosis (clot formation) as it pertains to stroke and important sex differences in thrombosis and responses to treatment. Finally, we describe recent data related to new therapeutic approaches to thrombolysis, with a particular focus on von Willebrand Factor (vWF).


Assuntos
Isquemia Encefálica , AVC Isquêmico , Trombose , Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/terapia , Feminino , Fibrinolíticos/uso terapêutico , Humanos , AVC Isquêmico/complicações , AVC Isquêmico/terapia , Masculino , Caracteres Sexuais , Trombose/tratamento farmacológico , Ativador de Plasminogênio Tecidual/uso terapêutico , Resultado do Tratamento
10.
Anesthesiology ; 137(1): 67-78, 2022 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-35412597

RESUMO

BACKGROUND: COVID-19 causes hypercoagulability, but the association between coagulopathy and hypoxemia in critically ill patients has not been thoroughly explored. This study hypothesized that severity of coagulopathy would be associated with acute respiratory distress syndrome severity, major thrombotic events, and mortality in patients requiring intensive care unit-level care. METHODS: Viscoelastic testing by rotational thromboelastometry and coagulation factor biomarker analyses were performed in this prospective observational cohort study of critically ill COVID-19 patients from April 2020 to October 2020. Statistical analyses were performed to identify significant coagulopathic biomarkers such as fibrinolysis-inhibiting plasminogen activator inhibitor 1 and their associations with clinical outcomes such as mortality, extracorporeal membrane oxygenation requirement, occurrence of major thrombotic events, and severity of hypoxemia (arterial partial pressure of oxygen/fraction of inspired oxygen categorized into mild, moderate, and severe per the Berlin criteria). RESULTS: In total, 53 of 55 (96%) of the cohort required mechanical ventilation and 9 of 55 (16%) required extracorporeal membrane oxygenation. Extracorporeal membrane oxygenation-naïve patients demonstrated lysis indices at 30 min indicative of fibrinolytic suppression on rotational thromboelastometry. Survivors demonstrated fewer procoagulate acute phase reactants, such as microparticle-bound tissue factor levels (odds ratio, 0.14 [0.02, 0.99]; P = 0.049). Those who did not experience significant bleeding events had smaller changes in ADAMTS13 levels compared to those who did (odds ratio, 0.05 [0, 0.7]; P = 0.026). Elevations in plasminogen activator inhibitor 1 (odds ratio, 1.95 [1.21, 3.14]; P = 0.006), d-dimer (odds ratio, 3.52 [0.99, 12.48]; P = 0.05), and factor VIII (no clot, 1.15 ± 0.28 vs. clot, 1.42 ± 0.31; P = 0.003) were also demonstrated in extracorporeal membrane oxygenation-naïve patients who experienced major thrombotic events. Plasminogen activator inhibitor 1 levels were significantly elevated during periods of severe compared to mild and moderate acute respiratory distress syndrome (severe, 44.2 ± 14.9 ng/ml vs. mild, 31.8 ± 14.7 ng/ml and moderate, 33.1 ± 15.9 ng/ml; P = 0.029 and 0.039, respectively). CONCLUSIONS: Increased inflammatory and procoagulant markers such as plasminogen activator inhibitor 1, microparticle-bound tissue factor, and von Willebrand factor levels are associated with severe hypoxemia and major thrombotic events, implicating fibrinolytic suppression in the microcirculatory system and subsequent micro- and macrovascular thrombosis in severe COVID-19.


Assuntos
Transtornos da Coagulação Sanguínea , COVID-19 , Síndrome do Desconforto Respiratório , Trombofilia , Trombose , Transtornos da Coagulação Sanguínea/complicações , COVID-19/complicações , Estado Terminal , Fibrinólise , Humanos , Hipóxia/complicações , Microcirculação , Oxigênio , Inibidor 1 de Ativador de Plasminogênio , Estudos Prospectivos , Estudos Retrospectivos , Trombofilia/complicações , Tromboplastina
11.
Eur J Neurol ; 29(11): 3273-3287, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35818781

RESUMO

BACKGROUND AND PURPOSE: Previous studies suggest that mechanisms and outcomes in patients with COVID-19-associated stroke differ from those in patients with non-COVID-19-associated strokes, but there is limited comparative evidence focusing on these populations. The aim of this study, therefore, was to determine if a significant association exists between COVID-19 status with revascularization and functional outcomes following thrombectomy for large vessel occlusion (LVO), after adjustment for potential confounding factors. METHODS: A cross-sectional, international multicenter retrospective study was conducted in consecutively admitted COVID-19 patients with concomitant acute LVO, compared to a control group without COVID-19. Data collected included age, gender, comorbidities, clinical characteristics, details of the involved vessels, procedural technique, and various outcomes. A multivariable-adjusted analysis was conducted. RESULTS: In this cohort of 697 patients with acute LVO, 302 had COVID-19 while 395 patients did not. There was a significant difference (p < 0.001) in the mean age (in years) and gender of patients, with younger patients and more males in the COVID-19 group. In terms of favorable revascularization (modified Thrombolysis in Cerebral Infarction [mTICI] grade 3), COVID-19 was associated with lower odds of complete revascularization (odds ratio 0.33, 95% confidence interval [CI] 0.23-0.48; p < 0.001), which persisted on multivariable modeling with adjustment for other predictors (adjusted odds ratio 0.30, 95% CI 0.12-0.77; p = 0.012). Moreover, endovascular complications, in-hospital mortality, and length of hospital stay were significantly higher among COVID-19 patients (p < 0.001). CONCLUSION: COVID-19 was an independent predictor of incomplete revascularization and poor functional outcome in patients with stroke due to LVO. Furthermore, COVID-19 patients with LVO were more often younger and had higher morbidity/mortality rates.


Assuntos
Isquemia Encefálica , COVID-19 , Procedimentos Endovasculares , Acidente Vascular Cerebral , COVID-19/complicações , Estudos Transversais , Procedimentos Endovasculares/métodos , Humanos , Masculino , Estudos Retrospectivos , Acidente Vascular Cerebral/cirurgia , Trombectomia/métodos , Resultado do Tratamento
12.
J Thromb Thrombolysis ; 52(4): 1182-1186, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34160743

RESUMO

BACKGROUND: Tandem occlusions exist in 17-32% of large vessel occlusion (LVO) strokes. A significant concern is bleeding when carotid stenting is performed in tandem with thrombectomy due the administration of antiplatelet agents such as glycoprotein IIb/IIIa inhibitors (GP2b3aI) after receiving rtPA, but data are limited in this setting. METHODS: A mutlicenter, retrospective chart review was conducted at two comprehensive stroke centers to assess the safety and efficacy of using GP2b3aI to facilitate carotid stent placement simultaneously with endovascular thrombectomy in patients who have received rtPA. RESULTS: Overall, 32 patients were included in this study, with average age of 66.3 ± 10.4 years and predominantly male (87.5%). The cause of stroke was mostly large artery atherosclerosis (59.4%) and the thrombectomy target vessels were typically first- or second segment middle cerebral artery (37.5% and 31.3%). Time from symptom onset to rtPA bolus was 1.8 h [interquartile range (IQR) 1.5-2.7], rtPA bolus to first pass was 2 h [IQR 1.5-3.1], rtPA bolus to GP2b3aI bolus was 2 h [IQR 1.6-3.5], and rtPA bolus to aspirin and clopidogrel administration was 4.3 h [IQR 2.6-8.9] and 6.6 h [IQR 4.5-11.6] respectively. No patients had acute in-stent thrombosis or post-op bleeding from the access site. Two patients (6.3%) had significant hemorrhagic conversion. CONCLUSION: The use of GP2b3aI in the setting of tandem occlusions that required emergent stent placement post-rtPA appears safe and effective. Given the small sample size, these findings should be interpreted cautiously, and need to be confirmed in a larger patient population.


Assuntos
Ativador de Plasminogênio Tecidual/uso terapêutico , Idoso , Procedimentos Endovasculares , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Acidente Vascular Cerebral , Trombectomia , Resultado do Tratamento
13.
Annu Rev Pharmacol Toxicol ; 57: 61-79, 2017 01 06.
Artigo em Inglês | MEDLINE | ID: mdl-28061688

RESUMO

Aptamers are single-stranded nucleic acid molecules that bind to and inhibit proteins and are commonly produced by systematic evolution of ligands by exponential enrichment (SELEX). Aptamers undergo extensive pharmacological revision, which alters affinity, specificity, and therapeutic half-life, tailoring each drug for a specific clinical need. The first therapeutic aptamer was described 25 years ago. Thus far, one aptamer has been approved for clinical use, and numerous others are in preclinical or clinical development. This review presents a short history of aptamers and SELEX, describes their pharmacological development and optimization, and reviews potential treatment of diseases including visual disorders, thrombosis, and cancer.


Assuntos
Aptâmeros de Nucleotídeos/administração & dosagem , Aptâmeros de Nucleotídeos/genética , Técnica de Seleção de Aptâmeros/métodos , Animais , Aptâmeros de Nucleotídeos/metabolismo , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto/métodos , Técnica de Seleção de Aptâmeros/tendências , Transtornos da Visão/tratamento farmacológico , Transtornos da Visão/metabolismo
14.
Mol Ther ; 27(7): 1228-1241, 2019 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-30987839

RESUMO

Endothelial surface and circulating glycoprotein von Willebrand factor (vWF) regulates platelet adhesion and is associated with thrombotic diseases, including ischemic stroke, myocardial infarction, and peripheral vascular disease. Thrombosis, as manifested in these diseases, is the leading cause of disability and death in the western world. Current parenteral antithrombotic and thrombolytic agents used to treat these conditions are limited by a short therapeutic window, irreversibility, and major risk of hemorrhage. To overcome these limitations, we developed a novel anti-vWF aptamer, called DTRI-031, that selectively binds and inhibits vWF-mediated platelet adhesion and arterial thrombosis while enabling rapid reversal of this antiplatelet activity by an antidote oligonucleotide (AO). Aptamer DTRI-031 exerts dose-dependent inhibition of platelet aggregation and thrombosis in whole blood and mice, respectively. Moreover, DTRI-031 can achieve potent vascular recanalization of platelet-rich thrombotic occlusions in murine and canine carotid arteries. Finally, DTRI-031 activity is rapidly (<5 min) and completely reversed by AO administration in a murine saphenous vein hemorrhage model, and murine toxicology studies indicate the aptamer is well tolerated. These findings suggest that targeting vWF with an antidote-controllable aptamer potentially represents an effective and safer treatment for thrombosis patients having platelet-rich arterial occlusions in the brain, heart, or periphery.


Assuntos
Aptâmeros de Nucleotídeos/farmacologia , Arteriopatias Oclusivas/tratamento farmacológico , Avaliação Pré-Clínica de Medicamentos/métodos , Fibrinolíticos/farmacologia , Trombose/tratamento farmacológico , Trombose/prevenção & controle , Fator de von Willebrand/antagonistas & inibidores , Animais , Antídotos/farmacologia , Aptâmeros de Nucleotídeos/síntese química , Aptâmeros de Nucleotídeos/metabolismo , Plaquetas/efeitos dos fármacos , Plaquetas/metabolismo , Lesões das Artérias Carótidas/tratamento farmacológico , Cães , Relação Dose-Resposta a Droga , Feminino , Voluntários Saudáveis , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Oligonucleotídeos/farmacologia , Adesividade Plaquetária/efeitos dos fármacos , Agregação Plaquetária/efeitos dos fármacos , Fator de von Willebrand/metabolismo
16.
J Vasc Interv Radiol ; 30(11): 1785-1794, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31530491

RESUMO

Inadvertent arterial placement of central venous catheters carries serious sequelae, including pseudoaneurysm development and stroke. Although numerous strategies for therapeutic repair after arterial injury have been employed, no treatment provides a definitive standard of care. All articles published between January 2000 and July 2018 involving the placement of central venous catheters in the brachiocephalic or subclavian arteries, carotid artery, vertebral artery, and aortic arch and subsequent treatment were systematically reviewed. Arterial repair consisted of manual pressure, endovascular techniques (balloon tamponade, percutaneous closure devices, and covered stent placement), and open surgery. Success rates favored endovascular techniques and surgery over manual compression.


Assuntos
Artérias/lesões , Cateterismo Venoso Central/efeitos adversos , Cateterismo Venoso Central/instrumentação , Cateteres Venosos Centrais , Lesões do Sistema Vascular/terapia , Algoritmos , Artérias/diagnóstico por imagem , Tomada de Decisão Clínica , Consenso , Técnicas de Apoio para a Decisão , Desenho de Equipamento , Medicina Baseada em Evidências , Humanos , Guias de Prática Clínica como Assunto , Fatores de Risco , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/etiologia
17.
Neurosurg Focus ; 42(6): E8, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28565989

RESUMO

OBJECTIVE The utilization of the Pipeline embolization device (PED) has increased significantly since its inception and original approval for use in large, broad-necked aneurysms of the internal carotid artery. While microsurgical clipping and advances in endovascular techniques have improved overall efficacy in achieving complete occlusion, recurrences still occur, and the best modality for retreatment remains controversial. Despite its efficacy in this setting, the role of PED utilization in the setting of recurrent aneurysms has not yet been well defined. This study was designed to assess the safety and efficacy of PED in the recurrence of previously treated aneurysms. METHODS The authors reviewed a total of 13 cases in which patients underwent secondary placement of a PED for aneurysm recurrence following prior treatment with another modality. The PEDs were used to treat aneurysm recurrence or residual following endovascular coiling in 7 cases, flow diversion in 2, and microsurgical clipping in 4. The mean time between initial treatment and retreatment with a PED was 28.1 months, 12 months, and 88.7 months, respectively. Clinical outcomes, including complications and modified Rankin Scale (mRS) scores, and angiographic evidence of complete occlusion were tabulated for each treatment group. RESULTS All PEDs were successfully placed without periprocedural complications. The rate of complete occlusion was 80% at 6 months after PED placement and 100% at 12 months in these patients who underwent PED placement following failed endovascular coiling; there were no adverse clinical sequelae at a mean follow-up of 26.1 months. In the 2 cases in which PEDs were placed for treatment of residual aneurysms following prior flow diversion, 1 patient demonstrated asymptomatic vessel occlusion at 6 months, and the other exhibited complete aneurysm occlusion at 12 months. In patients with aneurysm recurrence following prior microsurgical clipping, the rate of complete occlusion was 100% at 6 and 12 months, with no adverse sequelae noted at a mean clinical follow-up of 27.7 months. CONCLUSIONS The treatment of recurrent aneurysms with the PED following previous endovascular coiling, flow diversion, or microsurgical clipping is associated with a high rate of complete occlusion and minimal morbidity.


Assuntos
Procedimentos Endovasculares/instrumentação , Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/terapia , Complicações Pós-Operatórias/terapia , Stents , Adulto , Idoso , Artéria Carótida Interna/cirurgia , Angiografia Cerebral , Criança , Feminino , Seguimentos , Humanos , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Resultado do Tratamento
19.
J Spinal Disord Tech ; 27(1): 1-10, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-24441059

RESUMO

STUDY DESIGN: Systematic review. OBJECTIVE: To provide a systematic review of published literature on the impact of subsidence on clinical outcomes and radiographic fusion rates after anterior cervical discectomy and fusion with plates or without plates. BACKGROUND: Subsidence of interbody implants is common after anterior cervical spine fusions. The impact of subsidence on fusion rates and clinical outcomes is unknown. METHODS: Systematic literature review on published articles on anterior cervical discectomy and fusion, which objectively measured graft subsidence, radiographic fusion rates, and clinical outcomes between April 1966 and December 2010. RESULTS: A total of 35 articles that measured subsidence and provided fusion rates and/or clinical outcomes were selected for inclusion. The mean subsidence rate ranged from 19.3% to 42.5%. The rate of subsidence based on the type of implant ranged from 22.8% to 35.9%. The incidence of subsidence was not impacted by the type of implant (P=0.98). The overall fusion rate of the combined studies was 92.8% and was not impacted by subsidence irrespective of subsidence definition or the measurement technique used (P=0.19). Clinical outcomes were evaluated in 27 of 35 studies with all studies reporting an improvement in patient outcomes postoperatively. CONCLUSIONS: Subsidence irrespective of the measurement technique or definition does not appear to have an impact on successful fusion and/or clinical outcomes. A validated definition and standard measurement technique for subsidence is needed to determine the actual incidence of subsidence and its impact on radiographic and clinical outcomes.


Assuntos
Vértebras Cervicais/diagnóstico por imagem , Vértebras Cervicais/cirurgia , Discotomia/métodos , Fusão Vertebral/métodos , Fenômenos Biomecânicos , Placas Ósseas , Vértebras Cervicais/fisiopatologia , Demografia , Humanos , Radiografia , Resultado do Tratamento
20.
Interv Neuroradiol ; : 15910199241286756, 2024 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-39340468

RESUMO

BACKGROUND: Cardiac implantable electronic device (CIED) generally excludes patients from undergoing fixed, high-field magnetic resonance imaging (MRI). Acute ischemic stroke patients undergo MRI as a standard part of an assessment of infarct burden. The use of a portable MRI scanner may be useful in patients who have contraindications to high-field MRI. We present the first case of a patient with a CIED who required an endovascular thrombectomy (EVT) for large vessel occlusion. She underwent a low-field MRI in the operating room with the Hyperfine portable system. CASE: The patient is an 80-year-old female status post-CIED, on Eliquis who presented with an acute ischemic stroke. Her National Institutes of Health Stroke Scale (NIHSS) of 8. Imaging demonstrated a left M2 occlusion on computed tomography angiogram (CTA) of the head and neck. No lytics were used due to concomitant gastrointestinal bleed. While, admitted, her NIHSS increased to 15. A subsequent CTA demonstrated a left internal carotid artery terminus and M1 occlusion. She underwent EVT with thrombolysis in cerebral infarction (TICI) 3 revascularization. An MRI was performed intraoperatively using a Hyperfine system, which is a low-field, portable MRI, to assess infarct volume. CONCLUSION: Hyperfine Swoop brain MRI may be safe for use in patients with contraindications to high-field MRI scans. Continued technological refinement will improve the quality of diffusion-weighted imaging. Larger studies will be required to generalize Hyperfine MRI-based imaging for patients with devices that exclude them from high-field imaging.

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