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1.
N Engl J Med ; 390(14): 1277-1289, 2024 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-38598795

RESUMO

BACKGROUND: Trials of surgical evacuation of supratentorial intracerebral hemorrhages have generally shown no functional benefit. Whether early minimally invasive surgical removal would result in better outcomes than medical management is not known. METHODS: In this multicenter, randomized trial involving patients with an acute intracerebral hemorrhage, we assessed surgical removal of the hematoma as compared with medical management. Patients who had a lobar or anterior basal ganglia hemorrhage with a hematoma volume of 30 to 80 ml were assigned, in a 1:1 ratio, within 24 hours after the time that they were last known to be well, to minimally invasive surgical removal of the hematoma plus guideline-based medical management (surgery group) or to guideline-based medical management alone (control group). The primary efficacy end point was the mean score on the utility-weighted modified Rankin scale (range, 0 to 1, with higher scores indicating better outcomes, according to patients' assessment) at 180 days, with a prespecified threshold for posterior probability of superiority of 0.975 or higher. The trial included rules for adaptation of enrollment criteria on the basis of hemorrhage location. A primary safety end point was death within 30 days after enrollment. RESULTS: A total of 300 patients were enrolled, of whom 30.7% had anterior basal ganglia hemorrhages and 69.3% had lobar hemorrhages. After 175 patients had been enrolled, an adaptation rule was triggered, and only persons with lobar hemorrhages were enrolled. The mean score on the utility-weighted modified Rankin scale at 180 days was 0.458 in the surgery group and 0.374 in the control group (difference, 0.084; 95% Bayesian credible interval, 0.005 to 0.163; posterior probability of superiority of surgery, 0.981). The mean between-group difference was 0.127 (95% Bayesian credible interval, 0.035 to 0.219) among patients with lobar hemorrhages and -0.013 (95% Bayesian credible interval, -0.147 to 0.116) among those with anterior basal ganglia hemorrhages. The percentage of patients who had died by 30 days was 9.3% in the surgery group and 18.0% in the control group. Five patients (3.3%) in the surgery group had postoperative rebleeding and neurologic deterioration. CONCLUSIONS: Among patients in whom surgery could be performed within 24 hours after an acute intracerebral hemorrhage, minimally invasive hematoma evacuation resulted in better functional outcomes at 180 days than those with guideline-based medical management. The effect of surgery appeared to be attributable to intervention for lobar hemorrhages. (Funded by Nico; ENRICH ClinicalTrials.gov number, NCT02880878.).


Assuntos
Hemorragia Cerebral , Humanos , Hemorragia dos Gânglios da Base/mortalidade , Hemorragia dos Gânglios da Base/cirurgia , Hemorragia dos Gânglios da Base/terapia , Teorema de Bayes , Hemorragia Cerebral/mortalidade , Hemorragia Cerebral/cirurgia , Hemorragia Cerebral/terapia , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Resultado do Tratamento , Neuroendoscopia
2.
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
3.
Stroke ; 55(5): 1438-1448, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38648281

RESUMO

ARISE (Aneurysm/AVM/cSDH Roundtable Discussion With Industry and Stroke Experts) organized a one-and-a-half day meeting and workshop and brought together representatives from academia, industry, and government to discuss the most promising approaches to improve outcomes for patients with chronic subdural hematoma (cSDH). The emerging role of middle meningeal artery embolization in clinical practice and the design of current and potential future trials were the primary focuses of discussion. Existing evidence for imaging, indications, agents, and techniques was reviewed, and areas of priority for study and key questions surrounding the development of new and existing treatments for cSDH were identified. Multiple randomized, controlled trials have met their primary efficacy end points, providing high-level evidence that middle meningeal artery embolization is a potent adjunctive therapy to the standard (surgical and nonsurgical) management of neurologically stable cSDH patients in terms of reducing rates of disease recurrence. Pooled data analyses following the formal conclusion and publication of these trials will form a robust foundation upon which guidelines can be strengthened for cSDH treatment modalities and optimal patient selection, as well as delineate future lines of investigation.


Assuntos
Hematoma Subdural Crônico , Humanos , Consenso , Embolização Terapêutica/métodos , Hematoma Subdural Crônico/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto
4.
Stroke ; 55(2): 344-354, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38252761

RESUMO

Intracranial atherosclerotic disease and resultant intracranial stenosis is a global leading cause of stroke, and poses an ongoing treatment challenge. Among patients with intracranial stenosis, those with hemodynamic compromise are at high risk for recurrent stroke despite medical therapy and risk factor modification. Revascularization of the hypoperfused territory is the most plausible treatment strategy for these high-risk patients, yet surgical and endovascular therapies have not yet shown to be sufficiently safe and effective in randomized controlled trials. Advances in diagnostic and therapeutic technologies have led to a resurgence of interest in surgical and endovascular treatment strategies, with a growing body of evidence to support their further evaluation in the treatment of select patient populations. This review outlines the current and emerging endovascular and surgical treatments and highlights promising future management strategies.


Assuntos
Acidente Vascular Cerebral , Humanos , Constrição Patológica/cirurgia , Acidente Vascular Cerebral/cirurgia , Infarto Cerebral , Fatores de Risco
5.
Stroke ; 55(5): 1449-1463, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38648282

RESUMO

Brain arteriovenous malformations (bAVMs) are complex, and rare arteriovenous shunts that present with a wide range of signs and symptoms, with intracerebral hemorrhage being the most severe. Despite prior societal position statements, there is no consensus on the management of these lesions. ARISE (Aneurysm/bAVM/cSDH Roundtable Discussion With Industry and Stroke Experts) was convened to discuss evidence-based approaches and enhance our understanding of these complex lesions. ARISE identified the need to develop scales to predict the risk of rupture of bAVMs, and the use of common data elements to perform prospective registries and clinical studies. Additionally, the group underscored the need for comprehensive patient management with specialized centers with expertise in cranial and spinal microsurgery, neurological endovascular surgery, and stereotactic radiosurgery. The collection of prospective multicenter data and gross specimens was deemed essential for improving bAVM characterization, genetic evaluation, and phenotyping. Finally, bAVMs should be managed within a multidisciplinary framework, with clinical studies and research conducted collaboratively across multiple centers, harnessing the collective expertise and centralization of resources.


Assuntos
Malformações Arteriovenosas Intracranianas , Humanos , Hemorragia Cerebral/terapia , Procedimentos Endovasculares/métodos , Malformações Arteriovenosas Intracranianas/terapia , Radiocirurgia/métodos
6.
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
7.
Eur Radiol ; 34(3): 1624-1634, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37658137

RESUMO

OBJECTIVES: The Alberta Stroke Program Early CT Score (ASPECTS) is a semi-quantitative method to evaluate the severity of early ischemic change on non-contrast computed tomography (NCCT) in patients with acute ischemic stroke (AIS). In this work, we propose an automated ASPECTS method based on large cohort of data and machine learning. METHODS: For this study, we collected 3626 NCCT cases from multiple centers and annotated directly on this dataset by neurologists. Based on image analysis and machine learning methods, we constructed a two-stage machine learning model. The validity and reliability of this automated ASPECTS method were tested on an independent external validation set of 300 cases. Statistical analyses on the total ASPECTS, dichotomized ASPECTS, and region-level ASPECTS were presented. RESULTS: On an independent external validation set of 300 cases, for the total ASPECTS results, the intraclass correlation coefficient between automated ASPECTS and expert-rated was 0.842. The agreement between ASPECTS threshold of ≥ 6 versus < 6 using a dichotomized method was moderate (κ = 0.438, 0.391-0.477), and the detection rate (sensitivity) was 86.5% for patients with ASPECTS threshold of ≥ 6. Compared with the results of previous studies, our method achieved a slight lead in sensitivity (67.8%) and AUC (0.845), with comparable accuracy (78.9%) and specificity (81.2%). CONCLUSION: The proposed automated ASPECTS method driven by a large cohort of NCCT images performed equally well compared with expert-rated ASPECTS. This work further demonstrates the validity and reliability of automated ASPECTS evaluation method. CLINICAL RELEVANCE STATEMENT: The automated ASPECTS method proposed by this study may help AIS patients to receive rapid intervention, but should not be used as a stand-alone diagnostic basis. KEY POINTS: NCCT-based manual ASPECTS scores were poorly consistent. Machine learning can automate the ASPECTS scoring process. Machine learning model design based on large cohort data can effectively improve the consistency of ASPECTS scores.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Humanos , Isquemia Encefálica/diagnóstico por imagem , Alberta , Reprodutibilidade dos Testes , Acidente Vascular Cerebral/diagnóstico por imagem , Aprendizado de Máquina , Estudos Retrospectivos
8.
Acta Neurochir (Wien) ; 166(1): 294, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38990336

RESUMO

PURPOSE: Intracranial aneurysms present significant health risks, as their rupture leads to subarachnoid haemorrhage, which in turn has high morbidity and mortality rates. There are several elements affecting the complexity of an intracranial aneurysm. However, criteria for defining a complex intracranial aneurysm (CIA) in open surgery and endovascular treatment could differ, and actually there is no consensus on the definition of a "complex" aneurysm. This DELPHI study aims to assess consensus on variables defining a CIA. METHODS: An international panel of 50 members, representing various specialties, was recruited to define CIAs through a three-round Delphi process. The panelists participated in surveys with Likert scale responses and open-ended questions. Consensus criteria were established to determine CIA variables, and statistical analysis evaluated consensus and stability. RESULTS: In open surgery, CIAs were defined by fusiform or blister-like shape, dissecting aetiology, giant size (≥ 25 mm), broad neck encasing parent arteries, extensive neck surface, wall calcification, intraluminal thrombus, collateral branch from the sac, location (AICA, SCA, basilar), vasospasm context, and planned bypass (EC-IC or IC-IC). For endovascular treatment, CIAs included giant size, very wide neck (dome/neck ratio ≤ 1:1), and collateral branch from the sac. CONCLUSIONS: The definition of aneurysm complexity varies by treatment modality. Since elements related to complexity differ between open surgery and endovascular treatment, these consensus criteria of CIAs could even guide in selecting the best treatment approach.


Assuntos
Técnica Delphi , Procedimentos Endovasculares , Aneurisma Intracraniano , Aneurisma Intracraniano/cirurgia , Humanos , Procedimentos Endovasculares/métodos , Consenso , Feminino , Procedimentos Neurocirúrgicos/métodos
9.
Stroke ; 54(7): 1708-1717, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37222709

RESUMO

BACKGROUND: The optimal management of patients with isolated posterior cerebral artery occlusion is uncertain. We compared clinical outcomes for endovascular therapy (EVT) versus medical management (MM) in patients with isolated posterior cerebral artery occlusion. METHODS: This multinational case-control study conducted at 27 sites in Europe and North America included consecutive patients with isolated posterior cerebral artery occlusion presenting within 24 hours of time last well from January 2015 to August 2022. Patients treated with EVT or MM were compared with multivariable logistic regression and inverse probability of treatment weighting. The coprimary outcomes were the 90-day modified Rankin Scale ordinal shift and ≥2-point decrease in the National Institutes of Health Stroke Scale. RESULTS: Of 1023 patients, 589 (57.6%) were male with median (interquartile range) age of 74 (64-82) years. The median (interquartile range) National Institutes of Health Stroke Scale was 6 (3-10). The occlusion segments were P1 (41.2%), P2 (49.2%), and P3 (7.1%). Overall, intravenous thrombolysis was administered in 43% and EVT in 37%. There was no difference between the EVT and MM groups in the 90-day modified Rankin Scale shift (aOR, 1.13 [95% CI, 0.85-1.50]; P=0.41). There were higher odds of a decrease in the National Institutes of Health Stroke Scale by ≥2 points with EVT (aOR, 1.84 [95% CI, 1.35-2.52]; P=0.0001). Compared with MM, EVT was associated with a higher likelihood of excellent outcome (aOR, 1.50 [95% CI, 1.07-2.09]; P=0.018), complete vision recovery, and similar rates of functional independence (modified Rankin Scale score, 0-2), despite a higher rate of SICH and mortality (symptomatic intracranial hemorrhage, 6.2% versus 1.7%; P=0.0001; mortality, 10.1% versus 5.0%; P=0.002). CONCLUSIONS: In patients with isolated posterior cerebral artery occlusion, EVT was associated with similar odds of disability by ordinal modified Rankin Scale, higher odds of early National Institutes of Health stroke scale improvement, and complete vision recovery compared with MM. There was a higher likelihood of excellent outcome in the EVT group despite a higher rate of symptomatic intracranial hemorrhage and mortality. Continued enrollment into ongoing distal vessel occlusion randomized trials is warranted.


Assuntos
Isquemia Encefálica , Procedimentos Endovasculares , Acidente Vascular Cerebral , Humanos , Masculino , Idoso , Idoso de 80 Anos ou mais , Feminino , Isquemia Encefálica/terapia , Trombectomia , Estudos de Casos e Controles , Artéria Cerebral Posterior/diagnóstico por imagem , Procedimentos Endovasculares/efeitos adversos , Hemorragias Intracranianas/etiologia , Resultado do Tratamento
10.
Lancet ; 399(10321): 249-258, 2022 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-34774198

RESUMO

BACKGROUND: Trials examining the benefit of thrombectomy in anterior circulation proximal large vessel occlusion stroke have enrolled patients considered to have salvageable brain tissue, who were randomly assigned beyond 6 h and (depending on study protocol) up to 24 h from time last seen well. We aimed to estimate the benefit of thrombectomy overall and in prespecified subgroups through individual patient data meta-analysis. METHODS: We did a systematic review and individual patient data meta-analysis between Jan 1, 2010, and March 1, 2021, of randomised controlled trials of endovascular stroke therapy. In the Analysis Of Pooled Data From Randomized Studies Of Thrombectomy More Than 6 Hours After Last Known Well (AURORA) collaboration, the primary outcome was disability on the modified Rankin Scale (mRS) at 90 days, analysed by ordinal logistic regression. Key safety outcomes were symptomatic intracerebral haemorrhage and mortality within 90 days. FINDINGS: Patient level data from 505 individuals (n=266 intervention, n=239 control; mean age 68·6 years [SD 13·7], 259 [51·3%] women) were included from six trials that met inclusion criteria of 17 screened published randomised trials. Primary outcome analysis showed a benefit of thrombectomy with an unadjusted common odds ratio (OR) of 2·42 (95% CI 1·76-3·33; p<0·0001) and an adjusted common OR (for age, gender, baseline stroke severity, extent of infarction on baseline head CT, and time from onset to random assignment) of 2·54 (1·83-3·54; p<0·0001). Thrombectomy was associated with higher rates of independence in activities of daily living (mRS 0-2) than best medical therapy alone (122 [45·9%] of 266 vs 46 [19·3%] of 238; p<0·0001). No significant difference between intervention and control groups was found when analysing either 90-day mortality (44 [16·5%] of 266 vs 46 [19·3%] of 238) or symptomatic intracerebral haemorrhage (14 [5·3%] of 266 vs eight [3·3%] of 239). No heterogeneity of treatment effect was noted across subgroups defined by age, gender, baseline stroke severity, vessel occlusion site, baseline Alberta Stroke Program Early CT Score, and mode of presentation; treatment effect was stronger in patients randomly assigned within 12-24 h (common OR 5·86 [95% CI 3·14-10·94]) than those randomly assigned within 6-12 h (1·76 [1·18-2·62]; pinteraction=0·0087). INTERPRETATION: These findings strengthen the evidence for benefit of endovascular thrombectomy in patients with evidence of reversible cerebral ischaemia across the 6-24 h time window and are relevant to clinical practice. Our findings suggest that in these patients, thrombectomy should not be withheld on the basis of mode of presentation or of the point in time of presentation within the 6-24 h time window. FUNDING: Stryker Neurovascular.


Assuntos
Hemorragia Cerebral/epidemiologia , Procedimentos Endovasculares/efeitos adversos , Hemorragia Pós-Operatória/epidemiologia , Trombectomia/efeitos adversos , AVC Trombótico/cirurgia , Hemorragia Cerebral/etiologia , Procedimentos Endovasculares/métodos , Procedimentos Endovasculares/estatística & dados numéricos , Humanos , Hemorragia Pós-Operatória/etiologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Trombectomia/métodos , Trombectomia/estatística & dados numéricos , AVC Trombótico/mortalidade , Tempo para o Tratamento , Resultado do Tratamento
11.
Radiology ; 307(4): e222045, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37070990

RESUMO

Background Knowledge regarding predictors of clinical and radiographic failures of middle meningeal artery (MMA) embolization (MMAE) treatment for chronic subdural hematoma (CSDH) is limited. Purpose To identify predictors of MMAE treatment failure for CSDH. Materials and Methods In this retrospective study, consecutive patients who underwent MMAE for CSDH from February 2018 to April 2022 at 13 U.S. centers were included. Clinical failure was defined as hematoma reaccumulation and/or neurologic deterioration requiring rescue surgery. Radiographic failure was defined as a maximal hematoma thickness reduction less than 50% at last imaging (minimum 2 weeks of head CT follow-up). Multivariable logistic regression models were constructed to identify independent failure predictors, controlling for age, sex, concurrent surgical evacuation, midline shift, hematoma thickness, and pretreatment baseline antiplatelet and anticoagulation therapy. Results Overall, 530 patients (mean age, 71.9 years ± 12.8 [SD]; 386 men; 106 with bilateral lesions) underwent 636 MMAE procedures. At presentation, the median CSDH thickness was 15 mm and 31.3% (166 of 530) and 21.7% (115 of 530) of patients were receiving antiplatelet and anticoagulation medications, respectively. Clinical failure occurred in 36 of 530 patients (6.8%, over a median follow-up of 4.1 months) and radiographic failure occurred in 26.3% (137 of 522) of procedures. At multivariable analysis, independent predictors of clinical failure were pretreatment anticoagulation therapy (odds ratio [OR], 3.23; P = .007) and an MMA diameter less than 1.5 mm (OR, 2.52; P = .027), while liquid embolic agents were associated with nonfailure (OR, 0.32; P = .011). For radiographic failure, female sex (OR, 0.36; P = .001), concurrent surgical evacuation (OR, 0.43; P = .009), and a longer imaging follow-up time were associated with nonfailure. Conversely, MMA diameter less than 1.5 mm (OR, 1.7; P = .044), midline shift (OR, 1.1; P = .02), and superselective MMA catheterization (without targeting the main MMA trunk) (OR, 2; P = .029) were associated with radiographic failure. Sensitivity analyses retained these associations. Conclusion Multiple independent predictors of failure of MMAE treatment for chronic subdural hematomas were identified, with small diameter (<1.5 mm) being the only factor independently associated with both clinical and radiographic failures. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Chaudhary and Gemmete in this issue.


Assuntos
Embolização Terapêutica , Hematoma Subdural Crônico , Masculino , Humanos , Feminino , Idoso , Hematoma Subdural Crônico/diagnóstico por imagem , Hematoma Subdural Crônico/terapia , Estudos Retrospectivos , Artérias Meníngeas/diagnóstico por imagem , Artérias Meníngeas/cirurgia , Embolização Terapêutica/métodos , Anticoagulantes
12.
Brief Bioinform ; 22(2): 1476-1498, 2021 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-33623995

RESUMO

Coronavirus disease 2019 (COVID-19), an infectious disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has been declared a global pandemic by the World Health Organization, and the situation worsens daily, associated with acute increases in case fatality rates. The main protease (Mpro) enzyme produced by SARS-CoV-2 was recently demonstrated to be responsible for not only viral reproduction but also impeding host immune responses. The element selenium (Se) plays a vital role in immune functions, both directly and indirectly. Thus, we hypothesised that Se-containing heterocyclic compounds might curb the activity of SARS-CoV-2 Mpro. We performed a molecular docking analysis and found that several of the selected selenocompounds showed potential binding affinities for SARS-CoV-2 Mpro, especially ethaselen (49), which exhibited a docking score of -6.7 kcal/mol compared with the -6.5 kcal/mol score for GC376 (positive control). Drug-likeness calculations suggested that these compounds are biologically active and possess the characteristics of ideal drug candidates. Based on the binding affinity and drug-likeness results, we selected the 16 most effective selenocompounds as potential anti-COVID-19 drug candidates. We also validated the structural integrity and stability of the drug candidate through molecular dynamics simulation. Using further in vitro and in vivo experiments, we believe that the targeted compound identified in this study (ethaselen) could pave the way for the development of prospective drugs to combat SARS-CoV-2 infections and trigger specific host immune responses.


Assuntos
Antivirais/farmacologia , Proteases 3C de Coronavírus/antagonistas & inibidores , Compostos Heterocíclicos/farmacologia , Inibidores de Proteases/farmacologia , Selênio/análise , Antivirais/química , Biologia Computacional , Simulação por Computador , Proteases 3C de Coronavírus/química , Compostos Heterocíclicos/química , Humanos , Ligantes , Modelos Moleculares , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Inibidores de Proteases/química , Estrutura Terciária de Proteína , Pirrolidinas/química , Pirrolidinas/farmacologia , Reprodutibilidade dos Testes , Ácidos Sulfônicos
13.
Neuroradiology ; 65(4): 737-749, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36600077

RESUMO

PURPOSE: Radiomics features (RFs) extracted from CT images may provide valuable information on the biological structure of ischemic stroke blood clots and mechanical thrombectomy outcome. Here, we aimed to identify RFs predictive of thrombectomy outcomes and use clot histomics to explore the biology and structure related to these RFs. METHODS: We extracted 293 RFs from co-registered non-contrast CT and CTA. RFs predictive of revascularization outcomes defined by first-pass effect (FPE, near to complete clot removal in one thrombectomy pass), were selected. We then trained and cross-validated a balanced logistic regression model fivefold, to assess the RFs in outcome prediction. On a subset of cases, we performed digital histopathology on the clots and computed 227 histomic features from their whole slide images as a means to interpret the biology behind significant RF. RESULTS: We identified 6 significantly-associated RFs. RFs reflective of continuity in lower intensities, scattered higher intensities, and intensities with abrupt changes in texture were associated with successful revascularization outcome. For FPE prediction, the multi-variate model had high performance, with AUC = 0.832 ± 0.031 and accuracy = 0.760 ± 0.059 in training, and AUC = 0.787 ± 0.115 and accuracy = 0.787 ± 0.127 in cross-validation testing. Each of the 6 RFs was related to clot component organization in terms of red blood cell and fibrin/platelet distribution. Clots with more diversity of components, with varying sizes of red blood cells and fibrin/platelet regions in the section, were associated with RFs predictive of FPE. CONCLUSION: Upon future validation in larger datasets, clot RFs on CT imaging are potential candidate markers for FPE prediction.


Assuntos
Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Trombose , Humanos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/cirurgia , Trombose/patologia , Trombose/terapia , Trombectomia/métodos , Resultado do Tratamento , Fibrina , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/cirurgia
14.
Neurosurg Focus ; 54(6): E13, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37552697

RESUMO

OBJECTIVE: Computed tomography angiography (CTA) is the most widely used imaging modality for intracranial aneurysm (IA) management, yet it remains inferior to digital subtraction angiography (DSA) for IA detection, particularly of small IAs in the cavernous carotid region. The authors evaluated a deep learning pipeline for segmentation of vessels and IAs from CTA using coregistered, segmented DSA images as ground truth. METHODS: Using 50 paired CTA-DSA images, the authors trained (n = 27), validated (n = 3), and tested (n = 20) a deep learning model (3D DeepMedic) for cerebrovasculature segmentation from CTA. A landmark-based coregistration algorithm was used for registration and upsampling of CTA images to paired DSA images. Segmented vessels from the DSA were used as the ground truth. Accuracy of the model for vessel segmentation was evaluated using conventional metrics (dice similarity coefficient [DSC]) and vessel segmentation-specific metrics, like connectivity-area-length (CAL). On the test cases (20 IAs), 3 expert raters attempted to detect and segment IAs. For each rater, the authors recorded the rate of IA detection, and for detected IAs, raters segmented and calculated important IA morphology parameters to quantify the differences in IA segmentation by raters to segmentations by DeepMedic. The agreement between raters, DeepMedic, and ground truth was assessed using Krippendorf's alpha. RESULTS: In testing, the DeepMedic model yielded a CAL of 0.971 ± 0.007 and a DSC of 0.868 ± 0.008. The model prediction delineated all IAs and resulted in average error rates of < 10% for all IA morphometrics. Conversely, average IA detection accuracy by the raters was 0.653 (undetected IAs were present to a significantly greater degree on the ICA, likely due to those in the cavernous region, and were significantly smaller). Error rates for IA morphometrics in rater-segmented cases were significantly higher than in DeepMedic-segmented cases, particularly for neck (p = 0.003) and surface area (p = 0.04). For IA morphology, agreement between the raters was acceptable for most metrics, except for the undulation index (α = 0.36) and the nonsphericity index (α = 0.69). Agreement between DeepMedic and ground truth was consistently higher compared with that between expert raters and ground truth. CONCLUSIONS: This CTA segmentation network (DeepMedic trained on DSA-segmented vessels) provides a high-fidelity solution for CTA vessel segmentation, particularly for vessels and IAs in the carotid cavernous region.


Assuntos
Aprendizado Profundo , Aneurisma Intracraniano , Humanos , Angiografia Digital/métodos , Angiografia por Tomografia Computadorizada , Aneurisma Intracraniano/diagnóstico por imagem , Angiografia Cerebral/métodos
15.
Neurosurg Focus ; 54(5): E2, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37127038

RESUMO

OBJECTIVE: Flow diverter devices have revolutionized the treatment of intracranial aneurysms (IAs) since their approval in 2011 and have continued to evolve. The devices have been widely adopted across institutions and centers over the past decade; however, long-term follow-up after treatment with the Pipeline embolization device (PED) is not well described in the literature. The authors' institution was among the first to begin using PEDs, allowing them to report their series of patients treated with flow diverters ≥ 10 years ago. In this study, the authors aimed to evaluate the long-term angiographic and clinical outcomes of these patients and review lessons learned along the way. METHODS: The authors performed a retrospective review of their institution's IA database from January 2007 to July 2012. All patients with IAs treated with a PED prior to July 2012 were included. Clinical and angiographic characteristics were extracted. Available angiographic follow-up at 1, 3, 5, and 10 years was reported. RESULTS: A total of 83 patients with 92 aneurysms treated with a PED ≥ 10 years ago were identified and included in the study. The mean aneurysm dome diameter was 9.2 (SD 5.7) mm, the mean aneurysm height was 10.4 (SD 6.8) mm, and the mean neck width was 4.1 (SD 2.4) mm. Only 1 (1.1%) aneurysm was ruptured at presentation. Eight (8.7%) aneurysms were recurrences of previous treatment modalities. The morphology was saccular in 77 (83.7%) aneurysms, fusiform in 14 (15.2%), and blister-like in 1 (1.1%). Among saccular aneurysms, 60 (77.9%) were wide-necked. Seventy-five (81.5%) aneurysms were in the internal carotid artery, 12 (13.0%) were vertebrobasilar, 3 (3.3%) were in the middle cerebral artery, and 2 (2.2%) were in the posterior cerebral artery. Angiographic follow-up at 1, 3, 5, and 10 years was available for 75, 59, 50, and 15 patients, respectively. The complete occlusion rates at 1, 3, 5, and 10 years were 94.7%, 96.6%, 96.0%, and 100%, respectively. The retreatment rates at 1, 3, 5, and 10 years were 8.0%, 6.8%, 8.0%, and 6.7%, respectively. CONCLUSIONS: The authors provide their single-institution series of IA patients treated with a PED ≥ 10 years ago, with the first report of 10-year follow-up for the available patients.


Assuntos
Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/terapia , Resultado do Tratamento , Angiografia Cerebral , Estudos Retrospectivos , Seguimentos
16.
Sensors (Basel) ; 23(2)2023 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-36679565

RESUMO

An intelligent transportation system (ITS) aims to improve traffic efficiency by integrating innovative sensing, control, and communications technologies. The industrial Internet of things (IIoT) and Industrial Revolution 4.0 recently merged to design the industrial Internet of things-intelligent transportation system (IIoT-ITS). IIoT sensing technologies play a significant role in acquiring raw data. The application continuously performs the complex task of managing traffic flows effectively based on several parameters, including the number of vehicles in the system, their location, and time. Traffic density estimation (TDE) is another important derived parameter desirable to keep track of the dynamic state of traffic volume. The expanding number of vehicles based on wireless connectivity provides new potential to predict traffic density more accurately and in real time as previously used methodologies. We explore the topic of assessing traffic density by using only a few simple metrics, such as the number of surrounding vehicles and disseminating beacons to roadside units and vice versa. This research paper investigates TDE techniques and presents a novel Markov model-based TDE technique for ITS. Finally, an OMNET++-based approach with an implementation of a significant modification of a traffic model combined with mathematical modeling of the Markov model is presented. It is intended for the study of real-world traffic traces, the identification of model parameters, and the development of simulated traffic.


Assuntos
Benchmarking , Internet das Coisas , Indústrias , Tecnologia da Informação , Inteligência
17.
Neurosurg Rev ; 45(1): 49-61, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33913050

RESUMO

Hemodynamics plays a key role in the natural history of intracranial aneurysms (IAs). However, studies exploring the association between aneurysmal hemodynamics and the biological and mechanical characteristics of the IA wall in humans are sparse. In this review, we survey the current body of literature, summarize the studies' methodologies and findings, and assess the degree of consensus among them. We used PubMed to perform a systematic review of studies that explored the association between hemodynamics and human IA wall features using different sources. We identified 28 publications characterizing aneurysmal flow and the IA wall: 4 using resected tissues, 17 using intraoperative images, and 7 using vessel wall magnetic resonance imaging (MRI). Based on correlation to IA tissue, higher flow conditions, such as high wall shear stress (WSS) with complex pattern and elevated pressure, were associated with degenerated walls and collagens with unphysiological orientation and faster synthesis. MRI studies strongly supported that low flow, characterized by low WSS and high blood residence time, was associated with thicker walls and post-contrast enhancement. While significant discrepancies were found among those utilized intraoperative images, they generally supported that thicker walls coexist at regions with prolonged residence time and that thinner regions are mainly exposed to higher pressure with complex WSS patterns. The current body of literature supports a theory of two general hemodynamic-biologic mechanisms for IA development. One, where low flow conditions are associated with thickening and atherosclerotic-like remodeling, and the other where high and impinging flow conditions are related to wall degeneration, thinning, and collagen remodeling.


Assuntos
Aneurisma Intracraniano , Hemodinâmica , Humanos , Aneurisma Intracraniano/cirurgia , Imageamento por Ressonância Magnética , Estresse Mecânico
18.
Neurosurg Rev ; 45(6): 3511-3521, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36173528

RESUMO

Butterfly glioblastoma (bGBM) is a grade 4 glioma with a poor prognosis. Surgical treatment of these cancers has been reviewed in the literature with some recent studies supporting resection as a safe and effective treatment instead of biopsy and adjuvant therapy. This meta-analysis was designed to determine whether there are significant differences in overall survival (OS) and postoperative neurologic deficits (motor, speech, and cranial nerve) following intervention in patients who underwent tumor resection as part of their treatment, compared to patients who underwent biopsy without surgical resection. A literature search was conducted using PubMed (National Library of Medicine) and Embase (Elsevier) to identify articles from each database's earliest records to May 25, 2021, that directly compared the outcomes of biopsy and resection in bGBM patients and met predetermined inclusion criteria. A meta-analysis was conducted to compare the effects of the two management strategies on OS and postoperative neurologic deficits. Six articles met our study inclusion criteria. OS was found to be significantly longer for the resection group at 6 months (odds ratio [OR] 2.94, 95% confidence interval [CI] 1.23-7.05) and 12 months (OR 3.75, 95% CI 1.10-12.76) than for the biopsy group. No statistically significant differences were found in OS at 18 and 24 months. Resection was associated with an increased rate of postoperative neurologic deficit (OR 2.05, 95% CI 1.02-4.09). Resection offers greater OS up to 1 year postintervention than biopsy alone; however, this comes at the cost of higher rates of postoperative neurologic deficits.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Glioma , Humanos , Neoplasias Encefálicas/patologia , Glioma/cirurgia , Biópsia , Resultado do Tratamento
19.
J Neuroradiol ; 49(4): 324-328, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33340641

RESUMO

INTRODUCTION: The ANA™ (Anaconda Biomed) thrombectomy system is a novel stroke thrombectomy device comprising a self-expanding funnel designed to reduce clot fragmentation by locally restricting flow while becoming as wide as the lodging artery. Once deployed, ANA allows distal aspiration in combination with a stentretriever (SR) to mobilize the clot into the funnel where it remains copped during extraction. We investigate safety and efficacy of ANA™ in a first-in-man study. METHODS: Prospective data was collected on 35 consecutive patients treated as first line with ANA™ at a single centre. Outcome measures included per-pass reperfusion scores, symptomatic intracerebral hemorrhage (sICH), NIHSS at day 5, and mRS at 90 days. RESULTS: Median NIHSS was 12(9-18). Sites of primary occlusion were: 5 ICA, 15 M1-MCA, 15 M2-MCA. Primary performance endpoint, mTICI 2b-3 within 3 passes without rescue therapy was achieved in 91.4% (n = 32) of patients; rate of complete recanalization (mTICI 2c-3) was 65.7%. First pass complete recanalization rate was 42.9%, and median number of ANA passes 1(IQR: 1-2). In 17.1% (n = 6) rescue treatment was used; median number of rescue passes was 2(1-7), leading to a final mTICI2b-3rate of 94.3% (n = 33). There were no device related serious adverse events, and rate of sICH was 5.7% (n = 2). At 5 days median NIHSS was 1 (IQR 1-6) and 90 days mRS 0-2 was achieved in 60% of patients. CONCLUSIONS: In this initial clinical experience, the ANA™ device achieved a high rate of complete recanalization with a good safety profile and favourable 90 days clinical outcomes.


Assuntos
Trombólise Mecânica , Acidente Vascular Cerebral , Hemorragia Cerebral/epidemiologia , Humanos , Trombólise Mecânica/efeitos adversos , Trombólise Mecânica/instrumentação , Estudos Prospectivos , Acidente Vascular Cerebral/terapia , Resultado do Tratamento
20.
Stroke ; 52(11): e733-e738, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34496615

RESUMO

Background and Purpose: The modified Thrombolysis in Cerebral Infarct (mTICI) score is used to grade angiographic outcome after endovascular thrombectomy. We sought to identify factors that decrease the accuracy of intraprocedural mTICI. Methods: We performed a 2-center retrospective cohort study comparing operator (n=6) mTICI scores to consensus scores from blinded adjudicators. Groups were also assessed by dichotomizing mTICI scores to 0­2a versus 2b­3. Results: One hundred thirty endovascular thrombectomy procedures were included. Operators and adjudicators had a pairwise agreement in 96 cases (73.8%). Krippendorff α was 0.712. Multivariate analysis showed endovascular thrombectomy overnight (odds ratio [OR]=3.84 [95% CI, 1.22­12.1]), lacking frontal (OR, 5.66 [95 CI, 1.36­23.6]), or occipital (OR, 7.18 [95 CI, 2.12­24.3]) region reperfusion, and higher operator mTICI scores (OR, 2.16 [95 CI, 1.16­4.01]) were predictive of incorrectly scoring mTICI intraprocedurally. With dichotomized mTICI scores, increasing number of passes was associated with increased risk of operator error (OR, 1.93 [95 CI, 1.22­3.05]). Conclusions: In our study, mTICI disagreement between operator and adjudicators was observed in 26.2% of cases. Interventions that took place between 22:30 and 4:00, featured frontal or occipital region nonperfusion, higher operator mTICI scores, and increased number of passes had higher odds of intraprocedural mTICI inaccuracy.


Assuntos
Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/cirurgia , Procedimentos Endovasculares/métodos , Trombectomia/métodos , Resultado do Tratamento , Idoso , Angiografia Digital , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
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