High-Flow Vascular Malformations in Children.

Children can have a variety of intracranial vascular anomalies ranging from small and incidental with no clinical consequences to complex lesions that can cause substantial neurologic deficits, heart failure, or profoundly affect development. In contrast to high-flow lesions with direct arterial-to-venous shunts, low-flow lesions such as cavernous malformations are associated with a lower likelihood of substantial hemorrhage, and a more benign course. Management of vascular anomalies in children has to incorporate an understanding of how treatment strategies may affect the normal development of the central nervous system. In this review, we discuss the etiologies, epidemiology, natural history, and genetic risk factors of three high-flow vascular malformations seen in children: brain arteriovenous malformations, intracranial dural arteriovenous fistulas, and vein of Galen malformations

Bringing high-grade arteriovenous malformations under control: clinical outcomes following multimodality treatment in children.

OBJECTIVE:Brain arteriovenous malformations (AVMs) consist of dysplastic blood vessels with direct arteriovenous shunts that can hemorrhage spontaneously. In children, a higher lifetime hemorrhage risk must be balanced with treatment-related morbidity. The authors describe a collaborative, multimodal strategy resulting in effective and safe treatment of pediatric AVMs. METHODS:A retrospective analysis of a prospectively maintained database was performed in children with treated and nontreated pediatric AVMs at the University of California, San Francisco, from 1998 to 2017. Inclusion criteria were age ≤ 18 years at time of diagnosis and an AVM confirmed by a catheter angiogram. RESULTS:The authors evaluated 189 pediatric patients with AVMs over the study period, including 119 ruptured (63%) and 70 unruptured (37%) AVMs. The mean age at diagnosis was 11.6 ± 4.3 years. With respect to Spetzler-Martin (SM) grade, there were 38 (20.1%) grade I, 40 (21.2%) grade II, 62 (32.8%) grade III, 40 (21.2%) grade IV, and 9 (4.8%) grade V lesions. Six patients were managed conservatively, and 183 patients underwent treatment, including 120 resections, 82 stereotactic radiosurgery (SRS), and 37 endovascular embolizations. Forty-four of 49 (89.8%) high-grade AVMs (SM grade IV or V) were treated. Multiple treatment modalities were used in 29.5% of low-grade and 27.3% of high-grade AVMs. Complete angiographic obliteration was obtained in 73.4% of low-grade lesions (SM grade I-III) and in 45.2% of high-grade lesions. A periprocedural stroke occurred in a single patient (0.5%), and there was 1 treatment-related death. The mean clinical follow-up for the cohort was 4.1 ± 4.6 years, and 96.6% and 84.3% of patients neurologically improved or remained unchanged in the ruptured and unruptured AVM groups following treatment, respectively. There were 16 bleeding events following initiation of AVM treatment (annual rate: 0.02 events per person-year). CONCLUSIONS:Coordinated multidisciplinary evaluation and individualized planning can result in safe and effective treatment of children with AVMs. In particular, it is possible to treat the majority of high-grade AVMs with an acceptable safety profile. Judicious use of multimodality therapy should be limited to appropriately selected patients after thorough team-based discussions to avoid additive morbidity. Future multicenter studies are required to better design predictive models to aid with patient selection for multimodal pediatric care, especially with high-grade AVMs

Cessation and Resumption of Elective Neurointerventional Procedures during the Coronavirus Disease 2019 Pandemic and Future Pandemics

At the time of this writing, the coronavirus disease 2019 pandemic continues to be a global threat, disrupting usual processes, and protocols for delivering health care around the globe. There have been significant regional and national differences in the scope and timing of these disruptions. Many hospitals were forced to temporarily halt elective neurointerventional procedures with the first wave of the pandemic in the spring of 2020, in order to prioritize allocation of resources for acutely ill patients and also to minimize coronavirus disease 2019 transmission risks to non-acute patients, their families, and health care workers. This temporary moratorium on elective neurointerventional procedures is generally credited with helping to flatten the curve and direct scarce resources to more acutely ill patients; however, there have been reports of some delaying seeking medical care when it was in fact urgent, and other reports of patients having elective treatment delayed with the result of morbidity and mortality. Many regions have resumed elective neurointerventional procedures, only to now watch coronavirus disease 2019 positivity rates again climbing as winter of 2020 approaches. A new wave is now forecast which may have larger volumes of hospitalized coronavirus disease 2019 patients than the earlier wave(s) and may also coincide with a wave of patients hospitalized with seasonal influenza. This paper discusses relevant and practical elements of cessation and safe resumption of nonemergent neurointerventional services in the setting of a pandemic

Pediatric intracranial dural arteriovenous fistulas: age-related differences in clinical features, angioarchitecture, and treatment outcomes.

OBJECTIVE Intracranial dural arteriovenous fistulas (DAVFs) are rare in children. This study sought to better characterize DAVF presentation, angioarchitecture, and treatment outcomes. METHODS Children with intracranial DAVFs between 1986 and 2013 were retrospectively identified from the neurointerventional database at the authors' institution. Demographics, clinical presentation, lesion angioarchitecture, treatment approaches, angiographic outcomes, and clinical outcomes were assessed. RESULTS DAVFs constituted 5.7% (22/423) of pediatric intracranial arteriovenous shunting lesions. Twelve boys and 10 girls presented between 1 day and 18 years of age; boys presented at a median of 1.3 years and girls presented at a median of 4.9 years. Four of 8 patients ≤ 1 year of age presented with congestive heart failure compared with 0/14 patients > 1 year of age (p = 0.01). Five of 8 patients ≤ 1 year old presented with respiratory distress compared with 0/14 patients > 1 year old (p = 0.0021). Ten of 14 patients > 1 year old presented with focal neurological deficits compared with 0/8 patients ≤ 1 year old (p = 0.0017). At initial angiography, 16 patients harbored a single intracranial DAVF and 6 patients had 2-6 DAVFs. Eight patients (38%) experienced DAVF obliteration by the end of treatment. Good clinical outcome (modified Rankin Scale score 0-2) was documented in 77% of patients > 1 year old at presentation compared with 57% of patients ≤ 1 year old at presentation. Six patients (27%) died. CONCLUSIONS Young children with DAVFs presented predominantly with cardiopulmonary symptoms, while older children presented with focal neurological deficits. Compared with other pediatric vascular shunts, DAVFs had lower rates of angiographic obliteration and poorer clinical outcomes

Radiological and clinical features of vein of Galen malformations.

BackgroundVein of Galen malformations (VOGMs) are rare and complex congenital arteriovenous fistulas. The clinical and radiological features of VOGMs and their relation to clinical outcomes are not fully characterized.ObjectiveTo examine the clinical and radiological features of VOGMs and the predictors of outcome in patients.MethodsWe retrospectively reviewed the available imaging and medical records of all patients with VOGMs treated at the University of California, San Francisco between 1986 and 2013. Radiological and clinical features were identified. We applied the modified Rankin Scale to determine functional outcome by chart review. Predictors of outcome were assessed by χ(2) analyses.ResultsForty-one cases were confirmed as VOGM. Most patients (78%) had been diagnosed with VOGM in the first year of life. Age at treatment was bimodally distributed, with predominantly urgent embolization at <10 days of age and elective embolization after 1 year of age. Patients commonly presented with hydrocephalus (65.9%) and congestive heart failure (61.0%). Mixed-type (31.7%) VOGM was more common in our cohort than purely mural (29.3%) or choroidal (26.8%) types. The most common feeding arteries were the choroidal and posterior cerebral arteries. Transarterial embolization with coils was the most common technique used to treat VOGMs at our institution. Functional outcome was normal or only mildly disabled in 50% of the cases at last follow-up (median=3 years, range=0-23 years). Younger age at first diagnosis, congestive heart failure, and seizures were predictive of adverse clinical outcome. The survival rate in our sample was 78.0% and complete thrombosis of the VOGM was achieved in 62.5% of patients.ConclusionsVOGMs continue to be challenging to treat and manage. Nonetheless, endovascular approaches to treatment are continuing to be refined and improved, with increasing success. The neurodevelopmental outcomes of affected children whose VOGMs are treated may be good in many cases

Drug capture materials based on genomic DNA-functionalized magnetic nanoparticles

Chemotherapy agents are notorious for producing severe side-effects. One approach to mitigating this off-target damage is to deliver the chemotherapy directly to a tumor via transarterial infusion, or similar procedures, and then sequestering any chemotherapeutic in the veins draining the target organ before it enters the systemic circulation. Materials capable of such drug capture are yet to be fully realized. Here, we report the covalent attachment of genomic DNA to iron-oxide nanoparticles. With these magnetic materials, we captured three common chemotherapy agents—doxorubicin, cisplatin, and epirubicin—from biological solutions. We achieved 98% capture of doxorubicin from human serum in 10 min. We further demonstrate that DNA-coated particles can rescue cultured cardiac myoblasts from lethal levels of doxorubicin. Finally, the in vivo efficacy of these materials was demonstrated in a porcine model. The efficacy of these materials demonstrates the viability of genomic DNA-coated materials as substrates for drug capture applications

Inversão sísmica bayesiana com modelagem a priori integrada com física de rocha

Tese (doutorado) - Universidade Federal de Santa Catarina, Centro de Ciências Físicas e Matemáticas, Programa de Pós-Graduação em Física, Florianópolis, 2017.A inversão sísmica conjunta para as propriedades elásticas e petrofísicas é um problema inverso com solução não única. Existem vários fatores que afetam a precisão dos resultados como a relação estatística de física de rocha, os erros dos dados experimentais e de modelagem. Apresentamos uma metodologia para incorporar um modelo linearizado de física de rocha em uma distribuição Gaussiana multivariada. A proposta é usada para definir um modelo de mistura Gaussiana para a distribuiçãoconjunta a priori das propriedades elásticas e petrofísicas, no qual cada componente é interpretada como uma litofácies. Este processo permite introduzir uma correlação teórica entre as propriedades, com interpretação geológica específica dos parâmetros da física de rocha para cada fácies. Com base nesta modelagem a priori e no modelo convolucional, obtemos analiticamente as distribuições condicionais da amostragem de Gibbs. Em seguida, combinamos o algoritmo de amostragem com métodos de simulação geoestatística para obter a distribuição a posteriori de Bayes. Aplicamos a proposta em um conjunto de dados sísmicos reais, com três poços, para obter múltiplas realizações geoestatísticas tridimensionais das propriedades e das litofácies. A proposta é validada através de testes de poço cego e comparações com a inversão Bayesiana tradicional. Usando a probabilidade das litofácies, também calculamos a isosuperfície de probabilidade do reservatório de óleo principal do campo estudado. Além da proposta de inversão sísmica conjunta, apresentamos também uma formulação revisitada para o método de simulação geoestatística FFT-Moving Average. Nessa formulação, o filtro de correlação é derivado através de apenas um único ruído aleatório, o que permite a aplicação do método sem qualquer suposição sobre as características do ruído.Abstract : Joint seismic inversion for elastic and petrophysical properties is an inverse problem with a nonunique solution. There are several factors that affect the accuracy of the results such as the statistical rock-physics relation and observation errors. We present a general methodology to incorporate a linearized rock-physics model into a multivariate Gaussian distribution. The proposal is used to define a Gaussian mixture model for the joint prior distribution of the elastic and petrophysical properties, in which each component is interpreted as a lithofacies. This process allows to introduce a theoretical correlation between the properties with specific geological interpretation for the rock physicsparameters of each facies. Based on the prior model and on the convolutional model, we analytically obtain the conditional distributions of the Gibbs sampling. Then, we combine the sampling algorithm with geostatistical simulation methods to calculate the Bayesian posterior distribution. We applied the proposal to a real seismic data set with three wells to obtain multiple three-dimensional geostatistical simulations of the properties and the lithofacies. The proposal is validated through a blind well test and a comparison with the traditional Bayesian inversion. Using the probability of the reservoir lithofacies, we also calculated a 3D isosurface probability model of the main oil reservoir in the studied field