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1.
Acta Neurochir (Wien) ; 166(1): 66, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38316692

RESUMO

LITT is a minimally-invasive laser ablation technique used to treat a wide variety of intracranial lesions. Difficulties performing intraoperative mapping have limited its adoption for lesions in/near eloquent regions. In this institutional case series, we demonstrate the utility of fMRI-adjunct planning for LITT near language or motor areas. Six out of 7 patients proceeded with LITT after fMRI-based tractography determined adequate safety margins for ablation. All underwent successful ablation without new or worsening postoperative symptoms requiring adjuvant corticosteroids, including those with preexisting deficits. fMRI is an easily accessible adjunct which may potentially reduce chances of complications in LITT near eloquent structures.


Assuntos
Neoplasias Encefálicas , Terapia a Laser , Humanos , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Procedimentos Neurocirúrgicos/métodos , Terapia a Laser/métodos , Lasers
2.
NMR Biomed ; 36(6): e4785, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-35704275

RESUMO

Amine-weighted chemical exchange saturation transfer (CEST) magnetic resonance imaging (MRI) is particularly valuable as an amine- and pH-sensitive imaging technique in brain tumors, targeting the intrinsically high concentration of amino acids with exchangeable amine protons and reduced extracellular pH in brain tumors. Amine-weighted CEST MRI contrast is dependent on the glioma genotype, likely related to differences in degree of malignancy and metabolic behavior. Amine-weighted CEST MRI may provide complementary value to anatomic imaging in conventional and exploratory therapies in brain tumors, including chemoradiation, antiangiogenic therapies, and immunotherapies. Continual improvement and clinical testing of amine-weighted CEST MRI has the potential to greatly impact patients with brain tumors by understanding vulnerabilities in the tumor microenvironment that may be therapeutically exploited.


Assuntos
Aminas , Neoplasias Encefálicas , Humanos , Aminas/química , Concentração de Íons de Hidrogênio , Imageamento por Ressonância Magnética/métodos , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/química , Prótons , Microambiente Tumoral
3.
J Neurooncol ; 163(2): 417-427, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37294422

RESUMO

PURPOSE: There is limited knowledge about the associations between sodium and proton MRI measurements in brain tumors. The purpose of this study was to quantify intra- and intertumoral correlations between sodium, diffusion, and perfusion MRI in human gliomas. METHODS: Twenty glioma patients were prospectively studied on a 3T MRI system with multinuclear capabilities. Three mutually exclusive tumor volumes of interest (VOIs) were segmented: contrast-enhancing tumor (CET), T2/FLAIR hyperintense non-enhancing tumor (NET), and necrosis. Median and voxel-wise associations between apparent diffusion coefficient (ADC), normalized relative cerebral blood volume (nrCBV), and normalized sodium measurements were quantified for each VOI. RESULTS: Both relative sodium concentration and ADC were significantly higher in areas of necrosis compared to NET (P = 0.003 and P = 0.008, respectively) and CET (P = 0.02 and P = 0.02). Sodium concentration was higher in CET compared to NET (P = 0.04). Sodium and ADC were higher in treated compared to treatment-naïve gliomas within NET (P = 0.006 and P = 0.01, respectively), and ADC was elevated in CET (P = 0.03). Median ADC and sodium concentration were positively correlated across patients in NET (r = 0.77, P < 0.0001) and CET (r = 0.84, P < 0.0001), but not in areas of necrosis (r = 0.45, P = 0.12). Median nrCBV and sodium concentration were negatively correlated across patients in areas of NET (r=-0.63, P = 0.003). Similar associations were observed when examining voxel-wise correlations within VOIs. CONCLUSION: Sodium MRI is positively correlated with proton diffusion MRI measurements in gliomas, likely reflecting extracellular water. Unique areas of multinuclear MRI contrast may be useful in future studies to understand the chemistry of the tumor microenvironment.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Prótons , Imageamento por Ressonância Magnética , Glioma/diagnóstico por imagem , Glioma/patologia , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Imagem de Difusão por Ressonância Magnética , Perfusão , Necrose , Microambiente Tumoral
4.
Eur Radiol ; 2023 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-37882836

RESUMO

OBJECTIVE: To determine the feasibility and biologic correlations of dynamic susceptibility contrast (DSC), dynamic contrast enhanced (DCE), and quantitative maps derived from contrast leakage effects obtained simultaneously in gliomas using dynamic spin-and-gradient-echo echoplanar imaging (dynamic SAGE-EPI) during a single contrast injection. MATERIALS AND METHODS: Thirty-eight patients with enhancing brain gliomas were prospectively imaged with dynamic SAGE-EPI, which was processed to compute traditional DSC metrics (normalized relative cerebral blood flow [nrCBV], percentage of signal recovery [PSR]), DCE metrics (volume transfer constant [Ktrans], extravascular compartment [ve]), and leakage effect metrics: ΔR2,ss* (reflecting T2*-leakage effects), ΔR1,ss (reflecting T1-leakage effects), and the transverse relaxivity at tracer equilibrium (TRATE, reflecting the balance between ΔR2,ss* and ΔR1,ss). These metrics were compared between patient subgroups (treatment-naïve [TN] vs recurrent [R]) and biological features (IDH status, Ki67 expression). RESULTS: In IDH wild-type gliomas (IDHwt-i.e., glioblastomas), previous exposure to treatment determined lower TRATE (p = 0.002), as well as higher PSR (p = 0.006), Ktrans (p = 0.17), ΔR1,ss (p = 0.035), ve (p = 0.006), and ADC (p = 0.016). In IDH-mutant gliomas (IDHm), previous treatment determined higher Ktrans and ΔR1,ss (p = 0.026). In TN-gliomas, dynamic SAGE-EPI metrics tended to be influenced by IDH status (p ranging 0.09-0.14). TRATE values above 142 mM-1s-1 were exclusively seen in TN-IDHwt, and, in TN-gliomas, this cutoff had 89% sensitivity and 80% specificity as a predictor of Ki67 > 10%. CONCLUSIONS: Dynamic SAGE-EPI enables simultaneous quantification of brain tumor perfusion and permeability, as well as mapping of novel metrics related to cytoarchitecture (TRATE) and blood-brain barrier disruption (ΔR1,ss), with a single contrast injection. CLINICAL RELEVANCE STATEMENT: Simultaneous DSC and DCE analysis with dynamic SAGE-EPI reduces scanning time and contrast dose, respectively alleviating concerns about imaging protocol length and gadolinium adverse effects and accumulation, while providing novel leakage effect metrics reflecting blood-brain barrier disruption and tumor tissue cytoarchitecture. KEY POINTS: • Traditionally, perfusion and permeability imaging for brain tumors requires two separate contrast injections and acquisitions. • Dynamic spin-and-gradient-echo echoplanar imaging enables simultaneous perfusion and permeability imaging. • Dynamic spin-and-gradient-echo echoplanar imaging provides new image contrasts reflecting blood-brain barrier disruption and cytoarchitecture characteristics.

5.
Behav Res Methods ; 55(8): 4455-4477, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-36443583

RESUMO

Understanding what groups stand for is integral to a diverse array of social processes, ranging from understanding political conflicts to organisational behaviour to promoting public health behaviours. Traditionally, researchers rely on self-report methods such as interviews and surveys to assess groups' collective self-understandings. Here, we demonstrate the value of using naturally occurring online textual data to map the similarities and differences between real-world groups' collective self-understandings. We use machine learning algorithms to assess similarities between 15 diverse online groups' linguistic style, and then use multidimensional scaling to map the groups in two-dimensonal space (N=1,779,098 Reddit comments). We then use agglomerative and k-means clustering techniques to assess how the 15 groups cluster, finding there are four behaviourally distinct group types - vocational, collective action (comprising political and ethnic/religious identities), relational and stigmatised groups, with stigmatised groups having a less distinctive behavioural profile than the other group types. Study 2 is a secondary data analysis where we find strong relationships between the coordinates of each group in multidimensional space and the groups' values. In Study 3, we demonstrate how this approach can be used to track the development of groups' collective self-understandings over time. Using transgender Reddit data (N= 1,095,620 comments) as a proof-of-concept, we track the gradual politicisation of the transgender group over the past decade. The automaticity of this methodology renders it advantageous for monitoring multiple online groups simultaneously. This approach has implications for both governmental agencies and social researchers more generally. Future research avenues and applications are discussed.


Assuntos
Linguística , Humanos , Aprendizado de Máquina , Mídias Sociais
6.
Stroke ; 53(9): 2758-2767, 2022 09.
Artigo em Inglês | MEDLINE | ID: mdl-35862194

RESUMO

BACKGROUND: Expert opinion is that about 20% of emergency stroke patients should receive thrombolysis. Currently, 11% to 12% of patients in England and Wales receive thrombolysis, ranging from 2% to 24% between hospitals. The aim of this study was to assess how much variation is due to differences in local patient populations, and how much is due to differences in clinical decision-making and stroke pathway performance, while estimating a realistic target thrombolysis use. METHODS: Anonymised data for 246 676 emergency stroke admissions to 132 acute hospitals in England and Wales between 2016 and 2018 was obtained from the Sentinel Stroke National Audit Programme data. We used machine learning to learn decisions on who to give thrombolysis to at each hospital. We used clinical pathway simulation to model effects of changing pathway performance. Qualitative research was used to assess clinician attitudes to these methods. Three changes were modeled: (1) arrival-to-treatment in 30 minutes, (2) proportion of patients with determined stroke onset times set to at least the national upper quartile, (3) thrombolysis decisions made based on majority vote of a benchmark set of hospitals. RESULTS: Of the modeled changes, any single change was predicted to increase national thrombolysis use from 11.6% to between 12.3% to 14.5% (clinical decision-making having the most effect). Combined, these changes would be expected to increase thrombolysis to 18.3%, but there would still be significant variation between hospitals depending on local patient population. Clinicians engaged well with the modeling, but those from hospitals with lower thrombolysis use were most cautious about the methods. CONCLUSIONS: Machine learning and clinical pathway simulation may be applied at scale to national stroke audit data, allowing extended use and analysis of audit data. Stroke thrombolysis rates of at least 18% look achievable in England and Wales, but each hospital should have its own target.


Assuntos
Procedimentos Clínicos , Acidente Vascular Cerebral , Administração Intravenosa , Fibrinolíticos/uso terapêutico , Humanos , Aprendizado de Máquina , Acidente Vascular Cerebral/tratamento farmacológico , Terapia Trombolítica/métodos
7.
J Neurooncol ; 159(1): 81-94, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35704158

RESUMO

PURPOSE: Gliomas are the most common primary tumors of the central nervous system and are categorized by the World Health Organization into either low-grade (grades 1 and 2) or high-grade (grades 3 and 4) gliomas. A subset of patients with glioma may experience no tumor-related symptoms and be incidentally diagnosed. These incidental low-grade gliomas (iLGG) maintain controversial treatment course despite scientific advancements. Here we highlight the recent advancements in classification, neuroimaging, and surgical management of these tumors. METHODS: A review of the literature was performed. The authors created five subtopics of focus: histological criteria, diagnostic imaging, surgical advancements, correlation of surgical resection and survival outcomes, and clinical implications. CONCLUSIONS: Alternating studies suggest that these tumors may experience higher mutational rates than their counterparts. Significant progress in management of gliomas, regardless of the grade, has been made through modern neurosurgical treatment modalities, diagnostic neuroimaging, and a better understanding of the genetic composition of these tumors. An optimal treatment approach for patients with newly diagnosed iLGG remains ill-defined despite multiple studies arguing in favor of safe maximal resection. Our review emphasizes the not so benign nature of incidental low grade glioma and further supports the need for future studies to evaluate survival outcomes following surgical resection.


Assuntos
Neoplasias Encefálicas , Glioma , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Glioma/diagnóstico por imagem , Glioma/patologia , Glioma/cirurgia , Humanos , Procedimentos Neurocirúrgicos/métodos , Resultado do Tratamento
8.
Proc Natl Acad Sci U S A ; 114(38): 10220-10225, 2017 09 19.
Artigo em Inglês | MEDLINE | ID: mdl-28874539

RESUMO

Contrast-enhanced MRI is typically used to follow treatment response and progression in patients with glioblastoma (GBM). However, differentiating tumor progression from pseudoprogression remains a clinical dilemma largely unmitigated by current advances in imaging techniques. Noninvasive imaging techniques capable of distinguishing these two conditions could play an important role in the clinical management of patients with GBM and other brain malignancies. We hypothesized that PET probes for deoxycytidine kinase (dCK) could be used to differentiate immune inflammatory responses from other sources of contrast-enhancement on MRI. Orthotopic malignant gliomas were established in syngeneic immunocompetent mice and then treated with dendritic cell (DC) vaccination and/or PD-1 mAb blockade. Mice were then imaged with [18F]-FAC PET/CT and MRI with i.v. contrast. The ratio of contrast enhancement on MRI to normalized PET probe uptake, which we term the immunotherapeutic response index, delineated specific regions of immune inflammatory activity. On postmortem examination, FACS-based enumeration of intracranial tumor-infiltrating lymphocytes directly correlated with quantitative [18F]-FAC PET probe uptake. Three patients with GBM undergoing treatment with tumor lysate-pulsed DC vaccination and PD-1 mAb blockade were also imaged before and after therapy using MRI and a clinical PET probe for dCK. Unlike in mice, [18F]-FAC is rapidly catabolized in humans; thus, we used another dCK PET probe, [18F]-clofarabine ([18F]-CFA), that may be more clinically relevant. Enhanced [18F]-CFA PET probe accumulation was identified in tumor and secondary lymphoid organs after immunotherapy. Our findings identify a noninvasive modality capable of imaging the host antitumor immune response against intracranial tumors.


Assuntos
Glioblastoma/diagnóstico por imagem , Animais , Linhagem Celular , Feminino , Glioblastoma/terapia , Humanos , Imunoterapia , Imageamento por Ressonância Magnética , Camundongos , Camundongos Endogâmicos C57BL , Tomografia por Emissão de Pósitrons
9.
Vet Ophthalmol ; 23(6): 943-949, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33145924

RESUMO

OBJECTIVES: To describe the signalment, ophthalmic examination findings, and follow-up of dogs affected with a previously unreported retrocorneal pigmentary lesion. MATERIALS AND METHODS: Retrospective record evaluation spanning 2009-2019. RESULTS: Retrocorneal pigmentary lesions were described in 34 patients (46 eyes). German Shepherds (n = 7), Jack Russel terriers (n = 5), and terrier crosses (n = 4) made up 16/34 (47.1%) of the cases. The mean age was 13.5 years (range 1.4-14.2 years), and 16/30 (53.3%) dogs were female. Most dogs were affected unilaterally (22/34 (64.7%)), the others bilaterally, and 5/34 (14.7%) were referred for it while the others were incidentally diagnosed. The lesions affected the ventral, peripheral, inner cornea and had a round/undulated leading edge. The number of corneal clock hours affected was known for 41/46 (89.1%) eyes and involved 1-3 clock hours in 32/41 (78.1%) eyes, 4-6 in 6/41 (14.6%), 7-9 in 2/41 (4.9%), and 10 in 1/41 (2.4%). The central cornea was affected in 9/46 (19.6%) eyes, and in 5/9 (55.6%), the median corneal clarity score was G2 (scale: G0-G4). The commonest additional findings included free-floating uveal cysts (11/34 dogs, 32.4%), cataracts (6/34 dogs, 17.6%), and primary glaucoma (5/34 dogs, 14.7%). Gonioscopy was available in 16/34 (47.1%) dogs and was normal except in primary glaucoma cases. Follow-up was documented in 13/34 (38.2%) dogs with a mean follow-up of 17 months (range: 5-26 months). Lesion progression was documented in 6/13 (46.2%) dogs. CONCLUSIONS: Retrocorneal pigmentation occurs as a slowly progressive lesion of older dogs that could impact vision. Histological studies of affected eyes are warranted.


Assuntos
Doenças da Córnea/veterinária , Doenças do Cão/diagnóstico , Transtornos da Pigmentação/veterinária , Animais , Doenças da Córnea/diagnóstico , Doenças da Córnea/terapia , Progressão da Doença , Doenças do Cão/terapia , Cães , Feminino , Gonioscopia/veterinária , Masculino , Transtornos da Pigmentação/diagnóstico , Transtornos da Pigmentação/terapia , Estudos Retrospectivos
10.
Vet Anaesth Analg ; 46(2): 246-250, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30713055

RESUMO

OBJECTIVE: To describe a novel ultrasound-guided posterior extraconal block in the dog. STUDY DESIGN: Prospective experimental cadaveric study. ANIMALS: A total of 13 Beagle Cross cadaver heads. METHODS: After describing the ultrasound bony landmarks and posterior extraconal local regional technique in one head, 12 heads were used to evaluate the spreading of contrast and evaluate potential complications. A 5-8 MHz microconvex ultrasound probe was positioned caudal to the orbital ligament, with the beam orientated transversely, and then tilted caudally until the orbital fissure was visualized. After identifying the bony structures consistent with the orbital fissure, a needle was advanced using an in-plane technique and 0.5 mL of a 50:50 mixture of iohexol and methylene blue was injected. Computed tomography (CT) and dissection were used to evaluate successful injections and potential complications. The injection was considered successful if radiopaque contrast medium was 5 mm from the orbital fissure. Potential complications were defined as the presence of radiopaque contrast within the globe or the intracalvarial tissues. RESULTS: The CT images confirmed contrast at the target site in 15/24 (63%) of the injections. Only two injections were found in the temporalis muscle; the rest of the injections were located in the extraconal space. No potential complications such as intracranial spreading of contrast, intravascular or intraocular injection were found. CONCLUSIONS AND CLINICAL RELEVANCE: The technique can deliver contrast close to the main nerves which provide sensory and motor innervation to the eye. Further studies are needed to evaluate this technique in clinical cases.


Assuntos
Cães/fisiologia , Bloqueio Nervoso/veterinária , Órbita/inervação , Animais , Cadáver , Procedimentos Cirúrgicos Oftalmológicos/veterinária , Estudos Prospectivos , Ultrassonografia de Intervenção/veterinária
11.
J Neurooncol ; 139(2): 469-478, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29846894

RESUMO

INTRODUCTION: Surgery and radiation therapy are the standard treatment options for meningiomas, but these treatments are not always feasible. Expression profiling was performed to determine the presence of therapeutic actionable biomarkers for prioritization and selection of agents. METHODS: Meningiomas (n = 115) were profiled using a variety of strategies including next-generation sequencing (592-gene panel: n = 14; 47-gene panel: n = 94), immunohistochemistry (n = 8-110), and fluorescent and chromogenic in situ hybridization (n = 5-70) to determine mutational and expression status. RESULTS: The median age of patients in the cohort was 60 years, with a range spanning 6-90 years; 52% were female. The most frequently expressed protein markers were EGFR (93%; n = 44), followed by PTEN (77%; n = 110), BCRP (75%; n = 8), MRP1 (65%, n = 23), PGP (62%; n = 84), and MGMT (55%; n = 97). The most frequent mutation among all meningioma grades occurred in the NF2 gene at 85% (11/13). Recurring mutations in SMO and AKT1 were also occasionally detected. PD-L1 was expressed in 25% of grade III cases (2/8) but not in grade I or II tumors. PD-1 + T cells were present in 46% (24/52) of meningiomas. TOP2A and thymidylate synthase expression increased with grade (I = 5%, II = 22%, III = 62% and I = 5%, II = 23%, III = 47%, respectively), whereas progesterone receptor expression decreased with grade (I = 79%, II = 41%, III = 29%). CONCLUSION: If predicated on tumor expression, our data suggest that therapeutics directed toward NF2 and TOP2A could be considered for most meningioma patients.


Assuntos
Ensaios Clínicos como Assunto/métodos , Neoplasias Meníngeas/tratamento farmacológico , Neoplasias Meníngeas/metabolismo , Meningioma/tratamento farmacológico , Meningioma/metabolismo , Projetos de Pesquisa , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Criança , Estudos de Coortes , Feminino , Regulação Neoplásica da Expressão Gênica , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Meningioma/genética , Meningioma/patologia , Pessoa de Meia-Idade , Mutação , Gradação de Tumores , Adulto Jovem
12.
Vet Ophthalmol ; 21(4): 399-412, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29205744

RESUMO

OBJECTIVE: To describe the presentation of 15 rabbits with naturally occurring cataracts referred for phacoemulsification surgery, the procedure in 13 cases and the follow-up in 12. ANIMALS INCLUDED: Fifteen rabbits (30 eyes), nine of which stopped following visual cues in association with cataract progression. MATERIALS AND METHODS: Rabbits underwent preoperative ophthalmic and ocular ultrasound examination. RESULTS: Thirteen rabbits (22 eyes) had mature cataracts. Ten were bilateral and three unilateral. Two rabbits had an anterior chamber abscess. The cataract in one of these was incipient. One rabbit had bilateral immature cataracts. One rabbit had a subluxated lens, and one had a retinal detachment. Thirteen rabbits (22 eyes) underwent phacoemulsification. Eighteen, 13.5-mm capsular tension rings (CTRs) and seventeen, 13-mm IOLs (Acrivet® , Berlin, Germany) were fitted including one 41D 60V-model, and three 49D and thirteen 58D 20S-models. Intraoperative complications included one unilateral posterior-capsular tear, one lens subluxation, and one expulsive choroidal hemorrhage. One rabbit died during anesthetic recovery. Nine cases were PCR-tested for Encephalitozoon cuniculi, and only three were positive. The median follow-up time was 12 months (4-24 months). Rabbits that were not following visual cues preoperatively did so postoperatively, and surgery resulted in a clear visual axis for the follow-up period in every case except in two, due to reasons other than the surgery. CONCLUSIONS: Phacoemulsification with CTR and IOL implantation offers good long-term results and can improve the quality of life of pet rabbits. Retinal detachment, lens luxation, expulsive choroidal hemorrhage, and anesthetic death are potential complications.


Assuntos
Catarata/veterinária , Implante de Lente Intraocular/veterinária , Facoemulsificação/veterinária , Animais , Catarata/diagnóstico , Catarata/patologia , Progressão da Doença , Cristalino/patologia , Coelhos
13.
Water Sci Technol ; 77(9-10): 2184-2189, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29757170

RESUMO

This work presents a methodology for automatic detection of structural faults in sewers from CCTV footage, which has been improved by combining the outputs of different machine learning techniques. The predictions of support vector machine and random forest classifiers are combined using three distinct techniques: 'both', 'most likely' and 'stacking'. Each technique is tested on CCTV data taken from real surveys covering a range of pipes at locations in the south-west of the UK. The best tested technique, stacking, offers a 5% increase in accuracy for minimal impact in efficiency, proving useful for future development and implementation of the fault detection methodology.


Assuntos
Algoritmos , Máquina de Vetores de Suporte , Eliminação de Resíduos Líquidos/métodos , Águas Residuárias/química
14.
J Neurooncol ; 123(3): 425-32, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-26037466

RESUMO

Glioblastomas are characterized by immunosuppression, rapid proliferation, angiogenesis, and invasion into the surrounding brain parenchyma. Limitations in current therapeutic approaches have spurred the development of personalized, patient-specific treatments. Among these, active immunotherapy has emerged as a viable option for glioma treatment. The ability to generate an immune response utilizing patient-derived dendritic cells (DCs) (professional antigen-presenting cells) is especially attractive. This approach to glioma treatment allows for the immunologic targeting and destruction of malignant cells. Data acquired in multiple pre-clinical models and clinical trials have shown significant responses and prolonged survival. Here we provide an overview of the current status of DC vaccination for the treatment of gliomas.


Assuntos
Neoplasias Encefálicas/terapia , Células Dendríticas/imunologia , Glioblastoma/terapia , Imunoterapia/métodos , Animais , Neoplasias Encefálicas/imunologia , Glioblastoma/imunologia , Humanos
15.
Evol Comput ; 23(3): 481-507, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25950392

RESUMO

Mesh network topologies are becoming increasingly popular in battery-powered wireless sensor networks, primarily because of the extension of network range. However, multihop mesh networks suffer from higher energy costs, and the routing strategy employed directly affects the lifetime of nodes with limited energy resources. Hence when planning routes there are trade-offs to be considered between individual and system-wide battery lifetimes. We present a multiobjective routing optimisation approach using hybrid evolutionary algorithms to approximate the optimal trade-off between the minimum lifetime and the average lifetime of nodes in the network. In order to accomplish this combinatorial optimisation rapidly, our approach prunes the search space using k-shortest path pruning and a graph reduction method that finds candidate routes promoting long minimum lifetimes. When arbitrarily many routes from a node to the base station are permitted, optimal routes may be found as the solution to a well-known linear program. We present an evolutionary algorithm that finds good routes when each node is allowed only a small number of paths to the base station. On a real network deployed in the Victoria & Albert Museum, London, these solutions, using only three paths per node, are able to achieve minimum lifetimes of over 99% of the optimum linear program solution's time to first sensor battery failure.


Assuntos
Algoritmos , Evolução Biológica , Modelos Teóricos
16.
Evol Comput ; 22(3): 479-501, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-24605846

RESUMO

Multi-objective optimisation yields an estimated Pareto front of mutually non- dominating solutions, but with more than three objectives, understanding the relationships between solutions is challenging. Natural solutions to use as landmarks are those lying near to the edges of the mutually non-dominating set. We propose four definitions of edge points for many-objective mutually non-dominating sets and examine the relations between them. The first defines edge points to be those that extend the range of the attainment surface. This is shown to be equivalent to finding points which are not dominated on projection onto subsets of the objectives. If the objectives are to be minimised, a further definition considers points which are not dominated under maximisation when projected onto objective subsets. A final definition looks for edges via alternative projections of the set. We examine the relations between these definitions and their efficacy in many dimensions for synthetic concave- and convex-shaped sets, and on solutions to a prototypical many-objective optimisation problem, showing how they can reveal information about the structure of the estimated Pareto front. We show that the "controlling dominance area of solutions" modification of the dominance relation can be effectively used to locate edges and interior points of high-dimensional mutually non-dominating sets.


Assuntos
Algoritmos , Metodologias Computacionais , Computação Matemática , Modelos Teóricos , Simulação por Computador
17.
PLoS One ; 19(2): e0298135, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38329995

RESUMO

BACKGROUND: With a growing emphasis on value of care, understanding factors associated with rising healthcare costs is increasingly important. In this national study, we evaluated the degree of center-level variation in the cost of spinal fusion. METHODS: All adults undergoing elective spinal fusion were identified in the 2016 to 2020 National Inpatient Sample. Multilevel mixed-effect models were used to rank hospitals based on risk-adjusted costs. The interclass coefficient (ICC) was utilized to tabulate the amount of variation attributable to hospital-level characteristics. The association of high cost-hospital (HCH) status with in-hospital mortality, perioperative complications, and overall resource utilization was analyzed. Predictors of increased costs were secondarily explored. RESULTS: An estimated 1,541,740 patients underwent spinal fusion, and HCH performed an average of 9.5% of annual cases. HCH were more likely to be small (36.8 vs 30.5%, p<0.001), rural (10.1 vs 8.8%, p<0.001), and located in the Western geographic region (49.9 vs 16.7%, p<0.001). The ICC demonstrated 32% of variation in cost was attributable to the hospital, independent of patient-level characteristics. Patients who received a spinal fusion at a HCH faced similar odds of mortality (0.74 [0.48-1.15], p = 0.18) and perioperative complications (1.04 [0.93-1.16], p = 0.52), but increased odds of non-home discharge (1.30 [1.17-1.45], p<0.001) and prolonged length of stay (ß 0.34 [0.26-0.42] days, p = 0.18). Patient factors such as gender, race, and income quartile significantly impacted costs. CONCLUSION: The present analysis identified 32% of the observed variation to be attributable to hospital-level characteristics. HCH status was not associated with increased mortality or perioperative complications.


Assuntos
Fusão Vertebral , Adulto , Humanos , Estados Unidos , Hospitalização , Hospitais , Alta do Paciente , Custos de Cuidados de Saúde , Tempo de Internação , Complicações Pós-Operatórias , Estudos Retrospectivos
18.
Surg Neurol Int ; 15: 4, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38344093

RESUMO

Background: Chiari (type I) malformations are typically congenital. Occasionally, however, tonsillar herniation can arise secondary to cerebrospinal fluid leakage, posterior fossa or intraventricular mass lesions, or other etiologies. We present the first-ever case of an intramedullary subependymoma at the cervicomedullary junction associated with vertebral bone abnormalities and an acquired secondary Chiari malformation. Case Description: A 60-year-old woman presented with a 3-year history of occipital, tussive headaches. Preoperative imaging was negative for mass lesions but demonstrated a Chiari malformation. She was recommended posterior fossa decompression with tonsillar shrinkage. During surgery, an intramedullary mass was incidentally observed, obstructing the obex at the cervicomedullary junction. Histopathological analysis of the resected lesion revealed a diagnosis of subependymoma. Conclusion: Subependymomas can sometimes present a diagnostic challenge due to their subtle appearance in neuroimaging. Only rarely are such masses associated with an acquired Chiari malformation. No such case has previously been reported. We present a literature review on acquired Chiari malformations and discuss their management.

19.
Cancers (Basel) ; 16(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38893250

RESUMO

Although primary studies have reported the safety and efficacy of LITT as a primary treatment in glioma, they are limited by sample sizes and institutional variation in stereotactic parameters such as temperature and laser power. The current literature has yet to provide pooled statistics on outcomes solely for primary brain tumors according to the 2021 WHO Classification of Tumors of the Central Nervous System (WHO CNS5). In the present study, we identify recent articles on primary CNS neoplasms treated with LITT without prior intervention, focusing on relationships with molecular profile, PFS, and OS. This meta-analysis includes the extraction of data from primary sources across four databases using the Covidence systematic review manager. The pooled data suggest LITT may be a safe primary management option with tumor ablation rates of 94.8% and 84.6% in IDH-wildtype glioblastoma multiforme (GBM) and IDH-mutant astrocytoma, respectively. For IDH-wildtype GBM, the pooled PFS and OS were 5.0 and 9.0 months, respectively. Similar to rates reported in the prior literature, the neurologic and non-neurologic complication rates for IDH-wildtype GBM were 10.3% and 4.8%, respectively. The neurologic and non-neurologic complication rates were somewhat higher in the IDH-mutant astrocytoma cohort at 33% and 8.3%, likely due to a smaller cohort size.

20.
J Neurosurg ; 140(2): 338-349, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-37542437

RESUMO

OBJECTIVE: The objective of this study was to identify baseline clinical and radiological characteristics of brain metastases (BMs) associated with a higher probability of lesion-specific progression-free survival (PFS-L) after laser interstitial thermal therapy (LITT). METHODS: A total of 47 lesions in 42 patients with BMs treated with LITT were retrospectively examined, including newly diagnosed BM, suspected recurrent BM, and suspected radiation necrosis. The association of baseline clinical and radiological features with PFS-L was assessed using survival analyses. Radiological features included lesion size measurements, diffusion and perfusion metrics, and sphericity, which is a radiomic feature ranging from 1 (perfect sphere) to 0. RESULTS: The probability of PFS-L for the entire cohort was 88.0% at 3 months, 70.6% at 6 months, 67.4% at 1 and 2 years, and 62.2% at 3 years. For lesions progressing after LITT (n = 13), the median time to progression was 3.9 months, and most lesions (n = 11) progressed within 6 months after LITT. In lesions showing response to LITT (n = 17), the median time to response was 12.1 months. All 3 newly diagnosed BMs showed a long-term response. The mean (± SD) follow-up duration for all censored lesions (n = 34) was 20.7 ± 19.4 months (range 12 days to 6.1 years). The mean pretreatment enhancing volume was 2.68 cm3 and the mean sphericity was 0.70. Pretreatment small enhancing volume (p = 0.003) and high sphericity (p = 0.024) computed from lesion segmentation predicted a longer PFS-L after LITT. Lesions meeting optimal cutoffs of either enhancing volume < 2.5 cm3 (adjusted p = 0.004) or sphericity ≥ 0.705 (adjusted p = 0.019) had longer PFS-L, and their probability of PFS-L was 86.8% at 3 years. Lesions meeting both cutoffs showed a cumulative benefit (p < 0.0001), with a 100% probability of PFS-L at 3 years, which was unchanged at the end of follow-up (4.1 years). Manually computed estimates of lesion size (maximal axial diameter, p = 0.011) and sphericity (p = 0.043) were also predictors of PFS-L. Optimal cutoffs of diameter < 2 cm (adjusted p = 0.035) or manual sphericity ≥ 0.91 (adjusted p = 0.092) identified lesions with longer PFS-L, and lesions meeting both cutoffs showed a cumulative benefit (p = 0.0023). Baseline diffusion imaging did not predict PFS-L. A subset of lesions (n = 7) with highly perfused hotspots had worse PFS-L (adjusted p = 0.010), but perfusion signal contamination from vessels and cortex and underlying size differences were possible confounders. CONCLUSIONS: Small size and high sphericity are ideal baseline features for lesions considered for LITT treatment, with a cumulative PFS-L benefit when both features are present, that could aid patient selection.


Assuntos
Neoplasias Encefálicas , Terapia a Laser , Humanos , Terapia a Laser/métodos , Estudos Retrospectivos , Prognóstico , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/terapia , Neoplasias Encefálicas/patologia , Lasers
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