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1.
Neurosurg Focus ; 50(6): E5, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34062498

RESUMO

OBJECTIVE: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is used in spinal arthrodesis procedures to enhance bony fusion. Research has suggested that it is the most cost-effective fusion enhancer, but there are significant upfront costs for the healthcare system. The primary objective of this study was to determine whether intraoperative dosing and corresponding costs changed with surgeon cost awareness. The secondary objective was to describe surgical complications before and after surgeon awareness of rhBMP-2 cost. METHODS: A retrospective medical record review was conducted to identify patients who underwent spinal arthrodesis procedures performed by a single surgeon, supplemented with rhBMP-2, from June 2016 to June 2018. Collected data included rhBMP-2 dosage, rhBMP-2 list price, and surgical complications. Expected Medicare reimbursement was calculated. Data were analyzed before and after surgeon awareness of rhBMP-2 cost. RESULTS: Forty-eight procedures were performed using rhBMP-2, 16 before and 32 after surgeon cost awareness. Prior to cost awareness, the most frequent rhBMP-2 dosage level was x-small (38.9%, n = 7), followed by large (27.8%, n = 5) and small (22.2%, n = 4). After cost awareness, the most frequent rhBMP-2 dosage was xx-small (56.8%, n = 21), followed by x-small (21.6%, n = 8) and large (13.5%, n = 5). The rhBMP-2 average cost per surgery was $4116.56 prior to surgeon cost awareness versus $2268.38 after. Two complications were observed in the pre-cost awareness surgical group; 2 complications were observed in the post-cost awareness surgical group. CONCLUSIONS: Surgeon awareness of rhBMP-2 cost resulted in use of smaller rhBMP-2 doses, decreased rhBMP-2 cost per surgery, and decreased overall hospital admission charges, without a detectable increase in surgical complications.


Assuntos
Fusão Vertebral , Cirurgiões , Idoso , Proteína Morfogenética Óssea 2 , Humanos , Vértebras Lombares , Medicare , Proteínas Recombinantes , Estudos Retrospectivos , Fator de Crescimento Transformador beta , Estados Unidos
2.
Neurosurg Focus ; 50(6): E7, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-34062509

RESUMO

OBJECTIVE: Anterior cervical discectomy and fusion (ACDF) is the most common treatment for degenerative disease of the cervical spine. Given the high rate of pseudarthrosis in multilevel stand-alone ACDF, there is a need to explore the utility of novel grafting materials. In this study, the authors present a single-institution retrospective study of patients with multilevel degenerative spine disease who underwent multilevel stand-alone ACDF surgery with or without cellular allograft supplementation. METHODS: In a prospectively collected database, 28 patients who underwent multilevel ACDF supplemented with cellular allograft (ViviGen) and 25 patients who underwent multilevel ACDF with decellularized allograft between 2014 and 2020 were identified. The primary outcome was radiographic fusion determined by a 1-year follow-up CT scan. Secondary outcomes included change in Neck Disability Index (NDI) scores and change in visual analog scale scores for neck and arm pain. RESULTS: The study included 53 patients with a mean age of 53 ± 0.7 years who underwent multilevel stand-alone ACDF encompassing 2.6 ± 0.7 levels on average. Patient demographics were similar between the two cohorts. In the cellular allograft cohort, 2 patients experienced postoperative dysphagia that resolved by the 3-month follow-up. One patient developed cervical radiculopathy due to graft subsidence and required a posterior foraminotomy. At the 1-year CT, successful fusion was achieved in 92.9% (26/28) of patients who underwent ACDF supplemented with cellular allograft, compared with 84.0% (21/25) of patients who underwent ACDF without cellular allograft. The cellular allograft cohort experienced a significantly greater improvement in the mean postoperative NDI score (p < 0.05) compared with the other cohort. CONCLUSIONS: Cellular allograft is a low-morbidity bone allograft option for ACDF. In this study, the authors determined favorable arthrodesis rates and functional outcomes in a complex patient cohort following multilevel stand-alone ACDF supplemented with cellular allograft.


Assuntos
Fusão Vertebral , Aloenxertos , Discotomia , Seguimentos , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento
3.
Genes Dev ; 27(24): 2642-7, 2013 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-24352421

RESUMO

The self-renewal versus differentiation choice of Drosophila and mammalian neural stem cells (NSCs) requires Notch (N) signaling. How N regulates NSC behavior is not well understood. Here we show that canonical N signaling cooperates with a noncanonical N signaling pathway to mediate N-directed NSC regulation. In the noncanonical pathway, N interacts with PTEN-induced kinase 1 (PINK1) to influence mitochondrial function, activating mechanistic target of rapamycin complex 2 (mTORC2)/AKT signaling. Importantly, attenuating noncanonical N signaling preferentially impaired the maintenance of Drosophila and human cancer stem cell-like tumor-forming cells. Our results emphasize the importance of mitochondria to N and NSC biology, with important implications for diseases associated with aberrant N signaling.


Assuntos
Mitocôndrias/metabolismo , Complexos Multiproteicos/metabolismo , Células-Tronco Neoplásicas/metabolismo , Proteínas Quinases/metabolismo , Receptores Notch/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Animais , Neoplasias Encefálicas/fisiopatologia , Linhagem Celular Tumoral , Proliferação de Células , Drosophila melanogaster/genética , Drosophila melanogaster/metabolismo , Regulação da Expressão Gênica , Humanos , Alvo Mecanístico do Complexo 2 de Rapamicina , Microscopia Eletrônica de Transmissão , Mitocôndrias/enzimologia , Mitocôndrias/ultraestrutura , Complexos Multiproteicos/genética , Mutação , Proteínas Quinases/genética , Interferência de RNA , Serina-Treonina Quinases TOR/genética
4.
Neurosurg Focus ; 48(1): E4, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31896081

RESUMO

Diffuse intrinsic pontine glioma (DIPG) is a universally fatal pediatric brainstem tumor affecting approximately 300 children in the US annually. Median survival is less than 1 year, and radiation therapy has been the mainstay of treatment for decades. Recent advances in the biological understanding of the disease have identified the H3K27M mutation in nearly 80% of DIPGs, leading to the 2016 WHO classification of diffuse midline glioma H3K27M-mutant, a grade IV brainstem tumor. Developments in epigenetic targeting of transcriptional tendencies have yielded potential molecular targets for clinical trials. Chimeric antigen receptor T cell therapy has also shown preclinical promise. Recent clinical studies, including prospective trials, have demonstrated the safety and feasibility of pediatric brainstem biopsy in the setting of DIPG and other brainstem tumors. Given developments in the ability to analyze DIPG tumor tissue to deepen biological understanding of this disease and develop new therapies for treatment, together with the increased safety of stereotactic brainstem biopsy, the authors present a case for offering biopsy to all children with suspected DIPG. They also present their standard operative techniques for image-guided, frameless stereotactic biopsy.


Assuntos
Astrocitoma , Biópsia , Neoplasias do Tronco Encefálico , Padrão de Cuidado , Astrocitoma/patologia , Astrocitoma/cirurgia , Biópsia/métodos , Neoplasias do Tronco Encefálico/patologia , Neoplasias do Tronco Encefálico/cirurgia , Criança , Pré-Escolar , Epigenômica , Glioma/genética , Humanos , Biópsia Guiada por Imagem/métodos , Estudos Prospectivos
5.
Neurosurg Focus ; 48(4): E9, 2020 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-32234987

RESUMO

Functional hemispherectomy/hemispherotomy is a disconnection procedure for severe medically refractory epilepsy where the seizure foci diffusely localize to one hemisphere. It is an improvement on anatomical hemispherectomy and was first performed by Rasmussen in 1974. Less invasive surgical approaches and refinements have been made to improve seizure freedom and minimize surgical morbidity and complications. Key anatomical structures that are disconnected include the 1) internal capsule and corona radiata, 2) mesial temporal structures, 3) insula, 4) corpus callosum, 5) parietooccipital connection, and 6) frontobasal connection. A stepwise approach is indicated to ensure adequate disconnection and prevent seizure persistence or recurrence. In young pediatric patients, careful patient selection and modern surgical techniques have resulted in > 80% seizure freedom and very good functional outcome. In this report, the authors summarize the history of hemispherectomy and its development and present a graphical guide for this anatomically challenging procedure. The use of the osteoplastic flap to improve outcome and the management of hydrocephalus are discussed.


Assuntos
Córtex Cerebral/cirurgia , Epilepsia Resistente a Medicamentos/cirurgia , Hemisferectomia , Convulsões/cirurgia , Corpo Caloso/cirurgia , Epilepsia/cirurgia , Feminino , Hemisferectomia/métodos , Humanos , Masculino , Pediatria , Resultado do Tratamento
6.
Neurosurg Focus ; 48(1): E11, 2020 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-31896085

RESUMO

Herein, the authors describe the successful use of laser interstitial thermal therapy (LITT) for management of metastatic craniospinal disease for biopsy-proven atypical teratoid/rhabdoid tumor in a 16-month-old boy presenting to their care. Specifically, LITT was administered to lesions of the right insula and left caudate. The patient tolerated 2 stages of LITT to the aforementioned lesions without complication and with evidence of radiographic improvement of lesions at the 2- and 6-month follow-up appointments. To the authors' knowledge, this represents the first such published report of LITT for management of atypical teratoid/rhabdoid tumor.


Assuntos
Neoplasias Encefálicas/cirurgia , Terapia a Laser , Tumor Rabdoide/cirurgia , Teratoma/cirurgia , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/cirurgia , Diagnóstico Diferencial , Humanos , Lactente , Lasers , Masculino , Tumor Rabdoide/diagnóstico , Tumor Rabdoide/patologia , Teratoma/diagnóstico
7.
J Neurooncol ; 123(3): 449-57, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25682090

RESUMO

Advancements in immunotherapeutics promise new possibilities for the creation of glioblastoma (GBM) treatment options. Ongoing work in cancer stem cell biology has progressively elucidated the role of this tumor sub-population in oncogenesis and has distinguished them as prime therapeutic targets. Current clinical trials take a multifaceted approach with the intention of harnessing the intrinsic cytotoxic capabilities of the immune system to directly target glioblastoma cancer stem cells (gCSC) or indirectly disrupt their stromal microenvironment. Monoclonal antibodies (mAbs), dendritic cell (DC) vaccines, and chimeric antigen receptor (CAR) T cell therapies have emerged as the most common approaches, with particular iterations incorporating cancer stem cell antigenic markers in their treatment designs. Ongoing work to determine the comprehensive antigenic profile of the gCSC in conjunction with efforts to counter the immunosuppressive tumor microenvironment holds much promise in future immunotherapeutic strategies against GBM. Given recent advancements in these fields, we believe there is tremendous potential to improve outcomes of GBM patients in the continuing evolution of immunotherapies targeted to cancer stem cell populations in GBM.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Imunoterapia/métodos , Células-Tronco Neoplásicas/fisiologia , Animais , Neoplasias Encefálicas/imunologia , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/terapia , Glioblastoma/imunologia , Glioblastoma/patologia , Glioblastoma/terapia , Humanos , Terapia de Imunossupressão
8.
Nanomedicine ; 11(5): 1253-63, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25791811

RESUMO

Nanotechnology represents a major frontier with potential to significantly advance the field of bone tissue engineering. Current limitations in regenerative strategies include impaired cellular proliferation and differentiation, insufficient mechanical strength of scaffolds, and inadequate production of extrinsic factors necessary for efficient osteogenesis. Here we review several major areas of research in nanotechnology with potential implications in bone regeneration: 1) nanoparticle-based methods for delivery of bioactive molecules, growth factors, and genetic material, 2) nanoparticle-mediated cell labeling and targeting, and 3) nano-based scaffold construction and modification to enhance physicochemical interactions, biocompatibility, mechanical stability, and cellular attachment/survival. As these technologies continue to evolve, ultimate translation to the clinical environment may allow for improved therapeutic outcomes in patients with large bone deficits and osteodegenerative diseases. FROM THE CLINICAL EDITOR: Traditionally, the reconstruction of bony defects has relied on the use of bone grafts. With advances in nanotechnology, there has been significant development of synthetic biomaterials. In this article, the authors provided a comprehensive review on current research in nanoparticle-based therapies for bone tissue engineering, which should be useful reading for clinicians as well as researchers in this field.


Assuntos
Regeneração Óssea , Nanotecnologia/métodos , Engenharia Tecidual/métodos , Animais , Materiais Biocompatíveis/química , Materiais Biocompatíveis/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Humanos , Nanomedicina/métodos , Nanopartículas/química , Nanopartículas/metabolismo , Medicina Regenerativa/métodos , Coloração e Rotulagem/métodos , Alicerces Teciduais/química
9.
Childs Nerv Syst ; 30(10): 1625-43, 2014 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-25081217

RESUMO

INTRODUCTION: Neuroendoscopy has greatly impacted pediatric neurosurgery over the past few decades. Improved optics and microsurgical tools have allowed neuroendoscopes to be used for a multitude of neurosurgical procedures. DISCUSSION: In this review article, we present the breadth of intraventricular neuroendoscopic procedures for the treatment of conditions ranging from hydrocephalus and brain tumors to congenital cysts and other pathologies. We critically discuss treatment indications and reported success rates for neuroendoscopic procedures. We also present novel approaches, technical nuances, and variations from recently published literature and as practiced in the authors' institution.


Assuntos
Encefalopatias/cirurgia , Ventrículos Cerebrais/cirurgia , Neuroendoscopia/métodos , Ventriculostomia/métodos , Bases de Dados Factuais/estatística & dados numéricos , Humanos , Pediatria
10.
J Neurosurg ; : 1-8, 2024 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-38626477

RESUMO

Moyamoya disease (MMD) is characterized by idiopathic, progressive stenosis of the circle of Willis and the terminal portion of the internal carotid arteries with the development of prominent small collateral vessels and a characteristic moyamoya or puff-of-smoke radiographic appearance. The incidence and prevalence of MMD varies by region, age, and sex, with higher rates in Asian and East Asian populations compared to North American or European populations. There is a bimodal distribution of patients diagnosed with MMD. Pediatric patients are more commonly diagnosed within the 1st decade of life, whereas adult patients present in the 5th or 6th decade of life. Overall, there is a nearly 2:1 female-to-male ratio. Ischemic symptoms are the most common presentation in pediatric and adult populations, but adult patients are nearly twice as likely to present with intracranial hemorrhage compared to their pediatric counterparts. Surgical revascularization is indicated in symptomatic cases, and antiplatelet therapy may be a useful adjunct to prevent recurrent symptoms. Direct and combined bypass procedures seem to be more effective in adults, whereas children respond well to indirect bypass. The identification of key genetic, molecular, and environmental factors including RNF213 and GUCY1A3 loss-of-function mutations, angiogenic growth factors, autoantibodies, CNS infections, and radiation exposure suggest multiple pathways for the development of moyamoya arteriopathy. Further research is needed to better understand the heterogeneity of pathogenetic mechanisms that lead to moyamoya and to identify novel therapeutic targets to prevent, stabilize, and treat MMD.

12.
World Neurosurg ; 185: e491-e499, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38369109

RESUMO

OBJECTIVE: Post-traumatic hydrocephalus (PTH) is a complication following traumatic brain injury (TBI). Early diagnosis and treatment are essential to improving outcomes. We report the incidence and risk factors of PTH in a large TBI population while considering death as a competing risk. METHODS: We conducted a retrospective cohort study on consecutive TBI patients with radiographic intracranial abnormalities admitted to our academic medical center from 2009 to 2015. We assessed patient demographics, perioperative data, and in-hospital data as risk factors for PTH using survival analysis with death as a competing risk. RESULTS: Among 7,473 patients, the overall incidence of PTH requiring shunt surgery was 0.94%. The adjusted cumulative incidence was 0.99%. The all-cause cumulative hazard for death was 32.6%, which was considered a competing risk during analysis. Craniectomy (HR 11.53, P < 0.001, 95% CI 5.57-223.85), venous sinus injury (HR 4.13, P = 0.01, 95% CI 1.53-11.16), and age ≤5 (P < 0.001) were significant risk factors for PTH. Glasgow Coma Score (GCS) > 13 was protective against shunt placement (HR 0.50, P = 0.04, 95% CI 0.26-0.97). Shunt surgery occurred after hospital discharge in 60% of patients. CONCLUSIONS: We describe the incidence and risk factors for PTH in a large traumatic brain injury (TBI) population. Most cases of PTH were diagnosed after hospital discharge, suggesting that close follow-up and multidisciplinary diagnostic vigilance for PTH are needed to prevent morbidity and disability.


Assuntos
Lesões Encefálicas Traumáticas , Hidrocefalia , Humanos , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/epidemiologia , Lesões Encefálicas Traumáticas/cirurgia , Masculino , Feminino , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Hidrocefalia/epidemiologia , Incidência , Adulto , Estudos Retrospectivos , Pessoa de Meia-Idade , Fatores de Risco , Adulto Jovem , Adolescente , Criança , Idoso , Pré-Escolar , Estudos de Coortes , Escala de Coma de Glasgow , Lactente
13.
World Neurosurg ; 185: e631-e639, 2024 05.
Artigo em Inglês | MEDLINE | ID: mdl-38403017

RESUMO

BACKGROUND: Surgical management of pediatric patients with nonlesional, drug-resistant epilepsy, including patients with Lennox-Gastaut syndrome (LGS), remains a challenge given the lack of resective targets in most patients and shows seizure freedom rates <50% at 5 years. The efficacy of deep brain stimulation (DBS) is less certain in children than in adults. This study examined clinical and seizure outcomes for pediatric patients with LGS undergoing DBS targeting of the centromedian thalamic nuclei (CMTN). METHODS: An institutional review board-approved retrospective analysis was performed of patients aged ≤19 years with clinical diagnosis of LGS undergoing bilateral DBS placement to the CMTN from 2020 to 2021 by a single surgeon. RESULTS: Four females and 2 males aged 6-19 years were identified. Before surgery, each child experienced at least 6 years of refractory seizures; 4 children had experienced seizures since infancy. All took antiseizure medications at the time of surgery. Five children had previous placement of a vagus nerve stimulator and 2 had a previous corpus callosotomy. The mean length of stay after DBS was 2 days. No children experienced adverse neurologic effects from implantation; the mean follow-up time was 16.3 months. Four patients had >60% reduction in seizure frequency after surgery, 1 patient experienced 10% reduction, and 1 patient showed no change. No children reported worsening seizure symptoms after surgery. CONCLUSIONS: Our study contributes to the sparse literature describing CMTN DBS for children with drug-resistant epilepsy from LGS. Our results suggest that CMTN DBS is a safe and effective therapeutic modality that should be considered as an alternative or adjuvant therapy for this challenging patient population. Further studies with larger patient populations are warranted.


Assuntos
Estimulação Encefálica Profunda , Núcleos Intralaminares do Tálamo , Síndrome de Lennox-Gastaut , Humanos , Masculino , Feminino , Estimulação Encefálica Profunda/métodos , Síndrome de Lennox-Gastaut/terapia , Adolescente , Criança , Estudos Retrospectivos , Núcleos Intralaminares do Tálamo/cirurgia , Adulto Jovem , Resultado do Tratamento , Epilepsia Resistente a Medicamentos/terapia , Epilepsia Resistente a Medicamentos/cirurgia
14.
Cancers (Basel) ; 16(8)2024 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-38672676

RESUMO

High-grade gliomas (HGGs) have a poor prognosis and are difficult to treat. This review examines the evolving landscape of endovascular therapies for HGGs. Recent advances in endovascular catheter technology and delivery methods allow for super-selective intra-arterial cerebral infusion (SSIACI) with increasing precision. This treatment modality may offer the ability to deliver anti-tumoral therapies directly to tumor regions while minimizing systemic toxicity. However, challenges persist, including blood-brain barrier (BBB) penetration, hemodynamic complexities, and drug-tumor residence time. Innovative adjunct techniques, such as focused ultrasound (FUS) and hyperosmotic disruption, may facilitate BBB disruption and enhance drug penetration. However, hemodynamic factors that limit drug residence time remain a limitation. Expanding therapeutic options beyond chemotherapy, including radiotherapy and immunobiologics, may motivate future investigations. While preclinical and clinical studies demonstrate moderate efficacy, larger randomized trials are needed to validate the clinical benefits. Additionally, future directions may involve endovascular sampling for peri-tumoral surveillance; changes in drug formulations to prolong residence time; and the exploration of non-pharmaceutical therapies, like radioembolization and photodynamic therapy. Endovascular strategies hold immense potential in reshaping HGG treatment paradigms, offering targeted and minimally invasive approaches. However, overcoming technical challenges and validating clinical efficacy remain paramount for translating these advancements into clinical care.

15.
J Neurooncol ; 114(2): 209-18, 2013 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-23748573

RESUMO

The use of CyberKnife (CK) stereotactic radiosurgery (SRS) for the management of central nervous system chondrosarcomas has not been previously reported. To evaluate outcomes of primary, recurrent, and metastatic chondrosarcomas of the skull base and spine treated with CK SRS, a retrospective observational study of 16 patients treated between 1996 and 2011 with CK SRS was performed using an IRB-approved database at Stanford University Medical Center. Twenty lesions (12 cranial, 8 spinal) across six males and ten females were analyzed. The median age at SRS was 51 years and median follow-up was 33 months. Median tumor volume was 11.0 cm³ and median marginal dosages were 22, 24, 26, 27, and 30 Gy for one to five fractionations, respectively. Overall Kaplan-Meier survival rates were 88, 88, 80, and 66 % at 1, 3, 5, and 10 years after initial presentation. Survival rates at 1, 3, and 5 years after CK were 81, 67, and 55 %, respectively. Actuarial tumor control was 41 ± 13 % at 60 months. At 36 months follow-up, tumor control was 80 % in primary lesions, 50 % in recurrent lesions, and 0.0 % in metastatic disease (p = 0.07). Tumor control was 58 % in cranial lesions and 38 % in spinal lesions. Radiation injury was reported in one patient. CK SRS appears to be a safe adjuvant therapy and offers moderate control for primary cranial chondrosarcoma lesions. There appears to be a clinically, albeit not statistically, significant trend towards poorer outcomes in similarly treated metastatic, recurrent, and spinal chondrosarcomas (p = 0.07). Lesions not candidates for single fraction SRS may be treated with hypofractionated SRS without increased risk for radiation necrosis.


Assuntos
Condrossarcoma/cirurgia , Radiocirurgia/métodos , Neoplasias da Base do Crânio/cirurgia , Neoplasias da Coluna Vertebral/cirurgia , Adulto , Idoso , Condrossarcoma/patologia , Feminino , Seguimentos , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Neoplasias da Base do Crânio/patologia , Neoplasias da Coluna Vertebral/patologia , Resultado do Tratamento , Carga Tumoral
16.
NPJ Precis Oncol ; 6(1): 55, 2022 Aug 08.
Artigo em Inglês | MEDLINE | ID: mdl-35941215

RESUMO

Glioblastoma (GBM) is a heterogeneous tumor made up of cell states that evolve over time. Here, we modeled tumor evolutionary trajectories during standard-of-care treatment using multi-omic single-cell analysis of a primary tumor sample, corresponding mouse xenografts subjected to standard of care therapy, and recurrent tumor at autopsy. We mined the multi-omic data with single-cell SYstems Genetics Network AnaLysis (scSYGNAL) to identify a network of 52 regulators that mediate treatment-induced shifts in xenograft tumor-cell states that were also reflected in recurrence. By integrating scSYGNAL-derived regulatory network information with transcription factor accessibility deviations derived from single-cell ATAC-seq data, we developed consensus networks that modulate cell state transitions across subpopulations of primary and recurrent tumor cells. Finally, by matching targeted therapies to active regulatory networks underlying tumor evolutionary trajectories, we provide a framework for applying single-cell-based precision medicine approaches to an individual patient in a concurrent, adjuvant, or recurrent setting.

17.
J Clin Neurosci ; 105: 66-72, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36113244

RESUMO

Clinical significance of increased clopidogrel response measured by VerifyNow P2Y12 assay is unclear; management guidelines are lacking in the context of neuroendovascular intervention. Our objective was to assess whether increased clopidogrel response predicts complications from endovascular aneurysm treatment requiring dual antiplatelet therapy. A single-institution, 9-year retrospective study of patients undergoing endovascular treatments for ruptured and unruptured aneurysms requiring aspirin and clopidogrel was conducted. Patients were grouped according to preoperative platelet inhibition in response to clopidogrel measured by the VerifyNow P2Y12 assay (VNP; P2Y12 reactivity units, PRU). Demographic and clinical features were compared across groups. Hemorrhagic complication rates (intracranial, major extracranial, minor extracranial) and thromboembolic complications (in-stent stenosis, stroke/transient ischemic attack) were compared, controlling for potential confounders and multiple comparisons. Data were collected from 284 patients across 317 procedures. Pre-operative VNP assays identified 9 % Extreme Responders (PRU ≤ 15), 13 % Hyper-Responders (PRU 16-60), 62 % Therapeutic Responders (PRU 61-214), 16 % Hypo-Responders (PRU ≥ 215). Increased response to clopidogrel was associated with increased risk of any hemorrhagic complication (≤60 PRU vs > 60 PRU; 39 % vs 24 %, P = 0.050); all intracranial hemorrhages occurred in patients with PRU > 60. Thromboembolic complications were similar between therapeutic and subtherapeutic patients (<215 PRU vs ≥ 215 PRU; 15 % vs 16 %, P = 0.835). Increased preoperative clopidogrel response is associated with increased rate of extracranial hemorrhagic complications in endovascular aneurysm treatments. Hyper-responders (16-60 PRU) and Extreme Responders (≤15 PRU) were not associated with intracranial hemorrhagic or thrombotic complications. Hypo-responders who underwent adjustment of antiplatelet therapy and neurointerventions did not experience higher rates of complications.


Assuntos
Aneurisma da Aorta Abdominal , Implante de Prótese Vascular , Procedimentos Endovasculares , Aneurisma Intracraniano , Tromboembolia , Aneurisma da Aorta Abdominal/complicações , Aneurisma da Aorta Abdominal/cirurgia , Aspirina/efeitos adversos , Clopidogrel/uso terapêutico , Procedimentos Endovasculares/efeitos adversos , Humanos , Aneurisma Intracraniano/complicações , Aneurisma Intracraniano/tratamento farmacológico , Aneurisma Intracraniano/cirurgia , Inibidores da Agregação Plaquetária/efeitos adversos , Estudos Retrospectivos , Tromboembolia/tratamento farmacológico , Tromboembolia/etiologia , Resultado do Tratamento
18.
Neurosurgery ; 89(3): 364-371, 2021 08 16.
Artigo em Inglês | MEDLINE | ID: mdl-34133724

RESUMO

Telemedicine has received increased attention in recent years as a potential solution to expand clinical capability and patient access to care in many fields, including neurosurgery. Although patient and physician attitudes are rapidly shifting toward greater telemedicine use in light of the COVID-19 pandemic, there remains uncertainty about telemedicine's regulatory future. Despite growing evidence of telemedicine's utility, there remain a number of significant medicolegal barriers to its mass adoption and wider implementation. Herein, we examine recent progress in state and federal regulations in the United States governing telemedicine's implementation in quality of care, finance and billing, privacy and confidentiality, risk and liability, and geography and interstate licensure, with special attention to how these concern teleneurosurgical practice. We also review contemporary topics germane to the future of teleneurosurgery, including the continued expansion of reciprocity in interstate licensure, expanded coverage for homecare services for chronic conditions, expansion of Center for Medicare and Medicaid Services reimbursements, and protections of store-and-forward technologies. Additionally, we discuss recent successes in teleneurosurgery, stroke care, and rehabilitation as models for teleneurosurgical best practices. As telemedicine technology continues to mature and its expanse grows, neurosurgeons' familiarity with its benefits, limitations, and controversies will best allow for its successful adoption in our field to maximize patient care and outcomes.


Assuntos
COVID-19 , Telemedicina , Idoso , Humanos , Medicare , Neurocirurgiões , Pandemias , SARS-CoV-2 , Estados Unidos
19.
Oper Neurosurg (Hagerstown) ; 20(6): E436, 2021 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-33548927

RESUMO

Basilar tip aneurysm clipping is technically challenging because of the depth of operative corridor, rarity in presentation, and important perforators supplying deep, critical structures. Two major approaches to basilar tip aneurysms include (1) a frontotemporal (transorbital) trans-sylvian approach for most aneurysms and (2) a modified subtemporal approach for aneurysms with low-lying necks. A 53-yr-old woman presented to our institution with a large unruptured basilar tip aneurysm notable for a low, broad neck (6.4 mm). After discussion of risks and benefits of endovascular vs surgical options, the patient consented to operative intervention. She underwent a right frontotemporal craniotomy with zygomatic osteotomy, intradural petrous apicectomy, elective sectioning of the fourth cranial nerve (CN IV), and intracavernous removal of the dorsum sellae and posterior clinoid process to provide more space for aneurysm dissection. After temporary clipping of the basilar artery, the perforating arteries were dissected free from the aneurysm and the aneurysm occluded with 2 fenestrated clips. Important technical nuances of the approach include (1) achieving ample working room for temporary occlusion aneurysm dissection, (2) careful dissection of the perforators and contralateral P1, and (3) utilization of 2 fenestrated clips to accommodate and preserve the ipsilateral P1 segment. Postoperative angiogram showed complete aneur-ysmal occlusion. Postoperatively, the patient demonstrated mild cognitive impairment and a right CN IV palsy. At 6-wk follow-up, cognition recovered to normalcy. More recently, at 12-mo follow-up, the patient noted intermittent diplopia. Formal neuro-ophthalmologic assessment confirmed persistence of a CN IV palsy treated with prism lenses but no other neurological deficits.


Assuntos
Aneurisma Intracraniano , Artéria Basilar/cirurgia , Craniotomia , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Aneurisma Intracraniano/cirurgia , Sela Túrcica , Instrumentos Cirúrgicos
20.
World Neurosurg ; 145: 702-707, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32891833

RESUMO

BACKGROUND: Degenerative spine disease is common in athletes and can progress to requiring surgical intervention. Traditional open surgical techniques necessitate prolonged recovery time and time away from play. Newly developed endoscopic surgical techniques may promote faster healing and recovery, and increased return to play. The goal of this paper is to summarize the current evidence in return to play after spine surgery and to present our series of 3 athletes who underwent endoscopic spine surgery. METHODS: A complete search of all PubMed indexed articles pertaining to spine surgery in athletes was conducted. This was supplemented by a 3-patient case series of our own endoscopic spine experience in athletes. RESULTS: There are no current widely accepted guidelines for return to play after spinal surgery. The best evidence available cites a return to play of 81% at 5.2-8.7 months after traditional open and minimally invasive surgery, and endoscopic surgery produces an average 88% return to play rate at 3 months. CONCLUSIONS: Although return to play can vary widely, case-based evidence as well as biomechanical principles support endoscopic spine surgery as a viable surgical modality for the treatment of spinal pathologies in athletes.


Assuntos
Atletas , Futebol Americano/lesões , Neuroendoscopia/métodos , Futebol/lesões , Doenças da Coluna Vertebral/cirurgia , Traumatismos em Atletas/diagnóstico por imagem , Traumatismos em Atletas/etiologia , Traumatismos em Atletas/cirurgia , Humanos , Masculino , Doenças da Coluna Vertebral/diagnóstico por imagem , Doenças da Coluna Vertebral/etiologia , Adulto Jovem
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