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1.
Nature ; 592(7855): 537-540, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33883732

RESUMO

Recent multi-dimensional simulations suggest that high-entropy buoyant plumes help massive stars to explode1,2. Outwardly protruding iron (Fe)-rich fingers of gas in the galactic supernova remnant3,4 Cassiopeia A seem to match this picture. Detecting the signatures of specific elements synthesized in the high-entropy nuclear burning regime (that is, α-rich freeze out) would constitute strong substantiating evidence. Here we report observations of such elements-stable titanium (Ti) and chromium (Cr)-at a confidence level greater than 5 standard deviations in the shocked high-velocity Fe-rich ejecta of Cassiopeia A. We found that the observed Ti/Fe and Cr/Fe mass ratios require α-rich freeze out, providing evidence of the existence of the high-entropy ejecta plumes that boosted the shock wave at explosion. The metal composition of the plumes agrees well with predictions for strongly neutrino-processed proton-rich ejecta2,5,6. These results support the operation of the convective supernova engine via neutrino heating in the supernova that produced Cassiopeia A.

2.
Acta Neurochir (Wien) ; 166(1): 293, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38985334

RESUMO

OBJECTIVE: Intraoperative rupture (IOR) is the most common adverse event encountered during surgical clip obliteration of ruptured intracranial aneurysms. Besides increasing surgeon experience and early proximal control, no methods exist to decrease IOR risk. Thus, our objective was to assess if partial endovascular coil embolization to protect the aneurysm before clipping decreases IOR. METHODS: We conducted a retrospective analysis of patients with ruptured intracranial aneurysms that were treated with surgical clipping at two tertiary academic centers. We compared patient characteristics and outcomes of those who underwent partial endovascular coil embolization to protect the aneurysm before clipping to those who did not. The primary outcome was IOR. Secondary outcomes were inpatient mortality and discharge destination. RESULTS: We analyzed 100 patients. Partial endovascular aneurysm protection was performed in 27 patients. Age, sex, subarachnoid hemorrhage severity, and aneurysm location were similar between the partially-embolized and non-embolized groups. The median size of the partially-embolized aneurysms was larger (7.0 mm [interquartile range 5.95-8.7] vs. 4.6 mm [3.3-6.0]; P < 0.001). During surgical clipping, IOR occurred less frequently in the partially-embolized aneurysms than non-embolized aneurysms (2/27, 7.4%, vs. 30/73, 41%; P = 0.001). Inpatient mortality was 14.8% (4/27) in patients with partially-embolized aneurysms and 28.8% (21/73) in patients without embolization (P = 0.20). Discharge to home or inpatient rehabilitation was 74.0% in patients with partially-embolized aneurysms and 56.2% in patients without embolization (P = 0.11). A complication from partial embolization occurred in 2/27 (7.4%) patients. CONCLUSIONS: Preoperative partial endovascular coil embolization of ruptured aneurysms is associated with a reduced frequency of IOR during definitive treatment with surgical clip obliteration. These results and the impact of preoperative partial endovascular coil embolization on functional outcomes should be confirmed with a randomized trial.


Assuntos
Aneurisma Roto , Embolização Terapêutica , Aneurisma Intracraniano , Humanos , Aneurisma Intracraniano/cirurgia , Aneurisma Intracraniano/terapia , Masculino , Feminino , Aneurisma Roto/cirurgia , Embolização Terapêutica/métodos , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso , Resultado do Tratamento , Instrumentos Cirúrgicos , Adulto , Procedimentos Endovasculares/métodos , Complicações Intraoperatórias/etiologia , Complicações Intraoperatórias/prevenção & controle , Procedimentos Neurocirúrgicos/métodos
3.
J Neurooncol ; 162(1): 199-210, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36913046

RESUMO

BACKGROUND AND AIMS: The aim of this study was to analyze the trends, demographic differences in the type and time to initiation (TTI) of adjunct treatment AT following surgery for anaplastic astrocytoma (AA). MATERIAL AND METHODS: The National Cancer Database (NCDB) was queried for patients diagnosed with AA from 2004 to 2016. Cox proportional hazards and modeling was used to determine factors influencing survival, including the impact of time to initiation (TTI) of adjuvant therapy. RESULTS: Overall, 5890 patients were identified from the database. The use of combined RT + CT temporally increased from 66.3% (2004-2007) to 79% (2014-2016), p < 0001. Patients more likely to receive no treatment following surgical resection included elderly (> 60 years old), hispanic patients, those with either no or government insurance, those living > 20 miles from the cancer facility, those treated at low volume centers (< 2 cases/year). AT was received following surgical resection within 0-4 weeks, 4.1-8 weeks, and > 8 weeks in 41%, 48%, and 3%, respectively. Compared to patients who received RT + CT, patients were likely to receive RT only as AT either at 4-8 weeks or > 8 weeks after the surgical procedure. Patients who received AT within 0-4 weeks had the 3-year OS of 46% compared to 56.7% for patients who received treatment at 4.1-8 weeks. CONCLUSION: We found significant variation in the type and timing of adjunct treatment following surgical resection of AA in the United States. A considerable number of patients (15%) received no AT following surgery.


Assuntos
Astrocitoma , Humanos , Estados Unidos/epidemiologia , Idoso , Pessoa de Meia-Idade , Terapia Combinada , Quimiorradioterapia , Demografia
4.
Neurosurg Focus ; 54(6): E4, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37283447

RESUMO

OBJECTIVE: Gliomas exhibit high intratumor and interpatient heterogeneity. Recently, it has been shown that the microenvironment and phenotype differ significantly between the glioma core (inner) and edge (infiltrating) regions. This proof-of-concept study differentiates metabolic signatures associated with these regions, with the potential for prognosis and targeted therapy that could improve surgical outcomes. METHODS: Paired glioma core and infiltrating edge samples were obtained from 27 patients after craniotomy. Liquid-liquid metabolite extraction was performed on the samples and metabolomic data were obtained via 2D liquid chromatography-mass spectrometry/mass spectrometry. To gauge the potential of metabolomics to identify clinically relevant predictors of survival from tumor core versus edge tissues, a boosted generalized linear machine learning model was used to predict metabolomic profiles associated with O6-methylguanine DNA methyltransferase (MGMT) promoter methylation. RESULTS: A panel of 66 (of 168) metabolites was found to significantly differ between glioma core and edge regions (p ≤ 0.05). Top metabolites with significantly different relative abundances included DL-alanine, creatine, cystathionine, nicotinamide, and D-pantothenic acid. Significant metabolic pathways identified by quantitative enrichment analysis included glycerophospholipid metabolism; butanoate metabolism; cysteine and methionine metabolism; glycine, serine, alanine, and threonine metabolism; purine metabolism; nicotinate and nicotinamide metabolism; and pantothenate and coenzyme A biosynthesis. The machine learning model using 4 key metabolites each within core and edge tissue specimens predicted MGMT promoter methylation status, with AUROCEdge = 0.960 and AUROCCore = 0.941. Top metabolites associated with MGMT status in the core samples included hydroxyhexanoycarnitine, spermine, succinic anhydride, and pantothenic acid, and in the edge samples metabolites included 5-cytidine monophosphate, pantothenic acid, itaconic acid, and uridine. CONCLUSIONS: Key metabolic differences are identified between core and edge tissue in glioma and, furthermore, demonstrate the potential for machine learning to provide insight into potential prognostic and therapeutic targets.


Assuntos
Neoplasias Encefálicas , Glioma , Humanos , Neoplasias Encefálicas/genética , Ácido Pantotênico/genética , Ácido Pantotênico/metabolismo , Metilação de DNA , Glioma/genética , Glioma/cirurgia , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Metabolômica , Enzimas Reparadoras do DNA/genética , Enzimas Reparadoras do DNA/metabolismo , Niacinamida , Microambiente Tumoral
5.
Stroke ; 53(8): e363-e368, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35616021

RESUMO

BACKGROUND: Although complete nidal obliteration of brain arteriovenous malformations (AVM) is generally presumed to represent durable cure, postobliteration hemorrhage, and AVM recurrence have become increasingly recognized phenomena. The goal of the study was to define hemorrhage and nidal recurrence risks of obliterated AVMs treated with stereotactic radiosurgery (SRS). METHODS: This is a retrospective cohort study from the International Radiosurgery Research Foundation comprising AVM patients treated between 1987 and 2020. Patients with AVM obliteration on digital subtraction angiography (DSA) were included. Outcomes were (1) hemorrhage and (2) AVM recurrence. Follow-up duration began at the time of AVM obliteration and was censored at subsequent hemorrhage, AVM recurrence, additional AVM treatment, or loss to follow-up. Annualized risk and survival analyses were performed. A sensitivity analysis comprising patients with AVM obliteration on magnetic resonance imaging or DSA was also performed for postobliteration hemorrhage. RESULTS: The study cohort comprised 1632 SRS-treated patients with AVM obliteration on DSA. Pediatric patients comprised 15% of the cohort, and 42% of AVMs were previously ruptured. The mean imaging follow-up after AVM obliteration was 22 months. Among 1607 patients with DSA-confirmed AVM obliteration, 16 hemorrhages (1.0%) occurred over 2223 patient-years of follow-up (0.72%/y). Of the 1543 patients with DSA-confirmed AVM obliteration, 5 AVM recurrences (0.32%) occurred over 2071 patient-years of follow-up (0.24%/y). Of the 16 patients with postobliteration hemorrhage, AVM recurrence was identified in 2 (12.5%). In the sensitivity analysis comprising 1939 patients with post-SRS AVM obliteration on magnetic resonance imaging or DSA, 16 hemorrhages (0.83%) occurred over 2560 patient-years of follow-up (0.63%/y). CONCLUSIONS: Intracranial hemorrhage and recurrent arteriovenous shunting after complete nidal obliteration are rare in AVM patients treated with SRS, and each phenomenon harbors an annual risk of <1%. Although routine postobliteration DSA cannot be recommended to SRS-treated AVM patients, long-term neuroimaging may be advisable in these patients.


Assuntos
Malformações Arteriovenosas Intracranianas , Radiocirurgia , Encéfalo/patologia , Criança , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Malformações Arteriovenosas Intracranianas/radioterapia , Malformações Arteriovenosas Intracranianas/cirurgia , Hemorragias Intracranianas/etiologia , Radiocirurgia/efeitos adversos , Estudos Retrospectivos , Resultado do Tratamento
6.
J Neurooncol ; 160(2): 331-339, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36289149

RESUMO

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) is a useful adjunct for resection of primary malignant brain tumors (MBTs). The aim of our study is to investigate the impact of iMRI on health care utilization in patients who underwent craniotomy for resection of MBTs. MATERIALS AND METHODS: MarketScan database were queried using the ICD-9/10 and CPT 4th edition, from 2008 to 2020. We included patients ≥ 18 years of age who underwent a craniotomy with at-least one year follow-up. Outcomes were length of stay (LOS), discharge disposition, hospital/emergency room (ER) re-admissions, outpatient services, medication refills and corresponding payments. RESULTS: Of 6,640 patients who underwent craniotomy for MBTs, 465 patients (7%) had iMRI used during the procedure with 0.7% per year increase in iMRI use during the study period. Patients without iMRI use had higher complications at index hospitalization compared to those with iMRI use (19% vs. 14%, p = 0.04). There was no difference in the ER admission rates among the patients who underwent surgery with and without iMRI use at 6-months and 1-year after the index procedure. In terms of post-discharge payments, no significant differences were noted among the patients without and with iMRI use at 6-months ($81,107 vs. $ 81,458, p = 0.26) and 1-year ($132,657 vs. $ 118,113, p = 0.12). CONCLUSION: iMRI use during craniotomy for MBT gradually increased during the study period. iMRI did not result in higher payments at index hospitalization, 6-months, and 1-year after the index procedure.


Assuntos
Neoplasias Encefálicas , Monitorização Intraoperatória , Humanos , Monitorização Intraoperatória/métodos , Sobrecarga do Cuidador , Assistência ao Convalescente , Estudos Retrospectivos , Alta do Paciente , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/patologia , Imageamento por Ressonância Magnética/métodos
7.
BMC Neurol ; 21(1): 445, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34758765

RESUMO

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) represents a transient change in mental status with associated vasogenic edema of cortical and subcortical brain structures. It is often attributed to multifactorial etiology including hypertension and altered hemodynamics and disruption of vessel integrity. Patients with autoimmune disease and certain immune modulator therapies are at greater risk. CASE PRESENTATION: A 54-year-old female with past medical history of well-controlled multiple sclerosis on interferon-beta since 2013, presented with witnessed tonic colonic seizure. She also was noted to demonstrate left gaze deviation and left-sided hemiparesis. MRI fluid-attenuated inversion recovery sequence showed hyperintensity of the subcortical U fibers, concentrated in the occipital, parietal lobes and frontal lobes. Systolic blood pressure was 160 mmHg on arrival. The patient was started on seizure prophylxis and Interferon beta was discontinued. The patient's mentation, seizures and hemiapresis significantly improved in next 72 h with tight blood pressure control, and had notble improvement on MRI imaging and inflammatory markers. Lumbar puncture CSF results were devoid of infectious and autoimmune pathology. CONCLUSIONS: A middle-aged female with multiple sclerosis who was on chronic IFN-beta presented to the emergency room with a witnessed tonic-clonic seizure, with MRI T2 FLAIR imaging consistent with PRES. She had notable clinical improvement with decreased edema on imaging and improved inflammatory markers 72 h after cessation of IFN-beta therapy.


Assuntos
Síndrome da Leucoencefalopatia Posterior , Edema , Feminino , Humanos , Inflamação , Interferon beta/uso terapêutico , Imageamento por Ressonância Magnética , Pessoa de Meia-Idade , Síndrome da Leucoencefalopatia Posterior/diagnóstico por imagem , Síndrome da Leucoencefalopatia Posterior/tratamento farmacológico
8.
BMC Neurol ; 19(1): 214, 2019 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-31470816

RESUMO

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) is a rare neurological disorder usually associated with specific medical conditions that cause a disturbance of the CNS homeostasis. It has seldom been reported to be a consequence of an iatrogenic intervention causing intracranial hypotension. CASE PRESENTATION: We report the case of an individual 69-year-old male presenting with headache and blurred vision following cerebrospinal fluid (CSF) leak from resection of a sellar mass. The patient developed the condition following removal of the lumbar drain post-operatively. Magnetic Resonance Imaging showed bilateral occipital, parieto-occipital, and cerebellar T2 FLAIR hyper-intensities, suggesting a radiological diagnosis of posterior reversible encephalopathy syndrome (PRES). The patient's symptoms started to improve shortly afterwards and had completely resolved at 3 months follow-up. CONCLUSIONS: The absence of severe hypertension and presence of an intraoperative CSF leak requiring placement of the lumbar drain suggests that decreased CSF volume and associated reactive hyperemia could have a role in the pathophysiology of the disease.


Assuntos
Drenagem/métodos , Cefaleia/etiologia , Síndrome da Leucoencefalopatia Posterior/etiologia , Idoso , Cerebelo , Drenagem/efeitos adversos , Humanos , Imageamento por Ressonância Magnética/métodos , Masculino
9.
Neurosurg Focus ; 46(6): E4, 2019 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-31153143

RESUMO

OBJECTIVEThe purpose of this study was to describe effects of adjuvant radiotherapy (RT) for anaplastic meningiomas (AMs) on long-term survival, and to analyze patient and RT characteristics associated with long-term survival.METHODSThe authors queried a retrospective cohort of patients with AM from the National Cancer Database (NCDB) diagnosed between 2004 and 2015 to describe treatment trends. For outcome analysis, patients with at least 10 years of follow-up were included, and they were stratified based on adjuvant RT status and propensity matched to controls for covariates. Survival curves were compared. A data-driven approach was used to find a biologically effective dose (BED) of RT with the largest difference between survival curves. Factors associated with long-term survival were quantified.RESULTSThe authors identified 2170 cases of AM in the NCDB between 2004 and 2015. They observed increased use of adjuvant RT in patients treated with higher doses. A total of 178 cases met the inclusion criteria for outcome analysis. Forty-five percent (n = 80) received adjuvant RT. Patients received a BED of 80.23 ± 16.6 Gy (mean ± IQR). The median survival time was not significantly different (32.8 months for adjuvant RT vs 38.5 months for no RT; p = 0.57, log-rank test). Dichotomizing the patients at a BED of 81 Gy showed maximal difference in survival distribution with a decrease in median survival in favor of no adjuvant RT (31.2 months for adjuvant RT vs 49.7 months for no RT; p = 0.03, log-rank test), but this difference was not significant after false discovery rate correction. Age was a significant predictor for long-term survival.CONCLUSIONSAMs are aggressive tumors that carry a poor prognosis. Conventional adjuvant RT improves local control. However, the effect of adjuvant radiation on overall survival is unclear. Further investigation into this area is warranted.


Assuntos
Irradiação Craniana , Neoplasias Meníngeas/radioterapia , Meningioma/radioterapia , Radioterapia Adjuvante , Fatores Etários , Idoso , Terapia Combinada , Craniotomia , Gerenciamento Clínico , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/cirurgia , Meningioma/mortalidade , Meningioma/cirurgia , Pessoa de Meia-Idade , Modelos de Riscos Proporcionais , Radiocirurgia , Dosagem Radioterapêutica , Estudos Retrospectivos , Fatores Socioeconômicos , Resultado do Tratamento
10.
Neurosurg Focus ; 46(2): E15, 2019 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-30717045

RESUMO

OBJECTIVEThe development and recent widespread dissemination of flow diverters may have reduced the utilization of surgical bypass procedures to treat complex or giant unruptured intracranial aneurysms (UIAs). The aim of this retrospective cohort study was to observe trends in cerebral revascularization procedures for UIAs in the United States before and after the introduction of flow diverters by using the National (Nationwide) Inpatient Sample (NIS).METHODSThe authors extracted data from the NIS database for the years 1998-2015 using the ICD-9/10 diagnostic and procedure codes. Patients with a primary diagnosis of UIA with a concurrent bypass procedure were included in the study. Outcomes and hospital charges were analyzed.RESULTSA total of 216,212 patients had a primary diagnosis of UIA during the study period. The number of patients diagnosed with a UIA increased by 128% from 1998 (n = 7718) to 2015 (n = 17,600). Only 1328 of the UIA patients (0.6%) underwent cerebral bypass. The percentage of patients who underwent bypass in the flow diverter era (2010-2015) remained stable at 0.4%. Most patients who underwent bypass were white (51%), were female (62%), had a median household income in the 3rd or 4th quartiles (57%), and had private insurance (51%). The West (33%) and Midwest/North Central regions (30%) had the highest volume of bypasses, whereas the Northeast region had the lowest (15%). Compared to the period 1998-2011, bypass procedures for UIAs in 2012-2015 shifted entirely to urban teaching hospitals (100%) and to an elective basis (77%). The median hospital stay (9 vs 3 days, p < 0.0001), median hospital charges ($186,746 vs $66,361, p < 0.0001), and rate of any complication (51% vs 17%, p < 0.0001) were approximately threefold higher for the UIA patients with bypass than for those without bypass.CONCLUSIONSDespite a significant increase in the diagnosis of UIAs over the 17-year study period, the proportion of bypass procedures performed as part of their treatment has remained stable. Therefore, advances in endovascular aneurysm therapy do not appear to have affected the volume of bypass procedures performed in the UIA population. The authors' findings suggest a potentially ongoing niche for bypass procedures in the contemporary treatment of UIAs.


Assuntos
Revascularização Cerebral/tendências , Interpretação Estatística de Dados , Custos de Cuidados de Saúde/tendências , Aneurisma Intracraniano/epidemiologia , Aneurisma Intracraniano/cirurgia , Tempo de Internação/tendências , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Revascularização Cerebral/economia , Criança , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Lactente , Recém-Nascido , Aneurisma Intracraniano/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
11.
Proc Natl Acad Sci U S A ; 111(28): 10125-30, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-24982152

RESUMO

Combining biological components, such as cells and tissues, with soft robotics can enable the fabrication of biological machines with the ability to sense, process signals, and produce force. An intuitive demonstration of a biological machine is one that can produce motion in response to controllable external signaling. Whereas cardiac cell-driven biological actuators have been demonstrated, the requirements of these machines to respond to stimuli and exhibit controlled movement merit the use of skeletal muscle, the primary generator of actuation in animals, as a contractile power source. Here, we report the development of 3D printed hydrogel "bio-bots" with an asymmetric physical design and powered by the actuation of an engineered mammalian skeletal muscle strip to result in net locomotion of the bio-bot. Geometric design and material properties of the hydrogel bio-bots were optimized using stereolithographic 3D printing, and the effect of collagen I and fibrin extracellular matrix proteins and insulin-like growth factor 1 on the force production of engineered skeletal muscle was characterized. Electrical stimulation triggered contraction of cells in the muscle strip and net locomotion of the bio-bot with a maximum velocity of ∼ 156 µm s(-1), which is over 1.5 body lengths per min. Modeling and simulation were used to understand both the effect of different design parameters on the bio-bot and the mechanism of motion. This demonstration advances the goal of realizing forward-engineered integrated cellular machines and systems, which can have a myriad array of applications in drug screening, programmable tissue engineering, drug delivery, and biomimetic machine design.


Assuntos
Biomimética , Bioimpressão , Locomoção , Músculo Esquelético , Animais , Linhagem Celular , Colágeno Tipo I/química , Fator de Crescimento Insulin-Like I/química , Camundongos
13.
APL Bioeng ; 8(3): 036101, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-38946776

RESUMO

Glioblastoma (GBM) is a highly invasive, aggressive brain cancer that carries a median survival of 15 months and is resistant to standard therapeutics. Recent studies have demonstrated that intratumoral heterogeneity plays a critical role in promoting resistance by mediating tumor adaptation through microenvironmental cues. GBM can be separated into two distinct regions-a core and a rim, which are thought to drive specific aspects of tumor evolution. These differences in tumor progression are regulated by the diverse biomolecular and biophysical signals in these regions, but the acellular biophysical characteristics remain poorly described. This study investigates the mechanical and ultrastructural characteristics of the tumor extracellular matrix (ECM) in patient-matched GBM core and rim tissues. Seven patient-matched tumor core and rim samples and one non-neoplastic control were analyzed using atomic force microscopy, scanning electron microscopy, and immunofluorescence imaging to quantify mechanical, ultrastructural, and ECM composition changes. The results reveal significant differences in biophysical parameters between GBM core, rim, and non-neoplastic tissues. The GBM core is stiffer, denser, and is rich in ECM proteins hyaluronic acid and tenascin-C when compared to tumor rim and non-neoplastic tissues. These alterations are intimately related and have prognostic effect with stiff, dense tissue correlating with longer progression-free survival. These findings reveal new insights into the spatial heterogeneity of biophysical parameters in the GBM tumor microenvironment and identify a set of characteristics that may correlate with patient prognosis. In the long term, these characteristics may aid in the development of strategies to combat therapeutic resistance.

14.
Curr Oncol ; 31(3): 1183-1194, 2024 02 23.
Artigo em Inglês | MEDLINE | ID: mdl-38534921

RESUMO

BACKGROUND: Glioblastoma (GBM) tumors are rich in tumor-associated microglia/macrophages. Changes associated with treatment in this specific cell population are poorly understood. Therefore, we studied changes in gene expression of tumor-associated microglia/macrophages (Iba1+) cells in de novo versus recurrent GBMs. METHODS: NanoString GeoMx® Digital Spatial Transcriptomic Profiling of microglia/macrophages (Iba1+) and glial cells (Gfap+) cells identified on tumor sections was performed on paired de novo and recurrent samples obtained from three IDH-wildtype GBM patients. The impact of differentially expressed genes on patient survival was evaluated using publicly available data. RESULTS: Unsupervised analyses of the NanoString GeoMx® Digital Spatial Profiling data revealed clustering based on the transcriptomic data from Iba1+ and Gfap+ cells. As expected, conventional differential gene expression and enrichment analyses revealed upregulation of immune-function-related genes in Iba1+ cells compared to Gfap+ cells. A focused differential gene expression analysis revealed upregulation of phagocytosis and fatty acid/lipid metabolism genes in Iba1+ cells in recurrent GBM samples compared to de novo GBM samples. Importantly, of these genes, the lipid metabolism gene PLD3 consistently correlated with survival in multiple different publicly available datasets. CONCLUSION: Tumor-associated microglia/macrophages in recurrent GBM overexpress genes involved in fatty acid/lipid metabolism. Further investigation is needed to fully delineate the role of PLD phospholipases in GBM progression.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Humanos , Microglia/metabolismo , Microglia/patologia , Glioblastoma/genética , Glioblastoma/metabolismo , Glioblastoma/patologia , Neoplasias Encefálicas/patologia , Recidiva Local de Neoplasia/patologia , Macrófagos/metabolismo , Macrófagos/patologia , Ácidos Graxos/metabolismo
15.
J Natl Compr Canc Netw ; 11(6): 726-31, 2013 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-23744869

RESUMO

Chordoma is a primary bone cancer arising on the midline from the skull base to the sacrum. Diagnosis is often delayed because of insidious onset and nonspecific symptoms. Chordomas appear histologically low-grade but are highly invasive and often recur locally. Management centers primarily on radical en bloc surgical resection when possible. Radiation therapy using protons and/or photons is often necessary because complete resection is seldom possible due to critical location and invasion of the cancer cells into surrounding structures. No approved medical therapy exists. The high rate of recurrence is reflected by a median survival of 6 to 7 years. This article reviews the clinical management of chordoma and discusses ongoing research in the field.


Assuntos
Cordoma/diagnóstico , Cordoma/terapia , Cordoma/epidemiologia , Cordoma/etiologia , Humanos
16.
Neurosurg Focus ; 35(6): E16, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24289124

RESUMO

OBJECT: WHO Grade II and III intracranial meningiomas are uncommon, but they portend a significantly worse prognosis than their benign Grade I counterparts. The mainstay of current management is resection to obtain cytoreduction and histological tissue diagnosis. The timing and benefit of postoperative fractionated external beam radiation therapy and stereotactic radiosurgery remain controversial. The authors review the stereotactic radiosurgery outcomes for Grade II and III meningiomas. METHODS: A comprehensive literature search was performed using PubMed to identify all radiosurgery series reporting the treatment outcomes for Grade II and III meningiomas. Case reports and case series involving fewer than 10 patients were excluded. RESULTS: From 1998 to 2013, 19 radiosurgery series were published in which 647 Grade II and III meningiomas were treated. Median tumor volumes were 2.2-14.6 cm(3). The median margin doses were 14-21 Gy, although generally the margin doses for Grade II meningiomas were 16-20 Gy and the margin doses for Grade III meningiomas were 18-22 Gy. The median 5-year PFS was 59% for Grade II tumors and 13% for Grade III tumors, which may have been affected by patient age, prior radiation therapy, tumor volume, and radiosurgical dose and timing. The median complication rate following radiosurgery was 8%. CONCLUSIONS: The current data for radiosurgery suggest that it has a role in the management of residual or recurrent Grade II and III meningiomas. However, better studies are needed to fully define this role. Due to the relatively low prevalence of these tumors, it is unlikely that prospective studies will be feasible. As such, well-designed retrospective analyses may improve our understanding of the effect of radiosurgery on tumor recurrence and patient survival and the incidence and impact of treatment-induced complications.


Assuntos
Neoplasias Encefálicas/cirurgia , Neoplasias Meníngeas/cirurgia , Meningioma/cirurgia , Radiocirurgia/métodos , Bases de Dados Bibliográficas/estatística & dados numéricos , Feminino , Humanos , Masculino , Neoplasias Meníngeas/diagnóstico , Meningioma/diagnóstico , Estudos Retrospectivos , Resultado do Tratamento , Carga Tumoral
17.
World Neurosurg ; 171: 108-113, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36610643

RESUMO

BACKGROUND: Intraoperative neuromonitoring (IONM) is routinely used during neurosurgical procedures. Magnetic resonance imaging (MRI)-guided laser interstitial thermal therapy (LITT) is increasingly being used in patients with various brain lesions. Use of IONM (transcranial motor evoked potential [TcMEP] and electromyography [EMG]) during LITT of a brain lesion has not been described previously. METHODS: In this report, we describe a 70-year-old man who presented with motor weakness in whom imaging revealed a left thalamic lesion. Due to the difficulty in accessing the lesion and proximity to the motor tracts, patient was offered MRI-guided LITT using TcMEP and EMG. RESULTS: The patient underwent satisfactory ablation of the lesion with successful recording of the TcMEP and EMG. Technical nuances related to the set-up and procedure is discussed in this report. No procedure-related complications were encountered. CONCLUSIONS: We describe the first report of safety and feasibility of TcMEP and EMG during MRI-guided LITT for left thalamic glioblasatoma. This report paves the way for further prospective investigations regarding the utility of this technique for eloquent brain tumors.


Assuntos
Neoplasias Encefálicas , Glioblastoma , Terapia a Laser , Masculino , Humanos , Idoso , Glioblastoma/cirurgia , Potencial Evocado Motor/fisiologia , Eletromiografia , Estudos de Viabilidade , Neoplasias Encefálicas/cirurgia , Imageamento por Ressonância Magnética/métodos , Lasers , Terapia a Laser/métodos
18.
World Neurosurg ; 175: e984-e993, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37087034

RESUMO

OBJECTIVES: The trend of practice pattern and impact on health care utilization for surgery and radiation therapy (RT) in patients with glomus jugulare tumors (GJTs) is not well defined. METHODS: The IBM (Armonk, NY) MarketScan database was queried using the ICD-9/10 and CPT 4th edition, 2000-2020. We included patients ≥18 years of age who underwent either surgery or RT with at-least 1-year follow-up. We compared the health care utilization at 3-month, 6-month, and 1-year follow up using the inverse probability of treatment weight technique. RESULTS: A cohort of 333 patients was identified. Of these, 72.7% (n = 242) underwent RT and 27.3% (n = 91) underwent surgery. RT use increased from 2002-2004 (50%) to 2017-2019 (91%). Patients in the surgery cohort were younger (median age 49 vs. 56 years, P < 0.0001) and had a higher 3+ comorbidity index (34% vs. 30%, P = 0.43) compared with patients in the RT cohort. Patients who underwent surgery had higher complications at index hospitalization (22% vs. 6%, P < 0.0001) and at 30 days (14% vs. 5%, P = 0.0042). No difference in combined index and 6- or 12-month payments were noted (6-months: surgery, $66m108, RT: $43m509, P = 0.1034; 12-months: surgery, $73,259, RT: $51,576, P = 0.1817). Only 4% of patients who had initial RT underwent RT and none underwent surgery at 12 months, whereas 6% of patients who had initial surgery underwent RT and 2% underwent surgery at 12 months. CONCLUSIONS: RT plays an increasingly important role in the treatment for patients with GJTs, with fewer complications and a comparable health care utilization at 1 year.


Assuntos
Tumor do Glomo Jugular , Radiocirurgia , Humanos , Pessoa de Meia-Idade , Tumor do Glomo Jugular/patologia , Estudos Retrospectivos , Radiocirurgia/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Resultado do Tratamento , Seguimentos
19.
World Neurosurg ; 173: e341-e350, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36796626

RESUMO

OBJECTIVE: To compare the impact of different management strategies on diagnosis of new-onset mental health disorders (MHDs) in patients with vestibular schwannoma (VS) and health care utilization at 1-year follow-up. METHODS: MarketScan databases were queried using the International Classification of Diseases, Ninth Revision and Tenth Revision and Current Procedural Terminology, Fourth Edition, 2000-2020. We included patients ≥18 years old with a diagnosis of VS who underwent clinical observation, surgery, or stereotactic radiosurgery (SRS) with at least 1 year of follow-up. We looked at health care outcomes and MHDs at 3-month, 6-month, and 1-year follow-up. RESULTS: The database search identified 23,376 patients. Of these, 94.2% (n = 22,041) were managed conservatively with clinical observation at the initial diagnosis, and 2% (n = 466) underwent surgery. The surgery cohort had the highest incidence of new-onset MHDs followed by SRS and clinical observation cohorts at 3 months (surgery: 17%; SRS: 12%; clinical observation: 7%), 6 months (surgery: 20%; SRS: 16%; clinical observation: 10%), and 12 months (surgery: 27%; SRS: 23%; clinical observation: 16%) (P < 0.0001). The median difference in combined payments between patients with and without MHDs was highest in the surgery cohort followed by SRS and clinical observation cohorts at all time points (12 months: surgery: $14,469; SRS: $10,557; clinical observation: $6439; P = 0.0002). CONCLUSIONS: Compared with clinical observation only, patients who underwent surgery for VS were 2 times more likely and patients who underwent SRS were 1.5 times more likely to develop MHDs with corresponding increase in health care utilization at 1-year follow-up.


Assuntos
Neuroma Acústico , Radiocirurgia , Humanos , Adolescente , Resultado do Tratamento , Estudos Retrospectivos , Neuroma Acústico/complicações , Neuroma Acústico/cirurgia , Saúde Mental , Aceitação pelo Paciente de Cuidados de Saúde , Seguimentos
20.
J Clin Neurosci ; 111: 86-90, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-36989768

RESUMO

BACKGROUND: Intraoperative magnetic resonance imaging (iMRI) use in transsphenoidal approach (TSA) for pituitary tumors (PTs) has been reported to improve the extent of resection (EOR). The aim of this study is to report the trends and the impact of iMRI on healthcare utilization in patients who underwent TSA for PTs. MATERIALS AND METHODS: MarketScan database were queried using the ICD-9/10 and CPT-4, from 2004 to 2020. We included patients ≥ 18 years of age PTs with > 1 year follow-up. Outcomes were length of stay (LOS), discharge disposition, hospital/emergency room (ER) re-admissions, outpatient services, medication refills and corresponding payments. RESULTS: A cohort of 10,192 patients were identified from the database, of these 141 patients (1.4%) had iMRI used during the procedure. Use of iMRI for PTs remained stable (2004-2007: 0.85%; 2008-2011: 1.6%; 2012-2015:1.4% and 2016-2019: 1.46%). No differences in LOS (median 3 days each), discharge to home (93% vs. 94%), complication rates (7% vs. 13%) and payments ($34604 vs. $33050) at index hospitalization were noted. Post-discharge payments were not significantly different without and with iMRI use at 6-months ($8315 vs. $ 7577, p = 0.7) and 1-year ($13,654 vs. $ 14,054, p = 0.70), following the index procedure. CONCLUSION: iMRI use during TSA for PTs remained stable with no impact on LOS, complications, discharge disposition and index payments. Also, there was no difference in combined index payments at 6-months, and 1-year after the index procedure in patients with and without iMRI use for PTs.


Assuntos
Adenoma , Neoplasias Hipofisárias , Humanos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Assistência ao Convalescente , Adenoma/cirurgia , Alta do Paciente , Imageamento por Ressonância Magnética/métodos , Aceitação pelo Paciente de Cuidados de Saúde , Estudos Retrospectivos
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