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1.
Ophthalmic Plast Reconstr Surg ; 40(5): e184-e186, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38722765

RESUMEN

Dural carotid-cavernous fistulas (DCF) typically drain into the superior ophthalmic vein. Predominant involvement of the inferior ophthalmic vein (IOV) is rare, with only 4 documented cases in the literature. Here, the authors describe a case of a 51-year-old man who presented with acute left-sided proptosis, dysmotility, and vision loss and was found to have an IOV-dominant type D dural carotid-cavernous fistulas. The fistula could not be embolized by transfemoral endovascular access or orbitotomy alone and was ultimately managed with combined orbitotomy and direct IOV puncture. All previous reports of IOV-dominant dural carotid-cavernous fistulas in the literature were similarly inaccessible via the transfemoral approach. This case highlights the challenges of IOV cutdown and proposes an alternative management strategy. When IOV cutdown is precluded by the fragile, collapsed, or deep nature of the vessel, conversion to percutaneous IOV puncture may offer a safe and effective approach and mitigate the risks of direct puncture alone.


Asunto(s)
Fístula del Seno Cavernoso de la Carótida , Embolización Terapéutica , Órbita , Punciones , Humanos , Masculino , Persona de Mediana Edad , Embolización Terapéutica/métodos , Órbita/irrigación sanguínea , Punciones/métodos , Fístula del Seno Cavernoso de la Carótida/terapia , Fístula del Seno Cavernoso de la Carótida/diagnóstico , Fístula del Seno Cavernoso de la Carótida/cirugía , Venas/cirugía , Procedimientos Quirúrgicos Oftalmológicos/métodos
2.
Orbit ; 40(1): 44-50, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33317388

RESUMEN

Purpose: The authors aim to characterize oculofacial plastic surgery-related online interest that may be useful in forecasting demand and in designing patient-directed online resources. Methods: The authors queried Google Trends for over 100 oculofacial plastic surgery terms. The main outcome measure was the top 50 oculofacial plastic surgery-related search terms from 2004 to 2020. Secondary outcomes were trends, including seasonality, and search volume changes during the COVID-19 lockdown (March-May 2020) compared to 2018-2019. Terms were analyzed individually and in thematic categories; controlled against generic search terms to account for general internet traffic. Results: Between 2004 and 2020, searches for oculofacial plastic surgery altogether increased, surpassing the rate of internet traffic growth. One thematic category - eyelid malpositions - decreased month-over-month. The top five terms were "face lift," "Bell's palsy," "puffy eyes," "dark circles under eyes," and "chalazion." Eyelid neoplasms searches peaked in summer (R2  = 0.880) whereas cosmetic (R2  = 0.862), symptoms (R 2 = 0.907), and surgeries (R 2 = 0.140) peaked in winter. Overall, oculofacial-related searches decreased during the COVID-19 lockdown, although thyroid eye disease interest increased compared to 2018 or 2019 (+68.6%; adj. p = .005). Oculofacial plastic surgery interest in 2020 was inversely correlated to "COVID-19" searches (r = -0.76, p < .001). Conclusions: Oculofacial plastic surgery searches increased since 2004 at a pace greater than that ascribed to internet traffic growth. The most searched terms were "face lift," "Bell's palsy," "puffy eyes," "dark circles under eyes," and "chalazion." Almost all oculofacial-related searches decreased during the COVID-19 lockdown.


Asunto(s)
COVID-19/epidemiología , Sistemas en Línea/tendencias , Procedimientos de Cirugía Plástica/tendencias , SARS-CoV-2 , Motor de Búsqueda/tendencias , Cirugía Plástica/tendencias , Estudios Transversales , Humanos , Conducta en la Búsqueda de Información , Procedimientos Quirúrgicos Oftalmológicos , Ritidoplastia
4.
J Neurosurg Spine ; 41(1): 105-114, 2024 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-38608294

RESUMEN

OBJECTIVE: Chiari malformations (CMs) are a group of congenital or acquired disorders characterized by hindbrain overcrowding into an underdeveloped posterior cranial fossa. CM is considered largely sporadic-however, there exists growing evidence of transmissible genetic underpinnings. The purpose of this systematic review of all familial studies of CM was to investigate the existence of an inherited component and provide recommendations to manage and monitor at-risk family members. METHODS: This paper includes the following: 1) a unique case report of dizygotic twins who presented at the Toronto Western Hospital Spinal Cord Clinic with symptomatic CM type 1 (CM-1) and syringomyelia; and 2) a systematic review of familial CM. The EMBASE and MEDLINE databases were searched on June 27, 2023, in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Only articles in the English language concerning the diagnosis of CM in > 1 human family member presented as a case study, case series, or literature review were included. RESULTS: Among the 29 articles included in the final analysis, a total of 34 families with CM were analyzed. An average of 3 cases of CM were found per family among all generations. Eighty-one cases (88%) reported CM-1, whereas the other 11 (12%) cases reported either CM-0, CM-1.5, or tonsillar ectopia. A syrinx was present in 37 (54%) cases, with 14 (38%) of these patients also reporting a skeletal abnormality, the most common comorbidity. Most family members diagnosed with CM were siblings (18; 35%), followed by monozygotic twins/triplets (12; 23%). CONCLUSIONS: Patients most often presented with headaches, sensory disturbances, or generalized symptoms. Overall, there exists mounting evidence for a hereditary component of CM. It is unlikely to be explained by a classic mendelian inheritance pattern, but is rather a polygenic architecture influenced by variable penetrance, cosegregation, and entirely nongenetic factors. For first-degree relatives of those affected by CM, the authors' findings may influence clinicians to conduct closer clinical and radiographic monitoring, promote patient education, and consider earlier genetic testing.


Asunto(s)
Malformación de Arnold-Chiari , Humanos , Malformación de Arnold-Chiari/genética , Malformación de Arnold-Chiari/cirugía , Siringomielia/genética , Siringomielia/diagnóstico por imagen , Gemelos Dicigóticos/genética
5.
JMIR Ment Health ; 9(3): e35253, 2022 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-35357320

RESUMEN

BACKGROUND: The epidemiology of mental health disorders has important theoretical and practical implications for health care service and planning. The recent increase in big data storage and subsequent development of analytical tools suggest that mining search databases may yield important trends on mental health, which can be used to support existing population health studies. OBJECTIVE: This study aimed to map depression search intent in the United States based on internet-based mental health queries. METHODS: Weekly data on mental health searches were extracted from Google Trends for an 11-year period (2010-2021) and separated by US state for the following terms: "feeling sad," "depressed," "depression," "empty," "insomnia," "fatigue," "guilty," "feeling guilty," and "suicide." Multivariable regression models were created based on geographic and environmental factors and normalized to the following control terms: "sports," "news," "google," "youtube," "facebook," and "netflix." Heat maps of population depression were generated based on search intent. RESULTS: Depression search intent grew 67% from January 2010 to March 2021. Depression search intent showed significant seasonal patterns with peak intensity during winter (adjusted P<.001) and early spring months (adjusted P<.001), relative to summer months. Geographic location correlated with depression search intent with states in the Northeast (adjusted P=.01) having higher search intent than states in the South. CONCLUSIONS: The trends extrapolated from Google Trends successfully correlate with known risk factors for depression, such as seasonality and increasing latitude. These findings suggest that Google Trends may be a valid novel epidemiological tool to map depression prevalence in the United States.

6.
Cornea ; 40(3): 282-291, 2021 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-33177410

RESUMEN

PURPOSE: Our study fills the spatiotemporal gaps in dry eye disease (DED) epidemiology by using Google Trends as a novel epidemiological tool for geographically mapping DED in relation to environmental risk factors. METHODS: We used Google Trends to extract DED-related queries estimating users' intent from 2004 to 2019 in the United States. We incorporated national climate data to generate heat maps comparing geographic, temporal, and environmental relationships of DED. Multivariable regression models were constructed to generate quadratic forecasts predicting DED and control searches. RESULTS: Our results illustrated the upward trend, seasonal pattern, environmental influence, and spatial relationship of DED search volume across the US geography. Localized patches of DED interest were visualized in urban areas. There was no significant difference in DED queries across the US census regions (P = 0.3543). Regression model 1 predicted DED queries per state (R2 = 0.61), with the significant predictor being urban population [r = 0.56, adjusted (adj.) P < 0.001, n = 50]; model 2 predicted DED searches over time (R2 = 0.97), with significant predictors being control queries (r = 0.85, adj. P = 0.0169, n = 190), time (r = 0.96, adj. P < 0.001, n = 190), time2 (r = 0.97, adj. P < 0.001, n = 190), and seasonality (winter r = -0.04, adj. P = 0.0196, n = 190; spring r = 0.10, adj. P < 0.001, n = 190). CONCLUSIONS: Our study used Google Trends as a novel epidemiologic approach to geographically mapping the US DED. Importantly, urban population and seasonality were stronger risk factors of DED searches than temperature, humidity, sunshine, pollution, or region. Our work paves the way for future exploration of geographic information systems for locating DED and other diseases through online population metrics.


Asunto(s)
Bases de Datos Factuales/tendencias , Síndromes de Ojo Seco/epidemiología , Internet/tendencias , Clima , Estudios Epidemiológicos , Geografía , Humanos , Prevalencia , Factores de Riesgo , Estaciones del Año , Estados Unidos/epidemiología
7.
Cureus ; 13(4): e14261, 2021 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-33959444

RESUMEN

A 29-year-old man with a medical and social history notable for smoking presented with progressive orbital congestion, conjunctival injection, and extraocular muscle enlargement consistent with thyroid eye disease (TED). On ophthalmologic examination, tortuous episcleral vessels and blood in Schlemm's canal on gonioscopy clued an alternative diagnosis. Cavernous sinus enhancement on computed tomography also suggested a retro-orbital process. Digital subtraction angiography confirmed a low-flow indirect carotid-cavernous fistula (CCF). He subsequently underwent endovascular embolization treatment. Ocular symptoms resolved by seven weeks, and he remained ocular symptom free at six months. Eye redness and proptosis frequently cause patients to seek medical attention. In the absence of a mass or signs of infection, TED is high on the differential, especially with a smoking history and even with normal thyroid parameters. However, CCF may lurk; the authors describe key diagnostic features and management.

8.
Stem Cells Int ; 2021: 6655372, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33628267

RESUMEN

PURPOSE: One of the leading causes of irreversible blindness worldwide, age-related macular degeneration (AMD) is a progressive disorder leading to retinal degeneration. While several treatment options exist for the exudative form of AMD, there are currently no FDA-approved treatments for the more common nonexudative (atrophic) form. Mounting evidence suggests that mitochondrial damage and retinal pigment epithelium (RPE) cell death are linked to the pathogenesis of AMD. Human retinal progenitor cells (hRPCs) have been studied as a potential restorative therapy for degenerative conditions of the retina; however, the effects of hRPC treatment on retinal cell survival in AMD have not been elucidated. METHODS: In this study, we used a cell coculture system consisting of hRPCs and AMD or age-matched normal cybrid cells to characterize the effects of hRPCs in protecting AMD cybrids from cellular and mitochondrial damage and death. RESULTS: AMD cybrids cocultured with hRPCs showed (1) increased cell viability; (2) decreased gene expression related to apoptosis, autophagy, endoplasmic reticulum (ER) stress, and antioxidant pathways; and (3) downregulation of mitochondrial replication genes compared to AMD cybrids without hRPC treatment. Furthermore, hRPCs cocultured with AMD cybrids showed upregulation of (1) neuronal and glial markers, as well as (2) putative neuroprotective factors, responses not found when hRPCs were cocultured with age-matched normal cybrids. CONCLUSION: The current study provides the first evidence that therapeutic benefits may be obtainable using a progenitor cell-based approach for atrophic AMD. Our results suggest that bidirectional interactions exist between hRPCs and AMD cybrids such that hRPCs release trophic factors that protect the cybrids against the cellular and mitochondrial changes involved in AMD pathogenesis while, conversely, AMD cybrids upregulate the release of these neuroprotective factors by hRPCs while promoting hRPC differentiation. These in vitro data provide evidence that hRPCs may have therapeutic potential in atrophic AMD.

9.
World Neurosurg ; 133: e308-e319, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31520752

RESUMEN

OBJECTIVE: We performed a retrospective analysis in a cohort of 1185 patients at our institution who were identified as undergoing ≥1 head computed tomography (CT) examinations during their inpatient stay on the neurosurgery service, to quantify the number, type, and associated radiation burden of head CT procedures performed by the neurosurgery service. METHODS: CT procedure records and radiology reports were obtained via database search and directly validated against records retrieved from manual chart review. Next, dosimetry data from the head CT procedures were extracted via automated text mining of electronic radiology reports. RESULTS: Among 4510 identified adult head CT procedures, 88% were standard head CT examinations. A total of 3.65 ± 3.60 head CT scans were performed during an average adult admission. The most common primary diagnoses were neoplasms, trauma, and other hemorrhage. The median cumulative effective dose per admission was 5.66 mSv (range, 1.06-84.5 mSv; mean, 8.56 ± 8.95 mSv). The median cumulative effective dose per patient was 6.4 mSv (range, 1.1-127 mSv; mean, 9.26 ± 10.0 mSv). CONCLUSIONS: The median cumulative radiation burden from head CT imaging in our cohort equates approximately to a single chest CT scan, well within accepted limits for safe CT imaging in adults. Refined methods are needed to characterize the safety profile of the few pediatric patients identified in our study.


Asunto(s)
Cabeza/efectos de la radiación , Neuroimagen/efectos adversos , Seguridad del Paciente , Dosis de Radiación , Tomografía Computarizada por Rayos X/efectos adversos , Adolescente , Adulto , Factores de Edad , Anciano , Anciano de 80 o más Años , Niño , Preescolar , Femenino , Humanos , Lactante , Masculino , Persona de Mediana Edad , Admisión del Paciente , Estudios Retrospectivos , Adulto Joven
10.
Cureus ; 11(4): e4426, 2019 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-31245213

RESUMEN

Moyamoya disease (MMD) is a rare, chronic vaso-occlusive disease affecting the arteries of the Circle of Willis, leading to the development of characteristic collateral vessels. In this paper, we present a case of a 35-year-old Hispanic male who presented to the emergency department with new onset headaches. On examination, Glasgow Coma Scale score was 3T. The patient was investigated with head CT scan and cerebral angiogram, diagnosed as MMD, and treated with emergent ventriculostomy. Ultimately, the patient underwent extracranial-intracranial (EC-IC) bypass surgery for treatment of Moyamoya.

11.
Brain Tumor Res Treat ; 7(2): 122-131, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-31686443

RESUMEN

BACKGROUND: Racial differences in American patients undergoing brain tumour surgery remain poorly characterized within urban medical centres. Our objective was to assess racial differences in operative brain tumour patients at a single academic hospital in Los Angeles, California. METHODS: We reviewed medical records of adult patients undergoing craniotomy for tumour resection from March 2013 to January 2017 at UCLA Medical Centre. Patients were categorized as Asian, Hispanic, Black, or White. Racial cohorts were matched on demographic variables for comparisons. Our primary outcome was post-operative length of stay (LOS). Secondary outcomes included hospital mortality and discharge disposition. RESULTS: In this study, 462 patients identified as Asian (15.1%), Hispanic (8.7%), Black (3.9%), or White (72.3%). After cohort matching, non-White patients had elevated risk of prolonged LOS [odds ratio (OR)=2.62 (1.44, 4.76)]. No differences were observed in hospital mortality or non-routine discharge. Longer LOS was positively correlated with non-routine discharge [rpb (458)=0.41, p<0.001]. Black patients with government insurance had average LOS 2.84 days shorter than Black patients with private insurance (p=0.04). Among Hispanics, government insurance was associated with non-routine discharge [OR=4.93 (1.03, 24.00)]. CONCLUSION: Racial differences manifested as extended LOS for non-White patients, with comparable rates of hospital mortality and non-routine discharge across races. Prolonged LOS loosely reflected complicated clinical course with greater risk of adverse discharge disposition. Private insurance coverage predicted markedly lower risk of non-routine discharge for Hispanic patients, and LOS of three additional days among Black patients. Further research is needed to elucidate the basis of these differences.

12.
J Clin Neurosci ; 65: 112-120, 2019 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-31078378

RESUMEN

Superior semicircular canal dehiscence (SSCD) is caused by a fistula in the arcuate eminence, creating vestibular and auditory disturbances. We aim to determine the effects of gender and age on symptom prevalence and resolution in patients with SSCD. A Boolean search was conducted through four separate scientific databases. Full-text English articles for SSCD patients, who underwent surgery were included. Demographics and outcomes were extracted. A total of 198 patients were identified, and available for quantitative analysis. Between genders, there were no differences in the prevalence of pre- or post-operative symptomology. Both genders had statistically significant improvement in symptomatology with females experiencing significantly high rates of hearing loss improvement compared to male patients. Compared to their younger cohort, patients over 65 had similar symptom frequencies before and after surgery with similar rates of symptom resolution. SSCD repair is safe and effective for resolving auditory and vestibular symptoms. Gender and age may not be strong predictors of patient presentation or symptom resolution. Gender and age-associated factors may not influence patient outcomes.


Asunto(s)
Pérdida Auditiva/etiología , Complicaciones Posoperatorias , Canales Semicirculares/cirugía , Adulto , Factores de Edad , Anciano , Femenino , Trastornos de la Audición , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores Sexuales , Síndrome , Vestíbulo del Laberinto
13.
Oper Neurosurg (Hagerstown) ; 16(2): 138-146, 2019 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-29767779

RESUMEN

BACKGROUND: Survival outcomes for patients with liver disease who suffer an intracranial hemorrhage (ICH) have not been thoroughly investigated. OBJECTIVE: To understand survival outcomes for 3 groups: (1) patients with an admission diagnosis of liver disease (end-stage liver disease [ESLD] or non-ESLD) who developed an ICH in the hospital, (2) patients with ESLD who undergo either operative vs nonoperative management, and (3) patients with ESLD on the liver transplant waitlist who developed an ICH in the hospital. METHODS: We retrospectively reviewed hospital charts from March 2006 through February 2017 of patients with liver disease and an ICH evaluated by the neurosurgery service at a single academic medical center. The primary outcome was survival. RESULTS: We included a total of 53 patients in this study. The overall survival for patients with an admission diagnosis of liver disease who developed an ICH (n = 29, 55%) in the hospital was 22%. Of those patients with an admission diagnosis of liver disease, 27 patients also had ESLD. Kaplan-Meier analysis found no significant difference in survival for ESLD patients (n = 33, 62%) according to operative status. There were 11 ESLD patients on the liver transplant waitlist. The overall survival for patients with ESLD on the liver transplant waitlist who suffered an in-hospital ICH (n = 7, 13%) was 14%. CONCLUSION: ICH in the setting of liver disease carries a grave prognosis. Also, a survival advantage for surgical hematoma evacuation in ESLD patients is not clear.


Asunto(s)
Enfermedad Hepática en Estado Terminal/complicaciones , Hepatitis C Crónica/complicaciones , Mortalidad Hospitalaria , Hemorragias Intracraneales/terapia , Cirrosis Hepática Alcohólica/complicaciones , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Adulto , Anciano , Femenino , Humanos , Hemorragias Intracraneales/complicaciones , Estimación de Kaplan-Meier , Tiempo de Internación , Hepatopatías/complicaciones , Trasplante de Hígado , Masculino , Persona de Mediana Edad , Mortalidad , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Listas de Espera
14.
World Neurosurg ; 113: 244-248, 2018 May.
Artículo en Inglés | MEDLINE | ID: mdl-29374609

RESUMEN

OBJECTIVE: Duraplasty, a common neurosurgical intervention, involves synthetic or biological graft placement to ensure dural closure. The objective of this study is to advance our understanding of the use of dural substitutes in cranial surgery. METHODS: The PubMed database was systematically searched to identify studies published over the past decade (2007-2017) that described duraplasty procedures. Clinical data were disaggregated and analyzed for the comparisons of biological versus synthetic grafts. RESULTS: A total of 462 cases were included in the quantitative synthesis. Overall, the most common indication for duraplasty was tumor resection (53%). Allografts were more frequently used in decompression for Chiari malformations compared with xenografts and synthetic grafts (P < 0.001). Xenografts were more frequently used in decompressive hemicraniectomy procedures for evacuation of acute subdural hematomas over allografts and synthetics (P < 0.001). Synthetic grafts were more frequently used in tumor cases than biological grafts (P = 0.002). The cumulative complication rate for dural substitutes of all types was 11%. There were no significant differences in complication rates among the 3 types of dural substitutes. CONCLUSIONS: Dural substitutes are commonly used to ensure dural closure in a variety of cranial procedures. This study provides greater insight into duraplasty practices and highlights the moderate complication rate associated with the procedure. Future studies are needed to determine the safety and efficacy of such procedures in larger prospective cohorts.


Asunto(s)
Materiales Biocompatibles/administración & dosificación , Duramadre/cirugía , Procedimientos Neuroquirúrgicos/métodos , Complicaciones Posoperatorias/diagnóstico , Trasplante Autólogo/métodos , Materiales Biocompatibles/efectos adversos , Duramadre/patología , Humanos , Procedimientos Neuroquirúrgicos/efectos adversos , Complicaciones Posoperatorias/etiología , Estudios Prospectivos , Trasplante Autólogo/efectos adversos
15.
World Neurosurg ; 114: e42-e50, 2018 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-29452318

RESUMEN

BACKGROUND: Superior semicircular canal dehiscence (SSCD) is a bony defect in the osseous shell of the petrous temporal bone. The pathophysiological association between osteoporosis and SSCD remains poorly understood. We investigated the relationship between bone metabolic markers and symptoms in patients with SSCD. METHODS: We collected patient demographics and clinical parameters for adult patients diagnosed with SSCD on high-resolution computed tomography scans. We used point-biserial correlation analysis to investigate the relationship between bone metabolic markers and symptoms in patients with SSCD. We compared clinical symptoms before and after surgical repair of SSCD through a middle fossa craniotomy using McNemar's test for paired comparisons of binary measures. RESULTS: We included a total of 99 patients (64 females and 35 males; average age 52 years; 118 surgeries). The level of serum calcium correlated with the need for a second surgery (rpb = -0.35, P = 0.001). Postoperative calcium supplementation negatively correlated with improvement in dizziness (rpb = -0.36, P = 0.01). The level of 25-hydroxyvitamin D correlated with preoperative hyperacusis (rpb = -0.98, P = 0.02) and postoperative autophony (rpb = 0.96, P = 0.04). Postoperative vitamin D supplementation positively correlated with hearing decline (rpb = 0.04, P = 0.04) The level of thyroid stimulating hormone correlated with preoperative autophony, amplification, and tinnitus (rpb = -0.71, rpb = -0.75, rpb = -0.70, all P < 0.001). CONCLUSIONS: Bone metabolic markers could be important in the clinical assessment of SSCD patients and could be potential targets for symptom management.


Asunto(s)
Procedimientos Quirúrgicos Otológicos/efectos adversos , Canales Semicirculares/metabolismo , Dehiscencia de la Herida Operatoria/metabolismo , Acúfeno/metabolismo , Adulto , Anciano , Craneotomía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Procedimientos Quirúrgicos Otológicos/métodos , Estudios Retrospectivos , Dehiscencia de la Herida Operatoria/diagnóstico , Hueso Temporal/metabolismo , Hueso Temporal/cirugía , Acúfeno/cirugía , Vértigo/metabolismo , Vértigo/fisiopatología
16.
J Neurosurg ; : 1-6, 2018 Jun 01.
Artículo en Inglés | MEDLINE | ID: mdl-29932383

RESUMEN

OBJECTIVEMeningiomas that appear hypervascular on neuroimaging could be amenable to preoperative embolization. However, methods for measuring hypervascularity have not been described, nor has the benefit of preoperative embolization been adjudicated. The objective of this study was to show a relationship between flow void volume (measured on MRI) and intraoperative estimated blood loss (EBL) in nonembolized meningiomas.METHODSThe authors performed volumetric analyses of 51 intracranial meningiomas (21 preoperatively embolized) resected at their institution. Through the use of image segmentation software and a voxel-based segmentation method, flow void volumes were measured on T2-weighted MR images. This metric was named the Meningioma Vascularity Index (MVI). The primary outcomes were intraoperative EBL and perioperative blood transfusion.RESULTSIn the nonembolized group, the MVI correlated with intraoperative EBL when controlling for tumor volume (r = 0.55, p = 0.002). The MVI also correlated with perioperative blood transfusion (point-biserial correlation [rpb] = 0.57, p = 0.001). A greater MVI was associated with an increased risk of blood transfusion (odds ratio [OR] 5.79, 95% confidence interval [CI] 1.15-29.15) and subtotal resection (OR 7.64, 95% CI 1.74-33.58). In the embolized group, those relationships were not found. There were no significant differences in MVI, intraoperative EBL, or blood transfusion across groups.CONCLUSIONSThis study clearly shows a relationship between MVI and intraoperative EBL in nonembolized meningiomas when controlling for tumor volume. The MVI is a potential biomarker for tumors that would benefit from embolization.

17.
Neuro Oncol ; 20(6): 764-775, 2018 05 18.
Artículo en Inglés | MEDLINE | ID: mdl-29136244

RESUMEN

Background: Clinical trials of therapies directed against nodes of the signaling axis of phosphatidylinositol-3 kinase/Akt/mammalian target of rapamycin (mTOR) in glioblastoma (GBM) have had disappointing results. Resistance to mTOR inhibitors limits their efficacy. Methods: To determine mechanisms of resistance to chronic mTOR inhibition, we performed tandem screens on patient-derived GBM cultures. Results: An unbiased phosphoproteomic screen quantified phosphorylation changes associated with chronic exposure to the mTOR inhibitor rapamycin, and our analysis implicated a role for glycogen synthase kinase (GSK)3B attenuation in mediating resistance that was confirmed by functional studies. A targeted short hairpin RNA screen and further functional studies both in vitro and in vivo demonstrated that microtubule-associated protein (MAP)1B, previously associated predominantly with neurons, is a downstream effector of GSK3B-mediated resistance. Furthermore, we provide evidence that chronic rapamycin induces microtubule stability in a MAP1B-dependent manner in GBM cells. Additional experiments explicate a signaling pathway wherein combinatorial extracellular signal-regulated kinase (ERK)/mTOR targeting abrogates inhibitory phosphorylation of GSK3B, leads to phosphorylation of MAP1B, and confers sensitization. Conclusions: These data portray a compensatory molecular signaling network that imparts resistance to chronic mTOR inhibition in primary, human GBM cell cultures and points toward new therapeutic strategies.


Asunto(s)
Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Glioblastoma/patología , Proteínas Asociadas a Microtúbulos/metabolismo , ARN Interferente Pequeño/genética , Sirolimus/farmacología , Serina-Treonina Quinasas TOR/metabolismo , Animales , Antibióticos Antineoplásicos/farmacología , Apoptosis , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/metabolismo , Proliferación Celular , Quinasas MAP Reguladas por Señal Extracelular/antagonistas & inhibidores , Quinasas MAP Reguladas por Señal Extracelular/genética , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Glioblastoma/tratamiento farmacológico , Glioblastoma/genética , Glucógeno Sintasa Quinasa 3 beta/antagonistas & inhibidores , Glucógeno Sintasa Quinasa 3 beta/genética , Glucógeno Sintasa Quinasa 3 beta/metabolismo , Humanos , Masculino , Ratones , Ratones Endogámicos NOD , Ratones SCID , Proteínas Asociadas a Microtúbulos/antagonistas & inhibidores , Proteínas Asociadas a Microtúbulos/genética , Fosfatidilinositol 3-Quinasas/genética , Fosfatidilinositol 3-Quinasas/metabolismo , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/genética , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/antagonistas & inhibidores , Serina-Treonina Quinasas TOR/genética , Células Tumorales Cultivadas , Ensayos Antitumor por Modelo de Xenoinjerto
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