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PURPOSE OF REVIEW: Spinal cord injury (SCI) is a major cause of morbidity and mortality, posing a significant financial burden on patients and the healthcare system. While little can be done to reverse the primary mechanical insult, minimizing secondary injury due to ischemia and inflammation and avoiding complications that adversely affect neurologic outcome represent major goals of management. This article reviews important considerations in the acute critical care management of SCI to improve outcomes. RECENT FINDINGS: Neuroprotective agents, such as riluzole, may allow for improved neurologic recovery but require further investigation at this time. Various forms of neuromodulation, such as transcranial magnetic stimulation, are currently under investigation. Early decompression and stabilization of SCI is recommended within 24 h of injury when indicated. Spinal cord perfusion may be optimized with a mean arterial pressure goal from a lower limit of 75-80 to an upper limit of 90-95 mmHg for 3-7 days after injury. The use of corticosteroids remains controversial; however, initiation of a 24-h infusion of methylprednisolone 5.4 mg/kg/hour within 8 h of injury has been found to improve motor scores. Attentive pulmonary and urologic care along with early mobilization can reduce in-hospital complications.
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Cuidados Críticos , Traumatismos da Medula Espinal , Humanos , Traumatismos da Medula Espinal/terapia , Cuidados Críticos/métodos , Fármacos Neuroprotetores/uso terapêuticoRESUMO
PURPOSE: Respiratory failure following mechanical thrombectomy (MT) for acute ischemic stroke (AIS) is a known complication, and requirement of tracheostomy is associated with worse outcomes. Our objective is to evaluate characteristics associated with tracheostomy timing in AIS patients treated with MT. METHODS: The National Inpatient Sample was queried for adult patients treated with MT for AIS from 2016 to 2019. Baseline demographic characteristics, comorbidities, and inpatient outcomes were analyzed for associations in patients who received tracheostomy. Timing of early tracheostomy (ETR) was defined as placement before day 8 of hospital stay. RESULTS: Of 3505 AIS-MT patients who received tracheostomy, 915 (26.1%) underwent ETR. Patients who underwent ETR had shorter length of stay (LOS) (25.39 days vs 32.43 days, p < 0.001) and lower total hospital charges ($483,472.07 vs $612,362.86, p < 0.001). ETR did not confer a mortality benefit but was associated with less acute kidney injury (OR, 0.697; p = 0.013), pneumonia (OR, 0.449; p < 0.001), and sepsis (OR, 0.536; p = 0.002). CONCLUSION: An expected increase in complications and healthcare resource utilization is seen in AIS-MT patients receiving tracheostomy, likely reflecting the severity of patients' post-stroke neurologic injury. Among these high-risk patients, ETR was predictive of shorter LOS and fewer complications.
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Isquemia Encefálica , AVC Isquêmico , Acidente Vascular Cerebral , Adulto , Humanos , Traqueostomia , Resultado do Tratamento , Acidente Vascular Cerebral/etiologia , Trombectomia , Estudos Retrospectivos , Isquemia Encefálica/cirurgia , Isquemia Encefálica/complicaçõesRESUMO
STUDY DESIGN: Systematic review. OBJECTIVE: Evaluate characteristics of patients with thoracolumbar injury classification and severity (TLICS) score of 4 (To4) severity traumatic thoracolumbar injury. SUMMARY OF BACKGROUND DATA: The TLICS score is used to predict the need for operative versus nonoperative management in adult patients with traumatic thoracolumbar injury. Ambiguity exists in its application and score categorization. METHODS: A systematic review of the literature was performed. The databases of MEDLINE, Embase, Web of Science, and Cochrane Review were queried. Studies included adults with traumatic thoracolumbar injury with assigned TLICS score and description of management strategy. RESULTS: A total of 16 studies met inclusion criteria representing 1911 adult patients with traumatic thoracolumbar injury. There were 503 (26.32%) patients with To4, of which 298 (59.24%) were operative. Studies focusing on the thoracolumbar junction and AO Type A fracture morphology had To4 patient incidences of 11.15% and 52.94%, respectively. Multiple studies describe better quality of life, pain scores, and radiographic outcomes in To4 who underwent operative treatment patients. CONCLUSION: To4 injuries are more commonly AO Type A and located in the thoracolumbar junction in adult patients with traumatic thoracolumbar injury. Despite ambiguous recommendations regarding treatment provided by TLICS, outcomes favor operative intervention in this subset of traumatic thoracolumbar injury patients.
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Vértebras Lombares , Qualidade de Vida , Fraturas da Coluna Vertebral , Adulto , Humanos , Escala de Gravidade do Ferimento , Vértebras Lombares/diagnóstico por imagem , Vértebras Lombares/cirurgia , Vértebras Lombares/lesões , Estudos Retrospectivos , Fraturas da Coluna Vertebral/cirurgia , Vértebras Torácicas/cirurgia , Vértebras Torácicas/lesõesRESUMO
BACKGROUND: Due to prohibitive perioperative risk factors, optimal treatment for chronic subdural hematomas (cSDH) in the elderly remains unclear. Minimally invasive techniques are a viable option and include bedside subdural evacuation port system (SEPS), as well as prevention of recurrence with middle meningeal artery (MMA) embolization. We present a case series of elderly patients undergoing combined transradial MMA embolization and bed-side craniostomy as primary treatment for cSDH. METHODS: Patients 70 years and older from 2019 to 2020 that underwent single setting, awake transradial MMA embolization with concurrent SEPS placement under local anesthesia were included. Those with prior treatments, interventions performed under general anesthesia, or with less than 60-day follow-up were excluded. Descriptive analyses of baseline characteristics, radiologic parameters, comorbidities, and outcome measures were completed. RESULTS: Twenty elderly patients (mean age of 81.0 years) with multiple comorbidities underwent 28 MMA embolization+SEPS procedures as primary treatment for cSDH. Mean cSDH thickness was 1.8cm±0.6 cm with 7.3±3.9 mm midline shift. All patients tolerated the procedure well. 1/20 (5.0%) patients died within 30 days of the procedure. A majority of patients were discharged to home (12/20; 60.0%). There was an average of 3.6-month follow-up and one patient (5.0%) developed recurrence in the follow-up period requiring further intervention. CONCLUSIONS: In select elderly patients with high perioperative risk factors, primary treatment of cSDH using awake transradial MMA embolization+SEPS placement is a minimally invasive, feasible, and safe option. Further comparative studies are warranted to evaluate efficacy of the treatment.
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Embolização Terapêutica , Hematoma Subdural Crônico , Humanos , Idoso , Idoso de 80 Anos ou mais , Hematoma Subdural Crônico/cirurgia , Artérias Meníngeas/cirurgia , Vigília , Craniotomia/métodos , Embolização Terapêutica/métodos , Resultado do TratamentoRESUMO
BACKGROUND: Spinal meningiomas are benign extra-axial tumors that can present with neurological deficits. Treatment partly depends on the degree of disability as there is no agreed-upon patient selection algorithm at present. We aimed to elucidate general patient selection patterns in patients undergoing surgery for spinal meningioma. METHODS: Data for patients with spinal tumors admitted between 2016 and 2019 were extracted from the U.S. Nationwide Inpatient Sample. We identified patients with a primary diagnosis of spinal meningioma (using International Classification of Disease, 10th revision codes) and divided them into surgical and nonsurgical treatment groups. Patient characteristics were evaluated for intergroup differences. RESULTS: Of 6395 patients with spinal meningioma, 5845 (91.4%) underwent surgery. Advanced age, nonwhite race, obesity, diabetes mellitus, chronic renal failure, and anticoagulant/antiplatelet use were less prevalent in the surgical group (all P < 0.001). The only positive predictor of surgical treatment was elective admission status (odds ratio, 3.166; P < 0.001); negative predictors were low income, Medicaid insurance, anxiety, obesity, and plegia. Patients with bowel-bladder dysfunction, plegia, or radiculopathy were less likely to undergo surgical treatment. The surgery group was less likely to experience certain complications (deep vein thrombosis, P < 0.001; pulmonary embolism, P = 0.002). Increased total hospital charges were associated with nonwhite race, diabetes, depression, obesity, myelopathy, plegia, and surgery. CONCLUSIONS: Patients treated surgically had a decreased incidence of complications, comorbidities, and Medicaid payer status. A pattern of increased utilization of health care resources and spending was also observed in the surgery group. The results indicate a potentially underserved population of patients with spinal meningioma.
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Neoplasias Meníngeas , Meningioma , Anticoagulantes , Humanos , Neoplasias Meníngeas/cirurgia , Meningioma/epidemiologia , Meningioma/cirurgia , Obesidade , Paralisia , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
Background: There are known classifications that describe thoracolumbar (TL) burst type injury but it is unclear which have the most influence on management. Our objective is to investigate the association of classification publications with the quantity and type of the most influential articles on TL burst fractures. Methods: Web of Science was searched, and exclusion and inclusion criteria were used to extract the top 100 cited articles on TL burst fractures. The effects on type, number, and other variables were separated into four eras as defined by four major classification publications. Results: 30 out of the top 100 articles represent level 1 or 2 evidence. The most influential journal was Spine, accounting for 35 articles and 4,537 citations. The highest number of articles (53) was published between the years 1995-2005, culminating with the Thoracolumbar Injury Severity Classification Score (TLICS) paper. After 2005, there was an increase in average citations per year. Following 2013, the number of highly influential articles decreased, and systematic reviews (SRs) became a larger proportion of the literature. There was a statistically significant increase in the level of 1 and 2 evidence articles with time until the publication of TLICS. The predictive value of time for higher levels of evidence was only seen in the pre-2005 years (AUC: 0.717, 95% CI 0.579-0.855, p = 0.002). Conclusions: In 1994, two articles marked the beginning of an era of highly influential TL burst fracture literature. The 2005 TLICS score was associated with a preceding increase in LOE and productivity. Following 2005, the literature saw a decrease in productivity and an increase in systematic review/meta-analysis (SR-MAs). These trends represent an increase in scholarly discussion that led to a systematic synthesis of the existing literature after publication of the 2005 TLICS article.
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Intracerebral hemorrhage is a leading cause of morbidity and mortality worldwide. To date, there is no specific treatment that clearly provides a benefit in functional outcome or mortality. Surgical treatment for hematoma evacuation has not yet shown clear benefit over medical management despite promising preclinical studies. Minimally invasive treatment options for hematoma evacuation are under investigation but remain in early-stage clinical trials. Robotics has the potential to improve treatment. In this paper, we review intracerebral hemorrhage pathology, currently available treatments, and potential robotic approaches to date. We also discuss the future role of robotics in stroke treatment.
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Hemorragia Cerebral , Procedimentos Cirúrgicos Minimamente Invasivos , Hemorragia Cerebral/cirurgia , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Patients with aneurysmal subarachnoid hemorrhage (aSAH) may develop refractory arterial cerebral vasospasm requiring multiple endovascular interventions. The aim of our study is to evaluate variables associated with need for repeat endovascular treatments in refractory vasospasm and to identify differences in outcomes following one versus multiple treatments. METHODS: We retrospectively reviewed patients treated for aSAH between 2017 and 2020 at two tertiary care centers. We included patients who underwent treatment (intraarterial infusion of vasodilatory agents or mechanical angioplasty) for radiographically diagnosed vasospasm in our analysis. Patients were divided into those who underwent single treatment versus those who underwent multiple endovascular treatments for vasospasm. RESULTS: Of the total 418 patients with aSAH, 151 (45.9%) underwent endovascular intervention for vasospasm. Of 151 patients, 95 (62.9%) underwent a single treatment and 56 (37.1%) underwent two or more treatments. Patients were more likely to undergo multiple endovascular treatments if they had a Hunt-Hess score > 2 (odds ratio [OR] 5.10 [95% confidence interval (CI) 1.82-15.84]; p = 0.003), a neutrophil-to-lymphocyte ratio > 8.0 (OR 3.19 [95% CI 1.40-7.62]; p = 0.028), and more than two fevers within the first 5 days of admission (OR 7.03 [95% CI 2.68-20.94]; p < 0.001). Patients with multiple treatments had poorer outcomes, including increased length of stay, delayed cerebral ischemia, in-hospital complications, and higher modified Rankin scores at discharge. CONCLUSIONS: A Hunt-Hess score > 2, a neutrophil-to-lymphocyte ratio > 8.0, and early fevers may be predictive of need for multiple endovascular interventions in refractory cerebral vasospasm after aSAH. These patients have poorer functional outcomes at discharge and higher rates of in-hospital complications.
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Hemorragia Subaracnóidea , Vasoespasmo Intracraniano , Febre/etiologia , Febre/terapia , Humanos , Linfócitos , Neutrófilos , Estudos Retrospectivos , Hemorragia Subaracnóidea/cirurgia , Hemorragia Subaracnóidea/terapia , Resultado do Tratamento , Vasoespasmo Intracraniano/complicações , Vasoespasmo Intracraniano/terapiaRESUMO
The presence of intraventricular hemorrhage (IVH) portends a worse prognosis in patients presenting with spontaneous intracerebral hemorrhage (ICH). Intraventricular hemorrhage increases the rates of hydrocephalus, ventriculitis, and long-term shunt dependence. Over the past decade, novel medical devices and protocols have emerged to directly treat IVH. Presently, we review new technological adaptations to treating intraventricular hemorrhage in an effort to focus further innovation in treating this morbid neurosurgical pathology. We summarize current and historical treatments as well as innovations in IVH including novel procedural techniques, use of the Integra Surgiscope, use of the Artemis evacuator, use of BrainPath, novel catheter technology, large bore external ventricular drains, the IRRAflow, the CerebroFlo, and the future directions of the field. Technology and medical devices for both surgical and nonsurgical methods are advancing the treatment of IVH. With many promising new technologies on the horizon, prospects for improved clinical care for IVH and its etiologies remain hopeful.
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Hemorragia Cerebral , Hidrocefalia , Hemorragia Cerebral/cirurgia , Ventrículos Cerebrais/cirurgia , Drenagem , Humanos , Hidrocefalia/cirurgia , PrognósticoRESUMO
Optimal treatment for chronic subdural hematomas remains controversial and perioperative risks and comorbidities may affect management strategies. Minimally invasive procedures are emerging as alternatives to the standard operative treatments. We evaluate our experience with middle meningeal artery (MMA) embolization combined with Subdural Evacuating Port System (SEPS) placement as a first-line treatment for patients with cSDH. A single institution retrospective review was performed of all patients undergoing intervention. Patients were stratified by treatment with MMA embolization and SEPS placement, MMA embolization and surgery, SEPS placement only, and surgery only for cSDH from 2017 to 2020, and cohorts were compared against each other. Patients treated with MMA/SEPS were more likely to be older, be on anticoagulation, have significant comorbidities, have shorter length of stay, and less likely to have symptomatic recurrence compared to SEPS only cohort. Thus, MMA/SEPS appears to be a safe and equally effective minimally invasive treatment for cSDH patients with significant comorbidities who are poor surgical candidates.
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Embolização Terapêutica , Hematoma Subdural Crônico , Hematoma Subdural Crônico/cirurgia , Humanos , Artérias Meníngeas , Estudos Retrospectivos , Espaço SubduralRESUMO
Children's National Hospital held a virtual symposium on "The Clinic of the Future and Telehealth" in December 2020. The goal of the symposium was to explore future trends in these domains. We also discussed how the coronavirus disease 2019 (COVID-19) pandemic accelerated ongoing changes in healthcare. We explored what is on the horizon in these fields and how these changes might affect care delivery in the future. Specifically, we discussed the "Clinic of the Future" with clinical teams from genetics and metabolism, orthopedic surgery, and primary care while our telehealth discussion involved genetics and metabolism, psychiatry, and telerehabilitation. As one example, wearable technology could be adopted among primary care practices and drive a shift in outpatient care from center-based care to patient-based care. We also examined technological innovations in physical exam instruments, gait analysis, imaging integration, and cast technology that could modernize the orthopedic surgery clinic. Telemedicine has rapidly expanded among all fields of medicine, especially since the COVID-19 pandemic, and has spurred innovation to improve the effectiveness of virtual physician visits. The development of technology to improve the virtual physical exam, during a telemedicine visit, further increases the utility of online appointments and increases access to care in all specialties. The incorporation of photogrammetry technology, in genetics and metabolism dysmorphology exams, will offer standardized tracking of patients that could improve diagnosis and treatment. Psychiatry has found nearly equal efficacy in diagnosis and treatment with telehealth visits and the additional benefit of gaining insight in the setting of the patients' home. Robotics has become increasingly common in rehabilitation, which can now incorporate a gaming experience that can be remotely updated and increase engagement and adherence in pediatric patients. The continued exploration of new ideas promises to improve both in-person and virtual care options.
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Homozygous deletion of methylthioadenosine phosphorylase (MTAP) is one of the most frequent genetic alterations in glioblastoma (GBM), but its pathologic consequences remain unclear. In this study, we report that loss of MTAP results in profound epigenetic reprogramming characterized by hypomethylation of PROM1/CD133-associated stem cell regulatory pathways. MTAP deficiency promotes glioma stem-like cell (GSC) formation with increased expression of PROM1/CD133 and enhanced tumorigenicity of GBM cells and is associated with poor prognosis in patients with GBM. As a combined consequence of purine production deficiency in MTAP-null GBM and the critical dependence of GSCs on purines, the enriched subset of CD133+ cells in MTAP-null GBM can be effectively depleted by inhibition of de novo purine synthesis. These findings suggest that MTAP loss promotes the pathogenesis of GBM by shaping the epigenetic landscape and stemness of GBM cells while simultaneously providing a unique opportunity for GBM therapeutics. SIGNIFICANCE: This study links the frequently mutated metabolic enzyme MTAP to dysregulated epigenetics and cancer cell stemness and establishes MTAP status as a factor for consideration in characterizing GBM and developing therapeutic strategies.
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Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica , Glioblastoma/patologia , Células-Tronco Neoplásicas/patologia , Purina-Núcleosídeo Fosforilase/metabolismo , Purinas/metabolismo , Animais , Apoptose , Biomarcadores Tumorais/genética , Proliferação de Células , Glioblastoma/genética , Glioblastoma/metabolismo , Humanos , Camundongos , Células-Tronco Neoplásicas/metabolismo , Prognóstico , Purina-Núcleosídeo Fosforilase/genética , Taxa de Sobrevida , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
Despite decades of efforts, non-invasive sensitive detection of small malignant brain tumors still remains challenging. Here we report a dual-modality 124I-labeled gold nanostar (124I-GNS) probe for sensitive brain tumor imaging with positron emission tomography (PET) and subcellular tracking with two-photon photoluminescence (TPL) and electron microscopy (EM). Experiment results showed that the developed nanoprobe has potential to reach sub-millimeter intracranial brain tumor detection using PET scan, which is superior to any currently available non-invasive imaging modality. Microscopic examination using TPL and EM further confirmed that GNS nanoparticles permeated the brain tumor leaky vasculature and accumulated inside brain tumor cells following systemic administration. Selective brain tumor targeting by enhanced permeability and retention effect and ultrasensitive imaging render 124I-GNS nanoprobe promise for future brain tumor-related preclinical and translational applications.
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Neoplasias Encefálicas/diagnóstico , Diagnóstico por Imagem , Nanopartículas Metálicas/química , Animais , Neoplasias Encefálicas/diagnóstico por imagem , Neoplasias Encefálicas/ultraestrutura , Fluordesoxiglucose F18/química , Ouro/química , Ouro/toxicidade , Células HEK293 , Humanos , Radioisótopos do Iodo/química , Nanopartículas Metálicas/toxicidade , Nanopartículas Metálicas/ultraestrutura , Camundongos , Imagem Óptica , Especificidade de Órgãos , Tomografia por Emissão de Pósitrons combinada à Tomografia ComputadorizadaRESUMO
Hotspot mutations in the isocitrate dehydrogenase 1 (IDH1) gene occur in a number of human cancers and confer a neomorphic enzyme activity that catalyzes the conversion of α-ketoglutarate (αKG) to the oncometabolite D-(2)-hydroxyglutarate (D2HG). In malignant gliomas, IDH1R132H expression induces widespread metabolic reprogramming, possibly requiring compensatory mechanisms to sustain the normal biosynthetic requirements of actively proliferating tumor cells. We used genetically engineered mouse models of glioma and quantitative metabolomics to investigate IDH1R132H-dependent metabolic reprogramming and its potential to induce biosynthetic liabilities that can be exploited for glioma therapy. In gliomagenic neural progenitor cells, IDH1R132H expression increased the abundance of dipeptide metabolites, depleted key tricarboxylic acid cycle metabolites, and slowed progression of murine gliomas. Notably, expression of glutamate dehydrogenase GDH2, a hominoid-specific enzyme with relatively restricted expression to the brain, was critically involved in compensating for IDH1R132H-induced metabolic alterations and promoting IDH1R132H glioma growth. Indeed, we found that recently evolved amino acid substitutions in the GDH2 allosteric domain conferred its nonredundant, glioma-promoting properties in the presence of IDH1 mutation. Our results indicate that among the unique roles for GDH2 in the human forebrain is its ability to limit IDH1R132H-mediated metabolic liabilities, thus promoting glioma growth in this context. Results from this study raise the possibility that GDH2-specific inhibition may be a viable therapeutic strategy for gliomas with IDH mutations.Significance: These findings show that the homonid-specific brain enzyme GDH2 may be essential to mitigate metabolic liabilities created by IDH1 mutations in glioma, with possible implications to leverage its therapeutic management by IDH1 inhibitors. Cancer Res; 78(1); 36-50. ©2017 AACR.
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Neoplasias Encefálicas/genética , Glioma/genética , Glutamato Desidrogenase/metabolismo , Isocitrato Desidrogenase/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/patologia , Evolução Molecular , Regulação Neoplásica da Expressão Gênica , Técnicas de Introdução de Genes , Glioma/metabolismo , Glioma/mortalidade , Glioma/patologia , Glutamato Desidrogenase/química , Glutamato Desidrogenase/genética , Humanos , Isocitrato Desidrogenase/genética , Masculino , Camundongos Endogâmicos NOD , Camundongos Endogâmicos , Mutagênese Sítio-Dirigida , Prosencéfalo/embriologia , Domínios Proteicos , TransgenesRESUMO
Inactivating mutations in the transcriptional repression factor Capicua (CIC) occur in approximately 50% of human oligodendrogliomas, but mechanistic links to pathogenesis are unclear. To address this question, we generated Cic-deficient mice and human oligodendroglioma cell models. Genetic deficiency in mice resulted in a partially penetrant embryonic or perinatal lethal phenotype, with the production of an aberrant proliferative neural population in surviving animals. In vitro cultured neural stem cells derived from Cic conditional knockout mice bypassed an EGF requirement for proliferation and displayed a defect in their potential for oligodendrocyte differentiation. Cic is known to participate in gene suppression that can be relieved by EGFR signal, but we found that cic also activated expression of a broad range of EGFR-independent genes. In an orthotopic mouse model of glioma, we found that Cic loss potentiated the formation and reduced the latency in tumor development. Collectively, our results define an important role for Cic in regulating neural cell proliferation and lineage specification, and suggest mechanistic explanations for how CIC mutations may impact the pathogenesis and therapeutic targeting of oligodendroglioma. Cancer Res; 77(22); 6097-108. ©2017 AACR.
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Diferenciação Celular/genética , Proliferação de Células/genética , Mutação , Células-Tronco Neurais/metabolismo , Oligodendroglioma/genética , Proteínas Repressoras/genética , Animais , Linhagem Celular Tumoral , Células Cultivadas , Perfilação da Expressão Gênica/métodos , Humanos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Camundongos Knockout , Camundongos SCID , Camundongos Transgênicos , Oligodendroglioma/patologiaRESUMO
IDH1 mutations occur in the majority of low-grade gliomas and lead to the production of the oncometabolite, D-2-hydroxyglutarate (D-2HG). To understand the effects of tumor-associated mutant IDH1 (IDH1-R132H) on both the neural stem cell (NSC) population and brain tumorigenesis, genetically faithful cell lines and mouse model systems were generated. Here, it is reported that mouse NSCs expressing Idh1-R132H displayed reduced proliferation due to p53-mediated cell-cycle arrest as well as a decreased ability to undergo neuronal differentiation. In vivo, Idh1-R132H expression reduced proliferation of cells within the germinal zone of the subventricular zone (SVZ). The NSCs within this area were dispersed and disorganized in mutant animals, suggesting that Idh1-R132H perturbed the NSCs and the microenvironment from which gliomas arise. In addition, tumor-bearing animals expressing mutant Idh1 displayed a prolonged survival and also overexpressed Olig2, features consistent with IDH1-mutated human gliomas. These data indicate that mutant Idh1 disrupts the NSC microenvironment and the candidate cell-of-origin for glioma; thus, altering the progression of tumorigenesis. In addition, this study provides a mutant Idh1 brain tumor model that genetically recapitulates human disease, laying the foundation for future investigations on mutant IDH1-mediated brain tumorigenesis and targeted therapy.Implications: Through the use of a conditional mutant mouse model that confers a less aggressive tumor phenotype, this study reveals that mutant Idh1 impacts the candidate cell-of-origin for gliomas. Mol Cancer Res; 15(5); 507-20. ©2017 AACR.
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Neoplasias Encefálicas/patologia , Isocitrato Desidrogenase/genética , Ventrículos Laterais/citologia , Mutação , Animais , Neoplasias Encefálicas/genética , Diferenciação Celular , Proliferação de Células , Células Cultivadas , Metilação de DNA , Técnicas de Introdução de Genes , Humanos , Ventrículos Laterais/patologia , Camundongos , Camundongos Transgênicos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/patologia , Fator de Transcrição 2 de Oligodendrócitos/genética , Regiões Promotoras Genéticas , Microambiente TumoralRESUMO
Frequent mutations in isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) and the promoter of telomerase reverse transcriptase (TERT) represent two significant discoveries in glioma genomics. Understanding the degree to which these two mutations co-occur or occur exclusively of one another in glioma subtypes presents a unique opportunity to guide glioma classification and prognosis. We analyzed the relationship between overall survival (OS) and the presence of IDH1/2 and TERT promoter mutations in a panel of 473 adult gliomas. We hypothesized and show that genetic signatures capable of distinguishing among several types of gliomas could be established providing clinically relevant information that can serve as an adjunct to histopathological diagnosis. We found that mutations in the TERT promoter occurred in 74.2% of glioblastomas (GBM), but occurred in a minority of Grade II-III astrocytomas (18.2%). In contrast, IDH1/2 mutations were observed in 78.4% of Grade II-III astrocytomas, but were uncommon in primary GBM. In oligodendrogliomas, TERT promoter and IDH1/2 mutations co-occurred in 79% of cases. Patients whose Grade III-IV gliomas exhibit TERT promoter mutations alone predominately have primary GBMs associated with poor median OS (11.5 months). Patients whose Grade III-IV gliomas exhibit IDH1/2 mutations alone predominately have astrocytic morphologies and exhibit a median OS of 57 months while patients whose tumors exhibit both TERT promoter and IDH1/2 mutations predominately exhibit oligodendroglial morphologies and exhibit median OS of 125 months. Analyzing gliomas based on their genetic signatures allows for the stratification of these patients into distinct cohorts, with unique prognosis and survival.
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Glioma/classificação , Glioma/genética , Isocitrato Desidrogenase/genética , Mutação/genética , Regiões Promotoras Genéticas/genética , Telomerase/genética , Adulto , Biomarcadores Tumorais/genética , Feminino , Glioma/mortalidade , Glioma/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Prognóstico , Taxa de SobrevidaRESUMO
In this integrative review, current research on the effectiveness of intravenous (IV) securement devices is described and practical implications for evidence-based practice in IV care are provided.
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Cateterismo Periférico/instrumentação , Cateterismo Periférico/enfermagem , Segurança do Paciente , Cateterismo Periférico/efeitos adversos , Cateteres de Demora , Análise de Falha de Equipamento , Enfermagem Baseada em Evidências , Humanos , Padrão de CuidadoRESUMO
Chronic subdural hematoma (cSDH) is an increasingly common neurological disease process. Despite the wide prevalence of cSDH, there remains a lack of consensus regarding numerous aspects of its clinical management. We provide an overview of the epidemiology and pathophysiology of cSDH and discuss several controversial management issues, including the timing of post-operative resumption of anticoagulant medications, the effectiveness of anti-epileptic prophylaxis, protocols for mobilization following evacuation of cSDH, as well as the comparative effectiveness of the various techniques of surgical evacuation. A PubMed search was carried out through October 19, 2010 using the following keywords: "subdural hematoma", "craniotomy", "burr-hole", "management", "anticoagulation", "seizure prophylaxis", "antiplatelet", "mobilization", and "surgical evacuation", alone and in combination. Relevant articles were identified and back-referenced to yield additional papers. A meta-analysis was then performed comparing the efficacy and complications associated with the various methods of cSDH evacuation. There is general agreement that significant coagulopathy should be reversed expeditiously in patients presenting with cSDH. Although protocols for gradual resumption of anti-coagulation for prophylaxis of venous thrombosis may be derived from guidelines for other neurosurgical procedures, further prospective study is necessary to determine the optimal time to restart full-dose anti-coagulation in the setting of recently drained cSDH. There is also conflicting evidence to support seizure prophylaxis in patients with cSDH, although the existing literature supports prophylaxis in patients who are at a higher risk for seizures. The published data regarding surgical technique for cSDH supports primary twist drill craniostomy (TDC) drainage at the bedside for patients who are high-risk surgical candidates with non-septated cSDH and craniotomy as a first-line evacuation technique for cSDH with significant membranes. Larger prospective studies addressing these aspects of cSDH management are necessary to establish definitive recommendations.