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OBJECTIVE: Strong performance in neurosurgical sub-internships is a vital component of a successful residency application and requires adequate familiarity with clinical knowledge and technical skills that may not be covered in standard medical school curricula. Accordingly, a need exists for immersive and comprehensive sub-internship preparation programs that respect time and resource limitations, are optimized based on longitudinal student feedback, provide opportunities for mentorship, and foster enthusiasm for neurosurgery. Therefore, residents at a single institution designed and implemented a comprehensive curriculum for a 1-day sub-internship academy. METHODS: Academy curriculum involved hands-on and discussion-based elements split into 3 workshops. Anonymous surveys were conducted immediately following the academy and upon completion of sub-internships to evaluate participant perceptions on the utility of the academy. RESULTS: Twelve medical students participated in the inaugural neurosurgery sub-internship academy. Nine responded to the immediate postsurvey, which revealed the following ratings: the overall program was rated as having maximal impact on sub-internship readiness and enthusiasm for neurosurgery by 8 (88.9%) and 7 (77.8%) respondents, respectively. A largely positive impact on access to mentorship was observed. Six participants responded to a postsub-internship survey, and all 6 indicated they agreed or strongly agreed that the academy prepared them to perform well. CONCLUSIONS: Student perceptions of the relevance and utility of the sub-internship academy were positive, and the program fostered enthusiasm for neurosurgery and provided opportunities for mentorship. The participants indicated the academy positively impacted their sub-internship performance, and areas for improvement to guide future iterations of the academy were identified.
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Biological sex is an important risk factor in cancer, but the underlying cell types and mechanisms remain obscure. Since tumor development is regulated by the immune system, we hypothesize that sex-biased immune interactions underpin sex differences in cancer. The male-biased glioblastoma multiforme (GBM) is an aggressive and treatment-refractory tumor in urgent need of more innovative approaches, such as considering sex differences, to improve outcomes. GBM arises in the specialized brain immune environment dominated by microglia, so we explored sex differences in this immune cell type. We isolated adult human TAM-MGs (tumor-associated macrophages enriched for microglia) and control microglia and found sex-biased inflammatory signatures in GBM and lower-grade tumors associated with pro-tumorigenic activity in males and anti-tumorigenic activity in females. We demonstrated that genes expressed or modulated by the inactive X chromosome facilitate this bias. Together, our results implicate TAM-MGs, specifically their sex chromosomes, as drivers of male bias in GBM.
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ABSTRACT: Delays and risks associated with neurosurgical biopsies preclude timely diagnosis and treatment of central nervous system (CNS) lymphoma and other CNS neoplasms. We prospectively integrated targeted rapid genotyping of cerebrospinal fluid (CSF) into the evaluation of 70 patients with CNS lesions of unknown cause. Participants underwent genotyping of CSF-derived DNA using a quantitative polymerase chain reaction-based approach for parallel detection of single-nucleotide variants in the MYD88, TERT promoter, IDH1, IDH2, BRAF, and H3F3A genes within 80 minutes of sample acquisition. Canonical mutations were detected in 42% of patients with neoplasms, including cases of primary and secondary CNS lymphoma, glioblastoma, IDH-mutant brainstem glioma, and H3K27M-mutant diffuse midline glioma. Genotyping results eliminated the need for surgical biopsies in 7 of 33 cases (21.2%) of newly diagnosed neoplasms, resulting in significantly accelerated initiation of disease-directed treatment (median, 3 vs 12 days; P = .027). This assay was then implemented in a Clinical Laboratory Improvement Amendments environment, with 2-day median turnaround for diagnosis of CNS lymphoma from 66 patients across 4 clinical sites. Our study prospectively demonstrates that targeted rapid CSF genotyping influences oncologic management for suspected CNS tumors.
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Neoplasias do Sistema Nervoso Central , Linfoma , Humanos , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/terapia , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Linfoma/líquido cefalorraquidiano , Linfoma/genética , Linfoma/diagnóstico , Linfoma/terapia , Adulto , DNA de Neoplasias/líquido cefalorraquidiano , DNA de Neoplasias/genética , Idoso de 80 Anos ou mais , Mutação , Estudos Prospectivos , Adulto JovemRESUMO
BACKGROUND: Survival is variable in patients with glioblastoma IDH wild-type (GBM), even after comparable surgical resection of radiographically detectable disease, highlighting the limitations of radiographic assessment of infiltrative tumor anatomy. The majority of postsurgical progressive events are failures within 2 cm of the resection margin, motivating supramaximal resection strategies to improve local control. However, which patients benefit from such radical resections remains unknown. METHODS: We developed a predictive model to identify which IDH wild-type GBMs are amenable to radiographic gross-total resection (GTR). We then investigated whether GBM survival heterogeneity following GTR is correlated with microscopic tumor burden by analyzing tumor cell content at the surgical margin with a rapid qPCR-based method for detection of TERT promoter mutation. RESULTS: Our predictive model for achievable GTR, developed on retrospective radiographic and molecular data of GBM patients undergoing resection, had an area under the curve of 0.83, sensitivity of 62%, and specificity of 90%. Prospective analysis of this model in 44 patients found that 89% of patients were correctly predicted to achieve a residual volume (RV)â <â 4.9cc. Of the 44 prospective patients undergoing rapid qPCR TERT promoter mutation analysis at the surgical margin, 7 had undetectable TERT mutation, of which 5 also had a GTR (RVâ <â 1cc). In these 5 patients at 30 months follow-up, 75% showed no progression, compared to 0% in the group with TERT mutations detected at the surgical margin (Pâ =â .02). CONCLUSIONS: These findings identify a subset of patients with GBM that may derive local control benefits from radical resection to undetectable molecular margins.
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Neoplasias Encefálicas , Glioblastoma , Isocitrato Desidrogenase , Margens de Excisão , Mutação , Humanos , Glioblastoma/cirurgia , Glioblastoma/genética , Glioblastoma/patologia , Glioblastoma/mortalidade , Glioblastoma/diagnóstico por imagem , Isocitrato Desidrogenase/genética , Neoplasias Encefálicas/cirurgia , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/diagnóstico por imagem , Masculino , Feminino , Pessoa de Meia-Idade , Telomerase/genética , Estudos Retrospectivos , Idoso , Taxa de Sobrevida , Estudos Prospectivos , Adulto , Prognóstico , Seguimentos , Procedimentos Neurocirúrgicos/métodos , Regiões Promotoras GenéticasRESUMO
Recent clinical trials have highlighted the limited efficacy of T cell-based immunotherapy in patients with glioblastoma (GBM). To better understand the characteristics of tumor-infiltrating lymphocytes (TIL) in GBM, we performed cellular indexing of transcriptomes and epitopes by sequencing and single-cell RNA sequencing with paired V(D)J sequencing, respectively, on TILs from two cohorts of patients totaling 15 patients with high-grade glioma, including GBM or astrocytoma, IDH-mutant, grade 4 (G4A). Analysis of the CD8+ TIL landscape reveals an enrichment of clonally expanded GZMK+ effector T cells in the tumor compared with matched blood, which was validated at the protein level. Furthermore, integration with other cancer types highlights the lack of a canonically exhausted CD8+ T-cell population in GBM TIL. These data suggest that GZMK+ effector T cells represent an important T-cell subset within the GBM microenvironment and may harbor potential therapeutic implications. SIGNIFICANCE: To understand the limited efficacy of immune-checkpoint blockade in GBM, we applied a multiomics approach to understand the TIL landscape. By highlighting the enrichment of GZMK+ effector T cells and the lack of exhausted T cells, we provide a new potential mechanism of resistance to immunotherapy in GBM. This article is featured in Selected Articles from This Issue, p. 897.
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Neoplasias Encefálicas , Linfócitos T CD8-Positivos , Glioblastoma , Humanos , Neoplasias Encefálicas/imunologia , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Glioblastoma/imunologia , Glioblastoma/terapia , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Microambiente Tumoral/imunologiaRESUMO
BACKGROUND: Glucocorticoids suppress inflammation. Autoimmune disease may occur after remission of Cushing's disease (CD). However, the development of autoimmune disease in this context is not well described. OBJECTIVE: To determine 1) the incidence of autoimmune disease in patients with CD after surgical remission compared with patients with nonfunctioning pituitary adenomas (NFPAs) and 2) the clinical presentation of and risk factors for development of autoimmune disease in CD after remission. DESIGN: Retrospective matched cohort analysis. SETTING: Academic medical center/pituitary center. PATIENTS: Patients with CD with surgical remission and surgically treated NFPA. MEASUREMENTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery. Assessment for hypercortisolemia included late-night salivary cortisol levels, 24-hour urine free cortisol (UFC) ratio (UFC value divided by the upper limit of the normal range for the assay), and dexamethasone suppression tests. RESULTS: Cumulative incidence of new-onset autoimmune disease at 3 years after surgery was higher in patients with CD (10.4% [95% CI, 5.7% to 15.1%]) than in those with NFPAs (1.6% [CI, 0% to 4.6%]) (hazard ratio, 7.80 [CI, 2.88 to 21.10]). Patients with CD showed higher prevalence of postoperative adrenal insufficiency (93.8% vs. 16.5%) and lower postoperative nadir serum cortisol levels (63.8 vs. 282.3 nmol/L) than patients with NFPAs. Compared with patients with CD without autoimmune disease, those who developed autoimmune disease had a lower preoperative 24-hour UFC ratio (2.7 vs. 6.3) and a higher prevalence of family history of autoimmune disease (41.2% vs. 20.9%). LIMITATION: The small sample of patients with autoimmune disease limited identification of independent risk factors. CONCLUSION: Patients achieving surgical remission of CD have higher incidence of autoimmune disease than age- and sex-matched patients with NFPAs. Family history of autoimmune disease is a potential risk factor. Adrenal insufficiency may be a trigger. PRIMARY FUNDING SOURCE: Recordati Rare Diseases Inc.
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Insuficiência Adrenal , Doenças Autoimunes , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Humanos , Estudos de Coortes , Hidrocortisona , Estudos Retrospectivos , Hipersecreção Hipofisária de ACTH/complicações , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/complicações , Neoplasias Hipofisárias/cirurgia , Insuficiência Adrenal/complicações , Doenças Autoimunes/complicaçõesRESUMO
BACKGROUND AND OBJECTIVES: The Accreditation Council for Graduate Medical Education has approved 117 neurological surgery residency programs which develop and educate neurosurgical trainees. We present the current landscape of neurosurgical training in the United States by examining multiple aspects of neurological surgery residencies in the 2022-2023 academic year and investigate the impact of program structure on resident academic productivity. METHODS: Demographic data were collected from publicly available websites and reports from the National Resident Match Program. A 34-question survey was circulated by e-mail to program directors to assess multiple features of neurological surgery residency programs, including curricular structure, fellowship availability, recent program changes, graduation requirements, and resources supporting career development. Mean resident productivity by program was collected from the literature. RESULTS: Across all 117 programs, there was a median of 2.0 (range 1.0-4.0) resident positions per year and 1.0 (range 0.0-2.0) research/elective years. Programs offered a median of 1.0 (range 0.0-7.0) Committee on Advanced Subspecialty Training-accredited fellowships, with endovascular fellowships being most frequently offered (53.8%). The survey response rate was 75/117 (64.1%). Of survey respondents, the median number of clinical sites was 3.0 (range 1.0-6.0). Almost half of programs surveyed (46.7%) reported funding mechanisms for residents, including R25, T32, and other in-house grants. Residents received a median academic stipend of $1000 (range $0-$10 000) per year. Nearly all programs (93.3%) supported wellness activities for residents, which most frequently occurred quarterly (46.7%). Annual academic stipend size was the only significant predictor of resident academic productivity (R 2 = 0.17, P = .002). CONCLUSION: Neurological surgery residency programs successfully train the next generation of neurosurgeons focusing on education, clinical training, case numbers, and milestones. These programs offer trainees the chance to tailor their career trajectories within residency, creating a rewarding and personalized experience that aligns with their career aspirations.
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Internato e Residência , Humanos , Estados Unidos , Estudos Transversais , Educação de Pós-Graduação em Medicina , Neurocirurgiões , Inquéritos e QuestionáriosRESUMO
OBJECTIVE: This article reviews the presenting features, molecular characteristics, diagnosis, and management of selected skull base tumors, including meningiomas, vestibular schwannomas, pituitary neuroendocrine tumors, craniopharyngiomas, chordomas, ecchordosis physaliphora, chondrosarcomas, esthesioneuroblastomas, and paragangliomas. LATEST DEVELOPMENTS: Skull base tumors pose a management challenge given their complex location and, as a result, the tumors and treatment can result in significant morbidity. In most cases, surgery, radiation therapy, or both yield high rates of disease control, but the use of these therapies may be limited by the surgical accessibility of these tumors and their proximity to critical structures. The World Health Organization classification of pituitary neuroendocrine tumors was updated in 2022. Scientific advances have led to an enhanced understanding of the genetic drivers of many types of skull base tumors and have revealed several potentially targetable genetic alterations. This information is being leveraged in the design of ongoing clinical trials, with the hope of rendering these challenging tumors treatable through less invasive and morbid measures. ESSENTIAL POINTS: Tumors involving the skull base are heterogeneous and may arise from bony structures, cranial nerves, the meninges, the sinonasal tract, the pituitary gland, or embryonic tissues. Treatment often requires a multidisciplinary approach, with participation from radiation oncologists, medical oncologists, neuro-oncologists, and surgical specialists, including neurosurgeons, otolaryngologists, and head and neck surgeons. Treatment has largely centered around surgical resection, when feasible, and the use of first-line or salvage radiation therapy, with chemotherapy, targeted therapy, or both considered in selected settings. Our growing understanding of the molecular drivers of these diseases may facilitate future expansion of pharmacologic options to treat skull base tumors.
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Neoplasias Meníngeas , Tumores Neuroendócrinos , Neoplasias Hipofisárias , Neoplasias da Base do Crânio , Humanos , Neoplasias da Base do Crânio/diagnóstico , Neoplasias da Base do Crânio/genética , Neoplasias da Base do Crânio/terapia , Base do Crânio/patologia , Base do Crânio/cirurgia , Procedimentos Neurocirúrgicos , Neoplasias Hipofisárias/cirurgia , Neoplasias Meníngeas/diagnóstico , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/terapia , Tumores Neuroendócrinos/cirurgiaRESUMO
BACKGROUND: Arachnoid cysts are common intracranial mass lesions frequently discovered as incidental findings on radiographic imaging. It is routine practice to monitor these lesions as a large majority remain stable. Although traumatic cyst rupture is a known risk, it is rare for patients to present with spontaneous rupture. OBSERVATIONS: The authors report the case of a 32-year-old patient who required emergent neurosurgical intervention for spontaneous rupture of a left hemispheric arachnoid cyst. LESSONS: Patients with ruptured arachnoid cysts can present with vague, nonspecific symptoms that may delay diagnosis. If not diagnosed and treated promptly, arachnoid cyst rupture can progress to a neurosurgical emergency as the subdural collection may cause extensive mass effect and even cerebral herniation.
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IgG4-related disease-associated hypertrophic pachymeningitis (IgG4RD-HP) is a fibroinflammatory autoimmune disorder in which diagnosis is difficult without biopsy. Guidance on management of disease refractory to glucocorticoids and intravenous rituximab is limited. We present the case of a 68-year-old woman with IgG4RD-HP who developed sensorineural hearing loss with associated bulky basilar pachymeningeal enhancement. Her cerebrospinal fluid was inflammatory and had an elevated IgG4 concentration, strongly suggestive of IgG4RD-HP. Biopsy of involved meninges was not possible due to surgical risk. Over years she developed bilateral optic neuropathies and hydrocephalus, requiring intravenous rituximab and ventriculoperitoneal shunt. Her disease was refractory to glucocorticoids. Despite maintenance intravenous rituximab, she developed slowly progressive symptoms of intracranial hypertension and hydrocephalus with persistently inflammatory spinal fluid. Switching to intrathecal rituximab therapy led to dramatic improvement in gait and headache and reduced pachymeningeal bulk and metabolic activity. In patients with IgG4RD-HP refractory to glucocorticoids and intravenous rituximab, intrathecal rituximab may be an efficacious therapy.
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BACKGROUND: 5-aminolevulinic acid (5-ALA)-induced fluorescence of neoplastic tissue is known to occur in a number of high-grade gliomas. This fluorescence helps surgeons maximize safe resection by distinguishing previously indiscernible neoplastic tissue from brain parenchyma. Still, the effectiveness of 5-ALA has not been fully explored for all central nervous system tumors. Consequently, the full spectrum of tumors that would benefit from fluorescence-guided surgery using 5-ALA is unknown. OBSERVATIONS: This report describes successfully utilizing 5-ALA to achieve complete resection of a recurrent anaplastic pleomorphic xanthoastrocytoma (APXA). LESSONS: APXA tumor cells accumulate sufficient amounts of 5-ALA and its fluorescent metabolite to produce visible intraoperative fluorescence. However, further investigation is needed to determine if 5-ALA fluorescent labeling routinely occurs in patients with APXAs.
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Cushing's disease is the most common cause of endogenous hypercortisolemia, and transsphenoidal surgery remains the first line therapy for removal of the ACTH-secreting adenoma. While post-operative remission rates are high in experienced hands, there remains a 2% risk of recurrence per year. Patients with the highest chance for cure are those with small, non-invasive tumors that are visible on pre-operative MRI and identified during surgery and are performed by high-volume pituitary neurosurgeons. Surgery for persistent or recurrent disease is frequently indicated and is most successful in the hands of experienced surgeons and in cases where tumor is visible on MRI.
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Adenoma , Hipersecreção Hipofisária de ACTH , Neoplasias Hipofisárias , Humanos , Hipersecreção Hipofisária de ACTH/cirurgia , Neoplasias Hipofisárias/cirurgia , Reoperação , Adenoma/cirurgia , Hormônio Adrenocorticotrópico , Resultado do TratamentoRESUMO
Introduction: Angiogenesis in pituitary tumors is not fully understood, and a better understanding could help inform new pharmacologic therapies, particularly for aggressive pituitary tumors. Materials and Methods: 219 human pituitary tumors and 12 normal pituitary glands were studied. Angiogenic genes were quantified by an angiogenesis qPCR array and a TaqMan probe-based absolute qPCR. Angiogenesis inhibition in pituitary tumors was evaluated in vitro with the endothelial tube formation assay and in vivo in RbΔ19 mice. Results: 71 angiogenic genes, 40 of which are known to be involved in sprouting angiogenesis, were differentially expressed in pituitary tumors. Expression of endothelial markers CD31, CD34, and ENG was significantly higher in pituitary tumors, by 5.6, 22.3, and 8.2-fold, respectively, compared to in normal pituitary tissue. There was no significant difference in levels of the lymphatic endothelial marker LYVE1 in pituitary tumors compared with normal pituitary gland tissue. Pituitary tumors also expressed significantly higher levels of angiogenesis growth factors, including VEGFA (4.2-fold), VEGFB (2.2), VEGFC (19.3), PGF (13.4), ANGPT2 (9.2), PDGFA (2.7), PDGFB (10.5) and TGFB1 (3.8) compared to normal pituitary tissue. Expression of VEGFC and PGF was highly correlated with the expression of endothelial markers in tumor samples, including CD31, CD34, and ENG (endoglin, a co-receptor for TGFß). Furthermore, VEGFR inhibitors inhibited angiogenesis induced by human pituitary tumors and prolonged survival of RbΔ19 mice. Conclusion: Human pituitary tumors are characterized by more active angiogenesis than normal pituitary gland tissue in a manner consistent with sprouting angiogenesis. Angiogenesis in pituitary tumors is regulated mainly by PGF and VEGFC, not VEGFA and VEGFB. Angiogenesis inhibitors, such as the VEGFR2 inhibitor cabozantinib, may merit further investigation as therapies for aggressive human pituitary tumors.
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Acidentes por Quedas , Lobo Frontal/patologia , Linfoma Difuso de Grandes Células B/diagnóstico , Atividades Cotidianas , Idoso , Biópsia , Encéfalo/diagnóstico por imagem , Encéfalo/patologia , Depressão/etiologia , Diagnóstico Diferencial , Feminino , Humanos , Linfoma Difuso de Grandes Células B/complicações , Imageamento por Ressonância MagnéticaRESUMO
Human pituitary adenomas are one of the most common intracranial neoplasms. Although most of these tumors are benign and can be treated medically or by transsphenoidal surgery, a subset of these tumors are fast-growing, aggressive, recur, and remain a therapeutic dilemma. Because antibodies against immune checkpoint receptors PD-1 and CLTA-4 are now routinely used for cancer treatment, we quantified the expression of mRNA coding for PD-1, CLTA-4, and their ligands, PD-L1, PD-L2, CD80, and CD86 in human pituitary adenomas and normal pituitary glands, with the ultimate goal of exploiting immune checkpoint therapy in aggressive pituitary adenomas. Aggressive pituitary adenomas demonstrated an increased expression of PD-L2, CD80, and CD86 in compared to that of normal human pituitary glands. Furthermore, aggressive pituitary tumors demonstrated significantly higher levels of CD80 and CD86 compared to non-aggressive tumors. Our results establish a rationale for studying a potential role for immune checkpoint inhibition therapy in the treatment of pituitary adenomas.
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Adenoma/imunologia , Biomarcadores Tumorais/metabolismo , Proteínas de Checkpoint Imunológico/metabolismo , Recidiva Local de Neoplasia/imunologia , Neoplasias Hipofisárias/imunologia , Evasão Tumoral , Adenoma/genética , Adenoma/metabolismo , Adenoma/patologia , Biomarcadores Tumorais/genética , Estudos de Casos e Controles , Feminino , Seguimentos , Humanos , Proteínas de Checkpoint Imunológico/genética , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Neoplasias Hipofisárias/genética , Neoplasias Hipofisárias/metabolismo , Neoplasias Hipofisárias/patologia , PrognósticoRESUMO
Leptomeningeal disease (LMD) is a common complication from solid tumor malignancies with a poor prognosis and limited treatment options. We present a single arm Phase II study of 18 patients with LMD receiving combined ipilimumab and nivolumab until progression or unacceptable toxicity (NCT02939300). The primary end point is overall survival at 3 months (OS3). Secondary end points include toxicity, cumulative time-to-progression at 3 months, and progression-free survival. A Simon two-stage design is used to compare a null hypothesis OS3 of 18% against an alternative of 44%. Median follow up based on patients still alive is 8.0 months (range: 0.5 to 15.9 months). The study has met its primary endpoint as 8 of 18 (OS3 0.44; 90% CI: 0.24 to 0.66) patients are alive at three months. One third of patients have experienced one (or more) grade-3 or higher adverse events. Two patients have discontinued protocol treatment due to unacceptable toxicity (hepatitis and colitis, respectively). The most frequent adverse events include fatigue (N = 7), nausea (N = 6), fever (N = 6), anorexia (N = 6) and rash (N = 6). Combined ipilimumab and nivolumab has an acceptable safety profile and demonstrates promising activity in LMD patients. Larger, multicenter clinical trials are needed to validate these results.
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Antineoplásicos Imunológicos/administração & dosagem , Protocolos de Quimioterapia Combinada Antineoplásica , Neoplasias Encefálicas/tratamento farmacológico , Ipilimumab/administração & dosagem , Carcinomatose Meníngea/tratamento farmacológico , Neoplasias Meníngeas/tratamento farmacológico , Nivolumabe/administração & dosagem , Adulto , Idoso , Anorexia/induzido quimicamente , Anorexia/mortalidade , Anorexia/patologia , Antineoplásicos Imunológicos/efeitos adversos , Neoplasias Encefálicas/mortalidade , Neoplasias Encefálicas/secundário , Colite/induzido quimicamente , Colite/mortalidade , Colite/patologia , Exantema/induzido quimicamente , Exantema/mortalidade , Exantema/patologia , Fadiga/induzido quimicamente , Fadiga/mortalidade , Fadiga/patologia , Feminino , Febre/induzido quimicamente , Febre/mortalidade , Febre/patologia , Hepatite/etiologia , Hepatite/mortalidade , Hepatite/patologia , Humanos , Ipilimumab/efeitos adversos , Masculino , Carcinomatose Meníngea/mortalidade , Carcinomatose Meníngea/patologia , Neoplasias Meníngeas/mortalidade , Neoplasias Meníngeas/patologia , Pessoa de Meia-Idade , Náusea/induzido quimicamente , Náusea/mortalidade , Náusea/patologia , Nivolumabe/efeitos adversos , Análise de SobrevidaRESUMO
OBJECTIVE: Interictal discharges (IIDs) and high frequency oscillations (HFOs) are established neurophysiologic biomarkers of epilepsy, while microseizures are less well studied. We used custom poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) microelectrodes to better understand these markers' microscale spatial dynamics. METHODS: Electrodes with spatial resolution down to 50 µm were used to record intraoperatively in 30 subjects. IIDs' degree of spread and spatiotemporal paths were generated by peak-tracking followed by clustering. Repeating HFO patterns were delineated by clustering similar time windows. Multi-unit activity (MUA) was analyzed in relation to IID and HFO timing. RESULTS: We detected IIDs encompassing the entire array in 93% of subjects, while localized IIDs, observed across < 50% of channels, were seen in 53%. IIDs traveled along specific paths. HFOs appeared in small, repeated spatiotemporal patterns. Finally, we identified microseizure events that spanned 50-100 µm. HFOs covaried with MUA, but not with IIDs. CONCLUSIONS: Overall, these data suggest that irritable cortex micro-domains may form part of an underlying pathologic architecture which could contribute to the seizure network. SIGNIFICANCE: These results, supporting the possibility that epileptogenic cortex comprises a mosaic of irritable domains, suggests that microscale approaches might be an important perspective in devising novel seizure control therapies.
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Mapeamento Encefálico/métodos , Encéfalo/fisiopatologia , Eletroencefalografia/métodos , Epilepsia/fisiopatologia , Monitorização Neurofisiológica Intraoperatória/métodos , Microeletrodos , Adulto , Encéfalo/cirurgia , Eletroencefalografia/instrumentação , Epilepsia/diagnóstico , Epilepsia/cirurgia , Feminino , Humanos , Monitorização Neurofisiológica Intraoperatória/instrumentação , Masculino , Pessoa de Meia-Idade , Adulto JovemRESUMO
The diagnosis and management of mass lesions in the sellar and parasellar areas remain challenging. When approaching patients with possible sellar or hypothalamic masses, it is important not only to focus on imaging but also detect possible pituitary hormone deficits or excess, in order to establish an appropriate diagnosis and initiate treatment. The imaging modalities used to characterize hypothalamic and pituitary lesions have significantly evolved over the course of the past several years. Computed tomography (CT) and CT angiography play a major role in detecting various sellar lesions, especially in patients who have contraindications to magnetic resonance imaging (MRI) and can also yield important information for surgical planning. However, MRI has become the gold standard for the detection and characterization of hypothalamic and pituitary tumors, infections, cystic, or vascular lesions. Indeed, the imaging characteristics of hypothalamic and sellar lesions can help narrow down the differential diagnosis preoperatively. In addition, MRI can help establish the relationship of mass lesions to surrounding structures. A pituitary MRI examination should be obtained if there is concern for mass effect (including visual loss, ophthalmoplegia, headache) or if there is clinical suspicion and laboratory evidence of either hypopituitarism or pituitary hormone excess. The information obtained from MRI images also provides us with assistance in planning surgery. Using intraoperative MRI can be very helpful in assessing the adequacy of tumor resection. In addition, MRI images yield reliable data that allow for noninvasive monitoring of patients postoperatively.
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Adenoma , Craniofaringioma , Doenças da Hipófise , Neoplasias Hipofisárias , Humanos , Imageamento por Ressonância Magnética , Doenças da Hipófise/diagnóstico por imagem , Hipófise/diagnóstico por imagemRESUMO
PURPOSE: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. METHODS: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. RESULTS: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. CONCLUSIONS: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed "core" steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The "optional" steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world.
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Adenoma , Neoplasias Hipofisárias , Adenoma/cirurgia , Endoscopia , Humanos , Neoplasias Hipofisárias/cirurgia , Estudos Retrospectivos , Osso Esfenoide , Resultado do Tratamento , Fluxo de TrabalhoRESUMO
OBJECTIVE: Neuromonitoring of primary motor regions allows preservation of motor strength and is frequently employed during cranial procedures. Less is known about protection of sensory function and ability to modulate movements, both of which rely on integrity of thalamocortical afferents (TCA) to fronto-parietal regions. We describe our experience with TCA monitoring and their cortical relays during brain tumor surgery. METHODOLOGY: To study its feasibility and usefulness, continuous somatosensory evoked potentials (SSEP) recording via a subdural electrode was attempted in 32 consecutive patients. RESULTS: Median and posterior tibial SSEP were successfully monitored in 31 and 17 patients respectively. SSEP improved lesion localization and prevented unnecessary cortical stimulation in 9 and 16 cases respectively. A threshold of ≥30% SSEP amplitude decrease influenced management in 10 patients while a decrement of ≥50 % had a sensitivity of 0.89 and specificity of 1 in detecting worsening of sensory function. Simultaneous motor evoked potentials (MEP) and SSEP monitoring were performed in 10 cases, 9 of which showed short-lived fluctuations of the former. CONCLUSION: Direct cortical SSEP monitoring is feasible, informs management and predicts outcome. SIGNIFICANCE: Early intervention prevents sensory deficit. Concomitant MEP fluctuations may reflect modulation of motor activity by TCA.