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1.
World Neurosurg ; 2024 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-39362595

RESUMO

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 one-day sub-internship academy. METHODS: Academy curriculum involved hands-on and discussion-based elements split into three 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 post-survey, which revealed the following ratings: the overall program was rated as having maximal impact on sub-internship readiness and enthusiasm for neurosurgery by eight (88.9%) and seven (77.8%) respondents, respectively. A largely positive impact on access to mentorship was observed. Six participants responded to a post-sub-internship survey, and all six 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.

2.
Nat Commun ; 15(1): 7800, 2024 Sep 06.
Artigo em Inglês | MEDLINE | ID: mdl-39242511

RESUMO

Dynamic tracking of spinal instrumentation could facilitate real-time evaluation of hardware integrity and in so doing alert patients/clinicians of potential failure(s). Critically, no method yet exists to continually monitor the integrity of spinal hardware and by proxy the process of spinal arthrodesis; as such hardware failures are often not appreciated until clinical symptoms manifest. Accordingly, herein, we report on the development and engineering of a bio-adhesive metal detector array (BioMDA), a potential wearable solution for real-time, non-invasive positional analyses of osseous implants within the spine. The electromagnetic coupling mechanism and intimate interfacial adhesion enable the precise sensing of the metallic implants position without the use of radiation. The customized decoupling models developed facilitate the precise determination of the horizontal and vertical positions of the implants with incredible levels of accuracy (e.g., <0.5 mm). These data support the potential use of BioMDA in real-time/dynamic postoperative monitoring of spinal implants.


Assuntos
Metais , Próteses e Implantes , Coluna Vertebral , Dispositivos Eletrônicos Vestíveis , Humanos , Coluna Vertebral/cirurgia , Metais/química , Adesivos , Fusão Vertebral/instrumentação , Fusão Vertebral/métodos
3.
Neurosurgery ; 95(3): 576-583, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-39145650

RESUMO

BACKGROUND AND OBJECTIVES: Racial and socioeconomic disparities in spine surgery for degenerative lumbar spondylolisthesis persist in the United States, potentially contributing to unequal health-related quality of life (HRQoL) outcomes. This is important as lumbar spondylolisthesis is one of the most common causes of surgical low back pain, and low back pain is the largest disabler of individuals worldwide. Our objective was to assess the relationship between race, socioeconomic factors, treatment utilization, and outcomes in patients with lumbar spondylolisthesis. METHODS: This cohort study analyzed prospectively collected data from 9941 patients diagnosed with lumbar spondylolisthesis between 2015 and 2020 at 5 academic hospitals. Exposures were race, socioeconomic status, health coverage, and HRQoL measures. Main outcomes and measures included treatment utilization rates between racial groups and the association between race and treatment outcomes using logistic regression, adjusting for patient characteristics, socioeconomic status, health coverage, and HRQoL measures. RESULTS: Of the 9941 patients included (mean [SD] age, 67.37 [12.40] years; 63% female; 1101 [11.1%] Black, Indigenous, and People of Color [BIPOC]), BIPOC patients were significantly less likely to use surgery than White patients (odds ratio [OR] = 0.68; 95% CI, 0.62-0.75). Furthermore, BIPOC race was associated with significantly lower odds of reaching the minimum clinically important difference for physical function (OR = 0.74; 95% CI, 0.60; 0.91) and pain interference (OR = 0.77; 95% CI, 0.62-0.97). Medicaid beneficiaries were significantly less likely (OR = 0.65; 95% CI, 0.46-0.92) to reach a clinically important improvement in HRQoL when accounting for race. CONCLUSION: This study found that BIPOC patients were less likely to use spine surgery for degenerative lumbar spondylolisthesis despite reporting higher pain interference, suggesting an association between race and surgical utilization. These disparities may contribute to unequal HRQoL outcomes for patients with lumbar spondylolisthesis and warrant further investigation to address and reduce treatment disparities.


Assuntos
Disparidades em Assistência à Saúde , Vértebras Lombares , Qualidade de Vida , Espondilolistese , Humanos , Espondilolistese/cirurgia , Espondilolistese/etnologia , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Disparidades em Assistência à Saúde/estatística & dados numéricos , Disparidades em Assistência à Saúde/etnologia , Vértebras Lombares/cirurgia , Estudos de Coortes , Estados Unidos , Etnicidade/estatística & dados numéricos , Resultado do Tratamento , Dor Lombar/cirurgia , Dor Lombar/etnologia , Estudos Prospectivos , Fatores Socioeconômicos
4.
Blood ; 144(10): 1093-1100, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38776489

RESUMO

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.


Assuntos
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 Jovem
5.
Neuro Oncol ; 26(9): 1660-1669, 2024 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-38581292

RESUMO

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) < 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 (RV < 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 (P = .02). CONCLUSIONS: These findings identify a subset of patients with GBM that may derive local control benefits from radical resection to undetectable molecular margins.


Assuntos
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 Genéticas
6.
Clin Cancer Res ; 30(14): 2974-2985, 2024 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-38295147

RESUMO

PURPOSE: Primary central nervous system (CNS) gliomas can be classified by characteristic genetic alterations. In addition to solid tissue obtained via surgery or biopsy, cell-free DNA (cfDNA) from cerebrospinal fluid (CSF) is an alternative source of material for genomic analyses. EXPERIMENTAL DESIGN: We performed targeted next-generation sequencing of CSF cfDNA in a representative cohort of 85 patients presenting at two neurooncological centers with suspicion of primary or recurrent glioma. Copy-number variation (CNV) profiles, single-nucleotide variants (SNV), and small insertions/deletions (indel) were combined into a molecular-guided tumor classification. Comparison with the solid tumor was performed for 38 cases with matching solid tissue available. RESULTS: Cases were stratified into four groups: glioblastoma (n = 32), other glioma (n = 19), nonmalignant (n = 17), and nondiagnostic (n = 17). We introduced a molecular-guided tumor classification, which enabled identification of tumor entities and/or cancer-specific alterations in 75.0% (n = 24) of glioblastoma and 52.6% (n = 10) of other glioma cases. The overlap between CSF and matching solid tissue was highest for CNVs (26%-48%) and SNVs at predefined gene loci (44%), followed by SNVs/indels identified via uninformed variant calling (8%-14%). A molecular-guided tumor classification was possible for 23.5% (n = 4) of nondiagnostic cases. CONCLUSIONS: We developed a targeted sequencing workflow for CSF cfDNA as well as a strategy for interpretation and reporting of sequencing results based on a molecular-guided tumor classification in glioma. See related commentary by Abdullah, p. 2860.


Assuntos
Biomarcadores Tumorais , Ácidos Nucleicos Livres , Variações do Número de Cópias de DNA , Glioma , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Glioma/genética , Glioma/líquido cefalorraquidiano , Glioma/patologia , Glioma/diagnóstico , Feminino , Pessoa de Meia-Idade , Masculino , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Idoso , Adulto , Biomarcadores Tumorais/líquido cefalorraquidiano , Biomarcadores Tumorais/genética , Ácidos Nucleicos Livres/líquido cefalorraquidiano , Ácidos Nucleicos Livres/genética , Neoplasias do Sistema Nervoso Central/líquido cefalorraquidiano , Neoplasias do Sistema Nervoso Central/genética , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/patologia , Polimorfismo de Nucleotídeo Único , Adulto Jovem , Idoso de 80 Anos ou mais , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/líquido cefalorraquidiano , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/diagnóstico
7.
Biomaterials ; 305: 122431, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38169188

RESUMO

Tumors are complex materials whose physical properties dictate growth and treatment outcomes. Recent evidence suggests time-dependent physical properties, such as viscoelasticity, are crucial, distinct mechanical regulators of cancer progression and malignancy, yet the genesis and consequences of tumor viscoelasticity are poorly understood. Here, using Wide-bandwidth AFM-based ViscoElastic Spectroscopy (WAVES) coupled with mathematical modeling, we probe the origins of tumor viscoelasticity. From single carcinoma cells to increasingly sized carcinoma spheroids to established tumors, we describe a stepwise evolution of dynamic mechanical properties that create a nanorheological signature of established tumors: increased stiffness, decreased rate-dependent stiffening, and reduced energy dissipation. We dissect this evolution of viscoelasticity by scale, and show established tumors use fluid-solid interactions as the dominant mechanism of mechanical energy dissipation as opposed to fluid-independent intrinsic viscoelasticity. Additionally, we demonstrate the energy dissipation mechanism in spheroids and established tumors is negatively correlated with the cellular density, and this relationship strongly depends on an intact actin cytoskeleton. These findings define an emergent and targetable signature of the physical tumor microenvironment, with potential for deeper understanding of tumor pathophysiology and treatment strategies.


Assuntos
Carcinoma , Modelos Biológicos , Humanos , Elasticidade , Viscosidade , Citoesqueleto de Actina , Microambiente Tumoral
8.
J Neurosurg ; 141(1): 72-78, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38277657

RESUMO

OBJECTIVE: Foramen magnum (FM) meningiomas pose significant surgical challenges and have high morbidity and mortality rates. This study aimed to investigate the distribution of clinically actionable mutations in FM meningiomas and identify clinical characteristics associated with specific mutational profiles. METHODS: The authors conducted targeted next-generation sequencing of 62 FM meningiomas from three international institutions, covering all relevant meningioma genes (AKT1, KLF4, NF2, POLR2A, PIK3CA, SMO, TERT promoter, and TRAF7). Patients with a radiation-induced meningioma or neurofibromatosis type 2 (NF2) were excluded from the study. Additionally, patient and tumor characteristics, including age, sex, radiological features, and tumor location, were retrospectively collected and evaluated. RESULTS: The study cohort consisted of 46 female and 16 male patients. Clinically significant driver mutations were detected in 58 patients (93.5%). The most commonly observed alteration was TRAF7 mutations (26, 41.9%), followed by AKT1E17K mutations (19, 30.6%). Both mutations were significantly associated with an anterolateral tumor location relative to the brainstem (p = 0.0078). NF2 mutations were present in 11 cases (17.7%) and were associated with posterior tumor location, in contrast to tumors with TRAF7 and AKT1E17K mutations. Other common mutations in FM meningiomas included POLR2A mutations (8, 12.9%; 6 POLR2AQ403K and 2 POLR2AH439_L440del), KLF4K409Q mutations (7, 11.3%), and PIK3CA mutations (4, 6.5%; 2 PIK3CAH1047R and 2 PIK3CAE545K). POLR2A and KLF4 mutations exclusively occurred in female patients and showed no significant association with specific tumor locations. All tumors harboring AKT1E17K and POLR2A mutations displayed meningothelial histology. Ten tumors exhibited intratumoral calcification, which was significantly more frequent in NF2-mutant compared with AKT1-mutant FM meningiomas (p = 0.047). CONCLUSIONS: These findings provide important insights into the molecular genetics and clinicopathological characteristics of FM meningiomas. The identification of specific genetic alterations associated with tumor location, volume, calcification, histology, and sex at diagnosis may have implications for personalized treatment strategies in the future.


Assuntos
Forame Magno , Fator 4 Semelhante a Kruppel , Neoplasias Meníngeas , Meningioma , Mutação , Neurofibromina 2 , Humanos , Meningioma/genética , Meningioma/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Neoplasias Meníngeas/genética , Neoplasias Meníngeas/patologia , Neoplasias Meníngeas/diagnóstico por imagem , Adulto , Idoso , Estudos Retrospectivos , Neurofibromina 2/genética , Peptídeos e Proteínas Associados a Receptores de Fatores de Necrose Tumoral/genética , Proteínas Proto-Oncogênicas c-akt/genética , RNA Polimerase III/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Sequenciamento de Nucleotídeos em Larga Escala , Fatores de Transcrição Kruppel-Like/genética , Receptor Smoothened/genética , Análise Mutacional de DNA , Adulto Jovem , Telomerase
9.
Clin Cancer Res ; 30(1): 116-126, 2024 01 05.
Artigo em Inglês | MEDLINE | ID: mdl-37851071

RESUMO

PURPOSE: The 2021 World Health Organization (WHO) classification of central nervous system (CNS) tumors uses an integrated approach involving histopathology and molecular profiling. Because majority of adult malignant brain tumors are gliomas and primary CNS lymphomas (PCNSL), rapid differentiation of these diseases is required for therapeutic decisions. In addition, diffuse gliomas require molecular information on single-nucleotide variants (SNV), such as IDH1/2. Here, we report an intraoperative integrated diagnostic (i-ID) system to classify CNS malignant tumors, which updates legacy frozen-section (FS) diagnosis through incorporation of a qPCR-based genotyping assay. EXPERIMENTAL DESIGN: FS evaluation, including GFAP and CD20 rapid IHC, was performed on adult malignant CNS tumors. PCNSL was diagnosed through positive CD20 and negative GFAP immunostaining. For suspected glioma, genotyping for IDH1/2, TERT SNV, and CDKN2A copy-number alteration was routinely performed, whereas H3F3A and BRAF SNV were assessed for selected cases. i-ID was determined on the basis of the 2021 WHO classification and compared with the permanent integrated diagnosis (p-ID) to assess its reliability. RESULTS: After retrospectively analyzing 153 cases, 101 cases were prospectively examined using the i-ID system. Assessment of IDH1/2, TERT, H3F3AK27M, BRAFV600E, and CDKN2A alterations with i-ID and permanent genomic analysis was concordant in 100%, 100%, 100%, 100%, and 96.4%, respectively. Combination with FS and intraoperative genotyping assay improved diagnostic accuracy in gliomas. Overall, i-ID matched with p-ID in 80/82 (97.6%) patients with glioma and 18/19 (94.7%) with PCNSL. CONCLUSIONS: The i-ID system provides reliable integrated diagnosis of adult malignant CNS tumors.


Assuntos
Neoplasias Encefálicas , Neoplasias do Sistema Nervoso Central , Glioma , Adulto , Humanos , Estudos Retrospectivos , Reprodutibilidade dos Testes , Neoplasias do Sistema Nervoso Central/diagnóstico , Neoplasias do Sistema Nervoso Central/genética , Neoplasias Encefálicas/diagnóstico , Neoplasias Encefálicas/genética , Neoplasias Encefálicas/patologia , Glioma/diagnóstico , Glioma/genética , Glioma/cirurgia
10.
J Neurosurg Spine ; 40(3): 291-300, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-38039533

RESUMO

OBJECTIVE: The distributions and proportions of lean and fat tissues may help better assess the prognosis and outcomes of patients with spinal metastases. Specifically, in obese patients, sarcopenia may be easily overlooked as a poor prognostic indicator. The role of this body phenotype, sarcopenic obesity (SO), has not been adequately studied among patients undergoing surgical treatment for spinal metastases. To this end, here the authors investigated the role of SO as a potential prognostic factor in patients undergoing surgical treatment for spinal metastases. METHODS: The authors identified patients who underwent surgical treatment for spinal metastases between 2010 and 2020. A validated deep learning approach evaluated sarcopenia and adiposity on routine preoperative CT images. Based on composition analyses, patients were classified with SO or nonsarcopenic obesity. After nearest-neighbor propensity matching that accounted for confounders, the authors compared the rates and odds of postoperative complications, length of stay, 30-day readmission, and all-cause mortality at 90 days and 1 year between the SO and nonsarcopenic obesity groups. RESULTS: A total of 62 patients with obesity underwent surgical treatment for spinal metastases during the study period. Of these, 37 patients had nonsarcopenic obesity and 25 had SO. After propensity matching, 50 records were evaluated that were equally composed of patients with nonsarcopenic obesity and SO (25 patients each). Patients with SO were noted to have increased odds of nonhome discharge (OR 6.0, 95% CI 1.69-21.26), 30-day readmission (OR 3.27, 95% CI 1.01-10.62), and 90-day (OR 4.85, 95% CI 1.29-18.26) and 1-year (OR 3.78, 95% CI 1.17-12.19) mortality, as well as increased time to mortality after surgery (12.60 ± 19.84 months vs 37.16 ± 35.19 months, p = 0.002; standardized mean difference 0.86). No significant differences were noted in terms of length of stay or postoperative complications when comparing the two groups (p > 0.05). CONCLUSIONS: The SO phenotype was associated with increased odds of nonhome discharge, readmission, and postoperative mortality. This study suggests that SO may be an important prognostic factor to consider when developing care plans for patients with spinal metastases.


Assuntos
Sarcopenia , Neoplasias da Coluna Vertebral , Humanos , Sarcopenia/complicações , Neoplasias da Coluna Vertebral/complicações , Neoplasias da Coluna Vertebral/cirurgia , Obesidade/complicações , Prognóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia
11.
Neurosurgery ; 94(3): 529-537, 2024 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-37795983

RESUMO

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.


Assuntos
Internato e Residência , Humanos , Estados Unidos , Estudos Transversais , Educação de Pós-Graduação em Medicina , Neurocirurgiões , Inquéritos e Questionários
12.
Natl Med J India ; 36(1): 67-68, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37615150
13.
J Neurosurg Spine ; 39(4): 557-567, 2023 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-37439458

RESUMO

OBJECTIVE: Surgery for metastatic spinal tumors can have a substantial impact on patients' quality of life by alleviating pain, improving function, and correcting spinal instability when indicated. The decision to operate is difficult because many patients with cancer are frail. Studies have highlighted the importance of preoperative nutritional status assessments; however, little is known about which aspects of nutrition accurately inform clinical outcomes. This study investigates the interaction and prognostic importance of various nutritional and frailty measures in patients with spinal metastases. METHODS: A retrospective analysis of consecutive patients who underwent surgery for spinal metastases between 2014 and 2020 at the Massachusetts General Hospital was performed. Patients were stratified according to the New England Spinal Metastasis Score (NESMS). Frailty was assessed using the metastatic spinal tumor frailty index. Nutrition was assessed using the prognostic nutritional index (PNI), preoperative body mass index, albumin, albumin-to-globulin ratio, and platelet-to-lymphocyte ratio. Outcomes included postoperative survival and complication rates, with focus on wound-related complications. RESULTS: This study included 154 individuals (39% female; mean [SD] age 63.23 [13.14] years). NESMS 0 and NESMS 3 demonstrated the highest proportions of severely frail patients (56.2%) and nonfrail patients (16.1%), respectively. Patients with normal nutritional status (albumin-to-globulin ratio and PNI) had a better prognosis than those with poor nutritional status when stratified by NESMS. Multivariable regression adjusted for NESMS and frailty showed that a PNI > 40.4 was significantly associated with decreased odds of 90-day complications (OR 0.93, 95% CI 0.85-0.98). After accounting for age, sex, primary tumor pathology, physical function, nutritional status, and frailty, a preoperative nutrition consultation was associated with a decrease in postoperative wound-related complications (average marginal effect -5.00%; 95% CI -1.50% to -8.9%). CONCLUSIONS: The PNI was most predictive of complications and may be a key biomarker for risk stratification in the 90 days following surgery. Nutrition consultation was associated with a reduced risk of wound-related complications, attesting to the importance of this preoperative intervention. These findings suggest that nutrition plays an important role in the postsurgical course and should be considered when developing a treatment plan for spinal metastases.

14.
Neuro Oncol ; 25(12): 2239-2249, 2023 12 08.
Artigo em Inglês | MEDLINE | ID: mdl-37402650

RESUMO

BACKGROUND: Chimeric antigen receptor (CAR) T-cells targeting CD19 have been established as a leading engineered T-cell therapy for B-cell lymphomas; however, data for patients with central nervous system (CNS) involvement are limited. METHODS: We retrospectively report on CNS-specific toxicities, management, and CNS response of 45 consecutive CAR T-cell transfusions for patients with active CNS lymphoma at the Massachusetts General Hospital over a 5-year period. RESULTS: Our cohort includes 17 patients with primary CNS lymphoma (PCNSL; 1 patient with 2 CAR T-cell transfusions) and 27 patients with secondary CNS lymphoma (SCNSL). Mild ICANS (grade 1-2) was observed after 19/45 transfusions (42.2%) and severe immune effector cell-associated neurotoxicity syndrome (ICANS) (grade 3-4) after 7/45 transfusions (15.6%). A larger increase in C-reactive protein (CRP) levels and higher rates of ICANS were detected in SCNSL. Early fever and baseline C-reactive protein levels were associated with ICANS occurrence. CNS response was seen in 31 cases (68.9%), including a complete response of CNS disease in 18 cases (40.0%) which lasted for a median of 11.4 ±â€…4.5 months. Dexamethasone dose at time of lymphodepletion (but not at or after CAR T-cell transfusion) was associated with an increased risk for CNS progression (hazard ratios [HR] per mg/d: 1.16, P = .031). If bridging therapy was warranted, the use of ibrutinib translated into favorable CNS-progression-free survival (5 vs. 1 month, HR 0.28, CI 0.1-0.7; P = .010). CONCLUSIONS: CAR T-cells exhibit promising antitumor effects and a favorable safety profile in CNS lymphoma. Further evaluation of the role of bridging regimens and corticosteroids is warranted.


Assuntos
Neoplasias do Sistema Nervoso Central , Linfoma , Síndromes Neurotóxicas , Receptores de Antígenos Quiméricos , Humanos , Imunoterapia Adotiva/efeitos adversos , Proteína C-Reativa , Estudos Retrospectivos , Linfoma/terapia , Neoplasias do Sistema Nervoso Central/terapia , Síndromes Neurotóxicas/etiologia , Síndromes Neurotóxicas/terapia , Sistema Nervoso Central , Linfócitos T
16.
World Neurosurg ; 174: e26-e34, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36805503

RESUMO

OBJECTIVE: Group patients who required open surgery for metastatic breast cancer to the spine by functional level and metastatic disease characteristics to identify factors that predispose to poor outcomes. METHODS: A retrospective analysis included patients managed at 2 tertiary referral centers from 2008 to 2020. The primary outcome was a 90-day adverse event. A 2-step unsupervised cluster analysis stratified patients into cohorts using function at presentation, preoperative spine radiation, structural instability, epidural spinal cord compression (ESCC), neural deficits, and tumor location/hormone status. Comparisons were performed using χ2 test and one-way analysis of variance. RESULTS: Five patient "clusters" were identified. High function (HIGH) had thoracic metastases and an Eastern Cooperative Oncology Group (ECOG) score of 1.0 ± 0.8. Low function/irradiated (LOW + RADS) had preoperative radiation and the lowest Karnofsky scores (56.0 ± 10.6). Estrogen receptor or progesterone receptor (ER/PR) positive patients had >90% estrogen/progesterone positivity and moderate Karnofsky scores (74.0 ± 11.5). Lumbar/noncompressive (NON-COMP) had the fewest patients with ESCC grade 2 or 3 epidural disease (42.1%, P < 0.001). Low function/neurologic deficits (LOW + NEURO) had ESCC grade 2 or 3 disease and neurologic deficits. Adverse event rates were 25.0% in the HIGH group, 73.3% in LOW + RADS, 24.0% in ER/PR, 31.6% in NON-COMP, and 60.0% in LOW + NEURO (P = 0.003). CONCLUSIONS: Function at presentation, tumor hormone signature, radiation history, and epidural compression delineated postoperative trajectory. We believe our results can aid in expectation management and the identification of at-risk patients who may merit closer surveillance following surgical intervention.


Assuntos
Neoplasias da Mama , Leucemia Mieloide Aguda , Compressão da Medula Espinal , Neoplasias da Coluna Vertebral , Humanos , Feminino , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Estudos Retrospectivos , Inteligência Artificial , Neoplasias da Coluna Vertebral/secundário , Compressão da Medula Espinal/etiologia , Compressão da Medula Espinal/cirurgia , Compressão da Medula Espinal/patologia , Análise por Conglomerados
17.
Neurosurgery ; 92(1): 83-91, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36305664

RESUMO

BACKGROUND: Breast cancer molecular features and modern therapies are not included in spine metastasis prediction algorithms. OBJECTIVE: To examine molecular differences and the impact of postoperative systemic therapy to improve prognosis prediction for spinal metastases surgery and aid surgical decision making. METHODS: This is a retrospective multi-institutional study of patients who underwent spine surgery for symptomatic breast cancer spine metastases from 2008 to 2021 at the Massachusetts General Hospital and Brigham and Women's Hospital. We studied overall survival, stratified by breast cancer molecular subtype, and calculated hazard ratios (HRs) adjusting for demographics, tumor characteristics, treatments, and laboratory values. We tested the performance of established models (Tokuhashi, Bauer, Skeletal Oncology Research Group, New England Spinal Metastases Score) to predict and compare all-cause. RESULTS: A total of 98 patients surgically treated for breast cancer spine metastases were identified (100% female sex; median age, 56 years [IQR, 36-84 years]). The 1-year probabilities of survival for hormone receptor positive, hormone receptor positive/human epidermal growth factor receptor 2+, human epidermal growth factor receptor 2+, and triple-negative breast cancer were 63% (45 of 71), 83% (10 of 12), 0% (0 of 3), and 12% (1 of 8), respectively ( P < .001). Patients with triple-negative breast cancer had a higher proportion of visceral metastases, brain metastases, and poor physical activity at baseline. Postoperative chemotherapy and endocrine therapy were associated with prolonged survival. The Skeletal Oncology Research Group prognostic model had the highest discrimination (area under the receiver operating characteristic, 0.77 [95% CI, 0.73-0.81]). The performance of all prognostic scores improved when preoperative molecular data and postoperative systemic treatment plans was considered. CONCLUSION: Spine metastases risk tools were able to predict prognosis at a significantly higher degree after accounting for molecular features which guide treatment response.


Assuntos
Neoplasias da Mama , Neoplasias da Coluna Vertebral , Neoplasias de Mama Triplo Negativas , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias da Mama/cirurgia , Neoplasias da Mama/patologia , Prognóstico , Estudos Retrospectivos , Medição de Risco , Neoplasias da Coluna Vertebral/secundário
20.
J Neurosurg Spine ; : 1-9, 2022 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-35901764

RESUMO

OBJECTIVE: Posterior cervical spine fixation is a robust strategy for stabilizing the spine for a wide range of spinal disorders. With the evolution of spinal implant technology, posterior fixation with lateral mass screws in the subaxial spine is now common. Despite interest in variable rod diameters to meet a wide range of clinical needs such as trauma, revision, and deformity surgery, indications for use of posterior cervical spine fixation are not clear. This laboratory investigation evaluates the mechanical stability and kinematic properties of lateral mass fixation with various commercially available rod diameters. METHODS: The authors conducted an ex vivo experiment using 13 fresh-frozen human cervical spine specimens, instrumented from C3 to C6 with lateral mass screws, to evaluate the effects of titanium rod diameter on kinematic stability. Each intact spine was tested using a kinematic profiling machine with an optoelectrical camera and infrared sensors applying 1.5-Nm bending moments to the cranial vertebra (C2) simulating flexion-extension, lateral bending, and axial rotation anatomical motions. A compressive follower preload of 150 N was applied in flexion-extension prior to application of a bending moment. Instrumented spines were then tested with rod diameters of 3.5, 4.0, and 4.5 mm. The kinematic data between intact and surgical cases were studied using a nonparametric Wilcoxon signed-rank test. A multivariable, multilevel linear regression model was built to identify the relationship between segmental motion and rod diameter. RESULTS: Instrumentation resulted in significant reduction in range of motion in all three rod constructs versus intact specimens in flexion-extension, lateral bending, and axial rotation (p < 0.05). The maximum reductions in segmental ROM versus intact spines in 3.5-, 4.0-, and 4.5-mm rod constructs were 61%, 71%, and 81% in flexion-extension; 70%, 76%, and 81% in lateral bending; and 50%, 60%, and 75% in axial rotation, respectively. Segmental motion at the adjacent segments (C2-3 and C6-7) increased significantly (p < 0.05) with increasing rod diameter. The 4.5-mm rod construct had the greatest increase in motion compared to the intact spine. CONCLUSIONS: With increasing rod diameters from 3.5 to 4.0 mm, flexion-extension, lateral bending, and axial rotation across C3-6 were significantly reduced (p < 0.05). Similar trends were observed with a statistically significant reduction in motion in all anatomical planes when the rod diameter was increased to 4.5 mm. Although the increase in rod diameter resulted in a more rigid construct, it also created an increase (p < 0.05) in the kinematics of the adjacent segments (C2-3 and C6-7). Whether this increase translates into adverse long-term clinical effects in vivo requires further investigation and clinical assessment.

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