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1.
Int J Spine Surg ; 2024 Sep 20.
Artículo en Inglés | MEDLINE | ID: mdl-39304340

RESUMEN

BACKGROUND: Lumbar disc herniation (LDH) is a common cause of radicular pain with an annual incidence between 5 and 20 cases per 1000 adults. LDH is typically treated by microdiscectomy, of which more than 300,000 are performed in the United States each year. Despite this frequency, 25% to 33% of patients report poor surgical outcomes. This study sought to present a retrospective analysis of patients who underwent microdiscectomy surgery for the treatment of LDH with the aim of identifying demographic, historical, and surgical factors that may contribute to inadequate surgical results. METHODS: A retrospective study of 241 patients at Stony Brook Medicine from 2017 to 2022 was performed, 123 of whom had follow-up of 90 days or more and were included for final analysis. Data collection included demographics, medical/surgical history, and surgical methodology. Good outcomes were defined as meeting the absolute point change threshold (ACT)-3.5pt reduction in pain reported by the Numerical Rating System (NRS) or the resolution of either radicular pain or neurological symptoms. RESULTS: Univariate analysis revealed that 100% of patients with prior fusion surgery (P = 0.039) and 73.2% who underwent preoperative physical therapy (PT; P = 0.032) failed to meet the ACT. Additionally, 79.1% (P = 0.021) and 82.8% (P = 0.026) of patients who had PT had residual radicular pain and neurological symptoms, respectively. Multivariate logistic regression confirmed correlations between preoperative PT and failure to meet the ACT (P = 0.030, OR = 0.252) and resolution of radicular (P = 0.006, OR = 0.196) and neurological (P = 0.030, OR = 0.177) complaints. ACT directly correlated with higher preoperative NRS scores in univariate (P = 0.0002) and multivariate (P = 0.002, OR = 1.554) analyses. CONCLUSION: Our results show that higher preoperative NRS scores, PT, and prior fusion surgery are associated with poorer outcomes. While PT is considered a viable nonoperative treatment for LDH, our findings suggest detrimental effects when preceding surgery, indicating the need for additional research into the effects of PT on patients with high grade LDH.

2.
Sci Data ; 7(1): 116, 2020 04 14.
Artículo en Inglés | MEDLINE | ID: mdl-32286315

RESUMEN

Understanding the aberrant transcriptional landscape of neuroblastoma is necessary to provide insight to the underlying influences of the initiation, progression and persistence of this developmental cancer. Here, we present chromatin immunoprecipitation sequencing (ChIP-Seq) data for the oncogenic transcription factors, MYCN and MYC, as well as regulatory histone marks H3K4me1, H3K4me3, H3K27Ac, and H3K27me3 in ten commonly used human neuroblastoma-derived cell line models. In addition, for all of the profiled cell lines we provide ATAC-Seq as a measure of open chromatin. We validate specificity of global MYCN occupancy in MYCN amplified cell lines and functional redundancy of MYC occupancy in MYCN non-amplified cell lines. Finally, we show with H3K27Ac ChIP-Seq that these cell lines retain expression of key neuroblastoma super-enhancers (SE). We anticipate this dataset, coupled with available transcriptomic profiling on the same cell lines, will enable the discovery of novel gene regulatory mechanisms in neuroblastoma.


Asunto(s)
Epigenómica , Proteína Proto-Oncogénica N-Myc/genética , Neuroblastoma/genética , Línea Celular Tumoral , Cromatina/genética , Inmunoprecipitación de Cromatina , Perfilación de la Expresión Génica , Histonas/genética , Humanos
3.
Cell Rep ; 29(6): 1675-1689.e9, 2019 11 05.
Artículo en Inglés | MEDLINE | ID: mdl-31693904

RESUMEN

Accelerating cures for children with cancer remains an immediate challenge as a result of extensive oncogenic heterogeneity between and within histologies, distinct molecular mechanisms evolving between diagnosis and relapsed disease, and limited therapeutic options. To systematically prioritize and rationally test novel agents in preclinical murine models, researchers within the Pediatric Preclinical Testing Consortium are continuously developing patient-derived xenografts (PDXs)-many of which are refractory to current standard-of-care treatments-from high-risk childhood cancers. Here, we genomically characterize 261 PDX models from 37 unique pediatric cancers; demonstrate faithful recapitulation of histologies and subtypes; and refine our understanding of relapsed disease. In addition, we use expression signatures to classify tumors for TP53 and NF1 pathway inactivation. We anticipate that these data will serve as a resource for pediatric oncology drug development and will guide rational clinical trial design for children with cancer.


Asunto(s)
Neoplasias del Sistema Nervioso Central/genética , Neurofibromina 1/antagonistas & inhibidores , Leucemia-Linfoma Linfoblástico de Células Precursoras/genética , Proteína p53 Supresora de Tumor/antagonistas & inhibidores , Ensayos Antitumor por Modelo de Xenoinjerto , Animales , Línea Celular Tumoral , Neoplasias del Sistema Nervioso Central/metabolismo , Niño , Ensayos Clínicos como Asunto , Modelos Animales de Enfermedad , Genómica , Humanos , Ratones , Mutación , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neurofibromina 1/genética , Neurofibromina 1/metabolismo , Osteosarcoma/genética , Osteosarcoma/metabolismo , Leucemia-Linfoma Linfoblástico de Células Precursoras/metabolismo , Recurrencia , Rabdomiosarcoma/genética , Rabdomiosarcoma/metabolismo , Sarcoma de Ewing/genética , Sarcoma de Ewing/metabolismo , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo , Secuenciación del Exoma , Tumor de Wilms/genética , Tumor de Wilms/metabolismo
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