RESUMEN
OBJECTIVEAdult spinal deformity surgery is an effective way of treating pain and disability, but little research has been done to evaluate the costs associated with changes in health outcome measures. This study determined the change in quality-adjusted life years (QALYs) and the cost per QALY in patients undergoing spinal deformity surgery in the unique environment of a military healthcare system (MHS).METHODSPatients were enrolled between 2011 and 2017. Patients were eligible to participate if they were undergoing a thoracolumbar spinal fusion spanning more than 6 levels to treat an underlying deformity. Patients completed the 36-Item Short Form Health Survey (SF-36) prior to surgery and 6 and 12 months after surgery. The authors used paired t-tests to compare SF-36 Physical Component Summary (PCS) scores between baseline and postsurgery. To estimate the cost per QALY of complex spine surgery in this population, the authors extended the change in health-related quality of life (HRQOL) between baseline and follow-up over 5 years. Data on the cost of surgery were obtained from the MHS and include all facility and physician costs.RESULTSHRQOL and surgical data were available for 49 of 91 eligible patients. Thirty-one patients met additional criteria allowing for cost-effectiveness analysis. Over 12 months, patients demonstrated significant improvement (p < 0.01) in SF-36 PCS scores. A majority of patients met the minimum clinically important difference (MCID; 83.7%) and substantive clinical benefit threshold (SCBT; 83.7%). The average change in QALY was an increase of 0.08. Extended across 5 years, including the 3.5% discounting per year, study participants increased their QALYs by 0.39, resulting in an average cost per QALY of $181,649.20. Nineteen percent of patients met the < $100,000/QALY threshold with half of the patients meeting the < $100,000/QALY mark by 10 years. A sensitivity analysis showed that patients who scored below 60 on their preoperative SF-36 PCS had an average increase in QALYs of 0.10 per year or 0.47 over 5 years.CONCLUSIONSWith a 5-year extended analysis, patients who receive spinal deformity surgery in the MHS increased their QALYs by 0.39, with 19% of patients meeting the $100,000/QALY threshold. The majority of patients met the threshold for MCID and SCBT at 1 year postoperatively. Consideration of preoperative functional status (SF-36 PCS score < 60) may be an important factor in determining which patients benefit the most from spinal deformity surgery.
Asunto(s)
Análisis Costo-Beneficio , Atención a la Salud , Personal Militar/estadística & datos numéricos , Escoliosis/cirugía , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Periodo Posoperatorio , Calidad de Vida , Años de Vida Ajustados por Calidad de Vida , Estudios Retrospectivos , Fusión Vertebral/métodosRESUMEN
Low back pain due to spaceflight is a common complaint of returning astronauts. Alterations in musculoskeletal anatomy during spaceflight and the effects of microgravity (µg) have been well-studied; however, the mechanisms behind these changes remain unclear. The National Aeronautics and Space Administration has released the Human Research Roadmap to guide investigators in developing effective countermeasure strategies for the Artemis Program, as well as commercial low-orbit spaceflight. Based on the Human Research Roadmap, the existing literature was examined to determine the current understanding of the effects of microgravity on the musculoskeletal components of the spinal column. In addition, countermeasure strategies will be required to mitigate these effects for long-duration spaceflight. Current pharmacologic and nonpharmacologic countermeasure strategies are suboptimal, as evidenced by continued muscle and bone loss, alterations in muscle phenotype, and bone metabolism. However, studies incorporating the use of ultrasound, beta-blockers, and other pharmacologic agents have shown some promise. Understanding these mechanisms will not only benefit space technology but likely lead to a return on investment for the management of Earth-bound diseases.
Asunto(s)
Dolor de la Región Lumbar , Vuelo Espacial , Ingravidez , Humanos , Astronautas , Columna Vertebral , Ingravidez/efectos adversosRESUMEN
STUDY DESIGN: Controlled Laboratory Study. OBJECTIVE: To compare multilevel posterior cervical fusion (PCF) constructs stopping at C7, T1, and T2 under cyclic load to determine the range of motion (ROM) between the lowest instrumented level and lowest instrumented-adjacent level (LIV-1). SUMMARY OF BACKGROUND DATA: PCF is a mainstay of treatment for various cervical spine conditions. The transition between the flexible cervical spine and rigid thoracic spine can lead to construct failure at the cervicothoracic junction. There is little evidence to determine the most appropriate level at which to stop a multilevel PCF. METHODS: Fifteen human cadaveric cervicothoracic spines were randomly assigned to 1 of 3 treatment groups: PCF stopping at C7, T1, or T2. Specimens were tested in their native state, following a simulated PCF, and after cyclic loading. Specimens were loaded in flexion-extension), lateral bending, and axial rotation. Three-dimensional kinematics were recorded to evaluate ROM. RESULTS: The C7 group had greater flexion-extension motion than the T1 and T2 groups following instrumentation (10.17±0.83 degree vs. 2.77±1.66 degree and 1.06±0.55 degree, P <0.001), and after cyclic loading (10.42±2.30 degree vs. 2.47±0.64 degree and 1.99±1.23 degree, P <0.001). There was no significant difference between the T1 and T2 groups. The C7 group had greater lateral bending ROM than both thoracic groups after instrumentation (8.81±3.44 degree vs. 3.51±2.52 degree, P =0.013 and 1.99±1.99 degree, P =0.003) and after cyclic loading. The C7 group had greater axial rotation motion than the thoracic groups (4.46±2.27 degree vs. 1.26±0.69 degree, P =0.010; and 0.73±0.74 degree, P =0.003) following cyclic loading. CONCLUSION: Motion at the cervicothoracic junction is significantly greater when a multilevel PCF stops at C7 rather than T1 or T2. This is likely attributable to the transition from a flexible cervical spine to a rigid thoracic spine. Although this does not account for in vivo fusion, surgeons should consider extending multilevel PCF constructs to T1 when feasible. LEVEL OF EVIDENCE: Not applicable.
Asunto(s)
Enfermedades de la Columna Vertebral , Fusión Vertebral , Humanos , Fenómenos Biomecánicos , Vértebras Cervicales/cirugía , Cuello , Rango del Movimiento Articular , Rotación , Fusión Vertebral/métodosRESUMEN
BACKGROUND: Spinal cord metastatic lesions affect a high number of cancer patients usually resulting in spinal cord compression syndrome. A major obstacle in the research of spinal metastatic disease is the lack of a simple reproducible animal model that mimics the natural course of the disease. In this study, we present a highly reproducible rodent model that can be used for different types of cancers while mimicking the natural course of human metastatic spinal cord compression syndrome. RESULTS: All sixteen Fisher 344 rats survived the dorsal approach intraosseous implantation of CRL-1666 adenocarcinoma cells and both rats survived the sham control surgery. By Day 13 functional analysis via the modified Basso-Beattie-Bresnahan (BBB) locomotor rating scale showed significant decrease in motor function; median functional score was 3 for the tumor group (p = 0.0011). Median time to paresis was 8.7 days post-operatively. MR imaging illustrated repeated and consistent tumor formation, furthermore, onset of neurological sequale was the result of tumor formation and cord compression as confirmed by histological examination. CONCLUSIONS: Analysis of these findings demonstrates a repeatable and consistent tumor growth model for cancer spinal metastases in rats. This novel rat model requires a less intricate surgical procedure, and as a result minimizes procedure time while subsequently increasing consistency. Therefore, this model allows for the preclinical evaluation of therapeutics for spinal metastases that more closely replicates physiological findings.
Asunto(s)
Adenocarcinoma/complicaciones , Adenocarcinoma/patología , Trasplante de Neoplasias/métodos , Compresión de la Médula Espinal/etiología , Neoplasias de la Médula Espinal/complicaciones , Neoplasias de la Médula Espinal/patología , Animales , Línea Celular Tumoral , Modelos Animales de Enfermedad , Femenino , Imagen por Resonancia Magnética , Ratas , Ratas Endogámicas F344RESUMEN
We evaluated the safety and survival benefits of orally administered erlotinib monotherapy for patients with relapsed/refractory glioblastoma multiforme (GBM) or anaplastic astrocytoma (AA). A dose escalation schedule was administered with a starting dose of 150 mg/day for the first cycle (28 days), followed by 100 mg twice daily for 14 days, and 150 mg twice daily for another 14 days. Assuming no dose limiting toxicities were observed, dosage was maintained at 150 mg BID for 10 more cycles. Disease and tumor responses were assessed after every other cycle; toxicity assessments were conducted for a minimum of 10 weeks. Patients discontinued use of enzyme-inducing anticonvulsants (EIAED) and started non-EIAEDs. Patients with previous erlotinib exposure were ineligible. Eleven patients were enrolled: 8 (73%) GBM; 3 (27%) AA. Adverse events limited study accrual, originally intended to accrue 43 patients. Nine patients (90%) experienced rash within the first 2 cycles: 7 (64%) within cycle 1; 6 (60%) reported diarrhea within the first 2 cycles. Median progress-free survival (PFS) and overall survival (OS) was 1.9 months and 6.9 months. All patients showed disease progression while on the drug. Despite the sample size, the toxicity of erlotinib supersedes any marginal benefit it as a monotherapy for relapsed/refractory GBM/AA.
Asunto(s)
Astrocitoma/tratamiento farmacológico , Neoplasias Encefálicas/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Quinazolinas/administración & dosificación , Adulto , Anciano , Anticonvulsivantes/administración & dosificación , Astrocitoma/patología , Neoplasias Encefálicas/patología , Supervivencia sin Enfermedad , Clorhidrato de Erlotinib , Femenino , Glioblastoma/patología , Humanos , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/tratamiento farmacológico , Fosfohidrolasa PTEN/metabolismo , Inhibidores de Proteínas Quinasas/administración & dosificación , Inhibidores de Proteínas Quinasas/toxicidad , Quinazolinas/toxicidad , RecurrenciaRESUMEN
Intra-arterial bevacizumab (IA BV) has been recently identified to be safe in the treatment of recurrent GBM. In this study, we sought to perform a cost analysis of IA BV versus IV BV especially also taking account of patient progression free survival (PFS) and overall survival (OS). We show that IA BV is significantly more cost effective than conventional IV therapy.
Asunto(s)
Inhibidores de la Angiogénesis/administración & dosificación , Inhibidores de la Angiogénesis/economía , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/economía , Neoplasias del Sistema Nervioso Central/tratamiento farmacológico , Glioblastoma/tratamiento farmacológico , Adulto , Inhibidores de la Angiogénesis/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Bevacizumab , Ahorro de Costo , Supervivencia sin Enfermedad , Femenino , Humanos , Infusiones Intraarteriales/economía , Infusiones Intravenosas/economía , Estimación de Kaplan-Meier , Masculino , Persona de Mediana EdadRESUMEN
Introduction: The authors present a case of a 55-year-old male with T10 complete paraplegia diagnosed with Charcot arthropathy of the spine (CAS). Case presentation: He presented to an outside institution with vomiting and productive cough with subsequent computed tomography (CT) and MRI imaging revealing L5 osteomyelitis and a paraspinal abscess. Given the patient's inability to remain in good posture in his wheelchair he underwent a multilevel vertebrectomy and thoracolumbar fusion. Due to multiple co-morbidities, surgical recovery was complex, ultimately requiring revision circumferential fixation. Discussion: CAS is an uncommon, long-term complication of traumatic spinal cord injury (SCI). Surgical management is often complex and associated with significant complications. Currently, a consensus on CAS prevention, specific surgical fixation techniques and post-surgical nursing care management is lacking. In this case report we provide our experience in the management of a complex case of CAS to aid in decision making for future neurosurgeons who encounter this sequela of traumatic SCI.
Asunto(s)
Artropatía Neurógena/cirugía , Traumatismos de la Médula Espinal/complicaciones , Espondiloartropatías/cirugía , Artropatía Neurógena/etiología , Humanos , Masculino , Persona de Mediana Edad , Paraplejía/etiología , Fusión Vertebral/métodos , Espondiloartropatías/etiologíaRESUMEN
BACKGROUND: To decrease vehicular traffic in major metropolitan cities throughout the United States, multiple ridesharing companies have launched dockless electric scooters and bicycles throughout cities. From September 2017 through November 2018, Washington, DC, launched a 15-month dockless vehicle pilot program to allow for the rapid entry and growth of electric scooters within the metropolitan area. This rapid growth resulted in a number of minor and significant injuries. CASE DESCRIPTION: We reviewed the electronic medical record of The George Washington University Hospital to investigate and characterize the types of electric scooter-related injuries resulting in neurosurgical consultation in the 15-month period of the Washington, DC, scooter pilot program. Thirteen patients sustained injuries serious enough to merit neurosurgical consultation, including 1 patient whose symptoms required procedural intervention by a neurointerventional radiologist and another patient who was pronounced dead soon after arrival to the hospital. CONCLUSIONS: In this case series, we highlight more severe injuries that resulted in hospitalization or intervention, including skull fracture, central cord syndrome, and vertebral compression fracture. This case series aims to illustrate the potential severity of injuries related to electric scooters, raise awareness on the issues of safety and public health, and call for further investigation into injuries relating to electric scooters.
Asunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Motocicletas , Procedimientos Neuroquirúrgicos/estadística & datos numéricos , Adulto , Síndrome del Cordón Central/epidemiología , District of Columbia/epidemiología , Registros Electrónicos de Salud , Femenino , Fracturas por Compresión/epidemiología , Hospitalización/estadística & datos numéricos , Humanos , Masculino , Persona de Mediana Edad , Derivación y Consulta , Fracturas Craneales/epidemiología , Fracturas de la Columna Vertebral/epidemiología , Resultado del Tratamiento , Adulto JovenRESUMEN
Radiotherapy for the treatment of cancer is undergoing an evolution, shifting to the use of heavier ion species. For a plethora of malignancies, current radiotherapy using photons or protons yields marginal benefits in local control and survival. One hypothesis is that these malignancies have acquired, or are inherently radioresistant to low LET radiation. In the last decade, carbon ion radiotherapy facilities have slowly been constructed in Europe and Asia, demonstrating favorable results for many of the malignancies that do poorly with conventional radiotherapy. However, from a radiobiological perspective, much of how this modality works in overcoming radioresistance, and extending local control and survival are not yet fully understood. In this review, we will explain from a radiobiological perspective how carbon ion radiotherapy can overcome the classical and recently postulated contributors of radioresistance (α/ß ratio, hypoxia, cell proliferation, the tumor microenvironment and metabolism, and cancer stem cells). Furthermore, we will make recommendations on the important factors to consider, such as anatomical location, in the future design and implementation of clinical trials. With the existing data available we believe that the expansion of carbon ion facilities into the United States is warranted.
Asunto(s)
Carbono/química , Radioterapia de Iones Pesados/métodos , Neoplasias/radioterapia , Radioterapia/métodos , Ciclo Celular , Proliferación Celular , Ensayos Clínicos como Asunto , Glucosa/metabolismo , Humanos , Hipoxia , Transferencia Lineal de Energía , Neoplasias/metabolismo , Células Madre Neoplásicas/citología , Oxígeno/química , Células Madre , Microambiente TumoralRESUMEN
The misrepair of DNA double-strand breaks in close spatial proximity within the nucleus can result in chromosomal rearrangements that are important in the pathogenesis of haematopoietic and solid malignancies. It is unknown why certain epigenetic states, such as those found in stem or progenitor cells, appear to facilitate neoplastic transformation. Here we show that altering the transcriptional state of human astrocytes alters patterns of DNA damage repair from ionizing radiation at a gene locus-specific and genome-wide level. Astrocytes induced into a reactive state exhibit increased DNA repair, compared with non-reactive cells, in actively transcribed chromatin after irradiation. In mapping these repair sites, we identify misrepair events and repair hotspots that are unique to each state. The precise characterization of genomic regions susceptible to mutation in specific transcriptional states provides new opportunities for addressing clonal evolution in solid cancers, in particular those where double-strand break induction is a cornerstone of clinical intervention.
Asunto(s)
Astrocitos/efectos de la radiación , Transformación Celular Neoplásica/efectos de la radiación , Reparación del ADN , ADN/metabolismo , Transcripción Genética , Adulto , Animales , Astrocitos/citología , Astrocitos/metabolismo , Transformación Celular Neoplásica/genética , Transformación Celular Neoplásica/patología , Corteza Cerebral/citología , Corteza Cerebral/metabolismo , Corteza Cerebral/efectos de la radiación , Cromatina/química , Cromatina/metabolismo , Cromatina/efectos de la radiación , Evolución Clonal , ADN/química , Roturas del ADN de Doble Cadena , Feto , Rayos gamma , Expresión Génica , Genoma Humano , Histonas/genética , Histonas/metabolismo , Humanos , Macaca fascicularis , Mutación , Cultivo Primario de CélulasRESUMEN
Exosomes are nanometer-sized lipid vesicles released ubiquitously by cells, which have been shown to have a normal physiological role, as well as influence the tumor microenvironment and aid metastasis. Recent studies highlight the ability of exosomes to convey tumor-suppressive and oncogenic mRNAs, microRNAs, and proteins to a receiving cell, subsequently activating downstream signaling pathways and influencing cellular phenotype. Here, we show that radiation increases the abundance of exosomes released by glioblastoma cells and normal astrocytes. Exosomes derived from irradiated cells enhanced the migration of recipient cells, and their molecular profiling revealed an abundance of molecules related to signaling pathways important for cell migration. In particular, connective tissue growth factor (CTGF) mRNA and insulin-like growth factor binding protein 2 (IGFBP2) protein levels were elevated, and coculture of nonirradiated cells with exosomes isolated from irradiated cells increased CTGF protein expression in the recipient cells. Additionally, these exosomes enhanced the activation of neurotrophic tyrosine kinase receptor type 1 (TrkA), focal adhesion kinase, Paxillin, and proto-oncogene tyrosine-protein kinase Src (Src) in recipient cells, molecules involved in cell migration. Collectively, our data suggest that radiation influences exosome abundance, specifically alters their molecular composition, and on uptake, promotes a migratory phenotype.
RESUMEN
The cancer stem-cell hypothesis proposes that malignant tumors are likely to encompass a cellular hierarchy that parallels normal tissue and may be responsible for the maintenance and recurrence of glioblastoma multiforme (GBM) in patients. The purpose of this manuscript is to review methods for optimizing the derivation and culturing of stem-like cells also known as tumor stem cells (TSCs) from patient-derived GBM tissue samples. The hallmarks of TSCs are that they must be able to self-renew and retain tumorigenicity. The isolation, optimization and derivation of TSCs as outlined in this review, will be important in understanding biology and therapeutic applications related to these cells.