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OBJECTIVE: The management of cranioplasty infections has historically been explantation followed by delayed reimplantation/reconstruction. This treatment algorithm necessitates surgery, tissue expansion, and prolonged disfigurement. In this report, the authors describe a treatment approach consisting of serial vacuum-assisted closure (VAC) with hypochlorous acid (HOCl) solution (Vashe Wound Solution; URGO Medical) as a salvage strategy. METHODS: A 35-year-old man who sustained head trauma, neurosurgical complications, and severe syndrome of the trephined (SOT; devastating neurologic decline treated by cranioplasty) underwent titanium cranioplasty with free flap. Three weeks postoperation, he presented with pressure-related wound dehiscence/partial flap necrosis, exposed hardware, and bacterial infection. Given the severity of his precranioplasty SOT, hardware salvage was critical. He was treated with serial VAC with HOCl solution for 11 days followed by VAC for 18 days and definitive split-thickness skin graft placement over resulting granulation tissue. Authors also conducted a literature review of cranial reconstruction infection management. RESULTS: The patient remained healed 7 months postoperatively without recurrent infection. Importantly, his original hardware was retained, and his SOT remained resolved. Findings from the literature review support the use of conservative modalities to salvage cranial reconstructions without hardware removal. CONCLUSIONS: This study investigates a new strategy for managing cranioplasty infections. The VAC with HOCl solution regimen was effective in treating the infection and salvaging the cranioplasty, thus obviating the complications associated with explantation, new cranioplasty, and recurrence of SOT. There is limited literature on the management of cranioplasty infections using conservative treatments. A larger study to better determine the efficacy of VAC with HOCl solution is underway.
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Terapia de Presión Negativa para Heridas , Masculino , Humanos , Adulto , Terapia de Presión Negativa para Heridas/métodos , Resultado del Tratamiento , Infección de la Herida Quirúrgica/terapia , Cicatrización de Heridas , Colgajos Quirúrgicos , Complicaciones PosoperatoriasRESUMEN
BACKGROUND: The primary goal of this study was to evaluate patterns in acute postoperative pain in a mixed surgical patient cohort with the hypothesis that there would be heterogeneity in these patterns. METHODS: This study included 360 patients from a mixed surgical cohort whose pain was measured across postoperative days 1 through 7. Pain was characterized using the Brief Pain Inventory. Primary analysis used group-based trajectory modeling to estimate trajectories/patterns of postoperative pain. Secondary analysis examined associations between sociodemographic, clinical, and behavioral patient factors and pain trajectories. RESULTS: Five distinct postoperative pain trajectories were identified. Many patients (167 of 360, 46%) were in the moderate-to-high pain group, followed by the moderate-to-low (88 of 360, 24%), high (58 of 360, 17%), low (25 of 360, 7%), and decreasing (21 of 360, 6%) pain groups. Lower age (odds ratio, 0.94; 95% CI, 0.91 to 0.99), female sex (odds ratio, 6.5; 95% CI, 1.49 to 15.6), higher anxiety (odds ratio, 1.08; 95% CI, 1.01 to 1.14), and more pain behaviors (odds ratio, 1.10; 95% CI, 1.02 to 1.18) were related to increased likelihood of being in the high pain trajectory in multivariable analysis. Preoperative and intraoperative opioids were not associated with postoperative pain trajectories. Pain trajectory group was, however, associated with postoperative opioid use (P < 0.001), with the high pain group (249.5 oral morphine milligram equivalents) requiring four times more opioids than the low pain group (60.0 oral morphine milligram equivalents). CONCLUSIONS: There are multiple distinct acute postoperative pain intensity trajectories, with 63% of patients reporting stable and sustained high or moderate-to-high pain over the first 7 days after surgery. These postoperative pain trajectories were predominantly defined by patient factors and not surgical factors.
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Analgésicos Opioides/uso terapéutico , Morfina/uso terapéutico , Dolor Postoperatorio/fisiopatología , Factores de Edad , Estudios de Cohortes , Femenino , Florida , Humanos , Masculino , Persona de Mediana Edad , Dolor Postoperatorio/tratamiento farmacológico , Estudios Prospectivos , Índice de Severidad de la Enfermedad , Factores SexualesRESUMEN
BACKGROUND: Evidence suggests that increased early postoperative pain (POP) intensities are associated with increased pain in the weeks following surgery. However, it remains unclear which temporal aspects of this early POP relate to later pain experience. In this prospective cohort study, we used wavelet analysis of clinically captured POP intensity data on postoperative days 1 and 2 to characterize slow/fast dynamics of POP intensities and predict pain outcomes on postoperative day 30. METHODS: The study used clinical POP time series from the first 48 hours following surgery from 218 patients to predict their mean POP on postoperative day 30. We first used wavelet analysis to approximate the POP series and to represent the series at different time scales to characterize the early temporal profile of acute POP in the first 2 postoperative days. We then used the wavelet coefficients alongside demographic parameters as inputs to a neural network to predict the risk of severe pain 30 days after surgery. RESULTS: Slow dynamic approximation components, but not fast dynamic detailed components, were linked to pain intensity on postoperative day 30. Despite imbalanced outcome rates, using wavelet decomposition along with a neural network for classification, the model achieved an F score of 0.79 and area under the receiver operating characteristic curve of 0.74 on test-set data for classifying pain intensities on postoperative day 30. The wavelet-based approach outperformed logistic regression (F score of 0.31) and neural network (F score of 0.22) classifiers that were restricted to sociodemographic variables and linear trajectories of pain intensities. CONCLUSIONS: These findings identify latent mechanistic information within the temporal domain of clinically documented acute POP intensity ratings, which are accessible via wavelet analysis, and demonstrate that such temporal patterns inform pain outcomes at postoperative day 30.
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Dimensión del Dolor , Percepción del Dolor , Umbral del Dolor , Dolor Postoperatorio/diagnóstico , Análisis de Ondículas , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Redes Neurales de la Computación , Dolor Postoperatorio/etiología , Dolor Postoperatorio/fisiopatología , Dolor Postoperatorio/psicología , Valor Predictivo de las Pruebas , Estudios Prospectivos , Recuperación de la Función , Índice de Severidad de la Enfermedad , Factores de TiempoRESUMEN
Primary Objective: The purpose of this study was to determine the utility of CT imaging in patients with non-operative mild-moderate TBI with respect to changes in management.Methods: We conducted a retrospective analysis for 191 patients over a 5-year interval to examine whether follow-up CT initiated a change in management. We created a logistic regression model to incorporate different variables contributing to change in management.Results: Of 191 patients, 31 (16.2%) underwent a change in management. Change in management was associated with older age (65 yo vs. 55 yo, p = .011), diagnosis of subdural hematoma (p = .041), antiplatelet/anticoagulant therapy (p = .009), imaging performed (p = .16), and increased blood products on CT (p = <0.0001). For patients on antiplatelet/anticoagulant therapy, only those with worsening findings on CT required a change in management (p = .0002, 0.039). Surgical intervention was indicated in two patients.Conclusions: Limited clinical value exists in repeat CT scans for patients with mild TBI. Most patients with traumatic SAH, contusions, or asymptomatic patients should not have repeat imaging, as our study revealed only 2% of patients with positive CT finding and 0.6% requiring surgical intervention.
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Lesiones Traumáticas del Encéfalo , Anciano , Lesiones Traumáticas del Encéfalo/diagnóstico por imagen , Lesiones Traumáticas del Encéfalo/terapia , Escala de Coma de Glasgow , Hospitalización , Humanos , Estudios Retrospectivos , Tomografía Computarizada por Rayos XRESUMEN
INTRODUCTION: National and international trends continue to show greater emphasis on endovascular techniques for the treatment of cerebrovascular disease. The cerebrovascular neurosurgeon however must be adequately equipped to treat these patients via both open and endovascular techniques. METHODS: The decline in open cerebrovascular cases for aneurysm clipping has forced many trainees to pursue open cerebrovascular fellowships to increase case volume. An alternative strategy has been employed at our institution, which is early identification of subspecialty focus with resident driven self-selection of open cerebrovascular cases. RESULTS: This has allowed recent graduates to obtain enfolded endovascular training and a significant number of open cerebrovascular cases in order to obtain competence and exposure. DISCUSSION: We advocate for further self-selection paradigms supplemented with simulation training in order to obviate the need for extended post-residency fellowships.
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Procedimientos Endovasculares , Internado y Residencia , Neurocirugia , Humanos , Neurocirugia/educación , Procedimientos NeuroquirúrgicosRESUMEN
The development of novel therapies, imaging techniques and insights into the processes that drive growth of CNS tumors have allowed growing enthusiasm for the treatment of CNS malignancies. Despite this energized effort to investigate and treat brain cancer, clinical outcomes for most patients continue to be dismal. Recognition of diverse tumor subtypes, behaviors and outcomes has led to an interest in personalized medicine for the treatment of brain tumors. This new paradigm requires evaluation of the tumor phenotype at the time of diagnosis so that therapy can be specifically tailored to each individual patient. Investigating novel therapies involving stem cells, nanotechnology and molecular medicine will allow diversity of therapeutic options for patients with brain cancer. These exciting new therapeutic strategies for brain tumors are reviewed in this article.
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Neoplasias del Sistema Nervioso Central/terapia , Glioma/terapia , Medicina de Precisión , Trasplante de Células Madre , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/farmacocinética , Biomarcadores de Tumor/metabolismo , Barrera Hematoencefálica/metabolismo , Neoplasias del Sistema Nervioso Central/patología , Ensayos Clínicos como Asunto , Sistemas de Liberación de Medicamentos , Resistencia a Antineoplásicos , Glioma/patología , Humanos , NanotecnologíaRESUMEN
BACKGROUND/AIMS: Recombinant human bone morphogenetic protein-2 (rhBMP-2) is responsible for multiple different signaling processes including positive effects on bone formation and fusion. In 2002, rhBMP-2 was approved for use in anterior lumbar spinal fusion by the Food and Drug Administration. Since that time, rhBMP-2 use for spinal fusion has become widespread. The use of rh-BMP2 for pediatric spinal fusion, however, has not been widely reported. We report the experience of the use of rhBMP-2 for pediatric spinal fusion at the University of Florida. METHODS: Data on patients under the age of 18 years who underwent spinal fusion with rhBMP-2 as an adjunct were retrospectively collected. Of these, 17 met the inclusion criteria and were reviewed. Two patients did not have adequate postoperative imaging. Fifteen patients were included in the final review. RESULTS: All 15 patients showed osseous fusion. Complications included one CSF leak and one wound infection, one misplaced screw requiring revision, and one case of adjacent segment kyphosis requiring extension of the original construct. CONCLUSION: rhBMP-2 is a successful adjunct for fusion in pediatric patients. Many of these patients had congenital defects that historically decrease fusion rates. rhBMP-2 appears safe and has an associated high rate of osseous fusion.
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Proteína Morfogenética Ósea 2/uso terapéutico , Fusión Vertebral/métodos , Factor de Crecimiento Transformador beta/uso terapéutico , Adolescente , Niño , Preescolar , Terapia Combinada , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Proteínas Recombinantes/uso terapéutico , Estudios Retrospectivos , Fusión Vertebral/efectos adversos , Tomografía Computarizada por Rayos XRESUMEN
BACKGROUND AND OBJECTIVES: Patient experience has become a quality measure in hospitals across the United States. To improve our understanding of our neurosurgical patient population's satisfaction needs, we undertook a detailed survey to identify areas of needed improvement. METHODS: Upon institutional review board approval, a detailed survey adopted from the Swedish quality-of-care patient questionnaire was distributed to all patients being discharged from the neurosurgical ward over a month period. From June 2014 to July 2014, all patients admitted to the neurosurgery service through the emergency department, clinic, or other facilities were enrolled. There were no specific inclusion criteria except for age older than 18 years, intact cognition to complete the survey, and return of a completed survey. Data were collected in 6 major categories, including information availability, patient accessibility, treatment received, caring perception, hospital environment, and overall satisfaction. Patients were evaluated by age, gender, surgery, and admission type. RESULTS: Our analysis demonstrated an improved overall satisfaction in those patients being admitted electively from the clinic as compared with emergency department admissions or hospital transfers. In addition, patients admitted on an emergent basis reported a lower satisfaction pertaining to receiving information, specifically test results. CONCLUSIONS: Emergent admissions represent a subpopulation that may require additional strategies to improve patient satisfaction survey scores.
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Hospitales , Satisfacción del Paciente , Adolescente , Servicio de Urgencia en Hospital , Hospitalización , Humanos , Medición de Resultados Informados por el Paciente , Estados UnidosRESUMEN
OBJECTIVE: Acute postoperative pain intensity is associated with persistent postsurgical pain (PPP) risk. However, it remains unclear whether acute postoperative pain intensity mediates the relationship between clinical factors and persistent pain. MATERIALS AND METHODS: Participants from a mixed surgical population completed the Brief Pain Inventory and Pain Catastrophizing Scale before surgery, and the Brief Pain Inventory daily after surgery for 7 days and at 30 and 90 days after surgery. We considered mediation models using the mean of the worst pain intensities collected daily on each of postoperative days (PODs) 1 to 7 against outcomes of worst pain intensity at the surgical site endpoints reflecting PPP (POD 90) and subacute pain (POD 30). RESULTS: The analyzed cohort included 284 participants for the POD 90 outcome. For every unit increase of maximum acute postoperative pain intensity through PODs 1 to 7, there was a statistically significant increase of mean POD 90 pain intensity by 0.287 after controlling for confounding effects. The effects of female versus male sex (m=0.212, P=0.034), pancreatic/biliary versus colorectal surgery (m=0.459, P=0.012), thoracic cardiovascular versus colorectal surgery (m=0.31, P=0.038), every minute increase of anesthesia time (m=0.001, P=0.038), every unit increase of preoperative average pain score (m=0.012, P=0.015), and every unit increase of catastrophizing (m=0.044, P=0.042) on POD 90 pain intensity were mediated through acute PODs 1 to 7 postoperative pain intensity. DISCUSSION: Our results suggest the mediating relationship of acute postoperative pain on PPP may be predicated on select patient and surgical factors.
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Análisis de Mediación , Dolor Postoperatorio , Catastrofización , Femenino , Humanos , Masculino , Dimensión del Dolor , Estudios ProspectivosRESUMEN
Given the tremendous success of deep brain stimulation (DBS) for the treatment of movement and neuropsychiatric disorders, clinicians have begun to open up to the possible use of electrical stimulation for the treatment of patients with uncontrolled seizures. This process has resulted in the discovery of a wide array of DBS targets, including the cerebellum, hypothalamus, hippocampus, basal ganglia, and various thalamic nuclei. Despite the ambiguity of the mechanism of action and the unknowns surrounding potentially ideal stimulation settings, several recent trials have empirically demonstrated reasonable efficacy in selected cases of medication-refractory seizures. These exciting results have fueled a number of studies aimed at firmly establishing DBS as an effective treatment for selected cases of intractable epilepsy, and many companies are aiming at Food and Drug Administration approval. We endeavor to review the studies in the context of the various DBS targets and their relevant circuitry for epilepsy. Based on the unfolding research, DBS has the potential to play an important role in treating refractory epilepsy. The challenge, as in movement disorders, is to assemble interdisciplinary teams to screen, implant, and follow patients, and to clarify patient selection. The future will undoubtedly be filled with optimization of targets and stimulation parameters and the development of best practices. With tailored therapeutic approaches, epilepsy patients have the potential to improve with DBS.
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Encéfalo/fisiopatología , Estimulación Encefálica Profunda/métodos , Epilepsia/terapia , Estimulación Encefálica Profunda/tendencias , Resistencia a Medicamentos , Electroencefalografía/estadística & datos numéricos , Epilepsia/tratamiento farmacológico , Epilepsia/fisiopatología , Predicción , Humanos , Selección de Paciente , Resultado del TratamientoRESUMEN
Stereotactic neurosurgery has a rich history, beginning with the first stereotactic frame described by Horsley and Clarke in 1908. It is now widely used for delivery of radiation, surgical targeting of electrodes, and resection to treat tumors, epilepsy, vascular malformations, and pain syndromes. These treatments are now available due to the pioneering efforts of neurosurgeons and scientists in the beginning of the 20th century. Their efforts focused on the development of stereotactic instruments for accurate lesion targeting. In this paper, the authors review the history of the stereotactic apparatus in the early 20th century, with a focus on the fascinating people key to its development.
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Neurocirugia/historia , Procedimientos Neuroquirúrgicos/historia , Técnicas Estereotáxicas/historia , Mapeo Encefálico/instrumentación , Neoplasias Encefálicas/cirugía , Craneotomía/historia , Craneotomía/instrumentación , Epilepsia/cirugía , Historia del Siglo XX , Humanos , Microcirugia/historia , Microcirugia/instrumentación , Neurocirugia/instrumentación , Procedimientos Neuroquirúrgicos/instrumentación , Dolor/cirugía , Radioterapia/métodos , Técnicas Estereotáxicas/instrumentaciónRESUMEN
The search for efficacious, minimally invasive neurosurgical treatment has led to the development of the operating microscope, endovascular treatment, and endoscopic surgery. One of the most minimally invasive and exciting discoveries is the use of targeted, high-dose radiation for neurosurgical disorders. Radiosurgery is truly minimally invasive, delivering therapeutic energy to an accurately defined target without an incision, and has been used to treat a wide variety of pathological conditions, including benign and malignant brain tumors, vascular lesions such as arteriovenous malformations, and pain syndromes such as trigeminal neuralgia. Over the last 50 years, a tremendous amount of knowledge has been garnered, both about target volume and radiation delivery. This review covers the intense study of these concepts and the development of linear accelerators to deliver stereotactic radiosurgery. The fascinating history of stereotactic neurosurgery is reviewed, and a detailed account is given of the development of linear accelerators and their subsequent modification for radiosurgery.
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Neurocirugia/métodos , Aceleradores de Partículas , Radiocirugia/métodos , Neoplasias Encefálicas/cirugía , Historia del Siglo XX , Humanos , Neoplasias Meníngeas/cirugía , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Monitoreo Intraoperatorio , Neurocirugia/historia , Neurocirugia/instrumentación , Procedimientos Neuroquirúrgicos/historia , Procedimientos Neuroquirúrgicos/instrumentación , Procedimientos Neuroquirúrgicos/métodos , Neoplasias Hipofisarias/cirugía , Radiocirugia/historia , Radiocirugia/instrumentación , Radioterapia/métodos , Resultado del Tratamiento , Neuralgia del Trigémino/cirugíaRESUMEN
Once the accepted norm during Harvey Cushing's time, the mantra of work to the exclusion of family and lifestyle is now recognized as deleterious to overall well-being. A number of neurosurgical residency training programs have implemented wellness programs to enhance the physical, mental, and emotional well-being of trainees and faculty. This manuscript highlights existing organized wellness education within neurosurgery residency programs in order to describe the motivations behind development, structure, and potential implementation strategies, cost of implementation, and identify successes and barriers in the integration process. This manuscript is designed to serve as a "how-to" guide for other programs who may identify a need in their own trainees and begins the discussion of how to develop wellness, leadership, grit, and resiliency within our future generation of neurosurgeons.
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Promoción de la Salud/métodos , Salud Mental/educación , Neurocirujanos/psicología , Neurocirugia/educación , Neurocirugia/psicología , Humanos , Internado y ResidenciaRESUMEN
This article presents guidelines for imaging utilization in patients presenting with hearing loss or vertigo, symptoms that sometimes occur concurrently due to proximity of receptors and neural pathways responsible for hearing and balance. These guidelines take into account the superiority of CT in providing bony details and better soft-tissue resolution offered by MRI. It should be noted that a dedicated temporal bone CT rather than a head CT best achieves delineation of disease in many of these patients. Similarly, optimal assessment often requires a dedicated high-resolution protocol designed to assess temporal bone and internal auditory canals even though such a study will be requested and billed as a brain MRI. Angiographic techniques are helpful in some patients, especially in the setting of vertigo. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Pérdida Auditiva/diagnóstico por imagen , Neuroimagen/métodos , Tomografía Computarizada por Rayos X , Vértigo/diagnóstico por imagen , Diagnóstico Diferencial , Medicina Basada en la Evidencia , Humanos , Imagen por Resonancia Magnética , Sociedades Médicas , Estados UnidosRESUMEN
Visual loss can be the result of an abnormality anywhere along the visual pathway including the globe, optic nerve, optic chiasm, optic tract, thalamus, optic radiations or primary visual cortex. Appropriate imaging analysis of visual loss is facilitated by a compartmental approach that establishes a differential diagnosis on the basis of suspected lesion location and specific clinical features. CT and MRI are the primary imaging modalities used to evaluate patients with visual loss and are often complementary in evaluating these patients. One modality may be preferred over the other depending on the specific clinical scenario. Depending on the pattern of visual loss and differential diagnosis, imaging coverage may require targeted evaluation of the orbits and/or assessment of the brain. Contrast is preferred when masses and inflammatory processes are differential considerations. The American College of Radiology Appropriateness Criteria are evidence-based guidelines for specific clinical conditions that are reviewed annually by a multidisciplinary expert panel. The guideline development and revision include an extensive analysis of current medical literature from peer reviewed journals and the application of well-established methodologies (RAND/UCLA Appropriateness Method and Grading of Recommendations Assessment, Development, and Evaluation or GRADE) to rate the appropriateness of imaging and treatment procedures for specific clinical scenarios. In those instances where evidence is lacking or equivocal, expert opinion may supplement the available evidence to recommend imaging or treatment.
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Ceguera/diagnóstico por imagen , Enfermedades Orbitales/diagnóstico por imagen , Medios de Contraste , Diagnóstico Diferencial , Medicina Basada en la Evidencia , Humanos , Sociedades Médicas , Estados UnidosRESUMEN
OBJECT: To determine if the potent antiglioma chemotherapeutic agent gemcitabine could be delivered to the brainstem safely at therapeutic doses while monitoring its distribution using a surrogate magnetic resonance (MR) imaging tracer, the authors used convection-enhanced delivery to perfuse the primate brainstem with gemcitabine and Gd-diethylenetriamine pentaacetic acid (DTPA). METHODS: Six primates underwent convective brainstem perfusion with gemcitabine (0.4 mg/ml; two animals), Gd-DTPA (5 mM; two animals), or a coinfusion of gemcitabine (0.4 mg/ml) and Gd-DTPA (5 mM; two animals), and were killed 28 days afterward. These primates were observed over time clinically (six animals), and with MR imaging (five animals), quantitative autoradiography (one animal), and histological analysis (all animals). In an additional primate, 3H-gemcitabine and Gd-DTPA were coinfused and the animal was killed immediately afterward. In the primates there was no histological evidence of infusate-related tissue toxicity. Magnetic resonance images obtained during infusate delivery demonstrated that the anatomical region infused with Gd-DTPA was clearly distinguishable from surrounding noninfused tissue. Quantitative autoradiography confirmed that Gd-DTPA tracked the distribution of 3H-gemcitabine and closely approximated its volume of distribution (mean volume of distribution difference 13.5%). Conclusions. Gemcitabine can be delivered safely and effectively to the primate brainstem at therapeutic concentrations and at volumes that are higher than those considered clinically relevant. Moreover, MR imaging can be used to track the distribution of gemcitabine by adding Gd-DTPA to the infusate. This delivery paradigm should allow for direct therapeutic application of gemcitabine to brainstem gliomas while monitoring its distribution to ensure effective tumor coverage and to maximize safety.
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Antimetabolitos Antineoplásicos/administración & dosificación , Tronco Encefálico , Convección , Desoxicitidina/análogos & derivados , Infusiones Intralesiones/métodos , Terapia Asistida por Computador , Animales , Antimetabolitos Antineoplásicos/farmacocinética , Tronco Encefálico/metabolismo , Medios de Contraste , Desoxicitidina/administración & dosificación , Desoxicitidina/farmacocinética , Gadolinio DTPA , Macaca mulatta , Imagen por Resonancia Magnética , GemcitabinaRESUMEN
PURPOSE: To determine if the tumor-targeted cytotoxin interleukin 13 bound to Pseudomonas exotoxin (IL13-PE) could be delivered to the brainstem safely at therapeutic doses while monitoring its distribution in real-time using a surrogate magnetic resonance imaging tracer, we used convection-enhanced delivery to perfuse rat and primate brainstems with IL13-PE and gadolinium-bound albumin (Gd-albumin). EXPERIMENTAL DESIGN: Thirty rats underwent convective brainstem perfusion of IL13-PE (0.25, 0.5, or 10 microg/mL) or vehicle. Twelve primates underwent convective brainstem perfusion of either IL13-PE (0.25, 0.5, or 10 microg/mL; n = 8), co-infusion of 125I-IL13-PE and Gd-albumin (n = 2), or co-infusion of IL13-PE (0.5 microg/mL) and Gd-albumin (n = 2). The animals were permitted to survive for up to 28 days before sacrifice and histologic assessment. RESULTS: Rats showed no evidence of toxicity at all doses. Primates showed no toxicity at 0.25 or 0.5 microg/mL but showed clinical and histologic toxicity at 10 microg/mL. Quantitative autoradiography confirmed that Gd-albumin precisely tracked IL13-PE anatomic distribution and accurately showed the volume of distribution. CONCLUSIONS: IL13-PE can be delivered safely and effectively to the primate brainstem at therapeutic concentrations and over clinically relevant volumes using convection-enhanced delivery. Moreover, the distribution of IL13-PE can be accurately tracked by co-infusion of Gd-albumin using real-time magnetic resonance imaging.
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ADP Ribosa Transferasas/farmacocinética , Toxinas Bacterianas/farmacocinética , Barrera Hematoencefálica , Tronco Encefálico/química , Exotoxinas/farmacocinética , Interleucina-13/farmacocinética , Factores de Virulencia/farmacocinética , ADP Ribosa Transferasas/efectos adversos , Animales , Autorradiografía , Toxinas Bacterianas/efectos adversos , Neoplasias del Tronco Encefálico/tratamiento farmacológico , Medios de Contraste/administración & dosificación , Convección , Relación Dosis-Respuesta a Droga , Exotoxinas/efectos adversos , Gadolinio/administración & dosificación , Glioma/tratamiento farmacológico , Interleucina-13/efectos adversos , Macaca mulatta , Sustancias Macromoleculares , Imagen por Resonancia Magnética , Masculino , Ratas , Ratas Sprague-Dawley , Albúmina Sérica/administración & dosificación , Factores de Virulencia/efectos adversos , Exotoxina A de Pseudomonas aeruginosaAsunto(s)
Accidentes de Tránsito/estadística & datos numéricos , Traumatismos Craneocerebrales/epidemiología , Dispositivos de Protección de la Cabeza/estadística & datos numéricos , Motocicletas/estadística & datos numéricos , Centros Traumatológicos/estadística & datos numéricos , Adolescente , Adulto , Distinciones y Premios , Traumatismos Craneocerebrales/economía , Traumatismos Craneocerebrales/terapia , Femenino , Florida/epidemiología , Costos de Hospital/estadística & datos numéricos , Humanos , Seguro de Salud/estadística & datos numéricos , Masculino , Persona de Mediana Edad , Sistema de Registros/estadística & datos numéricos , Estudios Retrospectivos , Resultado del Tratamiento , Adulto JovenRESUMEN
BACKGROUND: Prophylactic use of antiepileptic drugs (AEDs) for patients undergoing brain tumor surgery is common practice despite lack of clear evidence. We hypothesized that prophylactic AED (pAED) use did not affect seizure rates in patients with brain tumor who underwent craniotomy for tumor resection. METHODS: A retrospective review was performed of 606 patients who underwent surgery for brain tumors from 2006 to 2013 at the University of Florida, excluding patients with preexisting seizure condition before tumor diagnosis. Data were analyzed to determine seizure incidence, AED use, and AED toxicities. RESULTS: Most patients (81%) had no seizure on presentation. Eight patients did not present with seizure but had seizure postoperatively, and 9 patients did not present with seizure or have seizure postoperatively but did have seizure on follow-up. Despite not presenting with a seizure preoperatively, 208 patients (43%) were placed on pAED preoperatively, 313 patients (64%) were on AED in the postoperative period, and 274 patients (56%) remained on AED at discharge. The pAED use odds ratio for seizures was 1.3 (95% confidence interval, 0.5-3.4; P = 0.599). At last follow-up, 34% of patients with no seizure on presentation remained on pAEDs. CONCLUSIONS: pAEDs did not significantly reduce postoperative seizures in patients with brain tumor in this analysis. In addition, pAED was often continued once prescribed even if the patient remained seizure free.