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1.
Artigo em Inglês | MEDLINE | ID: mdl-38864265

RESUMO

STUDY DESIGN: Retrospective, Multicenter. OBJECTIVE: Assess curve progression and occurrence of revision surgery following tether breakage after vertebral body tethering (VBT). SUMMARY OF BACKGROUND DATA: Tether breakage after VBT is common with rates up to 50% reported. In these cases, it remains unknown whether the curve will progress or remain stable. METHODS: Adolescent and juvenile idiopathic scoliosis patients in a multicenter registry with ≥2 year-follow-up after VBT were reviewed. Broken tethers were listed as postoperative complications and identified by increased screw divergence of >5° on serial radiographs. Revision procedures and curve magnitude at subsequent visits were recorded. RESULTS: Of 186 patients who qualified for inclusion, 84 (45.2%) patients with tether breakage were identified with a mean age at VBT of 12.4±1.4 years and mean curve magnitude at index procedure of 51.8°±8.1°. Tether breakage occurred at a mean of 30.3±11.8 months and mean curve of 33.9°±13.2°. Twelve patients (12/84, 14.5%) underwent 13 revision procedures after VBT breakage, including 6 tether revisions and 7 conversions to fusion. All tether revisions occurred within 5 months of breakage identification. No patients with curves <35° after breakage underwent revision. Revision rate was greatest in skeletally immature (Risser 0-3) patients with curves ≥35° at time of breakage (Risser 0-3: 9/17, 53% vs. Risser 4-5: 3/23, 13%, P=0.01).Curves increased by 3.1° and 3.7° in the first and second year, respectively. By two years, 15/30 (50%) progressed >5° and 8/30 (26.7%) progressed greater than 10°. Overall, 66.7% (40/60) reached a curve magnitude >35° at their latest follow-up, and 14/60 (23.3%) reached a curve magnitude greater than 45°. Skeletal maturity did not affect curve progression after tether breakage (P>0.26), but time to rupture did (P=0.048). CONCLUSION: While skeletal immaturity and curve magnitude were not independently associated with curve progression, skeletally immature patients with curves ≥35° at time of rupture are most likely to undergo additional surgery. Most patients can expect progression at least 5° in the first two years after tether breakage, though longer-term behavior remains unknown. LEVEL OF EVIDENCE: III.

2.
J Neurosurg Pediatr ; 34(1): 49-56, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38394661

RESUMO

OBJECTIVE: Treatment for Chiari malformation type I (CM-I) often includes surgical intervention in both pediatric and adult patients. The authors sought to investigate fundamental differences between these populations by analyzing data from pediatric and adult patients who required CM-I decompression. METHODS: To better understand the presentation and surgical outcomes of both groups of patients, retrospective data from 170 adults and 153 pediatric patients (2000-2019) at six institutions were analyzed. RESULTS: The adult CM-I patient population requiring surgical intervention had a greater proportion of female patients than the pediatric population (p < 0.0001). Radiographic findings at initial clinical presentation showed a significantly greater incidence of syringomyelia (p < 0.0001) and scoliosis (p < 0.0001) in pediatric patients compared with adult patients with CM-I. However, presenting signs and symptoms such as headaches (p < 0.0001), ocular findings (p = 0.0147), and bulbar symptoms (p = 0.0057) were more common in the adult group. After suboccipital decompression procedures, 94.4% of pediatric patients reported symptomatic relief compared with 75% of adults with CM-I (p < 0.0001). CONCLUSIONS: Here, the authors present the first retrospective evaluation comparing adult and pediatric patients who underwent CM-I decompression. Their analysis reveals that pediatric and adult patients significantly differ in terms of demographics, radiographic findings, presentation of symptoms, surgical indications, and outcomes. These findings may indicate different clinical conditions or a distinct progression of the natural history of this complex disease process within each population, which will require prospective studies to better elucidate.


Assuntos
Malformação de Arnold-Chiari , Descompressão Cirúrgica , Humanos , Malformação de Arnold-Chiari/cirurgia , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/complicações , Feminino , Masculino , Criança , Estudos Retrospectivos , Descompressão Cirúrgica/métodos , Adulto , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Resultado do Tratamento , Siringomielia/cirurgia , Siringomielia/diagnóstico por imagem , Siringomielia/complicações , Pré-Escolar , Fatores Etários , Escoliose/cirurgia , Escoliose/diagnóstico por imagem
3.
Neurosurgery ; 94(4): 764-770, 2024 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-37878410

RESUMO

BACKGROUND AND OBJECTIVES: Pediatric subdural empyemas (SDE) carry significant morbidity and mortality, and prompt diagnosis and treatment are essential to ensure optimal outcomes. Nonclinical factors affect presentation, time to diagnosis, and outcomes in several neurosurgical conditions and are potential causes of delay in presentation and treatment for patients with SDE. To evaluate whether socioeconomic status, race, and insurance status affect presentation, time to diagnosis, and outcomes for children with subdural empyema. METHODS: We conducted a retrospective cohort study with patients diagnosed with SDE between 2005 and 2020 at our institution. Information regarding demographics (age, sex, zip code, insurance status, race/ethnicity) and presentation (symptoms, number of prior visits, duration of symptoms) was collected. Outcome measures included mortality, postoperative complications, length of stay, and discharge disposition. RESULTS: 42 patients were diagnosed with SDE with a mean age of 9.5 years. Most (85.7%) (n = 36) were male ( P = .0004), and a majority, 28/42 (66.7%), were African American ( P < .0001). There was no significant difference in socioeconomic status based on zip codes, although a significantly higher number of patients were on public insurance ( P = .015). African American patients had a significantly longer duration of symptoms than their Caucasian counterparts (8.4 days vs 1.8 days P = .0316). In total, 41/42 underwent surgery for the SDE, most within 24 hours of initial neurosurgical evaluation. There were no significant differences in the average length of stay. The average length of antibiotic duration was 57.2 days and was similar for all patients. There were no significant differences in discharge disposition based on any of the factors identified with most of the patients (52.4%) being discharged to home. There was 1 mortality (2.4%). CONCLUSION: Although there were no differences in outcomes based on nonclinical factors, African American men on public insurance bear a disproportionately high burden of SDE. Further investigation into the causes of this is warranted.


Assuntos
Empiema Subdural , Humanos , Criança , Masculino , Feminino , Empiema Subdural/diagnóstico , Empiema Subdural/epidemiologia , Empiema Subdural/terapia , Estudos Retrospectivos , Disparidades Socioeconômicas em Saúde , Complicações Pós-Operatórias , Alta do Paciente
4.
Spine Deform ; 11(5): 1239-1251, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37074515

RESUMO

OBJECTIVE: Segmental spinal dysgenesis (SSD) is a rare congenital spinal abnormality affecting the thoracic and lumbar region of the spine, as well as the spinal cord of neonates and infants. The purpose of the study was to analyze our institution's surgical case series to provide insights into our best practices to contribute to SSD management principles, while conducting a comprehensive literature review. METHODS: Following institutional review board approval, a retrospective review of SSD surgical cases was examined to observe clinical findings, radiographic findings, management, surgical intervention, and outcomes. Keywords in the comprehensive literature review included SSD, congenital spinal dysgenesis, congenital spinal stenosis, spinal aplasia, and surgery. RESULTS: Three cases underwent successful surgical management with either improvement or maintenance of neurological baseline. Patients were diagnosed at an average age of 2.7 months, while surgical intervention averaged at 40.3 months with fecal incontinence, neurogenic bladders, spinal cord compression, clubfoot, and concerns for worsening spinal deformity as surgical indicators. The average time for follow-up was 33.7 months and no complications were reported. CONCLUSIONS: Operative management for SSD is a clinically complex decision that requires multidisciplinary input and care. Patients should be observed at neurological baseline and receive intervention at the appropriate time to allow sufficient growth for functioning without permitting drastic disease progression. Consideration of patient size and spinal instrumentation are significant towards surgical success.


Assuntos
Medula Espinal , Coluna Vertebral , Lactente , Recém-Nascido , Humanos , Coluna Vertebral/diagnóstico por imagem , Coluna Vertebral/cirurgia , Progressão da Doença , Região Lombossacral , Procedimentos Neurocirúrgicos
5.
Artigo em Inglês | MEDLINE | ID: mdl-35863322

RESUMO

Pediatric posterior fossa arteriovenous malformations (AVMs) are rare entities that pose significant cumulative lifetime risk of rupture and require treatment. Microsurgical resection remains a good option for definitively treating posterior fossa AVMs in one setting. The drawback of endovascular embolization is the lower rates of nidus obliteration. Although stereotactic radiosurgery is a safe alternative, it takes several years to achieve the treatment goal all the while predisposing the patient to the risk of AVM rupture.1,2 Accurate localization and visualization remain challenging for microsurgical treatment of posterior fossa AVMs.3-5 Small size of a nidus, prone position, and proximity to eloquent areas make these lesions particularly difficult to localize and resect. We present the operative case of a 6-year-old boy with a small, ruptured posterior fossa AVM. After undergoing hematoma evacuation, the patient underwent microsurgical resection of a small right vermian AVM assisted by the virtual reality platform, Surgical Theater (Gates Mills, OH). Our video demonstrates the utility of a virtual augmented reality platform for addressing the challenges posed by a small posterior fossa AVM with respect to the need for precise three-dimensional localization of small lesions. The patient consented to the procedure. The participants and any identifiable individuals consented to publication of his/her image.

6.
Acta Neurochir (Wien) ; 164(8): 2153-2157, 2022 08.
Artigo em Inglês | MEDLINE | ID: mdl-35415805

RESUMO

NeuroPace responsive neurostimulation (RNS®) therapy was used in a case of intractable focal epilepsy with bifrontal transmantle heterotopia subserving peculiar homotopic motor distribution in a 16-year-old, right-handed male with intractable seizures. Brain MRI demonstrated bifrontal transmantle heterotopia extending from the central sulcus to subjacent lateral ventricles along with polymicrogyria along the overlying cortex suspected to be the motor cortex. Functional MRI demonstrated homotopic distribution of finger and foot motor function (deeper) within the polymicrogyria. Invasive intracranial monitoring with depth electrodes and extraoperative brain mapping revealed eloquent cortical tissue which corresponded to the right leg and right shoulder motor function.


Assuntos
Coristoma , Estimulação Encefálica Profunda , Epilepsia Resistente a Medicamentos , Polimicrogiria , Adolescente , Encéfalo , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/terapia , Humanos , Masculino , Convulsões
7.
Childs Nerv Syst ; 38(3): 537-546, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34718866

RESUMO

INTRODUCTION: The increasing use of stereoelectroencephalography (SEEG) in the USA and the need for three-dimensional (3D) appreciation of complex spatial relationships between implanted stereotactic EEG depth electrodes and surrounding brain and cerebral vasculature are a challenge to clinicians who are used to two-dimensional (2D) appreciation of cortical anatomy having been traditionally trained on 2D radiologic imaging. Virtual reality and its 3D renderings have grown increasingly common in the multifaceted practice of neurosurgery. However, there exists a paucity in the literature regarding this emerging technology in its utilization of epilepsy surgery. METHODS: An IRB-approved, single-center retrospective study identifying all SEEG pediatric patients in which virtual reality was applied was observed. RESULTS: Of the 46 patients identified who underwent an SEEG procedure, 43.5% (20/46) had a 3D rendering (3DR) of their SEEG depth electrodes. All 3DRs were used during patient-family education and discussion among the Epilepsy multidisciplinary team meetings, while 35% (7/20) were used during neuronavigation in surgery. Three successful representative cases of its application were presented. DISCUSSION: Our institution's experience regarding virtual reality in the 3D representation of SEEG depth electrodes and the application to pre-surgical planning, patient-family education, multidisciplinary communication, and intraoperative neuronavigation demonstrate its applicability in comprehensive epilepsy patient care.


Assuntos
Epilepsia Resistente a Medicamentos , Epilepsia , Realidade Virtual , Encéfalo/diagnóstico por imagem , Encéfalo/cirurgia , Criança , Epilepsia Resistente a Medicamentos/diagnóstico por imagem , Epilepsia Resistente a Medicamentos/cirurgia , Eletrodos Implantados , Eletroencefalografia/métodos , Epilepsia/diagnóstico por imagem , Epilepsia/cirurgia , Humanos , Estudos Retrospectivos , Técnicas Estereotáxicas
8.
Childs Nerv Syst ; 37(9): 2891-2898, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34232379

RESUMO

PURPOSE: The role of an osseous-only posterior fossa decompression (PFD) for Chiari malformation type 1 (CM1) remains controversial. We reviewed long-term outcomes for patients with CM1 undergoing a PFD to evaluate if there was any difference for failure when compared to patients undergoing a PFD with duraplasty (PFDD). METHODS: Consecutive patients surgically treated at a single tertiary pediatric neurosurgery clinic over a 25-year period with at least 5 years of follow-up were evaluated. PFD patients were compared to those that initially received a PFDD. Demographics, surgical indications, surgical approach, outcomes, and complications were reviewed. RESULTS: A total of 60 patients were included in this study of which 25 (41.67%) underwent PFD and 35 (58.33%) underwent PFDD. Mean age at surgery was 7.41 years (range 0.4 to 18 years) with a mean follow-up of 8.23 years (range 5 to 21 years). Those that received a PFD had a lower rate of radiographic syrinx improvement (p = 0.03), especially in the setting of holocord syringes. Failure rate was significantly higher in the PFD group (20% vs 2.90%, p = 0.03). However, complications were significantly higher in the PFDD group (17.14% vs 4.0%, p = 0.04). CONCLUSIONS: PFD provides a safe treatment option with similar clinical improvements and lower post-operative complication rate compared to PFDD, albeit at the cost of greater chance of reoperation, especially in the setting of a holocord syrinx. Patients with a holocord syrinx should be considered for a PFDD as their initial procedure.


Assuntos
Malformação de Arnold-Chiari , Siringomielia , Adolescente , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/cirurgia , Criança , Pré-Escolar , Descompressão Cirúrgica , Dura-Máter/cirurgia , Humanos , Lactente , Estudos Retrospectivos , Siringomielia/cirurgia , Resultado do Tratamento , Adulto Jovem
9.
J Neurosurg Pediatr ; 28(1): 28-33, 2021 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-34020421

RESUMO

OBJECTIVE: The authors aimed to describe the natural history and optimal management of persistent syringomyelia after suboccipital craniectomy for Chiari malformation type I (CM-I). METHODS: A cohort of all patients who presented to a tertiary pediatric hospital with newly diagnosed CM-I between 2009 and 2017 was identified. Patients with persistent or worsened syringomyelia were identified on the basis of a retrospective review of medical records and imaging studies. The management of these patients and their clinical courses were then described. RESULTS: A total of 153 children with CM-I and syringomyelia were evaluated between 2009 and 2017. Of these, 115 (68.8%) patients underwent surgical intervention: 40 patients underwent posterior fossa decompression (PFD) alone, 43 underwent PFD with duraplasty, and 32 underwent PFD with duraplasty and fourth ventricle stent placement. Eleven (7.19%) patients had increased syringomyelia on subsequent postoperative imaging. Three of these patients underwent revision surgery because of worsening scoliosis or pain, 2 of whom were lost to follow-up, and 4 were managed nonoperatively with close surveillance and serial MRI evaluations. The syringes decreased in size in 3 patients and resolved completely in 1 patient. CONCLUSIONS: Persistent or worsened syringomyelia after CM-I decompression is uncommon. In the absence of symptoms, nonoperative management with close observation is safe for patients with persistent syrinx.

10.
J Neurosurg Pediatr ; 28(1): 54-61, 2021 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-33930869

RESUMO

OBJECTIVE: Children with medically refractory partial-onset epilepsy arising from eloquent cortex present a therapeutic challenge, as many are not suitable for resective surgery. For these patients, responsive neurostimulation may prove to be a potential tool. Although responsive neurostimulation has demonstrated utility in adults, little has been discussed regarding its utility in the pediatric population. In this study, the authors present their institution's experience with responsive neurostimulation via the RNS System through a case series of 5 pediatric patients. METHODS: A single-center retrospective study of patients who underwent RNS System implantation at Children's National Hospital was performed. RESULTS: Five patients underwent RNS System implantation. The mean patient age at treatment was 16.8 years, and the average follow-up was 11.2 months. All patients were considered responders, with a seizure frequency reduction of 64.2% without adverse events. CONCLUSIONS: All 5 patients experienced medium-term improvements in seizure control after RNS System implantation with decreases in seizure frequency > 50% from baseline preoperative seizure frequency. The authors demonstrated two primary configurations of electrode placement: hippocampal or amygdala placement via an occipitotemporal trajectory, as well as infratemporal surface electrodes and surface electrodes on the primary motor cortex. No adverse events were experienced in this case series.

11.
Plast Reconstr Surg Glob Open ; 9(3): e3484, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33747694

RESUMO

Tibial nerve entrapment is uncommon in the pediatric population, and presents diagnostic and treatment challenges. We present the unusual case of a 3-year-old male child with progressive lower leg atrophy of an unknown etiology. Preoperative electrodiagnostic testing and magnetic resonance imaging suggested proximal tibial neuropathy. Surgical exploration showed compression of the tibial nerve at the inferior fascial edge of the long head of the biceps femoris and at the soleal sling. Release and external neurolysis led to improvement of distal leg motor function.

12.
Childs Nerv Syst ; 37(4): 1191-1197, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33230572

RESUMO

OBJECTIVES: Chiari malformation type 1 (CM1) is an increasingly common incidental finding on magnetic resonance imaging (MRI). The proportion of children with an incidentally discovered CM1 who upon further evaluation require operative intervention for previously unrecognized signs and symptoms of neurological compromise or significant radiographic findings (syringomyelia) is unclear. An extensive long-term single-institution patient series was evaluated to better clarify the likelihood of surgery in patients who present with an incidentally discovered CM1. METHODS: This study was conducted using prospective data for patients up to 18 years old that were evaluated for a CM1 at a large tertiary pediatric neurosurgery clinic between February 2009 and June 2019. Patients were excluded if they did not have an incidentally discovered CM1 and at least 12 months of clinical follow-up. RESULTS: A total of 218 consecutive patients were included in this study. The mean age at the initial neurosurgical evaluation was 6.5 years (range 5 months to 18.4 years), and the mean duration of clinical follow-up was 40.6 months (range 12 to 114 months). Initial MR imaging was most commonly obtained for the evaluation of seizures (15.1%), nonspecific headaches (not occipital or tussive) (14.7%), trauma (9.6%), and developmental delay (7.8%). Of the patients studied that eventually required surgery, we identified two groups: those operated before 6 months since presentation and those operated after 6 months. A total of 36 patients (16.5%) underwent a decompression with 22 patients (61.1%) receiving surgery within 6 months and the remaining 14 patients (38.9%) beyond 6 months. Patients undergoing early surgery (10.1%) initially presented with a significant syrinx or were noted to have an occult neurological dysfunction, whereas a smaller subset of patients (6.4%) eventually required surgery over time due to the development of new symptoms or a de novo syrinx. Only the presence of syringomyelia was statistically significant for the need of a surgical intervention, while age, sex and degree of tonsillar herniation were not. CONCLUSION: Evaluation of a large group of patients with an incidentally discovered Chiari malformation demonstrated that most patients may be managed conservatively, especially in the absence of syringomyelia. However, there is a subset of patients who will go on to develop a de novo syrinx or neurological symptoms that are new or progressive during follow-up, which should be evaluated by imaging of the brain and spinal cord. The presence of syringomyelia was associated with need for early surgical intervention. However, for patients without syringomyelia, surgical intervention is uncommon but may be delayed up to several years after presentation; therefore, long-term clinical follow-up is recommended.


Assuntos
Malformação de Arnold-Chiari , Siringomielia , Malformação de Arnold-Chiari/diagnóstico por imagem , Malformação de Arnold-Chiari/cirurgia , Criança , Descompressão Cirúrgica , Humanos , Lactente , Imageamento por Ressonância Magnética , Estudos Prospectivos , Siringomielia/cirurgia , Resultado do Tratamento
13.
ACS Sens ; 5(7): 1959-1968, 2020 07 24.
Artigo em Inglês | MEDLINE | ID: mdl-32571014

RESUMO

Genetically encodable calcium ion (Ca2+) indicators (GECIs) based on green fluorescent proteins (GFP) are powerful tools for imaging of cell signaling and neural activity in model organisms. Following almost 2 decades of steady improvements in the Aequorea victoria GFP-based GCaMP series of GECIs, the performance of the most recent generation (i.e., jGCaMP7) may have reached its practical limit due to the inherent properties of GFP. In an effort to sustain the steady progression toward ever-improved GECIs, we undertook the development of a new GECI based on the bright monomeric GFP, mNeonGreen (mNG). The resulting indicator, mNG-GECO1, is 60% brighter than GCaMP6s in vitro and provides comparable performance as demonstrated by imaging Ca2+ dynamics in cultured cells, primary neurons, and in vivo in larval zebrafish. These results suggest that mNG-GECO1 is a promising next-generation GECI that could inherit the mantle of GCaMP and allow the steady improvement of GECIs to continue for generations to come.


Assuntos
Cálcio , Neurônios , Peixe-Zebra , Animais , Linhagem Celular , Células Cultivadas , Peixe-Zebra/genética
14.
Prev Med Rep ; 9: 102-106, 2018 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-29527461

RESUMO

The uneven diffusion of local and state laws restricting the use of electronic nicotine delivery systems (ENDS) in the United States may be a function of inconclusive scientific evidence and lack of guidance from the federal government. The objective of this study was to assess whether the rationale for amending clean indoor air acts (CIAAs) is being conflated by issues that are not directly relevant to protecting the health of ENDS non-users. Online sources were used in identifying bills (n = 25) that were presented in U.S. state legislatures from January 2009 to December 2015. The bills were categorized into one of three groups: 1) bills amending comprehensive CIAAs (n = 11), 2) bills prohibiting use of ENDS in places frequented by youth (n = 5), and 3) remaining bills that varied between the two categories (n = 9). Arguments presented in committee hearings were coded as scientific, public health, economic, enforcement, freedom, or regulatory. Arguments pertaining to amendment of clean indoor air acts spanned several categories, many of which were not directly relevant to the aims of the legislation. This finding could assist lawmakers and expert witnesses in making arguments that yield greater success in amending legislation. Alternatively, inconclusive scientific data on the hazards of ENDS aerosols might encourage lawmakers to propose legislation that prohibits ENDS use in places frequented by youths.

15.
Mol Pharmacol ; 91(4): 416-427, 2017 04.
Artigo em Inglês | MEDLINE | ID: mdl-28153854

RESUMO

Functional selectivity at the µ opioid receptor (µR), a prototypical G-protein-coupled receptor that is a physiologically relevant target for endogenous opioid neurotransmitters and analgesics, has been a major focus for drug discovery in the recent past. Functional selectivity is a cumulative effect of the magnitudes of individual signaling pathways, e.g., the Gαi-mediated and the arrestin-mediated pathways for µR. The present work tested the hypothesis that lifetimes of agonist-induced receptor-arrestin clusters at the cell surface control the magnitude of arrestin signaling, and therefore functional selectivity, at µR. We show that endomorphin-2 (EM2), an arrestin-biased ligand for µR, lengthens surface lifetimes of receptor-arrestin clusters significantly compared with morphine. The lengthening of lifetimes required two specific leucines on the C-terminal tail of µR. Mutation of these leucines to alanines decreased the magnitude of arrestin-mediated signaling by EM2 without affecting G-protein signaling, suggesting that lengthened endocytic lifetimes were required for arrestin-biased signaling by EM2. Lengthening surface lifetimes by pharmacologically slowing endocytosis was sufficient to increase arrestin-mediated signaling by both EM2 and the clinically relevant agonist morphine. Our findings show that distinct ligands can leverage specific sequence elements on µR to regulate receptor endocytic lifetimes and the magnitude of arrestin-mediated signaling, and implicate these sequences as important determinants of functional selectivity in the opioid system.


Assuntos
Endocitose , Receptores Opioides mu/química , Receptores Opioides mu/metabolismo , Transdução de Sinais , beta-Arrestinas/metabolismo , Sequência de Aminoácidos , Endocitose/efeitos dos fármacos , Ativação Enzimática/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Células HEK293 , Humanos , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Morfina/farmacologia , Mutação/genética , Oligopeptídeos/farmacologia , Receptores Opioides mu/genética , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
16.
Acta Derm Venereol ; 95(5): 516-24, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25520039

RESUMO

Despite advances in treatment and surveillance, melanoma continues to claim approximately 9,000 lives in the US annually (SEER 2013). The National Comprehensive Cancer Network currently recommends ipilumumab, vemurafenib, dabrafenib, and high-dose IL-2 as first line agents for Stage IV melanoma. Little data exists to guide management of cutaneous and subcutaneous metastases despite the fact that they are relatively common. Existing options include intralesional Bacillus Calmette-Guérin, isolated limb perfusion/infusion, interferon-α, topical imiquimod, cryotherapy, radiation therapy, interferon therapy, and intratumoral interleukin-2 injections. Newly emerging treatments include the anti-programmed cell death 1 receptor agents (nivolumab and pembrolizumab), anti-programmed death-ligand 1 agents, and oncolytic vaccines (talimogene laherparepevec). Available treatments for select sites include adoptive T cell therapies and dendritic cell vaccines. In addition to reviewing the above agents and their mechanisms of action, this review will also focus on combination therapy as these strategies have shown promising results in clinical trials for metastatic melanoma treatment.


Assuntos
Imunoterapia/métodos , Melanoma/secundário , Melanoma/terapia , Neoplasias Cutâneas/patologia , Neoplasias Cutâneas/terapia , Produtos Biológicos/uso terapêutico , Vacinas Anticâncer/uso terapêutico , Ensaios Clínicos Fase I como Assunto , Terapia Combinada , Feminino , Humanos , Injeções Intralesionais , Interferons/uso terapêutico , Masculino , Melanoma/patologia , Cirurgia de Mohs/métodos , Terapia de Alvo Molecular/métodos , Invasividade Neoplásica/patologia , Metástase Neoplásica , Estadiamento de Neoplasias , Prognóstico , Ensaios Clínicos Controlados Aleatórios como Assunto , Medição de Risco , Programa de SEER , Resultado do Tratamento
17.
J Drugs Dermatol ; 12(12): 1483-4, 2013 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-24301252

RESUMO

Dermatofibromas are benign skin lesions that may be treated if symptomatic or for cosmetic concerns. We present a case of an African American woman with an enlarging, pruritic dermatofibroma on the thigh that was treated with fractionated carbon dioxide (CO2) laser three times approximately 5 weeks apart. Between laser treatments, topical corticosteroids were applied to the lesion for a total of 13 weeks. The dermatofibroma completely flattened and became asymptomatic within 1 month after the final laser treatment. We hypothesize that the fractionated CO2 laser ablated a portion of the stromal component of the lesion and introduced microscopic channels that facilitated deeper penetration of the topical corticosteroids into the lesion. This is the first reported case demonstrating the successful treatment of a symptomatic dermatofibroma using combination therapy with fractionated CO2 laser and topical corticosteroids.


Assuntos
Glucocorticoides/uso terapêutico , Histiocitoma Fibroso Benigno/terapia , Lasers de Gás/uso terapêutico , Administração Cutânea , Terapia Combinada , Fármacos Dermatológicos/administração & dosagem , Fármacos Dermatológicos/uso terapêutico , Feminino , Seguimentos , Glucocorticoides/administração & dosagem , Histiocitoma Fibroso Benigno/patologia , Humanos , Pessoa de Meia-Idade , Resultado do Tratamento
18.
Clin Infect Dis ; 55(6): 781-8, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22670044

RESUMO

BACKGROUND: Since its emergence in 2000, epidemic spread of the methicillin-resistant Staphylococcus aureus (MRSA) clone USA300 has led to a high burden of skin and soft tissue infections (SSTIs) in the United States, yet its impact on MRSA bloodstream infections (BSIs) is poorly characterized. METHODS: To assess clonality of the MRSA isolates causing SSTI and BSI during the epidemic period, a stratified, random sample of 1350 unique infection isolates (from a total of 7252) recovered at the Community Health Network of San Francisco from 2000 to 2008 were selected for genotyping. Risk factors and outcomes for 549 BSI cases caused by the USA300 epidemic clone and non-USA300 MRSA clones were assessed by retrospective review of patient medical records. RESULTS: From 2000 to 2008, secular trends of USA300 SSTI and USA300 BSI were strongly correlated (Pearson r = 0.953). USA300 accounted for 55% (304/549) of BSIs as it was the predominant MRSA clone that caused community-associated (115/160), healthcare-associated community-onset (125/207), and hospital-onset (64/182) BSIs. Length of hospitalization after BSI diagnosis and mortality rates for USA300 and non-USA300 were similar. Two independent risk factors for USA300 BSI were identified: concurrent SSTI (adjusted relative risk, 1.4 [95% confidence interval {CI}, 1.2-1.6]) and anti-MRSA antimicrobial use in the preceding 30 days (0.7 [95% CI, .6-.8]). Isolates from concurrent SSTI were indistinguishable genotypically from the USA300 isolates that caused BSI. CONCLUSIONS: USA300 SSTIs serve as a source for BSI. Strategies to control the USA300 SSTI epidemic may lessen the severity of the concurrent USA300 BSI epidemic.


Assuntos
Bacteriemia/epidemiologia , Infecções Comunitárias Adquiridas/epidemiologia , Epidemias , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Infecções dos Tecidos Moles/epidemiologia , Infecções Cutâneas Estafilocócicas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Bacteriemia/microbiologia , Pré-Escolar , Infecções Comunitárias Adquiridas/microbiologia , Feminino , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/genética , Pessoa de Meia-Idade , Tipagem Molecular , Estudos Retrospectivos , São Francisco/epidemiologia , Infecções dos Tecidos Moles/microbiologia , Infecções Cutâneas Estafilocócicas/microbiologia , Adulto Jovem
19.
Melanoma Res ; 21(3): 235-43, 2011 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-21464773

RESUMO

There are limited treatment options for metastatic melanoma, which is almost universally fatal. We report the successful treatment of 64 of 64 cutaneous and subcutaneous melanoma metastases in three patients using high-dose (22 million units per 1.2 ml) intralesional interleukin 2 (IL-2) in combination with topical imiquimod and a retinoid cream. Before intralesional therapy, all patients had been treated surgically and were no longer considered surgical candidates. Rebiopsy of 15 of the treatment sites and long-term follow-up (10, 12, and 27 months) showed regression of all treated tumors. Six months after discontinuation of therapy, one patient developed multiple new cutaneous metastases, but these were also responsive to treatment with intralesional therapy. The other two patients did not experience recurrence of their cutaneous melanoma. However, one of the two patients developed lymph node and brain metastases 18 months after initiation of intralesional therapy, but is still alive, now at 27 months. The concentration of IL-2 used for the intralesional therapy was much higher than in previously reported cases, which may explain the excellent responses that were observed. These results support intralesional high-dose IL-2 as a very effective therapy for controlling cutaneous metastatic melanoma. Additional studies are needed to determine whether this therapy is associated with a survival benefit.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/administração & dosagem , Melanoma/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Administração Tópica , Idoso de 80 Anos ou mais , Aminoquinolinas/administração & dosagem , Humanos , Imiquimode , Injeções Intralesionais , Interleucina-2/administração & dosagem , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Retinoides/administração & dosagem , Neoplasias Cutâneas/patologia
20.
Vasc Med ; 15(6): 443-50, 2010 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21183651

RESUMO

To determine whether there are sex differences in the prevalence of peripheral artery disease, we performed an observational study of 1014 men and 547 women, aged ≥ 40 years, referred for elective coronary angiography. Women were slightly older, more obese, had higher low-density lipoprotein cholesterol (LDL-C) levels and systolic blood pressure (BP), and were more likely to be African American. Women had higher high-density lipoprotein cholesterol (HDL-C) levels, lower diastolic BP, and were less likely to smoke or to have a history of cardiovascular disease. Women had less prevalent (62% vs 81%) and less severe coronary artery disease (CAD) (p < 0.001 for both) by coronary angiography, but more prevalent peripheral artery disease (PAD) as determined by the ankle-brachial index (ABI) than men (23.6% versus 17.2%). Independent predictors of lower ABI were female sex, black race, older age, tobacco use, CAD, diabetes, and triglyceride level. In a full multivariable logistic regression model, women had a risk-adjusted odds ratio for PAD of 1.78 (95% CI 1.25-2.54) relative to men. Among patients referred for coronary angiography, women have less prevalent and less severe CAD, but more prevalent PAD, a sex difference that is not explained by traditional cardiovascular disease risk factors or CAD severity. Clinical Trial Registration-URL: http://clinicaltrials.gov. Unique identifier: NCT00380185.


Assuntos
Angiografia Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença Arterial Periférica/epidemiologia , Idoso , Índice Tornozelo-Braço , California/epidemiologia , Doença da Artéria Coronariana/epidemiologia , Estudos Transversais , Feminino , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Cidade de Nova Iorque/epidemiologia , Razão de Chances , Doença Arterial Periférica/diagnóstico , Prevalência , Medição de Risco , Fatores de Risco , Índice de Gravidade de Doença , Fatores Sexuais
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