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OBJECTIVE: The Pipeline-Embolization-Device (PED) has been used increasingly for intracranial-aneurysms. Despite the high-patency-rate of jailed branches following PED deployment, little is known about changes in these vessels size. This study measured change in size after PED. METHODS: This retrospective-study screened a database of 183-consecutive-patients treated with PED (07/2011-07/2017) across inclusion criteria. We included patients in whom the ophthalmic artery (OA) and/or the posterior communicating artery (PComA) were jailed by the PED. MRA was used to calculate change in cross-sectional-area (CSA) of these vessels. 29 patients who had MRA before and after treatment were included in the study. The CSA was measured automatically using Syngo®.via-software at fixed points along the analyzed vessels. After exclusion of low-quality and software non-capturable MRA-images, 16 OA and 23 PComA were included in the final analysis. Statistical Package for Social Sciences was used for analysis. RESULTS: The mean CSA of PComA, P1-segement of posteriror-cerebral-artery (P1-PCA), and OA was 3.3 ± 1.3, 4.1 ± 1.2, and 3.2 ± 0.9 mm2 at baseline and 1.9 ± 1.4, 4.3 ± 1.2, and 3.1 ± 0.7 mm2 at follow-up, respectively. The average follow-up was approximately 26 months. While the decrease in CSA of PComA was statistically significant, the increase in P1-PCA CSA was not. The change in OA CSA was not statistically significant. CONCLUSION: Jailing PComA with a PED resulted in a statistically significant decrease in PComA CSA and a statistically non-significant increase in ipsilateral P1 CSA. No statistically significant change in the CSA of OA was noted. Changes might be due to a balance between flow demand through the jailed ostium and presence of collateral flow.
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Embolização Terapêutica , Aneurisma Intracraniano , Embolização Terapêutica/efeitos adversos , Embolização Terapêutica/métodos , Humanos , Aneurisma Intracraniano/terapia , Artéria Oftálmica , Pais , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Spinal epidural arteriovenous fistulas are an uncommon entity. The authors present an interesting case of a 48-year-old man involved in a MVC five months prior to presenting with bilateral lower extremity weakness and hypoesthesia below the knees. MRI demonstrated a flow void in the L1 vertebral body burst fracture along with a dilated basivertebral vein draining in to engorged epidural venous plexus. Angiography confirmed an intraosseous arteriovenous fistula fed by T12 and L1arteries and epidural venous drainage. Complete obliteration by arterial embolization was precluded by origin of the artery of Adamkiewicz from the feeding L1 lumbar artery. Embolization using a transvenous approach allowed for successful obliteration of the fistula. Following the procedure, the patient had significant immediate improvement in the lower extremity symptoms. This is the first report of a posttraumatic spinal epidural arteriovenous fistula secondary to a vertebral burst fracture successfully treated by transvenous embolization.
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Fístula Arteriovenosa , Embolização Terapêutica , Doenças da Medula Espinal , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/etiologia , Fístula Arteriovenosa/terapia , Drenagem , Espaço Epidural , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
We present a case of a common femoral artery repair after losing access to the vessel in a 67-year-old woman using a Mynx-Grip vascular closure device. The hematoma over the right common femoral artery was accessed under fluoroscopic guidance. Then, the balloon of the closure device was inflated inside the artery and pulled back against the origin of the puncture site into the common femoral artery. Finally, the collagen plug was deployed and pressed against the outside of the vessel to occlude the puncture site.
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Treatment of non-saccular aneurysms of the posterior circulation poses a great challenge with unpredictable outcomes due to the absence of a true aneurysm neck and the presence of perforating vessels. In this article, we aim to compare endovascular treatment of unruptured posterior circulation non-saccular aneurysms with stent-assisted coiling (SAC) and flow diversion (FD) in terms of occlusion rate and clinical outcomes. A systematic search of electronic databases from inception to August 2019 identified 484 articles for screening. After proper inclusion/exclusion criteria, 15 articles were included and data were extracted and analyzed using meta-analysis of proportions. The pooled cohort consisted of 430 aneurysms: 128 (29.7%) treated with SAC in 5 studies and 302 (70.3%) treated with FD in 11 studies. Complete/near-complete occlusion was achieved in 83% after FD (95% CI 0.75 to 0.90; I2=45%) and 84% after SAC (95% CI 0.72 to 0.91; I2=22%), with no significant difference between techniques (p=0.95). Periprocedural complications were observed in 18% after FD (95% CI 0.14 to 0.23; I2=0%) and 6% after SAC (95% CI 0.02 to 0.13; I2=0%); the subgroup analysis was statistically significant (p=0.008). Furthermore, no statistically significant difference was observed in favorable clinical outcomes between groups. These results suggest similar efficacy in occlusion rate and favorable clinical outcome for posterior circulation non-saccular aneurysms treated with SAC and FD. Stroke was the most common complication regardless of treatment modality, and a lower periprocedural complication rate was noted with SAC. Further studies are needed with the primary focus of reducing the risk of stroke with either modality.
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Procedimentos Endovasculares/métodos , Aneurisma Intracraniano/terapia , Stents Metálicos Autoexpansíveis , Idoso , Procedimentos Endovasculares/instrumentação , Feminino , Humanos , Aneurisma Intracraniano/diagnóstico por imagem , Pessoa de Meia-Idade , Estudos Retrospectivos , Stents , Resultado do TratamentoRESUMO
BACKGROUND: This study aimed to review short- and long-term outcomes of all carotid artery stenting (CAS) in patients with radiation-induced (RI) internal carotid artery (ICA) stenosis compared with patients with atherosclerotic stenosis (AS). METHODS: We performed a single-center, multisite case-control study of transfemoral carotid artery intervention in patients stented for RI or AS. Cases of stented RI carotid arteries were identified using a CAS database covering January 2000 to December 2019. These patients were randomly matched 2:1 with stented patients because of AS by age, sex, and year of CAS. A conditional logistic regression model was performed to estimate the odds of reintervention in the RI group. Finally, a systematic review was performed to assess the outcomes of RI stenosis treated with CAS. RESULTS: There were 120 CAS in 113 patients because of RI ICA stenosis. Eighty-nine patients (78.8%) were male, and 68 patients (60.2%) were symptomatic. The reasons for radiation included most commonly treatment for diverse malignancies of the head and neck in 109 patients (96.5%). The mean radiation dose was 58.9 ± 15.6 Gy, and the time from radiation to CAS was 175.3 ± 140.4 months. Symptoms included 31 transient ischemic attacks (TIAs), 21 strokes (7 acute and 14 subacute), and 17 amaurosis fugax. The mean National Institutes of Health Stroke Scale in acute strokes was 8.7 ± 11.2. In asymptomatic patients, the indication for CAS was high-grade stenosis determined by duplex ultrasound. All CAS were successfully completed. Reinterventions were more frequent in the RI ICA stenosis cohort compared with the AS cohort (10.1% vs. 1.4%). Reinterventions occurred in 14 vessels, and causes for reintervention were restenosis in 12 followed by TIA/stroke in two vessels. On conditional regression modeling, patients with RI ICA stenosis were at a higher risk for reintervention (odds ratio = 7.1, 95% confidence interval = 2.1-32.8; P = 0.004). The mean follow-up was 33.7 ± 36.9 months, and the mortality across groups was no different (P = 0.12). CONCLUSIONS: In our single-center, multisite cohort study, patients who underwent CAS for RI ICA stenosis experienced a higher rate of restenosis and a higher number of reinterventions compared with CAS for AS. Although CAS is safe and effective for this RI ICA stenosis cohort, further data are needed to reduce the risk of restenosis, and close patient surveillance is warranted. In our systematic review, CAS was considered an excellent alternative option for the treatment of patients with RI ICA stenosis. However, careful patient selection is warranted because of the increased risk of restenosis on long-term follow-up.
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Artéria Carótida Interna/efeitos da radiação , Estenose das Carótidas/terapia , Procedimentos Endovasculares/instrumentação , Lesões por Radiação/terapia , Stents , Idoso , Artéria Carótida Interna/diagnóstico por imagem , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/etiologia , Bases de Dados Factuais , Procedimentos Endovasculares/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Lesões por Radiação/diagnóstico , Lesões por Radiação/etiologia , Retratamento , Estudos Retrospectivos , Medição de Risco , Fatores de Risco , Fatores de Tempo , Resultado do TratamentoRESUMO
BACKGROUND: Spinal arteriovenous fistulas have abnormal connections between spinal arteries and veins. Early diagnosis and management are essential for preventing permanent neurologic deficits. Although symptoms of myelopathy are commonly related to established types of spinal arteriovenous fistulas within the spine, extraspinal arteriovenous anomalies may also result in similar pathology and pose challenges to conventional endovascular treatment. CASE DESCRIPTION: A 61-year-old man presented with progressive weakness and decreasing sensation in the lower extremities. He had a remote history of craniopharyngioma surgery and deep venous thrombosis. Examination showed decreased strength and reflexes in the lower extremities. Magnetic resonance imaging demonstrated T2 cord signal changes and flow voids within the spinal canal. Angiogram showed bilateral internal iliac artery arteriovenous malformations with retrograde flow into a radicular vein and venous congestion of the medullary veins. Percutaneous transgluteal puncture of the superior gluteal vein was performed, and the abnormal inflow to the radicular vein was obliterated with coiling and Onyx embolization. The patient had significant clinical improvement, and follow-up imaging demonstrated resolution of T2 cord signal changes and flow voids. CONCLUSIONS: Extraspinal vascular malformations with vascular myelopathy are extremely rare. They include a broad spectrum of complex vascular disorders and often require alternate endovascular approaches.
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Fístula Arteriovenosa/patologia , Fístula Arteriovenosa/terapia , Embolização Terapêutica/métodos , Artéria Ilíaca/anormalidades , Fístula Arteriovenosa/complicações , Humanos , Masculino , Pessoa de Meia-Idade , Medula Espinal/irrigação sanguínea , Doenças da Medula Espinal/etiologiaRESUMO
OBJECTIVE: External ventricular drain (EVD) placement is one of first cranial procedures neurosurgery residents are expected to perform independently. While proper training improves patient outcomes, there are few options for practicing EVD placement prior to placing the EVD in patients in a clinical setting. Proposed solutions to this include using cadaveric models and virtual simulations, but barriers exist with these as well in regard to authenticity. EVD simulators using virtual reality technologies are a promising new technique for training, but the cost of these devices poses a barrier to general/widespread accessibility among smaller programs or underserved hospitals. The authors desribe a novel, yet simple, and cost-effective technique (less than $5 per mold) for developing a brain model constructed of homemade ballistics gelatin that can be used for teaching and practicing the placement of EVD. METHODS: A brain model is made with ballistics gelatin using an anatomically correct skull model as a mold. A 3D-printed ventricular system model is used to create a mold of an anatomically correct ventricular system in the brain model. A group of medical students (n = 10) were given a basic presentation about EVD placement, including standard landmarks and placement techniques, and were also shown a demonstration of EVD placement on the brain model. They were then allowed to perform an EVD placement using the brain model. The students were surveyed on their experience with using the brain model, including usability and practicality of the model. Accuracy of EVD placement by each student was also assessed, with adequate position of catheter tip being in the ipsilateral frontal horn. RESULTS: The final product is fairly inexpensive and easy to make. It is soft enough to pass a catheter through, but it is also firm enough to maintain its shape, including a cavity representing the lateral ventricles. The dense gelatin holds the catheter in its final resting position, while the two halves are separated and inspected. All participants in the test group of medical students reported that the brain model was easy to use, helped them understand the steps and technique of EVD placement, and provided good feedback on the ideal position of ventricular catheters. All of the participants in the group had adequate positioning of their ventricular catheters after one attempt. CONCLUSIONS: The presented brain model is easy to replicate, inexpensive, anatomically accurate, and provides a medium for neurosurgeons to teach and practice ventricular catheter placement in a risk-free environment.
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Cateterismo/métodos , Ventrículos Cerebrais , Drenagem/métodos , Modelos Anatômicos , Encéfalo/anatomia & histologia , Cadáver , Cateterismo/instrumentação , Análise Custo-Benefício , Drenagem/economia , Drenagem/instrumentação , Gelatina , Humanos , Impressão Tridimensional , VentriculostomiaRESUMO
BACKGROUND: The management of brain arteriovenous malformations (AVMs) remains a controversial topic. Given the relatively low incidence, high heterogeneity, and high morbidity and mortality of these lesions, consensus on treatment strategies is an issue of concern to organized neurosurgery. The present retrospective analysis examined and quantified the outcomes of patients with an initial presentation of intracranial hemorrhage from a Spetzler-Martin grade III or IV AVM, later ruled out as surgical candidates. METHODS: A total of 16 patients (5 females; 11 males) had presented with symptomatic hemorrhage confirmed by non-contrast-enhanced computed tomography and were deemed to not be surgical candidates owing to AVM location and/or architecture. The patients underwent combined endovascular embolization and gamma knife stereotactic radiosurgery (SRS). The modified Rankin scale was used to measure the clinical outcomes, comparing the scores at presentation, gamma knife treatment, and the last known follow-up examination. A radiographic evaluation was used to determine the level of AVM nidus involution after the procedure. RESULTS: The present study identified 16 patients with ruptured high-grade AVMs of high surgical risk. All the patients had undergone immediate embolization with delayed SRS for treatment of the hemorrhage and nidus of the AVM. A statistically significant proportion of patients showed marked improvement in the modified Rankin scale scores. No subsequent repeat hemorrhage or any associated complications after embolization occurred in any patient. CONCLUSION: These findings warrant consideration of endovascular embolization with adjuvant SRS as a powerful treatment option for cases with high surgical morbidity due to AVM characteristics.
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Fístula Arteriovenosa/terapia , Hemorragia Cerebral/terapia , Embolização Terapêutica/métodos , Malformações Arteriovenosas Intracranianas/terapia , Radiocirurgia/métodos , Adolescente , Adulto , Idoso , Fístula Arteriovenosa/diagnóstico por imagem , Hemorragia Cerebral/diagnóstico por imagem , Criança , Estudos de Coortes , Feminino , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do Tratamento , Adulto JovemRESUMO
Thoracic outlet syndrome (TOS) is an infrequent entity encountered by medical practitioners attributed to compression of the neurovascular structures passing through the thoracic outlet. Here, we report the presentation of a young adult who was referred for workup of cervical radiculopathy and was planned to undergo an anterior cervical discectomy and fusion. A dynamic cerebral angiogram was performed and confirmed the diagnosis of arteriogenic TOS. The etiology, presentation, and diagnostic workup of TOS are briefly discussed with emphasis placed on maintaining a healthy suspicion in order to differentiate from cervical radiculopathy, make an accurate diagnosis, and avoid inappropriate surgery.
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Angiografia Cerebral/métodos , Radiculopatia/diagnóstico por imagem , Síndrome do Desfiladeiro Torácico/diagnóstico por imagem , Adulto , Circulação Cerebrovascular , Diagnóstico Diferencial , Feminino , Humanos , Cervicalgia/etiologia , Valor Preditivo dos Testes , Síndrome do Desfiladeiro Torácico/complicações , Síndrome do Desfiladeiro Torácico/fisiopatologia , Síndrome do Desfiladeiro Torácico/cirurgia , Resultado do TratamentoRESUMO
The neurosurgical approach to the management of ischemic stroke has evolved dramatically over the past century with the bulk of these changes occurring over the past 25 years. With recent advances in technology and continued refinements in neurosurgical techniques there has been significant improvement to the safety and efficacy of our treatment options. The focus of this article will be to review the historical and recent reports in the literature related to revascularization techniques.
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Objectives. We describe a rare case of nonalcoholic Marchiafava-Bignami disease (MBD) in the setting of malnourishment after gastric bypass. Methods. A 44-year-old nonalcoholic Caucasian woman with malnutrition after gastric bypass presented with 2 weeks of weakness. The patient acutely became stuporous. Brain magnetic resonance imaging showed lesions in the corpus callosum and internal capsules consistent with MBD. After 10 days of treatment, the patient had resolution of her encephalopathy with return to baseline mental function, with radiological improvement. Results. MBD is a rare neurological disorder seen in alcoholics and can rapidly progress to coma or death. Our patient was successfully treated with a regimen typically used in alcoholics. We discuss the relevant literature supporting this regimen. Conclusions. This case demonstrates that since the pathophysiological etiology of the disease is malnutrition, MBD patients can be effectively treated with this regimen regardless of the underlying cause.
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BACKGROUND: Pituitary adenomas are one of the most common tumors of adulthood; however, subtypes such as Crooke cell adenoma are relatively rare. CASE DESCRIPTION: We present the case of a 55-year-old woman who presented with new-onset intermittent headache and dizziness. Clinical and laboratory investigations were not suggestive of corticotroph tumor. However, subsequent computed tomography and magnetic resonance imaging scans revealed the presence of a suprasellar pituitary adenoma displacing the optic chiasma superiorly, with hemorrhage and sellar expansion. The lesion was removed by transsphenoidal surgery and the biopsy confirmed the lesion to be a nonfunctioning pituitary macroadenoma. Further investigation revealed that the specimen demonstrated Crooke hyaline changes, with strong immunoreactivity for adrenocorticotropic hormone. However, initial workup and postoperative testing lacked evidence of Cushing disease. There was no sign of recurrence after 1-year follow-up. CONCLUSIONS: Clinically silent Crooke cell adenomas are rare occurrences, and as such we report this case with investigation of past cases.
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Adenoma Hipofisário Secretor de ACT/diagnóstico , Adenoma Hipofisário Secretor de ACT/cirurgia , Adenoma/diagnóstico , Adenoma/cirurgia , Adenoma Hipofisário Secretor de ACT/patologia , Adenoma/patologia , Diagnóstico Diferencial , Gerenciamento Clínico , Feminino , Humanos , Pessoa de Meia-IdadeRESUMO
BACKGROUND: There are few reported instances of intraspinal migration of a bullet fragment. The majority of these migrations occur caudally, typically below the level of T10. Even fewer cases demonstrate cephalad migration from the sacral spine to the lumbar spine. We report here for the first time a case of a cephalad migration intradurally from the thoracic spine to cervical spine. CASE DESCRIPTION: A 31-year old man presented to the emergency department with a suspected spinal cord injury following a GSW sustained to the left shoulder. A penetrating gunshot injury to the thoracic spine at the level of T2 was observed, and CT angiography revealed a cephalad migration of the bullet fragment to the level of C6. The patient had marked weakness of the bilateral upper extremities, with paraplegia of the lower extremities. There was a sensory deficit beginning at a level 1 cm below the clavicle, as well as a decrease in rectal tone. We performed a laminectomy at C6 with dural incision and removal of the main bullet fragment. Following the surgery, significant improvement in strength and sensation in the bilateral upper extremities was noted, but paraplegia and sensory loss below the level of T2 persisted. CONCLUSIONS: In this report, we review the previously reported cases in which intraspinal migration of bullets have occurred, and discuss the unique finding in this study of cephalad migration of a bullet within the dura. In addition, we detail considerations in the management of such injuries.
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Vértebras Cervicais/cirurgia , Migração de Corpo Estranho/cirurgia , Traumatismos da Medula Espinal/cirurgia , Vértebras Torácicas/lesões , Ferimentos por Arma de Fogo/cirurgia , Adulto , Vértebras Cervicais/diagnóstico por imagem , Migração de Corpo Estranho/diagnóstico por imagem , Humanos , Masculino , Paresia/diagnóstico por imagem , Paresia/etiologia , Paresia/cirurgia , Traumatismos da Medula Espinal/diagnóstico por imagem , Traumatismos da Medula Espinal/etiologia , Vértebras Torácicas/diagnóstico por imagem , Ferimentos por Arma de Fogo/diagnóstico por imagemRESUMO
Advances in endovascular embolization have improved morbidity and mortality among patients with vein of Galen malformations (VoGMs). The patient presented at 3 months of age with increased head circumference and a bruit over his anterior fontanelle. Diagnostic cerebral angiography confirmed the presence of a large mural-type VoGM. The decision was made to undergo a staged arterial embolization at 4 years of age after developing worsening right-sided hemiparesis. An attempt was made to occlude the posterior choroidal feeding vessel with a large 25 mm × 50 cm coil, followed by a 6 mm × 20 cm coil; however, the high flow of the lesion displaced both coils into the wall of the aneurysmal venous sac. Interval magnetic resonance imaging and angiography revealed partial occlusion of the VoGM at 7 months and complete thrombosis at 24 months post procedure, precluding a need for additional coiling. This case illustrates that a minimal change in intramural flow dynamics of VoGMs could lead to progressive thrombosis.
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Embolização Terapêutica/instrumentação , Embolização Terapêutica/métodos , Malformações da Veia de Galeno/cirurgia , Angiografia Cerebral , Pré-Escolar , Humanos , Processamento de Imagem Assistida por Computador , Estudos Longitudinais , Imageamento por Ressonância Magnética , Masculino , Malformações da Veia de Galeno/diagnóstico por imagemRESUMO
Patients with hyperhomocysteinemia (HHcy), or elevated plasma homocysteine (Hcy), are at higher risk of developing arrhythmias and sudden cardiac death; however, the mechanisms are unknown. In this study, the effects of HHcy on sinus node function, atrioventricular conduction, and ventricular vulnerability were investigated by electrophysiological (EP) analysis, and the role of magnesium (Mg(2+)), an endogenous N-methyl-D-aspartate (NMDA) receptor antagonist, in attenuating EP changes due to HHcy was explored. Wild-type mice (WT) and mice receiving Hcy in the drinking water for 12 weeks (DW) were subjected to electrocardiographic and EP studies. DW compared to WT had significantly shorter RR, PR, QT, and HV intervals, corrected sinus node recovery times (CSNRT), Wenckebach periodicity (WP), atrioventricular nodal effective refractory periods (AVNERP), and right ventricular effective refractory periods (RVERP). To examine the role of Mg(2+) in mitigating conduction changes in HHcy, WT, DW, and heterozygous cystathionine-ß-synthase knockout mice (CBS (+/-) ) were subjected to repeat EP studies before and after administration of low-dose magnesium sulfate (20 mg/kg). Mg(2+) had no effect on EP variables in WT, but significantly slowed CSNRT, WP, and AVNERP in DW, as well as WP and AVNERP in CBS (+/-) . These findings suggest that ionic channels modulated by Mg(2+) may contribute to HHcy-induced conduction abnormalities.
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Hiper-Homocisteinemia/fisiopatologia , Magnésio/metabolismo , Nó Sinoatrial/fisiopatologia , Potenciais de Ação , Animais , Cistationina beta-Sintase/genética , Cistationina beta-Sintase/metabolismo , Hiper-Homocisteinemia/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Período Refratário Eletrofisiológico , Nó Sinoatrial/metabolismoRESUMO
The presence of healthcare-related disparities is an ongoing, widespread, and well-documented societal and health policy issue. We investigated the presence of racial disparities among post-operative patients either with meningioma or malignant, benign, or metastatic brain tumors. We used the Medicaid component of the Thomson Reuter's MarketScan database from 2000 to 2009. Univariate and multivariate analysis assessed death, 30-day post-operative risk of complications, length of stay, and total charges. We identified 2321 patients, 73.7% were Caucasian, 57.8% were women; with Charlson comorbidity scores of <3 (56.2%) and treated at low-volume centers (73.4%). Among all, 26.3% of patients were of African-American ethnicity and 22.1% had meningiomas. Mortality was 2.0%, mean length of stay (LOS) was 9 days, mean total charges were US$42,422, an adverse discharge occurred in 22.5% of patients, and overall 30-day complication rate was 23.4%. In a multivariate analysis, African-American patients with meningiomas had higher odds of developing a 30-day complication (p=0.05) and were significantly more likely to have longer LOS (p<0.001) and greater total charges (p<0.001) relative to Caucasian counterparts. The presence of one post-operative complication doubled LOS and nearly doubled total charges, while the presence of two post-operative complications tripled these outcomes. Patients of African-American ethnicity had significantly higher post-operative complications than those of Caucasian ethnicity. This higher rate of complications seems to have driven greater healthcare utilization, including greater LOS and total charges, among African-American patients. Interventions aimed at reducing complications among African-American patients with brain tumor may help reduce post-operative disparities.
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Neoplasias Encefálicas/economia , Neoplasias Encefálicas/cirurgia , Disparidades em Assistência à Saúde , Medicaid/economia , Fatores Socioeconômicos , Adulto , Negro ou Afro-Americano/estatística & dados numéricos , Idoso , Neoplasias Encefálicas/mortalidade , Craniotomia/economia , Craniotomia/métodos , Bases de Dados Factuais/estatística & dados numéricos , Feminino , Humanos , Classificação Internacional de Doenças , Tempo de Internação , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Complicações Pós-Operatórias/economia , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/mortalidade , Complicações Pós-Operatórias/terapia , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Estados Unidos , População BrancaRESUMO
BACKGROUND: Excessive complement activation is an integral part of ischemia and reperfusion (IR) injury (IRI) of organs. In kidney transplantation, the pathologic consequence of IRI and complement activation can lead to delayed graft function, which in turn is associated with acute rejection. Previous strategies to reduce complement-induced IRI required systemic administration of agents, which can lead to increased susceptibility to infections/immune diseases. The objective of this study was to determine whether an increase in complement control defenses of rat kidney endothelium reduces IRI. We hypothesized that increased complement control on the endothelial barrier reduces IR-mediated complement activation and reduces kidney dysfunction. MATERIALS AND METHODS: Fischer 344 rats underwent left kidney ischemia for 45 min and treatment with a novel fusogenic lipid vesicle (FLVs) delivery system to decorate endothelial cells with vaccinia virus complement control protein (VCP), followed by reperfusion for 24 h. Assessment included renal function by serum creatinine and urea, myeloperoxidase assay for neutrophil infiltration, histopathology, and quantification of C3 production in kidneys. RESULTS: Animals in which the kidney endothelium was bolstered by FLVs+VCP treatment had better renal function with a significant reduction in serum creatinine compared with vehicle controls (P < 0.05). Also, C3 production was significantly reduced (P < 0.05) in treated animals compared with vehicle controls. CONCLUSION: Increasing complement control at the endothelial barrier with FLVs+VCP modulates complement activation/production during the first 24 h, reducing renal dysfunction following IRI.
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Ativação do Complemento/fisiologia , Complemento C3/antagonistas & inibidores , Nefropatias , Traumatismo por Reperfusão , Proteínas Virais/farmacologia , Animais , Ativação do Complemento/efeitos dos fármacos , Complemento C3/imunologia , Complemento C3/metabolismo , Creatinina/sangue , Células Endoteliais/efeitos dos fármacos , Células Endoteliais/imunologia , Células Endoteliais/metabolismo , Nefropatias/tratamento farmacológico , Nefropatias/imunologia , Nefropatias/metabolismo , Testes de Função Renal , Lipossomos/farmacologia , Masculino , Neutrófilos/imunologia , Neutrófilos/metabolismo , Permeabilidade/efeitos dos fármacos , Peroxidase/metabolismo , Ratos , Ratos Endogâmicos F344 , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/imunologia , Traumatismo por Reperfusão/metabolismo , Ureia/sangueRESUMO
Ischemia and reperfusion of organs is an unavoidable consequence of transplantation. Inflammatory events associated with reperfusion injury are in part attributed to excessive complement activation. Systemic administration of complement inhibitors reduces reperfusion injury but leaves patients vulnerable to infection. Here, we report a novel therapeutic strategy that decorates cells with an anti-complement peptide. An analog of the C3 convertase inhibitor Compstatin (C) was synthesized with a hexahistidine (His(6)) tag to create C-His(6). To decorate cell membranes with C-His(6), fusogenic lipid vesicles (FLVs) were used to incorporate lipids with nickel (Ni(2+)) tethers into cell membranes, and these could then couple with C-His(6). Ni(2+) tether levels to display C-His(6) were modulated by changing FLV formulation, FLV incubation time and FLV levels. SKOV-3 cells decorated with C-His(6) effectively reduced complement deposition in a classical complement activation assay. We conclude that our therapeutic approach appears promising for local ex vivo treatment of transplanted organs to reduce complement-mediated reperfusion injury.
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Elevated levels of serum homocysteine (Hcy) resulting in hyperhomocysteinemia (HHcy) have been implicated in cardiac pathological conditions including: coronary heart disease (CHD), acute myocardial infarction, arrhythmogenesis and sudden cardiac death (SCD). The mechanisms by which HHcy leads to arrhythmogenesis and SCD are unknown. Novel findings indicate that Hcy is an agonist of the N-methyl-D-aspartate receptor (NMDA-R), known to be present in cardiac tissue, and when activated, increases intracellular calcium leading to increased cell excitability. Also, HHcy induces oxidative stress in cardiac cells and activates matrix metalloproteinases (MMPs) that degrade cell membranes and proteins. Here we review the literature relevant to HHcy-induced oxidative stress leading to cardiac tissue remodelling that may adversely affect cell-to-cell impulse conduction, in particular on the heart's specialized conduction system, and may provide substrate for arrhythmogenesis and SCD. Efficacy of B vitamin supplementation in patient populations with HHcy and CHD is also reviewed.