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1.
Respir Care ; 68(5): 592-601, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36787913

RESUMO

BACKGROUND: In refractory respiratory failure, extracorporeal membrane oxygenation (ECMO) is a rescue therapy to prevent ventilator-induced lung injury. Optimal ventilator parameters during ECMO remain unknown. Our objective was to describe the association between mortality and ventilator parameters during ECMO for neonatal and pediatric respiratory failure. METHODS: We performed a secondary analysis of the Bleeding and Thrombosis on ECMO dataset. Ventilator parameters included breathing frequency, tidal volume, peak inspiratory pressure, PEEP, dynamic driving pressure, pressure support, mean airway pressure, and FIO2 . Parameters were evaluated before cannulation, on the calendar day of ECMO initiation (ECMO day 1), and the day before ECMO separation. RESULTS: Of 237 included subjects analyzed, 64% were neonates, of whom 36% had a congenital diaphragmatic hernia. Of all the subjects, 67% were supported on venoarterial ECMO. Overall in-hospital mortality was 35% (n = 83). The median (interquartile range) PEEP on ECMO day 1 was 8 (5.0-10.0) cm H2O for neonates and 10 (8.0-10.0) cm H2O for pediatric subjects. By multivariable analysis, higher PEEP on ECMO day 1 in neonates was associated with lower odds of in-hospital mortality (odds ratio 0.77, 95% CI 0.62-0.92; P = .01), with a further amplified effect in neonates with congenital diaphragmatic hernia (odds ratio 0.59, 95% CI 0.41-0.86; P = .005). No ventilator type or parameter was associated with mortality in pediatric subjects. CONCLUSIONS: Avoiding low PEEP on ECMO day 1 for neonates on ECMO may be beneficial, particularly those with a congenital diaphragmatic hernia. No additional ventilator parameters were associated with mortality in either neonatal or pediatric subjects. PEEP is a modifiable parameter that may improve neonatal survival during ECMO and requires further investigation.


Assuntos
Oxigenação por Membrana Extracorpórea , Hérnias Diafragmáticas Congênitas , Insuficiência Respiratória , Recém-Nascido , Humanos , Criança , Hérnias Diafragmáticas Congênitas/complicações , Hérnias Diafragmáticas Congênitas/terapia , Ventiladores Mecânicos , Respiração com Pressão Positiva , Insuficiência Respiratória/etiologia , Insuficiência Respiratória/terapia , Estudos Retrospectivos
2.
Exp Eye Res ; 120: 15-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24333760

RESUMO

Simultaneous non-invasive visualization of blood vessels and nerves in patients can be obtained in the eye. The retinal vasculature is a target of many retinopathies. Inflammation, readily manifest by leukocyte adhesion to the endothelial lining, is a key pathophysiological mechanism of many retinopathies, making it a valuable and ubiquitous target for disease research. Leukocyte fluorography has been extensively used in the past twenty years; however, fluorescent markers, visualization techniques, and recording methods have differed between studies. The lack of detailed protocol papers regarding leukocyte fluorography, coupled with lack of uniformity between studies, has led to a paucity of standards for leukocyte transit (velocity, adherence, extravasation) in the retina. Here, we give a detailed description of a convenient method using acridine orange (AO) and a commercially available scanning laser ophthalmoscope (SLO, HRA-OCT Spectralis) to view leukocyte behavior in the mouse retina. Normal mice are compared to mice with acute and chronic inflammation. This method can be readily adopted in many research labs.


Assuntos
Laranja de Acridina , Angiofluoresceinografia , Corantes Fluorescentes , Leucócitos/fisiologia , Artéria Retiniana/fisiologia , Veia Retiniana/fisiologia , Animais , Velocidade do Fluxo Sanguíneo , Movimento Celular/fisiologia , Diabetes Mellitus Tipo 1/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos NOD , Microscopia Confocal , Oftalmoscópios , Fluxo Sanguíneo Regional/fisiologia , Vasculite Retiniana/induzido quimicamente , Vasculite Retiniana/fisiopatologia , Tomografia de Coerência Óptica , Fator A de Crescimento do Endotélio Vascular/farmacologia , Gravação em Vídeo
3.
Elife ; 2: e00324, 2013 Jun 18.
Artigo em Inglês | MEDLINE | ID: mdl-23795287

RESUMO

Optimal phototransduction requires separation of the avascular photoreceptor layer from the adjacent vascularized inner retina and choroid. Breakdown of peri-photoreceptor vascular demarcation leads to retinal angiomatous proliferation or choroidal neovascularization, two variants of vascular invasion of the photoreceptor layer in age-related macular degeneration (AMD), the leading cause of irreversible blindness in industrialized nations. Here we show that sFLT-1, an endogenous inhibitor of vascular endothelial growth factor A (VEGF-A), is synthesized by photoreceptors and retinal pigment epithelium (RPE), and is decreased in human AMD. Suppression of sFLT-1 by antibodies, adeno-associated virus-mediated RNA interference, or Cre/lox-mediated gene ablation either in the photoreceptor layer or RPE frees VEGF-A and abolishes photoreceptor avascularity. These findings help explain the vascular zoning of the retina, which is critical for vision, and advance two transgenic murine models of AMD with spontaneous vascular invasion early in life. DOI:http://dx.doi.org/10.7554/eLife.00324.001.


Assuntos
Neovascularização de Coroide/metabolismo , Degeneração Macular/metabolismo , Células Fotorreceptoras de Vertebrados/metabolismo , Neovascularização Retiniana/metabolismo , Epitélio Pigmentado da Retina/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Visão Ocular , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Anticorpos/farmacologia , Estudos de Casos e Controles , Neovascularização de Coroide/genética , Neovascularização de Coroide/patologia , Modelos Animais de Doenças , Regulação para Baixo , Feminino , Humanos , Degeneração Macular/genética , Degeneração Macular/patologia , Masculino , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Camundongos Knockout , Células Fotorreceptoras de Vertebrados/patologia , Interferência de RNA , Neovascularização Retiniana/genética , Neovascularização Retiniana/patologia , Epitélio Pigmentado da Retina/patologia , Transdução de Sinais , Fator A de Crescimento do Endotélio Vascular/genética , Fator A de Crescimento do Endotélio Vascular/metabolismo , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/antagonistas & inibidores , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/deficiência , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética
4.
ACS Nano ; 7(4): 3264-75, 2013 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-23464925

RESUMO

Monthly intraocular injections are widely used to deliver protein-based drugs that cannot cross the blood-retina barrier for the treatment of leading blinding diseases such as age-related macular degeneration (AMD). This invasive treatment carries significant risks, including bleeding, pain, infection, and retinal detachment. Further, current therapies are associated with a rate of retinal fibrosis and geographic atrophy significantly higher than that which occurs in the described natural history of AMD. A novel therapeutic strategy which improves outcomes in a less invasive manner, reduces risk, and provides long-term inhibition of angiogenesis and fibrosis is a felt medical need. Here we show that a single intravenous injection of targeted, biodegradable nanoparticles delivering a recombinant Flt23k intraceptor plasmid homes to neovascular lesions in the retina and regresses CNV in primate and murine AMD models. Moreover, this treatment suppressed subretinal fibrosis, which is currently not addressed by clinical therapies. Murine vision, as tested by OptoMotry, significantly improved with nearly 40% restoration of visual loss induced by CNV. We found no evidence of ocular or systemic toxicity from nanoparticle treatment. These findings offer a nanoparticle-based platform for targeted, vitreous-sparing, extended-release, nonviral gene therapy.


Assuntos
DNA/administração & dosagem , Terapia Genética/métodos , Degeneração Macular/terapia , Nanocápsulas/administração & dosagem , Neovascularização Patológica/terapia , Retina/patologia , Receptor 1 de Fatores de Crescimento do Endotélio Vascular/genética , Animais , DNA/genética , Fibrose , Haplorrinos , Camundongos , Resultado do Tratamento
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