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1.
Br J Clin Pharmacol ; 89(1): 401-409, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36208427

RESUMO

Systemic administration of agents that inhibit vascular endothelial growth factor (VEGF) and therefore vascular proliferation is often used to treat various cancers. However, these agents are associated with a number of side effects, including proteinuria and renal injury. Intravitreal injection of anti-VEGF agents has become the cornerstone of macular disease treatment. Since these agents cross the blood-retina barrier and enter the circulation, systemic side effects have been reported. We report the novel case of a 57-year-old patient who presented with macular oedema secondary to central retinal vein occlusion, underwent three monthly loading-dose injections with the anti-VEGF agent ranibizumab, and 2 weeks after the second injection presented with biopsy-verified membranoproliferative glomerulonephritis. Twelve weeks after presenting with renal failure and 10 weeks after his last anti-VEGF injection, the patient demonstrated spontaneous recovery of his kidney function. The patient had a history that promoted renal fragility, including hypertension, liver transplantation 6 years earlier for alcohol-related cirrhosis and new-onset diabetes mellitus after transplant. Our literature review and case suggest that although adverse renal events after intravitreal anti-VEGF injections are very rare, ophthalmologists and nephrologists should be aware of this risk.


Assuntos
Inibidores da Angiogênese , Glomerulonefrite Membranoproliferativa , Humanos , Pessoa de Meia-Idade , Inibidores da Angiogênese/efeitos adversos , Bevacizumab , Fator A de Crescimento do Endotélio Vascular , Inibidores do Crescimento , Glomerulonefrite Membranoproliferativa/induzido quimicamente , Glomerulonefrite Membranoproliferativa/tratamento farmacológico , Injeções Intravítreas , Ranibizumab/uso terapêutico , Receptores de Fatores de Crescimento do Endotélio Vascular , Proteínas Recombinantes de Fusão
2.
PLoS One ; 19(3): e0298795, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38512953

RESUMO

PURPOSE: Identifying pre/perioperative factors that predict corneal endothelial-cell loss (ECL) after phacoemulsification may reveal ways to reduce ECL. Our literature analysis showed that 37 studies have investigated one or several such factors but all have significant limitations. Therefore, the data of a large randomized controlled trial (PERCEPOLIS) were subjected to post-hoc multivariate analysis determining the ability of nine pre/perioperative variables to predict ECL. METHODS: PERCEPOLIS was conducted in 2015-2016 to compare two phacoemulsification techniques (subluxation and divide-and-conquer) in terms of 3-month ECL. Non-inferiority between the techniques was found. In the present study, post-hoc univariate and multivariate analyses were conducted to determine associations between ECL and age, sex, cataract density, preoperative endothelial-cell density, phacoemulsification technique, effective phaco time (EPT), and 2-hour central-corneal thickness. The data are presented in the context of a narrative review of the literature. RESULTS: Three-month data were available for 275 patients (94% of the randomized cohort; mean age, 74 years; 58% women). Mean LOCSIII cataract grade was 3.2. Mean EPT was 6 seconds. Mean ECL was 13%. Only an older age (beta = 0.2%, p = 0.049) and higher EPT (beta = 1.2%, p = 0.0002) predicted 3-month ECL. Cataract density was significant on univariate (p = 0.04) but not multivariate analysis. The other variables did not associate with ECL. CONCLUSIONS: Older age may amplify ECL due to increased endothelial cell fragility. EPT may promote ECL via cataract density-dependent and -independent mechanisms that should be considered in future phacoemulsification research aiming to reduce ECL. Our literature analysis showed that the average ECL for relatively unselected consecutively-sampled cohorts is 12%.


Assuntos
Extração de Catarata , Catarata , Facoemulsificação , Humanos , Feminino , Idoso , Masculino , Facoemulsificação/efeitos adversos , Facoemulsificação/métodos , Perda de Células Endoteliais da Córnea/diagnóstico , Perda de Células Endoteliais da Córnea/etiologia , Extração de Catarata/efeitos adversos , Extração de Catarata/métodos , Implante de Lente Intraocular , Contagem de Células , Endotélio Corneano , Ensaios Clínicos Controlados Aleatórios como Assunto
3.
J Hosp Palliat Nurs ; 20(1): 88-94, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-30063619

RESUMO

Dysphagia is common in palliative patients and worsens quality of life. Nurses are the main provider of dysphagia care. An audit showed poor compliance with dysphagia measures among nurses, but little is known about what the barriers are. We sought to evaluate barriers to dysphagia care among hospice nurses. This was a stepwise, mixed-method study. Baseline knowledge and attitudes were assessed, and a lecture was crafted based on the assessment. The knowledge and attitudes were then reassessed to investigate for any change. A focus group and an open-ended questionnaire were then used to assess for other barriers and for the effectiveness of training. Knowledge scores were low at baseline, and training improved the scores. Nurses cited the lack of time and lack of families' involvement as barriers to dysphagia care. While nurses believed that preventing aspiration is important, they also felt that most patients would refuse a modified diet and that respecting their wishes is important. Most nurses felt that the training increased their ability to care for patients with dysphagia. Our study demonstrated that knowledge deficit was an important barrier in dysphagia care for nurses, and this can be improved with a short training. Even though nurses rightly believed that patients' preferences are important, they struggled with trying to balance these preferences with preventing aspiration. Supporting them in making these decisions, having more time for feeding patients, and involving family members may be important to reduce barriers to care for patients with dysphagia.


Assuntos
Transtornos de Deglutição/enfermagem , Cuidados Paliativos na Terminalidade da Vida/métodos , Adulto , Atitude do Pessoal de Saúde , Feminino , Grupos Focais/métodos , Conhecimentos, Atitudes e Prática em Saúde , Cuidados Paliativos na Terminalidade da Vida/normas , Humanos , Masculino , Pessoa de Meia-Idade , Pesquisa Qualitativa , Inquéritos e Questionários
4.
Eur J Hum Genet ; 23(11): 1482-7, 2015 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-25920557

RESUMO

The dual-specificity tyrosine-phosphorylation-regulated kinase 1A (DYRK1A) gene, located on chromosome 21q22.13 within the Down syndrome critical region, has been implicated in syndromic intellectual disability associated with Down syndrome and autism. DYRK1A has a critical role in brain growth and development primarily by regulating cell proliferation, neurogenesis, neuronal plasticity and survival. Several patients have been reported with chromosome 21 aberrations such as partial monosomy, involving multiple genes including DYRK1A. In addition, seven other individuals have been described with chromosomal rearrangements, intragenic deletions or truncating mutations that disrupt specifically DYRK1A. Most of these patients have microcephaly and all have significant intellectual disability. In the present study, we report 10 unrelated individuals with DYRK1A-associated intellectual disability (ID) who display a recurrent pattern of clinical manifestations including primary or acquired microcephaly, ID ranging from mild to severe, speech delay or absence, seizures, autism, motor delay, deep-set eyes, poor feeding and poor weight gain. We identified unique truncating and non-synonymous mutations (three nonsense, four frameshift and two missense) in DYRK1A in nine patients and a large chromosomal deletion that encompassed DYRK1A in one patient. On the basis of increasing identification of mutations in DYRK1A, we suggest that this gene be considered potentially causative in patients presenting with ID, primary or acquired microcephaly, feeding problems and absent or delayed speech with or without seizures.


Assuntos
Síndrome de Down/genética , Deficiência Intelectual/genética , Microcefalia/genética , Proteínas Serina-Treonina Quinases/genética , Proteínas Tirosina Quinases/genética , Adolescente , Adulto , Transtorno Autístico/genética , Transtorno Autístico/fisiopatologia , Criança , Pré-Escolar , Deleção Cromossômica , Cromossomos Humanos Par 21/genética , Feminino , Humanos , Deficiência Intelectual/fisiopatologia , Masculino , Microcefalia/fisiopatologia , Mutação , Fenótipo , Quinases Dyrk
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