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1.
Retina ; 41(3): 588-594, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33600134

RESUMO

PURPOSE: To assess early changes in spectral-domain optical coherence tomography during the loading phase with intravitreal aflibercept therapy in patients with neovascular age-related macular degeneration. METHODS: In this prospective, open-label, single-arm, multicenter study, patients with neovascular age-related macular degeneration, who were antivascular endothelial growth factor treatment-naïve, received three monthly initial doses of intravitreal aflibercept 2 mg. The primary outcome was the proportion of patients with dry spectral-domain optical coherence tomography at 12 weeks, defined as an absence of intraretinal edema, intraretinal cysts, subretinal fluid, and subretinal pigment epithelium fluid. RESULTS: Fifty eyes of 50 patients were investigated. At 12 weeks, 34.0% (17/50) had dry spectral-domain optical coherence tomography. Marked reductions were observed for all other spectral-domain optical coherence tomography parameters. The mean macular central thickness fell significantly from 463.2 ± 184.3 µm at baseline to 288.9 ± 76.8 µm at Week 12 (P < 0.0001). The mean best-corrected visual acuity also improved significantly from 61.0 ± 16.0 letters at baseline to 66.6 ± 19.0 letters at Week 12 (P = 0.0006). CONCLUSION: The anatomic and functional outcomes improved over the 12-week study period. All outcome variables peaked after the third aflibercept injection, confirming the benefit of three initial doses.

2.
Cell Rep ; 33(10): 108485, 2020 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-33296655

RESUMO

Immune responses differ between women and men, and type I interferon (IFN) responses following Toll-like receptor 7 (TLR7) stimulation are higher in women. The precise mechanisms driving these sex differences in immunity are unknown. To investigate possible genetic factors, we quantify escape from X chromosome inactivation (XCI) for TLR7 and four other genes (RPS6KA3, CYBB, BTK, and IL13RA1) at the single plasmacytoid dendritic cell (pDC) level. We observe escape from XCI for all investigated genes, leading to biallelic expression patterns. pDCs with biallelic gene expression have significantly higher mRNA levels of the respective genes. Unstimulated pDCs with biallelic TLR7 expression exhibit significantly higher IFNα/ß mRNA levels, and IFNα exposure results in significantly increased IFNα/ß protein production by pDCs. These results identify unanticipated heterogeneity in escape from XCI of several genes in pDCs and highlight the important contribution of X chromosome factors to sex differences in type I IFN responses, which might explain observed sex differences in human diseases.

3.
J Pediatr ; 2020 Dec 17.
Artigo em Inglês | MEDLINE | ID: mdl-33340549

RESUMO

OBJECTIVE: To describe 4 subgroups of pediatric patients treated with splenectomy, hydroxychloroquine, azathioprine, or rituximab as the first-option, second-line treatment for chronic immune thrombocytopenia. STUDY DESIGN: Selection of patients with chronic immune thrombocytopenia from the French national prospective cohort of pediatric autoimmune cytopenia OBS'CEREVANCE and VIGICAIRE study, treated by splenectomy, hydroxychloroquine, azathioprine, or rituximab as a first second-line treatment. RESULTS: For 137 patients, treated between 1989 and 2016, the median follow-up after diagnosis and after treatment initiation was 8.5 (2.8-26.4) years and 4.7 (1.1-25.1) years, respectively. Median age at diagnosis and at initiation of treatment were 9 (0.7; 16) and 12 (2; 18.1) years, respectively without significant difference between subgroups. For the whole cohort, 24-month event-free survival was 62% (95% CI 55; 71). It was 85% (95% CI 77; 95) for the 56 patients treated with splenectomy, 60% (95% CI 44; 84) for the 23 patients treated with rituximab, 46% (95% CI 30; 71) for the 24 patients treated with azathioprine, and 37% (95% CI 24; 59) for the 34 patients treated with hydroxychloroquine (log-rank P < .0001). For the splenectomy subgroup, being older than 10 years at splenectomy tended to improve event-free survival (P = .05). Female teenagers with antinuclear antibody positivity benefited from hydroxychloroquine therapy. CONCLUSIONS: This national study, limiting pitfalls in the analysis of the effects of second-line therapies, showed that splenectomy remains the treatment associated with the better response at 24 months.

5.
JACC Clin Electrophysiol ; 4(3): 397-408, 2018 03.
Artigo em Inglês | MEDLINE | ID: mdl-30089568

RESUMO

OBJECTIVES: The aim of this study was to identify using implantable loop recorder (ILR) monitoring the mechanisms leading to sudden death (SD) in patients undergoing hemodialysis (HD). BACKGROUND: SD accounts for 11% to 25% of death in HD patients. METHODS: Continuous rhythm monitoring was performed using the remote monitoring capability of the ILR device in patients undergoing HD at 8 centers. Clinical, biological, and technical HD parameters were recorded and analyzed. RESULTS: Seventy-one patients (mean age 65 ± 9 years, 73% men) were included. Left ventricular ejection fraction was <50% in 16%. Twelve patients (17%) had histories of atrial fibrillation or flutter at inclusion. During a mean follow-up period of 21.3 ± 6.9 months, 16 patients died (14% patient-years), 7 (44%) of cardiovascular causes. Four SDs occurred, with progressive bradycardia followed by asystole. The incidence of patients presenting with significant conduction disorder and with ventricular arrhythmia was 14% and 9% patient-years, respectively. In multivariate survival frailty analyses, a higher risk for conduction disorder was associated with plasma potassium >5.0 mmol/l, bicarbonate <22 mmol/l, hemoglobin >11.5 g/dl, pre-HD systolic blood pressure >140 mm Hg, the longer interdialytic period, history of coronary artery disease, previous other arrhythmias, and diabetes mellitus. A higher risk for ventricular arrhythmia was associated with potassium <4.0 mmol/l, no antiarrhythmic drugs, and previous other arrhythmias. With ILR monitoring, de novo atrial fibrillation or flutter was diagnosed in 14 patients (20%). CONCLUSIONS: ILR may be considered in HD patients prone to significant conduction disorders, ventricular arrhythmia, or atrial fibrillation or flutter to allow early identification and initiation of adequate treatment. Therapeutic strategies reducing serum potassium variability could decrease the rate of SD in these patients. (Implantable Loop Recorder in Hemodialysis Patients [RYTHMODIAL]; NCT01252823).


Assuntos
Arritmias Cardíacas/diagnóstico , Morte Súbita Cardíaca/prevenção & controle , Eletrocardiografia Ambulatorial/instrumentação , Diálise Renal/efeitos adversos , Idoso , Eletrodos Implantados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos
6.
JAMA Ophthalmol ; 135(11): 1259-1266, 2017 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-28973076

RESUMO

Importance: Nutritional uptake of lutein, zeaxanthin, and ω-3 polyunsaturated fatty acids may increase macular pigment optical density (MPOD) and thereby protect against the development of age-related macular degeneration (AMD). Objectives: To estimate the efficiency of dietary supplementation containing lutein, zeaxanthin, ω-3 polyunsaturated fatty acids, and vitamins to increase the density of macular pigment in first-generation offspring of parents with neovascular AMD. Design, Setting, and Participants: This study was a randomized clinical trial (Lutein Influence on Macula of Persons Issued From AMD Parents [LIMPIA]) with a 6-month treatment period, followed by a 6-month follow-up period. Analyses were based on the intent-to-treat principle. The setting was 2 university hospitals in France (at Bordeaux and Dijon) from January 2011 (first participant first visit) to February 2013 (last participant last visit). The analysis was conducted from January to November 2016. Participants were 120 individuals free of any retinal ocular disease. They were first-generation offspring of parents with neovascular AMD. Interventions: Participants were randomized in a 1:1 ratio to receive either 2 daily dietary supplementation capsules or placebo for 6 months. Main Outcomes and Measures: The primary assessment criterion was the evolution of MPOD after 6 months of supplementation (value of both eligible eyes) measured using the modified MPD-Visucam 200 (Carl Zeiss Meditec) and the modified Heidelberg Retina Angiograph (Heidelberg Engineering) (HRA) at 0.98° eccentricity. The statistical analysis was adjusted for hospital and for risk factors. Results: Overall, 120 participants (60 in each group) were included, and 239 eyes were analyzed (119 in the lutein plus zeaxanthin [L + Z] group and 120 in the placebo group). Their mean (SD) age was 56.7 (6.6) years, and 71.7% (n = 86) were female. A statistically significant increase in plasma lutein and zeaxanthin was shown in the L + Z group after 3 months and 6 months of treatment compared with the placebo group. However, the difference between groups in the evolution of MPOD measured by HRA 0.98° eccentricity between 6 months and baseline was 0.036 (95% CI, -0.037 to 0.110) (P = .33). Conclusions and Relevance: Among first-generation offspring of parents with neovascular AMD in the LIMPIA trial, MPOD as measured with the modified HRA and the MPD-Visucam was not modified after 6 months of lutein and zeaxanthin dietary supplementation despite plasma levels showing continuous exposure to lutein and zeaxanthin. Further research is necessary to understand the mechanism of absorption and metabolism of these nutrients in the macula, the best way to measure MPOD, and the clinical benefit for the patients. Trial Registration: clinicaltrials.gov Identifier: NCT01269697.


Assuntos
Ácidos Graxos Ômega-3/farmacocinética , Luteína/farmacocinética , Macula Lutea/efeitos dos fármacos , Pigmento Macular/metabolismo , Degeneração Macular Exsudativa/tratamento farmacológico , Zeaxantinas/farmacocinética , Adulto , Idoso , Suplementos Nutricionais , Relação Dose-Resposta a Droga , Método Duplo-Cego , Quimioterapia Combinada , Ácidos Graxos Ômega-3/administração & dosagem , Feminino , Seguimentos , Humanos , Luteína/administração & dosagem , Macula Lutea/metabolismo , Macula Lutea/patologia , Masculino , Pessoa de Meia-Idade , Oftalmoscopia , Estudos Retrospectivos , Resultado do Tratamento , Acuidade Visual , Vitaminas/administração & dosagem , Degeneração Macular Exsudativa/diagnóstico , Degeneração Macular Exsudativa/metabolismo , Zeaxantinas/administração & dosagem
7.
Acta Ophthalmol ; 95(8): e763-e769, 2017 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-28271618

RESUMO

PURPOSE: In numerous epidemiological studies, omega-3 polyunsaturated fatty acids (PUFAs) have been associated with a decreased risk of age-related macular degeneration (AMD). Beyond their structural, functional and neuroprotective roles, omega-3 PUFAs may favour the retinal accumulation of lutein and zeaxanthin and thus increase macular pigment optical density (MPOD). We examined the associations of MPOD with plasma omega-3 PUFAs in subjects with family history of AMD. METHODS: The Limpia study is a double-blind, placebo-controlled, prospective randomized clinical trial performed in 120 subjects. Subjects with at least one parent treated for neovascular AMD, aged 40-70, with a best corrected visual acuity (BCVA) >20/25, free of late AMD and other major eye conditions and with no use of supplement containing lutein or zeaxanthin the preceding year were recruited in Bordeaux and Dijon, France. At baseline, MPOD within 1° of eccentricity was measured by modified Heidelberg retinal analyser (Heidelberg, Germany) and plasma omega-3 PUFAs by gas chromatography. Medical history and lifestyle data were collected from a standardized questionnaire. Associations of MPOD with plasma omega-3 PUFAs were assessed at the baseline examination, using mixed linear models adjusted for age, gender, centre, body mass index, smoking, plasma high-density lipoprotein (HDL) cholesterol and lutein+zeaxanthin. RESULTS: After multivariate adjustment, high MPOD was significantly associated with higher level of plasma docosapentaenoic acid (DPA) (ß = 0.029, 95% CI: 0.003, 0.055; p = 0.03). Plasma alpha linolenic, eicosapentaenoic and docosahexaenoic acids were not significantly associated with MPOD. CONCLUSION: In the Limpia study, high MPOD within 1° was significantly associated with higher plasma levels of omega-3 DPA.


Assuntos
Ácidos Graxos Ômega-3/sangue , Luteína/administração & dosagem , Pigmento Macular/sangue , Degeneração Macular Exsudativa/sangue , Zeaxantinas/administração & dosagem , Adulto , Idoso , Biomarcadores/sangue , Cromatografia Gasosa , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Seguimentos , Humanos , Luteína/farmacocinética , Masculino , Pessoa de Meia-Idade , Linhagem , Prognóstico , Estudos Prospectivos , Degeneração Macular Exsudativa/dietoterapia , Degeneração Macular Exsudativa/genética , Zeaxantinas/farmacocinética
8.
Haematologica ; 96(5): 655-63, 2011 May.
Artigo em Inglês | MEDLINE | ID: mdl-21228033

RESUMO

BACKGROUND: Autoimmune hemolytic anemia is a rare condition in children. Little is known about its initial presentation and the subsequent progression of the disease. DESIGN AND METHODS: Since 2004, a national observational study has been aiming to thoroughly describe cases and identify prognostic factors. Patients from all French hematologic pediatric units have been included if they had a hemoglobin concentration less than 11 g/dL, a positive direct antiglobulin test and hemolysis. Evans' syndrome was defined by the association of autoimmune hemolytic anemia and immunological thrombocytopenic purpura. Data from patients' medical records were registered from birth to last follow-up. Autoimmune hemolytic anemia was classified as primary or secondary. Remission criteria, qualifying the status of anemia at last follow-up, were used with the aim of identifying a subgroup with a favorable prognosis in continuous complete remission. RESULTS: The first 265 patients had a median age of 3.8 years at diagnosis. In 74% of cases the direct antiglobulin test was IgG/IgG+C3d. Consanguinity was reported in 8% of cases and first degree familial immunological diseases in 15% of cases. Evans' syndrome was diagnosed in 37% of cases. Autoimmune hemolytic anemia was post-infectious in 10%, immunological in 53% and primary in 37% of cases. After a median follow-up of 3 years, 4% of children had died, 28% were still treatment-dependent and 39% were in continuous complete remission. In multivariate analysis, IgG and IgG+C3d direct antiglobulin tests were associated with a lower rate of survival with continuous complete remission (adjusted hazard ratio, 0.43; 95% confidence interval, 0.21-0.86). CONCLUSIONS: This nationwide French cohort is the largest reported study of childhood autoimmune hemolytic anemia. The rarity of this condition is confirmed. Subgroups with genetic predisposition and underlying immune disorders were identified.


Assuntos
Anemia Hemolítica Autoimune/diagnóstico , Anemia Hemolítica Autoimune/terapia , Adolescente , Anemia Hemolítica Autoimune/epidemiologia , Criança , Pré-Escolar , Feminino , França/epidemiologia , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Lactente , Recém-Nascido , Masculino , Análise Multivariada , Avaliação de Resultados em Cuidados de Saúde/estatística & dados numéricos , Prognóstico , Sistema de Registros/estatística & dados numéricos
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