Browsing by Author "Brito, C"
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- Análise Estrutural do Segmento Anterior por Tomografia de Coerência Ótica no Glaucoma Congénito PrimárioPublication . Vieira, L; Sá Cardoso, M; Anjos, R; Ferreira, C; Xavier, A; Maduro, V; Brito, CObjectivo: Analisar a morfologia do segmento anterior por tomografia de coerência ótica de segmento anterior (OCT-SA) em crianças com glaucoma congénito primário (GCP). Material e métodos: Realizou-se um estudo caso-controlo, prospetivo, em crianças com GCP e em crianças sem glaucoma (grupo controlo), seguidas em Consulta de Oftalmologia Pediátrica do Hospital Dona Estefânia, Centro Hospitalar de Lisboa Central. Efectuou-se avaliação oftalmológica completa e OCT-SA utilizando o protocolo A C biometry. Resultados: O estudo incluiu 27 olhos (17 crianças com OCP) e 22 olhos (11 crianças sem glaucoma). Detetaram-se valores significativamente superiores de profundidade central e largura da câmara anterior (CA) (p<0,001) e maiores distâncias de abertura do ângulo a 500 CP<0,001) e 750µm (p=0,00 l), áreas de espaço irido-trabecular a 500 e 750µm (p<0,001) e áreas do recesso do ângulo a 500 (p<0,00l) e 750µm (p=0,001), no grupo GCP. A espessura da íris foi significativamente mais fina a 500µm do ângulo (p=0,011), no centro da íris (p<0,001) e na região mais espessa da mesma (p=0,001) no grupo GCP, assim como o comprimento da íris foi superior (p<0,001). A largura de CA e a acuidade visual (logMAR) apresentam correlação positiva (r=0,688; p<0,001). Outros achados morfológicos: anteriorização e hipoplasia da íris, alteração da morfologia do ângulo no local de intervenção cirúrgica (goniotomia, trabeculotornia, trabeculectomia, válvula de Ahmed). Conclusão: Este primeiro estudo em crianças com GCP sugere que a OCT-SA é de aquisição relativamente fácil, poderá ajudar no seguimento clínico e cirúrgico e ser útil como fator prognóstico destes doentes.
- Chronic Urticaria in the Real-Life Clinical Practice Setting in Portugal: Baseline Results from the Non-Interventional Multicentre AWARE StudyPublication . Costa, C; Rosmaninho, I; Guilherme, A; Ferreira, J; Antunes, J; Pina, A; Prates, S; Gaspar-Marques, J; Azevedo, F; Cunha, AP; Brito, C; Massa, A; Sousa, JT; Velho, GC; Raposo, I; Pinto, GM; Sousa, Vi; Martins, ARThere is a paucity of information regarding chronic urticaria patients' care in a real-world setting. The objective of this study was to report and evaluate the baseline characteristics of Portuguese chronic urticaria patients refractory to H1-antihistamines included in the AWARE study. MATERIAL AND METHODS: This is a non-interventional cohort study. Adult patients with a diagnosis of chronic urticaria with symptoms for at least two months, refractory to H1-antihistamines, consulting one of the 10 participating urticaria centers throughout Portugal have been included in the study. Baseline sociodemographic data, medical history, clinical parameters, medication, weekly urticaria activity score, and dermatology quality of life index have been collected. RESULTS: Seventy six patients were included, of which 76.3% were women. The majority of patients had a diagnosis of chronic spontaneous urticaria (88.2%) and 39.5% had angioedema. Around 91.0% of patients were medicated with non-sedative H1-antihistamines and 35.4% with a third line therapy. Median dermatology quality of life index was 5.0 and median weekly urticaria activity score was 13.0. DISCUSSION: The baseline results suggest that patients with chronic urticaria refractory to H1-antihistamines are being under-treated in the real-world setting. CONCLUSION: The AWARE study demonstrates the real impact of chronic urticaria on Portuguese patients refractory to H1-antihistamines treatment, and 30% report a very large or extremely large deleterious effect on their quality of life. The follow-up of these patients will allow evaluating strategies aimed at optimizing disease control.
- Development of Dl1.72, a Novel Anti-DLL1 Antibody with Anti-Tumor Efficacy against Estrogen Receptor-Positive Breast CancerPublication . Silva, G; Sales-Dias, J; Casal, D; Alves, S; Domenici, G; Barreto, C; Matos, C; Lemos, A; Matias, A; Kucheryava, K; Ferreira, A; Moita, MR; Braga, S; Brito, C; Cabral, MG; Casalou, C; Barral, D; Sousa, P; Videira, P; Bandeiras, T; Barbas, AThe Notch-signaling ligand DLL1 has emerged as an important player and promising therapeutic target in breast cancer (BC). DLL1-induced Notch activation promotes tumor cell proliferation, survival, migration, angiogenesis and BC stem cell maintenance. In BC, DLL1 overexpression is associated with poor prognosis, particularly in estrogen receptor-positive (ER+) subtypes. Directed therapy in early and advanced BC has dramatically changed the natural course of ER+ BC; however, relapse is a major clinical issue, and new therapeutic strategies are needed. Here, we report the development and characterization of a novel monoclonal antibody specific to DLL1. Using phage display technology, we selected an anti-DLL1 antibody fragment, which was converted into a full human IgG1 (Dl1.72). The Dl1.72 antibody exhibited DLL1 specificity and affinity in the low nanomolar range and significantly impaired DLL1-Notch signaling and expression of Notch target genes in ER+ BC cells. Functionally, in vitro treatment with Dl1.72 reduced MCF-7 cell proliferation, migration, mammosphere formation and endothelial tube formation. In vivo, Dl1.72 significantly inhibited tumor growth, reducing both tumor cell proliferation and liver metastases in a xenograft mouse model, without apparent toxicity. These findings suggest that anti-DLL1 Dl1.72 could be an attractive agent against ER+ BC, warranting further preclinical investigation.
- Higher Order Aberrations in Amblyopic Children and their Role in Refractory AmblyopiaPublication . Dias-Santos, A; Rosa, R; Ferreira, J; Cunha, JP; Brito, C; Paixão, A; Toscano, AObjective: Some studies have hypothesized that an unfavourable higher order aberrometric profile could act as an amblyogenic mechanism and may be responsible for some amblyopic cases that are refractory to conventional treatment or cases of “idiopathic” amblyopia. This study compared the aberrometric profile in amblyopic children to that of children with normal visual development and compared the aberrometric profile in corrected amblyopic eyes and refractory amblyopic eyes with that of healthy eyes. Methods: Cross-sectional study with three groups of children – the CA group (22 eyes of 11 children with unilateral corrected amblyopia), the RA group (24 eyes of 13 children with unilateral refractory amblyopia) and the C group (28 eyes of 14 children with normal visual development). Higher order aberrations were evaluated using an OPD-Scan III (NIDEK). Comparisons of the aberrometric profile were made between these groups as well as between the amblyopic and healthy eyes within the CA and RA groups. Results: Higher order aberrations with greater impact in visual quality were not significantly higher in the CA and RA groups when compared with the C group. Moreover, there were no statistically significant differences in the higher order aberrometric profile between the amblyopic and healthy eyes within the CA and RA groups. Conclusions: Contrary to lower order aberrations (e.g., myopia, hyperopia, primary astigmatism), higher order aberrations do not seem to be involved in the etiopathogenesis of amblyopia. Therefore, these are likely not the cause of most cases of refractory amblyopia.
- Ocular Disease in Children with Type 1 DiabetesPublication . Basílio, AL; Proença, R; Crisóstomo, S; Paixão, A; Ferreira, C; Xavier, A; Brito, C; Toscano, ASpecialized care provided to diabetic patients, in developed countries, has contributed to the reduced number of ocular complications in pediatric age. The effectiveness of annual eye examinations in this group is unclear. The authors intend to determine the prevalence and onset of ocular disease in this population and adapt the results to the dynamics of a tertiary center, based on a retrospective study of type 1 diabetes patients’ medical records registered and monitored in Pediatric Endocrinology Department of Centro Hospitalar de Lisboa Central, between January of 2008 and July of 2015. Demographic characteristics, underlying and ocular disease, referral and follow-up of these patients in the Pediatric Ophthalmology Department were evaluated. Medical records of 304 patients with type 1 diabetes were analyzed. 110 patients referred to Ophthalmology Department had been included in the study. The mean age was 13.2 years (4-20 years), 57 were male and 53 female. Type 1 diabetes was diagnosed at 7.5 years on average (0.75-13 years) and mean disease duration was 6.0 years (1-14 years). The average of the last hemoglobin A1c value was 8.6% (4.9-14.4%). The first eye exam was performed at 9.4 years on average (2-19 years), in 55 cases the patients had less than 10 years and, of those, 29 were referred in the first year after diagnosis (mean duration diabetes of 2.0 years; 0-7 years). Regarding the 55 patients older than 9 years, 27 were referred in the first year after diagnosis (mean duration of diabetes 2.3 years, 0-9 years). In 54 patients ophthalmological exam was repeated after 1 year, 15 after 2 years, 1 after 3 years and 1 after 5 years. No diabetic retinopathy cases were found. 28 astigmatism, 12 hyperopia, 16 myopia, 5 strabismus, 2 blepharoptosis and 1 polar cataract were diagnosed. International Society for Pediatric and Adolescent Diabetes recommend ophthalmological initial screening 2 years after the diagnosis of type 1 diabetes, in patients above 10 years, and 5 years after, if lower ages. American Academy of Ophthalmology 2014 guidelines recommend that the first eye examination should begin 5 years after the diagnosis and repeated annually. A previous study conducted at Hospital Dona Estefânia, between 1999 and 2000, by Rodrigues P et al has described a low incidence of ocular lesions (6.4%) in the studied population, being in agreement with our results. Recent published studies are also consistent and demonstrate that the rare incidence of ocular complications of diabetes until puberty can justify new guidelines in the coming years.
- Perspectivas do Estudo da Diabetes Ocular numa Consulta PediátricaPublication . Rodrigues, P; Nepomuceno, J; Brito, C; Mesquita, JA duração da diabetes mellitus é um factor de risco no aparecimento de complicações oculares. A prevalência da retinopatia diabética é praticamente nula antes dos 10 anos de idade, independentemente da duração da doença, atingindo 95% após 20-30 anos de evolução. Na Consulta de Oftalmologia Pediátrica do Hospital D. Estefânia avaliámos retrospectivamente 62 crianças com diagnóstico de diabetes meliitus tipo I, no intervalo d etempo compreendido entre 1 de Janeiro de 1999 e 31 de Junho de 2000. As idades oscilavam entre os 3 e os 17 anos(média 11,8 anos), tendo sido 29 casos do sexo feminino e 33 do sexo masculino. O período de evolução da doença variava entre 6 meses e 16 anos (média 6,2 anos). Na população estudada constatámos uma incidência de 6,4% de lesões oculares. Vericámos 1 caso (1,6%) de retinopatia de fundo, numa adolescente de 17 anos de idade e 11 anos de evoluão da doença, e 3 casos (4,8%) de catarata bilateral. Na diabetes juvenil a probabilidade de ocorrência de lesões oculares precoces é baixa. Exceptuando a catarata que pode ocorrer com alguma precocidade, a retinopatia clínica é raramente demosntrável antes do inicio da puberdade.
- Retinal Structural Changes in Preterm Children without Retinopathy of PrematurityPublication . Maleita, D; Serras-Pereira, R; Passos, I; Elisa-Luís, M; Alves, M; Papoila, AL; Brito, C; Cunha, JP; Tavares Ferreira, JPurpose: The aim of this study was to compare all retinal layers' thickness in full-term and preterm children without retinopathy of prematurity (ROP). Methods: Cross-sectional study including two groups of patients: group 1 children with history of preterm gestation without ROP (gestational age < 37 weeks) and group 2 healthy children with history of full-term gestation. All subjects underwent an ophthalmic examination including spectral domain-optical coherence tomography. After automatic retinal segmentation, each retinal layer thickness (eight separate layers and overall thickness) was calculated in all nine Early Treatment Diabetic Retinopathy Study areas. Demographic, systemic, gestational, and birth data were collected. Generalized additive regression models were used to analyze the data. Results: Fifty-one children (51 eyes) were recruited, 19 full-term and 32 preterm children, mean age at ophthalmic examination of 10.58 (4.21) and 14.13 (3.16), respectively. In multivariable analysis, the preterm group's retinal thickness was significantly decreased in total retina nasal outer sector, ganglion cell layer (GCL), and inner plexiform layer (IPL), specifically GCL temporal outer (p = 0.010), GCL superior outer (p = 0.009), IPL temporal outer (p = 0.022), and IPL superior outer (p = 0.004), when compared with full-term group. From the variables compared only with birth head circumference that influenced the models, a non-linear association was identified and consequently modeled with splines through a generalized additive model. Conclusion: This study suggests that preterm children without ROP have structural retinal alterations, mostly in GCL and IPL in outer areas of the macula. Therefore, it is crucial to question gestational history since these retinal changes may be found later in life leading to useless investigation.
- Síndrome de Susac em Idade Pediátrica. Caso ClínicoPublication . Medeiros, M; Flores, R; Toscano, A; Brito, C; Vieira, JP; Nepomuceno, J