Browsing by Author "Cardigos, J"
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- Added Value of Lymphocyte Subpopulations in the Classification of Sjögren's SyndromePublication . Barcelos, F; Brás-Geraldes, C; Martins, C; Papoila, AL; Monteiro, R; Cardigos, J; Madeira, N; Alves, N; Vaz-Patto, J; Cunha-Branco, J; Borrego, LMSjögren's Syndrome (SjS) is a chronic systemic immune-mediated inflammatory disease characterized by lymphocytic infiltration and consequent lesion of exocrine glands. SjS diagnosis and classification remains a challenge, especially at SjS onset, when patients may have milder phenotypes of the disease or uncommon presentations. New biomarkers are needed for the classification of SjS, thus, we aimed to evaluate the added-value of lymphocyte subpopulations in discriminating SjS and non-Sjögren Sicca patients. Lymphocyte subsets from 62 SjS and 63 Sicca patients were characterized by flow cytometry. The 2002 AECG and the 2016 ACR/EULAR SjS classification criteria were compared with clinical diagnosis. The added discriminative ability of joining lymphocytic populations to classification criteria was assessed by the area under the Receiver-Operating-Characteristic Curve (AUC). Considering clinical diagnosis as the gold-standard, we obtained an AUC = 0.952 (95% CI: 0.916-0.989) for AECG and an AUC = 0.921 (95% CI: 0.875-0.966) for ACR/EULAR criteria. Adding Tfh and Bm1 subsets to AECG criteria, performance increased, attaining an AUC = 0.985 (95% CI: 0.968-1.000) (p = 0.021). Th1/Breg-like CD24hiCD27+ and switched-memory B-cells maximized the AUC of ACR/EULAR criteria to 0.953 (95% CI: 0.916-0.990) (p = 0.043). Our exploratory study supports the potential use of lymphocyte subpopulations, such as unswitched memory B cells, to improve the performance of classification criteria, since their discriminative ability increases when specific subsets are added to the criteria.
- Análise das Camadas Retinianas em Doentes com Lesão Isquémica da Artéria Cerebral Posterior Unilateral: um Estudo de Tomografia de Coerência ÓpticaPublication . Anjos, R; Cardigos, J; Costa, L; Borges, B; Alves, N; Amado, D; Ferreira, J; Cunha, JPIntrodução: A degeneração transneuronal retrógrada (DTR) das células ganglionares tem sido implicada na fisiopatologia de lesões na via visual posterior. Apesar de estarem descritas alterações nas camadas mais externas da retina na patologia do nervo óptico, esta relação com lesões a nível occipital permanece desconhecida. O objectivo do presente estudo é a avaliação das camadas nuclear interna (CNi), plexiforme externa (CPe), nuclear externa (CNe) e dos fotoreceptores (CFo) em doentes com lesões isquémicas da artéria cerebral posterior (ACP) com tomografia de coerência óptica (OCT). Métodos: Estudo transversal observacional, caso-controlo de doentes com hemianópsia homónima decorrente de lesão unilateral isquémica da ACP seguidos no departamento de Neuroftalmologia do Centro Hospitalar de Lisboa Central. Todos os doentes realizaram OCT macular em ambos os olhos. Após segmentação automática das diferentes camadas, foram obtidos os valores de espessuras correspondentes às regiões nasal e temporal entre 1 a 3mm (N1-3 e T1-3) e entre 3 e 6 mm (N3-6 e T3-6) centradas na fóvea. Resultados: Dez doentes com lesão da PCA e um grupo de controlo pareado para o sexo e idade foram incluidos no estudo. Quando comparados ambos os olhos do mesmo doente, verificou-se um aumento da espessura da CNi em N3-6 (p=0,005) do olho contralateral e em T3-6 (p=0,011) no olho ipsilateral, assim como da CPe em N3-6 (p=0,034) do olho contralateral. Não se verificaram diferenças estatisticamente significativas no grupo controle. Conclusão: Além da já documentada associação entre lesões isquémicas occipitais e as alterações nas camadas internas da retina, podemos ainda observar algumas alterações nas camadas retinianas mais externas. É possível que a DTR no sistema visual seja um processo que não se esgota nas células ganglionares, afectando camadas mais externas da retina.
- Aplicação de Membranas Amnióticas na Reconstrução da Superfície Ocular Externa em Idade PediátricaPublication . Crisóstomo, S; Proença, R; Cardigos, J; Basílio, AL; Maduro, V; Candelária, P; Toscano, AIntrodução: Vários estudos comprovam os benefícios da aplicação de membranas amnióticas na reconstrução da superfície ocular em idade adulta, pelos seus efeitos anti-inflamatorios, anti-adesivos e anti-apoptóticos. Em idade pediátrica, a reconstrução da superfície ocular carece de especial atenção e este procedimento encontra-se ainda pouco estudado. Não foi encontrado nenhum estudo especificamente dirigido à aplicação de membranas amnióticas na reconstrução da superfície ocular externa desta faixa etária, pelo que procurámos elucidá-lo. Material e métodos: Estudo retrospetivo englobando todos os doentes em idade pediátrica (7,1 anos +/- 4,17) submetidos a transplante de membrana amniótica no Centro Hospitalar de Lisboa Central entre 2008 e 2015, para reconstrução da superfície ocular externa. Entre os doentes (n=6 olhos de 6 crianças), quatro apresentavam patologia do foro neoformativo ou inflamatório e dois apresentavam queimaduras extensas da superfície ocular. Foi realizada divisão em dois grupos, com base na presença ou não de insuficiência de células limbares. Foram avaliadas características clínicas e demográficas, MAVC antes e após a cirurgia, tempo de reepitelização, amplitude de movimentos oculares antes e após a cirurgia, presença de recidiva ou complicações e resultado estético. O tempo de seguimento foi de 4 a 83 meses. Resultados: Verificaram-se sucessos completos em todos os doentes sem insuficiência limbar (50% do total de doentes), sucessos parciais em dois dos doentes com insuficiência limbar (33,3%) e um caso de falência terapêutica (16.7%). Nos doentes em que se observou recidiva, o tempo médio para esta ocorrência foi de 8,3 +/- 6,8 meses. Não se verificaram complicações em nenhum dos casos. Observou-se melhoria pós-operatória em um dos dois casos que tinham diminuição da acuidade visual pré-operatória (aumento da MAVC em 6 linhas). Verificou-se ainda uma melhoria da motilidade ocular e aspeto estético em todos os doentes com alterações prévias destes parâmetros. Conclusão: O transplante de membrana amniótica mostrou ser muito benéfico também em idade pediátrica. Pode ser realizado como tratamento isolado ou coadjuvante, sendo os resultados superiores nos casos de células limbares funcionantes. Não foi detetada maior incidência de complicações ou rejeições comparativamente ao descrito na literatura para a idade adulta.
- Association Between Memory B-Cells and Clinical and Immunological Features of Primary Sjögren’s Syndrome and Sicca PatientsPublication . Barcelos, F; Martins, C; Papoila, A; Geraldes, C; Cardigos, J; Nunes, G; Lopes, T; Alves, N; Vaz-Patto, J; Branco, J; Borrego, LMB-cells play a pivotal role in primary Sjögren's syndrome (pSS) pathogenesis. We aim to (1) evaluate the distribution of B-lymphocyte subpopulations in pSS and Sicca patients, (2) establish cut-off points that discriminate pSS from controls, (3) evaluate the association between memory B-cells and phenotypic features in pSS. We included 57 pSS patients, 68 Sicca and 24 healthy controls. Circulating B-cells were characterized by flow cytometry as naïve and memory subsets and classified from Bm1 to Bm5. Compared to controls, pSS patients had lower percentages (29.5 vs 44.4%) and absolute numbers (47 vs 106 cells/µl) of memory B-cells. Through ROC curves, a cut-off of ≤ 58 total memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.60 for pSS, and was met by 59.6% of pSS patients, 38.8% of Sicca and 12.5% of controls. A cut-off of < 23.5 Switched-memory B-cells/µl yielded a specificity of 0.88 and a sensitivity of 0.54 and was met by 54.4% of pSS patients, 37.3% of Sicca and 12.5% of controls. In pSS, lower total memory B-cells count was associated with longer disease duration (14.3 vs 8.1 years, p = 0.006) and more active disease profile, as evaluated by the European League Against Rheumatism (EULAR) Sjögren's Syndrome Disease Activity Index (ESSDAI) (3.1 vs 1.4, p = 0.043). Decreased numbers of memory B-cells clearly discriminated pSS from controls and can also have prognostic value. It remains to be clarified whether Sicca patients with decreased memory B-cells represent pSS and if B-cell profiling could help in the diagnosis of pSS.
- Bilateral Metastases to the Extraocular Muscles From Small Cell Lung CarcinomaPublication . Crisóstomo, S; Cardigos, J; Hipólito Fernandes, D; Luís, ME; Neri Pires, G; Duarte, AF; Magriço Boavida, ABilateral orbital metastases restricted to the extraocular muscles (EOMs) are exceedingly rare. We report a case of bilateral extraocular muscle metastases from a small cell lung carcinoma and provide a review of the relevant literature. A 56-year-old smoker presented with proptosis, motility changes, and a relative afferent pupillary defect of the left eye, with a previous history of a small cell lung carcinoma. An orbital computerized tomography scan revealed a mass restricted to the left medial rectus. An incisional biopsy confirmed metastasis. Visual acuity of the left eye decreased rapidly, and right globe proptosis became evident. Orbital magnetic resonance imaging at two months follow-up showed marked left orbital mass enlargement and a new right lateral rectus mass. The patient was maintained on palliative care and died from metastatic disease-related complications.
- Choroidal Binarization Analysis: Clinical ApplicationPublication . Crisóstomo, S; Cardigos, J; Hipólito Fernandes, D; Luís, ME; Figueiredo, R; Moura-Coelho, N; Cunha, JP; Abegão Pinto, L; Tavares-Ferreira, JIntroduction: Image processing of optical coherence tomography scans through binarization techniques represent a non-invasive way to separately asses and measure choroidal components, in vivo. In this review, we systematically search the scientific literature regarding binarization studies published so far. Methods: A systematic research was conducted at PubMed database, including English literature articles for all of the following terms in various combinations: binarization, choroid/al, enhanced depth spectral domain/swept source optic coherence tomography, and latest publications up to November 2018 were reviewed. Results: Thirty-seven articles were included and analyzed regarding studied disease, binarization method, studied variables, and outcomes. Most of the studies have focused on the more common retinal pathologies, such as age-related macular degeneration, central serous chorioretinopathy and diabetic retinopathy but binarization techniques have also been applied to the study of choroidal characteristics in ocular inflammatory diseases, corneal dystrophies and in postsurgical follow-up. Advantages and disadvantages of binarization techniques are also discussed. Conclusion: Binarization of choroidal images seems to represent a promising approach to study choroid subcomponents in an increasingly detailed manner.
- Corneal Sub‐Basal Nerve Plexus Assessment and its Association with Phenotypic Features and Lymphocyte Subsets in Sjögren's SyndromePublication . Barcelos, F; Hipólito‐Fernandes, D; Martins, C; Ângelo‐Dias, M; Cardigos, J; Monteiro, R; Alves, N; Vaz‐Patto, J; da Cunha‐Branco, J; Borrego, LMlPurpose: To assess and compare corneal sub-basal nerve plexus morphology with circulating lymphocyte subsets, immunologic status and disease activity in Sjögren syndrome (SjS) patients. Methods: Fifty-five SjS patients, 63 Sicca patients (not fulfilling SjS criteria), 18 rheumatoid arthritis (RA) patients and 20 healthy controls (HC) were included. Systemic disease activity in SjS was assessed with the ESSDAI score. Lymphocyte subpopulations were studied with flow cytometry. Corneal confocal microscopy and ImageJ software were used to characterize corneal sub-basal nerve plexus in terms of nerve density (CNFD), length (CNFL) and tortuosity (CNFT). Conventional dry eye tests were also performed. Results: CNFL and CNFD were lower in SjS, Sicca and RA groups, compared to HC (p < 0.001 for both SjS and Sicca); CNFL p = 0.005, CNFD p = 0.018 in RA). CNFT was higher in SjS, followed by Sicca, RA and HC. A negative correlation was found between ESSDAI score and CNFL (r=-0.735, p = 0.012). CNFL correlated negatively with IL21+ CD8+ T cells (r=-0.279, p = 0.039) and a positively with total memory (r = 0.299, p = 0.027), unswitched memory (r = 0.281, p = 0.038) and CD24Hi CD27+ (r = 0.278, p = 0.040) B cells. CNFD showed a tendency to significance in its negative correlation with ESSDAI (r=-0.592, p = 0.071) and in its positive correlation with switched memory B cells (r = 0.644, p = 0.068). Conclusions: This is the first study aiming to correlate ocular findings with lymphocyte subsets in SjS. The associations founded between CNFL and CNFD and disease activity, IL21+ follicular T cells and some B-cell subsets suggest that corneal nerve damage may parallel systemic disease activity and inflammatory cells' dynamics.
- Lymphocyte Subpopulations in Sjögren’s Syndrome Are Distinct in Anti-SSA-Positive Patients and Related to Disease ActivityPublication . Barcelos, F; Martins, C; Madeira, N; Dias, M; Cardigos, J; Alves, N; Vaz-Patto, J; Cunha-Branco, J; Borrego, LMObjectives: Sjögren's syndrome (SjS) patients exhibit great phenotypical heterogeneity, reinforced by the positiveness of anti-SSA antibody. We aimed to evaluate lymphocyte subpopulations in SSA-positive (SSA+SjS) and SSA-negative (SSA-SjS) SjS patients, Sicca patients, and healthy controls (HC), and to investigate associations between lymphocyte subpopulations and disease activity in SjS. Methods: According to the fulfilment of the ACR/EULAR 2016 classification criteria, patients were included as SjS or as Sicca. HC were selected from the Ophthalmology outpatient clinic. Lymphocyte subpopulations were characterized by flow cytometry. Statistical analysis was performed with GraphPad PrismTM, with statistical significance concluded if p < 0.05. Results: We included 53 SjS patients (38 SSA+ and 15 SSA-), 72 Sicca, and 24 HC. SSA+SjS patients presented increased IL-21+CD4+ and CD8+ T cells compared to Sicca and HC, whereas compared to SSA-SjS patients, only IL-21+CD4+ T cell percentages were increased and Tfh17 percentages and numbers were decreased. Compared to Sicca and HC, SSA+SjS patients had higher levels of CD24HiCD38Hi B cells, naïve B cells, and IgM-/+CD38++ plasmablasts, and lower levels of memory B cells, including CD24HiCD27+ B cells. SSA+SjS patients with clinically active disease had positive correlations between ESSDAI and IL-21+CD4+ (p = 0.038, r = 0.456) and IL-21+CD8+ T cells (p = 0.046, r = 0.451). Conclusions: In SjS, a distinct lymphocyte subset distribution profile seems to be associated with positive anti-SSA. Moreover, the association between ESSDAI and IL-21+CD4+ and IL-21+CD8+ (follicular) T cells in SSA+SjS patients suggests the involvement of these cells in disease pathogenesis and activity, and possibly their utility for the prognosis and assessment of response to therapy. Key Points • SSA+SjS patients have a pronounced naïve/memory B cell imbalance. • SSA+SjS patients have more active disease associated with IL-21+CD4+ and IL-21+CD8+ follicular T cell expansion. • IL-21+CD4+ and IL-21+CD8+ T cell quantification may be useful for the prognosis and assessment of response to therapy.
- A Morfologia Endotelial e a Espessura Central da Córnea em Idade PediátricaPublication . Cardigos, J; Neri, G; Crisóstomo, S; Paixão, A; Martins, M; Marques, M; Toscano, AIntrodução: O estudo morfológico e funcional do endotélio corneano é essencial para a criação de bases normativas de comparação, com utilidade na prática clínica e investigação científica. O objectivo deste estudo é a avaliação da morfologia endotelial e espessura central da córnea (ECC) em crianças saudáveis entre os 5 e os 15 anos, avaliando a sua variação segundo a idade. Métodos: Estudo de coorte transversal de 40 olhos de 40 crianças saudáveis, divididos em dois grupos. O grupo 1 formado por 20 crianças entre os 5-9 anos; o grupo 2 formado por 20 crianças entre os 10-15 anos. A densidade celular endotelial (DCE), o coeficiente de variação (CV) e a percentagem de células hexagonais (HEX) foram avaliados por microscopia especular de não contacto. A ECC foi avaliada por tomografia de segmento anterior. Resultados: A DCE revelou-se maior no grupo 1 (2906,05 ± 344,91 cel/mm2) comparativamente ao grupo 2 (2597,89 ± 276,61 cel/mm2), (p= 0,003). Não foram encontradas diferenças significativas relativas ao CV, HEX e ECC entre o grupo 1 e o grupo 2. ADCE correlacionou-se negativamente com a idade (r=-0,438 e p=0,005) e a percentagemde células hexagonais correlacionou-se negativamente com o CV (r= - 0,345; p= 0,029). Conclusão: A DCE diminui com o aumento da idade em crianças saudáveis. Não se verificaram variações significativas da CV, HEX e da ECC entre os dois grupos etários. Salienta-se a importância dos dados obtidos como base normativa e a sua relevância para estudo da patologia da superfície ocular na criança.
- Nanotechnology-Ocular Devices for Glaucoma Treatment: A Literature ReviewPublication . Cardigos, J; Ferreira, Q; Crisóstomo, S; Coelho, N; Cunha, JP; Abegão Pinto, L; Ferreira, JNanotechnology enabled the development of materials and devices with great utility in different fields of medicine. By using engineered-based nano-devices and structures, human biological systems may be controlled and repaired at a molecular scale, ultimately leading to a biological benefit. In particular, in the field of glaucoma treatment, nanotechnology may, for example, enhance drug residence time on the ocular surface and ocular bioavailability, as well as improve surgical success by both optimizing postoperative scarring and providing a wider safety window. Further studies are still needed to entirely explain the pharmacodynamics of nanotechnology-based therapeutic approaches and prove their biological consequences in human eyes. This review aims to summarize the literature concerning the advances in nanotechnology, specifically regarding ocular devices applied to the treatment of glaucoma.