The major purpose of this study was to evaluate alternative automated methods of collecting data ... more The major purpose of this study was to evaluate alternative automated methods of collecting data on health related quality of life (HR-QoL). In order to achieve this, we developed a study with the following objectives: (1) to evaluated the feasibility of electronic version in patients with different chronic pathologies of the immune system using Short Form 36version2 (SF-36v2), (2) to evaluate the construct validity of SF-36v2 using the electronic data capture, and (3) to compare electronic version questionnaires with paper questionnaires in terms of patients' acceptance, data quality, and reliability. Out-patients with chronic immune diseases (HIV infection, lupus, scleroderma, rheumatoid arthritis, Behçet and Sjögren), were randomly selected to completed electronic and paper SF-36v2 (n=50) before consultation in Clinical Immunology Unit, in Hospital Santo António-Centro Hospitalar do Porto (CI-HGSA). There were very high correlations in SF-36v2 responses (p< .001) between t...
The principle of treating-to-target has been successfully applied to many diseases outside rheuma... more The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet p...
Clinical and experimental immunology, Jan 24, 2017
FOXP3(+) regulatory T-cells (Tregs) are functionally deficient in Systemic Lupus Erythematosus (S... more FOXP3(+) regulatory T-cells (Tregs) are functionally deficient in Systemic Lupus Erythematosus (SLE), characterized by reduced surface CD25 (the IL-2 receptor alpha chain). Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined Treg subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus. We identified two separate, uncorrelated effects contributing to Treg CD25. (1) SLE patients and unaffected relatives remarkably shared CD25 reduction versus controls particularly in the developmentally earliest CD4(+) FOXP3(+) CD45RO(-) CD31(+) recent thymic emigrant Tregs. This first component effect influenced the proportions of circulating CD4(+) FOXP3(high) CD45RO(+) activated Tregs. (2) In contrast, patients and unaffected relatives sharply differed in t...
There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily... more There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning clas...
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology. It i... more Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology. It is characterized by symmetric, polyarticular pain, swelling, morning stiffness, and fatigue. RA has a variable course, often with periods of exacerbations and, less frequently, true remissions. Outcomes are also variable, ranging from the rarely seen remitting disease to severe disease that brings disability and in some patients premature death. Without treatment, the majority of patients will experience progressive joint damage and, in some patients, this results in significant disability within just a few years. Improvement in health related quality of life is one of the most important goals in the management of rheumatoid arthritis and therefore must be pursued as a crucial aim in clinical practice. This paper draws from 49 qualitative interviews conducted with RA patients, before starting a program of Spa Therapy and aims to get an overview of their main RA related difficulties, worri...
Gastroenterology and Hepatology From Bed to Bench, 2016
Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis p... more Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis patients. Background: There are only limited data describing pregnancy in patients with autoimmune hepatitis. Patients and methods: Retrospective analysis of pregnancies with autoimmune hepatitis followed in Centro Hospitalar do Porto, Portugal in the last ten years. Results: We reported nine pregnancies in seven patients with autoimmune hepatitis. Two patients had documented liver cirrhosis prior to the pregnancy. In this study, 66.7% of patients were treated with azathioprine and 88.9% with prednisolone. Clinical improvements were observed in 11.1% of pregnancies and 22.2% exacerbations were diagnosed. There were six live births and two preterm deliveries (preterm delivery rate of 33%). We also report three first trimester miscarriages (early gestation miscarriage rate of 33%). There were no neonatal or maternal deaths. Conclusion: The favorable obstetric outcome is a realistic expectat...
The Israel Medical Association journal : IMAJ, 2016
The effects of balneotherapy on rheumatoid arthritis (RA) are still controversial partly due to p... more The effects of balneotherapy on rheumatoid arthritis (RA) are still controversial partly due to poor methodology used in randomized controlled trials, as reported in the international medical literature. To determine whether spa therapy plus pharmacological treatment offers any benefit in the management of RA as compared to pharmacological treatment alone. We conducted a prospective, controlled, unblinded randomly assigned study of patients with RA according to American College of Rheumatology criteria. Following the 2007 recommendations of AFRETH, the method designed for this study was "immediate treatment versus delayed treatment." All patients were followed at the Centro Hospitalar do Porto and each physician observed the same patients throughout the study. Patients continued with their usual medications and maintained their daily life activities at home, at leisure and/or in the workplace. The spa therapy group received spa treatments for 21 days at S. Jorge Spa-Santa ...
Clinical and experimental rheumatology, Jan 5, 2015
To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk f... more To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosis patients. Endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), endostatin and endoglin were measured in an observational prospective cohort of 77 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. After the 3-year follow-up, 40 patients developed new digital ulcers. Logistic regression confirmed VEGF (HR 1.128, 95% CI 1.010-1.260, p=0.033) and ADMA (HR 0.995, 95% CI 0.991-0.998, p=0.006) as independent predictors of new digital ulcers. Patients with serum levels of ET-1>11.9pmol/ml (p<0.001) and VEGF<422.47 pg/ml (p=0.028) had significantly more DU in the 3-year follow-up. Although not significant, a trend towards increased serum levels of…
To investigate whether CCR5 deletion is associated with susceptibility to Behçet's disease (B... more To investigate whether CCR5 deletion is associated with susceptibility to Behçet's disease (BD) in a Portuguese population. A total of 122 BD patients and 227 ethnically-matched controls were studied. Genotyping of the CCR5Δ32 polymorphisms was performed using polymerase chain reaction product sizing. No significant differences were observed in the allelic frequencies of CCR532 between patients and controls (OR=0.820; p=0.512). Stratification for gender and for the presence of HLA-B*51 did not reveal any significant differences. These results indicate that CCR5Δ32 is unlikely to contribute to susceptibility to BD in Portuguese patients. This may be explained by the known functional redundancy of this signalling system.
The major purpose of this study was to evaluate alternative automated methods of collecting data ... more The major purpose of this study was to evaluate alternative automated methods of collecting data on health related quality of life (HR-QoL). In order to achieve this, we developed a study with the following objectives: (1) to evaluated the feasibility of electronic version in patients with different chronic pathologies of the immune system using Short Form 36version2 (SF-36v2), (2) to evaluate the construct validity of SF-36v2 using the electronic data capture, and (3) to compare electronic version questionnaires with paper questionnaires in terms of patients' acceptance, data quality, and reliability. Out-patients with chronic immune diseases (HIV infection, lupus, scleroderma, rheumatoid arthritis, Behçet and Sjögren), were randomly selected to completed electronic and paper SF-36v2 (n=50) before consultation in Clinical Immunology Unit, in Hospital Santo António-Centro Hospitalar do Porto (CI-HGSA). There were very high correlations in SF-36v2 responses (p< .001) between t...
The principle of treating-to-target has been successfully applied to many diseases outside rheuma... more The principle of treating-to-target has been successfully applied to many diseases outside rheumatology and more recently to rheumatoid arthritis. Identifying appropriate therapeutic targets and pursuing these systematically has led to improved care for patients with these diseases and useful guidance for healthcare providers and administrators. Thus, an initiative to evaluate possible therapeutic targets and develop treat-to-target guidance was believed to be highly appropriate in the management of systemic lupus erythematosus (SLE) patients as well. Specialists in rheumatology, nephrology, dermatology, internal medicine and clinical immunology, and a patient representative, contributed to this initiative. The majority convened on three occasions in 2012-2013. Twelve topics of critical importance were identified and a systematic literature review was performed. The results were condensed and reformulated as recommendations, discussed, modified and voted upon. The finalised bullet p...
Clinical and experimental immunology, Jan 24, 2017
FOXP3(+) regulatory T-cells (Tregs) are functionally deficient in Systemic Lupus Erythematosus (S... more FOXP3(+) regulatory T-cells (Tregs) are functionally deficient in Systemic Lupus Erythematosus (SLE), characterized by reduced surface CD25 (the IL-2 receptor alpha chain). Low-dose IL-2 therapy is a promising current approach to correct this defect. To elucidate the origins of the SLE Treg phenotype, we studied its role through developmentally defined Treg subsets in 45 SLE patients, 103 SLE-unaffected first-degree relatives and 61 unrelated healthy control subjects, and genetic association with the CD25-encoding IL2RA locus. We identified two separate, uncorrelated effects contributing to Treg CD25. (1) SLE patients and unaffected relatives remarkably shared CD25 reduction versus controls particularly in the developmentally earliest CD4(+) FOXP3(+) CD45RO(-) CD31(+) recent thymic emigrant Tregs. This first component effect influenced the proportions of circulating CD4(+) FOXP3(high) CD45RO(+) activated Tregs. (2) In contrast, patients and unaffected relatives sharply differed in t...
There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily... more There is currently no approved treatment for primary Sjögren’s syndrome, a disease that primarily affects adult women. The difficulty in developing effective therapies is -in part- because of the heterogeneity in the clinical manifestation and pathophysiology of the disease. Finding common molecular signatures among patient subgroups could improve our understanding of disease etiology, and facilitate the development of targeted therapeutics. Here, we report, in a cross-sectional cohort, a molecular classification scheme for Sjögren’s syndrome patients based on the multi-omic profiling of whole blood samples from a European cohort of over 300 patients, and a similar number of age and gender-matched healthy volunteers. Using transcriptomic, genomic, epigenetic, cytokine expression and flow cytometry data, combined with clinical parameters, we identify four groups of patients with distinct patterns of immune dysregulation. The biomarkers we identify can be used by machine learning clas...
Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology. It i... more Rheumatoid arthritis (RA) is a chronic, systemic, inflammatory disorder of unknown etiology. It is characterized by symmetric, polyarticular pain, swelling, morning stiffness, and fatigue. RA has a variable course, often with periods of exacerbations and, less frequently, true remissions. Outcomes are also variable, ranging from the rarely seen remitting disease to severe disease that brings disability and in some patients premature death. Without treatment, the majority of patients will experience progressive joint damage and, in some patients, this results in significant disability within just a few years. Improvement in health related quality of life is one of the most important goals in the management of rheumatoid arthritis and therefore must be pursued as a crucial aim in clinical practice. This paper draws from 49 qualitative interviews conducted with RA patients, before starting a program of Spa Therapy and aims to get an overview of their main RA related difficulties, worri...
Gastroenterology and Hepatology From Bed to Bench, 2016
Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis p... more Aim: The aim of this study was to review our experience with gestations in autoimmune hepatitis patients. Background: There are only limited data describing pregnancy in patients with autoimmune hepatitis. Patients and methods: Retrospective analysis of pregnancies with autoimmune hepatitis followed in Centro Hospitalar do Porto, Portugal in the last ten years. Results: We reported nine pregnancies in seven patients with autoimmune hepatitis. Two patients had documented liver cirrhosis prior to the pregnancy. In this study, 66.7% of patients were treated with azathioprine and 88.9% with prednisolone. Clinical improvements were observed in 11.1% of pregnancies and 22.2% exacerbations were diagnosed. There were six live births and two preterm deliveries (preterm delivery rate of 33%). We also report three first trimester miscarriages (early gestation miscarriage rate of 33%). There were no neonatal or maternal deaths. Conclusion: The favorable obstetric outcome is a realistic expectat...
The Israel Medical Association journal : IMAJ, 2016
The effects of balneotherapy on rheumatoid arthritis (RA) are still controversial partly due to p... more The effects of balneotherapy on rheumatoid arthritis (RA) are still controversial partly due to poor methodology used in randomized controlled trials, as reported in the international medical literature. To determine whether spa therapy plus pharmacological treatment offers any benefit in the management of RA as compared to pharmacological treatment alone. We conducted a prospective, controlled, unblinded randomly assigned study of patients with RA according to American College of Rheumatology criteria. Following the 2007 recommendations of AFRETH, the method designed for this study was "immediate treatment versus delayed treatment." All patients were followed at the Centro Hospitalar do Porto and each physician observed the same patients throughout the study. Patients continued with their usual medications and maintained their daily life activities at home, at leisure and/or in the workplace. The spa therapy group received spa treatments for 21 days at S. Jorge Spa-Santa ...
Clinical and experimental rheumatology, Jan 5, 2015
To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk f... more To investigate the role of endothelial dysfunction and angiogenesis vascular biomarkers as risk factors and their predictive value for digital ulcers in systemic sclerosis patients. Endothelin-1 (ET-1), asymmetric dimethylarginine (ADMA), vascular endothelial growth factor (VEGF), endostatin and endoglin were measured in an observational prospective cohort of 77 SSc patients. The primary outcome was the occurrence of one or more new ischaemic digital ulcers during a planned 3-year follow-up. After the 3-year follow-up, 40 patients developed new digital ulcers. Logistic regression confirmed VEGF (HR 1.128, 95% CI 1.010-1.260, p=0.033) and ADMA (HR 0.995, 95% CI 0.991-0.998, p=0.006) as independent predictors of new digital ulcers. Patients with serum levels of ET-1>11.9pmol/ml (p<0.001) and VEGF<422.47 pg/ml (p=0.028) had significantly more DU in the 3-year follow-up. Although not significant, a trend towards increased serum levels of…
To investigate whether CCR5 deletion is associated with susceptibility to Behçet's disease (B... more To investigate whether CCR5 deletion is associated with susceptibility to Behçet's disease (BD) in a Portuguese population. A total of 122 BD patients and 227 ethnically-matched controls were studied. Genotyping of the CCR5Δ32 polymorphisms was performed using polymerase chain reaction product sizing. No significant differences were observed in the allelic frequencies of CCR532 between patients and controls (OR=0.820; p=0.512). Stratification for gender and for the presence of HLA-B*51 did not reveal any significant differences. These results indicate that CCR5Δ32 is unlikely to contribute to susceptibility to BD in Portuguese patients. This may be explained by the known functional redundancy of this signalling system.
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Papers by Carlos Vasconcelos