Browsing by Author "Paula, F"
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- Changes in Iron Metabolism Induced by Anti-Interleukin-6 Receptor Monoclonal Antibody are Associated with an Increased Risk of InfectionPublication . Ribeiro, R; Batista, F; Paula, F; Alves, JD(1) Background: Treatment of patients with rheumatoid arthritis (RA) with an anti-IL-6 receptor (anti-IL-6R) monoclonal antibody (tocilizumab) has been found to influence iron metabolism. The objective of the present study was to ascertain whether changes in iron metabolism induced by anti-IL-6R biologic therapy were independently associated with an increased infection risk. (2) Methods: A prospective longitudinal study of patients with RA treated with tocilizumab was conducted. RA patients treated with an antitumor necrosis factor α monoclonal antibody were also included as a control group. The primary outcome was occurrence of infection during the first 24 months of biologic therapy. (3) Results: A total of 15 patients were included, with a mean age of 51.0 ± 4,1 and 73.3% (n = 11) female. A multivariate survival regression model, adjusted for confounding factors, was fitted for each of the iron metabolism variables. Hazard ratios for being above the median of each parameter was considered. Transferrin saturation above the median value (>32.1%) was associated with a higher infection risk (HR 4.3; 95%CI 1.0-19.69; p = 0.05). Similarly, although non-significantly, higher serum iron was strongly associated with infection occurrence. (4) Conclusions: This study identified a probable association between infection risk and higher serum iron and transferrin saturation in patients with RA on anti-IL-6R biologic therapy. We suggest that both these parameters should be considered relevant contributing factors for infection occurrence in patients on anti-IL-6R therapy.
- Cisticercose do tecido molePublication . Mocanu, I; Paula, F; Amaral, M
- Crise de retenção esplénica major num adulto com drepanocitosePublication . Paula, F; Amaral, M; Oliveira, Alves; Alves, JDA crise de retenção esplénica é uma complicação, frequentemente, fatal da drepanocitose. É rara em adultos, pela elevada incidência de autoesplenectomia durante a infância. Heterozigóticos com traços de drepanocitose e de beta-talassémia têm fenótipos menos graves, podendo manter um baço funcional até à idade adulta. Descrevemos um caso de crise de retenção esplénica num homem de 19 anos, com concentração mínima de hemoglobina de 2,9g/dL, que resolveu após esplenectomia emergente. Os poucos casos descritos na literatura acarretam uma mortalidade elevada. Um diagnóstico rápido e actuação imediata são necessários para garantir a sobrevivência. É apresentada uma revisão da fisiopatologia e da abordagem terapêutica desta entidade.
- Esclerose sistémica: casuística: análise retrospectiva dos doentes com esclerose sistémica seguidos desde Junho 2009 a Novembro 2013 seguidos no ServiçoPublication . Oliveira, S; Paula, F; Caetano, J; Alves, JD
- Extended Release-Niacin increases anti-ApoA-I antibodies that block the anti-oxidant effect of HDL-C: the EXPLORE clinical trial.Publication . Batuca, JR; Amaral, M; Favas, C; Paula, F; AMES, PR; Papoila, AL; Alves, JDExtended Release-Niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤ 40 mg/dL (men) or ≤ 50 mg/dL (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was non-significant (coefficient estimate 20.83U/L, 95% CI -9.88 to 51.53; p = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg/dL, 95% CI 1.16 to 9.25; p = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg/dL, 95% CI 0.57 to 4.34; p = 0.011) and HDL3 (coefficient estimate 2.73 mg/dL, 95% CI 0.47 to 4.98; p = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 µg/mL, 95% CI 0.09-0.40; p = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved anti-oxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.
- Extended-release niacin increases anti-apolipoprotein A-I antibodies that block the antioxidant effect of high-density lipoprotein-cholesterol: the EXPLORE clinical trial.Publication . Batuca, J; Amaral, M; Favas, C; Paula, F; Ames, P; Papoila, A; Alves, JDExtended-release niacin (ERN) is the most effective agent for increasing high-density lipoprotein-cholesterol (HDL-C). Having previously identified anti-HDL antibodies, we investigated whether ERN affected the antioxidant capacity of HDL and whether ERN was associated with the production of antibodies against HDL (aHDL) and apolipoprotein A-I (aApoA-I). METHODS: Twenty-one patients older than 18 years, with HDL-C ≤40 mg dl-1 (men) or ≤50 mg dl-1 (women) were randomly assigned to receive daily ERN (n = 10) or placebo (n = 11) for two sequential 12-week periods, with 4 weeks of wash-out before cross-over. Primary outcome was change of paraoxonase-1 (PON1) activity and secondary outcomes were changes in aHDL and aApoA-I antibodies. Clinical Trial Unique Identifier: EudraCT 2006-006889-42. RESULTS: The effect of ERN on PON1 activity was nonsignificant (coefficient estimate 20.83 U l-1 , 95% confidence interval [CI] -9.88 to 51.53; P = 0.184). ERN was associated with an increase in HDL-C levels (coefficient estimate 5.21 mg dl-1 , 95% CI 1.16 to 9.25; P = 0.012) and its subclasses HDL2 (coefficient estimate 2.46 mg dl-1 , 95% CI 0.57 to 4.34; P = 0.011) and HDL3 (coefficient estimate 2.73 mg dl-1 , 95% CI 0.47 to 4.98; P = 0.018). ERN was significantly associated with the production of aApoA-I antibodies (coefficient estimate 0.25 μg ml-1 , 95% CI 0.09-0.40; P = 0.001). aApoA-I titres at baseline were correlated with decreased PON activity. CONCLUSIONS: The rise in HDL-C achieved with ERN was not matched by improved antioxidant capacity, eventually hampered by the emergence of aApoA-I antibodies. These results may explain why Niacin and other lipid lowering agents fail to reduce cardiovascular risk.
- Manifestações oftalmológicas de doenças sistémicasPublication . Pina, S; Coutinho, I; Amaral, N; Bernardo, M; Melo, A; Paula, F; Batista, F; Amaral, M; Alves, JD
- Non-tumor necrosis factor-based biologic therapies for rheumatoid arthritis: present, future, and insights into pathogenesis.Publication . Paula, F; Alves, JDTherapeutic options for patients suffering from the more severe forms of spondyloarthritis have been rather limited in the last decades. There is now accumulating evidence that antitumor necrosis factor therapy is highly effective in spondyloarthritis, especially in ankylosing spondylitis and psoriatic arthritis. Based on the data recently published on more than 500 patients with ankylosing spondylitis and psoriatic arthritis, this treatment seems to be even more effective than in rheumatoid arthritis. The antitumor necrosis factor-alpha agents currently available, infliximab (Remicade), etanercept (Enbrel), and adalimumab (Humira), are approved for the treatment of rheumatoid arthritis in the United States and partly in Europe. The situation in spondyloarthritis is different from that of rheumatoid arthritis because there is an unmet medical need, especially in ankylosing spondylitis: no therapies with disease-modifying antirheumatic drugs are available for severely affected patients, especially with spinal disease. Thus, tumor necrosis factor blockers may even be considered a first-line treatment in a patient with active ankylosing spondylitis and psoriatic arthritis whose condition is not sufficiently controlled with nonsteroidal antiinflammatory drugs in the case of axial disease, and sulfasalazine or methotrexate in the case of peripheral arthritis. For infliximab, a dose of 5 mg/kg was required, and intervals between 6 and 12 weeks were necessary to suppress disease activity constantly-also a major aim for long-term treatment. The standard dosage of etanercept is 2 x 25 mg subcutaneously per week. There are no studies yet on adalimumab (standard rheumatoid arthritis dose, 20-40 mg subcutaneously every 1-2 weeks) in spondyloarthritis. Infliximab was very recently approved for AS in Europe. The efficacy of etanercept was first demonstrated in psoriatic arthritis, and it is now approved for this indication. A double-blind study has also been performed in ankylosing spondylitis, with similarly clear efficacy. There is preliminary evidence that both agents do also work in other spondyloarthritis, such as undifferentiated spondyloarthritis. Ideally, both agents will be approved soon for the short-term treatment of severe, uncontrolled spondyloarthritis. In parallel, studies should be performed to document the long-term efficacy of this treatment. There is hope that ankylosis may be preventable, but it remains to be shown whether patients benefit from long-term antitumor necrosis factor therapy and whether radiologic progression and ankylosis can be stopped. Severe adverse events have remained rare. Complicated infections including tuberculosis have been reported. These can be largely prevented by appropriate screening. At it stands now, the benefits of antitumor necrosis factor therapy in ankylosing spondylitis seem to outweigh these shortcomings.
- Peripapillary Retinal Nerve Fiber Layer Thickness and Peripheral Microcirculation in Raynaud’s DiseasePublication . Pedrosa, C; Pina, S; Paula, F; Amaral, M; Vaz, FPurpose: Normal-tension glaucoma has been associated with systemic vascular diseases such as peripheral vasospasm. This study aims to evaluate the influence of peripheral vasospasm on the thickness of the retinal nerve fiber layer (RNFL) in Raynaud's disease (RD), and the correlation between global RNFL and peripheral microcirculation features in RD patients. Methods: Observational cross-sectional study of 18 patients (35 eyes) with a diagnosis of RD followed in our clinic, and 20 healthy controls (39 eyes). RNFL parameters were obtained using spectral domain optical coherence tomography (SD-OCT Spectralis®, Heidelberg). Global and sectorial peripapillary RNFL thickness were registered. Age, gender, refractive error, best-corrected visual acuity and intraocular pressure were determined, and slit-lamp biomicroscopy and fundus examination were performed. Nailfold videocapillaroscopy (NC) was performed in the RD group to characterize capillary morphology and blood flow. Mann-Whitney and Fisher's exact tests were used for statistical analysis. Statistical significance level was set at p<0.05 (two-sided). Results: There was no significant difference in the global RNFL between RD patients and the control group (p=0.35). The presence of avascular areas in NC was associated with a lower global RNFL thickness (p=0.026). Conclusion: The association between avascular areas in NC and the lower global RNFL thickness in RD patients suggests that systemic vasospasm severity may be related to optic nerve damage propensity. Therefore, its presence in NC may identify RD patients at risk for optic nerve head damage. A larger sample with a long-term study is needed to support the clinical and therapeutic implications of our findings.
- Systemic sclerosis-related changes on nailfold videocapillaroscopy in genetic and metabolic myopathies.Publication . Paula, F; Ferreira, I; Amaral, M; Alves, JD