Browsing by Author "Favas, C"
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- Antibodies against HDL Components in Ischaemic Stroke and Coronary Artery DiseasePublication . Batuca, J; Amaral, M; Favas, C; Justino, G; Papoila, A; Ames, P; Alves, JDQuantitative and qualitative defects of high-density lipoprotein (HDL) are important in atherogenesis. In this study, we investigated whether antibodies against HDL components had additional value to conventional cardiovascular risk factors for the diagnosis of ischaemic stroke (IS) and coronary artery disease (CAD). Cross-sectional study was conducted on 53 patients with IS, 51 with CAD and 55 healthy controls, and in vitro studies to validate findings of the clinical study. We determined serum immunoglobulin G (IgG) antibodies against HDL (aHDL), apolipoproteins (aApoA-I, aApoA-II and aApoC-I) and paraoxonase-1 (aPON1) as well as PON1 activity (PON1a), total antioxidant capacity and biomarkers of endothelial activation (serum nitric oxide metabolites, 3-nitrotyrosine, VCAM-1 and ICAM-1); in vitro assays tested the capacity of IgG aHDL purified from high titer patients to inhibit PON1a and to reverse protective effect of HDL on endothelial cells. IgG aHDL, aApoA-I and aPON1 were higher in IS and CAD than controls (p < 0.001), predicted negatively PON1a and positively VCAM-1 and ICAM-1. By adding IgG aHDL and aApoA-I to a traditional cardiovascular risk factors model for IS and by adding IgG aHDL in a similar model for CAD, we obtained better discrimination of IS and CAD from healthy controls. IgG aHDL purified from IS and CAD inhibited PON1a by 38% (p < 0.01) and abrogated the protective effect of HDL on VCAM-1 expression by 126% compared with non-specific human IgG (p < 0.001). IgG against HDL components interfere with the antioxidant and anti-inflammatory properties of HDL and may represent novel biomarkers for vascular disease that need to be investigated in prospective studies.
- Etiology, Treatment and Prognosis of Acute PericarditisPublication . Serodio, J; Trindade, M; Achega, M; Faria, D; Maurício, J; Batista, F; Favas, C; Alves, JDIntroduction: Acute pericarditis is a common inflammatory condition of the pericardium usually assumed to be viral or idiopathic. Despite recent treatment improvements, information is scarce regarding etiology and prognosis. Our aim was to determine the incidence of pericarditis with a known etiology and assess clinical prognostic predictors. Material and Methods: A clinical retrospective analysis of hospitalized patients with acute pericarditis was conducted from 2012 to 2016. Population was characterized according to etiology, clinical presentation, treatment and prognosis. Outcomes of interest, evaluated at one year after hospital discharge, were pericarditis recurrence, hospitalization, constriction and overall mortality. Results: A total of 94 patients were enrolled, median age 46 years (inter-quartile range 32-61), 65% were male. Idiopathic etiology was responsible for 68% of cases. A specific etiology was found in the remaining 32% of patients, being the most frequent autoimmune disease (12%) and malignancy (5%). Idiopathic pericarditis was associated with myopericarditis (p = 0.049) and a known etiology with pericardial effusion (p = 0.001) and cardiac tamponade (p = 0.027). Recurrence of pericarditis was found in 13% of patients. Corticosteroid treatment in patients with an identified etiology was not associated with an increase in recurrence (p = 0.220). Overall 1-year mortality was 9%. A defined etiology was the only independent predictor of mortality at multivariate analysis (OR 40.3; 95% CI 1.9 – 137.2; p = 0.016). Conclusion: Up to one third of hospitalized patients with acute pericarditis have an identified cause of pericarditis and these patients are at increased risk of mortality.
- Evaluation of phosphatidylserine-dependent antiprothrombin antibody testing for the diagnosis of antiphospholipid syndrome: results of an international multicentre study.Publication . Amengual, O; Forastiero R, R; Sugiura-Ogasawara, M; Otomo, K; Oku, K; Favas, C; Alves, JD; Žigon, P; Ambrožič, A; Tomšič, M; Ruiz-Arruza, I; Ruiz-Irastorza, G; Bertolaccini, ML; Norman, GL; Shums, Z; Arai, J; Murashima, A; Tebo, AE; Gerosa, M; Meroni, PL; Rodriguez-Pintó, I; Cervera, R; Swadzba, J; Musial, J; Atsumi, TOBJECTIVE: A task force of scientists at the International Congress on Antiphospholipid Antibodies recognized that phosphatidylserine-dependent antiprothrombin antibodies (aPS/PT) might contribute to a better identification of antiphospholipid syndrome (APS). Accordingly, initial and replication retrospective, cross-sectional multicentre studies were conducted to ascertain the value of aPS/PT for APS diagnosis. METHODS: In the initial study (eight centres, seven countries), clinical/laboratory data were retrospectively collected. Serum/plasma samples were tested for IgG aPS/PT at Inova Diagnostics (Inova) using two ELISA kits. A replication study (five centres, five countries) was carried out afterwards. RESULTS: In the initial study (n = 247), a moderate agreement between the IgG aPS/PT Inova and MBL ELISA kits was observed (k = 0.598). IgG aPS/PT were more prevalent in APS patients (51%) than in those without (9%), OR 10.8, 95% CI (4.0-29.3), p < 0.0001. Sensitivity, specificity, positive (LR+) and negative (LR-) likelihood ratio of IgG aPS/PT for APS diagnosis were 51%, 91%, 5.9 and 0.5, respectively. In the replication study (n = 214), a moderate/substantial agreement between the IgG aPS/PT results obtained with both ELISA kits was observed (k = 0.630). IgG aPS/PT were more prevalent in APS patients (47%) than in those without (12%), OR 6.4, 95% CI (2.6-16), p < 0.0001. Sensitivity, specificity, LR + and LR- for APS diagnosis were 47%, 88%, 3.9 and 0.6, respectively. CONCLUSIONS: IgG aPS/PT detection is an easily performed laboratory parameter that might contribute to a better and more complete identification of patients with APS.
- 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.
- Persistency of low levels of anticardiolipin and anti-beta2 glycoprotein1 in thrombosisPublication . Amaral, M; Favas, C; Alves, JDBACKGROUND: Antiphospholipid antibodies, the hallmark of the antiphospholipid syndrome, are associated with both venous and arterial thrombosis. Despite some reports stating that this association may be present in patients with low titres of anticardiolipin antibodies, a clear association has only been established in the presence of a moderate to high concentrations (above 40 GPL or MPL). METHODS: In order to study whether low antibody titres could be associated with thrombosis, we reviewed the files of 196 patients, 94 with and 102 without thrombotic events, for a period of 4.4 and 5.1 years respectively. Files from patients with persistent low titres of antiphospholipid antibodies recorded in the unit database were selected, independently of the associated clinical history or diagnosis. Epidemiology, clinical and treatment information were collected and the serum variability of the antibody titres was analysed in relation to the presence of thrombotic events. RESULTS: Thrombotic events were classified as venous 81.9% and arterial 18.1%. 23/94 (24.5%) patients with thrombosis had miscarriages. There were no significant differences between serum concentrations of antiphospholipid antibodies in the thrombotic and non-thrombotic groups. However, there was a higher consistency of the antibody concentrations in patients with thrombosis, as seen by the significantly lower variability of IgG aCL and abeta2GP1 titres in patients with thrombosis when compared to non-thrombotic controls (p=0.0025 and p<0.0001, respectively). CONCLUSION: Consistency of low titres of antiphospholipid antibody levels may be associated with a higher risk of thrombotic events overall.
- A Rare Case of Bilateral ProptosisPublication . Serodio, J; Jonet, M; Trinidade, M; Coutinho, I; Favas, CA 65-year-old man presented with a 2-year history of severe bilateral proptosis, palpable lymphadenopathy and moderate hepatosplenomegaly. A blood test was positive for hepatitis C infection. CT showed palpebral infiltrative lesions with regional progression through the temporal and masticatory spaces to the pharynx and hypopharynx causing almost complete airway obstruction. A palpebral biopsy was consistent with low-grade Bcl-2+ extra-nodal MALT non-Hodgkin B-cell lymphoma. The patient received six cycles of rituximab-based chemotherapy with clinical remission at 9-month follow-up. Bilateral proptosis is a rare presentation of several diseases. When brain CT excludes cavernous sinus pathology, thyroid ophthalmopathy or haematological malignancy should be considered. LEARNING POINTS: Bilateral proptosis is a rare presentation with a broad differential diagnosis, and is most frequently is caused by cavernous sinus disease, thyroid ophthalmopathy or haematological malignancy.Hepatitis C may be associated with MALT lymphoma and presents mainly at non-gastric locations even with few hepatic manifestations of the infection.Long-term low-grade lymphoma may present with severe disseminated disease at diagnosis, but treatment response is generally good.
- Stress-related mucosal disease: incidence of bleeding and the role of omeprazole in its prophylaxisPublication . Amaral, M; Favas, C; Alves, JD; Riso, N; Riscado, MBACKGROUND: Upper gastrointestinal bleeding is the severe complication of stress-related mucosal disease in hospitalized patients. In intensive care units (ICU), risk factors are well defined and only mechanical ventilation and coagulopathy proved to be relevant for significant bleeding. On the contrary, in non-ICU settings there is no consensus about this issue. Nevertheless, omeprazole is still widely used in prophylaxis of bleeding. The objective of our study was to evaluate the relevance of stress-related mucosal disease bleeding in patients admitted to an internal medicine ward, and the role of omeprazole in its prophylaxis. METHODS: We conducted a retrospective study in which we analysed consecutive patients who were admitted to our ward over a year. We recorded demographic characteristics of the patients, potential risk factors for stress-related mucosal disease (clinical data, laboratory, and medication), administration of prophylactic omeprazole, and total cost of this prophylaxis. Patients with active gastrointestinal bleeding on the admission were excluded. We recorded every upper gastrointestinal bleeding event with clinical relevance. RESULTS: Five hundred and thirty-five patients, mean age 70 years, mean length of stay 9.6+/-7.7 days; 140 (26.2%) patients were treated with 40 mg of omeprazole intravenously, 193 (36.1%) with 20mg of omeprazole orally, and 202 (37.8%) patients had no prophylaxis. There was only one episode (0.2%) of clinically relevant bleeding. CONCLUSION: In patients admitted to an internal medicine ward, incidence of upper gastrointestinal bleeding as a complication of stress-related mucosal disease is low. We found that there is no advantage in prophylaxis with omeprazole