EDUARDO FERREIRA BORBA NETO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina - Docente
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- Penile anthropometry in systemic lupus erythematosus patients(2011) VECCHI, A. P.; BORBA, E. F.; BONFA, E.; COCUZZA, M.; PIERI, P.; KIM, C. A.; SILVA, C. A.The aim of this study was to evaluate penile anthropometry in systemic lupus erythematosus (SLE) patients compared with healthy controls and the possible relevant pubertal, clinical, hormonal and treatment factors that could influence penile dimensions. Twenty-five consecutive SLE patients were assessed by urological examination, sexual function, testicular ultrasound, hormones, sperm analysis, genetic analysis, clinical features and treatment. The control group included 25 age-matched healthy males. SLE patients had a lower median penis length and circumference [8 (7.5-10) vs. 10 (8-13) cm, p = 0.0001; 8 (7-10) vs. 10 (7-11) cm, p = 0.001; respectively], lower median testicular volume by right and left Prader [15 (10-25) vs. 20 (12-25) ml, p = 0.003; 15 (10-25) vs. 20 (12-25) ml, p = 0.006; respectively], higher median of follicle-stimulating hormone [5.8 (2.1-25) vs. 3.3 (1.9-9) IU/l, p = 0.002] and lower morning total testosterone levels (28% vs. 0%, p = 0.009) compared with controls. In spite of that, erectile dysfunction was not observed in patients or controls. Analyses of lupus patients revealed that the median penis circumference was lower in patients with disease onset before first ejaculation compared with those with disease onset after first ejaculation [7.8 (7-10) vs. 9.0 (7.5-10) cm, p = 0.026]. No differences were observed in the median penile anthropometry regarding sexual dysfunction (p = 0.610), lower morning total testosterone levels (p = 0.662), oligo/azoospermia (p = 0.705), SLE Disease Activity Index >= 4 (p = 0.562), Systemic Lupus International Collaborating Clinics/ACR Damage Index >= 1 (p = 0.478), prednisone cumulative dose (p = 0.789) and intravenous cyclophosphamide therapy (p = 0.754). Klinefelters syndrome (46XY/47XXY) was diagnosed in one (4%) SLE patient with decreased penile size whereas Y-chromosomal microdeletions was absent in all of them. In conclusion, we have identified reduced penile dimensions in SLE patients with no deleterious effect in erectile function. Disease onset before first ejaculation seems to affect penis development in pre-pubertal lupus. Lupus (2011) 20, 512-518.
- Increased corticotropin-releasing hormone (CRH) expression in cutaneous lupus lesions(2015) SCHMITZ, M. K.; BOTTE, D. A.; SOTTO, M. N.; BORBA, E. F.; BONFA, E.; MELLO, S. B. V. deObjective Corticotropin-releasing hormone (CRH) and pro-opiomelanocortin (POMC) axis activation leads to the production of hormones, such as adrenocorticotrophic hormone (ACTH) and the -melanocyte stimulating hormone (-MSH). Data regarding the role of these hormones in systemic lupus erythematosus (SLE) are scarce. In the present study we aim to evaluate the participation of this axis in the cutaneous involvement of SLE. Methods Seventeen SLE patients were clinically evaluated, and biopsies from affected and unaffected skin of these patients were compared with 17 healthy control individuals. Immunohistochemical analyses for CRH, ACTH, -MSH, and MC-1R were performed, and the serum levels of -MSH, IL-1, IL-1ra, IL-6, IL-10, IL-12p70, IL-17, TNF-, and IFN- were measured. Results The affected skin of the SLE patients exhibited higher CRH expression in the deep dermis compared to the skin of the controls (p=0.024), whereas the tissue expression of ACTH, cortisol, -MSH and its receptor MC-1R were comparable in SLE patients and controls. Higher serum levels of IFN- (p=0.041), TNF- (p=0.001) and IL-6 (p=0.049) were observed in SLE patients compared with controls, while -MSH levels were similar in both groups. Conclusion The novel finding of elevated CRH expression solely in the affected skin deep dermis supports the notion of a cutaneous local dysfunction of the CRH-POMC axis in the pathogenesis of cutaneous SLE lesions.
- Abnormal chronotropic reserve and heart rate recovery in patients with SLE: a case-control study(2011) PRADO, D. M. Leite do; GUALANO, B.; MIOSSI, R.; SA-PINTO, A. L.; LIMA, F. R.; ROSCHEL, H.; BORBA, E. F.; BONFA, E.Abnormal heart-rate (HR) response during or after a graded exercise test has been recognized as a strong and an independent predictor of all-cause mortality in healthy and diseased subjects. The purpose of the present study was to evaluate the HR response during exercise in women with systemic lupus erythematosus (SLE). In this case-control study, 22 women with SLE (age 29.5 perpendicular to 1.1 years) were compared with 20 gender-, BMI-, and age-matched healthy subjects (age 26.5 +/- 1.4 years). A treadmill cardiorespiratory test was performed and HR response during exercise was evaluated by the chronotropic reserve (CR). HR recovery (Delta HRR) was defined as the difference between HR at peak exercise and at both first (Delta HRR1) and second (Delta HRR2) minutes after exercising. SLE patients presented lower peak VO(2) when compared with healthy subjects (27.6 perpendicular to 0.9 vs. 36.7 perpendicular to 1.1 ml/kg/min, p = 0.001, respectively). Additionally, SLE patients demonstrated lower CR (71.8 +/- 2.4 vs. 98.2 +/- 2.6%, p = 0.001), Delta HRR1 (22.1 +/- 2.5 vs. 32.4 +/- 2.2%, p = 0.004) and Delta HRR2 (39.1 +/- 2.9 vs. 50.8 +/- 2.5%, p = 0.001) than their healthy peers. In conclusion, SLE patients presented abnormal HR response to exercise, characterized by chronotropic incompetence and delayed Delta HRR. Lupus (2011) 20, 717-720.
- Measurement properties of selected patient-reported outcome measures for use in randomised controlled trials in patients with systemic lupus erythematosus: a systematic review(2020) STRAND, Vibeke; SIMON, Lee S.; MEARA, Alexa Simon; TOUMA, Zahi; BORBA NETO, Eduardo FerreiraObjective The heterogeneous multisystem manifestations of SLE include fatigue, pain, depression, sleep disturbance and cognitive dysfunction, and underscore the importance of a multidimensional approach when assessing health-related quality of life. The US Food and Drug Administration has emphasised the importance of patient-reported outcomes (PROs) for approval of new medications and Outcome Measures in Rheumatology has mandated demonstration of appropriate measurement properties of selected PRO instruments. Methods Published information regarding psychometric properties of the Medical Outcomes Survey Short Form 36 (SF-36), Lupus Quality of Life Questionnaire (LupusQoL) and Functional Assessment of Chronic Illness Therapy-Fatigue Scale (FACIT-F), and their suitability as end points in randomised controlled trials (RCTs) and longitudinal observational studies (LOS) were assessed. A search of English-language literature using MEDLINE and EMBASE identified studies related to development and validation of these instruments. Evidence addressed content validity, reliability (internal consistency and test-retest reliability), construct validity (convergent and divergent) and longitudinal responsiveness, including thresholds of meaning and discrimination. Results All instruments demonstrated strong internal consistency, reliability and appropriate face/content validity, indicating items within each instrument that measure the intended concept. SF-36 and LupusQoL demonstrated test-retest reliability; although not published with FACIT-F in SLE supported by evidence from other rheumatic diseases. All instruments demonstrated convergent validity with other comparable PROs and responsivity to treatment. Conclusion The measurement properties of PRO instruments with published data from RCTs including: SF-36, LupusQoL and FACIT-F indicate their value as secondary end points to support labelling claims in RCTs and LOS evaluating the efficacy of SLE treatments.
- The Influence of Income and Formal Education on Damage in Brazilian Patients With Systemic Lupus Erythematosus(2017) TEIXEIRA, Roberto Cordeiro de Andrade; BORBA NETO, Eduardo Ferreira; CHRISTOPOULOS, Georges Basile; SATO, Emilia InoueObjective: The aim of this study was to evaluate the association of socioeconomic status and American College of Rheumatology/Systemic Lupus International Collaborating Clinics Damage Index (SDI) score in Brazilian patients with systemic lupus erythematosus (SLE). Methods: Five hundred twenty-three patients (SLE ACR criteria) 18 years or older who were at 12 months or greater since diagnosis were included. Socioeconomic status was assessed by per-capita income and years of education. Race was categorized as white and nonwhite. The SDI and Mexican SLE Disease Activity Index were used. Statistical Analysis: Mean +/- SD and median were used for descriptive analysis. Student t test, Mann-Whitney U test, chi(2) test, and Spearman rank correlation coefficient and univariate and multivariate regression analyses were performed. The level of significance was set at 5% for all statistical tests. Results: Ninety-six percent were female, 51.2% were nonwhite, and the mean age was 37.8 +/- 1.4 years. Disease duration was 8.2 +/- 10.3 years and formal education was 10.2 +/- 3.5 years. Unemployment among patients was 63.7%, with median monthly per-capita income of US $276. Mean SDI score was 1.4 +/- 1.52, and 65.6% had some type of damage (SDI >= 1). Patients with SDI of 1 or greater had lower income (P = 0.039). Nonwhite patients had higher SDI than did white patients (P = 0.005). The SDI presented a positive correlation with disease duration (P < 0.001) and age (P < 0.001) and a negative correlation with years of education (P = 0.001). Working patients had lower SDI than did inactive ones (P = 0.001). In a multivariate analysis, older age, higher disease duration, nonwhite race, low income, and out-of-work profile were associated with damage. Conclusions: Besides nonmodifiable characteristics such as longer disease duration and older age, low income was also associated with damage. Therefore, interventions to give adequate socioeconomic support are necessary to improve outcome, mainly in poorer and nonwhite SLE patients.
- Short-term Accrual 2019 European League Against Rheumatism/American College of Rheumatology Domains and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage in Lupus Patients With and Without Nephritis at Disease Onset(2023) MUNHOZ, Gabriela A.; AIKAWA, Nadia E.; SILVA, Clovis A.; PASOTO, Sandra G.; PEDROSA, Tatiana N.; SEGURO, Luciana P. C.; BONFA, Eloisa; BORBA, Eduardo F.ObjectiveTo determine in a historical inception cohort the impact of lupus nephritis at disease onset in short-term accrual 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) domains. The possible association with treatment and damage was also investigated.MethodsOne hundred thirty-three consecutive adult systemic lupus erythematosus patients according to the 2019 EULAR/ACR criteria were divided according to the presence (RENAL-lupus) or absence of renal involvement (NONRENAL-lupus) at disease onset. The 2019 EULAR/ACR score and Systemic Lupus International Collaborating Clinics/ACR (SDI) were longitudinally evaluated over 3 years.ResultsRENAL-lupus (n = 49 [36.8%]) and NONRENAL-lupus (n = 84 [63.2%]) were similar regarding age (p = 0.704), female sex (p = 0.313), and black race (p = 0.506). At study entry, RENAL-lupus had higher 2019 EULAR/ACR total domains (30 [12-42] vs. 22 [10-36], p < 0.001) and used more often glucocorticoid (p < 0.001), mycophenolate mofetil (p = 0.007), and cyclophosphamide (p = 0.001). After 3 years, a stable number of domain scores was observed for the RENAL-lupus (30 [12-42] vs. 30 [12-42], p = 0.125), whereas an increase was observed for the NONRENAL-lupus (22 [10-36] vs. 23 [10-40], p < 0.001) compared with baseline. Accordingly, RENAL-lupus patients had a lower frequency of additional domains (3/49 [6.1%] vs. 37/84 [44.0%], p < 0.0001). New kidney involvement occurred in 15 (44.1%) of 34 patients of the NONRENAL-lupus. Both groups evolved with a comparable increase in frequency of patients with damage (SDI >= 1) at the end of the study (23/49 [46.9%] vs. 34/89 [40.54%], p = 0.585) with a similar median of SDI (1 [0-4] vs. 0 [0-2], p = 0.132).ConclusionsThe distinct pattern of accrual 2019 EULAR/ACR domains in patients with and without nephritis at disease onset suggests that close surveillance for additional organ involvement, including kidney, is mandatory in NONRENAL lupus in the first 3 years of disease. The unexpected comparable early damage in both groups despite milder disease and less intense immunosuppression in NONRENAL lupus reinforces the need for new and tailored therapies for these patients.
- Primary cardiac disease in systemic lupus erythematosus patients: protective and risk factors-data from a multi-ethnic Latin American cohort(2014) GARCIA, Mercedes A.; ALARCON, Graciela S.; BOGGIO, Gabriela; HACHUEL, Leticia; MARCOS, Ana Ines; MARCOS, Juan Carlos; GENTILETTI, Silvana; CAEIRO, Francisco; SATO, Emilia I.; BORBA, Eduardo F.; BRENOL, Joao C. Tavares; MASSARDO, Loreto; MOLINA-RESTREPO, Jose Fernando; VASQUEZ, Gloria; GUIBERT-TOLEDANO, Marlene; BARILE-FABRIS, Leonor; AMIGO, Mary-Carmen; HUERTA-YANEZ, Guillermo F.; CUCHO-VENEGAS, Jorge M.; CHACON-DIAZ, Rosa; PONS-ESTEL, Bernardo A.Objectives. The aim of this study was to assess the cumulative incidence, risk and protective factors and impact on mortality of primary cardiac disease in SLE patients (disease duration <= 2 years) from a multi-ethnic, international, longitudinal inception cohort (34 centres, 9 Latin American countries). Methods. Risk and protective factors of primary cardiac disease (pericarditis, myocarditis, endocarditis, arrhythmias and/or valvular abnormalities) were evaluated. Results. Of 1437 patients, 202 (14.1%) developed one or more manifestations: 164 pericarditis, 35 valvulopathy, 23 arrhythmias, 7 myocarditis and 1 endocarditis at follow-up; 77 of these patients also had an episode of primary cardiac disease at or before recruitment. In the multivariable parsimonious model, African/Latin American ethnicity [odds ratio (OR) 1.80, 95% CI 1.13, 2.86], primary cardiac disease at or before recruitment (OR 6.56, 95% CI 4.56, 9.43) and first SLICC/ACR Damage Index for SLE assessment (OR 1.31, 95% CI 1.14, 1.50) were risk factors for the subsequent occurrence of primary cardiac disease. CNS involvement (OR 0.44, 95% CI 0.25, 0.75) and antimalarial treatment (OR 0.62, 95% CI 0.44, 0.89) at or before recruitment were negatively associated with the occurrence of primary cardiac disease risk. Primary cardiac disease was not independently associated with mortality. Conclusion. Primary cardiac disease occurred in 14.1% of SLE patients of the Grupo Latino Americano de Estudio de Lupus cohort and pericarditis was its most frequent manifestation. African origin and lupus damage were found to be risk factors, while CNS involvement at or before recruitment and antimalarial treatment were protective. Primary cardiac disease had no impact on mortality.
- Effectiveness of renoprotective approaches for persistent proteinuria in lupus nephritis: more than just immunosuppression(2018) CASTRO, M.; UGOLINI-LOPES, M.; BORBA, E. F.; BONFA, E.; SEGURO, L. P. C.Objective The objective of this study is to evaluate the efficacy of a tightly controlled renoprotective protocol in systemic lupus erythematosus (SLE) patients with persistent proteinuria. Methods Thirteen SLE patients with nephritis and persistent proteinuria (>1 g/24 hours) were included. The protocol consisted of regular clinical evaluations every two weeks to assess blood pressure (BP, target <130/80 mmHg), adherence to therapy, diet and smoking. No change in immunosuppressive drugs was allowed but reduction of glucocorticoid dose was permitted if indicated. Clinical, laboratory and treatment evaluations were performed at baseline and at the end of the study (after three months). Results SLE patients had a mean age of 37.85 +/- 7.68 years and disease duration of 9.85 +/- 7.29 years. At baseline, patients had a mean duration of maintenance therapy of 10.38 +/- 7.56 months, 12 with mycophenolate mofetil (92.3%) and one with azathioprine (7.7%). At least one dose optimization of antihypertensive regimen was required in all patients during the study. Seven patients (53.8%) had BP>130/80mmHg at baseline. At the end, 11 patients (84.6%) achieved stable BP target; 92.3% were using an angiotensin-converting enzyme inhibitor, 53.9% an angiotensin receptor blocker, and 46.2% were using combined therapy. All patients had a significant reduction in proteinuria levels (2.26 +/- 1.09 vs 0.88 +/- 0.54 g/24 hours, p < 0.001) and 61.5% achieved proteinuria <1 g/24 hours. A significant decrease in mean prednisone dose was observed (10.96 +/- 6.73 vs 5.38 +/- 3.36 mg/day, p = 0.013) as well as mean Systemic Lupus Erythematosus Disease Activity Index score (4.38 +/- 0.72 vs 3.08 +/- 1.86, p = 0.043). No significant changes were identified in serum creatinine, albumin, potassium, complement 3 and complement 4 levels (p > 0.05). Conclusion This study provides evidence that a tightly controlled renoprotective protocol is effective in reducing persistent proteinuria in lupus nephritis. The concomitant reduction of prednisone without any change in immunosuppression reinforces the importance of strategies beyond the treatment of nephritis activity.
article Efecto de los antimaláricos sobre los diferentes dominios del índice de daño SLICC en pacientes de la cohorte GLADEL(2018) PONS-ESTEL, Guillermo J.; QUINTANA, Rosana; WOJDYLA, Daniel; ALARCÓN, Graciela S.; SERRANO, Rosa María; UGARTE-GIL, Manuel; PIMENTEL-QUIROZ, Víctor; SORIANO, Enrique R.; CATOGGIO, Luis J.; SCOLNIK, Marina; SACNUN, Mónica; SAURIT, Verónica; CAEIRO, Francisco; ALVARELLOS, Alejandro; SARANO, Judith; GARCÍA, Mercedes; ONETTI, Laura; DRENKARD, Cristina; BERBOTTO, Guillermo; SCHERBARTH, Hugo R.; SATO, Emilia; BONFA, Eloisa; FERREIRA BORBA, Eduardo; COSTALLAT, Lilian; XAVIER, Ricardo; TAVARES BRENOL, Joao C.; DA SILVA, Nilzio A.; CAVALCANTI, Fernando; MASSARDO, Loreto; JACOBELLI, Sergio; NEIRA, Oscar; MOLINA, José F; VÁSQUEZ, Gloria; GÓMEZ-PUERTA, José A.; ALONSO GONZALEZ, Luis; IGLESIAS GAMARRA, Antonio; GUIBERT-TOLEDANO, Marlene; REYES, Gil A.; CARDIEL, Mario H.; PASCUAL-RAMOS, Virginia; GARCÍA DE LA TORRE, Ignacio; BARILE, Leonor; SILVEIRA, Luis H.; AMIGO, Mary-Carmen; SAUZA DEL POZO, María Josefina; ACEVEDO-VÁSQUEZ, Eduardo M.; ALFARO-LOZANO, José; SEGAMI, María Inés; CHACÓN-DÍAZ, Rosa; ABADI, Isaac; ESTEVA SPINETTI, María H; PONS-ESTEL, Bernardo A.Objective: To assess the effects of antimalarials (AM) over the items of the SLICC Damage Index (SDI). Methods: Patients with recent (≤2 years) diagnosis of systemic lupus erythematosus (SLE) from the GLADEL cohort were studied. End-point: increase in items SDI since cohort entry. Independent variables (socio-demographic, clinical, laboratory and treatment) were included. The effect of AM as a time dependent variable on most frequent SDI items (adjusting for potential confounders) was examined with a multivariable Cox regression model. Results: Of the 1466 patients included in this analysis, 1049 (72%) received AM with a median exposure time of 30 months (Q1-Q3: 11-57). Damage occurred in 665 (45%) patients during a median follow-up time of 24 months (Q1-Q3: 8-55). There were 301 integument, 208 renal, 149 neuropsychiatric, 98 musculoskeletal, 88 cardiovascular and 230 others less frequently represented damages. After adjusting for potential confounders at any time during follow-up, a lower risk of renal damage (HR 0.652; 95% CI: 0.472-0.901) and borderline for neuropsychiatric damage (HR 0.701, 95% CI: 0.481-1.024) was found. Conclusion: In the GLADEL cohort, after adjustment for possible confounding factors, AM were independently associated with a reduced risk of renal damage accrual.- The influence of obesity on hydroxychloroquine blood levels in lupus nephritis patients(2021) PEDROSA, Tatiana; KUPA, Leonard de Vinci Kanda; PASOTO, Sandra Gofinet; AIKAWA, Nadia Emi; BORBA, Eduardo Ferreira; DUARTE, Nilo J. C.; LEON, Elaine Pires; SILVA, Clovis Artur; BONFA, EloisaIntroduction In 2016 the American Academy of Ophthalmology(2016-AAO) recommended a maximum daily HCQ use of 5.0 mg/kg real body weight(RBW) taking into consideration minimizing eye toxicity. Retinopathy in systemic lupus erythematosus(SLE) patients was recently associated with obesity and this condition is progressively more common in these patients. However, the impact of obesity in HCQ blood levels remains controversial. Objective To determine if the 2016-AAO recommendation based on RBW with and without maximum daily dose restriction results in adequate and safe blood levels in obese lupus nephritis(LN) patients. Methods A cross-sectional study was performed with 108 LN patients under the prescribed 2016-AAO dose for at least 3 months. LN patients were assessed for demographic characteristics, body mass index(BMI), disease parameters, HCQ dose, concomitant treatment and HCQ blood levels measured by liquid chromatography-tandem mass spectrometry. Obesity was defined as BMI >= 30kg/m(2). Results Obesity was identified in 35/108(32%) LN patients. The calculation of HCQ daily dosage revealed that obese patients were under a lower prescribed daily dose according to the real body weight (RBW) [4.4(2.9-5.4) vs. 4.9(4-5.5)mg/Kg/day, p < 0.001] due to the maximum limit used. Regardless of that the median of HCQ blood levels was significantly higher in obese compared to non-obese patients (1562 +/- 548.6 vs. 1208 +/- 448.9 ng/mL, p = 0.002). Further analysis of patients under the 20016-AAO recommendation by RBW without the restriction of maximum daily dose confirmed that in spite of comparable daily dose in 14 obese patients and 61 non-obese patients [4.8 (4.5-5.4) vs. 5.0(4.5-5.5) mg/kg, p = 0.312], the median of HCQ blood levels was significantly higher in obese patients than in non-obese (1734 +/- 457.3 vs. 1189 +/- 449.4 ng/mL, p < 0.001). Conclusion Obese patients under the 2016-AAO prescribed dose of HCQ based on RBW with and without maximum daily dose restriction have a very high HCQ blood levels compared to non-obese patients, with a potential increased risk of ocular toxicity. The use of 2016-AAO dose of HCQ according to the ideal body weight for this group of patients should be considered.Clinicaltrials.gov #NCT0312243.