VALERIA DE FALCO CAPARBO
Projetos de Pesquisa
Unidades Organizacionais
Departamento de Clínica Médica, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
Instituto Central, Hospital das Clínicas, Faculdade de Medicina
LIM/17 - Laboratório de Investigação em Reumatologia, Hospital das Clínicas, Faculdade de Medicina
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- Visceral adipose tissue in granulomatosis with polyangiitis: association with disease activity parameters(2021) FURLAM, Pedro L.; PEREZ, Mariana O.; FRANCO, Andre S.; CAPARBO, Valeria F.; SHINJO, Samuel K.; PEREIRA, Rosa M. R.Objective To assess the body composition (BC) of patients with granulomatosis with polyangiitis (GPA) compared to healthy controls, emphasizing visceral adipose tissue (VAT) and associated BC parameters with disease activity, the damage index, and inflammatory parameters in patients with GPA. Methods This study was conducted in 43 patients with GPA and 43 healthy controls matched by sex, age, and body mass index (BMI). BC was analyzed using dual-energy X-ray absorptiometry (DXA). The fat mass parameters evaluated were total fat mass (FM), adiposity (%), the fat mass index (FMI: fat mass/ht(2)), and VAT (g, cm(2), cm(3)). Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). Damage was assessed by the Vasculitis Damage Index (VDI). C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured. Results Comparing patients with GPA with healthy controls, patients had a significantly greater VAT (VAT in g: 685.81 +/- 306.10 vs. 581.21 +/- 235.57, p = 0.04; VAT in cm(2): 142.23 +/- 63.48 vs. 119.84 +/- 49.54, p = 0.03; VAT in cm(3): 741.33 +/- 330.97 vs. 628.44 +/- 254.66, p = 0.04). Patients with higher VAT (>= 768 g) had an increased value of ESR (22.77 +/- 26.79 vs. 11.57 +/- 11.30 mm/1st hour, p = 0.04) and an increased value of BVAS (3.18 +/- 4.15 vs. 0.90 +/- 1.70, p = 0.01) when compared to patients with less VAT (< 768 g). Conclusion Patients with GPA have altered BC compared to healthy controls. Moreover, higher VAT was associated with disease activity and higher inflammatory markers, suggesting a relationship between GPA activity and adiposity parameters.
conferenceObject Bone Erosions and Osteophytes in Premenopausal Women with Long-standing Rheumatoid Arthritis: Association with Systemic Bone Involvement Using HR-pQCT(2021) PEREZ, Mariana; FIGUEIREDO, Camille; SALES, Lucas; MEDEIROS-RIBEIRO, Ana; TAKAYAMA, Liliam; DOMICIANO, Diogo; BONFIGLIOLI, Karina; CAPARBO, Valeria; PEREIRA, Rosa- Influence of vitamin D status on hospital length of stay and prognosis in hospitalized patients with moderate to severe COVID-19: a multicenter prospective cohort study(2021) REIS, Bruna Z.; FERNANDES, Alan L.; SALES, Lucas P.; SANTOS, Mayara D.; SANTOS, Caroline C. Dos; PINTO, Ana J.; GOESSLER, Karla F.; FRANCO, Andre S.; DURAN, Camila S. C.; SILVA, Carla B. R.; MACEDO, Marina B.; DALMOLIN, Henrique H. H.; BAGGIO, Janaina; BALBI, Guilherme G. M.; ANTONANGELO, Leila; CAPARBO, Valeria F.; GUALANO, Bruno; MURAI, Igor H.; PEREIRA, Rosa M. R.Background: Vitamin D acts as a mediator in the immune system regulating antiviral mechanisms and inflammatory processes. Vitamin D insufficiency has been suggested as a potential risk factor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, although its impact on the prognosis of hospitalized patients with coronavirus disease 2019 (COVID-19) remains unclear. Objective: This multicenter prospective cohort study was designed to investigate whether serum 25-hydroxyvitamin D [25(OH)D] concentration is associated with hospital length of stay and prognosis in hospitalized patients with COVID-19. Methods: Patients with moderate to severe COVID-19 (n = 220) were recruited from 2 hospitals in Sao Paulo, Brazil. Serum 25(OH)D concentrations were categorized as follows: <10 ng/mL, 10 to <20 ng/mL, 20 to <30 ng/mL, and >= 30 ng/mL, and <10 ng/mL and >= 10 ng/mL. The primary outcome was hospital length of stay and the secondary outcomes were the rate of patients who required invasive mechanical ventilation and mortality. Results: There were no significant differences in hospital length of stay when the 4 25(OH)D categories were compared (P = 0.120). Patients exhibiting 25(OH)D<10 ng/mL showed a trend (P = 0.057) for longer hospital length of stay compared with those with 25(OH)D >= 10 ng/mL [9.0 d (95% CI: 6.4, 11.6 d) vs. 7.0 d (95% CI: 6.6, 7.4 d)]. The multivariable Cox proportional hazard models showed no significant associations between 25(OH)D and primary or secondary outcomes. Conclusions: Among hospitalized patients with moderate to severe COVID-19, those with severe 25(OH)D deficiency (<10 ng/mL) exhibited a trend for longer hospital length of stay compared with patients with higher 25(OH)D concentrations. This association was not significant in the multivariable Cox regression model. Prospective studies should test whether correcting severe 25(OH)D deficiency could improve the prognosis of patients with COVID-19.
- Increased Serum Interleukin-6 and Tumor Necrosis Factor Alpha Levels in Fabry Disease: Correlation with Disease Burden(2021) ROSA, Nilton Salles; BENTO, Judith Campos de Barros; CAPARBO, Valeria de Falco; PEREIRA, Rosa Maria RodriguesOBJECTIVES: Fabry disease (FD) is an X-linked lysosomal disease caused by variants of the GLA gene; the formation of defective alpha-galactosidase A contributes to the accumulation of substrates in several organs. Chronic inflammation is thought to contribute to organ damage in FD patients. METHODS: In total, 36 classic FD patients (15 men/21 women) and 25 healthy controls (20 men/8 women) were assessed. The Mainz Severity Score Index (MSSI) was established after conducting interviews with the patients and chart review. Serum IL-6, IL-1 beta, and TNF-alpha levels were evaluated in both groups. RESULTS: The mean age (years) for FD patients was 43.1 +/- 15.4 and that for the controls was 47.4 +/- 12.2 (p>0.05). Twenty-two patients (59.5%) were treated with enzyme replacement therapy (ERT). Serum IL-6 and TNF-alpha levels were significantly higher in FD patients than in the controls. Patients treated with ERT had higher serum IL-6 and TNF-alpha levels than those not treated with ERT. There was no difference in the serum IL-1 beta levels between patients treated with ERT and those who were not. The MSSI scores in the patients were correlated with serum levels of IL-6 (r=0.60, p<0.001) and TNF-alpha (r=0.45, p<0.001). CONCLUSION: FD was associated with elevated serum levels of IL-6 and TNF-alpha in this cohort. The FD patients treated with ERT, particularly, women, exhibited higher levels of serum IL-6 and TNF-alpha than those not treated with ERT; the serum IL-6 and TNF-alpha levels were correlated with the MSSI scores reflecting greater disease burden.
- Bone erosion in the 2nd metacarpophalangeal head: association with its bone mineral density by HR-pQCT in rheumatoid arthritis patients(2021) FIGUEIREDO, Camille P.; PEREZ, Mariana O.; SALES, Lucas Peixoto; MEDEIROS, Ana Cristina; CAPARBO, Valeria F.; PEREIRA, Rosa M. R.BackgroundRheumatoid arthritis (RA) is a chronic autoimmune disease depicted by synovial inflammation leading to local and systemic bone loss. The aim of this study was to evaluate by a HR-pQCT (High Resolution Peripheral Quantitative Computed Tomography) study which parameters are associated with volume of bone erosions including bone mineral density (BMD) around erosions (VOI 1 to 4=volume of interest), BMD of metacarpophalangeal (MCP) head, BMD of radius, presence of osteophytes and joint space width (JSW).MethodsFifty female RA patients (18-50years) were enrolled in this study. Demographic and disease-specific data, laboratory inflammatory parameters and handgrip test were performed. All patients underwent HR-pQCT of 2nd and 3rd MCP joints and distal radius, according to established protocols. The volume of bone erosions was evaluated by MIAF (Medical Image Analysis Framework) software. Osteophytes were analyzed by manual method.ResultsThe mean of age and disease duration were 40.06.0yrs. and 10.8 +/- 4.8yrs., respectively. According to DAS-28 (Disease Activity Score), 54% (27) of the sample were in remission. However, when SDAI (Simplified Disease Activity Index) was used, only 18% (9) were under remission. The mean of HAQ (Health Assessment Questionnaire), ESR (Erythrocyte sedimentation rate) and CRP (C reactive protein) were 0.9 +/- 0.7, 13.9 +/- 12.2mm and 5.6 +/- 7.5mg/mL, respectively. Forty-six bone erosions (0.9 +/- 1.2 erosion/patient) and 14 osteophytes (0.3 +/- 0.7 osteophyte/patient) were found in 2nd MCP head. The median (IQR-Interquartile range) of volume of erosion and volume of osteophytes were 14.9 (5.7;35.9)mm(3) and 3.1 (2.1, 4.3)mm(3), respectively. The mean of JSW was 80.5 +/- 34.2mm(3). The volume of bone erosions was negatively correlated with BMD of 2nd MCP head, VOI-4 and JSW; and it was positively correlated with osteophytes number. Regarding absence or presence of erosion in 2nd MCP head, a significant difference was found between BMD of MCP head, osteophyte number and JSW. Multiple linear regression analysis showed that only BMD of 2nd MCP head was independently associated with volume of bone erosions.ConclusionBMD of MCP head was independently associated with volume of bone erosion, suggesting that this parameter should be used to analyze and monitoring bone destruction, as well as to evaluate treatment response in RA patients.
- Evaluation of bone erosion in rheumatoid arthritis patients by high-resolution peripheral quantitative computed tomography scans: Comparison between two semi-automated programs in a three-dimensional setting(2021) FIGUEIREDO, Camille Pinto; PEREZ, Mariana Ortega; SALES, Lucas Peixoto; CAPARBO, Valeria de Falco; PEREIRA, Rosa Maria RodriguesAim The aim of this study was to compare OsiriX software with the previous published Medical Image Analysis Framework (MIAF) method to assess the volume of erosion in patients with rheumatoid arthritis (RA). Methods Forty RA patients underwent high-resolution peripheral quantitative computed tomography scans of the second and third metacarpophalangeal joints, and thirty-four patients with any bone erosion were enrolled. Two techniques were applied to erosion evaluation: (a) semi-automated MIAF software, and (b) semi-automated segmentation by free open-source Digital Imaging and Communications in Medicine viewer, OsiriX software. MIAF has been published before, but this is the first time that OsiriX has been used in this way in rheumatology. Bland & Altman plots described agreement between methods. Results Forty-eight erosions from 34 patients were analyzed. Mean age was 40.74 +/- 5.32 years and mean disease duration was 10.68 +/- 4.96 years. Both methods demonstrated a strong correlation regarding erosion volume (r = 0.96, P < 0.001). Median (interquartile range) of erosion volume was 12.14 (4.5-36.07) when MIAF was considered, and 11.80 (3.45-29.42) when the OsiriX tool was used (P = 0.139). MIAF and OsiriX showed good agreement when the Bland & Altman plot was performed. Evaluation by MIAF took 22.69 +/- 6.71 minutes, whereas OsiriX took only 2.62 +/- 1.09 minutes (P < 0.001). Conclusion The three-dimensional segmentation of bone erosions can be done by both MIAF and OsiriX software with good agreement. However, because OsiriX is a widespread tool and faster, its method seems to be more feasible for evaluating peripheral bone damage, especially bone erosions.
- Incidence and risk factors for osteoporotic non-vertebral fracture in low-income community-dwelling elderly: a population-based prospective cohort study in Brazil. The Sao Paulo Ageing and Health (SPAH) study(2021) DOMICIANO, D. S.; MACHADO, L. G.; FIGUEIREDO, C. P.; CAPARBO, V. F.; OLIVEIRA, R. M.; MENEZES, P. R.; PEREIRA, R. M. R.We ascertained the incidence of non-vertebral fracture in a low-income Brazilian elderly cohort. To the best of our knowledge, this is the first population-based study to demonstrate the frequency of non-vertebral fracture in elderly Latin Americans. Age, prior fracture, and bone mineral density (BMD) at hip were predictors of fracture. Introduction No data on incidence of osteoporotic non-vertebral fracture have been reported in low-income countries where the population's aging has been faster. Even in developed countries, currently available prospective data on major fracture rates beyond hip are scarce. The aim of this study is to describe the incidence and risk factors for non-vertebral fracture in a longitudinal prospective Brazilian population-based elderly cohort. Methods Seven hundred seven older adults (449 women, 258 men) were evaluated at baseline and after a mean follow-up of 4.3 +/- 0.8 years. Clinical questionnaire, bone mineral density (BMD), and laboratory tests were performed at baseline. New non-vertebral fracture (hip, proximal humerus, rib, forearm) was determined during the follow-up. Multivariate Poisson regression models were used to identify independent predictors of fracture. Results The age-standardized incidence of non-vertebral fracture was 1562.3/100,000 (1085.7-2248.1/100,000) person-years (pyr) in women and 632.8/100,000 (301.7-1327.3/100,000) in men. Concerning to hip fractures, the incidence was 421.2/100,000 (210.7-842.3/100,000) pyr in women and 89.9/100,000 (12.7-638.5/100,000) in men. In a multivariate analysis, age (RR 2.07, 95% CI 1.13-3.82,p = 0.019, each 10-year increase), prior non-vertebral fracture (RR 3.08, 95% CI 1.36-6.95,p = 0.007), and total hip BMD (RR 1.68, 95% CI 1.11-2.56,p = 0.015, each 1 SD decrease) were predictors of new non-vertebral fracture. In men, fitting a model of risk factors for fracture was prevented by the limited number of events in male sample. Conclusion This is the first population-based study to ascertain the incidence of major non-vertebral fractures in elderly Latin Americans, confirming the high frequency of the disorder. Age, prior fracture, and hip BMD were predictors of the short-term incidence of fracture.
- Effect of a Single High Dose of Vitamin D-3 on Hospital Length of Stay in Patients With Moderate to Severe COVID-19 A Randomized Clinical Trial(2021) MURAI, Igor H.; FERNANDES, Alan L.; SALES, Lucas P.; PINTO, Ana J.; GOESSLER, Karla F.; DURAN, Camila S. C.; SILVA, Carla B. R.; FRANCO, Andre S.; MACEDO, Marina B.; DALMOLIN, Henrique H. H.; BAGGIO, Janaina; BALBI, Guilherme G. M.; REIS, Bruna Z.; ANTONANGELO, Leila; CAPARBO, Valeria F.; GUALANO, Bruno; PEREIRA, Rosa M. R.IMPORTANCE The efficacy of vitamin D-3 supplementation in coronavirus disease 2019 (COVID-19) remains unclear. OBJECTIVE To investigate the effect of a single high dose of vitamin D-3 on hospital length of stay in patients with COVID-19. DESIGN, SETTING, AND PARTICIPANTS This was a multicenter, double-blind, randomized, placebo-controlled trial conducted in 2 sites in Sao Paulo, Brazil. The study included 240 hospitalized patients with COVID-19 who were moderately to severely ill at the time of enrollment from June 2, 2020, to August 27, 2020. The final follow-up was on October 7, 2020. INTERVENTIONS Patients were randomly assigned to receive a single oral dose of 200 000 IU of vitamin D-3 (n = 120) or placebo (n = 120). MAIN OUTCOMES AND MEASURES The primary outcome was length of stay, defined as the time from the date of randomization to hospital discharge. Prespecified secondary outcomes included mortality during hospitalization; the number of patients admitted to the intensive care unit; the number of patients who required mechanical ventilation and the duration of mechanical ventilation; and serum levels of 25-hydroxyvitamin D, total calcium, creatinine, and C-reactive protein. RESULTS Of 240 randomized patients, 237 were included in the primary analysis (mean [SD] age, 56.2 [14.4] years; 104 [43.9%] women; mean [SD] baseline 25-hydroxyvitamin D level, 20.9 [9.2] ng/mL). Median (interquartile range) length of stay was not significantly different between the vitamin D-3 (7.0 [4.0-10.0] days) and placebo groups (7.0 [5.0-13.0] days) (log-rank P = .59; unadjusted hazard ratio for hospital discharge, 1.07 [95% CI, 0.82-1.39]; P = .62). The difference between the vitamin D-3 group and the placebo group was not significant for in-hospital mortality (7.6% vs 5.1%; difference, 2.5% [95% CI, -4.1% to 9.2%]; P = .43), admission to the intensive care unit (16.0% vs 21.2%; difference, -5.2% [95% CI, -15.1% to 4.7%]; P = .30), or need for mechanical ventilation (7.6% vs 14.4%; difference, -6.8% [95% CI, -15.1% to 1.2%]; P = .09). Mean serum levels of 25-hydroxyvitamin D significantly increased after a single dose of vitamin D-3 vs placebo (44.4 ng/mL vs 19.8 ng/mL; difference, 24.1 ng/mL [95% CI, 19.5-28.7]; P < .001). There were no adverse events, but an episode of vomiting was associated with the intervention. CONCLUSIONS AND RELEVANCE Among hospitalized patients with COVID-19, a single high dose of vitamin D-3, compared with placebo, did not significantly reduce hospital length of stay. The findings do not support the use of a high dose of vitamin D-3 for treatment of moderate to severe COVID-19.
- The crosstalk between bone metabolism, lncRNAs, microRNAs and mRNAs in coronary artery calcification(2021) WICIK, Zofia; JALES NETO, Levi H.; GUZMAN, Luis E. F.; PAVAO, Rodrigo; TAKAYAMA, Liliam; CAPARBO, Valeria F.; LOPES, Neuza H. M.; PEREIRA, Alexandre C.; PEREIRA, Rosa M. R.The association between Coronary Artery Calcification (CAC) and osteoporosis has been reported but not fully understood. Therefore, using an original bioinformatic framework we analyzed transcriptomic profiles of 20 elderly women with high CAC score and 31 ageand sex-matching controls from Sao Paulo Ageing & Health study (SPAH). We integrated differentially expressed microRNA (miRNA) and long-noncoding RNA (lncRNA) interactions with coding genes associated with CAC, in the context of bone-metabolism genes mined from literature. Top non-coding regulators of bone metabolism in CAC included miRNA 497-5p/195 and 106a-5p, and lncRNA FAM197Y7. Top non-coding RNAs revealed significant interplay between genes regulating bone metabolism, vascularization-related processes, chromatin organization, prostaglandin and calcium co-signaling. Prostaglandin E2 receptor 3 (PTGER3), Fibroblasts Growth Factor Receptor 1 (FGFR1), and One Cut Homeobox 2 (ONECUT2) were identified as the most susceptible to regulation by the top non-coding RNAs. This study provides a flexible transcriptomic framework including non-coding regulation for biomarker-related studies.