Publications by authors named "Rosa Maria Rodrigues Pereira"

104 Publications

Hydroxychloroquine blood levels predicts flare in childhood-onset lupus nephritis.

Lupus 2021 Dec 29:9612033211062515. Epub 2021 Dec 29.

Rheumatology Unit, Instituto da Criança da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Objective: Low hydroxychloroquine (HCQ) blood levels are predictors of flare in adult lupus. Childhood-onset systemic lupus erythematosus (cSLE) has high morbidity with renal involvement in up to 80% of cases. The aim of this study is to determine the HCQ cut-off levels which predicts flare in childhood-onset lupus nephritis (LN).

Methods: Sixty LN patients on HCQ use for at least 6-months were prospectively evaluated at baseline (BL) and about 6-months later for cSLE flare and HCQ blood levels (ng/mL) measured by liquid chromatography-tandem mass spectrometry.

Results: There were 19 patients (32%) with flare, during the study with median SLEDAI increase of 4 (0-8). Median (IQR) BL HCQ levels of the flare group were lower compared to stable patients [557.5 (68.6-980.3) vs. 1061.9 (534.8-1590.0 ng/mL); =0.012]. ROC curve analysis demonstrated that HCQ levels≤1075 ng/mL were associated with a 5.08 (95%CI 1.28-20.13; =0.021) times increased risk of flare. Six-month HCQ levels revealed that most patients 24/54 (44%) had persistently low levels (≤1075) during follow-up. Among those, 11/24 (46%) had flare. Multiple logistic regression analysis including prednisone use, baseline SLEDAI-2K, adherence based on pharmacy refill and BL HCQ blood levels as possible predictors of flare revealed that only HCQ blood level was independently associated with flare (OR 0.999, 95%CI 0.998-1.0, =0.013).

Conclusions: We demonstrated that HCQ blood cut-off level under 1075 ng/mL predicts flare in childhood-onset LN patients under prescribed HCQ dose of 4.0-5.5 mg/kg/day. We further observed that most of these patients have compliance issues reinforcing the need for a close surveillance particularly in those with levels below the defined cut-off.
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http://dx.doi.org/10.1177/09612033211062515DOI Listing
December 2021

Effect of a Single High-Dose Vitamin D3 on the Length of Hospital Stay of Severely 25-Hydroxyvitamin D-Deficient Patients with COVID-19.

Clinics (Sao Paulo) 2021;76:e3549. Epub 2021 Nov 26.

Divisao de Reumatologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR.

Objectives: In this ancillary analysis of a multicenter, double-blinded, randomized, placebo-controlled trial, we investigated the effect of a single high dose of vitamin D3 on the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19.

Methods: The primary outcome was length of hospital stay, defined as the total number of days that patients remained hospitalized from the date of randomization until the date of hospital discharge. Secondary outcomes included serum levels of 25-hydroxyvitamin D, mortality during hospitalization, number of patients admitted to the intensive care unit, and number of patients who required mechanical ventilation. ClinicalTrials.gov: NCT04449718.

Results: Thirty-two patients were included in the study. The mean (SD) age was 58.5 (15.6) years, body mass index was 30.8 (8.6) kg/m2, and 25-hydroxyvitamin D level was 7.8 (1.6) ng/mL. No significant difference was observed in the median interquartile range of length of hospital stay between the vitamin D3 group (6.0 [4.0-18.0] days) versus placebo (9.5 [6.3-15.5] days) (log-rank p=0.74; hazard ratio, 1.13 [95% confidence interval (CI), 0.53-2.40]; p=0.76). Vitamin D3 significantly increased serum 25-hydroxyvitamin D levels in the vitamin D3 group compared with that in the placebo group (between-group difference, 23.9 ng/mL [95% CI, 17.7-30.1]; p<0.001).

Conclusions: A dose of 200.000 IU of vitamin D3 did not significantly reduce the length of hospital stay of patients with severe 25-hydroxyvitamin D deficiency and COVID-19.
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http://dx.doi.org/10.6061/clinics/2021/e3549DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8595591PMC
December 2021

Immunogenicity and safety of primary fractional-dose yellow fever vaccine in autoimmune rheumatic diseases.

PLoS Negl Trop Dis 2021 11 29;15(11):e0010002. Epub 2021 Nov 29.

Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil.

Background: Brazil faced a yellow fever(YF) outbreak in 2016-2018 and vaccination was considered for autoimmune rheumatic disease patients(ARD) with low immunosuppression due to YF high mortality.

Objective: This study aimed to evaluate, prospectively for the first time, the short-term immunogenicity of the fractional YF vaccine(YFV) immunization in ARD patients with low immunossupression.

Methods And Results: A total of 318 participants(159 ARD and 159 age- and sex-matched healthy controls) were vaccinated with the fractional-dose(one fifth) of 17DD-YFV. All subjects were evaluated at entry(D0), D5, D10, and D30 post-vaccination for clinical/laboratory and disease activity parameters for ARD patients. Post-vaccination seroconversion rate(83.7%vs.96.6%, p = 0.0006) and geometric mean titers(GMT) of neutralizing antibodies[1143.7 (95%CI 1012.3-1292.2) vs.731 (95%CI 593.6-900.2), p<0.001] were significantly lower in ARD compared to controls. A lower positivity rate of viremia was also identified for ARD patients compared to controls at D5 (53%vs.70%, p = 0.005) and the levels persisted in D10 for patients and reduced for controls(51%vs.19%, p = 0.0001). The viremia was the only variable associated with seroconvertion. No serious adverse events were reported. ARD disease activity parameters remained stable at D30(p>0.05).

Conclusion: Fractional-dose 17DD-YF vaccine in ARD patients resulted in a high rate of seroconversion rate(>80%) but lower than controls, with a longer but less intense viremia. This vaccine was immunogenic, safe and did not induce flares in ARD under low immunosuppression and may be indicated in YF outbreak situations and for patients who live or travel to endemic areas.

Trial Registration: This clinical trial was registered with Clinicaltrials.gov (#NCT03430388).
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http://dx.doi.org/10.1371/journal.pntd.0010002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8659329PMC
November 2021

Home-based exercise program for adolescents with juvenile dermatomyositis quarantined during COVID-19 pandemic: a mixed methods study.

Pediatr Rheumatol Online J 2021 Nov 13;19(1):159. Epub 2021 Nov 13.

Applied Physiology and Nutrition Research Group, School of Physical Education and Sport, Universidade de São Paulo, São Paulo, Brazil.

Background: Exercise has been suggested to prevent deterioration of health-related quality of life (HRQL) and overall health in pediatric rheumatologic diseases during the COVID-19 pandemic. Herein we describe the effects of a 12-week, home-based, exercise program on overall health and quality of life among quarantined patients with juvenile dermatomyositis (JDM).

Method: This prospective, quasi-experimental, mixed methods (qualitative and quantitative) study was conducted between July and December 2020, during the most restricted period of COVID-19 pandemic in Brazil. The home-based exercise program consisted of a 12-week, three-times-a-week, aerobic and strengthening (bodyweight) training program. Qualitative data were systematically evaluated. Strengths and Difficulties Questionnaire (SDQ), Pediatric Quality of Life Inventory (PedsQOL) and Pittsburgh Sleep Quality Index (PSQI) evaluate symptoms of mental health disorder, HRQL, and quality of sleep.

Findings: 11 patients (out of 27) met the inclusion criteria (91% female; mean ± SD age: 13.5 ± 3.2 years). Adherence to the intervention was 72.6%. Barriers to exercise involved poor internet connectivity, excessive weekly sessions, and other commitments. Even though not statistically significant, Self-report SDQ subscales Total Difficulties Score, Emotional Problems Score, and PedsQOL School Functioning Score improved after intervention (- 2.4; 95%confidence interval [CI] -5.1; 0.2, p = 0.06; - 1.0; 95%CI -2.2; 0.2, p = 0.09 and; 11.7; 95%CI -2.5; 25.8, p = 0.09, respectively). Remaining SDQ subscales were not altered. Six themes emerged from patients' and parents' comments (qualitative results). Patients engaged in exercise reported other health-related benefits including increased motivation, concentration and strength.

Interpretation: A home-based exercise program was associated with qualitative perceptions of improvements in overall health and HRQL by quarantined adolescents with JDM during COVID-19 pandemic. Lessons from this trial may help developing interventions focused on tackling physical inactivity in JDM.
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http://dx.doi.org/10.1186/s12969-021-00646-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8590116PMC
November 2021

A retracted diagnosis-when liver capsule retraction is not what it seems.

Clin Res Hepatol Gastroenterol 2021 Oct 29;46(2):101823. Epub 2021 Oct 29.

Rheumatology Division, Faculdade de Medicina (FMUSP), Universidade de Sao Paulo, Av. Dr. Arnaldo, 455, 3º andar-sala 3193, Cerqueira César, São The patient had normal liver enzymes.Paulo, SP 01246-903, Brazil.

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http://dx.doi.org/10.1016/j.clinre.2021.101823DOI Listing
October 2021

Physical and mental health impacts during COVID-19 quarantine in adolescents with preexisting chronic immunocompromised conditions.

J Pediatr (Rio J) 2021 Oct 12. Epub 2021 Oct 12.

Universidade de São Paulo (HCFMUSP), Faculdade de Medicina, Hospital das Clínicas, Instituto da Criança e do Adolescente, São Paulo, SP, Brazil; Universidade de São Paulo (HCFMUSP), Faculdade de Medicina, Hospital das Clínicas, Divisão de Reumatologia, São Paulo, SP, Brazil. Electronic address:

Objective: To evaluate physical and mental health indicators in adolescents with preexisting chronic immunocompromised conditions during coronavirus disease 2019 (COVID-19) quarantine.

Methods: A cross-sectional study included 355 adolescents with chronic conditions and 111 healthy adolescents. An online self-rated survey was used to investigate socio-demographic features, healthcare routine, and the quarantine impact on physical and mental health. The validated self-reported version of the Strengths and Difficulties Questionnaire (SDQ) was also applied.

Results: The median of age [14 (10-18) vs. 15 (10-18) years, p = 0.733] and frequencies of female (61% vs. 60%, p = 0.970) were similar between adolescents with preexisting chronic conditions and healthy adolescents during quarantine of COVID-19 pandemic. The frequencies of abnormal total difficulties score of SDQ were similar in patients and controls (30% vs. 31%, p = 0.775). Logistic regression analysis showed that being female (OR = 1.965; 95% CI = 1.091-3.541, p = 0.024), fear of underlying disease activity/complication (OR = 1.009; 95%CI = 1.001-1.018, p = 0.030) were associated with severe psychosocial dysfunction in adolescents with chronic conditions, whereas school homework (OR = 0.449; 95% CI = 0.206-0.981, p = 0.045) and physical activity (OR = 0.990; 95% CI = 0.981-0.999, p = 0.030) were protective factors. Further analysis of patients with chronic immunocompromised conditions and previous diagnosis of mental disorders (9%) compared with patients without diagnosis showed higher median of total difficulties score (p = 0.001), emotional (p = 0.005), conduct (p = 0.007), peer problems (p = 0.001) and hyperactivity (p = 0.034) in the former group.

Conclusion: Adolescents with preexisting chronic immunocompromised conditions during COVID-19 quarantine were not at higher risk of adverse health indicators. Being female, fear of underlying disease activity/complication, and household members working outside of the home were relevant issues for adolescents with preexisting chronic conditions. This study reinforces the need to establish mental health strategies for teens with chronic conditions, particularly during the pandemic.
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http://dx.doi.org/10.1016/j.jped.2021.09.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8506207PMC
October 2021

Efficacy of platelet-rich plasma and plasma for symptomatic treatment of knee osteoarthritis: a double-blinded placebo-controlled randomized clinical trial.

BMC Musculoskelet Disord 2021 Sep 24;22(1):822. Epub 2021 Sep 24.

Rheumatology Division, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Background: Platelet-rich plasma (PRP) has a still conflicting efficacy for knee osteoarthritis (KOA) and might be a minimally invasive and safe treatment alternative. The potential benefit of only plasma (non-enriched) has never been investigated. Our aim was to evaluate the efficacy of intra-articular platelet-rich plasma (PRP) and plasma to improve pain and function in participants with KOA over 24 weeks.

Methods: Randomized, double-blind, placebo-controlled trial with 3 groups (n = 62): PRP (n = 20), plasma (n = 21) and saline (n = 21). Two ultrasound-guided knee injections were performed with a 2-week interval. The primary outcome was visual analog scale 0-10 cm (VAS) for overall pain at week 24, with intermediate assessments at weeks 6 and 12. Main secondary outcomes were: KOOS, OMERACT-OARSI criteria and TUGT.

Results: At baseline, 92% of participants were female, with a mean age of 65 years, mean BMI of 28.0 Kg/mand mean VAS pain of 6.2 cm. Change in pain from baseline at week 24 were -2.9 (SD 2.5), -2.4 (SD 2.5) and -3.5 cm (SD 3.3) for PRP, plasma and saline, respectively (p intergroup = 0.499). There were no differences between the three groups at weeks 6 and 12. Similarly, there were no differences between groups regarding secondary outcomes. The PRP group showed higher frequency of adverse events (65% versus 24% and 33% for plasma and saline, respectively, p = 0.02), mostly mild transitory increase in pain.

Conclusions: PRP and plasma were not superior to placebo for pain and function improvement in KOA over 24 weeks. The PRP group had a higher frequency of mild transitory increase in pain.

Trial Registration: ClinicalTrials.gov, NCT03138317 , 03/05/2017.
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http://dx.doi.org/10.1186/s12891-021-04706-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8461850PMC
September 2021

Corrigendum to 'Physical inactivity and sedentary behavior: Overlooked risk factors in autoimmune rheumatic diseases?' [Autoimmunity Reviews 16/7 (2017) 667-674].

Autoimmun Rev 2022 Jan 1;21(1):102928. Epub 2021 Sep 1.

Applied Physiology and Nutrition Research Group, Universidade de Sao Paulo, Av. Professor Mello Moraes, 65 - Cidade Universitaria, Sao Paulo, SP 05508-030, Brazil; Rheumatology Division, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Rua Dr. Ovídio Pires de Campos, 225 - Cerqueira Cesar, Sao Paulo, SP 05403-010, Brazil. Electronic address:

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http://dx.doi.org/10.1016/j.autrev.2021.102928DOI Listing
January 2022

Home-Based Exercise Training in Childhood-Onset Takayasu Arteritis: A Multicenter, Randomized, Controlled Trial.

Front Immunol 2021 28;12:705250. Epub 2021 Jul 28.

Applied Physiology & Nutrition Research Group, Laboratory of Assessment and Conditioning in Rheumatology, Faculdade de Medicina da Universidade de São Paulo (FMUSP), Universidade de Sao Paulo, São Paulo, Brazil.

Introduction: Childhood-onset Takayasu Arteritis (c-TA) is a rare, large-vessel vasculitis seen in children that could predisposing patients to a high risk of mortality. Exercise has the potential to improve overall health in several diseases, but evidence remains scant in c-TA. The main objective of this study was to investigate the safety and potential therapeutic effects of exercise in c-TA.

Methods: This was a 12-week, multicenter, randomized, controlled trial, to test the effects of a home-based, exercise intervention . standard of care in c-TA patients in remission. The primary outcomes were arterial inflammation, assessed by [F] FDG- PET/MRI and systemic inflammatory markers. Secondary outcomes included, physical activity levels, functionality, body composition, disease-related parameters, and quality of life.

Results: Thirty-seven patients were assessed for eligibility, which represents the total number of c-TA patients being followed by the three specialized medical ambulatory services in Sao Paulo. After exclusions, fourteen c-TA patients (71.4% females) aged 12-25 years were randomly allocated into exercised (n=5) and non-exercised groups (n=9). Exercise did not exacerbate arterial inflammation. In fact, exercised patients had a reduction in the frequency of vessel segments with severe inflammation, whereas the non-exercised patients had an opposite response (=0.007). Greater improvements in visceral fat, steps per day, functionality and physical component SF-36 were observed in the exercised patients ( 0.05).

Conclusions: Exercise is safe and may improve visceral fat, physical activity levels, functionality, and physical component SF-36 in c-TA patients. Thus, exercise arises as a novel, evidence-based intervention to improve general health in c-TA.

Clinical Trial Registration: https://www.clinicaltrials.gov/ct2/show/NCT03494062?term=NCT03494062&draw=2&rank=1, identifier NCT03494062.
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http://dx.doi.org/10.3389/fimmu.2021.705250DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355888PMC
December 2021

Decreased Native T1 Values and Impaired Myocardial Contractility in Anabolic Steroid Users.

Int J Sports Med 2021 Aug 2. Epub 2021 Aug 2.

Instituto do Coração (InCor), Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Anabolic androgenic steroid (AAS) abuse leads to myocardial toxicity. Human studies are conflicting about the myocardial fibrosis in AAS users. We evaluated cardiac tissue characterization, left ventricle (LV) function, and cardiac structure by cardiovascular magnetic resonance (CMR). Twenty strength-trained AAS users (AASU) aged 29±5 yr, 20 strength-trained AAS nonusers (AASNU), and 7 sedentary controls (SC) were enrolled. Native T1 mapping, late-gadolinium enhancement (LGE), extracellular volume (ECV), and myocardial strain were evaluated. AASU showed lower Native T1 values than AASNU (888±162 vs. 1020±179 ms p=0.047). Focal myocardial fibrosis was found in 2 AASU. AASU showed lower LV radial strain (30±8 vs. 38±6%, p<0.01), LV circumferential strain (-17±3 vs. -20±2%, p<0.01), and LV global longitudinal strain (-17±3 vs. -20±3%, p<0.01) than AASNU by CMR. By echocardiography, AASU demonstrated lower 4-chamber longitudinal strain than AASNU (-15±g3 vs. -18±2%, p=0.03). ECV was similar among AASU, AASNU, and SC (28±10 vs. 28±7 vs. 30±7%, p=0.93). AASU had higher LV mass index than AASNU and SC (85±14 vs. 64±8 vs. 58±5 g/m, respectively, p<0.01). AAS abuse may be linked to decreased myocardial native T1 values, impaired myocardial contractility, and focal fibrosis. These alterations may be associated with maladaptive cardiac hypertrophy in young AAS users.
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http://dx.doi.org/10.1055/a-1518-7953DOI Listing
August 2021

Increased Serum Interleukin-6 and Tumor Necrosis Factor Alpha Levels in Fabry Disease: Correlation with Disease Burden.

Clinics (Sao Paulo) 2021 16;76:e2643. Epub 2021 Jul 16.

Divisao de Reumatologia, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, BR.

Objectives: 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-1β, and TNF-α 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-α levels were significantly higher in FD patients than in the controls. Patients treated with ERT had higher serum IL-6 and TNF-α levels than those not treated with ERT. There was no difference in the serum IL-1β 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-α (r=0.45, p<0.001).

Conclusion: FD was associated with elevated serum levels of IL-6 and TNF-α in this cohort. The FD patients treated with ERT, particularly, women, exhibited higher levels of serum IL-6 and TNF-α than those not treated with ERT; the serum IL-6 and TNF-α levels were correlated with the MSSI scores reflecting greater disease burden.
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http://dx.doi.org/10.6061/clinics/2021/e2643DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8266164PMC
August 2021

DYNAMIC POSTURAL BALANCE IS MEDIATED BY ANTHROPOMETRY AND BODY COMPOSITION IN OLDER WOMEN.

Acta Ortop Bras 2021 Mar-Apr;29(2):87-91

Universidade São Judas Tadeu, São Paulo, SP, Brazil.

Objective: To investigate the relationship between anthropometry and body composition with dynamic postural balance in elderly women with low bone mineral density (BMD).

Methods: 45 older women (≥ 60 years), low BMD and nutritional diagnosis of low weight to overweight. For the assessment of body composition, Dual energy X-ray emission densitometry and anthropometric examination were used to measure: body mass (kg), height (cm) and BMI (k/m). The assessment of dynamic postural balance was performed by the mini Balance Master Evaluation System clinical test and the computerized Balance Master System test by the Sit to Stand and Step Up/Over tests.

Results: There was a negative correlation between miniBESTest (r = - 0.566; p ≤ 0.001) and time to ascend and descend step (r = - 0.393; p ≤ 0.007) with fat mass, and positive correlation with miniBESTest (r = 0.526; p ≤0.001) and time to go up and down a step with muscle mass (r = 0.297; p ≤ 0.04). As for anthropometric variables, only height showed a positive correlation (r = 0.296; p ≤ 0.04) with the speed in the sit and stand test.

Conclusion: Lean mass reduces postural oscillations; in contrast, fat mass negatively interfered with dynamic postural balance in women with low BMD. Height was related to dynamic postural balance, the taller the elderly, the worse their balance.
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http://dx.doi.org/10.1590/1413-785220212902237921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8244842PMC
May 2020

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.

Int J Rheum Dis 2021 Jul 20;24(7):948-953. Epub 2021 Jun 20.

Bone Metabolism Laboratory, Rheumatology Division, Faculdade de Medicina FMUSP Universidade de Sao Paulo, Sao Paulo, Brazil.

Aim: 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.
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http://dx.doi.org/10.1111/1756-185X.14157DOI Listing
July 2021

Sacubitril/valsartan versus enalapril on exercise capacity in patients with heart failure with reduced ejection fraction: A randomized, double-blind, active-controlled study.

Am Heart J 2021 09 14;239:1-10. Epub 2021 May 14.

Instituto Do Coração (InCor), Hospital Das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Sacubitril/valsartan reduces mortality in patients with heart failure with reduced ejection fraction (HFrEF) when compared with enalapril. However, it is unknown the effect of both treatments on exercise capacity. We compared sacubitril/valsartan versus enalapril in patients with HFrEF based on peak oxygen consumption (VO) and 6-minute walk test (6-MWT).

Methods: We included 52 participants with HFrEF with a left ventricular ejection fraction <40% to receive either sacubitril/valsartan (target dose of 400 mg daily) or enalapril (target dose of 40 mg daily). Peak VO was measured by using cardiopulmonary exercise testing. Six-minute walk test was also performed.

Results: At 12 weeks, the sacubitril/valsartan (mean dose 382.6 ± 57.6 mg daily) group had increased peak VO of 13.1% (19.35 ± 0.99 to 21.89 ± 1.04 mL/kg/min) and enalapril (mean dose 34.4 ± 9.2 mg daily) 5.6% (18.58 ± 1.19 to 19.62 ± 1.25 mL/kg/min). However, no difference was found between groups (P = .332 interaction). At 24 weeks, peak VO increased 13.5% (19.35 ± 0.99 to 21.96 ± 0.98 mL/kg/min) and 12.0% (18.58 ± 1.19 to 20.82 ± 1.18 mL/kg/min) in sacubitril/valsartan (mean dose 400 ± 0 mg daily) and enalapril (mean dose 32.7 ± 11.0 mg daily), respectively. However, no differences were found between groups (P= .332 interaction). At 12 weeks, 6-MWT increased in both groups (sacubitril/valsartan: 459 ± 18 to 488 ± 17 meters [6.3%] and enalapril: 443 ± 22 to 477 ± 21 meters [7.7%]). At 24 weeks, sacubitril/valsartan increased 18.3% from baseline (543 ± 26 meters) and enalapril decreased slightly to 6.8% (473 ± 31 meters), but no differences existed between groups (P= .257 interaction).

Conclusions: Compared to enalapril, sacubitril/valsartan did not substantially improve peak VO or 6-MWT after 12 or 24 weeks in participants with HFrEF. (NEPRIExTol-HF Trial, ClinicalTrials.gov number, NCT03190304).
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http://dx.doi.org/10.1016/j.ahj.2021.05.005DOI Listing
September 2021

Innate and Th1/Th17 adaptive immunity in acute and convalescent Brazilian borreliosis disease.

Braz J Infect Dis 2021 Mar-Apr;25(2):101575. Epub 2021 Apr 10.

Faculdade de Medicina FMUSP, Universidade de São Paulo, São Paulo, SP, Brazil.

Introduction: Brazilian borreliosis (BB) disease is an infectious disease transmitted by ticks that mimics Lyme disease (LD) from the Northern Hemisphere. The BB clinical picture is characterized by a pathognomonic skin lesion (migratory erythema) and joint, neurological, cardiac and psychiatric symptoms. Innate and Th1/Th17 adaptive immunity seem to play an important role in the pathogenesis of Lyme disease.

Objective: The aim of this study was to characterize the role of innate and Th1/Th17 adaptive immunity in BB patients with acute (<3 months) and convalescent (>3 months) disease.

Methods: Fifty BB patients (28 with acute and 22 with convalescent disease) without treatment and 30 healthy subjects were evaluated. Levels of 20 cytokines or chemokines associated with innate and Th1/Th17 adaptive immunity were analyzed using Luminex (Millipore Corp., Billerica, MA).

Results: Overall, BB patients had increased levels of IL-8 (6.29 vs 2.12 p = 0.002) and MIP-1α/CCL3 (5.20 vs 2.06, p = 0.030), associated with innate immunity, and MIP3B/CCL19 (Th1; 297.86 vs 212.41, p = 0.031) and IL-17A (Th17; 3.11 vs 2.20, p = 0.037), associated with adaptive immunity, compared with the levels of healthy controls. When comparing acute BB vs. convalescent BB subjects vs. healthy controls, IL-1β, IL-8 and MIP-1α/CCL3 (innate mediators) levels were highest in patients in the acute phase of disease (p < 0.05). TNF-α was associated with disseminated symptoms and with humoral reactivity against Borrelia burgdorferi. IL-10 was significantly correlated with IL-6 (r = 0.59, p = 0.003), IL-8 (r = 0.51, p < 0.001), MIP-1α/CCL3 (r = 0.42, p < 0.001) and MIP-3β/CCL19 (r = 0.40, p = 0.002) in all BB patients.

Conclusions: This is the first study describing that innate and Th1/Th17 adaptive immunity play a crucial role in BB disease. Furthermore, innate mediators are particularly important in acute BB disease, and TNF-α is associated with evolution of BB symptoms.
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http://dx.doi.org/10.1016/j.bjid.2021.101575DOI Listing
May 2021

Coexistence of Takayasu's Arteritis in Patients with Inflammatory Bowel Diseases.

Gastroenterol Res Pract 2021 12;2021:8831867. Epub 2021 Feb 12.

Department of Gastroenterology and Division of Colorectal Surgery, University of Sao Paulo School of Medicine, São Paulo, Brazil.

Background: Takayasu's arteritis (TA) and inflammatory bowel disease (IBD) are chronic inflammatory granulomatous disorders that have rarely been concomitantly reported in case reports and small case series.

Objective: We report a series of seven cases of TA and IBD association in two referral centers with a comprehensive review of literature.

Methods: We analyzed retrospectively the electronic medical charts of TA-IBD patients at the University Hospital of São Paulo, Brazil, and at the Sheba Medical Center at Tel Aviv University, Israel.

Results: Overall, five patients had Crohn's disease (DC) and two had ulcerative colitis (UC), and they were mostly female and non-Asian. All patients developed IBD first and, subsequently, TA. Two underwent colectomy and one ileocecectomy due to IBD activity, while three required cardiovascular surgery due to TA activity. Most patients are currently in clinical remission of both diseases with conventional drug treatment.

Conclusion: Although the coexistence of TA and IBD is uncommon, both seem to be strongly associated through pathophysiological pathways.
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http://dx.doi.org/10.1155/2021/8831867DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7895552PMC
February 2021

Exercise Enhances the Effect of Bariatric Surgery in Markers of Cardiac Autonomic Function.

Obes Surg 2021 03 27;31(3):1381-1386. Epub 2020 Oct 27.

Applied Physiology & Nutrition Research Group; Laboratory of Assessment and Conditioning in Rheumatology; Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil.

Background: Bariatric surgery improves cardiovascular health, which might be partly ascribed to beneficial alterations in the autonomic nervous system. However, it is currently unknown whether benefits from surgery on cardiac autonomic regulation in post-bariatric patients can be further improved by adjuvant therapies, namely exercise. We investigated the effects of a 6-month exercise training program on cardiac autonomic responses in women undergoing bariatric surgery.

Methods: Sixty-two women eligible for bariatric surgery were randomly allocated to either standard of care (control) or an exercise training intervention. At baseline (PRE) and 3 (POST3) and 9 (POST9) months after surgery, we assessed chronotropic response to exercise (CR%; i.e., percentage change in heart rate from rest to peak exercise) and heart rate recovery (HRR30s, HRR60s, and HRR120s; i.e., decay of heart rate at 30, 60, and 120 s post exercise) after a maximal exercise test.

Results: Between-group absolute changes revealed higher CR% (Δ = 8.56%, CI95% 0.22-19.90, P = 0.04), HRR30s (Δ = 12.98 beat/min, CI95% 4.29-21.67, P = 0.01), HRR60s (Δ = 22.95 beat/min, CI95% 11.72-34.18, P = 0.01), and HRR120s (Δ = 34.54 beat/min, CI95% 19.91-49.17, P < 0.01) in the exercised vs. non-exercised group.

Conclusions: Our findings demonstrate that exercise training enhanced the benefits of bariatric surgery on cardiac autonomic regulation. These results highlight the relevance of exercise training as a treatment for post-bariatric patients, ensuring optimal cardiovascular outcomes.
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http://dx.doi.org/10.1007/s11695-020-05053-7DOI Listing
March 2021

Muscle mass, muscle strength, and functional capacity in patients with heart failure of Chagas disease and other aetiologies.

ESC Heart Fail 2020 10 28;7(5):3086-3094. Epub 2020 Aug 28.

Department of Cardiology and Pneumology, University of Göttingen Medical Center (UMG), Robert-Koch-Strasse 40, Göttingen, D - 37075, Germany.

Aims: Patients with Chagas disease and heart failure (HF) have a poor prognosis similar to that of patients with ischaemic or dilated cardiomyopathy. However, the impact of body composition and muscle strength changes in these aetiologies is still unknown. We aimed to evaluate these parameters across aetiologies in two distinct cohort studies [TESTOsterone-Heart Failure trial (TESTO-HF; Brazil) and Studies Investigating Co-morbidities Aggravating Heart Failure (SICA-HF; Germany)].

Methods And Results: A total of 64 male patients with left ventricular ejection fraction ≤40% were matched for body mass index and New York Heart Association class, including 22 patients with Chagas disease (TESTO-HF; Brazil), and 20 patients with dilated cardiomyopathy and 22 patients with ischaemic heart disease (SICA-HF; Germany). Lean body mass (LBM), appendicular lean mass (ALM), and fat mass were assessed by dual energy X-ray absorptiometry. Sarcopenia was defined as ALM divided by height in metres squared <7.0 kg/m (ALM/height ) and handgrip strength cut-off for men according to the European Working Group on Sarcopenia in Older People. All patients performed maximal cardiopulmonary exercise testing. Forearm blood flow (FBF) was measured by venous occlusion plethysmography. Chagasic and ischaemic patients had lower total fat mass (16.3 ± 8.1 vs. 19.3 ± 8.0 vs. 27.6 ± 9.4 kg; P < 0.05) and reduced peak oxygen consumption (VO ) (1.17 ± 0.36 vs. 1.15 ± 0.36 vs. 1.50 ± 0.45 L/min; P < 0.05) than patients with dilated cardiomyopathy, respectively. Chagasic patients showed a trend towards decreased LBM when compared with ischaemic patients (48.3 ± 7.6 vs. 54.2 ± 6.3 kg; P = 0.09). Chagasic patients showed lower handgrip strength (27 ± 8 vs. 37 ± 11 vs. 36 ± 14 kg; P < 0.05) and FBF (1.84 ± 0.54 vs. 2.75 ± 0.76 vs. 3.42 ± 1.21 mL/min/100 mL; P < 0.01) than ischaemic and dilated cardiomyopathy patients, respectively. There was no statistical difference in the distribution of sarcopenia between groups (P = 0.87). In addition, FBF correlated positively with LBM (r = 0.31; P = 0.012), ALM (r = 0.25; P = 0.046), and handgrip strength (r = 0.36; P = 0.004). In a logistic regression model using peak VO as the dependent variable, haemoglobin (odds ratio, 1.506; 95% confidence interval, 1.043-2.177; P = 0.029) and ALM (odds ratio, 1.179; 95% confidence interval, 1.011-1.374; P = 0.035) were independent predictors for peak VO adjusted by age, left ventricular ejection fraction, New York Heart Association, creatinine, and FBF.

Conclusions: Patients with Chagas disease and HF have decreased fat mass and exhibit reduced peripheral blood flow and impaired muscle strength compared with ischaemic HF patients. In addition, patients with Chagas disease and HF show a tendency to have greater reduction in total LBM, with ALM remaining an independent predictor of reduced functional capacity in these patients. The percentage of patients affected by sarcopenia was equal between groups.
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http://dx.doi.org/10.1002/ehf2.12936DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7524247PMC
October 2020

Long-term evaluation of alendronate treatment on the healing of calvaria bone defects in rats. Biochemical, histological and immunohistochemical analyses.

Arch Oral Biol 2020 Sep 2;117:104779. Epub 2020 Jun 2.

Department of Diagnosis and Surgery, São Paulo State University (UNESP), School of Dentistry, Araraquara Sao Paulo, Brazil; Advanced Research Center in Medicine, Union of the Colleges of the Great Lakes (UNILAGO), São José do Rio Preto, S.P., Brazil.

Objective: The aim of this study was to investigate the effects of the long-term alendronate administration on bone healing in defects created in rat calvarias.

Materials And Methods: Female Wistar rats were randomly distributed into 2 groups: Control (CTL): animals received saline solution once a week; and Alendronate (ALD): rats underwent alendronate treatment (1 mg/kg/weekly). After 120 days from the commencement of treatment, a critical size defect was created in all animals, and 10 animals from each group were sacrificed at 5, 10, 15, 20, 25, 30, 45 and 60-days after the defect creation. On the day of sacrifice, urine and blood samples were collected for determination of the serum levels of bone resorption and formation markers by enzyme linked immunosorbent assay, and the urinary concentration of deoxypyridinoline. Bone mineral density (BMD) in the femurs, descriptive histology, tartrate-resistant acid-phosphatase staining and immunohistochemical analyzes were assessed in the calvaria.

Results: Alendronate group showed increased BMD compared to the test group. The concentration of C-terminal telopeptide of type I collagen and deoxypyridinoline decreased significantly, and the concentration of aminoterminal propeptide of procollagen type 1 and osteocalcin were significant lower in the alendronate group. Immunohistochemical analysis showed significant downregulation in the inducible nitric oxide synthase, runt-related transcription factor-2, cathepsin-K and receptor activator of nuclear factor kappa-B ligand expression in the alendronate group. Vascular endothelial growth factor and osteopontin were upregulated in the later periods of alendronate group.

Conclusions: Our results suggest that long-term treatment with alendronate did not compromise the repair processing of critical size defects in rat.
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http://dx.doi.org/10.1016/j.archoralbio.2020.104779DOI Listing
September 2020

Number of high-protein containing meals correlates with muscle mass in pre-frail and frail elderly.

Eur J Clin Nutr 2020 07 7;74(7):1047-1053. Epub 2020 Apr 7.

Applied Physiology and Nutrition Research Group - School of Physical Education and Sport, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, SP, Brazil.

Background: Aging is accompanied by the inability to optimally respond to anabolic stimulus of nutrition, with consequent loss of muscle mass and functionality. It has been speculated that not only total protein intake, but also the per meal protein dose may have important implications to protein balance and, hence, muscle mass in middle-aged and older adults, but evidence is lacking in a more vulnerable population such as the frail elderly. The aim was to investigate possible associations between total protein intake and its per meal dose with multiple measures of muscle mass, strength, and functionality in a cohort of pre-frail and frail elderly individuals.

Methods: One-hundred-and-fifty-seven pre-frail and frail elderly individuals were assessed for total and per meal protein intake (food diaries), total and appendicular lean mass (DXA), vastus lateralis cross-sectional area [(CSA) B-mode ultrasound], and muscle function [leg-press and bench press 1-RM, timed-stands test, timed-up-and-go test, handgrip, and risk of falls (Biodex Balance System®)].

Results: Protein intake and number of meals with either ≥20 g or ≥30 g of protein were significantly associated (after controlling for confounding factors) with greater total and appendicular lean mass and vastus lateralis CSA.

Conclusions: We found that not only total protein intake but also the number of high-protein containing meals are associated with muscle mass in frail and pre-frail elderly.
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http://dx.doi.org/10.1038/s41430-020-0618-3DOI Listing
July 2020

Android to gynoid fat ratio and its association with functional capacity in male patients with heart failure.

ESC Heart Fail 2020 06 27;7(3):1101-1108. Epub 2020 Mar 27.

Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, Brazil.

Aims: We studied the association between android (A) to gynoid (G) fat ratio and functional capacity (peak VO ) in male patients with heart failure with reduced ejection fraction (HFrEF).

Methods And Results: We enrolled 118 male patients with HFrEF with left ventricular ejection fraction (LVEF) <40%. Body composition (by using dual x-ray absorptiometry) and peak VO (by cardiopulmonary exercise testing) were measured. Sarcopenic obesity was defined according to the Foundation for the National Institutes of Health criteria (FNIH). Blood sample for metabolic and hormonal parameters were measured. Fifteen patients (12.7%) showed sarcopenic obesity (body mass index > 25 kg/m with FNIH index < 0.789). The median A/G ratio was 0.55. A/G ratio > 0.55 was detected in 60 patients. Relative peak VO was lower in patients with A/G ratio > 0.55 than in patients with A/G ratio <0.55 (18.7 ± 5.3 vs. 22.5 ± 6.1 mL/kg/min, P < 0.001). Logistic regression analysis showed A/G ratio >0.55 to be independently associated with reduced peak VO adjusted for age, body mass index, LVEF, presence of sarcopenia, anabolic hormones, and haemoglobin (odds ratio 3.895, 95% confidence interval 1.030-14.730, P = 0.045).

Conclusions: Body fat distribution, particularly android and gynoid fat composition, together with other cofactors, might have an important adverse role on functional capacity in male patients with HFrEF. Future studies are needed to address possible mechanisms involved in this relationship.
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http://dx.doi.org/10.1002/ehf2.12657DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7261564PMC
June 2020

A randomized controlled trial to reduce sedentary time in rheumatoid arthritis: protocol and rationale of the Take a STAND for Health study.

Trials 2020 Feb 12;21(1):171. Epub 2020 Feb 12.

Applied Physiology and Nutrition Research Group; Laboratory of Assessment and Conditioning in Rheumatology; Hospital das Clínicas HCFMUSP, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Av. Dr. Arnaldo, 455, 3° andar, São Paulo, SP, 01246-903, Brazil.

Background: Patients with rheumatoid arthritis spend most of their daily hours in sedentary behavior (sitting), a predisposing factor to poor health-related outcomes and all-cause mortality. Interventions focused on reducing sedentary time could be of novel therapeutic relevance. However, studies addressing this topic remain scarce. We aim to investigate the feasibility and efficacy of a newly developed intervention focused on reducing sedentary time, and potential clinical, physiological, metabolic and molecular effects in rheumatoid arthritis.

Methods: The Take a STAND for Health study is a 4-month, parallel-group, randomized controlled trial, in which postmenopausal patients with rheumatoid arthritis will set individually tailored, progressive goals to replace their sedentary time with standing and light-intensity activities. Patients will be recruited from the Clinical Hospital (School of Medicine, University of Sao Paulo) and will be assessed at baseline and after a 4-month follow up. Outcomes will include objectively measured sedentary behavior (primary outcome) and physical activity levels, clinical parameters, anthropometric parameters and body composition; aerobic fitness, muscle function, blood pressure, cardiovascular autonomic function, vascular function and structure, health-related quality of life, and food intake. Blood and muscle samples will be collected for assessing potential mechanisms, through targeted and non-targeted approaches.

Discussion: Findings will be of scientific and clinical relevance with the potential to inform new prescriptions focused on reducing sedentary behavior, a modifiable risk factor that thus far has been overlooked in patients with rheumatoid arthritis.

Trial Registration: ClinicalTrials.gov, NCT03186924. Registered on 14 June 2017.
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http://dx.doi.org/10.1186/s13063-020-4104-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7014778PMC
February 2020

Epidemiologic Features of Systemic Vasculitides in the Southeast Region of Brazil: Hospital-Based Survey.

J Clin Rheumatol 2020 Oct;26(7S Suppl 2):S106-S110

From the Rheumatology Division, Department of Medicine, Universidade Federal de São Paulo-Escola Paulista de Medicina (Unifesp-EPM).

Background/objective: The epidemiology of vasculitis is variable in different geographic areas, and this issue has not been approached in Brazil yet. The objective of this study was to assess the frequency of vasculitis in specialized centers in Brazil.

Methods: This cross-sectional study was performed in 9 vasculitis outpatient clinics from 6 different states mainly from the Southeast and the Northeast regions of Brazil between 2015 and 2017. Diagnosis and/or classification criteria for Behçet disease (BD), Takayasu arteritis (TA), giant cell arteritis (GCA), polyarteritis nodosa (PAN), granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA), and cryoglobulinemic vasculitis (CryoVas) were used to include patients with at least 6 months of follow-up in this hospital-based survey.

Results: A total of 1233 patients with systemic vasculitis were included from the Southeast region. Behçet disease was the most frequent vasculitis (35.0%) followed by TA (26.4%), GPA (16.2%), PAN (5.8%), GCA (5.8%), EGPA (4.3%), MPA (3.4%), and CryoVas (3.0%). Up to 7.8% of vasculitis patients had a juvenile onset, and the frequency of vasculitides found in children and adolescents was as follows: TA (52.6%), BD (24.7%), GPA (12.4%), and PAN (10.3%). No cases of EGPA, MPA, and CryoVas were diagnosed before the age of 18 years. As a comparator, 103 vasculitis patients were included in the Northeast of Brazil where TA was found in 36.9% and BD in 31.1% of vasculitis cases. No GCA cases were found in the Northeast part of Brazil.

Conclusions: Similar to the epidemiology of vasculitis in Asia, BD and TA are the most frequent vasculitis in Southeastern Brazilian referral centers.
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http://dx.doi.org/10.1097/RHU.0000000000001041DOI Listing
October 2020

Comparison of urinary parameters, biomarkers, and outcome of childhood systemic lupus erythematosus early onset-lupus nephritis.

Adv Rheumatol 2020 02 1;60(1):10. Epub 2020 Feb 1.

Pediatric Rheumatology Division, Faculdade de Medicina de Botucatu, Universidade Estadual Paulista (UNESP), Botucatu, Brazil.

Background: Urinary parameters, anti-dsDNA antibodies and complement tests were explored in patients with childhood-Systemic Lupus Erythematosus (cSLE) early-onset lupus nephritis (ELN) from a large multicenter cohort study.

Methods: Clinical and laboratory features of cSLE cases with kidney involvement at presentation, were reviewed. Disease activity parameters including SLEDAI-2 K scores and major organ involvement at onset and follow up, with accrued damage scored by SLICC-DI, during last follow up, were compared with those without kidney involvement. Autoantibodies, renal function and complement tests were determined by standard methods. Subjects were grouped by presence or absence of ELN.

Results: Out of the 846 subjects enrolled, mean age 11.6 (SD 3.6) years; 427 (50.5%) had ELN. There was no significant difference in the ELN proportion, according to onset age, but ELN frequency was significantly higher in non-Caucasians (p = 0.03). Hematuria, pyuria, urine casts, 24-h proteinuria and arterial hypertension at baseline, all had significant association with ELN outcome (p < 0.001). With a similar follow up time, there were significantly higher SLICC-DI damage scores during last follow up visit (p = 0.004) and also higher death rates (p < 0.0001) in those with ELN. Low C3 (chi-square test, p = 0.01), but not C3 levels associated significantly with ELN. High anti-dsDNA antibody levels were associated with ELN (p < 0.0001), but anti-Sm, anti-RNP, anti-Ro, anti-La antibodies were not associated. Low C4, C4 levels, low CH50 and CH50 values had no significant association. High erythrocyte sedimentation rate (ESR) was associated with the absence of ELN (p = 0.02).

Conclusion: The frequency of ELN was 50%, resulting in higher morbidity and mortality compared to those without ELN. The urinary parameters, positive anti-dsDNA and low C3 are reliable for discriminating ELN.
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http://dx.doi.org/10.1186/s42358-020-0114-4DOI Listing
February 2020

A High-Intensity Exercise Intervention Improves Older Women Lumbar Spine and Distal Tibia Bone Microstructure and Function: A 20-Week Randomized Controlled Trial.

IEEE J Transl Eng Health Med 2020 3;8:2100108. Epub 2020 Jan 3.

1Laboratory of Biomechanics, School of Physical Education and SportsUniversity of São PauloSão Paulo05508-220Brazil.

The effects of ageing on bone can be mitigated with different types of physical training, such as power training. However, stimuli that combine increasing external and internal loads concomitantly may improve bone quality. The goal of this study was to assess the efficacy of a combined power and plyometric training on lumbar spine and distal tibia microstructure and function. 38 sedentary elderly women between 60 and 70 years were randomly allocated in experimental (N = 21) and control group (N = 17). The effects of the 20-week protocol on lumbar spine microstructure and tibia microstructure and function were assessed by trabecular bone score (TBS), high resolution peripheral quantitative computed tomography (HR-pQCT) and microfinite element analysis. when compared to the effects found in the control group, the experimental group showed significant improvements in lumbar spine TBS (Hedges' g = 0.77); and in distal tibia trabecular thickness (g = 0.82) and trabecular bone mineral density (g=0.63). our findings underscore the effectiveness of the proposed intervention, suggesting it as a new strategy to slow down and even reverse the structural and functional losses in the skeletal system due to ageing.
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http://dx.doi.org/10.1109/JTEHM.2019.2963189DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6964965PMC
January 2020

Higher rate of rheumatic manifestations and delay in diagnosis in Brazilian Fabry disease patients.

Adv Rheumatol 2020 01 6;60(1). Epub 2020 Jan 6.

Rheumatology Division, Faculdade de Medicina da Universidade de São, Paulo, São Paulo, Brazil.

Background: Fabry disease (FD) is an X-linked lysosomal disorder due to mutations in the GLA gene resulting in defective enzyme alpha-galactosidase A. FD patients are frequently misdiagnosed, commonly for rheumatic diseases. Determining pathogenicity of a mutation depends of in silico predictions but mostly on available clinical information and interpretation may change in light of evolving knowledge. Similar signs and symptoms in carriers of GLA gene genetic variants of unknown significance or of benign variants may hamper diagnosis. This study reviews rheumatic and immune-mediated manifestations in a cohort of Brazilian FD patients with classic mutations and also in subjects with GLA gene A143T and R118C mutations. Misdiagnoses, time to correct diagnosis or determination of GLA gene status, time to treatment initiation and reasons for treatment prescription in A143T and R118C subjects are reviewed.

Methods: Genotype confirmed classic FD patients (n = 37) and subjects with GLA gene mutations A143T and R118C (n = 19) were referred for assessment. Subjects with R118C and A143T mutations had been previously identified during screening procedures at hemodialysis units. All patients were interviewed and examined by a rheumatologist with previous knowledge of disease and/or mutation status. A structured tool developed by the authors was used to cover all aspects of FD and of common rheumatic conditions. All available laboratory and imaging data were reviewed.

Results: Thirty-seven consecutive FD patients were interviewed - 16 male / 21 female (mean age: 43.1 years) and 19 consecutive subjects with GLA gene mutations R118C and A143T were evaluated - 8 male / 11 female (mean age: 39.6 years); 15 [R118C] / 4 [A143T]. Misdiagnosis in FD patients occurred in 11 males (68.8%) and 13 females (61.9%) of which 10 males and 9 females were previously diagnosed with one or more rheumatic conditions, most frequently rheumatic fever or "rheumatism" (unspecified rheumatic disorder). Median time for diagnosis after symptom onset was 16 years (range, 0-52 years). Twenty-two patients were treated with enzyme replacement therapy (ERT) - 13 male and 9 female. Median time to ERT initiation after FD diagnosis was 0.5 years (range, 0-15 years). Rheumatic manifestations occurred in 68.4% of R118C and A143T subjects. Two subjects had been prescribed ERT because of renal disease [R118C] and neuropsychiatric symptoms [A143T].

Conclusion: Misdiagnoses occurred in 64.8% of FD patients, most frequently for rheumatic conditions. Median time for correct diagnosis was 16 years. Rheumatic manifestations are also frequent in subjects with GLA gene R118C and A143T mutations. These results reinforce the need to raise awareness and increase knowledge about Fabry disease among physicians, notably rheumatologists, who definitely have a role in identifying patients and determining disease burden. Decision to start treatment should consider expert opinion and follow local guidelines.
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http://dx.doi.org/10.1186/s42358-019-0111-7DOI Listing
January 2020

Discriminating sarcopenia in overweight/obese male patients with heart failure: the influence of body mass index.

ESC Heart Fail 2020 02 26;7(1):84-91. Epub 2019 Dec 26.

Heart Institute (InCor), University of São Paulo Medical School, Av. Dr. Enéas de Carvalho Aguiar, 44-Cerqueira César, CEP, 05403-90(4), São Paulo, Brazil.

Aims: The definition of sarcopenia based on appendicular lean mass/height (ALM/height ) is often used, although it can underestimate the prevalence of sarcopenia in overweight/obese patients with heart failure. Therefore, new methods have been proposed to overcome this limitation. We aimed to evaluate the prevalence of sarcopenia by three methods and compare body composition in this population.

Methods And Results: We enrolled 168 male patients with heart failure (left ventricular ejection fraction <40%). Sixty-six patients (39.3%) were identified with sarcopenia by at least one method. The lower 20th percentile defined as the cut-off point for sarcopenia was 7.03 kg/m , -2.32 and 0.76 for Baumgartner's (20.8%), Newman's (21.4%), and Studenski's methods (21.4%), respectively. Patients with body mass index (BMI) <25 kg/m were more likely to be identified by Baumgartner's than Studenski's method (P < 0.001). However, in patients with BMI ≥ 25 kg/m , Studenski's and Newman's methods were more likely to detect sarcopenia than Baumgartner's method (both P < 0.005). Patients were further divided into three subgroups: (i) patients classified in all indexes (n = 8), (ii) patients classified in Baumgartner's (sarcopenic; n = 27), and (iii) patients classified in both Newman's and Studenski's methods (sarcopenic obesity; n = 31). Comparing body composition among groups, all sarcopenic groups presented lower total lean mass compared with non-sarcopenic patients, whereas sarcopenic obese patients had higher total lean mass than lean sarcopenic patients.

Conclusions: Our results demonstrate that the prevalence of sarcopenia in overweight/obese patients is similar to lean sarcopenic patients when other methods are considered. In patients with higher BMI, Studenski's method seems to be more feasible to detect sarcopenia.
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http://dx.doi.org/10.1002/ehf2.12545DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7083394PMC
February 2020

Depression, sleep disturbances, pain, disability and quality of LIFE in Brazilian Fabry disease patients.

Mol Genet Metab Rep 2020 Mar 2;22:100547. Epub 2019 Dec 2.

Rheumatology Division, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.

Background: Fabry disease (FD) is a lysosomal disease in which mutations affect the gene located on the X chromosome. The defective product, the enzyme alpha-galactosidase A, causes accumulation of substrate and contributes to the disruption of cell function in several organs, with variable severity and consequent damage of tissue or organ function. Patient reported outcomes (PROs) enable patients to provide information regarding the consequences of their disease and its treatment and are often recognized as the most important outcomes for them.

Objectives: To evaluate pain, depression, sleep disturbances, disability and disease impact on quality of life in a cohort of Brazilian FD patients and compare between groups stratified by the Mainz Symptom Severity Index (MSSI) Methods: Thirty-seven genotype confirmed classic FD patients - 16 male and 21 female - (mutations: C142R, A156D, L180F, R227X, W262X, G271A, P293S, Y264SX) were evaluated and answered the following questionnaires: Brief Pain Inventory (BPI), Hamilton Depression Rating Scale (HAM-D), Pittsburgh Sleep Quality Index (PSQI), Health Assessment Questionnaire Disability Index (HAQ-DI), Short-Form Health Survey 36 (SF-36).

Results: In FD patients, mean ± SD BPI severity result was 2.78 ± 2.66 for severe; 2.80 ± 2.55 for moderate and 1.55 ± 2.38 for mild severity patients. Mean ± SD BPI interference result was 2.55 ± 2.44 for severe; 2.80 ± 3.18 for moderate and 1.36 ± 2.83 for mild patients. BPI severity and interference values correlated with MSSI scores ( = 0.24;  < .001 /  = 0.25; p < .001). Application of HAM-D indicated depression in 21 patients (56.8%). HAM-D results had positive correlation with MSSI values ( = 0.21;  < .001), with BPI severity ( = 0.54;  < .001) and interference ( = 0.65; p < .001). PSQI depicted sleep disturbances in 22 patients (59.5%). PSQI values correlated with MSSI values ( = 0.25;  < .001), with HAM-D results ( = 0.65;  < .001) and BPI severity ( = 0.47;  < .001) and interference ( = 0.66;  < .001). Mean HAQ-DI result was 0.490 for severe; 0.274 for moderate and 0.157 for mild severity patients.

Conclusions: Depression, sleep disturbances and disability were under-recognized in FD patients. HAQ-DI revealed worse disability according to MSSI severity status. The lowest raw scores from the SF-36 questionnaire were for the domains general health perception and physical role functioning. Standardized assessments should be routine care and started as early as diagnosis of Fabry disease is made.
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http://dx.doi.org/10.1016/j.ymgmr.2019.100547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6909105PMC
March 2020

Intramastoid Phosphaturic Mesenchymal Tumor Causing Hypophosphatemic Osteomalacia Detected on Ga-DOTATATE PET/CT But Not on Tc-Sestamibi and F-FDG Scans.

Nucl Med Mol Imaging 2019 Dec 14;53(6):436-441. Epub 2019 Nov 14.

1Rheumatology Division, Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo, São Paulo, SP Brazil.

Ga-DOTATATE uptake in mesenchymal tumors causing hypophosphatemic osteomalacia has been recently described. Herein, we present a case of Ga-DOTATATE uptake in an intramastoid phosphaturic mesenchymal tumor that had not been depicted in previous Tc-Sestamibi and F-FDG scans. The lesion was surgically removed and the phosphorus level increased to the normal range.
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http://dx.doi.org/10.1007/s13139-019-00616-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6898704PMC
December 2019

Telmisartan use in rats with preexisting osteoporotics bone disorders increases bone microarchitecture alterations via PPARγ.

Life Sci 2019 Nov 10;237:116890. Epub 2019 Oct 10.

Department of Physiological Sciences, Federal University of Espirito Santo, Vitória, ES, Brazil. Electronic address:

Aims: Telmisartan (TEL), an angiotensin II type I receptor blocker and PPARγ partial agonist, has been used for to treat hypertension. It is known that PPARγ activation induces bone loss. Therefore, we evaluate the effects of telmisartan on PPARγ protein expression, biomechanics, density and bone microarchitecture of femurs and lumbar vertebrae in SHR ovariectomized animals, a model of hypertension in which preexisting bone impairment has been demonstrated.

Main Methods: SHR females (3 months old) were distributed into four groups: sham (S), sham + TEL (ST), OVX (C) and OVX + TEL (CT). TEL (5 mg/kg/day) or vehicle were administered according to the groups. After the protocol, blood pressure was measured and density, microarchitecture and biomechanics of bone were analyzed. Western blotting analysis was performed to evaluate PPARγ protein expression in the bones.

Key Findings: Castration induced a deleterious effect on mineral density and trabecular parameters, with telmisartan enhancing such effects. Telmisartan increased PPARγ levels, which were at their highest when the treatment was combined with castration. As to biomechanical properties, telmisartan reduced the stiffness in the castration group (CT vs. S or C group), as well as resilience and failure load in ST group (vs. all others groups).

Significance: These results demonstrated that telmisartan compromised bone density and microarchitecture in animals that shows preexisting osteoporotic bone disorders, probably via mechanisms associated with increased PPARγ. If this translates to humans, a need for greater caution in the use of telmisartan by patients that have preexisting bone problems, as in the postmenopausal period, may be in order.
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http://dx.doi.org/10.1016/j.lfs.2019.116890DOI Listing
November 2019
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