Immunotherapeutic potential of collagen V oral administration in mBSA/CFA-induced arthritis.

We hypothesized that after synovial injury, collagen V (Col V) expose occult antigens, and Col V autoantibodies develop, indicating the loss of immune tolerance against this molecule, thus leading to damage to mesenchymal-derived cells as well as the extracellular matrix in experimental arthritis. Thus, the present study investigated the effects of oral administration of Col V on the synovium after the development of inflammation in mBSA/CFA-induced arthritis. After fourteen days of intraarticular administration of mBSA, 10 male Lewis rats were orally administered Col V (500 µg/300 µL) diluted in 0.01 N acetic acid (IA-Col V group). The arthritic group (IA group, n = 10) received only intraarticular mBSA. An intra-articular saline injection (20 µL) was given to the control group (CT-Col V, n = 5). IA group presented damaged synovia, the expansion of the extracellular matrix by cellular infiltrate, which was characterized by T and B lymphocytes, and fibroblastic infiltration. In contrast, after Col V oral immunotherapy IA-Col V group showed a significant reduction in synovial inflammation and intense expression of IL-10+ and FoxP3+ cells, in addition to a reduction in Col V and an increase in Col I in the synovia compared to those in the IA group. Furthermore, an increase in IL-10 production was detected after IA-Col V group spleen cell stimulation with Col V in vitro. PET imaging did not differ between the groups. The evaluation of oral treatment with Col V, after mBSA/CFA-induced arthritis in rats, protects against inflammation and reduces synovial tissue damage, through modulation of the synovial matrix, showing an immunotherapeutic potential in inhibiting synovitis.

A rare giant geode of humeral head in an uncontrolled rheumatoid arthritis: a case report.

INTRODUCTION: Rheumatoid Arthritis (RA) is a chronic inflammatory disease depicted by peripheral bone erosive damage leading to joint destruction, deformity and functional impairment. Shoulder involvement is less frequent than hands, wrists and feet, and relevant joint damage may be underdiagnosed if a lower threshold for careful analysis of this joint is not settled, especially in uncontrolled disease. CASE REPORT: A 70-year-old male with a difficult-to-manage RA since 2010, presenting severe shoulder arthritis with MRI showing a striking giant geode in the left humeral head. CONCLUSION: An impressive MRI image showing a giant geode in poorly controlled RA should alert rheumatologists to raise suspicion of shoulder involvement for early investigation and treatment.

Robust immunogenicity to the H3N2 component of influenza A vaccine in primary Sjögren syndrome.

INTRODUCTION: Influenza A (H3N2) virus is the major cause of morbidity/mortality due to seasonal influenza over 50 years. Data about the safety/immunogenicity of influenza A/Singapore (H3N2) vaccine are scarce in primary Sjögren syndrome (pSS). METHODS: Twenty-one consecutive pSS patients and 42 HC (healthy control individuals) were immunized with influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus. Rates of SP (seroprotection) and SC (seroconversion), GMT (geometric mean titers), FI-GMT (factor increase in GMT), ESSDAI (EULAR Sjögren's Syndrome Disease Activity Index), and adverse events were appraised before and 4 weeks post-vaccination. RESULTS: pSS and HC had similar mean age (51.2 ± 14.2 vs. 50.6 ± 12.1 years, p = 0.886). Pre-vaccination SP rates were high in pSS and HC (90.5% vs. 71.4%, p = 0.114), and GMT were higher in pSS [80.0 (52.4-160.0) vs. 40.0 (20.0-80.0), p = 0.001]. The percentage of influenza vaccination in the preceding two years was elevated and similar in pSS and HC (94.1% vs. 94.6%, p = 1.000). GMT values augmented in both groups four weeks after vaccination and persisted higher in the first group [160.0 (80.0-320.0) vs. 80.0 (40.0-80.0), p < 0.001] with equivalent FI-GMT [1.4 (1.0-2.8) vs. 1.4 (1.0-2.0), p = 0.410]. Both groups had low and similar SC rates (19.0% vs. 9.5%, p = 0.423). ESSDAI values persisted steadily during the study (p = 0.313). No serious adverse events have occurred. CONCLUSION: The novel demonstration that the influenza A/Singapore (H3N2) vaccine induces a different pattern of immunogenicity from other influenza A constituents in pSS, featured by a desirable high pre- and post-vaccination immunogenicity, is in line with reported differences in immune responses between strains in trivalent vaccines and may be related to pre-existing immunity. CLINICALTRIALS: gov: #NCT03540823. Key Points • This prospective study demonstrated a robust pre- and post-vaccination immunogenicity to influenza A/Singapore/INFIMH-16-0019/2016 (H3N2)-like virus in primary Sjögren's syndrome (pSS). • This high immunogenicity pattern may be related to pre-existing immunization, or else it is related to immunogenicity differences of each strain. • This vaccine had an adequate safety profile in pSS, with no impact on disease activity.

Serum Uric Acid Levels and Subclinical Atherosclerosis: Results From the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil).

High serum uric acid (sUA) has been associated with coronary artery calcium (CAC) and increased carotid intima-media thickness (cIMT) in people at high cardiovascular risk. However, association is unclear in apparently healthy individuals. Our study aims to evaluate association between sUA and subclinical atherosclerosis measures: CAC and increased cIMT, in apparently healthy adults enrolled in ELSA-Brasil. A total of 4096 participants without previous coronary artery disease, stroke, and use of urate-lowering drugs, underwent CAC and cIMT assessment. All analyses were stratified by sex. Serum uric acid categorized by quintiles was the exposure variable. Thorough cardiovascular risk factor evaluation was performed, and association between sUA quintiles and CAC and cIMT was analyzed by linear regression using ln(CAC + 1) and cIMT, both as continuous variables. Median age of the sample was 49.0 (44.0-56.0) years (women: 55.1%; 59.1% were white). Mean values of sUA were 6.5 ± 1.4 mg/dL for men, and 4.9 ± 1.2 mg/dL for women. The highest quintile (Q5) of sUA was independently associated with cIMT in women (beta-coefficient: 0.022; 95% CI: 0.007-0.036; P = 0.003) and men (beta-coefficient: 0.020; 95% CI: 0.002-0.038; P = 0.032). Regarding CAC, no association was found: men's Q5 (beta-coefficient: -0.142; 95% CI: -0.436 to 0.153; P = 0.347) and women's Q5 (beta-coefficient: 0.046; 95% CI: -0.152 to 0.245; P = 0.647). In this cohort, the highest sUA quintiles were independently associated with cIMT in both women and men. No association was found between sUA and the presence of CAC.

Knee osteoarthritis pre-screening questionnaire (KOPS): cross-cultural adaptation and measurement properties of the brazilian version-KOPS Brazilian version.

BACKGROUND: Despite the criteria already established for the classification of knee osteoarthritis (OA), a radiographic and/or clinical knee OA diagnosis usually occurs in cases of fully manifest or more advanced disease, which can make health promotion, prevention, and functional rehabilitation in more advanced stages of the disease less effective. In addition, radiographic knee OA can generate more financial costs for health services. Therefore, developing and validating screening instruments to assess the probability of development and progression of knee OA would be of great value for both clinical practice and science. OBJECTIVE: To cross-culturally adapt and investigate the measurement properties of the Knee OA Pre-screening Questionnaire Brazilian version. METHODS: A total of 250 individuals of both sexes aged between 35 and 92 years [(mean (standard deviation): 63 (11) years old; 74.1 (15.1) kg; 1.59 (0.09) m; 29.38 (5.44) kg/m2] participated in this study. The cross-cultural adaptation and analyses of the measurement properties of the KOPS Brazilian version included: (1) assessment of conceptual and item equivalence; (2) assessment of semantic equivalence; (3) assessment of operational equivalence; and (4) assessment of measurement equivalence, reliability, and validity. RESULTS: Cronbach's alpha for the internal consistency among the six components of the KOPS Brazilian version was 0.71. The test-retest 72 h apart for each component resulted in a coefficient correlation intraclass ranging from 0.74 to 1.00. The probability of an individual randomly chosen from the population having KL ≥ 1 and KOPS Brazilian version ≥ 21 points was 0.74 (area under the curve of the Receiver Operating Characteristic - AUC of ROC); furthermore, the AUC for KL ≥ 2 and the KOPS Brazilian version ≥ 23 points was 0.77. CONCLUSION: The KOPS Brazilian version is a reliable and valid instrument for early screening of knee OA in individuals aged 35 years and over in the Brazilian context.

Immunogenicity decay and case incidence six months post Sinovac-CoronaVac vaccine in autoimmune rheumatic diseases patients.

The determination of durability and vaccine-associated protection is essential for booster doses strategies, however data on the stability of SARS-CoV-2 immunity are scarce. Here we assess anti-SARS-CoV-2 immunogenicity decay and incident cases six months after the 2nd dose of Sinovac-CoronaVac inactivated vaccine (D210) in 828 autoimmune rheumatic diseases patients compared with 207 age/sex-balanced control individuals. The primary outcome is the presence of anti-S1/S2 SARS-CoV-2 IgG at 6 months compared to 6 weeks after 2nd vaccine dose for decay evaluation. Secondary outcomes are presence of neutralizing antibodies, percent inhibition by neutralizing, geometric mean titers and cumulative incident cases at 6 months after 2nd dose. Anti-S1/S2 IgG positivity and titers reduce to 23.8% and 38% in patients (p < 0.001) during the six-month follow up and 20% and 51% in controls (p < 0.001), respectively. Neutralizing antibodies positivity and percent inhibition declines 41% and 54% in patients (p < 0.001) and 39.7% and 47% in controls (p < 0.001). Multivariate logistic regression analysis show males (OR = 0.56;95% CI0.40-0.79), prednisone (OR = 0.56; 95% CI0.41-0.76), anti-TNF (OR = 0.66;95% CI0.45-0.96), abatacept (OR = 0.29; 95% CI0.15-0.56) and rituximab (OR = 0.32;95% CI0.11-0.90) associate with a substantial reduction in IgG response at day 210 in patients. Although cellular immunity was not assessed, a decrease of COVID-19 cases (from 27.5 to 8.1/100 person-years; p < 0.001) is observed despite the concomitant emergence and spread of the Delta variant. Altogether we show a reduction in immunity 6-months of Sinovac-CoronaVac 2nd dose, particularly in males and those under immunosuppressives therapies, without a concomitant rise in COVID-19 cases. (CoronavRheum clinicaltrials.gov:NCT04754698).

Reference range of serum uric acid and prevalence of hyperuricemia: a cross-sectional study from baseline data of ELSA-Brasil cohort.

BACKGROUND: Most of the few studies that have established reference ranges for serum uric acid (SUA) have not taken into account factors which may interfere with its levels and followed rigorous laboratory quality standards. The aim of this study was to establish reference ranges for SUA and determine the prevalence of hyperuricemia. METHOD: Cross-sectional study including 15,100 participants (all sample) aged 35 to 74 years from baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicentric cohort of volunteer civil servants from five universities and one research institute located in different regions of Brazil. It was established a reference sample excluding participants with factors that directly influence SUA levels: glomerular filtration rate lower than 60 ml/min, excessive alcohol intake, use of diuretics, aspirin, estrogen or urate-lowering therapy. SUA was measured using the uricase method and following rigorous international quality standards. Reference ranges were defined as values between percentiles 2.5 (P2.5) and 97.5 (P97.5) of SUA distribution in the reference sample, stratified by sex. Hyperuricemia was defined as SUA ≥ 7 mg/100 ml in the all sample. RESULTS: The reference sample was composed of 10,340 individuals (55.3% women, median age 50 years). Reference ranges (P2.5 to P97.5) for SUA were: 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Sex was a major determinant for SUA levels (median [IQR], mg/100 ml: 6.1 [5.3-7.0] for men versus 4.5 [3.9-5.3] for women, p < 0.001). Higher levels of SUA were found in patients with higher BMI. Higher age had (a modest) influence only for women. The prevalence of hyperuricemia for all sample (N = 15,100) was 31.9% (95% confidence interval [CI] 30.8-33.0%) in men and 4.8% (95% CI 4.3-5.3%) in women. CONCLUSION: SUA reference ranges were 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Prevalence of hyperuricemia was 31.9% in men and 4.8% in women. Updated SUA reference ranges and prevalence of hyperuricemia are higher nowadays and might be used to guide laboratories and the screening for diseases related to SUA.

Increment of immunogenicity after third dose of a homologous inactivated SARS-CoV-2 vaccine in a large population of patients with autoimmune rheumatic diseases.

OBJECTIVE: To determine the immunogenicity of the third dose of CoronaVac vaccine in a large population of patients with autoimmune rheumatic diseases (ARD) and the factors associated with impaired response. METHODS: Adult patients with ARD and age-balanced/sex-balanced controls (control group, CG) previously vaccinated with two doses of CoronaVac received the third dose at D210 (6 months after the second dose). The presence of anti-SARS-CoV-2 S1/S2 IgG and neutralising antibodies (NAb) was evaluated previously to vaccination (D210) and 30 days later (D240). Patients with controlled disease suspended mycophenolate mofetil (MMF) for 7 days or methotrexate (MTX) for 2 weekly doses after vaccination. RESULTS: ARD (n=597) and CG (n=199) had comparable age (p=0.943). Anti-S1/S2 IgG seropositivity rates significantly increased from D210 (60%) to D240 (93%) (p<0.0001) in patients with ARD. NAb positivity also increased: 38% (D210) vs 81.4% (D240) (p<0.0001). The same pattern was observed for CG, with significantly higher frequencies for both parameters at D240 (p<0.05). Multivariate logistic regression analyses in the ARD group revealed that older age (OR=0.98, 95% CI 0.96 to 1.0, p=0.024), vasculitis diagnosis (OR=0.24, 95% CI 0.11 to 0.53, p<0.001), prednisone ≥5 mg/day (OR=0.46, 95% CI 0.27 to 0.77, p=0.003), MMF (OR=0.30, 95% CI 0.15 to 0.61, p<0.001) and biologics (OR=0.27, 95% CI 0.16 to 0.46, p<0.001) were associated with reduced anti-S1/S2 IgG positivity. Similar analyses demonstrated that prednisone ≥5 mg/day (OR=0.63, 95% CI 0.44 to 0.90, p=0.011), abatacept (OR=0.39, 95% CI 0.20 to 0.74, p=0.004), belimumab (OR=0.29, 95% CI 0.13 to 0.67, p=0.004) and rituximab (OR=0.11, 95% CI 0.04 to 0.30, p<0.001) were negatively associated with NAb positivity. Further evaluation of COVID-19 seronegative ARD at D210 demonstrated prominent increases in positivity rates at D240 for anti-S1/S2 IgG (80.5%) and NAb (59.1%) (p<0.0001). CONCLUSIONS: We provide novel data on a robust response to the third dose of CoronaVac in patients with ARD, even in those with prevaccination COVID-19 seronegative status. Drugs implicated in reducing immunogenicity after the regular two-dose regimen were associated with non-responsiveness after the third dose, except for MTX. Trial registration number NCT04754698.

Immunogenicity and safety of two doses of the CoronaVac SARS-CoV-2 vaccine in SARS-CoV-2 seropositive and seronegative patients with autoimmune rheumatic diseases in Brazil: a subgroup analysis of a phase 4 prospective study.

BACKGROUND: We aimed to examine the immunogenicity pattern induced by the inactivated SARS-CoV-2 vaccine CoronaVac (Sinovac Life Sciences, Beijing, China) in SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases compared with seropositive controls, seronegative patients with autoimmune rheumatic diseases, and seronegative controls. METHODS: CoronavRheum is an ongoing, prospective, controlled, phase 4 study, in which patients aged 18 years or older with autoimmune rheumatic diseases, and healthy controls were recruited from a single site (Rheumatology Division of Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo) in São Paulo, Brazil Participants were vaccinated with two doses of CoronaVac (intramuscular injection, 3 µg in 0·5 mL of ß-propiolactone inactivated SARS-CoV-2) on day 0 and on day 28. Blood samples were taken pre-vaccination on day 0, day 28, and also on day 69. For this subgroup analysis, participants were defined as being SARS-CoV-2 seropositive or seronegative prevaccination via anti-SARS-CoV-2 spike (S)1 or S2 IgG (cutoff of 15·0 arbitrary units [AU] per mL) or neutralising antibody titres (cutoff of ≥30%) and were matched for age and sex, via convenience sampling, in a 1:3:1:1 ratio (seropositive patients to seronegative patients to seropositive controls to seronegative controls). The primary outcomes were rates of anti-SARS-CoV-2 S1 and S2 IgG seropositivity and SARS-CoV-2 neutralising antibody positivity at day 28 and day 69 and immunogenicity dynamics assessed by geometric mean titres (GMTs) of IgG and median neutralising activity in seropositive patients with autoimmune rheumatic diseases compared with seronegative patients and seropositive and seronegative controls. We assessed safety in all participants randomly selected for this subgroup analysis. This study is registered with ClinicalTrials.gov, NCT04754698, and is ongoing for long-term immunogenicity evaluation. FINDINGS: Between Feb 4 and Feb 8, 2021, 1418 patients and 542 controls were recruited, of whom 1685 received two vaccinations (1193 patients and 492 controls). After random sampling, our immunogenicity analysis population comprised 942 participants, of whom 157 were SARS-CoV-2 seropositive patients with autoimmune rheumatic diseases, 157 were seropositive controls, 471 were seronegative patients, and 157 were seronegative controls; the median age was 48 years (IQR 38-56) and 594 (63%) were female and 348 (37%) were male. For seropositive patients and controls, an increase in anti-SARS-CoV-2 S1 and S2 IgG titres (seropositive patients GMT 52·3 [95% CI 42·9-63·9] at day 0 vs 128·9 [105·6-157·4] at day 28; seropositive controls 53·3 [45·4-62·5] at day 0 vs 202·0 [174·8-233·4] at day 28) and neutralising antibody activity (seropositive patients 59% [IQR 39-83] at day 0 vs 82% [54-96] at day 28; seropositive controls 58% [41-79] at day 0 vs 92% [79-96] at day 28), was observed from day 0 to day 28, without further increases from day 28 to day 69 (at day 69 seropositive patients' GMT was 137·1 [116·2-161·9] and neutralising antibody activity was 79% [57-94]); and seropositive controls' GMT was 188·6 [167·4-212·6] and neutralising antibody activity was 92% [75-96]). By contrast, for seronegative patients and controls, the second dose was required for maximum response at day 69, which was lower in seronegative patients than in seronegative controls. GMTs in seronegative patients were 2·3 (95% CI 2·2-2·3) at day 0, 5·7 (5·1-6·4) at day 28, and 29·6 (26·4-33·3) at day 69, and in seronegative controls were 2·3 (2·1-2·5) at day 0, 10·6 (8·7-13·1) at day 28, and 71·7 (63·5-81·0) at day 69; neutralising antibody activity in seronegative patients was 15% (IQR 15-15) on day 0, 15% (15-15) at day 28, and 39% (15-65) at day 69, and in seronegative controls was 15% (15-15) at day 0, 24% (15-37) at day 28, and 61% (37-79) at day 69. Neither seronegative patients nor seronegative controls reached the GMT or antibody activity levels of seropositive patients at day 69. INTERPRETATION: By contrast with seronegative patients with autoimmune rheumatic diseases, seropositive patients have a robust response after a single dose of CoronaVac. Our findings raise the possibility that the reduced immunogenicity observed in seronegative patients might not be the optimum response potential to SARS-CoV-2 vaccination, and therefore emphasise the importance of at least a single booster vaccination in these patients. FUNDING: Fundação de Amparo à Pesquisa do Estado de São Paulo, Conselho Nacional de Desenvolvimento Científico e Tecnológico, and B3-Bolsa de Valores do Brasil. TRANSLATION: For the Portuguese translation of the abstract see Supplementary Materials section.

Reference range of serum uric acid and prevalence of hyperuricemia: a cross-sectional study from baseline data of ELSA-Brasil cohort

Abstract Background: Most of the few studies that have established reference ranges for serum uric acid (SUA) have not taken into account factors which may interfere with its levels and followed rigorous laboratory quality standards. The aim of this study was to establish reference ranges for SUA and determine the prevalence of hyperuricemia. Method: Cross-sectional study including 15,100 participants (all sample) aged 35 to 74 years from baseline data of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), a multicentric cohort of volunteer civil servants from five universities and one research institute located in different regions of Brazil. It was established a reference sample excluding participants with factors that directly influence SUA levels: glomerular filtration rate lower than 60 ml/min, excessive alcohol intake, use of diuretics, aspirin, estrogen or urate-lowering therapy. SUA was measured using the uricase method and following rigorous international quality standards. Reference ranges were defined as values between percentiles 2.5 (P2.5) and 97.5 (P97.5) of SUA distribution in the reference sample, stratified by sex. Hyperuricemia was defined as SUA ≥ 7 mg/100 ml in the all sample. Results: The reference sample was composed of 10,340 individuals (55.3% women, median age 50 years). Reference ranges (P2.5 to P97.5) for SUA were: 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Sex was a major determinant for SUA levels (median [IQR], mg/100 ml: 6.1 [5.3-7.0] for men versus 4.5 [3.9-5.3] for women, p < 0.001). Higher levels of SUA were found in patients with higher BMI. Higher age had (a modest) influence only for women. The prevalence of hyperuricemia for all sample (N = 15,100) was 31.9% (95% confidence interval [CI] 30.8- 33.0%) in men and 4.8% (95% CI 4.3-5.3%) in women. Conclusion: SUA reference ranges were 4.0 to 9.2 mg/100 ml for men and 2.8 to 6.9 mg/100 ml for women. Prevalence of hyperuricemia was 31.9% in men and 4.8% in women. Updated SUA reference ranges and prevalence of hyperuricemia are higher nowadays and might be used to guide laboratories and the screening for diseases related to SUA.

Knee osteoarthritis pre-screening questionnaire (KOPS): cross-cultural adaptation and measurement properties of the brazilian version—KOPS Brazilian version

Abstract Background: Despite the criteria already established for the classification of knee osteoarthritis (OA), a radiographic and/or clinical knee OA diagnosis usually occurs in cases of fully manifest or more advanced disease, which can make health promotion, prevention, and functional rehabilitation in more advanced stages of the disease less effective. In addition, radiographic knee OA can generate more financial costs for health services. Therefore, developing and validating screening instruments to assess the probability of development and progression of knee OA would be of great value for both clinical practice and science. Objective: To cross-culturally adapt and investigate the measurement properties of the Knee OA Pre-screening Questionnaire Brazilian version. Methods: A total of 250 individuals of both sexes aged between 35 and 92 years [(mean (standard deviation): 63 (11) years old; 74.1 (15.1) kg; 1.59 (0.09) m; 29.38 (5.44) kg/m2] participated in this study. The cross-cultural adaptation and analyses of the measurement properties of the KOPS Brazilian version included: (1) assessment of conceptual and item equivalence; (2) assessment of semantic equivalence; (3) assessment of operational equivalence; and (4) assessment of measurement equivalence, reliability, and validity. Results: Cronbach's alpha for the internal consistency among the six components of the KOPS Brazilian version was 0.71. The test-retest 72 h apart for each component resulted in a coefficient correlation intraclass ranging from 0.74 to 1.00. The probability of an individual randomly chosen from the population having KL ≥ 1 and KOPS Brazilian version ≥ 21 points was 0.74 (area under the curve of the Receiver Operating Characteristic - AUC of ROC); furthermore, the AUC for KL ≥ 2 and the KOPS Brazilian version ≥ 23 points was 0.77. Conclusion: The KOPS Brazilian version is a reliable and valid instrument for early screening of knee OA in individuals aged 35 years and over in the Brazilian context.

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

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).

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

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/m2and 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.

Influenza A/Singapore (H3N2) component vaccine in systemic lupus erythematosus: A distinct pattern of immunogenicity.

INTRODUCTION: Influenza A (H3N2) virus is the most important cause of seasonal influenza morbidity and mortality in the last 50 years, surpassing the impact of H1N1. Data assessing immunogenicity and safety of this virus component are lacking in systemic lupus erythematosus (SLE) and restricted to small reports with other H3N2 strains. OBJECTIVE: This study aims to evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in SLE. METHODS: 81 consecutive SLE patients and 81 age- and sex-matched healthy controls (HC) were vaccinated with the influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Seroprotection (SP) and seroconversion (SC) rates, geometric mean titers(GMT), and factor increase in GMT(FI-GMT) and adverse events were assessed before and 4 weeks post-vaccination. Disease activity and therapies were also evaluated. RESULTS: Before immunization, SLE and HC groups had high SP rates (89% vs 77%, p = 0.061) and elevated GMT titer with higher levels in SLE (129.1(104.1-154.1) vs 54.8(45.0-64.6), p < 0.001). Frequency of two previous years' influenza vaccination was high and comparable in SLE and HC (89% vs 90%, p = 1.000). Four weeks post-vaccination, median GMT increased for both groups and remained higher in SLE compared to HC (239.9(189.5-290.4) vs 94.5(72.6-116.4), p < 0.0001) with a comparable FI-GMT (2.3(1.8-2.9) vs 1.9(1.5-2.3), p = 0.051). SC rates were low and comparable for both groups (16% vs 11%, respectively, p = 0.974). Disease activity scores remained stable throughout the study (p = 1.000) and severe adverse events were not identified. CONCLUSION: Influenza A/Singapore (H3N2) vaccine has an adequate safety profile. The distinct immunogenicity pattern from other influenza A components characterized by a remarkably high pre- and post-vaccination SP rate and high GMT levels may be associated with previous influenza A vaccination. (www.clinicaltrials.gov, NCT03540823).

Post-Adipose-Derived Stem Cells (ADSC) Stimulated by Collagen Type V (Col V) Mitigate the Progression of Osteoarthritic Rabbit Articular Cartilage.

Collagen is essential for cartilage adhesion and formation. In the present study, histology, immunofluorescence, morphometry, and qRT-PCR suggested that adipose-derived stem cells (ADSCs) stimulated by type V collagen (Col V) induce a significant increase of type II collagen (Col II) in the degenerative area of surgical-induced osteoarthritic rabbit articular cartilage (OA). In vitro, the effects of Col V on the proliferation and differentiation of ADSC were investigated. The expression of the cartilage-related genes Col2a1 and Acan was significantly upregulated and Pou5fl was downregulated post-ADSC/Col V treatment. Post-ADSC/Col V treatment, in vivo analyses revealed that rabbits showed typical signs of osteoarthritic articular cartilage regeneration by hematoxylin and eosin (H&E) and Safranin O/Fast Green staining. Immunohistochemical staining demonstrated that the volume of Col II fibers and the expression of Col II protein were significantly increased, and apoptosis Fas ligand positive significantly decreased post-ADSC/Col V treatment. In conclusion, the expression of Col II was higher in rabbits with surgical-induced osteoarthritic articular cartilage; hence, ADSC/Col V may be a promising therapeutic target for OA treatment.

Nephrolithiasis in gout: prevalence and characteristics of Brazilian patients

Abstract Background: The aims of this article were to assess the prevalence of nephrolithiasis and the factors associated with nephrolithiasis in Brazilian patients with primary gout. Methods: One hundred twenty-three patients with primary gout were recruited from a tertiary referral hospital in São Paulo, Brazil. All patients underwent ultrasonography and had their clinical and laboratory characteristics assessed. Results: One hundred fifteen (93.5%) patients were male, with a mean age of 62.9 ± 9.4 years. Twenty-three (18.7%) patients had asymptomatic nephrolithiasis (detected only by ultrasonography), 7 (6.0%) had symptomatic nephrolithiasis (detected by ultrasonography and a positive clinical history), and 13 (10.0%) had a history of kidney stones, but ultrasonography at evaluation did not show nephrolithiasis. Therefore, 35.0% of the patients had nephrolithiasis (detected either by ultrasonography and/or a positive clinical history). Nephrolithiasis was associated with male gender (43 [100%] vs 72 [90%], p = 0.049), the use of potassium citrate (13 [30.2%] vs 0, p < 0.001) and the use of medications for diabetes (10 [23.3%] vs 8 [10%], p = 0.047) and dyslipidemia (15 [34.9%] vs 10 [12.5%], p = 0.003); benzbromarone had an inverse association with nephrolithiasis (21 [48.8%] vs 55 [68.8%], p = 0.030). In patients with and without nephrolithiasis, no differences were found in the laboratory and ultrasonography characteristics, including serum uric acid levels, urinary uric acid excretion and urine pH. Conclusions: The prevalence of nephrolithiasis in primary gout was 35.0%, and 18.7% of the patients were asymptomatic. Nephrolithiasis was associated with male gender, diabetes and dyslipidemia. A positive history of nephrolithiasis probably biased the prescription of potassium citrate and benzbromarone.(AU)

Nephrolithiasis in gout: prevalence and characteristics of Brazilian patients.

BACKGROUND: The aims of this article were to assess the prevalence of nephrolithiasis and the factors associated with nephrolithiasis in Brazilian patients with primary gout. METHODS: One hundred twenty-three patients with primary gout were recruited from a tertiary referral hospital in São Paulo, Brazil. All patients underwent ultrasonography and had their clinical and laboratory characteristics assessed. RESULTS: One hundred fifteen (93.5%) patients were male, with a mean age of 62.9 ± 9.4 years. Twenty-three (18.7%) patients had asymptomatic nephrolithiasis (detected only by ultrasonography), 7 (6.0%) had symptomatic nephrolithiasis (detected by ultrasonography and a positive clinical history), and 13 (10.0%) had a history of kidney stones, but ultrasonography at evaluation did not show nephrolithiasis. Therefore, 35.0% of the patients had nephrolithiasis (detected either by ultrasonography and/or a positive clinical history). Nephrolithiasis was associated with male gender (43 [100%] vs 72 [90%], p = 0.049), the use of potassium citrate (13 [30.2%] vs 0, p <  0.001) and the use of medications for diabetes (10 [23.3%] vs 8 [10%], p = 0.047) and dyslipidemia (15 [34.9%] vs 10 [12.5%], p = 0.003); benzbromarone had an inverse association with nephrolithiasis (21 [48.8%] vs 55 [68.8%], p = 0.030). In patients with and without nephrolithiasis, no differences were found in the laboratory and ultrasonography characteristics, including serum uric acid levels, urinary uric acid excretion and urine pH. CONCLUSIONS: The prevalence of nephrolithiasis in primary gout was 35.0%, and 18.7% of the patients were asymptomatic. Nephrolithiasis was associated with male gender, diabetes and dyslipidemia. A positive history of nephrolithiasis probably biased the prescription of potassium citrate and benzbromarone.

Public social security burden of musculoskeletal diseases in Brasil-Descriptive study.

BACKGROUND: To present data on the social security burden of diseases of the musculoskeletal system and connective tissue (DSOTC) in Brasil in 2014, and evolution of these social security expenditures between 2009 and 2014. METHOD: Compilation and analysis of data on the granting of disability pensions and sickness benefits in the year 2014, available on the official website of Social Security, classified according to ICD 10. It was evaluated the evolution between 2009 and 2014, using the F test to compare the curves with the growth of the active age population (PIA). RESULTS: Among the 22 disease groups classified according to ICD-10, the DSOTC group led benefits grants in 2014, with 19% of the sickness benefits and 13.5% of the disability pensions. The main causes of sickness benefit and disability retirement were, respectively: dorsopathies (43.3% and 41.2%), soft tissue diseases (27.3% and 19.7%), osteoarthritis (7.6% % And 27.8%) and chronic inflammatory arthropathies (2.8% and 7.9%). In the evolution of the number of sickness benefits granted between 2009 and 2014, both INSS and DSOTC totals showed an increasing tendency (35.9 and 35.3%, respectively, with p = 0.000 for both). As for disability retirement, there was a 5.9% increase in the INSS total (p = 0.039), while for the DSOTC there was a decrease of 7.6% (p = 0.005). CONCLUSIONS: These data point to a progressive increase in the granting of sickness pensions and disability benefits in the country, superior to the growth of the PIA, as well as a high participation of DSOTC in these benefits.

Public social security burden of musculoskeletal diseases in Brasil-Descriptive study

SUMMARY BACKGROUND: To present data on the social security burden of diseases of the musculoskeletal system and connective tissue (DSOTC) in Brasil in 2014, and evolution of these social security expenditures between 2009 and 2014. METHOD: Compilation and analysis of data on the granting of disability pensions and sickness benefits in the year 2014, available on the official website of Social Security, classified according to ICD 10. It was evaluated the evolution between 2009 and 2014, using the F test to compare the curves with the growth of the active age population (PIA). RESULTS: Among the 22 disease groups classified according to ICD-10, the DSOTC group led benefits grants in 2014, with 19% of the sickness benefits and 13.5% of the disability pensions. The main causes of sickness benefit and disability retirement were, respectively: dorsopathies (43.3% and 41.2%), soft tissue diseases (27.3% and 19.7%), osteoarthritis (7.6% % And 27.8%) and chronic inflammatory arthropathies (2.8% and 7.9%). In the evolution of the number of sickness benefits granted between 2009 and 2014, both INSS and DSOTC totals showed an increasing tendency (35.9 and 35.3%, respectively, with p = 0.000 for both). As for disability retirement, there was a 5.9% increase in the INSS total (p = 0.039), while for the DSOTC there was a decrease of 7.6% (p = 0.005). CONCLUSIONS: These data point to a progressive increase in the granting of sickness pensions and disability benefits in the country, superior to the growth of the PIA, as well as a high participation of DSOTC in these benefits.

RESUMO OBJETIVOS: Apresentar dados sobre o ônus previdenciário das doenças do sistema osteomuscular e tecido conjuntivo (DSOTC) no Brasil no ano de 2014, e sua evolução entre 2009 e 2014. MÉTODO: Compilação e análise de dados sobre a concessão de aposentadorias por invalidez e auxílios-doença no ano de 2014 disponíveis no portal oficial da Previdência Social, classificados segundo o CID 10. Avaliação da evolução entre 2009 e 2014, utilizando-se o teste F para comparar as curvas com o crescimento da população em idade ativa (PIA). RESULTADOS: Entre 22 grupos de doenças classificados de acordo com o CID 10, o das DSOTC liderou as concessões de benefícios em 2014, com 19% dos auxílios-doença e 13,5% das aposentadorias por invalidez. As principais causas de concessão de auxílio-doença e aposentadoria por invalidez foram, respectivamente: dorsopatias (43,3% e 41,2%), doenças de partes moles (27,3% e 19,7%), osteoartrite (7,6% e 27,8%) e artropatias inflamatórias crônicas (2,8% e 7,9%). Na evolução do número de auxílios-doença concedidos entre 2009 e 2014, tanto o total do INSS quanto o do grupo DSOTC apresentaram tendência crescente (35,9 e 35,3%, respectivamente, com p = 0,000 para ambos). Já para aposentadoria por invalidez, houve aumento de 5,9% no total do INSS (p = 0,039), enquanto que para as DSOTC houve um decréscimo de 7,6% (p = 0,005). CONCLUSÕES: Verificou-se uma elevação progressiva na concessão de auxílio-doença e aposentadoria por invalidez no País, superior ao aumento da população em idade ativa. As DSOTC foram o grupo com maior participação relativa nesses benefícios.

Serum uric acid levels are associated with lupus nephritis in patients with normal renal function.

Uric acid has been recognised as a potential marker of endothelial dysfunction and kidney disease but there are scarce data about its importance in systemic lupus erythematosus (SLE) nephritis. This study aimed to evaluate serum uric acid (UA) levels in lupus nephritis (LN), by comparing SLE patients with normal renal function, with and without nephritis. Forty-six female SLE patients were consecutively selected and divided in two groups according to renal activity at the evaluation: presence of a recently diagnosed lupus nephritis (LN+, n = 18) and absence of lupus nephritis (LN-, n = 28). Age-matched healthy women were selected (CONTROL, n = 28). Patients with gout, creatinine clearance lower than 80 ml/min and use of drugs that interfere in UA were excluded. Laboratory and clinical data were analysed by appropriate tests. A multivariate analysis was performed, and a receiver operating characteristic (ROC) curve was plotted, and the area under the curve was calculated to assess the diagnostic strength of UA in LN. The mean age was similar among LN+, LN- and CONTROL groups (32.44 ± 6.09 vs. 30.68 ± 5.36 vs. 30.86 ± 5.00 years, p = 0.52). UA was significantly higher in LN+ compared to LN- (5.54 ± 1.67 vs. 3.65 ± 1.090 mg/dL, p < 0.001) and CONTROL (5.54 ± 1.67 vs. 3.92 ± 0.95 mg/dL p < 0.001). Multivariate analysis confirmed that high UA was an independent variable related to LN (p < 0.001). The cut-off value for UA using the ROC curve was 4.47 mg/dL (AUC 0.86, p = 0.00004, CI 95% 0.75-0.96). Lupus nephritis was associated with higher UA. Hyperuricemia as a predictor of renal damage in SLE needs to be evaluated in further studies.