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Aims: To evaluate the presence of temporomandibular disorders (TMD) in systemic sclerosis (SSc) patients and its possible association with the severity of skin involvement. Methods: The presence of TMD was evaluated in 35 SSc women and 30 age- and sex-matched healthy controls by means of the anamnestic (Ai) and clinical (Di) Helkimo indices; the jaw mobility was further analyzed (MI). Skin involvement was scored by the Modified Rodnan Skin Score (MRSS). Results: Signs and symptoms of TMD were more frequent in SSc patients than in controls, the frequency distribution of the different clinical dysfunction indices differing significantly (P < .001) between patients (Di0 8.6%, DiI 48.6%, DiII 22.8%, and DiIII 20%) and controls (Di0 50%, DiI 33.3%, and DiII 16.7%). Cyclophosphamide for severe and rapidly progressive cutaneous fibrosis was prescribed in six out of seven patients with severe signs (DiIII), in contrast this treatment was indicated for only two out of 25 patients with mild to moderate signs (DiI and DiII, P < .001). Impaired jaw mobility was more frequent in SSc patients than controls (P < .001). It was severe in 77.1% (MIII) and mild in 22.9% (MII) of the cases, in contrast to controls (MI0 33.4%, MII 53.3%, and MIII 13.3%; P < .001). Approximately half of SSc patients with severe (MIII) but none of those with mild impairment were on cyclophosphamide treatment for severe cutaneous fibrosis (P = .02). Conclusion: Severe signs of TMD according to the anamnestic and clinical Helkimo indices were very frequent in SSc patients. J Orofac Pain 2010;24:197-202. [ABSTRACT FROM AUTHOR]

Proteinuria is a major feature of lupus nephritis (LN) and reflects podocyte injury. Analysis of podocyte biomarkers was performed attempting to identify if podocyte phenotype is distinct in pure membranous and proliferative LN. Expression of synaptopodin, Wilms tumor protein 1 (WT1), glomerular epithelial protein 1 (GLEPP1) and nephrin was evaluated in 52 LN biopsies by immunohistochemistry. Preserved synaptopodin expression was observed in only 10 (19.2%) of all biopsies while 42 (80.8%) had reduced expression. Both groups had comparable proteinuria at the time of biopsy (p = 0.22); however, in the mean follow-up of four years there was a tendency toward lower mean levels of proteinuria in patients with preserved synaptopodin staining (0.26±0.23 vs. 0.84±0.90 g/24 h, p = 0.05) compared with those with diminished expression. Thirty-nine (75%) biopsies were classified as proliferative and 13 (25%) as pure membranous. Comparison of podocyte biomarkers demonstrated a predominance of preserved staining of synaptopodin (69.2%), WT1 (69.2%), GLEPP1 (53.9%) and nephrin (60%) in the pure membranous group whereas only <10% of the proliferative showed preserved expression. Our data suggest that in proliferative forms there seems to occur structural podocyte damage, whereas in the pure membranous the predominant preserved pattern suggests a dysfunctional podocyte lesion that may account for the better long-term prognosis of proteinuria outcome. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To evaluate the beneficial effect of antimalarial treatment on lupus survival in a large, multiethnic, international longitudinal inception cohort. METHODS: Socioeconomic and demographic characteristics, clinical manifestations, classification criteria, laboratory findings, and treatment variables were examined in patients with systemic lupus erythematosus (SLE) from the Grupo Latino Americano de Estudio del Lupus Eritematoso (GLADEL) cohort. The diagnosis of SLE, according to the American College of Rheumatology criteria, was assessed within 2 years of cohort entry. Cause of death was classified as active disease, infection, cardiovascular complications, thrombosis, malignancy, or other cause. Patients were subdivided by antimalarial use, grouped according to those who had received antimalarial drugs for at least 6 consecutive months (user) and those who had received antimalarial drugs for <6 consecutive months or who had never received antimalarial drugs (nonuser). RESULTS: Of the 1,480 patients included in the GLADEL cohort, 1,141 (77%) were considered antimalarial users, with a mean duration of drug exposure of 48.5 months (range 6-98 months). Death occurred in 89 patients (6.0%). A lower mortality rate was observed in antimalarial users compared with nonusers (4.4% versus 11.5%; P< 0.001). Seventy patients (6.1%) had received antimalarial drugs for 6-11 months, 146 (12.8%) for 1-2 years, and 925 (81.1%) for >2 years. Mortality rates among users by duration of antimalarial treatment (per 1,000 person-months of followup) were 3.85 (95% confidence interval [95% CI] 1.41-8.37), 2.7 (95% CI 1.41-4.76), and 0.54 (95% CI 0.37-0.77), respectively, while for nonusers, the mortality rate was 3.07 (95% CI 2.18-4.20) (P for trend < 0.001). After adjustment for potential confounders in a Cox regression model, antimalarial use was associated with a 38% reduction in the mortality rate (hazard ratio 0.62, 95% CI 0.39-0.99). CONCLUSION: Antimalarial drugs were shown to have a protective effect, possibly in a time-dependent manner, on SLE survival. These results suggest that the use of antimalarial treatment should be recommended for patients with lupus. [ABSTRACT FROM AUTHOR]

OBJECTIVE: The novel description of antibodies to lipoprotein lipase (anti-LPL) associated with dyslipoproteinemia prompted us to analyze the association of anti-LPL with clinical and serologic features in patients with systemic lupus erythematosus (SLE) and its link to markers of inflammation that are known to be involved in atherogenesis. METHODS: Enzyme-linked immunosorbent assay was used to test for the presence of anti-LPL antibodies in 66 consecutive patients with SLE. Clinical and laboratory evaluation, including a fasting lipid profile, autoantibody screening, an assessment for markers of inflammation (C-reactive protein [CRP], erythrocyte sedimentation rate [ESR]), and the SLE Disease Activity Index (SLEDAI) were performed at the time of inclusion in the study. Exclusion criteria were any conditions that affect the lipid profile. SLE patients were categorized into 2 groups according to detection of these anti-LPL antibodies, as follows: anti-LPL+ and anti-LPL-. RESULTS: Anti-LPL antibody IgG was detected in 25 SLE patients (37.8%). Triglyceride levels were significantly higher in the anti-LPL+ group (112.4 +/- 50.2 versus 89.9 +/- 54.5 mg/dl in the anti-LPL- group; P = 0.033), but no significant differences between the 2 groups were detected for total, high-density lipoprotein, and low-density lipoprotein cholesterol levels. A higher frequency of elevated CRP levels and ESRs was observed in the anti-LPL+ group compared with the anti-LPL- group (44% and 17.1%, respectively [P = 0.023] and 52% and 19.5%, respectively [P = 0.013]). Moreover, SLE patients with anti-LPL antibodies also had significantly higher levels of CRP (11.1 +/- 16.4 versus 2.4 +/- 2.6 mug/ml; P = 0.036) and higher ESRs (33.4 +/- 29.8 versus 16.5 +/- 11.8 mm/hour; P = 0.020). Anti-LPL titers had a significant positive correlation with the CRP level (r = 0.56, P < 0.001), the ESR (r = 0.55, P < 0.001), the SLEDAI score (r = 0.45, P < 0.001), anti-double-stranded DNA (anti-dsDNA; r = 0.52, P < 0.001), and anticardiolipin IgG antibodies (r = 0.25, P = 0.04), and a significant negative correlation was detected with total hemolytic complement activity (CH100) (r = -0.34, P = 0.005). Reinforcing these findings, multiple regression analysis also revealed a significant association of anti-LPL with the CRP level (P = 0.025) and anti-dsDNA (P < 0.001). Importantly, a comparison of positive and negative anti-dsDNA sera revealed similar mean CRP levels (P = 0.56) and ESRs (P = 0.102), contrasting with the SLEDAI score (P = 0.004) and CH100 (P = 0.008). CONCLUSION: These data support the link between inflammation, immune response, and dyslipoproteinemia in SLE, introducing anti-LPL as a possible new player that may ultimately help in understanding the complex events of atherogenesis in this disease. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the possible reversibility of PAH to a normopressoric state in SLE after induction immunosuppressive (IS) and predictors of response., Methods: We retrospectively evaluated all SLE-PAH patients who underwent IS therapy at our center. PAH reversion was defined as the normalization of pulmonary arterial pressure (PAP), either by the presence of systolic PAP <40 mmHg on echocardiogram or mean PAP <20 mmHg on right heart catheterization (RHC). SLE patients were divided in Reversion and No-Reversion of SLE-PAH groups for comparative analysis at baseline and after IS., Results: Among 2,074 SLE patients, 28 SLE-PAH received IS therapy (1.3%). Ten patients (35.7%) achieved SLE-PAH reversion. Demographic data, disease duration, SLEDAI-2K, and SDI Damage scores were similar between Reversion and No-Reversion of SLE-PAH groups ( p > 0.05). At baseline, Reversion of SLE-PAH had lower sPAP ( p = 0.032), lower right ventricle dilatation ( p = 0.003) and hypokinesia ( p = 0.017) frequencies on echocardiogram, and also lower BNP levels ( p = 0.041) and risk stratification score ( p = 0.014). Hemodynamic parameters were similar among groups ( p > 0.05). After IS, a significant decrease in CRP levels was identified only in Reversion of SLE-PAH ( p = 0.013), although both groups had a significant reduction in SLEDAI-2K ( p < 0.05). Both groups had significant improvement in risk stratification score ( p = 0.009 and p < 0.001) with a better survival rate in Reversion of SLE-PAH ( p = 0.047)., Conclusion: This is the first study that identified that more than one third of SLE-PAH had a complete reversion of PAH after IS therapy with a significant impact on their survival. These findings strongly support the notion of an underlying inflammatory etiology of this condition, which reinforces the use of immunosuppressive treatment for all SLE patients at PAH onset., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objective: To examine the predictors of the occurrence of severe thrombocytopenia and its impact on damage accrual and mortality in SLE patients., Methods: Factors associated with time to severe thrombocytopenia (platelet count ≤20,000/mm 3 ) occurring from the onset of SLE symptoms were assessed by Cox proportional hazards regressions. The association of severe thrombocytopenia with mortality was evaluated by logistic regression analyses while its impact on damage was by negative binomial regression., Results: Of 1,217 patients, 33 (2.7%) developed severe thrombocytopenia over a mean (SD) follow-up time of 5.9 (3.6) years. The median time from the onset of SLE symptoms to severe thrombocytopenia occurrence was 22 months (IQR 8.7-62.0). Mestizo (60.6%) was the predominant ethnic group, followed by Caucasian (27.3%), while African Latin American exhibited the lowest frequency (12.1%). By multivariable analysis, Mestizo ethnicity (HR 2.67, 95% CI 1.12-6.37, p = 0.027), and autoimmune hemolytic anemia (AIHA) at baseline (HR 3.99; 95% CI 1.05-15.19, p = 0.042) were associated with a shorter time to the occurrence of severe thrombocytopenia while middle/high socioeconomic status (HR 0.23; 95% CI 0.08-0.69, p = 0.008) was associated with a longer time. Severe thrombocytopenia contributed neither to damage nor to mortality., Conclusions: Severe thrombocytopenia occurs during the early course of SLE. Mestizo ethnicity and AIHA at baseline emerged as independent predictors of a shorter time to severe thrombocytopenia occurrence while a middle/high socioeconomic status seems to be protective against its occurrence. Damage and mortality did not seem to be impacted by the occurrence of severe thrombocytopenia., Competing Interests: Declaration of competing interest The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The use of a fixed theoretical-proportional-factor (TPF 15 ) is one of the indirect highest-oxygen-consumptions (HOC) assessment methods, but it may not accurately reflect the physiological differences across various sports (cycling-triathlon-running-football-multisport). The aim of this study is to evaluate the variability of TPF across different sports, proposing a series of sport-specific new TPF values for more accurate HOC estimation., Methods: A sample of 340 adults (26.01 ± 7.18 years) performed a maximal-incremental-test using sport-specific-ergometers. HOC was considered for cycling  V ˙ O 2peak , whereas for the other investigated sports it was considered V ˙ O 2max . HOC was directly measured using a gas-analyzer, and TPF values were calculated using heart rate (HR): the ratio of HR max /HR rest multiplied for the measured values of HOC. A one-way ANOVA was used to measure differences and Bland-Altman plots were constructed to compare predicted and actual  V ˙ O 2max / V ˙ O 2peak ., Results: Actual HOC was significantly greater than those predicted by the fixed TPF 15 (P < 0.001). Sport-specific new TPF values ranged from 16.55 in multisport to 20.15 in cycling, consistently exceeding the old fixed TPF 15 , and predicting therefore better HOC. The new TPF exhibited a closer agreement with the directly measured V ˙ O 2max / V ˙ O 2peak  compared to the TPF 15 . Furthermore, the new TPF reduced the typical-measurement-error (14.94-17.78%) compared to TPF 15 (15.63-24.13%)., Conclusion: This study suggests that new TPF values predict V ˙ O 2max / V ˙ O 2peak  with higher accuracy compared to the traditional method. The use of HR max and HR rest values allows to customize training programs for different athletes. Future research should focus on validating these findings across larger populations of athletes., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Introduction: DNA hypomethylation in patients with systemic lupus erythematosus (SLE) has been recently documented in the literature. Low levels of DNA methylation have been observed globally and in genes associated with immune and inflammatory pathways in SLE's CD4+T lymphocytes. Given that certain micronutrients can either donate methyl groups within one-carbon metabolism pathways or serve as cofactors for enzymes involved in the DNA methylation process, this randomised, double-blind, placebo-controlled trial aims to investigate whether a 3-month supplementation of folic acid and vitamin B 12 will modulate the DNA methylation profile in subcutaneous adipose tissue (primary outcome) of women with SLE and normal weight or excess body weight. As secondary objectives, we will assess gene expression, telomere length and phenotypic characteristics (ie, clinical parameters, body weight and composition, abdominal circumference, food intake and disordered eating attitude, physical activity, lipid profile, serum concentrations of leptin, adiponectin, and cytokines)., Methods and Analysis: Patients will be classified according to their nutritional status by body mass index in normal weight or excess body weight. Subsequently, patients in each group will be randomly assigned to either a placebo or an intervention group (folic acid (400 mcg) and vitamin B 12 (2000 mcg) supplementation). Endpoint evaluations will be conducted using both intention-to-treat and per-protocol analyses. This study has the potential to design new personalised nutritional approaches as adjunctive therapy for patients with SLE., Ethics and Dissemination: This study has been reviewed and approved by the Ethical Committee from Clinical Hospital of the School of Medicine of the University of Sao Paulo, Brazil (CAAE.: 47317521.8.0000.0068)., Trial Registration Number: NCT05097365 (first version)., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Understanding the changes in running mechanics caused by fatigue is essential to assess its impact on athletic performance. Changes in running biomechanics after constant speed conditions are well documented, but the adaptive responses after a maximal incremental test are unknown. We compared the spatiotemporal, joint kinematics, elastic mechanism, and external work parameters before and after a maximal incremental treadmill test. Eighteen recreational runners performed 2-minute runs at 8 km·h-1 before and after a maximal incremental test on a treadmill. Kinematics, elastic parameters, and external work were determined using the OpenCap and OpenSim software. We did not find differences in spatiotemporal parameters and elastic parameters (mechanical work, ankle, and knee motion range) between premaximal and postmaximal test conditions. After the maximal test, the runners flexed their hips more at contact time (19.4°-20.6°, P = .013) and presented a larger range of pelvis rotation at the frontal plane (10.3°-11.4°, P = .002). The fatigue applied in the test directly affects pelvic movements; however, it does not change the lower limb motion or the spatiotemporal and mechanical work parameters in recreational runners. A larger frontal plane motion of the pelvis deserves attention due to biomechanical risk factors associated with injuries.

Firefighting requires a high level of physical fitness and causes substantial psychological stress, engendering musculoskeletal, mental, and cardiac issues. Consequently, it is necessary to measure the preparation of the firefighters daily through the Firefighting Physical Ability Tests (FPATs). According to the literature, some variables are more important for performance in the FPAT. Therefore, we aimed to summarize evidence that relates physical and mental aspects to the FPAT performance. We used the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) method, screening 1055 records from databases and selecting 15 that met inclusion criteria. No emotional and psychological variables were correlated with the FPAT. Most research shows significant correlations between the FPAT performance and the following: aerobic fitness, upper body endurance and strength, anaerobic capacity, body fat, and age. Lower body endurance and strength, as well as anaerobic power, had a low number of investigations and need to be further explored. Abdominal endurance showed weak correlations, while flexibility did not show any correlations in most studies, although these should be considered for injury prevention. We recommend that fitness programs and evaluations include a global analysis considering the evidence presented for methodological improvements.

Objectives: Transcranial direct current stimulation (tDCS) combined with aerobic exercise (tDCS-AE) effectively reduces fatigue in patients with fibromyalgia. However, no study has assessed this method in systemic lupus erythematosus (SLE) patients with significant fatigue. Therefore, we evaluated the safety and efficacy of tDCS-AE for significant fatigue symptoms in adult female SLE patients., Methods: This randomised, sham-controlled, double-blind study included 25 patients with SLE in remission or low disease activity (SLEDAI-2K £4) and with significant fatigue [≥36 points on the Fatigue Severity Scale (FSS) or ≥38 points on the Modified Fatigue Scale (MFIS)]. The patients received sham or tDCS for five consecutive days. The anode and cathode were positioned at M1 and Fp2, respectively (international 10-20 EEG system). tDCS was applied at an intensity of 2mA, and density of 0.057mA/cm2 in the tDCS-AE group. Both groups underwent combined low-intensity treadmill exercise. FSS, MFIS, pain visual analogue scale, physical activity, and sleep quality were evaluated at baseline and on days 7, 30, and 60. Adherence and safety were assessed using a standardised questionnaire., Results: Improvement in fatigue levels was observed in both groups. However, a sustained reduction in fatigue levels on days 30 and 60 occurred only with tDCS-AEs (p<0.05). No significant differences were observed in pain level, sleep quality, or physical activity. No disease flares occurred and the adverse effects were mild and transient. Finally, the patient's adherence to the treatment was satisfactory., Conclusions: Despite isolated AEs, there was an improvement in fatigue, however, only tDCS-AE maintained significant and sustained improvement.

Background: Systemic lupus erythematosus (SLE) is characterised by increased cardiovascular morbidity and mortality risk. We aimed to examine the prevalence of traditional cardiovascular risk factors and their control in an international survey of patients with systemic lupus erythematosus., Methods: In this multicentre, cross-sectional study, cardiovascular risk factor data from medical files of adult patients (aged ≥18) with SLE followed between Jan 1, 2015, and Jan 1, 2020, were collected from 24 countries, across five continents. We assessed the prevalence and target attainment of cardiovascular risk factors and examined potential differences by country income level and antiphospholipid syndrome coexistence. We used the Systemic Coronary Risk Evaluation algorithm for cardiovascular risk estimation, and the European Society of Cardiology guidelines for assessing cardiovascular risk factor target attainment. People with lived experience were not involved in the research or writing process., Findings: 3401 patients with SLE were included in the study. The median age was 43·0 years (IQR 33-54), 3047 (89·7%) of 3396 patients were women, 349 (10.3%) were men, and 1629 (48·1%) of 3390 were White. 556 (20·7%) of 2681 patients had concomitant antiphospholipid syndrome. We found a high cardiovascular risk factor prevalence (hypertension 1210 [35·6%] of 3398 patients, obesity 751 [23·7%] of 3169 patients, and hyperlipidaemia 650 [19·8%] of 3279 patients), and suboptimal control of modifiable cardiovascular risk factors (blood pressure [target of <130/80 mm Hg], BMI, and lipids) in the entire SLE group. Higher prevalence of cardiovascular risk factors but a better blood pressure (target of <130/80 mm Hg; 54·9% [1170 of 2132 patients] vs 46·8% [519 of 1109 patients]; p<0·0001), and lipid control (75·0% [895 of 1194 patients] vs 51·4% [386 of 751 patients], p<0·0001 for high-density lipoprotein [HDL]; 66·4% [769 of 1158 patients] vs 60·8% [453 of 745 patients], p=0·013 for non-HDL; 80·9% [1017 of 1257 patients] vs 61·4% [486 of 792 patients], p<0·0001 for triglycerides]) was observed in patients from high-income versus those from middle-income countries. Patients with SLE with antiphospholipid syndrome had a higher prevalence of modifiable cardiovascular risk factors, and significantly lower attainment of BMI and lipid targets (for low-density lipoprotein and non-HDL) than patients with SLE without antiphospholipid syndrome., Interpretation: High prevalence and inadequate cardiovascular risk factor control were observed in a large multicentre and multiethnic SLE cohort, especially among patients from middle-income compared with high-income countries and among those with coexistent antiphospholipid syndrome. Increased awareness of cardiovascular disease risk in SLE, especially in the above subgroups, is urgently warranted., Funding: None., Competing Interests: Declaration of interests AGS has received speaker fees from Merck and Schering-Plough, Bristol Myers Squibb, UCB, Pfizer, Novartis, Lilly and Women's College Hospital, Toronto, ON, Canada. AMK has received speaker fees from Boehringer Ingelheim and Sanofi; has participated on advisory boards for Pfizer, Gilead, and Boehringer Ingelheim; and has received congress sponsorship from Pfizer, Celgene, UCB, Mylan, and Roche. GJP-E has received grants from Janssen; consulting fees from GSK, AstraZeneca, Janssen, Novartis, and Bago; speakers fees from GSK, Werfen, Janssen, AstraZeneca, and Novartis; support for attending meetings and travel from GSK, AstraZeneca, and Boehringer Ingelheim; and for participation on a data safety monitoring board or advisory board from RemeGen, AstraZeneca, and Janssen. GAK has received consulting fees from Janssen and Scipher; and for participation on a data safety monitoring board or advisory board from Janssen. MFU-G has received grant support from Janssen and Pfizer; has been a speaker for GSK and AstraZeneca; and has been a member of advisory boards for AstraZeneca and Ferrer. NC-C has received grants from Roche and UCB. EH has received consulting fees and meeting fees from Johnson & Johnson, Boehringer Ingelheim, Bayer, GSK, Roche-Chugai, and Sanofi-Genzyme; speaking fees from Johnson & Johnson, GSK, and Roche-Chugai; and research funding from Commonwealth Serum Laboratories Behring, GSK, Roche-Chugai, and Johnson & Johnson. NP has received grants from Gilead Sciences Hellas and the European Centre for Disease Prevention and Control. OAM has received speaker's fees or payment for advisory boards from AbbVie, APSEN, AstraZeneca, Boehringer Ingelheim, Celltrion, GSK, and Janssen. MS has received research grants and consulting fees, and has participated as a speaker for: AbbVie, Bristol Myers Squibb, GSK, Janssen, Lilly, Pfizer, Roche, and AstraZeneca. ACSM has received speaker fees from GSK and AstraZeneca. All other authors and SURF-SLE and APS Collaborators declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Objective: To develop the second evidence-based Brazilian Society of Rheumatology consensus for diagnosis and treatment of lupus nephritis (LN)., Methods: Two methodologists and 20 rheumatologists from Lupus Comittee of Brazilian Society of Rheumatology participate in the development of this guideline. Fourteen PICO questions were defined and a systematic review was performed. Eligible randomized controlled trials were analyzed regarding complete renal remission, partial renal remission, serum creatinine, proteinuria, serum creatinine doubling, progression to end-stage renal disease, renal relapse, and severe adverse events (infections and mortality). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was used to develop these recommendations. Recommendations required ≥82% of agreement among the voting members and were classified as strongly in favor, weakly in favor, conditional, weakly against or strongly against a particular intervention. Other aspects of LN management (diagnosis, general principles of treatment, treatment of comorbidities and refractory cases) were evaluated through literature review and expert opinion., Results: All SLE patients should undergo creatinine and urinalysis tests to assess renal involvement. Kidney biopsy is considered the gold standard for diagnosing LN but, if it is not available or there is a contraindication to the procedure, therapeutic decisions should be based on clinical and laboratory parameters. Fourteen recommendations were developed. Target Renal response (TRR) was defined as improvement or maintenance of renal function (±10% at baseline of treatment) combined with a decrease in 24-h proteinuria or 24-h UPCR of 25% at 3 months, a decrease of 50% at 6 months, and proteinuria < 0.8 g/24 h at 12 months. Hydroxychloroquine should be prescribed to all SLE patients, except in cases of contraindication. Glucocorticoids should be used at the lowest dose and for the minimal necessary period. In class III or IV (±V), mycophenolate (MMF), cyclophosphamide, MMF plus tacrolimus (TAC), MMF plus belimumab or TAC can be used as induction therapy. For maintenance therapy, MMF or azathioprine (AZA) are the first choice and TAC or cyclosporin or leflunomide can be used in patients who cannot use MMF or AZA. Rituximab can be prescribed in cases of refractory disease. In cases of failure in achieving TRR, it is important to assess adherence, immunosuppressant dosage, adjuvant therapy, comorbidities, and consider biopsy/rebiopsy., Conclusion: This consensus provides evidence-based data to guide LN diagnosis and treatment, supporting the development of public and supplementary health policies in Brazil., (© 2024. The Author(s).)

Introduction: Polyarticular juvenile idiopathic arthritis (pJIA) is a childhood-onset autoimmune disease. Immune cells contribute to persistent inflammation observed in pJIA. Despite the crucial role of monocytes in arthritis, the precise involvement of classical monocytes in the pathogenesis of pJIA remains uncertain. Here, we aimed to uncover the transcriptomic patterns of classical monocytes in pJIA, focusing on their involvement in disease mechanism and heterogeneity., Methods: A total of 17 healthy subjects and 18 premenopausal women with pJIA according to ILAR criteria were included. Classical monocytes were isolated, and RNA sequencing was performed. Differential expression analysis was used to compare pJIA patients and healthy control group. Differentially expressed genes (DEGs) were identified, and gene set enrichment analysis (GSEA) was performed. Using unsupervised learning approach, patients were clustered in two groups based on their similarities at transcriptomic level. Subsequently, these clusters underwent a comparative analysis to reveal differences at the transcriptomic level., Results: We identified 440 DEGs in pJIA patients of which 360 were upregulated and 80 downregulated. GSEA highlighted TNF-α and IFN-γ response. Importantly, this analysis not only detected genes targeted by pJIA therapy but also identified new modulators of immuno-inflammation. PLAUR , IL1B , IL6 , CDKN1A , PIM1 , and ICAM1 were pointed as drivers of chronic hyperinflammation. Unsupervised learning approach revealed two clusters within pJIA, each exhibiting varying inflammation levels., Conclusion: These findings indicate the pivotal role of immuno-inflammation driven by classical monocytes in pJIA and reveals the existence of two subclusters within pJIA, regardless the positivity of rheumatoid factor and anti-CCP, paving the way to precision medicine., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Hounkpe, Sales, Ribeiro, Perez, Caparbo, Domiciano, Figueiredo, Pereira and Borba.)

Background: Systemic lupus erythematosus (SLE) often mimics symptoms of other diseases, and the interval between symptom onset and diagnosis may be long in some of these patients. Aims: To describe the characteristics associated with the time to SLE diagnosis and its impact on damage accrual and mortality in patients with SLE from a Latin American inception cohort., Methods: Patients were from a multi-ethnic, multi-national Latin-American SLE inception cohort. All participating centers had specialized lupus clinics. Socio-demographic, clinical/laboratory, disease activity, damage, and mortality between those with a longer and a shorter time to diagnosis were compared using descriptive statistical tests. Multivariable Cox regression models with damage accrual and mortality as the end points were performed, adjusting for age at SLE diagnosis, gender, ethnicity, level of education, and highest dose of prednisone for damage accrual, plus highest dose of prednisone, baseline SLEDAI, and baseline SDI for mortality., Results: Of the 1437 included in these analyses, the median time to diagnosis was 6.0 months (Q1-Q3 2.4-16.2); in 721 (50.2%) the time to diagnosis was longer than 6 months. Patients whose diagnosis took longer than 6 months were more frequently female, older at diagnosis, of Mestizo ethnicity, not having medical insurance, and having "non-classic" SLE symptoms. Longer time to diagnosis had no impact on either damage accrual (HR 1.09, 95% CI 0.93-1.28, p = 0.300) or mortality (HR 1.37, 95% CI 0.88-2.12, p = 0.200)., Conclusions: In this inception cohort, a maximum time of 24 months with a median of 6 months to SLE diagnosis had no apparent negative impact on disease outcomes (damage accrual and mortality)., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Objectives: To analyze longstanding polyarticular juvenile idiopathic arthritis (pJIA) for possible associations between localized bone damage (erosions), and systemic bone loss. Besides, to compare the systemic bone mass of pJIA with healthy controls., Methods: Thirty-four pJIA women and 99 healthy controls (HC) were included. Radius and tibia of all subjects were scanned by HR-pQCT. Volumetric bone mineral density (vBMD), bone microarchitecture, and -finite element parameters were analyzed. Patients underwent HR-pQCT of 2nd and 3rd metacarpophalangeal (MCP) and proximal interphalangeal (PIP) joints of the dominant hand, for bone erosions quantification., Results: The mean age of patients was 31.5 ± 7.4yrs with a mean disease duration of 21.7 ± 9.2yrs. Bone erosions were detectable in 79% of patients. The number of bone erosions was positively correlated with cortical porosity (Ct.Po) at tibia (r = 0.575, p = 0.001), and radius (r = 0.423, p = 0.018); and negatively correlated with cortical vBMD at tibia (r=-0.420, p = 0.015). In a logistic regression analysis, adjusted for anti-CCP, the presence of bone erosions was independently associated with Ct.Po at radius (p = 0.018) and cortical vBMD at tibia (p = 0.020). Moreover, cortical and trabecular vBMD, trabecular number, and μ-finite element parameters were decreased in patients compared to HC (p < 0.05)., Conclusion: Bone erosions in longstanding pJIA women were associated with decreased cortical bone parameters, and these patients showed systemic bone impairment at peripheral sites compared with healthy controls., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Introduction: Seasonal influenza A (H3N2) virus is an important cause of morbidity and mortality in the last 50 years in population that is greater than the impact of H1N1. Data assessing immunogenicity and safety of this virus component in juvenile systemic lupus erythematosus (JSLE) is lacking in the literature., Objective: To evaluate short-term immunogenicity and safety of influenza A/Singapore (H3N2) vaccine in JSLE., Methods: 24 consecutive JSLE patients and 29 healthy controls (HC) were vaccinated with influenza A/Singapore/INFIMH-16-0019/2016(H3N2)-like virus. Influenza A (H3N2) seroprotection (SP), seroconversion (SC), geometric mean titers (GMT), factor increase in GMT (FI-GMT) titers were assessed before and 4 weeks post-vaccination. Disease activity, therapies and adverse events (AE) were also evaluated., Results: JSLE patients and controls were comparable in current age [14.5 (10.1-18.3) vs. 14 (9-18.4) years, p = 0.448] and female sex [21 (87.5%) vs. 19 (65.5%), p = 0.108]. Before vaccination, JSLE and HC had comparable SP rates [22 (91.7%) vs. 25 (86.2%), p = 0.678] and GMT titers [102.3 (95% CI 75.0-139.4) vs. 109.6 (95% CI 68.2-176.2), p = 0.231]. At D30, JSLE and HC had similar immune response, since no differences were observed in SP [24 (100%) vs. 28 (96.6%), p = 1.000)], SC [4 (16.7%) vs. 9 (31.0%), p = 0.338), GMT [162.3 (132.9-198.3) vs. 208.1 (150.5-287.8), p = 0.143] and factor increase in GMT [1.6 (1.2-2.1) vs. 1.9 (1.4-2.5), p = 0.574]. SLEDAI-2K scores [2 (0-17) vs. 2 (0-17), p = 0.765] and therapies remained stable throughout the study. Further analysis of possible factors influencing vaccine immune response among JSLE patients demonstrated similar GMT between patients with SLEDAI < 4 compared to SLEDAI ≥ 4 (p = 0.713), as well as between patients with and without current use of prednisone (p = 0.420), azathioprine (p = 1.0), mycophenolate mofetil (p = 0.185), and methotrexate (p = 0.095). No serious AE were reported in both groups and most of them were asymptomatic (58.3% vs. 44.8%, p = 0.958). Local and systemic AE were alike in both groups (p > 0.05)., Conclusion: This is the first study that identified adequate immune protection against H3N2-influenza strain with additional vaccine-induced increment of immune response and an adequate safety profile in JSLE. ( www., Clinicaltrials: gov , NCT03540823)., (© 2023. The Author(s).)

Introduction: Evidence-based data suggest that under inflammatory conditions, classical monocytes are the main source of osteoclasts and might be involved in bone erosion pathophysiology. Here, we analyze the transcriptomic profile of classical monocytes in erosive and non-erosive rheumatoid arthritis patients in order to better understand their contribution to bone erosion., Methods: Thirty-nine premenopausal RA patients were consecutively enrolled and divided into two groups based on the presence of bone erosions on hand joints. Classical monocytes were isolated from peripheral blood through negative selection, and RNA-seq was performed using a poly-A enrichment kit and Illumina® platform. Classical monocytes transcriptome from healthy age-matched women were also included to identify differentially expressed genes (DEGs). Therefore, gene sets analysis was performed to identify the enriched biological pathways., Results: RNA-seq analysis resulted in the identification of 1,140 DEGs of which 89 were up-regulated and 1,051 down-regulated in RA patients with bone erosion compared to those without bone erosions. Among up-regulated genes, there was a highlighted expression of IL18RAP and KLF14 related to the production of pro-inflammatory cytokines, innate and adaptive immune response. Genes related to collagen metabolism ( LARP6 ) and bone formation process ( PAPPA ) were down-regulated in RA patients with erosions. Enriched pathways in patients with erosions were associated with greater activation of immune activation, and inflammation. Interestingly, pathways associated with osteoblast differentiation and regulation of Wnt signaling were less activated in RA patients with erosions., Conclusion: These findings suggest that alterations in expression of monocyte genes related to the inflammatory process and impairment of bone formation might have an important role in the pathophysiology of bone erosions in RA patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Sales, Hounkpe, Perez, Caparbo, Domiciano, Borba, Schett, Figueiredo and Pereira.)

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., (© 2023. The Author(s), under exclusive licence to International League of Associations for Rheumatology (ILAR).)

Objective: To determine in a historical inception cohort the impact of lupus nephritis at disease onset in short-term accrual 2019 European League Against Rheumatism (EULAR)/American College of Rheumatology (ACR) domains. The possible association with treatment and damage was also investigated., Methods: One hundred thirty-three consecutive adult systemic lupus erythematosus patients according to the 2019 EULAR/ACR criteria were divided according to the presence (RENAL-lupus) or absence of renal involvement (NONRENAL-lupus) at disease onset. The 2019 EULAR/ACR score and Systemic Lupus International Collaborating Clinics/ACR (SDI) were longitudinally evaluated over 3 years., Results: RENAL-lupus (n = 49 [36.8%]) and NONRENAL-lupus (n = 84 [63.2%]) were similar regarding age ( p = 0.704), female sex ( p = 0.313), and black race ( p = 0.506). At study entry, RENAL-lupus had higher 2019 EULAR/ACR total domains (30 [12-42] vs. 22 [10-36], p < 0.001) and used more often glucocorticoid ( p < 0.001), mycophenolate mofetil ( p = 0.007), and cyclophosphamide ( p = 0.001). After 3 years, a stable number of domain scores was observed for the RENAL-lupus (30 [12-42] vs. 30 [12-42], p = 0.125), whereas an increase was observed for the NONRENAL-lupus (22 [10-36] vs. 23 [10-40], p < 0.001) compared with baseline. Accordingly, RENAL-lupus patients had a lower frequency of additional domains (3/49 [6.1%] vs. 37/84 [44.0%], p < 0.0001). New kidney involvement occurred in 15 (44.1%) of 34 patients of the NONRENAL-lupus. Both groups evolved with a comparable increase in frequency of patients with damage (SDI ≥1) at the end of the study (23/49 [46.9%] vs. 34/89 [40.54%], p = 0.585) with a similar median of SDI (1 [0-4] vs. 0 [0-2], p = 0.132)., Conclusions: The distinct pattern of accrual 2019 EULAR/ACR domains in patients with and without nephritis at disease onset suggests that close surveillance for additional organ involvement, including kidney, is mandatory in NONRENAL lupus in the first 3 years of disease. The unexpected comparable early damage in both groups despite milder disease and less intense immunosuppression in NONRENAL lupus reinforces the need for new and tailored therapies for these patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

The etiology of systemic lupus erythematosus (SLE) remains unclear, with both genetic and environmental factors potentially contributing. This study aimed to explore the relationship among gut microbiota (GM), intestinal permeability, and food intake with inflammatory markers in inactive SLE patients. A total of 22 women with inactive SLE and 20 healthy volunteers were enrolled, and dietary intake was assessed through 24-h dietary recalls. Plasma zonulin was used to evaluate intestinal permeability, while GM was determined by 16S rRNA sequencing. Regression models were used to analyze laboratory markers of lupus disease (C3 and C4 complement and C-reactive protein). Our results showed that the genus Megamonas was significantly enriched in the iSLE group ( p < 0.001), with Megamonas funiformis associated with all evaluated laboratory tests ( p < 0.05). Plasma zonulin was associated with C3 levels ( p = 0.016), and sodium intake was negatively associated with C3 and C4 levels ( p < 0.05). A combined model incorporating variables from each group (GM, intestinal permeability, and food intake) demonstrated a significant association with C3 complement levels ( p < 0.01). These findings suggest that increased Megamonas funiformis abundance, elevated plasma zonulin, and higher sodium intake may contribute to reduced C3 complement levels in women with inactive SLE.

To verify the association between the practice of physical activity and dietary patterns and psychological distress before and during the lockdown due to COVID-19, a cross-sectional study was performed with 2000 Brazilians (mean [M] = 35.78 years; standard deviation [SD] = 11.20; 59.6% women) recruited through convenience sampling via digital media. Participants completed an electronic questionnaire containing sociodemographic and clinical information, nutritional patterns, physical activity, and psychological distress. Data were analyzed using descriptive statistics and multinomial regression. Before the COVID-19 lockdown, the chance of women presenting very high stress, in relation to men, was six times higher (OR = 6.32; 95% CI 4.20-9.51), a behavior that remained similar during the lockdown (OR = 6.63; 95% CI 4.40-10.00). Before the lockdown, insufficient physical activity doubled the chance of having very high stress in relation to those who engaged in physical activities six to seven times a week (OR = 2.11; 95% CI 1.10-4.02). However, during the lockdown, this probability was higher, from twice to 10 times the chance (OR = 10.19; 95% CI 4.85-21.41). Not exercising alone (OR = 2.18; 95% CI 1.52-3.11) and a decreasing physical activity frequency (OR = 2.28; 95% CI 1.40-3.71) were also associated with very high stress during the lockdown. Additionally, the consumption of smaller amounts of food showed an inverse association with very high stress (OR = 0.28; 95% CI 0.18-0.43). The maintenance of physical activity and an adequate eating frequency are measures that should be considered to cope with higher levels of anxiety and depression.