Ultrasound assessment of diaphragm and quadriceps muscles and its relationship with handgrip and respiratory muscle strength in patients with systemic sclerosis: a cross-sectional study.

BACKGROUND: Muscle dysfunction may cause disability and reduce the quality of life of patients with systemic sclerosis (SSc) when compared to healthy individuals. However, the literature on the topic is scarce and uses several criteria for assessing muscle dysfunction in this population. OBJECTIVES: To compare diaphragm and quadriceps muscle thickness, diaphragm mobility, and handgrip strength between patients with SSc and healthy individuals. METHOD: This cross-sectional study included 16 patients with SSc and 16 self-reported healthy individuals matched for age. We assessed quadriceps and diaphragm thickness and diaphragmatic mobility (ultrasound), handgrip strength (hand-held dynamometer), and respiratory muscle strength (manovacuometer). Patients also responded to the Health Assessment Questionnaire Disability Index and the International Physical Activity Questionnaire. RESULTS: Patients with SSc presented lower quadriceps thickness (p < 0.0001), diaphragmatic mobility (p = 0.01), handgrip (p < 0.0001), and respiratory muscle strength (p < 0.0001) than healthy individuals. A moderate positive correlation was observed between handgrip strength and quadriceps thickness in patients with SSc (rho = 0.576; p = 0.02). CONCLUSIONS: Patients with SSc presented reduced quadriceps thickness, diaphragmatic mobility, handgrip, and respiratory muscle strength when compared to healthy individuals Also, handgrip strength was correlated with quadriceps thickness in patients with SSc, suggesting that loss of muscle mass accompanies loss of peripheral muscle strength group of patients. Key Points • SSc patients presented reduced quadriceps thickness and diaphragmatic mobility • SSc patients have reduced handgrip and respiratory muscle strength • Lower handgrip muscle strength correlated with lower quadriceps thickness.

PPARγ partial agonist LPSF/GQ-16 prevents dermal and pulmonary fibrosis in HOCl-induced systemic sclerosis (SSc) and modulates cytokine production in PBMC of SSc patients.

Thiazolidinediones (TZD) are synthetic molecules that have a range of biological effects, including antifibrotic and anti-inflammatory, and they may represent a promising therapeutic strategy for systemic sclerosis (SSc). The aim of this study was to investigate the immunomodulatory and antifibrotic properties of LPSF/GQ-16, a TZD derivative, in peripheral blood mononuclear cells (PBMC) from SSc patients and in a murine model of SSc HOCl-induced. The PBMC of 20 SSc patients were stimulated with phytohemagglutinin (PHA) and treated with LPSF/GQ-16 for 48 h, later cytokines in the culture supernatants were quantified by sandwich enzyme-linked immunosorbent assay (ELISA) or cytometric bead array (CBA). Experimental SSc was induced by intradermal injections of hypochlorous acid (HOCl) for 6 weeks. HOCl-induced SSc mice received daily treatment with LPSF/GQ-16 (30 mg/kg) through intraperitoneal injections during the same period. Immunological parameters were evaluated by flow cytometry and ELISA, and dermal and pulmonary fibrosis were evaluated by RT-qPCR, hydroxyproline dosage and histopathological analysis. In PBMC cultures, it was possible to observe that LPSF/GQ-16 modulated the secretion of cytokines IL-2 (p < 0.001), IL-4 (p < 0.001), IL-6 (p < 0.001), IL-17A (p = 0.006), TNF (p < 0.001) and IFN-γ (p < 0.001). In addition, treatment with LPSF/GQ-16 in HOCl-induced SSc mice promoted a significant reduction in dermal thickening (p < 0.001), in the accumulation of collagen in the skin (p < 0.001), down-regulated the expression of fibrosis markers in the skin (Col1a1, α-Sma and Tgfß1, p < 0.001 for all) and lungs (Il4 and Il13, p < 0.001 for both), as well as reduced activation of CD4 + T cells (p < 0.001), B cells (p < 0.001) and M2 macrophages (p < 0.001). In conclusion, LPSF/GQ-16 showed immunomodulatory and antifibrotic properties, demonstrating the therapeutic potential of this molecule for SSc.

The effect of myofascial release of the physiological chains on the pain and health status in patients with fibromyalgia, compared to passive muscle stretching and a control group: a randomized controlled clinical trial.

OBJECTIVE: To explore the potential effectiveness of myofascial release compared to passive muscle stretching and to a control group in modulating pain intensity and health status in adults diagnosed with fibromyalgia (FM). MATERIALS AND METHODS: A preliminary randomized controlled clinical trial was conducted, consisting of eight weekly sessions. The participants were divided into three groups: myofascial release group (RG = 13), a muscle stretching group (SG = 13), and a control group (CG = 12), which received advice from a rheumatologist. The outcomes measured were the visual analogue pain scale (VAS), the fibromyalgia impact questionnaire (FIQ) (representing health status), and the number of painful areas. Univariate analyzes of covariance (ANCOVA) were performed at baseline, after 4 weeks (during treatment), after 8 weeks (post-treatment), and after 12 weeks (follow-up). The International Physical Activity Questionnaire (IPAQ), the Beck Depression Inventory (BDI) and the Pain Catastrophizing Scale (PCS) were included as covariates. Clinical trial registration number: NCT: 03408496. RESULTS: After eight weeks, the RG showed lower VAS scores compared to the CG (mean difference 95% CI: -5.10 to -1.26) and the SG (mean difference 95% CI: -4.9 to -0.23) with no difference between the SG and the CG. The total FIQ score for the RG was lower than the CG after 4 weeks (95% CI: -49.92 to -5.61), and 8 weeks (mean difference 95% CI: -52.72 to -15.73), although there was no difference between the RG and SG, as well as between the SG and CG, at both time points. The number of painful body areas was similar in all groups at the four time points. CONCLUSION: Preliminary results suggest that the RG possibly showed greater improvements in pain intensity and health status compared to the CG, and possibly greater improvements in pain intensity compared to the SG.

Myofascial release in fibromyalgia may potentially have greater improvements on pain modulation and health status when compared to medical counseling.Myofascial release, when compared to stretching, may potentially offer greater improvement in pain modulation in fibromyalgia.Myofascial release was not effective in decreasing the number of painful body areas of patients with fibromyalgia.

Synergism between chikungunya virus infection and rheumatoid arthritis on cytokine levels: Clinical implications?

Post-chikungunya virus (CHIKV) chronic arthritis shares several immunopathogenic mechanisms with rheumatoid arthritis (RA), which has led to discussions about the probable relationship between the two diseases. Indeed, some studies have suggested a role for CHIKV infection in RA development. However, to the best of our knowledge, the influence of CHIKV on previous RA has not yet been demonstrated. Herein, we analyzed the potential synergism between CHIKV infection and RA on cytokine and chemokine levels. For this, we compared the IL-1ß, IL-6, IL-10, IL-17A, CCL2, CXCL8, CXCL9 and CXCL10 levels, in addition to rheumatoid factor (RF) and C-reactive protein (CRP), in patients with post-CHIKV chronic arthritis (named CHIKV group), patients with RA (RA group), and patients with previous RA who were later infected by CHIKV (RA-CHIKV). History of CHIKV infection was confirmed by serology (IgG, ELISA). Cytokines/chemokines were quantified by flow cytometry. RF, CRP, age and sex data were obtained from medical records. IL-1ß, IL-6, IL-10 and IL-17A levels were significantly higher in RA-CHIKV compared to the other groups. CXCL8 levels were higher in the CHIKV group than in RA. CXCL9 was higher in CHIKV than in the RA-CHIKV group. CXCL10 was higher in CHIKV than in the other groups. FR levels were higher in RA than in the CHIKV group, and in RA-CHIKV than in CHIKV. No significant difference was observed in CCL2 and CRP, as well as in age and sex. Finally, our findings suggest an interplay between CHIKV infection and RA, which must be analyzed for its possible clinical impact.

High serum levels of galectins 1 and 4 in osteoarthritis patients.

BACKGROUND: Although immunostaining of galectins is associated with cartilage damage, the serum levels of these lectins in osteoarthritis (OA) are not fully understood. OBJECTIVE: Therefore, we evaluate the concentrations of galectins-1, 3, 4, and 7 in patients with osteoarthritis and correlate them with clinical parameters. METHODS: This cross-sectional study involved 60 osteoarthritis patients and 43 healthy volunteers, who had serum samples collected for galectins titration by Enzyme-Linked Immunosorbent Assay (ELISA). RESULTS: Our finds showed that the median values of gal-1 and 4 serum levels in patients were statistically higher (13,990 and 969.1 pg/mL, respectively) than in healthy controls (1,798 and 519.5 pg/mL) with p < 0.001. Further, gal-1 expressed higher levels in patients who had joint edema at the time of collection with a median value of 14,970 pg/mL. CONCLUSION: Surprisingly, galectin-4 appears to be involved in the osteoarthritis inflammation process as the well-known galectin-1.

Vitamin D receptor gene polymorphisms influence on clinical profile and bone mineral density at different skeletal sites in postmenopausal osteoporotic women.

Bone remodeling is marked by bone synthesis and absorption balance, and any altered dynamic in this process leads to osteoporosis (OP). The interaction of hormonal, environmental and genetic factors regulate bone metabolism. Since vitamin D displays a classic role in bone metabolism regulation, acting through vitamin D receptor (VDR), the genetic variants within VDR were the first ones associated with bone density and remodelling. Therefore, we investigated whether three single nucleotide polymorphisms (SNPs) within VDR were associated with OP differential susceptibility and clinical profile from postmenopausal versus healthy women from Northeast Brazil. Genetic association study enrolling 146 postmenopausal osteoporotic women as the patient group and 95 healthy age-matched women as the control group. We assessed three SNPs within VDR (rs11168268, rs1540339 and rs3890733), considering the clinical profile of all patients. Our results showed an association of rs11168268 G/G genotype with higher bone mineral density (BMD) mean for the total hip (A/A = 0.828 ± 0.09; A/G = 0.081 ± 0.13; G/G = 0.876 ± 0.12, p = .039), and the rs3890733 T/T genotype was associated with increased OP risk in patients below 60 years old (odds ratio [OR] = 5.12, 95% confidence interval [CI ]= 1.13-23.27, p = .012). The rs1540339 T/T genotype was associated with protection for individuals with low melanin deposition when compared to the high melanin deposition group (OR = 0.24, 95%CI = 0.06-0.94, p = .029). Additionally, 61% of patients presented deficient vitamin D serum levels. The SNP rs11168268 G/G was associated with a significantly increased mean total hip BMD in patients OP, highlighting this SNP and its relationship with BMD.

Association between axial spondyloarthritis and temporomandibular disorders: A systematic review.

This study aimed to assess the frequency of temporomandibular disorders (TMDs) in patients with axial spondyloarthritis (axSpA) compared with the healthy individuals. We systematically searched PubMed, Embase, Scopus, Web of Science, CINAHL, and Google Scholar databases from their inception until 2022, without language restriction. A standardized dataset was used to extract data from the observational studies. Patients were required to have axial spondyloarthritis and clinical and/or radiographic evidence of temporomandibular joint dysfunction. Meta-analysis was performed with a random effects model. A systematic review was registered under number CRD42020206283. We identified seven relevant studies, which provided data for 745 patients and 216 temporomandibular disorders events. The combined odds ratio (OR) showed that the risk of temporomandibular disorders in individuals with axial spondyloarthritis was higher than the control group (pooled OR = 5.26, 95% CI 2.50-11, 06; p < 0.02; I2  = 58%). Also, these individuals do not appear to refer possible temporomandibular joint symptoms to the rheumatologist or dentist. The results of this systematic review and meta-analysis suggest that patients with axial spondyloarthritis have an increased frequency of temporomandibular disorders. TMDs seem to be secondary to postural alterations rather than direct involvement of the temporomandibular joints (TMJs).

Association between autoimmune rheumatic diseases and head and neck cancer: Systematic review and meta-analysis.

BACKGROUND: Personal history of autoimmune rheumatic diseases has been implicated in the development of malignant neoplasms. Our aim was to assess the risk of head and neck (H&N) cancers in patients with autoimmune rheumatic diseases. METHODS: The articles search included PubMed, EMBASE, LILACS, The Cochrane Library, CINAHL, Scopus, Web of Science, and Google Scholar with no language restrictions for studies published from inception of the databases to August 20, 2022, assessing the risk of H&N cancer in patients with autoimmune rheumatic diseases. Studies were included if they reported the standardized incidence ratio (SIR) with corresponding 95% confidence intervals (CIs). The primary outcome was risk of H&N cancers in patients with autoimmune rheumatic diseases compared with the general population. Pooled summary estimates were calculated using a random-effects model, and subgroup analyses were done to establish whether risk of H&N cancers varied according to study site. RESULTS: Our search identified 5378 records, of which 32 cohort studies were eligible for systematic review and 24 for meta-analysis (including 273 613 patients). A significant association was found between H&N cancer and autoimmune rheumatic diseases (SIR = 2.35; 95% CI: 1.57-3.50; p < 0.01, I2  = 94%). CONCLUSION: Our study suggests that patients with autoimmune rheumatic diseases had a significantly increased risk of H&N cancer compared with the general population, including thyroid, oral, and nasopharyngeal cancers. These findings have implications for the individualized screening of these patients and the planning of oncology units. The protocol is registered with PROSPERO, number CRD42020197827.

Vitamin D Presented In Vitro Immunomodulatory Property on T Lymphocyte-Related Cytokines in Systemic Lupus Erythematosus.

Inflammatory T lymphocyte cytokines contribute to tissue damage in SLE patients. Vitamin D (Vit D) has a well-established immunomodulatory action, but few studies have addressed the effect of 1,25 dihydroxyvitamin D3 (1,25 (OH)2D3) on peripheral blood mononuclear cells (PBMCs) in SLE patients. The aim of this study was to evaluate the immnunomodulatory effect of 1,25 (OH)2D3 on T lymphocyte-related cytokines. Blood from 27 female SLE patients was collected for PBMC isolation and anti-DNA, complement, and serum 25 (OH)D3 level measurements. PBMCs were stimulated with anti-CD3/anti-CD28 in the presence or absence of dexamethasone or various concentrations of 1,25 (OH)2D3 for 48 h. We assessed IL-17A, IL-22, IL-21, IL-9, IFN-γ, IL-4, IL-10, IL-2, IL-6, and TNF by cytometric bead assay (CBA) and enzyme immune assay (ELISA) on culture supernatant. The mean age of patients was 36.2 (± 10.5 years) and the median Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) was 4 (0-6). The addition of 1,25 (OH)2D3 in PBMC culture reduced IL-17 A, IL-22, IL-9, and IFN-γ levels at 100 nM (p ≤ 0.0001). Furthermore, the addition of 1,25 (OH)2D3 at all concentrations increased IL-4 (p ≤ 0.0006), and 0.1 and 1 nM increased IL-10 (p ≤ 0.0004) and 0.1 nM increased IL-2 levels (p ≤ 0.0001). There was no difference regarding IL-21 and TNF levels. The addition of 1,25 (OH)2D3 in PBMC culture presented an inhibitory effect on proinflammatory cytokines and increased immunoregulatory cytokines in SLE patients, suggesting the beneficial effect of this vitamin.

Treatment with biological therapy is associated with faster recovery and lower frequency of treatment switch among rheumatic patients with Chikungunya fever.

BACKGROUND/OBJECTIVE: The effects of Chikungunya virus (CHIKV) infection on patients with rheumatic diseases have not been extensively studied. Our aim was to compare the clinical course of patients with rheumatoid arthritis and spondyloarthritis, categorized according to the use or not of biologic disease modifying anti-rheumatic drugs (bDMARDs), during and after infection by CHIKV. METHODS: Patients from a northeastern Brazilian city that suffered an epidemic outbreak of Chikungunya fever (CHIK) between Oct 2015 and Jul 2016, on regular follow-up in a longitudinal registry of rheumatic patients (BiobadaBrasil), were invited to participate. Participants underwent a standardized clinical interview and collection of blood sample for serological tests (IgM/IgG) for CHIKV. A positive IgG was considered evidence of previous CHIKV infection. RESULTS: 105 patients (84 with rheumatoid arthritis, 17 with ankylosing spondylitis, and 4 with psoriatic arthritis) were evaluated. Most patients (58, 55.2%) were on therapy with bDMARDs. The overall prevalence of seropositivity for CHIKV was 47.6% (39.7% in patients on bDMARDs and 57.4% in those exclusively on conventional synthetic (cs-) DMARDs (p = 0.070). Among seropositive patients, asymptomatic disease had similar frequency in those treated and not treated with bDMARDs (39.1% versus 33.3%, respectively; p = 0.670). However, patients exclusively on csDMARDs presented significantly higher prevalence of articular symptoms beyond 3 months and switched treatment more often than patients on bDMARDs (p < 0.05 for both comparisons). CONCLUSIONS: Among rheumatic patients with CHIK, those on bDMARDs had shorter persistence of articular symptoms and switched treatment scheme less often than patients exclusively treated with csDMARDs.

Awareness of patients receiving bisphosphonates: a cross-sectional study.

The aim of this study was to evaluate the awareness of patients using bisphosphonates (BP) regarding their risks and benefits. Sixty-five patients using BP were included. Each participant completed a self-administered questionnaire consisting of 13 questions, including sociodemographic and general information on BP. Data were analyzed using descriptive statistics, and a binomial test was used to assess patient knowledge about BP, considering a 5% significance level. Fifty-nine (90.2%) patients were unaware or had never heard of BP drugs and only 3 (4.6%) knew their indications. Only 6 patients (9.2%) said they knew about the oral complications caused by BP. Sixty-three patients (96.9%) said they were not referred to the dentist before starting BP treatment. Patients using BP do not have satisfactory knowledge regarding the risks and benefits of BP. Physicians and dentists must be prepared to inform and counsel BP users about their adverse effects and possible risk factors. Our results emphasize the importance of public policies, whether individual or collective, to be taken to increase knowledge about BP to avoid medication-related osteonecrosis of the jaw.

Factors associated with hospitalizations for Covid-19 in patients with rheumatoid arthritis: data from the Reumacov Brazil registry.

BACKGROUND: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID-19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID-19 hospitalizations in patients with RA. METHODS: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID-19 were compared to 220 patients who tested negative for COVID-19 (control group). All patient data were collected from the Research Electronic Data Capture database. RESULTS: The participants were predominantly female (90.6%) with a mean age of 53 ± 12 years. Of the patients with COVID-19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR = 4.61, 95% CI 1.06-20.02. P < 0.001) and current use of glucocorticoids (OR = 20.66, 95% CI 3.09-138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR = 0.26; 95% CI 0.10-0.67, P < 0.005). CONCLUSION: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID-19 in patients with RA. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials - RBR-33YTQC.

Differential distribution of vitamin D receptor (VDR) gene variants and its expression in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder that displays an important genetic background. Vitamin D3 (VD3 ) through its receptor (VDR) plays an important immunomodulatory role in autoimmune misbalance, being capable of modulating immune responses. Genetic alterations in VDR gene may contribute to an altered risk in SLE development and clinical manifestations. We investigated VDR SNPs (single nucleotide polymorphisms) frequencies in 128 SLE patients and 138 healthy controls (HC) and mRNA differential expression in 29 patients and 17 HC regarding SLE susceptibility as well as clinical features. We observed that rs11168268 G allele (OR = 1.55, p = .01) and G/G genotype (OR = 2.69, p = .008) were associated with increased SLE susceptibility. The rs2248098 G allele and A/G and G/G genotypes were associated to lower SLE susceptibility (OR = 0.66, p = .01; OR = 0.46, p = .01; OR = 0.44, p = .02, respectively). Regarding clinical features, we observed lower risk for: rs11168268 A/G genotype and nephritis (OR = 0.31, p = .01); rs4760648 T/T genotype and photosensitivity (OR = 0.24, p = .02); rs1540339 T/T genotype and antibody anti-dsDNA (OR = 0.19, p = .015); rs3890733 T/T genotype and serositis (OR = 0.10, p = .01). We identified a significant downregulation in VDR expression levels when compared patients and controls overall (p = 1.04e-7 ), in Cdx-2 A/G and G/G (p = .008 and p = .014, respectively) and in patients with nephritis (p = .016) Our results suggested that VDR SNPs influence upon SLE susceptibility and in particular clinical features, acting on mRNA expression in SLE patients overall and the ones with nephritis.

Joint mobilization and therapeutic exercises in the hands of patients with systemic sclerosis: A preliminary randomized controlled trial.

OBJECTIVE: To investigate the effectiveness of Maitland's joint mobilization and therapeutic exercises on the functionality of the hands in patients with systemic sclerosis. DESIGN: Randomized controlled trial. SETTING: Tertiary university hospital. SUBJECTS: Twenty-four patients diagnosed with systemic sclerosis according to ACR/EULAR 2013 criteria; age ⩾18 years and Cochin Hand Functional Scale (COCHIN) score ⩾10. They were randomized to physical therapy group (n = 12) or control group (n = 12). INTERVENTIONS: The physical therapy group received joint mobilization and undertook therapeutic exercises, twice a week, for 12 weeks, and received a booklet with information about the disease. The control group only received the booklet about the disease. MAIN MEASURES: The primary outcome measure was functionality of the hands (COCHIN). The secondary outcomes measures were disability (SHAQ), pain (visual analogic scale), range of motion (HAMIS and Delta finger-to-palm), grip strength (JAMAR dynamometer), and quality of life (SF12). RESULTS: Twenty-two patients were female, with a mean age of 47.4 ± 11.1 years and 18 had limited cutaneous form. The physical therapy group showed a decrease of 11.33 points in the COCHIN in comparison with the control group (P = 0.09). There was a significant increase in range of motion by HAMIS (3.00 ± 1.48 vs 5.42 ± 2.64, P = 0.008), reduction in pain VAS (3.42 ± 2.78 vs 7.75 ± 2.53, P < 0.001), and increase in the physical component of SF12 (38.51 ± 9.60 vs 32.65 ± 9.10, P = 0.038). CONCLUSION: Maitland's joint mobilization and therapeutic exercises improved the functionality of the hands, reduced pain in the hands and wrists, increased range of motion, and improved quality of life in patients with systemic sclerosis.

Awareness of patients receiving bisphosphonates: a cross-sectional study

Abstract The aim of this study was to evaluate the awareness of patients using bisphosphonates (BP) regarding their risks and benefits. Sixty-five patients using BP were included. Each participant completed a self-administered questionnaire consisting of 13 questions, including sociodemographic and general information on BP. Data were analyzed using descriptive statistics, and a binomial test was used to assess patient knowledge about BP, considering a 5% significance level. Fifty-nine (90.2%) patients were unaware or had never heard of BP drugs and only 3 (4.6%) knew their indications. Only 6 patients (9.2%) said they knew about the oral complications caused by BP. Sixty-three patients (96.9%) said they were not referred to the dentist before starting BP treatment. Patients using BP do not have satisfactory knowledge regarding the risks and benefits of BP. Physicians and dentists must be prepared to inform and counsel BP users about their adverse effects and possible risk factors. Our results emphasize the importance of public policies, whether individual or collective, to be taken to increase knowledge about BP to avoid medication-related osteonecrosis of the jaw.

Factors associated with hospitalizations for Covid-19 in patients with rheumatoid arthritis: data from the Reumacov Brazil registry

Abstract Background: Patients using immunosuppressive drugs may have unfavorable results after infections. However, there is a lack of information regarding COVID 19 in these patients, especially in patients with rheumatoid arthritis (RA). Therefore, the aim of this study was to evaluate the risk factors associated with COVID 19 hospitalizations in patients with RA. Methods: This multicenter, prospective cohort study is within the ReumaCoV Brazil registry and included 489 patients with RA. In this context, 269 patients who tested positive for COVID 19 were compared to 220 patients who tested negative for COVID 19 (control group). All patient data were collected from the Research Electronic Data Capture database. Results: The participants were predominantly female (90.6%) with a mean age of 53 ±12 years. Of the patients with COVID 19, 54 (20.1%) required hospitalization. After multiple adjustments, the final regression model showed that heart disease (OR =4.61, 95% CI 1.06-20.02. P < 0.001) and current use of glucocorticoids (OR =20.66, 95% CI 3.09-138. P < 0.002) were the risk factors associated with hospitalization. In addition, anosmia was associated with a lower chance of hospitalization (OR =0.26; 95% CI 0.10-0.67, P < 0.005). Conclusion: Our results demonstrated that heart disease and the use of glucocorticoids were associated with a higher number of hospital admissions for COVID 19 in patients with RA. Trial registration: Brazilian Registry of Clinical Trials RBR 33YTQC.

Recommendations of the Brazilian Society of Rheumatology for the use of JAK inhibitors in the management of rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic and autoimmune systemic inflammatory disease that can cause irreversible joint deformities, with increased morbidity and mortality and a significant impact on the quality of life of the affected individual. The main objective of RA treatment is to achieve sustained clinical remission or low disease activity. However, up to 40% of patients do not respond to available treatments, including bDMARDs. New therapeutic targets for RA are emerging, such as Janus kinases (JAKs). These are essential for intracellular signaling (via JAK-STAT) in response to many cytokines involved in RA immunopathogenesis. JAK inhibitors (JAKi) have established themselves as a highly effective treatment, gaining increasing space in the therapeutic arsenal for the treatment of RA. The current recommendations aim to present a review of the main aspects related to the efficacy and safety of JAKis in RA patients, and to update the recommendations and treatment algorithm proposed by the Brazilian Society of Rheumatology in 2017.

Chronic use of hydroxychloroquine did not protect against COVID-19 in a large cohort of patients with rheumatic diseases in Brazil.

BACKGROUND: There is a lack of information on the role of chronic use of hydroxychloroquine during the SARS-CoV-2 outbreak. Our aim was to compare the occurrence of COVID-19 between rheumatic disease patients on hydroxychloroquine with individuals from the same household not taking the drug during the first 8 weeks of community viral transmission in Brazil. METHODS: This baseline cross-sectional analysis is part of a 24-week observational multi-center study involving 22 Brazilian academic outpatient centers. All information regarding COVID-19 symptoms, epidemiological, clinical, and demographic data were recorded on a specific web-based platform using telephone calls from physicians and medical students. COVID-19 was defined according to the Brazilian Ministry of Health (BMH) criteria. Mann-Whitney, Chi-square and Exact Fisher tests were used for statistical analysis and two binary Final Logistic Regression Model by Wald test were developed using a backward-stepwise method for the presence of COVID-19. RESULTS: From March 29th to May 17st, 2020, a total of 10,443 participants were enrolled, including 5166 (53.9%) rheumatic disease patients, of whom 82.5% had systemic erythematosus lupus, 7.8% rheumatoid arthritis, 3.7% Sjögren's syndrome and 0.8% systemic sclerosis. In total, 1822 (19.1%) participants reported flu symptoms within the 30 days prior to enrollment, of which 3.1% fulfilled the BMH criteria, but with no significant difference between rheumatic disease patients (4.03%) and controls (3.25%). After adjustments for multiple confounders, the main risk factor significantly associated with a COVID-19 diagnosis was lung disease (OR 1.63; 95% CI 1.03-2.58); and for rheumatic disease patients were diagnosis of systemic sclerosis (OR 2.8; 95% CI 1.19-6.63) and glucocorticoids above 10 mg/ day (OR 2.05; 95% CI 1.31-3.19). In addition, a recent influenza vaccination had a protective effect (OR 0.674; 95% CI 0.46-0.98). CONCLUSION: Patients with rheumatic disease on hydroxychloroquine presented a similar occurrence of COVID-19 to household cohabitants, suggesting a lack of any protective role against SARS-CoV-2 infection. Trial registration Brazilian Registry of Clinical Trials (ReBEC; RBR - 9KTWX6).

Genetic variants in LGALS3 are related to lower galectin-3 serum levels and clinical outcomes in systemic sclerosis patients: A case-control study.

INTRODUCTION: Systemic sclerosis (SSc) is a rare complex disease characterized by vascular damage, autoimmunity, and extensive skin and internal organs fibrosis. Galectin-3 (Gal-3) is encoded by gene LGALS3 (Lectin, Galactoside-Binding, Soluble, 3; 14q22.3) and it has been reported to play a central role in self-tolerance, inflammation, and fibrosis. OBJECTIVE: To investigate associations among LGALS3 single nucleotide polymorphisms (SNPs) and serum levels Gal-3 and SSc susceptibility and their clinical features. METHODS: A case-control study with 88 patients and 151 matched controls was performed. LGALS3 variants were analyzed by the TaqMan real-time polymerase chain reaction (PCR) system whereas Gal-3 serum levels were measured by sandwich enzyme linked immunosorbent assay (ELISA). Associations among genotypes, clinical features, and Gal-3 levels were performed by univariable and multivariable analysis through statistical packages. RESULTS: The LGALS3 rs4652 A/C genotype was more frequent in SSc patients than controls according to overdominant model [OR 1.89 (CI 95% 1.01 - 3.52); p = .046]. Also, LGALS3 rs4652 C/C polymorphic genotype was associated with lower patient Gal-3 levels (p = .03) and control group (p = 0.005), as noted by generalized linear model (GLM). The LGALS3 rs1009977 G/T controls showed higher Gal-3 levels than wild-type and polymorphic genotypes (p = .03); however, in SSc patients, no difference was found. None of the LGALS3 SNPs or Gal-3 levels was associated with clinical manifestations in SSc patients. Considering only the SSc group, GLM analysis pointed LGALS3 rs4652 and rs2075601, pulmonary arterial hypertension (PAH), myopathy, and health assessment questionnaire (HAQ) and scleroderma health assessment questionnaire (SHAQ) as important predictors for Gal-3 levels. CONCLUSION: The LGALS3 rs4652 A/C was more frequent in SSc patients and related to lower Gal-3 levels. These findings were corroborated through a GLM to estimate Gal-3 values. Also, by model equations, Gal-3 levels may be predicted by HAQ, SHAQ, PAH, myopathy, and LGALS3 rs4652 and rs2075601 factors. In these ways, we suggest that galectins may be promising biomarkers to identify susceptibility to SSc as well as to identify HAQ, SHAQ, PAH, and myopathy outcomes.