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Objectives To evaluate immunogenicity and safety of an inactivated SARS-CoV-2 vaccine in systemic autoimmune myopathies (SAMs) and the possible influence of baseline disease parameters, comorbidities and therapy on immune response. Methods This prospective controlled study included 53 patients with SAMs and 106 non-immunocompromised control group (CTRL). All participants received two doses of the Sinovac-CoronaVac vaccine (28-day interval). Immunogenicity was assessed by anti-SARS-CoV-2 S1/S2 IgG seroconversion (SC), anti-S1/S2 IgG geometric mean titre (GMT), factor increase GMT (FI-GMT), neutralizing antibodies (NAb) positivity, and median neutralizing activity after each vaccine dose (D0 and D28) and six weeks after the second dose (D69). Participants with pre-vaccination positive IgG serology and/or NAb and those with RT-PCR confirmed COVID-19 during the protocol were excluded from immunogenicity analysis. Results Patients and CTRL had comparable sex (P> 0.99) and age (P= 0.90). Immunogenicity of 37 patients and 79 CTRL-naïve participants revealed at D69, a moderate but significantly lower SC (64.9% vs 91.1%, P< 0.001), GMT [7.9 (95%CI 4.7–13.2) vs 24.7 (95%CI 30.0–30.5) UA/ml, P< 0.001] and frequency of NAb (51.4% vs 77.2%, P< 0.001) in SAMs compared with CTRL. Median neutralizing activity was comparable in both groups [57.2% (interquartile range (IQR) 43.4–83.4) vs 63.0% (IQR 40.3–80.7), P= 0.808]. Immunosuppressives were less frequently used among NAb+ patients vs NAb- patients (73.7% vs 100%, P= 0.046). Type of SAMs, disease status, other drugs or comorbidities did not influence immunogenicity. Vaccine-related adverse events were mild with similar frequencies in patients and CTRL (P> 0.05). Conclusion Sinovac-CoronaVac is safe and has a moderate short-term immunogenicity in SAMs, but reduced compared with CTRL. We further identified that immunosuppression is associated with diminished NAb positivity. Trial registration COVID-19 CoronaVac in Patients With Autoimmune Rheumatic Diseases and HIV/AIDS (CoronavRheum), http://clinicaltrials.gov/ct2/show/NCT04754698 [ABSTRACT FROM AUTHOR]

Objectives To document the work situation, the work ability and the expectation of returning to work among adult patients with systemic autoimmune myopathies (SAMs), and to identify the factors associated with each of these outcomes. Methods Cross-sectional study. The work situation (performing paid work vs out of work) was ascertained via a structured questionnaire. For those who were working, we applied the Work Ability Index (WAI; scale 7–49); and for those who were out of work, we applied the Return-to-Work Self-Efficacy questionnaire (RTW-SE; scale 11–66). Results Of the 75 patients with SAMs included, 33 (44%) were doing paid work and 42 (56%) were out of work. The work situation was independently associated with physical function, assessed by the Health Assessment Questionnaire-Disability Index (HAQ-DI). A 1-point increase in the HAQ-DI (scale 0–3) decreased the chance of doing paid work by 66% (95% CI: 0.16, 0.74; P  = 0.007). Patients performing paid work had a mean WAI of 33.5 (6.9). The following variables were associated with a decrease in the WAI score in the regression model: female sex (−5.04), diabetes (−5.94), fibromyalgia (−6.40), fatigue (−4.51) and severe anxiety (−4.59). Among those out of work, the mean RTW-SE was 42.8 (12.4). Cutaneous manifestations and >12 years of education were associated with an average increase of 10.57 and 10.9 points, respectively, in the RTW-SE. A 1-point increase in the HAQ-DI decreased the RTW-SE by 4.69 points. Conclusion Our findings highlight the poor work participation in a well-characterized sample of working-age patients with SAMs. Strategies to improve work-related outcomes in these patients are urgently needed. [ABSTRACT FROM AUTHOR]

The article discusses the benefits of antimalarial treatment among patients who have a medical history of systemic lupus erythematosus (SLE). It mentions several criteria to be considered including laboratory findings, socioeconomic and demographic characteristics of the patient. It states that antimalarial treatment should be recommended for patients with a history of SLE since protective effects have been noted.

Mycophenolate mofetil (MMF) has recently been reported as a useful alternative immunosuppressive drug in autoimmune diseases including in Takayasu arteritis (TA). The aim of this study was to verify the efficacy and tolerability of MMF administration in controlling TA disease activity and allowing glucocorticosteroid reduction. Ten consecutive active TA patients followed at the Vasculitis Clinic were enrolled from January 2003 to 2006 and received oral MMF (2 g/day) for an average of 23.3 months. Disease activity assessed using the National Institutes of Health criteria, clinical features, and inflammatory laboratory findings were evaluated. Five patients had received at least one immunosuppressive drug before administration of MMF (four methotrexate, two azathioprine, and one chlorambucil) but had not achieved clinical and laboratory remission. The other five patients received MMF as their first immunosuppressive drug because of an important disease flare during steroid dose reduction. Clinical activity disappeared in all patients with MMF therapy, except in one patient who abandoned the study because of an important headache, attributed to the drug. Moreover, the MMF therapy allowed significant tapering of the prednisone dose in the rest of the nine patients (24.5 ± 17.1 vs 5.8 ± 7.8 mg/day; p = 0.0019). Reinforcing this finding, a significant reduction in inflammatory laboratory parameters, erythrocyte sedimentation rate (24.7 ± 15.5 vs 12.8 ± 10.8 mm/h; p = 0.036) and C-reactive protein (24.0 ± 14.9 vs 11.2 ± 10.7 mg/l; p = 0.0167), was observed. In summary, MMF therapy reduced clinical and laboratory parameters of TA disease activity, suggesting that this drug is a promising immunosuppressive drug, particularly in refractory cases and as a steroid-sparing agent. [ABSTRACT FROM AUTHOR]

Objectives: To evaluate factors associated with COVID-19 severity outcomes in patients with systemic lupus erythematosus (SLE). Methods: This was a cross-sectional analysis of baseline data of a prospective, multi-stage cohort study—"The ReumaCoV Brazil"—designed to monitor patients with immune-mediated rheumatologic disease (IMRD) during the SARS-CoV-2 pandemic. SLE adult patients with COVID-19 were compared with those without COVID-19. SLE activity was evaluated by the patient global assessment (PGA) and SLE Disease Activity Index 2000 (SLEDAI-2K). Results: 604 SLE patients were included, 317 (52.4%) with COVID-19 and 287 (47.6%) in the control group. SLE COVID-19 patients reported a lower frequency of social isolation and worked more frequently as health professionals. There was no difference in the mean SLEDAI-2K score between groups in the post–COVID-19 period (5.8 [8.6] vs. 4.5 [8.0]; p = 0.190). However, infected patients reported increased SLE activity according to the Patient Global Assessment (PGA) during this period (2.9 [2.9] vs. 2.3 [2.6]; p = 0.031. Arterial hypertension (OR 2.48 [CI 95% 1.04–5.91], p = 0.041), cyclophosphamide (OR 14.32 [CI 95% 2.12–96.77], p = 0.006), dyspnea (OR: 7.10 [CI 95% 3.10–16.23], p < 0.001) and discontinuation of SLE treatment medication during infection (5.38 [CI 95% 1.97–15.48], p = 0.002), were independently associated with a higher chance of hospitalization related to COVID-19. Patients who received telemedicine support presented a 67% lower chance of hospitalization (OR 0.33 [CI 95% 0.12–0.88], p = 0.02). Conclusion: Hypertension and cyclophosphamide were associated with a severe outcome, and telemedicine can be a useful tool for SLE patients with COVID-19. [ABSTRACT FROM AUTHOR]

Objectives To assess immunogenicity of a heterologous fourth dose of an mRNA (BNT162b2) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine in autoimmune rheumatic diseases (ARD) patients with poor/non-response to inactivated vaccine (Sinovac-CoronaVac). Methods A total of 164 ARD patients who were coronavirus disease 2019 (COVID-19) poor/non-responders (negative anti-SARS-CoV-2 S1/S2 IgG and/or neutralizing antibodies—NAb) to the third dose of Sinovac-CoronaVac received an additional heterologous dose of mRNA (BNT162b2) 3 months after last dose. IgG and NAb were evaluated before and after the fourth dose. Results Significant increases were observed after the fourth dose in IgG (66.4 vs 95.1%, P  < 0.001), NAb positivity (5.5 vs 83.5%, P  < 0.001) and geometric mean titre (29.5 vs 215.8 AU/ml, P  < 0.001), and 28 (17.1%) remained poor/non-responders. Patients with negative IgG after a fourth dose were more frequently under rituximab (P  = 0.001). Negative NAb was associated with older age (P  = 0.015), RA (P  = 0.002), SSc (P  = 0.026), LEF (P  = 0.016) and rituximab use (P  = 0.007). In multiple logistic regression analysis, prednisone dose ≥7.5 mg/day (OR = 0.34; P  = 0.047), LEF (OR = 0.32, P  = 0.036) and rituximab use (OR = 0.19, P  = 0.022) were independently associated with negative NAb after the fourth vaccine dose. Conclusions This is the largest study to provide evidence of a remarkable humoral response after the fourth dose of heterologous mRNA SARS-CoV-2 vaccination in ARD patients with poor/non-response to the third dose of an inactivated vaccine. We further identified that treatment, particularly rituximab and prednisone, impaired antibody response to this additional dose. Trial registration ClinicalTrials.gov, https://clinicaltrials.gov , CoronavRheum #NCT04754698. [ABSTRACT FROM AUTHOR]

Objective To evaluate the long-term effects of pulse i.v. methylprednisolone (IVMP) or IVIG administered during the first year of diagnosis in DM and PM patients. Methods This is a retrospective single-centre cohort study of patients with PM/DM followed for up to 4 years from 2001 to 2017. We used Cox regression models to estimate hazard ratios (HRs) and assess the effects of early pulse IVMP or IVIG on three outcomes: complete clinical response, CS discontinuation, and survival. Analysis was adjusted for clinical, laboratory and treatment covariates. Results A total of 204 patients were included and categorized into four initial treatment groups: pulse IVMP (n  = 46), pulse IVMP + IVIG (n  = 55), IVIG (n  = 10), and without IVMP or IVIG (n  = 93). The groups of early pulse IVMP and pulse IVMP + IVIG had a higher HR for complete clinical response in the multivariate models (HR = 1.56, 95% CI: 1.05, 2.33, P   =  0.029; and HR = 1.58, 95% CI: 1.02, 2.45, P   =  0.041, respectively). Only the group of pulse IVMP + IVIG had a significant association with CS discontinuation in the multivariate analysis (HR = 1.65, 95% CI: 1.02, 2.68, P   =  0.043). Early pulse IVMP or IVIG had no impact on mortality. Conclusion Despite having a more severe disease profile, patients with PM/DM submitted to pulse IVMP or pulse IVMP + IVIG during the first year of diagnosis had a higher HR for complete clinical response, whereas the combination of pulse IVMP + IVIG had an association with CS discontinuation. Prospective long-term studies are warranted to confirm these benefits of early pulse IVMP and IVIG on patients with PM/DM. [ABSTRACT FROM AUTHOR]

Exercise is a treatment in rheumatoid arthritis, but participation in moderate-to-vigorous exercise is challenging for some patients. Light-intensity breaks in sitting could be a promising alternative. We compared the acute effects of active breaks in sitting with those of moderate-to-vigorous exercise on cardiometabolic risk markers in patients with rheumatoid arthritis. In a crossover fashion, 15 women with rheumatoid arthritis underwent three 8-h experimental conditions: prolonged sitting (SIT), 30-min bout of moderate-to-vigorous exercise followed by prolonged sitting (EX), and 3-min bouts of light-intensity walking every 30 min of sitting (BR). Postprandial glucose, insulin, c-peptide, triglycerides, cytokines, lipid classes/subclasses (lipidomics), and blood pressure responses were assessed. Muscle biopsies were collected following each session to assess targeted proteins/genes. Glucose [-28% in area under the curve (AUC), P = 0.036], insulin (-28% in AUC, P = 0.016), and c-peptide (-27% in AUC, P = 0.006) postprandial responses were attenuated in BR versus SIT, whereas only c-peptide was lower in EX versus SIT (-20% in AUC, P = 0.002). IL-1b decreased during BR, but increased during EX and SIT (P = 0.027 and P = 0.085, respectively). IL-1ra was increased during EX versus BR (P = 0.002). TNF-α concentrations decreased during BR versus EX (P = 0.022). EX, but not BR, reduced systolic blood pressure (P = 0.013). Lipidomic analysis showed that 7 of 36 lipid classes/subclasses were significantly different between conditions, with greater changes being observed in EX. No differences were observed for protein/gene expression. Brief active breaks in sitting can offset markers of cardiometabolic disturbance, which may be particularly useful for patients who may find it difficult to adhere to exercise. [ABSTRACT FROM AUTHOR]

The present study of Helicobacter pylori infection was conducted in family units of Japanese Brazilians living in São Paulo city. The authors attempted to determine the seroprevalence of H. pylori infection within family units of Japanese Brazilians and to identify risk factors associated with intrafamilial transmission. The seroprevalence was determined in 1037 healthy and asymptomatic volunteer subjects aged 0–69 years (530 adults and 507 children) of 265 families. Demographic data and details of living conditions were obtained from each family. H. pylori seropositive infection was found in 39.2% of the parents and 9.3% of the children. A reduced risk of H. pylori infection was found for girls (odds ratio [OR] 0.45; 95% confidence interval [CI], 0.23–0.86). The prevalence of infection was 3.5% for children with uninfected parents; 9.9% (OR, 2.51; 95% CI, 0.95–6.61) for those with a seronegative mother and a seropositive father; 14.9% (OR, 4.93; 95% CI, 1.86–13.06) for those with a seropositive mother and a seronegative father; and 16.0% (OR, 5.29; 95% CI, 1.98–14.14) for those with seropositive parents. On multivariate analysis, the use of a pacifier, and mother's symptoms of nausea and vomiting were significantly associated with the risk of H. pylori infection for children, and the child having her/his own room was significantly associated with a reduced risk. Income was not associated with H. pylori infection in children and was inversely associated in parents. The prevalence of H. pylori infection in family units of Japanese Brazilians supports the hypothesis of a predominant role for mother–child transmission of H. pylori infection, mainly through contact with regurgitated gastric juice in the mother's mouth. [ABSTRACT FROM AUTHOR]

Objective: To assess the body composition (BC) of patients with granulomatosis with polyangiitis (GPA) compared to healthy controls, emphasizing visceral adipose tissue (VAT) and associated BC parameters with disease activity, the damage index, and inflammatory parameters in patients with GPA. Methods: This study was conducted in 43 patients with GPA and 43 healthy controls matched by sex, age, and body mass index (BMI). BC was analyzed using dual-energy X-ray absorptiometry (DXA). The fat mass parameters evaluated were total fat mass (FM), adiposity (%), the fat mass index (FMI: fat mass/ht2), and VAT (g, cm2, cm3). Disease activity was assessed by the Birmingham Vasculitis Activity Score (BVAS). Damage was assessed by the Vasculitis Damage Index (VDI). C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were measured. Results: Comparing patients with GPA with healthy controls, patients had a significantly greater VAT (VAT in g: 685.81 ± 306.10 vs. 581.21 ± 235.57, p = 0.04; VAT in cm2: 142.23 ± 63.48 vs. 119.84 ± 49.54, p = 0.03; VAT in cm3: 741.33 ± 330.97 vs. 628.44 ± 254.66, p = 0.04). Patients with higher VAT (≥ 768 g) had an increased value of ESR (22.77 ± 26.79 vs. 11.57 ± 11.30 mm/1st hour, p = 0.04) and an increased value of BVAS (3.18 ± 4.15 vs. 0.90 ± 1.70, p = 0.01) when compared to patients with less VAT (< 768 g). Conclusion: Patients with GPA have altered BC compared to healthy controls. Moreover, higher VAT was associated with disease activity and higher inflammatory markers, suggesting a relationship between GPA activity and adiposity parameters. Key points • Granulomatosis with polyangiitis patients have increased visceral adipose tissue when compared to health controls; • Granulomatosis with polyangiitis patients with higher values of visceral adipose tissue have worse disease activity and higher inflammatory markers; • This paper represents important contribution to the well-studied association between vasculitis and inflammatory markers, adding the role of adipose visceral tissue in the disease physiopathology. [ABSTRACT FROM AUTHOR]

Exercise seems to enhance the beneficial effect of bariatric (Roux-en-Y gastric bypass [RYGB]) surgery on insulin resistance. We hypothesized that skeletal muscle extracellular matrix (ECM) remodeling may underlie these benefits. Women were randomized to either a combined aerobic and resistance exercise training program following RYGB (RYGB + ET) or standard of care (RYGB). Insulin sensitivity was assessed by oral glucose tolerance test. Muscle biopsy specimens were obtained at baseline and 3 and 9 months after surgery and subjected to comprehensive phenotyping, transcriptome profiling, molecular pathway identification, and validation in vitro. Exercise training improved insulin sensitivity beyond surgery alone (e.g., Matsuda index: RYGB 123% vs. RYGB + ET 325%; P ≤ 0.0001). ECM remodeling was reduced by surgery alone, with an additive benefit of surgery and exercise training (e.g., collagen I: RYGB -41% vs. RYGB + ET -76%; P ≤ 0.0001). Exercise and RYGB had an additive effect on enhancing insulin sensitivity, but surgery alone did not resolve insulin resistance and ECM remodeling. We identified candidates modulated by exercise training that may become therapeutic targets for treating insulin resistance, in particular, the transforming growth factor-β1/SMAD 2/3 pathway and its antagonist follistatin. Exercise-induced increases in insulin sensitivity after bariatric surgery are at least partially mediated by muscle ECM remodeling. [ABSTRACT FROM AUTHOR]

Helicobacter pylori, especially the cytotoxin-associated antigen A ( cagA)-positive strains, plays a crucial role in the development of gastric atrophy and gastric cancer. CagA delivered into gastric epithelial cells combines with src homology 2 domain-containing protein tyrosine phosphatase-2 (SHP-2), possibly leading to atrophy/cancer. Our previous study found that a single-nucleotide polymorphism (SNP; IMS-JST057927) of the PTPN11 gene encoding SHP-2, was associated with gastric atrophy among H. pylori-seropositive subjects. This study aimed to examine the reproducibility of the association among Japanese residing in a different circumstance. The subjects were 918 healthy adult Japanese Brazilians from four different areas in Brazil. Blood was sampled from March to May 2001. The target SNP in intron 3 of PTPN11 was genotyped by polymerase chain reaction with confronting two-pair primers (PCR-CTPP). Gastric atrophy was evaluated with serum pepsinogens (PGs); PG I, less than 70 ng/dl and PG I/II ratio, less than 3. The genotype frequency of PTPN11 was in Hardy-Weinberg equilibrium: 65.5% for G/ G, 30.4% for G/ A, and 4.1% for A/ A. The PTPN11 polymorphism had no significant association with H. pylori seropositivity. Among the H. pylori-seropositive subjects, the odds ratios (ORs) of gastric atrophy were 0.93 (95% confidence interval [CI], 0.59–1.47) for the G/ A genotype and 0.31 (95% CI, 0.10–0.95) for the A/ A genotype, compared with the G/ G genotype. The present study reproduced the significant association between the A/ A genotype and reduced risk of gastric atrophy among Japanese outside Japan. According to the Japan Single Nucleotide Polymorphisms (JSNP) database (db)SNP data, the G allele is very frequent among Japanese and rare in Caucasians. This fact may partly explain the distribution of gastric atrophy/cancer in the world. [ABSTRACT FROM AUTHOR]

Background Methods. The subjects were 291 seropositive individuals (129 males and 162 females; age, 30 to 69 years) out of 656 Japanese-Brazilian volunteers in SÃo Paulo city. Information on lifestyle factors was obtained using a self-administered questionnaire. Atrophic gastritis was defined as a PG1 serum level less than 70 ng/ml and PG1/PG2 ratio less than 3. Results. The prevalence of atrophic gastritis was 31.9% (95% confidence intervals, 26.6%–37.6%). The proportion of subjects with atrophic gastritis increased with age, but there were no significantly marked differences in the proportions of subjects with atrophic gastritis among the three generations studied (first generation [Issei], second generation [Nisei], and third generation [Sansei]) for any 10-year age group. The associations with smoking and alcohol drinking were not significant. Length of education was inversely associated with gastric atrophy, while infrequent rice intake was preventive; the odds ratio relative to everyday rice intake was 0.13 (95% confidence intervals, 0.39–0.46) on multivariate analysis. Conclusions. The present study demonstrated that frequent rice intake was a risk factor for atrophic gastritis among the H. pylori-infected Japanese-Brazilians, suggesting that diet including rice plays a role in the step from H. pylori infection to gastric atrophy. Studies of lifestyle factors related to gastric atrophy development in Helicobacter pylori-infected individuals are limited. The present cross-sectional study aimed to examine the associations between lifestyle factors and serum pepsinogens (PGs) among anti-H. pylori antibody-seropositive Japanese in Brazil, where gastric cancer mortality was reported to be as high as in Japanese in Japan, and seropositive individuals were still frequently detected. [ABSTRACT FROM AUTHOR]