Gathering patients and rheumatologists' perceptions to improve outcomes in idiopathic inflammatory myopathies

Objective: Therapeutic targets in Idiopathic Inflammatory Myopathies (IIM) are based on the opinions of physicians/specialists, which may not reflect the main concerns of patients. The authors, therefore, assessed the outcome concerns of patients with IIM and compared them with the concerns of rheumatologists in order to develop an IIM outcome standard set. Methods: Ninety-three IIM patients, 51 rheumatologists, and one physiotherapist were invited to participate. An open questionnaire was initially applied. The top 10 answers were selected and applied in a multiple-choice questionnaire, inquiring about the top 3 major concerns. Answers were compared, and the agreement rate was calculated. Concerns were gathered in an IIM outcome standard set with validated measures. Results: The top three outcome concerns raised by patients were medication side effects/muscle weakness/prevention functionality loss. The top three concerns among rheumatologists were to prevent loss of functionality/to ensure the quality of life/to achieve disease remission. Other's outcomes concerns only pointed out by patients were muscle pain/diffuse pain/skin lesions/fatigue. The agreement rate between both groups was 41%. Assessment of these parameters guided the development of an IIM standard set which included Myositis Disease Activity Assessment Visual Analogue Scale/Manual Muscle Testing/fatigue and pain Global Visual Analogue Scale/Health Assessment Questionnaire/level of physical activity. Conclusion: The authors propose a novel standard set to be pursued in IIM routine follow-up, which includes not only the main patients/rheumatologist outcome concerns but also additional important outcomes only indicated by patients. Future studies are necessary to confirm if this comprehensive approach will result in improved adherence and ultimately in better assistance

Anti-SARS-CoV-2 inactivated vaccine in patients with ANCA-associated vasculitis: Immunogenicity, safety, antibody decay and the booster dose

Objective: To evaluate inactivated CoronaVac prime vaccination, antibody decay, booster dose, and safety in ANCA-Associated Vasculitis (AAV) patients. Methods: Fifty-three AAV patients and 106 Controls (CG) received CoronaVac on days: D0 (first dose), D28(second dose), and D210 (booster dose, 32 AAV: 32 CG). The primary outcome was immunogenicity after the second vaccine dose (day 69) assessed by Seroconversion Rates (SC) of anti-SARS-CoV-2 S1/S2 IgG and Neutralizing Antibodies (NAb). Secondary outcomes were safety, immunogenicity (D28/D240), 6-months antibody decay (D210) and the booster dose response (D240). Results: At D69 SC (65.1% vs. 96.8%, p = 0.0001), GMT (21.3 UA/mL vs. 67.7 UA/mL, p < 0.001) and NAb- positivity (53.7% vs. 80.6%, p = 0.001) were moderate but lower in naïve-AAV patients than CG. Patients without SC used more often IS (93.3% vs. 53.3%, p = 0.015), mycophenolate mofetil (20% vs. 0%, p = 0.037) and prednisone (60.0% vs. 28.6%, p = 0.057) than seroconverted. NAb negativity in AAV patients was associated with prednisone treatment (57.9% vs. 18.2%, p = 0.015) and IS (84.2% vs. 55.0%, p = 0.046). Logistic regression analysis models showed that only prednisone was associated with lower seroconversion (OR = 0.2, 0,95% CI 0.05‒0.86, p = 0.030) and with lower NAb positivity (OR = 0.2, 0,95% CI 0.05‒0.88, p = 0.034). After six months (D69‒D210) a decrease in IgG positivity occurred in 32 AAV patients (15.7%, p = 0.074) and 32 CG (18.7%, p = 0.041). For the NAb positivity, the 6-month decrease was not significant (p = 0.114) whereas a major reduction occurred for CG (p < 0.001). A booster dose (D240) resulted in an increment in IgG-positivity (21.9%, p = 0.023) and NAb-positivity (34.4%, p = 0.006) in AAV patients. No moderate/severe adverse events attributable to the vaccine were observed. Conclusion: This study provides novel data on the excellent safety and moderate immunogenicity of CoronaVac in AAV patients. A six-month mild antibody waning was observed with a good response to the booster dose, although levels remained lower than CG (CoronavRheum-NCT04754698)

Acute cardiometabolic effects of brief active breaks in sitting for patients with rheumatoid arthritis

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-1β 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. NEW & NOTEWORTHY Exercise is a treatment in rheumatoid arthritis but is challenging for some patients. Light-intensity breaks in sitting could be a promising alternative. Our findings show beneficial, but differential, cardiometabolic effects of active breaks in sitting and exercise in patients with rheumatoid arthritis. Breaks in sitting mainly improved glycemic and inflammatory markers, whereas exercise improved lipidomic and hypotensive responses. Breaks in sitting show promise in offsetting aspects of cardiometabolic disturbance associated with prolonged sitting in rheumatoid arthritis

Development and Implementation of the AIDA International Registry for Patients with Non-Infectious Uveitis

Introduction: The aim of this paper is to point out the design, development and deployment of the AutoInflammatory Disease Alliance (AIDA) International Registry for paediatric and adult patients with non-infectious uveitis (NIU). Methods: This is a physician-driven, population- and electronic-based registry implemented for both retrospective and prospective collection of real-world demographics, clinical, laboratory, instrumental and socioeconomic data of patients with uveitis and other non-infectious inflammatory ocular diseases recruited through the AIDA Network. Data recruitment, based on the Research Electronic Data Capture (REDCap) tool, is thought to collect standardised information for real-life research and has been developed to change over time according to future scientific acquisitions and potentially communicate with other similar instruments. Security, data quality and data governance are cornerstones of this platform. Results: Ninety-five centres have been involved from 19 countries and four continents from 24 March to 16 November 2021. Forty-eight out of 95 have already obtained the approval from their local ethics committees. At present, the platform counts 259 users (95 principal investigators, 160 site investigators, 2 lead investigators, and 2 data managers). The AIDA Registry collects baseline and follow-up data using 3943 fields organised into 13 instruments, including patient's demographics, history, symptoms, trigger/risk factors, therapies and healthcare utilization for patients with NIU. Conclusions: The development of the AIDA Registry for patients with NIU will facilitate the collection of standardised data leading to real-world evidence and enabling international multicentre collaborative research through inclusion of patients and their families worldwide

Applications of Non-invasive Neuromodulation for the Management of Disorders Related to COVID-19

Background: Novel coronavirus disease (COVID-19) morbidity is not restricted to the respiratory system, but also affects the nervous system. Non-invasive neuromodulation may be useful in the treatment of the disorders associated with COVID-19. Objective: To describe the rationale and empirical basis of the use of non-invasive neuromodulation in the management of patients with COVID-10 and related disorders. Methods: We summarize COVID-19 pathophysiology with emphasis of direct neuroinvasiveness, neuroimmune response and inflammation, autonomic balance and neurological, musculoskeletal and neuropsychiatric sequela. This supports the development of a framework for advancing applications of non-invasive neuromodulation in the management COVID-19 and related disorders. Results: Non-invasive neuromodulationmaymanage disorders associated with COVID- 19 through four pathways: (1) Direct infection mitigation through the stimulation of regions involved in the regulation of systemic anti-inflammatory responses and/or autonomic responses and prevention of neuroinflammation and recovery of respiration; (2) Amelioration of COVID-19 symptoms of musculoskeletal pain and systemic fatigue; (3) Augmenting cognitive and physical rehabilitation following critical illness; and (4) Treating outbreak-relatedmental distress including neurological and psychiatric disorders exacerbated by surrounding psychosocial stressors related to COVID-19. The selection of the appropriate techniques will depend on the identified target treatment pathway. Conclusion: COVID-19 infection results in a myriad of acute and chronic symptoms, both directly associated with respiratory distress (e.g., rehabilitation) or of yet-tobe- determined etiology (e.g., fatigue). Non-invasive neuromodulation is a toolbox of techniques that based on targeted pathways and empirical evidence (largely in non- COVID-19 patients) can be investigated in the management of patients with COVID-19

Distribution and composition of glycosaminoglycans in the left human coronary arterial branches under myocardial bridge

The distribution and composition of glycosaminoglycans (GAGs) are reported in the anterior interventricular branch under the intermyocardial bridge (MB) and the ventricular branch without bridge, both from the left human coronary artery. Chondroitin sulfate (CS), dermatan sulfate (DS) and heparan sulfate (HS) were purified and quantified by a combination of electrophoretic migration and enzymatic degradation. the absolute amounts of GAGs in the intermyocardial bridge segment (MB) increased by 47%, when compared to the pre (PreMB) and post (PostMB) segments and the ventricular arterial branch (VB). Furthermore, the relative distribution of GAGs in the intermyocardial bridge segment differs when compared to the pre and post segments as well as in the ventricular arterial branch, due to a change in the proportion of DS and CS of 41.9 and 32.4%, compared to 36.4 and 39.7%, respectively. These findings give support to the possible involvement of GAGs in the intermyocardial bridge segment, avoiding local thrombus deposition, reducing atherosclerotic development and moreover giving protection against vessel deformation caused by the systolic pressure. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.Universidade Federal de São Paulo, Dept Biochem, Escola Paulista Med, BR-04044020 São Paulo, SP, BrazilUniv São Paulo, Inst Ciencias Biomed, Dept Anat, BR-05508 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Biochem, Escola Paulista Med, BR-04044020 São Paulo, SP, BrazilWeb of Scienc

Safety and possible effects of low-intensity resistance training associated with partial blood flow restriction in polymyositis and dermatomyositis

Abstract Introduction Our aim was to evaluate the safety and efficacy of a low-intensity resistance training program combined with partial blow flow restriction (BFR training) in a cohort of patients with polymyositis (PM) and dermatomyositis (DM). Methods In total, 13 patients with PM and DM completed a 12-week twice a week low-intensity (that is, 30% one-repetition-maximum (1RM)) resistance exercise training program combined with partial blood flow restriction (BFR). Assessments of muscle strength, physical function, quadriceps cross sectional (CSA) area, health-related quality of life, and clinical and laboratory parameters were assessed at baseline and after the intervention. Results The BFR training program was effective in increasing the maximal dynamic strength in both the leg-press (19.6%, P <0.001) and knee-extension exercises (25.2% P <0.001), as well as in the timed-stands (15.1%, P <0.001) and timed-up-and-go test (−4.5%, P =0.002). Quadriceps CSA was also significantly increased after the intervention (4.57%, P =0.01). Similarly, all of the components of the Short Form-36 Health Survey, the Health Assessment Questionnaire scores, and the patient- and physician reported Visual Analogue Scale were significantly improved after training (P <0.05). Importantly, no clinical evidence or any other self-reported adverse event were found. Laboratory parameters (creatine kinase and aldolase) were also unchanged (P >0.05) after the intervention. Conclusions We demonstrated that a 12-week supervised low-intensity resistance training program associated with partial blood flow restriction may be safe and effective in improving muscle strength and function as well as muscle mass and health-related quality of life in patients with PM and DM. Trial registration Clinicaltrials.gov NCT01501019 . Registered November 29, 2011

Exercise Increases Insulin Sensitivity and Skeletal Muscle AMPK Expression in Systemic Lupus Erythematosus: A Randomized Controlled Trial

Systemic lupus erythematosus (SLE) patients may show increased insulin resistance (IR) when compared with their healthy peers. Exercise training has been shown to improve insulin sensitivity in other insulin-resistant populations, but it has never been tested in SLE. Therefore, the aim of the present study was to assess the efficacy of a moderate-intensity exercise training program on insulin sensitivity and potential underlying mechanisms in SLE patients with mild/inactive disease. A 12-week, randomized controlled trial was conducted. Nineteen SLE patients were randomly assigned into two groups: trained (SLE-TR, n = 9) and non-trained (SLE-NT, n = 10). Before and after 12 weeks of the exercise training program, patients underwent a meal test (MT), from which surrogates of insulin sensitivity and beta-cell function were determined. Muscle biopsies were performed after the MT for the assessment of total and membrane GLUT4 and proteins related to insulin signaling [Akt and AMP-activated protein kinase (AMPK)]. SLE-TR showed, when compared with SLE-NT, significant decreases in fasting insulin [−39 vs. +14%, p = 0.009, effect size (ES) = −1.0] and in the insulin response to MT (−23 vs. +21%, p = 0.007, ES = −1.1), homeostasis model assessment IR (−30 vs. +15%, p = 0.005, ES = −1.1), a tendency toward decreased proinsulin response to MT (−19 vs. +6%, p = 0.07, ES = −0.9) and increased glucagon response to MT (+3 vs. −3%, p = 0.09, ES = 0.6), and significant increases in the Matsuda index (+66 vs. −31%, p = 0.004, ES = 0.9) and fasting glucagon (+4 vs. −8%, p = 0.03, ES = 0.7). No significant differences between SLT-TR and SLT-NT were observed in fasting glucose, glucose response to MT, and insulinogenic index (all p &gt; 0.05). SLE-TR showed a significant increase in AMPK Thr 172 phosphorylation when compared to SLE-NT (+73 vs. −12%, p = 0.014, ES = 1.3), whereas no significant differences between groups were observed in Akt Ser 473 phosphorylation, total and membrane GLUT4 expression, and GLUT4 translocation (all p &gt; 0.05). In conclusion, a 12-week moderate-intensity aerobic exercise training program improved insulin sensitivity in SLE patients with mild/inactive disease. This effect appears to be partially mediated by the increased insulin-stimulated skeletal muscle AMPK phosphorylation.Clinical Trial Registrationwww.ClinicalTrials.gov, identifier NCT01515163

Antimalarial treatment may have a time-dependent effect on lupus survival: Data from a multinational Latin American inception cohort

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 &lt;6 consecutive months or who had never received antimalarial drugs (nonuser). Result