ACR open rheumatology最新文献

Objective: The epidemiology of urinary incontinence (UI) in systemic lupus erythematosus (SLE) remains understudied. We estimated the prevalence and life burden of UI and examined associations of UI with SLE activity and disease damage in a population-based US SLE cohort.

Methods: Participants (N = 425; mean age, 46.3 years; 82.8% Black; 92.0% women) were recruited from an ongoing adult SLE cohort (October 2019 to May 2022) for a single study visit. UI was assessed via questionnaire and defined as any urinary leakage occurring at least monthly. SLE activity and cumulative organ damage were measured using the Systemic Lupus Activity Questionnaire and Brief Index of Lupus Damage and dichotomized (higher vs lower) at the median score. Logistic regression models adjusted for age, sex, education, and body mass index were used to evaluate associations of SLE activity and cumulative disease damage with UI.

Results: Overall, 36.2% reported UI at least monthly. Of those with UI, 57.7%, 18.8%, and 19.6% reported mixed-type, stress, and urge UI; 39.0% reported that UI was a substantial bother, and 16.2% reported that UI had a substantial impact on daily activities. UI prevalence was higher in women and in participants who were older and who had obesity. Higher disease activity was independently associated with 3-fold higher prevalence odds of UI (odds ratio = 3.02, 95% confidence interval: 1.91-4.76). Higher cumulative disease damage was associated with 36% higher odds of UI, but the association was not statistically significant.

Conclusion: UI is common in those with SLE and associated with higher disease activity, highlighting the need for updated clinical UI screening and management strategies in this unique population.

Although individually occurring in less than 1 in 2,000 people, cumulatively, more than 7,000 rare diseases affect approximately 6% of the population worldwide. Children and young people are disproportionally challenged in number and severity, which may be explained by the large proportion of genetic conditions among rare diseases (70%-80%). Indeed, an estimated 30% of children with rare diseases do not survive past their fifth birthday. Because rare diseases are frequently missed or diagnosed with a delay of several years and <5% of rare diseases have a licensed treatment, the impact of rare diseases on the indivual affected (independent of age) and wider society is significant. To address these challenges sufficiently, rare disease expert centers combining research activity with patient care are needed to develop diagnostic tests, prognostic tools, and new treatments. This expert-driven approach promises expedited diagnosis and efficacious treatment and care. Although restricted by chronic underfunding, rare disease research keeps delivering new exciting treatment options and technologies, some of which have revolutionized care not only in niche areas of medicine but also common diseases (the use of interleukin-1 blockers in gout or COVID-19-associated hyperinflammation, etc). However, rare disease research and care will only be successful in collaborative, mutidisciplinary and multiprofessional teams that involve patients and families as equal partners and span across institutional and national borders. Lastly, the use of state-of-the-art computational approaches to share knowledge and associate molecular with clinical phenotypes, treatment responses, and disease outcomes will amplify our ability to serve patients and the society.

Objective: Pathogenic inflammation in psoriatic arthritis (PsA) includes tumor necrosis factor (TNF) signaling. We observed that lower absolute lymphocyte count (ALC) was associated with greater mortality in persons with rheumatoid arthritis, and the start of TNF inhibitor (TNFi) therapy was associated with increased ALC. The effect of TNFi on ALC and mortality in PsA is not known.

Methods: Using the VA Corporate Data Warehouse, we identified patients with PsA that initiated TNFi in 2010 through 2015 with laboratory tests before and 3 to 24 months after therapy initiation. Patients with PsA seen in rheumatology clinics were matched by age, sex, race and ethnicity with controls. In a subset of local patients and controls, we evaluated markers of inflammation and other correlates of ALC.

Results: Among 1923 patients with PsA, ALC increased by a mean of 0.22 × 10³ cell/μL (95% confidence interval [CI] = 0.20, 0.25) following TNFi initiation, whereas in controls, there was minimal change in ALC (0.01 × 10³ cell/μL, 95% CI = 0.00, 0.02). Survival curves differed significantly among patients with PsA with baseline ALC above 1.2 × 10³ cell/μL, below 1.2 × 10³ cell/μL that remained low after start of TNFi, and below 1.2 × 10³ cell/μL that increased to above 1.2 × 10³ cell/μL with therapy. Higher ALC at baseline and increased ALC at follow-up were associated with higher subsequent survival. Local cohort analysis indicated lower circulating T cell effector and terminal effector memory frequencies in PsA that positively correlated with ALC. Patients with PsA treated with TNFi had lower interleukin-6 (IL-6) levels that negatively correlated with ALC.

Conclusion: TNFi therapy increases the peripheral blood ALC in patients with PsA, and this is associated with lower subsequent mortality. Mechanisms underlying this relationship may include effects of PsA, TNFi, and IL-6 on T cell subset homeostasis.

Juvenile idiopathic arthritis is a rare but severe childhood-onset arthritis that carries a high risk of structural joint damage. We report the case of a 32-year-old man with a history of juvenile idiopathic arthritis who underwent bilateral hip arthroplasty at age 23 and bilateral ankle arthroplasty at age 24. His subsequent orthopedic course was complex, involving a left ankle prosthetic infection, spacer implantation, and eventual reimplantation of the prosthesis. Despite these interventions, he developed persistent left ankle pain, swelling, and warmth, consistent with residual synovitis. The patient was treated with adalimumab and had no evidence of active arthritis at other sites. Non-steroidal anti-inflammatory drugs, sural nerve neuromodulation, and intra-articular glucocorticoid injections failed to provide adequate relief. Selective transarterial embolization of the malleolar branch of the anterior tibial artery was therefore performed, resulting in marked improvement in pain and swelling. In conclusion, transarterial embolization proved feasible and led to meaningful short-term clinical benefit, supporting its potential as an adjunctive therapeutic option in carefully selected cases of residual refractory ankle arthritis.

Objective: Up to 60% of youth with childhood-onset systemic lupus erythematosus (cSLE) experience cognitive dysfunction, impacting their quality of life and medication adherence. This study explored self-reported executive function (EF) and its links to patient-reported outcomes and disease-related factors in cSLE.

Methods: This cross-sectional study compared patients aged 10 to 17 years with cSLE to age- and sex-matched controls. The Behavior Rating Inventory of Executive Function Self-Report Global Executive Composite (GEC) T score measured daily EF activities, whereas Patient-Reported Outcomes Measurement Information System (PROMIS) questionnaires assessed pain, sleep, fatigue, anxiety, and depression. Group differences in GEC and correlations with PROMIS scores were analyzed. For patients with cSLE, hierarchical regression evaluated GEC variance explained by income, PROMIS scores, and disease-related factors (activity, damage, and glucocorticoid use).

Results: We recruited 94 participants, including 52 patients with cSLE and 42 controls. The analysis revealed no group difference in GEC T scores. In the cSLE group, worse depression and sleep disturbance correlated with worse GEC T scores, whereas pain interference and fatigue correlated with GEC in both groups. The hierarchical regression model explained 30% (P = 0.003) of EF variability in cSLE. PROMIS measures accounted for 14% (P = 0.013) of EF variability when controlling for household income. Disease-related factors contributed an additional 14% of EF variability, with higher disease activity and lower glucocorticoid use associated with worse GEC T scores.

Conclusion: Self-reported EF was similar in patients with cSLE and control patients but correlated uniquely with depression, sleep disturbance, disease activity, and glucocorticoid use. Further research is needed to improve EF in cSLE.

Objective: To determine the demographic and clinical characteristics associated with use of the EuroLupus or modified National Institutes of Health (NIH) cyclophosphamide (CYC) regimen for treatment of lupus nephritis (LN) at North American pediatric centers.

Methods: A retrospective cohort study was conducted at 11 North American centers. Patients <22 years of age with active LN treated with CYC using the EuroLupus or NIH regimen between July 2014 and June 2021 were included. Data were extracted via electronic medical record review. Demographic and clinical characteristics were compared at CYC initiation. A multivariable generalized estimating equation with logit link was fit to model EuroLupus use. An exchangeable correlation structure was used to account for correlation within centers. Independent variables were chosen using elastic net regression.

Results: The cohort consisted of 191 patients (85 EuroLupus, 106 NIH) with a median age of 15.3 years at CYC initiation. In multivariable analysis, characteristics significantly associated with EuroLupus regimen use (vs NIH regimen use) included more recent year of CYC initiation, longer disease duration, Hispanic ethnicity and Asian race (as compared to Black), previous CYC treatment, renal impairment (dialysis or mild kidney impairment), and absence of neuropsychiatric involvement.

Conclusion: For children and young adults with LN requiring CYC, use of the EuroLupus regimen increased over time and is associated with demographic and clinical factors such as race or Hispanic ethnicity, renal impairment, and absence of neuropsychiatric involvement. The differences in regimen use with severe renal impairment and neuropsychiatric lupus highlight areas for future study in CYC dosing.

Objective: It is unclear how people with osteoarthritis feel about online Tai Chi. This study aimed to explore the experiences of people with knee osteoarthritis who participated in an online unsupervised Tai Chi program.

Methods: A qualitative study nested within a randomized controlled trial was conducted. Semistructured phone interviews were held with 20 participants with knee osteoarthritis who took part in a 12-week online unsupervised Tai Chi program. Interviews explored participant experiences and were audio recorded, transcribed verbatim, and analyzed thematically using an inductive approach.

Results: Four themes (each with two subthemes) were developed: (1) online unsupervised Tai Chi offers flexibility (the ability to pause, rewind, and repeat facilitates learning; able to practice anytime, anywhere); (2) variable user experience (most found it enjoyable and calming; some found it repetitive and boring); (3) learning challenges and strategies (the lack of feedback can be challenging; practice makes better); and (4) online unsupervised Tai Chi is effective for most but not all (improved outcomes and motivated to be more active; no perceived changes in outcomes).

Conclusion: Most people with knee osteoarthritis reported positive experiences with a 12-week online unsupervised Tai Chi program. The identified challenges and relevant improvements have the potential to inform modifications and refine the program before its planned public release, with the aim to enhance Tai Chi exercise accessibility and uptake among people with osteoarthritis in the broader community.

Objective: A cardiovascular safety issue has been associated with JAK inhibitors (JAKi). This study compares the effects of distinct approved JAKi on endothelial cell (EC) dysfunction and apoptosis during inflammation.

Methods: Massive inflammation was induced in human vascular ECs by tumor necrosis factor (TNF) with interleukin-17A (IL-17A) treated or not treated with tofacitinib, baricitinib, upadacitinib, peficitinib, ruxolitinib, and fedratinib at 1 or 10 μM. Levels of IL-6 and IL-8 were measured by enzyme-linked immunosorbent assay. Variations in gene expression of adhesion molecules and factors of blood coagulation and fibrinolysis pathways were quantified by quantitative reverse transcriptase-polymerase chain reaction. Endothelial apoptosis was measured by Annexin V staining.

Results: All JAKi decreased IL-6 release of ECs stimulated with TNF+IL-17A. In contrast, only baricitinib and fedratinib decreased IL-8 overproduction, from 1 μM. Fedratinib decreased the up-regulation of vascular adhesion molecule 1 (VCAM-1) and E-selectin expression at 1 and 10 μM. Tofacitinib reduced intercellular adhesion molecule 1 (ICAM-1) and E-selectin induction at 1 μM. However, at 10 μM, tofacitinib, baricitinib, upadacitinib, peficitinib, and ruxolitinib enhanced induction of VCAM-1 and ICAM-1 triggered by TNF+IL-17A. Peficitinib and fedratinib at 1 and 10 μM decreased tissue factor up-regulation induced by TNF+IL-17A, whereas ruxolitinib was effective only at 1 μM. None of the JAKi could prevent the down-regulation of the anticoagulant molecule thrombomodulin. Fedratinib and peficitinib were both proapoptotic and cytotoxic for ECs.

Conclusion: All JAKi reduced EC inflammation but most JAKi could not prevent the up-regulation of adhesion molecules or the increase in procoagulant and the decrease in anticoagulant factors triggered by proinflammatory cytokines. Peficitinib and fedratinib exhibited cytotoxic effects causing EC apoptosis.