ACR open rheumatology最新文献

Objective: This study characterized brachial artery reactivity, an ultrasound indicator of endothelial function, in young adults who had clinically quiescent juvenile dermatomyositis (JDM) compared with matched controls.

Methods: Twenty young adults with previous documentation of JDM 14.2 ± 3.9 years (mean ± SD) after onset of their JDM symptoms, who were no longer taking medications were enrolled, with 20 healthy control participants matched for age, race, sex and body mass index. They obtained ultrasound brachial artery reactivity testing and nailfold end row capillary loop count.

Results: Participants were 21.8 ± 4.2 years old (70% female) and were aged 7.6 ± 3.7 years at JDM onset. The JDM Disease Activity Score (DAS) was 1.9 ± 2.5 and primarily based on active skin symptoms. Compared to controls, participants with JDM had fewer end row capillary loops/mm (mean ± SD 6.35 ± 1.29 vs 7.40 ± 0.58; P = 0.002) and were shorter in stature (mean ± SD 163.68 ± 9.69 cm vs 170.49 ± 9.60 cm; P = 0.032). Their end row capillary loop count was associated with their DAS (r = -0.401, P = 0.011). After adjusting for height, age, sex, and resting brachial artery diameter, the brachial artery reactivity in the adults with JDM was significantly lower than that in controls (β = 2.51%, 95% CI -4.62 to -0.40, P = 0.026).

Conclusion: This pilot study provides new evidence of endothelial dysfunction, as assessed by brachial artery reactivity, in asymptomatic adults who had classic JDM symptoms in childhood.

Objective: In the phase 3 head-to-head MANDARA study (NCT04157348), benralizumab demonstrated noninferiority to mepolizumab in inducing remission (defined as Birmingham Vasculitis Activity Score [BVAS] of 0 and oral glucocorticoid [OGC] dosage ≤4 mg/day at weeks 36 and 48) in patients with eosinophilic granulomatosis with polyangiitis (EGPA). This analysis investigated a more stringent definition of remission that included discontinuation of OGCs and being relapse-free.

Methods: Patients aged ≥18 years with documented relapsing or refractory EGPA receiving OGCs at ≥7.5 mg/day with or without immunosuppressive therapy for ≥4 weeks before enrollment were randomized (1:1) to benralizumab at 30 mg or mepolizumab at 300 mg subcutaneously every 4 weeks for 52 weeks. The proportion of patients achieving remission off OGCs, defined as BVAS of 0, OGC dose of 0 mg/day (at weeks 36 and 48) and no relapses during the double-masked period, was assessed.

Results: Patients (n = 140) were randomized to benralizumab (n = 70) or mepolizumab (n = 70). The adjusted percentage of patients with remission off OGCs was 23.5% (n = 16) with benralizumab versus 11.1% (n = 8) with mepolizumab (difference 12.47 [95% confidence interval 0.46-24.48], P = 0.042). Of those who achieved remission off OGCs, 100% of benralizumab-treated patients and 98.6% of mepolizumab-treated patients achieved remission within the first 36 weeks of treatment.

Conclusion: The administration of anti-interleukin-5/receptor (IL-5/R) therapies, benralizumab and mepolizumab, enable discontinuation of OGCs in some patients with EGPA, while avoiding relapses. These findings suggest that adding anti-IL-5/R therapy to standard primary treatment for patients with EGPA may improve response.

Objective: Falls are common after total hip arthroplasty (THA) and can cause serious complications. Understanding preoperative factors linked to falls post-THA can inform discharge planning and management to lower fall risk. We aimed to identify preoperative factors associated with falls occurring within one year following THA in older adults.

Methods: We performed a retrospective cohort study using records within a large hospital system. Adults aged ≥65 years with a recorded THA between March 2012 and March 2022 were included. The primary outcome was a fall occurrence (yes vs no) within one year post-THA. A fall was identified through International Classification of Diseases, Ninth/Tenth Revision codes, documentation for fall-related emergency room visit(s), or mention of a fall in the medical record. Purposeful selection of variables in logistic regression models identified preoperative factors associated with a fall.

Results: Among 4,501 patients (age 72.7 ± 6.0 years), 683 (15.2%) experienced at least one fall within one year post-THA. The strongest risk factors were a fall within one year pre-THA (odds ratio [OR] = 2.67, 95% confidence interval [CI] = 2.22-3.22) and depression (OR = 1.95, 95% CI = 1.62-2.35). Other factors included neurologic conditions, insomnia, revision or conversion hip arthroplasty, knee pain, lumbar conditions, body mass index (BMI) <20 kg/m², and older age. A BMI of 25 to 29.9 was protective against falls.

Conclusion: This longitudinal cohort study identified multiple independent factors associated with fall occurrences within one year post-THA. Findings highlight the opportunity to address modifiable factors and provide individuals with tailored discharge planning and management strategies (eg, fall prevention programs) to reduce fall risk.

Objective: Systemic lupus erythematosus (SLE) is thought to accelerate the aging process. However, there is limited research on geriatric syndromes, such as falls, in this potentially vulnerable population. This study aimed to describe the prevalence of and contributors to falls in the SLE population.

Methods: Participants were recruited from an ongoing population-based cohort of individuals with validated SLE. Falls (number of falls and fall-related injuries requiring medical attention over the past year) and perceived contributing factors were self-reported. Descriptive statistics were calculated, and age-, sex-, and race-adjusted odds ratios (aORs) of participant characteristics with falls were estimated using multivariable logistic regression.

Results: Nearly one-third (30.7%) of participants (overall N = 447; 40.9% aged ≥50 years, 91.7% female, and 82.6% Black) reported falling in the past year; 19.2% fell twice or more. Loss of balance (78.1% of falls), slipping/tripping (64.2%), and weakness (53.3%) were the most commonly reported contributing factors. Age and sex were not associated with falls, but higher physical performance (aOR, 0.78; 95% confidence interval [CI], 0.71-0.87) was associated with lower odds of falls. Higher SLE activity (aOR, 1.78; 95% CI, 1.44-2.21) and damage (aOR, 1.22; 95% CI, 1.00-1.49), greater depressive symptoms (aOR, 1.43; 95% CI, 1.14,1-80), and taking fall risk-increasing drugs (antidepressants: aOR, 1.82; 95% CI, 1.13-2.93; pain medications: aOR, 2.60; 95% CI, 1.68-4.00; opioids: aOR, 4.52; 95% CI, 2.39-8.56) were associated with higher odds of falls.

Conclusion: Falls were common in our cohort, regardless of age. Our results suggest potential interventions for reducing falls, like better control of SLE, physical therapy, depression screening, and medication review.

Objective: To assess associations of ancestry with juvenile idiopathic arthritis (JIA) categories and clinical Juvenile Arthritis Disease Activity Scores (cJADAS10) at presentation to pediatric rheumatology care in a multicultural country with universal health care.

Methods: Parents reported their child's ancestry in the Research in Arthritis in Canadian Children Emphasizing Outcomes (ReACCh-Out) cohort. For each ancestry reported for ≥30 children, we compared JIA category distribution and median cJADAS10 scores among three groups: only that ancestry, with that and other ancestries, and without that ancestry. Chi-square, Fisher's exact, and Kruskal-Wallis tests compared the three groups and multivariable linear regression assessed factors associated with cJADAS10 scores.

Results: Among 1,407 participants, 629 (44.7%) reported more than one ancestry. British ancestry was associated with higher median cJADAS10 scores (7.5) and higher frequency of enthesitis-related arthritis (18.7%) and psoriatic arthritis (10.0%), French ancestry was associated with lower cJADAS10 scores (5.8) and higher oligoarthritis (51.2%), Indigenous ancestry was associated with higher cJADAS10 scores (11.0) and higher rheumatoid factor-positive polyarthritis (21.9%), Black ancestry was associated with higher rheumatoid factor-positive polyarthritis (16.0%), and Eastern European ancestry was associated with lower cJADAS10 scores (3.6). Associations of ancestry with cJADAS10 scores were largely explained by differences in JIA categories (total R² = 0.28, with R² = 0.25 for JIA category alone). Black ancestry was associated with longer time from symptom onset to diagnosis (27 vs 18.9 weeks).

Conclusions: British and French ancestries had distinct associations with JIA categories and cJADAS10 scores, and many children had multiple ancestries, questioning the use of a single "European" reference group. Higher cJADAS10 scores were largely explained by differences in JIA categories across ancestries.

Objective: The Foundation for the National Institutes of Health (FNIH) OA Biomarkers Consortium aims to identify, develop, and qualify biomarkers to support drug development in knee osteoarthritis (OA). The project's second phase, the PROGRESS OA study, aims to externally validate prognostic and response biomarkers identified in the earlier phase (phase 1). Here we present results assessing external validation of prognostic imaging biomarkers.

Design: PROGRESS OA included data from the control arms of several completed randomized controlled trials (RCTs) for symptomatic knee OA. Radiographic progression was defined as joint space width loss (JSWL) ≥0.7 mm. Symptomatic progression was defined as increase of nine or more points in Western Ontario and McMaster Universities Arthritis Index pain (0-100 scale). Imaging biomarkers included quantitative measures of cartilage thickness and semiquantitative (SQ) assessments. Associations between baseline biomarkers and outcomes over 12 to 36 months were examined using logistic regression.

Results: A total of 320 participants from four RCTs were included. Forty-one participants (13%) had JSWL ≥0.7 mm and 64 (20%) had worsening symptoms. In univariable logistic regression, measures of quantitative and SQ cartilage, SQ Hoffa-synovitis, effusion-synovitis, and meniscal extrusion were consistently selected to predict JSWL ≥0.7 mm, similar to phase 1. SQ Hoffa-synovitis and lateral meniscal damage were consistently selected to predict symptomatic progression. Cross-validated areas under the curve were 0.69 (95% confidence interval [CI]: 0.53-0.85) for JSWL ≥0.7 mm and 0.77 (95% CI: 0.65-0.87) for symptomatic progression.

Conclusion: The selected prognostic imaging biomarkers are candidates for enriching OA trials for structural and/or symptomatic progressors. Ongoing work includes pursuit of formal biomarker qualification by regulatory agencies, and the use of these biomarkers to capture structural progression with high sensitivity to change.

Objective: To explore the cerebrospinal fluid (CSF) proteome in systemic lupus erythematosus (SLE) and the associations between the CSF proteomic patterns and clinical manifestations.

Methods: CSF samples from 29 female outpatients with SLE were analyzed with label-free liquid chromatography tandem mass spectrometry. Inclusion and CSF collection were conducted irrespective of clinical manifestations and disease duration. Proteomic data were used for sample clustering and analyzed for clinical variance. Proteins were clustered using Weighted Gene Co-expression Correlation Network Analysis. Modules were biologically characterized and analyzed for correlation to the clinical dataset.

Results: Three patient clusters were identified. Cluster 1 was characterized by the highest frequency of nephritis, depression, and cognitive dysfunction. Cluster 2 showed the highest frequency of alopecia and Sjogren disease antigen A-antibodies (anti-SSA) and a low frequency of cognitive impairment. Cluster 3 had a higher frequency of autonomic neuropathy and headache. Six protein modules were identified (module 1 [M1]-M6). Modules were characterized by nervous tissue proteins (M1), central nervous system (CNS) lipoproteins (M2), macrophage proteins (M3), plasma proteins (M4), Ig (M5), and intracellular metabolic proteins (M6). M1 and M2 proteins were most abundant in cluster 1 and correlated with nephritis, depression, and cognitive impairment. Increased abundance of M4 and M5 proteins were most distinct in cluster 2 and inversely correlated to cognitive impairment and brain atrophy.

Conclusion: Patients clustered by their CSF proteomic pattern had different disease phenotypes. Nephritis and neuronal damage defined the group with higher levels of neuronal proteins in CSF, which may suggest shared pathogenetic pathways in SLE affecting the kidney and CNS.

Objective: To describe severe maternal morbidity (SMM) among veterans with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) who use Department of Veterans Affairs (VA) health care.

Methods: We conducted a secondary analysis of VA national administrative data to compare rates of SMM among veterans with and without SLE or RA. Our sample included veterans aged 18 to 45 years who had at least one pregnancy between October 2009 and September 2019 and at least one documented VA primary care visit within the year before pregnancy. International Classification of Diseases, Ninth and Tenth Revision codes were used to identify SLE, RA, and medical and mental health comorbidities within two years before pregnancy. SMM was assessed using Centers for Disease Control and Prevention definitions and included events during and up to 42 days after pregnancy.

Results: Among 29,713 veterans, 113 had SLE, and 92 had RA. Of these veterans, 36% with SLE and 30.4% with RA experienced a nonlive birth outcome, including stillbirth, ectopic pregnancy, and spontaneous abortion, compared with 25.2% of other veterans. Nearly 10% of veterans with SLE and 4.3% of veterans with RA experienced SMM, compared with 3.2% of other veterans.

Conclusion: To our knowledge, this is the first study of SMM among veterans with SLE and RA. Veterans with SLE appear to have an elevated risk of SMM, and veterans with SLE and RA appear to have high rates of pregnancy loss. Our findings highlight the potential utility of comprehensive maternity care models for these veterans with SLE and RA within the VA health care system.

We report two patients with scleromyositis with anti-RuvBL1/2 antibodies, recently identified rare autoantibodies associated with older age at onset, diffuse sclerodactyly, skeletal and cardiac myositis, and interstitial lung disease (ILD). Both patients showed sclerodactyly and skeletal myositis. Muscle biopsy revealed lymphocytes and macrophage infiltration in an 83-year-old woman with cardiac involvement and immune-mediated necrotizing myopathy in a 68-year-old woman with ILD, guiding diagnosis and treatment decisions. Glucocorticoids and immunosuppressants led to clinical improvement. These cases highlight the clinical and pathologic spectrum of anti-RuvBL1/2 antibody-associated disease and the value of antibody detection and tissue analysis.

Objective: Recommendations have been made to use electrocardiograms (EKGs) to screen for cardiac disease in systemic sclerosis (SSc). The objective of this study was to compare the prevalence of EKG abnormalities in SSc and controls to help determine if the EKG should be used as a screening tool.

Methods: EKGs from patients with SSc were compared with those from a random sample of age- and gender-matched controls. Two cardiologists read all EKGs using a standardized approach. The groups were compared using t-tests, chi-squared tests, and Fisher exact tests.

Results: Patients with SSc (n = 833, mean ± SD disease duration 11.3 ± 9.3 years; 39.4% had diffuse cutaneous SSc) and controls (n = 832) were included. The prevalence of conduction and rhythm abnormalities were similar in the SSc and control groups. More patients with SSc than controls had possible right atrial enlargement (5% vs 0.1%, P < 0.001), right axis deviation (3.2% vs 0.4%, P < 0.001), left atrial enlargement (9.2% vs 1.6%, P < 0.001), poor/abnormal R progression (5.6% vs 2.2%, P < 0.001) and nonspecific T wave abnormalities (6.1% vs 3.4%, P = 0.008).

Conclusion: Our findings suggest that conduction abnormalities are not more prevalent in those with SSc than in controls. Evidence of right heart stress on EKG in SSc may be secondary to pulmonary hypertension and left atrial enlargement, and poor R wave progression in precordial leads may indicate myocardial damage. Future studies are required to determine if these EKG abnormalities represent underlying structural heart disease, and, until that is proven, EKGs should not be considered a screening tool for cardiac abnormalities in SSc.