Surgical treatment for forefoot deformities in patients with rheumatoid arthritis (RA) has recently shifted toward joint-preserving procedures for all toes. In contrast, resection arthroplasty was previously commonly performed for lesser toes. Advances in drug therapy have improved life expectancy, resulting in an increased number of long-term survivors who previously underwent resection arthroplasty. With increased activity levels, recurrence of plantar callosities in the forefoot has become more frequent, often leading to gait disturbance. In general, revision surgery for such cases often involves additional bone resection; however, this approach may result in further shortening of the metatarsals and increase the risk of further recurrence. Therefore, we applied metatarsal shortening offset osteotomy, which we typically perform as a primary procedure, as a salvage procedure to reduce the risk of recurrence. We report three cases treated using this strategy. In all cases, the second to fifth metatarsal heads had been resected, but the resection stumps were covered with pseudo-cartilaginous tissue. This allowed metatarsal shortening offset osteotomy to be performed as a procedure similar to that used in primary surgery, achieving the planned correction. Consequently, both radiographic and clinical improvements were observed. These findings suggest that metatarsal shortening offset osteotomy may be a possible salvage option after primary resection arthroplasty for forefoot deformity in patients with RA.

To understand the roles of physician associates [PAs] and nurse practitioners [NPs] in rheumatology care delivery, we examined the pharmacoepidemiology of disease-modifying antirheumatic drug [DMARD] prescriptions among Medicare beneficiaries. The intent was to inform regulatory decisions, optimize prescribing, and better manage risk in older populations. An observational, retrospective cohort study of Medicare Part D claims from 2013 to 2023 compared rheumatologist prescribers with primary care providers (family practice [FP] and internal medicine [IM]) and with PAs and NPs. Trends in DMARD prescriptions and prescriber counts were reported as absolute numbers and percentages and presented graphically. Over the 10-year period from 2013 to 2023, 13 of the most commonly prescribed DMARDs in Medicare Part D claims were tracked. Methotrexate was the most frequently prescribed, followed by hydroxychloroquine. The share of DMARD claims by rheumatologists remained relatively steady (58-60%) during this period, whereas the shares for PAs and NPs increased. Expressed as unique prescriber counts, the trends are even stronger: in 2013, NPs and PAs represented 6.7% and 4.2% of DMARD prescribers, respectively, increasing to 19.2% and 8.9% by 2023, while the percentages of IM and FP physicians declined from 45.7% to 35.8% to 32.7% and 30.0%, respectively, during this same period. DMARD prescriptions for the Medicare population increased from 2013 to 2023, with NPs and PAs assuming a growing role in prescribing.

Background Spinal degenerative lesions are prevalent on MRI scans and radiographs in the general population and axial spondyloarthritis (axSpA) cohorts. However, their interrelationships remain poorly understood. Purpose To investigate longitudinal relationships between spinal degenerative lesions in axSpA over 10 years. Materials and Methods This secondary analysis of a prospective cohort (Devenir des Spondylarthropathies Indifférenciées Récentes [DESIR]) included whole-spine MRI scans and cervical and lumbar radiographs from individuals with axSpA assessed for 10 MRI and six radiographic degenerative lesions by three readers at baseline, 5 years, and 10 years. Patients with two or more time points were included. Multilevel logistic regression analyses using a generalized estimating equations approach (logit link, binomial family) were developed to assess whether the presence of a lesion at one time point was associated with subsequent lesions at the same and adjacent vertebral units. Time-lagged and autoregressive models evaluated inter- and intralesion temporal relationships, accounting for within-patient, within-reader, and within-vertebral unit dependence, and were adjusted for age, sex, HLA-B27 status, body mass index, smoking, job type, and biologic agents during follow-up. Results Imaging was available for 329 patients (mean age, 35 years ± 9 [SD]; 175 women). At MRI, longitudinal associations were found between disk degeneration and subsequent herniation (odds ratio [OR], 3.97 [95% CI: 3.41, 4.62]; P < .001), high-intensity zone (OR, 1.77 [95% CI: 1.49, 2.11]; P < .001), and Modic type 1 lesions (OR, 4.53 [95% CI: 3.53, 5.80]; P < .001) within the same vertebral unit. Modic type 1 lesions were associated with subsequent Modic type 2 lesions within the same unit (OR, 49.36 [95% CI: 34.66, 70.28]; P < .001). Herniations persisted over time (OR, 184.00 [95% CI: 154.00, 221.00]; P < .001). On radiographs, disk height loss was associated with osteophyte formation (OR, 4.33 [95% CI: 3.63, 5.17]; P < .001). MRI lesions were associated with the appearance of corresponding degenerative lesions on subsequent radiographs at the same level (OR, 2.49 [95% CI: 2.18, 2.83]; P < .001). Conclusion Long-term imaging analyses in axial spondyloarthritis demonstrated temporal relationships between spinal degenerative lesions on MRI scans and radiographs, highlighting the progressive nature of spinal degeneration. © RSNA, 2026 Supplemental material is available for this article.

Systemic lupus erythematosus (SLE) is a chronic autoimmune disease with diverse manifestations, including rash, arthritis, and nephritis. Although autoantibodies are a key feature of SLE, their levels often poorly reflect disease severity, suggesting the involvement of additional contributing factors. The tripartite motif-containing protein (TRIM) family, which regulates immunity, may play a role in SLE. Although TRIM21 is a known autoantigen, the roles of other TRIM family members remain unclear. The present study examined TRIM expression in SLE and evaluated the potential of TRIM proteins as biomarkers. TRIM expression in peripheral blood mononuclear cells was measured using reverse transcription quantitative polymerase chain reaction (PCR) and compared between patients with SLE (n = 33) and healthy controls (n = 20). Associations of TRIM expression with disease activity (active/inactive), renal involvement (nephritis/nonnephritis), clinical manifestations, and laboratory parameters were analyzed. The expression levels of several TRIM genes, specifically TRIM5, TRIM11, TRIM21, and TRIM72, were higher in patients with inactive SLE, nonnephritic disease, or low disease activity than in patients with active disease, nephritic disease, or relapsed SLE and healthy controls. The expression levels of these genes were considerably and negatively associated with clinical symptoms but not laboratory parameters. Hydroxychloroquine users exhibited higher levels of TRIM21 expression than did nonusers. Overall, specific TRIM proteins are inversely correlated with SLE disease activity and clinical phenotypes, which indicates their potential as biomarkers. Hydroxychloroquine may regulate TRIM21 expression. Further investigation into underlying mechanisms and continued TRIM monitoring are necessary to develop new SLE treatments and better assess disease progression.

The hemoglobin, albumin, lymphocyte, and platelet (HALP) score is a potential composite biomarker that integrates nutritional and immune-inflammatory profiles. However, its association with rheumatoid arthritis (RA) prevalence remains undefined. In this large-scale cross-sectional study, we investigated the relationship between HALP and RA, explored the cross-sectional association between HALP score and RA prevalence, and evaluated HALP as a concurrent composite biomarker reflecting immune-inflammatory and nutritional status in RA. Our analysis included 34,079 participants from the National Health and Nutrition Examination Survey 1999-2018 cycles. We calculated the HALP score using the following formula: Hemoglobin (g/L) × albumin (g/L) × lymphocyte count (×109/L)/platelet count (×109/L). Weighted multivariable logistic regression models, adjusted for demographic and clinical covariates, were used to assess the HALP-RA association, with restricted cubic splines evaluating potential nonlinearity. We performed comprehensive sensitivity analyses and subgroup examinations to test result robustness. For cross-sectional discriminative modeling, we used a 3-stage variable selection process: Univariate screening, least absolute shrinkage and selection operator regression with 10-fold cross-validation for dimension reduction, and multivariable logistic regression. Model performance was assessed to evaluate how well HALP and clinical variables distinguish participants with prevalent RA from those without. In this large national study, the HALP score was inversely and nonlinearly associated with RA, consistent across subgroups. HALP score is inversely and nonlinearly associated with prevalent RA in a large US population. Given the cross-sectional design, HALP likely represents a consequence of established RA rather than a predictive risk factor. These findings are hypothesis-generating and require validation in clinically confirmed RA cohorts. Current evidence does not support using HALP for RA case identification or prediction. In this cross-sectional study of 34,079 participants, including 2166 unweighted RA cases (unweighted percentage 6.36%, weighted prevalence 4.85%), higher ln(HALP) levels were inversely associated with RA (adjusted odds ratio, 0.74; 95% confidence interval, 0.64-0.85; P < .001), with a nonlinear inverse association (P for nonlinearity < .001). Subgroup analyses showed no significant effect modification (all P for interaction > .05). A HALP-integrated cross-sectional discriminative model yielded an area under the curve of 0.747, which was mainly driven by conventional clinical variables. The incremental value of HALP was not evaluated.

Chimeric antigen receptor (CAR) T cell therapy can result in impressive remissions in hematological malignancies, but relapse is common because a minority of infused cells acquire a long-lived, memory-like state. All US Food and Drug Administration-approved CAR T cell products incorporate either 4-1BB or CD28 costimulatory domains, each conferring distinct phenotypic outcomes, but how these signals control early fate decisions is incompletely understood. Here we show that costimulatory domains control memory fate acquisition through asymmetric cell division. CD28 CAR T cells have higher CAR surface expression and enhanced surface proteome asymmetry after the first division, yet paradoxically they show muted transcriptional, epigenetic and metabolic divergence between daughter cells, correlating with reduced long-term persistence. Conversely, 4-1BB CAR T cells have less surface polarization but more pronounced transcriptional, metabolic and epigenetic divergence, yielding proximal effector-prone and distal persistence-prone daughters. Integrating surface proteomics, transcriptomics, metabolomics and chromatin accessibility, we show how costimulatory domains tune asymmetric cell division to shape CAR T cell fate, providing a mechanistic foundation for optimizing cellular immunotherapy.

This Health Policy compares the current recommendations from the US Food and Drug Administration (FDA) and the European Medicines Agency (EMA) for new treatments in rheumatoid arthritis, highlighting where they align, where they differ, and how harmonisation could make drug development more efficient. We examined the EMA's Guidelines on Clinical Trials of Medicinal Products for the Treatment of rheumatoid arthritis and the FDA's draft guidance rheumatoid arthritis Development of Drugs for Treatment, together with relevant cross-indication FDA guidelines and labelling decisions in rheumatoid arthritis in the last two decades. The key aspects of trial design, including study populations, endpoints, safety requirements, and statistical considerations were analysed. The findings were reviewed and interpreted by a panel of rheumatologists, who proposed strategies for aligning regulatory expectations. The FDA and EMA agree on several core principles such as the use of composite clinical endpoints, validated patient-reported outcomes, the importance of preventing structural joint damage, need for adequate long-term safety exposure, and limits on placebo duration. The EMA, however, favours remission or low disease activity as the preferred primary endpoints, generally requires two pivotal trials in distinct rheumatoid arthritis populations, and background methotrexate unless contraindicated. The FDA offers more flexibility in primary endpoint selection, allows for a single pivotal trial if supported by strong confirmatory evidence, and places greater emphasis on early dose-response characterisation. Greater alignment between FDA and EMA requirements could help reduce duplication, streamline global data interpretation, and speed patient access to effective rheumatoid arthritis therapies globally.

Exercise is a key non-pharmacological component of therapy in axial spondyloarthritis (axSpA). Evidence for yoga as a mind-body intervention remains limited. This study aimed to assess the effects of an 8-week yoga program on mobility, function, disease activity, activity-related competences, and psychological outcomes in axSpA compared with physiotherapy and healthy individuals. We conducted a prospective, non-randomized, study (University Hospital Erlangen, May 2021-January 2024). AxSpA patients participated either in weekly yoga sessions for 8 weeks (approximately 60 min; online format) or received standard individual physiotherapy (≥ 30 min/week). A healthy control group completed the same yoga program. Health related outcomes at baseline and follow-up were measured and changes were analysed using linear mixed-effects models. Seventy-six participants were included. In axSpA, spinal mobility improved in the yoga group (BASMI Δ - 0.31; p = 0.002), while the physiotherapy group worsened (Δ + 0.29; p = 0.003). Physical activity related health competency (control competence Δ + 1.10; p = 0.001; self-regulation Δ + 0.72; p = 0.021) and psychological outcomes improved in the yoga group with increased quality of life mental scores (Δ + 6.62; p < 0.001) and reduced kinesiophobia (TSK Δ - 3.25; p = 0.008); physiotherapy showed no meaningful changes. Disease activity showed a significant decrease in the yoga group (BASDAI Δ -0.44; p = 0.049). Healthy individuals showed similar directional changes with smaller effects. An 8-week yoga intervention was associated with improvements in mobility, psychological outcomes and activity-related competences. Findings support yoga as a complementary treatment addressing both physical and psychological dimensions of axSpA. The study was registered in the German Clinical Trials Register (DRKS-ID: DRKS00025215).