Objective To evaluate whether an integrated, smartphone‐enabled, physician‐supervised treat‐to‐target (T2T) care model improves serum urate (SUA) target attainment compared with usual care, and to explore its effects on gout flares and systemic metabolic parameters. Methods This 12‐month, single‐center, open‐label, superiority randomized controlled trial enrolled 280 men with gout. Participants were randomized (1:1) to an integrated digitally supported care model (the "1CARE" platform combining automated behavioral reminders, tiered education, remote SUA monitoring, and weekly physician review) or Usual Care. The primary outcome was the proportion of patients achieving serum urate (SUA) <360μmol/L. Secondary outcomes included gout flares and metabolic parameters. Results At 12 months, 85.0% (119/140) of participants in the App‐Led group achieved the primary therapeutic target of SUA<360μmol/L, compared with 48.6% (68/140) in the Usual Care group (risk ratio 1.75 [95% CI 1.46 to 2.10]; P < 0.0001). The App‐Led Care group also showed a significantly lower annualized gout flare frequency (0.02 vs 0.10 flares/year; P < 0.01). Exploratory metabolic outcomes favored the App‐Led Care group, with greater reductions in fasting plasma glucose, HbA1c, total cholesterol, and LDL cholesterol (all P < 0.05), alongside higher medication adherence. Adverse event rates were comparable between the two groups. Conclusion An integrated, physician‐supervised, digitally supported T2T care model significantly improved SUA target attainment and reduced gout flares compared with usual care over 12 months. Multi‐center trials will be needed to fully evaluate the generalizability, cost‐effectiveness, and optimal configuration of this approach.
Objective Osteoarthritis (OA) is a heterogeneous joint disease, yet mechanistic insights derive predominantly from knee OA and are often extrapolated to other joints. We investigated joint‐associated differences in the spatial molecular organization of hip and knee OA synovium. Methods Synovial tissues from patients undergoing arthroplasty for primary hip or knee OA were analyzed by histology ( hip, n=10; knee, n=10 ), mass spectrometry–based bulk proteomics ( hip, n=10; knee, n=8 ), and NanoString GeoMx Digital Spatial Profiling ( hip, n=5; knee, n=5 ). Spatial proteomic profiling was performed across intimal and subintimal regions segmented into CD45 + immune and CD45 ‐ non‐immune compartments. Results Hip OA synovium exhibited greater vessel density than knee OA synovium ( P < 0.001 ), whereas histological synovitis severity did not differ significantly. Bulk proteomics showed enrichment of angiogenesis in hip OA ( FDR q=0.001 ) and fatty acid metabolism in knee OA ( FDR q<0.001 ). Spatial proteomic profiling revealed a vascular–stromal remodeling signature in the hip OA subintimal CD45 ‐ compartment, with higher abundance of VEGFR2, vWF, α‐SMA, PDGFB, and YAP1. Hip OA also showed higher CD3E/CD3G abundance in the subintimal CD45 + compartment and higher calreticulin abundance across multiple compartments. In contrast, knee OA exhibited a GLP‐1/GLP‐1R–associated metabolic signature in the intimal CD45 + compartment. The knee OA subintimal CD45 ‐ compartment also showed higher HK2 abundance and enrichment of lipid‐associated LXR/RXR signaling. Conclusion Hip and knee OA synovium exhibit distinct spatially organized molecular phenotypes, highlighting the importance of joint‐specific context in OA pathobiology. image
Objective Tissue‐resident memory T (T RM ) cells have been implicated in organ‐specific immune pathology; however, the pathological relevance of T RM ‐like CD8 + T cells in systemic lupus erythematosus (SLE) remains unclear. We investigated their differentiation mechanisms and pathological significance in SLE, including associations with disease activity and organ involvement. Methods Peripheral blood samples from 30 treatment‐naïve patients with SLE, 40 patients with rheumatoid arthritis (RA), and 30 healthy donors (HDs) were analyzed by flow cytometry. Renal biopsy specimens from 20 patients with SLE were examined by immunofluorescence. Naïve CD8 + T cells from HDs were stimulated with cytokines to induce T RM ‐like differentiation, followed by phenotypic, functional, transcriptional, and metabolic analyses. The effects of Janus kinase (JAK) inhibitors were assessed. Results Circulating CD8 + CD69 + CD103 + T RM ‐like cells were more frequent in SLE than in RA and HDs ( P=0.022 and P<0.001 , respectively) and correlated with anti‐dsDNA antibodies (rs=0.468, P=0.016 ) and CH50 (rs=−0.397, P=0.045 ). Patients with active kidney involvement (renal BILAG A/B; n=17) had higher T RM ‐like cell proportions than those without active kidney involvement (n=13; P<0.05 ). CD3 + CD103 + cells in renal lesions expressed granzyme B or interferon‐γ. Patients with baseline T RM ‐like cell proportions ≥0.40% had higher urine protein‐to‐creatinine ratios and SELENA‐SLEDAI scores at week 24 (both P<0.05 ). IL‐15 plus TGF‐β1 induced T RM ‐like differentiation with effector, transcriptional, survival, and metabolic features, whereas JAK inhibition suppressed differentiation and granzyme B expression. Conclusion Circulating T RM ‐like CD8 + T cells were associated with SLE activity and kidney involvement. IL‐15/TGF‐β1‐dependent differentiation partly involved JAK/STAT signaling, supporting further evaluation as a biomarker and therapeutic target. image
