Background: Knee osteoarthritis (KOA) in people with overweight or obesity is clinically heterogeneous, reflecting mechanical loading, synovial and systemic inflammation, metabolic dysfunction, structural severity, and pain-related factors. We evaluated multidomain outcomes after semaglutide initiation and characterized clinically relevant response patterns. Methods: This retrospective, self-controlled cohort included 93 adults treated in routine rheumatology care; 88 completed a six-month follow-up. There was no untreated concurrent comparator; within-patient changes and exposure–outcome associations were therefore interpreted as non-causal. Changes in pain, Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) function, anthropometry, inflammatory markers, glycated hemoglobin (HbA1c), lipids, dose exposure, and safety were evaluated. Joint multivariable models included percentage weight loss and maximum achieved dose. Exploratory K-means phenotyping integrated dose, weight loss, body mass index (BMI) decrease, visual analog scale (VAS) and WOMAC improvement, and C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), and HbA1c reductions, with candidate solutions and resampling stability examined. Results: At six months, mean weight decreased by 10.88 kg, VAS pain score by 2.47 points, WOMAC total by 22.50 points, CRP by 2.67 mg/L, ESR by 7.62 mm/h, and HbA1c by 0.51 percentage points (all p < 0.001). Weight loss remained independently associated with WOMAC improvement, while achieved dose retained positive adjusted associations with pain, function, inflammatory, and metabolic changes. Exploratory clustering identified five clinically interpretable patterns along a broader response-intensity gradient, including high-burden multidomain response, high-dose concordant response, dose-modified intermediate response, inflammation-preserved response despite moderate weight loss, and dose-limited graded response. These observational coefficients and clusters cannot distinguish treatment-related effects from residual confounding or co-interventions. Conclusions: Substantial within-patient improvements were observed, but the uncontrolled design precludes causal attribution. The exploratory patterns may be compatible with contributions from baseline disease burden, dose exposure, mechanical unloading, and residual inflammatory variation; they do not establish weight-independent pharmacologic effects or validated patient subtypes. Prospective controlled, multicenter validation is required.

Objective: To quantify early and mid-term changes in ultrasound-detected synovitis and enthesitis after initiating guselkumab in psoriatic arthritis (PsA) and to contextualize imaging responses alongside clinical outcomes. Methods: We conducted a retrospective single-center cohort study of consecutive CASPAR-classified adults (n = 20) initiating guselkumab 100 mg (week 0/week 4, then q8w; q4w intensification per routine practice). Power Doppler ultrasound (PDUS) followed EULAR–OMERACT standards at baseline (T0), Month 3 (T3), and Month 6 (T6). The primary endpoint was within-patient change in 24-joint GLOESS. Secondary endpoints included OMERACT entheseal scores (activity-only; activity + structure), DAPSA states, PASI, and 6-month persistence. Within-patient changes were assessed using Wilcoxon signed-rank tests (two-sided). Results: All 20 patients completed T6. GLOESS decreased from T0 to T3 (mean Δ −4.05 ± 2.78; p = 0.0312) and to T6 (mean Δ −5.70 ± 4.05; p = 0.0001). Component summaries showed a numerically larger early decrease in synovial PD signal than in grayscale synovial hypertrophy (descriptive). Enthesitis scores improved: OMERACT activity-only median Δ −2.0 at T3 (p = 0.0313) and −3.5 at T6 (p = 0.016); activity + structure median Δ −1.5 at T3 (p = 0.0412) and −3.0 at T6 (p = 0.031). The estimated structural component (OMERACT-1 minus OMERACT-2) was similar across visits (descriptive), indicating improvements driven predominantly by inflammatory signal suppression rather than detectable changes in structural lesions over 6 months. Among patients with baseline PD-positive enthesitis (n = 7), PD negativity (OMERACT-2 = 0) occurred in 2/7 (28.6%) by T6. Clinical domains (DAPSA, PASI) improved in parallel, and 6-month persistence was high. Conclusions: In routine care, guselkumab was associated with a significant improvement in PD-inclusive ultrasound synovitis scores by 3 months, which deepened by 6 months, alongside an improvement in entheseal activity measures. Over 6 months, entheseal structural burden appeared stable; these findings should be considered hypothesis-generating and warrant confirmation in prospective controlled studies.

Background and Objectives: Foot bone marrow edema of presumed algodystrophic or bone marrow edema syndrome-like origin is clinically difficult to classify, and the relationship between MRI extent, pain severity, and functional impairment remains insufficiently defined. This study aimed to describe MRI distribution patterns and short-term clinical changes in a small real-world cohort of patients with persistent NSAID-resistant foot pain and presumed algodystrophic/BMES-like bone marrow edema. Materials and Methods: This retrospective single-center observational cohort study included 19 consecutive patients with persistent foot pain; MRI-demonstrated bone marrow edema; inadequate response to NSAIDs; management with a multimodal protocol that included neridronate, vitamin D supplementation, and, in selected patients, adjunctive physiotherapy and magnetotherapy; and available 3-month follow-up. The protocol consisted of intramuscular neridronate 25 mg once daily for 16 consecutive days, resulting in a total cumulative dose of 400 mg, together with vitamin D supplementation. Eleven patients also underwent adjunctive physiotherapy and magnetotherapy. MRI findings were categorized by anatomical location group, multilocalization, and compartment involvement. Clinical outcomes included baseline and 3-month Visual Analog Scale scores, WOMAC scores, and descriptive changes in NSAID use. Nonparametric paired and exploratory subgroup analyses were performed. Results: Mean age was 51.3 ± 14.9 years, and 52.6% of patients were female. MRI showed predominant midfoot involvement, with the navicular and third cuneiform most frequently affected. Median VAS changed from 8.0 at baseline to 3.0 at 3 months, and median WOMAC changed from 80.0 to 41.0; because no control group was available, these paired changes should be interpreted descriptively. Daily NSAID use decreased from 78.9% at baseline to 0% at follow-up. These findings describe clinical improvement after a multimodal management approach but do not establish the independent treatment effect of neridronate. In exploratory analyses, only two patients had multi-compartment involvement; therefore, any apparent pain-severity signal in this subgroup was considered unstable and hypothesis-generating only. Edema location group and multilocalization were not statistically associated with VAS or WOMAC outcomes. Conclusions: In this small retrospective single-center case series, presumed algodystrophic/BMES-like foot bone marrow edema most commonly involved the midfoot, particularly the navicular and cuneiform region. Pain scores, WOMAC scores, and daily NSAID use decreased over 3 months after multimodal care. However, the uncontrolled design, small sample size, concomitant vitamin D supplementation, adjunctive physiotherapy or magnetotherapy in many patients, and self-limiting nature of BMES-like conditions prevent attribution of these changes to neridronate or to any single treatment component. The apparent relationship between multi-compartment edema and greater pain severity was based on only two patients and should be regarded only as a weak exploratory observation.