Objective In this study, we sought to refine histologic scoring of rheumatoid arthritis (RA) synovial tissue by training with gene expression data and machine learning. Methods Twenty histologic features were assessed in 129 synovial tissue samples (n = 123 RA patients and n = 6 osteoarthritis [OA] patients). Consensus clustering was performed on gene expression data from a subset of 45 synovial samples. Support vector machine learning was used to predict gene expression subtypes, using histologic data as the input. Corresponding clinical data were compared across subtypes. Results Consensus clustering of gene expression data revealed 3 distinct synovial subtypes, including a high inflammatory subtype characterized by extensive infiltration of leukocytes, a low inflammatory subtype characterized by enrichment in pathways including transforming growth factor β, glycoproteins, and neuronal genes, and a mixed subtype. Machine learning applied to histologic features, with gene expression subtypes serving as labels, generated an algorithm for the scoring of histologic features. Patients with the high inflammatory synovial subtype exhibited higher levels of markers of systemic inflammation and autoantibodies. C‐reactive protein (CRP) levels were significantly correlated with the severity of pain in the high inflammatory subgroup but not in the others. Conclusion Gene expression analysis of RA and OA synovial tissue revealed 3 distinct synovial subtypes. These labels were used to generate a histologic scoring algorithm in which the histologic scores were found to be associated with parameters of systemic inflammation, including the erythrocyte sedimentation rate, CRP level, and autoantibody levels. Comparison of gene expression patterns to clinical features revealed a potentially clinically important distinction: mechanisms of pain may differ in patients with different synovial subtypes.

Flares are frequent in patients with RA undergoing arthroplasty. Higher baseline disease activity significantly increases the risk. Although more patients stopping biologics flared, this did not independently predict flaring. The effect of early postsurgery flares requires further study.

A 60-year-old woman underwent revision total hip arthroplasty with a modular dual-mobility articulation for recurrent dislocation. At 1-year follow-up, the patient reported no dislocations but had occasional clicking and discomfort with extreme motion. A Dunn radiograph identified notching of the femoral stem, attributed to impingement. Metal ions were elevated without adverse local-tissue reaction. After 4.5 years of observation, the notch size remained stable. She denied pain. Neither stem fracture nor prosthetic dislocation occurred. Impingement against cobalt-chromium acetabular bearing surfaces can result in notching of titanium femoral components after total hip arthroplasty. Increased anteversion intended to protect against posterior dislocation may be a risk factor. Posterior notching is best visualized on Dunn views, so incidence may be underestimated. No associated femoral implant fractures were identified on literature review.

BackgroundImmunosuppressive medications are often stopped prior to arthroplasty to mitigate infection risk, but this may increase the risk of disease flares post surgery in patients with rheumatoid arthritis (RA).ObjectivesTo describe rates, characteristics, and risk factors for flare after total hip (THA) and total knee (TKA) arthroplasty surgery.MethodsPre- and post-operative characteristics were examined in 58 RA patients undergoing TKA/THA. Perioperative medication use was standard of care: biologics were stopped before surgery, while steroids and methotrexate (MTX) continued. Clinicians evaluated RA clinical characteristics, on average, 0–2 weeks before and 6 weeks post-surgery. Post-surgery, patients completed weekly questions about RA symptoms, impact, and flare status using the OMERACT Flare Questionnaire. Baseline characteristics were compared using t-tests and chi-square, and multivariate logistic regression was used to identify baseline characteristics associated with post-surgical RA flares.ResultsOf 68 patients, 10 (15%) were flaring prior to surgery and were excluded. 88% met 2010/1987 RA criteria; those who did not meet criteria were included by rheumatologist diagnosis. Patients had a mean [SD] age of 61 [12], BMI of 30.6 [7.2], and RA duration of 16 [12] yrs. 59 (87%) were female, 53 (78%) were white, 33 (49%) were having THA, and 35 (52%) were on biologics. 35 (60%) had flared by 6 weeks post surgery. At baseline, flarers had significantly (p<.05) higher BMI, higher disease activity indicators (DAS28, RAPID3), inflammatory markers (ESR, CRP), and pain, and more were undergoing THA and used biologics (Table 1). After controlling for age, surgical joint, and baseline DAS28, the odds of flaring by 6 weeks post-surgery were significantly higher in patients who had discontinued biologics (OR 14.9, 95% CI 2.0, 112.0) or were obese (OR 6.0, 95% CI 1.1, 33.0).Table 1.Characteristics of RA patients who did and did not flare in the first 6 weeks post hip or knee arthroplasty (N=58)Flare (n=35)No Flare (n=23)SignificanceAge (yrs)58.2 (13.5)63.9 (10.4)0.073Female Sex32 (91%)18 (78%)0.155BMI32.6 (7.2)28.6 (6.5)0.040Minority Race10 (29%)2 (9%)0.099Hip arthroplasty22 (63%)6 (26%)0.006HOOS39.8 (21.9)52.2 (22)0.230KOOS44.0 (27.5)44.9 (14.2)0.914RA Duration (yrs)16.4 (12.0)16.1 (13.2)0.920DAS284.1 (1.2)2.9 (1.3)0.001RAPID316.0 (4.1)13.2 (5.4)0.032ESR (mm/hr)23.9 (20.2)11.0 (11.2)0.003CRP (mg/dl)2.3 (3.6)0.9 (0.8)0.043MD Global4.1 (1.6)3.3 (1.9)0.092Patient Global5.1 (1.9)4.0 (2.5)0.064Pain (10mm VAS)7.0 (2.0)5.7 (2.7)0.053MD HAQ3.9 (1.6)3.5 (1.5)0.282Biologics24 (69%)7 (30%)0.004MTX20 (57%)14 (61%)0.778Data shown as mean (SD) or n (%).ConclusionsFlares are frequent in RA patients undergoing arthroplasty, particularly THA. Discontinuing biologics and obesity significantly increased the risk of flaring post-arthroplasty.AcknowledgementThis study was supported by the Clinical Translational Science Center (CTSC) (UL1-TR000457–06).Disclosure of InterestNone declared