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.

Background: While total joint replacements (TJR) are frequently performed, there is little qualitative research to define the outcomes most important to patients. Methods: Patients who had received total hip (THR) or total knee replacements (TKR) participated in 8 nominal groups to answer the question "What result/results matter the most to a patient undergoing/having a knee or hip replacement?" Total 270 votes were allocated. Results: Eight nominal groups were performed with 45 patients, 6 groups with mean age (71.1 ± 9.3), and 2 with 9 younger patients (mean age 36.8 ± 7.4). All had TJR between 2016 and 2018; overall, 40% were male, 15.6% were Black, and 75% were performed for osteoarthritis. While all groups ranked the same top 3 outcomes, responses varied with age: 1) relief of pain (46% vs. 35% in the young groups); 2) improved function including mobility (29% vs. 18% in the young groups); 3) restored quality of life (13% vs 33% of votes in the younger group). Conclusion: Relief of pain and restoration of function, and improved quality of life are the 3 outcomes ranked highest by patients, confirming their inclusion in TJR clinical trials.

Objective Morning stiffness is a hallmark symptom of rheumatoid arthritis (RA), but its etiology is poorly understood. This study was undertaken to determine whether any histologic features of synovium are associated with this symptom. Methods Data on patient‐reported morning stiffness duration and severity, and Disease Activity Score in 28 joints (DAS28) were collected from 176 patients with RA undergoing arthroplasty. Synovium was scored for 10 histopathologic features: synovial lining hyperplasia, lymphocytes, plasma cells, Russell bodies, binucleate plasma cells, fibrin, synovial giant cells, detritus, neutrophils, and mucin. Fibrinolysis of clots seeded with various cell types was measured in turbidimetric lysis assays. Results Stiffness severity and morning stiffness duration were both significantly associated with DAS28 (P = 0.0001 and P = 0.001, respectively). None of the synovial features examined were associated with patient‐reported stiffness severity. The presence of neutrophils and fibrin in RA synovial tissue were significantly associated (P < 0.0001) with patient‐reported morning stiffness of ≥1 hour, such that 73% of patients with both synovial fibrin and neutrophils reported morning stiffness of ≥1 hour. Further, neutrophils and fibrin deposits colocalized along the synovial lining. In in vitro analyses, fibrin clots seeded with necrotic neutrophils were more resistant to fibrinolysis than those seeded with living neutrophils or no cells (P = 0.008). DNase I treatment of necrotic neutrophils abrogated the delay in fibrinolysis. Conclusion In RA, prolonged morning stiffness may be related to impaired fibrinolysis of neutrophil‐enmeshed fibrin deposits along the synovial membrane. Our findings also suggest that morning stiffness severity and duration may reflect distinct pathophysiologic phenomena.

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