Scott T. Persellin

Tricuspid valve papillary fibroelastoma : echocardiographic characterization

We report a tricuspid valve papillary fibroelastoma initially detected by transthoracic two-dimensional echocardiography and subsequently characterized by transesophageal two-dimensional echocardiography. The mass was excised during open heart operation, and the diagnosis was verified grossly and histopathologically. Transesophageal echocardiography usually provides images far superior to those from transthoracic echocardiography and may be a useful adjunct for intraoperative localization of intracardiac tumors for excision.

Detection of Migratory Silicone Pseudotumor With Use of Magnetic Resonance Imaging

A patient with silicone gel breast implants, who experienced capsular contracture of the left breast that was treated by closed capsulotomy, sought medical attention because of numbness and pain in the left medial forearm and hand. Inflammatory masses subsequently developed in the left anterior axillary and antecubital regions. Magnetic resonance imaging revealed silicone pseudotumors, and mammography confirmed implant rupture and gel extrusion along fascial planes into the axillary region.

Patient-provider discordance between global assessments of disease activity in rheumatoid arthritis: a comprehensive clinical evaluation

BackgroundDiscordance between patients with rheumatoid arthritis (RA) and their rheumatology health care providers is a common and important problem. The objective of this study was to perform a comprehensive clinical evaluation of patient-provider discordance in RA.MethodsA cross-sectional observational study was conducted of consecutive RA patients in a regional practice with an absolute difference of ≥ 25 points between patient and provider global assessments (possible points, 0–100). Data were collected for disease activity measures, clinical characteristics, comorbidities, and medications. In a prospective substudy, participants completed patient-reported outcome measures and underwent ultrasonographic assessment of synovial inflammation. Differences between the discordant and concordant groups were tested using χ2 and rank sum tests. Multivariable logistic regression was used to develop a clinical model of discordance.ResultsPatient-provider discordance affected 114 (32.5%) of 350 consecutive patients. Of the total population, 103 patients (29.5%) rated disease activity higher than their providers (i.e., ‘positive’ discordance); only 11 (3.1%) rated disease activity lower than their providers and were excluded from further analysis. Positive discordance correlated with negative rheumatoid factor and anticyclic citrullinated peptide antibodies, lack of joint erosions, presence of comorbid fibromyalgia or depression, and use of opioids, antidepressants, or anxiolytics, or fibromyalgia medications. In the prospective study, the group with positive discordance was distinguished by higher pain intensity, neuropathic type pain, chronic widespread pain and associated polysymptomatic distress, and limited functional health status. Depression was found to be an important mediator of positive discordance in low disease activity whereas the widespread pain index was an important mediator of positive discordance in moderate-to-high disease activity states. Ultrasonography scores did not reveal significant differences in synovial inflammation between discordant and concordant groups.ConclusionsThe findings provide a deeper understanding of patient-provider discordance than previously known. New insights from this study include the evidence that positive discordance is not associated with unrecognized joint inflammation by ultrasonography and that depression and fibromyalgia appear to play distinct roles in determining positive discordance. Further work is necessary to develop a comprehensive framework for patient-centered evaluation and management of RA and associated comorbidities in patients in the scenario of patient-provider discordance.

Determinants of disability in rheumatoid arthritis: A community-based cohort study

Longitudinal care of a community-based cohort of patients with rheumatoid arthritis (RA) was evaluated retrospectively. Candidate determinants of disability included visual analog scales (VAS) for patient global assessment and pain, comorbidities, and medications. The outcome was the ‘patient-acceptable symptom state’ for disability as defined by the Health Assessment Questionnaire (HAQ) disability index, using a cutoff of <1.04. Two-sample t tests and multivariable logistic regression were used to determine odds ratios (OR) for associations between predictor variables and disability. Out of a total of 99 patients, 28 (28%) patients had HAQ ≥1.04 at their last visit. The greatest odds of not attaining the patient-acceptable symptom state in a multivariable model was associated with corticosteroids (OR: 5.1; p=0.02), antidepressants (OR: 5.3; p=0.02), and female sex (OR: 6.5; p=0.05). In the era of biologic therapy, female sex, corticosteroids, and antidepressants remain profound determinants of disability highlighting the need to understand the underlying mechanisms.

ID: 133: SINGLE CELL GENE EXPRESSION IN CLASSICAL MONOCYTES CORRELATES WITH TREATMENT RESPONSE TO TNF-ALPHA INHIBITION IN RHEUMATOID ARTHRITIS

Background In management of rheumatoid arthritis (RA), initiating effective treatment as soon as possible within the so-called therapeutic “window of opportunity” is the strategy, and disease remission is a primary goal. Recent work from our group demonstrated that pre-treatment serum type I IFN-β/α activity ratio>1.3 can predict non-response to anti-TNF-alpha therapy in RA patients. The cellular mechanisms that underlie the IFN-β/α activity ratio that predicts response are not known. Effects of IFN on single immune cells and uncommon cell populations may be masked in whole blood or mixed cell populations. Methods To better understand the underpinnings of the pre-treatment IFN-β/α activity ratio, we used single cell expression analysis to investigate whether monocyte gene expression differs significantly between RA patients according to their pre-TNF-α inhibitor serum IFN-β/α activity ratio. Single classical (CL) and single non-classical (NCL) blood-derived monocytes were isolated from 15 seropositive RA subjects prior to biologic therapy. Total serum type I IFN, IFN-α, and IFN-β activity were measured using a functional reporter cell assay. Subjects were grouped by pre-TNF-α inhibitor serum IFN-β/α activity ratio into two groups, IFN-β/α>1.3 (n=6) and IFN-β/α<1.3 (n=9). Comparisons between groups were by Mann-Whitney. Hierarchical clustering of 87 target genes was done to determine if there were functional gene expression differences between groups. Results Hierarchical clustering revealed striking differences of expression of gene sets in CL monocytes between patients with IFN-β/α<1.3 and IFN-β/α>1.3, the groups which correspond to response/non-response to anti-TNF-α agents. This same clustering was not observed in NCL monocytes, and the differentiation between anti-TNF-α response patient groups was lost when hierarchical clustering was done on total monocytes (CL and NCL). Two major gene sets which differentiated subjects with IFN-β/α>1.3 (non-response to anti-TNF-α group) in CL monocytes included TLR and IFN pathway genes, cell surface markers and cytokines as follows: cluster 1 (TLR2, CD16, JAK1, IFI27, IL1A, and MAVS) and cluster 2 (GMCSF, TLR7, STAT2, ILT7, MYD88). Conclusion These within-cell expression patterns demonstrate biological differences in CL monocytes of RA patients with an IFN-β/α>1.3, the ratio of type I IFNs previously found to be predictive of non-response to anti-TNF-α therapy. Differentiation by gene expression among the response/non-response patient groups is lost when comparing gene expression in single NCL monocytes and single mixed population monocytes (CL and NCL), suggesting that further study of CL monocytes will likely illuminate molecular differences that determine treatment response to TNF-α inhibition in RA. This work will help to develop a more individualized approach to therapy in RA based upon the underlying biology of disease in a given patient.

FRI0074 The Patient Global Assessment of Disease Activity in Rheumatoid Arthritis: Identification of Underlying Latent Factors Using Principal Components Analysis

Background The patient global assessment of disease activity is a crucial component of validated disease activity scores, response criteria, and the ACR/EULAR definition of remission in rheumatoid arthritis (RA). Recent work has shown that the patient global reflects persistent undifferentiated symptoms of pain, fatigue, and functional disability, occasionally despite seeming attainment of low inflammatory disease activity. The absence of a conceptual framework for evaluating patients in this scenario is a critical barrier to improving patient-centered outcomes. Objectives To identify underlying latent factors driving the patient global assessment of disease activity using a quantitative, multivariable data reduction approach. Methods This was a prospective cross-sectional study of 70 patients with RA fulfilling the ACR/EULAR 2010 classification criteria. Data were collected from the most recent rheumatology visit, including the patient and provider global assessments of disease activity (0–100 mm), tender and swollen joint counts, and current RA drug therapies. The patient sample was stratified to include 50 “discordant” patients (i.e., patient global assessments of disease activity were ≥25 mm higher than the provider global assessments) and 20 “concordant” patients. Co-morbid anxiety, depression, osteoarthritis, and fibromyalgia by provider diagnosis were abstracted from the complete electronic medical records. Participants completed several validated patient-reported outcome measures (PROMs), including measures of pain and pain interference, fibromyalgia, physical function, ability to participate, anxiety, depression, and fatigue. Data were evaluated using exploratory principal component analysis (PCA) as a data reduction method to determine the latent constructs in the data. Linear regression models were then used to determine the variability in patient global assessment explained by the PCA scores. Results The 70 patients had a mean age of 61 years, mean RA duration of 8.0 years, and 73% were female. The mean Clinical Disease Activity Index was 12.9. The mean (SD) for the patient global assessment of disease activity was 44.6 (22.7) and for the provider global assessment was 20.1 (17.7). PCA yielded 8 factor scores that represented domains of pain, fatigue, anxiety, depression, advanced age and degenerative arthritis, physical disability, fibromyalgia, and unknown. Linear regression analysis showed that pain explained the greatest variability in the patient global assessment of any of the factor scores (adjusted R-squared value: 0.06). The factor scores for pain, depression and anxiety, inability to participate, fibromyalgia, and advanced age were all significantly associated with the patient global assessment and altogether explained 33% of the variability in the patient global assessment. Conclusions Pain, depression and anxiety symptoms, inability to participate, fibromyalgia, and advanced age are key drivers of the patient global assessment. Future studies are warranted to develop a standardized approach to management of these factors toward the realization of patient-centered treat-to-target strategies for RA. Disclosure of Interest None declared