Relationship Between Lymph Node Volume and Pain Following Certolizumab Therapy for Rheumatoid Arthritis Flare: A Pilot Study.

OBJECTIVES: The mechanisms that trigger flare in rheumatoid arthritis (RA) are unknown. In murine arthritis models, dysfunctional lymph node (LN) drainage is associated with joint flare. To examine if LN alterations are associated with RA flare, we analyzed the change in LN volume via contrast-enhanced magnetic resonance imaging (CE-MRI) in patients with active joint flare at baseline and 16 weeks after certolizumab pegol (CZP) therapy. We also assessed the changes in popliteal or epitrochlear LN volumes versus the Rheumatoid and Arthritis Outcome Score (RAOS) (knee), or the Michigan Hand Questionnaire (MHQ; wrist/hand), and Disease Activity Score 28 (DAS28), at baseline and 16 weeks. RESULTS: Total LN volume in 7 of 10 patients with measurable LN on CE-MRI significantly decreased 16 weeks after CZP therapy (mean decrease 37%; P = 0.0019). Improvement in knee pain measured by the RAOS (P = 0.03) inversely correlated with a decrease in total popliteal LN volume (R2 = 0.94). All patients demonstrated significant improvement in DAS28 (mean decrease 1.48; P = 0.0002). For flare in the hand, significant improvement in activities of daily living (ADL) as measured by the MHQ was observed (left hand mean improvement 20%; P = 0.02; right hand mean improvement 37%; P = 0.03). CONCLUSION: RA patients with the smallest change in LN volume during anti-tumor necrosis factor (anti-TNF) therapy experienced the greatest pain relief in symptomatic knee joints. Moreover, the remarkably linear inverse correlation between LN volume and joint pain observed in this small clinical pilot provides initial evidence to support the concept that dynamic changes in draining LN volume are a biomarker of clinical response to therapy in RA.

Divergent gene activation in peripheral blood and tissues of patients with rheumatoid arthritis, psoriatic arthritis and psoriasis following infliximab therapy.

OBJECTIVE: The immune inflammatory disorders rheumatoid arthritis (RA), psoriatic arthritis (PsA) and psoriasis (Ps) share common pathologic features and show responsiveness to anti-tumor necrosis factor (TNF) agents yet they are phenotypically distinct. The aim of this study was to examine if anti-TNF therapy is associated with divergent gene expression profiles in circulating cells and target tissues of patients with these diseases. METHODS: Peripheral blood CD14+ and CD14- cells were isolated from 9 RA, 12 PsA and 10 Ps patients before and after infliximab (IFX) treatment. Paired synovial (n=3, RA, PsA) and skin biopsies (n=5, Ps) were also collected. Gene expression was analyzed by microarrays. RESULTS: 26 out of 31 subjects responded to IFX. The transcriptional response of CD14+ cells to IFX was unique for the three diseases, with little overlap (<25%) in significantly changed gene lists (with PsA having the largest number of changed genes). In Ps, altered gene expression was more pronounced in lesional skin (relative to paired, healthy skin) compared to blood (relative to healthy controls). Marked suppression of up-regulated genes in affected skin was noted 2 weeks after therapy but the expression patterns differed from uninvolved skin. Divergent patterns of expression were noted between the blood cells and skin or synovial tissues in individual patients. Functions that promote cell differentiation, proliferation and apoptosis in all three diseases were enriched. RA was enriched in functions in CD14- cells, PsA in CD14+ cells and Ps in both CD14+ and CD14- cells, however, the specific functions showed little overlap in the 3 disorders. CONCLUSION: Divergent patterns of altered gene expression are observed in RA, PsA and Ps patients in blood cells and target organs in IFX responders. Differential gene expression profiles in the blood do not correlate with those in target organs.

Counselling interventions to address the psychological consequences of screening mammography: a randomised trial.

We examined the effectiveness of offering counselling to women undergoing screening mammography who are recalled for further investigations that do not lead to a diagnosis of cancer. Women were randomised to being offered either face-to-face (n = 66) or telephone counselling (n = 68) or usual care (n = 71) at the recall clinic after being told that their screen-detected abnormality was not cancer. The PCQ (a reliable and valid measure of the psychological consequences of screening mammography) measured the emotional, social and physical functioning of women at the recall clinic (Time 1) and after the counselling intervention (Time 2). Analyses of covariance (ANCOVA) showed no main effects for intervention on Time 2 levels of functioning after adjustment for the respective covariate of Time 1 functioning. Time 1 levels significantly predicted Time 2 levels of functioning. When data were analysed according to whether women actually received any type of counselling versus not receiving counselling, participation in counselling was associated with lower scores on dysfunction scales at Time 2, after adjusting for Time 1 levels.