Fusion of the First Metatarsophalangeal Joint and Second to Fifth Metatarsal Head Resection for Rheumatoid Forefoot Deformity.

The goals of the present study were to evaluate the mid-term results of first metatarsophalangeal joint fusion combined with second to fifth metatarsal head resection in rheumatoid forefoot deformity and identify the prognostic factors. The inclusion criteria were 2010 American College of Rheumatology and/or European League Against Rheumatism criteria for rheumatoid arthritis; symptomatic forefoot deformity; first metatarsophalangeal joint fusion and second to fifth metatarsal head resection; and a minimum of 4 years of follow-up data available. The patients were evaluated using the Disease Activity Score 28 for rheumatoid arthritis, Health Assessment Questionnaire for Rheumatoid Arthritis, Foot Function Index, forefoot American Orthopaedic Foot and Ankle Society scale, and weightbearing radiographs. Different pre-, intra-, and postoperative variables were investigated to identify the prognostic factors. Sixty-two patients (89 feet) with a mean age of 60.8°± 9.4 years and 85.5°± 22.4 months of follow-up data were included. The preoperative American Orthopaedic Foot and Ankle Society scale score was 33.4 ± 16 points and improved significantly (p < .001) after surgery (mean 82.9 ± 11.7 points). The mean Foot Function Index improved significantly (p < .001) from 131.6 ± 37.4 to 77.4 ± 46.3 points at the last follow-up visit. Only the revision surgery variable was significantly (p = .02) related to poor outcomes. Revision was necessary in 8 feet (9%). This procedure produced satisfactory results. Poor outcomes were significantly related to the necessity for revision surgery for nonunion, malunion, inadequate metatarsal resection, and painful hardware.

Arthroscopic synovectomy of the knee in rheumatoid arthritis defined by the 2010 ACR/EULAR criteria.

BACKGROUND: The aims of this study were: (1) to evaluate the mid-term results and survivorship of arthroscopic synovectomy (AS) of the knee in rheumatoid arthritis (RA) defined with the 2010 American College of Rheumatology (ACR)/European League Against Rheumatism (EULAR) criteria; and (2) to identify prognostic factors. METHODS: Patients matching the 2010 ACR/EULAR criteria, with symptomatic knee synovitis for at least six months, treated with arthroscopic synovectomy of the knee at a minimum of three year followup were included. Pre-operative evaluation included Larsen, HAQ, DAS28, and Laurin scores. Post-operatively, Laurin, WOMAC, and patient satisfaction scores were evaluated. Different variables were investigated to find associations with the outcomes. Kaplan-Meier survival analysis was performed. RESULTS: Sixty-four patients met the inclusion criteria. Seven patients (9.6%) were lost to followup, leaving 57 patients (66 knees) for the present study. The average followup was 96.3months (SD 41). The pre-operative Laurin score was 3.91 points (SD 1.3) and significantly (P<0.001) improved after surgery (mean 8.2, SD 2). The post-operative average WOMAC score was 73.9 points (SD 45.9). Eighteen knees (27.3%) underwent revision procedures at an average of 48.6 months (SD 39.8). Joint degeneration (Larsen grade III) and range of movement (ROM) reduction (>10%) were identified as negative prognostic factors. Kaplan-Meier survivorship with total knee replacement as endpoint was: 78% at one year, 28% at four years, and six percent at 10 years. CONCLUSIONS: Although AS of the knee has still a role as a salvage procedure in the treatment of RA synovitis with initial joint degeneration (less than Larsen grade III) and good ROM, high revision rates and limited survivorship are reported.

Estrogens interfere with leflunomide modulation of cytokine production by human activated monocytes.

Rheumatoid arthritis (RA) prevalence is greater in females than in males, supporting estrogens as modulators of immune response. Leflunomide (LEF) is employed in the RA treatment. We studied the combinatory effects of LEF active metabolite A77 1726 (LEF-M) and 17beta-estradiol (E2) on inflammatory cytokine production by cultured macrophages obtained from activated human monocytes (THP-1 cells). Macrophages were cultured with LEF-M alone and in combination with E2. IL-6, TNF-alpha, and TGF-beta were evaluated by immunocytochemistry (ICC), Western blot (WB), and reverse transcriptase-polymerase chain reaction (RT-PCR). ICC, as well as WB and RT-PCR, showed that LEF-M, in respect to untreated cells, significantly downregulated the cytokine production (IL-6 P < 0.01, TNF-alphaP < 0.001, TGF-betaP < 0.01). On the contrary, E2 increased the cytokine production, a result that was significantly reversed when LEF-M was subsequently added (IL-6, TNF-alpha, TGF-betaP < 0.001 vs. E2). E2 seems to contrast the LEF-M activity. These results might support a more efficient therapeutical effect of LEF in male with respect to female RA patients.

CTLA4-Ig interacts with cultured synovial macrophages from rheumatoid arthritis patients and downregulates cytokine production.

INTRODUCTION: Co-stimulatory signal B7(CD80/CD86):CD28 is needed in order to activate T cells in immune response. Cytotoxic T lymphocyte-associated antigen-4-immunoglobulin (CTLA4-Ig) binding to the B7 molecules on antigen-presenting cells downregulates this activation and represents a recent biological treatment in rheumatoid arthritis (RA). Objectives of the study were to investigate the presence of the B7.2 (CD86) molecule and its masking by CTLA4-Ig on cultures of both RA synovial macrophages (RA SM), and of macrophages differentiated from THP-1 cells (M). In addition, the anti-inflammatory effects of CTLA4-Ig on co-cultures of RA SM and M with activated T cells were tested. METHODS: All macrophages were co-cultured for 24 hours with activated T cells, without or with CTLA4-Ig (10, 100, 500 microg/ml for 1 hour, 3 hours and overnight, respectively). Immunofluorescence (IF) staining for B7.2, and an analysis of inflammatory cytokine expression (interleukin (IL) -6, tumor necrosis factor (TNF) alpha, IL-1beta, transforming growth factor (TGF) beta) by immunocytochemistry (ICC), western blot (WB) and reverse transcriptase-polymerase chain reaction (RT-PCR) were performed. RESULTS: Macrophages showed intense B7.2 expression. CTLA4-Ig/B7.2 masking was evident for all macrophages, even after only 1 hour of cell culture (range from 10 to 100 microg/ml). ICC of co-cultures showed a dose-dependent decrease in inflammatory cytokines (P < 0.001 for IL-6, TNFalpha, IL-1beta and TGFbeta). Data were confirmed by WB and RT-PCR analysis. CONCLUSIONS: Optimal concentrations of CTLA4-Ig for the CTLA4-Ig/B7.2 masking on activated macrophages were identified and were found to induce significant downregulation in the cell production of IL-6, TNFalpha, IL1-beta and TGFbeta. In conclusion, macrophages would appear to be a sensitive target for CTLA4-Ig treatment in RA.

Sex hormones modulate the effects of Leflunomide on cytokine production by cultures of differentiated monocyte/macrophages and synovial macrophages from rheumatoid arthritis patients.

Immune response is greater in females than in males and lymphocytes/monocytes from female subjects (or tested in vitro with estrogens) show higher immune/inflammatory reactivity. In order to test in vitro the interactions between 17beta-estradiol (E2--10(-9) M), testosterone (T--10(-8) M) and the antiproliferative/immune suppressive drug Leflunomide metabolite A77 1726 (LEF-M--30 microM) employed in rheumatoid arthritis (RA), their combined effects were evaluated on inflammatory cytokine (CK) expression/production in cultures of differentiated macrophages (M) (from activated THP-1 monocytes) and primary cultures of RA synovial macrophages (SM). TNFalpha, IL-6 and TGFbeta were detected by immunocytochemistry (ICC), Western blot analysis (WB) and reverse transcriptase-polymerase chain reaction (RT-PCR). The ICC, WB and RT-PCR showed a significant down-regulation induced by LEF-M on CK expression by cultured M when compared to untreated cells (IL-6 p < 0.01, TNFalpha p < 0.001, TGFbeta p < 0.01). At ICC analysis E2 increased CK expression, whereas T decreased the expression, confirmed by WB and RT-PCR (range between p < 0.05 and p < 0.001). LEF-M treatment significantly downregulated the CK expression in E2/T treated M: the effect was more significant in LEF-M plus T-treated cells versus controls (range between p < 0.01 and p < 0.001). Concerning the RA SM, the results were replicated (range between p < 0.05 and p < 0.001). E2 seems to contrast, but T seems to synergize the LEF-M activity. Results might support a stronger therapeutical efficacy, at least for LEF, in male RA patients, as already reported by clinical evidences.