The paper analyzes the efficiency and tolerability of a combination of rituximab (RTM) and leflunomide (LEF) for the treatment of rheumatoid arthritis (RA) versus the conventional combination of RTM and methotrexate (MT). The results of 24-week therapy were assessed in the RA patients included into the Russian Biological Therapy Register. A good effect of therapy was achieved in 31.8% of the patients who had received RTM+LEF (p = 0.1). The development of clinical remissions in RA was observed at a practically equal frequency of 13.6 and 11.7%, respectively. The doses of glucocorticoids and nonsteroidal anti-inflammatory drugs used in concurrent anti-inflammatory therapy could be substantially reduced in both groups. In both groups, the rate of side effects was very equal: 21.7% for the RTM+LEF group and 25.7% for the RTM+MT group. Thus, the combination therapy of RTM and LEF in real clinical practice is not considerably different from the most commonly used combination of RMT and MT in efficiency and tolerability and may be successfully used if there are any contraindications to the use of MT.

Objective. To study the specific features of rheumatoid arthritis (RA) in real practice.
Subjects and methods. The study included 1810 patients with RA (including 1520 women) whose mean age was 54 years. The history of the disease averaged 7 years. The extensive and late clinical stages of RA were predominant (86% as a whole); 64.6% of the patients were found to have a high inflammatory disease activity (DAS 28 >5.1).
Results. The mean interval between the emergence of the first symptoms of RA and the moment of this diagnosis was 24 [8; 44] months. The diagnosis of RA was shown to be established in only 18% of the patients in the first 6 months of the disease onset. However, this indicator increased up to 68% if the patient immediately visited a rheumatologist, by disregarding medical advice from other physicians. Every eight (13%) RA patients aged 55 years require endoprosthetic joint replacement 13 years after the disease onset. These patients had a higher inflammatory process activity (DAS 28 = 6.0) at the moment of the study; their mean methotrexate dose was not greater than 10 mg/week and the interval between the disease onset and the moment of diagnosis was significantly longer that that in the general sample of patients with RA and averaged 31 months. Conclusion. Inadequate training of physicians in rheumatology problems increases the interval between the disease onset and the moment of outpatient diagnosis results in early disability and makes it necessary to make endoprosthetic replacement of large joints in patients with RA.

Objective. To estimate the serum levels of interleukins (IL) 6 and 10, tumor necrosis factor-α (TNF-α) and vascular endothelial growth factor (VEGF) in patients with psoriatic arthritis (PSA) and their relationship with the clinical and laboratory parameters of inflammation and with erythrocyte aggregation (EA).
Material and methods. The authors measured the serum levels of C-reactive protein (CRP) by immunonephelometry (BN, ProSPEC, Siemens) and those of TNF-α, IL-6 and IL-10, and VEGF by X-MAP technology using a BioPlex-200 system (Panel Human 27-Plex Bio-Rad, USA) in 80 patients with PSA [45 women and 35 men; mean age 41.7±10.5 years, mean duration of PSA and psoriasis was 5.0 (2.0; 12,5) and 15 (4; 26) years, respectively; DAS 3.9 (3.09; 5.16)]. The blood samples from 16 healthy donors matched to the examinees for gender and age served as a control. The parameters of EA [Т1(с); Кt (arb. units); β (с-1), I2,5 (%)] were estimated, by recording the rate of back light scattering. The median (Me) and interquartile range [Q25; Q75], and mean and standard deviations (M±σ) were calculated; the indicators were compared by the Mann-Whitney test and Student's t test. Correlation analysis was made using the Spearman rank correlation coefficient (R); p < 0.05 was considered statistically significant.
Results. There were significantly higher serum levels of IL-6 and IL-10, TNF-α, and VEGF in patients with PSA than in the controls, and impaired blood rheological properties. There were significant correlations of the level of most cytokines (IL-6 and IL-10, VEGF) with both the values of the clinical and laboratory activity of PSA (self-rated pain, the number of swollen and tender joints, a physician's assessment of disease activity, DAS, erythrocyte sedimentation rate, and fibrinogen) and most parameters of EA (Т1, Kt и I2.5). No significant relationships were found between VEGF and CRP.
Conclusion. The enhanced clinical and laboratory activity of PSA is attended by the systemic activation of immunological mediators of inflammation and neoangiogenesis and by impaired blood rheological properties, which supports the interaction of these factors in the immunopathogenesis of the diseases.

Objective. To study the relationship between the activity of collagen type II cleavage and the pattern of expression of the genes responsible for chondrocyte differentiation in the areas of intact cartilaginous tissue and in those of early focal cartilage lesions similar to those observed in elderly people with osteoarthrosis (OA).
Material and methods. The distal femoral articular surface of the knee joint that articulated with the patella and had focal lesions was examined in the elderly. Collagen type II cleavage was estimated by enzyme immunoassay. Gene expression was determined with reverse-transcription polymerase chain reaction.
Results. The activity of collagen type II cleavage was shown to be increased in the area of age-related OA-like cartilage lesions. This was accompanied by the high expression of collagenases of metalloproteinases (MMP) 1, 14 (MT1-MMP), aggrecanases - desintegrin and MMP with thrombospondin type 1 motif (ADAMTS) 5, the cytokines of interleukins (IL) 1α/β and tumor necrosis factor-α (TNF-α), as well as the genes associated with chondrocyte hypertrophy of type X collagen (C0L10A1), MMP 13 and 9, Indian hedgehog (Ihh) and cas-pase 3 in the immediate vicinity of a lesion area. At the same time, there was a high expression of growth factors associated with the proliferation phase of chondrocytes, namely: parathyroid hormone-related peptide (PTHrP), fibroblast growth factor-2 (FGF-2), transforming growth factor β1/2 (TGF-β1/2), as well as macromolecules of matrix of type II collagen (C0L2A1) and aggrecan in both the areas adjacent to the lesions and at a considerable distance from their center. However, these areas showed no higher collagen cleavage activity. Nether higher collagen cleavage, nor excess expression of the genes examined were observed in the absolutely intact cartilage areas. Conclusion. Our studies have indicated that the area of very early age-related OA-like focal cartilage lesions exhibits enhanced type II collagen cleavage that is attended by the expression of the genes associated with chondrocyte differentiation in the embryonic growth plate.

The paper describes a clinical observation of the efficiency of local therapy with autologous platelet-rich plasma for .skin ulcer defect in a female with chronic lymphocytic leukemia

Objective: to analyze the course of rheumatoid arthritis (RA), to assess its previous therapy, and to evaluate the efficiency of endoprosthetic replacement of knee or hip joints (EKJ or EHJ).
Subjects and methods. The study enrolled 50 patients with RA who had undergone EKJ (Group 1; n = 32) or EKJ (Group 2; n = 18); their mean age was 51.8±11.6 and 48.7±8.5 years and the disease duration was 16.5±7.8 and 15.5±7.5 years, respectively. Their quality of life (QL) was estimated by the EQ-5D and SF-36 questionnaires; joint functional capacity was assessed by the HAQ index and the Harris and Insall scales. Results and discussion. Before surgical treatment, the majority of patients took methotrexate (MT) in a weekly dose of 7.5-10 mg, which was prescribed 7-10 years after the disease onset. Oral glucocorticoids (GC) were given to 65.4 and 84.6% of the patients of Groups 1 and 2, respectively. Six months after endoprosthetic replacement, there was functional improvement: the HAQ index decreased from 1.64±0.7 to 1.40±0.6 after EKJ (p = 0.003) and from 2.07±0.6 to 1.72-0.7 after EHJ (p = 0.04). The EQ-5D QL index increased from 0.52 [0.0- 0.61] to 0.59 [0.52-0.69] scores after EKJ (p = 004) and from -0.02 [-0.02-0.52] to 0.52 [-0.02-0.62] scores after EHJ (p = 0.096). There was a significant improvement in the SF-36 physical component summary (PCS): APCS = 4.3 (p = 0.04) after EKJ and APCS = 5.7 (p = 0.02) after EHJ and a trend towards stabilization of the patients' mental status.
Conclusion. The majority of patients had not initially received adequate disease-modifying anti-inflammatory therapy for many years. Endoprosthetic replacement of the lower limb joints in the first 6 months after surgery improved the functional capacity of the operated joint, by increasing QL in the patients as a whole. There was no substantial decrease in global disease activity 6 months following surgery.

The objective of the investigation was to study the results of ankle arthrodesis in rheumatoid arthritis (RA). The long-term results of treatment were analyzed and studied in 9 RA patients with synovitis. These were assessed using the Luboshitz-Mathis procedure: 6 (66.7%) patients achieved a good result; 1 (11.1%) and 2 (22.2%) had satisfactory and poor results, respectively. It was found that synovectomy should be performed during arthrodesis and the latter should itself be attended by minimal shortening. The paper describes the authorXs procedure of osteoplastic ankle arthrodesis that minimizes limb shortening. The essence of the operation is to cut out two autografts from the ankle and shin bones with cylindrical hollow milling cutters. The grafts are turned through a certain angle to block the ankle joint area and are fixed by spirally wedging. The proposed procedure makes it possible to perform arthrodesis rapidly and with minimum blood loss and to have bony ankylosis within 2-3 months ahead.

The mechanisms of action of currently used genetic engineering biological agents (GEBAs) include inhibition of cytokines, interleukins, and T cells and depletion of B cells. GEBAs were originally accessible mainly for the treatment of refractory juvenile idiopathic arthritis (JIA), including systemic-onset JIA (Still's disease), which allowed one to do away with the long-term use of high doses of glucocorticoids or cytostatics. Since 2000, a number of randomized double-blind placebo-controlled and open-label pilot studies have convincingly demonstrated the efficacy of GEBAs in children and adolescents. Although the tumor necrosis factor-a (TNF-a) inhibitors etanercept and adalimumab are chiefly used to treat refractory polyarticular JIA, interleukin 1 and 6 blockers showed satisfactory results in treating systemic JIA. Abacept is regarded as a treatment option for patients with polyarticular JIA when disease modifiers and TNF-a inhibitors are ineffective. The place of rituximab in the management of JIA has not certainly defined so far.
However, GEBA therapy cannot completely cure the disease as before despite the progress achieved. GEBAs have potentially a number of serious side effects, among which there are severe infections and there is a risk of developing malignancies and autoimmune processes. Their administration requires careful monitoring to reveal the early development of serious adverse reactions, thus preventing a poor outcome.