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The response rate to therapy for rheumatoid arthritis (RA) rarely exceeds 60%. Mental disorders (MDs) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) substantially affect the evaluation of the efficiency of RA therapy. Adequate psychopharmacotherapy is one of the possible approaches to optimizing the treatment of RA. The factors influencing the efficiency of RA therapy with standard disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs) in combination with adequate psychopharmacotherapy have not been previously identified. Objective: to determine the predictors of response to therapy in patients with RA receiving DMARDs and BAs with or without adequate psychopharmacotherapy for ADS disorders. Subjects and methods. The investigation included 128 patients (13% men and 87% women) with a reliable diagnosis of RA. At baseline, 75.1% of patients received DMARDs; 7.8% – BAs. ADS disorders were detected in 123 (96.1%) patients. Psychopharmacotherapy was offered to all the patients with MDs; 52 patients agreed to treatment and 71 refused. The following therapeutic groups were identified according to the performed therapy: 1) DMARDs (n = 39); 2) DMARDs + psychopharmacotherapy (n = 43); 3) DMARDs + BAs (n = 32); 4) DMARDs + BAs + psychopharmacotherapy (n = 9). The changes of MDs symptoms and the outcomes of RA were assessed in 83 (67.5%) patients at five-year follow-up. The efficiency of RA therapy was evaluated with DAS28 (EULAR criteria). Predictors of response to therapy were determined using linear regression modeling. Results and discussion. At 5 years, 22 (26.5%) and 37 (44.6%) patients were recorded to show good and moderate responses to therapy, respectively; 24 (28.9%) patients were non-respondents. The linear regression model included 14 factors (p

Calprotectin (CP) belongs to the S100 leukocyte protein family, consists of two calcium-binding protein molecules, S100A8 and S100A9 (MRP8/14, calgranulin A/B). MRP8/14 is the main intracellular protein of neutrophil granulocytes and monocytes, which exerts a proinflammatory effect on phagocytes, endothelial cells in vitro and favors the development of the inflammatory process in vivo; it is an important mediator of many regulatory functions, such as chemotaxis; activation of neutrophil degranulation and phagocytosis; inhibition of immunoglobulin synthesis, cell proliferation and differentiation. CP is currently considered as a potential acute-phase marker in many inflammatory and autoimmune diseases. In rheumatoid arthritis (RA), CP maintains chronic inflammation, by activating the endothelium and increasing the migration of neutrophils into the inflamed synovial fluid. A number of studies have demonstrated the role of CP in monitoring RA activity, detecting subclinical inflammation, and predicting disease exacerbations. CP is of great importance in monitoring the efficiency of RA therapy with disease-modifying antirheumatic drugs and biological agents. The value of CP in spondyloarthritis (SpA) is ambiguous: on the one hand, this marker is highly expressed in the synovial tissue of patients with SpA and correlates with the level of acute-phase reactants; on the other hand, its correlation with disease activity indices is very contradictory and requires further clarification. By and large, CP is a promising laboratory marker of great clinical significance.

Mental disorders (MDs) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) substantially deteriorate the course and efficiency of therapy for rheumatoid arthritis (RA). There have been practically no studies on the impact of psychopharmacotherapy (PPT) for MDs on the efficacy of standard disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs).Objective: to investigate the impact of adequate PPT for MDs of ADS on the efficacy of DMARDs and BAs in patients with RA.Subjects and methods. The investigation included 128 patients (13% men and 87% women) with documented RA in accordance with the 1987 American College of Rheumatology (ACR) criteria. The patients’ mean age was 47.4±0.9 years; the median duration of RA was 96 [48; 228] months. DAS28 averaged 5.34±0.17. 75.1% of the patients received DMARDs. The diagnosis of MDs was based on the ICD-10 codes, by applying a semi-structured interview and the Hospital Anxiety and Depression Scale. Changes in the pattern and severity of ADS were evaluated using the Hamilton Anxiety Scale and the Montgomery–Asberg Depression Rating Scale. Clinical and psychological procedures were used to diagnose CI. At baseline, ADS was detected in 123 (96.1%) patients: major depression in 41 (32.1%), minor depression in 53 (41.4%), and anxiety disorders in 29 (22.6%). CI was diagnosed in 88 (68.7%). PPT was offered to all the patients with MDs; 52 agreed to treatment and 71 refused. The following therapeutic groups were identified according to the performed therapy: 1) DMARDs (n = 39); 2) DMARDs + PPT (n = 43); 3) DMARDs + BAs (n = 32); 4) DMARDs + BAs + PPT (n = 9). The dynamics of MDs and the outcomes of RA were estimated in 112 (91.0%) and in 83 (67.5%) of the 123 patients at one- and five-year follow-ups, respectively. The efficiency of RA therapy was evaluated from the changes in DAS28 and SDAI.Results and discussion. One year later, the patients who had received the complete cycle of PPT and took DMARDs achieved a satisfactory effect twice more frequently (58.1 and 32.3%, respectively; relative risk (RR) = 0.53; 95% confidence interval (CI), 0.2–1.39; p = 0.024) and did not respond to therapy 3 times less often (21.0 and 58.1%, respectively; RR = 2.41; 95% CI, 0.87–6.71; p = 0.001) according to the EULAR criteria than those who had refused PPT. The patients with MDs who received DMARDs + PPT during one year were unresponsive to therapy significantly less frequently than those who received DMARDs and BAs without PPT (21 and 44.8%, respectively; RR = 0.6; 95% CI, 0.21–1.7; p = 0.029). After 5 years of follow-up, the probability of no response to RA therapy in MD patients who received only DMARDs was 3.6 times higher than in those who had PPT (66.7% and 10.4%, respectively; RR = 3.58; 95% CI 0.82–15.5; p < 0.001). The patients adequately treated with DMARDs and BAs for MDs according to the DAS28 showed 1.3-fold more frequently good and satisfactory results (100 and 76.2%, respectively; p = 0.14) than those who refused PPT, but these differences were not statistically significant because the DMARD+BA+PPT group was small. Five-year follow-up indicated that DAS28 remission was more common in the patients receiving DMARDs and PPT than in those who had DMARDs and no PPT (34.5 and 8.3%, respectively; RR = 1.79; 95% CI, 0.34–9.24; p = 0.024). DAS28 remission was somewhat more frequently observed among the patients receiving DMARDs, BAs, and PPT than among those taking DMARDs and BAs (33.3 19.0%, respectively; RR = 1.64; 95% CI, 0.28–9.57; p = 0.34), but these differences were insignificant. Remissions according to the 2011 ACR/EULAR criteria were achieved by only the patients having DMARDs and PPT (6.9% and 13.8% after 1 and 5 years, respectively).Conclusion. Adequate treatment of MDs in RA patients results in a significant increase in the efficiency of antirheumatic therapy.

Objective: to analyze the impact of methotrexate (MTX) therapy on percentage and absolute content of FoxP3+ regulatory T lymphocytes (Treg) in the peripheral blood of patients with early rheumatoid arthritis (RA) who had not previously received MTX.Subjects and methods. The investigation included 45 patients with early RA (2010 ACR/EULAR criteria) who had not previously received MTX, including 39 women; median age was 52.0 [32.5; 57.5] years; disease duration, 5 [4; 6] months, DAS28, 5.01 [4.18; 5.8]; 71.1% of the patients were positive for rheumatoid factor and 88.9% – for anticyclic citrullinated peptide antibodies. As the first disease-modifying antirheumatic drug, all the patients were assigned to receive subcutaneous MTX at an initial dose of 10 mg/week with its rapid escalation up to 20–25 mg/week. The percentage and absolute count of Treg (FoxP3+CD25+; CD152+surface; CD152+intracellular; FoxP3+CD127-; CD25+CD127-; FoxP3+ICOS+; FoxP3+CD154+; and FoxP3+CD274+) were measured by immunofluorescence staining and multicolor flow cytometry.Results and discussion. At 24 weeks after starting the therapy, median DAS28, SDAI, and CDAI were 3.1 [2.7; 3.62], 7.4 [4.2; 11.4], and 7.0 [4.0; 11.0], respectively; DAS28 and SDAI remission/low disease activity was reached by 22 (56.4%) and 25 (64.1%) patients, respectively; 4 (10.3%) patients had no MTX treatment effect according to the EULAR criteria. After a 6-month course of MTX therapy, the whole group had increases in the percentage of CD4+cells (from 45.0 [38.0; 49.2] to 46.8 [39.9; 53.2]%) and in the percentage and absolute number of CD152+surface from 0.65 [0.22; 1.67] to 2.07 [1.11; 3.81]% and from 0.0002 [0.0001; 0.0008]•109 to 0.0007 [0.0004; 0.002]•109, and a moderate decrease in the percentage and absolute content of FoxP3+ICOS+ cells from 5.3 [2.1; 11.3] to 4.07 [1.6;6.6]% and from 0.002 [0.001-0.006]•109 to 0.0015 [0.0006-0.003]•109 (p

Rheumatoid arthritis (RA) is an autoimmune rheumatic disease characterized by chronic erosive arthritis (synovitis) and a systemic inflammatory lesion of the internal organs, which results in early disability and worse quality of life in patients. The accumulated data on the efficacy, safety, and cost-effectiveness of anti-B cell therapy allow identification of rituximab (RTM) as an extremely important drug of first- or second-line therapy with biological agents after ineffective treatment with tumor necrosis factor-α (TNF-α) inhibitors. In this connection, the choice of a personalized treatment regimen remains relevant in each specific case as before. Clinical experience with RTM suggests that the drug is highly effective in improving both clinical manifestations and quality of life in patients with active RA that is characterized by resistance to disease-modifying antirheumatic drugs and TNF-α inhibitors, as well as in those with early RA. The current literature presents a large amount of data on the role of prior therapy and the impact of the stage of RA when using different RTM doses on its efficiency, some of which will be discussed in this review.

Rheumatoid arthritis (RA) is the most common and severe chronic joint inflammatory disease leading to early disability and shorter lifespan in patients. A number of studies have demonstrated that short-term and long-term prognosis of the disease is much more favorable in achieving remission in the early stages of the disease; however, the efficacy of drugs varies widely from patient to patient, which is due to the heterogeneity of the disease itself and to a number of other causes. In this connection, the problem of searching for biomarkers that allow the personalized choice of a treatment regimen in each specific case remains relevant as before.Rituximab (RTM) that is a chimeric monoclonal antibodies against CD20 membrane antigen of B cells causing the depletion of various B lymphocyte subpopulations is one of the effective and safe drugs used to treat RA. Compared to other biological agents, RTM has a long-term efficacy of one treatment cycle, which persists for 6 months or more. The current literature presents a large amount of data on the role of cellular and molecular biomarkers in predicting the efficiency of RTM therapy for RA, some of which are considered in this review.

The paper gives the draft guidelines elaborated by the Expert Spondyloarthritis Diagnosis and Treatment Group by order of the Association of Rheumatologists of Russia. The guidelines include the essentials of how to use nonsteroidal anti-inflammatory drugs in axial spondyloarthrititides, including ankylosing spondylitis, contain instructions for how long they should be administered, and describe possible patient management tactics in the most common clinical situations and a preferential algorithm for evaluating the efficiency and safety of treatment.

The review of Russian and foreign literature provides a detailed analysis of topical issues associated with the impact of comorbid anxiety and depressive disorders and cognitive impairments on the efficiency of anti-inflammatory and disease-modifying therapy in patients with rheumatoid arthritis.

Aim. To estimate the incidence of acute myeloid leukemias (AML) in Moscow adults and to evaluate the efficiency of their treatment. Subjects and methods. Data on Moscow residents who were first diagnosed with AML in 2010 were retrospectively collected. The efficiency of their treatment was evaluated from the rates of complete remissions (CR), recurrences, deaths, and 4-year overall (OS) and relapse-free survival (RFS). The data as of September 1, 2013, were analyzed. Results. According to the 2010 pooled materials of the city’s municipal hematology departments, AML (non-M3 types) was diagnosed in 286 patients whose median age at diagnosis was 64.9 years (range, 18.2-92.0 years). The notified incidence rate was 2.9 (3.3 for men and 2.6 for women) cases per 100,000 population. 118 (41%) patients received intensive chemotherapy (ICT); 119 (42%) had chemotherapy with low-dose cytarabine (LDC); 7 (2%) had that with hypomethylating agents (HA); and 42 (15%) had palliative therapy (PT). During first-line therapy, none of the patients underwent allogeneic hematopoietic stem cell transplantation (allo-HSCT). In the entire group, the early (within the first 60 days) mortality rates were 42% (119 deaths); that of patients with primary refractory disease was 32% (90 deaths). CR was achieved in 77 (27%) patients: 57 (48%) on ICT, 17 (14%) on LDC, and 3 (43%) on HA. Recurrences occurred in 37 (48%) of the 77 patients who had achieved CR at a median follow-up of 43.9 months. Four-year OS in all the patients receiving PT was 9.8±1.9% (18.2±3.9% in the patients on ICT versus 4.5±2% in those of LDC; p=0.028); 4-year RFS was 36.1±5.7% (39.6±6.7% in the patients on ICT versus 31.3±11.6% in those on LDC; p=0.8). Conclusion. High mortality rates in the induction, which are caused by the limited resources of accompanying therapy, poor sanitary conditions, and no own opportunities to perform allo-HSCT, remain a key problem of AML therapy in adults.

Objective: to study the pattern and rate of comorbid diseases in patients with rheumatoid arthritis (RA) in the Saratov Region.Subjects and methods. The investigation enrolled 328 RA patients treated at the Rheumatology Unit, Saratov Regional Clinical Hospital, in 2011 to 2013. RA was diagnosed using the 1987 ACR criteria and the 2010 ACR/EULAR ones. The investigation included the patients receiving disease-modifying antirheumatic drugs (DMARD) at a stable dose for 3 months or longer. A questionnaire survey and objective examination were made in the patients; data from their medical records were taken into account.Results and discussion. Comorbidities were identified in 86.6% of the patients; 57.9% had a concurrence of two or more comorbid conditions. Osteoarthritis, hypertension, and coronary heart disease were detected in 50.7, 57.7, and 30.9% of the RA patients, respectively. Out of the inflammatory diseases, gastrointestinal tract lesion was most common (80.3%); urinary tract infections were slightly less common (19.7%).Conclusion. The high rate of comorbidity was noted in patients with RA. The pattern of comorbidities shows a preponderance of hypertension and osteoarthritis and an exacerbation of gastrointestinal and urinary tract diseases frequently makes the choice of DMARD difficult.

Aim. To evaluate the efficiency of the original ALL-MB-2002 protocol within the multicenter study of treatment of acute lymphoblastic leukemia (ALL) in children. Subjects and methods. A total of 1873 primary patients with ALL aged 1 to 18 years, of whom 1544 patients were enrolled in this study, were notified at 36 clinics of Russia and Belarus from April 15, 2002, to January 1, 2008. Results. With the median observation of 4.12 years, 7-year event-free survival (EFS) was 73±13%; overall survival (OS) 78±2%; relapse-free survival 82±1%. The rates of EFS and OS were equal and amounted to 76±2 and 80±2% in the standard-risk group (SRG) and intermediate-risk group (ImRG), respectively. In the high-risk group (HRG) patients, EFS and OS were as high as 30±6 and 37±6%, respectively. The frequency of relapses with central nervous system lesion was as much as 4.7% in all the patients, 6-year cumulative risk for isolated neurorecurrences being 2.5% in the SRG patients. Adolescents, patients with the baseline leukocytosis (more than 100109/l), and those with a splenic size of over 4 cm or more from the costal arch margin had substantially worse survival rates. A poor early response to therapy (on induction days 8 and 15) was also associated with its lower efficiency. Conclusion. Despite a considerable rise in the number of centers and a slight increase in the intensity of therapy, the results of the new ALL-MB-2002 protocol are as minimum equivalents obtained in the use of the previous ALL-MB-91 protocol. A significant improvement in the overall results of therapy and a reduction in the cumulative risk for isolated neurorecurrences were noted in the ImRG patients.

Aim. To assess dynamics of glycated hemoglobin levels and insulin doses per kg bw in children and adolescents with poorly controlled type 1 diabetes mellitus using insulin pumps. Materials and methods. Retrospective analysis of HbA1c levels and insulin doses per kg bw in children aged 2-17 years with DM1 (mean duration 5.3?3.1) before and 18 months after onset of insulin pump therapy (Medtronic Minimed 712 and 722) with a short-acting insulin analog Novopramid (Novo Nordisk) or Humalog (Ely Lilly) given to 55 (52,4%) and 50 (47,6%) of the patients respectively. НbА1с level and mean daily insulin dose per kg bw were determined when a patient visited the doctors office every 3 months. Results. Insulin pump therapy in patients with initially poorly controlled DM1 resulted in a decrease of HbA1c from 9.8?0.8 to 7,8?0,5% within 18 months after its beginning (p