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Upadacitinib (UPA), a JAK inhibitor, is a new therapeutic option that allows patients with insufficient response to therapy with basic anti-inflammatory drugs (DMARDs) or genetically engineered biological drugs (GEBDs) to achieve the goals of therapy for rheumatoid arthritis (RA). Despite the availability of convincing data from international randomized clinical trials, there is insufficient information about the efficacy and safety profile of UPA, the quality of life of patients receiving the drug in real clinical practice.Aim of the study – to assess the efficacy and tolerability of the UPA drug at a dose of 15 mg/day in patients with rheumatoid arthritis with moderate and high disease activity and to assess their quality of life in real clinical practice.Materials and methods. The study included 41 patients with RA with insufficient effect of previous therapy with DMARDs or GEBDs, persisting moderate or high disease activity, who were initiated with UPA therapy in 7 rheumatological centers of the Russian Federation. To assess the activity of the disease, standard indices were used: DAS28- ESR, DAS28-CRP, SDAI, CDAI. Functional ability was assessed according to the HAQ questionnaire, quality of life – according to the EQ-5D questionnaire, the activity of the disease according to the patient’s opinion – according to the RAPID-3 index. The HADS scale was used to identify the states of depression, anxiety and emotional disorder.Results. During the first week of taking the drug, there was a marked decrease in pain from 60 to 30 mm on a visual analogue scale, which lasted until the third month of therapy. There was a statistically significant decrease in morning stiffness, the number of painful and swollen joints, health assessments by the doctor and patient, erythrocyte sedimentation rate and C-reactive protein (p≤0.001). A decrease in disease activity was also noted according to the dynamics of the activity indices DAS28, SDAI, CDAI (pConclusions. The first results of the use of UPA in RA patients with insufficient efficacy of previous therapy with DMARDs or GEBDs in real clinical practice indicate its efficacy and safety, an improvement in the functional state and quality of life of patients by the 12th week of the study.

The development and scientific priorities of European urology of the second half of the XIX and early XX centuries are analyzed. The main dates of life and scientific and practical activity of Prof. Leopold Kasper are presented. The scientific views and thoughts of the scientist are noted. He specialized in urology under the leadership of G. Thompson, P. Freyer, F. Guyon, I. Albarran and L. Dittel after graduating from the University of Berlin in 1883. L. Kasper was the founder of a large German urological school. In addition, he is the author of many works, among which research on cystoscopy, endoscopic operations, functional diagnosis of kidneys diseases, treatment of renal tuberculosis and kidney stone disease, prostate diseases, transurethral galvanocaustics of bladder tumors, etc. are particularly distinguished. He constructed a special catheterization cystoscope (1895) through which for the first time it became possible to study the functional ability of each kidney individually, which greatly facilitated the recognition and treatment of surgical diseases of the kidneys and upper urinary tract. He improved and put into practice a functional renal test with floridzine and cryoscopic urine examination obtained from each kidney separately by catheterization of the ureters. It is noted that L. Kasper was one of the founders of the Society of German urologists, whose founding meeting was held in 1907 in Vienna. In the same year, L. Kasper, together with other prominent surgeons and urologists, founded the journal «Zeitschrift für Urologie», of which he was editor for decades. L. Kasper was an honorary member of nineteen scientific societies, including the Society of Moscow urologists, of which he was elected an honorary member in 1924.

Aim : to conduct a comparative clinical and economic analysis of using three SYSADOA drugs containing chondroitin sulfate or modifying its biosynthesis in patients with stage II knee osteoarthritis in an outpatient setting. Material and methods . This was a retrospective comparative study, with the inclusion of data from medical records of outpatients with stage II knee arthritis according to the Kellgren & Lawrence classification. We calculated the cost-effectiveness from the direct costs and treatment efficiency based on the dynamics of pain, functional ability of the joint according to the Lequesne index, as well as the VAS index, the WOMAC index, ultrasound results and quality of life according to the EuroQol-5D questionnaire. The medical records of patients (n = 90) with stage II knee osteoarthritis are systematized according to inclusion / exclusion criteria. All patients were divided into 3 groups: group 1 (n = 30) received chondroitin sulfate, 100 mg in 1 ml (Chondroguard ® , Sotex, Russia), i /m, every other day, the first 3 injections of 100 mg each with good tolerance starting from the 4th injection of 200 mg, the course of treatment was 25 injections over 50 days; group 2 (n = 30) received an active substance-glycosaminoglycan-peptide complex (Romania), on the 1st day – 0.3 ml, on the 2nd day – 0.5 ml and then 3 times a week for 1 ml, the course of treatment – 20 injections per 44 days; group 3 (n = 30) received the active substance – bioactive concentrate from small sea fish (Romania), 1 ml per day, course of treatment – 20 injections, 20 days. Results . It is shown that the treatment of stage II osteoarthritis of the knee with Chondroguard ® is the most economically feasible in terms of the cost-effectiveness ratio (CER=9182). Conclusion . The study results are recommended for decision making on the use of SYSADOA at the level of doctors and health care providers.

Chronic shoulder pain caused by shoulder impingement syndrome (SIS) is a common pathology that leads to worse quality of life and disability. The local administration of platelet-rich plasma (PRP) is a promising treatment for SIS.Objective: to evaluate the efficiency of subacromial injection of PRP in chronic shoulder pain caused by SIS.Patients and methods. The investigation enrolled 30 patients (13 women and 17 men; mean age, 45.8±14.1 years) with chronic shoulder pain lasting ≥3 months after rotator tendons injury confirmed by ultrasound and/or magnetic resonance imaging and inefficiency of previously medical therapy. All the patients received three subacromial injections of 5 ml of PRP at a 7-day interval. The investigators assessed the course of pain during movement (100-mm visual analogue scale (VAS)) and functional ability according to the ASES and CSC questionnaires at baseline and 1, 3 and 6 months after treatment.Results and discussion. During the treatment, there was a considerable improvement in all indicators. At baseline and 1 and 3 months, the mean pain severity measured on VAS was 49.3±10.3, 32.4±21.3, and 20.6±21.3 mm, respectively; in this case, the positive effect persisted at 6-month follow-up: 10 [0; 30] mm (pConclusion. Subacromial injection of PRP is an effective and safe treatment for chronic shoulder pain associated with SIS.

Infectious mononucleosis is a widespread disease caused by certain members of Herpesviridae family. Acute infectious mononucleosis develops predominantly in children and is accompanied by an increase of the number of circulating naive CD4+ and naive CD8+ T-lymphocytes in the peripheral blood. The normalization of immunological parameters is achieved within 4–6 months after recovery and that is an indicator of a proper functioning of the immune system. CD95 and DR3 death receptors are involved in the initiation of apoptosis of naive T-lymphocytes in healthy people and in patients with infectious mononucleosis. The aim of the study was to evaluate the ability of CD95 and DR3 receptors to initiate apoptosis of naive CD4+ and naive CD8+ T-lymphocytes in children with infectious mononucleosis during convalescence. The material for the study was the samples of the peripheral blood of children who previously had infectious mononucleosis. The blood sampling was carried out again after 4–6 months after the disease. At the time of the study, children did not display clinical and laboratory signs of infectious mononucleosis. Same children who were examined earlier in the period of the development of acute infectious mononucleosis, as well as relatively healthy children were used as the comparison groups. Isolation of naive CD4+ and naive CD8+ T-lymphocytes was performed by negative magnetic immunoseparation. For specific stimulation of CD95 and DR3 receptors monoclonal antibodies were used. The level of apoptosis and expression of death receptors were evaluated by flow cytometry. Freshly isolated cells were analyzed, as well as cells cultured with the addition of appropriate monoclonal antibodies. It was shown that the recovery period was accompanied by increased apoptosis of freshly isolated naive CD4+ and naive CD8+ T-lymphocytes compared with the acute phase of infectious mononucleosis. Thus in both populations of naive T-cells showed an increase of CD95+ cells’ susceptibility to apoptosis. CD95 stimulation in the cell culture did not lead to the change in the level of apoptosis of naive CD4+ and naive CD8+ T-lymphocytes. The freshly isolated naive CD4+ and naive CD8+ T-lymphocytes DR3+ cells were resistant to apoptosis, and in the process of cultivating their sensitivity varied depending on the subpopulation belonging. Thus in the culture of naive CD4+ T-lymphocytes DR3 was not involved in the transfer of pro-apoptotic signal. In the culture of naive CD8+ T-lymphocytes DR3+ cells were possible to increase the apoptosis of DR3-negative cells. At the same time the DR3 activation by monoclonal antibodies in the culture caused the death of DR3+ naive CD8+ T-lymphocytes that naturally associated with decreased proapoptotic activity of these cells and resulted in inhibition of apoptosis of total pool of naive CD8+ T-lymphocytes. Thus, the functional ability of CD95 and DR3 receptors to trigger an apoptosis of naive T-lymphocytes in children during convalescence of infectious mononucleosis varied and depended on their belonging to naive CD4+ or naive CD8+ T-lymphocytes.

Objective : to carry out a comparative clinical and economic analysis of treatment regimens for primary gonarthrosis (GA) Stage II with a combination of dosage forms of Sustaguard ® Artro (ampoules) + Sustaguard ® Artro (powder for oral solution) and Dona ® (ampoules) + Dona ® (powder for oral solution) in outpatient practice. Patients and methods . A retrospective comparative study was conducted using data from medical records of outpatients with GA radiographically classified as Kellgren–Lawrence Stage II. The investigators made cost-effectiveness and budget impact analyses and missed opportunity calculation for pharmacoeconomic examination, by taking into account direct costs and treatment effectiveness on the basis of assessment of the dynamics of pain syndrome, joint functional ability by the Lequesne index, visual analogue scale, WOMAC index, knee joint ultrasound data, and quality of life according to the EuroQol-5D questionnaire. The materials from the medical records of 60 patients with stage II GA were systematized according to the inclusion/exclusion criteria. All the patients were divided into two groups: 1) 30 patients received therapy with intramuscular (IM) Sustaguard ® Artro 3 ml thrice weekly; the treatment cycle was 12 injections for 28 days + 1.5-g Sustaguard ® Artro powder in a package, dissolved in 200 ml of water, once daily; the treatment cycle was 40 days; the full therapy cycle was 68 days; 2) 30 patients had therapy with IM Dona ® 3 ml thrice weekly; the treatment cycle was 12 injections for 28 days + 1.5-g Dona ® powder, dissolved in 200 ml of water, once daily; the treatment cycle was 40 days; the full therapy cycle was 68 days. The patients of both groups had a cycle of therapy with a nonsteroidal anti-inflammatory drug (nimesulide) at a dose of 100 mg twice daily for 15 days. Results and discussion . Sustaguard ® Artro treatment for Stage II GA was shown to be more economically feasible in terms of the cost-effectiveness ratio compared to Dona ® therapy for 68 days, with the long-term results of treatment being maintained for 2 months after the start of therapy. The effective technology of Sustaguard ® Artro therapy makes it possible to save significant budgetary funds (as many as 1.2 million rubles) and to additionally treat 50 patients. Conclusion . The clinical and economic study has established that the use of Sustaguard ® Artro as a treatment for primary GA Stage II is more economically feasible in terms of cost-effectiveness ratio.

Background: Early diagnosis of stroke, its treatment and rehabilitation are considered priorities in the state health care policy. Pharmacological intervention is used as a strategy to protect the neurons from the ischemic penumbra. Aim: To evaluate changes of functional state and levels of endothelial progenitor cells (EPC) in the circulation in ischemic stroke patients under administration of citicoline. Materials and methods: We assessed 11 patients in their early rehabilitation period of ischemic stroke (9 men and 2 women, mean age 58.4 ± 9.2 years). Patients from group 1 (n = 7) were given citicoline at dose 2000 mg/daily for 14 days, whereas patients from group 2 (n = 4) received regular treatment. Two healthy volunteers served as a control group. Circulatory EPC phenotype was assessed by multicolor laser flow cytometry and monoclonal antibody assay. Stroke severity and functional abilities were measured with NIHSS, Rankin scale and Rivermead mobility index. Results: Patients with ischemic stroke had decreased levels of early EPC, compared to healthy subjects. After 7 days of treatment in the group 1, there was a significant increase of circulatory EPC expressing VEGFR2+ up to 25.5 ± 20.9%, as well as an increase of early EPC numbers (CD117+ / CD133+) up to 18.8 ± 14.6%, compared to their respective baseline levels (21.9 ± 19.2 and 9.4 ± 5.4%) and compared to respective parameters in the group 2 (8.1 ± 2.7 and 5.5 ± 3.4%). In the group 1, severity of stroke and functional ability at baseline and at day 7 were as follows: NIHSS scores, 5.8 ± 4.9 and 3.5 ± 0.7, Rankin scale scores, 2.7 ± 1.3 and 2.3 ± 0.5, Rivermead mobility index, 8.8 ± 4.9 and 9.4 ± 4.8, respectively. In the group 2 corresponding parameters scored as 4.5 ± 2.3 and 3.3 ± 0.5, 2.5 ± 0.6 and 2.5 ± 0.4, 12.5 ± 1.3 and 12.7 ± 0.7, respectively. Conclusion: Treatment with citicoline in acute ischemic stroke promoted almost a 2-fold increase in early EPC levels. A decrease in neurologic deficiency and an improvement of functional status of patients with ischemic stroke were observed.

Objective: to study the nanostructure of red blood cell membranes and erythrocyte index in preterm neonatal infants. Subjects and methods . The trial enrolled 47 neonatal infants, including 33 preterm infants who were included in a study group and 14 fullterm infants who formed a comparative group. The gestational age of the preterm infants was 33.3±1.9 weeks and the birth weight was 2065.4±304.8 g. Red blood cell counts, hemoglobin, and erythrocyte indices were estimat ed and the red blood cells were examined using an atomicforce microscope. Results . At birth, the preterm infants showed macrocytosis, intrauterine poikylocytosis, and the impaired nanostructure of red blood cell membranes. Intrauterine hypoxia affects the red blood cell membrane nanostructures: a phospholipid bilayer and a spectrin matrix, without damaging the membrane protein component. The detected changes are reversible and directed to maintaining the functional ability of red blood cells in a critical situation. At birth, gestational age, a baby's weight, hemoglobin, and blood cholesterol and standard bicarbonate levels influence the parameters of a red blood cell component. The early neonatal period was characterized by an active process on the red blood cell membranes and a change of morphological forms, suggesting the continuing postnatal rearrangement of erythropoiesis and a preterm infant's adaptation to new environmental conditions.