The problem of infective endocarditis (IE) remains relevant due to the high mortality rate and the development of severe complications. IE is a polyetiological disease, the occurrence and development of which can be caused by an extremely extensive list of pathogens, which is replenished almost annually. The pronounced clinical polymorphism of IE determines the importance of its early diagnosis, including the use of new medical technologies. Timely informing physicians about the modern principles of monitoring of patients with IE is of great practical importance. Part I of the article describes the clinical features, basic principles of diagnosis and differential diagnosis of IE, taking into account the recommendations of the European Society of Cardiology 2023.

   Objective: to investigate the efficacy and safety of olokizumab (OKZ) in patients with knee osteoarthritis (OA) with synovitis, persistent pain and ineffectiveness of previous conservative therapy.

   Material and methods. The study included 15 patients with stage II–III knee OA who fulfilled the ACR criteria and had pain ≥50 mm on a visual analogue scale (VAS), synovitis and treatment failure. The age of patients ranged from 54 to 75 years; the duration of the disease was from 1 to 23 years. The duration of the study was 12 weeks, during which the patients received 3 subcutaneous injections of OKZ at a dose of 64 mg. The effectiveness of the treatment was assessed by the dynamics of pain intensity according to VAS, WOMAC and KOOS indices, the values of the DN4 questionnaire and the quality of life according to EQ-5D. In addition, the general assessment of the patient's health (GHA) according to VAS, the assessment of treatment efficacy by doctor and patient and the need for non-steroidal anti-inflammatory drugs (NSAIDs) were considered. All patients underwent laboratory testing.

   Results and discussion. During treatment, there was a significant decrease in pain intensity according to VAS, a statistically significant improvement in the KOOS and WOMAC indices (p<0.05), quality of life according to the EQ-5D questionnaire and GHA. Patients and doctors rated the treatment results very positively: an improvement or significant improvement was observed in 92.3% of cases. Adverse events were identified in 4 patients, which in 2 cases served as the reason for discontinuation of OKZ treatment and termination of participation in the study. During treatment with OKZ, a statistically significant decrease in CRP and ESR values, an increase in the concentration of interleukin 6 (p = 0.003), COMP (p = 0.03) and PIINP (p = 0.01) were observed.

   Conclusion. The results obtained suggest a significant symptomatic and anti-inflammatory effect of OKZ in patients with the inflammatory phenotype of OA.

   In the context of the new coronavirus infection (NCI) COVID-19 pandemic, the rheumatological community is facing new challenges in the treatment of immune-inflammatory rheumatic diseases (IIRDs). It has been shown that rheumatological patients have an increased risk of infections and a severe course of NCI and that IIRD therapy also influences the disease outcomes. In particular, the use of the anti-B-cell medication rituximab (RTM) is associated with a higher risk of severe NCI and increased mortality. The COVID-19 pandemic has highlighted the need to find alternative and safe treatment options for these patients. This work is the continuation of a 12-week study on the efficacy and safety of olok-izumab (OKZ) therapy in patients with rheumatoid arthritis (RA) after switching from anti-B-cell therapy during the SARS-CoV-2 pandemic.

   Objective: to evaluate the efficacy and safety of OKZ (Artlegia®; solution for subcutaneous administration, 160 mg/ml – 0.4 ml) for the treatment of patients with RA in real-life clinical practice after switching from RTM during the COVID-19 pandemic.

   Material and methods. The study included 19 patients with a confirmed diagnosis of RA who had received RTM at a dose of 500–1000 mg twice every 14 days at least 6 months ago. As disease activity increased, RTM was replaced with OKZ while therapy with synthetic disease-modifying anti-rheumatic drugs (DMARDs) was continued. At weeks 0, 4, 8, 12 and 24 after switching the biologic DMARD, the number of tender (TJN) and swollen (SJN) joints out of 28, pain intensity on a visual analogue scale, ESR, CRP level, disease activity indices CDAI, DAS28-ESR, DAS28-CRP, HAQ index and the safety profile of the therapy were assessed at each visit.

   Results and discussion. After 4, 8, 12 and 24 weeks of OKZ administration, there was a statistically significant decrease in mean TJN (from 10 to 6.0, 3.0, 5.0 and 4.0, respectively; p < 0.05) and SJN (from 7.0 to 3.0 by week 4 and to 2.0 by weeks 8, 12 and 24; p < 0.05). At the same time, a decrease in CRP and ESR values was also observed: median CRP decreased from 18 to 0.6 mg/l by week 4 and to 0.5 mg/l by weeks 8, 12 and 24 (p < 0.05), ESR from 30 to 5 mm/h in each study period (p < 0.05). CRP levels normalized by week 4, regardless of baseline values. All RA activity indices showed a positive dynamic compared to baseline values from week 4 onwards in each assessment period. After weeks 4, 8, 12 and 24, the median DAS28-ESR decreased from 5.50 to 3.57; 3.30; 3.08 and 3.01 (p < 0.05); DAS28-CRP – from 5.30 to 3.46; 3.23; 3.26 and 3.12 (p < 0.05); CDAI – from 27.0 to 17.0; 12.0; 15.0 and 12.0 (p < 0.05), respectively. All patients showed a decrease in pain by the 4^th week of observation. A statistically significant improvement in functional status was observed after the 4^th week of therapy and was maintained until week 24. The median HAQ index decreased from 1.62 to 1.50 at weeks 4, 8 and 12 and to 1.12 at week 24 (p < 0.05).

   Conclusion. The study showed that the non-medical switch from RTM to OKZ during the COVID-19 pandemic was effective and safe.

   The efficacy and safety of levilimab (LVL) in patients with active rheumatoid arthritis (RA) has been confirmed in controlled clinical trials. This article presents the results of a preliminary analysis of a non-interventional observational study of LVL in RA patients.

   Objective: to evaluate the efficacy and safety of LVL in the treatment of patients with RA in real-world clinical practice.

   Materials and methods. The HELIOS study is a retrospective-prospective, multicenter, non-interventional study of retention rate of LVL therapy and the safety of LVL in patients with RA in real-world clinical practice. Patients received medical care, including LVL, according to routine clinical practice for the treatment of RA and Russian instructions for medical use of the drug. This article presents the results of an analysis of the efficacy and safety of LVL after 12 and 24 weeks of treatment. Efficacy was assessed using the DAS28-CRP/ESR, SDAI, CDAI and patient assessment of pain, fatigue and morning stiffness according to VAS (0–100 mm).

   Results and discussion. 524 patients from 42 medical centers in the Russian Federation were enrolled in the study from June 2022 to November 2023. The majority of patients were female (83.2 %) and the mean age of patients was 53 years. A statistically significant decrease in DAS28-CRP/ESR, SDAI, CDAI, patient assessment of pain, fatigue and morning stiffness (VAS) was observed after 12 and 24 weeks of treatment, regardless of previous treatment with biologics or Jak inhibitors (JAKi). LVL was well tolerated by patients, the most frequently reported adverse events were infections, changes in peripheral blood and laboratory abnormalities characteristic of treatment with IL-6R inhibitors.

   Conclusion. In real-world clinical practice, LVL has been shown to be highly effective and well tolerated in patients with RA when prescribed as the first biologic disease-modifying antirheaumatic drus (bDMARD) and after switching from other bDMARDs or JAKi.

   Currently, the prognosis for systemic lupus erythematosus (SLE) has improved significantly, but the relative risk of death in these patients is still
higher than in the general population. Thrombotic complications are one of the leading causes of death in SLE.

   Objective: to analyze the survival rate and structure of lethal outcomes in Orenburg population of patients with SLE, including deaths due to thrombotic complications.

   Material and methods. A two-stage study of SLE progression and patient survival was conducted from 2007 to 2022. Clinical signs of the disease
were analyzed in all patients at baseline (n = 68) and in survivors (n = 50) after 15 years. The median age at the time of enrolment in the study was 35 [29; 45] years, the disease duration – 7.5 [3; 13.5] years. During the second stage, the characteristics of the course of the disease in the survived patients and the causes of death in those who died over 15-year period were determined.

   Results and discussion. The 10-, 15- and 20-year survival rates in Orenburg population of patients with SLE reached 98.5, 95.5 and 86.3%, respectively. During this period, 18 (26.5 %) deaths were registered, the median age of the deceased was 48.5 [39; 57] years, and the duration of the disease was 22 [16; 30] years. The most common causes of death were thrombotic complications (n = 14, 78 %) due to antiphospholipid syndrome, lupus nephritis, and arterial hypertension. Less frequently, infectious complications were the cause of death (n = 4, 22 %). Patients with thrombotic complications had a 20-year survival rate of 80.2% that was significantly lower than in the SLE group without thrombosis.

   Conclusion. The results obtained allow to consider the presence of thrombotic complications in patients with SLE in Orenburg population as an unfavorable prognostic factor.

   Objective: to evaluate nutritional status, muscle strength, functional status of skeletal muscles and physical activity (PHA) and their relationship with the osteopenic body composition phenotype in women in post menopause with rheumatoid arthritis (RA).

   Material and methods. The case-control study included 134 women in post menopause with RA, 52 of them had osteosarcopenia (OSP) according to densitometry and 82 had no decrease in bone mineral density (BMD) and muscle mass (mean age 62.0 ± 7.2 and 59.6 ± 7.5 years, respectively; p > 0.05). A clinical and laboratory examination as well as tests to assess muscle strength and functional status were performed. The MNA-SF and IPAQ questionnaires were used to determine nutritional status and physical activity.

   Results and discussion. Malnutrition was found in 51.9 % of patients, and low and average levels of PHA were found in 5.8 and 50.0 % of patients with OSP, respectively. Factors associated with OSP were identified: nutritional status according to MNA-SF < 12 points (odds ratio, OR 2.52; 95 % confidence interval, CI 1.10–5.77; p = 0.029), dietary calcium intake < 500 mg/day (OR 3.23; 95 % CI 1.49–7.01; p = 0.003), 25(OH)D level < 30 ng/ml (OR 4.55; 95 % CI 1.86–11.16; p = 0.001), moderate PHA < 1 hour per day (OR 2.67; 95 % CI 1.06–6.75; p = 0.037), walking < 1 hour per day and < 4 hours per week (OR 3.25; 95 % CI 1.26–8.38; p = 0.015 and OR 3.17; 95 % CI 1.19–8.46; p = 0.021, respectively).

   Conclusion. Reduced nutritional status was found in 51.9 % and average or low levels of PHA in 55.8 % of patients with OSP. The risk of OSP development was increased by low nutritional status, inadequate dietary calcium intake, low vitamin D levels, short duration of daily moderate exercise, and inadequate daily and weekly walking time.

   Local injection therapy (LIT) with hyaluronic acid (HA) medications is one of the most promising methods for the treatment of periarticular soft tissue pathology (PASTP) caused by injury or overuse.

   Objective: to evaluate the efficacy and safety of LIT with HA medication with a molecular weight of 500–730 kDa in patients with various post-traumatic PASTP.

   Material and methods. The study included 30 patients with rotator cuff syndrome (RCS), lateral epicondylitis (LE) and plantar fasciitis (PF) after trauma. Inclusion criteria were the presence of moderate/severe pain (≥40 mm on a visual analogue scale (VAS)) over a 3-month period and the absence of effect of LIT with glucocorticoids. All patients were administered HA peritendinously three times (7 days apart) under ultrasound guidance. Treatment results were evaluated after 1 and 3 months based on the dynamics of pain intensity (VAS) and functional indicators using the ASES (American Shoulder and Elbow Surgical Evaluation), MES (Mayo Elbow Score) and FFI (Foot Functional Index) questionnaires.

   Results and discussion. In the general group, there was a statistically significant decrease in pain intensity after 1 and 3 months from a mean of 57.6 ± 14.7 to 37.0 ± 14.8 and 35.0 ± 14.3 mm according to VAS respectively (p < 0.05). In the patient groups with different PASTP, the average assessment of pain intensity and functional impairment at baseline and after 1 and 3 months was: for RCS (n = 11) 59.0 ± 15.1, 39.0 ± 15.7, 36.3 ± 16.2 mm according to VAS and 49.1 ± 14.3, 60.1 ± 13.7, 61.7 ± 3.8 according to ASES, respectively; with LE (n = 10) 54.0 ± 13.4, 35.0 ± 9.7, 34.0 ± 11.7 mm according to VAS and 71.5 ± 11.1, 78.3 ± 9.0, 81.5 ± 8.3 according to MES; with PF (n = 9) 61.0 ± 16.5, 36.6 ± 19.3, 34.4 ± 15.8 mm according to VAS and 47.2 ± 22.8, 39.6 ± 39.7, 39.0 ± 29.9 according to FFI. None of the patients experienced any adverse events during treatment.

   Conclusion. HA medication with a molecular weight of 500–730 kDa showed good efficacy and safety in LIT of PASTP of the shoulder, elbow joint and foot. Further studies are needed to evaluate the possibility of a broad use of the drug for the treatment of PASTP in real clinical practice.

   Objective: to evaluate differences in the expression of genes associated with β-oxidation and de novo synthesis of fatty acids (FAs) in the blood of patients with the late stage of knee osteoarthritis (OA) before total knee arthroplasty (TA) depending on the development of postoperative pain (POP) in order to determine the molecular mechanisms responsible for the development of chronic POP.

   Material and methods. Blood of 50 patients with stage III–IV knee OA complaining of constant pain and joint dysfunction was analyzed prior to TA. The control group consisted of 26 healthy individuals. Pain intensity was assessed using a visual analogue scale (VAS) and the BPI questionnaire. In addition, pain, stiffness and physical functioning were assessed using WOMAC index and the presence of neuropathic pain was assessed using the DN4 and PainDETECT questionnaires. The development of POP was assessed 3 and 6 months after TA. Total RNA isolated from blood was used to determine the expression of ACLY, ACC1, MLYCD, FASN and CPT1A genes by real-time quantitative reverse transcriptase-polymerase chain reaction.

   Results and discussion. POP ≥ 30 mm by VAS was detected in 17 patients. Before TA, the expression of most of the analyzed genes was significantly increased compared to controls, while the expression of the FASN gene was comparable in patients with OA and healthy individuals. There were no differences in clinical and functional parameters between the groups of patients with and without POP. Before surgery, patients who subsequently developed POP had significantly higher expression of ACLY and CPT1A genes than patients who were satisfied with the results of TA. At the same time, no differences in the expression of ACC1, MLYCD and FASN were found in the groups analyzed.

   Conclusion. The development of POP is associated with an increased supply of FAs to the mitochondria caused by overexpression of the CPT1A gene, as well as with the accumulation of acetyl-CoA, a product of high expression of the ACLY gene, which can be measured in the blood of OA patients before TA.

   This article describes the experience of using the type I interferon inhibitor anifrolumab (AFM) in a patient with a torpid course of systemic lupus erythematosus. The reason for prescribing AFM was the need for a quick achievement of low disease activity due to a planned hip replacement. Dynamic observational data over a six-month period confirmed that AFM enables a rapid achievement of low disease activity without increasing the dose of glucocorticoids, significantly improve the patient's quality of life and even prepare them for major surgery without exacerbating the underlying process.

   Intravenous immunoglobulins (IVIG) are the most commonly used immunobiological agents produced from donor blood. They were first used in the mid-twentieth century for the treatment of primary immunodeficiencies. Later, they were successfully used to treat a variety of autoimmune, inflammatory and other diseases. There are currently a growing number of basic and clinical studies looking at the mechanism of action and efficacy of different doses of IVIG. At the same time, much remains unclear, contradictory, and some data are mutually exclusive.

   Despite the high efficacy of currently available targeted synthetic disease-modifying antirheumatic drugs (tsDMARDs) and biologic DMARDs (bDMARDs), approximately 40 % of patients with ankylosing spondylitis (AS) fail to achieve treatment goals according to clinical, laboratory and imaging tests. In addition, comorbidities in AS, which require an integrated approach involving different specialists, may limit the use of such therapy. In view of the above, as well as the peculiarities of bone metabolism in AS, new therapeutic approaches for this disease have recently been sought, one of which is the use of bisphosphonates. This article discusses some aspects of bone metabolism and unconventional therapeutic options – the use of bisphosphonates in AS complicated by severe comorbidities, in patients with insufficient efficacy of bDMARDs and/or DMARDs.

   Systemic lupus erythematosus (SLE) is a complex, multifactorial autoimmune disease characterized by multisystem involvement. Although the pathogenesis of SLE is not fully understood, numerous studies have shown that the composition of the microbiota can influence the course of the disease. The microbiota plays a key role in the development of immune defense and is an integral part of immune homeostasis. Dysbiosis of the intestinal, oral and vaginal microbiota can have a significant impact on the development of inflammatory and autoimmune diseases. The review addresses recent studies on the microbiota, with a particular focus on changes in the composition of the gut microbiota and their impact on SLE. Data from several studies suggest that there is a link between SLE and certain patterns of dysbiosis.

   Patients with immune-inflammatory rheumatic diseases (IIRDs) often present with non-inflammatory musculoskeletal pain associated with nociceptive dysfunction, central sensitization, and secondary fibromyalgia (FM). In recent years, an increasing number of publications have appeared dealing with FM in rheumatoid arthritis and systemic connective tissue diseases in adult patients, while this problem is little discussed in pediatric rheumatology, partly due to the differences between the existing diagnostic criteria in children and adults, which complicate the diagnosis of juvenile secondary FM. The consequence of this is often the unfounded prescription or switching of synthetic disease-modifying antirheumatic drugs (DMARDs) or biologic DMARDs in patients who do not require intensified antirheumatic therapy, but rather psychotherapy and psychopharmacotherapy, as well as the wider use of physical and rehabilitation medicine methods. In a brief narrative review, we tried to trace the investigation of FM in a rheumatological clinic, including children with IIRD, from a historical perspective, to summarize current literature data on this problem and to point out possible solutions.

   Hyaluronic acid (HA) is an effective and safe medication for local injection therapy (LIT) widely used in the treatment of osteoarthritis (OA) of large joints. The therapeutic effect of HA is determined both by the replacement of the lubricating function of natural hyaluronate (viscosupplementation), which leads to an improvement in the biomechanical parameters of the joint, and by the biological effects that unfold when interacting with cellular receptors (CD44, RHAMM, etc.), resulting in an anti-inflammatory, anti-nociceptive and anabolic effect of HA. HA therapy has a reliable evidence base. According to a number of clinical studies and meta-analyses, LIT with HA – reduces pain intensity by 28–54 % and improves the function of the affected joint by 9–32 % compared to baseline over a 12-24 week observation period. Repeated administration of HA can delay the need for orthopedic surgery. HA extremely rarely causes serious adverse events and can also be prescribed to patients with concomitant diseases. The use of HA for the treatment of OA is included in Russian and several foreign clinical guidelines (in particular OARSI and ESCEO). A new direction in LIT for OA is therapy with combined (hybrid) HA preparations containing high molecular weight (HMW) and low molecular weight (LMW) fractions. A new HA preparation has appeared in our country, which is a stabilized, highly purified hydrogel containing 80 % HMW HA (molecular weight – 30,000 kDa) with transverse "crosslinking" BDDE (innovative ECHATM technology) and 20 % "uncluttered" linear HA (molecular weight – 1500 kDa). This product is characterized by favorable rheological parameters, which guarantee a long-term improvement in the biomechanics of the affected joint and a rapid onset of biological effects, reduction in pain and inflammation and activation of the synthesis of natural hyaluronate.

   The best results in combating gout are achieved through a combination of diet and drug therapy. Urate-lowering therapy, which includes febuxostat, has been shown to be more effective and convenient than diet when it comes to achieving and maintaining target uric acid (UA) levels in gout patients. Febuxostat, a xanthine oxidase inhibitor, helps to reduce UA levels in the blood by blocking its formation. This helps prevent the deposition of urate crystals in joints and tissues and reduces the frequency and severity of gout attacks. At the same time, a diet of low purine foods may also have some effect on UA levels. Diet can improve the results of drug treatment by reducing the need for medications and minimizing the risk of side effects. However, without adequate drug therapy, diet will not produce the desired results. Therefore, febuxostat remains the preferred urate-lowering treatment option for gout, especially given its proven efficacy in these patients.

   Systemic lupus erythematosus (SLE) is a heterogeneous autoimmune disease characterized by unpredictable exacerbations and outcome. Many SLE patients receiving standard therapy (ST) do not achieve the recommended treatment goal of remission or Lupus Low Disease Activity State (LLDAS). Currently, there is still great dissatisfaction with ST in SLE, especially with long-term treatment with glucocorticoids and immunosuppressants. The recently approved type I interferon receptor antagonist anifrolumab (AFM) may be promising in SLE patients who do not respond adequately to ST. Phase III efficacy studies of AFM have demonstrated higher remission rate and lower LLDAS activity in patients treated with AFM compared to placebo. This publication contains comments from Russian experts on the article by Y. Tanaka “Viewpoint on anifrolumab in patients with systemic lupus erythematosus and a high unmet need in clinical practice”.

   Fatigue is a persistent and debilitating feeling of tiredness that limits the ability to perform daily activities and is a common and difficult-to-treat condition in patients with rheumatic diseases (RD). Fatigue is a major challenge for the physician. However, methods to treat it have not yet been developed, as fatigue is usually considered an insignificant background condition. This article provides an overview of the 2023 EULAR recommendations, which outline the guiding principles and strategy for the management of fatigue in patients with RD. The EULAR recommendations are based on an understanding of fatigue as a complex condition that requires an individualized approach in choosing the correction methods. It is important that the assessment of fatigue becomes part of the routine practice of rheumatologists and other physicians. Patient education recommendations emphasize the importance of an individualized approach tailored to the needs of the individual, including optimizing physical activity and psychoeducational interventions.

   On 30 May, 2024, an expert meeting was held to update the approaches for the treatment of axial spondyloarthritis (axSpA). A new approach to the treatment of axSpA was considered, which consists of depleting autoreactive TRBV9+ T- lymphocytes by introducing a monoclonal antibody – the drug seniprutug. The value of the drug seniprutug in the treatment of the disease was discussed and key aspects for the incorporation of the drug seniprutug into real-world clinical rheumatological practice were agreed.