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, which can be caused by an extremely extensive list of pathogens, which is replenished almost annually. At the same time, effective antimicrobial therapy is made considerably more difficult by the increasing resistance of IE pathogens to antibiotics and the growing etiological role of infectious agents that were previously very rare.
Part II of the article presents the basic principles of treatment and prevention of IE, considering the latest recommendations of the European Society of Cardiology 2023. 

Biologic disease-modifying antirheumatic drugs (bDMARDs) and Janus kinase inhibitors (JAKis) do not always allow to achieve remission and low inflammatory activity in rheumatoid arthritis (RA), necessitating switching of therapy.
Objective: to evaluate the clinical characteristics and features of pharmacotherapy in patients with RA requiring a switch from bDMARD/JAKi.
Material and methods. The study group consisted of 103 patients with RA (85.4% women, mean age 46.9±13.7 years) who had persistent disease activity (DAS28-CRP – 5.42±0.9) despite treatment with bDMARD/JAKi or who experienced adverse events requiring therapy switching. Patients were divided into three groups: Group 1 – patients who underwent one switch (n=50), Group 2 – 2 switches (n=39), Group 3 – ≥3 switches (n=14) of bDMARD/JAKi therapy. Clinical manifestations, disease activity and pharmacotherapy were assessed.
Results and discussion. The main reason for switching therapy was ineffectiveness of bDMARD/JAKi (in 81.6% of patients). There was a tendency towards higher DAS28-ESR (p=0.052) and DAS28-CRP values (p=0.057) in groups 2 and 3 compared to group 1, as well as significant differences in CDAI (p_1–2=0.015 and p_1–3=0.011) and SDAI (p_1–2=0.013 and p_1–3=0.01). In group 3, there was a tendency towards higher DAS28-CRP, CDAI and SDAI values compared to group 2: 5.82±0.92 and 5.53±0.89; 40.5 [33.0; 45.0] and 35.2 [30.3; 43.9]; 36 [32; 42] and 32.0 [28.5; 38.5], respectively. However, these differences were statistically insignificant. Patients in groups 2 and 3 had a significantly higher number of painful joints compared to patients in group 1 (p_1–2=0.048 and p_1–3=0.036) and a significantly higher patient global assessment of disease activity (p_1–2=0.004 and p_1–3=0.013). Patients in group 3 took glucocorticoids significantly longer and at higher doses than patients in group 1. Tumour necrosis factor-α inhibitors were used more frequently in groups 1 and 2 (50.0 and 41.0%, respectively), and interleukin-6 inhibitors in group 3 (50.0%).
Conclusion. Patients with RA who required ≥2 switches of bDMARD/JAKi had higher disease activity compared to patients who required only one switch of therapy.

Objective: to investigate the clinical and instrumental manifestations of axial psoriatic arthritis (axPsA) in combination with hyperuricemia (HU).
Material and methods. The study included 71 patients with psoriatic arthritis (PsA): 59 (83%) men and 12 (17%) women. These patients had clinical and imaging evidence of inflammatory changes in the spine and were diagnosed with axPsA. The mean age of patients was 45.7±11.3 years, duration of psoriasis (Ps) was 209.3±163.4 months, and duration of PsA was 51.9±45.5 months. Patients underwent standard clinical, laboratory and radiological examinations. Patients completed the PsAID-12, FACIT-F and FiRST questionnaires and their LEI, MASES, DAPSA, BASDAI, BASFI, BASMI, ASDAS-CRP and BSA indices were assessed. Data on concomitant diseases and drug therapy were also collected. HU was diagnosed at uric acid (UA) level of >360 μmol/L. Patients were divided into two groups – with HU (group 1, n=24, 33.8%) and without HU (group 2, n=47, 66.2%).
Results and discussion. The mean UA level was 329.96±80.2 μmol/l. The age of the patients, the duration of Ps and PsA were comparable in both groups. The activity of PsA and spondylitis in the two groups also did not differ. No significant differences were found between the groups in frequency of sacroiliitis or presence of erosions. In the 1st group, the total number of syndesmophytes in two sections of the spine was significantly higher (n=26, 108%) than in the 2nd group (n=39, 83%), p=0.04. In the group of patients with HU, there was a higher intensity of nocturnal spinal pain compared to the group without HU (5.0±2.7 and 3.6±2.8, respectively; p=0.04), more pronounced sleep disturbances (11±5.2 and 7±5.9; p=0.04), higher triglyceride levels (median 0.92 [0; 1.66] and 0.3 [0; 0.6]; p=0.03) and a higher frequency of hypertriglyceridemia (n=2, 8.3% and n=0; p=0.04) and liver steatosis (n=7, 29.1% and n=5, 10.6%; p=0.04, respectively). Patients with HU received antihypertensive therapy (n=10, 41.7% and n=14, 29.8% respectively; p=0.04) and urate-lowering medications (n=4, 16.6% and n=1, 2.1% respectively; p=0.02) significantly more often than patients without HU.
Conclusion. HU was present in one third of patients with axPsA. They were more likely to have multiple syndesmophytes in the spine, metabolic disturbances, more severe nocturnal spinal pain and more pronounced sleep disturbances.

This article presents the results of the 3-year use of netakimab (NTK), a monoclonal antibody against interleukin 17, in patients with psoriatic arthritis (PsA) as part of the phase III PATERA study.
Objective: to evaluate the long-term efficacy and safety of NTK in patients with PsA over a period of 3 years.
Material and methods. PATERA is a double-blind, multicenter, randomized, phase III clinical trial. 194 patients with active PsA were randomized 1:1 to NTX or placebo/NTX. NTX/placebo was administered at weeks 0, 1, 2, 4, 6, 8, 10 and 14. Placebo patients who did not achieve a 20% improvement according to ACR criteria (ACR20) at week 16 received NTX at weeks 18 and 22. Patients who achieved ACR20 received placebo at weeks 18 and 22. Subsequently, all patients received NTX. At week 54, patients who did not meet ACR20 criteria were withdrawn from the study and the remaining patients were treated in the extension phase. The total duration of NTX use in all groups was 3 years.
Results and discussion. Therapeutic response achieved in the first year of treatment was maintained in the extended phase of the study. Against the background of NTX use, a significant long-term decrease in clinical manifestations of PsA was observed. Adverse events occurred mainly in the form of laboratory abnormalities and infectious diseases, which were mostly mild to moderate. Antibodies against NTK were detected in 9.3% of patients and in most cases they were formed at the end of the first and beginning of the second year of therapy.
Conclusion. NTK showed a favorable safety profile with long-term use over 3 years. The clinical effect on all manifestations of PsA was maintained in most patients over a long period of time without significant loss of response. 

Objective: validation of the Russian-language version of Ankylosing Spondylitis Quality of Life (ASQoL) specific questionnaire for patients with ankylosing spondylitis (AS). 
Materials and methods. Тhe study included 100 patients with a definite diagnosis of AS according to the modified New York criteria of 1984. Patients were mostly men (58.5%), average age – 38.6±10 years, disease duration – 10.3±7.0 years, median disease activity by ASDAS-CRP – 2.32 [1.45; 2.94]. At the initial visit and after 3 months, all patients underwent a standard rheumatological examination, with assessment of the tender joint count (TJC) and swollen joint count (SJC) out of 44 joints assessed, the number of inflamed entheses using MASES index, spinal mobility using BASMI index. Assessment of patient reported outcomes included an assessment of spinal pain, night spinal pain, spinal pain during the day using a numerical rating scale, patient’s global assessment of health, assessment of functional status using BASFI index and health related quality of life (HRQoL) using EQ-5D, SF-36 and ASQoL questionnaires. To determine reliability of ASQoL questionnaire, a test-retest analysis and determination of internal consistency by calculating the Cronbach's α coefficient were used.
The reliability of the questionnaire was analyzed in 39 patients. To assess the validity of the ASQoL questionnaire, i.e. its ability to reliably measure its inherent characteristics, construct and criterion validity were determined. The sensitivity of the questionnaire was assessed after 3 months during therapy in 79 patients.
Results and discussion. According to the test-retest analysis, there was no difference between the initial assessment and re-assessment after 3 days (p>0.05), the Cronbach α coefficient was 0.884, indicating high reliability. Construct validity analysis was carried out using factor analysis and the “known groups” method. 3 main factors were identified: pain, physical health, emotional health. The “known groups” method showed that in patients with high disease activity according to ASDAS-CRP and BASDAI, HRQoL was significantly worse than in patients with low disease activity (р<0,05). To calculate criterion validity, the relationship of ASQoL to “external criteria” and interchangeability with general questionnaires SF-36 and EQ-5D were evaluated by a correlation analysis. It was shown that this questionnaire is highly interchangeable. To determine sensitivity of ASQoL, its changes were analyzed in relation to the effect of therapy after 3 months. Significant changes in the subscales of the questionnaire were observed in patients who achieved low disease activity according to ASDAS-CRP during therapy, reflecting its good sensitivity.
Conclusion. The ASQoL has good psychometric properties and is able to reflect changes in a patient's health status over time along with disease activity. 

Objective: to investigate in a multicenter study relationship between type 2 diabetes mellitus (DM) and clinical manifestations of osteoarthritis (OA).
Material and methods. The study involved 767 patients aged 40–75 years with a confirmed diagnosis of stage I–III knee OA who had signed an informed consent form. The mean age of patients was 57.9±9.6 years, body mass index (BMI) was 30.8±6.4 kg/m2  and median duration of disease was 5 [2; 11] years. An individual record card was filled out for each patient, it contained anthropometric parameters, medical history and clinical examination data, knee pain assessment using a visual analogue scale (VAS), WOMAC, parameters of KOOS questionnaire and patient's global assessment of health.
Results and discussion. DM was detected in 17.2% of cases. Patients were categorized into two groups according to the presence or absence of DM. In the presence of DM, more severe clinical manifestations of OA were noted. However, patients with DM were older, had higher BMI values, longer disease duration and were more frequently diagnosed with radiological stage III OA. After stratification by age and disease duration, individuals with DM retained worse pain scores according to VAS compared to patients without DM (median 51.5 [41.5; 70] mm versus 36 [25; 50] mm, p=0.049), total WOMAC index (1047.5 [792; 1260] mm versus 823 [536; 1145] mm; p=0.005) and its components (pain – 200 [160; 254] mm versus 155 [108; 230] mm, p=0.002; stiffness – 90 [50; 115] mm versus 60.5 [35; 100] mm, p=0.03; functional impairment – 765 [550; 918] mm versus 595 [350; 820] mm, p=0.009).
Conclusion. Type 2 DM is common in patients with OA (in 17.2% of cases) and is associated with more severe clinical manifestations: greater pain intensity according to VAS and higher WOMAC scores (total index and its components). 

Objective: to evaluate the efficacy of a single or double administration of a preparation of high molecular weight hyaluronic acid (HLA) with chondroitin sulfate (CS) in post-traumatic knee osteoarthritis (OA).
Material and methods. The study included 91 patients with stage III post-traumatic knee OA. All patients received intra-articular (i/a) injection of high molecular weight HLA with CS; 36 patients received the drug once (group 1) and 55 twice (group 2) with an average interval of 7±2 days. Before the start of treatment and 2 weeks, 1, 3, 6 and 12 months after i/a injection of HLA, pain intensity at rest and during movement was assessed using a visual analogue scale (VAS) and function was assessed using KOOS questionnaire (Knee injury and Osteoarthritis Outcome Score).
Results and discussion. In general, patients receiving single and double i/a injections of HLA, pain during movement at baseline, and after 2 weeks, 1, 3, 6 and 12 months was 6.7±1.1; 4.0±0.7; 4.3±0.8; 4.6±1.0; 4.5±1.1 and 5.3±0.4 cm; pain at rest – 2.7±0.6; 1.5±0.2; 1.8±0.2; 2.1±0.5; 2.2±0.3 and 2.6±0.2 cm, and KOOS score was 35.9±13.6; 43.5±13.6; 49.2±17.6; 57.0±12.5; 51.5±11.7 and 40.3±10.2, respectively. In group 1, pain during movement at the same time line reached 6.7±1.2; 4.0±0.7; 4.3±1.1; 4.6±.08; 4.5±0.6 and 5.3±1.3 cm; pain at rest – 2.7±0.5; 1.5±0.3; 1.8±0.4; 2.1±0.4; 2.2±0.6 and 2.6±0.6 cm; KOOS score – 37.2±8.7; 39.1±10.1; 43.0±12.3; 47.0±13.6; 49.5±14.7 and 35.7±12.4, respectively.In the 2nd group, pain during movement was 6.1±1.5; 3.3±0.7; 3.6±0.6; 3.4±0.5; 3.7±0.4 and 4.4±0.3 cm; pain at rest was 2.6±0.3; 1.9±0.2; 1.1±0.2; 0.9±0.1; 0.7±0.1 and 1.7±0.3 cm; KOOS score was 34.7±9.4; 47.1±11.1; 59.3±11.5; 61.4±12.7; 57.2±14.3 and 45.7±12.4, respectively.
Conclusion. In patients with stage III knee OA, double injections of HLA with HS were more effective. The maximum pain reduction and functional improvement were observed in the first 3 months after local injection therapy. 

Antineutrophil cytoplasmic antibody-associated systemic vasculitis (ANCA-SV) is a group of rare and potentially severe systemic diseases. The search for reliable methods to assess ANCA-SV activity remains relevant. Among the indicators of neutrophil activation that have emerged in clinical practice, the level of serum calprotectin (CLP) stands out, which can be a marker for monitoring vasculitis activity and identifying patients at risk of disease relapse.
Objective: to determine serum CLP levels in patients with ANCA-SV.
Material and methods. The study group comprised 64 patients (37 with granulomatosis with polyangiitis, 11 with eosinophilic granulomatosis with polyangiitis and 16 with microscopic polyangiitis) aged 18 years and older with a confirmed diagnosis of ANCA-SV. The control group consisted of 30 healthy individuals. ANCA-SV activity was determined using the BVAS index; high activity corresponded to a BVAS value of >3. 
Damage was assessed using the VDI index. Depending on ANCA-SV activity, patients were divided into two groups: high activity group (group 1, n=33) and low activity group (group 2, n=31). In addition to the generally accepted indicators, serum CLP levels were assessed in all patients with ANCA-SV and healthy donors.
Results and discussion. Statistically significant differences (p<0.001) were found in CLP levels in patients with ANCA-SV in groups 1 and 2. A significant correlation was found between CLP concentration and leukocyte count, neutrophil count, neutrophil-to-lymphocyte ratio (NLR) and systemic inflammatory index (SII). Blood CLP levels in ANCA-SV were associated with creatinine levels and not with glomerular filtration rate and urinary sediment. Although CLP concentration depended on disease activity, it did not correlate with acute phase indicators, including ESR and CRP concentration.
Conclusion. Serum CLP concentration is significantly higher in patients with active ANCA-SV and is related to NLR and SII inflammatory indices, so we consider the possibility of using this indicator to assess disease activity. 

The search for new biomarkers for the early diagnosis of systemic lupus erythematosus (SLE) is a crucial task.
Objective: a comparative study of concentrations of conservative protein nucleobindin 1 (NUCB1) in the blood serum of patients with SLE and healthy donors and assessment of correlation of NUCB1 level with clinical and serological manifestations of the disease.
Material and methods. The study included 21 patients with SLE who fulfilled SLICC criteria and 23 healthy donors. SLEDAI-2K index was used to assess SLE activity. Organ damage was assessed using SLICC damage index. Standard laboratory markers of SLE were analyzed in all patients. Concentration of NUCB1 in blood serum was determined using the enzyme immunoassay method.
Results and discussion. The group of SLE patients included 20 women and 1 man (median age 33 [27; 40] years, disease duration 5 [3; 10] years), mainly with high disease activity (median SLEDAI-2K 8.5 [6.0; 14.0]). Kidney involvement was found in 52% of cases (nephritis), involvement of joints – in 67% (arthritis), vessels – in 33%, skin – in 67%, pericarditis – in 29%, hematological abnormalities – in 71%, antinuclear factor – in 76% and antibodies against double-stranded DNA – in 71%.
An increase in the mean NUCB1 level to 3881 ng/ml was found in the blood serum of SLE patients compared to the control group (2766 ng/ml; p=0.048). Correlations of NUCB1 levels with vascular damage (r=0.653; p<0.05) and pericarditis (r=-0.490; p<0.05) were found.
Conclusion. Elevated NUCB1 levels in the blood serum of SLE patients may indicate involvement of this protein in autoimmune and apoptotic processes. The observed correlation of NUCB1 levels with vascular affection and pericarditis is the basis for further studies on the involvement of this protein in the development of various diseases, including SLE.

Objective: to investigate the efficacy of Alflutop therapy in patients with knee osteoarthritis (OA) with or without concomitant diseases.
Material and methods. The large-scale, multicenter prospective, open-label, observational, non-interventional ISKRA study (Study: Prescribing the drug Alflutop, solution for injection, for OA in real world clinical practice) included 22,525 patients, 10,616 of whom had knee OA. The mean age of patients with knee OA was 60.1±11.7 years, body mass index (BMI) was 28±4.6 kg/m² , and median disease duration was 60 [24; 120] months. All patients had significant comorbidities: arterial hypertension in 90% of cases, and ischemic heart disease, diabetes mellitus and obesity in one in three cases. Alflutop was administered daily 1 ml intramuscularly (IM), No. 20, or every second day 2 ml IM, No. 10. The efficacy of the treatment was assessed by the dynamics of pain intensity using a visual analogue scale (VAS), patient's general health assessment (PHA) using VAS and quality of life using EQ-5D, and the need for non-steroidal anti-inflammatory drugs (NSAIDs).
Results and discussion. After one course of treatment, median pain intensity decreased from 60 [40; 70] to 20 [10; 40] mm, quality of life improved – median EQ-5D increased from 0.59 [0.36; 0.69] to 0.85 [0.73; 1]) and PHA from 50 [37; 70] to 80 [60; 90] mm, and the need for NSAIDs decreased. Female gender, older age, high BMI, severe pain, radiological stages III and IV, poorer quality of life, presence of concomitant diseases and lower adherence to treatment were associated with a less significant response to therapy.
Conclusion. The results of the use of Alflutop in knee OA suggest that widespread use in real-life clinical practice is possible. The inclusion of additional therapeutic targets in the OA treatment strategy, as well as the identification and correction of factors associated with a less pronounced analgesic effect of the drug, will potentially improve treatment efficacy.

The article discusses the pathogenesis and clinical manifestations of cutaneous vasculitis in rheumatoid arthritis (RA) and the role of autoimmune disturbances in the development of micro- and macrovascular thrombosis of the venous and arterial vessels caused by SARS-CoV-2 virus infection.
A clinical case is described in which skin necrosis in the elbow joint area developed in a patient with a long-term course of RA after COVID-19. The process subsided against the background of treatment with an interleukin-6 inhibitor.

Therapy of systemic lupus erythematosus (SLE) remains a difficult task. Long-term use of glucocorticoids (GC) and cytostatic drugs significantly improves the prognosis of life, but at the same time contributes to the accumulation of irreversible damage to the internal organs and, as a result, to the deterioration of the quality of life, disability, social disadaptation and premature mortality. Preventing such consequences, achieving and maintaining long-term remission and reducing the need in high and medium doses of GC remain important tasks in SLE therapy, which has been facilitated by introduction of biologic disease-modifying antirheumatic drugs (bDMARDs) into clinical practice. Belimumab is the first bDMARD to be approved for the treatment of SLE. The accumulated experience allows conclusions to be drawn about its therapeutic properties and efficacy in a specific subtype of the disease, but feasibility and safety of long-term use of bDMARDs have not been sufficiently investigated.
In this article, three clinical cases are presented in which belimumab was successfully used over a period of 9–10 years. 

The treatment of juvenile-onset systemic lupus erythematosus (jSLE) is a complex task in view of the diversity of clinical manifestations and the course of the disease as well as the high risk of organ damage. The need to create separate therapeutic principles for jSLE is justified by the greater intensification of therapy due to both the doses used and the combination of a larger number of different drugs in a patient. However, the basis for the treatment of jSLE today is mainly the extrapolation of data obtained in studies with adult patients.
The review reflects modern ideas about the spectrum of drugs used in jSLE, with particular emphasis on efficacy, safety and timing of therapy as well as possible optimization options. 

This review presents the latest data on the long-term use of the selective Janus kinase inhibitor (JAKi) baricitinib (BARI) in patients with rheumatoid arthritis (RA) in real-world clinical practice. The results of long-term use (up to 9.5 years) of BARI in RA suggest that its efficacy is comparable or even superior to that of biologic disease-modifying antirheumatic drugs (bDMARDs) and tofacitinib, while the drug is more effective in patients who have not previously received bDMARDs or JAKi. It has been shown that the BARI dose can be reduced to 2 mg/day once the treatment goal has been reached in most patients without a decrease in efficacy, and that exacerbations that have occurred after reduction of the dosage (or treatment interruption) are relieved when returning to the full dose of the drug. According to data from registries from many countries and open observational studies, BARI is well tolerated during long-term use, even in elderly patients with ≥1 risk factor for cardiovascular disease. A high survival rate with BARI therapy has also been observed, which according to some registries exceeds that of tumor necrosis factor α inhibitors. Against the background of BARI therapy, a rapid (within 1 to 3 months) statistically significant reduction in pain has been demonstrated, regardless of the degree of suppression of disease activity, which correlates with an improvement in the functional status and general condition of patients. The possibility of suppressing the progression of structural damage in patients with RA was also demonstrated, allowing the choice of individualized tactics for the management of such patients. 

Patients with immune-mediated inflammatory rheumatic diseases (IIRD) are more likely to develop herpes zoster (HZ) than individuals in the general population. Live attenuated vaccines and inactivated recombinant vaccines with adjuvant are available to prevent the disease and its complications. Live attenuated vaccine can be used in patients with IIRD if certain conditions are met, although these cannot always be fulfilled. The advantage of the inactivated recombinant adjuvant vaccine is that it can be used against a background of anti-rheumatic therapy. The review analyzes foreign studies on the safety, immunogenicity and efficacy of recombinant adjuvant vaccine against HZ in patients with IIRD. 

Osteoarthritis (OA) is one of the leading causes of disability in the world, but the efficacy and safety of its treatment remain extremely low. This review presents epidemiology of OA, mechanism of its development and modern possibilities of pharmacological regulation of immune-mediated inflammation in OA. We analyze the immunological aspects of oral tolerance phenomenon and the prospects for its use to suppress autoinflammation in OA using combined pharmaconutraceutical preparation Chondroguard® TRIO as an element of nutritional support for patients with this disease. It is emphasized that it is advisable to develop a scientifically based rational approach to the treatment of OA that alleviates symptoms, reduces autoinflammatory affection of articular cartilage and improves its regeneration with the involvement of extracellular matrix components.