Artem A. Kondrashov

Objective: to evaluate the efficacy and safety of complex therapy for knee osteoarthritis (OA) using a combination of chondroitin sulfate (CS) and glucosamine (G), as well as intra-articular (IA) administration of a medical device (MD) containing polyacrylamide gel (PAAG). Material and methods. The study included 22 patients aged 40–75 years with definite knee OA, radiographic stage II–III. Median age was 64.5 [59.0; 68.0] years. All patients received comprehensive therapy: a single IA injection of 4.0 ml of the PAAG-containing MD into the target knee in combination with oral CS (800 mg/day) and G (1000 mg/day) for 6 months. Total follow-up duration was 9 months (6 months of treatment and 3 months of follow-up). Results and discussion. During complex therapy, a significant reduction in knee pain intensity on the visual analog scale was observed, along with improvement in all WOMAC components, patient global assessment of health status, the Lequesne index, and quality of life according to EQ-5D (pConclusion. The study results confirm the significant efficacy and safety of a complex approach to OA therapy, including the use of a combination of disease-modifying drugs for OA and IA administration of an MD containing PAAG.

Immune checkpoint inhibitors are relatively new and effective agents for treatment of malignant tumors, widely used to combat neoplasms of various locations. Nevertheless, these drugs can cause unwanted immune-mediated phenomena, one of which is capillary leak syndrome. Capillary leak syndrome is characterized by leakage of the liquid part of the plasma from the vascular lumen and is complicated by development of generalized edematous syndrome and hypovolemic shock. Although this complication is rare, it is associated with high risk of fatal outcome, and currently there are no established diagnostic and therapeutic approaches. The aim of our review was to present modern data on capillary leak syndrome caused by immune checkpoint inhibitors. We performed a search and comparative analysis of articles describing this complication. In the PubMed / Medline, Scopus, Web of Science, Google Scholar, and eLibrary databases, 30 clinical case descriptions from 2019 to 2025 were found, 25 of which were included in the review. Development of this complication was most often associated with the use of pembrolizumab (44 %). The median time to development was 12.7 weeks. In one patient, the complication developed against the background of tumor progression. Peripheral edema was described in 96 % of patients. Pleural effusion was the 2nd most common clinical manifestation (68 %). For the management of the complication, 1st-line systemic glucocorticoids were used in 80 % of patients, and they were effective in approximately one third of cases. 13 patients received 2nd-line immunosuppressants, mostly intravenous immunoglobulin. The mortality rate during follow-up was 28 %. With accumulating clinical experience of immune checkpoint inhibitor use, the spectrum and frequency of associated adverse events, including capillary leak syndrome, are expected to grow. This underscores the need to develop diagnostic and therapeutic strategies for this adverse reaction.

Aim. To identify prognostically unfavorable predictors of loss of ability to work in patients with systemic sclerosis. Material and methods. The analysis included 60 patients of working age (mean age 50.18 ± 9.86 years) with confirmed diagnosis of systemic sclerosis established based on the American College of Rheumatology (ACR) and European League Against Rheumatism (EULAR) criteria (2013). The ratio of men to women was 1:5. Median duration of the disease from the onset of Raynaud’s phenomenon was 7.5 (interquartile range from 3 to 17.5) years, and from the first symptom not related to Raynaud’s phenomenon – 6.5 (interquartile range from 2 to 12.5) years. The severity of clinical, laboratory, and instrumental characteristics of systemic sclerosis, the level of anxiety and depression according to the Hospital Anxiety and Depression Scale (HADS), the degree of reduction of quality of life according to the SF-36 questionnaire, the degree of functional disorders according to the Health Assessment Questionnaire (HAQ) and the Sclerosis Health Assessment Questionnaire (SHAQ) were assessed. The severity of dyspnea was evaluated using the modified Medical Research Council (mMRC) scale. All patients included in the analysis were divided into two groups based on their status: employed or unemployed (due to systemic sclerosis). In this study, ability to work and the status of an employed were considered synonyms. The “unemployed” category included patients who had lost their ability to work due to systemic sclerosis. Patients unemployed for other reasons were excluded from the study. Results. Univariate analysis using binary logistic regression showed that significant predictors of loss of ability to work are functional disorders HAQ ≥0.43 (odds ratio (OR) 17.82; 95 % confidence interval (CI) 3.04–104.61; p 0.001), SHAQ score 0.71 (OR 13.51; 95 % CI 2.53–72.06; p = 0.002), low physical health score per the SF-36 PCS (Physical Component Summary) 36.24 (OR 0.9; 95 % CI 0.84–0.96; p = 0.001), depression per the HADS-Depression scale ≥7 (OR 1.21; 95 % CI 1.03–1.42; p = 0.02), dyspnea per the mMRC ≥2 (OR 3.63; 95 % CI 1.68–7.81; p 0.001), systolic pressure in the pulmonary artery 27.5 mmHg (OR 1.21; 95 % CI 0.07–1.37; p = 0.002), tricuspid regurgitation velocity ≥2.4 m / s (OR 1.04; 95 % CI 1.01–1.07; p = 0.001), decreased distance in the six minute walk test ≤500 m (OR 1.63; 95 % CI 1.16–2.29; p = 0.011), decrease in forced vital capacity ≤90 % from predicted (OR 1.21; 95 % CI 1.03–1.43; p = 0.02), manual labor (OR 16.2; 95 % CI 1.57–167.74; p =0.02). Multivariate analysis using multiple logistic regression with sensitivity 84.6 % and specificity 85.3 % showed that loss of ability to work in systemic sclerosis is affected by dyspnea level per the mMRC ≥2 (OR 33.5; 95 % CI 3.05–367.81; p = 0.004) and tricuspid regurgitation velocity ≥2.4 m / s (OR 69.8; 95 % CI 7.75–625.04; p 0.001). Conclusion. The importance of assessing the severity of dyspnea using the mMRC scale and tricuspid regurgitation velocity as determined by echocardiography in relation to predicting the loss of work ability underscores the necessity of evaluating these parameters in routine rheumatological practice.

Aim. To illustrate a comprehensive approach to management of a patient with long-standing generalized tophaceous gout, taking into account concomitant comorbidities, as well as to analyze the factors influencing adherence to therapy and lifestyle modification.Material and methods. Patient N., 54 years old, with a 16-year history of gout, multiple tophi, hyperuricemia, stage C2 chronic kidney disease (glomerular filtration rate 69.8 ml/min/1.73 m2), dyslipidemia, grade 1 obesity, and nephrolithiasis. A comprehensive clinical, laboratory, and instrumental diagnostic evaluation was performed, and the nature of joint changes and the comorbidity degree were verified. Specialists prescribed uric acid-lowering therapy with febuxostat (80 mg/day), along with preventing therapy for recurrent gouty arthritis using colchicine (0.5 mg/day), rosuvastatin (10 mg/day), and measures for dietary and weight correction.Results. Against the background of the ongoing therapy, a sustained clinical and laboratory effect was achieved over four months: serum uric acid levels decreased to 282 µmol/L, no arthritis recurrences were recorded, and positive dynamics in the volume of tophaceous infiltration were observed. The patient demonstrates a high level of compliance, following the treatment regimen and recommendations on diet and physical activity.Conclusion. Modern management of gout requires a comprehensive approach that includes pharmacotherapy and lifestyle modification. However, in practice, only a few patients achieve target uric acid levels, indicating the need to strengthen prevention, educational programs, and improve adherence to treatment.

Systemic connective tissue diseases may be associated with various forms of pulmonary hypertension (PH). The prevalence of PH varies among different systemic connective tissue diseases, with systemic scleroderma (SSc) having the highest rate, ranging from 8 to 12 %. With SSc, PH is one of the severe and life-threatening manifestations, which necessitates the study of this problem. The pathogenesis of PH in SSc varies and depends on the predominant organ damage. PH can be represented by pulmonary arterial hypertension (PAH) (group 1) with isolated damage to the pulmonary vessels, or with more rare conditions such as veno-occlusive disease, portopulmonary hypertension, or drug toxicity. Venous PH can also develop due to damage to the left chambers of the heart, such as myocardial fibrosis, diastolic dysfunction of the left ventricle, or valve pathology (group 2). PH associated with lung damage may develop due to interstitial lung Systemic connective tissue diseases may be associated with various forms of pulmonary hypertension (PH). The prevalence of PH varies among different systemic connective tissue diseases, with systemic scleroderma (SSc) having the highest rate, ranging from 8 to 12 %. With SSc, PH is one of the severe and life-threatening manifestations, which necessitates the study of this problem. The pathogenesis of PH in SSc varies and depends on the predominant organ damage. PH can be represented by pulmonary arterial hypertension (PAH) (group 1) with isolated damage to the pulmonary vessels, or with more rare conditions such as veno-occlusive disease, portopulmonary hypertension, or drug toxicity. Venous PH can also develop due to damage to the left chambers of the heart, such as myocardial fibrosis, diastolic dysfunction of the left ventricle, or valve pathology (group 2). PH associated with lung damage may develop due to interstitial lung diseases, such as nonspecific and usual interstitial pneumonia (group 3). Patients with SSc are more susceptible to thrombosis and pulmonary embolism due to formation of antiphospholipid antibodies, which can lead to the development of chronic thromboembolic PH (group 4). A characteristic feature of SSc is that one patient may have several reasons for PH development. The variety of pathogenetic variants of PH in SSc requires personalized and comprehensive diagnostic approaches to each patient. Management of the patient and determination of indications for appointment of PAH-specific therapy depend on the variant and pathogenesis of PH.

Phosphopenic osteomalacia (PPOM) is a rare variant of paraneoplastic syndrome caused by tumor synthesis of fibroblast growth factor 23 (FGF23). FGF23 secretion leads to a decrease in phosphate reabsorption and calcitriol levels, which leads to the development of severe hypophosphataemia and hypocalcaemia. FGF23 synthesis is predominantly associated with benign mesenchymal tumors, but has also been described in malignant neoplasms. The main clinical manifestations of PPOM are generalized myalgias and myopathy, ostealgia, pathological fractures, etc. The diagnosis of the disease requires a step-by-step investigation using somatostatin receptor-based imaging techniques, as these have the highest sensitivity for the detection of neoplasms causing osteomalacia. Surgical intervention is clearly the treatment of choice. Promising non-surgical methods include treatment with burosumab and somatostatin analogues.

Aim. To consider new mechanisms of gout pathogenesis of and possibilities of influencing the pathological process. Gout is a chronic joint disease caused by the deposition of monosodium urate crystals in various tissues and subsequent inflammation in individuals with hyperuricemia, caused by exocrine and/or genetic factors. In recent years, new knowledge about gout diagnostics, genetics, pathogenesis, comorbidities and various data indicate new strategies to improve control of the disease and its exacerbations, as well as to prevent comorbid conditions. The discovery of new mechanisms concerning sodium monourate crystal-induced inflammation, proposed new methods of treating not only gout, but also other systemic diseases, including renal and cardiovascular diseases using xanthine oxidase inhibitors, including febuxostat. The case of colchicine is very indicative, which recently, taking into account the significant results of laboratory and clinical experiments, received approval from the US Federal Food and Drug Administration for the Prevention of cardiovascular Diseases. This has provided opportunities for the combinedadministration of febuxostat and colchicine to treat gout, recurrent arthritis attacks and reduce the risk of cardiovascular complications.

In the article, the authors answered the following questions: How often do anxious patients occur in clinical practice? Why do most patients with anxiety see primary care physicians rather than a psychiatrist? What complaints and manifestations help to suspect anxiety in the patient? How can a non-psychiatrist identify and diagnose anxiety? How to manage a patient with diagnosed anxiety? Short-term and long-term outcomes/prognosis.

Aim. To present a clinical case of osteomalacia associated with fibroblast growth factor-23-secreting tumor under the mask of ankylosing spondylitis (AS).Materials and methods. Clinical observation of a 31-year-old patient with long-time diagnosis of AS is presented. Underestimation of back pain cause at the initial stage of diseaseled to an erroneous diagnosis of AS. A thorough assessment of the anamnesis, additional examination using modern imaging methods in combination with laboratory analysis (low blood phosphorus level, hyperphosphaturia, normal value of C-reactive protein, erythrocyte sedimentation rate, negative HLA-B27), made it possible to establish the correct diagnosis of “mesenchymal phosphaturic tumor of the left foot (surgical intervention dated 11.26.2020), secondary hypophosphatemic tumor-induced osteomalacia complicated by multiple bone fractures”, to carry out timely treatment with full recovery.Results. The literature data on epidemiology, pathogenetic mechanisms, clinical manifestations and management approaches of tumor induced phosphopenic osteomalacia are presented. An algorithm for examining patients with suspected of this disease is described, taking into account the expression of somatostatin transmembrane receptors on the surface of a mesenchymal phosphaturic tumor.Conclusion. One of the rarest causes of specific back pain is osteomalacia, which can be caused by various diseases, for example, a tumor secreting FGF23 The complexity of the diagnosis lies in the non-specificity of clinical manifestations – generalized myalgia and myopathy, ossalgia, pathological fractures, etc. Timely diagnosis and radical treatment makes it possible to achieve stable remission with complete leveling of symptoms, therefore surgical excision of the tumor is the “gold” standard of therapy.

In patients with systemic sclerosis (SSc), interstitial lung disease (ILD) is a factor in the decline of functional capacity up to disability and is also the leading cause of death. Therefore, one of the most important tasks in the treatment of this group of patients is not only to detect involvement of respiratory system, but also to predict the likelihood of its development.Objective: to study the possibility of predicting the development of ILD and advanced ILD in patients with SSc.Material and methods. The study included 79 patients with SSc (mean age 64.4±11.5 years; 94.9% women) from the Registry of myositis, SSc and Mixed Connective Tissue Diseases (РЕМИССиС) who underwent high-resolution computed tomography (HRCT) of the lungs. Classification trees (CTr) were constructed to predict the development of widespread ILD using the CHAID algorithm (exhaustive). All patients were tested for antibodies against Scl-70 (anti-Scl-70), CENP-B (anti-CENP-B), and PmScl (anti-PmScl).Results and discussion. ILD signs according to HRCT were detected in 53 patients. Fibrotic (34.2%) and cellular (15.2%) types of nonspecific interstitial pneumonia were the most common, and common interstitial pneumonia was less frequent (11.4%).The presence of ILD and advanced ILD (involvement of more than 20% of the lung parenchyma) were significantly associated with the detection of any autoantibodies, except anti-centromere antibodies, an increase in pulmonary artery systolic pressure, a decrease in forced vital capacity, diffusing capacity of the lungs, blood oxygen saturation at rest, and all parameters of six-minute walk test (6MWT), and complaints of shortness of breath. In addition, the presence of extensive ILD was also significantly associated with diffuse SSc and with SSc without skin manifestations.In establishing the CTr, it was found that the development of widespread ILD was unlikely in individuals who were able to walk more than 440 m in 6MWT and had neither anti-Scl-70 nor anti-PmScl.Significant associations were also found between the radiological pattern of ILD and the types of disease-specific antibodies.Conclusion. The 6MWT data in conjunction with the results of testing for SSc-specific autoantibodies provide a very accurate prediction of the presence and extent of ILD. It is advisable to include these indicators in the algorithm for screening and monitoring patients with SSc.