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.

Aim. To identify the phenotypes of patients with asymptomatic hyperuricemia (HU) in the Russian Federation by analyzing demographic and clinical and laboratory parameters in outpatient practice.

Material and methods. The data obtained in the framework of the non-interventional multicenter program “Assessment of epidemiological data on the detection of serum uric acid levels in patients with arterial hypertension, combined with metabolic syndrome, diabetes mellitus, and joint pain”, conducted in the Russian Federation, are presented. All study participants were examined according to the same single protocol.

Results. Asymptomatic HU was detected in every 10th patient, predominantly in women, every 2nd person worked, 1/3 of the persons had a higher education, the majority had a family. Among comorbidities, the most common were arterial 

hypertension (AH), coronary heart disease, osteoarthritis. In HU, the risk of AH was elevated more than 2-fold, atrial fibrillation (AF) – 3-fold, osteoarthritis – 2-fold. A direct correlation of HU with age (p = 0.004; r = 0.17), female sex (p = 0.001; r = 0.76), retired status (p = 0.002; r = 0.19), AH (p = 0.018; r = 0.18), AF (p = 0.007; r = 0.16), osteoarthritis (p = 0.032; r = 0.13) was determined. Association of HU with age (odds ratio (OR) 1.04; 95 % confidence interval (CI) 1.02–1.07; p = 0.002), retired status (OR 2.59; 95 % CI 1.35–3.77; p = 0.002), AH (OR 2.27; 95 % CI 1.13–4.53; p = 0.021), AF (OR 3.07; 95 % CI 1.31–7.20; p = 0.010), osteoarthritis (OR 1.90; 95 % CI 1.05–3.43; p = 0.033) was confirmed.

Conclusion. The phenotypes of patients with asymptomatic HU living in the Russian Federation were determined. An association of HU with a number of socio-demographic indicators, concomitant cardiovascular diseases, and osteoarthritis has been established.

Aim. To compare patients with bradyarrhythmias and obstructive sleep apnea (OSA) and patients without OSA; to study the predictive capabilities of questionnaires in OSA screening.

Material and methods. The study included 134 patients with bradyarrhythmias hospitalized for pacemaker implantation or pacemaker replacement. The median age was 67.5 years (interquartile range 59 to 72 years). Sleep apnea screening was performed using the Berlin questionnaire, the STOP-BANG sleep apnea risk scale, and the Epworth sleepiness scale. All patients underwent blood tests and instrumental examinations (respiratory monitoring and echocardiography).

Results. Patients with OSA were older (68 years versus 64 years; p = 0.032), had a larger waist circumference (116 cm versus 108 cm; p = 0.044), and body mass index (33.7 kg/m² versus 31.03 kg/m²; p = 0.016) compared to patients without OSA. The Berlin questionnaire (area under the curve (AUC) 0.79; sensitivity 92 %, specificity 38 %; p <0.0001) and the STOP-BANG risk scale (AUC 0.75; sensitivity 82 %, specificity 23 %; p <0.0001) had a high predictive power to identify sleep apnea while the Epworth sleepiness scale had a low predictive power (AUC 0.463; sensitivity 12 %, specificity 85 %). According to laboratory and instrumental data, patients with sleep apnea had significantly higher C-reactive protein levels (7.17 mg/L versus 1.73 mg/L; p = 0.012) and more frequently had interventricular septal hypertrophy (12 mm versus 10 mm; p = 0.02). Third-degree atrioventricular block was significantly more common in patients with sleep apnea (17.91 % versus 5.97 %; odds ratio 0.363; 95 % confidence interval 0.131–1.001; p = 0.045). In patients with sleep apnea, cardiac pacing for more than 5 years was more common (11.94 % versus 4.48 %; odds ratio 0.35; 95 % confidence interval 0.116–1.054; p = 0.049).

Conclusion. High frequency of OSA was observed in patients with bradysystolic heart rate. The Berlin questionnaire and the STOP-BANG sleep apnea risk scale can be used to screen for OSA in patients with bradyarrhythmias. Elevated C-reactive protein levels and interventricular septal hypertrophy accentuate the importance of early diagnosis and treatment of OSA for improved prognosis.

Aim. To investigate predictors of achieving low disease activity (LDA) in patients with difficult-to-treat (DtT) rheumatoid arthritis (RA) and to assess the role of interleukin 6 (IL-6) inhibitors in reaching the target disease activity in this patient population.

Material and methods. Analysis of medical records of 1145 patients with a confirmed diagnosis of RA was conducted. Patients with a follow-up duration of less than 6 months, those who had not undergone conventional disease-modifying antirheumatic drug (DMARD) therapy, and patients later reclassified with a different diagnosis were excluded. In the selected group (n = 966) DtT patients were identified as those with RA who received recommended treatment with conventional DMARD but failed to achieve LDA or remission after therapy with two classes of biologic disease-modifying antirheumatic drugs (bDMARDs) or janus kinase inhibitors (JAKi)/bDMARDs, or had their treatment discontinued due to adverse events. In the DtT group, two subgroups were distinguished: those who achieved LDA after being classified as DtT due to a change in JAKi/bDMARDs and those who did not achieve LDA.

Results. Median duration of the disease in the DtT cohort was 186 months (interquartile range 104–278), and median duration of DtT status at the time of the last observation was 27.8 months (interquartile range 10.2–56.0 months). A total of 484 treatment episodes involving JAKi/bDMARDs among DtP patients were analyzed. Comparison of the group that achieved LDA (LDA+, n = 172; 35.5 %) with the group that did not achieve LDA (LDA–, n = 312; 64.5 %) revealed that the LDA+ was characterized by younger age of RA onset (p = 0.005), later initiation of DMARD (p = 0.005) and JAKi/bDMARDs (p = 0.034) therapies from the onset of RA, and more frequent presentation with stage IV radiological findings per Steinbroker (p = 0.007). Additionally, glucocorticoids were used less frequently at the last visit in the LDA+ group (p = 0.042). Comparison of the frequency of LDA or remission within the DtP cohort revealed no significant differences among classes or individual medications. In the highest percentage of cases, abatacept and IL-6 inhibitors achieved target disease activity (40.5 % and 40.4 % respectively). Among the IL-6 inhibitors, the highest success rates were observed with levilimab (48.0 %) and tocilizumab (41.3 %).

Conclusion. Patients with late-stage RA and pronounced radiological changes show potential for achieving LDA. The administration of abatacept and IL-6 inhibitors as first-line therapies may reduce the likelihood of developing DtT status, and in cases with this status occurs, target disease activity can be achieved in 40.5 % and 40.4 % of cases, respectively.

Aim. To present a clinical case and describe the features of dermatomyositis (DM) with myositis-specific anti-Mi2 antibodies (MSAs).

Material and methods. Clinical manifestations, abnormalities of laboratory and immunologic tests, strategy and efficacy of pharmacotherapy in a patient with DM are described.

Results. A clinical case of DM is presented in a patient born in 1992. The disease manifested through lesions in the skin (periorbital edema with heliotropic rash, Gottron papules, diffuse alopecia, cheilitis, digital ulcers), mucous membranes (enanthem), muscles (myalgia), joints (polyarthritis), peripheral nervous system (polyneuropathy), and constitutional symptoms (weight loss, general weakness, subfebrile temperature). Laboratory examination showed increased erythrocyte sedimentation rate of 40 mm/h and lactate dehydrogenase level of 672 U/L, antinuclear factor was measured at 1:320, and anti-Mi2 antibodies were detected by MSAs panel. Combination immunosuppressive therapy with methylprednisolone at an initial dose of 1 mg/kg/day and subcutaneous methotrexate at a dose of 15 mg/week was initiated, followed by correction depending on the clinical and laboratory dynamics. This case demonstrates benign course of anti-Mi2 antibody-positive DM. Classic skin symptoms (periorbital edema with heliotrope rash, Gottron papules) and muscle damage completely regressed after 21 months of combination pharmacotherapy with methylprednisolone and methotrexate. Stable immunological seroconversion of MSAs and drug-free clinical remission were achieved. Low risk of malignant neoplasms with this DM serotype is emphasized. Atypical symptoms of polyneuropathy and myalgia are considered.

Conclusion. The presented clinical case demonstrates the characteristic features of the DM subtype with anti-Mi2 antibodies: a combination of classic skin symptoms with muscle damage, benign course during two-year combination pharmacotherapy with a glucocorticoid and a cytostatic, persistent immunological seroconversion of MSAs, drug-free clinical remission. Presumably, determination of DM serotype can be useful in clinical practice for predicting the course of the disease, response to pharmacotherapy, and the risk of developing neoplasia.

Osteoarthritis (OA) is increasingly recognized as a complex degenerative joint disease that develops under the influence of mechanical, biochemical and genetic factors. The pathogenesis of OA includes a complex of interactions at both cellular and molecular levels, leading to progressive damage to joint tissues – cartilage degeneration, synovial inflammation, remodeling of the subchondral bone, and periarticular changes. In the last decade, the term “early osteoarthritis” has been increasingly mentioned in the scientific literature. The concept of early OA was largely determined by the experience of rheumatoid arthritis treatment. Given the heterogeneity of OA, pathological processes at the cellular and molecular levels, reflecting the early stage of the disease, are diverse and depend on the factors that induce the disease. Symptoms of early OA of the knee joint can be suspected with the appearance of intermittent pain or discomfort in the joint, short-term “initial” stiffness and functional limitations. Clinical examination in most cases reveals pain on palpation of the joint, crepitation or moderate articular effusion. X-ray data are of limited importance at an early stage of the disease, since one of the typical signs of OA – narrowing of the articular gap – may not appear for many years. Quantitative, contrast-enhanced magnetic resonance imaging methods, as well as hybrid methods are used to visualize OA at an early stage. The final goals of developing classification criteria for early OA and early diagnosis of the disease in real clinical practice differ. Early OA represents a “window of opportunity” to prevent disease progression before OA becomes clinically apparent. It is necessary to continue research on the definition and classification of early OA of other localizations. Pharmacological innovations, regenerative methods, and gene therapy represent the future of OA treatment, including at an early stage of the disease. One of the modern drugs that modify the course of OA is Elmosa, a unique combination of glucosamine sulfate, boswellic acids combined with acetyl-L-carnitine and B vitamins.

Aim. To investigate the effectiveness and safety of Cellex® drug (active substance is polypeptides from the brain of pig embryos) in nontraumatic intracranial hemorrhage.

Material and methods. The study included 116 patients with hypertensive intracranial hemorrhage aged between 30 and 80 years. Patients of the treatment group (n = 61) in addition to the basic therapy were administered 0.1 mg (1 mL) of Cellex® once a day for 10 days while patients of the control group (n = 55) only received basic therapy in accordance with the clinical guidelines on management of patients with hypertensive intracranial hemorrhage. For 30 days, dynamics per the Glasgow Coma Scale, stroke severity per the National Institute of Health Stroke Scale (NIHSS), patient disability per the Modified Rankin Scale (mRаnkin), Barthel and Rivermead scales, speech disorders per the Speech Questionnaire, cognitive functions per the Montreal Cognitive Assessment and a number of other characteristics were evaluated.

Results. Percentage of survived patients (96.7 %) was higher in the Cellex® group compared to the control group (p = 0.0237). In the Cellex ® group, speech function per the Speech Questionnaire improved from 17.0 (14.0–22.0) to 24.0 (21.0–27.0) (p = 0.009) while in the control group no significant improvement in speech function was observed. A trend toward more significant decrease in stroke severity per NIHSS, patient disability per the mRаnkin, Barthel and Rivermead scales in the Cellex® group compared to the control group was observed. Cognitive functions per the Montreal Cognitive Assessment improved in the Cellex® group from 14.0 (12.0–22.5) to 20.0 (14.5–25.0) points. No adverse events were observed in the patient group receiving Cellex®.

Conclusion. High efficacy and safety of Cellex® drug in patients with hypertensive intracranial hemorrhage were confirmed.

The review describes the molecular architecture and physiology of the blood-brain barrier (BBB), modern methods for assessing the condition of the BBB, the role of its dysfunction in some neurodegenerative diseases, and the contribution of vascular pathology. The pathogenetic mechanisms by which violation of BBB leads to neurodegeneration are discussed. Early diagnosis in these nosologies is crucial for adequate therapy and a favorable prognosis. In this regard, the possibility of identifying neuroimaging patterns indicating violations of BBB permeability is being considered, and the pathoanatomical characteristics of BBB dysfunction are also being studied.