[Efficacy and safety of the use of alirocumab in real clinical practice].

AIM: To evaluate the results of two-year use of alirokumab in Karelia Republic. MATERIALS AND METHODS: The observation group consisted of 27 patients (17 patients with familial hypercholesterolemia, 10 patients with the history of myocardial infarction), mean age 53.4±4.3 years, 70.3% men, follow-up duration from one year to 2.5 years, 18 (66.6%) patients received therapy for more than 2 years. 19 patients received alirocumab at a dose of 75 mg/ml once every 2 weeks, eight - at a dose of 150 mg/ml once every 2 weeks. Before the start of therapy, the majority received maximally tolerated statin therapy, 10 patients received statin therapy in combination with ezetemibe, 3 patients received ezetemibe monotherapy due to statin intolerance. The target levels of LDL cholesterol were considered for very high risk patients less than 1.4 mmol/L, high risk - less than 1.8 mmol/L, extreme risk - less than 1 mmol/L. RESULTS: The reduction of LDL on therapy with alirocumab was 58%; target levels of LDL were achieved in 77.8%. The level of decrease in LDL cholesterol less than 50% was noted only in 7.4% of cases. Patients requiring a large dose of the drug were classified as very high risk, had higher cholesterol and LDL-C levels. The level of Lp(a) decrease on 29.7% by 6-12 months. No destabilization of coronary heart disease, new cases of stroke were registered. CONCLUSION: The inclusion of alirocumab in the treatment regimen contributed to the stable course of atherosclerosis-associated diseases, the achievement of LDL cholesterol targets in 77.8% of patients, was not accompanied by side effects during 2.5 years therapy.

[Experience of anticipatory therapy with IL-6 receptor inhibitors and perspectives for its use in the evolution of COVID-19].

The Advisory Board chaired by the chief specialist in infectious diseases of the Ministry of Health of Russian Federation, Professor V.P. Chulanov was held on June 18, 2022 in Saint Petersburg. Aim. The main purpose of the Board was following discussion: the analysis of the real-world data of levilimab as an anticipatory therapy for COVID-19 in hospitalized patients; the review of the experience and perspectives of levilimab as an anticipatory anti-inflammatory option for outpatient patients who meet defined clinical and laboratory criteria. Results. The analyzed data on clinical efficacy and safety formed the basis of recommendations proposed by experts for the use of levilimab in the inpatient and outpatient medical care for COVID-19.

[Experience of the use of the PCSK9 inhibitor Alirocumab in patients with extremely high cardiovascular risk].

Aim To study the efficacy and safety of alirocumab in patients with high and very high cardiovascular risk in the Republic of Karelia and to evaluate their compliance with the alirocumab therapy.Materials and methods Study design: observational, noncomparative. The observation group consisted of 9 patients receiving alirocumab (Praluent®) (mean age, 48.6±4.7 years; 7 men). 7 patients had familial hypercholesterolemia of the type diagnosed by DLCN criteria; five patients had MI. Lipid profile, concentrations of transaminases, creatinine, glucose, and lipoprotein a (LP(a)) were measured at 3, 6, 12, and 18 months. Electrocardiography was performed, and the clinical picture (development of acute coronary syndrome, acute cerebrovascular disease, transient ischemic attacks, myocardial revascularization, and cardiovascular death) was evaluated. Efficacy criteria included the absence of these clinical conditions, the proportion of patients who achieved the LDL CS goal, and the decrease in LP(a). Safety was evaluated by clinical and laboratory data, such as levels of transaminases, total bilirubin, creatinine, and blood glucose. The observation lasted for 6 months to 1.5 years.Results LDL CS goals were achieved in 7 (77.8%) patients receiving alirocumab. The mean level of LP(a) decreased from 0.39 to 0.28 g/l; the degree of decrease ranged from 20 to 33 %. No cases of IHD instability (acute coronary syndrome) or new cases of acute cerebrovascular disease and transient ischemic attacks were observed. None of the patients had to stop the alirocumab treatment; adverse effects, including local ones, were not observed.Conclusion LDL CS goals were achieved in 7 (77.8%) patients. The level of LP(a) decreased by 20-33% in patients receiving the PCSK9 inhibitor. In real-life clinical practice, the alirocumab treatment was characterized with high compliance and good tolerability without side effects, including local ones.

[Improvement of outcomes in patients with recent acute coronary syndrome: the place of PCSK9 inhibitors. The Resolution of National Advisory Board].

On April 9, 2018, the national advisory board "Improvement of outcomes in patients with recent ACS: the place of PCSK9 inhibitors" was held in Moscow. Leading Russian experts in the field of atherosclerosis and lipid-lowering treatment attended the board. The purpose of the Board was to determine the place of PCSK9 inhibitors in the improvement of outcomes in patients with recent (less than 1 year) acute coronary syndrome (ACS). During the Board, three major aspects of lipid-lowering treatment were discussed: 1) issues in reaching the target levels of LDL cholesterol in real clinical practice among patients with recent ACS; 2) the results of ODYSSEY OUTCOMES study and their role in the improvement of outcomes in patients with recent ACS; 3) treatment with PCSK9 inhibitors in the management of patients with recent (less than 1 year) ACS in everyday clinical practice, the role of lipid centers.

Very late biolimus-eluting coronary stent thrombosis: case report.

The case of very late everolimus-eluting stent thrombosis in left arteria descendant (LAD) was presented. Risk factors and possible ways of this complication prevention are discussed.

[Evolution of laboratory markers for systemic bacterial infections]. / Évoliutsiia laboratornykh markerov sistemnykh bakterial'nykh infektsii.

The paper reviews the data available in the literature on existing laboratory markers for systemic bacterial infection, among which C-reactive protein, proinflammatory cytokines, procalcitonin test, and presepsin receive primary emphasis.

[Subpopulations of Regulatory T-lymphocytes in the Peripheral Blood of Patients with Rheumatoid Arthritis].

BACKGROUND: Rheumatoid arthritis (RA) is an inflammatory rheumatic disease associated with a dysfunction of the T cell-mediated tolerance and leading to the disability of working population. The regulatory CD4' T cells play an important role in the regulation of autoimmunity and can suppress immune responses. With that, there is no consensus on the content of these lymphocytes and their role in the pathogenesis of RA. Objective: The aim of the study was to assess the content ofperipheral blood regulatory Tcells (Treg) according to the expression of membrane markers CD4, CD25, CD127 and intracellular FOXP3 marker, as well as the expression of two functional molecules (CTLA-4 and CCR4) in Treg cells of patients with RA. METHODS: Peripheral blood samples of RA patients (median age 65,5 years [54;68,3) and healthy controls (median age 58 years [44; 66]) were analyzed. Cell count and the expression level of molecules were assessed by flow cytometry. RESULTS: Peripheral blood samples of 36 RA patients and 20 healthy donors were analyzed. The number of the cells with Treg-associated phenotypes CD4⁺CD25hi and CD4⁺CD25hiCD127low/⁻ was higher in RA patients in comparison with healthy donors. Increased levels of RA CD4⁺ T cells expressing FOXP3 were also observed. This may be due to increasing in the number of CD4⁺FOXP3⁺CD25⁻ lymphocytes, whereas the content of RA CD4⁺FOXP3⁺CD25⁺ Treg cells was at the level of the control. The expression of the functional molecule CTLA-4 in Treg cells of patients with RA was not different from the control, while the expression level of the chemokine receptor CCR4 which provides migration of lymphocytes at sites of inflammation and barrier tissues was significantly increased in RA patients. CONCLUSION: Increase in the levels of certain Treg-associated lymphocyte populations were detected in peripheral blood of RA patients. During the natural course of RA, alterations in the level of the chemokine receptor CCR4 might indicate the enhanced lymphocyte migration.

The level of cytokines and expression of caspase genes in rheumatoid arthritis.

The level of TNFα and IL6 in the blood plasma of patients with rheumatoid arthritis (RA) who received antiinflammatory therapy with methotrexate (MT) was significantly lower than in the patients without MT treatment. The level of caspase 6 and 9 gene transcripts in peripheral blood lymphocytes in patients with rheumatoid arthritic diagnosed for the first time and in patients with MT treatment were not significantly different. At the same time, the level of caspase 3 mRNA expression was significantly higher in the cells of the RA patients with MT therapy compared to the patients without MT therapy.

[A case of irreversible cardiomyopathy induced by polychemotherapy].

The paper describes a case of irreversible dilated cardiomyopathy in a young female patient receiving polychemotherapy for breast cancer.

[Ten-year risk of osteoporotic fractures in patients with chronic obstructive pulmonary disease estimated by FRAX method].

The study included 104 long-smoking men with COPD. The 10-year risk of osteoporotic fractures was estimated using the FRAX software. It was shown that patients with grade 2 COPD were at minimal risk of fractures of forearm, arm and vertebrae while those with COPD-4 were at maximum risk. The risk of fractures in COPD-2 was significantly different from that in COPD-3 and 4. The 10-year risk of osteoporotic fractures significantly correlated with BMI and DLCO. It is concluded that the use of FRAX makes it possible to reveal patients with COPD at risk of osteoporotic fractures.

[Bone mineral density in patients with chronic obstructive pulmonary disease].

AIM: To study of bone mineral density (BMD) in patients with chronic obstructive pulmonary disease (COPD). SUBJECTS AND METHODS: 104 patients with COPD were examined. A study group comprised men with a long smoking history. BMD of the lumbar spine in the frontal view and that of the proximal femur (the neck, Ward's area, greater trochanter) were studied by dual-energy X-ray absorptiometry using a Lunar DPX-NT densitometer. RESULTS: Osteoporosis of the lumbar spine was most frequently detected in patients with COPD (37.2%). That of the femoral neck was diagnosed in 19.77% of the patients with COPD. In the advanced stage of COPD, the BMD values in all areas were significantly decreased. CONCLUSION: Osteoporosis is a significant disease in patients with COPD.

[Clinical, instrumental, and laboratory characteristics of early stages of gonarthrosis].

UNLABELLED: AIM. To provide rationale for early basic therapy in patients with gonarthrosis. SUBJECTS AND METHODS. Three hundred and eight female and male patients with early stages of gonarthrosis and 50 healthy individuals were examined. Clinical, X-ray, and arthrosonographic studies were performed; the levels of interleukin (IL) 1beta, IL-1B receptor antagonist, and IL-6 were measured and quality of life was assessed. RESULTS. The findings have led to the conclusion that the early stages of gonarthrosis are characterized by significant clinical symptomatology and lower femur condylar cartilage height; synovitis is frequently revealed by arthrosonography; there is IL-1beta hyperproduction; the quality of life in the patients is worse than that in the healthy individuals from the control group CONCLUSION: Therapy aimed at alleviating the symptoms of gonarthrosis and local inflammation and reducing the rate of articular cartilage degradation and X-ray progression of the disease should be initiated at the earliest, including pre-X-ray, stages of the pathological process.

[Content of C-reactive protein, interleukin-1, interleukin-6 and interleukin-1 receptor antagonist in the blood of patients with early osteoarthrosis of the knee joints].

AIM: To analyse the levels of C-reactive protein (CRP), IL-1, IL-6 and IL-1 receptor antagonist (IRA) in the blood of patients with early gonarthrosis (GA). MATERIAL AND METHODS: Clinical, x-ray and arthrosonographic examinations to stage GA, to identify knee joint synovitis, degree of pain and joint dysfunction were made in 62 males and females with early GA and 20 healthy donors. The levels of CRP, IL-1, IL-6 and IRA were measured with reference to GA stage and activity of the inflammatory process. RESULTS: CRP levels did not differ significantly in synovitis and no synovitis, in different GA stages, in patients and normal controls. Cytokines, except IL-6, were significantly higher in patients with knee joint osteoarthrosis (KJO). The highest levels of IL-1 and the lowest of IRA occurred in the group of roentgen-negative patients versus patients with the pathological process of stage I and II. The cytokines content did not reflect severity of inflammation in the knee joints. CONCLUSION: In early GA inflammation may be not systemic. CRP level does not correlate with activity of local joint inflammation. Most active cartilage tissue degradation takes place at the earliest (preroentgenological) stage of KJO. This stage is most appropriate for initiation of active pathogenetic therapy of the disease.

[Cartilage oligomeric matrix protein, a possible marker of synovitis in early knee joint osteoarthrosis].

Serum levels of cartilage oligomeric matrix protein (COMP) were measured in 88 patients with early knee joint osteoarthrosis and 20 healthy donors. All the patients were examined clinically, by radiography and arthrosonography. COMP was measured with respect to the stage of knee joint osteoarthrosis and to the presence or absence of synovitis. It was lowest in patients showing no changes on X-ray images and free from synovitis. The COMP level increased as the pathogenic process progressed. In patients with synovitis, it was significantly higher than in the absence of joint inflammation. It is concluded that COMP level may be a useful marker of synovitis in early gonarthrosis.

[Osteogenon in therapy of distal radial bone fractures in patients with secondary osteoporosis].

AIM: To assess efficacy of osteogenon in consolidation of solitary fractures of distal part of the radial bone (RB) in patients with secondary osteoporosis (SO) due to rheumatoid arthritis (RA) and chronic renal failure (CRF). MATERIAL AND METHODS: The study group consisted of 7 patients with documented RA and 8 patients with CRF caused by chronic glomerulonephritis or chronic pyelonephritis in the predialysis period. The control group comprised 13 patients (6 and 7 patients, respectively). The patients were matched by clinico-demographic and therapy characteristics. Patients of the study group received osteogen from the fracture diagnosis to its consolidation. RESULTS: Osteogenon has an analgetic effect, improves well being, raises physical activity, reduces duration of fracture consolidation in patients with SO.

[Radiation-modifying effect of oxygen barotherapy in complex treatment of patients with rheumatoid arthritis and osteoarthrosis]. / Radiomodifitsiruiushchii éffekt oksigenobaroterapii v kompleksnom lechenii bol'nykh revmatoidnym artritom i osteoartrozom.

AIM: To evaluate the efficiency of radiotherapy (RT) in combination with oxygen barotherapy (OBT) versus PT used in the complex therapy for rheumatoid arthritis (RA) and osteoarthrosis (OA). MATERIALS AND METHODS: 46 patients with RA and 18 patients with OA were examined, of them 24 patients with RA and 10 with OA received complex therapy involving a course of OBT. The groups of patients had no statistically significant differences in the characteristics of their disease and in the nature of the therapy performed. All the patients received RT as radiation therapy. The patients were followed up for 2 years by assessing basic clinical (the Richi articular index, total pain index, local articular index, pain index for knee and hand joints, circumference of knee and wrist joints) and ultrasound (the magnitude of exudate, an erosive process, osteophytes, articular fissure stenosis, the thickness of the synovial membrane and cartilage) indices. RESULTS: Use of OBT in patients with RA and OA just before articular radiation therapy brought about a more pronounced positive effect of complex therapy. In addition to significant positive changes in clinical parameters, there was a slow progression of a pathological process, as evidenced by ultrasound study. CONCLUSION: By reducing needs for drug therapy, for nonsteroidal antiflammatory drugs in particular, OBT produces a pharmacoeconomic effect.

[Radionuclide diagnosis of local inflammation in patients with rheumatoid arthritis]. / Radionuklidnaia diagnostika lokal'nogo vospaleniia u bol'nykh revmatoidnym artritom.

Radionuclide scintigraphy with osteotropic radiopharmaceuticals labelled 99Tc proved highly sensitive in assessment of local inflammation. Osteoscintigraphy allows detection of preclinical and pre-x-ray lesions in the joints in RA and assessment of the treatment efficacy. Characteristic signs of the radionuclide distribution and accumulation can serve as a prompt in differential diagnosis of RA, DOA, reactive and gouty arthritis.