[Efficacy and safety of levilimab in the treatment of patients with rheumatoid arthritis].

AIM: Evaluation in real clinical practice of the effectiveness and safety of levilimab therapy in patients with highly and moderately active rheumatoid arthritis (RA). MATERIALS AND METHODS: A prospective observational study (6 months) involving 35 patients with RA (29 women and 6 men, mean age 53.17±13.2 years) who were treated at the Ochapovsky Regional Clinic Hospital of Krasnodar Region. All patients included in the study were prescribed the drug levilimab (Ilsira). RESULTS: After 1 month of observation, there was a decrease in the clinical and laboratory activity of the process in the form of a decrease in the number of painful joints - 17.0 (14.0; 20.0) vs 8.0 (6.0; 10.0); p=0.000001, number of swollen joints - 3.0 (2.0; 4.0) vs 0.0 (0.0; 0.0); p=0.000002, reduction in pain intensity according to visual analog scale - 60.0 (60.0; 70.0) mm vs 30.0 (20.0; 40.0) mm (p=0.000001). Also, by the end of the first month of therapy, there was a decrease in clinical activity indices DAS28-ESR by 43%, SDAI by 60%, CDAI by 55%. Positive dynamics of laboratory parameters were noted - a decrease in erythrocyte sedimentation rate by 76%, a decrease in C-reactive protein level by 98%. By the 6th month of therapy, a decrease in RF by 36% and ACCP by 11% was recorded, but the dynamics of these indicators did not reach statistical significance. By the end of 4 weeks of treatment, 24 (68.6%) patients showed an increase in the level of total blood cholesterol - 5.1 (3.91; 6.0) mmol/L vs 6.1 (4.99; 7.07) mmol/L (p=0.000006), while 11 (45.8%) patients from this group had initially elevated cholesterol levels (6.4±0.6 mmol/L). In 5 (14.3%) patients, an increase in alanine aminotransferase (ALT) was recorded in the 4th week - 17.0 (11.0; 25.0) U/L vs 32.0 (22.0; 43.0) U/L (p=0.000062) and aspartate aminotransferase (AST) - 19.0 (14.0; 24.0) U/L vs 25.0 (18.0; 36.0) U/L (p=0.000171), in 1 (2.85%) of the patient, an increase in ALT and AST above normal was noted (ALT 144 U/L, AST 52 U/L), which required discontinuation of levilimab. In 2 (5.7%) patients, by the end of the 4th week a decrease in the absolute number of neutrophils was registered - 3.2 (2.6; 4.0)×10E9/L vs 2.3 (2.0; 2.5)×10E9/L (p=0.002), which did not require discontinuation of treatment, since the number of cells remained more than 1×10E9/L. During treatment with levilimab 162 mg subcutaneously once a week, the proportion of patients taking prednisolone decreased from 46% at the start of therapy to 11% at the end of 6 months of therapy. CONCLUSION: Levilimab is a highly effective drug for the treatment of patients with highly and moderately active RA and has a favorable tolerability and safety profile.

[Efficacy of manual correction of cervical spine osteochondrosis in the treatment of arterial hypertension syndrome and prediabetes]. / Effektivnost' manual'noi korrektsii osteokhondroza sheinogo otdela pozvonochnika v terapii sindroma arterial'noi gipertenzii i prediabeta.

Cardiovascular diseases and diabetes mellitus, debuting as arterial hypertension (AH) syndrome and prediabetes, are common types of chronic non-communicable processes, that are the leading cause of death in the world. The main treatment method for above mentioned disorders, according to the current guidelines, is pharmacotherapy. However, it is possible to effectively apply non-pharmacological correction methods, aimed at the probable etiological factor and inversive mechanism involved in AH maintenance, in the early stages when no permanent changes are maintaining a high level of blood hypertension (BH) and glycemia. Frequently, this mechanism is hypoxia in the vertebral arteries system due to cervical spine osteochondrosis. OBJECTIVE: To evaluate the therapeutic effect of non-pharmacological methods of restoring brainstem blood supply in patients with AH and prediabetes. MATERIAL AND METHODS: The number of patients equal 125 (57 men and 68 women, mean age 63.3±11.5 and 65.4±11.8 y.o., respectively) with prediabetes and 1st degree of AH without target organs damage, among whom 102 patients with prehypertension or 1st degree of hypertension and 24 ones with 2nd degree of hypertension, were examined. The original method of manually restoring brainstem blood supply developed in the Shishonin's Clinic was applied to all patients. The control group included patients with the same disorder, who did not receive manipulations. Blood pressure (BP) measurement, ultrasound and triplex ultrasonography of vertebral arteries, biochemical blood test, and estimation of glycemia and glycated hemoglobin were performed. RESULTS: All patients of the study group had decreased levels of systolic BP (by 23.8±10.7 mm Hg for men and 32.8±11.9 mm Hg for women), an increase of flow velocity in vertebral arteries (by 20.6±7.5 and 21.5±7.2 cm/s, respectively), a decrease of glycated hemoglobin concentration (by 0.32±0.51 and 0.34±0.41%, respectively). In the comparison group, there were no patients with improvement in these indicators. CONCLUSION: The effectiveness of the author's manual method of cervical spine osteochondrosis correction in the reduction of BP and glycemia levels in the early stages of the disease is shown.

[Theory of centralized aerobic-anaerobic energy balance compensation and non-pharmaceutical treatment methods of arterial hypertension]. / Teoriya tsentralizovannoi kompensatsii aerobno-anaerobnogo energeticheskogo balansa i nelekarstvennye metody lecheniya arterial'noi gipertenzii.

Several chronic non-communicable diseases are associated with arterial hypertension and are closely related to increased blood pressure. The theory of centralized aerobic-anaerobic energy balance compensation (TCAAEBC) was formulated in connection with the above-mentioned processes. This theory, including the hypothesis of the «egoistic brain¼, is a broader concept. The key point of TCAAEBC is hypoxic anaerobic metabolism, which affects reflex vascular zones, including the neurons of the respiratory and cardiovascular centers of the rhomboid fossa of the medulla oblongata. Hypoxia correction using manual techniques, physical exercises, and other non-pharmaceutical methods under certain conditions can stabilize the level of blood pressure and has a curative effect in the case of arterial hypertension syndrome.

[Method of manual-physical correction in the treatment of hypertensive disease and normalization of psychoneurological status in patients with degenerative-dystrophic processes of the musculoskeletal system]. / Metod manual'no-fizicheskoi korrektsii pri lechenii gipertonicheskoi bolezni i normalizatsii psikhonevrologicheskogo statusa u patsientov s degenerativno-distroficheskimi protsessami oporno-dvigatel'nogo apparata.

There are some non-communicable diseases (NCD) associated with arterial hypertension (AHT) that are cured after recovery from AHT. Recently confirmed the theory of centralized aerobic-anaerobic energy balance compensation (TCAAEBC) originated some NCDs with the obstructions of arterial blood flow access to the rhomboid fossa. For some sergeants, this has already been demonstrated. Since neurological NCDs are similarly considered by TCAAEBC, it is logical to analyze dynamics of such musculoskeletal neurological problem as isolated musculoskeletal chest pain (IMCP) in connection with the therapy based on TCAAEBC. We retrospectively evaluated the medical records of adult patients with AHT, simultaneously suffering from IMCP. All these patients underwent complex treatment including manual techniques that restore arterial blood flow to the rhomboid fossa, followed by therapy that strengthens the muscular corset primarily of the cervical region. This, in addition to the normalization of AHT, led to a decrease in the musculoskeletal pain syndrome. The dynamic of pain was recorded according to four questionaries - Oswestry Disability Index (ODI) Hospital Anxiety and Depression Scale (HADS), Numerical Rating Scale (NRS), and the Quality-of-life assessment questionnaire (SF-12). The collected data were analyzed with the Wilcoxon signed-rank test, which confirms the recovery of the patients from both AHT and IMCP.

[Physical methods of correction of arterial hypertension: modern concepts. (A literature review)]. / Fizicheskie metody korrektsii arterial'noi gipertenzii: sovremennye predstavleniya. (Obzor literatury).

Arterial hypertension is a major risk factor for cardiovascular disease, affecting a large proportion of the population worldwide. The study of the listed literature made it possible to assess the effectiveness and necessity of physical exercise in the treatment of hypertension syndrome, including various types of exercise, intensity, duration, and frequency, since drug treatment is not enough for successful therapy. To prevent and treat hypertension, a comprehensive approach is required, including aerobic exercise, which will lower blood pressure by dilating blood vessels.

Comparative study of the serum hepcidin level of patients with pneumonia in COVID-19 and Pneumocystis pneumonia.

In the context of a pandemic caused by the SARS-CoV-2 virus, for a patient with respiratory symptoms and bilateral lung damage, COVID-19 becomes the first disease in the differential diagnostic search. Pneumonia in COVID-19 shares many characteristics with Pneumocystis pneumonia. One of the possible markers of the severe course of COVID-19 is hepcidin, a peptide hormone that negatively regulates iron metabolism. There are no data on the value of hepcidin in Pneumocystis pneumonia in the published scientific literature. The purpose of this study is to conduct a comparative analysis of hepcidin in the blood serum of patients with pneumonia in COVID-19 and Pneumocystis pneumonia to clarify their pathogenetic features. A case-control observational study was conducted, including 68 patients with pneumonia in COVID-19 and 44 patients with HIV infection and Pneumocystis pneumonia (PCP/HIV). Determination of hepcidin was carried out by ELISA using the ELISA Kit for Hepcidin. Statistical data processing was carried out using the MedCalc 19.2.6 software. Results. Comparative analysis of serum hepcidin levels in the study groups showed that hepcidin is statistically significantly higher in PCP/HIV than in COVID-19 - the median value is 22 times higher (p <0.0001). When examining the ROC curve for hepcidin, it was found that this biomarker has a high diagnostic potential and indicates a higher probability of COVID-19 than PCP/HIV at values ≤768.044 pg / ml. In the context of the COVID-19 pandemic, it is necessary to remember about other diseases that manifest themselves with a similar clinical and radiological picture. COVID-19 and PCP/HIV share many similarities; the peptide hormone hepcidin has shown itself as a potential differential diagnostic marker between them, and therefore the need for further studies of hepcidin is justified, taking into account the severity of the course of COVID-19, the presence of comorbidities and in a comparative aspect with pathologies that «mimic¼ under COVID-19.

[Iron metabolism and indicators reflecting its changes in pulmonary tuberculosis (literature review).]

Iron is an essential element for human and bacteria, including mycobacterium tuberculosis. Over review includesthe literature on the problem of iron metabolism in patients with tuberculosis and with comorbid pathology HIV infection and tuberculosis. The literature was searched for when writing this review using the RSCI, CyberLeninka, Scopus, Web of Science, MedLine, PubMed databases using the following keywords: iron, ferritin, hepsidin, lactoferrin, tuberculosis, pneumonia, HIV infection. Iron compounds are involved in many redox reactions: oxygen transport, cellular respiration, the trichloroacetic acid cycle, DNA biosynthesis, and others. The ratio of intracellular and extracellular iron in the body is regulated by the low molecular weight hormone hepcidin, the mechanism of action of which is to block the function of ferroportin, an exporter of iron from cells, which leads to the accumulation of the intracellular iron pool and the prevention of the toxic effect of free iron. The role of iron in the interaction of the human body with ferro-dependent bacteria has been established. Iron is necessary for the growth and development of bacterial cells, and the methods for its production from the host are different. Information on the effect of iron metabolism on pulmonary tuberculosis is scarce and contradictory: some authors have identified a decrease in hemoglobin and transferrin in combination with elevated levels of ferritin in patients with tuberculosis; according to other sources, hyperferritinemia in tuberculosis cannot be predictive, but is a marker inflammation. At the same time, there are studies that indicate a significant increase in ferritin in patients with disseminated tuberculosis relative to other clinical forms. Currently, the incidence of tuberculosis in patients with HIV infection is increasing, while diagnostic tests are not very informative. The search for diagnostic markers in terms of iron metabolism may open up new possibilities for the diagnosis of pulmonary tuberculosis.

[Hereditary afibrinogenemia: A literature review and clinical observations]. / Nasledstvennaia afibrinogenemiia: obzor literatury i klinicheskie nabliudeniia.

Afibrinogenemia is a rare congenital coagulopathy that leads to life-threatening bleeding. In afibrinogenemia, plasma fibrinogen levels are less than 0.1 g/L. The clinical manifestations of the disease can be both bleeding and thromboses of different localizations, which is determined by the multifunctional role of fibrinogen in hemostasis. The described cases demonstrate different clinical phenotypes of the disease. In both cases the diagnosis was confirmed by genetic examinations that revealed homozygous mutations in the fibrinogen A genes. The nature of the mutations assumes consanguineous marriages, as confirmed by the results of a genealogical analysis. Fibrinogen preparations are promising in treating afibrinogenemia in Russia.

Neuroprotective effects of glycine for therapy of acute ischaemic stroke.

The aim of this randomized, double-blind, placebo-controlled trial was to assess the safety and the efficacy of the pharmaceutic drug glycine in 200 patients with acute (<6 h) ischaemic stroke in the carotid artery territory. Fifty patients received placebo, 49 glycine 0.5 g/day, 51 glycine 1.0 g/day and 50 glycine 2.0 g/day for 5 days in each group. The efficacy of glycine was assessed by clinical analysis, by an enzyme-linked immunosorbent assay of levels of blood serum autoantibodies to NMDA-binding proteines, by detection of excitatory (glutamate, aspartate) and inhibitory (glycine, GABA) amino acid concentrations and lipid peroxidation products (TBARS) in CSF. The trial confirmed the safety profile of the glycine treatment. Slight sedation was observed in 9 patients (4. 5%) as a side-effect. Other marked side-effects or adverse events were absent. The glycine treatment at the dose of 1.0-2.0 g/day was accompanied by a tendency to a decreased 30-day mortality (5.9% in 1. 0 g/day glycine and 10% in 2.0 g/day glycine groups vs. 14% in the placebo and 14.3% in 0.5 g/day glycine groups), to an improved clinical outcome on the Orgogozo Stroke Scale (p < 0.01) and the Scandinavian Stroke Scale (p < 0.01) and to a favourable functional outcome on the Barthel index (p < 0.01 in 1.0 g/day glycine vs. placebo group in patients with no or mild disability). An early normalization of autoantibody titres to NMDA-binding proteins in serum was found (p < 0.01 vs. placebo), a reduction of glutamate and aspartate levels (p < 0.05 vs. placebo), an increase in GABA concentrations (p < 0.01 vs. placebo in severe stroke patients) and also a reduction of TBARS levels (p < 0.05 vs. placebo) in CSF by day 3. Thus, the trial suggests that sublingual application of 1.0-2. 0 g/day glycine started within 6 h after the onset of acute ischaemic stroke in the carotid artery territory is safe and can exert favourable clinical effects. These results will be verified in further trials with a larger number of patients.