Том 8, № 4 (2022)

Currently, for the prevention and treatment of thrombosis, drugs from the group of glucose K antagonists (VKAs) and direct oral anticoagulants are widely used. Prolonged significant antithrombotic therapy (ATT) increases the risk of hemorrhagic complications. Purpose of the study was analysis of possible causes of the development of intracranial hemorrhagic complications against the background of prolonged oral anticoagulant therapy in real clinical practice. Material and methods. A prospective clinical study included an analysis of intracranial hemorrhagic complications during prolonged oral antithrombotic therapy on an outpatient basis. We studied the presence of probable factors that could lead to the development of hemorrhagic complications, the outcomes of complications and their frequency, data on the drug, indications for the appointment of ATT, concomitant diseases and their pharmacotherapy, the level of international normalized ratio (INR) for patients receiving VKA, features of pharmacogenetic profile of the patient, as well as the level of blood pressure (BP) when the patient is admitted to the hospital. Results. At admission, 93,5% of patients had arterial hypertension without reaching the target BP value, (in 60,9% of cases, grade 3 hypertension) was recorded at admission, requiring pharmacotherapy with antihypertensive drugs. Concomitant therapy was represented by drugs that interact with the level of cytochrome 450 with the antithrombotic agents used. Laboratory monitoring of drug hypocoagulation during warfarin therapy showed that at the time of hospitalization the INR level was above 3.0 units in 91,67% of cases. In the group of patients with ICH, polymorphism of the MORHC/Tl MDR11G/T) genes may have influenced the development of bleeding. Conclusion. Insufficient adherence of the patient to pharmacotherapy, underestimation of kidney function leads to adverse consequences in the form of bleeding, increased mortality and, consequently, increased health care costs.

One of the most significant polymorphisms of the vitamin D receptor (VDR) gene that modulates the biological effects of this vitamin is the single nucleotide polymorphism BsmI (A>G) of the VDR gene. Objective: to determine the possible genetic contribution to the pleiotropic effects of vitamin D3 after correction of serum 25(OH)D insufficiency and deficiency by loading and maintenance doses of cholecalciferol in postmenopausal women. Material and methods. During the period from October 2018 to March 2020, 100 late postmenopausal patients were performed: diagnosis of comorbid pathology, molecular genetic study of the BsmI (A>G) polymorphism of the VDR gene by PCR-RT, evaluation of serum 25(OH)D level by the ECLIA method, assessment of modified menopausal index (MMI), mental status (MMSE scale), and quality of life (SF-36 questionnaire). To correct the level of 25(OH)D in the blood serum, an aqueous solution of cholecalciferol (Aquadetrim) was used in standard doses recommended by the Russian Association of Endocrinologists. Results. The frequency distribution of the BsmI polymorphic marker genotypes of the VDR gene was 13, 47, and 40% for minor homozygote AA, heterozygote AG, and homozygote GG, respectively. Patients with the GG-genotype of the BsmI polymorphic marker of the VDR gene demonstrated lower values of the Charlson comorbidity index (p=0,042), severity of menopausal disorders (p=0,023) and higher quality of life scores for pain intensity that can limit daily activity (p=0,025) compared to patients with Aa/AG genotypes. Women homozygous for the minor A allele demonstrated an increase in cognitive abilities according to the MMSE scale (p=0,001) and a decrease in the severity of psychoemotional disorders of the MMI (p=0,027) after the use of standard loading and maintenance doses of cholecalciferol. Conclusion. A possible protective role of the G allele of the BsmI polymorphic marker of the VDR gene in relation to the Charlson comorbidity index, menopausal disorders, and quality of life in late postmenopausal patients has been demonstrated.

The developers of KDIGO clinical practice guidelines for acute kidney injury (AKI) believe that, in addition to serum creatinine, the introduction of new biomarkers is necessary to assess the risk of developing the disease. The aim of the study is examination and estimation the prognostic and diagnostic significance of NGAL and KIM-1 markers in the blood in patients with AKI receiving antibacterial therapy. Material and methods. The incidence of AKI was estimated in 276 postoperative patients of the Department of urology and coloproctology using a prospective analysis method in accordance with the KDIGO clinical practice guidelines criteria after antibiotics were prescribed. The criterion for selecting patients in the study was antibiotic therapy initiation. Estimation of the level of serum concentrations of new markers, creatinine and proteinuria was carried out before the prescription of an antibiotic, 24-48 hours after the prescription of an antibacterial drug, and in patients with AKI -after 72-96 hours, and then once a day until the restoration of kidney function. Results. The critical KIM-1 level for the development of AKI 24-48 hours after antibiotic administration was И17 pg/mL (OR 24,2; 95% CI: 7,2-75,8). The critical level of NGAL as determined by the ROC analysis was «103 ng/mL before antibiotics prescription (OR 15,1; 95% CI: 5,8-39,3), p <0,0001. Conclusion. Fixing the levels of NGAL and KIM-1 in patients at risk of AKI developing can improve the prognosis of the development and diagnosis of this disease, which in turn creates background for improving the effectiveness of therapy and reducing the risk of serious nephrotoxic reactions during antibacterial drugs treatment. The level of NGAL less than 103 ng/ml can serve as a prognostic factor for the development of AKI in the appointment of antibacterial agents. An increase in serum KIM-1 of more than 117 pg/ml during the first 24-48 hours after antibiotics prescription can be considered as an early diagnostic criterion for the development of AKI.

Urinary tract (UT) infections are among the most common bacterial diseases worldwide and the most common cause of antibiotic prescriptions and infection-related hospitalizations. The aim of the study: to perform a clinical and economic evaluation of the implementation of a local UT sanitation protocol based on the analysis of the spectrum dynamics and sensitivity to fosfomycin and fluoroquinolones of leading microorganisms isolated from the urine of patients admitted for elective hip (THA) or knee (KJ) arthroplasty during the period 2018-2020. Material and methods. A retrospective analysis of urine microbiological findings in patients admitted for elective hip or knee arthroplasty between 2018 and 2020 was performed. All positive results without regard to the obtained bacterial titer were included in the study. Leading pathogens included microorganisms with a proportion of more than 5%. Pharmacoeconomic modeling of fosfomycin and fluoroquinolones use for UT sanitation of was performed. Medical costs for a course of UT sanitation with these antibiotics were calculated, efficiency of each strategy was calculated, cost-effectiveness ratio was calculated, cost-minimization analysis was carried out. Results. During the study period 872 positive urine cultures were obtained and 1266 microorganisms were isolated. E coli (43%), K pneumoniae (16%), E faecalis (15%) were leading in the spectrum of uropathogens. The proportion of ESBL producers, among E colisolates, was 32,2%, K pneumoniae -37,7%. The majority of E coli, K pneumoniae strains retain sensitivity to fosfomycin (99 and 79%), sensitivity to fluoroquinolones is much lower (53 and 46%), the proportion of E. faecalis strains sensitive to ciprofloxacin was 76,5%. Direct medical costs for a course of UT sanitation with fluoroquinolones are 32% higher than with fosfomycin. The strategy efficiency of using fosfomycin (EF) was 70%, and fluoroquinolones - 47%; the cost-effectiveness ratio (CER) for fluoroquinolones was 2,2 times higher than for fosfomycin. Conclusion. Taking into account the spectrum of pathogens of UT infection, their sensitivity to antibacterial agents, data of the pharmacoeconomic study, we can conclude that it is reasonable to include fosfomycin in the local protocol for UT sanitation in orthopaedic patients.

Type 2 diabetes mellitus (DM 2) is characterized by a high risk of developing coronary heart disease, myocardial infarction, stroke, heart failure. The aim: assessment of the condition of the coronary arteries in persons with angina pectoris in combination with or without DM 2. Material and methods. The data are analyzed and the results of a clinical study conducted in a medical institution of the Republic of Ingushetia are compared. The simultaneous clinical study included 145 men and women aged 45 to 74 years with stable angina pectoris, of which 70 patients (34 men and 36 women) had concomitant DM 2. Results. According to the localization of stenosis in the segments of the coronary arteries, it can be concluded that in men with angina pectoris and DM 2 in all three segments (proximal, middle and distal), its frequency is on average comparable, and is 30-41%. In women with angina pectoris and DM 2, stenosis of the distal segment is detected most often (in every second), while stenosis of the remaining segments is no more than 33%. In men with stress angina without DM, stenosis of the proximal segment is detected in every second patient, while stenosis of the distal segment is detected 3,5 times less often. Conclusion. According to coronary angiography, men and women with DM have moderate and severe coronary artery lesions. There is a more pronounced lesion of the trunk of the left coronary artery and the right coronary artery compared with patients with angina pectoris without DM. There is a predominant lesion of the distal coronary arteries. The total number of points on the anatomical SYNTAX Score scale in diabetic patients was 20% higher compared to patients without DM.

Janus kinase (JAK) inhibitors are included in both domestic and a number of international guidelines for novel coronavirus infection treatment. In order to assess the safety of the use of this class of drugs for preventive pathogenetic therapy of COVID-19, a systematic review with a metaanalysis of the results was carried out. Material and methods. Using queries in international and Russian databases, we searched for controlled trials of baricitinib and tofacitinib recommended for use in Russia as a preventive therapy for COVID-19 mild and moderate clinical cases. Result. Data were obtained from three randomized clinical trials. A meta-analysis of their results regarding the total number of serious adverse events and adverse events belonging to the class «Infections and invasions» showed statistically significant data on the greater safety of baricitinib and tofacitinib in relation to the risks of these events compared with standard therapy. The risk ratio for serious adverse events in the control groups was 0,82 (95% CI: 0,69-0,96; p=0,02), the risk ratio for «Infections and invasions» was 0,78 (95% CI: 0,63-0,97, p=0,03); in both cases the result was in favor of the use of JAK inhibitors. Conclusion. Performing of various design studies in a wider patient population will allow to make more accurate assessment of the risks of developing secondary bacterial infections against the background of short-term use of JAK inhibitors as part of the preventive pathogenetic therapy for COVID-19.

The article presents a clinical case of a combination of anemia of chronic diseases and a heterozygous mutation His63Asp (H63D) of the HFE hemochromatosis gene in a female patient. The observed patient had no clinical signs of hemochromatosis, but hyperferritinemia was observed, and the carriage of the heterozygous mutation His63Asp (H63D) of the HFE hemochromatosis gene was also determined. The heterozygous H63D mutation variant does not confirm the diagnosis of hereditary hemochromatosis, however, its carriers may show a persistent increase relative to the reference values of ferritin levels (>500 ng/ml) and serum transferrin saturation coefficient, which must be taken into account when interpreting laboratory data and making a diagnosis.

One of the reasons for the development of restrictive cardiomyopathy is amyloidosis of the heart, leading to free, refractory to therapy heart failure. Despite the identified identified heart damage in amyloidosis, it is diagnosed quite late due to the absence of characteristic symptoms. Sometimes the diagnosis is verified according to the pathological and anatomical autopsy. The article describes a clinical case of systemic amyloidosis, which debuted with resistant heart failure and arrhythmias in the form of atrial fibrillation. Early screening for amyloidosis is very important as it allows for rapid initiation of specific therapy. The presented observation confirms the importance of early screening for amyloidosis, which allows timely initiation of specific therapy.

In modern conditions, the appointment of rational pharmacotherapy for patients is far from being the easiest task. Lifestyle changes, as well as a gradual increase in life expectancy of the population, have led to the fact that the previously existing approach «one patient - one disease» is outdated and cannot be used in clinical practice. In this regard, the selection of an effective and at the same time safe drug therapy for such patients with several diseases at the same time requires a doctor to have a wide range of knowledge both in terms of pathophysiology and clinical pharmacology, in particular, knowledge of drug safety and organoprotective properties of medicines is of particular importance. The proposed article highlights the issues of effective and safe pharmacotherapy in comorbid patients with an emphasis on cardiovascular diseases. It also presents a clinical case that discusses the rational pharmacotherapy of arterial hypertension, namely the use of the thiazide-like diuretic indapamide as part of combination therapy, in a patient with obesity and dyslipidemia.