LEADING ARTICLE
The purpose of the study: to develop a general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary heart disease (CHD). Materials and methods. Examination of 60 patients with CHD: stable angina pectoris of I-III functional classes was performed. According to the standard general clinical methods for verifying the diagnosis were used: ECG, Doppler echocardiography, coronary angiography, lipid profile, complete blood count, coagulogram, renal, hepatic complex. Also the condition of stress-realizing and stress-limiting systems of the functional system of adaptation was deeply examined in patients: determination of the level of personal anxiety by the method of questioning, determination of the concentration of cortisol, insulin, cAMP and cGMP in blood serum by the method of enzyme immunoassay; determination of the endothelial and inducible nitric oxide synthase levels in erythrocyte lysate by the method of enzyme immunoassay; the study of ATP and ADP concentrations in blood serum and erythrocytes, also the study of 2,3-DFG concentration in erythrocytes by spectrophotometric methods. The individual reactivity of blood leukocytes’ mitochondria of patients was estimated in vitro under the influence of metabolic drugs (trimetazidine, meldonium, cytoflavin) by confocal microscopy according to the technique developed and patented by us (mitochondria were stained with pyrene). The materials were processed statistically. Results. Two variants of the leukocyte mitochondrial response in patients with CHD to the introduction of metabolic correctors in vitro were found — in the form of their activation or inhibition, depending on numerous parameters of the initial state of patients, which served as the basis for the development of a general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary heart disease. According to this concept, the individual reactivity of a patient with CHD to the administration of a metabolic drug depends on the initial state of the functional adaptation system, which can be determined by the activity of stress-realizing and stress-limiting systems (cortisol/insulin ratio, serum cAMP/cGMP, eNOS, iNOS of erythrocyte lysate) and by the degree of preservation of the structure and function of effector organs. It is appropriate to prescribe drugs that stimulate energy metabolism in cells only to patients with initial hypoergosis, reduced mitochondrial activity at the phases of activation or resistance of the general adaptation syndrome, while maintaining reserves for energy adaptation, by short courses. Conclusion. A general concept of a patient-oriented approach to the use of drugs with cytoprotective activity in patients with coronary artery disease has been developed, according to which metabolic correctors should be prescribed in short courses, provided that individual reserves for energy adaptation are preserved in patients with initial mitochondrial hypoergosis in the activation or resistance phase of the general adaptation syndrome.
CARDIOVASCULAR SURGERY
Aim: to improve surgical treatment results in patients with primary permanent vascular access. Materials and methods: the results of the treatment of 168 patients with native arteriovenous radiocephalic fistula were analyzed. The results of treatment within 1 year were tracked According to the observation results, patients were divided into 2 groups: the 1st group — patients who did not develop thrombosis of an arteriovenous fistula for 1 year of hemodialysis, and the 2nd group — patients who had vascular access due to thrombosis during the first year. Results: the factors with the greatest degree of influence on the risk of thrombosis during time periods up to 6 months and from 6 months to 1 year were identified. However, not all of them by their characteristics, satisfied the conditions for constructing a multidimensional logistic regression and a predictive model based on it. On the basis of the identified factors, prognostic models have been established that assess the risk of thrombosis of permanent vascular access at time intervals of up to 6 months and from 6 months to 1 year. Conclusion: the formation of a predictive model considering a variety of factors can give an answer to the risk of thrombosis formation and determine ways to reduce it.
INFECTIOUS DISEASES
Actuality. Herpesvirus diseases are characterized by a wide distribution, polymorphism of clinical manifestations and severity of the course up to the development of lethal outcomes. The purpose of the study: to identify the features of the damage to the nervous system in herpes infections in modern conditions. Materials and methods. Under observation there were 60 patients with lesions of the nervous system due to herpesvirus infections, hospitalized in the Infectious Clinical Hospital in 2015-2021. Results and discussion. The analysis of the main clinical and laboratory parameters was carried out and the features of the damage to the nervous system in herpesvirus infections were established. Conclusion. The results of the study showed that patients with VZV infection prevailed among all patients — 78.3%. The range of lesions of the nervous system was presented in the form of serous meningitis (48.3%), meningoencephalitis (43.3%), encephalitis (8.4%).
GERONTOLOGY AND GERIATRICS
The postgraduate education of doctors in the principles of rational pharmacotherapy, conducted on the educational program «Polypragmasia in a therapeutic and preventive organization: a problem and a solution» of 36 academic hours, allowed to reduce the total number of simultaneously prescribed medications in elderly patients of a cardiological profile in a gerontological hospital (the number of medications received by patients older than 75 years before and after training, respectively 9.48±2.6 vs 7.12±1.9, p<0.001). A decrease in polypragmasia contributed to a decrease in the frequency of suspected unforeseen serious adverse reactions, which included falls associated with taking medications. The simultaneous introduction of Safety Protocols, Standard Operating Procedures for identifying patients at high risk of falling and conducting incident analysis led to the analysis of each case of an elderly and senile patient falling in a hospital and a review of the treatment received.
TRAUMATOLOGY AND ORTHOPEDICS
Relevance. Relapses of deformities of the lower extremities after their surgical correction in patients with hypophosphatemic rickets reach 95%, which requires improved approaches to the treatment of this pathology. The aim of the study was to study the efficacy and safety of staged surgical treatment, including osteotomy, sequential transosseous and intraosseous blocking osteosynthesis-reinforcement, in a patient with completed growth, suffering from X-linked dominant form of hypophosphatemic rickets. Materials and methods. A patient with completed growth with an X-linked dominant form of hypophosphatemic rickets at the age of 21–28 years underwent 11 operations on the lower extremities due to their pronounced multiplanar multiapical deformities, segment length inequality against the background of osteomalacia. Simultaneous corrections were made on the femurs using osteotomies and intraosseous blocking osteosynthesis-reinforcement. On the bones of the lower legs, staged corrections were performed using osteotomies, bone autoplasty, sequential transosseous and intraosseous blocking osteosynthesis-reinforcement. Results. The inequality of the lengths of the femurs and lower legs is eliminated. The axes of the lower extremities were corrected to normal. The patient's height has increased by 8 cm. He walks up to 25,000 steps a day without additional support. When observing the patient for 8 years, no relapses of deformities and other complications were noted. Conclusion. Our experience testifies to the high efficiency and safety of staged surgical treatment using osteotomies, transosseous and intraosseous blocking osteosynthesis-reinforcement for the correction of pronounced multiplanar multiapical deformities, inequality in the length of the bones of the lower extremities against the background of osteomalacia in the patient with completed growth, suffering from an X-linked dominant form of hypophosphatemic rickets.
PHARMACOGENETICS
Relevance. The reasons for the unsatisfactory results of treatment of atherosclerotic diseases of the arteries of the lower extremities are associated not only with the limited possibilities of conservative and operative methods of treatment, but also with the lack of objective criteria that allow predicting the course of this pathology and the effectiveness of planned therapeutic measures. The purpose of the study. Improving the results of treatment of patients with atherosclerosis of the arteries of the lower extremities on the basis of predicting the effectiveness of conservative and surgical treatment, taking into account genetic polymorphism. Materials and methods. The results of treatment and specially conducted studies were analyzed in 226 patients with atherosclerosis of the arteries of the lower extremities aged 40 to 89 years. The median age was 66.7 years. There were 157 males (69.5%) and 69 females (30.5%). Standard research methods were aimed at determining the biochemical status and assessing the state of arterial blood flow of patients. Genetic studies of 17 genes in the blood serum of patients were carried out using the polymerase chain reaction method. Results. It was revealed that the genes encoding elements of the renin-angiotensin-aldosterone system (angiotensinogen genes AGT:704 and AGT:521, angiotensin II receptor AGTR1:1166 and AGTR2:1675, aldosterone synthetase CYP11B2) have clinical significance; genes regulating intracellular ion homeostasis (G protein beta-3 subunit GNB3, alpha-adductin ADD1:1378); genes determining the structure of endothelial NO synthase (NOS3:894 and NOS3:786); hemostasis genes (F5 Leiden factor, prothrombin F2, plasminogen activator inhibitor PAI-1, platelet receptor fibrinogen GPIIIA, fibrinogen FGB); cytochrome P-450 CYP2D6 and CYP2C9 genes; genes of glycoprotein P MDR1. The dependence of gene polymorphism on the level of occlusion and the stage of the disease has been established. In order to determine the possibilities of predicting the effectiveness of therapeutic measures, a comparative assessment of the indicators of genetic testing was carried out, depending on the result of conservative therapy and surgical treatment. Conclusions. Genetic polymorphism determines the progression of obliterating atherosclerosis of the arteries of the lower extremities and is associated with the effectiveness of conservative and surgical therapeutic measures. The use of genetic testing using methods of multidimensional statistics makes it possible to predict the effectiveness of reconstructive operations in patients with chronic lower limb ischemia, taking into account not only clinical, laboratory and instrumental data, but also on the basis of changes in gene polymorphism.
Relevance. Defects of innate and acquired immunity, intestinal microflora disorders, environmental factors against the background of genetic predisposition play a role in the development of ulcerative colitis and Crohn's disease. The question of the influence of genetic factors on the appearance of these diseases remains open. The purpose of the study. To develop approaches to assessing the course of ulcerative colitis and Crohn's disease, taking into account mutations of genes regulating tumor necrosis factor (TNF-a), vascular endothelial growth factor (VEGFA), interleukin-6 (IL-6) and polymorphic variants of the CARD15/NOD2 gene (Gly908Arg, Leu3020insC). Materials and methods. Polymorphic gene variants were studied in 50 patients with ulcerative colitis aged 18 to 79 years, 28 men (56%) and 22 women (44%). Age: under 35 years (38%), from 36 to 50 years (30%), over 51 years (32%). According to the extent of the pathological process, patients with total colitis prevailed (84%). Patients with left-sided colitis (14%) or proctitis (2%) were less common. In 28 patients (56%), chronic continuous course was observed, in 14 (28%) — chronic recurrent, in 8 (16%) — acute course. According to the severity of the attack: moderate (42%), light (28%) and heavy (32%) attacks were observed less frequently. Among the examined patients, surgical intervention was performed in 8 patients (16%), the remaining patients (84%) were treated conservatively. The diagnosis of ulcerative colitis was made on the basis of clinic data, ultrasound, colonoscopy, visual assessment of the pathological process during surgery and histological examination of the surgical material. The frequency of two polymorphic variants of the CARD15/NOD2 gene (Gly908Arg, Leu3020insC) was studied in 40 patients with Crohn's disease. All patients were admitted to the surgical hospital in an emergency. The diagnosis of Crohn's disease was made on the basis of clinic data, ultrasound examination, visual assessment of the pathological process during surgery and histological examination of the surgical material. The studies were conducted within a period of 1 to 10 years from the moment of discharge from the hospital. Results. In ulcerative colitis, mutations of the gene encoding IL-6 for the homozygous variant G174G occurred in 24%, mutations of the gene encoding VEGFA for the homozygous variant C634C occurred with a frequency of 12%. Mutations in the gene encoding tumor necrosis factor (TNF-α) were not detected in the study group. IL-6 gene mutation is almost equally found among groups of patients who underwent surgery and patients after conservative treatment, namely in 25% and 23.8%, respectively. However, mutations of the VEGFA gene were significantly more common (p=0.03) among patients with a history of surgical treatment (37.5%). Genetic testing in patients with ulcerative colitis makes it possible to predict the effectiveness of therapeutic measures, the likelihood of an increased risk of surgical treatment and can act as one of the criteria for the implementation of a personalized approach in this contingent of patients. In patients with Crohn's disease, polymorphisms of the CARD15/NOD2 gene according to the heterozygous variant occurred with a frequency of 35%, polymorphic variant Leu3020insC in 30% of patients, Gly908Arg in 2.5% of cases. Both polymorphic variants were observed in 2.5% of patients. The polymorphic variant Leu3020insC is associated with the localization of a pathological focus and dominates inflammation in the area of the ileocecal angle. Conclusions. In ulcerative colitis, the frequency of IL-6 gene mutations reaches 24%. Mutations of the VEGFA gene were 2 times less common (12%). Mutations in the TNF-α gene were not detected. It was found that mutations in the IL-6 gene are more common among male patients older than 51 years. According to the length of the process, IL-6 gene mutations are associated with left-sided colitis, and EGFR mutations with total intestinal damage. Mutation of the VEGFA gene to a certain extent may indicate the likelihood of an increased risk of surgical treatment. In Crohn's disease, the frequency of gene polymorphism reaches 35%. The polymorphic variant Leu3020insC is associated with the localization of a pathological focus and dominates inflammation in the area of the ileocecal angle. The appearance of a polymorphic variant of Gly908Arg to a certain extent may indicate a possible relapse of the disease.
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Генеральный директор Афанасьева Елена Владимировна
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