Background. The number of studies devoted to the molecular genetics of oral mucosal leukoplakia and squamous cell carcinoma is small, while the obtained results are usually preliminary in nature. We can assume the existence of region-specific pathogenic genetic variants involved in the development of oral mucosal leukoplakia and squamous cell carcinoma. With the knowledge of such variants, it would become possible to develop PCR (polymerase chain reaction) and NGS (next-generation sequencing) test systems for the detection of clinically significant germline mutations.

Objectives — to identify pathogenic germline genetic variants in patients with oral mucosal leukoplakia accompanied by grade 1 epithelial dysplasia, as well as oral mucosal squamous cell carcinoma, using new-generation sequencing.

Methods. Study design: prospective, observational, cross-sectional, without a control group. The sample included patients (48 persons) of either sex (18 years of age or older) with the following proven and morphologically confirmed diagnoses: oral mucosal leukoplakia accompanied by grade 1 squamous intraepithelial neoplasia of epithelium (24 people) and oral mucosal squamous cell carcinoma (24 people), who sought medical care at the Vitebsk Regional Clinical Dental Center and Vitebsk Regional Clinical Oncological Center in 2019–2020. The identified pathogenic and presumably pathogenic genetic variants involved in the development of these diseases were quantitatively assessed. The study was conducted at the Shareable Core Facilities GENOME of the Institute of Genetics and Cytology of the National Academy of Sciences of Belarus. In order to isolate deoxyribonucleic acid (DNA) from blood samples, a QIAamp DNA FFPE Tissue Kit (Qiagen, Germany) was used. The preparation of DNA libraries and sequencing were carried out by means of an Illumina NextSeq 550 sequencing system (Illumina, Inc., USA) using an Illumina Nextera DNA Exome kit (USA). Bioinformatic analysis was conducted using Illumina BaseSpace specialized software (USA) and Galaxy Project (Galaxy Community, an international non-profit project) in accordance with current guidelines. The obtained data were statistically processed employing specialized software packages Statistica 12 (StatSoft, Inc., USA) and MedCalc 18.9.1 (MedCalc Software, Ltd, Belgium).

Results. Next-generation whole-exome sequencing of deoxyribonucleic acid samples isolated from the blood of patients with oral mucosal leukoplakia and squamous cell carcinoma has been conducted in the Republic of Belarus for the first time. The total number of unique germline genetic variants in the exome of both groups of patients was shown to be very high, yet most of them were not pathogenic. In the examined patients, the majority of germline mutations were found to be localized only in 19 exome genes: MAP2K3, DNAH5, HSPG2, OBSCN, SYNE1, HLA-DRB1, HLA-DQA1, HLA-DQB1, HLA-A, HLA-B, PKD1L2, TTN, AHNAK2, PDE4DIP, MUC3A, MUC4, MUC12, MUC16, and MUC17. In both clinical groups, the greatest number of genetic variants (> 40% of the total number) was detected in MUC3A, MUC4, MUC12, and MUC16, responsible for the synthesis of the glycoprotein mucin family.

Conclusion. Oral mucosal leukoplakia and squamous cell carcinoma can arise from the pathogenic variants of MUC3A, MUC4, MUC12, and MUC16.

Background. In drug addiction treatment, the diagnostic process is based on the chemical toxicological determination of the intoxication substrate or its metabolite. Laboratory monitoring and prediction issues that could form the basis of secondary prevention remain unresolved. Specific nervous tissue proteins are considered to be the most promising laboratory markers of drug pathology.

Objective — to determine some potential biomarkers of protein-chemical nature in the plasma of patients with drug dependence syndrome.

Methods. The study was conducted according to the design of an observational clinical trial at the Narcological Dispensary of Krasnodar Krai in the period from 07.2021 to 07.2022. The main group (group 2) included 31 patients diagnosed with substance dependence syndrome. The control group (group 1, n = 15) consisted of healthy subjects submitted to occupational medical examinations. During the detoxification-stabilization therapy and rehabilitation, 5 proteins were determined in the plasma: brainand glial-derived neurotrophic factors, neuron-specific enolase, alpha-synuclein and calcium-binding protein S100B. Statistical analysis of the data involved the Mann-Whitney test for comparing the values of the control and experimental groups and the Wilcoxon test for comparing the values of one group obtained at different stages of observation. The calculations were carried out using StatPlus version 7 (AnalystSoft Inc., USA).

Results. A total of 31 patients were included in the main group, 18 of them were followed up with a diagnosis of opioid dependence syndrome (n = 11) or psychostimulant dependence syndrome (n = 7). Patients dropped out of the study due to their refusal to participate in the study or undergo rehabilitation, or due to relapse of the disease. When admitted to the hospital, patients indicated a 45% decrease in brain-derived neurotrophic factor in the plasma ( p < 0.001), and a 3.9-fold decrease after rehabilitation course ( p < 0.001). Glial-derived neurotrophic factor in the plasma exceeded the controls 1.9 times ( p < 0.001) upon admission to hospital, but rapidly returned to normal values thereafter. Level of neuron-specific enolase in the plasma was also poor, 36% lower than the controls ( p <0.001), but approached the control values by the end of rehabilitation.

Conclusion. The study obtained data indicating the changes in neurotrophic factors in the blood plasma of patients with opioid or psychostimulant dependence. The rehabilitation period was marked by a relatively rapid improving level of neurotrophins; however, brain-derived neurotrophic factor remained reduced despite the successful treatment, which may indicate the irreversible changes.

Background. Anterior cruciate ligament rupture is the most common knee joint injury, especially in young people with a healthy and active lifestyle. The concept of quality of life has been dynamically developing. The scope of its application is expanding in various fields of medicine to provide a comprehensive assessment of treatment and rehabilitation efficacy.

Objective — to assess the feasibility of complex individual physical rehabilitation of patients after early and delayed arthroscopic reconstruction of the anterior cruciate ligament (ACL).

Methods. Open simple non-randomized trial enrolled 834 patients with the anterior cruciate ligament rupture of the knee joint. In the first group (431 patients), ACL plastic surgery was performed in the early stages — between weeks 2 and 6. In the second group (403 patients), ACL reconstruction was performed in the later stages — from week 7 to 1 year, inclusive. Each group was divided into two subgroups — the main one, in which restorative treatment and comprehensive individual rehabilitation were carried out, and the control group, with rehabilitation treatment in accordance with the standards of postoperative treatment. The study was conducted in Traumatology, Orthopedics and Medical Rehabilitation Unit of Clinical Hospital No. 1. Patients were included in the trial from 2016 to 2021. The follow-up period for each patient was one year. Statistical data processing was performed by means of Statistica 12.0 (StatSoft, Inc., USA). Independent samples were compared using non-parametric criteria: Mann — Whitney U-test and Wilcoxon T-test.

Results. No statistical differences were found in the distribution according to gender, age and body mass index. A comparative analysis of scale medians of Medical Outcomes Study 36Item Short-Form Health Survey (MOSSF-36), conducted in patients before surgery, revealed no statistically significant differences ( p>0.05) between the main and control subgroups in both groups. Analyzing medians before ACL reconstruction showed a significant decrease in comparison with population studies ( p < 0.0001, Mann — Whitney U-test). The analysis of physical and mental component summaries via MOSSF-36 revealed statistically significant differences in the effectiveness of treatment of patients in 1 year after ACL plastic surgery and complex individual rehabilitation. Thus, in the main subgroups, the values of treatment efficacy medians were significantly higher than in the control ones, regardless of the timing of ACL plastic surgery ( p < 0.001, Mann — Whitney U-test). The results testify to higher median efficacy values in patients of the main subgroup of group 1 than in other subgroups ( p < 0.001, Mann — Whitney U-test). The study of correlative relationships demonstrated a stronger relationship between the medians of physical and mental component summaries in the main subgroup of the first group (correlation coefficient = 0.76), if compared to the main subgroup of the second group (coefficient = 0.67).

Conclusion. The study testified to the treatment efficacy proved using the scales of physical and mental component summaries. They demonstrated more significant treatment efficacy one year after arthroscopic ACL reconstruction and individual rehabilitation in the main subgroup of group 1 than in the other subgroups.

Background. Artificial neural network models can be used to analyze and predict structural components within the value dimension of the main processes in an outpatient clinic as indicators of patient satisfaction.

Objective — to form and test the methodology for analyzing and predicting structural components within the value dimension of the main processes in an outpatient clinic, as indicators of patient satisfaction with availability and quality of medical care, using artificial intelligence.

Methods. The results of questionnaires administered to 525 patients were used to analyze their satisfaction with GP appointments. A network ensemble consisting of radial basis network and multilayer perceptron was chosen as the basis for a neural network model. The model testing involved five outpatient clinics in Kirov. The total number of respondents comprised 217 patients. Statistical processing included data description and analysis. Qualitative attributes were represented by relative values (P, %). The statistical significance of differences in qualitative data was assessed using the Chi-square test. The correlation between the observed and predicted data was assessed by means of nonparametric Spearman correlation analysis. The value of p <0.05 was chosen as the significance level ( p). Statistical data processing was performed using Statistica 13.0.

Results. Analysis of the value dimensions of satisfaction showed a predominance of “pre-appointment” stage: work of a registrar (85.29% significance in the receiving medical services), waiting time for an appointment with a doctor (66.76% respondents noted its significance), duration of waiting directly at the office (important for 69.11% of respondents). “Appointment” stage was formed according to the common procedure of a GP appointment (interview, examination, recommendations) and was assessed from the value perspective of the patient. The priority components included sufficiency of appointment duration (significant in 88.27% of cases), satisfaction with examination (significant in 85.14% of cases), as well as completeness and informativeness of consultation (significant in 89.9% of cases). A strong direct correlation between the observed and predicted data (ρxy = 0.9; p < 0.05) was found out. Statistically significant differences between the observed and predicted levels of general patient satisfaction were not revealed in all medical organizations.

Conclusion. The suggested neural network models can be used as the basis when creating information management systems that monitor meeting the effectiveness criteria for a new model of a medical organization; as well as an essential support for administrative decisions related to organizing the optimal patient management.

Background. Assessing the dynamic characteristics of basic public health indicators is essential to ensure the sustainable human development, quality of life and health care system performance in the Arctic and Subarctic regions of Russia. The study is based on the need for constant monitoring of the medical and demographic situation in order to provide timely correction of measures for improving the health care system performance.

Objective — to assess the trends in basic medical and demographic indicators characterizing the population health of the Arkhangelsk Oblast. Target population: population of the Arkhangelsk Oblast, no impacts, no outcomes.

Methods. Criteria for sample or group formation: the research was performed by means of a continuous method based on the study of population of medical and demographic events. The main inclusion criterion was the availability of information about a medical and demographic event in the Arkhangelsk Oblast in the Russian Fertility and Mortality database (RusFMD), the database of the Federal State Statistics Service (Rosstat). Estimated parameters: life expectancy, infant mortality, disability, morbidity, natural population growth and chronicity rates related to the population of the Arkhangelsk Oblast excluding the Nenets Autonomous Okrug. The study was conducted between 2021 and 2022. The following measurement methods were used: autoregressive and integrated moving average, Irwin method to identify abnormal values, linear regression, time series dynamics, and method of chain substitutions. The research was performed by means of a continuous method based on studying the population of medical and demographic events.

Results. Natural population growth and chronicity rates showed a stable negative trend, which indicated a decrease in the reproduction potential of the population, and an increase in chronic forms of diseases. Life expectancy, primary morbidity, and primary disability demonstrated a positive trend, but with a tendency to exhaust the positive potential. Infant mortality was the only indicator that consistently showed a positive trend. No additional results of the research were reported.

Conclusion. The results of the study demonstrated the deterioration in population health of the Arkhangelsk Oblast, which may be due to a decline in living standards and quality of life as well as to a decrease in health care system performance and a rise in its dysfunctionality. The study has no limitations.

Background. In the majority of cases, contemporary pharmacological correction mainly focuses on the most effective analgesia. Therefore, the search for and research into new analgesic drugs are a priority in modern pharmacology.

Objective — to establish the level of analgesic activity in eight novel heterocyclic compounds of 1,4-dihydropyridine derivatives synthesized in a classic test of orofacial trigeminal pain in animal experiments.

Methods. An experimental preclinical randomized trial of the analgesic activity in 1,4-dihydropyridine derivatives was carried out. The experiment was conducted on 100 white male outbred rats in the laboratory of the Fundamental and Clinical Pharmacology Department, St. Luke Lugansk State Medical University, Lugansk People’s Republic. Novel 1,4-dihydropyridine derivatives were preliminarily investigated in a virtual biological screening by means of Swiss Target Prediction tool (Swiss Institute of Bioinformatics, Switzerland). The laboratory animals were divided into a control group (rats were exposed to acute pain syndrome by injecting 0.1 ml of 5% formalin solution into the vibrissae area without pharmacological correction), a comparison group (rats which received metamizole sodium (OOO Farmstandard) at a dose of 7 mg/kg 1.5 hour prior to acute pain syndrome modeling in the vibrissae area), and eight experimental groups (1.5 hours before formalin administration, novel 1,4-dihydropyridine derivatives under study at a dose of 5 mg/ kg were intragastrically injected). 10, 15 and 20 minutes after simulating acute pain, the number of scratching movements of the forelegs around orofacial region per minute was counted. Statistical processing of the results involved methods of mathematical statistics for quantitative variability and was carried out using Statistica 12.5 (IBM, USA).

Results. Animals treated with 1,4-dihydropyridine derivatives d02-133 and d02-172 under the experimental conditions showed a significant (13–21 times) decrease in scratching movements frequency by the 10th minute of observation in comparison with the control group. By 15th minute, the analgesic activity of the cyanothioacetamide derivatives increased 14 and 11 times as compared to these indicators of the reference group. After 20 minutes, the analgesic activity of these compounds in terms of inhibiting nociceptive impulses, as compared to the control group, was also high, as the number of scratching movements in the vibrissae area in animals of these experimental groups was 8–9 times lower than in control group. The orofacial trigeminal pain test detected the most exhibited analgesic activity in novel cyanothioacetamide derivatives d02-139, d02-133, and d02-172, which appeared to be higher than that of metamizole sodium.

Conclusion. It was found that novel original derivatives of 1,4-dihydropyridine showed a high degree of analgesic activity.

Background. The use of regional blockades for the purpose of analgesia is widely used in all fields of medicine, however, the analgesic efficacy of the pterygopalatine blockade, as an independent method of treating pain of various genesis, has not been studied enough. Therefore, there is a need to analyze the results of clinical trials to evaluate the analgesic efficacy of the pterygopalatine blockade as an independent method of anesthesia.

Objective — to investigate the analgesic effect of pterygopalatine blockade as a monotherapy in patients with pain of various origins of oculotemporal area, conducting a meta-analysis of published results of randomized clinical trials.

Methods. The methodology involved a systematic literature search by means of PubMed, MEDLINE, EMBASE, and Cochrane Library search engines. The search covered the period of the past 10 years and had the following criteria: a double-blind, randomized, controlled study of the use of pterygopalatine blockade with a local anesthetic versus placebo. For each included study, a standardized magnitude of the analgesic effect of pterygopalatine blockade compared to placebo was calculated, with pain assessing in 15, 30, and 60 minutes after the blockade was performed. Meta-analyses were conducted for each endpoint. Meta-analysis was performed using Stata 11.0 application programs ((The Cochrane Collaboration, Oxford, United Kingdom).

Results. Five randomized controlled trials involving 269 patients met the inclusion criteria, and involved analyzing the pterygopalatine blockade with local anesthetic (n=140) against placebo (n=129). In 15 minutes after pterygopalatine blockade was performed, the difference in mean pain intensity compared to the control group was -2.5 points, the mean level was lower in the pterygopalatine blockade group, MD=-2.5 [95% CI -3.7; -1.7]. After 30 minutes: -2.7 points, MD=-2.7 [95% CI -4.5; -1.5], after 60 minutes: -1.7 points, MD=-1.7 [95% CI -4.0; -0.5]. The relative risk of adverse effects, such as nasopharyngeal symptoms, after performing a pterygopalatine blockade with a local anesthetic accounted for (RR =1.31 [95% CI 0.5–3.04]). In this regard, the incidence of complications and their variants that can be caused by pterygopalatine blockade is a matter for further clinical research.

Conclusion. The results obtained in the meta-analysis testify to the analgesic effect of the pterygopalatine blockade as a monotherapy in patients with pain of different origins oculotemporal area in 15, 30, and 60 minutes after its performance. These data may be relevant when choosing a method for first-line anesthetic management of pain syndrome of oculotemporal area.

Background. Polyarteritis nodosa is an acute, subacute or chronic immune complex disease associated with peripheral and visceral artery involvement, predominantly of middle and small sizes, development of destructive-proliferative arteritis and subsequent peripheral and visceral ischaemia.

Cases description. The present paper describes two clinical cases of polyarteritis nodosa in patient R., aged 12, and patient A., aged 9, and demonstrates the difficulties of diagnosing the disease in its early stages. Patient R., aged 12, was admitted to the Rheumatology Unit of the Krasnodar Krai Children’s Clinical Hospital with complaints of red, patchy, dense rash on the palms and plantar surface of the feet. The child has been ill since September 2017, and after a history of tonsillitis suffered a fever of 37 °C, pain in the right heel area, nodular thickening on the feet, livedo reticularis, swelling of both hands. The disease had a recurrent course. The boy was treated with prednisolone, mycophenolate mofetil, hydroxychloroquine and three courses of rituximab (April 2018, January 2019, September 2020). Repeated courses of human normal immunoglobulin and alprostadil therapy were carried out. The treatment showed positive dynamics, fever was eliminated, general well-being improved, and acute inflammatory markers in blood became normal. The skin retained minimal manifestation of livedo, nodularities on the feet did not progress in dynamics. Patient A. was admitted to the Rheumatology Unit of the Krasnodar Krai Children’s Clinical Hospital in April 2022 with complaints of weakness, myalgia of the lower extremities and necrosis foci in the left lumbar region. The medical history indicates that in March 2022, the boy, being in good health before, developed a bluish, painful rash on his lower legs after a workout. Skin changes and soreness resolved on their own without treatment. After examination, a diagnosis was made as follows: juvenile polyarteritis nodosa, activity score — 3.

Conclusion. The diagnosis of polyarteritis nodosa can be often problematic due to the very character of the disease featured by absence of specific symptoms, by polymorphism of clinical manifestations, and by lack of clear diagnostic and laboratory markers.

Background. Radical surgeries for phlegmons, abscesses, necrotizing infection are often followed by extensive wounds which require an individual approach to their rapid closure by means of plastic surgery methods. In such a case, the optimal wound therapy is primary healing with the use of vacuum therapy.

Cases description. The study involved three clinical trials of patients with acute purulent-necrotic diseases of soft tissues of various localizations, volumes and grades, for which vacuum therapy was used as a part of complex therapy. Surgical interventions are proved to be urgently performed in acute purulent-necrotic diseases. Early reconstructive skin and bone plastic surgery aimed at closing post-operative wound defects is also very important.

Conclusion. In the demonstrated clinical cases, the purulent process was stopped and wound therapy was performed by means of primary healing, which undoubtedly ensures medical and social rehabilitation of such patients. Notably, vacuum drainage is not an independent method, but an important component in the complex active surgical treatment of purulent wounds.