The objective: to identify factors influencing the development of dyspepsia in children during treatment with anti-tuberculosis drugs.

Results: out of 243 children during chemotherapy, 22.6% developed dyspepsia as an adverse reaction. Risk factors significantly associated with the development of dyspepsia were as follows: formula feeding at birth, comorbidities of the gastrointestinal tract, decreased total protein and elevated leukocyte counts by the admission to hospital, tuberculosis treatment as per regimens IV or V, and inclusion of protionamide or para-aminosalicylic acid to the regimen. Based on the method of logistic regression, the following has been developed: the method to predict the risk of developing dyspepsia during anti-tuberculosis chemotherapy in children with a sensitivity of 93%; the PC software to calculate such a risk.

Reporting of the «transferred out» outcome leads to significantly worse treatment results of tuberculosis patients treated in the institutions of the Federal Penitentiary Service of Russia.

The objective: to investigate the patients’ routes that led to reporting of the «transferred out» outcome, and propose measures to reduce the risk of this outcome.

Subjects and Methods. We studied the places of registration and routes of 1,496 pulmonary tuberculosis patients registered for treatment in 2019 (new cases and relapses) with the outcome of «transfered out».

Results. In the structure of transferred out patients, in 631/1,496 (42.2%) patients, the «transferred out» outcome was associated with their transfer between institutions within the penitentiary system. Additionally 462/1,496 (30.9%) patients were released in the region where they continued their treatment, 85/1,496 (5.7%) were released and moved to a different region, 301/1,496 (20.6%) were released from pre-trial detention , and 10/1,496 (0.6%) left Russia and moved abroad.

Conclusion: the procedure should be developed to transfer the information about patients moving within the penitentiary system and beyond it. To motivate the patient immediately after the detection of tuberculosis, it is necessary to conduct individual conversations explaining the nature of the disease, importance and necessity of treatment. Tuberculosis patients in pre-trial detention centers should be provided with leaflets containing information about medical organization where patients can continue treatment, patients released from penitentiary units should be informed about the system of social adaptation and services available for tuberculosis patients.

The objective: to analyze the association of the Asp299Gln (rs 4986790) and Thr399Ile(rs 4986791) polymorphisms of the TLR4 gene with the risk of pulmonary sarcoidosis in the Russian population of the Republic of Karelia.

Subjects and Methods. 253 people were examined: 122 patients diagnosed with morphologically verified sarcoidosis with lung involvement (average age – 41.00 ± 12.56 years) (Sarcoidosis Group) and 131 healthy donors (Control Group) (average age – 44.00 ± 14.23 years). All subjects in both groups considered themselves Russians by ethnicity, as reported in the survey. The distribution of alleles and genotypes by the polymorphic markers Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) of the TLR4 gene was studied in the group of patients with pulmonary sarcoidosis and the group of healthy individuals. Genotyping was carried out by PCR-RFLP.

Results. There were no statistically significant differences in the distribution of allele and genotype frequencies for the Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) polymorphic markers of the TLR4 gene between the group of patients with pulmonary sarcoidosis and the control group: (χ² = 0, df = 1, p = 0.997 и χ² = 1.0, df = 2, p = 0.606; χ² = 0.785, df = 1, p = 0.376 и χ² = 0, df = 2, p = 1.0).

Conclusion. The polymorphic marker Asp299Gln (rs 4986790) and Thr399Ile (rs 4986791) of the TLR4 gene is not associated with the risk of pulmonary sarcoidosis in the Russian population of the Republic of Karelia.

The objective: to determine the frequency of resistance of Mycobacterium tuberculosis (MTB) to the most effective anti-tuberculosis drugs in tuberculosis patients in the Republic of Karelia, to characterize cases of amplification of MTB drug resistance during chemotherapy (CT).

Subjects and Methods. MTB cultures of 1,137 tuberculosis patients were studied, the patients received chemotherapy from 2016 to 2021, among them 634 (55.8%) had multiple drug resistance (MDR). Among MBT cultures with MDR, there was a high frequency of MTB with extensive drug resistance (XDR) – 42.3% (268/634) including new cases. It provided a negative impact on the chemotherapy efficacy. Most often, amplification of MTB drug resistance was observed in patients treated as per regimen IV – 37/49 (75.5%) cases. MTB drug resistance amplified more often in the cases who were already resistant to 3 and more anti-tuberculosis drugs, 31/49 (63.3%). Most often, amplification was noted in aminoglycosides (Km, Am) and glycopeptide (Cm), (71.6% of cases). The high frequency of MTB drug resistance amplification from MDR up to XDR was due to the lack of rapid molecular genetic methods to test drug susceptibility to fluoroquinolones and aminoglycosides.

The objective: to evaluate the possibility of using linezolid, amikacin, levofloxacin and bedaquiline mixed with bone cement for the treatment of patients with tuberculous arthritis taking into account changes in mechanical properties of bone cement, antimycobacterial activity of drugs and characteristics of their release.

Subjects and Methods. The antimycobacterial, elution and strength characteristics of bone cement mixed with the drugs known for their anti-tuberculosis activity were studied: linezolid, amikacin, levofloxacin, and bedaquiline. The antimycobacterial effect was evaluated by the minimum inhibitory concentration (MIC) of the reference strain of Mycobacterium tuberculosis H37RV sensitive to anti-tuberculosis drugs (TB drugs). To study the kinetics of elution, the methods of high-performance mass spectrometry and spectrophotometry were used. The strength characteristics were determined using LFM-50 electromechanical testing machine.

Results. The obtained results demonstrated satisfactory elution and antimycobacterial parameters for linezolid and amikacin, thus they can be mixed with bone cement, and the cement retained its strength characteristics. Levofloxacin showed antimycobacterial activity only within 1 day after the cement sample was immersed in the solution. Bedaquiline showed negative elution and antimycobacterial characteristics in the cement sample.

The objective: to study the level of serum cytokines IL-4, IFN-γ and the activity of IgE production in patients with bronchial asthma (BA) with the consideration of the Gln27Glu-polymorphism of the β₂-AR gene.

Subjects and Methods. 130 people of Uzbek ethnicity were examined including 83 patients with BA. BA patients were divided into groups according to the international classification of the World Health Organization and the GINA 2006 diagnostic criteria. Genotyping was performed by polymerase chain reaction technology and restriction fragment analysis.

Results. In the group with allergic BA, patients with the Gln27Gln-polymorphic variant of the β₂-adrenergic receptor gene had an average IgE value (1,664.20 ± 293.29 pg/ml) higher versus patients with the Gln27Glu genotype (338.40 ± 121.33 pg/ml; p < 0.01). No significant relationship between the Gln27Glu polymorphism of the β₂-adrenergic receptor gene and the activity of inductor cytokines was found. The Gln27Gln genotype of the β₂-adrenergic receptor gene in patients with bronchial asthma, especially in the allergic form of the disease, is associated with hyperproduction of IgE.

The objective: to evaluate safety and efficacy of bedaquiline in the treatment of patients with multiple drug resistant tuberculosis (MDR-TB).

Subjects and Methods. Clinical data of 523 patients above 18 years old registered for MDR TB treatment as per regimen 4 were retrospectively analyzed. HIV-negative patients were selected and divided into two groups by the use of bedaquiline in the chemotherapy regimen.

Results. In MDR TB treatment regimen containing bedaquiline, adverse reactions were observed in 95.7% of cases, the majority of them (65.2%) were of mild or moderate degree of severity. In 30.4% of such cases, bedaquiline was temporarily discontinued (mostly due to hepatotoxic reactions). No cardiotoxicity was observed as a response to bedaquiline, the median corrected QT interval made 413 ms, the maximum value was 438 ms. Adding bedaquiline to the regimen resulted in faster (in the first 3 months of treatment) and more frequent (in 94.7%) sputum conversion by culture (in the regimens with no bedaquiline, it was achieved in 63.8% of cases, p = 0.019). Treatment with regimens containing bedaquiline was effective in 82.61% of patients, while regimens with no bedaquiline were effective in 65.2% of cases, p = 0.085.

The epidemic situation is monitored by numerous rates that may not reflect it objectively which will subsequently lead to higher incidence rates and severe forms of tuberculosis in both adults and children in the regions with the most unfavorable situation.

The objective: to evaluate epidemiological rates for tuberculosis in the Northwestern Federal District to identify the most significant, and assess the epidemic situation in the region using these most significant rates.

Subjects and Methods. We analyzed the main epidemiological rates of pediatric tuberculosis according to federal statistics (Forms 8 and 33) in 11 districts of the Northwestern District in 2019-2021. Annual figures were obtained from open demographic data of the state statistics (https://www.fedstat.ru). Statistical analysis was pe`rformed using the free software R (v.3.5.1) and the commercial Statistical Package for the Social Sciences (SPSS Statistics for Windows, Version 24.0, IBM Corp., 2016). Hierarchical cluster analysis and k-means clustering were used with the selection of the lowest and highest values of rates. A formula is proposed for calculating the coefficient of full coverage with preventive screening (COP) for tuberculosis of the population which allows adjusting the analyzed epidemic rates taking into account the maximum coverage of the population with preventive screening and determining the accuracy of previous analysis.

Results. According to the data obtained, in 2017 and 2018, Vologda Oblast and Nenets Autonomous Okrug were epidemically favorable regions, while in 2020 and 2021 Kaliningrad, Leningrad and Novgorod Oblasts were regarded as favorable regions that were steadily improving their performance. Regions with unfavorable tuberculosis situation include Pskov Oblast, St. Petersburg and the Komi Republic. At the same time, the first two regions occupy this position stably from 2017 to 2021. The use of the coefficient of low coverage with screening for tuberculosis made it possible to determine that Murmansk Oblast, St. Petersburg, Leningrad and Pskov Oblasts in 2020 and 2021 are prognostically unfavorable regions despite a decline in official tuberculosis rates. The data obtained correlate with a high percentage of positive tests with the tuberculosis recombinant tuberculosis allergen (TRA) in children in the regions mentioned above.

Conclusions. The analysis of the data clearly demonstrates the possibility of determining the epidemically most favorable or unfavorable regions using four rates: coverage with preventive screening, incidence in the adult population, incidence in children aged 0 to 17 years, and tuberculosis mortality. Cluster analysis using these rates, calculation of rates using the developed coefficient of low coverage with screening for tuberculosis, and analysis of positive results of TRA test in children allows identifying the most epidemically unfavorable regions, despite the decrease in some rates that can be regarded as favorable.

In the regions with the high prevalence of HIV infection, it is necessary to perform differential diagnosis of lung injury caused by COVID-19 and pneumocystis pneumonia.

The main complaints in COVID-19 and pneumocystis pneumonia are similar and include dyspnea, weakness, cough, fever, and ground glass radiographic syndrome. However, sputum production was more common in pneumocystis pneumonia. The most important differences were frequent anosmia in COVID-19 and its absence in pneumocystis pneumonia, frequent detection of oropharyngeal candidiasis in pneumocystis pneumonia which was not seen in COVID-19.

Serum hepcidin concentration has a high diagnostic potential and indicates a greater likelihood of COVID-19 than pneumocystis pneumonia at values ≤ 768.044 pg/ml (ROC AUC 0.977; p < 0.001).