The objective:  analysis of tuberculosis epidemiological rates in children and adolescents in the Siberian Federal District in 2020-2022.

Subjects and Methods. Offi  cial statistical reporting data (Forms No. 30, 33, 8, and 61) and additional information requested from the regions of the Siberian Federal District were used for analysis.

Results.  In 2020 in the Siberian Federal District, tuberculosis incidence among children and adolescents aged 0–17 falsely reduced, possibly due to the «deprivation» of the medical care during the COVID-19 pandemic.  In 2021 and 2022, the rate increased, there was an increase in the proportion of new patients in the group of 0–14 years old, an increase in the number of cases of secondary tuberculosis which may indicate a deterioration of tuberculosis situation in the District. In 2022, the incidence of extrathoracic tuberculosis increased in adolescents aged 15–17 years. The number of cases of TB/HIV co-infection is growing. There are single lethal cases due to tuberculosis in children in the regions of the Siberian Federal District over the past 5 years, and this rate continues to decline.

The objective: to analyze the quality of phthisiosurgical care in the Siberian and Far Eastern Federal Districts monitored by Novosibirsk Tuberculosis Research Institute (NTRI).

Subjects and Methods. Statistical reports for 2019 from phthisiosurgical departments of 17 Russian regions within the Siberian and Far Eastern Federal Districts were analyzed. The reports refl ected the initial period of the pandemic.

Results. The analysis of the quality of phthisiosurgical care in the Siberian and Far Eastern Federal Districts covered the areas monitored by Novosibirsk Tuberculosis Research Institute, the Russian Ministry of Health. The main performance rates of phthisiosurgical departments of 17 Russian regions are presented for 2019, they demonstrate a positive trend, and their facilities and resources have signifi cantly improved. The trend towards reduction of phthisiosurgical beds is observed in the regions, which may be due to the service centralization and improved access to surgical and high-tech care in federal institutions. Surgical departments possesses substantial reserves for increasing the number of surgeries, one of which is the revision of cohorts.

The objective: to study results of bronchial block in pulmonary tuberculosis patients depending on the presence of local infl ammatory changes in their bronchial tree, the frequency and nature of complications in this category of patients.

Subjects and Methods. In order to achieve the above objective, in 2018–2019 in Novosibirsk Tuberculosis Research Institute, all patients who had indications for bronchial block were enrolled in the study. 275 tuberculosis patients were divided into 2 groups: Main Group (n=108) consisted of the patients with infl ammatory changes in their bronchial tree, while Comparison Group (n=167) included patients with no such changes. The valve bronchial block was implanted, effi  cacy of treatment and complications that developed were evaluated. 

Results. Effi  cacy of valve bronchial blocking did not depend on the presence of local infl ammatory changes in the bronchi, so it can be used without waiting for the relief of infl ammatory changes. The profi le of complications in the groups was comparable.

The objective: to study the frequency and nature of postoperative complications, immediate and postponed results of resection interventions in pulmonary tuberculosis patients depending on the presence and pathomorphological parameters of local infl ammatory changes in the bronchial tree.

Subjects and Methods. 147 pulmonary tuberculosis patients who underwent pulmonary resection were enrolled in the prospective cohort study. Main Group (n=49) included patients with local infl ammatory changes in the bronchi before surgery; Comparison Group (n=98) included patients with no infl ammatory changes in the bronchi.

Results. The presence of local infl ammatory changes in the bronchial tree detected by bronchoscopy, did not have a signifi cant impact on the development of complications during surgical treatment - neither on their number nor on structure. The incidence of complications of resection interventions depends on severity of tuberculosis lesions in the lung.

The objective: to evaluate the main eff ects of surfactant inhalations during the intensive phase of chemotherapy with the regimen containing bedaquiline and linezolid in HIV-infected patients with multiple drug resistant tuberculosis.

Subjects and Methods. A single-center, open-label, controlled prospective cohort study was conducted. 80 patients with MDR-TB/HIV were enrolled in the study and randomized into two groups: ST+ Group included 40 patients who in addition to anti-tuberculosis therapy containing bedaquiline and linezolid during the intensive phase received inhalation of the suspension of Surfactant-BL according to a certain regimen. The course of 28 inhalations took 2 months, the total dose of surfactant was 700 mg. ST- Group included 40 patients who received anti-tuberculosis therapy only. To assess the severity of respiratory symptoms in patients, we used our own scoring. All patients also received antiretroviral therapy.

Results. In the ST+ Group versus ST- Group, there was a decrease in the severity of tuberculosis clinical manifestations and timing of their relief, higher frequency of cavity healing by 21.2%, and faster sputum conversion by 28.6%. These rates are higher than in ST- Group and this is a short period of 10 weeks. None of the patients developed adverse reactions to surfactant inhalations. Patients tolerated well the combination of surfactant therapy, MDR TB chemotherapy containing bedaquiline and linezolid, and ART.

The objective: to study the impact of transcranial mesodiencephalic modulation on eff ectiveness of comprehensive treatment of pulmonary tuberculosis patients with various comorbidities.

Subjects and Methods. 48 patients who received standard regimens of anti-tuberculosis chemotherapy participated in the study; the patients were divided into two groups. In Group 1, patients additionally underwent sessions of mesodiencephalic modulation (MDM), while in Group 2, no MDM was administered.

Results. Two months after the start of the study, in Group 1, positive radiological changes were recorded more often – in 91,7% (22/24), in Group 2, positive changes were observed in 62,5% (15/24) of patients (p=0,047; χ2); the same pattern was observed with positive changes of laboratory rates – 91,7% (22/24) versus 66,7% (16/24), (p=0,033; χ2), respectively. In patients of Group 1 compared to Group 2, symptoms of tuberculosis and comorbid conditions fully disappeared or became less intensive in 79,2% (19/24) versus 41,7% (10/24), (p=0,009; χ2). In Group 1, adverse drug reactions were registered in 16,7% (4/24), in Group 2 – 43,5% (10/24), (p=0,05; χ2).

The objective: to study the potential otoprotective and antioxidant activity of cytoflavin in new pulmonary tuberculosis patients receiving aminoglycoside amikacin.

Subjects and Methods. A randomized controlled trial was conducted and included 90 patients with new infiltrative pulmonary tuberculosis with decay, of both genders aged from 20 to 50 years old. Clinical, paraclinical and statistical methods were used in the study. Audiometric screening was carried out by Diagnostic Audiometer AD 226. The degree of antioxidant protection was determined by the oxidation reaction of ABTS in blood serum and plasma.

Results. The study included 4 groups of tuberculosis patients and 1 group of healthy donors. Dissemination of pulmonary tuberculosis in 4 groups was approximately the same and was measured by scores. Prior to the start of treatment in all 4 groups (the group receiving standard chemotherapy (CTX) without amikacin, the group receiving «CTX+amikacin», the group receiving «CTX+cytofl avin», the group receiving «CTX+amikacin+cytofl avin») there was a decrease in blood antioxidant activity compared to Control Group. After 3 months of tuberculosis treatment in all 4 groups, the results improved, while in «CTX+Cytofl avin» Group they were similar to Control Group, and «CTX+Amikacin+Cytofl avin Group», they were only 4.8% less. The elevated level of leukocytes decreased by 10.6% in CTX Group, 16.9% in «CTX+Amikacin» Group, 38.3% in «CTX+Cytofl avin» Group, and 72.3% in «CTX+Amikacin+Cytofl avin» Group. In the study, manifestations of oto- and vestibulotoxicity were found only in the «CTX+Amikacin» Group (in 4/20 (5%)). There were no such cases in «Amikacin+Cytofl avin» Group consisting of 23 patients.

The objective: to study the efficacy of antimicrobial photodynamic therapy (APDT) using hydroxyaluminum phthalocyanine (Photosens) as a photosensitizer in the experimental model of tuberculosis infection in mice.

Subjects and Methods. Balb/cmice were infected with the multiple drug resistant (MDR) strain of M. tuberculosis Beijing BO/W148. APDT with hydroxyaluminum phthalocyanine and red laser light exposure were started on Day 45. A total of 4 sessions of APDT on the projection of both lungs, liver and spleen were performed. On Day 60, the therapeutic eff ect of APDT

was assessed by evaluation of severity of mycobacterial load and specific granulomatous infiltration in the lungs, liver and spleen. The absorption of light energy of laser radiation by the chest and abdominal walls, as well as tissues of lungs, liver and spleen was determined by photometry using afluovisor.

Results. The tissues of the experimental animal retain a significant amount of light energy, however, the residual value of light transmission is sufficient to provide a pronounced therapeutic effect which manifests itself as a significant decrease of mycobacterial load and specific inflammatory process in all the studied internal organs.

Conclusion. APDT may be an effective tool to treat some forms of tuberculous infection including those caused by M. tuberculosis with MDR.

The objective: in an in vitro experiment, we compared phagocytic parameters of mesenchymal stromal cells (MSCs) and macrophages to tuberculous mycobacteria, assessed the ability of MSCs and macrophages to lyse mycobacteria or maintain their intracellular growth, their effect on formation of phenotypic drug resistance of mycobacteria, as well as the effect of tuberculous mycobacteria on the type of MSCs cell death.

Subjects and Methods. Balb/c male mice, aged 6 to 8 weeks, were used in the experiment. Bone marrow MSCs were obtained from femurs and tibias by further cultivation, peritoneal macrophages were elicited with 4% alpha-glucan. The intracellular content of mycobacteria was counted using a confocal microscope with x 400 magnification. Susceptibility of mycobacteria to isoniazid and development of phenotypic drug resistance after culturing MSCs and macrophages with MTB on Lowenstein–Jensen medium was assessed by counting CFU. In 5 days after the infection, the number of apoptotic and necrotic MSCs and macrophages was determined by a flow cytometer.

Results. On Day 1, the total number of phagocytosed MTB, as well as the number of phagocytic-active macrophages, exceeds the corresponding figures for MSCs more than twice. MSCs phagocytize tuberculous mycobacteria in a smaller amount, but MTB reproduces in them more actively: the number of CFU after 7 days of cell cultivation with MTB exceeded the corresponding parameter by almost 50 times after 24 hours of cultivation. In cultures of infected MSCs cultivated for 7 days, regardless of the presence of isoniazid, there was a rapid growth of tuberculous mycobacteria. On Day 5 after infection of macrophage culture with tuberculous mycobacteria, the number of necrotic cells was 2.7 times greater than that of uninfected necrotic macrophages, but the number of apototic cells in these groups differed slightly. In the culture of MSCs, there were 8.5 times more infected nectrotic cells versus uninfected necrotic MSCs, and the number of necrotic MSCs was 4.5 times higher than the number of MSCs with apoptosis, while in the culture of infected macrophages, the number of necrotic cells was the same as number of apoptotic cells. Unlike macrophages, treatment of MSCs with isoniazid did not inhibit the intracellular proliferation of MTB.

Conclusion. MSCs have the ability to phagocytose mycobacteria, but they do it less actively than macrophages and, unlike macrophages, they are not able to restrain the reproduction of tuberculous mycobacteria. Mycobacteria have phenotypic drug resistance in MSCs. In MSCs, when infected with tuberculous mycobacteria, there is a pronounced shift towards necrosis in the type of cell death, which can lead to dissemination of MTB and development of local destructive changes.

The article describes a clinical case of surgical treatment of tuberculous spondylitis and tuberculous pleurisy in a HIV positive patient with disseminated pulmonary tuberculosis. A severe pain syndrome in tuberculous spondylitis was the fi rst clinical manifestation of generalized multiple drug resistant tuberculosis.

Surgical treatment of spinal deformity relieved the pain syndrome, microbiological results of surgical biopsy of the vertebrae and pleura allowed prescribing the eff ective treatment for generalized tuberculosis

The article describes a clinical case of successful treatment of the patient (37 years old) with focal tuberculosis of the single left lung in the consolidation phase, empyema of the right pleural cavity, who developed multiple organ failure syndrome, hypercoagulation and sepsis, caused by a triple coinfection with M. tuberculosis, P. aeruginosa, and Kl. pneumoniae.