VIZEL ALEXANDER A., ORCID ID: 0000-0001-5028-5276; SPIN code: 5918-5465; Author ID: 195447, Dr. sc. med., Professor, Head of the Department of Phthisiopulmonology, Kazan State Medical University, 49 Butlerov str., 420012 Kazan, Russia. Tel.: +7-987-296-25-99. E-mail: lordara@inbox.ru

AVDEEV SERGEY N., ORCID ID: 0000-0002-5999-2150; Dr. sc. med., Professor, Member of the Russian Academy of Sciences, Head of the Department of Pulmonology, N.V. Sklifosovsky Institute of Clinical Medicine, I.M. Sechenov First Moscow State Medical University (Sechenov University), Leading Researcher, Federal Pulmonology Research Institute, Federal Medical and Biological Agency of Russia. 3 Bolshaya Sukharevskaya Square, 107045 Moscow, Russia. Tel.: +7-495-708-35-76. E-mail: serg_avdeev@list.ru

VIZEL IRINA YU., ORCID ID: 0000-0002-8855-8177; SPIN code: 6000-3813, Dr. sc. med., Professor at the Russian Academy of Natural Sciences, Associate Professor at the Department of Phthisiopulmonology, Kazan State Medical University, 49 Butlerov str., 420012 Kazan, Russia. Tel.: +7-917-903-91-13. E-mail: tatpulmo@mail.ru

SHAKIROVA GULNAZ R., ORCID ID: 0000-0002-2551-5671; Cand. sc. med., Assistant Professor at the Department of Phthisiopulmonology, Kazan State Medical University, 49 Butlerov str., 420012 Kazan, Russia. Tel.: +7-917-884-30-39. E-mail: adeleashakirova@mail.ru

AMIROV NAIL B., ORCID ID: 0000-0003-0009-9103; SCOPUS Authоr ID: 7005357664; Dr. sc. med., Professor at the Department of Outpatient Medicine and General Medical Practice, Kazan State Medical University, 49 Butlerov str., 420012 Kazan, Russia. Tel.: +7-843-291-26-76. E-mail: namirov@mail.ru

VIZEL LEONID A., ORCID ID: 0009-0003-1219-4957; Student, Kazan (Volga Region) Federal University, 18 Kremlevskaya str., 420008 Kazan, Russia. Tel. +7-843-233-75-76. E-mail: laskaleo2004@mail.ru

Abstract. Introduction. Sarcoidosis is the epithelioid cell granulomatosis, the exact cause of which is unknown. In 5-20% of cases, pulmonary fibrosis develops that can adversely affect the patient’s prognosis. Aim. Assessing the clinical manifestations of fibrosing pulmonary sarcoidosis and comparing patients relevant to its various phenotypes, according to computed tomography findings. Materials and Methods. Findings in 81 pulmonary fibrosis patients were analyzed using high-resolution computed tomography. All patients were examined by a pulmonologist. Along with the assessment of laboratory, functional, and radiology findings in all patients, four phenotypes of fibrosis manifestations were compared according to high-resolution computed tomography findings, which were accepted using the international Delphi consensus technique. Results and Discussion. Among the patients, there were 43 (53.1%) women and 38 (46.9%) men, and their average age was 51.81±11.5 years. The median fibrosis formation duration was 8.20 [3.0; 11.0] years from the detection date. The primary examination was conducted in multidisciplinary institutions (53.1%), in tuberculosis dispensaries (31.1%), in oncology dispensaries (11.1%), and 3 patients were initially examined in federal research institutes. Decreased forced vital lung capacity was found in 58% of patients, increased blood calcium levels were in 6.5%, and in 17.5% it was found increased in their daily urine, and the increased angiotensin-converting enzyme levels were found in 38.3% of the patients studied. When analyzing the therapy performed prior to the fibrosis development, all three prerequisites of the Federal Clinical Guidelines (observation for at least 3 months after diagnosis, an initial dose of systemic glucocorticosteroid of at least 20 mg, and duration of at least 10 months) were only met in 11 patients (17.5%). 55.4% of patients received the repeated courses of systemic glucocorticosteroid therapy for relapses and exacerbations. Phenotypes B and C, which are closest to idiopathic pulmonary fibrosis according to high- resolution computed tomography, were accompanied by the greatest decrease in forced vital lung capacity and DLco. With these phenotypes, systemic glucocorticosteroids were more often prescribed immediately after detection, while all the requirements of clinical guidelines were met less often, pentoxifylline and vitamin E were used the least often as starting therapy, and pulse therapy was only performed with these phenotypes. Conclusions. Possible reasons for the unfavorable course included late detection and late referral to a third-level specialist, as well as failure to comply with clinical recommendations at the initial stage of sarcoidosis treatment. Manifestations of pulmonary fibrosis in sarcoidosis are heterogeneous in laboratory and functional parameters. Phenotypes of fibrosing pulmonary sarcoidosis recently agreed upon by high-resolution computed tomography had differences in the degree of respiratory impairment and saturation, which indicates the practical significance of such division of patients by the radiographic picture.

Keywords: sarcoidosis, fibrosis, computed tomography, phenotypes.

For reference: Vizel AA, Avdeev SN, Vizel IYu, et al. Fibrosing pulmonary sarcoidosis: Computed tomography-based clinical characteristics and phenotypes // Вестник современной клинической медицины. – 2024. – Т. 17, вып. 5. – С.7-16. DOI: 10.20969/VSKM.2024.17(5).7-16.

REFERENCES

1. Bonham CA, Sharp M. New updates in sarcoidosis research: defining and renewing the quest. Am J Physiol Lung Cell Mol Physiol. 2024; 326 (4): L480-L481. DOI: 10.1152/ajplung.00082.2024

2. Asif H, Ribeiro Neto M, Culver D. Pulmonary fibrosis in sarcoidosis. Sarcoidosis Vasc Diffuse Lung Dis. 2023; 40 (3): e2023027. DOI: 10.36141/svdld.v40i3.14830

3. Nunes H, Brillet PY, Bernaudin JF, et al. Fibrotic pulmonary sarcoidosis. Clin Chest Med. 2024; 45 (1): 199-212. DOI: 10.1016/j.ccm.2023.08.011

4. Bandyopadhyay D, Mirsaeidi MS. Sarcoidosis-associated pulmonary fibrosis: joining the dots. Eur Respir Rev. 2023; 32 (169): 230085. DOI: 10.1183/16000617.0085-2023

5. Ghazipura M, Mammen MJ, Herman DD, et al. Nintedanib in progressive pulmonary fibrosis: A systematic review and meta-analysis. Ann Am Thorac Soc. 2022; 19 (6): 1040-1049. DOI: 10.1513/AnnalsATS.202103-343OC

6. Baughman RP, Gupta R, Judson MA, et al. Value of pulmonary function testing identifying progressive pulmonary disease in fibrotic sarcoidosis: results of a prospective feasibility study. Sarcoidosis Vasc Diffuse Lung Dis. 2022; 39 (2): e2022011. DOI: 10.36141/svdld. v39i2.12940

7. Desai SR, Sivarasan N, Johannson KA, et al. High-resolution CT phenotypes in pulmonary sarcoidosis: a multinational Delphi consensus study. Lancet Respir Med. 2024; 12 (5): 409-418. DOI: 10.1016/S2213-2600(23)00267-9

8. Kouranos V, Wells AU. The role of primary care in sarcoidosis. Curr Opin Pulm Med. 2023; 29 (5): 493-500. DOI: 10.1097/MCP.0000000000000991

9. Yang W, Jiang J, Zhao Q, et al. A case of tuberculosis misdiagnosed as sarcoidosis and then confirmed by NGS testing. Clin Lab. 2024; 70 (3). DOI: 10.7754/Clin. Lab.2023.230823

10. Hoornaert E, Yildiz H, Pothen L, et al. A comparison study of lymph node tuberculosis and sarcoidosis involvement to facilitate differential diagnosis and to establish a predictive score for tuberculosis. Pathogens. 2024; 13: 398. DOI: 10.3390/pathogens13050398

11. Rezaee M, Azizi N, Danaei B, et al. TB and interstitial lung disease: a systematic review and meta-analysis. Int J Tuberc Lung Dis. 2024; 28 (3): 130-135. DOI: 10.5588/ ijtld.23.0428

12. Namsrai T, Phillips C, Desborough J, et al. Diagnostic delay of sarcoidosis: Protocol for an integrated systematic review. PLoS One. 2023; 18 (2): e0269762. DOI: 10.1371/ journal.pone.0269762

13. Shkolnik B, Sore R, Salick M, et al. The Relationship Between Serum Angiotensin Converting Enzyme Level and the Decision to Escalate Treatment of Sarcoidosis. Lung. 2023; 201 (4): 381-386. DOI: 10.1007/s00408-023-00629-3

14. Crouser ED, Maier LA, Wilson KC, et al. Diagnosis and detection of sarcoidosis: An Official American Thoracic Society Clinical Practice Guideline. Am J Respir Crit Care Med. 2020; 201 (8): e26-e51. DOI: 10.1164/rccm.202002-0251ST

15. Obi ON, Alqalyoobi S, Maddipati V, et al. High-resolution ct scan fibrotic patterns in stage iv pulmonary sarcoidosis: Impact on pulmonary function and survival. Chest. 2024; 165 (4): 892-907. DOI: 10.1016/j.chest.2023.10.021

16. Flaherty KR, Wells AU, Cottin V, et al. Nintedanib in progressive fibrosing interstitial lung diseases. N Engl J Med. 2019; 381 (18): 1718-1727. DOI: 10.1056/ NEJMoa1908681

17. Wijsenbeek M, Swigris JJ, Inoue Y, et al. Effects of nintedanib on symptoms in patients with progressive pulmonary fibrosis. Eur Respir J. 2024; 63 (2): 2300752. DOI: 10.1183/13993003.00752-2023

 ANALYSIS OF THE DRUG RESISTANCE SPECTRUM OF THE MYCOBACTERIUM TUBERCULOSIS STRAINS CIRCULATING IN THE REGIONS OF THE SIBERIAN AND FAR EASTERN FEDERAL DISTRICTS OF RUSSIA

GORDEEVA ELIZAVETA I., ORCID ID: 0000-0002-3288-5259, Applicant for the Cand. sc. biol. degree, Biologist, Bacteriological Laboratory, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +7 (913) 0690582. E-mail: mbtnniit20@gmail.com

GUSELNIKOVA ELENA P., Applicant for the Cand. sc. med. degree, Head of the Bacteriological Laboratory, Bacteriologist, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +79538572720. E-mail: epguselnikova@nsk-niit.ru

STAVITSKAYA NATALIA V., ORCID ID: 0000-0003-2616-6693, Dr. sc. med., Director of Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +7 (383) 203-78-25. E-mail: director@nsk-niit.ru

Abstract. Introduction. Today, in the Siberian and Far Eastern Federal Districts of Russia, the situation with the incidence of tuberculosis is one of the most unfavorable. Aim. To analyze the phenotypic antituberculosis drug resistance spectrum of the Mycobacterium tuberculosis strains obtained from patients treated at Novosibirsk Tuberculosis Research Institute in 2020–2023. Materials and Methods. Standard bacteriological and molecular genetic methods of laboratory studies were used for this research. Results and Discussion. Resistance of the Mycobacterium tuberculosis strains obtained from patients ranges 52.8%–76.1% for the main antituberculosis drugs, while it ranges 38%–47% for fluoroquinolones, 29%–35% for aminoglycosides, 40% for capreomycin, 57.3% for ethionamide/prothionamide, 29.6% for aminosalicylic acid 29.6%, 8.9% for bedaquiline, and 7.5% for linezolid. The long-lasting and multiplying mycobacterial population supports the inflammatory process, which leads to its progression and, as a result, complicates the treatment. The incidence of drug-resistant strains to new antituberculosis drugs in sputum samples obtained from people excreting bacteria was for bedaquiline: 1.6% among newly diagnosed patients, 3.6% for the cases of the disease recurrence, and 1.3% for the cases of the chronic disease course; for linezolid: 3.2% for newly diagnosed patients, 4.3% for the cases of the disease recurrence, and 6.2% for the cases of the chronic disease course. Conclusions. The trend towards an increase in strains resistant to a wide range of antituberculosis drugs in the regions under study is observed for all antituberculosis drugs, which emphasizes the urgent need for both the intensive epidemiological monitoring of such resistance and, possibly, a revision of the algorithms for prescribing such drugs.

 PREVALENCE AND TRANSMISSIBILITY OF NONTUBERCULOUS MYCOBACTERIA IN HUMANS AND ANIMALS IN NOVOSIBIRSK OBLAST

GUSELNIKOVA ELENA P., ORCID ID: 0009-0002-5743-5489, Head of the Bacteriology Laboratory, Bacteriologist, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel. +79538572720. E-mail: epguselnikova@nsk-niit.ru

IONINA SVETLANA V., Cand. sc. biol., Leading Researcher, Siberian Federal Research Centrе of Agro-ВioTechnologies of the Russian Academy of Sciences (SFSCA RAS), 8 Tsentralnaya str., 630501 Krasnoobsk, Russia. Tel. + 79137142895. E-mail: labtub@mail.ru

GORDEEVA ELIZAVETA I., ORCID ID: 0000-0002-3288-5259, Junior Researcher, Biologist, Bacteriological Laboratory, Novosibirsk Tuberculosis Research Institute, , 81a Okhotskaya str., 630040, Novosibirsk, Russia. Tел. +7 (913) 0690582. E-mail: mbtnniit20@gmail.com

Abstract. Introduction. Nontuberculous mycobacteria are found everywhere in the environment, including in various ecological reservoirs among wild and domestic animals, birds, fish, in human life, in soil, dust particles, in natural reservoirs, and in water distribution systems. Aim. To study the prevalence of various types of nontuberculous mycobacteria in humans and farm animals in Novosibirsk Oblast and assess the correlation of the prevalence of mycobacteriosis foci detected in medical and veterinary care systems. Materials and Methods. 219 samples of animal biomaterial consisting of lymph nodes of cattle and pigs, cattle lungs and small intestine, and the internal organs of pigeons from the farms of Novosibirsk Oblast were analyzed. The study included 50 cultures of nontuberculous mycobacteria obtained from pathomorphological material of animals, 54 samples from environmental objects, such water from various sources, manure, soil from pastures and grazing, and foods (silage, straw, and haylage). Species of cultures were further identified on the basis of Novosibirsk Tuberculosis Research Institute using the time-of-flight mass spectrometry method and on microchips. Results and Discussion. Among the pathogenic fast-growing non- tuberculous mycobacteria in Novosibirsk Oblast, M. abscessus, M. fortuitum, M. chelonae, and less often M. magerityand M. mucogenicum were found most frequently. Among non-pathogenic slow-growing species, M. septicum, M. perigrinum, M. duvalii, M. senegalense, and M. monacense were found. M. gordonae was more common, in addition to Novosibirsk, in the Kochenevsky, Ordynsky, Iskitim, and Toguchinsky districts. M.chelonae/M.abscessus complex was found in Novosibirsk and the Vengerovsky district, M. perigrinum in the Suzunsky district, while M. nonchromogenicumand M. fortuitum only in Novosibirsk. Among the samples obtained from animals, representatives of MAComplex were most often found: M. avium and M. intracellulare. M.avium was more common than M. intracellulare and was found in Vengerovsky, Karasuksky, Krasnozersky, Kochkovsky, Chulymsky, and Orda districts and in Novosibirsk. Conclusions.3 possible foci were found in which cases of infection with mycobacteria of both humans and animals were detected. Therefore, humans and animals are able to create reservoirs of infection that increase the cross-infection likelihood.

Keywords: nontuberculous mycobacteria, farm animals, Novosibirsk Oblast, prevalence.

1. Альховик О. И., Мешков И. О., Петренко Т. И., Евдокимова Л. С. Выявление нетуберкулезных микобактерий, циркулирующих в разных регионах Сибири, и анализ их лекарственной устойчивости. Туберкулёз и болезни лёгких. – 2019. – Т. 97 (10). – С.5-11. [Al’hovik OI, Meshkov IO, Petrenko TI, Evdokimova LS. Vyyavlenie netuberkuleznyh mikobakterij, cirkuliruyushchih v raznyh regionah Sibiri, i analiz ih lekarstvennoj ustojchivosti [Identification of non-tuberculous mycobacteria circulating in different regions of Siberia and analysis of their drug resistance]. Tuberkulyoz i bolezni lyogkih [Tuberculosis and lung diseases].2019; 97 (10): 5-11. (In Russ.)]. DOI:10.21292/2075-1230-2019-97-10-5-11

2. Анисимов А.Н., Васильевых М.В. Микобактериозы сегодня // I Всероссийская научно-практическая конференция «Cовременная патология: опыт, проблемы, перспективы» с международным участием Сборник материалов под редакцией Ректора СамГМУ, профессора РАН А.В. Колсанова. – Самара, 2020. – С.7-14 [Anisimov AN, Vasil’evyh MV. Mikobakteriozy segodnya [Mikobakteriozy segodnya]. I Vserossijskaya nauchno-prakticheskaya konferenciya «Sovremennaya patologiya: opyt, problemy, perspektivy» s mezhdunarodnym uchastiem; Sbornik materialov pod redakciej Rektora SamGMU professora RAN AV Kolsanova [The Bulletein of Modern pathology: experience, problems, prospects; A collection of materials edited by the Rector of Samara State Medical University, Professor of the Russian Academy of Sciences AV Kolsanov]. Samara [Samara]. 2020; 7-14. (In Russ.)].

3. Бородина Г.Л., Суркова Л.К., Залуцкая О.М., [и др.]. Микобактериозы легких: учебно-методическое пособие. - Минск: БГМУ, 2018. – 1-9 c. [Borodina GL, Surkova LK, Zaluckaja OM, et al. Mikobakteriozy legkih: uchebno-metodicheskoe posobie [Mycobacterioses of lungs: educational and methodical manual]. Minsk: BGMU [Minsk: BSMU]. 2018; 30 p. (In Russ.)].

4. Гунтупова Л.Д., Французевич Л.Н., Акишина Ю.П., [и др.]. Клинические рекомендации: Микобактериозы органов дыхания // Межрегиональная общественная организация Российское Респираторное Общество, Московское общество фтизиатров. – Москва, 2022. – 35 с. [Guntupova LD, Francuzevich LN, Akishina YP, et al. Klinicheskie rekomendacii: Mikobakteriozy organov dyhaniya [Federal clinical recommendation Mycobacteriosis of the respiratory system]. Moskva: Mezhregional’naya obshchestvennaya organizaciya Rossijskoe Respiratornoe Obshchestvo, Moskovskoe obshchestvo ftiziatrov [Moscow: Interregional public organization Russian Respiratory Society, Moscow Society of Phthisiologists]. 2022; 35 p. (In Russ.)].

5. Зюзя Ю.Р., Кузина М.Г., Пархоменко Ю.Г. Морфологические особенности микобактериозов, вызванных нетуберкулезными микобактериями // Клиническая и экспериментальная морфология. – 2017. – No 4. – С.4-14. [Zjuzja JR, Kuzina MG, Parhomenko JG. Morfologicheskie osobennosti mikobakteriozov, vyzvannyh netuberkuleznymi mikobakteriyami [Morphological features of Mycobacterioses caused by non-tuberculous mycobacteria]. Klinicheskaya i eksperimental’naya morfologiya [Clinical and experimental morphology]. 2017; 4: 4–14 p. (In Russ.)].

6. Лямин А.В., Исматуллин Д.Д., Жестков А.В., [и др.]. Сравнительный анализ методов идентификации нетуберкулезных микобактерий, выделенных из клинического материала // Инфекция и иммунитет. – 2017. – No7(3). – С.285-291. [Ljamin AV, Ismatullin DD, Zhestkov AV, et al. Sravnitel’nyj analiz metodov identifikacii netuberkuleznyh mikobakterij, vydelennyh iz klinicheskogo materiala [Comparative analysis of identification methods of non-tuberculous mycobacteria isolated from clinicalmaterial]. Infekciya i immunitet [Infection and immunity]. 2017; 7 (3): 285-291. (In Russ.)]. DOI: 10.15789/2220–7619-2017-3-285-291

7. Макарова М.В., Гунтупова Л.Д. Нетуберкулезные микобактерии // БИОпрепараты. Профилактика, диагностика, лечение. – 2020. – No20.– С.98-99. [Makarova MV, Guntupova LD. Netuberkuleznye Mikobakterii [Nontuberculosis Mycobacterium]. BIOpreparaty: profilaktika, diagnostika, lechenie [Biological products: prevention, diagnosis, treatment]. 2020; 20: 98-99. (in Russ.)].

8. Мишина А.В., Мишин В.Ю., Эргешов А.Э., Романов В.В. Диагностика и клиника диссеминированных поражений легких у больных на поздних стадиях ВИЧ-инфекцией с иммуносупрессией (обзор) // Поликлиника. –2019. – No2, вып.14. – С.13-21. [Mishina AV, Mishin VJ, Jergeshov AJ, Romanov VV. Diagnostika i klinika disseminirovannyh porazhenij legkih u bol’nyh na pozdnih stadiyah VICh-infekciej s immunosupressiej (obzor) [Diagnosis and clinic of disseminated lung lesions in patients with late-stage HIV infection with immunosuppression (review). Poliklinika [Clinic]. 2019; 2 (14): 13-21. (In Russ.)].

9. Савченко М.А. Клинические и эпидемиологические аспекты микобактериоза у пациентов с ВИЧ-инфекцией // ВИЧ-инфекция и иммуносупрессии. – 2019. – No11(2). – С.27-33. [Savchenko MA. Klinicheskie i epidemiologicheskie aspekty mikobakterioza u pacientov s VICh-infekciej [Clinical and epidemiological aspects of Mycobacteriosis in patients with HIV infection]. VICH-infektsiya i immunosupressii [HIV infection and immunosuppression]. 2019; 11 (2): 27-33. (In Russ.)]. DOI: 10.22328/2077-9828-2019-11-2-27-33

10. Смирнова Т.Г., Андреевская С.Н., Ларионова Е.Е., [и др.]. Смешанные популяции микобактерий у больных туберкулезом и микобактериозом: частота выявления и спектр видов // Туберкулёз и социально значимые заболевания. – 2023. – Т. 11, No 2 (42). – С.19-24. [Smirnova TG, Andreevskaya SN, Larionova EE, et al. Smeshannye populyacii mikobakterij u bol’nyh tuberkulezom i mikobakteriozom: chastota vyyavleniya i spektr vidov [Mixed populations of mycobacteria in patients with tuberculosis and Mycobacteriosis: frequency of detection and range of species]. Tuberkulyoz i social’no znachimye zabolevaniya [Tuberculosis and socially significant diseases]. 2023; 11, 2 (42): 19-24. (In Russ.)]. DOI: 10.54921/2413-0346-2023-11-2-19-24

11. Старкова Д. А, Журавлев В.Ю., Вязовая А.А., [и др.]. Видовое разнообразие нетуберкулезных микобактерий у больных микобактериозом на территориях Северо-Западного федерального округа России // Туберкулез и болезни легких. – 2019. – No7 (6). – С.16-22. [Starkova DA, Zhuravlev VJ, Vjazovaja AA, et al. Vidovoe raznoobrazie netuberkuleznyh mikobakterij u bol’nyh mikobakteriozom na territoriyah Severo- Zapadnogo federal’nogo okruga Rossii [Species diversity of non-tuberculous mycobacteria in patients with mycobacteriosis in the North-Western Federal District of Russia]. Tuberkulez i bolezni legkikh [Tuberculosis and lung diseases]. 2019; 97 (6): 16-22 (In Russ.)].

12. Суркова Л.К., Залуцкая О.М., Николенко Е.Н., [и др.]. Распространение разных видов нетуберкулёзных микобактерий среди пациентов с заболеваниями лёгких за период 2014-2021гг. // В сборнике: БГМУ в авангарде медицинской науки и практики. – Минск, 2022. – С.410-414. [Surkova LK, Zaluckaya OM, Nikolenko EN, et al. Rasprostranenie raznyh vidov netuberkulyoznyh mikobakterij sredi pacientov s zabolevaniyami lyogkih za period 2014-2021 goda; V sbornike: BGMU v avangarde medicinskoj nauki i praktiki [Distribution of different types of non-tuberculous mycobacteria among patients with lung diseases for the period 2014-2021; In the collection: BSMU at the forefront of medical science and practice]. Minsk [Minsk]. 2022; 410-414. (In Russ.)].

13. Haworth CS, et al. British Thoracic Society guidelines for the management of non-tuberculous mycobacterial pulmonary disease (NTM-PD). Thorax. 2017; 72 (2): 1-64. DOI: 10.1136/thoraxjnl-2017-210927

14. Hoefsloot W, van Ingen J, Andrejak C, et al. The geographic diversity of non-tuberculous mycobacteria isolated from pulmonary sample. J Eur Respir. 2013; 42 (6): 1604-1613. DOI: 10.1183/09031936.00149212

15. Pereira AC, Ramos B, Reis AC, Cunha MV. Non-tuberculous Mycobacteria: molecular and physiological bases of virulence and adaptation to ecological niches. Microorganisms. 2020; 8 (9): 13-80. DOI: 10.3390/ microorganisms8091380

16. Yoshifumi U, Tomoyasu N, Yasunori S, et al. Low serum estradiol levels are related to Mycobacterium avium complex lung disease: a cross-sectional study. J BMC Infectious Diseases. 2019; 19, 1 (1055); 2-8. DOI: 10.1186/ s12879-019-4668-x

17. Zulipikaer M, Zhuo L, Chi X, et al. Non-TuberculosisMycobacterium periprosthetic joint infections following total hip and knee arthroplasty: case series and review of the literature. J Orthop Surg. 2023; 15 (6): 1488-1497. DOI: 10.1111/os.13661

 PROTON PUMP INHIBITORS IN THE COMBINED TREATMENT OF PATIENTS WITH MULTIDRUG-RESISTANCE TUBERCULOSIS

ZHUKOVA ELENA M., ORCID ID: 0000-0002-6156-84124; Dr. sc. med., Leading Researcher, Novosibirsk Tuberculosis Research Institute, 81A Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: zhukovaem.niit@yandex.ru

MALKOVA TATYANA A., ORCID ID: 0009-0008-2948-5888; Therapist, Outpatient Consultation Department, Novosibirsk Tuberculosis Research Institute, 81A Okhotskaya str., 630040 Novosibirsk, Russia.

SEROV OLEG A., ORCID ID: 0009-0006-3892-4083; Cand. sc. med., Senior Researcher, Novosibirsk Tuberculosis Research Institute, 81A Okhotskaya str., 630040 Novosibirsk, Russia.

Abstract. Introduction. Prevalence of multidrug-resistance tuberculosis requires the use of repurposed drugs, considering the molecular mechanisms of drug resistance. Combining mycobacterium efflux pump inhibitors and anti- tuberculosis drugs appears to be a potential synergistic combination for the treatment of multidrug-resistance tuberculosis.Aim of the study was to examine the effectiveness of treatment of multidrug-resistance tuberculosis patients additionally managed with proton pump inhibitor in the intensive phase of chemotherapy, including new anti-tuberculosis drugs, bedaquiline and linezolid. Materials and Methods. A retrospective study was conducted in the medical records of 77 patients with infiltrative/disseminated multidrug-resistance tuberculosis/ pre-extensive drug resistance tuberculosis, who were divided into 2 groups,. The main group consisted of 35 patients with concomitant gastrointestinal pathology who, in addition to anti-tuberculosis therapy, received treatment with a proton pump inhibitor. The comparison group included 42 patients without gastrointestinal pathology who received only anti-tuberculosis therapy. Statistical data processing was performed using Microsoft Excel 2007 and Statistica 6.0 by both nonparametric and parametric methods. Results and Discussion. During therapy with a proton pump inhibitor, more pronounced favorable changes were detected in the underlying disease. None of the patients had adverse reactions to combined therapy with a proton pump inhibitor and anti-tuberculosis drugs. The achieved effect is associated with the ability of this drug to both inhibit the export of anti-tuberculosis remedies in mycobacteria and activate immunocompetent cells, i.e., macrophages, with an increase in their bactericidal properties. Conclusions. The use of a proton pump inhibitor in the intensive phase of chemotherapy regimens, including new anti-tuberculosis drugs bedaquiline and linezolid, in multidrug-resistance tuberculosis patients is safe and increases the frequency of closure of decay cavities and cessation of bacterial excretion (by 29.2% and 30.1% by the 4th month, respectively); as well as the elimination of clinical manifestations of the disease. The data obtained can be used in the development of combination tuberculosis therapy, considering the molecular mechanisms of drug resistance.

1. Васильева И.А., Самойлова А.Г., Зимина В.Н., [и др.]. Химиотерапия туберкулеза в России – история продолжается // Туберкулёз и болезни лёгких. – 2023. – No 101 (2). – С.8–12. [Vasil’eva IA, Samojlova AG, Zimina VN, et al. Himioterapiya tuberkuleza v Rossii – istoriya prodolzhaetsya [Tuberculosis chemotherapy in Russia – the story continues]. Tuberkulyoz i bolezni lyogkih [Tuberculosis and lung diseases]. 2023; 101 (2): 8–12. (In Russ.)]. DOI: 10.58838/2075-1230-2023-101-2-8-12

2. Кукурика А.В., Веселова Е.И., Перегудова А.Б. Генетические аспекты лекарственной устойчивости микобактерий туберкулеза к новым препаратам с противотуберкулезной активностью // Туберкулёз и болезни лёгких. – 2023. – Т. 101, No 4. – С.87–93. [Kukurika AV, Veselova EI, Peregudova AB. Geneticheskie aspekty lekarstvennojustojchivosti mikobakterij tuberkuleza k novym preparatam s protivotuberkuleznoj aktivnost’yu [Genetic aspects of drug resistance of Mycobacterium tuberculosis to new drugs with anti-tuberculosis activity] Tuberkulyoz i bolezni lyogkih [Tuberculosis and lung diseases]. 2023; 101 (4): 87–93 (In Russ.)]. DOI: 10.58838/2075-1230-2023-101-4-87-93

3. Можокина ГН, Самойлова АГ, Абрамченко АВ, [и др.]. Стратегия «терапии хозяина» при туберкулезе. Значение интерферона-гамма в патогенезе и терапии туберкулезной инфекции // Туберкулёз и болезни лёгких. – 2024. – Т. 102, No1. – С.72–81. [Mozhokina GN, Samojlova AG, Abramchenko AV, et al. Strategiya «terapii hozyaina» pri tuberkuleze; Znachenie interferona-gamma v patogeneze iterapii tuberkuleznoj infekcii [The strategy of “host therapy” in tuberculosis; The importance of interferon-gamma in the pathogenesis and therapy of tuberculosis infection]. Tuberkulyoz I bolezni lyogkih [Tuberculosis and lung diseases]. 2024; 102 (1): 72–81. (In Russ.)]. DOI: 10.58838/2075-1230-2024-102-1-72-81

4. Андреевская С.Н., Ларионова Е.Е., Киселева Е.А., [и др.]. Сравнительная молекулярно-генетическая характеристика культур Mycobacterium tuberculosis, выделенных в Европейской части Российской Федерации в 1998–2003 гг. и 2016–2021 гг. // Туберкулёз и болезни лёгких. - 2023. – Т. 101, No3. – С.27–36. [Andreevskaya SN, Larionova EE, Kiseleva EA, et al. Sravnitel’naya molekulyarno-geneticheskaya harakteristika kul’tur Mycobacterium tuberculosis, vydelennyh v Evropejskoj chasti Rossijskoj Federacii v 1998–2003 i 2016–2021 godah [Comparative molecular and genetic characteristics of Mycobacterium tuberculosis cultures isolated in the European part of the Russian Federation in 1998-2003 and 2016-2021]. Tuberkulyoz I bolezni lyogkih [Tuberculosis and lung diseases]. 2023; 101 (3): 27–36]. DOI: 10.58838/2075-1230-2023-101-3-27-36

5. Swain SS, Sharma D, Hussain T, Pati S. Molecular mechanisms of underlying genetic factors and associated mutations for drug resistance in Mycobacterium tuberculosis. Emerging Microbes & Infections. 2020; 9(1): 1651– 1663.

6. Blair JM, Webber MA, Baylay AJ, et al. Molecular mechanisms of antibiotic resistance. Nat Rev Microbiol. 2015; 13 (1): 42–51.

7. Marquez B. Bacterial efflux systems and efflux pumps inhibitors. Biochimie. 2005; 87: 1137–1147.

8. Tegos GP, Haynes M, Strouse JJ, et al. Microbial Efflux Pump Inhibition: Tactics and Strategies. Curr Pharm Des. 2011; 17 (13): 1291–1302. DOI: 10.2174/138161211795703726

9. Saier MH Jr. A Functional-Phylogenetic Classification System for Transmembrane Solute Transporters. Microbiol Mol Biol Rev. 2000; 64 (2): 354–411. DOI: 10.1128/ MMBR.64.2.354-411.2000

10. Bapna A, Federici L, Venter H, et al. Two proton translocation pathways in a secondary active multidrug transporter. J Mol Microbiol Biotechnol. 2007; 12: 197–209.

11. Braibant M, Gilot P, Content J. The ATP binding cassette (ABC) transport systems of Mycobacterium tuberculosis. FEMS Microbiol Rev. 2000; 24 (4): 449–467.

12. Grzegorzewicz AE, Pham H, Gundi V, et al. Inhibition of mycolic acid transport across the Mycobacterium tuberculosis plasma membrane. Nat Chem Biol. 2012; 8: 334–341.

13. Lingjun Z, Wang J, Wang L, Qin C. The correlation of drug resistance and virulence in Mycobacterium tuberculosis. Biosaf Health. 2020; 2 (1): 18–24.

14. Mazurkiewicz P, Poelarends GJ, Driessen AJ, Konings WN. Facilitated drug influx by an energy-uncoupled secondary multidrug transporter. J Biol Chem. 2004; 279: 103–108.

15. Melly G, Purdy GE. MmpL Proteins in physiology and pathogenesis of M tuberculosis. Microorganisms. 2019; 7 (3): 70. DOI:10.3390/microorganisms7030070

16. Rodríguez JE, Ramírez A, Salas L, et al. Transcription of genes involved in sulfolipid and polyacyltrehalose biosynthesis of Mycobacterium tuberculosis in experimental latent tuberculosis infection. PLoS One. 2013; 8 (3): e58378. DOI:10.1371/journal.pone.0058378

17. Sharma A, Gupta VK, Pathania R. Efflux pump inhibitors for bacterial pathogens: From bench to bedside. Indian J Med Res. 2019; 149 (2): 129–145.

18. Nakashima R, Sakurai K, Yamasaki S, Nishino K, Yamaguchi A. Structures of the multidrug exporter AcrB reveal a proximal multisite drug-binding pocket. Nature. 2011; 480: 565–569. DOI: 10.1038/nature10641

19. Фелькер И.Г., Гордеева Е.И., Ставицкая Н.В., [и др.]. Перспективы и препятствия для клинического применения ингибиторов эффлюксных помп Mycjbacterium tuberculosis. Биологические мембраны. – 2021. – Т.38, No5. – С. 317–339. [Fel’ker IG, Gordeeva EI, Stavickaya NV, et al. Perspektivy I prepyatstviya dlya klinicheskogo primeneniya ingibitorov efflyuksnyh pomp Mycjbacterium tuberculosis [Prospects and obstacles for the clinical use of Mycobacterium tuberculosis efflux pump inhibitors]. Biologicheskie membrany [Biological membranes]. 2021; 38 (5): 317–339. (In Russ.)]. DOI:10.31857/ S0233475521050054

20. Gupta S, Cohen KA, Winglee K, et al. Efflux inhibition with verapamil potentiates bedaquiline in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 2014; 58 (1): 574–576.

21. Singh M, Jadaun GP, Srivastava K, et al. Effect of efflux pump inhibitors on drug susceptibility of ofloxacin resistant Mycobacterium tuberculosis isolates. Indian J Med Res. 2011; 133 (5): 535–540.

22. Radchenko M, Symersky J, Nie R, Lu M. Structural basis for the blockade of MATE multidrug efflux pumps. Nat Commun. 2015; 6: 7995. DOI:10.1038/ncomms8995

23. Adams KN, Szumowski JD, Ramakrishnan L. Verapamil and Its metabolite norverapamil, inhibit macrophage-induced, bacterial efflux pumpmediated tolerance to multiple anti-tubercular drugs. J Infect Dis. 2014; 210 (3): 456–466.

24. Gupta S, Tyagi S, Almeida DV, et al. Acceleration of tuberculosis treatment by adjunctive therapy with verapamil as an efflux inhibitor. Am J Respir Crit Care Med. 2013; 188 (5): 600–607.

25. Li G, Zhang J, Guo Q, et al. Study of efflux pump gene expression in rifampicin-monoresistant Mycobacterium tuberculosis clinical isolates. J Antibiot (Tokyo). 2015; 68 (7): 431–435 (2015). DOI: 10.1038/ja.2015.9

26. Machado D, Couto I, Perdigao J, Rodrigues L, Portugal I, et al. Contribution of efflux to the emergence of isoniazid and multidrug resistance in Mycobacterium tuberculosis. PLoS One. 2012; 7 (4): e34538. DOI: 10.1371/journal. pone.0034538

27. Singh K, Kumar M, Pavadai E, et al. Synthesis of new verapamil analogues and their evaluation in combination with rifampicin against Mycobacterium tuberculosis and molecular docking studies in the binding site of efflux protein Rv1258c. Bioorg Med Chem Lett. 2014; 24 (14): 2985–2990.

28. Adams KN, Takaki K, Connolly LE, et al. Drug tolerance in replicating mycobacteria mediated by a macrophage-induced efflux mechanism. Cell. 2011; 145 (1): 39–53.

29. Roy SK, Pahwa S, Nandanwar H, Jachak SM. Phenylpropanoids of Alpinia galanga as efflux pump inhibitors in Mycobacterium smegmatis mc2 155. Fitoterapia. 2012; 83 (7): 1248–1255.

30. Gupta S, Tyagi S, Bishai WR. Verapamil increases the bactericidal activity of bedaquiline against Mycobacterium tuberculosis in a mouse model. Antimicrob Agents Chemother. 2015; 59 (1): 673–676.

31. Jones RM, Adams KN, Eldesouky HE, Sherman DR. The evolving biology of Mycobacterium tuberculosis drug resistance. Front Cell Infect Microbiol. 2022; 12: 1027394.

32. Kim RD, et al. Pulmonary nontuberculous mycobacterial disease: Prospective study of a distinct preexisting syndrome. Am J Respir Crit Care Med. 2008; 178: 1066–1074.

33. Lakea MA, Adamsc KN, Nied F, et al. The human proton pump inhibitors inhibit Mycobacterium tuberculosis rifampicin efflux and macrophage-induced rifampicin tolerance. MicrobioIogy. 2023; 120 (7): 1-10, e2215512120. DOI: 10.1073/pnas.2215512120

34. Robinson M, Horn J. Clinical pharmacology of proton pump inhibitors: What the practising physician needs to know. Drugs. 2003; 63: 2739–2754.

35. Rybniker J, et al. Lansoprazole is an antituberculous prodrug targeting cytochrome bc1. Nat Commun. 2015; 6: 7659.

36. Fan WC et al. Increased risk of pulmonary tuberculosis in patients with gastroesophageal reflux disease. Int J Tuberc Lung Dis. 2016; 20: 265–270.

37. Hsu WH et al. Acid suppressive agents and risk of Mycobacterium tuberculosis: Case-control study. BMC Gastroenterol. 2014; 14: 91.

38. Ishizaki T, Horai Y. Cytochrome P450 and the metabolism of proton pump inhibitors - emphasis on rabeprazole. Aliment Pharmacol Ther. 1999; 13: 27–36.

39. Kamiya C, et al. Effect of co-administered inducer or inhibitor on omeprazole pharmacokinetics based on CYP2C19 genotype. J Pharmacol Sci. 2019; 139: 361–366.

40. Song HJ, Park H, Park S, Kwon J-W. The association between proton pump inhibitor use and the risk of tuberculosis: A case-control study. Pharmacoepidemiol Drug Saf. 2019; 28: 830–839.

 CLINICAL SIGNIFICANCE OF A HISTOPATHOLOGICAL EXAMINATION IN THE DIFFERENTIAL DIAGNOSIS OF DISSEMINATED PROCESSES IN LUNGS

MENTYUKOVA-SUZDALTSEVA IRINA YU., ORCID ID: 0009-0008-0259-5286, Pathologist, Head of the Pathology Unit, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia.
E-mail: i.suzdalceva@nsk-niit.ru

TURSUNOVA NATALYA V., ORCID ID: 0000-0003-3051-2632, Cand. sc. biol., Leading Researcher, Scientific and Organizing Department, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: us-nniit@mail.ru

Abstract. Introduction. Disseminated processes in the lungs include more than two hundred diseases and syndromes, similar in clinical, radiological and laboratory manifestations, which is the main reason for the difficulty of differential diagnosis. In most cases, histopathological examination plays a key role in making the correct diagnosis. Aim is to analyze the current state of the problem of diagnosing disseminated processes in lungs exemplified by the experience of an anti-tuberculosis hospital and assess the algorithm for the differential diagnosis of pulmonary dissemination using histological methods. Materials and Methods. Histopathological findings (156 clinical cases) were obtained at Novosibirsk Tuberculosis Research Institute for the period of 2022-2023. The diagnostic material was biopsy tis- sue samples. Sections were stained with hematoxylin-eosin by the methods of Van Gieson or Weigert-Van Gieson, Ziehl-Neelsen, Grocott, and Perls. Results and Discussion. The study presents an analysis of cases of differential diagnosis of disseminated lung diseases of unknown etiology and provides the clinical examples of histopathological examination of biopsy material from hospital inpatients. Most often, in the presence of granulomatous processes, the preliminary diagnosis of pulmonary tuberculosis was confirmed. The second place in frequency was taken by chronic nonspecific pulmonary diseases (about 1⁄4 of the total number of patients, which can be explained by their significant prevalence among the population). Chronic infections of fungal etiology were found in the samples, especially in immunosuppressed individuals. Conclusions. Diagnosis of disseminated processes in the lungs using analysis of histologi- cal material obtained through transbronchial lung biopsy, diagnostic thoracotomy, mediastinoscopy, or video-assisted thoracoscopy is the most accurate and allows the medical professional to quickly identify the nature of dissemination. The main morphological assessing algorithm includes the identification of inflammation and the subsequent clarification of the type of pathogen, using additional stains.

1. Бородулина Е.А. Яковлева Е.В. Диссеминированный туберкулез легких: современные аспекты // Science & Innovations in Medicine. – 2017. – Т. 2, No 6. – С. 39–43. [Borodulina EA, Yakovleva EV. Disseminirovannyj tuberkulez legkih: sovremennye aspekty. [Disseminated pulmonary tuberculosis: modern aspects]. Science & Innovations in Medicine. 2017; 2 (6): 39–43. (In Russ.)].

2. Яблонский П.К., Старшинова А.А. 95 лет Санкт-Петербургскому институту фтизиопульмонологии: основные направления исследований за последние десятилетия по профилактике, диагностике и лечению туберкулеза // Туберкулез и болезни легких. – 2018. – Т. 96, No 12. – С.72–78. [Yablonskij PK, Starshinova AA. 95 let Sankt-Peterburgskomu institutu ftiziopul’monologii: osnovnye napravleniya issledovanij za poslednie desyatiletiya po profilaktike, diagnostike i lecheniyu tuberkuleza [95 years of the St. Petersburg Institute of Phthisiopulmonology: main areas of research over the past decades on the prevention, diagnosis and treatment of tuberculosis]. Tuberkulez i bolezni legkih [Tuberculosis and lung diseases]. 2018; 96 (12): 72–78. (In Russ.)].

3. Valeyre D, Duchemann B, Nunes H, et. al. Interstitial lung diseases. In: Respiratory Epidemiology. ERS. 2014: 79– 87. https://www.researchgate.net/publication/290520994_ Interstitial_lung_diseases.

4. Илькович М.М. Интерстициальные заболевания легких:рассуждения на актуальную тему. Часть 2 // Болезни органов дыхания. Приложение к журналу Consilium Medicum. – 2014. – No 1. – С.7–9. [Il’kovich MM. Intersticial’nye zabolevaniya legkih: rassuzhdeniya na aktual’nuyu temu: Chast’ 2 [Interstitial lung diseases: considerations on a current topic: Part 2]. Сonsilium medicum; Prilozhenie: Bolezni organov dyhaniya [Сonsilium medicum; Application: Respiratory diseases]. 2014; 1: 7–9. (In Russ.)].

5. Шостак Н.А., Клименко А.А., Кондрашов А.А. Интерстициальные заболевания легких: ключевые мишени для терапии // Клиницист. – 2017. – Т. 11, No 3–4. – С.10–6. [Shostak NA, Klimenko AA, Kondrashov AA. Intersticial’nye zabolevaniya legkih: klyuchevye misheni dlya terapii [Interstitial lung diseases: key targets for therapy]. Klinicist [Clinician]. 2017; 11 (3–4): 10–6. (In Russ.)].

6. Быхалов Л.С., Смирнов А.В. Патоморфологические изменения в легких при туберкулезе на разных стадиях ВИЧ-инфекции // Вестник ВолгГМУ. – 2014. – Вып.2, No 50. – C.27–31. [Byhalov LS, Smirnov AV. Patomorfologicheskie izmeneniya v legkih pri tuberkuleze na raznyh stadiyah VICH-infekcii [Pathomorphological changes in the lungs in tuberculosis at different stages of HIV infection]. Vestnik VolgGMU [Bulletin of VolgSMU]. 2014; 2 (50): 27–31. (In Russ.)].

7. Саркоидоз. Клинические рекомендации. – Москва: Министерство здравоохранения Российской Федерации, 2022. – 63 с. [Sarkoidoz: Klinicheskie rekomendacii [Sarcoidosis: Clinical guidelines]. Moskva: Ministerstvo zdravookhraneniya Rossiyskoy Federatsii [Moscow: Ministry of Health of the Russian Federation]. 2022; 63 p. (In Russ.)]. https://cr.minzdrav.gov.ru/schema/736_1

8. Semenova LA, Radenska-Lopovok SG, Burtseva SA, Berezovskiĭ IuS, Lepekha LN. Necrotizing sarcoid granulomatosis. Russian Journal of Archive of Pathology. 2016; 78 (5): 45–49.

9. Самсонова М.В., Черняев А.Л. Гистологическая дифференциальная диагностика гранулематозных болезней легких (часть I) // Архив патологии. – 2019. – Т.81, No 1. – С.65–70. [Samsonova MV, Chernyaev AL. Gistologicheskaya differencial’naya diagnostika granulematoznyh boleznej legkih (chast’ I). [Histological differential diagnosis of granulomatous lung diseases (part I)]. Arhiv patologii [Pathology Archive]. 2019; 81 (1): 65–70. (In Russ.)].

10. Трофименко И.Н., Черняк Б.А. Поражения легких при системных заболеваниях соединительной ткани // Пульмонология. – 2019. – Т. 29, No5. – С.604–611. [Trofimenko IN, Chernyak B. Porazheniya legkih pri sistemnyh zabolevaniyah soedinitel’noj tkani [Lung lesions in connective tissue diseases]. Pul’monologiya [Russian Pulmonology]. 2019; 29 (5): 604–611 (in Russ.)]. DOI: 10.18093/0869-0189-2019-29-5-604-611

11. Стародубцев А.Л., Рагулин Ю.А., Курильчик А.А., [и др.]. Отдалённые результаты комбинированного лечения метастазов сарком опорно-двигательного аппарата в лёгких // Злокачественные опухоли. – 2014. – No 3. – С.48–51. [Starodubcev AL, Ragulin YuA, Kuril’chik AA, et al. Otdalyonnye rezul’taty kombinirovannogo lecheniya metastazov sarkom oporno-dvigatel’nogo apparata v lyogkih [Long-term results of combined treatment of metastases of musculoskeletal sarcomas in the lungs]. Zlokachestvennye opuholi [Malignant tumors]. 2014; 3: 48–51. (In Russ.)].

12. Шалыга А.В, Мишин А.В., Козловская Т.В., [и др.]. Идиопатический гемосидероз легких (Синдром Целена-Геллерстдта) // Проблемы здоровья и экологии. – 2016. – No 1. – C. 90–94. [Shalyga AV, Mishin AV, Kozlovskaya TV, et al. Idiopaticheskij gemosideroz legkih (Sindrom Celena-Gellerstdta) [Idiopathic pulmonary hemosiderosis (Zelen-Gellerstdt syndrome)]. [Health and environmental issues]. 2016; 1: 90–94. (In Russ.)].

13. Владимирова Е.Б., Шмелев Е.И., Зайцева А.С., [и др.]. Нетуберкулезный микобактериоз легких – возможности диагностики в практике пульмонолога // Терапевтический архив. – 2019. – Т. 91, No 11. – C.26–31. [Vladimirova EB, Shmelev EI, Zaytseva AS, et al. Non-tuberculous mycobacteriosis of the lungs – diagnostic possibilities in the practice of the pulmonologist]. Terapevticheskii arkhiv [Therapeutic archive]. 2019; 91 (11): 26–31. (In Russ.)]. DOI: 10.26442/00403660.2019.11.000306

14. Двораковская И.В., Майская М.Ю., Насыров Р.А., [и др.]. Морфологическое исследование в дифференциальной диагностике туберкулеза и саркоидоза // Архив патологии. – 2014. – No 1. – С.27–31. [Dvorakovskaya IV, Majskaya MYU, Nasyrov RA, et al. Morfologicheskoe issledovanie v differencial’noj diagnostike tuberkuleza i sarkoidoza [Morphological study in the differential diagnosis of tuberculosis and sarcoidosis]. Arhiv patologii [Pathology Archive]. 2014; 1: 27–31. (In Russ.)].

15. Самсонова М.В., Черняев А.Л., Гистологическая дифференциальная диагностика гранулематозных болезней легких (часть II) // Архив патологии. – 2019. – No2. – С.59–65. [Samsonova MV, Chernyaev AL. Gistologicheskaya differencial’naya diagnostika granulematoznyh boleznej legkih (chast’ II). [Histological differential diagnosis of granulomatous lung diseases (part II)]. Arhiv patologii [Pathology Archive]. 2019; 81 (2): 59–65. (In Russ.)].

16. Половников И.В., Юкина Г.Ю., Сухорукова Е.Г. Патоморфологическая характеристика лимфангиолейомиоматоза легких // Журнал анатомии и гистопатологии. – 2023. – Т.12, No 4. – С.89–97. [Polovnikov IV, Yukina GYu, Suhorukova EG. Patomorfologicheskaya harakteristika limfangiolejomiomatoza legkih [Pathomorphological characteristics of pulmonary lymphangioleiomyomatosis]. Zhurnal anatomii i gistopatologii [Journal of Anatomy and Histopathology]. 2023; 12 (4): 89–97 (In Russ.)]. DOI: 10.18499/2225-7357-2023-12-4-89-97

 INQUIRY INTO THE CAUSES OF THE POSTRESECTION RECURRENCES OF PULMONARY TUBERCULOSIS IN SIBERIA AND THE FAR EAST

MOROZOV PAVEL S., ORCID ID: 0009-0001-4785-9483, Postgraduate Student, Thoracic Surgeon, Department of Tuberculosis & Pulmonary Surgery, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: sodzo1868@gmail.com

GRISCHENKO NIKOLAY G., ORCID ID: 0009-0001-8730-743X, RSCI Author ID 304381, Dr. sc. med., Chief Researcher, Thoracic Surgeon, Department of Tuberculosis & Pulmonary Surgery, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: gng950@mail.ru

SKVORTSOV DMITRY A., ORCID: ID 0000-0003-0943-9266, RSCI Author ID 304381, Cand. sc. med., Thoracic Surgeon, Head of the Department of Tuberculosis & Pulmonary Surgery, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel. +7(383)203-79-06. E-mail: d.skvorcov@nsk-niit.ru

Abstract. Introduction. Relapsing pulmonary tuberculosis after medication and after surgical treatment is one of the most pressing problems in phthisiology. The frequency of respiratory tuberculosis relapses is one of the indicators characterizing the intensity of the epidemiological situation regarding tuberculosis. Therefore, the problem of relapses is most relevant in territories that are epidemically unfavorable for tuberculosis, such as the Siberian and the Far Eastern Federal Districts of Russia. Aim is to define the clinical determinants of pulmonary tuberculosis relapses after radical surgery in the Siberian and the Far Eastern Federal Districts of Russia. Materials and Methods. In total, clinical cases of 122 patients were analyzed, who had been re-operated at Novosibirsk Tuberculosis Research Institute in the period of 2018-2022. Results and Discussion. In the studied cohort of patients, 58% of patients were found clinically cured after surgical treatment of tuberculosis, and a relapse developed in 42% of cases, respectively. The proportion of re- lapses that developed within 5 years after surgery in the analyzed cohort of patients was 65% of cases, while those developed within 5 to 10 years amounted to half as much. The predominant type of surgical intervention (80% of cases) performed initially was an atypical resection. An unreasonably selected area of the initial surgical intervention led to the development of relapse. This study has found that the proportion of concomitant immunodeficiency conditions (HIV infections) is represented in 4% of cases. Positive clinical success was achieved mainly due to repeated resections with minimal postoperative complications (3% of cases). Conclusions. The main clinical determinants of tuberculosis relapse development in previously operated patients were the fibrous-cavernous form of tuberculosis, chronic obstruc- tive pulmonary disease as a concomitant disease, the unreasonable strategies of the initial surgical interventions, such as insufficient resection area, complicated postoperative course, inadequate anti-tuberculosis therapy, and withdrawal of patients from treatment.

1. Гиллер Д.Б., Мургустов И.Б., Мартель И.И., [и др.]. Повторные резекции легкого у больных с послеоперационным рецидивом туберкулеза в оперированном легком (обзор литературы и собственные данные) // Хирургия. – 2015. – Т. 8, No 2. – С.14–19. [Giller DB, Murgustov IB, Martel II, et al. Povtornye rezekcii legkogo u bol’nyh s posleoperacionnym recidivom tuberkuleza v operirovannom legkom (obzor literatury i sobstvennye dannye) [Repeated lung resections in patients with postoperative recurrence of tuberculosis in the operated lung (literature review and own data)]. Hirurgiya [Syrgery]. 2015; 8 (2): 14–19. (in Russ)]. DOI: 10.17116/hirurgia20158214-19

 NEUTROPHILS’ ABILITY TO FORM NETS EX VIVO AND THE CITRULLINATED HISTONE H3 LEVELS IN BLOOD DURING THE PREVENTIVE CHEMOTHERAPY OF LATENT TUBERCULOSIS INFECTION

NOVIKOV DMITRIJ G., ORCID ID: 000–0002–4339–2222; Cand. sc. med., Associate Professor, Cand. sc. med., Head of the Central Research Laboratory, Omsk State Medical University, 12 Lenin str., 644099 Omsk, Russia. E–mail: novikov.dm.omsk@gmail.com

ZOLOTOV ALEXANDER N., ORCID ID: 0000–0002–6775–323Х; Cand. sc. med., Senior Researcher at the Central Research Laboratory, Associate Professor at the Department of Pathophysiology, Omsk State Medical University, 12 Lenin str., 644099 Omsk, Russia. E–mail: azolotov@mail.ru

MORDYK ANNA V., ORCID ID: 0000–0001–6196–7256; Dr. sc. med., Professor, Head of the Department of Phthisiology, Phthisiosurgery and Infectious Diseases, Omsk State Medical University, 12 Lenin str., 644099 Omsk, Russia. E–mail: amordik@mail.ru

INDUTNY ANTON V., ORCID ID: 0000–0003–1951–5824; Dr. sc. med., Associate Professor, Head of the Department of Clinical Laboratory Diagnostics, including Postgraduate Training Courses, Omsk State Medical University, 15/1 20 let RKKA str., 644001 Omsk, Russia. E–mail: anton@indutny.com

KIRICHENKO NIKOLAJ А., ORCID ID: 0000–0002–8411–0973; Junior Researcher at the Central Research Laboratory, Omsk State Medical University, 15/1 20 let RKKA str., 644001 Omsk, Russia. E–mail: honomer_1608@mail.ru

ROMANOVA MARIYA А., ORCID ID: 0000–0002–1775–607X; Cand. sc. med., Associate Professor at the Department of Phthisiology, Phthisiosurgery and Infectious Diseases, Omsk State Medical University, 12 Lenin str., 644099 Omsk, Russia. E–mail: rmari1@mail.ru

PTUKHIN ALEXANDER О., ORCID ID: 0000–0002–2830–161Х; Postgraduate Student at the Department of Phthisiology, Phthisiourgery and Infectious Diseases, Omsk State Medical University, 12 Lenin str., 644099 Omsk, Russia. E–mail: ptuhin.aleksandr@gmail.com

Abstract. Introduction. Assessment of changes in the cellular link of innate immunity can enhance the informativeness of approaches to the diagnosis of latent tuberculosis infection. The process of forming neutrophil extracellular traps, NETosis, was described relatively recently, and there is no information in scientific publications about changes in neutrophils’ NETosis ability during preventive chemotherapy in latent tuberculosis infection. Aim. To determine the ability of peripheral blood neutrophils to form extracellular traps ex vivo, and the contents of citrullinated histone H3, PAD4, dynamin–like protein–1, and interleukins 1 and 8 in blood after a 6–month course of preventive chemotherapy for latent tuberculosis infection in children. Materials and Methods. Peripheral blood neutrophils’ ability to form extracellular traps after exposure to a nonspecific antigenic stimulant was studied, as well as the concentrations of citrullinated histone H3, Peptidyl arginine deiminase 4, dynamin–like protein–1, and interleukins 1 and 8 in blood. Group 1 (“Control”) included 30 healthy children with negative tuberculin reaction to tuberculin. Group 2 included 27 children with latent tuberculosis infection, having a positive tuberculosis recombinant allergen test reaction. In this group, all studies were performed at two study points: Point 1 – at the time of initial detection of the infection, point 2 – 6 months after the start of preventive chemotherapy. Results and Discussion. Neutrophils’ ability to form extracellular traps in Group 2 at Point 1 was significantly higher compared to that in the Control Group, with neutrophils more often forming filamentous traps (p=0.0419). After preventive chemotherapy (Point 2), we observed a decrease in the proportion of thread traps (p=0.0357) to the level of the Control Group (p=0.0724). The content of citrullinated histone H3 in the blood of patients from Group 2 at Point 1 was Me=5.60 (Q1=2.80; Q3=12.00) and, statistically, significantly higher (p=0.0002) as compared to the values of the Control Group: Me=1.41 (Q1=0.91; Q3=1.78). In preventive chemotherapy, the analyte concentration decreased: Me=1.20 (Q1=0.90; Q3=1.50), reaching the values that did not differ from those observed in the Control Group. Examining the concentrations of PAD4, dynamin–like protein–1, and interleukins 1 and 8 in blood did not reveal statistically significant differences between the groups studied. Conclusions. In the preventive chemotherapy of latent tuberculosis infection against the background of achieving positive clinical results, normalization of neutrophils’ ability to form extracellular traps was observed, and the proportion of filamentous traps decreased. Decrease in the citrullinated histone H3 content in the blood probably indicated weakening of the intensity of nephrosis. These indicators can be considered as probable and promising markers of the positive results of the chemotherapy of latent tuberculosis infection.

Keywords: children, latent tuberculosis infection, preventive chemotherapy, NETosis, neutrophil extracellular traps, NETosis biomarkers

For reference: Novikov DG, Zolotov AN, Mordyk AV, et al. Neutrophils’ ability to form NETs ex vivo and the citrullinated histone H3 levels in blood during the preventive chemotherapy of latent tuberculosis infection. The Bulletin of Contemporary Clinical Medicine. 2024; 17 (5): 54-63. DOI: 10.20969/VSKM.2024.17(5).54-63.

2. Cohen A, Mathiasen VD, Schön T, Wejse C. The global prevalence of latent tuberculosis: a systematic review and meta–analysis. Eur Respir J. 2019; 54 (3): 1900655. DOI: 10.1183/13993003.00655–2019. PMID: 31221810.

3. Sterling TR, Njie G, Zenner D, et al. Guidelines for the Treatment of Latent Tuberculosis Infection: Recommendations from the National Tuberculosis Controllers Association and CDC, 2020. MMWR Recomm Rep. 2020; 69 (1): 1–11. DOI: 10.15585/mmwr.rr6901a1

4. WHO consolidated guidelines on tuberculosis. Module 1: Prevention – Tuberculosis preventive treatment, second edition [Internet]. Geneva: World Health Organization; 2024. Режим доступа [URL]: https://www.who.int/ publications/i/item/9789240097773

5. Kontsevaya I, Cabibbe AM, Cirillo DM, et al. Update on the diagnosis of tuberculosis. Clin Microbiol Infect. 2024; 30 (9): 1115–1122. DOI: 10.1016/j.cmi.2023.07.014

6. Мордык А.В., Золотов А.Н., Новиков Д.Г., [и др.]. Нетозобразующая способность нейтрофилов у детей с латентной туберкулезной инфекцией при положительной пробе с аллергеном туберкулезным рекомбинантным // Вопросы практической педиатрии. – 2023. – Т. 18, No 5. – С.7–12. [Mordyk AV, Zolotov AN, Novikov DG, et al. Netozobrazuyushchaya sposobnost’ nejtrofilov u detej s latentnoj tuberkuleznoj infekciej pri polozhitel’noj probe s allergenom tuberkuleznym rekombinantnym [NETosis–forming ability of neutrophils in children with latent tuberculosis infection with the positive test with a tuberculosis recombinant allergen]. Voprosy prakticheskoj pediatrii [Clinical Practice in Pediatrics]. 2023; 18 (5): 7–12. (In Russ.)]. DOI: 10.20953/1817–7646–2023–5–7–12

7. Brinkmann V, Reichard U, Goosmann C, et al. Neutrophil extracellular traps kill bacteria. Science. 2004; 303 (5663): 1532–1535. DOI: 10.1126/science.1092385

8. Воробьева Н.В., Кулаков В.В. Роль белка DRP1, ответственного за фрагментацию митохондрий, в окислительном взрыве и нетозе нейтрофилов человека // Российский иммунологический журнал. – 2019. – Т. 22, No2–2. – C.733–735. [Vorobjeva NV, Kulakov VV. Rol’ belka DRP1, otvetstvennogo za fragmentaciyu mitohondrij, v okislitel’nom vzryve i netoze nejtrofilov cheloveka [The role of DRP1 protein, responsible for mitochondrial fragmentation, in the oxidative burst and netosis of human neutrophils]. Rossijskij immunologicheskij zhurnal [Russian Journal of Immunology]. 2019; 22 (2–2): 733– 735. (In Russ.)]. DOI: 10.31857/S102872210006720–7

9. Патент No 2768152 C1 Российская Федерация, МПК G01N 33/569, G01N 33/533, G01N 33/577. Способ обнаружения нейтрофильных внеклеточных ловушек в суправитально окрашенном препарате крови: No 2021129097: заявл. 06.10.2021: опубл. 23.03.2022 / Д.Г. Новиков, А.Н. Золотов, Н.А. Кириченко, А.В. Мордык; заявитель федеральное государственное бюджетное образовательное учреждение высшего образования «Омский государственный медицинский университет» Министерства здравоохранения Российской Федерации. – 20 c.: ил. – Текст: непосредственный. [Novikov DG, Zolotov AN, Kirichenko NA, Mordyk AV. Patent No 2768152 C1 Russian Federation, IPC G01N 33/569, G01N 33/533, G01N 33/577: Sposob obnaruzhenija nejtrofil’nyh vnekletochnyh lovushek v supravital’no okrashennom preparate krovi No 2021129097 [Patent No 2768152 C1 Russian Federation, IPC G01N 33/569, G01N 33/533, G01N 33/577: Method for detection of neutrophil extracellular traps in supravital stained blood preparation No 2021129097]. Omsk: Omskii gosudarstvennii medicinskii universitet [Omsk: Omsk State Medical University]. 2022; 20 р. (In Russ.)].

10. Глушаков И.А., Лозовская М.Э., Гуткин М.Г., [и др.]. Латентная туберкулезная инфекция у детей и подростков: вопросы превентивного лечения // Children’s Medicine of the North–West. – 2024. – Т. 12, No 2. – С.187–194. [Glushakov IA, Lozovskaya ME, Gutkin MG, et al. Latentnaya tuberkuleznaya infekciya u detej i podrostkov: voprosy preventivnogo lecheniya [Latent tuberculosis infection in children and adolescents: preventive treatment issues].Children’sMedicineoftheNorth–West[Children’s Medicine of the North–West]. 2024; 12 (2): 187–194. (In Russ.)]. DOI: 10.56871/CmN–W.2024.88.83.018

11. Аксенова В.А., Клевно Н.И., Казаков А.В., [и др.]. Превентивная химиотерапия у детей из очагов туберкулеза с множественной лекарственной устойчивостью возбудителя // Туберкулез и болезни легких. – 2019. – Т. 97, No 6. – С. 36–43. [Aksenova VA, Klevno NI, Kazakov AV, et al. Preventivnaya himioterapiya u detej iz ochagov tuberkuleza s mnozhestvennoj lekarstvennoj ustojchivost’yu vozbuditelya [Preventive chemotherapy in children exposed to multiple drug resistant tuberculosis]. Tuberkulez i bolezni legkih [Tuberculosis and Lung Diseases]. 2019; 97 (6): 36–43. (In Russ.)]. DOI: 10.21292/2075–1230–2019–97–6–36–43

12. Mokrousov I, Vyazovaya A, Sinkov V, et al. Practical approach to detection and surveillance of emerging highly resistant Mycobacterium tuberculosis Beijing 1071–32– cluster. Sci Rep. 2021; 11 (1): 21392. DOI: 10.1038/ s41598–021–00890–7

13. Vinogradova T, Dogonadze M, Zabolotnykh N, et al. Extremely lethal and hypervirulent Mycobacterium tuberculosis strain cluster emerging in Far East, Russia. Emerg Microbes Infect. 2021; 10 (1): 1691–1701. DOI: 10.1080/22221751.2021.1967704

14. Ramos–Kichik V, Mondragón–Flores R, Mondragón–Castelán M, et al. Neutrophil extracellular traps are induced by Mycobacterium tuberculosis. Tuberculosis (Edinb). 2009; 89 (1): 29–37. DOI: 10.1016/j.tube.2008.09.009

 ASSESSING THE SIGNIFICANCE OF LOCAL INFLAMMATORY CHANGES IN THE BRONCHIAL TREE FOR THE EFFICACY OF PULMONARY TUBERCULOSIS TREATMENT

PETRENKO TATYANA I., ORCID ID: 0000-0002-9624-5234; Dr. sc. med, Associate Professor, Head of the Department of Phthisiopulmonology, Novosibirsk State Medical University, 52 Krasny Prospekt str., 630091 Novosibirsk, Russia. E-mail: tipetrenko@gmail.com

1. Кольникова О.В., Гудова С.В. Особенности выявления туберкулеза бронха как осложнения туберкулеза внутригрудных лимфатических узлов у пациента пожилого возраста // Современные проблемы науки и образования. – 2020. – No 5. [Shkolnikova OV, Gudkova SV. Osobennostivyyavleniya tuberkuleza bronha kak oslozhneniya tuberkuleza vnutrigrudnyh limfaticheskih uzlov u pacienta pozhilogo vozrasta [Features of the detection of bronchial tuberculosis as a complication of tuberculosis of the intrathoracic lymph nodes in an elderly patient]. Sovremennye problemy nauki i obrazovaniya [Modern problems of science and education]. 2020; 5. (In Russ.)]. Режим доступа [URL]: https://science-education. ru/article/view?id=30224 DOI: 10.17513/spno.30224

2. Агеева Т.С., Волкова Л.И., Мишустина Е.Л., Мишустин С.П. Туберкулез бронхов в общеврачебной практике // Фундаментальные исследования. - 2014. - No 10-7. - С.1265-1268. [Ageeva TS, Volkova LI, Mishustina EL, Mishustin SP. Tuberkulez bronhov v obshchevrachebnoj praktike [Bronchial tuberculosis in general medical practice]. Fundamental’nye issledovaniya [Fundamental research]. 2014; 10 (7): 1265-1268 (In Russ.)].

3. Кузиев А.А, Парпиева Н.Н., Иргашев А.А. Поражение бронхов при ограниченных и распространенных формах туберкулеза легких // Туберкулез и болезни легких. – 2011. – No 4. – С.220. [Kuziev AA, Parpieva NN, Irgashev AA. Porazhenie bronhov pri ogranichennyh i rasprostranennyh formah tuberkuleza legkih [Bronchial lesion in limited and widespread forms of pulmonary tuberculosis]. Tuberkulez i bolezni legkih [Tuberculosis and lung diseases]. 2011; 4: 220. (In Russ.)].

4. Стрелис А.К. Комплексная диагностика бронхиальной патологии и ее значение в клинике, течении, исходах вторичного туберкулеза легких: монография // Томск: Томский университет, 1980. – 185 с. [Strelis AK. Kompleksnaya diagnostika bronhial’noj patologii i ee znachenie v klinike, techenii, iskhodah vtorichnogo tuberkuleza legkih: monografiya [Comprehensive diagnosis of bronchial pathology and its significance in the clinic, course, and outcomes of secondary pulmonary tuberculosis: monograph]. Tomsk: Tomskij universitet [Tomsk: Tomsk University]. 1980; 185 p. (In Russ.)].

5. Kim HJ, Kim HS, Ma JE. Clinical characteristics of endobronchial tuberculosis that develops in patients over 70 years of age. Tuberculosis and Respiratory Diseases. 2007; 63 (5): 412-416. DOI: 10.4046/trd.2007.63.5.412.4

6. Исмаилов Ш.Ш., Аденов М.М., Имамбаев Ж.А. Ступенчатая биопсия в диагностике туберкулеза бронхов // Проблемы туберкулеза. – 2000. – No1. – С.21-22. [Ismailov ShSh, Allenov MM, Imanbayeva JA. Stupenchataya biopsiya v diagnostike tuberkuleza bronhov [Step biopsy in the diagnosis of bronchial tuberculosis]. Problemy tuberkuleza [Problems of tuberculosis]. 2000; 1: 21-22. (In Russ.)].

7. Малиев Б.М., Грачева М.П., Беляев Д.Л. Роль патологии трахеобронхиального дерева в эффективности лечения больных туберкулезом легких // Проблемы туберкулеза и болезней легких. – 2007. – No 8. – С.19-24 [Maliev BM, Gracheva MP, Belyaev DL. Rol’ patologii traheobronhial’nogo dereva v effektivnosti lecheniya bol’nyh tuberkulezom legkih [The role of pathology of the tracheobronchial tree in the effectiveness of treatment of patients with pulmonary tuberculosis]. Problemy tuberkuleza i boleznej legkih [Problems of tuberculosis and lung diseases]. 2007; 8: 19-24 (In Russ.)].

8. Фтизиатрия. Национальные клинические рекомендации / под ред. П. К. Яблонского. – М.: ГЭОТАР-Медиа, 2015. – 240 с. [Yablonsky PK ed. Ftiziatriya: Nacional’nye klinicheskie rekomendacii [Phthisiology: National clinical guidelines]. Moskva: GEOTAR-Media [Moscow: GEOTAR-Media]. 2015; 240 p. (In Russ.)].

9. Kashyap S, Mohapatra PR, Saini V. Endobronchial tuberculosis. Indian J Chest Dis Allied Sci. 2003; 45 (4): 247-256.

10. Wilson NJ. Bronchoscopic observation in tuberculous tracheobronchitis-Clinical and pathological correlation. Diseases of the Chest. 1945; 11 (1): 34-36. DOI: 10.1378/ chest.11.1.36

11. uan Wang, Xin-Shan Zhang. Endobronchial Tuberculosis: Report of 102 Cases. CHEST. 1994; 105 (6): 1910. DOI: 10.1378/chest.105.6.1910a

 SPECTRUM OF NON-SPECIFIC MICROFLORA IN PULMONARY TUBERCULOSIS PATIENTS IN THE REGIONS OF SIBERIA AND THE FAR EAST

SALMIN ALEXEY V., ORCID ID: 0009-0009-6941-0888; Junior Researcher, Novosibirsk Tuberculosis Research Institute, 81A Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: salmin.a@list.ru

TURSUNOVA NATALYA V., ORCID ID: 0000-0003-3051-2632; Cand. sc. boil., Leading Researcher, Scientific and Organizational Department, Novosibirsk Tuberculosis Research Institute of Tuberculosis, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +7(383)203-83-58. E-mail: us-nniit@mail.ru

NEMKOVA ELIZAVETA K., ORCID ID: 0000-0003-2724-9546; Junior Researcher, Novosibirsk Tuberculosis Research Institute, 81A Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: elizaveta.nemkova@mail.ru

Abstract. Introduction. Disruption of the lung microbiota in tuberculosis patients contributes to the aggravation of the course of the underlying disease, increased processes of alteration and exudation in the lesions, and a decrease in the treatment efficacy. Depending on the parameters of the external environment and the characteristics of the tuberculous process, the nature of the nonspecific microflora may change. Current data on monitoring the prevalence of nonspecific microflora are important for choosing a correct chemotherapy regimen. Aim: to study the spectrum of nonspecific microflora in inpatients admitted from the regions of Siberia and the Far East with different clinical forms of pulmonary tuberculosis. Materials and Methods. Microbiological studies of sputum samples from 520 pulmonary tuberculosis patients were analyzed, who were at the inpatient stage of treatment in the period of 2021-2022, using generally accepted bacteriological methods. The statistical significance of differences was assessed using the Chi- square test and considered significant at p ≤ 0.05. Results and Discussion. Of the 520 patients in the study, there were 472 patients from the regions of Siberia, 48 people from the regions of the Far East (Novosibirsk Oblast, Omsk, Republic of Tyva, Republic of Khakassia and Altai Territory, Amur Region, Kamchatka Territory, and Republic of Yakutia). In total, in sputum cultures of the pulmonary tuberculosis patients under study, bacterial flora was detected in 52% of cases, while fungal flora was found in 48% of cases; there were mainly Saccharomycetaceae, Enterobacteriaceae, andStaphylococcaceae, to a lesser extent there were Pseudomonadaceae and Yersiniaceae. The nonspecific microflora families and species composition of were similar in the regions of both districts. Conclusions. In the sputum of patients from the regions of the Siberian and Far Eastern Federal Districts, predominantly fungal microflora (C. albicans) was detected because of long-term antibiotic therapy. Bacterial microflora was more often represented by gram-negative species, such as H. parainfluenzae, Kl. pneumoniae, E. coli, etc. In this sample of patients, there was no significant difference between the regions of the Siberian and Far Eastern Federal Districts in the composition and ratio of families and species of nonspecific microflora. With drug-resistant strains of Mycobacterium tuberculosis, the growth of nonspecific microflora increased almost twice and, on the contrary, decreased almost 3 times for the families of Alcaligenaceae andStreptococcaceae. Bacterial nonspecific microflora mainly showed sensitivity to broad-spectrum antibiotics, nonspecific in the treatment of tuberculosis. S. aureus and Kl. pneumoniae remained susceptible to fluoroquinolones and amikacin, respectively. In all tuberculosis forms, fungal microflora prevailed. In fibrous-cavernous and infiltrative forms and in tuberculoma, bacteria of the Pseudomonadaceae family were cultured significantly more frequently (p<0.05) than in disseminated tuberculosis.

1. Лушникова А.В., Великая О.В. Туберкулёз лёгких и ХОБЛ // Современные проблемы науки и образования. – 2013. – No 6. – С. 13. [Lushnikova AV, Velikaya OV Pulmonary tuberculosis and COPD [Pulmonary tuberculosis and COPD]. Modern problems of science and education [ Modern problems of science and education]. 2013; 6: 13. (In Russ.)].

2. Спиридонова Л.Г., Тен М.Б., Лабутин И.В., Межебовский В.Р. Проблема лекарственной устойчивости вторичной микрофлоры у больных туберкулезом легких. Текст научной статьи по специальности «Клиническая медицина» // Оренбургский медицинский вестник. – 2019. – Т. VII, No 3(27). – С.29-34. [Spiridonova LG, Ten MB, Labutin IV, Mezhebovsky VR. The problem of drug resistance of secondary microflora in patients with pulmonary tuberculosis. Text of a scientific article on the specialty “Clinical medicine” [The problem of drug resistance of secondary microflora in patients with pulmonary tuberculosis. Text of a scientific article on the specialty “Clinical medicine]. Orenburg medical bulletin [Orenburg medical bulletin] 2019; VII (3): 29-34. (In Russ.)].

3. Орлова Е.А., Огарков О.Б., Колесникова Л.И. Особенности микробиоты легких при туберкулезной инфекции // Бюллетень сибирской медицины. – 2024. – Т. 23, вып 1. – С.166-175. [Orlova EA, Ogarkov OB, Kolesnikova LI. Features of the lung microbiota in tuberculosis infection[Features of the lung microbiota in tuberculosis infection]. Bulletin of Siberian Medicine [Bulletin of Siberian Medicine]. 2024; 23 (1): 166–175. (In Russ.)]. DOI: 10.20538/1682-0363-2024-1-166-175

4. Mokrousov I. Chernyaeva E, Vyazovaya A, et al. Next-generation sequencing of Mycobacterium tuberculosis. Emerg Infect Dis. 2016; 22 (6): 1127–1129. DOI: 10.3201/ eid2206.152051.15

5. Sinkov VV, Ogarkov OB, Plotnikov AO, et al. Metagenomic analysis of mycobacterial transrenal DNA in patients with HIV and tuberculosis coinfection. Infect Genet Evol. 2020; 77: 104057 DOI: 10.1016/j.meegid.2019.104057

6. Galeeva J, Babenko V, Bakhtyev R, et al. 16S rRNA gene sequencing data of the upper respiratory tract microbiome in the SARS-CoV-2 infected patients. Data Br. 2022; 40: 107770. DOI: 10.1016/j.dib.2021.107770

7. Cui Z., Zhou Y., Li H., et al. Complex sputum microbial composition in patients with pulmonary tuberculosis. BMC Microbiol. 2012;12:276. DOI: 10.1186/1471-2180-12-276

8. Cheung MK, Lam WY, Fung WYW, et al. Sputum microbiota in tuberculosis as revealed by 16S rRNA pyrosequencing. PLoS One. 2013; 8 (1): e54574. DOI: 10.1371/journal.pone.0054574

9. Wu J, Liu W, He L, et al. Sputum microbiota associated with new, recurrent and treatment failure tuberculosis. PLoS One. 2013; 8 (12): 83445. DOI: 10.1371 journal. pone.0083445

10. Botero LE, Delgado-Serrano L, Cepeda ML, et al. Respiratory tract clinical sample selection for microbiota analysis in patients with pulmonary tuberculosis. Microbiome. 2014; 2: 29. DOI: 10.1186/2049-2618-2-29

11. Стогова Н.А. Неспецифическая бактериальная и грибковая инфекция респираторного тракта у больных туберкулезным плевритом // Туберкулез и социально значимые заболевания. – 2022. – Т. 10, No 1 (37). – С.8-12. [Stogova NA. Nonspecific bacterial and fungal infection of the respiratory tract in patients with tuberculous pleurisy [Nonspecific bacterial and fungal infection of the respiratory tract in patients with tuberculous pleurisy]. Tuberculosis and socially significant diseases [Tuberculosis and socially significant diseases]. 2022; 10 (1): 8-12. (In Russ.)].

12. Лавриненко А.В., Азизов И.С., Колесниченко С.И., [и др.]. Спектр и лекарственная чувствительность неспецифической флоры у больных туберкулезом с множественной лекарственной устойчивостью // Туберкулез и болезни легких. – 2019. – Т.97, No9.– С.11-16. [Lavrinenko АV, Аzizov IS, Kolesnichenko SI, et al. Pattern and drug sensitivity of non-specific bacterial population in tuberculosis patients with multiple drug resistance [Pattern and drug sensitivity of non-specific bacterial population in tuberculosis patients with multiple drug resistance]. Tuberculosis and Lung Diseases [Tuberculosis and Lung Diseases]. 2019; 97 (9): 11-16. (In Russ.)]. DOI: 10.21292/2075-1230-2019-97-9-11-16

13. Groschel MI, Omansen TF, de Lange W, et al. Multidrug-resistant tuberculosis complicated by nosocomial infection with multidrug-resistant enterobacteriaceae. Am J Trop Med Hyg. 2016; 94 (3): 517-518. DOI: 10.4269/ ajtmh.15-0690

14. Спиридонова Л.Г., Тен М.Б., Лабутин И.В., Межебовский В.Р. Выявление неспецифической микрофлоры и ее лекарственной резистентности у больных туберкулезом легких» // Эффективная фармакотерапия. – 2019. – Т. 15, No 7. – С.8–11. [Spiridonova LG, Ten MB, Labutin IV, Mezhebovsky VR. Vyyavleniye nespetsificheskoy mikroflory i yeye lekarstvennoy rezistentnosti u bol’nykh tuberkulezom legkikh [Identification of nonspecific microflora and its drug resistance in patients with pulmonary tuberculosis]. Effektivnaya farmakoterapiya [Effective pharmacotherapy]. 2019; 15 (7) 8-11. (In Russ.)]. DOI: 10.33978/2307-3586-2019-15-7-8-11

15. Николаян Л.Т., Давтян А.Г. Сопутствующая неспецифическая микрофлора у больных туберкулезом при разной лекарственной устойчивости микобактерий туберкулеза // Туберкулез и болезни легких. – 2018. – Т. 96, No7. – С. 68-69 [Nikolayan LT, Davtyan АG. Soputstvuyushchaya nespetsificheskaya mikroflora u bol’nykh tuberkulezom pri raznoy lekarstvennoy ustoychivosti mikobakteriy tuberkuleza [Concomitant nonspecific microflora in tuberculosis patients with different drug resistance of mycobacterium tuberculosis]. Tuberkulez i bolezni legkikh [Tuberculosis and Lung Diseases]. 2018; 96 (7): 68-69. (In Russ.)]. DOI: 10.21292/2075-1230-2018-96-7-68-69

16. Fujimura KE, Johnson CC, Ownby DR, et al. Man’s best friend? The effect of pet ownership on house dust microbial communities. J Allergy Clin Immunol. 2010; 126: 410–412. DOI: 10.1016/j.jaci.2010.05.042

 SOME MEDICAL AND SOCIAL FACTORS ASSOCIATED WITH ANXIETY AND DEPRESSION IN RESPIRATORY TUBERCULOSIS PATIENTS

SEROV OLEG A., ORCID ID: 0009-0006-3892-4083; Cand. sc. med., Senior Researcher at the Department of Applied Scientific Research, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +7(383)203-83-58. E-mail: o.serov@nsk-niit.ru

ZHUKOVA ELENA M., ORCID ID: 0000-0002-6156-84124; Dr. sc. med., Leading Researcher at the Department of Applied Scientific Research, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +7(383)203-83-58. E-mail: e.zhukova@nsk-niit.ru

TURSUNOVA NATALYA V., ORCID ID: 0000-0003-3051-2632; Cand. sc. biol., Leading Researcher, Scientific and Organizational Department, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +7(383)203-83-58. E-mail: us-nniit@mail.ru

Abstract. Introduction. Negative impact of anxiety and depression on the patient’s adherence to tuberculosis treatment necessitates the creation of adequate socio-psychological interventions, considering factors that increase their development risks. Aim. Too study the prevalence of anxiety and depression symptoms, as well as their relationship to medical and social factors in pulmonary tuberculosis patients during their inpatient treatment. Materials and Methods. The study involved 273 patients with various forms of pulmonary tuberculosis, who were treated in the departments of Novosibirsk Tuberculosis Research Institute in 2021-2023. The patients were tested psychologically according to the Hospital Anxiety and Depression Scale (HADS). Statistics of indicators were assessed, such as patients’ place of residence (village/city, house/apartment), education, employment/unemployment, and marital status. The results were processed in the STATISTICS 22.0 program using nonparametric and parametric methods. Results and Discussion. 148 people (54.2%) out of 273 were identified with symptoms of subclinical and clinical anxiety and depression. Medical, biological, and clinical features in patients with severe anxiety were female gender, low body weight, short stature, lack of the bacteriological confirmation of the tuberculosis diagnosis, and the focal form of the disease. Greater depression in the study was associated with short stature in men, high heart rate, and the presence of fibrocavernous tuberculosis (FCT). Social factors associated with more frequent manifestations of anxiety and depression: Living in a rural area and/or a private house, lack of higher education, living alone, and being unemployed. Social factors most often present in patients with depression: Living in a rural area, living in a private house, lack of higher education, living without a partner, and being unemployed. Conclusions. Symptoms of anxiety and depression observed in more than a half of tuberculosis patients undergoing inpatient treatment, are closely related to medical, biological, and social factors, as well as to the characteristics of the tuberculosis course. The findings can be used in the development of socio-psychological patient-oriented programs in the tuberculosis treatment.

 ANALYSIS OF THE FUNCTIONING OF PHTISIOSURGICAL SERVICE IN THE SIBERIAN AND FAR EASTERN FEDERAL DISTRICTS OF RUSSIA IN 2020–2022

SKVORTSOV DMITRY A., ORCID ID: 0000-0003-0943-9266, RSCI Author ID 304381, Cand. sc. med., Thoracic Surgeon, Head of the Department of Tuberculosis Pulmonary-Surgery, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +7(383)203-79-06. E-mail: d.skvorcov@nsk-niit.ru

GRISCHENKO NIKOLAY G., ORCID ID: 0009-0001-8730-743X, RSCI Author ID 304381, Dr. sc. med., Chief Researcher, Thoracic Surgeon at the Department of Tuberculosis Pulmonary-Surgery, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: gng950@mail.ru

NARYSHKINA SVETLANA L., ORCID ID: 0000-0003-1671-8095, Cand. sc. med., Phthisiologist, Methodology Expert, Organizational and Methodological Department, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str.,630040 Novosibirsk, Russia. E-mail: nsl65@bk.ru

MOROZOV PAVEL S., ORCID ID: 0009-0001-4785-9483, Postgraduate Student, Thoracic Surgeon at the Department of Tuberculosis Pulmonary-Surgery, Novosibirsk Tuberculosis Research Institute, 81 a Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: sodzo1868@gmail.com

STAVITSKAYA NATALYA V., ORCID ID: 0000-0003-2616-6693 Dr. sc. med., Director of Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str.,630040 Novosibirsk, Russia. E-mail: director@nsk-niit.ru

Abstract. Introduction. In recent years, the Russian Federation has achieved some improvement in the epidemic situation regarding tuberculosis. However, in the Siberian and Far Eastern Federal Districts of Russia, epidemiological indicators remain above the Russian average. Surgical treatment of pulmonary tuberculosis contributes to the radical elimination of the main source of infection in the tissue and facilitates the therapy tasks. Aim of this study is to analyze the provision of phthisiosurgical care in the “Thoracic Surgery” profile to respiratory tuberculosis inpatients in the tuberculosis pulmonary-surgery departments of regional and local tuberculosis dispensaries of the Siberian and Far Eastern Federal Districts in 2020-2022. Materials and Methods. To assess the general characteristics of the phthisiosurgical service in the above districts, we analyzed the personnel composition, bed capacity, thoracic bed operation, surgical activities, average bed turnover, implementation of the bed-day plan, and the number of operations performed on respiratory tuberculosis patients. The study was basedon materials provided by the statistical departments of regional and local TB dispensaries. Results and Discussion. When comparing the indicators for the years of 2020 and 2022, a worsening personnel shortage was found: The number of surgeons decreased from 30 to 17 in the Far Eastern Federal District and from 35 to 29 in the Siberian Federal District. Over the past 3 years, there has been a significant decrease in the phthisiosurgical bed capacity in the Far East. In the Siberian Federal District and, especially, in the Far Eastern Federal District, beds in phthisiothoracic departments are often used for the purposes other than their intended one. In both the Siberian Federal District and the Far Eastern Federal District, surgical activity rates remain quite high or is recovering after the pandemic, except for Transbaikalia, the Republic of Buryatia, and the Amur Oblast. Conclusions. Analysis of the performance of phthisiosurgical departments in Siberia and the Far East in 2020-2022 shows that it is necessary to increase the number of specialized operations and improve the material and technical base of surgical departments in the above districts, although with the increase in multidrug resistance of Mycobacterium tuberculosis to anti-tuberculosis drugs, the role of surgical treatment methods increases. Today, only federal centers meet all the standards established for providing surgical care to tuberculosis patients.

Keywords: tuberculosis, phthisiosurgery, surgical treatment.

For reference: Skvortsov DA, Grishchenko NG, Naryshkina SL, et al. Analysis of the functioning of phthisiosurgical service in the Siberian and Far Eastern Federal Districts of Russia in 2020-2022. The Bulletin of Contemporary Clinical Medicine. 2024; 17 (5): 88-98. DOI: 10.20969/VSKM.2024.17(5).88-98.

1. Нечаева О.Б. Эпидемическая ситуация по туберкулезу в России // Туберкулез и болезни легких. – 2018. – No 96 (8). – С.15–24. [Nechaeva OB. Epidemicheskaya situaciya po tuberkulezu v Rossii [Epidemiological situation of tuberculosis in Russia]. Tuberkulez i bolezni legkih [Tuberculosis and lung diseases]. 2018; 96 (8): 15–24. (In Russ.)].

2. Васильева И.А., Белиловский Е.М., Борисов С.Е. [и др.]. Заболеваемость, смертность и распространенность как показатель бремени туберкулеза в регионах ВОЗ, странах мира и в Российской Федерации. Часть 1. Заболеваемость и распространенность туберкулеза // Туберкулез и болезни легких. – 2017. – No 95 (6). – С.9–21. [Vasil’eva IA, Belilovskij EM, Borisov SE, et al. Zabolevaemost’, smertnost’ i rasprostranennost’ kak pokazatel’ bremeni tuberkuleza v regionah VOZ, stranah mira i v Rossijskoj Federacii; CHast’ 1: Zabolevaemost’ i rasprostranennost’ tuberkuleza [Incidence, mortality and prevalence as an indicator of the burden of tuberculosis in WHO regions, countries of the world and in the Russian Federation; Part 1: Incidence and prevalence of tuberculosis]. Tuberkulez i bolezni legkih [Tuberculosis and lung diseases]. 2017; 95 (6): 9–21. (In Russ.)].

3. Павленок И.В., Турсунова Н.В., Лацких И.В., [и др.]. Основные показатели противотуберкулезной деятельности в Сибирском и Дальневосточном федеральном округе (статистические материалы). – Новосибирск: ИПЦ НГМУ, 2023. – 120 с. [Pavlenok IV, Tursunova NV, Latskikh IV. Osnovnye pokazateli protivotuberkuleznoj deyatel’nosti v Sibirskom i Dal’nevostochnom federal’nom okruge (statisticheskie materialy) [Key indicators of antituberculosis activity in the Siberian and Far Eastern Federal District (statistical materials)]. Novosibirsk: IPC NGMU [Novosibirsk: IPC NGMU]. 2023; 120 p. (in Russ.)].

4. Грищенко Н.Г., Краснов Д.В., Нарышкина С.Л., Скворцов Д.А. Хирургическое лечение больных туберкулезом органов дыхания в Сибирском и Дальневосточном федеральных округах в начальный период пандемии COVID-19 // Туберкулез и болезни легких. – 2023. – No 101 (1S). – С.13–20. [Grishchenko NG, Krasnov DV, Naryshkina SL, Skvorcov DA. Hirurgicheskoe lechenie bol’nyh tuberkulezom organov dyhaniya v Sibirskom i Dal’nevostochnom federal’nyh okrugah v nachal’nyj period pandemii COVID-19 [Surgical treatment of patients with tuberculosis of the respiratory organs in the Siberian and Far Eastern Federal Districts during the initial period of the COVID-19 pandemic]. Tuberkulez i bolezni legkih [Tuberculosis and lung diseases]. 2023; 101 (1S): 13–20. (in Russ.)].

5. Фтизиатрия. Национальные клинические рекомендации / под ред. П. К. Яблонского. – М.: ГЭОТАР–Медиа, 2015. – 240 с. [YAblonskii PK ed. Ftiziatriya: Nacional’nye klinicheskie rekomendacii [Phthisiology; National clinical guidelines]. Moskva: GEOTAR–Media [Moscow: GEOTAR–Media]. 2015; 240 p. (In Russ.)].

6. Отс О.Н., Агкацев Т.В., Перельман М.И. Хирургическое лечение туберкулеза легких при устойчивости микобактерий к химиопрепаратам // Туберкулез и болезни легких. – 2009. – No2. – С.42–49. [Ots ON, Agkacev TV, Perel’man MI. Hirurgicheskoe lechenie tuberkuleza legkih pri ustojchivosti mikobakterij k himiopreparatam [Surgical treatment of pulmonary tuberculosis in case of mycobacterial resistance to chemotherapy drugs]. Tuberkulez i bolezni legkih [Tuberculosis and lung diseases]. 2009; 2: 42–49. (In Russ.)].

7. Рогожкин П.В., Бородулина Е.А. Радикальная резекция легких в лечении туберкулеза легких // Наука и инновации в медицине. – 2017. – Т. 2, No 2. – C.56–59. [Rogozhkin PV, Borodulina EA. Radikal’naya rezekciya legkih v lechenii tuberkuleza legkih [Radical resection of the lungs in the treatment of pulmonary tuberculosis]. Nauka i innovacii v medicine [Science and innovations in medicine]. 2017; 2 (2): 56–591. (In Russ.)]. DOI: 10.35693/2500-1388-2017-0-2-56-59

8. Краснов Д.В., Карнаухов В.А., Скворцов Д.А. Хирургическое лечение больных двусторонним туберкулезом легких // Уральский медицинский журнал. – 2018. – Т. 163, No 8. – С.59–64. [Krasnov DV, Karnaukhov VA, Skvortsov DA. Khirurgicheskoye lecheniye bol’nykh dvustoronnim tuberkulezom legkikh [Surgical treatment of patients with bilateral pulmonary tuberculosis]. Ural’skiy meditsinskiy zhurnal [Ural Medical Journal]. 2018; 163 (8): 59–64. (In Russ.)]. DOI: 10.25694/URMJ.2018.05.53

9. Ворончихин Т.А., Аветисян А.О., Васильев И.В., [и др.]. Результаты комплексного лечения ограниченного фиброзно-кавернозного туберкулеза легких // Медицинский альянс. – 2018. – No 3. – С.56–64. [Voronchihin TА, Avetisyan AO, Vasil’ev IV, et al. Rezul’taty kompleksnogo lecheniya ogranichennogo fibrozno-kavernoznogo tuberkuleza legkih [Results of complex treatment of limited fibrous-cavernous pulmonary tuberculosis]. Medicinskij al’yans [Medical Alliance]. 2018; 3: 56–64. (In Russ.)].

10. Subotic D, Yablonskiy P, Sulis G, et al. Surgery and pleuropulmonary tuberculosis: a scientific literature review. J Thorac Dis. 2016; 8 (7): E474-E485. DOI: 10.21037/ jtd.2016.05.59

11. Sihoe ADL. Role of Surgery in the Diagnosis and Management of Tuberculosis. Microbiol Spectr. 2017; 5: 10. DOI: 10.1128/microbiolspec.tnmi7-0043-2017

12. Синицын М.В., Белиловский Е.М., Воробьев А.А., [и др.]. Эффективность хирургического лечения больных туберкулезом на стационарном этапе ведения пациентов в городе Москве // Туберкулез и социально-значимые заболевания. – 2020. – No 2. – С.39–43. [Sinitsyn MV, Belilovskiy YEM, Vorob’yev AA, et al. Effektivnost’ khirurgicheskogo lecheniya bol’nykh tuberkulezom na statsionarnom etape vedeniya patsiyentov v gorode Moskve [Efficiency of surgical treatment of patients with tuberculosis at the inpatient stage of patient management in the city of Moscow]. Tuberkulez i sotsial’no-znachimyye zabolevaniya [Tuberculosis and socially significant diseases]. 2020; 2: 39–43. (In Russ.)].

13. Скорняков С.Н., Мотус И.Я., Кильдюшева Е.И., [и др.]. Хирургия деструктивного лекарственно-устойчивого туберкулеза легких // Туберкулез и болезни легких. – 2015. – No3. – С.15–21. [Skornyakov SN, Motus IYa, Kil’dyusheva EI, et al. Khirurgiya destruktivnogo lekarstvenno-ustoychivogo tuberkuleza legkikh [Surgery of destructive drug-resistant pulmonary tuberculosis]. Tuberkulez i bolezni legkikh [Tuberculosis and lung diseases]. 2015; 3: 15–21. (In Russ.)].

14. Гиллер Д.Б., Асанов Б.М., Гиллер Г.В., [и др.]. Малоинвазивные методы хирургического лечения двустороннего деструктивного туберкулеза легких // Туберкулез и болезни легких. – 2010. – No 5. – С.52–59. [Giller DB, Asanov BM, Giller GV, i dr. Maloinvazivnyye metody khirurgicheskogo lecheniya dvustoronnego destruktivnogo tuberkuleza legkikh [Minimally invasive methods of surgical treatment of bilateral destructive pulmonary tuberculosis]. Tuberkulez i bolezni legkikh [Tuberculosis and lung diseases]. 2010; 5: 52-59. (In Russ.)].

15. Перельман М.И., Отс О.Н., Агкацев Т.В. Хирургическое лечение туберкулеза легких при устойчивости микобактерий к препаратам // Consilium Medicum. – 2011. – Т. 13, No3. – С.5–10. [Perel’man MI, Ots ON, Agkatsev TV. Khirurgicheskoye lecheniye tuberkuleza legkikh pri ustoychivosti mikobakteriy k preparatam [Surgical treatment of pulmonary tuberculosis in case of mycobacterial resistance to drugs]. Consilium Medicum [Consilium Medicum]. 2011; 13 (3): 5–10. (In Russ.)].

 EFFECT OF LOCAL INFLAMMATORY CHANGES IN THE TRACHEOBRONCHIAL TREE ON THE TREATMENT OUTCOMES IN PATIENTS AFTER COLLAPSE SURGERY

SKLYUEV SERGEY V., ORCID ID: 0000-0001-8547-7067; Cand. sc. med, Head of the Endoscopy Department, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. E-mail: sklyuev.sergey@gmail.com

KRASNOV DENIS V., ORCID ID: 0000-0003-0727-9940; Dr. sc. med, Associate Professor at the Department of Phthisiopulmonology, Novosibirsk State Medical University, 52 Krasny Prospekt str., 630091 Novosibirsk, Russia. E-mail: krasnov77@bk.ru

PETRENKO TATYANA I., ORCID ID: 0000-0002-9624-5234; Dr. sc. med, Associate Professor, Head of the Department of Phthisiopulmonology, Novosibirsk State Medical University, 52 Krasny Prospekt str., 630091 Novosibirsk, Russia. E-mail: tipetrenko@gmail.com

Abstract. Introduction. Against the background of the low therapeutic treatment effects and the persistence of destructive changes in the lungs, surgical treatments, including resection, are becoming increasingly important. Surgical treatment is an important component in the treatment of pulmonary tuberculosis patients. The therapeutic treatments of pulmonary tuberculosis patients have their own capabilities and limits. Aim. The aim of the study was to investigate the frequency and nature of postoperative complications, as well as the immediate and long–term outcomes of collapse surgeries in pulmonary tuberculosis patients, based on the presence of local inflammatory changes in the bronchial tree. Materials and Methods. A prospective cohort study was conducted, including 132 pulmonary tuberculosis patients who underwent collapse surgeries: Those having inflammatory changes in their bronchial trees were in the first, main group (n = 109), while those without any inflammatory changes in their bronchi were in the second, comparison group (n = 23). Treatment efficacy, postoperative complications, and changes in the indices of external respiration function were assessed. Results and Discussion. It was found that the presence of local inflammatory phenomena of the tracheobronchial tree in pulmonary tuberculosis patients initially affects the indices of external respiration function in patients with damaged tracheobronchial tree: Vital capacity of the lungs was on average 10.03% lower than in the second group. Collapse-surgery treatment leads to a more significant (on average, by 5%) decrease in the vital capacity of the lungs and forced vital capacity of the lungs in the first group than in the second group. By the 12th month, a significant improvement was achieved in 64.22% of patients in the first group. In 21.1% of patients in the first group and 21.74% of patients in the second group, progression of the tuberculosis process was noted after surgery. Conclusions.Conducting collapse surgery leads to a more significant (on average by 5%) decrease in the vital capacity of the lungs and forced vital capacity of the lungs in the first group than in the second group (p <0.001); by the 12th month, significant improvement was achieved in 64.22% of patients in the first group; the presence of local inflammatory phenomena of the tracheobronchial tree in pulmonary tuberculosis patients initially affects the indices of external respiration function: Vital capacity of the lungs is on average 10.03% lower than in the second group (p <0.001), forced vital capacity is 8.18% lower than in the second group (p <0.001), the Tiffno index is 10.3% lower (p <0.001).

1. Антипов А. Г., Аралова И. С., Матросов М. В. [и др.] Сравнительный анализ туберкулеза бронхов в зависимости от ВИЧ-статуса больных // Туберкулез и болезни легких. – 2014. – No. 9. – C.8–9. [Antipov AG, Aralova IS, Matrosov MV, et al. Sravnitel’nyj analiz tuberkuleza bronhov v zavisimosti ot VICh-statusa bol’nyh [Comparative analysis of bronchial tuberculosis depending on the HIV status of patients]. Tuberkulez i bolezni legkih [Tuberculosis and Lung Diseases]. 2014; 9: 8–9. (In Russ.)].

2. Агеева Т.С., Волкова Л.И., Мишустина Е.Л., Мишустин С.П. Туберкулез бронхов в общеврачебной практике // Фундаментальные исследования. – 2014. – No 10–7. – С.1265–1268. [Ageeva TS, Volkova LI, Mishustina EL, Mishustin SP. Tuberkulez bronhov v obshchevrachebnoj praktike [Bronchial tuberculosis in general medical practice]. Fundamental’nye issledovaniya [Fundamental research]. 2014; 10 (7): 1265–1268. (In Russ.)].

3. Афанасьев Е.И., Русских О.Е. Современные тенденции в эпидемиологии туберкулеза и ВИЧ-инфекции в мире и в Российской Федерации // РМЖ. – 2021. – No3. – С.24–26. [Afanasyev EI, Russkikh OE. Sovremennye tendencii v epidemiologii tuberkuleza i VICh-infekcii v mire i v Rossijskoj Federacii [Modern trends in the epidemiology of tuberculosis and HIV infection in the world and in the Russian Federation]. RMZH. 2021; 3: 24–26. (In Russ.)].

4. Giller DB, Giller BD, Giller GV, et al. Treatment of pulmonary tuberculosis: past and present. Eur J Cardiothorac Surg. 2018; 53: 967–972. DOI: 10.1093/ ejcts/ezx447

5. Омельчук Д.Е., Краснов Д.В., Петренко Т.И. Структура интраи послеоперационных осложнений после операций по поводу фиброзно-кавернозного туберкулеза легких и их влияние на исход операции // Туберкулез и болезни легких. – 2022. – Т.100, No 4. – С.33–40. [Omelchuk DE, Krasnov DV, Petrenko TI. Struktura intra- i posleoperacionnyh oslozhnenij posle operacij po povodu fibrozno-kavernoznogo tuberkuleza legkih i ih vliyanie na iskhod operacii [The structure of intra- and postoperative complications after operations for fibrotic cavernous pulmonary tuberculosis and their effect on the outcome of surgery]. Tuberkulez i bolezni legkih [Tuberculosis and lung diseases]. 2022; 100 (4): 33–40. (In Russ.)]. DOI: 10.21292/2075-1230-2022-100-4-33-40

6. Грищенко Н.Г., Краснов В.А., Андренко А.А., [и др.]. Роль хирургических методов в лечении больных фиброзно-кавернозным туберкулезом легких // Проблемы туберкулеза и болезни легких. – 2003. – No2. – С.36–38. [Grishchenko NG, Krasnov VA, Andrenko AA, et al. Rol’ hirurgicheskih metodov v lechenii bol’nyh fibrozno-kavernoznym tuberkulezom legkih [The role of surgical methods in the treatment of patients with fibrotic cavernous pulmonary tuberculosis]. Problemy tuberkuleza i bolezni legkih [Problems of tuberculosis and lung disease]. 2023; 2: 36–38. (In Russ.)].

7. Отс О.Н., Агкацев Т.В., Перельман М.И. Хирургическое лечение туберкулеза легких при устойчивости микобактерий к химиопрепаратам // Туберкулез и болезни легких. – 2009. – No2. – С.42 – 49. [Ots ON, Agkatsev TV, Perelman MI. Hirurgicheskoe lechenie tuberkuleza legkih pri ustojchivosti mikobakterij k himiopreparatam [Surgical treatment of pulmonary tuberculosis with mycobacterium resistance to chemotherapy drugs]. Tuberkulez i bolezni legkih [Tuberculosis and lung diseases]. 2009; 2: 42–49. (In Russ.)].

8. Перельман М.И., Отс О.Н., Агкацев Т.В. Хирургическое лечение туберкулеза легких при устойчивости микобактерий к химиопрепаратам. // Consilium. – 2011. – Т.3, No 13. – С.5–10. [Perelman MI, Ots ON, Agkatsev TV. Hirurgicheskoe lechenie tuberkuleza legkih pri ustojchivosti mikobakterij k himiopreparatam [Surgical treatment of pulmonary tuberculosis with mycobacterium resistance to chemotherapy drugs]. Consilium [Consilium]. 2011; 3 (13): 5–10. (In Russ.)].

9. Алексеева Т.В., Ревякина О.В., Филиппова О.П., Краснов В.А. Туберкулез в Сибирском и Дальневосточном федеральных округах (2007–2016 гг.) // Туберкулез и болезни легких. – 2017. – Т.95, No 8. – С.12–17. [Аlekseeva TV, Revyakina OV, Filippova OP, Krasnov VА. Tuberkulez v Sibirskom i Dal’nevostochnom federal’nyh okrugah (2007–2016 gg) [Tuberculosis in Siberian and Far Eastern Federal Districts (2007–2016)]. Tuberkulez i bolezni legkih [Tuberculosis and Lung Diseases]. 2017; 95 (8): 12–17. (In Russ.)]. DOI: 10.21292/2075-1230-2017-95-8-12-17

10. Пехтусов В.А., Татаринцев А.В., Гиллер Д.Б., [и др.]. Влияние хирургической санации контингентов больных деструктивным туберкулезом на основные показатели распространенности и смертности от туберкулеза // Хирургия. – 2020. – No 2. – С.48–52. [Pakhtusov VA, Tatarintsev AV, Giller DB, et al. Vliyanie hirurgicheskoj sanacii kontingentov bol’nyh destruktivnym tuberkulezom na osnovnye pokazateli rasprostranennosti i smertnosti ot tuberkuleza [The influence of surgical rehabilitation of patients with destructive tuberculosis on the main indicators of prevalence and mortality from tuberculosis]. Hirurgiya [Surgery]. 2020; 2: 48–52. (In Russ.)]. DOI: 10.17116/hirurgia202002148

 AMINOGLYCOSIDES IN THE TREATMENT OF MULTIDRUG-RESISTANT TUBERCULOSIS PATIENTS: ADVERSE EVENTS AND WAYS TO CORRECT THEM

SOLOKHA ANGELINA A., ORCID ID: 0009–0004–4979–5358, Researcher at the Department of Applied Scientific Research, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel. +7(913)957–64–99. E–mail: angelinka_89@inbox.ru

GORDEEVA ELIZAVETA I., ORCID ID: 0000–0002–3288–5259, Applicant for the Cand. sc. biol. degree, Biologist, Bacteriological Laboratory, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel. +7 (913) 0690582. E–mail: mbtnniit20@gmail.com

1. Global tuberculosis report 2023. World health organization. 2023; 75 p.

2. Перельман М.И. О концепции Национальной Российской программы борьбы с туберкулезом // Проблемы туберкулеза. – No 3. – 2000. – С.51 – 55. [Perelman MI. O koncepcii Nacional’noj Rossijskoj programmy bor’by s tuberkulezom [On the concept of the National Russian Tuberculosis Control Program]. Problemy tuberkuleza [Problems of tuberculosis]. 2000; 3: 51–55. (in Russ.)].

3. Павленок И.В., Турсунова Н.В., Лацких И.В., [и др.]. Основные показатели противотуберкулезной деятельности в Сибирском и Дальневосточном федеральном округе (статистические материалы). – Новосибирск: ИПЦ НГМУ, 2023. – 120 с. [Pavlenok IV, Tursunova NV, Latskikh IV. Osnovnye pokazateli protivotuberkuleznoj deyatel’nosti v Sibirskom i Dal’nevostochnom federal’nom okruge (statisticheskie materialy) [Key indicators of anti–tuberculosis activity in the Siberian and Far Eastern Federal District (statistical materials)]. Novosibirsk: IPC NGMU [Novosibirsk: IPC NGMU]. 2023; 120 p. (in Russ.)].

4. Общероссийская общественная организация «Российское общество фтизиатров», «Национальная ассоциация некоммерческих организаций фтизиатров «Ассоциация фтизиатров». Туберкулез у взрослых. Клинические рекомендации. – Москва, 2024. – 167 с. [Obshcherossiyskaya obshchestvennaya organizatsiya «Rossiyskoye obshchestvo ftiziatrov», «Natsional’naya assotsiatsiya nekommercheskikh organizatsiy ftiziatrov «Assotsiatsiya ftiziatrov» [All–Russian public organization “Russian Society of Phthisiologists”, “National Association of non–profit organizations of phthisiologists “Association of Phthisiologists”]. Tuberkulez u vzroslyh: Klinicheskie rekomendacii [Tuberculosis in adults: Clinical recommendations]. Moskva [Moscow]. 2024; 167 p. (In Russ.)]

5. Литусов Н.В. Микобактерии туберкулеза. Иллюстрированное пособие. – Екатеринбург: Изд-во ГБОУ ВПО УГМУ, 2015. – 52 с. [Litusov NV. Mikobakterii tuberkuleza: Illyustrirovannoe posobie [Mycobacterium tuberculosis: An illustrated manual]. Yekaterinburg: Izdatel’stvo GBOU VPO UGMU [Ekaterinburg: Publishing house of GBOU VPO UGMU]. 2015; 52 p. (in Russ.)].

6. Вольф С.Б. Нежелательные побочные реакции на химиотерапию туберкулеза // Журнал Гродненского государственного медицинского университета. – 2016. – No 3. – С.141–146. [Wolf SB. Nezhelatel’nye pobochnye reakcii na himioterapiyu tuberkuleza [Undesirable adverse reactions to tuberculosis chemotherapy]. Zhurnal Grodnenskogo gosudarstvennogo medicinskogo universitet [Journal of Grodno State Medical University]. 2016; 3: 141–146. (in Russ.)].

7. Суханов Д.С., Тимофеев Е.В., Алексеева Ю.С., Азовцев Д.Ю. Лекарственные поражения печени при туберкулезе. Механизмы развития и методы диагностики // Juvenis scientia. – 2023. – Т.9., No 1. – С.24–42. [Sukhanov DS, Timofeev EV, Alekseeva YS, Azovtsev DY. Lekarstvennye porazheniya pecheni pri tuberkuleze: Mekhanizmy razvitiya i metody diagnostiki [Medicinal liver lesions in tuberculosis: Mechanisms of development and diagnostic methods]. Juvenis scientia [Juvenis scientia]. 2023; 9 (1): 24–42. (in Russ.)]. DOI: 10.32415/ jscientia_2023_9_1_24–42

8. Гусейнов Н.М., Фисенко В.Р., Асланов П.Р. Влияние ототоксических лекарственных средств на биоэлектрические реакции в коре головного мозга и улитке // Вестник Украинской медицинской стоматологической академии. – 2020. – Т.20. – No2 (70). – С.124–128. [Huseynov NM, Fisenko VR, Aslanov PR. Vliyanie ototoksicheskih lekarstvennyh sredstv na bioelektricheskie reakcii v kore golovnogo mozga i ulitke [The effect of ototoxic drugs on bioelectric reactions in the cerebral cortex and cochlea]. Vestnik ukrainskoj medicinskoj stomatologicheskoj akademii [Bulletin of the Ukrainian Medical Dental Academy]. 2020; 20 (2 (70)): 124–128. (in Russ.)].

9. Громова О.А., Торшин И.Ю., Стаховская А.В. Опыт применения мексидола в неврологической практике // Журнал неврологии и психиатрии. – 2018. – Т.118, No 10. – С.97–107. [Gromova OA, Torshin IYu, Stakhovskaya AV. Opyt primeneniya meksidola v nevrologicheskoj praktike [Experience of using Mexidol in neurological practice]. Zhurnal nevrologii i psihiatrii [Journal of Neurology and psychopathry]. 2018; 118 (10): 97–107. (in Russ.)].

10. Бахадирова И.Б., Арифов С.С. Ототоксический эффект цитостатических препаратов, содержащих платину // Российская оториноларингология. – 2021. – Т.20, No2. – С.78–84. [Bakhadirova IB, Arifov SS. Ototoksicheskij effekt citostaticheskih preparatov, soderzhashchih platinu [Ototoxic effect of cytostatic drugs containing platinum]. Rossijskaya otorinolaringologiya [Russian otorhinolaryngology]. 2021; 20 (2): 78–84. (in Russ.)].

11. Страчунский Л.С., Белоусов Ю.Б., Козлов С.Н. Практическое руководство по антиинфекционной химиотерапии. – Смоленск: МАКМАХ, 2007. – 464 с. [Strachunsky LS, Belousov YuB, Kozlov SN. Prakticheskoe rukovodstvo po antiinfekcionnoj himioterapii. [Practical guide to anti–infectious chemotherapy]. Smolensk: MAKMAKH [Smolensk: MAKMAKH]. 2007; 464 p. (in Russ.)].

12. Шубникова Е.В., Вельц Н.Ю. Ототоксичность аминогликозидов: современные представления // Антибиотики и химиотерапия. – 2022. – Т. 67, No 11–12. – С.79–90. [Shubnikova EV, Velts NY. Ototoksichnost’ aminoglikozidov sovremennye predstavleniya [Ototoxicity of aminoglycosides: modern concepts]. Antibiotiki i himioterapiya [Antibiotics and chemotherapy]. 2022; 67 (11–12): 79–90. (in Russ.)]. DOI: 10.37489/0235-2990-2022-67-11-12-79-90

13. Махонько М.Н. Ототоксичные лекарственные препараты в современной клинической фармакологии // Современные проблемы науки и образования. – 2023. – No 4. – С.1–13. [Makhonko MN. Ototoksichnye lekarstvennye preparaty v sovremennoj klinicheskoj farmakologii [Ototoxic drugs in modern clinical pharmacology]. Sovremennye problemy nauki i obrazovaniya [Modern problems of science and education]. 2023; 4: 1–13. (in Russ.)].

14. Белогурова М.Б., Гарбарук Е.С., Субора Н.В. Исследование эффекта ототоксичности у детей, получавших химиотерапию препаратами платины // Вопросы гематологии/онкологии и иммунопатологии в педиатрии. – 2018. – Т.17, No 3. – С.22–27. [Belogurova MB, Garbaruk ES, Subora NV. Issledovanie effekta ototoksichnosti u detej, poluchavshih himioterapiyu preparatami platiny [Investigation of the effect of ototoxicity in children receiving chemotherapy with platinum preparations]. Voprosy gematologii/onkologii i immunopatologii v pediatrii [Issues of hematology/oncology and immunopathology in pediatrics]. 2018; 17 (3): 22–27 (in Russ.)].

15. Богомильский М.Р., Ишанова Ю.С., Рахманова И.В., [и др.]. Скрининговый аудиологический контроль детей разного возраста после приема ототоксических препаратов // Вестник оториноларингологии. – 2020. – Т. 85, No 1. – С.40–44. [Bogomil’skij MR, Ishanova YuS, Rahmanova IV, et al. Skriningovyj audiologicheskij kontrol’ detej raznogo vozrasta posle priema ototoksicheskih preparatov [Screening audiological control of children of different ages after taking ototoxic drugs]. Vestnik otorinolaringologii [Bulletin of otorhinolaryngology]. 2020; 85 (1): 40–44 (in Russ.)].

16. Бурд С.Г., Лебедева А.В., Рублева Ю.В., [и др.]. Эпилептические синдромы, ассоциированные со снижением слуха // Журнал неврологии и психиатрии им. С.С. Корсакова. – 2023. – Т.123 (1). – С.28–33. [Burd SG, Lebedeva AV, Rubleva YuV, et al. Epilepticheskie sindromy, associirovannye so snizheniem sluha [Epileptic syndromes associated with hearing loss]. Zhurnal nevrologii i psihiatrii imeni SS Korsakova [Journal of Neurology and Psychiatry named after SS Korsakov]. 2023; 123 (1): 28–33 (in Russ.)].

17. Бурчинский С.Г. Возможности антиоксидантной фармакотерапии при хронической ишемии головного мозга // Международный неврологический журнал. – 2019. – Т. 106(4). – С. 58–62. [Burchinsky SG. Vozmozhnosti antioksidantnoj farmakoterapii pri hronicheskoj ishemii golovnogo mozga [The possibilities of antioxidant pharmacotherapy in chronic cerebral ischemia]. Mezhdunarodnyj nevrologicheskij zhurnal [International Neurological Journal]. 2019; 106 (4): 58–62. (in Russ.)].

18. Национальная медицинская ассоциация оториноларингологов. Нейросенсорная тугоухость у взрослых. Клинические рекомендации. – Москва, 2022. – 47 с. [Nacional’naya medicinskaya associaciya otorinolaringologov [National Medical Association of Otorhinolaryngologists]. Nejrosensornaya tugouhost’ u vzroslyh: Klinicheskie rekomendacii [Sensorineural hearing loss in adults: Clinical recommendations]. Moskva [Moscow]. 2022: 47р (in Russ.)].

19. Солоха А.А., Ставицкая Н.В., Петренко Т.И., Шварц Я.Ш. Ототоксичность противотуберкулезных препаратов: профилактика, диагностика, алгоритм действий: учебное пособие. – Новосибирск: ФГБУ «ННИИТ» Минздрава России, 2022 – 40 с. [Soloha AA, Stavickaya NV, Petrenko TI, Shvarc YaSh. Ototoksichnost’ protivotuberkuleznyh preparatov: profilaktika, diagnostika, algoritm dejstvij: uchebnoe posobie [Ototoxicity of antituberculosis drugs: prevention, diagnosis, algorithm of actions: a textbook]. Novosibirsk: FGBU «NNIIT» Minzdrava Rossii [Novosibirsk: FSBI “NNIIT” of the Ministry of Health of Russia]. 2022; 40 p. (in Russ.)].

20. Российское общество фтизиатров. Федеральные клинические рекомендации по организации и проведению микробиологической и молекулярно-генетической диагностики туберкулеза. – Москва, 2014. – 29 с. [Rossijskoe obshchestvo ftiziatrov [Russian Society of Phthisiologists]. Federal’nye klinicheskie rekomendacii po organizacii i provedeniyu mikrobiologicheskoj i molekulyarno-geneticheskoj diagnostiki tuberkuleza [Federal clinical guidelines for the organization and conduct of microbiological and molecular genetic diagnosis of tuberculosis]. Moskva [Moscow]. 2014; 29 p. (in Russ.)].

 NON-TUBERCULOSIS MYCOBACTERIA SPECIES CIRCULATING IN THE SIBERIAN FEDERAL DISTRICT OF RUSSIA

TURSUNOVA NATALYA V., ORCID ID: 0000-0003-3051-2632; Cand. sc. boil., Leading Researcher at the Scientific and Organizational Department, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel.: +7(383)203-83-58. E-mail: us-nniit@mail.ru

GUSELNIKOVA ELENA P., Applicant for the Cand. sc. med. degree, Head of the Bacteriological Laboratory, Bacteriologist, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040 Novosibirsk, Russia. Tel. +79538572720. E-mail: epguselnikova@nsk-niit.ru

GORDEEVA ELIZAVETA I., ORCID ID: 0000-0002-3288-5259, Applicant for the Cand. sc. biol., Biologist at the Bacteriological Laboratory, Novosibirsk Tuberculosis Research Institute, 81a Okhotskaya str., 630040, Novosibirsk, Russia. Tel. +7 (913) 0690582. E-mail: mbtnniit20@gmail.com

Abstract. Introduction. Non-tuberculous mycobacteria are ubiquitous; they are widespread in soil and water, including plumbing, aquariums, hot water supply systems, and air conditioning systems. Currently, more than 200 species of non-tuberculous mycobacteria are known, of which about 60 species have proven clinical significance, the rest are widespread in the environment, and little is known about their ability to cause diseases. Aim. The purpose of this study was to investigate the species diversity of non-tuberculous mycobacteria circulating in the Siberian Federal District of Russia. Materials and Methods. Two typical regions of the Siberian Federal District were selected for the study: Novosibirsk and Tomsk regions. Mycobacteria were cultured from patients’ sputum samples: 45 samples from the State Regional Clinical Tuberculosis Hospital and 106 from the Regional Department of Tomsk Phthisiopulmonology Medical Center. Further, non-tuberculous mycobacteria were identified by species, using the time-of-flight mass-spectrometry and the extraction with formic acid on an instrument according to the study protocol. Statistical processing of the study results was carried out using Microsoft Excel 2016 computer programs for Windows. Extensive indicators (the percentage of patients with detected pathogen drug resistance to the total number of patients, whose material was tested) were also calculated, and the boundaries of 95% confidence intervals (95% CI) were defined for the proportion (Fisher’s method). Statistical calculation of the research results was carried out in Microsoft Excel 2016. Results and Discussion. Among the slow-growing non-tuberculous mycobacteria species, Mycobacterium Avium complex is most common. Mycobacterium simie complex, Mycobacterium lentiflavum, and Mycobacterium parascorfulaceum were found less frequently. There were also Mycobacterium terrae complex and Mycobacterium nonchromogenicum found. The slow-growing mycobacteria, currently not grouped into a complex, include Mycobacterium Mycobacterium szulgaeand Mycobacterium gordonae. Mycobacterium abscessus / Mycobacterium chelonae complex dominated among the fast-growing mycobacteria species. Mycobacterium fortuitum complex was a less common complex. Conclusions.For the first time, diversity was assessed and the dominant strains of mycobacteria circulating in the Novosibirsk and Tomsk regions were identified, which gives an idea of the main target strains, at which the main preventive and sanitizing measures should be targeted.

 PROLONGED ARTIFICIAL VENTILATION AND LONG-TERM TRACHEOSTOMY IN A PATIENT WITH FIBROUS-CAVERNOUS PULMONARY TUBERCULOSIS: A CLINICAL CASE

LUKYANOVA MARINA V., ORCID ID: 0009-0009-1600-558X, RSCI Author ID 231962, Cand. sc. med., Intensivist, Anesthesia and Intensive Care Department, Novosibirsk Tuberculosis Research Institute, Russian Ministry of Health, 81а Okhotskaya str., 630040 Novosibirsk, Russia. Tel. +7(383)203-72-61. E-mail: chernova.m.nniit@mail.ru

2. Kao K-C, Hu H-C, Fu J-Y, et al. Renal replacement therapy in prolonged mechanical ventilation patients with renal failure in Taiwan. Journal Critical Care. 2011; 26: 600–607. DOI:10.1016/j.jcrc.2011.03.005

3. Lone NI, Walsh TS. Prolonged mechanical ventilation in critically ill patients: Epidemiology, outcomes and modelling the potential cost consequences of establishing a regional weaning unit. Critical Care. 2011; 15: R102 DOI:10.1186/ cc10117

4. Shih C-Y, Hung M-C, Lu H-M, et al. Incidence, life expectancy and prognostic factors in cancer patients under prolonged mechanical ventilation: A nationwide analysis of 5,138 cases during 1998–2007. Critical Care. 2013; 17: R144. DOI:10.1186/cc12823

5. Wu Y-K, Kao K-C, Hsu K-H, et al. Predictors of successful weaning from prolonged mechanical ventilation in Taiwan. Respiratory Medicine. 2009; 103: 1189–1195. DOI: 10.1016/j.rmed.2009.02.005

6. Jubran A, Grant BJB, Duffner LA, Collins EG, et al. Long-Term Outcome after Prolonged Mechanical Ventilation. A Long-Term Acute-Care Hospital Study. American Journal Respiratory Critical Care Medicine. 2019; 199: 1508–1516. DOI:10.1164/rccm.201806-1131OC

7. Damuth E, Mitchell JA, Bartock JL, Roberts BW, Trzeciak S. Long-term survival of critically ill patients treated with prolonged mechanical ventilation: A systematic review and meta-analysis. Lancet Respiratory Medicine. 2015; 3: 544–553. DOI:10.1016/S2213-2600(15)00150-2

8. Angus DC. Caring for the critically ill patient: Challenges and opportunities. JAMA. 2007; 298: 456–458. DOI: 10.1001/jama.298.4.456

9. Bissett B, Gosselink R, Van Haren FMP. Respiratory Muscle Rehabilitation in Patients with Prolonged Mechanical Ventilation: A Targeted Approach. Critical Care. 2020; 24: 103. DOI:10.1186/s13054-020-2783-0

10. Chen Y-H, Lin H-L, Hsiao H-F, et al. Effects of Exercise Training on Pulmonary Mechanics and Functional Status in Patients with Prolonged Mechanical Ventilation. Respiratory Care. 2012; 57: 727–734. DOI:10.4187/ respcare.01341

11. Chen Y-H, Lin H-L, Hsiao H-F, et al. Effects of an additional pressure support level on exercise duration in patients on prolonged mechanical ventilation. Journal Formos Medical Association. 2015; 114: 1204–1210. DOI: 10.1016/j. jfma.2014.09.002

12. Dunn H, Quinn L, Corbridge SJ, et al. Mobilization of prolonged mechanical ventilation patients: An integrative review. Heart Lung. 2017; 46: 221–233. DOI: 10.1016/j. hrtlng.2017.04.033

13. Ho S-C, Lin H-C, Kuo H-P, et al. Exercise training with negative pressure ventilation improves exercise capacity in patients with severe restrictive lung disease: A prospective controlled study. Respiratory Res. 2013; 14: 22. DOI:10.1186/1465-9921-14-22

14. Huang H-Y, Chou P-C, Joa W-C, et al. Pulmonary rehabilitation coupled with negative pressure ventilation decreases decline in lung function, hospitalizations, and medical cost in COPD: A 5-year study. Medicine. 2016; 95: e5119. DOI:10.1097/MD.0000000000005119

15. Huang H-Y, Lo C-Y, Yang L-Y, et al. Maintenance Negative Pressure Ventilation Improves Survival in COPD Patients with Exercise Desaturation. Journal Clinical Medicine. 2019; 8: 562. DOI:10.3390/jcm8040562

16. Schreiber AF, Ceriana P, Ambrosino N, et al. Physiotherapy and Weaning From Prolonged Mechanical Ventilation. Respiratory Care. 2018; 64: 17–25. DOI:10.4187/ respcare.06280

17. Van Wetering CR, Hoogendoorn M, Mol SJ, et al. Short- and long-term efficacy of a community-based COPD management programme in less advanced COPD: A randomised controlled trial. Thorax. 2010; 65: 7–13. DOI:10.1136/thx.2009.118620