Наукові праці. Кафедра інфекційних хвороб, дитячих інфекційних хвороб, фтизіатрії та пульмонології
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Item Chest X-ray alone is insufficient for predicting drug-resistant pulmonary tuberculosis(Elsevier B.V., 2024-05) Pedersen, Ole Skouvig; Butova, Tetiana; Borovok, Natalia; Akymenko, Oleksandra; Sapelnik, Nadiya; Tantsura, Oleksandr; Knysh, Vitaliy; Fløe, Andreas; Butov, DmytroItem Drug-Resistant Tuberculosis, Georgia, Kazakhstan, Kyrgyzstan, Moldova, and Ukraine, 2017–2022(Centers for Disease Control and Prevention (CDC), 2024-04-04) Dahl, Victor Naestholt; Butova, Tetiana; Rosenthal, Alex; Grinev, Alina; Gabrielian, Andrei; Vashakidze, Sergo; Shubladze, Natalia; Toxanbayeva, Bekzat; Chingissova, Lyailya; Crudu, Valeriu; Chesov, Dumitru; Kalmambetova, Gulmira; Saparova, Gulbarchyn; Wejse, Christian Morberg; Butov, DmytroIn 2021, the World Health Organization recommended new extensively drug-resistant (XDR) and pre-XDR tuberculosis (TB) definitions. In a recent cohort of TB patients in Eastern Europe, we show that XDR TB as currently defined is associated with exceptionally poor treatment outcomes, considerably worse than for the former definition (31% vs. 54% treatment success).Item Human chemerin induces eryptosis at concentrations exceeding circulating levels(Tech Science Press, 2024) Tkachenko, Maryna; Onishchenko, Anatolii; Tryfonyuk, Liliya; Butov, Dmytro; Kot, Kateryna; Novikova, Viktoriia; Fan, Liwei; Prokopiuk, Volodymyr; Kot, Yurii; Anton TkachenkoIntroduction: Human chemerin is an adipokine that regulates chemotaxis, inflammation, and glucose metabolism. In addition, accumulating evidence suggests that chemerin promotes apoptosis, autophagy, and pyroptosis. However, there are no data on its impact on eryptosis. The current study aimed to analyze the effects of human active Glu21-Ser157 chemerin on eryptosis in vitro. Materials and Methods: Human chemerin 0-2-10-50 µg/mL was incubated for 24 h with human erythrocytes (hematocrit 0.4%) obtained from eight healthy individuals. Flow cytometry-based determination of phospholipid scrambling, reactive oxygen species (ROS) production, and intracellular Ca2+ levels was performed. To supplement data on ROS and Ca2+ signaling in chemerin-mediated eryptosis, incubation in the presence or absence of antioxidants vitamin C and N-acetylcysteine and Ca2+-binding agent EGTA was carried out, respectively. Confocal microscopy-based techniques were used to detect reactive nitrogen species (RNS) generation, involvement of caspase-3 and caspase-8, as well as the state of lipid order in cell membranes of erythrocytes exposed to human Glu21-Ser157 chemerin. Results: Our observations suggest that human Glu21-Ser157 chemerin had no impact on eryptosis parameters at 2 µg/mL. However, chemerin stimulated phosphatidylserine externalization, ROS production, and Ca2+ accumulation at higher concentrations suggesting activation of eryptosis. Ca2+ uptake turned out to be at least partly required for chemerin-mediated eryptosis. Chemerin-mediated erythrotoxicity was additionally mediated by RNS, caspase-3, and caspase-8. Moreover, Glu21-Ser157 chemerin promoted reduction in the liquid-ordered phase of cell membranes in erythrocytes. Conclusions: The present study first discloses that human chemerin can induce eryptosis via Ca2+-dependent mechanisms at concentrations noticeably exceeding circulating levels. Thus, chemerin-induced eryptosis can hardly contribute to eryptosis-mediated anemia in diseases associated with enhanced levels of chemerin in blood.Item Neutrophil extracellular traps characterize caseating granulomas(Nature Publishing Group, 2024-07-31) Zlatar, Leticija; Knopf, Jasmin; Singh, Jeeshan; Wang, Han; Muñoz-Becerra, Marco; Herrmann, Irmgard; Chukwuanukwu, Rebecca C.; Eckstein, Markus; Eichhorn, Philip; Rieker, Ralf J.; Naschberger, Elisabeth; Burkovski, Andreas; Krenn, Veit; Bilyy, Rostyslav; Butova, Tetiana; Liskina, Iryna; Kalabukha, Ihor; Khmel, Oleg; Boettcher, Michael; Schett, Georg; Butov, Dmytro; Tkachenko, Anton; Herrmann, MartinTuberculosis (TB) remains one of the top 10 causes of death worldwide and still poses a serious challenge to public health. Recent attention to neutrophils has uncovered unexplored areas demanding further investigation. Therefore, the aim of this study was to determine neutrophil activation and circulatory neutrophil extracellular trap (NET) formation in various types of TB. Sera from TB patients (n = 91) and healthy controls (NHD; n = 38) were analyzed for NE-DNA and MPO–DNA complexes, cell-free DNA (cfDNA), and protease activity (elastase). We show that these NET parameters were increased in TB sera. Importantly, NET formation and NE activity were elevated in TB patients with extensive tissue damage when compared to those with minor damage and in patients with relapse, compared to new cases. We discuss the importance of balancing NET formation to prevent tissue damage or even relapse and argue to analyze circulating NET parameters to monitor the risk of disease relapse. To investigate the tissues for NETs and to find the source of the circulating NET degradation products, we collected sections of granulomas in lung and lymph node biopsies. Samples from other diseases with granulomas, including sarcoidosis (SARC) and apical periodontitis (AP), served as controls. Whereas NET formation characterizes the caseating granulomas, both caseating and non-caseating granulomas harbor DNA with unusual conformation. As TB is associated with hypercoagulation and thromboembolism, we further imaged the pulmonary vessels of TB patients and detected vascular occlusions with neutrophil aggregates. This highlights the dual role of neutrophils in the pathology of TB.Item Treatment outcomes and risk factors for an unsuccessful outcome among patients with highly drug-resistant tuberculosis in Ukraine(Elsevier B.V., 2024) Pedersen, Ole Skouvig; Butova, Tetiana; Kapustnyk, Valeriy; Miasoiedov, Valerii; Kuzhko, Mykhailo; Hryshchuk, Leonid; Kornaha, Svitlana; Borovok, Natalia; Raznatovska, Olena; Fedorec, Andrii; Bogomolov, Artemii; Tkhorovskiy, Mykhaylo; Akymenko, Oleksandra; Klymenko, Iurii; Kulykova, Olena; Karpenko, Zhanna; Shapoval, Tetiana; Chursina, Nataliia; Kondratyuk, Natalia; Parkhomenko, Olha; Sazonenko, Inna; Ostrovskyy, Mykola; Makoida, Iryna; Markovtsiy, Lyubov; Skryp, Vasyl; Lubenko, Victoriya; Hrankina, Nataliia; Bondarenko, Leonid; Hlynenko, Valentyna; Dahl, Victor Næstholt; Butov, DmytroObjectives: To describe demographics, clinical features, and treatment outcomes of patients with highly drug-resistant tuberculosis (TB) in Ukraine, and to evaluate risk factors for an unsuccessful outcome. Methods: Data from patients with multi-, pre-extensively, or extensively drug-resistant TB were collected prospectively from TB dispensaries in 15 out of 24 Ukrainian oblasts (regions) from 2020 to 2021. Treatment outcomes were evaluated using WHO definitions. Risk factors for an unsuccessful outcome were identified using a multivariable logistic regression model. Results: Among 1748 patients, the overall proportion of successful outcomes was 58% (95% confidence interval [95% CI] 56e60) (n ¼ 1015/1748), ranging from 65% (95% CI: 62e69) (n ¼ 531/814) for multidrug resistant TB to 54% (95% CI: 49e58) (n ¼ 301/563) for pre-extensively drug-resistant TB and 49% (95% CI: 44e55) (n ¼ 183/371) for extensively drug-resistant TB. Results were similar across oblasts, with few exceptions. The strongest risk factors for an unsuccessful outcome were extensively drug-resistant TB (adjusted OR [aOR] 3.23; 95% CI: 1.88e5.53), total serum protein below 62 g/L in adults and below 57 g/L for children and adolescents (aOR 2.79; 95% CI: 1.93e4.04), psychiatric illness (aOR 2.79; 95% CI: 1.46 e5.33), age at TB diagnosis >65 years (aOR 2.50; 95% CI: 1.42e4.42), and alcohol misuse (aOR 2.48; 95% CI: 1.89e3.26). Discussion: The overall proportion of successful outcomes among Ukrainians treated for highly drug resistant TB was 58%, notably better compared with previous years, but still low for extensively drug resistant TB. Risk factors for unsuccessful outcomes highlight that addressing socioeconomic factors in TB management is crucial. Efforts in maintaining TB dispensaries during and following the ongoing war are highly warranted.