Ural research Institute of Phthisiopulmonology

The objective : evaluation of potential of modern methods of rifampicin susceptibility testing in detection of heteroresistance of Mycobacterium tuberculosis cultures. Subjects and Methods . Mixtures of susceptible (H37Rv) and resistant (strain 5521 with XDR, with the rpoB Ser531Leu mutation) Mycobacterium tuberculosis strains were artificially created in proportions from 0% to 100%. Phenotypic methods (BACTEC MGIT 960, proportion method on Middlebrook 7H10 medium) and molecular genetic tests (TB-TEST, Amplitub-MLU-RV, AmpliTest MBT-Resist I) were used to test resistance to rifampicin. Results . Phenotypic methods revealed resistance to rifampicin with 1% resistant cells in the mixture. Molecular genetic methods showed variable detection thresholds: 5% (AmpliTest MBT-Resist I), 20% (TB-TEST), and 30% (Amplitub-MDR-RV). The authors demonstrate possibility of enhancing the sensitivity of domestic molecular genetic test systems by improving PCR data interpretation software, as well as the need to develop algorithms for tuberculosis diagnosing, taking into account limitations of the methods used.

Background/Objectives: Tuberculosis (TB) remains the leading cause of death from a single infectious agent worldwide. In line with the World Health Organization’s (WHO) goal to end TB by 2035, the rapid development and clinical implementation of new, effective vaccines is urgently needed. To support global TB control efforts, we developed a novel candidate subunit multistage vaccine. Methods: This vaccine incorporates multiple Mycobacterium tuberculosis antigens expressed during both dormant and active stages of infection, fused into a single recombinant protein (ESAT6-CFP10-Ag85A-Rv2660c-Rv1813c). The antigen was encapsulated in biodegradable poly(D,L-lactide-co-glycolide) (PLGA) nanoparticles along with the pattern recognition receptor (PRR) agonists monophosphoryl lipid A (MPLA) and muramyl dipeptide (MDP), which function as adjuvants. Results: Using a mixed intramuscular/nasal prime-boost regimen, the vaccine elicited a mixed Th1/Th17 cell-mediated immune response, as well as a robust humoral response characterized by sustained systemic IgG (lasting at least one year) and prominent local secretory IgA. The vaccine demonstrated protective efficacy as a prophylactic booster following BCG priming in both murine and guinea pig models and was also effective in a therapeutic setting in a murine infection model. Conclusions: The results of this study provide empirical evidence that multistage tuberculosis vaccines represent a promising strategy for achieving global TB control.

Introduction. Tezepelumab is the first biologic targeting TSLP approved for uncontrolled severe asthma (SA) regardless of phenotype/endotype. Data on its effectiveness in real-world clinical practice In Russia are limited. Aim. To evaluate the clinical effectiveness and safety of tezepelumab in patients with SA over 3 and 6 months of therapy. Mat erials and methods. A prospective, multicenter study included 21 patients with SA (16 with T2-endotype, 5 with non-T2endotype). Effectiveness was assessed at baseline, 3, and 6 months based on dynamics in asthma control (ACT questionnaire), exacerbation rate, systemic glucocorticosteroids (SGCS), short-acting bronchodilators (SABD) use, lung function (FEV ), blood eosinophil count, and nasal symptoms (SNOT-22). Re sult s. At 3 months, significant improvement in asthma control was achieved: the ACT score increased from 15.00 [10.00–18.00] to 22.00 [20.00–24.00] (p < 0.001). The proportion of patients with uncontrolled asthma decreased from 94.4% to 22.2%. SABD use decreased from 28.00 to 14.00 doses/week (p < 0.001), and regular SGCS use was discontinued in all patients. Response heterogeneity was observed: the T2-subgroup showed a significant reduction in annualized exacerbation rate from 4.33 ± 2.67 to 2.00 ± 2.70 (p = 0.032), whereas a trend towards increase was noted in the non-T2-subgroup. Nasal symptoms (SNOT-22) significantly decreased from 35.00 to 28.50 points (p = 0.007). In 5 patients followed for 6 months, the positive dynamics persisted. No adverse events were reported. Conclusions. Tezepelumab demonstrated high effectiveness and safety in real-world clinical practice in patients with SA, particularly those with a T2-endotype. The findings underscore the need for further data accumulation on tezepelumab use in real-world practice across different patient groups.

BackgroundThe prevalence of Mycobacterium tuberculosis (MTB) strains resistant to anti-TB drugs (ATD) remains a major challenge for TB treatment. Surgically obtained lung material plays an important role in assessing both the pathogen’s drug resistance and the host immune response. The relationship between molecular DR markers, the morphological activity of inflammation and treatment outcomes warrants further investigation.ObjectivesTo evaluate microbiological and histological characteristics of pulmonary resection specimens from patients receiving standardized anti-TB chemotherapy, and to determine correlations between treatment efficacy, morphological markers of inflammatory activity and presence of drug resistance-associated mutations in the MTB genome.Materials and methodsA cohort of 150 adult patients underwent lung resection in 2024 for localized TB. Patients with HIV or significant comorbidities were excluded. Indications for elective surgery, selection of treatment regimens and evaluation of their effectiveness were conducted in accordance with national Clinical Guidelines. MTB isolates from resected lung tissue were tested for phenotypic drug susceptibility and screened for resistance mutations to isoniazid (H), rifampicin (R) and fluoroquinolones (Fq). Histological activity of inflammation was graded as active (predominant exudative-necrotic inflammation), moderately active (intermediate patterns), or low (fibrosis predominance with minimal inflammatory response). Correlation between treatment effectiveness and morphological activity was assessed using Kendall’s τ (α=0.05).ResultsViable MTB were cultured from 20 of 150 patients; 17 showed active and 3 moderately active inflammation. In all these patients, H+R resistance was found, combined with DR to a wide range of reserve ADT, while only 5 (25%) patients registered a match in the structure of drug resistance to the set of drugs used before surgery. MTB DNA was detected in all specimens. Resistance mutations were identified in 23 patients for H, in 5 for R, in 60 for H+R and in 17 for combined H+R+Fq resistance. Inflammatory activity was highest in patients with H+R+Fq resistance (78% with high activity), intermediate with H+R (50% high) and mostly moderate in cases of monoresistance. When therapy regimens were adequately matched to resistance profiles, no significant association between mutations and inflammation was observed. A significant negative correlation (τ=–0.76, critical T=0.51) was found between chemotherapy effectiveness and inflammation activity. Among 41 patients whose treatment regimen corresponded to molecular data, 61% exhibited moderate and 39% low inflammation. Among patients with regimens inconsistent with molecular findings, 52% showed high activity, 33% moderate and only 15% low inflammatory activity. Resistance markers most frequently in combination with active inflammatory process were detected in patients who received preoperative treatment regimens for drug-susceptible TB due to the lack of baseline data on DR of the pathogen (in 4 out of 5, 80%).DiscussionDirect comparison of detailed histological grading of tuberculous inflammation with molecular resistance profiles and chemotherapy outcomes underscores the importance of incorporating morphological criteria in the assessment of treatment outcomes.ConclusionsHistological features of active inflammation are a critical indicator of insufficient chemotherapy effectiveness and the necessity for treatment modification. The presence of resistance mutations, provided that ADT is correctly selected, does not significantly affect the severity of histological signs of inflammation.

The cyst of Hattori is a rare pathology occurring only in women. Only about 45 – 50 cases have been described in literature up until now. All cases were reported in foreign sources, there were no reports in Russian-speaking media. The etiology of disease is still unknown, however the disorder of Mullerian duct development (embryonal anlage of female reproductive system) was suggested as the cause. X-ray imaging of the cyst of Hattori is very nonspecific. The cyst should be differentiated with pleural tumors, lung tumors, bronchogenic and celomic mediastinal cysts. The diagnosis is verified by histology augmented with immunohistochemistry assays of the surgical sample.The aim of the review was to inform the pulmonologists, general practitioners, infectious disease specialists, thoracic surgeons, oncologists and gynecologists about the cyst of posterior mediastinum that develops from the remnants of Mullerian duct, about its diagnosis, clinical course, and treatment. Also we present one clinical case of patient with Hattori’s cyst.Conclusion. The cyst of Hattori is very rare in clinical practice. However, physicians should know about it and include it into differential diagnosis when rounded shadows are identified in mediastimun by chest X-ray. The development of the disease is related to the embryonal disorders of Mullerian duct formation. Not only the light microscopy, but also immunohistochemical assays are necessary for the morphological confirmation of the diagnosis. The specific feature of cyst of Hattori is positive staining for the estrogen and progesterone receptors of the cells lining the cyst. Surgical excision is recommended for diagnosis, to improve the symptoms, and to exclude potential origin of the malignant transformation in the embryonal tissues of Mullerian duct. A forecast for the cyst of Hattori is favorable.

The article presents «Chronic obstructive pulmonary disease. COPD 2024» clinical guidelines (short version), prepared on the basis of «Chronic obstructive pulmonary disease-2024» clinical guidelines, developed by the Russian Respiratory Society and the Russian Scientific Medical Society of Physicians and approved by the Scientific and Practical Council of the Ministry of Health of Russia.

Two novel gold(iii) complexes with doubly protonated forms of phenanthrolines, (neocH2)[AuCl4]·Cl (1) and (1,7-phenH2)[AuCl4]·NO3 (2), were synthesized using the phenanthrolines.

The increase in the incidence of tuberculosis, especially in the post-Covid period, associated with the presence of latent infections and multiple drug resistance, dictates the need to develop new antimicrobial drugs. Here we wish to report the synthesis of 3,6-disubstituted 1,2,4,5-tetrazine derivatives containing N-, O- and C-nucleophile residues, as well as pharmacophoric hydrazone and oligooxyethylene fragments, and their screening against the pathogen Mycobacterium tuberculosis. Substances with pronounced antimycobacterial activity in vitro were identified (MIC = 0.18–3.12 μg/ml). An acute toxicity in vivo and membranotropic properties towards biometals have been studied for the most active compounds.