The objective: to study the conditions of implementation of short-course (4 and 9 months) treatment regimens in tuberculosis patients and simulate their impact on the frequency of early treatment interruption (ETI) by patients.

Subjects and Methods. Data on the treatment duration from enrollment to chemotherapy interruption in 8,029 tuberculosis patients were studied. Data were obtained from the Federal Register of Tuberculosis Cases for 2020. Of these, 3,379 patients were treated with regimens for susceptible or suspected susceptible tuberculous mycobacteria excluding isoniazid resistant tuberculosis, and 4,650 patients received regimens for rifampicin-resistant tuberculous mycobacteria.

Results. The median duration of treatment from onset to ETI was 124 (95% CI 120-128) days in 3,379 patients, 224 (95% CI 215-233) days in 4,650 patients, or 170 (95% CI 157-181) days if there was a history of treatment interruption. Simulation of ETI terms when short-course chemotherapy regimens were introduced has shown that we can expect a 2-fold decrease in the proportion of patients who interrupted chemotherapy among patients with preserved/suspected susceptibility of tuberculous mycobacteria, and 1.3-1.7-fold decrease among patients with confirmed/presumed drug resistance of tuberculous mycobacteria at least to rifampicin.

The objective: to determine the significance of chronic cor pulmonale (CCP) as a cause of death in pulmonary tuberculosis patients.

Subjects and Methods. Out of 194 autopsies of tuberculosis patients who died in Hospital no. 1 of Ulyanovsk Regional Clinical TB Dispensary in 2017-2020, autopsy reports of 87 patients with pathomorphological signs of chronic cor pulmonale were selected. The nature and prevalence of pathomorphological manifestations of tuberculosis and the causes of deaths were analyzed. Statistical analysis of the results was performed using the STATISTICA-10. The significance of differences in the frequency of events was determined using the χ2 criterion in a four-field 2х2 table.

Results. Chronic cor pulmonale was confirmed pathomorphologically in 44.8% of deceased pulmonary tuberculosis patients. Chronic cor pulmonale was diagnosed in 67.8% of patients in their lifetime, and in 32.2%, it was diagnosed post mortem. Of 87 deceased patients with pulmonary tuberculosis complicated by chronic cor pulmonale, 28.7% had fibrous cavernous pulmonary tuberculosis, 26.4% had infiltrative form and 44.9% had disseminated form of the disease. Decompensated chronic cor pulmonale leading to death was detected in 42.5% of the deceased, and it was predominant in the structure of causes of death in fibrous cavernous tuberculosis (84%), and this pathology was also found in the patients with infiltrative (52.5%) and disseminated (10.3%) pulmonary tuberculosis.

The objective: to determine the effectiveness and safety (tolerability) of non-injection chemotherapy regimens containing bedaquiline in pediatric patients with multiple drug resistant respiratory tuberculosis.

Subjects and Methods. Effectiveness and safety of treatment regimens containing non-injection drugs and Bdq were studied in 45 children from Main Group (MG) aged from 5 to 17 years old inclusive who were ill with multiple drug resistant tuberculosis. Control Group (CG) included patients of the same age with MDR TB who were treated with chemotherapy regimens containing injectable drugs (a retrospective study).

Results. After 24 weeks (the period during which patients took bedaquiline), clinical effectiveness of chemotherapy regimens was achieved in all patients. By the end of week 24 of treatment, significant positive radiographic changes were noted in 84.4% of  patients in MG and in 75.7% in CG (OR 1.741; 95% CI 0.658–4.611), healing of cavities was achieved in 42 (93.3%) and 66 (94.3%) patients, respectively (OR 0.848, 95% CI 0.181-3.982). No tuberculous mycobacteria were not detected in 100% of cases in both groups by month 6 of chemotherapy. The number of adverse reactions (AR) per patient averaged 1.25 and 1.26 in MG and CG. ARs occurred in patients receiving aminoglycosides in 41.4%: in MG – in 33.3%; 4/70 (5.7%) children from CG receiving injectable drugs developed adverse reactions requiring replacement of anti-tuberculosis drugs. No irreversible ARs were observed in MG.

The objective: to identify structural features of genital tuberculosis in men depending on their HIV status.

Subjects and Methods. The medical records of 95 patients with genitourinary tuberculosis were analyzed, and records of patients with isolated tuberculosis of the male genital organs were selected.

Results. Among 95 male patients with genitourinary tuberculosis, 72 (75.8%) were HIV-negative, and 23 (24.2%) were HIV-positive. Among 72 HIV-negative male patients, 33 had isolated genital tuberculosis. Among 23 HIV-positive male patients, 9 had isolated genital tuberculosis. HIV infection had a significant impact on the structure of genital tuberculosis in male patients; among cases of isolated genital tuberculosis, tuberculosis of the testicle and its epididymis prevailed (88.9%). In HIV-negative male patients, the prostate gland was affected most often (prostate tuberculosis alone or in combination with tuberculous orchiepididymitis was diagnosed in 90.9% of patients).

The objective: to evaluate the effectiveness of 39- and 24-week treatment regimens in patients with multiple drug resistant or rifampicin-resistant tuberculosis (MDR/RR-TB).

Subjects and Methods. We evaluated the effectiveness of 39- and 24-week treatment regimens containing bedaquiline, levofloxacin, linezolid, clofazimine, and cycloserine or delamanid (modified short-course regimens - mSCR) and bedaquiline, pretomanid, linezolid, and moxifloxacin (BPaLM), in cohorts of patients with MDR/RR-TB.

Results. Of the 550 and 139 patients were included in the mSCR and SMARRTT Studies (BPaLM regimen) from December 2019 to October 2021 and from March 2022 to August 2022, 90.7% (487/537) and 94.2% (131/139) achieved a successful treatment outcome, respectively, 13 patients were excluded from the mSCR Study and continued treatment according to an individual regimen. Median (ME) and quartiles [Q1-Q3] of sputum culture conversion time in patients treated with mSCR and BPaLM made 30.0 (25.0-56.0) and 27.0 (25.0-29.8) days (p<0.01) respectively. The prognostic factor for an unfavorable outcome for the BPaLM and mSCR regimens was a positive sputum microscopy result before treatment (OR – 7.92, 95% CI 1.5 – 41.0, p = 0.014; OR – 1.97, 95% CI 1.1–3.5, p=0.02, respectively), and for the mSCR regime, the time of sputum culture conversion >90 days was an additional prognostic factor (OR – 3.35, 95% CI 1.2–9.5, p=0.03) .

Conclusions. The effectiveness of the mSCR and BPaLM regimens in patients with MDR/RR-TB is high (90.7% and 94.2%, respectively). Patients with positive sputum microscopy and late sputum culture conversion have a lower chance of cure.

The objective: to define the type and evaluate the severity of respiratory functional disorders after COVID-19. \

Subjects and Methods. A retrospective observational study was conducted. The following parameters were analyzed: demographic data, data from chest computed tomography during the acute period of the disease (CTmax), parameters of pulmonary function tests (PFT) – spirometry, body plethysmography and diffusion test. Those data were collected in 341 patients, 262 (76.8%) of them were men (median age – 48 (41.5–57) years, median durtaion of Period A (onset of COVID-19 before PFT) made 53 (28.5–111) days). Depending on duration of Period A, patients were divided into three groups: Group 1 – up to 90 days (n=221), Group 2 – 90-180 days (n=80), and Group 3 – more than 180 days (n=40). In patients of Groups 1, 2 and 3, in 68.3%, 47.5% and 32,5% of cases, respectively, disorders of diffusing lung capacity were recorded, which were associated to a greater extent with CTmax, and to a lesser extent with duration of Period A. The restrictive type of ventilation disorders was observed in 33.5% and 11% of cases in Groups 1 and 2, no restriction was detected in Group 3, airway obstruction was detected in 8%, 5%, 7.5% of cases in Groups 1, 2 and 3 respectively.

Conclusion. Disorder of diffusing lung capacity was the most common functional disorder of the respiratory system after COVID-19, and therefore it is advisable to include a diffusion test along with spirometry to the examination plan of such patients.

The objective: to evaluate expanded monitoring of cardiovascular disorders in older children and adolescents with multiple drug resistant tuberculosis receiving bedaquiline (Bq) as a part of anti-tuberculosis therapy.

Subjects and Methods: A cohort retrospective-prospective study (2015-2021) was conducted, which included 36 patients aged 13-17 years old who received Bq. The prospective part included 19 patients (Main Group), they underwent extended monitoring (EM) of cardiotoxic reactions; this extended monitoring program was developed in Central Tuberculosis Research Institute. The retrospective part included 17 patients (Control Group), in whom cardiotoxic reactions were assessed using standard monitoring recommended by the Russian Society of Phthisiologists at that time. The relationship between the studied risk factor (monitoring by standard ECG) and the outcome (Bq discontinuation) was assessed using the Pearson χ² test.

Results. Prolongation of the QTc interval > 0.440 ms was noted in 17.6% of cases in Control Group and it was regarded as a cardiotoxic effect of Bq, the drug was discontinued. In Main Group, prolongation was noted in 47.3% of cases which was considered a functional disorder of the cardiovascular system according to EM, the drug was not discontinued, χ² = 3.896; p = 0.049. EM can be used in older children and adolescents with multiple drug resistant respiratory tuberculosis, which will make it possible to safely include Bq to chemotherapy regimens.

The COVID-19 pandemic has led to the discontinuation of many support programs for tuberculosis patients worldwide, and lower coverage of population with screening for tuberculosis.

The objective: To build a model describing the spread of tuberculosis depending on the population coverage with preventive screening, and to obtain a long-term forecast of the infection spread using this model.

Subjects and Methods. We analyzed official statistical data on incidence, mortality, preventive screening coverage (PSC), and revalence of sputum smear-positive tuberculosis in the Russian Federation from 2008 to 2021. The model was built up based on fluctuations in those rates in 2020, when there was a sharp reduction in tuberculosis control interventions due to the COVID-19 pandemic. Statistical analysis was performed using the R Software (v.4.2.1).

Results. A simple mathematical model describing the dependence of incidence and sputum smear-positive tuberculosis in the current year on sputum smear-positive tuberculosis in the past year and population coverage with preventive screening in the current and past years was built up. The adjusted coefficient of determination of the model (adjusted R-squared) was 0.9969, which meant that the model contained almost no random components. It showed that tuberculosis cases missed due to low population coverage with preventive screening lead to future spread of tuberculous infection and a significant increase in the number of new tuberculosis cases. Comparison of projected rates and data for 2022 demontrated correct formation of models. However, the projected rates were slightly higher than the actual rates for 2022 due to the influence of factors other than the population coverage with preventive screening for tuberculosis.

Conclusions. The findings demonstrate the need for mass screening of the population in the context of significant spread of tuberculosis infection for timely detection of patients with sputum smear-positive tuberculosis.

The objective: to evaluate the effectiveness and safety of preventive treatment with fixed-dose combination of anti-tuberculosis drugs (FDCs) in children from groups at high risk of developing tuberculosis.

Subjects and Methods. Effectiveness of preventive treatment was analyzed in 318 children from groups at high risk of developing tuberculosis. Also, we studied the possibility of successful completion of the full course of treatment using FDCs and preventive treatment regimens containing at least two single drugs. Inclusion criteria were as follows: the child at high risk of developing tuberculosis; no clinical and radiological signs of active tuberculosis; lack of information about the resistance to first-line drugs at the suspected source of infection; and negative HIV status. A group of children (172 people) underwent preventive treatment using FDCs, of them 126 patients received FDCs containing isoniazid 150 mg + pyrazinamide 500 mg + pyridoxine hydrochloride 15 mg, and 46 patients received FDCs containing isoniazid 150 mg + ethambutol 400 mg + pyridoxine hydrochloride 15 mg. The comparison group (CG) included 146 children who received preventive treatment with single drugs: 111 children received isoniazid and pyrazinamide, and 35 children received isoniazid and ethambutol.

Results. When assessing the safety and effectiveness, no statistically significant differences were found when using FDCs and single-drug regimens. 91.9% of children receiving FDCs and 86.3% of children receiving single-drug regimens successfully completed the full course of treatment. When taking FDCs, there was a tendency to lower incidence of adverse events. With the FDC (isoniazid 150 mg + pyrazinamide 500 mg + pyridoxine hydrochloride 15 mg), the proportion of adverse events did not exceed 4.0%. There were no adverse events with the FDC (isoniazid 150 mg + ethambutol 400 mg + pyridoxine hydrochloride 15 mg).

Conclusion. Preventive treatment of children with tuberculosis infection with FDC is a modern and effective technology.

The objective: to evaluate the effectiveness of treatment with autologous mesenchymal stromal cells (MSCs) in patients with drug resistant pulmonary tuberculosis (DR TB).

Subjects and Methods. 120 patients with drug resistant tuberculosis aged 18 to 61 years old were enrolled in the study. They all were treated at the Republican Scientific and Practical Center of Pulmonology and Phthisiology from 2009 to 2018. Against the background of anti-tuberculosis treatment, patients (60 people) from Main Group (MG) underwent bone marrow sampling and then intravenous administration of autologous MSCs.

Results. The average dose of administered cells was 1x10⁶ per kg of the patient body weight. The average duration of MSC cultivation made 35 days. Treatment effectiveness in MG made 90% versus 71% in Control Group (CG). All patients who were successfully cured of tuberculosis (TB) using autologous MSCs had no tuberculosis relapses during 5 years of follow-up. In Control Group, 8 (19%) cases of relapse were reported. In Main Group versus Comparison Group, the rates indicating healing of cavities and absence of relapse are statistically significantly better.

Conclusion. The use of autologous MSCs in patients with drug resistant tuberculosis has shown its high effectiveness.

The article describes a clinical case of Wegener's granulomatosis, which manifested in the post-COVID period in a young man; also it discusses diagnostic difficulties. 

The article describes a clinical case of successful treatment of COVID-19 in a patient who previously underwent lung transplantation due to cystic fibrosis.

The article describes a clinical case pulmonary and lymph node sarcoidosis which development coincided with the implantation of mammary gland implants and their partial destruction. It discusses the differential diagnosis of sarcoidosis and sarcoid reaction to the contents of implants.

The review presents the analysis of 50 publications describing treatment of multiple drug resistant tuberculosis with regimens containing the new drug of delamanid. Delamanid possesses a dual bactericidal effect not only against active but also dormant Mycobacterium tuberculosis. The results of clinical studies on the efficacy and safety of delamanid within comprehensive chemotherapy are presented. The review demonstrates prospects for expanding the use of delamanid for treatment of adults and children.