eThe rate of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB) has been steadily increasing in countries of the former USSR. The availability of rapid and reliable methods for the detection of drug resistance to second-line drugs is vital for adequate patient management. We evaluated the performance of the Genotype MTBDRsl assay compared to that of phenotypic drug susceptibility testing (Becton Dickinson Bactec MGIT 960 system) with a test panel of 200 Mycobacterium tuberculosis isolates at four sites in Eastern Europe. The interpretability of the Genotype MTBDRsl assay was over 95%. The sensitivity for the detection of resistance to fluoroquinolones, ethambutol, amikacin, and capreomycin varied between 77.3% and 92.3%; however, it was much lower for kanamycin (42.7%). The sensitivity for the detection of XDR TB was 22.6%. The test specificity was over 82% for all drugs. The assay presents a good screening tool for the rapid detection of resistance to individual second-line drugs and can be recommended for use in countries with a high burden of MDR/XDR TB. The sensitivity for the detection of kanamycin resistance needs improvement.

Objective and MethodsA long-term observational study was conducted in Samara, Russia to assess the survival and risk factors for death of a cohort of non-multidrug resistant tuberculosis (non-MDRTB) and multidrug resistant tuberculosis (MDRTB) civilian and prison patients and a civilian extensive drug-resistant tuberculosis (XDRTB) cohort.ResultsMDRTB and XDRTB rates of 54.8% and 11.1% were identified in the region. Half (50%) of MDRTB patients and the majority of non-MDRTB patients (71%) were still alive at 5 years. Over half (58%) of the patients died within two years of establishing a diagnosis of XDRTB. In the multivariate analysis, retreatment (HR = 1.61, 95%CI 1.04, 2.49) and MDRTB (HR = 1.67, 95%CI 1.17, 2.39) were significantly associated with death within the non-MDR/MDRTB cohort. The effect of age on survival was relatively small (HR = 1.01, 95%CI 1.00, 1.02). No specific factor affected survival of XDRTB patients although median survival time for HIV-infected versus HIV-negative patients from this group was shorter (185 versus 496 days). The majority of MDRTB and XDRTB strains (84% and 92% respectively) strains belonged to the Beijing family. Mutations in the rpoB (codon 531 in 81/92; 88.8%), katG (mutation S315T in 91/92, 98.9%) and inhA genes accounted for most rifampin and isoniazid resistance respectively, mutations in the QRDR region of gyrA for most fluroquinolone resistance (68/92; 73.5%).ConclusionsAlarmingly high rates of XDRTB exist. Previous TB treatment cycles and MDR were significant risk factors for mortality. XDRTB patients' survival is short especially for HIV-infected patients. Beijing family strains comprise the majority of drug-resistant strains.

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Former Soviet Union countries including the Baltic States (Latvia, Lithuania, and Estonia) are hot spots for an emerging epidemic of drug resistant tuberculosis (TB). As a part of the development of a co-ordinated network of centers for diagnostic trials across Eastern Europe we conducted a retrospective multicenter analysis of the performance of the GenoType® MTBDRPlus assay for TB identification and susceptibility to isoniazid (INH) and rifampicin (RIF) in routine settings. A total of 1,045 primary samples, 1045 TB cultures derived from these specimens and 306 separate M. tuberculosis isolates tested in 2007-2010 at four participating sites (Tartu, Estonia; Riga, Latvia; Vilnius, Lithuania; and Samara, Russian Federation) were included in the analysis. The pooled sensitivity and specificity values for RIF and INH were 95.3% and 95.5%, 89.9 and 87.1%, respectively; there were no statistically significant variations in performance across sites. The proportion of multidrug resistant (MDR) strains in the collections ranged from 21.8% (in Estonia) to 55.9% (in Russia). In a routine non-trial context, the assay reliably detected both rifampicin and isoniazid resistance. The absence of statistically significant differences between sites suggested that the comparable performance obtained using these assays has helped demonstrate the formation of a successful diagnostic trial network.

The Russian Federation is a high-tuberculosis (TB)-burden country with high rates of drug resistance, including multidrug and extensive drug resistance to TB (M/XDRTB). Rapid diagnosis of resistance to fluoroquinolones (FQs) using molecular assays is essential for the implementation of appropriate drug regimens and prevention of the transmission of XDR strains. A total of 51 individual MDRTB strains were tested by pyrosequencing of the quinolone resistance determining region of the gyrA gene and the GenoType MTBDRsl assay (Hain Lifescience, GmbH, Nehren, Germany), and the results were evaluated against those obtained by phenotypic drug susceptibility testing (DST). Mutations were detected in 25 (78.1%) FQ-resistant strains, with the majority of mutations (n ‫؍‬ 19 [73.0%]) found in codon 94 of the gyrA gene; the novel mutation 1457 C3⌻ was found in the gyrB gene. Three mixed allelic variants were detected, which is a well-known phenomenon in areas with high TB and drug-resistant TB rates. The sensitivity and specificity of pyrosequencing (86.2 and 100%, respectively) and MTBDRsl (86.2 and 100%, respectively) were high; however, the results for 5.9% of the analyzed strains were unreadable when MTBDRsl was used. The MTBDRsl and pyrosequencing assays offer a rapid and accurate means for diagnosing resistance to FQs in high-TB-burden areas.Tuberculosis (TB) remains a major threat to public health worldwide and in the developing world in particular, causing almost 2 million deaths annually. The real magnitude of drug resistance is not yet known, although the Indian subcontinent, China, and Russia are believed to account for the majority of cases globally (48).Multidrug-resistant TB (MDRTB), caused by TB bacilli resistant to both isoniazid (INH) and rifampin (RIF), poses difficulties in diagnosis and treatment, with lower survival rates (especially in HIV-infected persons) and the associated high costs of TB control programs. The World Health Organization (WHO) estimates current MDRTB rates in new and previously treated cases globally to be 2.9 and 15.3%, respectively (50).The Russian Federation is a high-TB-burden country with high rates of TB drug resistance, dominated by TB strains of the Beijing family reported to be associated with MDRTB (7, 42). The Samara Oblast (Central Russia) is a hot spot for both TB and HIV epidemics; ca. 20% of new TB cases are MDR, with rates even higher in previously treated cases and in the prison sector (8). Converging TB, drug-resistant TB, and HIV epidemics pose a serious problem for low-and middle-income countries such as Russia where access to second-and third-line drug therapy is limited (2, 8).The rate of extensively drug-resistant TB (XDRTB) (which is caused by MDRTB bacilli with additional resistance to a fluoroquinolone [FQ] and one or more injectable drugs) has been increasing in Russia (36) due to multiple incomplete treatment regimens and poor infection control practice. Cases of XDRTB show a high rate of treatment failure and mortality especially in XDRTB patients with c...

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Цель. Изучить структурно-функциональные особенности левых отделов сердца и артерий у больных с постоянной формой фибрилляции предсердий (ФП) в сочетании с хроническая сердечная недостаточность (ХСН) ишемической этиологии в зависимости от цистатин С-обусловленной скоростью клубочковой фильтрации (СКФ). Материал и методы. 60 пациентов в возрасте от 35 до 60 лет с постоянной формой ФП ишемической этиологии. Всем пациентам были выполнены эхокардиография с верификацией дисфункции: систолическая функция оценивалась по фракции выброса левого желудочка по методу Simpson, для оценки диастолической дисфункции производилось определение скоростных характеристик трансмитрального кровотока и тканевой визуализации движения фиброзного кольца митрального клапана; суточное монито-рирование ЭКГ, объемная сфигмоплетизмография периферических артерий, оценка почечной функции с использованием формулы Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) по креатинину и цистатину С, оценка статуса коллагенообразования по уровню тканевого ингибитора матриксных металлопротеиназ 1 типа (TIMP-1) определение N-терминального фрагмента мозгового натрийуретического гормона (NT-proBNP). В первой части исследования пациенты были разделены на три группы -по уровню СКФ <30 мл/мин/1,73 м 2 , 30-60 мл/мин/1,73 м 2 и >60 мл/мин/1,73 м 2 . Во второй -по уровню цистатина С ниже и выше референсного значения. Результаты. У больных постоянной формой ФП и ХСН ишемической этиологии концентрация цистатина С в крови имеет прямые сильной степени зависимости взаимосвязи с NT-proBNP (r=0,60; р=0,003), индекс массы миокарда левого желудочка (r=0,68; р=0,005), E/e' среднее (r=0,73; p<0,001), время изоволюмического расслабления (r=0,53; р=0,012), cреднесуточной частоты сердечных сокращений (r=0,51; р=0,016), низкой степени зависимости -с TIMP-1 (r=0,26, p=0,002), обратные сильной степени зависимости -с SDNN (r=-0,59; р<0,001). СКФ (CKD-EPIcys) имеет обратные сильной степени зависимости взаимосвязи с septal e' (r=-0,51 р=0,041), c R-AI (r=-0,74; p<0,001), c CAVI1 (r=-0,53; р=0,008), и прямые средней степени зависимости -с SDNN (r=0,42; р<0,001). Заключение. Определение концентрация цистатина С в крови и цистатин С-зависимой СКФ у больных постоянной формой ФП и ХСН ишемической этиологии являются не только ранними маркерами ХБП, но и факторами риска развития и прогрессирования поражения органов-мишеней (сердца, сосудов). REMODELING OF THE HEART AND VESSELS IN ATRIAL FIBRILLATION PATIENTS WITH CHRONIC HEART FAILURE ACCORDING TO CYSTATIN C-RELATED GLOMERULAR FILTRATION RATEMironova S. V., Polyanskaya E. A., Surovtseva M. V.Aim. To investigate on structural and functional specifics of the left cardiac chambers and arteries in patients with permanent atrial fibrillation (AF) comorbid with chronic heart failure (CHF) of ischemic origin, with relation to cystatin C-dependent glomerular filtration rate (GFR). Material and methods. Sixty patients, age 35-60 y. o., with permanent AF of ischemic origin. All patients underwent echocardiography for the dysfunction verifica...

The review presents data on the prevalence of atrial fibrillation in patients on dialysis therapy. It is shown that dialysis-dependent patients with non-valve atrial fibrillation prognosis is extremely unfavorable, significantly increased risk of death due to both ischemic and hemorrhagic complications. Scales to assess the risk of thromboembolic and hemorrhagic complications in patients with atrial fibrillation on program dialysis are not validated. The lack of data from randomized clinical trials makes it much more difficult to choose anticoagulant therapy in patients with terminal stage of chronic kidney disease on dialysis who have undergone kidney transplantation. Therefore, the need for anticoagulant therapy and the choice of drugs in patients in this category should be made on the basis of a personalized multidisciplinary approach, taking into account comorbid pathology and the patient’s preferences.