Tuberculosis in patients with different HIV-status in Novokuznetsk

Goal. To study the results of treatment for newly diagnosed tuberculosis in patients with different HIV status. Materials and methods. A retrospective study of all new TB cases among adults (n = 1036) registered in 2013-2014: 664 patients with HIV-free tuberculosis (TB) and 372 patients with HIV (HIV) and TB. Results. The average age of the patients was 39 ± 13 years; of men was 63.8% (n = 661). The median number of CD4-lymphocytes was 185 cells / μl (0-2064 cells / μl). most patients with HIV and (69.8%, n = 260) did not receive antiretroviral therapy. TB in HIV-1 and more often than in patients without HIV and was detected by treatment (74.7%, n = 278 vs. 49.4%, n = 328) (P 0.001), and among the clinical forms more often disseminated TB (43.1%, n = 156 vs 15.8%, n = 103) (P <0.001). Bacteriovenectomy by any of the methods for HIV and / or TB was detected more often than in patients without HIV without TB (72.1%, n = 261 vs 54.7%, n = 356) (P <0.0001), including number when sowing on dense nutrient media (64.1%, n = 232, vs 46.0%, n = 299) (P <0.001). For HIV and TB with preserved drug sensitivity, it was less common (31.9%, n = 67 vs 50.9%, n = 137) (P <0.001), and with primary multidrug resistance (MDR) 1.5 times more often than with monoinfection (51.4% and 33.5%, respectively) (P <0.001). In the absence of data on drug resistance, patients were treated with drugs of the main series. Treatment of MDR TB was conducted 64.4% (n = 58) in patients with TB and 42.6% (n = 46) with HIV and / or TB patients; in the remaining cases, MDR preparations of the reserve were not assigned because of refusal, lack of commitment or obtaining information about drug resistance after death. Cure for HIV / TB was less frequent than with monoinfection of TB (38.2% vs 61.7%) (P <0.001), and the share of deaths from all causes in HIV-TB was significantly higher (40.9% % vs 12.1%) (P <0.001). The conclusion. In patients with HIV, tuberculosis in most cases was detected during treatment, they were more often registered with bacterial excretion and primary MDR, and the effectiveness of treatment for HIV and / or TB was significantly lower than in patients with negative HIV status, mainly due to high mortality.Цель. Изучить результаты лечения впервые выявленного туберкулеза у больных с различным ВИЧ-статусом. Материалы и методы. ретроспективное исследование всех новых случаев ТБ среди взрослых (n=1036), зарегистрированных в 2013-2014 гг.: 664 больных с туберкулезом (ТБ) без ВИЧ-инфекции и 372 пациента с ВИЧ-инфекцией (ВИЧ-и) и ТБ. результаты. Средний возраст пациентов составил 39±13 лет; мужчин было 63,8% (n=661). Медиана количества CD4-лимфоцитов составляла 185 кл./мкл (0-2064 кл./мкл.); большинство больных ВИЧ-и (69,8%, n=260) не получали анти-ретровирусной терапии. тБ при ВИЧ-и чаще, чем у пациентов без ВИЧ-и выявлялся при обращении (74,7%, n=278 vs 49,4%, n=328) (P<0,001), а среди клинических форм чаще диагностировали диссеминированный ТБ (43,1%, n=156 vs 15,8%, n=103) (P<0,001). Бактериовыделение любым из методов при ВИЧ-и/ТБ обнаруживали чаще, чем у больных ТБ без ВИЧ-и (72,1%, n=261 vs 54,7%, n=356) (P<0,0001), в том числе при посевах на плотные питательные среды (64,1%, n=232, vs 46,0%, n=299) (P<0,001). При ВИЧ-и ТБ с сохраненной лекарственной чувствительностью встречался реже (31,9%, n=67 vs 50,9%, n=137) (P<0,001), а с первичной множественной лекарственной устойчивостью (МЛУ) - в 1,5 раза чаще, чем при моноинфекции (51,4% и 33,5% соответственно) (P<0,001). В отсутствие сведений о лекарственной устойчивости пациенты получали лечение препаратами основного ряда. Лечение МЛУ ТБ проводилось 64,4% (n=58) больным с ТБ и 42,6% (n=46) больным ВИЧ-и/ТБ; в остальных случаях МЛУ препараты резерва не назначались из-за отказа, отсутствия приверженности или получения сведений о лекарственной устойчивости после смерти. Излечение при ВИЧ-/ТБ достигали реже, чем при моноинфекции ТБ (38,2% vs 61,7%) (р<0,001), а доля летальных исходов от всех причин у ВИЧ-и/ТБ была значительно выше (40,9% vs 12,1%) (р<0,001). Заключение. У больных ВИЧ-и туберкулез в большинстве случаев выявлялся при обращении, у них чаще регистрировали бактериовыделение и первичную МЛУ, а эффективность лечения ВИЧ-и/ТБ была существенно ниже, чем у пациентов с негативным ВИЧ-статусом, преимущественно за счет высокой летальности

РАДИОХИРУРГИЧЕСКОЕ ЛЕЧЕНИЕ МЕТАСТАЗОВ РАКА ЯИЧНИКОВ В ГОЛОВНОЙ МОЗГ

Introduction. Radiosurgical treatment is the method of choice for brain metastases. In clinical practice, there are tumors with a relatively small frequency of secondary brain damage, for which the use of stereotactic radiosurgery has not been studied enough. One example of such diseases is malignant tumors of the female reproductive system.Materials and methods. We described the application of stereotactic radiosurgery of ovarian cancer metastases to the brain using a three-fold hypofractionated stereotactic radiosurgery. We resorted to this method in order to reduce the negative effect on the functional area of the brain and preserve the performance of radiation in the treatment of metastasis located in the subcortical nuclei. To evaluate the results, were performed magnetic  resonance imaging and volumetry of pathological volume in the program for planning stereotactic radiosurgery Leksell Gamma plan® 10.1.Results. Long term local control was observed on the part of all irradiated tumors with the same results of single irradiation and hypofractionated radiosurgery. Discussion. If there is a restriction to conduct a stereotactic radiosurgery associated with the localization of a pathological focus in the eloquent zone of the brain, it is possible to irradiate it in the hypofractionation mode. The method provides local control of tumor growth without a high risk of radiation toxicity.Введение. Радиохирургическое лечение является методом выбора при метастатическом поражении головного мозга. В клинической практике встречаются опухоли с относительно небольшой частотой вторичного поражения головного мозга, для которых применение стереотаксической радиохирургии изучено недостаточно. Одним из  примеров таких заболеваний являются злокачественные опухоли женской репродуктивной системы.Материалы и методы. Нами описано применение стереотаксической радиохирургии метастазов рака яичника в головной мозг с использованием режима трехкратного гипофракционирования дозы. Мы прибегли к этому методу с целью снижения негативного воздействия на функциональную зону головного мозга и  сохранения эффективности облучения при лечении метастатического очага, расположенного в области подкорковых ядер. С целью оценки результатов проводили  магнитнорезонансную томографию с последующей волюметрией патологических очагов в программе для планирования стереотаксической радиохирургии Leksell Gamma plan® 10.1.Результаты и их обсуждение. При динамическом наблюдении отмечен  продолжительный локальный контроль со стороны всех облученных опухолей с  идентичными результатами применения однократного облучения и режима  гипофракционирования. При наличии ограничения к проведению однократного  стереотаксического радиохирургического лечения, связанного с локализацией  патологического очага в элоквентной зоне головного мозга, существует возможность его  облучения в режиме гипофракционирования. Метод позволяет достичь локального контроля роста опухоли без высокого риска развития лучевой токсичности. 

Профессиональный хронический бронхит: роль полиморфных вариантов генов ферментов-антиоксидантов в формировании предрасположенности к заболеванию

Distributions of alleles and genotypes of GSTP1Ile105Val and Ala114Val, CAT С(-262)T and C1167T, NQO1 C609T and C465T, GPX1Pro197Leu, GSTM1, GSTT1 polymorphic loci have been studied in patients with occupational chronic bronchitis and in healthy workers. No statistically significant difference was determined in distribution of alleles and genotypes of GSTP1 Ala114Val, CAT С(-262)T and C1167T, NQO1 C609T, GPX1Pro197Leu, GSTM1, GSTT1 polymorphisms between these groups. Polymorphic marker NQO1 C465T was associated with higher risk of occupational chronic bronchitis (OR = 3.68; CI 95 %: 1.68-8.31) suggesting involvement of this gene in development of this pathology.Изучено распределение аллелей и генотипов полиморфных локусов Ile105Val и Ala114Val гена GSTP1, С(-262)T и C1167T гена CAT, C609T и C465T гена NQO1, Pro197Leu гена GPX1 и делеционных локусов генов GSTM1, GSTT1 в группе больных профессиональным хроническим бронхитом и в группе здоровых рабочих. Нами не выявлены статистически значимые различия в распределении аллелей и генотипов полиморфизмов Ala114Val гена GSTP1, С(-262)T и C1167T гена CAT, C609T гена NQO1, Pro197Leu гена GPX1 и делеций генов GSTM1, GSTT1 между исследуемыми группами. Обнаружена ассоциация полиморфного маркера С465Т гена NQO1 с повышенным риском развития профессионального хронического бронхита (отношение шансов – 3,68, 95%-ный доверительный интервал – 1,688,31), что свидетельствует о вовлеченности данного гена и его белкового продукта в патогенез заболевания

ГЕНЕТИЧЕСКИЕ МАРКЕРЫ РИСКА РАЗВИТИЯ ПОВЕРХНОСТНОГО И ИНВАЗИВНОГО РАКА МОЧЕВОГО ПУЗЫРЯ

To reveal possible associations of the polymorphic variants of the cytochrome P450 and enzymes glutathione-S-transferase genes with the risk for bladder cancer (BC), the authors analyzed the frequency of genotypes and alleles at the polymorphic loci of the CYP1A1 (A2454G), GSTM1 (del), and GSTP1 (A313G) genes in 208 patients diagnosed as having BC (104 patients with invasive BC and 104 with superficial BC) and in 367 patients without identified oncopathology. The *1A*2C (OR = 3.42) and *2C*2С (OR = 6.98) genotypes, *2C (OR = 3.73) allele of the CYP1A1 gene and the GG (OR = 2.53) genotype of the GSTP1 gene were ascertained to be genetic markers for a risk for BC. The presence of the *2C (OR = 1.69) allele of the CYP1A1 gene, the G (OR = 2.40) allele and the AG genotype (OR = 2.40) of the GSTP1 gene was associated with the invasive forms of BC. There were no substantial differences in the distribution of the frequency of genotypes of the GSTM1 gene between the samples of patients and healthy individuals.С целью выявления возможных ассоциаций полиморфных вариантов генов цитохрома P450 и ферментов глутатион-S-трансферазы с риском развития рака мочевого пузыря (РМП) нами проведен анализ частот встречаемости генотипов и аллелей полиморфных локусов генов CYP1A1 (A2454G), GSTM1 (del), GSTP1 (A313G) у 208 больных с диагнозом РМП (104 пациента с инвазивным и 104 – с поверхностным раком) и у 367 пациентов без выявленной онкопатологии. Установлено, что генетическими маркерами риска развития РМП являются генотипы *1A*2C (ОP 3,42) и *2C*2С (ОР 6,98), аллель *2C (ОР 3,73) гена CYP1A1, генотип GG (ОР 2,53) гена GSTP1. Наличие аллеля *2C (ОР 1,69) гена CYP1A1, аллеля G (ОР 2,40) и генотипа AG (ОР 2,40) гена GSTP1 ассоциировано с инвазивными формами РМП. Существенных различий в распределении частот встречаемости генотипов гена GSTM1 между выборками больных и здоровых не выявлено

Improved functionalization of oleic acid-coated iron oxide nanoparticles for biomedical applications

Superparamagnetic iron oxide nanoparticles can providemultiple benefits for biomedical applications in aqueous environments such asmagnetic separation or magnetic resonance imaging. To increase the colloidal stability and allow subsequent reactions, the introduction of hydrophilic functional groups onto the particles’ surface is essential. During this process, the original coating is exchanged by preferably covalently bonded ligands such as trialkoxysilanes. The duration of the silane exchange reaction, which commonly takes more than 24 h, is an important drawback for this approach. In this paper, we present a novel method, which introduces ultrasonication as an energy source to dramatically accelerate this process, resulting in high-quality waterdispersible nanoparticles around 10 nmin size. To prove the generic character, different functional groups were introduced on the surface including polyethylene glycol chains, carboxylic acid, amine, and thiol groups. Their colloidal stability in various aqueous buffer solutions as well as human plasma and serum was investigated to allow implementation in biomedical and sensing applications.status: publishe

Non-High Density Lipoprotein Cholesterol: A Modern Benchmark for Assessing Lipid Metabolism Disorders

Aim. To perform a population analysis of Non-High Density Lipoprotein Cholesterol level (non-HDL-c) in Russian population and to evaluate its association with cardiovascular events.Material and Methods. The material consisted of results obtained from 11 regions of the ESSE-RF1 Study and from 4 regions of the ESSE-RF2 Study. Study protocols were identical. The studies were performed in 2012-2014 and 2017, respectively. Endpoints were assessed in 19041 people aged 35-64 years. The median follow-up was 6.5 years in ESSE RF (1) and 3.8 years in ESSE RF(2). Analysis was performed for three lipid variables: total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and non-HDLC in two samples: the general population sample and the same sample without individuals with coronary heart disease (CHD), myocardial infarction (MI) and/or stroke history and not taking statins (the population sample of "without a history of cardiovascular diseases [CVD]". The analysis of nonlinear associations was performed using the generalized additive Cox model. The combined cardiovascular endpoint was represented by cardiovascular death and nonfatal MI and stroke. Traditional and laboratory FRs, socio-demographic parameters were analyzed. The significance level for all tested hypotheses was set to be 0.05.Results. The prevalence of elevated non-HDL-C level (&gt;3.7 mmol/l) was found to be 74.6%. No gender differences were found: there was 74.6% for men and 74.5% for women. Both mean values and prevalence of elevated non-HDL-C were increased with age in women, and its level was slightly decreased in men after 55 years old. Almost all analyzed RFs were significantly associated with elevated non-HDL-C in these two population samples. In both samples elevated total CH and elevated LDL-C were associated with all-cause mortality after correction for all RFs. On the contrary, the non-HDL-C was associated with CVD combined end pints. It has been shown that the risk of these end points increases uniformly with increase in levels of non HDL cholesterol, no nonlinear associations were found.Conclusion. The results of a population-based analysis of non-HDL-C performed in the Russian population for the first time confirmed that elevated non-HDL-C levels contribute significantly to determining the risk of cardiovascular events in the medium term. It can be assumed that the new risk scales (SCORE2 and SCORE OP) proposed by the European Society of Cardiology and the European Society of Preventive Cardiology, which include non-HDL C instead of TC, will allow adequate assessment of 10-year cardiovascular risk for Russians. However, continued monitoring of endpoints in order to obtain stable associations is required

Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

GENETIC RISK MARKERS FOR SUPERFICIAL AND INVASIVE BLADDER CANCER

<p>To reveal possible associations of the polymorphic variants of the cytochrome P450 and enzymes glutathione-S-transferase genes with the risk for bladder cancer (BC), the authors analyzed the frequency of genotypes and alleles at the polymorphic loci of the CYP1A1 (A2454G), GSTM1 (del), and GSTP1 (A313G) genes in 208 patients diagnosed as having BC (104 patients with invasive BC and 104 with superficial BC) and in 367 patients without identified oncopathology. The *1A*2C (OR = 3.42) and *2C*2С (OR = 6.98) genotypes, *2C (OR = 3.73) allele of the CYP1A1 gene and the GG (OR = 2.53) genotype of the GSTP1 gene were ascertained to be genetic markers for a risk for BC. The presence of the *2C (OR = 1.69) allele of the CYP1A1 gene, the G (OR = 2.40) allele and the AG genotype (OR = 2.40) of the GSTP1 gene was associated with the invasive forms of BC. There were no substantial differences in the distribution of the frequency of genotypes of the GSTM1 gene between the samples of patients and healthy individuals.</p