АССОЦИАЦИИ ПОЛИМОРФИЗМА ГЕНА ADRA2B С ФАКТОРАМИ РИСКА СЕРДЕЧНО-СОСУДИСТЫХ ЗАБОЛЕВАНИЙ В ПОПУЛЯЦИИ КОРЕННЫХ ЖИТЕЛЕЙ ГОРНОЙ ШОРИИ

Study objectives: examine the frequency of genotypes and alleles of I/D polymorphism of gene ADRA2B of native people living in Mountain Shoria (the Shors), as well as their association with risk factors for cardiovascular diseases.Material and methods. Overall 221 native people of Shoria were examined. The average age is51.07 ± 1.46 among males, 52.93 ± 0.96 among females (p = 0.286). Anthropometric characteristics, lipid levels of blood and I/D polymorphism of ADRA2B were studied.Results. DD genotype of the gene ADRA2B in the native population of the Shor people is associated with adiposis and high index of "waist/hip", hypertriglyceridemia. The average values of Quetelet index is higher in carriers of this genotype compared with carriers of genotype ID. Average waist indications in homozygous insertions were lower than those in homozygous deletions and heterozygotes. Patients with genotype DD have higher average levels of triglycerides, atherogenic index, cholesterol, very low density lipoproteins.Conclusion. DD allele ADRA2B genotype is responsible for adiposis and high levels of TG among native population of Shoria.Научно-исследовательский институт комплексных проблем сердечно-сосудистых заболеваний Сибирского отделения РАН, Кемерово; Новокузнецкий государственный институт усовершенствования врачей, НовокузнецкЦель исследования – изучить частоты генотипов и аллелей I/D полиморфизма гена ADRA2B в популяции коренных жителей Горной Шории (шорцев), а также их ассоциацию с факторами риска сердечно-сосудистых заболеваний.Материал и методы. Проведено клинико-эпидемиологическое исследование коренного населения труднодоступных районов Горной Шории. Сплошным методом обследован 221 человек, выборка состояла из взрослого населения (лица в возрасте 18 лет и старше). Средний возраст обследуемых составил (51,07 ± 1,46) лет у мужчин, (52,93 ± 0,96) лет у женщин (p = 0,286). Изучены антропометрические данные, показатели липидного спектра крови, I/D полиморфизм гена ADRA2B.Результаты. Генотип DD гена ADRA2B в популяции шорцев ассоциируется с ожирением и повышенным индексом «талия/бедро», гипертриглицеридемией. Средние значения индекса Кетле выше у носителей данного генотипа по сравнению с носителями генотипа ID. У гомозигот по инсерции средние показатели окружности талии оказались меньше, чем у гомозигот по делеции и у гетерозигот. Средние уровни триглицеридов, индекса атерогенности, холестерина липопротеинов очень низкой плотности были выше у лиц с генотипом DD.Заключение. В популяции шорцев маркером генетической предрасположенности к ожирению, нарушению распределения жировой ткани и гипертриглицеридемии является аллель D гена а2В-адренорецептора

Оценка токсичности и эффективности терапии комбинацией FOLFIRI и афлиберцепта при метастатическом раке толстой кишки в РФ: первые результаты многоцентрового ретроспективного исследования

oai:oai.tumors.elpub.ru:article/629Purpose. To assess the incidence and severity of adverse events; to explore clinical factors associated with grade 3–4 non-hematologic toxicity; to assess the immediate efficacy and progression-free survival during treatment with the FOLFIRI regimen in combination with aflibercept in Russia.Materials and Methods. A retrospective multicenter study has been conducted with data collected from 20 clinics in 15 regions of Russia. There was no statistical hypothesis. Progression-free survival was the main efficacy criterion. The statistical analysis was performed using IBM SPPS Statistics v. 20 software.Results. FOLFIRI and Aflibercept combination was administered to 264 patients. The mean number of treatment cycles was 6 (1 to 29). The toxicity of aflibercept was addressed by dose reduction and dosing delay in 10.1 % and 11.4 % of patients, respectively, and dose reductions and dosing delays in any of FOLIFRI components were reported in 20.1 % of participants. The objective response rate was 20.3 %. The median progression-free survival in patients receiving second-line treatment was 6 months (95 % CI: 5.3–6.6 months). Seventy-two percent of patients experienced any grade of adverse events most of which were limited to grade 1–2 (62.1 %). Non-hematologic toxicity was reported in 64 % of patients (grade 3–4 in 17.9 %). Hematologic events were detected in only 17.9 % of patients. Multifactorial analysis has shown that drug therapy for concomitant diseases (OR 1.98, 95 % CI: 1.04–3.78, p = 0.037) and the number of chemotherapy lines prior to aflibercept (ОR 1.5, 95 % CI: 1.06–2.11, p = 0.02) were independent predictors of grade 3–4 non-hematologic toxicity.Conclusions. Objective response rate, progression-free survival, and frequency of toxicity-related aflibercept discontinuations in the Russian study with patients receiving aflibercept in combination with FOLFIRI regimen as a second-line treatment has shown the results that were comparable with VELOUR study. Comorbidities requiring drug treatment and the number of prior chemotherapy lines appear to be risk factors for grade 3–4 nonhematological toxicity events. Цель исследования. Оценить частоту развития и тяжесть нежелательных явлений; изучить клинические факторы, ассоциированные с развитием негематологической токсичности 3-4 степени; оценить непосредственную эффективность выживаемость без прогрессирования при применении комбинации FOLFIRI с афлиберцептом в РФ.Материалы и методы. Проведено ретроспективное многоцентровое исследование. Собраны данные 20 клиник 15 регионов РФ. Статистическая гипотеза отсутствовала. В качестве основного критерия эффективности рассматривалась выживаемость без прогрессирования. Статистический анализ проводился с помощью программ статистического пакета SPSS (IBM SPPS Statistics v. 20).Результаты. Режим FOLFIRI афлиберцепт был назначен у 264 пациентов. Среднее число составило 6 (от 1 до 29). В связи с токсичностью доза афлиберцепта в процессе терапии была редуцирована у 10,1% пациентов, задержали очередное введение афлиберцепта — у 11,4%; отсрочка и редукция доз химиопрепаратов в режиме FOLFIRI описана у 20,1 %. Частота объективных эффектов составила 20,3%. Во второй линии терапии медиана выживаемости без прогрессирования составила 6 месяцев (95% ДИ 5,3-6,6 месяцев). Нежелательные явления любой степени зарегистрированы у 72 % пациентов и чаще были ограничены 1-2 степенью (62,1%). Негематологические осложнения развились у 64% (3-4 степень — у 17,9%). Гематологические осложнения представлены только у 17,9 % пациентов. По результатам многофакторного анализа лекарственная терапия по поводу сопутствующей патологии (ОШ 1,98, 95%ДИ 1,04-3,78, р=0,037) и число линий терапии (ОШ 1,5, 95%ДИ 1,06-2,11, р=0,02), предшествующих афлиберцепту, явились независимыми предсказывающими факторами развития нежелательных явлений негематологического профиля 3-4 степени.Выводы. Частота объективных эффектов, выживаемость без прогрессирования и частота отмены афлиберцепта в связи с токсическими реакциями при применении комбинации FOLFIRI + афлиберцепт во второй линии среди пациентов в РФ аналогична результатам исследования VELOUR. Сопутствующая патология, требующая медикаментозной коррекции, и число линий терапии предшествующих афлиберцепту, по-видимому, являются факторами риска развития негематологических явлений 3-4 степени

Efficacy and safety of 3D-therapy at HCV-related subcompensated liver cirrhosis (genotype 1b)

Aim of the study. To estimate efficacy and safety of 3D mode of interferon­free therapy in patients with subcompensated liver cirrhosis (LC) of HCV etiology (genotype 1b). Material and methods. Original study included the data of 66 patients (26 men and 40 women) with subcompensated LC of HCV etiology (genotype 1b) who underwent interferon­free therapy by ombitasvir/paritaprevir/ritonavir, dasabuvir and ribavirin for 12 weeks (the latter was cancelled at receiving the new data on treatment efficacy after 4 weeks of therapy) in September, 2015, before the drug instruction was updated. Mean age of patients was 56.4±10.0 years. At onset of etiological therapy 21 patients (31.8%) had Child­Pugh score of 9, eleven patients (16.7%) had Child­Pugh 8, 34 patients (51.5%) had Child­Pugh 7. The causes of inefficacy of previous modes of combined antiviral therapy (CAT) included absence of virologic response in 43.9% of the cases, recurrence of HCV replication - in 30.3%, virological breakthrough - in 16.7%, development of serious adverse effects - in 9.1%. Taking into account the change of the group quantity during the course of therapy because of treatment cancellation for safety reasons and the subsequent assessment of its efficacy in patients with early treatment cancellation, the modified «intent­to­treat» (ITT) analysis was the basic method of results evaluation. Along with that «per protocol» (PP) analysis was carried out as well. Results. During the treatment course aviremia in 14 days was achieved in 53.8% of patients (in 35 patients of 65), prompt virologic response - at 79.7% (in 51 of 64 patients). All patients underwent complete 12 week course of CAT (n=60) and those for whom treatment was canceled for safety reasons (n=3) - in terms from 14 to 30 days - sustained virologic response (SVR) in 12 weeks and SVR in 24 weeks was registered. The assessment of liver function compensation degree in 6 months after CAT termination demonstrated 3 to 4 points reduction of the Child-Pugh Score in 21 patients (33.9 %), 1 to 2 points in 35 patients (56.5 %). According to the MELD score the clinical improvement was achieved in 66.1% of patients. The early treatment termination was caused by progression of hepatic encephalopathy symptoms and/or jaundice development (4 cases). Most cases of the progression­related treatment termination due to liver failure were reversible after CAT interruption. Three lethal outcomes after the early treatment termination and 1 patients death in follow­up period were registered. Conclusion. Antiviral therapy in 3D mode for subcompensated LC is highly effective not only in those patients who received complete treatment course, but also in those with early treatment secession. Profiling of 3D therapy safety demonstrated that development of serious adverse effects during the treatment is comparable to outcomes at natural course of subcompensated LC in the absence of etiological therapy

Interim results of the Ph-negative acute lymphoblastic leukemia treatment in adult patients (results of Russian research group of ALL treatment (RALL))

An interim analysis of long-term treatment results for 202 patients with acute lymphoblastic leukemia (ALL), aged 15–60 years, received therapy according protocol ALL-2009 was shown. The basic principle of ALL-2009 was non-aggressive, but continued cytostatic exposure, as well as the reproducibility in a regional hematology centers. Long-term treatment results of ALL-2009 are 2 times higher than the previously obtained in adult ALL patients within the Russian clinical multicenter studies of adult ALL. The 5‑year overall survival of patients younger than 30 years was 73.6 %, relapse-free survival (RFS) – 71.5 %, compared with 52.7 % and 61.8 % in patients aged 30 years and older, respectively. In patients with B-precursor ALL with normal karyotype of blast cells significantly higher 5‑year RFS (82.1 %) compared to patients with abnormal karyotype (58.8 %) was registered. For T-ALL cytogenetic characteristics of blast cells had no prognostic significance. For patients with T-ALL important to perform autologous stem cell transplantation as a later consolidation, as this significantly reducerelapse rate (from 33 to 0 %).</p

Interim results of the Ph-negative acute lymphoblastic leukemia treatment in adult patients (results of Russian research group of ALL treatment (RALL))

An interim analysis of long-term treatment results for 202 patients with acute lymphoblastic leukemia (ALL), aged 15–60 years, received therapy according protocol ALL-2009 was shown. The basic principle of ALL-2009 was non-aggressive, but continued cytostatic exposure, as well as the reproducibility in a regional hematology centers. Long-term treatment results of ALL-2009 are 2 times higher than the previously obtained in adult ALL patients within the Russian clinical multicenter studies of adult ALL. The 5‑year overall survival of patients younger than 30 years was 73.6 %, relapse-free survival (RFS) – 71.5 %, compared with 52.7 % and 61.8 % in patients aged 30 years and older, respectively. In patients with B-precursor ALL with normal karyotype of blast cells significantly higher 5‑year RFS (82.1 %) compared to patients with abnormal karyotype (58.8 %) was registered. For T-ALL cytogenetic characteristics of blast cells had no prognostic significance. For patients with T-ALL important to perform autologous stem cell transplantation as a later consolidation, as this significantly reducerelapse rate (from 33 to 0 %)

Management of coronary disease in patients with advanced kidney disease

BACKGROUND Clinical trials that have assessed the effect of revascularization in patients with stable coronary disease have routinely excluded those with advanced chronic kidney disease. METHODS We randomly assigned 777 patients with advanced kidney disease and moderate or severe ischemia on stress testing to be treated with an initial invasive strategy consisting of coronary angiography and revascularization (if appropriate) added to medical therapy or an initial conservative strategy consisting of medical therapy alone and angiography reserved for those in whom medical therapy had failed. The primary outcome was a composite of death or nonfatal myocardial infarction. A key secondary outcome was a composite of death, nonfatal myocardial infarction, or hospitalization for unstable angina, heart failure, or resuscitated cardiac arrest. RESULTS At a median follow-up of 2.2 years, a primary outcome event had occurred in 123 patients in the invasive-strategy group and in 129 patients in the conservative-strategy group (estimated 3-year event rate, 36.4% vs. 36.7%; adjusted hazard ratio, 1.01; 95% confidence interval [CI], 0.79 to 1.29; P=0.95). Results for the key secondary outcome were similar (38.5% vs. 39.7%; hazard ratio, 1.01; 95% CI, 0.79 to 1.29). The invasive strategy was associated with a higher incidence of stroke than the conservative strategy (hazard ratio, 3.76; 95% CI, 1.52 to 9.32; P=0.004) and with a higher incidence of death or initiation of dialysis (hazard ratio, 1.48; 95% CI, 1.04 to 2.11; P=0.03). CONCLUSIONS Among patients with stable coronary disease, advanced chronic kidney disease, and moderate or severe ischemia, we did not find evidence that an initial invasive strategy, as compared with an initial conservative strategy, reduced the risk of death or nonfatal myocardial infarction

Health status after invasive or conservative care in coronary and advanced kidney disease

BACKGROUND In the ISCHEMIA-CKD trial, the primary analysis showed no significant difference in the risk of death or myocardial infarction with initial angiography and revascularization plus guideline-based medical therapy (invasive strategy) as compared with guideline-based medical therapy alone (conservative strategy) in participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease (an estimated glomerular filtration rate of &lt;30 ml per minute per 1.73 m2 or receipt of dialysis). A secondary objective of the trial was to assess angina-related health status. METHODS We assessed health status with the Seattle Angina Questionnaire (SAQ) before randomization and at 1.5, 3, and 6 months and every 6 months thereafter. The primary outcome of this analysis was the SAQ Summary score (ranging from 0 to 100, with higher scores indicating less frequent angina and better function and quality of life). Mixed-effects cumulative probability models within a Bayesian framework were used to estimate the treatment effect with the invasive strategy. RESULTS Health status was assessed in 705 of 777 participants. Nearly half the participants (49%) had had no angina during the month before randomization. At 3 months, the estimated mean difference between the invasive-strategy group and the conservative-strategy group in the SAQ Summary score was 2.1 points (95% credible interval, 120.4 to 4.6), a result that favored the invasive strategy. The mean difference in score at 3 months was largest among participants with daily or weekly angina at baseline (10.1 points; 95% credible interval, 0.0 to 19.9), smaller among those with monthly angina at baseline (2.2 points; 95% credible interval, 122.0 to 6.2), and nearly absent among those without angina at baseline (0.6 points; 95% credible interval, 121.9 to 3.3). By 6 months, the between-group difference in the overall trial population was attenuated (0.5 points; 95% credible interval, 122.2 to 3.4). CONCLUSIONS Participants with stable ischemic heart disease, moderate or severe ischemia, and advanced chronic kidney disease did not have substantial or sustained benefits with regard to angina-related health status with an initially invasive strategy as compared with a conservative strategy