The state and environmental management: general regulatory issues

The authors set the task based on the importance of the role of the state- to analyze the state policy of Russia and several foreign countries in the direction of environmental management. The research focus concerned the classification of the main policy areas of environmental management regulation and the identification of problems related to special state activities in this are

Аневризма общей печеночной артерии

Common hepatic artery aneurism is a rare pathology. Today there are only isolated instances in the world medical literature. The risk of common hepatic artery and celiac arteries aneurism rupture is very high, and it reaches 50%. Mortality as a result of common hepatic artery aneurism rupture is 75%. Most visceral branches of aorta aneurisms occur asymptomatically unless there is a rupture. Diagnostics of common hepatic artery aneurism includes duplex ultrasound, X-ray computed tomography, magnetic resonance tomography with intravenous contrast and angiography. Differential diagnosis of common hepatic artery aneurism is between pancreas space-occupying lesion (pseudocysts) and paragangliomas. The article describes the clinic-diagnostic case of common hepatic artery aneurism.Целью исследования явилось изучение комплексного лучевого обследования аневризмы ветвей брюшного отдела аорты. Аневризма общей печеночной артерии – редкая патология. В настоящее время в мировой медицинской литературе отмечены лишь единичные наблюдения. Риск разрыва аневризм общей печеночной и чревных артерий весьма высок и достигает 50%. Летальность в результате разрыва аневризмы общей печеночной артерии составляет 75%. Большинство аневризм висцеральных артерий не вызывает начальной симптоматики, пока не происходит их разрыв. Диагностика аневризм висцеральных артерий включает ультразвуковое исследование органов брюшной полости с дуплексным сканированием сосудов, рентгеновскую компьютерную, магнитно-резонансную томографию с внутривенным контрастированием и ангиографию. Дифференциальную диагностику аневризмы общей печеночной артерии проводят с объемными образованиями головки поджелудочной железы (в том числе кистами) и параганглиомами. Описан клинико-диагностический случай аневризмы общей печеночной артерии

ПРЕДИКТИВНЫЕ МАРКЕРЫ ОТВЕТА НА БЛОКАТОРЫ КОНТРОЛЬНЫХ ТОЧЕК ИММУННОГО ОТВЕТА

Despite the unprecedented success in using immune checkpoint inhibitors in the treatment of lung cancer, melanoma, hypermutable tumors of various localization, etc., a significant proportion of patients receiving these drugs do not respond to treatment. Predictive markers routinely used in the selection of patients for immunotherapy, in particular, the level of expression of PD -L1 and the presence of microsatellite instability, have certain limitations. Over the past decade, many other biomarkers designed to predict response to immunotherapy have been proposed, namely: tymor mutation burden, composition of lymphocytic infiltrate; allelic composition of the major histocompatibility complex; relationship between the numbers of different formed elements of blood as well as between its biochemical parameters; microflora of the digestive tract, etc. These markers can directly or indirectly reflect the immunogenicity of the tumor itself, as well as the state of systemic and intratumoral immune response. The predictive power and reliability of these markers are extremely different. When preparing this review, we conducted a literature search for recent studies regarding predictors of efficacy for immune checkpoint inhibitors published in the journals included in the databases, such as Pubmed, Web of Science, and Scopus.Несмотря на беспрецедентный успех применения ингибиторов контрольных точек иммунного ответа в терапии рака легкого, меланомы, гипермутабельных новообразований различной локализации и проч., существенная доля пациентов, получающих препараты этой группы, не демонстрирует ответа на лечение. Предиктивные маркеры, рутинно используемые при отборе больных для прохождения иммунотерапии, в частности уровень экспрессии PD -L1 и наличие микросателлитной нестабильности, имеют определённые ограничения. За последнее десятилетие было предложено множество иных биомаркеров, призванных предсказать эффект на назначение иммунотерапии: внутриопухолевая мутационная нагрузка, состав лимфоцитарного инфильтрата; аллельная композиция главного комплекса гистосовместимости; соотношения между количеством различных форменных элементов крови и ее биохимическими показателями; особенности микрофлоры ЖКТ и т. д. Эти маркеры могут прямо или косвенно отражать иммуногенность самой опухоли, а также состояние системного и внутриопухолевого иммунитета. Предсказательная сила, достоверность и степень их близости к практическому применению чрезвычайно различны. При подготовке данного обзора был проведен поиск литературы последних лет, касающейся изучения предикторов эффективности ингибиторов контрольных точек иммунного ответа, в журналах, входящих в базы данных Pubmed, Web of Science, Scopus

КЛИНИКО-МОРФОЛОГИЧЕСКИЕ ОСОБЕННОСТИ НАСЛЕДСТВЕННОГО РАКА ЯИЧНИКА

Germ-line mutations in BRCA1 and BRCA2 genes are the most established risk factors for hereditary breast and ovarian cancers. The purpose of the study was to analyze BRCA1/2 testing in ovarian cancer patients. Materials and methods. We analyzed 222 patients with ovarian cancer (OC) who underwent genetic testing. Results. Recurrent Slavic mutations in these genes were detected in 60/222 (27%) patients.104 patients lacked any clinical signs of hereditary form of the disease, however BRCA1/2 genetic defects were identified among 11 (11%) of these women. BRCA1/2-associated carcinomas were characterized by more advanced stage at diagnosis and predominance of high-grade serous histological tumor subtype. Conclusion. These results emphasize the need for BRCA1/2 testing for all patients with OC. BRCA1/2-associated carcinomas have clinical and pathological cgaracteristics, which should be considered while planning therapy. Наследственные мутации в генах BRCA1 и BRCA2 являются наиболее известными и изученными факторами риска карцином молочной железы и яичника. Цель исследования – анализ опыта BRCA1/2- тестирования больных раком яичника. Материал и методы. Проанализированы данные 222 больных раком яичника (РЯ), направленных на генетическое тестирование. Результаты. Генетический дефект в генах BRCA1/2 был выявлен у 60 (27 %) из 222 пациенток. В группе женщин без клинических признаков наследственной формы заболевания генетические дефекты BRCA1/2 были обнаружены у 11 (11 %) из 104 пациенток. BRCA1/2-ассоциированные карциномы характеризовались более поздней стадией заболевания и преобладанием низкодифференцированного серозного гистологического типа опухоли. Заключение. BRCA1/2-ассоциированные опухоли составляют значимую часть злокачественных новообразований яичника, что обусловливает целесообразность генетического тестирования для всех пациенток с РЯ. BRCA1/2-ассоциированные карциномы имеют клинические и морфологические особенности, которые необходимо учитывать при планировании терапии.

Endothelial dysfunction and prognosis after coronary interventions in patients with coronary heart disease and arterial hypertension

Aim. To assess the effects of endothelial dysfunction (ED) on the post-coronary intervention (CI) prognosis in patients with acute and chronic coronary heart disease (CHD) and arterial hypertension (AH). Material and methods. In total, the study included 142 CHD patients and 64 blood donors (control group, CG). Group I included patients with chronic CHD, who underwent CI 5-8 years ago (sub-groups A and B included, respectively, patients with good and poor post-CI prognosis). Group II included patients with chronic CHD, treated conservatively. Group III and IV, respectively, included patients with myocardial infarction (MI), treated by CI or conservatively. ED assessment was performed, using the levels of nitrates and nitrites (NOx), nitrates only (NO3-), citrulline (LC), arginine (LА), and desquamated endotheliocytes (DE).Results. Plasma concentrations of NO3-, LА, and DE, or NOx, LC, and DE comprised one integral parameter of endothelial dysfunction (EDIP). In Groups I and II, EDIP levels were similar and close to 0. Compared to Group I, Group IV demonstrated a decrease in NOх and LC, DE increase, and a substantial EDIP reduction. In Group III, NOx and LC levels, as well as EDIP, were increased. At baseline, Group I subgroup A had lower DE levels than subgroup B. Five-eight years after CI, subgroup A demonstrated increased NO production and reduced endothelial desquamation. Based on EDIP values, subgroup B had significantly more pronounced ED, both at baseline and after CI. Conclusion. A complex index EDIP was developed. In patients with chronic CHD, ED was compensated regardless of therapeutic strategy. In MI patients, decompensation of the NO-endothelium system was followed by its relatively fast post-CI recovery. Among individuals with poor post-CI prognosis, ED was manifested to a greater extent than in patients with good prognosis

CLINICAL AND MORPHOLOGICAL FEATURES OF HEREDITARY OVARIAN CANCER

Germ-line mutations in BRCA1 and BRCA2 genes are the most established risk factors for hereditary breast and ovarian cancers. The purpose of the study was to analyze BRCA1/2 testing in ovarian cancer patients. Materials and methods. We analyzed 222 patients with ovarian cancer (OC) who underwent genetic testing. Results. Recurrent Slavic mutations in these genes were detected in 60/222 (27%) patients.104 patients lacked any clinical signs of hereditary form of the disease, however BRCA1/2 genetic defects were identified among 11 (11%) of these women. BRCA1/2-associated carcinomas were characterized by more advanced stage at diagnosis and predominance of high-grade serous histological tumor subtype. Conclusion. These results emphasize the need for BRCA1/2 testing for all patients with OC. BRCA1/2-associated carcinomas have clinical and pathological cgaracteristics, which should be considered while planning therapy

Efficacy of lorlatinib in lung carcinomas carrying distinct ALK translocation variants: The results of a single-center study

Background: Lorlatinib is a novel potent ALK inhibitor, with only a few studies reporting the results of its clinical use. Methods: This study describes the outcomes of lorlatinib treatment for 35 non-small cell lung cancer patients with ALK rearrangements, who had 2 (n = 5), 1 (n = 26) or none (n = 4) prior tyrosine kinase inhibitors and received lorlatinib mainly within the compassionate use program. Results: Objective tumor response (OR) and disease control (DC) were registered in 15/35 (43%) and 33/35 (94%) patients, respectively; brain metastases were particularly responsive to the treatment (OR: 22/27 (81%); DC: 27/27 (100%)). Median progression free survival (PFS) was estimated to be 21.8 months, and median overall survival (OS) approached to 70.1 months. Only 4 out of 35 patients experienced no adverse effects; two of them were the only subjects who had no clinical benefit from lorlatinib. PFS and OS in the no-adverse-events lorlatinib users were strikingly lower as compared to the remaining patients (1.1 months vs. 23.7 months and 10.5 months vs. not reached, respectively; p < 0.0001 for both comparisons). ALK translocation variants were known for 28 patients; there was no statistical difference between patients with V.1 and V.3 rearrangements with regard to the OS or PFS. Conclusion: Use of lorlatinib results in excellent disease outcomes, however caution must be taken for patients experiencing no adverse effects from this drug