High frequency of BRCA1, but not CHEK2 or NBS1 (NBN), founder mutations in Russian ovarian cancer patients

<p>Abstract</p> <p>Background</p> <p>A significant portion of ovarian cancer (OC) cases is caused by germ-line mutations in BRCA1 or BRCA2 genes. BRCA testing is cheap in populations with founder effect and therefore recommended for all patients with OC diagnosis. Recurrent mutations constitute the vast majority of BRCA defects in Russia, however their impact in OC morbidity has not been yet systematically studied. Furthermore, Russian population is characterized by a relatively high frequency of CHEK2 and NBS1 (NBN) heterozygotes, but it remains unclear whether these two genes contribute to the OC risk.</p> <p>Methods</p> <p>The study included 354 OC patients from 2 distinct, geographically remote regions (290 from North-Western Russia (St.-Petersburg) and 64 from the south of the country (Krasnodar)). DNA samples were tested by allele-specific PCR for the presence of 8 founder mutations (BRCA1 5382insC, BRCA1 4153delA, BRCA1 185delAG, BRCA1 300T>G, BRCA2 6174delT, CHEK2 1100delC, CHEK2 IVS2+1G>A, NBS1 657del5). In addition, literature data on the occurrence of BRCA1, BRCA2, CHEK2 and NBS1 mutations in non-selected ovarian cancer patients were reviewed.</p> <p>Results</p> <p>BRCA1 5382insC allele was detected in 28/290 (9.7%) OC cases from the North-West and 11/64 (17.2%) OC patients from the South of Russia. In addition, 4 BRCA1 185delAG, 2 BRCA1 4153delA, 1 BRCA2 6174delT, 2 CHEK2 1100delC and 1 NBS1 657del5 mutation were detected. 1 patient from Krasnodar was heterozygous for both BRCA1 5382insC and NBS1 657del5 variants.</p> <p>Conclusion</p> <p>Founder BRCA1 mutations, especially BRCA1 5382insC variant, are responsible for substantial share of OC morbidity in Russia, therefore DNA testing has to be considered for every OC patient of Russian origin. Taken together with literature data, this study does not support the contribution of CHEK2 in OC risk, while the role of NBS1 heterozygosity may require further clarification.</p

Успешное применение комбинированной экстракорпоральной поддержки жизнеобеспечения при лечении новой коронавирусной инфекции, осложненной развитием полиорганной дисфункции у беременной

Pregnant and postpartum women are at a higher risk of infection with SARS-CoV-2 as well as a higher risk of adverse outcomes for the mother and fetus. Standard approaches to the management of COVID-19-associated multiple organ dysfunction may not always be implemented in this category of patients. In the clinical case of a patient, who developed multiple organ dysfunction syndrome (severe ARDS, coagulopathy) associated with COVID-19 in the postpartum period, we demonstrate the successful use of combined extracorporeal life support that included veno-venous extracorporeal membrane oxygenation, therapeutic plasma exchange and renal replacement therapy with the universal oXiris set.Беременные и родильницы подвержены более высокому риску заражения новой коронавирусной инфекцией и неблагоприятным исходам как для матери, так и для плода. Стандартные подходы к ведению полиорганной дисфункции, ассоциированной с COVID-19, не всегда могут быть осуществлены в этой группе больных за счет измененной физиологии дыхательной системы у беременных и неблагоприятного влияния на плод. На примере пациентки, у которой на фоне COVID-19 развился синдром множественной органной дисфункции (острый респираторный дистресс-синдром тяжелой степени (PaO2/FiO 2 96), коагулопатия), продемонстрировано успешное применение в послеродо­вом периоде комбинированной экстракорпоральной поддержки жизнедеятельности, сочетающей в себе вено-венозную экстракорпоральную мембранную оксигенацию, терапевтический плазмообмен и заместительную почечную терапию с использованием универсального сета oXiris

Определение происхождения природного битума в мумифицирующих смолах древнеегипетских мумий из собрания ГМИИ им. А.С. Пушкина

This work presents the results of a study of the resins of seven Ancient Egyptian mummies from the collection of the Pushkin State Museum of Fine Arts using a complex of analytical methods: gas chromatography, atomic emission and mass spectrometry. Natural bitumen and beeswax were identified in the resins using the gas chromatography–mass spectrometry method. Based on the results of hydrocarbon distribution in the profiles of n-alkanes in the resin coatings of the mummies and naturally occurring bitumen, it was assumed that the Dead Sea bitumen was used. The gas chromatography–mass spectrometry studies of mummy resins in the selected ion mode (m/z 217 and 191) provided additional evidence of the bitumen’s geographic origin. Atomic emission spectrometry with inductively coupled plasma was used as a means to determine the content of microelements. Vanadium, nickel and molybdenum were found in the tar of five mummies. The determined relative amounts of vanadium, nickel, and molybdenum in the resins of the studied mummies showed a good correlation with the available data on the content of these elements in the Dead Sea bitumen, as well as the Fayum mummy resin based on this bitumen. The advantages of using the method of identifying bitumen in mummy resins based on relative content of vanadium, nickel, and molybdenum were revealed.В работе представлены результаты исследования составов смол семи древнеегипетских мумий из коллекции Государственного музея изобразительных искусств имени А.С. Пушкина с применением комплекса аналитических методов: газовой хроматографии (ГХ), атомно-эмиссионной и масс-спектрометрии (МС). Методом ГХ–МС в них идентифицированы природный битум и пчелиный воск. По результатам распределений углеводородов в профилях н-алканов в смоляных покрытиях мумий и природных битумов высказано предположение об использовании битума Мертвого моря. Дополнительные доказательства географического происхождения битума получены ГХ–МС-исследованием смол мумий в режиме мониторинга заданных ионов (m/z 217 и 191). Методом атомно-эмиссионной спектрометрии с индуктивно связанной плазмой определено содержание микроэлементов и показано, что в смолах пяти мумий присутствуют ванадий, никель и молибден. Полученные результаты свидетельствуют об удовлетворительной корреляции их с литературными данными по содержанию указанных элементов в битуме Мертвого моря и смоле Фаюмской мумии на основе этого битума. Выявлены преимущества использования метода идентификации битума в смолах мумий по относительному содержанию ванадия, никеля и молибдена

Cause of Death and Predictors of All-Cause Mortality in Anticoagulated Patients With Nonvalvular Atrial Fibrillation : Data From ROCKET AF

M. Kaste on työryhmän ROCKET AF Steering Comm jäsen.Background-Atrial fibrillation is associated with higher mortality. Identification of causes of death and contemporary risk factors for all-cause mortality may guide interventions. Methods and Results-In the Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) study, patients with nonvalvular atrial fibrillation were randomized to rivaroxaban or dose-adjusted warfarin. Cox proportional hazards regression with backward elimination identified factors at randomization that were independently associated with all-cause mortality in the 14 171 participants in the intention-to-treat population. The median age was 73 years, and the mean CHADS(2) score was 3.5. Over 1.9 years of median follow-up, 1214 (8.6%) patients died. Kaplan-Meier mortality rates were 4.2% at 1 year and 8.9% at 2 years. The majority of classified deaths (1081) were cardiovascular (72%), whereas only 6% were nonhemorrhagic stroke or systemic embolism. No significant difference in all-cause mortality was observed between the rivaroxaban and warfarin arms (P=0.15). Heart failure (hazard ratio 1.51, 95% CI 1.33-1.70, P= 75 years (hazard ratio 1.69, 95% CI 1.51-1.90, P Conclusions-In a large population of patients anticoagulated for nonvalvular atrial fibrillation, approximate to 7 in 10 deaths were cardiovascular, whereasPeer reviewe

Effect of aliskiren on post-discharge outcomes among diabetic and non-diabetic patients hospitalized for heart failure: insights from the ASTRONAUT trial

Aims The objective of the Aliskiren Trial on Acute Heart Failure Outcomes (ASTRONAUT) was to determine whether aliskiren, a direct renin inhibitor, would improve post-discharge outcomes in patients with hospitalization for heart failure (HHF) with reduced ejection fraction. Pre-specified subgroup analyses suggested potential heterogeneity in post-discharge outcomes with aliskiren in patients with and without baseline diabetes mellitus (DM). Methods and results ASTRONAUT included 953 patients without DM (aliskiren 489; placebo 464) and 662 patients with DM (aliskiren 319; placebo 343) (as reported by study investigators). Study endpoints included the first occurrence of cardiovascular death or HHF within 6 and 12 months, all-cause death within 6 and 12 months, and change from baseline in N-terminal pro-B-type natriuretic peptide (NT-proBNP) at 1, 6, and 12 months. Data regarding risk of hyperkalaemia, renal impairment, and hypotension, and changes in additional serum biomarkers were collected. The effect of aliskiren on cardiovascular death or HHF within 6 months (primary endpoint) did not significantly differ by baseline DM status (P = 0.08 for interaction), but reached statistical significance at 12 months (non-DM: HR: 0.80, 95% CI: 0.64-0.99; DM: HR: 1.16, 95% CI: 0.91-1.47; P = 0.03 for interaction). Risk of 12-month all-cause death with aliskiren significantly differed by the presence of baseline DM (non-DM: HR: 0.69, 95% CI: 0.50-0.94; DM: HR: 1.64, 95% CI: 1.15-2.33; P < 0.01 for interaction). Among non-diabetics, aliskiren significantly reduced NT-proBNP through 6 months and plasma troponin I and aldosterone through 12 months, as compared to placebo. Among diabetic patients, aliskiren reduced plasma troponin I and aldosterone relative to placebo through 1 month only. There was a trend towards differing risk of post-baseline potassium ≥6 mmol/L with aliskiren by underlying DM status (non-DM: HR: 1.17, 95% CI: 0.71-1.93; DM: HR: 2.39, 95% CI: 1.30-4.42; P = 0.07 for interaction). Conclusion This pre-specified subgroup analysis from the ASTRONAUT trial generates the hypothesis that the addition of aliskiren to standard HHF therapy in non-diabetic patients is generally well-tolerated and improves post-discharge outcomes and biomarker profiles. In contrast, diabetic patients receiving aliskiren appear to have worse post-discharge outcomes. Future prospective investigations are needed to confirm potential benefits of renin inhibition in a large cohort of HHF patients without D

The use of active intraocular drying in macular holes surgery

Purpose: to design a method of active drying ofa fragment of internal limiting membrane (ILM) to achieve its strong adhesion to the retina in the surgical treatment of idiopathic macular hole (MH). Material and methods.The study included 10 patients (10 eyes) with large idiopathic MH. The best corrected visual acuity ranged from 0.03 to 0.1. All patients underwent active drying of inverted ILM fragment during MH surgical treatment by additional air supply through a long blunt cannula. The follow-up was up to 3 months after surgery. Results. The inverted ILM fragment retained a stable position without displacement or deformation, and had dense adhesion to the retina in all cases during the follow-up. According to SOCT, improvement of the anatomical condition of the retina in the foveal area was achieved in all patients; the closure of the MH with the preservation of the defect at the level of the ellipsoid zone of the photoreceptors of the retina was noted. Final visual acuity was from 0.2 to 0.4 (0.26±0.08 in average). Central sensitivity increased to 22.36 ± 2.29 dB, total sensitivity rose to 23.7 ± 1.43 dB. Absolute scotoma was found to disappear in the center of the fovea. Conclusions. Further investigations on larger clinical material are necessary for a reliable assessment of the effectiveness of the method. For citations: Belyy Yu.A., Tereschenko A.V., Trifanenkova I.G., Shkvorchenko D.O., Shilov N.M. The use of active intraocular drying in macular holessurgery. Russian ophthalmological journal. 2017; 10 (3): 6-12. doi: 10.21516/2072-0076-2017-10-3-6-12 (in Russian

COMPLEX ASSESSMENT OF EFFECTIVENESS OF THE DRUG GROUP ANTIHYPOXANTSIN PATIENTS WITH ANGINA AND HIGH LEVEL ANXIETY

It has been studied the efficiency of ethylmethylhydroxypyridine succinate in patients with angina FC II, depending on the level of anxiety. There was high positive correlation between the number of angina attacks and high level of anxiety in patients with angina FC II. Also, there were some special effects of ethylmethylhydroxypyridine succinate as quantity of attacks, blood pressure level, and the frequency and nature of cardiac arrhythmias, heart rate variability, life quality and, as a consequence, frequency of seeking care

Role of IL13 genetic polymorphism in the development of bronchial asthma in children

Bronchial asthma is a multifactorial disease, with both environmental factors and genetic predisposal affecting its development. A number of gene associations have been obtained between polymorphisms of cytokine genes produced by different types of immune cells and asthma development. Interleukin-13 is involved in allergic inflammation, increased bronchial hypersensitivity, regulation of eosinophil levels and IgE production by B cells, thus making it promising for studying IL13 gene polymorphisms in bronchial asthma coupled to development of the disease. The aim of this study was to investigate possible association between asthma and IL13 rs1800925 polymorphism in the children of Caucasian origin in Eastern Siberia. Four groups of patients with asthma were examined (mean age 12.8±1.2 years): with a controlled (n = 95) and uncontrolled course (n = 107), with severe (n = 71) and moderate severity (n = 131) diseases. The control group consisted of healthy individuals: children (n = 33) and adults (n = 102). DNA was isolated with sorbent method; genotyping was carried out using RT-PCR using specific oligonucleotide primers and fluorescent TaqMan probes. The allele and genotype frequencies were compared by the χ-square test using an online calculator. The odds ratio (OR) with a 95% confidence interval (CI) was performed to link genetic markers with pathological phenotypes. The CT IL13 rs1800925 genotype was shown to be associated with moderate asthma and cases of uncontrollable clinical course, whereas the TT genotype was associated with severe asthma. Thus, rs1800925 polymorphism of IL13 gene (the T* variant is known to be associated with increased IL-13 expression) may be associated with bronchial asthma in children. Our data are consistent with results of other authors. E.g., Liu Z. et al. revealed an association between rs1800925 IL13 and the risk of developing asthma in children, with CT and TT genotypes being more common in the patient group. Radhakrishnan A. et al., was studied rs1800925 IL13 in adult population of Malaysia and found that the T* allele frequency in the group of patients significantly exceeds the frequency of this allele in the control group. Thus, the results of our study showed that IL13 rs1800925 polymorphism is associated with bronchial asthma in children, especially, with level of its control and severity of the disease