DNA Sequence Profiles of the Colorectal Cancer Critical Gene Set KRAS-BRAF-PIK3CA-PTEN-TP53 Related to Age at Disease Onset

The incidence of colorectal cancer (CRC) increases with age and early onset indicates an increased likelihood for genetic predisposition for this disease. The somatic genetics of tumor development in relation to patient age remains mostly unknown. We have examined the mutation status of five known cancer critical genes in relation to age at diagnosis, and compared the genomic complexity of tumors from young patients without known CRC syndromes with those from elderly patients. Among 181 CRC patients, stratified by microsatellite instability status, DNA sequence changes were identified in KRAS (32%), BRAF (16%), PIK3CA (4%), PTEN (14%) and TP53 (51%). In patients younger than 50 years (n = 45), PIK3CA mutations were not observed and TP53 mutations were more frequent than in the older age groups. The total gene mutation index was lowest in tumors from the youngest patients. In contrast, the genome complexity, assessed as copy number aberrations, was highest in tumors from the youngest patients. A comparable number of tumors from young (<50 years) and old patients (>70 years) was quadruple negative for the four predictive gene markers (KRAS-BRAF-PIK3CA-PTEN); however, 16% of young versus only 1% of the old patients had tumor mutations in PTEN/PIK3CA exclusively. This implies that mutation testing for prediction of EGFR treatment response may be restricted to KRAS and BRAF in elderly (>70 years) patients. Distinct genetic differences found in tumors from young and elderly patients, whom are comparable for known clinical and pathological variables, indicate that young patients have a different genetic risk profile for CRC development than older patients

Possibilities of cardio- and nephroprotective eff ects of drugs of the SGLT2 inhibitor group

This work is an attempt to analyze the data on the mechanisms of cardio- and nephroprotection of drugs of the SGLT2 inhibitor group (Sodium / glucose cotransporter 2). The data of recent studies are shown to indicate the eff ect of drugs of this group on the indices of central hemodynamics, on the volume of circulating plasma in particular, which can reduce the risk of progression and decompensation of chronic heart failure (CHF). The ability of empaglifl ozin to reduce pulsatility, a marker of increased vascular wall stiff ness, has been demonstrated. Also, SGLT2 inhibitors improve the energy supply of the myocardium and kidney tissue by increasing the concentration of ketone bodies in the blood, which are a more effi cient energy substrate than glucose and fatty acids. A direct pleiotropic eff ect on the myocardium, improvement of diastolic myocardial dysfunction is also not excluded. It is known that SGLT2 inhibitors also reduce cortical hypoxia, decrease intraglomerular hypertension and increase glomerular fi ltration rate, lessen incidence of nephropathy, its severity and rate of progression. Some studies have revealed antioxidant, anti-infl ammatory, antifi brotic eff ect of type 2 sodium glucose cotransporter inhibitors. The use of this group of drugs also leads to a decrease in body weight. This eff ect is more pronounced in combination with other drugs intended for the treatment of obesity. All this makes SGLT2 inhibitors a promising group of drugs that have a large number of pathogenetic points of application in relation to cardiorenal syndrome.</jats:p

Clinical and pathogenetic characteristics and management of patients with atrial fibrillation in a cardiology department at the present time

Aim. To assess clinical and pathogenetic characteristics of patients with atrial fibrillation (AF) hospitalized in cardiology department of the regional clinical hospital, and to clarify the related management strategy.Material and methods. A total of 1164 patients were hospitalized in cardiology department of N.A. Semashko Nizhny Novgorod Regional Clinical Hospital in 2017, of which 331 (28,4%) had AF. These patients were included in the study. We analyzed history data of all patients, standard diagnostic tests were carried out. The CHA2DS2-VASc score was used to determine the risk of thromboembolic events, and the HASBLED score — to determine the bleeding risk.Results. The average age of patients was 63,2±10,0 years. In all patients, AF was diagnosed before admission to the hospital. All patients were hospitalized according to hospital waiting lists due to underlying diseases. The most common diseases were coronary artery disease, mainly in combination with hypertension, inflammatory and dystrophic myocardial disorders. Twenty-four patients were hospitalized due to heart failure progression. Nonvalvular AF prevailed among patients. Most patients had a permanent AF (58,3%), the second place took pa - roxysmal AF (36,8%). Much less frequently (4,9%), a persistent AF was observed. Stratification of risk factors for stroke, systemic thromboembolism, as well as for bleeding when indicated for anticoagulant therapy was carried out. Based on the results, oral anticoagulants were indicated for 260 (78,8%) of participants, while only 38,8% received them before hospitalization.Conclusion. Among patients hospitalized in the cardiology department, 28,4% had AF. The most common was nonvalvular AF, associated mainly with coronary artery disease, essential hypertension and their combination. Anticoagulant therapy was indicated for 78,8% of patients, while only 38,8% received it before. This requires further optimization of management of AF patients

Possibilities for treating aspirin-i lesions of the stomach and duodenum in patients with chronic coronary heart disease

To evaluate possibilities of aspirin-induced gastroduodenopathy treatment in the patients with chronic ischemic heart disease by means of applying the internal endogenous prostaglandins stimulant.  Material and methods. 340 patients suffering from chronic coronary heart disease and receiving a long-term acetylsalicylic acid (ASA) therapy were examined on the base of the cardiovascular care unit of The Nizhny Novgorod Regional Clinical Hospital named after N.A. Semaschko. There were evaluated frequency, nature and severity of the aspirin-induced gastroduodenopathy. The patients with coronary heart disease and aspirin-induced gastroduodenopathy were divided in two groups. In the first group of patients there was applied rebamipide therapy (in a single daily dose 300 mg) in combination with the proton pump inhibitor (PPI) — pantoprazole. In the second group there was applied only pantoprazole therapy. For the purpose of specification of AIG pathogenetic mechanisms development, all the examined chronic coronary heart disease cases were tested on the prostaglandin E2 (PGE2) level in blood serum before the therapy beginning and after the treatment. The control group was formed of chronic coronary heart disease patients showing no AIG evidence. Statistical processing of the received data was fulfilled with the program «Statistika 10.0». Results. AIG was registered in 15% out of 340 chronic coronary heart disease patients. According to the endoscopic examination erosive disease of the body and antrum prevailed among the patients. The PGE2 level in the blood serum was significantly lower (р = 0,00087) in these patients in comparison with the control group. In association with PPI and rebamipide mixed therapy, esophagogastroduodenoscopy results showed no pathological findings in gastrointestinal mucosa and statistically significant (р = 0,00067) blood serum PGE2 level growing in all the treated patients. As a result of exclusive PPI therapy there was marked positive dynamics in endoscopic view in 19 out of 25 patients and a tendency to normalization of PGE2 level in the blood serum. However, PGE2 level growing was insignificant. Conclusion. The presented research demonstrates the possibility of AIG treatment with the use of internal endogenous prostaglandins stimulant — rebamipide in complex with proton pump inhibitor PPI therapy.</jats:p

Clinical and pathogenetic characteristics and management of patients with atrial fibrillation in a cardiology department at the present time

Aim. To assess clinical and pathogenetic characteristics of patients with atrial fibrillation (AF) hospitalized in cardiology department of the regional clinical hospital, and to clarify the related management strategy.Material and methods. A total of 1164 patients were hospitalized in cardiology department of N.A. Semashko Nizhny Novgorod Regional Clinical Hospital in 2017, of which 331 (28,4%) had AF. These patients were included in the study. We analyzed history data of all patients, standard diagnostic tests were carried out. The CHA2DS2-VASc score was used to determine the risk of thromboembolic events, and the HASBLED score — to determine the bleeding risk.Results. The average age of patients was 63,2±10,0 years. In all patients, AF was diagnosed before admission to the hospital. All patients were hospitalized according to hospital waiting lists due to underlying diseases. The most common diseases were coronary artery disease, mainly in combination with hypertension, inflammatory and dystrophic myocardial disorders. Twenty-four patients were hospitalized due to heart failure progression. Nonvalvular AF prevailed among patients. Most patients had a permanent AF (58,3%), the second place took pa - roxysmal AF (36,8%). Much less frequently (4,9%), a persistent AF was observed. Stratification of risk factors for stroke, systemic thromboembolism, as well as for bleeding when indicated for anticoagulant therapy was carried out. Based on the results, oral anticoagulants were indicated for 260 (78,8%) of participants, while only 38,8% received them before hospitalization.Conclusion. Among patients hospitalized in the cardiology department, 28,4% had AF. The most common was nonvalvular AF, associated mainly with coronary artery disease, essential hypertension and their combination. Anticoagulant therapy was indicated for 78,8% of patients, while only 38,8% received it before. This requires further optimization of management of AF patients.</jats:p