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

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

Aspirin-induced gastrointestinal lesions in patients with chronic coronary artery disease: special aspects and therapeutic options

Aim. To assess the prevalence, structure, and features of aspirin-induced gastroduodenal lesions in patients with chronic coronary artery disease (CAD) and outline therapeutic options.Material and methods. The study included 340 patients with chronic CAD who received long-term low-dose acetylsalicylic acid (ASA) therapy. The diagnosis of chronic CAD was verified using a complex examination with selective coronary angiography (SCA). Further, esophagogastroduodenoscopy was performed in patients with chronic CAD to diagnose aspirin-induced gastroduodenal lesions. We also assessed their prevalence and structure. An endogenous prostaglandin-inducer rebamipide (300 mg daily) in combination with a proton pump inhibitor (PPI) pantoprazole were used to treat aspirin-induced gastroduodenal lesions. The comparison group consisted of patients with chronic CAD who received only pantoprazole. To clarify the pathogenesis of aspirin-induced gastroduodenal lesions before and after treatment, the levels of following serum pro-inflammatory cytokines were determined: interleukin-6 (IL-6), interleukin-1-beta (IL-1β), tumor necrosis factor alpha (TNF-α). The control group consisted ofpatients with chronic CAD and without signs of gastrointestinal lesions. Statistical processing was carried out using Statistica 10.0 software package.Results. Aspirin-induced gastroduodenal lesions were recorded in 15% of patients. Results of esophagogastroduodenoscopy revealed that gastric erosions of body and antrum prevailed among aspirin-induced lesions. The level of pro-inflammatory cytokines in these patients was significantly higher than in patients of control group. Therapy with PPI resulted in a positive endoscopic response in 19 of 25 patients and a slight decrease in cytokines. Combination of PPI with rebamipide led to mucosal reconstruction in all subjects and a statistically significant decrease in levels of serum pro-inflammatory cytokines. Conclusion. The current study showed aspects of development and possible therapeutic options in aspirin-induced gastrointestinal lesions in patients with chronic CAD