A novel preliminary metabolomic panel for IHD diagnostics and pathogenesis.

Cardiovascular disease (CVD) represents one of the main causes of mortality worldwide and nearly a half of it is related to ischemic heart disease (IHD). The article represents a comprehensive study on the diagnostics of IHD through the targeted metabolomic profiling and machine learning techniques. A total of 112 subjects were enrolled in the study, consisting of 76 IHD patients and 36 non-CVD subjects. Metabolomic profiling was conducted, involving the quantitative analysis of 87 endogenous metabolites in plasma. A novel regression method of age-adjustment correction of metabolomics data was developed. We identified 36 significantly changed metabolites which included increased cystathionine and dimethylglycine and the decreased ADMA and arginine. Tryptophan catabolism pathways showed significant alterations with increased levels of serotonin, intermediates of the kynurenine pathway and decreased intermediates of indole pathway. Amino acid profiles indicated elevated branched-chain amino acids and increased amino acid ratios. Short-chain acylcarnitines were reduced, while long-chain acylcarnitines were elevated. Based on these metabolites data, machine learning algorithms: logistic regression, support vector machine, decision trees, random forest, and gradient boosting, were used for IHD diagnostic models. Random forest demonstrated the highest accuracy with an AUC of 0.98. The metabolites Norepinephrine; Xanthurenic acid; Anthranilic acid; Serotonin; C6-DC; C14-OH; C16; C16-OH; GSG; Phenylalanine and Methionine were found to be significant and may serve as a novel preliminary panel for IHD diagnostics. Further studies are needed to confirm these findings.

[Nonimmunogenic staphylokinase in the treatment of acute ischemic stroke (FRIDA trial results)]. / Neimmunogennaya stafilokinaza ­ novyi tromboliticheskii preparat v lechenii ishemicheskogo insul'ta (rezul'taty issledovaniya FRIDA).

AIM OF THE STUDY: To investigate the efficacy and safety of non-immunogenic staphylokinase (NS) compared with alteplase (A) in patients with acute ischemic stroke (AIS) within 4.5 h after symptom onset. MATERIAL AND METHODS: 336 patients with IS within 4.5 h after symptom onset were included in a randomized, open-label, multicenter, parallel-group, non-inferiority comparative trial of NS vs A (168 patients in each group). NS was administered as an intravenous bolus in a dose of 10 mg, regardless of body weight, over 10 s, A was administered as a bolus infusion in a dose of 0.9 mg/kg, maximum 90 mg over 1 hour. The primary efficacy endpoint was a favorable outcome, defined as a modified Rankin scale (mRS) score of 0-1 on day 90. Safety endpoints included all-cause mortality on day 90, symptomatic intracranial haemorrhage, and other serious adverse events (SAEs). RESULTS: At day 90, 84 (50%) patients reached the primary endpoint (mRS 0-1) in the NS group, 68 (41%) patients - in the A group (p=0.10, OR=1.47, 95% CI=0.93-2.32). The difference between groups NS and A was 9.5% (95% CI= -1.7-20.7) and the lower limit of the 95% CI did not cross the margin of non-inferiority (pnon-inferiority<0.0001). There were no significant differences in the frequency of deaths between the groups: on day 90, 17 (10%) patients in the NS group and 24 (14%) in the A group had died (p=0.32). There was a trend towards significant differences in the frequency of symptomatic intracranial haemorrhage: NS group - 5 (3%) patients, A group - 13 (8%) patients (p=0.087, OR=0.37, 95% CI=0.1-1.13). There were significant differences in the number of patients with SAEs: in the NS group - 22 (13%) patients, in the A group - 37 (22%) patients (p=0.044, OR=0.53, 95% CI=0.28-0.98). CONCLUSION: The presented results of the FRIDA trial are the first in the world to use a drug based on NS in patients with IS. It has been shown that a single bolus (within 10 s) administration of NS at a standard dose of 10 mg, regardless of body weight, allows to conduct fast, effective and safe thrombolytic therapy in patients with IS within 4.5 h after symptom onset. In further clinical tials of NS, it is planned to expand the therapeutic window beyond 4.5 h after symptom onset in patients with IS.

On respiratory manifestations of gastroesophageal reflux disease.

One of the manifestations of gastroesophageal reflux disease (GERD) is extraesophageal symptoms, in particular, from the upper and lower respiratory tract. Gastroesophageal reflux is capable of both causing respiratory symptoms independently and aggravating the course of already existing diseases of the respiratory system. The article presents available in the literature current information on the pathogenesis of GERD respiratory symptoms, their clinical course, considerations of diagnosis and treatment.

[The estimation of selen content in blood serum and the diet correction in patients with acute Q-wave myocardial infarction].

The use of selenium-containing specialized food products in prophylactic and therapeutic diets is based on hypothesis that selenium as antioxidant can potentially decrease the risk of oxidative stress induced diseases. There is a hypothesis, which is strongly supported during last 10-15 years that the reactive oxygen species are generated during ischemic myocardium reperfusion and cardiomyocyte damage. In addition selenium as an important component of glutationperoxidaze, it promotes protection against ischemic damage, improvement of functional regeneration and reduction of morphological changes in cardiomyocytes. We established a low serum selenium level in patients with acute and subacute stage of Q-wave myocardial infarction (75.5±1.8 mcg/L). New dietary product - jam made of seaweed with dried apricot enriched with selenium - was included in patient diet. We observed 72 persons (40-75 years old) who were randomized in a control group (30 patients) on standard treatment and a main group (42 patients) that received the dietary product (80 mcg Se) in addition to the standard treatment. Critical serum selenium level was found initially in 16 main group patients (38%), in 2 patients (7%) 2 weeks later and in none of patients in a month of dietary jam treatment. Selen concentration in blood serum increased from basal value 78.3±3.1 mcg/L after 2 weeks of treatment by 16% and after one month of treatment by 20% (p <0.05). In the control group the serum selenium level remained on critical and selenium-deficient levels during a month on standard treatment without dietary compensation. No adverse events were revealed in patients of main group, the investigated product was well tolerated.

[About standardization of specialized medical care].

The article presents materials of studying of such important problem of health care as standardization of specialized medical care provided in conditions of hospital and modernization of regional health care. The issues of standardization of specialized medical care are considered in medical, economic and social aspects. The implementation of medical standards was determined as one of main tasks of the regional program of modernization of health care. The program was developed with direct involvement of the authors of article. The comparative analysis of classes of diseases and nosologic forms on main indices of hospitalized morbidity and lethality was used for substantiation of priority of implementing medical standards in the region. The questionnaire survey was carried out on sampling of 510 patients of hospitals. The sociological questionnaire survey was applied to sampling of 8732 patients comprised by system of mandatory medical insurance. Such an approach determined reliability of derived results. The expertise of medical standards was implemented by 124 experienced and competent physicians participating in implementation of medical standards. The results of expertise confirmed expediency of implementation of medical standards. Kepy following shortcomings were established: inadequate financing; lacking of modern equipment and analysis techniques in hospitals, etc. The article presents evidences of effectiveness of process of standardization of specialized of medical care provided in hospital conditions. The basis of such an assumption was reliable increasing of level of satisfaction of quality of its organization and achievement of planned indices of "road map" in the section of increasing of salary of medical workers and decreasing of mortality of population because of controllable causes.

[The content of selen in blood plasma in patients with acute Q-wave myocardial infarction].

The level of blood plasma selenium was analyzed by microfluorimetric method in in-patients and out-patients with acute coronary syndrome with ST-elevation resulting in acute Q-wave myocardial infarction. 72 patients, 40-75 years old, with acute Q-wave myocardial infarction were followed during a month. The initial decreased concentration of blood plasma selenium was recorded in most patients in the acute period of the myocardial infarction: deficiency of the microelement (< 90 mcg/l) was found in 30 subjects, the critical ranges (< 70 mcg/l) were stated in 33 patients. Just 2 patients had optimal concentration and 7 patients had a suboptimal one (90-114 mcg/l). Blood plasma level of the microelement increased in 2 weeks after myocardial infarction (in subacute stage) but it was still within deficient or critical levels. No difference was detected in selen concentration depending on gender, age, location on myocardial infarction, accompanying diseases, presence of some risk factors (smoking, alcohol abuse, hereditary predisposition to coronary artery disease). At the same time we revealed a significant Spearman rank correlation in patients with Q-wave myocardial infarction between basal level of blood serum selenium on the one hand, and electrocardiography indices (reflecting the rate of myocardial lesion and necrosis), echocardiography. data (which characterize myocardium reparation processes and remodeling), CPK (a prognostic marker of the myocardial necrosis), HDL-cholesterol (lipid profile index), blood potassium level and BMI on the other.

[Clinical assessment of dietary correction of metabolic syndrome by using specialized food product enriched with chrome].

Effectiveness of Laminaria jam enriched with chromium has been investigated in ambulatory patients with metabolic syndrome. 50 patients ranging in age from 30 to 65 years (mean age 53.4 +/- 7.5) were under observation during 6 months. 30 patients from comparison group were given recommendations on modeling of lifestyle (diet, reduced and controlled dosed physical loading) and they received medical treatment. Main group of patients (20 people) in addition received dietary product--Laminaria jam, enriched with chromium, which daily dose (20 g) contain 280 microg of iodine and 66 microg of chromium. In both groups declines of overweight, improving clinical and laboratory parameters, adaptive organism reserves and quality of life has been registered. Patients from the main group referred good organoleptic properties of dietary product, it was well tolerated by patients without causing unwanted side effects. After 6 months of a dietary correction mean relative body mass reduction in the main group amounted to 5.0% while in the comparison group--3.0%. Positive dynamics of the circumference of the waist in patients accounted for 5.9% in main group and 3.1% in comparison group. Systolic and diastolic blood pressure decreased in the main group, an average of 20.5 and 24.2%; in the comparison group--10.5 and 13.3% respectively. The average reduction in LDL-C reached 28.3% in the main group and 18.3% in the comparison group. Triglyceride levels decrease was an average of 18.9% in the studied group, that was significantly higher than in the control group (3.7%). The dynamics of OGTT in main group amounted to 13.1% while in the comparison group--8.6%. Differences between group indices were statistically significant for most of the variables. The inclusion of the dietary product in a range of therapeutic and preventive activities under metabolic syndrome has been shown to improve clinical and metabolic indicators (body mass, arterial pressure, lipid and carbohydrate metabolism parameters) compared with standard therapy.

[Osteoarthrosis in patients with type 2 diabetes mellitus].

AIM: To estimate the frequency of a comorbidity of type 2 diabetes mellitus (DM) and osteoarthrosis (OA) in relation to patient age and to identify risk factors for degenerative and dystrophic changes in the joints. SUBJECTS AND METHODS: 160 patients with type 2 diabetes (23 men and 137 women at the age of 44 to 82 years; body mass index 33 +/- 5 kg/m2 were examined. A control group consisted of 112 age- and gender-matched subjects without type 2 DM. RESULTS: Degenerative and dystrophic changes in the joints were found in 60% of the patients with type 2 DM, which exceeded the similar values in the control subjects (42.9%; p < 0.05). Moreover, OA developed earlier in the patients with DM than in the general population, but the difference became leveled after the age 60 years. The development of OA was found to be associated with lipid metabolic disturbances: the incidence of obesity, hypercholesterolemia, and triglyceridemia was higher in the group of type 2 DM patients with OA (p < 0.05). CONCLUSION: The patients with type 2 DM showed the higher incidence of OA, the age of disease manifestation is less than in the general population. DM and overweight are risk factors for OA.

[Use of the microalgae Spirulina platensis and its selenium-containing form in nutrition of patients with nonspecific ulcerative colitis]. / Ispol'zovanie mikrovodorosli spiruliny platensis i ee selensoderzhashcheé formy v pitanii bol'nykh nespetsificheskim iazvennym kolitom.

The vitamin security and selenium status were measured in the patients with unspecific ulcerative colitis. There were used food microalgae Spirulina platensis and it's preparation enriched with selenium as auxiliary tools of dietetic treatment for these patients. It's shown that there is a combined deficiency of beta-carotene and selenium and occasionally some other micronutrients in a significant part of the patients. The doses used of said food supplements were not enough sufficient for a dietary correction of deficiency of micronutrients with antioxidative properties.