[Development and validation of Russian olfactory test]. / Otechestvennyi obonyatel'nyi test: razrabotka i validizatsiya.

Olfactory disorders is one of the first symptoms of diseases from various departments of medicine (otorhinolaryngology, psychology, neurology, etc.). Based on international clinical recommendations, olfactory tests are the gold standard for the diagnosis of olfactory disorders. There are many different psychophysical tests: UPSIT (USA, Pennsylvania), Sniffin' Sticks test (Germany), BAST-24 (Spain), etc. Currently, there is an acute shortage of olfactory tests available for clinical practice In Russia. This problem is related to the fact that there are no olfactory tests registered as medical devices on the territory of the Russian Federation. Also, a significant limitation is the unrecognizability of odors by the population of our country, which include foreign analogues (licorice, anise, turpentine, etc.). OBJECTIVE: To develop and validate the national olfactory test on healthy volunteers. MATERIAL AND METHODS: The development and validation of the olfactory test included several stages. First, the development of an olfactory test was carried out, the selection of aromas to assess the threshold and identification ability of olfaction. 25 dilutions of n-butanol were used for the assessment of the threshold olfactory ability. For the stage of assessing the identification ability of the sense of smell, in our previous study, an assessment of the recognition of odor names in the territory of the Russian Federation was carried out. A total of 3.000 people from 8 federal districts of the Russian Federation were interviewed. During the development of the test, 20 names of flavors with the highest rating were used. By the 8th, the selection of monocomponent substances was carried out. Commercially available certified food and perfume flavorings have been used for fragrances whose equivalent in the test cannot be a monocomponent substance. A group of 25 healthy volunteers selected a flavor or a monocomponent for each of the 20 positions. To carry out the identification stage of testing, a booklet was developed with answer options for each fragrance, including 80 images associated with the smell. A methodology for conducting diagnostics has been created. Next, the validation of the developed olfactory test was carried out on 150 healthy volunteers. The study included an assessment of the threshold and identification ability of the sense of smell using the developed test and conducting a comparative analysis with a set of flavors and descriptors corresponding to the Sniffin' Sticks test. RESULTS: The developed test includes: 2 panels - panel 1 to assess the threshold ability of smell, panel 2 to assess the identification ability of smell, a booklet with 80 images and captions to them. The norms of threshold and identification olfactory abilities were also determined in the developed test. The domestic test was validated against the relative foreign Sniffin' Sticks test. Spearman's correlation between the accuracy values of the domestic test (17-20; 85.00-100.00%) and the values of the foreign test (11-16; 68.75-100.00%) did not reveal statistically significant differences (rs=0.065, p=0.432), which confirms the equally effective assessment of olfactory ability by the domestic olfactory test in comparison with its foreign counterpart. CONCLUSION: In this work, a methodology for the use of Russian olfactory test was developed and validated on healthy volunteers. The features of the developed test are an assessment of the threshold and identification ability of smell, an adapted set of odors for the Russian population, the use of paper blotters when applying flavor and visual images of descriptors. Despite the wide variety of psychophysical tests, this problem requires further study and comparative analysis of olfactory tests available In Russia and foreign analogues in order to obtain a universal and effective diagnostic method for the populations of our country.This work was supported by the Russian Foundation for Basic Research (Project No. 24-25-00415).

[Forensic medical diagnostics of age by the Cameriere method]. / Sudebno-meditsinskaya diagnostika vozrasta po metodu Cameriere.

THE AIM OF THE STUDY: Was to conduct the comparative analysis of the age groups' separation accuracy (<18 years old; ≥18 years old) by orthopantomogram depending on the examination's side in Russian population sample. The number of orthopantomograms equal 600 (190 of male and 410 of female) aged from 14 to 23 were investigated. Index value of third molar (Im3) was calculated by the R. Cameriere method, in female and male, on the right and left sides. Index of third molar on the right and left sides shows a high correlation. In the male sample the result specificity was 0.97 on the left and 1.0 on the right, the sensitivity was 0.96 on the left and 0.94 on the right. In the female sample the values were as follows: the specificity was 0.96 on the left and 0.98 on the right, the sensitivity was 0.92 on the left and 0.94 on the right. The results showed the possibility of Im3 (0.08) use to determine the target age group for Russian citizens of both sexes regardless of examination side.

[Remote Monitoring of the QT Interval During Polychemotherapy].

Aim      To evaluate the incidence of prolonged corrected QT interval (QTc) by remote single-channel electrocardiogram (ECG) monitoring in primary oncological patients with elective polychemotherapy (PCT).Material and methods  This study included 49 oncological patients with elective PCT. A single-channel portable CardioQVARK electrocardiograph was used to record single-channel, one-lead ECG between the first and second courses of PCT.Results Analysis of QTc interval detected a prolonged QTc interval >500 msec in 8.2 % of cases, prolonged QTc >480 msec in 18.3 % f cases, and prolonged QTc interval >60 msec compared to baseline in 12.2 % of cases.Conclusion      Remote recording of single-channel ECG using a portable electrocardiograph is an effective method for recording and detecting various forms of heart rhythm disorders.

COVID-19-Associated Stroke.

The COVID-19 pandemic has had significant influences on the incidence of acute cerebrovascular accidents and the structure of mortality. SARS-CoV-2 increases the risks of developing both ischemic and hemorrhagic stroke. The key pathogenetic element underlying the development of cerebral stroke in COVID-19 consists of impairments to the operation of angiotensin 2 receptors, which are accompanied by accumulation of excess quantities of angiotensin 2, endothelial dysfunction, hypercoagulation, overproduction of proinflammatory cytokines, and an oxidative storm. In patients with stroke and COVID-19, lesion severity is associated with dual mechanisms of ischemia - systemic and cerebral. The possibilities of medication-based correction of both systemic impairments associated with coronavirus infection and local impairments due to ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity may potentially be effective in patients with stroke and COVID-19. Data from a number of clinical rials indicate that Mexidol significantly improves functional outcomes in ischemic stroke. Use of Mexidol in patients with stroke and COVID-19 is advised.

Results of Register in Patients with Acute Coronary Syndrome and Atrial Fibrillation Receiving Rivaroxaban.

Aim      To evaluate outcomes in patients with acute coronary syndrome and atrial fibrillation who receive rivaroxaban and the patients' compliance with the antithrombotic therapy.Material and methods  The study was performed from October 2017 through December 2019 and included 129 patients. Events between the discharge from the hospital and 12 months of follow-up were recorded. The primary endpoint was development of major, minor or requiring medical attention bleeding according to the TIMI scale. The secondary endpoint was a combination of recurrent myocardial infarction, nonfatal acute ischemic cerebrovascular disease, nonfatal systemic embolism, stent thrombosis, and cardiovascular mortality.Results 32 (24.8%) patients early terminated the antiplatelet treatment and 22 (17.1%) patients terminated the rivaroxaban treatment. 26 (20.2 %) patients had hemorrhagic complications. The highest incidence of hemorrhage was observed within the first 2 months after the discharge. None of the bleedings was fatal. Composite endpoint events were observed in 24 (18.6 %) patients, including 14 (10.9 %) who died from cardiovascular causes.Conclusion      The compliance with the antiplatelet therapy was insufficient. The incidence of hemorrhagic complications was relatively high; minor and requiring medical attention hemorrhages mostly contributed to the structure of these complications. The observed incidence of recurrent ischemic events associated with a high mortality presents a more serious problem compared to hemorrhagic complications of the combination antiplatelet therapy and warrants a more aggressive tactics of the antiplatelet treatment in high-risk patients.

Clinical Characteristics and Factors Associated with Poor Outcomes in Hospitalized Patients with Novel Coronavirus Infection COVID-19.

Aim      To evaluate the clinical picture and factors associated with unfavorable outcomes in admitted patients with COVID-19.Material and methods This study included all patients admitted to the COVID Center of the National Research Center of Cardiology of the Russian Ministry of Health Care from May 1 through May 31, 2020. Clinical demographic, laboratory, and instrumental indexes and associated factors were studied with one-way and multivariate logistic regression analysis.Results This study included 402 patients aged 18 to 95 years (mean age, 62.9±14.6 years); 43.0 % of them were older than 65 years. COVID-19 was frequently associated with chronic comorbidities, including arterial hypertension (74.4 %), obesity (41.6 %), history of ischemic heart disease (12.9 %), atrial fibrillation (18.9 %), type 2 diabetes mellitus (DM) (13.0 %), and oncological diseases (9.2 %). 13.0 % of patients were smokers; less than 10% had chronic lung diseases. 3.9% of patients had a combination of COVID-19 and acute coronary pathology, including acute myocardial infarction (MI) in 3.2 % (13) and unstable angina in 0.7 % (3). The most frequent clinical manifestation of COVID-19 were four symptoms: cough (81.1 %), weakness (80.3 %), shortness of breath (71.6 %), and fever (62.7 %). 46.5% of patients had shortage of breath and chest pain/compression, 40.3% had headache, 31.1% had myalgia, 28.8% had anosmia, and 25.5% had ageusia. Arterial oxygen saturation was <93.0 % in 55.7 % of cases. According to laboratory blood tests the patients had anemia (58.2 %), lymphopenia (34.8 %), neutropenia (19.2 %), thrombocytopenia (11.9 %), and increased levels of high-sensitivity C-reactive protein (hsCRP, 87.3 %), interleukin-6 (89.3 %), ferritin (62.1 %), and D-dimer (49.2 %). 56.2% of patients required various regimens of oxygen support. 83 (20.6%) patients were admitted to intensive care and resuscitation units; invasive artificial ventilation was performed only for 34 (8.5 %) patients. In-hospital mortality was 7.7 % (31 / 402). One-way regression analysis identified major factors associated with death during the stay in the hospital: age >55 years, NEWS scale score >4.0, oxygen saturation <92.0 %, blood glucose >5.4 mmol/l, hs-CRP >25.7 mg/l, and creatinine clearance <72.0 ml/min. Furthermore, the risk increased with increasing degree of changes in each factor. According to results of the multivariate regression analysis, three most significant predictors of the hard endpoint, all-cause death during the stay in the hospital, were more than 5-fold increases in aspartate aminotransferase and/or alanine aminotransferase compared to normal levels (relative risk (RR) 16.8 at 95 % confidence interval (CI) 5.0-56.3, р<0.001), pronounced changes in the lungs consistent with a CT-4 picture as shown by computed tomography (CT) (RR 13.4; 95 % CI 3.9-45.5, р<0.001), and MI/unstable angina during the stay in the hospital (RR 11.3; 95 % CI 1.4-90.6, р=0.023). The probability of death was also considerably increased by chronic obstructive pulmonary disease, impaired kidney function (creatinine clearance estimated by Cockcroft-Gault <60.0 ml/min), type 2 DM, oncological diseases, and dementia.Conclusion      This study established factors associated with unfavorable outcomes in admitted patients with COVID-19. This will allow identifying in advance patients with a high risk of complications that require increased attention to take more active diagnostic and therapeutic measures at prehospital and hospital stages.

[COVID-19 related stroke]. / Insul't, assotsiirovannyi s COVID-19.

The COVID-19 pandemic had a significant impact on both the incidence of acute cerebral circulatory disorders and the structure of mortality. SARS-CoV-2 increases the risk of both ischemic and hemorrhagic stroke. The key pathogenetic links underlying the development of cerebral stroke in COVID-19 are impaired functioning of angiotensin 2 receptors, accompanied by the accumulation of excess angiotensin 2, endothelial dysfunction, hypercoagulation, hyperproduction of proinflammatory cytokines and oxidative storm. In patients with stroke and COVID-19, the severity of the lesion is associated with a dual mechanism of ischemia - systemic and cerebral. The possibilities of medical correction of systemic disorders associated with coronavirus infection, as well as local ones caused by ischemic or hemorrhagic brain damage, are limited. Substances with antioxidant activity could potentially be effective in patients with stroke and COVID-1.

[Safety performance of rivaroxaban versus warfarin in patients with atrial fibrillation and advanced chro-nic kidney disease].

Aim To evaluate safety of using rivaroxaban in patients with stage 4 chronic kidney disease (CKD) or transient, stable decline of glomerular filtration rate (GFR) to 15-29 ml /min / 1.73 m2 in the presence of atrial fibrillation (AF).Material and methods This multicenter prospective, randomized study included patients admitted to cardiology departments from 2017 through 2019. Of 10 224 admitted patients 109 (3 %) patients with AF and stage 4 CKD or a stable decline of GFR to 15-29 ml /min / 1.73 m2 were randomized at 2:1 ratio to the rivaroxaban 15 mg /day (n=73) treatment group or to the warfarin treatment group (n=36). The primary endpoint was development of BARC and ISTH major, minor, and clinically relevant minor bleeding. Mean follow-up duration was 18 months.Results Patients receiving warfarin had a significantly higher incidence of BARC (n=26 (72.2 %) vs. n=31 (42.4 %), р<0.01) and ISTH (n=22 (61.1 %) vs. n=27 (36.9 %), p<0.01) minor bleeding and all ISTH clinically relevant (minor clinically relevant and major bleedings) n=10 (27.7 %) vs. n=8 (10.9 %), р=0.03]. The number of repeated hospitalizations was 65 (43% of patients) in the rivaroxaban treatment group and 27 (48% of patients) in the warfarin treatment group (р=0.57), including 24 (36.9 %) and 11 (40.7 %) emergency admissions in the rivaroxaban and warfarin treatment groups, respectively (р=0.96). Significant improvement of changes in creatinine clearance and GFR (by CKD-EPI and Cockroft-Gault) was observed in the rivaroxaban treatment group.Conclusion The study provided evidence for a more beneficial safety profile of rivaroxaban compared to warfarin in patients with AF and advanced CKD.

[Circulating Neuregulin-1 and Chronic Heart Failure with Preserved Ejection].

Chronic heart failure (CHF) with preserved ejection fraction (CHFpEF) is an unsolved, socially relevant challenge since it is associated with a high level of morbidity and mortality. Early markers for this pathology are unavailable, and therapeutic approaches are undeveloped. This necessitates extensive studying the mechanisms of CHFpEF to identify therapeutic targets. According to current notions, systemic inflammation and endothelial dysfunction play an important role in the pathogenesis of CHFpEF. These processes induce the development of myocardial fibrosis and impairment of cardiomyocyte relaxation, thereby resulting in diastolic dysfunction and increased left ventricular (LV) filling pressure. Neuregulin-1 (NRG-1) is a paracrine growth factor and a natural agonist of ErbB receptor family synthesized in the endothelium of coronary microvessels. The NRG-1 / ErbB4 system of the heart is activated at early stages of CHFpEF to enhance the cardiomyocyte resistance to oxidative stress. Preclinical and clinical (phases II and III) studies have shown that the recombinant NRG-1 therapy results in improvement of myocardial contractility and in LV reverse remodeling. Results of recent studies suggest possible anti-inflammatory and antifibrotic effects of NRG-1, which warrants studying the activity of this system in patients with CHFpEF.