[Association between cardio-ankle vascular index and markers of thrombosis in hospitalized patients COVID-19].

AIM: To evaluate the relationship between the cardio-ankle vascular index (CAVI) and the marker of procoagulant state - D-dimer in hospitalized patients with coronavirus disease 2019 (COVID-19). MATERIALS AND METHODS: This cross-sectional study involved adult patients admitted to the University hospital with clinically diagnosed or laboratory-confirmed COVID-19. We compared groups of patients with normal and elevated CAVI. Univariate and multivariate logistic regression analyses were performed to assess the association between risk factors and elevated D-dimer levels; odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to determine the strength of association. A p<0.05 was considered statistically significant. RESULTS: The study included 152 patients [64 (42.1%) men and 88 (57.9%) women], mean age 59.10±12.74 years. 45 (29.6%) had elevated CAVI. Patients with elevated CAVI were older, had more comorbid diseases, a higher Charlson comorbidity index and D-dimer levels. Age, the comorbidity index, and CAVI above 9.5 were associated with elevated D-dimer levels in patients with COVID-19. In a multivariate logistic regression, CAVI above 9.5 was an independent predictor of increased D-dimer in patients with COVID-19 (OR 2.513, 95% CI 1.050-6.012; p=0.038). CONCLUSION: In this study, for the first time, the association between a vascular stiffness marker, elevated CAVI, and increased D-dimer levels in COVID-19 patients was shown. This relationship may be a consequence of endothelial dysfunction and can be used as an additional marker of coagulopathy developing as part of COVID-19.

[Predictors of thromboembolic complications in patients with severe SARS-CoV-2 coronavirus infection].

AIM: To identify predictors of the development of thromboembolic complications (TECs) in patients with severe SARS-CoV-2 coronavirus infection. MATERIALS AND METHODS: A single-center observational retrospective study included 1634 patients with a confirmed diagnosis of SARS-CoV-2 coronavirus infection. The patients were divided into 2 groups depending on the availability of the feasibility study. The criterion for inclusion of patients in the main group was the presence of venous feasibility studies in 127 patients (group I), the comparison group consisted of 1507 patients in whom the course of COVID-19 was not complicated by the development of feasibility studies (group II). RESULTS: When performing computed tomography of the chest organs, it was revealed that patients with a feasibility study had a higher percentage of lung tissue damage than patients in the comparison group: 55% [37.5; 67.5] and 37.5% [25.0; 47.5], respectively (p<0.001). The average values of C-reactive protein in I patients group were 129 [60.1; 211] ng/l, which was significantly higher than in II patients group - 41.0 [12.2; 97.6] ng/l (p<0.001), interleukin-6 - 176 [52.9; 471] pg/ml and 39.4 [11.0; 107] pg/ml (p<0.001), respectively. A one-factor regression analysis proved a significant contribution of comorbid pathology to the development of feasibility studies in patients with COVID-19. The presence of three nosologies at the same time: arterial hypertension, coronary heart disease (CHD) and chronic kidney disease increased the probability of a feasibility study by 4.81 times (odds ratio 4.8117, 95% confidence interval 3.2064-7.2207), in patients with arterial hypertension, CHD, chronic kidney disease and type 2 diabetes - by 5.63 times (odds ratio 5.6321, 95% confidence interval 3.1870-9.9531). CONCLUSION: The presence of severe comorbid pathology significantly increased the risk of developing a feasibility study in patients with COVID-19. The most significant predictors of the development of feasibility studies in patients with severe SARS-CoV-2 coronavirus infection. They are: CHD, arterial hypertension and type 2 diabetes.

Clinical Significance of Matrix Metalloproteinases in Blood Plasma of Patients with Gastric Cancer.

Plasma levels of MMP-2, MMP-7, and MMP-9 and their tissue inhibitor TIMP-2 were measured in 89 patients with gastric cancer and the relationship between these parameters and the main clinical morphological characteristics of the disease was analyzed. Plasma levels of the proteins were measured using standard direct ELISA kits. The level of MMP-7 in patients with gastric cancer was significantly higher than in the control group (medians 2.7 and 1.2 ng/ml, respectively; p<0.01), but only in 51% patients this parameter surpassed the upper threshold normal value (2.35 ng/ml; 95% percentile of control). The level of MMP-9 in gastric cancer patients was lower than in control group by 1.6 times (medians 167 and 267 ng/ml, respectively; p<0.01). Plasma levels of MMP-2 and TIMP-2 in patients with gastric cancer and healthy subjects were similar. No appreciable associations of plasma matrixins and TIMP-2 with the main clinical morphological characteristics of the disease were detected. The patients were followed up for 8 to 85 months (median 70.8 months). Low level of MMP-2 and high level of MMP-7 in the plasma proved to be unfavorable prognostic factors for overall survival. At MMP-2<268 ng/ml, the 5-year overall survival was 32% vs. 60% for patients with the marker level higher than this threshold value (p=0.016). The differences in overall survival in relation to their MMP-7 levels for 5-year observation did not surpass 16% (39% at marker level >2.7 ng/ml and 55% at lower level; p=0.048). Plasma levels of MMP-2 and TIMP-2 were not significantly associated with overall survival. Multivariate analysis showed that only T index (p=0.034) and plasma MMP-7 level (p=0.007) were essential for overall survival. The increase in plasma or serum MMP-7 levels is a universal phenomenon in tumors of different histogenesis, which precluded the use of this parameter as a specific diagnostic marker of gastric cancer. At the same time, it could be useful for monitoring the treatment efficiency and detection of relapses. In addition, high plasma level of MMP-7 remained an independent factor of unfavorable prognosis for overall survival of patients with gastric cancer.

Calculation of dose conversion factors for doses in the fingernails to organ doses at external gamma irradiation in air.

Absorbed doses to fingernails and organs were calculated for a set of homogenous external gamma-ray irradiation geometries in air. The doses were obtained by stochastic modeling of the ionizing particle transport (Monte Carlo method) for a mathematical human phantom with arms and hands placed loosely along the sides of the body. The resulting dose conversion factors for absorbed doses in fingernails can be used to assess the dose distribution and magnitude in practical dose reconstruction problems. For purposes of estimating dose in a large population exposed to radiation in order to triage people for treatment of acute radiation syndrome, the calculated data for a range of energies having a width of from 0.05 to 3.5 MeV were used to convert absorbed doses in fingernails to corresponding doses in organs and the whole body as well as the effective dose. Doses were assessed based on assumed rates of radioactive fallout at different time periods following a nuclear explosion.

[Methods of individual retrospective physical dosimetry in the problem of estimation of consequences of accidental irradiation].

The overview of the results of development, verification and application of the methods of individual retrospective physical dosimetry among population of settlements contaminated with radionuclides, which suffered from irradiation as a result of the accident in Chernobyl NPP, and among the population located in the vicinity of the Semipalatinsk nuclear test site is presented in the paper. The estimations of sensitivity of the methods of physical retrospective dosimetry are shown. The data on individual doses among population, which was irradiated as a result of accidental irradiation are presented as well.

[Influence of the environmental hygienic state on the intellectual development of Voronezh schoolchildren].

Voronezh belongs to the areas that have a poor hygienic situation in the environmental pollution with heavy metal compounds. The subject of the studies was pupils from 2 Voronezh schools situated in the areas hygienically contrast in the ambient air and soil pollution with heavy compounds. Their intellectual development was studied. A total of 245 pupils from the 2nd, 7th, and 10th forms were examined. The best intellectual development indices were recorded among all age groups of children living in the hygienically favorable areas. The findings are in agreement with the data published by Russian and foreign investigators.

ESR investigation of joint use of dentin and tooth enamel to estimate photon and neutron dose components of a mixed field.

In the case of mixed photon and neutron field, estimation of photon and neutron dose components from the ESR signal of tooth enamel alone is impossible. To differentiate neutron and photon components using the method described in ICRU 26 for twin chambers, enamel and dentin sensitivities to photon and to neutron were investigated. Enamel and dentin relative sensitivities were, respectively, estimated at 0.03 +/- 0.02 and 0.14 +/- 0.10 for fission neutrons. Basing on this result, calculation of neutron and photon doses was performed in realistic case of criticality accident. Estimation of neutron and photon dose components was found in good agreement with reference dosimetry.

The Third International Intercomparison on EPR Tooth Dosimetry: part 2, final analysis.

The objective of the Third International Intercomparison on EPR Tooth Dosimetry was to evaluate laboratories performing tooth enamel dosimetry <300 mGy. Final analysis of results included a correlation analysis between features of laboratory dose reconstruction protocols and dosimetry performance. Applicability of electron paramagnetic resonance (EPR) tooth dosimetry at low dose was shown at two applied dose levels of 79 and 176 mGy. Most (9 of 12) laboratories reported the dose to be within 50 mGy of the delivered dose of 79 mGy, and 10 of 12 laboratories reported the dose to be within 100 mGy of the delivered dose of 176 mGy. At the high-dose tested (704 mGy) agreement within 25% of the delivered dose was found in 10 laboratories. Features of EPR dose reconstruction protocols that affect dosimetry performance were found to be magnetic field modulation amplitude in EPR spectrum recording, EPR signal model in spectrum deconvolution and duration of latency period for tooth enamel samples after preparation.

Comparison of three methods of numerical procedures for ESR dosimetry of human tooth enamel.

Three numerical methods were employed to examine how gamma ray doses ranging from 100 mGy to 1Gy could be reconstructed using five human molar teeth. For samples above 28 0mGy, the obtained doses are consistent with each other within the errors but slightly larger than actually given doses. Background doses range from 20 to 170 mGy depending on the methods and samples. Further precise studies would be needed to characterize each method, but it would be recommended to apply several methods to check the reliability of the obtained doses.

The 3rd international intercomparison on EPR tooth dosimetry: Part 1, general analysis.

The objective of the 3rd International Intercomparison on Electron Paramagnetic Resonance (EPR) Tooth Dosimetry was the evaluation of laboratories performing tooth enamel dosimetry below 300 mGy. Participants had to reconstruct the absorbed dose in tooth enamel from 11 molars, which were cut into two halves. One half of each tooth was irradiated in a 60Co beam to doses in the ranges of 30-100 mGy (5 samples), 100-300 mGy (5 samples), and 300-900 mGy (1 sample). Fourteen international laboratories participated in this intercomparison programme. A first analysis of the results and an overview of the essential features of methods applied in different laboratories are presented. The relative standard deviation of results of all methods was better than 27% for applied doses in the range of 79-704 mGy. In the analysis of the unirradiated tooth halves 8% of the samples were identified as outliers with additional absorbed dose above background dose.

Review of the correlation between results of cytogenetic dosimetry from blood lymphocytes and EPR dosimetry from tooth enamel for victims of radiation accidents.

The goal of this study was to compare dose estimates from electron paramagnetic resonance (EPR) dosimetry with teeth and cytogenetic dosimetry with blood lymphocytes for 30 victims of radiation accidents. The whole-body exposures estimated by tooth enamel EPR dosimetry were ranging from 0.01 to 9.3 Gy. Study group comprised victims exposed to acute and prolonged irradiation at high and low dose rate in different accidents. Blood samples were taken from each of them for cytogenetic analysis. Aberrations were scored and analysed according to International Atomic Energy Agency (IAEA) guidelines for conventional and FISH analysis. Tooth samples were collected in dental clinics after they had been extracted during ordinary practice. EPR dosimetry was performed according to the IAEA protocol. EPR dosimetry showed good correlation with dosimetry based on chromosomal analysis. All estimations of cytogenetic dose below detection limit coincide with EPR dose estimates within the ranges of uncertainty. The differences between cytogenetic and EPR assays may occur in a case of previous unaccounted exposure, non-homogeneous irradiation and due to contribution to absorbed dose from neutron irradiation.

EPR tooth enamel dosimetry: optimization of the automated spectra deconvolution routine.

A computer routine was developed for automatic deconvolution of electron paramagnetic resonance spectra of tooth enamel samples for individual radiation dose reconstruction in the low dose region. The deconvolution routine uses the non-linear least square fit of a model simulating a tooth enamel spectrum by superposition of derivative Gaussian functions to obtain the amplitude of the dosimetric radiation induced signal. The parameters of the model and of the routine were optimized on a dose response level using a criterion of the least standard deviation of the derived radiation induced signal amplitude from the regression line vs. the nominal doses for the series of spectra of samples irradiated in known doses in the range 0-500 mGy. It was found that for the series of spectra of the heterogeneous samples (every sample is prepared from different teeth of different persons), it is essential to vary in the least square fit the parameters describing the shape of the native background signal in order to obtain the best accuracy. In the case of the series of spectra of the homogeneous (pooled) samples, almost the same accuracy of the results was obtained using the procedures with varied and fixed background signal parameters. The standard error of the dose reconstruction by the optimized deconvolution procedure was estimated as about 30 mGy for heterogeneous samples and 20 mGy for homogeneous samples.

Dose reconstruction by EPR spectroscopy of tooth enamel: application to the population of Zaborie village exposed to high radioactive contamination after the Chernobyl accident.

Individual irradiation doses were determined by electron paramagnetic resonance spectroscopy of the tooth enamel of the inhabitants of Zaborie, the most contaminated inhabited settlement not evacuated after the Chernobyl accident. Dose determination was performed using a specially developed automatic spectrum processing procedure. Spectrum processing was carried out in different operating modes, and average results were taken in order to reduce the contribution of uncertainty in dose determination caused by spectrum processing. The absorbed doses determined in enamel were corrected to take into account the contribution of natural background radiation and to determine the individual excess dose due to radioactive contamination of the territory. Individual excess doses are compared to calculated individualized doses to teeth, estimated using the local radioactive contamination levels, dose rates, and information concerning individual behavior. The individual excess doses measured by electron paramagnetic resonance spectroscopy and the calculated individualized doses are fully independent. Mean square variation between results of two methods was found to be 34 mGy, which is consistent with error estimation for both methods. This result can validate both the methodology of signal processing presented here when using electron paramagnetic resonance dosimetry of tooth enamel for low doses and the methodology of individualized dose calculation.

Individual dose reconstruction among residents living in the vicinity of the Semipalatinsk nuclear test site using EPR spectroscopy of tooth enamel.

Individual accumulated doses were determined by EPR spectroscopy of tooth enamel for 26 adult persons residing in territories adjacent to the Semipalatinsk Nuclear Test Site (SNTS). The absorbed dose values due to radiation from nuclear tests were obtained after subtracting the contribution of natural background radiation from the total accumulated dose. The determined dose values ranged up to 250 mGy, except for one person from Semipalatinsk city with a measured dose of 2.8 +/- 0.4 Gy. Increased dose values were determined for the individuals whose teeth were formed before 1962, the end of the atmospheric nuclear tests. These values were found to be significantly larger than those obtained for a group of younger residents of heavily exposed territories and the residents of territories not exposed to radioactive fallout. These increased dose values are consistent with those based on officially registered data for the Northeastern part of Kazakstan adjacent to SNTS, which was exposed to high levels of radioactive fallout from nuclear tests in period 1949-1962.

Dosimetry studies in Zaborie village.

Dosimetry studies in Zaborie, a territory in Russia highly contaminated by the Chernobyl accident, were carried out in July, 1997. Studies on dosimetry for people are important not only for epidemiology but also for recovery of local social activity. The local contamination of the soil was measured to be 1.5-6.3 MBq/m2 of Cs-137 with 0.7-4 microSv/h of dose rate. A case study for a villager presently 40 years old indicates estimations of 72 and 269 mSv as the expected internal and external doses during 50 years starting in 1997 based on data of a whole-body measurement of Cs-137 and environmental dose rates. Mean values of accumulated external and internal doses for the period from the year 1986 till 1996 are also estimated to be 130 mSv and 16 mSv for Zaborie. The estimation of the 1986-1996 accumulated dose on the basis of large scale ESR teeth enamel dosimetry provides for this village, the value of 180 mSv. For a short term visitor from Japan to this area, external and internal dose are estimated to be 0.13 mSv/9d (during visit in 1997) and 0.024 mSv/50y (during 50 years starting from 1997), respectively.

Application of EPR retrospective dosimetry for large-scale accidental situation.

Above 3000 tooth enamel samples, collected at population of radioactive contaminated territories after Chernobyl accident, the Chernobyl liquidators, the retired military of high radiation risk and the population of control radiation free territories were investigated by EPR spectroscopy method in order to obtain accumulated individual exposure doses. Results of EPR spectra measurements are stored in data bank; enamel samples are also stored in order to provide the possibility to repeat the measurements in future. Statistical analysis of results has allowed to detect the contribution into EPR signal in tooth enamel due to the action of the natural background radiation, and the radioactive contamination of territory. In general, the average doses of external exposure of the population obtained with EPR spectroscopy of teeth enamel are consistent with results based on other methods of direct and retrospective dosimetry. Essential exceeding of the individual doses above the average level within the population groups was observed for some persons. That gave the possibility to detect the individuals with overexposure, which were included into groups for medical monitoring.

Tooth enamel EPR dosimetry: sources of errors and their correction.

Some of the most important sources of systematic errors in dose determination using tooth enamel EPR spectroscopy and ways of reducing those errors are discussed. Enamel from the outside of the front teeth should not be used for dose determination because of induction of paramagnetic centers by solar light. The accuracy of the method in the low dose range is limited by variation in the shape of the EPR signal of unirradiated enamel, which can be described by an initial intrinsic signal and which varies for different samples with standard deviation of 20-30 mGy. The energy dependence of enamel sensitivity should be taken into account in the form of a correction factor. The value of this factor is estimated at 1.1-1.3 for real radiation fields in radiation contaminated territories. Variation in enamel sensitivity for different samples is shown to be within limits of 10-15% of the average value.

Possibility of using porcelain samples of high-voltage line insulators for radiation dose reconstruction by EPR spectroscopy.

In electron paramagnetic resonance spectra of irradiated porcelain samples from high-voltage supply line insulators three overlapping single signals were observed. The dependencies of the amplitude of these signals on the microwave power, irradiation dose and the stability in darkness and in natural light were investigated. It was concluded that for dosimetric purposes it is reasonable to use the radiation-induced signal with g = 2.001, which could be ascribed to the E' centres of quartz. The microwave power dependence of the amplitude of this signal is saturated at 1 mW, the dose dependence is saturated at about 60 mGy. A minimal level of dose determination is about 1 Gy, and it is limited mainly by the accuracy of subtraction of the background signal existing in the unirradiated sample. The radiation-induced signal is stable in the darkness, but rapidly faded in natural light, therefore, for dosimetric purposes it is possible to use only insulators covered with dark glaze or ceramic samples from the very interior of the insulators.

Comparison of sample preparation and signal evaluation methods for EPR analysis of tooth enamel.

In dose reconstruction by EPR dosimetry with teeth various methods are applied to prepare tooth enamel samples and to evaluate the dosimetric signal. A comparison of seven frequently used methods in EPR dosimetry with tooth enamel was performed. The participating Institutes have applied their own procedure to prepare tooth enamel samples and to evaluate the dosimetric signal. The precision of the EPR measurement and the dependence of the estimated dosimetric signal with irradiation up to 1000 mGy were compared. The obtained results are consistent among the different methods. The reproducibility of the dosimetric signal and its estimated relation with the absorbed dose was found to be very close for the applied methods with one possible exception.

Elimination of the background signal in tooth enamel samples for EPR-dosimetry by means of physical-chemical treatment.

A method of elimination of the background EPR signal in tooth enamel is proposed. This method implies treatment of enamel powder by highly active reduction reagent hydrazine with subsequent washing out by ethanol-water solution. Such treatment results in reducing both the native background signal (which is assumed to be originated by the organic component) and the mechanical induced EPR signal in enamel. Testing of the efficiency of hydrazine treatment is made for different sizes of enamel powder. It is shown that the optimal results are obtained for a powder fraction of about 100-200 microm. The radiation-induced EPR signal in enamel is practically not changed after treatment by hydrazine.