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Background: We conducted a study to determine the relationships between perirenal fat (PRF) thickness and urinary levels of monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) in patients with hypertension (HTN)., Methods: In 338 HTN patients (aged 63.51±12.3 on average), MCP-1 and NGAL levels were studied using enzyme-linked immunosorbent assay (ELISA). To measure PRF thickness, all patients underwent CT scans., Results: We considered PRF thickness ≥1.91 cm as the diagnostic threshold for perirenal obesity. Patients with excessive PRF thickness exhibited significantly lower levels of MCP-1 and NGAL compared with those with PRF thickness ≥1.91 cm: 0.98 pg/mL (interquartile range, 0.21 to 2.05) vs. 2.35 pg/mL (0.37 to 5.22) for MCP-1 and 50.0 pg/mL (48.9 to 67.8) vs. 98.3 pg/mL (68.4 to 187.1) for NGAL. We found a relationship of PRF thickness with both MCP-1 (r=0.46, P <0.05) and NGAL (r=0.53, P <0.05), the levels of which were significantly different in patients with first- and third-stage chronic kidney disease: 0.33 pg/mL (0.21 to 1.35) vs. 4.47 pg/mL (0.23 to 10.81); 50.0 pg/mL (49.4 to 85.5) vs. 126.45 pg/mL (57.5 to 205.15), respectively ( P =0.04). Patients with metabolically healthy obesity (MHO) had significantly lower MCP-1 levels than those with metabolically unhealthy obesity (MUHO): 0.65 pg/mL (0.21 to 2.15) vs. 3.28 pg/mL (2.05 to 5.22) ( P =0.014). MHO patients showed significantly lower NGAL levels than MUHO patients: 50.0 pg/mL (49.4 to 62.2) vs. 98.3 pg/mL (50.0 to 174.8) ( P =0.04). Multiple linear regression analysis revealed significant relationships of MCP-1 with PRF thickness (β±standard error, 0.41±0.15; P <0.001) and smoking (0.26±0.13; P =0.01) and of NGAL with age (0.45±0.16; P <0.01) and PRF thickness (0.49±0.15; P <0.001)., Conclusion: We identified higher concentrations of renal fibrosis markers in patients with perirenal and metabolically unhealthy obesity as well as a link between PRF thickness and MCP-1 and NGAL levels in urine.

Background: The high prevalence of traditional cardiovascular risk factors among the patients without cardiovascular disease (CVD) allows us to predict an increase in cardiovascular morbidity rate in the future. Arterial stiffness is one of the most important predictors and pathogenetic mechanisms of CVD development. The aim of our study was to evaluate the predictive differences of age-related and age-independent (universal) cardio-ankle vascular index (CAVI) reference values for detecting increased arterial stiffness in individuals without CVD., Methods: The study included 600 patients (43% men and 57% women, mean age 36.0 ± 18.3 years). All the patients underwent anthropometric measurements with obesity markers evaluation, assessment of arterial stiffness by sphygmomanometry. To create predictive models, we used universal and age-related CAVI thresholds: ≥ 9.0 (CAVI ≥ 9 ) and CAVI Age according to the "Consensus of Russian experts on the evaluation of arterial stiffness in clinical practice"., Results: In the < 50 years group, both the CAVI Age and CAVI ≥ 9 models were significant (CAVI Age : b = 4.8, standard error b (st.err.b) = 0.27, P < 0.001; CAVI ≥ 9 : b = 3.2, st.err.b = 1.6, P < 0.001). The CAVI Age model demonstrated high sensitivity and specificity (> 70%) compared to the CAVI ≥ 9 model (sensitivity 62%, specificity 58%). In the receiver operating characteristic (ROC) curve analysis, the CAVI Age model had a significantly higher area under the ROC curve (AUC) = 0.802 than the CAVI ≥ 9 model: AUC = 0.674. In the ≥ 50 years group, both models were significant: CAVI Age (b = 2.6, st.err.b = 1.13, P < 0.001) and CAVI ≥ 9 (b = 5.3, st.err.b = 0.94, P < 0.001). Both models demonstrated high sensitivity and specificity (> 70%). When ROC curves were analyzed for the CAVI Age model, the AUC value of 0.675 was significantly lower when compared to the CAVI ≥ 9 model (AUC = 0.787, P = 0.031)., Conclusions: In the < 50 years group, the model based on age-specific CAVI thresholds has the higher predictive value, sensitivity, and specificity for identifying individuals with increased arterial stiffness. In contrast, in the ≥ 50 years group, a predictive model using a universal threshold value of CAVI ≥ 9 has advantages., Competing Interests: The authors declare that they have no conflict of interest., (Copyright 2024, Bragina et al.)

We conducted a systematic review and meta-analysis aimed at estimating the association between perivascular adipose tissue (PVAT) and some of the cardiovascular risk factors. A systematic search was conducted from January 1980 up to and including 2022 to identify studies that examined the relationship between PVAT and cardiovascular risk factors as obesity and its indices, hypertension, lipids, and glucose intolerance/diabetes. The Medline and Embase databases were searched using the PubMed and Scopus. Data were extracted from 23 studies that fit the criteria. To conduct meta-analysis, we used an approximation of equating the method of correlating assessment because different authors used either Pearson or Spearman correlation. Interrelations of PVAT and body mass index were analyzed in eight studies. Most studies revealed reliable direct correlation; the results of the meta-analysis also showed a significant ( P  = 0.37, P  < 0.01, n  = 12,346) correlation. PVAT and waist circumference were analyzed in six studies. Meta-analysis on the selected sample ( n  = 10,947) showed a significant ( r  = 0.45, P  < 0.01) correlation. Relationship between PVAT and hypertension was revealed in three studies. Direct correlations were found in all studies. Meta-analysis showed the reliability of the correlation dependence ( r  = 0.21, P  < 0.01, n  = 3996). PVAT and blood glucose was evaluated in three studies ( n  = 3689). In each study a reliable ( P  < 0.05) direct correlation was obtained. Meta-analysis showed a significant correlation of weak strength ( r  = 0.24, P  < 0.01). We demonstrated significant positive correlations of PVAT with the levels of total cholesterol ( r  = 0.05, P  < 0.01), low-density lipoprotein cholesterol ( r  = 0.13, P  < 0.01), and triglycerides ( r  = 0.29, P  < 0.01), and a negative relationship with high-density lipoprotein cholesterol ( r  = -0.18, P  < 0.01) in this meta-analysis. Despite some limitations, the findings of this systematic review and meta-analysis confirmed that PVAT significantly correlates with studied cardiovascular risk factors. Because PVAT presents a great interest in terms of cardiovascular remodeling and cardiovascular disease, its assessment in patients with and without cardiovascular pathology needs further research.

Background: COVID-19 is characterized by an acute inflammatory response with the formation of endothelial dysfunction and may affect arterial stiffness. Studies of cardio-ankle vascular index in COVID-19 patients with considered cardiovascular risk factors have not been conducted., Objective: The purpose of our study was to assess the association between cardio-ankle vascular index and COVID-19 in hospitalized patients adjusted for known cardiovascular risk factors., Methods: A cross-sectional study included 174 people hospitalized with a diagnosis of moderate COVID-19 and 94 people without COVID-19. Significant differences in the cardio-ankle vascular index values measured by VaSera VS - 1500N between the two groups were analyzed using parametric (Student's t-criterion) and nonparametric (Mann-Whitney) criteria. Independent association between COVID-19 and an increased cardio-ankle vascular index ≥ 9.0 adjusted for known cardiovascular risk factors was assessed by multivariate logistic regression., Results: There were significantly higher values of the right cardio-ankle vascular index 8.10 [7.00;9.40] and the left cardio-ankle vascular index 8.10 [6.95;9.65] in patients undergoing inpatient treatment for COVID-19 than in the control group - 7.55 [6.60;8.60] and 7.60 [6.60;8.70], respectively. A multivariate logistic regression model adjusted for age, hypertension, plasma glucose level, glomerular filtration rate and diabetes mellitus showed a significant association between increased cardio-ankle vascular index and COVID-19 (OR 2.41 [CI 1.09;5.30])., Conclusion: Hospitalized patients with COVID-19 had significantly higher cardio-ankle vascular index values compared to the control group. An association between an increased cardio-ankle vascular index and COVID-19 was revealed, independent of age, hypertension, plasma glucose level, glomerular filtration rate and diabetes mellitus., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Aim: To determine the frequency, distribution and characteristics of ectopic obesity in patients without manifested cardiovascular disease., Materials and Methods: We examined 320 patients without manifested cardiovascular disease (average age 63.813.9 years), 38 of them without cardiovascular risk factors (healthy referent group). Anthropometric indicators were measured, body mass index (BMI) was calculated. Degree, type of obesity, lipid profile were evaluated. All patients underwent multi-detector chest computed tomography in spiral mode on Toshiba Aquilion Prime scanner using standardized protocol. Perivascular adipose tissue (PVAT) and pericardial adipose tissue (PAT) were detected using specialized semi-automatic software Tissue Composition Module QCTPro (Mindways Software, Inc., USA) after scanner calibration with special phantom. PAT and PVAT exceeding the 90th percentile in the healthy referent group were considered as ectopic obesity. Statistical analysis was performed using Statistica 10.0 software (StatSoft Inc., USA)., Results: PAT volume 3.2 cm3 and PVAT volume 0.4 cm3 were criteria for high pericardial and high perivascular fat; 81 (25.2%) patients had ectopic obesity, 85 (26.5%) patients abdominal obesity; 146 (42.9%) people had high pericardial fat, 134 (39.4%) high perivascular fat. The frequency of ectopic obesity in patients with arterial hypertension (AH) was statistically significantly higher compared to persons without AH. Significantly more often ectopic forms of obesity were detected in patients with overweight and obesity. The high pericardial fat and high perivascular fat were found in patients with overweight and normal body weight. When comparing the clinical characteristics of patients with abdominal and ectopic obesity, metabolic parameters, as well as the incidence of hypertension and dyslipidemia, did not differ significantly., Conclusion: Ectopic obesity can develop outside of global obesity. In addition, this type of obesity is accompanied by metabolic disorders and AH, regardless of the abdominal distribution of adipose tissue.

Objective: Study of embryotoxicity, teratogenicity and reproductive toxicity of the new drug Lipophtalocyan in rats., Material and Methods: Studies were conducted on 210 non-inbred female rats and 105 non-inbred male rats. The drug was administered daily via i. v. injection for 48 days (males) and for 15 days (females) in 2 total doses corresponding to the therapeutic dose (TD) for mice when converted to rats and 10 TD., Results and Conclusion: When mating with intact female rats, no changes in sexual behavior were observed, but the index of the ability to fertilize and conceive decreased when compared to the values of the control group by 35-40% (TD index=60%) and by 75-80% (10 TD index=20%). The index of the ability to fertilize and conceive differed from the values of the control group by 90% (TD index=5%) and by 15% (10 TD index=80%). There were no differences in the indicator of embryotoxicity and teratogenicity in intact and drug-treated female rats, compared with the control group. Lipophtalocyan has a negative effect on the male and female reproductive function in rats and has an embryotoxic effect according to the index of the ability to fertilize and conceive, as well as the indices of preimplantation and post-implantation fetal death. The drug does not have a teratogenic effect, neither it affects the physical development of offspring or the rate of maturation of sensory-motor reflexes during feeding., Competing Interests: The authors declare no conflict of interest., (Thieme. All rights reserved.)

Results of foreign and Russian studies indicate a higher mortality rate of patients with concomitant cardiovascular diseases (CVD) due to the new coronavirus infection COVID-19. It has been proven that arterial hypertension, as one of the significant risk factors for the development of concomitant cardiovascular diseases, is associated with a more severe prognosis of COVID-19. This article presents the results of modern studies and large meta-analyzes of necessity and safety of the use of blockers of the renin-angiotensin-aldosterone system in patients with arterial hypertension and COVID-19. The data of studies show that an angiotensin-converting enzyme inhibitor (ACE inhibitor) and a thiazide-like diuretic is a pathogenetically rational combination. It realizes various ways of lowering blood pressure by reducing the activity of the renin-angiotensin-aldosterone system, which is achieved by using an ACE inhibitor, and natriuresis due to diuretics. As an example, a highly effective fixed combination of drugs is considered, characterized by good tolerance, which consists of an ACE inhibitor lisinopril and a thiazide-like diuretic indapamide of prolonged action. The authors expressed the opinion that the appointment of the fixed combination drug Diroton Plus (Gedeon Richter) will contribute to effective control of blood pressure and organoprotection in conditions of increased thrombogenic and prooxidative potential, characteristic of COVID-19 both in the acute stage and within the post-COVID Syndrome.

We conducted a prospective study to establish factors associated with survival in tuberculosis patients in Russia including social, clinical and pathogen-related genetic parameters. Specifically we wished to determine whether different strains/clades of the Beijing lineage exerted a differential effect of survival. HIV-negative culture-confirmed cases were recruited during 2008-2010 across Samara Oblast and censored in December 2011. Molecular characterization was performed by a combination of spoligotyping, multilocus VNTR typing and whole genome sequencing (WGS). We analyzed 2602 strains and detected a high prevalence of Beijing family (n=1933; 74%) represented largely by two highly homogenous dominant clades A (n=794) and B (n=402) and non-A/non-B (n=737). Multivariable analysis of 1366 patients with full clinical and genotyping data showed that multi- and extensive drug resistance (HR=1.86; 95%CI: 1.52, 2.28 and HR=2.19; 95%CI: 1.55, 3.11) had the largest impact on survival. In addition older age, extensive lung damage, shortness of breath, treatment in the past and alcohol abuse reduced survival time. After adjustment for clinical and demographic predictors there was evidence that clades A and B combined were associated with poorer survival than other Beijing strains (HR=0.48; 95%CI 0.34, 0.67). All other pathogen-related factors (polymorphisms in genes plcA, plcB, plcC, lipR, dosT and pks15/1) had no effect on survival. In conclusion, drug resistance exerted the greatest effect on survival of TB patients. Nevertheless we provide evidence for the independent biological effect on survival of different Beijing family strains even within the same defined geographical population. Better understanding of the role of different strain factors in active disease and their influence on outcome is essential., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Reliable laboratory diagnosis of tuberculosis (TB), including laboratory biomarkers of cure, remains a challenge. In our study we evaluated the performance of a Propidium Monoazide (PMA) assay for the detection of viable TB bacilli in sputum specimens during anti-TB chemotherapy and its potential use as a TB biomarker. The study was conducted at three centres on 1937 sputum specimens from 310 adult bacteriologically confirmed pulmonary TB patients obtained before commencing anti-TB treatment and at regular intervals afterwards. Performance of the PMA assay was assessed using various readout assays with bacteriology culture results and time to positivity on liquid media used as reference standards. Treatment of sputum with N-acetyl-cysteine was found to be fully compatible with the PMA assay. Good sensitivity and specificity (97.5% and 70.7-80.0%) for detection of live TB bacilli was achieved using the Xpert(®) MTB/RIF test as a readout assay. Tentative Ct and ΔCt thresholds for the Xpert(®) MTB/RIF system were proposed. Good correlation (r = 0.61) between Ct values and time to positivity of TB cultures on liquid media was demonstrated. The PMA method has potential in monitoring bacterial load in sputum specimens and so may have a role as a biomarker of cure in TB treatment., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Pyrazinamide (PZA) is a prodrug that is converted to pyrazinoic acid by the enzyme pyrazinamidase, encoded by the pncA gene in Mycobacterium tuberculosis. Molecular identification of mutations in pncA offers the potential for rapid detection of pyrazinamide resistance (PZA(r)). However, the genetic variants are highly variable and scattered over the full length of pncA, complicating the development of a molecular test. We performed a large multicenter study assessing pncA sequence variations in 1,950 clinical isolates, including 1,142 multidrug-resistant (MDR) strains and 483 fully susceptible strains. The results of pncA sequencing were correlated with phenotype, enzymatic activity, and structural and phylogenetic data. We identified 280 genetic variants which were divided into four classes: (i) very high confidence resistance mutations that were found only in PZA(r) strains (85%), (ii) high-confidence resistance mutations found in more than 70% of PZA(r) strains, (iii) mutations with an unclear role found in less than 70% of PZA(r) strains, and (iv) mutations not associated with phenotypic resistance (10%). Any future molecular diagnostic assay should be able to target and identify at least the very high and high-confidence genetic variant markers of PZA(r); the diagnostic accuracy of such an assay would be in the range of 89.5 to 98.8%. Importance: Conventional phenotypic testing for pyrazinamide resistance in Mycobacterium tuberculosis is technically challenging and often unreliable. The development of a molecular assay for detecting pyrazinamide resistance would be a breakthrough, directly overcoming both the limitations of conventional testing and its related biosafety issues. Although the main mechanism of pyrazinamide resistance involves mutations inactivating the pncA enzyme, the highly diverse genetic variants scattered over the full length of the pncA gene and the lack of a reliable phenotypic gold standard hamper the development of molecular diagnostic assays. By analyzing a large number of strains collected worldwide, we have classified the different genetic variants based on their predictive value for resistance which should lead to more rapid diagnostic tests. This would assist clinicians in improving treatment regimens for patients., (Copyright © 2014 Miotto et al.)