Objective. The cytochrome 11B2 aldosterone synthase gene (CYP11B2) that links to aldosterone synthase enzyme synthesis changes and blood pressure regulation is of particular interest among the renin-angiotensin-aldosterone system encoding genes.Methods. One-hundred hypertensive patients with target-organ damaging (2nd stage), moderate, high or very high cardiovascular risk were involved in the case-control study. Mean age was 59.87±8.02 years. Diabetes Mellitus type 2 (DM2) was in 28 persons. Chronic kidney disease (CKD) was diagnosed in 29 persons according to the National Kidney Foundation recommendations (2012) after glomerular filtration rate (GFR) decline <60 ml/min/1.73m2 for ≥3 months (measured by CKD-EPI equations). Aldosterone, cystatin-C, and creatinine levels were measured in serum. Control group included 48 practically healthy persons of relevant age. Gene’s nucleotide polymorphism CYP11B2 (-344C/T) was examined by polymerase chain reaction.Results. CKD evolution in hypertensive patients followed by higher systolic and diastolic blood pressure (SBP, DBP) values increased creatinine, cystatin-C, and aldosterone serum concentrations by 28.76%, 28.41% and 29.43% (р<0.05), respectively. Polymorphic site of CYP11B2 (rs1799998) gene is associated with SBP and DBP increase (p<0.05), reduced GFR preferably calculated by CKDEPI-cystatin C (F=10.79–14.45; p<0.001) and elevated aldosterone content (F=55.84; p<0.001), creatinine and cystatin-С as well (F=4.16–5.08; p<0.05) mainly in the ТТ-genotype female carriers (p<0.001). Hypertensive women with DM2 demonstrated stronger relations of CYP11B2 gene polymorphic site with the increased aldosterone content (F=47.52; p<0.001), than women without DM2 (p<0.001) and male patients (p=0.014).Conclusions. Genetic variations involving CYP11B2 might influence the kidney function, hypertension course, and severity via aldosterone secretion upregulation.

Essential arterial hypertension (EAH) is a polygenic disease due to environmental, genetic, and epigenomic factors. The study aimed to establish the association of single nucleotide polymorphism (SNP) of AGTR1 (rs5186) and VDR (rs2228570) genes with the blood pressure (BP) elevation in EAH patients. 100 EAH subjects with hypertensive-mediated organ damaging (2nd stage), moderate, high, or very high cardiovascular risk were recruited into the case-control study. There were 70.83% females and 29.17% males, mean age 57.86±7.81 y.o. The control group included 60 healthy individuals of relevant age and gender distribution. Estimation of AGTR1 (rs5186) and VDR (rs2228570) gene polymorphism was performed by Real-Time Polymerase Chain Reaction. In EAH patients, the AGTR1 gene (rs5186) mutation occurs with a frequency of 2.78% in the absence of such among healthy individuals. The VDR (rs2228570) gene mutation occurs with a frequency of 23% cases. The C-allele carriers’ (AGTR1 gene) numbers with 2nd and 3rd BP values degree dominate over AA-genotype patients by 25.32% (χ2=4.52; р=0.033). VDR gene (rs2228570) polymorphic variants do not link to BP elevation values. Thus, the C-allele of the AGTR1 gene (rs5186) is associated with BP elevation in hypertensive patients. BP values do not depend on VDR gene (rs2228570) polymorphic variants.

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Objective: to evaluate the association of essential arterial hypertension (EAH) and its severity with genes polymorphism of NOS3 (rs2070744) and GNB3 (rs5443) in West-Ukrainian population. Materials and methods. One-hundred EAH patients (48 – healthy control) participated in the cohort case-control study. Blood pressure (BP), Creatinine, glucose, lipids panel were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFX96™Real-Time PCR). Risk assessed by Relative Risk, Odds Ratio and 95% Confidential intervals. Results. A mutation of the NOS3 gene (786T>C, rs2070744) and the GNB3 gene (825C>T, rs5443) in the homozygous state in the West-Ukrainian population suffers from EAH occurs with a frequency of 16.67% and 8.33%, with no differences with the control subjects (p>0.05). In both groups dominate the T-allele of the NOS3 gene and the C-allele of the GNB3 gene: in patients by 12.5% ​​(c2=4.50; p=0.034) and 41.66% (c2=50.0; p<0.001), in the control – by 25.0% (c2=12.0; p<0.001) and 40.0% (c2=33.33; p<0.001), respectively. The results of the binary logistic regression analysis did not confirm the prediction of the EAH appearance by polymorphic variants of the NOS3 (rs2070744) and GNB3 (rs5443) genes. However, the TT genotype of the GNB3 gene (rs5443) increases unreliably the EAH risk almost twice as likely [OR=2.0; OR 95%CI:0.40-10.82; p>0.05]. Epidemiological analysis did not confirm the association of the NOS3 gene with the EAH severity. But T-allele of the GNB3 gene increases the probability of high normal BP almost 5 times [OR=4.86; OR 95%CI:0.99-24.75; p=0.042]. Conclusions: NOS3 (rs2070744) and GNB3 (rs5443) genes polymorphisms are not associated with blood pressure values and EAH severity as well.

The mechanisms orchestrating the balance between nitric oxide and endothelium-derived contracting factors, and genetic predisposition to endothelial dysfunction in hypertensive patients remain to be determined. One-hundred hypertensive patients participated in the case-control study to clarify the risk of endothelial dysfunction and carotid "intima media" thickness (IMT) changes depending on NOS3 (rs2070744) and GNB3 (rs5443) genes' polymorphisms. It is found that presence of NOS3 gene's С-allele significantly elevates the risk of atherosclerotic plaques on carotid arteries (OR95%CI: 1.24-11.20; р = 0.019) and the probability of low NOS3 gene expression (OR95%CI: 17.72-520.0; р < 0.001). Homozygous carriage of С-allele of GNB3 gene is protective and corresponds to the lowest chances of the carotid IMT increase, atherosclerotic plaques formation and sVCAM-1 elevation (OR = 0.10-0.34; OR95%CI: 0.03-0.95; р ≤ 0.035-0.001). Vice versa, Т-allele of GNB3 gene significantly augments the risk of the carotid IMT increase (OR95%CI: 1.09-7.74; р = 0.027) including development of atherosclerotic plaques, associating GNB3 (rs5443) with cardiovascular pathology.

Objective:The crucial function of endothelium’s regulatory mechanisms is to maintain the balance between Monoxide Nitrogen (NO) release and endothelium-derived contracting factors production. Therefore, it is prognostically important to clarify the endothelial function (EF) deterioration pathway through the early biomarkers of EF and carotid intima media thickness (IMT) changes depending on GNB3 (rs5443) and NOS3 (rs2070744) genes’ polymorphism in essential arterial hypertension (EAH).Design and method:One-hundred EAH patients with hypertensive-mediated organ damage (moderate-very high cardiovascular risks, aged 45–65 years) and 48 practically healthy (control) participated in the cohort case-control study. Soluble Vascular Cell Adhesion Molecule (sVCAM-1), total NO metabolites (NO2-/NO3-), transcriptional activity of NOS3 gene, Endothelium-Dependent Flow-Mediated Dilation of the Brachial Artery (FMD BA) and carotid IMT were studied. GNB3 (rs5443) and NOS3 (rs2070744) genotyping performed by TaqMan probes (CFx96ÔReal-Time PCR).Results:The connections of NOS3 (rs2070744) with decreased total NO metabolites (F = 71.11; p < 0.001), reduced NOS3 gene’s transcription activity (F = 8.71; p < 0.001) and sVCAM-1 increase (F = 6.96; p = 0.002) were found, especially in the C-allele carriers (particularly in CC-genotype patients with lower total NO metabolites value – by 16.46% and 40.88% (p < 0.001), lower transcription activity of NOS3 gene – 46.03% and 7 times (p < 0.001), higher sVCAM-1 – 35.48% and 89.48% (p < 0.001), respectively). ANOVA analysis didn’t confirm association of GNB3 (rs5443) gene with EF and carotid IMT. Severe EAH is associated with increased carotid IMT – 50.0% (p < 0.001) and 57.14% (p < 0.007), dilated carotid arteries – 17.36% (p = 0.012) and 21.79% (p = 0.004), decreased NOS3 gene’s transcription activity – 34.54% (p = 0.003). Severe structural carotid IMT changes in EAH patients (IMT > 0.9 mm) is followed by higher blood pressure values (p < 0.001), deterioration of EF: FMD BA decrease – 11.80% with compensatory increase of carotid arteries diameters – 17.38% and 21.99% (p < 0.001) and serum sVCAM-1 concentration – by 20.49% (p = 0.005).Conclusions:NOS3 (rs2070744), but not GNB3 (rs5443) gene associate with endothelial function impairment and carotid IMT in EAH patients.

Background The incidence of the highly morbid and potentially lethal gangrenous cholecystitis was reportedly increased during the COVID-19 pandemic. The aim of the ChoCO-W study was to compare the clinical findings and outcomes of acute cholecystitis in patients who had COVID-19 disease with those who did not. Methods Data were prospectively collected over 6 months (October 1, 2020, to April 30, 2021) with 1-month follow-up. In October 2020, Delta variant of SARS CoV-2 was isolated for the first time. Demographic and clinical data were analyzed and reported according to the STROBE guidelines. Baseline characteristics and clinical outcomes of patients who had COVID-19 were compared with those who did not. Results A total of 2893 patients, from 42 countries, 218 centers, involved, with a median age of 61.3 (SD: 17.39) years were prospectively enrolled in this study; 1481 (51%) patients were males. One hundred and eighty (6.9%) patients were COVID-19 positive, while 2412 (93.1%) were negative. Concomitant preexisting diseases including cardiovascular diseases (p < 0.0001), diabetes (p < 0.0001), and severe chronic obstructive airway disease (p = 0.005) were significantly more frequent in the COVID-19 group. Markers of sepsis severity including ARDS (p < 0.0001), PIPAS score (p < 0.0001), WSES sepsis score (p < 0.0001), qSOFA (p < 0.0001), and Tokyo classification of severity of acute cholecystitis (p < 0.0001) were significantly higher in the COVID-19 group. The COVID-19 group had significantly higher postoperative complications (32.2% compared with 11.7%, p < 0.0001), longer mean hospital stay (13.21 compared with 6.51 days, p < 0.0001), and mortality rate (13.4% compared with 1.7%, p < 0.0001). The incidence of gangrenous cholecystitis was doubled in the COVID-19 group (40.7% compared with 22.3%). The mean wall thickness of the gallbladder was significantly higher in the COVID-19 group [6.32 (SD: 2.44) mm compared with 5.4 (SD: 3.45) mm; p < 0.0001]. Conclusions The incidence of gangrenous cholecystitis is higher in COVID patients compared with non-COVID patients admitted to the emergency department with acute cholecystitis. Gangrenous cholecystitis in COVID patients is associated with high-grade Clavien-Dindo postoperative complications, longer hospital stay and higher mortality rate. The open cholecystectomy rate is higher in COVID compared with non -COVID patients. It is recommended to delay the surgical treatment in COVID patients, when it is possible, to decrease morbidity and mortality rates. COVID-19 infection and gangrenous cholecystistis are not absolute contraindications to perform laparoscopic cholecystectomy, in a case by case evaluation, in expert hands. Graphical abstract

Objective:Endothelial nitric oxide synthase (eNOS) gene meet the criteria for candidate genes of cardiovascular disease, including essential arterial hypertension (EAH). The aim of the study was to evaluate the association of eNOS gene polymorphism (894G>T, 786T>C) with EAH risk, lipids profile and some concomitant diseases.Design and method:100 EAH patients with target-organ damage, moderate, high/very high cardiovascular risk were involved in the case-control study. 79.0% females and 21.0% males, mean age 59.87 ± 8.02; disease duration 6–25 years. Control included 48 practically healthy persons of relevant age. eNOS gene polymorphisms (894G>T, 786T>C) was examined by Real-Time PCR. Lipids’ profile was studied by total cholesterol (TC), high-, low density cholesterol (HDL-C, LDL-C), triglycerides (TG) and atherogenic index (AI).Results:eNOS gene mutants’ T-allele of 894G>T and C-allele of 786T>C were observed in 34.2% and 32.2% patients, that was almost 2 times less, than G-allele carriers (p = 0.006) and T-allele patients (p = 0.004) respectively. eNOS gene T-allele (894G>T) and C-allele (786T>C) were associated with increased relative risk of EAH 1.8 times [OR = 2.43; 95%CI:1.20–4.95] and 2.15 times [OR = 3.48; 95%CI:1.58–7.68], also with higher risk of concomitant Diabetes Mellitus type 2, cerebrovascular disease and acute myocardial infarction in anamnesis 1.53–1.72 times (p < 0.05). eNOS gene haplotype analysis proved the contribution of -894G/786C and -894T/786C haplotypes to EAH risk increase 2.05 times [OR95%CI:1.18–4.04] and 3.18 times [OR95%CI:1.27–7.29], elevation of TG level and atherogenic index by 10.5–18.7% (p < 0.05) and 12.65–14.19% (p < 0.05) accordingly. The HDL-C level was significantly lower in -894G/786C and -894T/786C carriers by 18.16% (p < 0.01) and 22.07% (p < 0.001). -894G/786T genotypes combination played a protective role against EAH [OR = 0.55; 95%CI:0.39–0.76; P < 0.001].Conclusions:eNOS gene -894G/786C and -894T/786C increased the EAH risk and lipids profile metabolism disorders.