Host genetic variants associated with COVID-19 reconsidered in a Slovak cohort.

We present the results of an association study involving hospitalized coronavirus disease 2019 (COVID-19) patients with a clinical background during the 3rd pandemic wave of COVID-19 in Slovakia. Seventeen single nucleotide variants (SNVs) in the eleven most relevant genes, according to the COVID-19 Host Genetics Initiative, were investigated. Our study confirms the validity of the influence of LZTFL1 and 2'-5'-oligoadenylate synthetase (OAS)1/OAS3 genetic variants on the severity of COVID-19. For two LZTFL1 SNVs in complete linkage disequilibrium, rs17713054 and rs73064425, the odds ratios of baseline allelic associations and logistic regressions (LR) adjusted for age and sex ranged in the four tested designs from 2.04 to 2.41 and from 2.05 to 3.98, respectively. The OAS1/OAS3 haplotype 'gttg' carrying a functional allele G of splice-acceptor variant rs10774671 manifested its protective function in the Delta pandemic wave. Significant baseline allelic associations of two DPP9 variants in all tested designs and two IFNAR2 variants in the Omicron pandemic wave were not confirmed by adjusted LR. Nevertheless, adjusted LR showed significant associations of NOTCH4 rs3131294 and TYK2 rs2304256 variants with severity of COVID-19. Hospitalized patients' reported comorbidities were not correlated with genetic variants, except for obesity, smoking (IFNAR2), and hypertension (NOTCH4). The results of our study suggest that host genetic variations have an impact on the severity and duration of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Considering the differences in allelic associations between pandemic waves, they support the hypothesis that every new SARS-CoV-2 variant may modify the host immune response by reconfiguring involved pathways.

Angiotensin II constricts mouse iliac arteries: possible mechanism for aortic aneurysms.

Abdominal aortic aneurysms (AAA) result from maladaptive remodeling of the vascular wall and reduces structural integrity. Angiotensin II (AngII) infusion has become a standard laboratory model for studying AAA initiation and progression. We determined the different vasoactive responses of various mouse arteries to Ang II. Ex vivo isometric tension analysis was conducted on 18-week-old male C57BL/6 mice (n = 4) brachiocephalic arteries (BC), iliac arteries (IL), and abdominal (AA) and thoracic aorta (TA). Arterial rings were mounted between organ hooks, gently stretched and an AngII dose response was performed. Rings were placed in 4% paraformaldehyde for immunohistochemistry analysis to quantify peptide expression of angiotensin type 1 (AT1R) and 2 receptors (AT2R) in the endothelium, media, and adventitia. Results from this study demonstrated vasoconstriction responses in IL were significantly higher at all AngII doses when compared to BC, and TA and AA responses (maximum constriction-IL: 68.64 ± 5.47% vs. BC: 1.96 ± 1.00%; TA: 3.13 ± 0.16% and AA: 2.75 ± 1.77%, p < 0.0001). Expression of AT1R was highest in the endothelium of IL (p < 0.05) and in the media and (p < 0.05) adventitia (p < 0.05) of AA. In contrast, AT2R expression was highest in endothelium (p < 0.05), media (p < 0.01, p < 0.05) and adventitia of TA. These results suggest that mouse arteries display different vasoactive responses to AngII, and the exaggerated response in IL arteries may play a role during AAA development.

Flavonoids attenuate cancer metabolism by modulating Lipid metabolism, amino acids, ketone bodies and redox state mediated by Nrf2.

Metabolic reprogramming of cancer cells is a common hallmark of malignant transformation. The preference for aerobic glycolysis over oxidative phosphorylation in tumors is a well-studied phenomenon known as the Warburg effect. Importantly, metabolic transformation of cancer cells also involves alterations in signaling cascades contributing to lipid metabolism, amino acid flux and synthesis, and utilization of ketone bodies. Also, redox regulation interacts with metabolic reprogramming during malignant transformation. Flavonoids, widely distributed phytochemicals in plants, exert various beneficial effects on human health through modulating molecular cascades altered in the pathological cancer phenotype. Recent evidence has identified numerous flavonoids as modulators of critical components of cancer metabolism and associated pathways interacting with metabolic cascades such as redox balance. Flavonoids affect lipid metabolism by regulating fatty acid synthase, redox balance by modulating nuclear factor-erythroid factor 2-related factor 2 (Nrf2) activity, or amino acid flux and synthesis by phosphoglycerate mutase 1. Here, we discuss recent preclinical evidence evaluating the impact of flavonoids on cancer metabolism, focusing on lipid and amino acid metabolic cascades, redox balance, and ketone bodies.

Procalcitonin kinetics following abdominal aortic surgery and its value for postoperative intestinal ischaemia detection.

OBJECTIVE: The purpose of our study was to describe perioperative kinetics of procalcitonin (PCT) in patients undergoing aortic surgery, to compare the kinetics in the open abdominal aortic aneurysm (AAA) repair and aortobifemoral bypass for aortoiliac occlusive disease (AIOD), and to evaluate the ability of PCT to detect intestinal ischaemia. METHODS: A prospective non-randomized observational cohort study in 80 patients (62 men and 18 women) undergoing elective aortic surgery was performed. Serum PCT was measured at baseline and defined intraoperative and postoperative timepoints up to postoperative day 7. MRI contrast-enhanced imaging was used to detect intestinal ischaemia. RESULTS: The comparison of the AAA and AIOD cohort did not show any significant difference in PCT levels. Patients with intestinal ischaemia had higher serum PCT at multiple timepoints postoperatively. The most accurate timepoints for early diagnosis were postoperative day 3, followed by 24 h after declamping of the vascular reconstruction, and postoperative day 7. The sensitivity and negative predictive values were 100% in all mentioned timepoints. However, event at the best timepoint the specificity was 89% and the positive predictive value 43%. CONCLUSIONS: Procalcitonin levels in the postoperative period at proper timepoints might help to detect postoperative intestinal ischaemia. The limitation of this marker is its low specificity for intestinal ischaemia and low positive predictive value. The highest value of this marker is that it can rule out this complication because normal PCT levels mean that intestinal ischaemia is very unlikely.

Impact of drugs on venous thromboembolism risk in surgical patients.

PURPOSE: This review focuses on the most common drugs administered to surgical patients during the perioperative period that affect the risk of venous thromboembolism (VTE). RESULTS: Among analgesics, the risk of VTE is increased in patients treated with diclofenac, ibuprofen, and rofecoxib, but not naproxen, while metamizole can confer a protective effect. The relationship between sedatives and VTE has not been sufficiently studied. Tricyclic antidepressants, low-potency serotonin reuptake inhibitors, and antipsychotics have been associated with increased risk of VTE. The use of diuretics in the perioperative period is poorly researched; however, hyponatremia is considered a risk factor. Other factors that may influence the risk of VTE include bridging anticoagulation, allogeneic transfusion, and hemostatic management before surgery. Pharmacotherapy for HIV or cancer may also increase VTE risk. CONCLUSION: Increased monitoring for VTE is therefore advisable in surgical patients and those receiving antipsychotics, antidepressants, diuretics, or analgesics.

Polymorphism rs2073618 of the osteoprotegerin gene as a potential marker of subclinical carotid atherosclerosis in Caucasians with type 2 diabetes mellitus.

BACKGROUND: The OPG/RANKL/RANK (osteoprotegerin/receptor-activator of nuclear factor κB ligand/receptor-activator of nuclear factor κB) axis has been recently linked to the development of atherosclerosis and plaque destabilization. We have investigated whether polymorphism rs2073618 of the OPG gene is associated with subclinical markers of carotid atherosclerosis in subjects with type 2 diabetes mellitus (T2DM). PATIENTS AND METHODS: 595 subjects with T2DM were enrolled in the cross-sectional study. Subclinical markers of carotid atherosclerosis (carotid intima media thickness, plaque thickness, and plaques presence) were assessed with ultrasound at the time of recruitment. Genotyping for rs2073618 (a missense variant located in exon I of the OPG gene) was performed, and OPG serum levels were determined by ELISA. RESULTS: Compared to the GG genotype, the CC genotype of the rs2073618 polymorphism had a significantly increased risk for the presence of carotid plaque (OR = 2.54, 95 % CI = 1.22-5.28, p = 0.01). No statistically significant difference could be detected (p = 0.68) upon comparing median values of serum OPG levels among studied genotype groups in subjects with T2DM. Multivariable linear regression analyses in T2DM subjects demonstrated that GC and CC genotypes (p = 0.03 and p = 0.003), together with statin therapy (p = 0.009), were independent predictors of the number of carotid segments with plaques. CONCLUSIONS: Despite the fact that OPG rs2073618 genotypes failed to predict the serum OPG levels as there was no statistical difference among compared genotypes, our results demonstrate that the rs2073618 polymorphism could be a possible genetic marker for the prediction of increased risk for carotid plaque burden as a measure of advanced subclinical atherosclerosis in T2DM subjects.

Influence of Prescribed Blood Products on the Incidence of Deep Vein Thrombosis and Pulmonary Embolism in Surgical Patients.

Deep vein thrombosis (DVT) and pulmonary embolisms (PEs) are common complications after surgical procedures. The influence of prescribed blood products on the occurrence of DVT and PE was evaluated in postsurgical patients in this retrospective case-control study. The records of 286 surgical patients were analyzed: DVT (n = 52), PE (n = 92), and a control group (n = 142). The amounts of prescribed blood, blood products, and vitamin K were reviewed, together with appropriate prescribing of low-molecular-weight heparins. The influence of prescribed blood products on the occurrence of DVT or PE was analyzed using multinomial logistic regression. We demonstrated a significant difference between the test and control groups ( P < .05) in relation to receiving packed red blood cells. Treatment with red blood cells was associated with an increased risk of PE but not DVT. Patients who developed PE after surgery were hospitalized for longer (median 10 days) than patients with DVT (median 6 days). There was no difference between the test and control groups concerning treatment with fresh frozen plasma. Inadequate thromboprophylaxis significantly increased the likelihood of DVT. There is a connection between receiving packed red blood cells and occurrence of postoperative PE in surgical patients. Thus, patients receiving red blood cells should be monitored more closely after surgery, as they are more likely to develop PE postoperatively.

Evidence for CD34/SMA positive cells in the left main coronary artery in atherogenesis.

UNLABELLED: Regression of atherosclerosis is a key aspect of preventing further coronary artery disease and understanding which cell type forms smooth muscle cells in atherosclerotic fibrous caps will aid in reducing CAD. Atherogenesis is a complex interplay of cells migrating and proliferating into the vascular wall. CD34 positive hemapoetic stem cells are believed to not transform into vascular smooth muscle cells (SMC). The current study hypothesised that there would be no evidence for CD34(+)/α SMC actin(+) cells in atherosclerotic coronary arteries. AIMS: To identify CD34+/α actin positive cells in the fibrous cap and wall of atherosclerotic plaques in the coronary artery. METHODS: Male New Zealand White rabbits were fed a diet containing 0.5% cholesterol and 1% methionine for 4 weeks, then 9 weeks of normal diet to induce regression. Immunohistochemistry was used to detect CD34(+) haematopoietic progenitor cells and α SMC actin. RESULTS: In the fibrous cap, the majority of cells were CD34(-)/α SMC actin(+) spindle shaped cells. However very rare populations of CD34(+)/α SMC actin(+) and CD34(+)/α SMC actin(-) cells were also present but these cells were not spindle shaped. CONCLUSION: Our study found that CD34(+)/α SMC actin(-) spindle shaped cells were absent from the fibrous cap. Moreover, the predominant cell population were the vascular smooth muscle cells (CD34(-)/α SMC actin(+)) but (CD34(+)/α SMC actin(+)) cells were also present. This model could be used to understand the role of each SMC population subtype to hasten atherosclerotic regression in the coronary artery.

The monitoring of antiaggregation effect of acetylsalicylic acid therapy by measuring serum thromboxane B2 in patients with coronary artery bypass grafting.

Cardiovascular patients take acetylsalicylic acid (ASA) for preventing myocardial infarction and other thromboembolic complications. It is already known that in some patients this therapy is not effective. The aim of this study was to assess the percentage of ASA resistance on the sample of patients with coronary artery bypass grafting. Our study included 105 patients with coronary artery bypass grafting treated with ASA 150 mg/day or lesser. Platelet aggregation was measured by serum thromboxane B2 level as well as impedance aggregometry from whole blood to determine ASA antiaggregation effect. The percentage of ASA resistance was 41.9% with impedance aggregometry, and after determining the serum thromboxane B2 level this percentage was only 8.6%. The correlation between these two methods was weak (r = 0.443; P < 0.0001). Thromboembolic complications still occur in ASA-treated patients because some patients are resistant to ASA therapy. It would be useful to monitor the effectiveness of ASA therapy and give another antiaggregation drug to these patients to reduce adverse events. The problem is which test is ideal because different tests show different percentages of ASA resistance.

[Present and future in the management of venous vascular diseases]. / Súcasnost a budúcnost v manazmente vénových vaskulárnych chorôb.

The prevalence and the incidence of chronic and acute venous vascular disease has been shown to be globally very high, in both industrialized and developing countries. Chronic venous diseases of lower extremities are being an integral part of the third millennium's deadly angiopandemy, at the present time. The rate of the most severe cases with advanced stage of venous failure is approximately twice as high in the population (2.1 %) as has been assumed so far. Among venoactive drugs (VAD), micronized purified flavonoid fraction (MPFF) of diosmin hesperidin remains the agent with the highest degree of recommendation and it also indicated to pharmacotherapeutical support of leg ulcer healing, along with sulodexide and pentoxifylline. Compressive sclerotherapy, liquid or foam, is a safe and effective invasive method to treat telangiectasias, reticular varicose veins and subcutaneous varicose veins. Direct oral anticoagulants (DOAC) represent one of the therapeutic and preventive options of deep venous thrombosis (DVT) and of venous thromboembolism (VTE) with a limitation in patients with malignant conditions and in pregnancy. The most effective is triple simultaneous pharmaco-kinezio-mechano-phlebothromboemboloprophylaxis. Superficial vein thromboses longer than 5 cm are indicated to anticoagulant therapy too.

Small high-density lipoprotein is associated with monocyte subsets in stable coronary artery disease.

OBJECTIVE: High-density lipoprotein (HDL) particles are heterogeneous in structure and function and the role of HDL subfractions in atherogenesis is not well understood. It has been suggested that small HDL may be dysfunctional in patients with coronary artery disease (CAD). Monocytes are considered to play a key role in atherosclerotic diseases. Circulating monocytes can be divided into three subtypes according to their surface expression of CD14 and CD16. Our aim was to examine whether monocyte subsets are associated with HDL subfractions in patients with atherosclerosis. METHODS: We included 90 patients with angiographically stable CAD. Monocyte subsets were defined as classical monocytes (CD14++CD16-; CM), intermediate monocytes (CD14++CD16+; IM) and non-classical monocytes (CD14+CD16++; NCM). HDL subfractions were measured by electrophoresis on polyacrylamide gel. RESULTS: Serum levels of small HDL correlated with circulating pro-inflammatory NCM and showed an inverse relationship to circulating CM independently from other lipid parameters, risk factors, inflammatory parameters or statin treatment regime, respectively. IM were not associated with small HDL. In particular, patients with small HDL levels in the highest tertile showed dramatically increased levels of NCM (14.7 ± 7% vs. 10.7 ± 5% and 10.8 ± 5%; p = 0.006) and a decreased proportion of CM (79.3 ± 7% vs. 83.7 ± 6% and 83.9 ± 6%; p = 0.004) compared to patients in the two lower tertiles. In contrast, intermediate HDL, large HDL and total HDL were not associated with monocyte subset distribution. CONCLUSION: Small HDL levels are associated with pro-inflammatory NCM and inversely correlated with CM. This may suggest that small HDL could have dysfunctional anti-inflammatory properties in patients with established CAD.

The effects of treatment on lipoprotein subfractions evaluated by polyacrylamide gel electrophoresis in patients with autoimmune hypothyroidism and hyperthyroidism.

BACKGROUND: Atherogenic dyslipoproteinemia is one of the most important risk factor for atherosclerotic changes development. Hypothyroidism is one of the most common causes of secondary dyslipidemias which results from reduced LDL clearance and therefore raised levels of LDL and apoB. Association between small dense LDL (sdLDL) presentation and thyroid status has been examinated using polyacrylamide gel electrophoresis for lipoprotein subfractions evaluation. METHODS: 40 patients with diagnosed autoimmune hypothyroidism and 30 patients with autoimmune hyperthyroidism were treated with thyroxine replacement or thyreo-suppressive treatment. In both groups lipid profiles, LDL subractions, apolipoproteins (apoA1, apoB), apoA1/apoB ratio and atherogenic index of plazma (AIP) were examined before treatment and in state of euthyreosis. RESULTS: Thyroxine replacement therapy significantly reduced levels of total cholesterol (TC), LDL, triglycerides (TG) and also decreased levels of sdLDL (8,55±11,671 vs 0,83±1,693mg/dl; p<0,001), apoB and AIP. For estimation of atherogenic lipoprotein profile existence an AIP evaluation seems to be better than apoB measurement because of the more evident relationship with sdLDL (r=0,538; p<0,01). Thyreo-suppressive therapy significantly increased levels of TC, LDL, TG and apoB. The sdLDL was not found in hyperthyroid patients. CONCLUSIONS: Atherogenic lipoprotein profile was present in 52.5% of hypothyroid subjects, which is higher prevalence than in normal, age-related population. Substitution treatment leads to an improvement of the lipid levels, TG, apoB, AIP and LDL subclasses. It significantly changed the presentation of sdLDL - we noticed shift to large, less atherogenic LDL particles. Significantly positive correlation between sdLDL and TAG; sdLDL and VLDL alerts to hypertriglyceridemia as a major cardiovascular risk factor.

[Mesenterointestinocolonovascular arterial ischemic disease: guidelines of the angiology section of Slovak Medical Chamber (AS SMC, 2013)]. / Mezentériointestinokolonovaskulárna artériová ischemická choroba Odporúcania Sekcie angiológov Slovenskej lekárskej komory (2013).

Organovascular arterial ischemic diseases (cardiovascular, cerebrovascular, extremitovascular, renovascular, genitovascular, pulmovascular, mesenterovascular, dermovascular, oculovascular, otovascular, stomatovascular etc.) are an important manifestations of systemic atherosclerosis and other arterial diseases of vascular system (arteriolosclerosis/arteriolonecrosis; diabetic macroangiopathy; diabetic microangiopathy; Mönckeberg´s mediosclerosis/mediocalcinosis; arteritis - vasculitis; syndromes of arterial compression; fibromuscular dysplasia; cystic adventitial degeneration; arterial thrombosis; arterial embolism/thromboembolism; traumatic and posttraumatic arteriopathies; physical arteriopathies; chemical and toxic arteriopathies; iatrogenic arterial occlusions; dissection of aorta and of arteries; coiling; kinking; complicated arterial aneurysms; arteriovenous fistula, rare vascular diseases). Key clinical-etiology-anatomy-pathophysiology (CEAP) aspects of the mesenteriovascular arterial ischemic diseases are discussed in this article (project Vessels).