Genotypes and Variants of BKPyV in Organ Donors after Brain Death.

Kidney transplantation from a donor with latent BKPyV might be the cause of serious complications, such as BK virus-associated nephropathy. The aim of the study was to determine the prevalence of BKPyV infection in donors after brain death (DBDs), to analyse the molecular variation of BKPyV and to compare clinical and inflammation parameters of DBDs infected with various genotypes of BKPyV. BKPyV was investigated in blood and urine samples of 103 DBDs using PCR followed by sequencing and bioinformatic analysis, and the viral load was assessed by qPCR. Clinical parameters, including cellular markers of inflammation were assessed. The results confirm high prevalence of BKPyV (48%),and genotype IV (49%) over genotype I (43%) and the co-infection with genotypes I and IV in 8.2%. Viral load ranged from 102 to 107 copies/mL, with an average of 1.92 × 106 copies/mL. No specific markers for BKPyV infection were detected among the parameters tested. Infection with genotype I may be associated with the adverse impact on thekidney function, while infection with genotype IV was associated with the anemia Not only the viral load but also the genotype of BKPyV may have an impact on the course of infection.

Molecular Epidemiology and Variation of the BK Polyomavirus in the Population of Central and Eastern Europe Based on the Example of Poland.

The BK polyomavirus (BKPyV) is a widespread pathogen in humans. Polymorphism of the region encoding the VP1 protein of BKPyV provides the basis for classifying the virus into types and subtypes, whose frequency varies depending on geographic location. The aim of our study was to determine the frequency of BKPyV in the Polish population and to assess its variation by analysing polymorphism in the typing region. The study was conducted on 168 healthy, Polish volunteers, whose blood (plasma) and urine were sampled. The virus was detected using PCR, products, sequenced and subjected to bioinformatic analysis. In addition, viral load was assessed by qPCR. The presence of the genetic material of the BK virus was noted in 61/168 urine samples but in none of the plasma sample. Sequencing and phylogenetic analysis confirmed that the BKPyV isolates were of types I and IV, dominant in Europe (63.93% and 36.07%, respectively). All isolates from genotype I belonged to subtype Ib-2, showing polymorphism at position 1809 with a frequency of 61.54% (G1809A) and 38.46% (G1809C). To the best of our knowledge, this is the first study of this magnitude on the genetic variation of BKPyV among healthy volunteers in Poland.

BK Polyomavirus-Biology, Genomic Variation and Diagnosis.

The BK polyomavirus (BKPyV), a representative of the family Polyomaviridae, is widespread in the human population. While the virus does not cause significant clinical symptoms in immunocompetent individuals, it is activated in cases of immune deficiency, both pharmacological and pathological. Infection with the BKPyV is of particular importance in recipients of kidney transplants or HSC transplantation, in which it can lead to the loss of the transplanted kidney or to haemorrhagic cystitis, respectively. Four main genotypes of the virus are distinguished on the basis of molecular differentiation. The most common genotype worldwide is genotype I, with a frequency of about 80%, followed by genotype IV (about 15%), while genotypes II and III are isolated only sporadically. The distribution of the molecular variants of the virus is associated with the region of origin. BKPyV subtype Ia is most common in Africa, Ib-1 in Southeast Asia, and Ib-2 in Europe, while Ic is the most common variant in Northeast Asia. The development of molecular methods has enabled significant improvement not only in BKPyV diagnostics, but in monitoring the effectiveness of treatment as well. Amplification of viral DNA from urine by PCR (Polymerase Chain Reaction) and qPCR Quantitative Polymerase Chain Reaction) is a non-invasive method that can be used to confirm the presence of the genetic material of the virus and to determine the viral load. Sequencing techniques together with bioinformatics tools and databases can be used to determine variants of the virus, analyse their circulation in populations, identify relationships between them, and investigate the directions of evolution of the virus.

Atypical Cardiac Location of Melanoma of Unknown Origin.

The subject was a 66-year-old woman, suffering from the chest pain evoked by physical activity. Transthoracic echocardiography (TTE) revealed an abnormal structure, 41 × 29 mm. In MSCT, a hypodensic mobile tissue lesion that was infiltrating the whole thickness of left ventricle was confirmed. PET excluded the existence of other remote lesions. After surgical tumor removal, histopathological differential diagnosis revealed melanoma, myoepithelial cancer, and MPNST "high-grade" sarcoma. A control TTE detected a tumor that was 14 × 10 mm. After immunohistochemical results, immunotherapy with pembrolizumab was used, which resulted in complete tumor resolution. Presently, surgical resection and neoadjuvant targeted immunochemotherapy remain the treatment of choice for clinical stage III/IV melanoma.

Paraoxonase 1 Activity, Polymorphism and Atherosclerosis Risk Factors in Patients Undergoing Coronary Artery Surgery.

BACKGROUND: Paraoxonase1 (PON1), an enzyme connected to high density lipoproteins (HDL) particles, plays an important role in protecting arteries against atherosclerosis. The serum activity and concentration of PON1 depends on several genetic polymorphisms as well as environmental factors. MATERIALS AND METHODS: Investigated population consisted of 71 patients aged 43⁻76 years with confirmed coronary heart disease (CHD). Established risk factors of CHD such as hypertension, elevated total cholesterol and LDL cholesterol (LDL-C), low HDL cholesterol (HDL-C), diabetes mellitus, obesity, smoking and premature CHD in family history were assessed. PON1 genotype for ⁻108C/T promotor region was determined by polymerase chain reaction-restriction fragments length polymorphism (PCR⁻RFLP) method. Paraoxonase activity towards paraoxon and arylesterase activity towards phenyl acetate were measured spectrophotometrically. RESULTS: Significant correlations between diabetes mellitus and paraoxonase activity (R = ⁻0.264, p = 0.026) and between the premature coronary heart disease in family history and PON1 activity (R = ⁻0.293, p = 0.013) were found. In multivariate analysis, PON1 paraoxonase activity was independently of confounding factors associated with diabetes (OR = 0.985; p = 0.024) and premature CHD in family history (OR = 0.983; p = 0.027). PON1 activity towards aryl acetate positively correlated with HDL-C level (R = 0.255, p = 0.032). In patients treated with statins, PON1 paraoxonase activity was significantly (p = 0.033) higher than in patients without treatment. CONCLUSIONS: In diabetic patients with CHD, paraoxonase activity is lower than in normoglycemic patients despite similar lipid profiles. Diabetes and positive family history in patients with overt CHD are associated with the serum PON1 activity, which might be an additional factor helpful in evaluating cardiovascular risk in this group of patients.

Dynamic changes of paraoxonase 1 activity towards paroxon and phenyl acetate during coronary artery surgery.

BACKGROUND: Serum paraoxonase 1 (PON1), an enzyme associated with high - density lipoproteins (HDL) particles, inhibits the oxidation of serum lipoproteins and cell membranes. PON1 activity is lower in patients with atherosclerosis and in inflammatory diseases. The systemic inflammatory response provoked during cardiopulmonary bypass grafting may contribute to the development of postoperative complications. The aim of the present study was to estimate the dynamic changes in paraoxonase 1 (PON1) activity towards paraoxon and phenyl acetate during and after coronary artery surgery. METHODS: Twenty six patients with coronary heart disease undergoing coronary artery bypass grafting (CABG) were enrolled into the study. Venous blood samples were obtained preoperatively, after aortic clumping, after the end of operation, at 6, 18, 30 and 48 h after operation. Paraoxonase activity was measured spectrophotometrically in 50 mM glycine/NaOH buffer (pH 10.5) containing 1.0 mM paraoxon, and 1.0 mM CaCl2. Arylesterase activity was measured in 20 mM TrisCl buffer (pH 8.0) containing 1 mM phenyl acetate and 1 mM CaCl2. RESULTS: PON1 activity toward paraoxon and phenyl acetate significantly decreased after aorta cross clumping and increased directly after operation. PON1 activity towards paraoxon in preoperative period and PON1 activity towards phenyl acetate in seventh stage of experiment tended to inversely correlate with the occurrence of postoperative complications. CONCLUSION: The paraoxonase 1 plasma activity is markedly reduced during CABG surgery.

[Current views on the interaction between the treatment of osteoporosis and cardiovascular diseases].

The most common medical conditions after menopause are osteoporosis and atherosclerotic disease. Traditionally these two conditions were considered unrelated and their coexistence has been attributed to independent processess exclusively reated to age. The possible link between cardiovascular disease and osteoporosis stimulates today to analyse not only the evidence of a possible association, but also to identify mutual beneficial and adverse effects of drugs used in these two diseases. That's why, the focus on the interference between osteoporosis treatment and drugs used for atherosclerosis is made. Moreover side effects of cardiological drug considering bones are analysed. Additionally possible advantages of selected drugs used for cardiovascular diseases on osteoporosis prevention are evaluated. Drugs used for osteoporosis treatment may heave adverse effects on cardiovascular system. The article has detailed analyses of current drug classes, such as the bisphosphonates, strontium ranelate as well as a review of the controversy surrounding hormone replacement therapy (HRT) and the selective oestrogen receptor modulators (SERMs). Lastly discussion of adverse effects on the heart of calcium and drugs influencing calcium metabolism such as vitamin D, parathormone and calcitonin is performed.

Prognostic value of paraoxonase 1 in patients undergoing coronary artery bypass grafting surgery.

BACKGROUND: The aim of this study was to evaluate whether -108C/T polymorphism of the paraoxonase 1 (PON1) gene and the plasma enzyme activity are risk factors for adverse cardiac events after coronary artery bypass grafting (CABG). MATERIAL AND METHODS: Seventy-one patients with coronary heart disease (CHD) undergoing CABG were enrolled in the study. Genomic DNA was extracted from the venous blood using the Gen Elute™ Blood Genomic DNA kit (Sigma) according to the manufacturer's instructions. PON1 activity was measured in 50 mM glycine/NaOH buffer (pH 10.5) containing 1.0 mM paraoxon, and 1.0mM CaCl2. RESULTS: The mean PON1 activity toward paraoxon and toward phenyl acetate was equal (166.5 ± 86.9 U/ml and 96.0 ± 47.2 U/ml, respectively) in patients with CHD. The -108C/T polymorphism of PON1 gene was tested. In CABG patients, PON1 activities in dependence on genotypes were significantly different and equalled 266.2 ± 117.9 U/ml for CC, 178.8 ± 64.7 U/ml for CT, and 98.9 ± 59.2 U/ml for TT genotype. Patients with PON1 activity lower than 193.5 U/ml exhibited significantly increased risk of a serious cardiac event in comparison with patients with PON1 activity higher or equal to this value (p=0.03). Additionally, TT genotype was significantly associated with shorter time of event-free survival in comparison with CT and CC genotypes (p=0.009). CONCLUSIONS: The PON1 polymorphism and enzyme plasma activity are associated with CHD occurrence. High PON1 activity connected with the presence of CC and CT genotypes decreases the recurrence of symptoms of coronary heart disease and improve prognosis after CABG.

[The concomitance of pericarditis constrictiva in patient with Silver-Russell syndrome, primary hyperparathyroidism and oncologic history: causal coincidence or pathogenetic sequence?]. / Zaciskajace zapalenie osierdzia u pacjentki z zespolem Silver-Russella, pierwotna nadczynnoscia przytarczyc i wywiadem onkologicznym: przypadkowa koincydencja czy sekwencja patogenetyczna?

The most common cause of calcific pericarditis is idiopathic. We report a case of a 24 year-old woman with Silver-Russell syndrome, history of Wilms' tumour in childhood, constrictive pericarditis and primary hyperparathyroidism. We analyse pathologic mechanisms of disseminated calcification and possible genetic factors that may contribute to aetiology and clinical presentation of calcific pericarditis.

Uric acid as a link between renal dysfunction and both pro-inflammatory and prothrombotic state in patients with metabolic syndrome and coronary artery disease.

BACKGROUND: Hyperuricaemia has long been known to be associated with cardiovascular disease, and it is particularly common in patients with kidney disease, metabolic syndrome and diabetes mellitus. Metabolic syndrome is associated with pro-inflammatory and prothrombotic state. AIM: To examine the association between renal function, serum uric acid and markers of both pro-inflammatory and prothrombotic state in patients with diabetes mellitus (DM), metabolic syndrome and coronary artery disease. METHODS: The study population consisted of 91 patients (58 men, 33 women) aged 57.6 ± 10.3 years with metabolic syndrome and type 2 DM. Patients were selected from a large group of patients scheduled for routine coronary angiography between 2006 and 2009. The patients were evaluated for the common risk factors for atherosclerosis: smoking, hypertension, DM, family history and hyperlipidaemia. Laboratory tests included complete blood counts, serum urea and creatinine, aminotransferases, C-reactive protein (CRP), fibrinogen, uric acid, total cholesterol, LDL-cholesterol, HDL-cholesterol, triglycerides, fasting glucose, glycated haemoglobin (HbA1c), glomerular filtration rate (GFR) and urinary protein. We also measured body mass, height, waist circumference, hip circumference and calculated body mass index (BMI) and waist-to-hip ratio (WHR). RESULTS: The following significant correlations were observed: body mass vs serum creatinine (r = 0.291; p = 0.009), WHR vs serum creatinine (r = 0.672; p < 0.001), WHR vs GFR (r = -0.706; p < 0.001), WHR vs uric acid (r = -0.341; p = 0.001), WHR vs uric acid (r = 0.295; p = 0.05), BMI vs CRP (r = 0.231; p = 0.031), WHR vs CRP (r = 0.236; p = 0.024), serum creatinine vs uric acid (r = 0.362; p < 0.001), GFR vs uric acid (r = -0.341; p = 0.001), uric acid vs CRP (r = 0.251; p = 0.016), CRP vs fibrinogen (r = 0.470; p < 0.001), CRP vs platelet count (r = 0.282; p = 0.04) and HbA(1c) vs platelet count (r = 0.263; p = 0.0112). Multiple stepwise regression analysis showed that uric acid level was independently associated with WHR, GFR and CRP. CONCLUSIONS: In patients with ischaemic heart disease, DM and metabolic syndrome, obesity, particularly visceral obesity, is associated with renal dysfunction and elevated markers of pro-inflammatory state. Renal dysfunction co-exists with elevated serum uric acid. Elevated serum uric acid is associated with markers of pro-inflammatory state. Markers of pro-inflammatory state correlate with prothrombotic markers such as serum fibrinogen and platelet count. Uric acid should be taken into consideration as a link between renal dysfunction and both pro-inflammatory and prothrombotic state in patients with metabolic syndrome and coronary artery disease.

Safety of pharmacotherapy of osteoporosis in cardiology patients.

The commonest medical conditions following menopause are osteoporosis and atherosclerotic disease. This review considers the safety of pharmacotherapy of osteoporosis in cardiology patients. Drugs used for osteoporosis treatment may have adverse effects on the cardiovascular system. This article has detailed analysed of current drug classes, such as the bisphosphonates and strontium ranelate, as well as reviewed of the controversy surrounding hormone replacement therapy (HRT) and the selective estrogen receptor modulators (SERMs). Additionally, we discuss the adverse effects on the heart of calcium and drugs influencing calcium metabolism such as vitamin D, parathormone and calcitonin. We look at the interference between osteoporosis treatment and the drugs used for atherosclerosis. Moreover, the side effects on bones of cardiology drugs are analysed. Lastly, the possible advantages of selected drugs used for cardiovascular diseases in terms of osteoporosis prevention are evaluated.

Spatial QRS-T angle in peritoneal dialysis patients: association with carotid artery atherosclerosis, coronary artery calcification and troponin T.

BACKGROUND: Abnormal values of the spatial angle between the directions of ventricular depolarization and repolarization (QRS-T) predict potently arrhythmic events and mortality in various patients groups. The study was designed to estimate QRS-T in a group of peritoneal dialysis (PD) patients, and to assess the possible association between QRS-T and coronary artery calcification (CAC), atherosclerosis, and some biochemical measurements. METHODS: The angular differences between the maximum spatial QRS and T vectors were reconstructed from ECGs in 57 selected PD patients and in 54 controls. In patients CAC score was performed by using multi-row computed tomography. Atherosclerotic disease was assessed by measuring carotid arteries' intima-media thickness (IMT) and plaque score (sum of the maximum thicknesses in mm of all plaques on both sides) by using an ultrasound scanner. RESULTS: QRS-T was higher in patients compared with controls (34.79% B111.97 and 14.95% B17.87 respectively; P < 0.001). Median CAC score equalled 104.5 Agatson units (Au) (range, 0-2478). IMT was 0.832% B10.208, and atherosclerotic plaques were detected in 82.5% of patients. The plaque score was 7.97% B14.49. QRS-T was higher in patients with CAC score >400 Au compared with patients with CAC score <400 Au (P = 0.011). The results of univariate linear regression analysis showed correlation between QRT-T and dialysis duration (r = 0.305, P = 0,020), LVMI (r = 0.311, P = 0.017), HDL (r = -0.361, P = 0.006), cTnT (r = 0.442, P < 0.001), plaque score (r = 0.403, P = 0.001) and CAC score (r = 0.451, P < 0.001). On multivariate analysis, CAC score, plaque score and troponine T were found to be independent predictors of QRS-T values. CONCLUSIONS: QRS-T is high in PD patients and is mainly associated with coronary artery calcium burden, atherosclerosis and troponin T elevation. The possible clinical importance of the higher QRS-T in PD patients remains to be confirmed in further studies.

Aortic stiffness and valvular calcifications in patients with end-stage renal disease.

OBJECTIVES: To evaluate the presence and extent of cardiac calcifications and aortic stiffness in patients with end-stage renal disease (ESRD). PATIENTS AND METHODS: The study group consisted of 60 patients with ESRD with a mean age of 51.7 years, treated with peritoneal dialysis. In all patients transthoracic echocardiogram was performed to assess the following parameters: left ventricular end-systolic diameter, left ventricular end-diastolic diameter (LVEDd), interventricular septum end-diastolic diameter (IVSDd), posterior wall end-diastolic diameter (PWDd), ejection fraction (EF), fractional shortening (FS), aortic maximal and minimal diameter, aortic valve area, mitral valve area (MVA), left ventricular ejection time (LVET), maximal aortic velocity. Aortic stiffness index (AS) was calculated. Aortic and mitral valve calcifications were assessed. RESULTS: Patients with ESRD had a larger left ventricle (LVEDd 5.4 cm vs. 4.76 cm) and its wall was thicker (IVSDd 1.36 cm vs. 1.02 cm; PWDd 1.31 cm vs. 0.94 cm). Patients had poorer left ventricle contractility (EF 56.1 vs. 61.6%; FS 28.5 vs. 33.2%). Atherosclerotic plaques, calcified plaques and valvular calcifications were more frequently detected in patients with ESRD. Patients with ESRD had significantly higher values of the AS index: (5.34 vs. 3.24). Among ESRD subjects with the stiffer aorta, atherosclerotic plaques including calcificones and the aortic valve damage were more frequently detected. CONCLUSIONS: Patients with ESRD are characterized by increased aortic stiffness. Atherosclerotic plaques in the aorta as well as cardiac and large vessels calcifications are more common among patients with ESRD. In patients with ESRD there is a correlation between an increase in aortic stiffness and damage of aortic valvular leaflets as well as calcifications of atherosclerotic plaques in the aorta. The degree of aortic stiffness is not related to impairment of mitral valvular leaflets and extravalvular calcifications. A relationship between aortic stiffness and aortic or aortic valve calcifications suggest a different pathogenesis of aorta calcification as compared to that underlying calcifications of other localizations.

Relationship between aortic valve calcification and aortic atherosclerosis: a transoesophageal echocardiography study.

INTRODUCTION: Clinical and laboratory data provide an increasing amount of information regarding the common aetiopathogenetic background of acquired heart defects with calcification and arterial atherosclerosis. AIM: To evaluate the relationship between presence and severity of calcifications of the aortic semilunar valves and the intensity of atherosclerotic lesions in the aorta and aortic stiffness (AS). METHODS: The study group comprised 80 subjects (49 males and 31 females) aged 72.2 (+/-8.0) years with an aortic valve defect found on echocardiography. Patients were divided into two subgroups depending on the severity of valvular disease. Subgroup I comprised 42 patients with small valvular lesions (0--absence of calcification of the valve, or +--trivial valvular calcifications, possible to find on detailed evaluation of the valve). Subgroup II consisted of 38 patients with intense calcifications (++--large, easily found valve calcifications, +++--massive calcifications affecting leaflet mobility). All patients underwent transoesophageal echocardiography to evaluate atherosclerotic lesions in the aorta. The assessment included the following: location of the lesions in the aorta, intimal thickness, presence of calcifications and mobile parts of plaques and possible associated thrombi. Aortic stiffness was also measured using the formula: AS=log (SBP/DBP)/Ao(max)-Ao(min)/Ao(min). RESULTS: Atherosclerotic plaques were more frequent in patients with more prominent calcifications of the aortic valve (19 vs 10 patients, p <0.05). Intimal thickness was larger in patients with more pronounced valve calcifications (3.9+/-0.8 mm vs 2.2+0.6 mm, p <0.05). Presence of calcifications in the aortic wall was also more frequent in patients from group II, as they were found in 10 subjects compared to only 3 cases in group I. Mobile plaque parts were observed in 3 patients from group II; also thrombi were found in 3 individuals from this group. Patients with more prominent calcifications of the aortic valve had decreased aortic wall elasticity (AS 5.5+/-1.2 cm vs 3.4+/-0.9 cm, p <0.05). CONCLUSIONS: Severity of aortic valve calcification indicates simultaneous changes in the thoracic aorta. Stiffness of the aortic wall is greater in patients with a more pronounced defect of the aortic valve. Prevalence of atherosclerosis risk factors is increased in patients with aortic valve defect, enhanced atherosclerosis and rigidity of the aorta. Defect of the aortic valve and increased aortic rigidity may be different manifestations of atherosclerosis.

[Non-surgical retrieval of coronary stent from the left ventricle following failed stent deployment in the left anterior descending coronary artery--a case report]. / Usuniecie stentu z lewej komory serca po nieudanej próbie implantacji do galezi miedzykomorowej przedniej lewej tetnicy wiencowej.

A case of a 66-year-old male with acute myocardial infarction (MI) treated with streptokinase is presented. Due to the recurrence of angina six days from the acute phase of MI, the patient underwent coronary angiography which revealed critical stenosis of the left anterior descending coronary artery. During intracoronary intervention, stent was lost and migrated to the left ventricular cavity, being trapped in chordae tendinae of the posterior mitral leaflet. The procedure was stopped. After transferring the patient to our department a few days later, a successful non-surgical retrieval of stent with the use of biopsy forceps was performed. Treatment of dislodged coronary stents is discussed.