Cancer-associated thrombosis - treatment and prevention with direct oral factor Xa inhibitors.

BACKGROUND: Venous thromboembolism (VTE) is a frequent cause of morbidity and mortality in patients with cancer. Moreover, management of VTE is frequently connected with complications, namely risk of recurrent VTE and bleeding. Low molecular weight heparins (LMWH) therapy administrated for 3-6 months is currently considered a standard for the treatment of cancer-associated VTE (CA-VTE). Direct oral factor Xa inhibitors (FXaI) apixaban, edoxaban and rivaroxaban have emerged as a new possibility for long-term antithrombotic therapy for VTE. These agents expose several advantages in individuals with cancer, and might overcome several disadvantages connected with LMWH therapy. PURPOSE: First clinical studies with oral FXaI for the treatment of CA-VTE with very promising results were recently published. The article summarizes current data regarding the use of oral FXaI in the treatment of CA-VTE.

Cardiovascular risk assessment prior to kidney transplantation.

OBJECTIVES: The objective was to find out risk factors indicating the patients directly to selective coronarography (SCG) to avoid unnecessary non-invasive testing and in their absence to asses low cardiovascular risk and faster inclusion on the waiting list. BACKGROUND: Cardiovascular diseases (CVD) are the most frequent cause of death in dialysed patients. The aim of our retrospective analysis was to identify risk factors for coronary artery disease (CAD) before kidney transplantation (KTx). METHODS: Our retrospective analysis consisted of 55 dialysed patients (46 males, 9 females, p < 0.0001), undergoing SCG before KTx. We divided the patients according to SCG results (negative, n = 40, positive finding, n = 15). RESULTS: We confirmed a significantly lower incidence of diabetic nephropathy (p = 0.0484), ischaemic heart disease (p = 0.0174) and CAD (p = 0.0001) in patients without percutaneous coronary intervention (PCI; negative finding). Haemodynamically significant coronary stenosis correlated with the occurrence of stroke in a patient's history (p = 0.0104). We identified predictors for performing PCI (positive result): type 2 diabetes mellitus (DM) (p = 0.0472), high-density lipoprotein cholesterol ≤ 1.03 mmol/l (p = 0.0359), total calcium level ≤ 2 mmol/l (p = 0.0309), phosphate level ≥ 1.45 mmol/l (OR 0.2034; p = 0.0351). CONCLUSION: In our analysis, patients with DM and poorly managed chronic kidney disease/mineral bone disease were the riskiest subset of the patients with a positive SCG finding (Tab. 4, Fig. 2, Ref. 30). Text in PDF www.elis.sk Keywords: kidney transplantation, coronary artery disease, selective coronarography, cardiovascular risk.

Kidney transplantation as a treatment of choice for AA amyloidosis due to periodic fever syndrome.

Renal AA amyloidosis is the most serious complication of periodic fever syndrome, which, inadequate suppression, due to persistent inflammation, leads to nephrotic syndrome and renal failure over several years. In most cases, periodic fever syndromes begin to manifest clinically in early childhood. Occurrence in adulthood is considered rare and is associated with a poorer clinical course. Kidney transplantation (KT) is an effective and safe treatment for end-stage chronic kidney disease (CKD) based on AA amyloidosis. In this paper, we present cases of two patients after deceased donor KT, who have been diagnosed with adult periodic fever syndrome. In the first one, diagnosis and treatment began in advanced stage of CKD and therefore underwent KT with compensated disease, while in the second patient, the disease manifested and diagnosed in the post-KT period. Timely initiation of treatment ensured protection of the graft from amyloid deposition.

The role of proteinuria, paricalcitol and vitamin D in the development of post-transplant diabetes mellitus.

INTRODUCTION: Post-transplant diabetes mellitus (PTDM) occurs most frequently during the first year after transplantation. We focused on parameters of calcium-phosphate metabolism and proteinuria as possible new risk factors for PTDM after kidney transplantation. MATERIALS AND METHODS: We have prospectively identified risk factors for post-transplant diabetes mellitus with follow-up of 12 months in a set of 167 patients after kidney transplantation. Patients with diabetes mellitus type 1 and type 2 as well as patients using ciclosporin A or mTOR inhibitor have been excluded from the monitoring. From the perspective of immunosuppression it was a homogeneous set of patients. RESULTS: We identified the following independent risk factors for PTDM in our set: average proteinuria > 0.300 g/24 h (HR 3.0785, (95 % CI 1.6946-5.5927), p=0.0002), level of vitamin D<20 ng/ml (HR 5.4517, (95 % CI 2.3167-11.8209), p1.45 mmol/l (HR0.0821, (95 % CI0.0042-1.5920), p=0.0439). The lowest occurrence of PTDM and proteinuria was recorded in patients whose treatment included paricalcitol (p<0.0001) and these patients had at the same time the highest level of vitamin D (p<0.0001). CONCLUSION: Deficit of vitamin D, proteinuria and hyperphosphatemia have been independent risk factors for the development of PTDM in our set. We identified the usage of paricalcitol as protective factor with regard to the PTDM development (Tab. 6, Fig. 4, Ref. 29).

Flow Cytometry Panel-Reactive Antibody Screening of Anti-HLA Antibodies in the Waiting List Significantly Reduces the Occurrence of Acute Rejection After Kidney Transplantation.

INTRODUCTION: The presence of preformed HLA-reactive antibodies in recipient serum before transplantation has long been recognized as a prominent risk factor for a generally worse graft outcome. Screening and identification of HLA antibodies can be used to stratify patients into high- and low-risk categories. MATERIALS AND METHODS: We determined patients' anti-HLA antibodies using flow cytometry panel-reactive antibody (flowPRA) screening, specifying more than 5% after positive screening. According to the results of the screening test, patients were allocated to the induction immunosuppressive protocol according to the actual immunologic risk. RESULTS: In the group of 78 patients, screening with flowPRA of anti-HLA antibodies was done twice a year. Patients were divided into 2 groups of immunologic risk (low or medium), and we chose the induction immunosuppressive protocol according to the risk. Stratification of the risk was correct, because the only predictor for development of acute rejection in the monitored period of 12 months was delayed graft function (odds ratio 33.2501; 95% confidence interval 10.0095-110.4508; P < .0001). The occurrence of acute rejection upon implementing the screening was reduced in our transplant center from 44% to 19% (P < .0001). No difference was recorded in the 12-month survival of grafts and patients according to the applied induction immunosuppressive protocol. CONCLUSION: We confirmed significantly reduced occurrence of acute rejection in the follow-up period of 12 months by using individualized induction according to flowPRA screening of anti-HLA antibodies. FlowPRA screening represents a suitable alternative for screening and specification of anti-HLA antibodies in case the Luminex methodology is unavailable.

Metabolic syndrome and new onset diabetes after kidney transplantation.

AIMS: The metabolic syndrome developed after kidney transplantation is the result of several factors which are identical with the risk factors in normal population, however, also some factors typical for the transplanted patients-especially the effects of immunosuppressive therapy. MATERIAL AND METHODS: In the groupof 268 patients after kidney transplantation, which had no type 1 or type 2 diabetes mellitus before transplantation, we identified patients with metabolic syndrome(based on IDF criteria), 12 months from the kidney transplantation. In all patients, we recorded the following parameters: age at the time of transplantation, type of immunosuppression, waist measure, the value of triacylglycerols, the value of HDL cholesterol, presence of arterial hypertension, andthe value of glycaemia in fasting state (or presence of diabetes mellitus). The groupof patients was divided into the control group and the group of patients with metabolic syndrome. RESULTS: The average age of patients was 46.1±11.6years. The control group included 149 patients (55.6%),and we identified the metabolicsyndromein 119patients (44.4%). The patients with metabolicsyndrome were significantly older (P<0.0001), had significantly larger waist (both the entiregroup and the males andfemales) P<0.0001.The femaleswith metabolic syndrome had significantly lower value of HDL-cholesterol (P=0.0013), and significantly higher number of patients with metabolic syndrome had hyperglycaemia in fasting state or diabetes mellitus (P=0.0006). CONCLUSION: By controlling the weight and waist, we may identify the risk patients for development of metabolic syndrome after kidney transplantation.

Incidence of Diabetes Mellitus After Kidney Transplantation in Slovakia: Multicentric, Prospective Analysis.

BACKGROUND: The incidence rate of post-transplant diabetes mellitus (PTDM) after kidney transplantation (KT) is 5% to 40%. The objective of this analysis was to identify the risk factors of PTDM after KT in the Slovak Republic (SR). METHODS: In the group of 133 patients/non-diabetics, we identified the risk factors of PTDM in the monitored period of 12 months from transplantation. RESULTS: The incidence of PTDM in the SR in 2014 was 38.3%. By logistic regression, we discovered that the age at the time of KT [odds ratio, 1.0885; 95% CI, 1.0222-1.1592; P = .0082], the value of body mass index (BMI) at the time of KT [odds ratio, 1.4606; 95% CI, 1.0099-2.1125; P = .0442], and the value of insulin resistance index (homeostatic model assessment for insulin resistance) at the time of KT [odds ratio, 2.5183; 95% CI, 1.7119-3.4692; P < .0001] represented predictive factors of PTDM. The independent risk factors of PTDM in our group were age at the time of KT of more than 60 years [HR 0.3871; 95% CI 0.1659-1.7767; P = .0281], waist circumference at the time of KT in men more than 94 cm and in women more than 80 cm [HR, 3.4833; 95% CI, 1.2789-9.4878 (P = .0146)], BMI at the time of KT [HR 3.0011; 95% CI 1.0725-8.3977 (P = .0363)], and triacylglycerols at the time of KT more than 1.7 mmol/L [HR, 2.9763; 95% CI, 1.0141-8.7352; P = .0471]. CONCLUSIONS: In the group of Slovak patients after kidney transplantation, the dominating risk factor for PTDM development was insulin resistance prior to KT.

Correlation between CMV Infection and Post-transplantation New-onset Diabetes Mellitus.

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT) is a well-known complication of transplantation. OBJECTIVE: To determine the correlation between CMV infection and NODAT. METHODS: Retrospectively, we detected CMV replication (PCR) in every month after renal transplantation in the first 12 months of the procedure in a homogenous group of patients from the immunosuppression point of view. RESULTS: In 167 patients (64 with NODAT and 103 in the control group), the average amount of CMV viremia was not significantly different between the NODAT and the control group (p=0.929). In the 10th month of transplantation, we recorded a significantly higher CMV viremia in the NODAT group (p<0.0001), however, in the multivariant analysis, the observed statistical difference vanished. The survival of patients and grafts was 12 months after kidney transplantation without any statistically significant difference between the studied groups (p=0.611 and p=0.538, respectively). CONCLUSION: CMV is not a risk factor for NODAT.

Age of obesity onset in MC4R mutation carriers.

OBJECTIVES: The mutations in gene for the melanocortin-4 receptor (MC4R) are the most common etiology factors of monogenic obesity development. Recently, it has been shown that current life style has a significant impact on the phenotype of MC4R mutation carriers - increases the penetrance of the mutations. We aimed to study the impact of the current age on the time of obesity onset among MC4R mutation carriers. METHODS: DNA analysis of the MC4R gene was performed in 268 unrelated Slovak and Moravian obese children and adolescents 18 years and 28 blood relatives >18 years of the probands with a mutation. RESULTS: Three different previously described heterozygous loss of function MC4R mutations (p.Ser19Alafs*34, p.Ser127Leu, and p.Gly181Asp) were found in 3 <18 years probands, 3 adult probands, and 6 adult obese/overweight family relatives. The age of obesity onset in mutation carriers was 1 year in all probands in the children group and 1-35 years (median 11 years) in adults. The age of the obesity onset significantly correlated (R=0.809, p=0.028) with the current age in all of the MC4R mutation carriers. CONCLUSIONS: The age of obesity onset in the present child generation of MC4R mutation carriers is decreasing compared to the age of onset in their parents' generation. This is in agreement with similarly increasing penetrance of obesity in MC4R mutation carriers and it points out to escalation of obesogenic potential of environment.

Twelve-Month and Five-Year Analyses of Risk Factors for New-Onset Diabetes After Transplantation in a Group of Patients Homogeneous for Immunosuppression.

OBJECTIVE: In the case of new-onset diabetes after transplantation (NODAT) development, it is suitable to reduce calcineurin inhibitors and corticosteroids. But change of immunosuppression can be counterproductive and can cause development of rejection and leads to further NODAT aggravation. METHODS: We retrospectively evaluated risk factors after kidney transplantation. Comparison groups were homogeneous in terms of administered immunosuppression, and individual monitored parameters were not distorted by the immunosuppression administered. RESULTS: In the 12-month analysis we identified these risk factors for NODAT: age at the time of transplantation, 50-59 years (P = .0034); age at the time of transplantation, ≥ 60 years (P < .0001); positive family anamnesis for diabetes mellitus type 2 (P < .0001); body mass index at the time of transplantation, ≥ 30 kg/m(2) (P = .0236); prediabetes before transplantation (P < .0009); and proteinuria, >0.15 g/d (P < .0002). In the 5-year analysis, we identified patients who were diagnosed with NODAT after the 1st year. We identified age ≥ 50 years at the time of transplantation to be an independent risk factors for NODAT. CONCLUSIONS: It is advisable to carry out the oral glucose tolerance test even in patients with physiologic levels of fasting glycemia.

Melanocortin-4 receptor gene mutations in obese Slovak children.

The most common etiology of non-syndromic monogenic obesity are mutations in gene for the Melanocortin-4 receptor (MC485) with variable prevalence in different countries (1.2-6.3 % of obese children). The aim of our study was 1) to search for MC4R mutations in obese children in Slovakia and compare their prevalence with other European countries, and 2) to describe the phenotype of the mutation carriers. DNA analysis by direct Sanger sequencing of the coding exons and intron/exon boundaries of the MC4R gene was performed in 268 unrelated Slovak children and adolescents with body mass index above the 97(th) percentile for age and sex and obesity onset up to 11 years (mean 4.3+/-2.8 years). Two different previously described heterozygous loss of function MC4R variants (i.e. p.Ser19Alafs*34, p.Ser127Leu) were identified in two obese probands, and one obese (p.Ser19Alafs*34), and one lean (p.Ser127Leu) adult family relatives. No loss of function variants were found in lean controls. The prevalence of loss-of-function MC4R variants in obese Slovak children was 0.7 %, what is one of the lowest frequencies in Europe.

Monitoring the efficacy of ADP inhibitor treatment in patients with acute STEMI post-PCI by VASP-P flow cytometry assay.

INTRODUCTION: Dual antiplatelet treatment (DAPT) with clopidogrel and aspirin represents common approach in prevention of thromboembolic events in patients with acute coronary syndrome undergoing percutaneous coronary intervention (PCI). The drawback of clopidogrel treatment is large interindividual variability in response. AIM: Our article aims to suggesting the most convenient method in monitoring the DAPT of post-PCI patients. METHODS: We analyzed the on-treatment platelet reactivity by light transmission aggregometry and vasodilator-stimulated phosphoprotein (VASP) flow cytometric assay. Samples were obtained in 3 intervals: first prior to PCI, then 1, and 30 days after PCI. RESULTS: Based on VASP-platelet reactivity index (PRI), we observed 100% response rate in prasugrel-treated patients and 62% to 73 % in the clopidogrel group. Overall, only 2 (7%) patients with the VASP-PRI value in therapeutic range had major adverse cardiovascular events. CONCLUSION: Our results hint VASP-phosphorylation assay as a relevant method for guiding and tailoring DAPT.

The detection of early myocardial changes in asymptomatic diabetic individuals by 99mTc - Myoview gated-SPET and heart rate variability measurement.

AIMS: Incidence of early myocardial changes in asymptomatic diabetic individuals is not clearly documented. In the present study, we examined diabetic patients without a history of cardiovascular disease with negative treadmill test and no signs of systolic dysfunction for presence of cardiac autonomic neuropathy established by measurement of heart rate variability (HRV) and (99m)Tc - Myoview gated-SPET. MATERIALS AND METHODS: 47 type I and type II diabetic patients were subjected to prospective study including echocardiography and HRV measurement using the combination of Ewing´s testing and spectral analysis. Subsequently, patients underwent treadmill test and stress myocardial perfusion scintigraphy. Additionally, vascular and metabolic parameters were collected. RESULTS: Treadmill test was negative in all patients. Diastolic dysfunction was found in 10 % of T1DM and 11 % of T2DM patients by echocardiography, whereas none of the patients had systolic dysfunction. SPET confirmed hypoperfusion in 35 % T1DM (p=0.01) and in 60 % T2DM (p=0.001). Diagnosis of cardiac autonomic neuropathy based on Ewing´s testing and HRV examination was established in 60 % of T1DM patients (p=0.001) and 77 % of T2DM patients (p=0.001). In T1DM group, significant association was found between cardiac autonomic neuropathy (CAN) and frequency of hypoglycaemia (p=0.04). No such correlations were found in patients with T2DM. CONCLUSION: The results of the present study show high incidence of myocardial hypoperfusion and cardiac autonomic neuropathy among asymptomatic diabetic patients, whereas the standard diagnostic approaches including treadmill test and echocardiography failed to show any changes. Therefore, we conclude that diabetic heart disease remains underdiagnosed by standard approaches, but could be detected in asymptomatic patients by more sensitive methods, such as HRV measurement and myocardial scintigraphy (Tab. 2, Fig. 2, Ref. 26).

[Indicators of inflammation in patients with coronary atherosclerosis - role of usCRP in diagnosis and disease progression prediction]. / Indikátory zápalu u pacientov s koronárnou aterosklerózou - úloha usCRP v diagnostike a predikcii prognózy ochorenia.

Atherosclerosis is being nowadays defined as chronic subclinical inflammatory disease. Recently published clinical and laboratory studies have shown that subclinical inflammation represents main role in initiation of creation, in progress and destabilization of atherosclerotic plaque. Screening including traditional cardiovascular risk factors fails in identification in more than 50% of individuals with later development of acute coronary syndrome. According to above mentioned reason indicators are being searched for, which would be usable to monitor the activity of atherosclerotic process. According to role of subclinical inflammatory process in pathogenesis of atherosclerosis, the determination of C-reactive protein using ultrasensitive method is being showed as perspective marker. Ultrasensitive C-reactive protein represents a strong, independent predictor of future cardiovascular events in apparently heal-thy individuals and has also prognostic utility in patients with acute coronary syndromes. Predictive capacity of C-reactive protein determination is independent of traditional risk factors and offers prognostic advantage as opposed to determination of lipids alone. The paper provides a review of currently available knowledge of possibilities for utilization of C-reactive protein laboratory assessment, as the main representative of acute phase proteins, in monitoring of creation and severity of coronary atherosclerosis, in possibilities of the disease prognosis determination and prediction of its acute complications, and also in prediction of prognosis in patient with already existing acute complication.

[Prevalence of diabetic retinopathy and distal symmetrical diabetic polyneuropathy, and glomerular filtration screening upon the diagnosis of type 2 diabetes mellitus - a cohort study]. / Prevalencia diabetickej retinopatie, distálnej symetrickej diabetickej polyneuropatie a screening glomerulárnej filtrácie v case dia-gnózy diabetes mellitus 2. typu -  kohortná stúdia.

The prospective cohort study analyzes the prevalence of microvascular complications at the time of dia-gnosis type 2 diabetes (DM 2). We were monitoring 200 outpatients (117 men and 83 women, aged from 30 to 92 years) with newly diagnosed and previously untreated type 2 diabetes mellitus during the period of August 2007 -  August 2011 accidentally sending GP or internists. Prevalence of diabetic retinopathy in men was 0.85% and in women 1.2%. The prevalence of diabetic distal symetric polyneuropathy in men was 53% and in women 62%. The median of glomerular filtration based on a simplified MDRD 4 equation (according to the study Modification of Diet in Renal Disease) was 1.27 ± 0.6 ml/ s/ 1.73 m2 for men and 1.05 ± 0.32 ml/ s/ 1.73 m2 for women. At baseline, 16.6% of men and 46.2% of women enrolled in our cohort study had glomerular filtration rate < 1 ml/ s/ 1.73 m2.

[The value of ECG assessment in pulmonary embolism diagnostics]. / Význam hodnotenia EKG v diagnostike plúcnej embólie.

Acute pulmonary embolism is one of the most frequent and risky cardiovascular diseases. Despite accessability of different examinig methods and rich clinical experience, pulmonary embolism is demanding disease especially in diagnostics. The reason might be in clinical picture, that is not typical everytime and leads to incorrect choice of diagnostic methods, that delay the disease assessment. Regarding this, precise evaluation of every each symptom and basal, resp. supplemental examinations is important step to rapid and right assessment of this diagnose.

[The arrhytmias in patients with diabetes mellitus]. / Poruchy srdcového rytmu u pacientov s diabetes mellitus.

Cardiovascular disorders are the most common reason of morbidity and mortality worldwide. The prevalence of diabetes mellitus, which is strongly associated with cardiac and cerebrovascular events, is increasing during the last decades. Based on the results of clinical studies we summarize in the review article the risk factors and patomechanisms connecting diabetes mellitus to incidence of arrhythmias and sudden cardiac death. The paper analyzes influence of diabetes mellitus on atrial fibrillation and arrhythmogenic effect of antidiabetic drugs.

[Paraneoplastic hypoglyacemia]. / Paraneoplastická hypoglykémia -  popis prípadu a prehlad problematiky.

Paraneoplastic hypoglyacemia (PH) is a relatively rare phenomenon, which may be caused by insulinomas or nonislet cell tumours (NICT). Both types are among the major "fasting" hypoglyacemia as opposed to reactive postprandial hypoglyacemia. The most common group of nonislet cell tumours causing hypoaglycemia are large mesenchymal tumours, which account for over 50 % of all neoplasms associated with hypoglyacemia. Neuroglycopenic symptoms in patients with NICT may be present for months or years before the actual diagnosis of the underlying disease. Differentiation and correct diagnosis of this type of disease leads to significant improvement in the quality of life of these patients.

[Syncope as first and only sign of left atrial myxoma]. / Synkopa ako prvý a jediný príznak myxómu lavej predsiene.

Myxoma is the most frequent primary heart tumor. It is localised in the left atrium in majority of cases, but each of heart chambers may be affected. Left atrial myxoma becomes symptomatic in case it leads into mitral valve obstruction, systemic embolisation or it manifests with unspecific systemic symptoms. Echocardiography is a golden standard of myxoma diagnostics. We present a case of 61-years old woman patient in whom exercise induced syncope was the first and only sign of far gone left atrial myxoma with left ventricle inflow tract obstruction, leading to mitral pseudostenosis.

[Hyponatremia - carbamazepine medication complications]. / Hyponatrémia - komplikácia liecby karbamazepínom.

Hyponatremia can be defined like the low sodium concentration, lower that 135 mmol/l. It becomes really serious when the concentration is lower than 120 mmol/l. The most frequent causes of hyponatremia are: the extrarenal loss (GIT, skin, bleeding, sequestration), the renal loss (diuretics, nephritis with the salt loss, osmotical diuresis, the Addison disease), hypothyroidism, the lack of glucocorticoids, emotional stress, pain, pseudohyponatremia (incorrect taking, dyslipoproteinemia). There is fatigue, exhaustion, headache and vertigoes dominating in the clinical record file. By the deficit increasing a patient becomes delirious, comatose even with the shock development. It is necessary to separate sufficient supply of sodium from much more often reason, which is loss of sodium which can be caused by: excessive sweating, vomitting with the metabolical alkalosis development, diarrhoea with the metabolical acidosis development, renal losses (a phase of renal failure). Treatment of hyponatremia: intensive treatment starts at the level of plasmatic concentration of sodium under 120 mmol/l or when neurological symptoms of brain oedema are present. In the therapy it is necessary to avoid fast infusions of hypertonic saline solutions (3-5% NaCl solutions) because of the danger of the development of serious CNS complications (intracranial bleeding, etc.). It is recommended to adjust the plasmatic concentration of sodium up to 120 mmol/l during the first four hours and a subsequent correction should not be higher than 2 mmol per an hour. Treatment of the basic illness is very important. We present 2 case histories: a 74-year old female patient and a 69-year old female patient both with the hyponatremia caused by taking of carbamazepine. We want to inform and warn about not only a well known side effect during long-term treatment but about hyponatremia that arose within 48 hours after the start of taking medicine as well.