Showing papers in "Vnitr̆ní lékar̆ství in 2013"

Practice guideline and trends for immunosuppressive treatment of glomerulonephritides according to KDIGO (Clinical Practice Guideline for Glomerulonephritis)

Abstract: We summarize recommendations for glomerulonephritis treatment, established by internationally recognized experts in the field and sponsored by KDIGO (Kidney Disease Improving Global Outcomes). Up till now, the KDIGO review has been the most prestigious analysis of therapeutic trials on immunosuppressive treatment of glomerulonephritides. The 167 recommendations addresses the following forms of glomerulopathies: steroid-sensitive nephrotic syndrome and steroid resistant nephrotic syndrome in children; minimal change disease and idiopathic focal segmental glomerulosclerosis in children and adults; idiopathic membranous nephropathy; idiopathic membranoproliferative glomerulonephritis; glomerulonephritis associated with infection; immunoglobulin A nephropathy and Henoch-Schonlein purpura nephritis; lupus nephritis; pauci-immune focal and segmental necrotizing glomerulonephritis; and anti--glomerular basement membrane antibody glomerulonephritis. We focused our attention on progress in this topic in the last decade.

Cardiorenal syndrome by heart failure

Abstract: Cardiorenal (CR) syndrome is defined for the purposes of the following text mainly as primary cardiac dysfunction with a consequent failure of renal haemodynamics. Heart failure leads to a decrease in cardiac output and to the activation of vasoconstrictors; this gradually precipitates a decrease in the level of renal perfusion, the vasoconstriction of renal vessels and a decrease in glomerular filtration with a gradual development of renal failure. The following paper analyses the pathophysiological mechanisms, the characteristics of the patients, the role of medication during CR syndrome, the relationship between proteinuria and anaemia during CR syndrome and the application of bio-markers and pulmonary hypertension in the prognosis of patients with CR syndrome.

[SAVOR TIMI 53 - Saxagliptin and cardiovascular outcomes in patients with type 2 diabetes mellitus].

Abstract: BACKGROUND The type 2 Diabetes Mellitus treatment is currently effective but still not ideal. A therapy based on the incretins, which represents a significant qualitative progress, is close to an ideal. The first completed mortality study with dipeptidyl peptidase (DPP 4) inhibitors is the study called SAVOR as presented in Amsterdam during the European Cardiology Congress in 2013. METHODOLOGY SAVOR (Saxagliptin and Cardiovascular Outcomes in Patients with Type 2 Diabetes Mellitus) randomised 16,492 patients with Type 2 Diabetes Mellitus and a high-risk of cardiovascular events treated with current per oral antidiabetics and patients treated with saxagliptin or placebo. Eight thousand eight hundred and twenty patients were randomised to be treated with saxagliptin and 8,212 were randomised to be treated with placebo. The average monitored period was 2.1 years. RESULTS The primary goal (cardiovascular death, nonfatal myocardial infarction and nonfatal CMP) occurred in 7.3% (613) patients treated with saxagliptin and in 7.2% (609) patients treated with placebo (HR 1.00, p < 0.001 for non inferiority). The main secondary goal (cardiovascular death, myocardial infarction, vascular stroke, hospitalisation for a heart failure or angina pectoris and myocardial revascularisation) occurred in 12.8% (1,059) patients treated with saxagliptin and in 12.4% (1,034) patients treated with placebo. The number of hospitalisations for heart failure was 289 (3.5%) in the group treated with saxagliptin and 228 (2.8%) in the group treated with placebo (p = 0.007). CONCLUSION DPP 4 inhibitor saxagliptin did not increase the occurrence of ischemic cardiovascular events but it inclined to an increased hospitalisation for heart failure in patients with the already present heart failure. It did not increase the occurrence of pancreatitis. Simultaneously it significantly improved the Diabetes Mellitus control, which could signal a future improvement in cardiovascular goals.

[Inflammatory response and C -reactive protein value in patient with acute coronary syndrome].

Abstract: Inflammation plays an important role in the pathophysiology of acute coronary syndrome as well as in the process of atherosclerosis in general. At the moment of myocardial ischaemia, local and systemic inflammatory reaction is amplified; in ischaemic myocardium there is increased expression of proinflammatory cytokines, particularly interleukin-6, which mediates C reactive protein (CRP) production by hepatocytes. CRP activates the complement cascade and thereby contributes to the lysis and removal of damaged cardiomyocytes. Whereas in a healthy population CRP levels range from 1.2 to 2.0 mg / l, in patients with ACS the levels of CRP significantly increase with the peak of 2nd to 4th day from the onset of myocardial infarction. Peak CRP levels ranged from 20 to 250 mg / l in patients with STEMI treated conservatively, the median of peak of CRP levels was 79 mg/ l in patients with anterior wall STEMI treated with primary PCI. There is a recommendation of CRP evaluation within the early risk stratification of patients with ACS according to the current ESC guidelines. In patients with NSTEMI, CRP levels > 10 mg/ l are associated with increased longterm mortality. In patients with STEMI treated with primary PCI, CRP levels > 79 mg/ l could predict negative left ventricle remodelation. The predictive value of GRACE risk score was improved using CRP, levels > 22 mg/ l predicted worse prognosis in patients with either STEMI or NSTEMI treated invasively. However, if also cardiac troponin and natriuretic peptides in addition to GRACE risk score were used, CRP levels were useless in further risk stratification improvement. In clinical practice, in terms of coinciding infection, problems with CRP levels interpretation can occur as well. Several patients either in cardiogenic shock or after cardiopulmonary resuscitation have signs of systemic inflammatory response, and sometimes it is very difficult to decide whether there is a necessity to iniciate the antibio-tic therapy because of infectious cause. In patients after cardiopulmonary resuscitation, CRP levels > 180 mg/ l indicate highly probable infection, but with the poor sensitivity. For patients in cardiogenic shock, procalcitonin appears to be more useful for the detection of infection; in this group of patients, procalcitonin levels > 2 ng/ ml are common, and levels > 10 ng/ ml indicate infection undoubtedly.

Patophysiology of diabetic retinopathy

Abstract: Diabetic retinopathy (DR) is the affection of the retina in patients with diabetes mellitus (DM). The basic causative factor is prolonged hyperglycaemia. DR is microangiopathy, ie impairment of retinal capillaries. Pathophysiology of DR is very complex and there are involved in many factors. The first and most fundamental factor is the failure blood-retinal barrier (BRB). The major mechanism causing malfunction of BRB are advanced glycation end-products (AGE). In the failure of the inner BRB are involved losses of endothelial cells in capillaries, together with the losses of pericytes. A very important role in the failure of BRB plays too increased adhesivity of leukocytes. Further important role play also AGE and their receptor RAGE. They stimulate cascade of pathological processes damaging BRB. The second important factors in the pathophysiology of DR are vasoactive factors. The most important is vascular endothelial growth factor (VEGF), further than protein kinase C (PKC), histamine, angiotensin II, matrix metaloproteinases. The third important factor in the pathophysiology of DR is the vitreoretinal interface. There plays important role detachment of posterior vitreous, cortical vitreous, internal limiting membrane.

The environmental estrogen bisphenol A and its effects on the human organism

Abstract: Bisphenol A (BPA), i.e. an environmental estrogen, is one of the most common synthetic chemicals which enter the human body from plastic bottles, food packaging and dental materials. As many studies show, a longterm exposure to BPA is connected with a risk of developing various diseases and endocrine disorders. Exposure to BPA, particularly during development, increases the risk of breast carcinoma, obesity, diabetes mellitus type 2 as well as reproductive disorders. It also increases the risk of testes carcinoma and prostate carcinoma. Some isolated studies support also the relation between BPA and the risk of cardiovascular and autoimmune diseases. The effect of other xenoestrogens, such as polychlorinated biphenyls, phthalates, dioxins, as well as others, is similar or perhaps even stronger. For the time being, however, the exact pathophysiologic mechanisms of these relations are not quite clear and require further experimental, but especially human, studies.

Differential diagnosis and treatment of hyponatremia

Abstract: Hyponatremia is one of the most common metabolic disorders in clinical medicine. The value of Na+ in serum equalling 135 mmol/ l and lower is regarded as hyponatremia. Its clinical manifestations are the following: headaches, nausea, vomiting, seizures, numbness, coma and death. Hyponatremia caused by nonosmotic hypersecretion of vasopressin can be divided into: a) hypovolemic, b) normovolemic and c) hypervolemic. Hyponatremia which is not caused by the hypersecretion of vasopressin is the so called pseudohyponatremia, water intoxication, cerebral salt loss syndrome. Hypovolemic hyponatremia is caused by the loss of Na+ and fluid loss from the organism. It occurs, for example, after using thiazide diuretics, after recurrent diarrhoea, vomiting, after significant blood loss and other causes. Treatment of this disorder must focus on the producing cause and on the parenteral administration of 0.9% NaCl. Normovolemic hyponatremia can be with or without symptoms. Acute normovolemic hyponatremia is treated by the intravenous administration of 3% NaCl and with the simultaneous use of loop diuretics (20- 40 mg Furosemide/ 24 hrs) and restriction of fluid intake. In the case of chronic normovolemic hyponatremia, refractory to the previous treatment, caused by the inappropriate secretion of arginine vasopressin, it is recommended to use perorally its V2- receptor blocker, Tolvaptan. Hypervolemic hyponatremia occurs in the case of cardiovascular failure, with hepatic cirrhosis, nephrotic syndrome, renal failure, porphyric disease and other conditions. Symptoms occurring with it are swellings, ascites, distension of jugular veins and the presence of unaccented rales in the lungs, which can be detected during physical examination. For treatment it is recommended to restrict fluid intake and to administer NaCl as well as diuretic therapy. Recently it has been recommended to use Tolvaptan which increases excretion of free water (aquaresis), decreases osmolality in the urine, and leads to the increase in serum Na+. Apart from that, we present our three clinical laboratory observations in the paper: 1. Contrary to the data in the literature, after the Kosice Marathon (42.125 km) the serum concentration of Na+ in the runners increased (from 144.4 ± 2.1 mmol/ l to 147 ± 2.8 mmol/ l, p < 0.01) in spite of a significant reduction in the body weight (from 73.2 ± 5.7 kg to 71.9 ± 5.2 kg, p < 0.05), intensive perspiration and dehydration (blood haemoglobin before the run: 150.4 ± 5.5 g/ l, after the run: 152.1 ± 4.8 g/ l, p < 0.05). Apart from that, we detected a significant decrease in the fractional excretion of sodium (FENa) from 1.16 ± 0.30% to 0.34 ± 0.10%, p < 0.01. 2. One patient with chronic intermittent porphyria displayed the syndrome of inappropriate antidiuretic hormone secretion, which had been positively influenced by the restriction of fluid intake in the long term and by peroral administration of 1- 3 g NaCl/ 24 hrs. 3. In 15 haemodialysed patients with chronic renal failure, who displayed recurrent hypervolemic hyponatremia, we achieved, by means of adequate ultrafiltration and a dialysis solution containing Na+ 145 mmol/ l, the serum concentration of Na+ 142 mmol/ l at the end of haemodialysis.

[Treatment of AL amyloidosis in 2012; the benefit of new drugs (bortezomib, thalidomide, and lenalidomide). Summary of published clinical trials].

Abstract: Until 2011, the gold standard of treatment for patients with AL amyloidosis was the combination of alkylating cytostatics (melphalan or cyclophosphamide) and dexamethasone. For a selected group of patients under 65 years of age with only moderate damage to their body caused by amyloid and with good cardiac function (EF> 40%), high-dose chemotherapy with autologous hematopoietic cell transplantation seems to be optimal. Patients with AL amyloidosis and low bone marrow plasma cell count generally undergo the harvest of hematopoietic cells from peripheral blood, followed by high-dose chemotherapy immediately after they are diagnosed. In contrast to multiple myeloma, high-dose chemotherapy is not preceded by several months of conventional treatment. The year 2012 witnessed a release of reports about extensive experience with new drugs that were used in Phase I and Phase II clinical trials, and in isolated cases also in Phase III, for the treatment of patients with AL amyloidosis. Based on these studies it can be concluded that among the new available drugs (bortezomib, thalidomide and lenalidomide) bortezomib is the drug with the greatest curative effect in patients with AL amyloidosis; it achieved 24-37% of complete remissions in monotherapy. The greatest number of treatment responses was reported during the treatment that combined bortezomib, alkylating cytostatics and dexamethasone. This treatment showed significantly more treatment responses during the first-line drug therapy than during therapies that followed. Clinical trials with lenalidomide combined with other drugs saw a lower number of treatment responses than the number described in treatment with bortezomib combined with other drugs. That is the reason why lenalidomide combinations are not considered the optimal first-line therapy, with the exception of AL amyloidosis with bortezomib contraindication (severe neuropathy caused by AL amyloidosis). It was confirmed that lenalidomide combined with other drugs could cause remission in patients whose disease was resistant to the initial bortezomib therapy. Lenalidomide (or alternatively also thalidomide) can therefore be used as second-line therapy if bortezomib therapy proves unsuccessful, with the possibility of achieving a complete remission. The increase in the number of complete remissions brought about by bortezomib therapies in patients with AL amyloidosis poses a question about which treatment should be used for younger patients with only moderate damage to their body, i.e. high-dose chemotherapy with autologous hematopoietic cell transplantation or combined treatment with bortezomib. Additional comparative studies are required to be able to answer that question and determine which of the aforesaid therapy modalities is optimal. A question still remains whether the increase in the number of complete remissions due to bortezomib will also bring about longer survival comparable to the results of high-dose chemotherapy treatment with autologous hematopoietic cell transplantation.

Progression of diabetic retinopathy in pregnancy

Abstract: Pregnancy is a risk factor for the development of diabetic retinopathy and diabetic macular edema. Ideally, it is appropriate to perform laser treatment of advanced forms diabetic retinopathy before pregnancy, but in case of progression of diabetic retinopathy during pregnancy is laser treatment also indicated. The authors present a case of a young diabetic, who unexpectedly became pregnant. During pregnancy were accelerated changes of diabetic retinopathy. The visual acuity improved in both eye after repeated retinal laser treatment and pars plana vitrectomy in the left eye. The course of disease was documented with digital color fundus pictures, fluorescein angiography and optical coherence tomography.

Diuretics in monotherapy and in combination with other diuretics and nondiuretics in the treatment of hypertension

Abstract: Diuretics belong to the basic group of medicines for the treatment of hypertension and heart failure. In the case of hypertension treatment, their main indication is higher age and isolated systolic hypertension. In the case of heart failure they are used for the treatment of swellings and shortness of breath. The most frequently prescribed group of diuretics is thiazides and similar products. In patients with renal insufficiency, loop diuretics are administered. In the case of hypertension, diuretics are mainly used in the combination treatment. The most frequently used diuretic in combination is again hydrochlorothiazide, which is combined with reninangiotensin system blockers. It is mainly the combination of an ACE inhibitor + indapamide that seems to be modern and promising, and it is, on the basis of large clinical trials, recommended also for diabetics (ADVANCE) or for secondary prevention following a cerebrovascular accident (PROGRESS) or for the elderly (HYVET). Also a combination of two diuretics is popular - mainly hydrochlorothiazide + amiloride. A combination of a betablocker and diuretic is less suitable.

[Immunosuppression after liver transplant, now and in future].

Abstract: The development of immunosuppression has significantly affected the development of liver transplantation and has helped to switch from the experimental method to a standard treatment of life threatening liver conditions. Tacrolimus is the basic immunosuppressant for patients after a liver transplant and thanks to its prolonged-release dosage form, which due to its simplicity and reliability of use, replaces tacrolimus twice daily early after the transplant and in the longterm administration, will apparently, for a while, defend its position. Other widely used medicines include mycophenolic acid and mTOR inhibitors, sirolimus and everolimus. The induction with antilymphocyte antibodies is used in less than 10% of liver recipients. Only a few new immunosuppresants in this century have passed later stages of clinical studies; the last 2 medicines registered for patients after liver transplantation include Advagraf (Astellas) and Certican (Novartis). Personalised immunosuppression should respect at least the following basic clinical situations: recipients renal function, hepatitis C virus infection, and hepatocellular carcinoma as the liver transplant indication. The results of immunotolerance bio-marker research are necessary for a more successful conduct of protocols minimising immunosuppression and leading to immunotolerance, especially under the efforts of complete withdrawal of immunosupression.

Comparison of MRCP a ERCP in diagnosis of choledocholithiasis

Abstract: INTRODUCTION: Choledocholithiasis is the most common cause of biliary obstruction. Each of the testing methods used in its diagnosis has its advantages and disadvantages. OBJECTIVE OF THE STUDY: The objective of this prospective study is to compare endoscopic retrograde cholangiopancreatography with magnetic resonance cholangiopancreatography in the diagnosis of choledocholithiasis on the basis of own experience and literature data. Set of patients and methodology: The set was studied from the beginning of 2007 to the end of 2012 (i.e. six years). The study assessed prospectively 45 patients (age range 28- 72 years) with symptoms of biliary obstruction, who first underwent magnetic resonance cholangiopancreatography and subsequently endoscopic retrograde cholangiopancreatography. RESULTS: The sensitivity, specificity and diagnostic accuracy of magnetic resonance cholangiopancreatography was lower, both in our set of patients and according to the literature data, compared to the endoscopic retrograde cholangiopancreatography (92%, 91% or 93 %). CONCLUSION: Considering the frequency of complications (in some cases serious ones) following endoscopic retrograde cholangiopancreatography, the magnetic resonance cholangiopancreatography is, in spite of its lower sensitivity, the method of choice in the diagnosis of choledocholithiasis by means of noninvasive methods, on the basis of which it is possible to refer the patients subsequently for therapeutic endoscopic retrograde cholangiopancreatography.

Relationship of bilirubin to diseases caused by increased oxidative stress

Abstract: Oxidative stress contributes importantly to pathogenesis of numerous civilization diseases, including cardiovascular diseases, cancer, as well as autoimmune and neurodegenerative conditions. Bilirubin is the major product of the heme catabolic pathway in the intravascular compartment. For long time, bilirubin was considered to be only a waste product, however, recent data from the last 2 decades have proved its important antioxidant properties, which contributes to defense against increased oxidative stress. Numerous experimental as well as clinical studies have demonstrated association between low bilirubin concentrations and cardiovascular diseases, diabetes, certain cancers, autoimunne diseases, such as lupus erythematodes, or rheumatoid arthritis or neurological psychiatric disorders, such as schizofrenia. On the other hand, subjects with mildly elevated blood bilirubin levels, typical for Gilbert syndrome, have decreased risk of these diseases.

[The "Short Physical Performance Battery" in the Czech Republic - the pilot and validation study in older persons].

Abstract: INTRODUCTION Population ageing increases number of seniors with decline of physical capabilities and functional deficits. Targeted interventions to maintain or increase physical performance are most effective before the development of full frailty, in so-called "prefrail" period. One of the assessment tools for evaluation of the physical performance and/ or frailty in older persons is the "Short Physical Performance Battery" - SPPB. The aim of the study was to introduce the assessment battery to clinical practice in the CR and to evaluate its selected psychometric properties. METHOD Original English SPPB was translated into Czech language and back translated to ensure linguistic accuracy. SPPB was applied in the selected sample of older persons and validated against other performance tools for cognition, self- care and nutrition status used in CR and selected psychometric properties evaluated. RESULTS We examined 145 older persons (108 women, i.e. 74.48 % and 37 men, i.e. 25.52 %) mean age 80.38 years (54- 101 years, SD ± 8,47). We found good physical performance in 35 (24.1 %) older persons (SPPB 10- 12 points), 21 (14.5 %) were identified as prefrail (SPPB 7- 9 points) and 89 (61.4 %) as frail in high risk of future disability or already disabled (SPPB 6 points). We found statistically significant correlation of global SPPB score with nutritional status (MNA- Short Form), activities of daily living performance (ADL) and cognitive performance (MMSE) - (Spearman correlation ρ = 0.51; 0.53 and 0.38 respectively). The Cronbachs a for SPPB variables scored 0.821, which is consistent with good internal consistency of SPPB battery. When evaluating 3 age groups [ 75 years (n = 41), 76- 85 (n = 62) and 86- 101 years (n = 42)] the most significant correlations were found between SPPB and MNA, ADL and MMSE in the young elderly (ρ = 0.74, 0.79 and 0.64 respectively) and they diminished with increasing age. CONCLUSION We confirmed significant correlations between SPPB and self care activities, cognitive performance and nutritional status and good internal consistency of the battery. SPPB test is simple, easy to perform, with low time and cost requirements. It could be recommended for clinical practice in both community and hospitalized older patients to evaluate their overall physical performance and identify persons at risk of frailty and disability who may profit from targeted interventions.

Spondylodiscitis and epidural empyema as a complication of diabetic foot

Abstract: UNLABELLED Spinal column infection (vertebral osteomyelitis, discitis, epidural empyema/ abscess) is a rare condition, albeit its incidence has been increasing in recent years. Staphylococcus aureus is the most frequent pathogen. The routes of infection are predominantly hematogenous. Any delay in making correct diagnosis increases risk of adverse outcome of the patient. The authors present 3 case reports of patients with diabetic foot syndrome, who were diagnosed with spondylodicitis in the period of 2009- 2012, two patients had associated epidural empyema. Apart of a chronic neuropathic foot wound, the patients reported severe or deteriorated dorsal pain (2 in the lumbal region, one in thoracic spine), had no new neurologic lesion in the beginning, some had fever, but all had high laboratory parameters of inflammation that did not correlate with local finding on the foot. Methicillin sensitive Staphylococcus aureus cultured from the foot defect in all cases, in two patients from blood cultures and from epidural empyema. They were patients with recurrent local infectious complications of diabetic foot ulcers. Two patients had a concomitant diabetic nephropathy, classified into stages 3- 4/ 5 according to K/ DOQI. Glycemic control (Type 1, Type 2 and secondary DM) ranged from excellent to unsatisfactory (HbA1c 43- 100 mmol/ mol). Apart of patient history and clinical examination, the magnetic resonance imaging of the spine was essential for the diagnosis of spondylodiscitis, or epidural empyema. The treatment was founded on longterm (initially parenteral) antibiotic treatment, bed rest, then mobilization with orthosis. Neurosurgical procedure was necessary in the patients with epidural empyema. All patients were mobile following a varied time period of convalescence and rehabilitation. CONCLUSION Dorsal pain and degenerative changes of the spinal column belong to common findings in our population. When searching for the origin of an infection in patients with elevated inflammatory parameters (inadequate finding for a diabetic ulcer), the history of dorsal pain suddenly becomes the fundamental clue for diagnosis of spondylodiscitis with or without epidural empyema.

Effect of liver cirrhosis on pharmacokinetics and pharmacodynamics of drugs

Abstract: Metabolic liver functions are significantly involved in the total clearance of a number of drugs. In liver cirrhosis the reduced drug elimination is a result of the blood flow through the liver, hepatocytes function and volume of hepatic tissue. Pharmacokinetic and pharmacodynamic changes depend on the nature and degree of hepatic impairment and on the characteristics of the dosed drug. Hepatocytes have a different extraction ability with respect to the individual drugs. The following are examples of drugs with high hepatic extraction: anodyne, propranolol, metoprolol, verapamil and lidocaine. These drugs are significantly dependent on the first passage through the liver. Intrahepatic and extrahepatic collateral blood flows significantly increase their bio-logical availability and reduce the clearance. The reduction in hepatic clearance of drugs with low extraction coefficient, such as chlordiazepoxide, diazepam or furosemide, is a result of its own limited functional capacity to eliminate the drug. Predicting a hepatic metabolic disorder based on a common bio-chemical assessment of enzyme activities is not sufficient. In advanced liver cirrhosis a higher risk is demonstrated for drugs with a narrow therapeutic width. It is always necessary to take into account whether the pharmacotherapy is necessary, use small doses and cautiously monitor the patient.

The benefits of a remote monitoring system in longterm follow up of patients with implantable cardioverter defibrillators

Abstract: Introduction An increasing number of patients with implantable devices in cardiology raises the need for better and more efficient outpatient followup. Telemonitoring (remote monitoring) can be widely used as an important part of care for the patient and the device itself due to the technological progress in communication and transmission systems and implantable devices themselves. Objectives To evaluate the benefits of continuous remote monitoring system using Home Monitoring (HM)TM (BIOTRONIK) compared with standard outpatient controls. Patients and methods 198 patients (67 ± 12 years, 80.8 % men) who have been implanted a single chamber or dual- chamber implantable cardioverter defibrillator (ICD) (163/ 35) in 2008- 2009 in the primary or secondary prevention (75/ 123) of sudden cardiac death were followed prospectively. Planned and emergency visits, hospitalization for events related to ICD, delivered shock therapies and their adequacy were evaluated in a group of patients followed in a standard way of outpatient visits (HM- ) and a group telemonitored by HM system (HM+). Results A significant reduction was achieved in the number of planned (48 %) and total controls (45 %) during a three years follow up. There was a comparable number of patients who experienced one or more shock therapy (only with a trend to a lower number of patients who obtained a shock in HM+ group, p = 0.25), and there was equivalent mortality of both groups and the number of patients hospitalized in relation to ICD. However there was a success in significant reduction in the number and proportion of inadequate shocks delivered in HM+ patient group by 80 % in ambulatory follow up and by 90 % including multiple shocks, which required a hospitalization. Conclusion The HM system demonstrates an effective and safe way of ICD patients followup which helps to reduce the number of outpatient visits and inadequate shock therapies in longterm monitoring.

Does physical activity produce clinically significant changes during discontinuation of insulin pump in type 1 diabetic patients

Abstract: INTRODUCTION Discontinuation of insulin pump treatment (CSII) before, during and after physical activity is a common practice among a number of patients. The aim of the study was to evaluate the course of insulinemia during a 3- hour insulin pump suspension and after consecutive insulin bolus administration, and additionally, to assess the effect of physical activity (mid intensity aerobic exercise). PATIENT AND METHODS We enrolled 12 patients with diabetes mellitus type 1 in the study (men, mean age 33.4 ± 8.66 years, diabetes duration 16.3 ± 8.76 years, CSII treatment duration 6.9 ± 4.60 years, BMI 25.7 ± 3.75 mg/ m2, HbA1c 8.4 ± 0.95%, total insulin dose 50.3 ± 12.50 IU/ day). The tests were performed after night fasting at usual insulin doses, without serving breakfast and morning bolus dose. In the course of the test, insulin administration by a pump was suspended for 3 hours. Blood for assessment of blood glucose and insulinemia was taken in 30- minute intervals during the test. A test with or without physical exercise on bicycle ergometer was performed in each patient 2 weeks later. RESULTS We did not prove any influence of physical exercise on insulinemia during suspended insulin deli-very by an insulin pump. Insulinemia of approximately 50% of the original value persisted for another 90 minutes following insulin pump suspension. A rapid increase in insulinemia occurred after bolus administration in the 180th minute of the test. However, the decrease in blood glucose level did not occur until after another 90 minutes. CONCLUSION When modifying CSII treatment by reduction or suspension of insulin delivery it is essential to bear in mind the gradual decrease in insulinemia as well as the delay in insulin action following bolus administration.

[Opinion of the Czech Atherosclerosis Society's committee (CSAT) on the ESC/EAS guidelines related to the diagnostics and treatment of dyslipidemias issued in 2011].

Abstract: This position statement of the Executive Committee of the Czech Society for Atherosclerosis (CSAT) summarizes the most important aspects and novelties of the latest European guidelines for the management of dyslipidemia. In particular the position statement comments on: cardiovascular risk stratification, indications for plasma lipid and lipoprotein levels assessment as well as target lipid values, evaluation of current options for both lifestyle and pharmacological treatment of lipid metabolism disorders and, also, recommendation for laboratory monitoring of patients treated with lipid lowering agents. The statement deals with actual concepts of management of dyslipiemia in everyday practice, e.g. therapy of dyslipidemia in special patients´ groups. This statement does not replace the latest guidelines but focuses on the changes from the former guidelines for dyslipidemia management, published by CSAT in 2007.

[Primary hyperaldosteronism: common cause of secondary hypertension with higher cardiovascular risk].

Abstract: Primary hyperaldosteronism (PH) is common cause of secondary hypertension with autonomous aldosterone overproduction by adrenal cortex with high plasma aldosterone, suppressed renin and high blood pressure. Patients with PH have compared to essential hypertension (EH) more frequent subclinical organ damage and higher cardiovascular risk (CV). Higher carotid IMT, arterial stiffness and microalbuminuria was found in PH. Early specific therapy of PH may lead to the regression of target organ damage and decrease of CV risk. Early diagnostic and therapeutic measures are very important due to high prevalence of PH.

Liver disorders in diabetic patients

Abstract: There is a mutual relationship between diabetes and liver disorders. Diabetic patients suffer from liver disorders more frequently and, vice versa, patients with liver disorders are at a higher risk of developing diabetes. Diabetes is probably the most common cause of chronic liver disorders in developed countries. Liver disorders related to diabetes include a wide spectrum of conditions, from a simple steatosis related to a slight elevation of liver tests through nonalcoholic steatohepatitis with various degrees of fibrosis up to cirrhosis, hepatocellular carcinoma and acute liver failure. Non alcoholic liver steatosis is the most common pathological condition that is, at present, considered to be a component of or to actually be the liver manifestation of metabolic syndrome, accompanied with an insulin resistance and other clinical components, such as central obesity, dyslipidemia, arterial hypertension and the already mentioned type 2 diabetes mellitus. The steatosis itself is a benign condition and the unfavourable development of the liver disorder is related to an inflammatory reaction (steatohepatitis) and subsequent fibrosis. There is no specific treatment for nonalcoholic steatohepatitis. The basic measures include weight reduction, lifestyle changes and treatment of the concurrent conditions, such as diabetes and dyslipidemia. Formerly popular "hepatoprotective" substances do not play an important role in the treatment of steatohepatitis.

[Is there dependence between the level of adipocyte fatty acid-binding protein and calcium score in asymptomatic relatives of patients with cardiovascular diseases?].

Abstract: UNLABELLED The objective of our study was to determine a correlation between the level of adipocyte fatty acid-binding protein (A-FABP) (as a possible link between metabolic syndrome and atherosclerosis), the calcium score (CS) and laboratory parameters, including insulin resistance indices in asymptomatic first degree relatives of patients with cardiovascular diseases. SET AND METHODOLOGY: Examination was conducted in 82 persons (53 male) with the average age of 52.79 ± 9.6. The examinations consisted of anthropometric and physical tests (determination of body weight, height, body mass index - BMI and casual blood pressure measurement), laboratory analysis (uric acid, creatinine, lipid panel, insulin, glucose, C-reactive protein, fibrinogen, glycated hemoglobin, adipocyte fatty acid-binding protein - A-FABP) and determination of insulin resistance indices HOMA and QUICKI. Total calcium score (CS) was determined by the Agatston method without the need to administer a contrast agent. RESULTS The value of the A-FABP level does not show a statistically significant dependence on the categorised CS or on non-categorised CS values. There is a statistically significant positive dependence of the level of A-FABP on the HOMA index (p = 0.00688) and a statistically significant negative dependence on the QUICKI index (p = 0.0068). The A-FABP level is statistically significantly higher in women (p = 0.048), in elder persons (p = 0.043), and in persons with higher BMI values (p = 0.029). Among continuous variables, statistically significant is the difference in the A-FABP level in relation to age (p = 0.002), creatinine (p = 0.026), insulin (p = 0.005), and BMI (p = 0.031). CONCLUSION Our study confirmed the correlation of the A-FABP level with insulin resistance indices, BMI, age, gender, and insulin and creatinine levels in a group of asymptomatic first degree relatives of patients with cardiovascular diseases. A-FABP could potentially be a marker when determining the risk of CVD; however, this conclusion requires additional clinical trials.

Liver transplant outcomes in Brno

Abstract: The first liver transplant in the former Czechoslovakia took place in Brno on 2 February 1983; the patient concerned has lived for more than 30 years with a normally functioning liver and is one of the longest surviving patients after a liver transplant in Europe. The Cardiovascular and Transplantation Surgery Centre (CTSC) in Brno has experienced an increased development in the area of liver transplants since the mid 1990s. At present, about 30 patients a year undergo a transplantation, with 451 liver transplants in total as of 31 December 2012. The primary indication concerns liver cirrhosis of various etiologies, with an increasing number of cases of cirrhosis resulting from hepatitis C. Urgent liver transplants (for acute liver failure or primary dysfunction of first liver graft) amount to 11% of cases. There were 18 retransplants performed as of 31 December 2012, with 50% five year survival. The primary graft dysfunction was present in 7 patients (i.e. 1.5%). The 1 year survival rate of all patients after a liver transplant performed in CTSC is 92%, 5 year survival rate is 80%, and 10 year survival rate is 71%. Currently the parameters such as recipients age, donors age, and transplant waiting time has been statistically increasing; small recipients with a body weight below 70 kg especially have to wait for a significantly longer period of time (waiting median of 178 days). In CTSC Brno 14 combined simultaneous transplants (13 transplants of liver + kidney and one combined simultaneous transplants of liver + heart + kidney in 2005) have been performed as of 31 December 2012.

[Diabetic nephropathy/diabetic kidney disease].

Abstract: Diabetic kidney disease (DKD), which belongs to the triad of diabetic microvascular complications, is currently the main cause of end-stage renal disease in developed countries. DKD usually simultaneously leads to a deteriorated long-term control of glucose metabolism and blood pressure, and to the development of diabetic retinopathy, neuropathy and atherosclerotic complications, which are the main causes of patients' mortality. Screening of the initial stages of DKD is to be based on the detection of increased albumin leak into the urine, microalbuminuria, and the reduction of renal function by means of estimates of glomerular filtration rate based on the serum creatinine level. The main objective of the prophylactic and treatment measures is to prevent the onset of DKD, or at least to stop its transition into an irreversible, progressive stage characterised by a permanent, often nephrotic proteinuria. The basic procedures in the prevention and treatment of DKD are maintaining the optimal metabolic control of diabetes and intensive hypertension treatment based on the inhibition of the renin-angiotensin system. Reaching the stage of progressive renal insufficiency (serum creatinine level approximately > or = 200 micromol/l) is an indication for further follow-up in the nephrology department, which will then take the necessary preparatory measures for dialysis treatment. The optimal method of kidney function replacement for patients with DKD is kidney transplantation, or combined kidney-pancreas transplantation in patients with type 1 diabetes.

Treatment of chronic hepatitis C virus infection at the beginning of a new era

Abstract: After 2010 the therapy of chronic HCV infection entered a completely new era - the era that is marked with the gradual introduction of the so-called directly acting antivirals into treatment schemes of this serious disease. The term directly acting antivirals (DAA) covers low-molecular substances that inhibit viral nonstructural proteins - enzymes involved in the HCV replication cycle. At present, the first 2 representatives of DAA, Boceprevir and Telaprevir, have been approved for chronic HCV infection indication. The synoptic article pays the greatest attention to these 2 representatives, along with mentioning some other substances that are under later phases of clinical development and are likely to be approved in the near future.

Reactivation of chronic hepatitis B

Abstract: Hepatitis B (HBV) is a DNA virus, which cannot be eradicated completely from the organism by treatment, only its replication can be suppressed to low levels. The pathogenesis of liver damage due to HBV is immune mediated, the infected hepatocytes represent the target structures of immune reaction. In individuals who spontaneously achieved the state of inactive carriage of the virus or even achieved HBsAg negativity, we deal only with immune control of viral replication. Chemotherapy or immunosuppressive treatment disrupt the immune control of HBV infection, the virus replication substantially increases and hepatitis B reactivates. HBV reactivation manifests as further flareup of chronic inflammation with rapid progression of liver cirrhosis or even as a fulminant hepatitis with liver failure. The risk of reactivation increases with degree of induced immunosuppression, the highest risk is associated with corticosteroid and rituximab therapy. HBV reactivation threatens patients during solid tumours treatment as well as haemato oncological malignancies, patients treated with immunosuppressive and bio-logical therapies for systemic inflammatory diseases and inflammatory bowel diseases, as well as patients on maintenance haemodialysis, after kidney transplantation and patients with HBV/ HIV co infection. HBV reactivation increases both morbidity and mortality in listed groups of patients. The patients threatened by HBV reactivation can be identified easily based on HBV serological markers assessment. Preemptive therapy with nucleos(t)ide analogues significantly reduces the risk of HBV reactivation, the effect of longterm antiviral therapy is described in detail in kidney transplant recipients in whom the 3rd generation antivirals (entecavir and tenofovir) completely obviate the negative impact of HBV on longterm survival. In oncological patients who are treated for a determined time period, we can use lamivudine, which is not suitable for longterm treatment due to high risk of resistance emergence.

Gluten induced diseases

Abstract: The introduction of cereals in human nutrition 10 000 years ago caused the occurrence of gluten induced diseases. This protein complex is involved in pathogenesis of wheat allergy, celiac disease, and gluten sensitivity. Wheat allergy and celiac disease are mediated by the system of adaptive immunity. Gluten sensitivity is a recently defined entity induced by innate immune mechanisms. These subjects present various intestinal and particularly extraintestinal symptoms. The differences between celiac disease and gluten intolerance include permeability of the intestinal mucosal barrier, histology of duodenal biopsy, and mucosal gene expression. The symptoms of gluten sensitivity may also have another genetic background of food intolerance independent of the HLADQ2, - DQ8 system and tissue transglutaminase (eg. in some psychiatric disorders). At present, there is no specific bio-marker of gluten sensitivity. The diagnosis is possible only by exclusion of other causes of symptoms and improvement on a glutenfree diet applied in a doubleblind placebo controlled manner with optional sequence of both stages to exclude the placebo effect due to nutritional intervention.

[Hepatic involvement in patients with non-Hodgkins lymphoma].

Abstract: Non-Hodgkins lymphoma (NHL) represent the most frequent hematological malignancy with frequent extranodal involvement. We have identified 79 pts (4.6%) out of 1,712 patients with NHL, who were diagnosed in our center between 1999-2010. Five cases were primary extranodal lymphomas and we have observed one primary hepatic lymphoma (0.015%). The most frequent (61.3%) NHL subtype in our cohort was diffuse large B-cell lymphoma. B-NHL formed 92.4% of all lymphomas. We have observed high number of HBsAg positive patients (10%). The whole group have poor prognostic features with high number of patients (85%) with intermediate-high and high risk according to international prognostic index. The patients were treated with chemotherapy in 95%, B-NHL patients recieved immunochemotherapy with rituximab in 77%. The median progression free survival, resp. overall survival 4.6, resp. 8.4 years in the whole group and 1.4, resp. 8.4 years in diffuse large B-cell lymphoma were observed with median follow-up 4.5 years. The outcome of T-NHL patients was significantly worse with overall survival median 1.2 vs 8.4 years (p < 0.033). The patients with B-NHL treated by immunochemoterapy with rituximab had significant death risk reduction (HR 0.44, p = 0.03) compared to the patients treated with chemotherapy.

Lipids and the size of lipoprotein particles in newly diagnosed and untreated patients with type 2 diabetes mellitus

Abstract: Type 2 diabetes mellitus leads to the typical known form of dyslipidaemia among the patients. This dyslipiademia type re-presents prognostically important type of atherogenic dyslipiadaemia, that significantly increases the risk of atherothrombosis. Estimation of the size of lipoprotein particles with Lipoprint method among newly diagnosed, untreated patients with these patients have not been evaluated yet. Dyslipidaemia among patients with type 2 diabetes mellitus has its course and changes after the treatment. At the beginning i tis characterized by the significant increase of VLDL, large and middle size IDL lipoprotein particles, as well as by lowering of HDL particles. This lipoprotein profile has its own atherogenic potential. The course of the disease later leads to the change of dyslipidaemia, characterized by the increase of LDL levels (small dense particles), triglyceride levels and the persistence of the lower levels of HDLcholesterol. Hypolipidemic treatment leads to the significant lowering of cardiovascular risk, however despite treatment with statin or fibrate residual cardiovascular risk remains still very high.

[Hypertension in patients with polycystic kidney disease - incidence, pathogenesis, prognosis, therapy].

Abstract: Hypertension is common in patients with autosomal dominant polycystic kidney disease (ADPKD) very early usually already in adolescence and its occurrence precedes the decrease of glomerular filtration rate. Expansion of renal cysts causing local renal ischemia and activation of the reninangiotensin system is believed to play a decisive role in its pathogenesis. Hypertension in ADPKD leads to early development of left ventricle hypertrophy and definitely contributes to the progression of chronic renal insufficiency. In ADPKD optimal control of blood pressure dramatically decreases the risk of left ventricle hypertrophy and contributes to its regression, but the beneficial effect of optimal compared to standard blood pressure control on the progression of chronic renal insufficiency has yet to be unequivocally demonstrated. Angiotensin converting enzyme inhibitors and/ or angiotensin receptor blockers are the drugs of choice in the treatment of hypertension in ADPKD. New drugs blocking the growth of renal cysts (e. g. inhibitors of V2 vasopressin antagonists) may have in ADPKD positive impact not only of the growth of the cysts and kidney volume, but also on the rate of loss of glomerular filtration rate. The influence of these drugs on the control of blood pressure, if any, remains uncertain.