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Ascorbic acid is a well-described molecule which acts as a cofactor in many reactions and mediates a variety of biological functions. Despite its simple structure, vitamin C has a wide range of interesting effects that bring enormous potential to the clinical practice. The article summarizes available data on efficacy and safety in oncology.

Contrast induced nephropathy is associated with worse clinical outcome in patients undergoing coronary intervention. The most profound risk factor is advanced chronic renal insufficiency. Due to the increasing number of coronary interventions on severally ill patients, there is a need of modern therapeutic approach that could reduce the volume of contrast media to minimum or even zero. Herein, the authors present a case report of a 68-year-old patient with chronic kidney disease, who required elective coronary intervention (PCI) due to a significant lesion of the left anterior descending coronary artery. During this intervention, maximum emphasis was given on reduction of contrast media. To the best of our knowledge, this was the first similar intervention performed in the Czech Republic. Minimum contrast PCI guided by the intracoronary ultrasound, i.e. the IVUS-guided zero-contrast PCI may serve as a potential alternative to standard, angiography-guided PCI.

Thanks to developments in pharmacological and non-pharmacological treatment of heart failure over the last half century, there has been improved quality of life and reduced mortality and morbidity. Despite these advances, the prognosis of advanced heart failure remains poor and the number of patients with terminal heart failure is currently increasing. In the general medical community, knowledge of pharmacological and device therapy with implantable cardioverter-defibrillator or resynchronization therapy is prevalent. However, only a limited number of professionals, mostly in tertiary centres, have personal experience with the use of long-term mechanical circulatory support (MCS) in patients with advanced heart failure after the above conventional therapeutic options have been exhausted. The purpose of this communication is, therefore, to provide the general medical community with basic information about benefits, limitations and referral strategies for MCS.

The guidelines provide evidence-based recommendations for the management of COVID-19. The clinical manifestations of the disease are described and indication criteria for hospital admission of patients with COVID-19 are listed. Polymerase chain reaction and antigen testing are used in direct diagnostics. Indirect detection of infection by antibodies is currently of limited value. There are a number of hematological and biochemical laboratory test used to diagnose COVID-19. Pathological values of some laboratory parameters are associated with severity of COVID-19. Of the imaging studies, chest X-ray, chest computer tomography and lung ultrasound are used. COVID-19 therapy includes symptomatic and specific therapy (antivirals, immunotherapeutics and anticoagulants) and intensive care in the severe and critical forms of the disease. Remdesivir and favipiravir are available as antiviral agents. Immunotherapeutics include monoclonal antibodies (casirivimab/imdevimab, bamlanivimab/etesevimab), dexamethas one, baricitinib and tocilizumab. Low-molecular-weight heparin is a dominant form of anticoagulant therapy. The guidelines provide specific therapeutic recommendations for each stage of the disease. Antibiotics are recommended only if bacterial superinfection is suspected or demonstrated, which is not common in the early stages of the disease.

Vaccination is essential to manage the COVID-19 pandemic. Vaccination significantly protects against severe COVID-19, hospitalization and death; it also protects against symptomatic infection and reduces the risk of transmission to other people. Protection against the new SARS-CoV-2 variants may be lower, but protection against severe course and death remains high. Two mRNA vaccines (BNT162b2 and mRNA-1273) and two vector vaccines (AZD1222 and Ad26.COV2.S) are currently available in the Czech Republic. Vaccination of persons over 60 years of age and immunocompromised persons, who are demonstrably at the highest risk of a serious course of the disease, is of the utmost importance. In order to achieve adequate vaccination coverage, it is necessary to motivate other groups of people to be vaccinated, including children over 12 years of age and young adults. Vaccination is also recommended in pregnant women in the 2nd and 3rd trimesters and in breastfeeding women. For selected groups of vaccines, a third dose of vaccination is recommended (additional third dose 4 weeks after the second dose or a booster dose 8 to 12 months after the second dose). The side effects are usually mild, with serious complications (including anaphylaxis, thrombocytopenia with thrombosis syndrome, myocarditis, Guillain-Barré syndrome and capillary leak syndrome) being rare.

Chronic total occlusion is characterised by total discontinuation of a blood flow in coronary vessel present for at least three months. Typical finding involves filling of the distal arterial segments by collateral flow. Well developed collaterals usually provide sufficient supply to preserve myocardial viability, but frequently are not capable of preventing excercise ischemia in the occluded territory. Percutaneous intervention of a CTO is focused on ischemia reduction, improvement of excercise capacity and quality of life. A succesful recanalization of a CTO leads to an improvement of left ventricular systolic function. Patients presenting with acute coronary syndromes and a coincident CTO in non-infarct related artery show worse short and long-term outcomes as compared to patients without a CTO. Technolocigal and procedural evolvement over past decades with implementation of novel techniques used by experienced operators lead to a substantial succes rate imprevement with acceptable complications rate in contemporary CTO interventions.

Chronic obstructive pulmonary disease (COPD) is a heterogenous condition affecting hundreds of millions of people worldwide. COPD is a major health problem associated with significant morbidity and mortality. In this review, the authors present the current concept of care for patients with COPD in the Czech Republic, along with a summary of treatment recommendations formulated by the expert group of the Czech Pneumological and Phthisiological Society. A more detailed version of the position paper was published in 2020. The aim of this work was to transform the most recent scientific knowledge into the context of daily practice in the Czech Republic. Our concept of care for patients with COPD uses a complex approach with special emphasis on individual phenotypic features of the disease. Maximal effort has been put into individualization of treatment according to the presence of certain clinical phenotypes/treatable traits with respect to current scientific knowledge.

COVID-19 is an acute infectious disease, predominantly affecting the respiratory tract, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).

The manual contains basic information about the diagnosis, treatment and organization of care for COVID-19 patients staying in general wards.

Aim: Treatment with sacubitril/valsartan (S/V) significantly improves cardiovascular morbidity, mortality, quality of life and prolongs the survival of chronic heart failure patients with reduced ejection fraction. The aim of the study was to evaluate changes in ejection fraction, NT-proBNP and glomerular filtration after 12 months of sacubitril/valsartan treatment., Methods: 30 patients (28 men) with chronic heart failure with reduced ejection fraction, functional classes NYHA II-III, EF LK < 40%, NT-proBNP (> 450 ng/l), with glomerular filtration > 0.5 ml/s/1.73 m2, with a potassium < 5.4 mmol/l were classified in the study. S/V treatment was started at systolic blood pressure > 100 mmHg. Ejection fraction, glomerular filtration rate and NT-proBNP values were compared before treatment and after 12 months of S/V treatment. The number of hospitalizations and deaths was also monitored., Results: During 12 months of S/V treatment there was a significant improvement in left ventricular ejection fraction (median initial 26.3%, after treatment 36.3%, difference 7.5%, p.

Stroke is one of the most severe complications of atrial fibrillation. Oral anticoagulation is the first choice therapy in prevention of cardiac embolic events. Particularly in patients with the history of serious bleeding, oral anticoagulation may be contraindicated. Percutaneous left atrial appendage closure represents an alternative in prophylaxis of cardiac embolic events. This review article describes physiology and pathophysiology of the left auricle, the most frequently used devices and their indications and scientific rationale.

The worldwide population is burdened with chronic kidney disease (CKD) from 10-13 %. Patients with CKD subsequently die to cardiovascular disease (CVD) and their complications. In the Czech population, in 2016, the number of patients with end stage renal disease (ESRD) on regular dialytic treatment was 6 739, or 674/1 000 000 inhabitants. Overall mortality in regular dialysis treatment patients was 18.4 % in 2016, of which 43 % died of cardiovascular complications. In view of this fact, a number of expert groups are concerned, among other things, with the problems of lipid metabolism disorders, with the aim of finding a common predictive marker (preferably also therapeutically qualifiable) to stratify patients dialyzed or potentially indicating hypolipidemic therapy. The aim of possible interventions is to minimize cardiovascular risk and subsequent complications resulting from cardiovascular disease (CVD), thus improving the quality of life of regular dialysis treatment patients.

Extremitovascular arterial ischemic disease (lower extremity peripheral arterial disease - PAD) is an important manifestation of systemic atherosclerosis and other arterial diseases of vascular system. The lower the ankle-brachial pressure index, the greater the risk of serious acute instable organovascular events (e. g. acute myocardial infarction, stroke). Complex prevention and treatment of extremitovascular arterial disease is discussed in this article. Angiology/vascular medicine is the fastest growing field of internal medicine.

Obesity reaches the dimensions of the global epidemic. It directly contributes to an increase in the prevalence of systemic diseases associated with obesity. Obesity and overweight globally cause 3.5 million deaths annually [1]. Non-alcoholic fatty liver disease has become the most common chronic liver disease in developed countries and is considered to be a liver manifestation of metabolic syndrome. The extent and burden of the disease are increasing and reaching epidemic proportions because of its close association with the epidemic of obesity and diabetes mellitus type [2]. It affects 30 % of the adult population [2]. There is an alarming increase in prevalence among children and adolescents. However, in the group of patients with high cardiometabolic risk, we can see a significantly higher prevalence of NAFLD. Prevalence in obese patients is 75 -92 %, in diabetic patients prevalence is between 60 -70 % [3]. A significant proportion of patients with NAFLD will suffer from a progressive form of the disease - non-alcoholic steatohepatitis (NASH), which is associated with the development of advanced liver fibrosis, cirrhosis, and its complications. The growing prevalence of NASH in the near future will bring the advanced cohort of our patients to the stage of an advanced liver disease. If the adverse epidemiological trend is not reversed, in the next decade the most common cause of liver transplantation will be NASH. A steadily rising trend can be seen in an increase in the number of cases of hepatocellular carcinoma causally related to NASH [4]. Treatment based on the influence of key pathogenetic mechanisms could alter the individual's future as well as the global burden arising with NASH. New molecules with anti-inflammatory and antifibrotic effects will play a key role in the future. Key words: cirrhosis - insulin resistance - metabolic syndrome - NASH.

Spine pain is one of the most common medical problems. Yearly incidence is reported between 15 and 45 %, lifelong is 60-90 %. Neurological examination, radiology examination, CT or magnetic resonance imaging are the basic diagnostics. Acute back pain is usually treated monotherapeutically, NSAIDs is the base. Chronic back pain treatment is multidisciplinary, it combines pharmacotherapy, physiotherapy, psychotherapy and other methods. In pharmacotherapy we proceed according to the WHO three-step ladder, including strong opioid medication for strong back pain. Neuropathic component of pain is usually eased with antidepressants or anticonvulsants.

Palliative care has evolved in the last half a century from a philosophy of care aiming at care of dying patients to specific/standalone medical specialization caring of patients with incurable diseases. Patients with advanced cancer suffer from physical and psychical symptoms, existential and social distress and have limited prognosis. Today we have strong clinical data about feasibility and usefulness of early integration of palliative care in oncology in terms of better quality of life, symptom control and survival. The question is not if, but when, whom and how is the best way to integrate palliative care into modern oncology. This article reviews data from clinical trials, presents models of cooperation for early integration and raises questions remained to be solved in a future.

A disease associated with immunoglobulin IgG4 is a rare unit with very variable symptoms. We describe the course and treatment of the disease in a patient who presented with multiple lymphadenopathy and infiltrates in the area of the retroperitoneum and pelvis and signs of chronic sclerosing pancreatitis. The disease was clinically manifested by a significant loss of weight, but also by a loss of perception of taste and smell. The diagnosis was made based on a high amount of IgG4 expressing plasma cells in the sampled tissue and an increased concentration of immunoglobulins of type IgG and mainly subclass IG4. Rituximab in 475 mg/m2 dose was used in the treatment, the initial four doses of rituximab were administered at 14-day intervals, always with a one-off administration of a 40 mg dose of dexamethasone. According to FDG-PET/CT, only partial remission of the disease was reached after 4 applications of rituximab and dexamethasone. The patient recovered its sense of smell and taste. In another 4 cycles ritu-ximab was administered on day 1 of a 28-day cycle. On days 1 and 15 of the cycle dexamethasone at 40 mg and cyclophosphamide at 600 mg were administered by intravenous infusion. After the completion of 8 cycles of treatment based on rituximab and dexamethasone and with cyclophosphamide added in the second half of the treatment, the control FDG-PET/CT examination proved the complete remission. Before the treatment commencement the concentration of the subclass of immunoglobulin IgG4 was equal to 51.0 g/l, after the completion of the aforementioned treatment it dropped to 3.5 g/l. The patient tolerated the treatment without any adverse effects. Ritu-ximab, dexamethasone and cyclophosphamide induced the complete remission of this disease.Key words: IgG4-associated/releated disease - rituximab.

Introduction: Autoimmune thyroiditis (AIT) and type 2 diabetes mellitus (DM2T) are the two most common endocrinological diseases worldwide. The relationship between T1DM and autoimmune thyreopathies is known and described, but the relationship between thyreopathies and diabetes type 2 is not clarified sufficiently through that studies manifest increasingly the connection between them., Objective: Investigate the prevalence of DM2T in patients with AIT in hypothyroid stadium and compare with common population and investigate a possible association between thyroid and glucose metabolism parameters., Material and Methods: The group consisted of 100 patients (33 men and 67 women) with AIT without until now documented glucose metabolism disorder, average age 65.63 ± 19.05 years. The control group (CG) consisted of 100 subjects without until now documented thyreopathy and glucose metabolism disorder (37 men and 63 women), average age 63.85 ± 18.98 years. We realised venous blood sampling and determined thyroidal and glycid metabolism parameters., Results: The study did not confirm higher prevalence of diabetes in patients with AIT [3 (3 %) vs 4 (4 %), p = 1]. There were no statistical significant differences between glycid metabolism parameters in patients with AIT and CG. Also no glycid metabolism parameters correlated to thyroidal parameters., Conclusion: We did not confirm higher prevalence of DM in patients with AIT.Key words: autoimmune thyroiditis - diabetes mellitus type 2.

Background: Patients with sensitive EGFR mutations are already being treated with first and second generation tyrosine kinase inhibitors (TKIs). However, resistance to these drugs occurs over time, and over half of all cases is caused by a mutation (T790M) in the EGFR kinase domain. Osimertinib offers a new treatment option that overcomes this problem. Unfortunately, resistance to this drug also develops after several months of treatment and is caused by another mutation (C797S) in EGFR., Case Report: Our case report provides evidence for the progressive development of EGFR-TKI resistance in a patient with a deletion of exon 19 in the EGFR gene. First, based on a mutation (T790M) identified after afatinib treatment and a subsequent mutation (C797S) mutation identified after osimertinib treatment. We mention overcoming this resistance (C797S) mutation by using 4th generation EGFR-TKI and other alternative procedures (chemotherapy, immunotherapy, and combinations of older EGFR-TKI generations). We also mention a rare case of peritoneal metastasis that occurred after previous treatment with osimertinib that we attempted to ameliorate by using erlotinib because the impaired condition of the patient did not allow treatment by chemotherapy. There are documented cases in which erlotinib has been successfully given to patients with peritoneal metastases and patients with the EGFR mutation C797S following progression to afatinib. This was not the case in our patient, probably because of the remaining EGFR mutation T790M., Conclusion: In our case report, erlotinib did not show efficacy after progression to osimetinib. Nowadays, chemotherapy is the only possible treatment in patients with good a performance status. The next-generation of TKIs are undergoing promising developments.Key words: EGFR - deletion on exon 19 - mutation T790M - mutation C797S - afatinib - osimertinibSubmitted: 12. 9. 2017Accepted: 12. 10. 2017 This project was supported by grant AZV 17-30 748A. The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study. The Editorial Board declares that the manuscript met the ICMJE recommendation for biomedical papers.

States associated with insulin resistance, as overweight/obesity, type 2 diabetes mellitus (DM2), cardiovascular diseases (CVD), some cancers and neuropsychiatric diseases are characterized with a decrease of long-chain polyunsaturated fatty acids (LC-PUFA) levels. Amounts of LC-PUFA depend on the exogenous intake of their precursors [linoleic (LA) and α-linolenic acid (ALA)] and by rate of their metabolism, which is influenced by activities of enzymes, such as Δ6-desaturase (D6D, FADS2), D5D, FADS1, elongases (Elovl2, -5, 6).Altered activities of D5D/D6D were described in plenty of diseases, e.g. neuropsychiatric (depressive disorders, bipolar disorder, dementia), metabolic (obesity, metabolic syndrome, DM2) and cardiovascular diseases (arterial hypertension, coronary heart disease), inflammatory states and allergy (Crohns disease, atopic eczema) or some malignancies. Similar results were obtained in studies dealing with the associations between genotypes/haplotypes of FADS1/FADS2 and above mentioned diseases, or interactions of dietary intake of LA and ALA on one hand and of the polymorphisms of minor allels of FADS1/FADS2, usually characterized by lower activities, on the other hand.The decrease of the desaturases activities leads to decreased concentrations of products with concomitant increased concentrations of substrates. Associations of some SNP FADS with coronary heart disease, concentrations of plasma lipids, oxidative stress, glucose homeostasis, and inflammatory reaction, were described. Experimental studies on animal models and occurrence of rare diseases, associated with missing or with marked fall activities of D5D/D6D emphasized the significance of desaturases for healthy development of organism as well as for pathogenesis of some disease.

Basic overview of diagnostic errors with particular focus on cognitive biases and strategies to minimize or avoid them.

Differential diagnosis of solid pancreatic masses using EUS FNA is in 1015 % of cases still challenging. Promising method, which helps to distinguish between chronic pancreatitis and cancer, is point mutations of the proto-oncogene KRAS test. This method is not established in routine clinical practice yet.Objectives were the determination of the sensitivity of the KRAS assay using various kinds of samples of patients with pancreatic mass and testing the effect of the presence of KRAS mutations on the prognosis of survival. 147 patients underwent EUS-FNA examination of pancreatic mass, accompanied by blood sampling with subsequent separation of plasma for the detection of circulating tumor DNA. Part of biopsy sample was left native in a stabilizing solution and part as cytological smear. Samples (native aspirates, cytological smears, plasma) were examined for the presence of KRAS mutation by heteroduplex analysis, denaturing capillary electrophoresis.Among 147 patients with pancreatic masses, 118 were diagnosed as a cancer, 26 chronic pancreatitis, 3 neuroendocrine tumor. In total 147 native aspirates, 118 cytological smears and 94 plasma samples were examined. The highest sensitivity of KRAS mutation was reached in the group of pancreatic cancer patients using cytology, in which 90 % of KRAS mutation was detected (106/118 of the samples). When using the native cellular aspirates, mutation was detected in 78 % (92/118 samples), and examination of plasma was positive in 27 % (24/90 samples). In four patients with chronic pancreatitis KRAS mutations was detected, although none has been cytologically confirmed as a cancer. Two of these four patients were confirmed in the course of the disease as a cancer, one patient died because of alcoholic delirium and the last one was indicated for surgery recently.Examination of KRAS mutations can be performed in all patients undergoing EUS-FNA, with the cytology being the most reliable type of sample for genetic tests. KRAS examination would be reasonable to introduce into routine clinical practice in a group of patients with unclear differential diagnosis of chronic pancreatitis, especially in those with suspicion of cancer in inflammatory terrain.Kexwords: pancreatic cancer, chronic pancreatitis, KRAS mutation , EUS-FNA.

Traditionally, parenteral (i. e. intravenous) antimicrobial therapy has been used in inpatients with various bacterial infections. In recent decades there has been growing experience with outpatient parenteral antimicrobial therapy, mainly in the USA and western Europe. This article provides basic information on OPAT, based on available literature and the author´s experience on running OPAT service in the UK.

Preimplantation genetic diagnosis (PGD) is a complex approach for detecting genetic abnormalities in early-stage embryos using genetic or molecular cytogenetic methods. Recently, single cell genomic methods based on DNA microarrays have been used for PGD. In the presented paper, we discuss and demonstrate the possibility to detect copy number variation (CNVs) in trophectoderm cells biopsied from 5-day embryos using 60-mer oligonucleotide-based array-CGH with CytoSure 8 × 15K Aneuploidy Array. Whereas this microarray platform was originally designed for analysis of unamplified DNA derived from many cells, the new methods, developed for single-cell genomics, allow the application of oligo arrays technology in preimplanation genetic diagnosis. Preclinical validation of single cell array-CGH was made by analysis of 30 positive and negative controls. Validation process included whole genome amplification of DNA from 5-10 cells with normal karyotype and from samples with known aneuploidies and structural aberrations. Subsequently, we analyzed the whole genome profiles in 118 embryos; aneuploidies of chromosomes were observed in 26.7%; segmental imbalances were proved in 6.8% of embryos. Our first experience confirmed that this oligonucleotide-based array technique enables high-resolution preimplantation aneuploidy screening of all the 23 chromosome pairs and sensitive preimplantation diagnosis of segmental imbalances such as deletions, duplications and amplifications.

In this experiment, newly synthesized ultrashort-acting blockers of β-adrenergic receptors were tested. Compounds were synthesized at the Department of Chemical Drugs of Pharmaceutical Faculty VFU Brno as esters of aryloxyaminopropanol, thereby gaining a very short half-life in blood plasma. Experiment was conducted in vivo in a rat model. Changes in systolic blood pressure and heart rate were monitored by invasive method in normotensive rats. The values ​​of blood pressure and heart rate were recorded for 20 minutes following the i.v. administration of tested substances or placebo into the jugular vein. In the experiment was tested a series of four substances (2MC2, 2MC2b, 2MC2c, 2MC2d) with different alkyl chain length at a dose of 3.0 mg·kg⁻¹. After evaluation of results was carried out the second part of the experiment, i.e. testing of substances 2MC2c and 2MC2d at a lower dose of 1.0 mg·kg⁻¹. The results show the best effect of 2MC2d, asubstance with longest alkyl chain and highest lipophilicity.

Soft tissue tumors (SSTs) constitute a broad spectrum of neoplasms with diverse biological properties. Rare or unusual types are often difficult to classify. Recent studies show, that a significant subset of SSTs including many types of sarcomas are associated with specific genetic changes such as chromosomal translocations producing chimeric genes, which play a role in the pathogenesis of SSTs. Because SSTs represent a diagnostically challenging group of tumors, molecular-genetic techniques (FISH or PCR) are useful as supplementary and/or confirmatory diagnostic tools. In the present paper we demonstrate the usefulness of a combined diagnostic approach using the tools of classical histopathology and immunohistochemistry together with the molecular diagnostic approach in selected nosologic entites.

Introduction: Light microscopy and electron microscopy rank among methods to diagnose of cardiomyopathy in forensic medicine, and, recently, the methods of molecular biology., Methods: Investigation of 27 year old man who collapsed on his way to work. The Rescuers did not succeed resuscitation of vital function. Samples were H-E stained and processed for the electron microscopy. RNA was isolated from the tissue for the alpha, beta, gama actine primer investigation., Results: By H-E staining we proved irregular hypertrophic cardiomyocytes (disarray) with the links and loci patches of thin fibrosis. Ultrastructurally we diagnosed a disarray of Z-bands, accumulation of mitochondria, rectangular nuclei of cardiomyocytes. We have detected rare plasmocytes and leucocytes with specific granules in cytoplasma. In the electronogrames we can see myofibriles oriented longitudinally and transversally. A genetic examination demonstrated beta actin mutation., Conclusion: Cardiomyopathy can be a cause of sudden and unexpected death in young individuals and its diagnostics requires an interdisciplinary collaboration., Keywords: Sudden and unexpected death - hypertrophic cardiomyopathy - ultrastructure of cardiomyocyte - gene mutation.

Background: Lymphomatoid granulomatosis (LyG) is a rare multisystemic angiocentric and angiodestructive B lymphoproliferative disease that was first described by Liebow in 1972. Disease was then in the "gray zone" between vasculitis and lymphoproliferative disease. LyG is currently categorized as a primary B lymphoproliferative disease associated with Epstein-Barr (EB) virus according to the World Health Organization (WHO) classification of tumours. EPIDEMIOLOGY, CLINICAL COURSE AND TREATMENT: Lymphomatoid granulomatosis is a rare disease with unknown prevalence. It occurs more often in males (male : female ratio 2 : 1) between the 5th to 6th decade of life and is more frequent in Europe than in Asia. Lungs are typically the predominantly affected organ; the disease spreads predominantly by extralymphatic manner. Spleen and lymph nodes are affected at an advanced stage. The clinical features are often nonspecific. Dyspnea, cough, hemoptysis, chest pain are the most common features with/without B symptoms (fever, night sweats, weight loss) in the pulmonary involvement. The radiographic finding of the lung is very diverse, but when there are multiple bilateral nodular lesions with basal predominance in perilymphatic distribution, we should think of this disease, although LyG rarely occurs. The histopathologic examination of affected tissue (most commonly the lung) is necessary to confirm the diagnosis. The thoracoscopy is used mainly. When the pulmonary findings are without any response to antibiotics, the autoimmune cause and other granulomatous inflammations (tuberculosis, sarcoidosis, etc.) are excluded, this diagnostic performance is indicated. Prognosis is variable - from spontaneous remission to progressive disease, often with aggressive behavior. Median survival is 14 months from diagnosis and mortality rate is 60% in the first year - despite the treatment. Treatment strategy is chosen depending on the histological grade. The therapy is not yet standardized. Interferon α, rituximab, glucocorticoids, cyclophosphamide and combined immunochemotherapy have been used for the treatment. The disease may lead to pulmonary failure, fatal CNS (central nervous system) involvement and sometimes develops into progressive EB virus positive lymphoproliferative disorder., Conclusion: Improvements in understanding of the biology of LyG, especially in determining the precise role of EB virus infection in its pathogenesis may lead to optimization of treatment strategies for this disease. Novel treatment modalities are urgently needed due to unfavourable prognosis. Adoptive immunotherapy appeals to be a promising approach.

Lipoxygenases (LOX, linoleate: oxygen oxidoreductases, EC 1.13.11.12) constitute a family of dioxygenases, which contain non-heme, non-sulfide iron. These enzymes occur not only in animals, but in plants as well. They have been detected in coral, moss, fungi and also in some bacteria. LOXs catalyse the regiospecific and stereospecific insertion of molecular oxygen into the molecule of polyunsaturated fatty acid with the cis,cis- -1,4-pentadiene system to yield the corresponding hydroperoxides. This step of dioxygenation leads to a cascade of reactions called the lipoxygenase (octadecanoid) pathway. The products of this pathway (called oxylipins) play an important role as signal molecules in wound healing and defence processes in plants. In animals they are involved in inflammation, asthma and heart diseases.

Aim: Analysis of the incidence of tick-borne encephalitis (TBE) in the Czech Republic (CR) in 2001-2011 in different administrative regions and municipalities with extended power (MEPs)., Material and Methods: Each TBE case reported to the EPIDAT system was matched to the respective MEP or Prague according to the place of residence. The annual TBE incidence was calculated per 100 000 permanent residents (mean) of each administrative region and MEP. The overall incidence, age-specific incidence, and average incidence by administrative region per year and per the eleven-year period were calculated., Results: In the study period, the highest TBE incidence rates were found in the Plzeň Region, South Bohemian Region, and Highlands Region, neighbouring with Germany and Austria. The overall TBE incidence in the CR had a slightly upward trend resulting from different subtrends in various administrative regions. The overall trend was most influenced by the most affected regions with opposite trends - the Highlands Region and the South Bohemian Region. The South Bohemian Region with the highest average incidence in the study period of 23.4/100 000 population also showed the maximum effect on the country-wide age-specific incidence due to the trend in the age--specific incidence, sharply rising to peak in the age group 60-64. As it had long been the region with the highest incidence in the Czech Republic, vaccination campaigns were organized repeatedly there, targeting high-risk areas and children. The vaccine coverage rate in school-age children in the last decade was about 50%. The analysis of age group trends showed no considerable increase in 0-14-year-olds in 2011, i.e. the year with the second highest TBE incidence ever reported in the CR, in contrast to 15 to 44-year-olds where the TBE incidence rates were three times as high. From this it can be inferred that the post-vaccination antibody level and its protective effect wane over years unless a booster dose is given. The incidence trend for TBE in 45-64-year-olds, i.e. the age group who lived life long inside or close to the most active TBE foci, suggests that the contact with the TBE virus does not induce protective herd immunity. The analysis of TBE incidence in the population of smaller administrative areas provides more detailed information. In six MEPs, the average TBE incidence over the 11-year period was more than 30/100 000, with a peak of 58/100 000., Conclusion: Although the most important epidemiological information for a disease with natural focality is the place of acquisition of infection, the long-term evaluation of TBE incidence according to the patients place of residence is also relevant. The data on TBE incidence in the population of 205 MEPs provide helpful information for campaigns to reduce the risk of TBE infection targeted to human behaviour in TBE natural foci and preventive measures, particularly vaccination. It cannot be excluded that residents of high-risk areas will continue risky behaviour even in the future.

When making prescriptions for total parenteral nutrition (TPN) it is necessary to take into consideration also substitution with calcium and phosphorus. Under some clinical conditions, or in certain groups of patients, it is necessary to supply these substances in high doses with a reduced volume, which due to mutual interactions may be problematic. This experimental paper therefore examined the compatibility of commercially available or individual preparations containing the compounds of calcium and phosphorus. These preparations were examined in a mixture with clinically employed solutions of amino acids or with solutions of glucose. The evaluation was performed by titration until the development of a visible precipitate and also by means of the pharmacopoeial method of evaluation of particles below the level of visibility. Hydrogen phosphate was found to possess a lower compatibility and stability in mixtures containing calcium salts in comparison with dihydrogen phosphate or organic phosphate. Nevertheless, no significant differences were found between dihydrogen phosphate and organic phosphate. The experiment confirmed a better stability of organic calcium salt versus the inorganic one only in the samples containing solutions of amino acids. Of the solutions of amino acids under study, the best stabilizing properties were found in the solutions intended for use in neonatology and paediatrics.

Background: Statin monotherapy for dyslipidemia only rarely achieves recommended target values of plasma lipids. Statin plus ezetimibe is a feasible treatment option. The aim of the present study was to test efficacy and safety of statin plus ezetimibe combination in the treatment of severe dyslipidemia in patients coming to an ordinary lipid and diabetology department., Methods and Results: A retrospective evaluation of 3 months treatment in 82 dyslipidemia patients (25 male, 57 female) with unsatisfactory statin monotherapy results (average equivalent of 30 mg atorvastatin) was performed. Ezetimibe 10 mg per day was added to preceding treatment. The group included 26 diabetics type 2. The addition of ezetimibe resulted in statistically significant decrease of plasma total cholesterol (TC) (-21%), LDL-C (-28%), triacylglyceroles (TAG) (-26%) and HDL-C (-6%). The recommended values of LDL-C were achieved in 42% of patients. In the diabetic subgroup a significant decrease of TC (24%), LDL-C (33%) and TAG (18%) was observed. There was no significant decrease of HDL-C. The recommended value of LDL-C was achieved in 48% of diabetics. There were no unfavourable side effects., Conclusions: The addition of ezetimib in a dose of 10 mg in hyperlipidaemia patients who had not achieved the recommended target values of LDL-C resulted in a subsequent significant decrease of both TC and LDL-C. It also enabled to increase the number of patients achieving the recommended target plasma lipid values. The treatment was safe and was not associated with adverse effects.

Background: Pedal bypass grafting has been the method of choice at Na Homolce Hospital's Vascular Surgery Department since 2008., Methods and Results: During the period from June 2008 to December 2011, 29 pedal bypass procedures were performed in 27 patients. No perioperative mortality was recorded. Early occlusion of the graft occurred in three patients and two patients experienced delayed occlusion. Loss of the limb as a result of graft occlusion was unavoidable in two cases and one amputation had to be performed despite a patent graft. The primary patency rate for the period under review is 82.75%, and we were able to salvage the limb in 89.65% of cases. Follow-up results for our cohort are comparable with those from other centres dealing with the same problem., Conclusions: Pedal bypass has excellent early and long-term results and makes a significant contribution to reducing the number of major amputations of the lower limbs.

Minimally invasive surgery provides an attractive alternative compared with conventional surgical approaches and is popular with patients, particularly because of its favourable cosmetic results. Vascular surgery has taken its inspiration from general surgery and, over the past few years, has also been reducing the invasiveness of its operating methods. In addition to traditional laparoscopic techniques, we most frequently encounter the endovascular treatment of aneurysms of the thoracic and abdominal aorta and, most recently, robot-assisted surgery in the area of the abdominal aorta and pelvic arteries. Minimally invasive surgical interventions also have other advantages, including less operative trauma, a reduction in post-operative pain, shorter periods spent in the intensive care unit and overall hospitalization times, an earlier return to normal life and, finally, a reduction in total treatment costs.

Vast knowledge has accumulated recently on the role of reactive oxygen and nitrogen species (RONS) in clinical medicine. Strong evidence was disclosed on their important role in the pathogenesis of several diseases. Free radicals have unpaired electron and this is the reason for extreme reactivity causing propagation reactions that lead to the multiple damage to cells. Oxidizing agents belong to the family of reactive species. Reactive oxygen species are produced during biochemical processes such as oxidative phosphorylation, phagocytosis and metabolism of purins. Overproduction of reactive oxygen species can cause the tissue damage. Reactive nitrogen species are produced by inhibition of nitric oxide synthase by the action of asymmetric dimethylarginine. Peroxisomal oxidases, NAD(P) oxidase, xanthinoxidase, nitric oxide synthase, myeloperoxidase and lipooxygenase catalyze biochemical reactions producing reactive oxygen and nitrogen species. Biochemical and molecular processes in cells are negatively influenced by chemical modification of DNA, proteins and lipids caused by the action of reactive oxygen and nitrogen species. Antioxidant metabolites and enzymes work together to stop and to prevent oxidative modification of biomolecules. Reactive oxygen and nitrogen species play an important role in the pathogenesis of many diseases such as atherosclerosis, diabetes, hyperlipidaemia and neurodegenerative diseases.

Events following which anti-D immunoglobulin should be given to all RhD negative women with no anti-D antibodies: First trimester indications (50 microg)--termination of pregnancy, spontaneous abortion followed by instrumentation, ectopic pregnancy, chorionic villus sampling, partial molar pregnancy; Second and third trimester indications (100 microg)--amniocentesis, cordocentesis, other invasive prenatal diagnostic or therapeutic procedures, spontaneous or induced abortion, intrauterine fetal death, attempt at external cephalic version of a breech presentation, abdominal trauma, obstetric haemorrhage; Antenatal prophylaxis at 28th weeks of gestation (250 microg); Delivery of an RhD positive infant * (100 microg); Minimal dose: before 20 weeks gestation--50 microg (250 IU), after 20 weeks gestation **--100 microg (500 IU); Timing: as soon as possible, but no later than 72 hours after the event. In cases where prevention of RhD alloimmunization is not performed within 72 hours of a potentially sensitising event, it is still reasonable to administer anti-D immunoglobulin (IgG anti-D) within 13 days, and in special cases, administration is still recommended up to a maximum interval of 28 days postpartum.; FMH (fetomaternal haemorrhage)--If the amount of fetal erythrocytes which entered the maternal circulation is quantitatively determined, administration of 10 microg IgG anti-D per 0.5 ml of fetal erythrocytes or 1 ml of whole blood is indicated. *also if the RhD type of the infant has not been determined or is in doubt, **in conjunction with a test to assess the volume of any fetomaternal hemorrhage.

Background: The overall fatty acid (FA) composition, and especially proportions of n-6 and n-3 polyunsaturated fatty acids in plasma and membrane lipids, greatly impacts on cell and organ functions as well as on many biological processes., Material and Methods: Polyunsaturated FA determine membrane fluidity and thus modulate activities of membrane proteins (enzymes, carriers and receptors). They also are precursors of pro- and anti-inflammatory eicosanoids and other autacoids (resolvins, protectins). Thus, alterations in lipid FA composition of critically ill patients affect reactivity of the organism to numerous pathological stimuli. The objective of this study was to analyse FA composition of plasma triacylglycerols, cholesteryl esters, plasma phospholipids and erythrocyte phospholipids in septic patients., Results: The study group consisted of 30 septic patients, 19 of whom were available for three samplings: Sampling 1 was 24 hours after the onset of sepsis, Sampling 2 was 7 days after Sampling 1, and Sampling 3 was 7 days after recovery from sepsis. Eight septic patients died. Compared to healthy controls, a decrease in n-6 polyunsaturated fatty acids accompanied by increase in monounsaturated fatty acids in cholesteryl esters, plasma phospholipids and erythrocyte phospholipids persisted in all three samplings of septic patients., Conclusions: This effect of sepsis was significantly greater in cholesteryl esters and plasma phospholipids of non-surviving septic patients than in surviving ones. Moreover, non-survivors had lower proportions of n-3 polyunsaturated fatty acids in plasma phospholipids compared to survivors. The significant decrease in proportion of polyunsaturated fatty acids in lipids of septic patients in the course of sepsis reflects the severity of their critical state and supports the importance of appropriate nutritional polyunsaturated fatty acids supplementation.

Background: Despite the introduction of new imaging methods, the prognosis of pancreatic carcinoma (PC) remains hopeless. Therefore, there has been exerted much effort to elucidate the risk factor enabling the diagnosis of PC in the "preclinical state". At the time of PC diagnosis, more than 30% of patients suffer from diabetes mellitus, much more often than in the rest of the population. It is not clear whether DM is a risk factor for PC onset or DM appears secondary to the destruction of the gland by the tumor progression or by the effect of unknown factors produced by the cancer cells., Methods and Results: We enrolled 204 individuals into the study, 69 of them were controls, 70 patients had type 2 diabetes mellitus and 65 cases had newly diagnosed PC. The patients with PC had in 68% of cases disturbed glucose homeostasis and significantly higher values of insulin resistance index (HOMA-IR) in comparison with the control group. The presence of glucose homeostasis disturbances does not influence tumor staging and localization., Conclusions: Results of our pilot study confirmed the so far unsatisfactory state of PC diagnostics (majority of cases fall to stages III and IV) and corroborated the close relation to DM. The early markers for the risk of pancreatic carcinoma development should be searched among the factors participating in the regulation of the glucose homeostasis and insulin sensitivity.

Purpose of the Study: To present the results of surgical treatment of carpometacarpal joint arthritis of the thumb, using cannulated screw fixation which is stable and, after bony union, allows the patient to do also harder manual work, Material: In the years 2000 to 2005, this method was used for 20 operations in 18 patients (16 women and two men); one man and one woman had bilateral surgery. The right hand was operated on in seven cases and the left one in 13 cases. The average age of the patients was 61 years., Methods: The procedure was performed from the dorsoradial approach, access to the joint was gained between the extensor pollicis brevis and abductor pollicis longus tendons, and care was taken to protect the superficial branch of the radial nerve. The articular surface of the trapezium bone and the first metacarpal base including osteophytes were resected and arthrodesis was carried out by means of a 4.5 mm cannulated screw. The final position of the thumb axis was at 40 degrees to 45 degrees palmar abduction, 20 degrees to 25 degrees extension and 10 degrees to 15 degrees pronation. A plaster hand splint was applied for 6 to 8 weeks post- operatively. The patients were capable of full use of the hand at 3 months after surgery., Results: Evaluation included a pain scale of 1 to 5 grades, range of motion, reduction of muscle strength and fine motor function. All operative wounds healed by first intention, no infection or neurological complications were recorded. Primary union was achieved in 18 cases, two developed pseudoarthrosis. The patients reported improvement on the pain scale by 2 grades on average. However, in thumb opposition tasks, the range between the tip of the thumb and the fifth metacarpophalangeal joint decreased on average by 20 mm. Fourteen patients reported deterioration of fine motor function. All patients were satisfied with improved muscle strength enabling them to do more demanding physical work., Discussion: The results of carpometacarpal joint arthrodesis by means of a cannulated screw are comparable with those of arthrodesis using other implants. The final thumb position is discussed as well as the use of suitable fixation material in order to prevent pseudoarthrosis. Issues such as the use of interpositioned tissue, shortening of the radial column and the resultant limited muscle strength in resection arthroplasty, and the choice of a most suitable implant and possibility of its failure in alloplasty are also discussed., Conclusions: Arthrodesis with cannulated screw fixation is best for treatment of the carpometacarpal joint of the thumb with stage III rhizarthritis (Eaton classification). It results in an axis-stable thumb that is pain free and capable of physical activity and firm grip.

Purpose of the Study: The treatment of femoral neck fractures shows a relatively high number of poor outcomes, usually due to late complications, such as avascular necrosis of the femoral head or pseudoarthrosis. The latter may develop when the osteosynthesis of osteoporotic bone fails. The aim of this retrospective study was to evaluate a group of patients treated by osteo- synthesis for intra-capsular femoral neck fractures at our department, and to verify indication criteria and identify the therapeutic procedures that are best suited to our conditions., Material: In the 1997-2001 period, a total of 81 patients with intra-capsular femoral neck fractures were operated on. Of these, 64 treated by dynamic hip screw (DHS) fixation were followed up for at least 5 years. There were 33 women and 31 men; the average age was 21.5 years (range, 21 to 74 years)., Methods: The Garden classification was used to evaluate the displacement of femoral neck fractures. Preferably, osteosynthesis was carried out by closed reduction; only exceptionally was an extension device for the operating table used. A 135-degree sliding hip screw, with a short thread, directed to the head centre and a two-hole side plate were used most often.The average follow-up was 6.9 years. Evaluated were: the occurrence of late complications in relation to the length of time between injury and surgery, quality of fracture reduction, use of an anti-rotation screw and necessity of repeat surgery., Results: Garden I or II fractures were diagnosed in 13 patients, 51 had Garden III or Garden IV fractures. Bone union without complications was achieved in 73.4 % of the patients within 12 months of surgery. Late complications were found in 26.6 %; of these, only one had Garden I fracture and the rest were Garden III and IV fractures. An anti-rotation screw was used in 39 patients (60.9 %) and its use had no effect on the development of late complications. Of the seven patients who developed pseudoarthrosis, the screw was used in four (57.1%); out of the nine patients with avascular necrosis, it was used in six (66.7 %). In the whole group, an unsatisfactory outcome of post-operative reduction was recorded in 29.7 %. In the patients with late complications this was found in 52.9 %, which was a statistically significant difference. Of the 17 patients with poor outcomes, 14 underwent total hip arthroplasty; in the patients with necrosis, arthroplasty was carried out at an average of 26 months post-operatively, in those with pseudoarthrosis it was at 7 months post-operatively., Discussion: For the treatment of intra-capsular fractures of the femoral neck, surgery is the most frequent approach, but there are controversial views on various relevant issues. An important factor affecting the treatment outcome is the patient's bone quality., Conclusions: Our results show a direct relationship between the extent of fracture displacement and late complications, i.e., avascular necrosis and non-union. The quality of fracture reduction had a greater effect on fracture non-union than on the development of femoral head necrosis. The length of time between injury and surgery played a lesser role than it is believed. The use of an anti-rotation screw was not significantly related to the occurrence of late complications. The DHS method is economical and available, and provided sufficient results whose comparisons with the literature data show that this therapeutic approach is correct.

Background: Combination of cetuximab and irinotecan is an efficacious second- (and further-)-line treatment-alternative in patients with EGFR-positive metastatic colorectal cancer refractory to irinotecan. In this retrospective study we present treatment results of patients treated combination of cetuximab and irinotecan in Masaryk Memorial Cancer Institute., Patients and Methods: Results were collected on forty-seven patients who started the therapy from July 2005 to February 2008. Primary outcomes were: response rate, time to progression and overall survival. Secondary outcomes were: treatment-related toxicity and identification of any predictive and prognostic markers. P-value was based on Gehan-Wilcoxon test or chi-square test and P-values < or = 0.05 were considered significant. The Kaplan-Meier method was used to estimate overall (OS) and progression-free survival (PFS)., Results: Forty-two patients were valuable for the treatment response. Objective response rate (complete and partial remission) was 35.7% (15 patients) and disease control (response and disease stabilization) was achieved in 30 patients (71.4%). The median time to progression was 6, 4 months (range 1, 5-25 months). On the date of statistical processing (median follow-up: 9, 2 months, range 2, 5-27 months) there were 26 patients alive and the median overall survival was 17, 1 months. We have confirmed correlation between the grade of the skin rush and the treatment response (p = 0.05) and time to progression ( p = 0.01), on the other hand there was no association between EGFR expression and these parameters. The therapy was also effective in 8 of 14 patients (57%), who had documented resistance to irinotecan., Conclusions: We have confirmed the efficacy of cetuximab and irinotecan combination for the therapy of patients with pretreated metastatic colorectal cancer. Our results are optimistic, but have to be validated in the course of time. The existence of nonresponding patients and by reason of pharmacoeconomy, we should give attention to the new molecular predictive and prognostic markers such as: K-ras-mutation and EGFR gene copy number.

Introduction: Trastuzumab is a humanized monoclonal antibody directed against the HER-2 receptor. Trastuzumab-based therapy significantly improves response rate (RR), time to progression (TTP) and overall survival (OS) for women with HER-2 positive metastatic breast cancer. Despite its initial efficacy, acquired resistance to trastuzumab develops in a majority of patients with MBC, and a large subset never responds, demonstrating primary resistance. The purpose of this retrospective study was to determine prognostic factors applicable to clinical practice., Methods: We enrolled 112 women with metastatic breast cancer, who started the trastuzumab-based therapy at Masaryk Memorial Cancer Institute until January 2007. Clinical and laboratory factors, such as: patients conditions, character ofmetastatic spread, histology, estrogen, progesterone and Her-2 receptor status, Her-2/neu gene amplification, and serum tumor markers CEA, CA 15-3 and extracellular domain of Her-2 receptor (S-HER-2 ECD) were monitored. The association of all factors to response to therapy, time to progression (TTP) and overall survival (OS) was assessed., Results: In 95% patients, the trastuzumab was combined with cytostatics (83% taxanes), 88,4% of patients started the trastuzumab as the first or second-line anticancer treatment. The median TTP was 284 days (9,3 months) and the median OS was 612 days (20,1 months) for all patients, RR was 54,5%. The highest RR was associated with the first-line treatment (p<0.0001) and with HER-2 gene/Chromosome 17 ratio > 2,2 (p=0,0092). Eleven patients (9,8%) discontinued the treatment because of toxicity, 7 patients did it as a result of cardiotoxicity (6,2%). CNS metastases occurred in 31 patients (27,7%). The S-HER-2 ECD was the most frequently elevated serum marker at the time of the treatment initialization (72,5%) and at the time of the progression (55,9%). Cox regression analysis identified S-HER-2 ECD levels at the beginning and between day 90 and 130 of the trastuzumab therapy as the best predictors of TTP. On the other hand the best predictor of OS was level of CEA before the treatment started and level of S-HER-2 ECD between day 90 and 130 of the trastuzumab therapy., Conclusions: We confirmed that the only one predictive marker for response to trastuzumab therapy is a proof of HER-2 tumor positivity.The highest prevalence of S-HER-2 ECD positivity among serum tumor markers and the strong association between initial and subsequent S-HER-2 ECD serum concentrations and time to progression and overall survival make the S-HER-2 ECD the most significant prognostic marker.

Background: Glioblastoma multiforme is the most frequent primary brain tumor in adults. Despite advances in surgery, radiotherapy and chemotherapy, its treatment remains unsatisfactory with very limited overall survival. In the year 2001, in cooperation with Department of Neurosurgery, Nemocnice Na Homolce and Nuclear Research Institute in Rez, we have started to treat glioblastoma patients with boron neutron capture therapy (BNCT)., Methods and Results: Cells of malignant brain tumors, especially that of glioblastomas, are able to accumulate boron compounds. If BNCT should be successful, it is necessary to reach selective accumulation of sufficient amount of 10B in the tumor and low accumulation in the normal brain tissue. After BSH administration, radiation with low energy thermal neutrons is delivered. It results in nuclear capture and fission reactions with subsequent selective damage of tumor cells. At the time of analysis 9 patients have been enrolled. Therapy was completed in 5 patients. Treatment has been very well tolerated. We observed minimal acute toxicity associated with radiation and no laboratory abnormalities after administrations of BSH. Unfortunately treatment results were quite unsatisfactory. The median time to progression and overall survival were shorter then expected with conventional treatment., Conclusions: BNCT is very well tolerated with only a modest toxicity. In contrast to standard radiation, BNCT patients receive only one dose of radiation. Nevertheless, in this small pilot study first results were inferior when compared either to outcomes of conventional therapy or to results reported from other BNCT groups. It might be explained that lower dose of radiation had been used. Further study will show whether the higher dose radiation can improve treatment results.

An immunochemical method was proposed for simultaneous determination of aflatoxin and ochratoxin A with the use of mixed solutions of the following reagents: standards of both mycotoxins, antiserums against the mycotoxins, and radioligands of 125I-aflatoxin B1 and 125I-ochratoxin A. The result of the analytical procedure is the value of concentration of the aflatoxin + ochratoxin A sum in the sample. The procedure needs half the amount of reagents as separate determination of each of the two mycotoxin, and is far less laborious. The proposed simultaneous immunoanalysis is suitable for large-are inspection of grain and feed safety from the viewpoint of aflatoxin and ochratoxin A levels.