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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.

Bronchiectasis is a clinically important, but poorly understood, pulmonary condition characterized by dilated and thick-walled bronchi. Bronchiectasis remains a significant cause of morbidity and mortality around the world. Targeted effort to early high-resolution computed tomography diagnosis and detailed confirmation of causation are in the spotlight of respiratory physicians in the developed countries. The risk population consists of subjects with persistent and/or productive cough, where another clear diagnosis has not been performed. Specific treatment tailored on underlying diseases and non-specific airway clearance techniques are able to improve symptoms, and reduce lung impairment. Evidence-based treatment algorithms for anti-inflammatory, and antibiotic treatment of stable non-CF BE will have to await large-scale, long-term controlled studies. Surgery should be reserved for individuals with highly symptomatic, localized bronchiectasis who have failed medical management. Unfortunately, there have been few well designed longitudinal or cross-sectional studies in the field of bronchiectasis. To give truly meaningful and generalizable results, a longitudinal observational study of bronchiectasis would require to enrol several thousand patients, more than any one center can enrol. The European Bronchiectasis Registry will create an open, pan-European registry of patients with non-CF bronchiectasis. The authors emphatically recommend that all respiratory specialist managed non-CF BE subjects should be actively involved in the European Bronchiectasis Registry.Key words: bronchiectasis - diagnosis - registry - treatment.

The disease referred to eponymically as Whipple's disease (WD) in medical literature was thoroughly described by the American physician and pathologist George Hoyot Whipple (1878-1976) in 1907 and given a temporary denomination of "intestinal lipodystrophy". According to literature, WD is rare, but its precise incidence has not yet been established. Familial incidence of the disease is acknowledged, and its immunogenetic pathogenesis is assumed. The incidence ofWD is prevailingly observed in middle-aged men (mean age 55), exceptionally at child age - the ratio being 3 to 6 for men and women, respectively. 1. Clinical diagnosis is based on symptoms in the GIT region and, in rare cases, on extraintestinal symptoms. Clinical symptomatology includes: abdominal pain with persistent diarrhoea (steatorrhoea), symptoms typical of malabsorption connected with weight loss, fevers, polyarthritic symptoms, swollen lymph nodes and, in part of patients, skin hyperpigmentation. Anaemia and hypoalbuminaemia (reduced IgA) are typically detected in laboratory tests. Rarer extraintestinal symptoms of the disease are of a diverse nature: cardiac lesions, cerebral lesions, ocular symptoms, conspicuous or even tumour-like enlargement of lymph nodes, lesions of the hemopoietic system. The clinical course ofWD is of progressive or remittent nature and the disease is fatal without treatment. Long-term therapy with antibiotics, especially a combination oftetracyclines (doxycyclin) and corticoids (dexametazone), or chloramphenicol in case of cerebral lesion, have a significantly positive effect on the course and prognosis of WD. From the point of view of pathology, WD is a multisystem infectious disease (Tropheryma whipplei) primarily affecting the GIT (39, 47, 52, 103) or different extraintestinal locations. Due to the known diversity of clinical symptoms, no clinical-diagnostic standard has been established for WD. Differential diagnosis includes different multisystem diseases, primarily malignant lymphomas (especially Hodgkin's disease). From the pathogenetic point of view, we can either assume the effect of a particular cytokine (or TNFalpha) activating macrophage phagocytosis or, if its production is normal, a disorder or defect of the respective receptor in the macrophage cellular membrane. The identification of "Whipple's bacteria" - Tropheryma whipplei - gen. nov. et sp. nov. was made possible by modern molecular biology research methodologies. Its cultivation allows both for the acquisition of the specific antibody and of detailed knowledge of its genoma (PCR, 16S rRNA sequencing).

The paper is aimed at differential diagnosis of increased sedimentation rate (ESR) from the point of internal medicine. After the interpretation of the term we describe the technique of the examination and possible errors in pre-analytical as well as analytical phase. The paper includes ranges for conventional FW assessment (analysis of ESR based on Fahraeus-Westergren) and the characteristics of newer methods. We list the overview of the most common causes that affect faster or slower ESR. The stress is put on the assessment of the causes of increased ESR and its persistence from the perspective of clinical practice, we also describe diseases with slower ESR. Attention is drawn to the comparison of the results of the most common acute phase reactants, especially to discordant results of ESR, CRP and procalcitonin in the serum, and to the contribution of the analysis of ESR and CRP in selected diseases. The final part is aimed at the correct diagnostic approach when assessing increased ESR of unknown etiology, underlining the significance of the patient´s history, physical examination and the position of basic as well as complementary laboratory methods and examinations including imaging techniques.

Decisions related to the treatment of oncological diseases bring various ethical dilemmas to healthcare providers caring for cancer patients. Along with the development of medicine and new therapeutic methods, there are also increased demands on the appropriate selection of eligible patients for allocation to a particular treatment method, which causes a number of ethical connotations. The paper deals with ethical issues in the course of oncology treatment, with theoretical bases for ethical decision-making and with ethical aspects of communication with patients suffering from oncological diseases. The paper also contains results of studies that dealt with methods of ethical reasoning of health professionals in relation with the Do Not Resuscitate (DNR) decision in oncology, and with understanding of the concept of ethical competence of health professionals in order to make, or be involved in, DNR decisions, and how relevant skills can be developed. Among others, the results of the studies pointed out that in order to make ethically based DNR decisions in oncology, physicians and nurses need to improve their knowledge of ethical theories.

The most common immune-mediated inflammatory rheumatic diseases, rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis and have reached significant advances in recent years with the introduction of biological therapies against cytokines and immune cells, but also against intracellular enzymes, specifically Janus kinases (JAKs). Intracellular JAK signalling is activated by binding of various cytokines or growth factors to the respective cellular receptors, allowing the activation of STAT (Signal Transducers and Activators of Transcription) transcription factors and ultimately the transcription of genes with important roles during the innate and adaptive immune response. Four Janus kinases have been described: JAK1, JAK2, JAK3 and tyrosine kinase-2 (TYK2). Four JAK inhibitors (tofacitinib, baricitinib, upadacitinib and filgotinib) are currently approved for the treatment of rheumatoid arthritis, and some for the treatment of psoriatic arthritis and axial spondyloarthritis. JAK inhibitors have varying selectivity against individual kinases. Some JAK inhibitors are being tested in other rarer systemic connective tissue diseases. The general advantages of JAK inhibitors are oral administration, rapid onset of action, and efficacy in monotherapy. The safety profile of JAK inhibitors compared with biologic therapy appears to be comparable, with a higher incidence of herpes zoster, and an increased incidence of major cardiovascular disease, thromboembolic complications, and cancer in at-risk patients is discussed. The aim of this paper will be to summarize the latest findings on JAK inhibitors in approved indications for the most common rheumatic diseases.

The paper focuses on conducting clinical trials on medicinal products for human use during the COVID-19 pandemic, which has brought entirely new ethical dilemmas to clinical research professionals, as well as to the general public. Growing ethical concerns emphasized the need for partially modified or completely new procedures in order to ensure the safety of clinical trial participants, compliance with good clinical practice, and minimizing risks to the clinical trial integrity and validity of data obtained from clinical trials conducted during the pandemic. The paper acquaints with emergency measures issued by the State Institute for Drug Control during the COVID-19 public health emergency, discusses quality management, methods of efficient verification of the safety of subjects and data validity, and last but not least, presents risk areas and their ethical aspects in conducting clinical trials during the COVID-19 pandemic.

Castleman disease (CD) describes a group of heterogeneous hematologic disorders with characteristic histopathological features. CD can present with unicentric (UCD) or multicentric (MCD) regions of lymph node enlargement. Some cases of MCD are caused by human herpesvirus-8 (HHV-8), whereas others are HHV-8-negative/idiopathic (iMCD). Treatment of iMCD is challenging, and outcomes can be poor. In this paper, we briefly report about symptoms of iMCD and about the International, evidencebased consensus diagnostic criteria for HHV-8-negative/idiopathic multicentric Castleman disease and International evidence based consensus treatment guidelines for idiopathic multicentric Castleman disease.

Immunoglobulin IgG4 related disease (IgG4-RD) is a heterogeneous disorder with multi-organ involvement recognised as a separate entity at the beginning of this century only. Evolving therapy is reviewed in this paper. Glucocorticoids are first choice drug but long administration of glucocorticoids is connected with many adverse effects. In case of combination glucocorticoids and immunosuppressive agents lower doses of glucocorticoids are needed, the response rate is higher and therapy is better tolerated. Rituximab is drug, that is possible use as monotherapy or in combination with glucocorticoids and immunosuppressive drugs. Only one study compared two immunosuporessive drugs, mycophenolate mofetil and cyclophosphamide. The response rated was similar but remissions were longer after glucocorticoids with cyclophosphamide then glucocorticoids with mycofenolat mofetil. No other comparative study of combination of various imunossupressive drugs with glucocorticoids was published. Rituximab has high number (90 %) of response rate in monotherapy, but can be used in combination with glucocorticoids and immunosuppressives. Rituximab is now preferred and recommended for maintenance therapy administered in 6-month interval. In case of advanced disease, we prefer therefore combination of rituximab, cyclofosphamide and dexamethasone for initial therapy followed by maintenance with rituximab in 6 months interval. There are two new drugs under investigation abatacept and dupilimab with promising results. Although we have very intensive therapies for good results of therapy early diagnosis before irreversible fibrotic changes in IgG4-RD involved organs is still needed.

Primary cardiac synovial sarcoma is an extremely rare tumor with a higher incidence in young men. The mean age of occurrence is 32 years. Synovial sarcomas are tumors with high aggressiveness, proliferate rapidly and metastasize to regional and distant lymph nodes or surrounding organs. The typical location of synovial sarcoma of the heart is the atrial and ventricular septum. Its size, the degree of infiltration of the surrounding tissues and the presence of metastases influence clinical symptoms, which are very non-specific. The low specificity of the symptoms complicates the clinical diagnosis and in most cases the tumor is detected during its progression or incidentally. The final diagnosis is based on histological examination. The primary and only method of treatment is a surgical solution with an effort to completely resect the tumor, followed by aggressive palliative chemotherapy. In the following paper, we present a case report of a 32-year-old man who was diagnosed with synovial cardiac sarcoma only on the basis of exacerbation of non-specific subjective complaints due to the complication in the form of of aneurysmal bleeding of the tumor mass.

Background: The terminology of adherence (or compliance) describing the patients medication taking behavior is often used inconsistently and fragmented in the literature. Therefore, the English original of so-called ABC Taxonomy was developed to classify and unify the terminology. The aim of this paper was to establish the first consensual translation of Czech terminology dealing with the issue of medication taking behavior using Delphi method., Methods: In the period from February to May 2021, a three-round anonymous online Delphi questionnaire survey was conducted. The questionnaire contained items for translations of seven terms and their definitions based on the ABC Taxonomy, while the resulting consensus was established by a predefined degree of agreement of the respondents., Results: Out of 106 contacted panelists representing different healthcare professions, 46 (43.4%) answered in the first round. Sufficient consensus ( 85%) was reached for the translation of two definitions. In the second round, 32 respondents managed to establish a consensus (> 75%) of one term and four definitions and 24 respondents in the third round established a mild (> 50%) to strong (> 95%) consensus for all remaining terms and definitions. The set of terms related to medication taking for the Czech language was as follows: adherence k léčbě, zahájení léčby, zavedení léčby, přerušení léčby, setrvání na léčbě, management adherence and obory související s adherencí., Conclusion: The consensual translations of all Czech terms and definitions related to medication adherence can contribute to greater harmonization and comparability of scientific papers as well as to enhance the communication between scientific and clinical community. However, this consensus needs to be confirmed by a larger number of experts dealing with adherence issue, including the involvement of professional societies.

Type 2 diabetes mellitus (T2DM) is common in patients with chronic heart failure and is associated with high morbidity and mortality. Significant advances have recently occured in the treatment of diabetes mellitus type 2 (T2DM) and cardiovascular diseases. Several new glucose lowering drugs have shown either neutral or positive cardiovascular effect especially on hospitalisations, but also on mortality. Some of these drugs have safety characteristics with strong practical implication in heart failure, for example sodium-glucose co-transporters type 2 inhibitors (SGLT-2). Position paper of the European Society of Cardiology/Heart Failure Association was published in October 2019 and in June 2020. The results of EMPEROR reduced study were presented on European congress in september 2020. In this phase III, placebo-controlled trial, 3730 patients with New York Heart Association class II, III, or IV heart failure and an ejection fraction of 40% or less were randomly assigned to receive either empagliflozin (10 mg once daily) or placebo, in addition to recommended therapy. Over a median of 16 months, the primary outcome (cardiovascular mortality and hospitalisation for heart failure) occurred in 361 of 1863 patients (19.4%) in the empagliflozin group and in 462 of 1867 patients (24.7%) in the placebo group (hazard ratio, 0.75; 95% confidence interval [CI], 0.65 to 0.86; P.

Hereditary hemorrhagic telangiectasia (HHT), also known as Osler-Weber-Rendu syndrome, is an autosomal dominant disorder that causes abnormal blood vessel formation. Patients with HHT may have telangiectasias and later may develop arteriovenous malformations in various organs. Pacients suffer from many complications caused by the malformations and therefore by patients with HHT must by performed screening of this arteriovenous malformations. Optimal treatment of this malformations is best delivered throught a multidisciplinary approach. Farmacological treatment is described in next paper.

Renal parenchymal disease is the most common cause of secondary hypertension, accounting for up to 5% cases of all cases of systemic hypertension. Renal parenchymal hypertension occurs as a complication of a wide variety of glomerular and tubulointerstitial diseases and may aggravate the decline of kidney function. The pathophysiology of renal parenchymal hypertension represents a combined interaction of the impaired sodium handling leading to volume expansion, alteration of the renin-angiotensin system, abnormalities in endogenous vasodepressor compounds and possibly enhanced activity of vasoactive substances. Renal parenchymal hypertension can occur in acute and chronic kidney disease, manifesting early in the renal function impairment. It often requires complex pharmacological treatment of blood pressure and is prognostically unfavorable in terms of cardiovascular and renal complications. This form of secondary hypertension can often be successfully treated by therapy of the underlying renal disease. In case of insufficient blood pressure compensation, renal impairment progresses. The aim of this paper is to give a brief overview of renoparenchymatous hypertension, current diagnostic possibilities and principles of therapy.

Objective: The aim of this paper is a complex evaluation of clients medication in the geriatric care facility Domov Vlčí mák (DVM) with regard to the most common drug related risk factors in elderly. The paper shows ways of identification, resolution and prevention of drug related problems from the perspective of a clinical pharmacist., Methods: The medication was evaluated in 74 DVM clients. The sample consisted of 45 women (61 %) and 29 men (39 %) with an average age of 90 years. The project took place in the period from April to June 2020. Patients pharmacotherapy was graded as low, medium or high risk in accordance with the methodology and concept of clinical pharmaceutical care in the Czech Republic developed by the Czech Professional Society of Clinical Pharmacy ČLS JEP. For all clients, medication was also assessed in terms of the risk of falls., Results: There was a total of 62 (84 %) high, 4 (5 %) medium and 8 (11 %) low risk clients. A plan for medication adjustments was proposed for a total of 67 clients in the form of pharmacotherapeutic recommendations. A total of 170 drug related problems was identified and pharmacotherapeutic intervention was performed. The most common problem (in 42 % of cases) was a missing drug in terms of effective therapy. Medication discontinuation was recommended in 33 % of cases, mainly due to the risk of side effects, missing indications or drug necessity. Inadequate dosing was found in 15 % of cases, usually it was recommended to reduce the dose to the so-called “senior dose”. In 6 % of cases laboratory testing was indicated and in 4 % of cases timing of the drug administration was changed., Conclusion: Identified drug related problems did not represent major errors that could endanger the quality or safety of the healthcare provided. One of the reasons for the good outcome is an established multidisciplinary cooperation in this facility.

Type 1 diabetes is often associated with the early manifestation of atherosclerosis, which represents the morphological basis for macrovascular complications of diabetics. Atherosclerosis in patients with type 1 diabetes shows certain specific features that result from different proportions of risk factors, the presence of diabetes and its complications. The paper deals with the possibilities of influencing and detecting the atherosclerotic process in these risk patients.

Long lasting, low intensity depressive episodes have been diversely integrated according to the classifications types or the psychodynamic points of view. The concept of anxious persistent lasting depression, neurotic depressive states, neurotic depression have been unified into the dysthymic disorder category of the DSM classification. This concept unification have been a topic of dispute considering that dysthymic disorder was a restrictive, heterogeneous an extensively comorbid diagnosis. Nevertheless the definition of this category offers the opportunity to place the notions of temperament, personality, adjustment disorder. Including dysthymic disorders as a category inside of the mood disorders classification suggests the interest of using an antidepressive medication in presence of chronic depressive states not included in the major depressive disorder category. But the most important treatment is psychotherapy, because dysthymie is connected with pathologic cognition and interpretation of reality. This paper describes that dysthymia induced similar problems in the family members of dysthymic persons, and even induced somatic disorders in sensitive persons, as described in this paper.

The histiocytoses are rare disorders characterized by the accumulation of cells thought to be derived from dendritic cells or macrophages. Their clinical behaviour ranges from mild to disseminated and, sometimes, life-threatening forms. The incidence of this diseases is much smaller, then the incidence of diseases derived from lymphocytic or myeloid lineage. Langerhans cell histiocytosis is most frequent disease from this group. The last version of WHO classification from 2017 and last version of classification published by Histiocyte Society is summarised in this paper.

C2 deficiency represents the most frequent type of a complement deficiency. Clinical manifestation includes infections caused by encapsulated bacteria (Steptococcus pneumoniae, Neisseria meningitidis) such as meningitis, gonitis, pneumonia or septicaemia. A causative treatment has not been available yet. A prophylactic vaccination and/or a long-term antibiotics prophylaxis are recommended. Here we report 2 patients from 2 unrelated families. The first patient suffered from recurrent otitis in his childhood. He underwent osteomyelitis, meningitis complicates with hear-loss, and one episode of pneumonia during adulthood. The second index patient underwent uncomplicated meningitis in his preschool age. He has been treated for recurrent upper-airways infections later. His sister has been completely asymptomatic. The deletion 28 bp (c.841-849+19del28) in C2-gene was detected in all of them in homozygous form. Our paper highlights the variability of a clinical manifestation in homozygous carriers, ranged from asymptomatic cases to patients with history of severe complications. The diagnosis is frequently made even in adulthood.

Pioglitazone belongs to the drugs primarily reducing insulin resistance. Currently, it is the only insulin sensitizer available. In addition to hypoglycaemic action, it has a number of other metabolically beneficial effects that are responsible for its positive effect on the vascular wall. The paper provides an overview of cardiovascular clinical trials with pioglitazone, its safety profile and practical recommendations for its administration.

Cardiovascular complications are main cause of increased mortality in patients with type 2 diabetes. Decrease of overall cardiovascular risk and subsequently cardiovascular morbidity and mortality in type 2 diabetes patients is therefore an important treatment aim. To this end, intensive intervention of classical risk factors such as dyslipidemia, arterial hypertension, smoking along with lifestyle intervention is necessary. Good diabetes control optimally with the use of antidiabetic medication and smoking with positive effect on cardiovascular complication is of high importance as well. Incretin-based therapy includes an approach based on an increase of endogenous GLP-1 concentrations by inhibition of its breakdown by dipeptidyl-peptidase 4 (DPP-4 inhibitors or gliptins) or he use of GLP-1 receptor agonists that owing to modified structure have much longer half-life than endogenous GLP-1 and act the use through stimulation of GLP-1 receptor. The aim of this paper is to summarize the use of these two groups of antidiabetic drugs - gliptins and GLP-1 receptor agonists - in patients with type 2 diabetes focusing on the their cardiovascular effects and their influence on cardiovascular complications.

While terminal palliative care focuses primarily on the management of symptoms of immediate dying, early palliative care provides an opportunity for the patient and his loved ones to understand the trajectory of the illness, to receive support for coping with the diagnosis, increase the quality of decision-making to match the patients values and preferences. The emphasis is on realistic expectations of the outcome of treatment and timely anticipation of further disease course. The paper focuses on an overview of the evidence of palliative and supportive interventions, comparing the different trigger mechanisms for palliative intervention and presents the content of the intervention of the palliative team. The establishment and integration of the consultative palliative team in the tertiary hospital is described. An illustrative care report describes the goals of care conversation and its impact on advance care planning. Palliative care is widely accepted and recommended standard of high quality care for seriously ill patients. In the Czech Republic, it is necessary to extend its availability for patients hospitalized in acute care setting.

Insulin pump therapy represents nowadays the way of insulin administration most similar to the physiological insulin secretion. This form of intensified insulin regime is used mostly (but not exclusively) in type 1 diabetes patients. Insulin pump therapy can be efficiently combined with continuous glucose monitoring. Even there are available insulin pumps which can serve as continuous glucose monitoring signal receiver themselves and are capable to stop automatically basal insulin infusion to prevent hypoglycemia. By this technological combination it is possible to reach near normoglycemia without increasing the risk of severe hypoglycemia. In the Czech Republic this therapy is covered by insurance when defined indication criteria are fulfilled. To reach this therapy full potential the patient as well as the professionals must be trained properly to know all technical aspects of this therapy as well as it is necessary to gain further knowledge. Particularly important is knowledge on food nutrition content and on the glycemic effect of different meals. All these factors are discussed in details in the paper.

In this paper, the authors summarize current findings on the relationship between diabetes mellitus (DM) and oral tissue diseases. They study the effect of diabetes on the condition of hard dental tissues, oral mucosa and salivary glands and explain how these undesirable changes occur. They focus primarily on the bilateral relationship between diabetes and periodontitis, common pathogenetic traits of both diseases and on the effect of periodontal treatment on basic metabolic diseases. They show that diabetes not only negatively affects the condition of periodontal tissues, but inflammatory disease of periodontium is also a risk factor for hyperglycemia. The authors point to the emerging closer co-operation between diabetologists and parodontologists (Perio-Diabetes Workshop in 2017) and consider possibilities of effective prevention and better motivation of diabetics for oral health care.

Availability of an ultrasound device at the critical care setting significantly enhances possible diagnostic ways and makes the management of critically ill patients more effective. Growing amount of papers confirms that qualified intensivists with background in medicine and anaesthesiology may provide accurate, safe and extensive diagnosis of the haemodynamic system with the aid of echocardiography. Examination of lungs, pleural space, quantification of pleural fluid and eventual exclusion of ventral pneumothorax should be an integral part of transtoracic echocardiographic examination. Interrogation of abdomen in sepsis of unknown origin, acute abdominal syndrome or in acute renal failure may direct further diagnostic and therapeutic steps in critically ill patient. Time factor is particularly important in shock and during admission of severe trauma where patient´s survival depends on correctly launched diagnostic algorithm. Ultrasound plays a key role here. Interrogation with ultrasound helps also before performing a percutanneous dilatational tracheostomy. The same technique may locate a vessel before cannulation in high risk patient and avoid potential complication and also unnecessary transfusion of platelets. Ultrasound has an established role in exploration of vessels in perfusion disorders and suspected deep venous thrombosis. Transcranial Doppler ultrasonography is an important aid in diagnostics of cerebral blood flow particularly in subarachnoid bleeding and intracranial hypertension. The cost of multimodal ultrasonic device is substantial however, the device may save a life of a patient and save time, complications and costs for the department in the hands of a skilled intensivist.

The paper provides a brief overview of the key studies focused on PCSK9 inhibitors. It mainly examines positive results of the FOURIER studies on evolocumab, the SPIRE study on boccocizumab and the ODYSSEY Outcomes study on alirocumab. All these studies have not only shown a significant decrease in LDL-cholesterol levels, but also the reduction of cardiovascular events just correlating with these levels. The treatment leading to a dramatic drop in LDL-cholesterol levels was safe and well tolerated by patients. All the studies provided with comments demonstrate a positive impact of biological treatment of hypercholesterolemia on cardiovascular disease and confirm validity of the hypothesis saying “the lower the better”, at least for LDL-cholesterol. In conclusion, Professor Braunwalds hypothesis is mentioned saying that this treatment might eventually lead to as much as eradication of atherothrombotic cardiovascular diseases. Key words: alirocumab - bococizumab - evolocumab - FOURIER - cardiovascular disease - LDL-cholesterol - ODYSSEY Outcomes - SPIRE.

This article summarize molecular-genetic basis of hemoglobinopathies, their classification and phenotypic manifestations. The description of individual subgroups is supplemented with a case reports of patients diagnosed in the Czech population. This paper provides an overview of 14 types of α-thalassemic mutations, 34 β-thalassemic alleles, 4 δβ-thalassemic alleles and 22 hemoglobin variants identified in the Czech population in 876 persons from 579 families. In more detail are described hemoglobinopathies, that have been diagnosed and described as novel: β-thalassemic mutation CD 38/39 (-C); Hb Olomouc; Hb Hana; Hb Hradec Kralove and 18.3 kb deletion downstream of α-globin cluster leading to a new mechanism of α-thalassemia-2. The fact that until the end of 2017 hemoglobinopathies were diagnosed in nearly 900 patients shows that they are not rare in the Czech Republic. This brings increased demands for their diagnostics, including prenatal diagnosis. Key words: hemoglobinopathies - hemoglobinopathy with high affinity to oxygen - sickle cell anemia - thalassemia - thalassemic hemoglobinopathy - unstable hemoglobins.

This review summarizes the pathophysiology, genetic background and clinical symptoms of anemias belonging to the group of inherited bone marrow failure syndromes with unilineage failure of erythropoiesis. It sums up the current knowledge of three diseases: Diamond-Blackfan anemia, congenital dyserythropoietic anemia and Fanconi anemia whose pathophysiology was elucidated in detail during the last decade, owing to the rapid development of new molecular-genetic techniques, especially next-generation sequencing. Fanconi anemia is included in this overview because of macrocytosis and/or anemia detected in the majority of the patients before they develop bone marrow failure. The paper also aims at pointing out typical associated anomalies in these diseases which might be overlooked and which can lead to early diagnosis. Unfortunately, the correct diagnosis is often established later in adulthood and, in some cases, as late as at the time of manifestation of malignant disease. Accurate and timely diagnosis of these conditions is extremely important for the determination of appropriate treatment approach, diagnosis of affected family members (especially in the process of bone marrow donor search), and genetic counselling, which can substantially influence the prognosis of these diseases. Key words: congenital dyserythropoietic anemia - Diamond-Blackfan anemia - DNA repair - dyserythropoiesis - Fanconi anemia - inherited bone marrow failure - ribosomopathies.

In this paper I present the strongest argument, in my opinion, in favour of moral admissibility of euthanasia. In the introduction I briefly mention two important arguments in support of euthanasia - out of respect for autonomy and as a last act of grace, however I refuse them as insufficient. I propose a definition of both forms of assisted death: euthanasia and assisted suicide. I present the basic ideas underlying the theory of the good life and deal with hedonism in greater depth. I define a deprivation concept of the badness of death and, employing hedonism, I specifically describe when death is bad and when it is good. Next I present consequentialism and utilitarianism and show how it is possible to proceed from the reflections on the good life and badness of death toward the concrete normative conclusions about euthanasia. In conclusion I extend my reflections also to other theories of the good life, such as preferentialism or the theory of objective desire and the objective pluralistic theory. The paper arrives at the defense of the thesis that there exist situations in medical practice in which euthanasia presents a morally acceptable choice. Key words: concept of badness of death - consequentialism - deprivation - desire-fulfilment theory - euthanasia - hedonism - preferentialism - utilitarianism.

The current discussion of the moral admissibility or inadmissibility of euthanasia should, in my opinion, consider the greatest possible number of the shared premises of the two opinion camps. That is why I followed a thesis in this paper that the question of the good life is the focus of ethical interest, as this is what connects the advocates and the opponents to euthanasia. In the first part of the paper I critically discuss the two main theories of the good life widely embraced among the advocates of euthanasia: hedonism and desire-fulfilment theory. My focus is to show that both of them are descriptively inadequate, not quite in agreement with the intuitions and ideas that we have about the good life. From this critique I proceed towards the objective theory of full-fledged human development known as the natural law theory. Within this framework I discuss in depth the nature of life as the objective goodness and go over to a brief criticism of utilitarianism, the theory dominating bioethics today; I derive several normative conclusions from the nature of the fundamental goods, leading to the conclusion that an innocent human life cannot be ended under any circumstances. The second part of this paper focuses on the current critique of the medical practice which, as physicians assert, adheres to the norm forbidding to end a patients life, while the actual practice is different. I undertake a detailed analysis of the possibility of distinguishing between the behaviours and classifying them under 1 of 2 categories: causing injury (including termination of life) and allowing injury to happen (including death). I am trying to show that it is possible to make this distinction. In the final part I briefly outline the method of supplying arguments in support of a thesis that there exists a moral asymmetry between the two categories of behaviour, so the moral admissibility of one (letting die) cannot form a basis for the moral admissibility of the other.Key words: allowing harm - consequentialism - desire fulfillment theory - doing harm - euthanasia - hedonism - natural law ethics - preferentialism - utilitarianism.

The paper describes the history and the present of non-invasive ventilation, the therapeutic method which plays an essential role in the therapy of acute as well as chronic respiratory illnesses. It focuses on indications and contraindications, adverse effects as well as some pitfalls of this therapy.Key words: non-invasive ventilation (NIV) - respiratory insufficiency.

Sarcopenia is defined as generalized and progressive age-related loss of skeletal muscle mass, muscle strength and physical performance below a defined threshold. In sarcopenia skeletal muscle mass - the largest body organ - is failing in its function and the term "muscle failure" was suggested. Sarcopeniat is now recognized as a serious clinical problem compromising healthy aging concept and quality of life of affected older people. Sarcopenia has a complex multifactorial pathogenesis, which involves not only age-related changes in neuromuscular function, muscle protein turnover, and hormone levels and sensitivity, but also a chronic pro-inflammatory state, oxidative stress, and behavioral factors - particularly nutritional status and degree of physical activity. The paper provides detailed review of screening and diagnostic methods and consensus-based cut off values and biomarkers of potential patophysiologic mechanisms involved in sarcopenia development in individual patient. Further, detailed description of current preventive and therapeutic strategies for sarcopenia is included. These involve structured physical activities, namely progressive resistance training and aerobic activities which prevent muscle loss and improve muscle performance. The effect of exercise is enhanced by nutritional supplementation, particularly through proteoanabolic effect of proteins and some amino acids. There are no currently registered drugs with indication of sarcopenia but there are promising substances in higher phases of clinical trials (such as antimyostatin human monoclonal antibodies, selective androgen receptor modulators) which have the potential to be introduced into clinical practice soon. Conclusions Sarcopenia is a new clinical diagnosis of organ failure of the skeletal muscle function leading to multiple adverse health outcomes. Physicians should be aware of clinical symptoms and diagnostic algorithm and target treatment according to sarcopenia leading causes. Key words: clinical diagnosis and treatment - muscle failure - muscle mass, strength and function - sarcopenia.

In 2011/2012, the US Food and Drug Administration issued a warning about the effect of citalopram on the QT interval and decreased its dosing. Further studies addressing this issue have been published since then. The authors were interested to know whether or not the studies have furnished new information that could modify or further specify the FDA-issued recommendations. After analyzing the most relevant studies, the authors concluded that even papers published within the last 5 years confirmed that, of the SSRI class of drugs, citalopram prolongs the QT interval most significantly. While the QT interval prolongation in young and otherwise healthy individuals is small and treatment with citalopram relatively safe, in elderly comorbid patients with polypharmacy, use of even currently recommended doses may result in significant QT interval prolongation. Hence, the decision about future therapy will depend on the degree of risk of each individual patient. Judging by the most recent data, citalopram is not more effective compared with the other SSRIs. As a result, therapy with citalopram will presumably show a declining trend, particularly in elderly patients.Key words: citalopram - escitalopram - QT interval - SSRI.

Ventricular assist devices are an important therapeutic modality in advanced surgical therapy of end-stage heart failure. Previously most frequently used devices generated mainly non-pulsatile blood flow. Despite indisputable clinical success of this therapy, we encounter complications specific to the devices generating continuous flow. Complications are mainly attributed to changes in shear stress and subsequent changes of the blood vessel characteristics, mainly of endothelium. Effect of continuous flow on the vasculature and blood elements, therefore, became a subject of intense recent research. Effect of continuous flow on the vascular bed is subject of intensive research. Widespread methods used in angiology measuring the state of vasculature are based mainly on imaging modalities and on the presence of pulsatile flow; therefore, under circumstances of non-pulsatile flow their use is limited and the attention is shifted also to laboratory methods, namely to detection of circulating indicators of vascular damage. Therefore, in our recent studies of the effect of mechanical ventricular assist devices on the blood flow we exploit combination of imaging and laboratory methods, including measurements of circulating microparticles and endothelial progenitor cells. Based on these studies interesting data were obtained studying the effect of implantation of mechanical cardiac support on the dynamics of vascular changes taking into account also response to changes of blood flow characteristics. In this paper we summarize our observations.Key words: continuous flow - endothelial progenitor cells - mechanical circulatory support - microparticles - vascular damage.

Aging is an inevitable process in the life of each organism and it is no different in the human world. According to the world statistics and demographic data, an ever increasing group in our population live to a ripe old age. The paper deals with pharmacological therapy for overactive bladder (OAB) in older women while also considering frequent comorbidities in older age. The prevalence of OAB at this life stage is greater as compared to other, more serious diseases. There are less clinical studies on geriatric patients than those focusing on younger age categories. The effect of pharmacotherapy with antimuscarinics against placebo is demonstrable within all age groups including people aged over 75. With regard to polypharmacotherapy in older adults, antimuscarinics may intervene in drug interactions. Therefore the authors draw attention to these risk factors and the ways to prevent them. Key words: drug interactions - geriatry - overactive bladder - urinary incontinence.