Light Chain Deposition Disease (LCDD) is a very rarely diagnosed condition affecting the kidneys. We describe a case where this diagnosis was morphologically confirmed in a biopsy of a transplanted kidney, and retrospectively identified in a previous kidney biopsy where the changes were not correctly classified. The biopsy of the transplanted kidney was performed due to worsening graft function. Subsequent testing focused on monoclonal gammopathy, revealing elevated serum concentrations of free kappa light chains (FLC) with a maximum FLC kappa value of 226 mg/l and FLC lambda at only 6 mg/l. The FLC kappa / FLC lambda ratio was clearly pathological at 37 (normal range 0.26-1.65). Serum and urine immunofixation electrophoresis were repeatedly negative. Bone marrow cytology described 8% pathological plasma cells, and flow cytometry demonstrated 0.7% plasma cells among all nuclear bone marrow cells. These plasma cells were 100% clonal, of the abnormal kappa + phenotype. The diagnosis was thus concluded as a non-malignant gammopathy of the type „monoclonal gammopathy of clinical significance“ with renal damage in a morphological form corresponding to LCDD. A combination of daratumumab, bortezomib, cyclophosphamide and dexamethasone was chosen for treatment LCDD. Free light kappa chains decreased below the lower limit of the norm during the first two months of anti-CD38 therapy. LCDD is one of the many forms of kidney damage that can occur in non-malignant gammopathies. Therefore, FLC testing should always be performed as part of the differential diagnosis of renal failure. For kidney damage by monoclonal immunoglobulin, a classification created by The International Kidney and Monoclonal Gammopathy Research Group was accepted. It is advisable to inform the evaluating morphologists of the possible presence of pathological concentrations of FLC and/or M-Ig so that they can focus the diagnosis in this direction, otherwise these rare forms of kidney injury may remain unrecognized.

Low incidence of multiple myeloma (MM) in the general population is one of the reasons for absence of a screening program. Kidney dysfunction is one of the most common types of end-organ damage in MM patients. Some transplant centers, therefore, established a screening to detect monoclonal immunoglobulin, mostly employing serum protein electrophoresis (SPEP) with or without immunofixation of serum and urine. If only monoclonal free light chain is produced, however, the sensitivity of SPEP and immunofixation is low. Here, we describe a case report of patient with newly diagnosed MM only after kidney transplantation. This case report emphasis the need for screening of monoclonal gammopathy (MG) in patients whose cause of kidney failure is unknown.

Myocardial free wall rupture is a rare, but serious complication of acute myocardial infarction with high mortality. We present a case of a 64-year-old patient with this devastating complication of an anterior ST segment elevation myocardial infarction (STEMI) with a prolonged time delay. Cardiac surgery was not performed due to prohibitive surgical risk and predicted poor prognosis. We describe our successful therapeutic intervention consisting of immediate pericardial drainage, vasoactive and inotropic support, intraaortic balloon pump placement and continuous veno-venous hemodialysis. This combined therapy led to patient stabilization and after incremental clinical improvement the patient was able to return to a normal life. After several months a long-term mechanical circulatory support was implanted as a bridge to heart transplant.

Monoclonal gammopathy of clinical significance (MGCS) is an umbrella term to describe a broad spectrum of disorders with remarkable organ dysfunctions related to the underlying non-malignant B or plasma cell clone. Although the clone itself is typically very small, it is associated with diverse clinical manifestations through different mechanisms, such as monoclonal protein deposition, the biological activity of the monoclonal immunoglobulin, or angiogenic/inflammatory cytokine hyper-secretion, or the ethiopathogensis is still unknown. Some predominantly involve a single organ, commonly peripheral nerves, kidney, skin and eye, while others are systemic diseases with syndromic presentations. Recognizing the clinical features with appropriate workups, analysis of monoclonal immunoglobulin in serum and urine and free light chain analysis in serum with particular tissue biopsies, are the key to making a timely diagnosis, especially when the kidney or skin is affected. Treatment strategy is similar to multiple myeloma or Waldenström macroglobulinemia, complete remission of gammopathy is prerequisite of significant improvement of clinical symptoms and reversal of organ dysfunctions. Therapy is based on clone-directed therapy, application of high effective antiplasmocytic or antilymphocytic therapy with monoclonal antibody (anti-CD20 or anti-CD38) with high probability of total disappearing of monoclonal immunoglobulin. Other therapeutic possibility is immunomodulation with high-dose intravenous immunoglobulin 2g/kg administered in 28days interval as maintenance therapy.

Progress in multiple myeloma (MM) treatment is remarkable. Combined regimens for newly diagnosed MM patients achieve progression-free survival of more than seven years. In the Czech Republic, the approval of a four-drug combination of anti-CD38 monoclonal antibody (mAb) with a proteasome inhibitor (PI), immunomodulatory agent (IMiD) and dexamethasone is expecting in 2025. It is not yet clear whether consolidation with autologous transplantation will be beneficial in terms of extending the time to progression. The development of immunotherapy has literally exploded. Autologous chimeric antigen receptor T-cell therapy (CAR T-cells) targeting the BCMA antigen have already been approved for second-line therapy in the USA. The development of bispecific antibodies (bsAb) is even faster. Bispecific antibodies targeting BCMA and GPRC5D antigens are available in late relapse. Clinical trials are testing additional therapeutic targets (e.g., FcRH5) and combination regimens (e.g., bsAb, PI, IMiD). Response rates to these combinations in the first line treatment are 90-100 %, with a high percentage of patients achieving minimal residual disease (MRD) negativity. In 2024, assessment of MRD was approved as a primary outcome in clinical trials and it is likely that we are now moving to wals an era of MRD-driven therapy.

The ultimate goal in the treatment of asthma is the achievement of disease control and minimization of the risk for future exacerbation. Despite using medium/high dose of inhaled corticosteroids (ICS) in fixed combination with long-acting beta-2 agonists (LABA), many patients still do not achieve an adequate level of disease control and remain at risk of exacerbations. Disease severity may be related to poor treatment adherence or improper inhaler technique. LAMA is suggested as the first add-on therapy to moderate dose ICS + LABA (GINA 2024), called as triple therapy. GINA recommends triple therapy (LAMA to ICS/LABA) as a further option at step 4 and as first choice at step 5. Therefore, it is useful to know strategy this treatment and adequate indicate free and fixed triple therapy in patients with bronchial asthma. It offers to achieve therapeutic control of asthma. Despite evidence of its efficacy and safety, inhaled triple therapy (ITT) is still not mostly used in patients with asthma.

Basal insulin analogues still play an irreplaceable role in the treatment of type 2 diabetes mellitus (T2DM) and are indicated when patients are poorly controlled with oral antidiabetic drugs. In the multicentre prospective observational BIGGER (Biosimilar Insulin GlarGin czEch Real-life non-interventional study) trial, the efficacy of biosimilar insulin glargine (Semglee) and its good safety profile were confirmed. Aim: To determine the efficacy and safety of biosimilar insulin glargine (Semglee) in adult patients with T2DM in real clinical practice and to evaluate the effect of previous therapy on the course of treatment. Patient population (material) and method: Results from 1 066 patients with T2DM who were referred for treatment with insulin glargine were processed. Treatment efficacy and safety indicators were assessed at the initial visit and after one, two and six months of treatment. Results: All study participants experienced significant reductions in HbA1c and weight over the six months. The mean HbA1c values decreased from 69.7 ± 13.16 to 59.9 ± 12.01 mmol/mol; p < 0.001 in the entire study population. The decrease was most significant in the insulin naive group, from 74.7 ± 12.12 to 59.9 ± 10.69 mmol/mol; < 0.001. In patients with previous insulin treatment there was a reduction - human insulin group (from 69.4 ± 13.53 to 58.8 ± 12.52 mmol/mol; < 0,001), 1st generation insulin analogues (from 67.1 ± 12.44 to 59.7 ± 12.10 mmol/mol; < 0.001), 2nd generation insulin analogues (from 70.7 ± 13.05 to 61.7 ± 13.51 mmol/mol; <0,001). In patients with previous treatment with 1st generation basal insulin analogues, mean baseline body weight values were significantly lower compared to patients with previous treatment with 2nd generation basal insulin analogues (90.0 ± 17.39 kg vs. 95.2 ± 19.54 kg; p = 0.016). The incidence of hypoglycaemia was comparable to that before treatment and the incidence of ketoacidosis during treatment was rare. Conclusion: Treatment with the biosimilar insulin glargine (Semglee) led to a mean decrease in HbA1c of 9.8 mmol/mol over 6 months in patients with T2DM. The greatest improvement was achieved in patients with no previous insulin therapy. Early initiation of basal insulin therapy and subsequent dose titration is crucial to ensure good treatment outcomes. Patient education and regular monitoring for ongoing assessment of status leads to improved patient adherence and increases treatment success.

Introduction:
Assessment of serum levels of free light chains (FLC-κ and FLC-λ) and recently heavy/light chain pairs of immunoglobulin (HLC-κ and HLC-λ) and their ratio (FLC-r and HLC-r) has significantly enriched traditional algorithm of multiple myeloma (MM) evaluation. The aim of the presented study was to assess the relationship of classical prognostic parameters of MM, standard FLC-κ/λ and HLC-κ/λ ratio (^sFLC-r and ^sHLC-r), modified ratio of "involved/uninvolved" FLC and HLC (^mFLC-r and ^mHLC-r ), the difference between "involved - uninvolved" FLC and HLC (FLC-dif. and HLC-dif.) to current stratification models of MM based on the result of cytogenetic analysis.
Patients and methods:
In a group of 97 patients with MM we assessed serum levels of FLC by Freelite^TM method, and we calculated ^sFLC-r, ^mFLC-r and FLC-dif. indices by Hevylite^TM method. For cytogenetic analysis we used FICTION (fluorescence immunophenotyping and interphase cytogenetics as a tool for the investigation of neoplasms). For MM stratification we used standard staging systems according to Durie-Salmon (D-S) and International Staging System (ISS) as well as novel stratification systems based on the results of cytogenetic analysis, ie. "Mayo Stratification of Myeloma and Risk-Adapted Therapy" (mSMART) and "Revised International Staging System" (R-ISS).
Results:
Stratification mSMART and R-ISS has significantly different representation of "standard" or "low-risk" (71, 15.5, 11.3 a 29.9 %), "intermediate risk" (15.5, 53.6, 34 a 33 %) and "high risk" patients (13.4, 30.9, 54.7 a 37.1 %) compared to standard staging systems. mSMART stratification was compared to prognostic factors of MM (Hb, albumin, β₂-M, creatinine and LDH), and the only significant relationship was found in the case of β₂-M, R-ISS had relationship only to Hb and creatinine. In the case of D-S staging we found significant relationship of stages 1-3 and substages A and B to the levels of ^mFLC-r, FLC-dif. and ^mHLC-r, ISS had moreover relationship to k HLC-dif. and MIg concentration. Analysis of mSMART stratification showed primarily significant relationship of risk categories 1-3 to ^mFLC-r and ^sHLC-r indices, and R-ISS to ^mHLC-r index and MIg concentration. In both cytogenetics-based stratifications there was a lack of relationship to ^sFLC-r, FLC-dif. and HLC-dif. indices.
Conclusion:
Comparison of the results of standard staging systems according to D-S and ISS with cytogenetics based models mSMART and R-ISS showed different representation of risk groups, and significantly different relationship to classical prognostic factors together with original relationship of sMART stratification to ^mFLC-r and ^sHLC-r, and R-ISS to ^mHLC-r and MIg concentration.

Celiac disease is a lifelong autoimmune disorder that occurs in genetically predisposed people when consuming gluten. Its prevalence is around 1% of the population with about twice higher proportion of women. Celiac disease is one of the most common causes of malabsorption, however, its manifestations can be quite diverse - from completely asymptomatic to fully developed malabsorption syndrome. Extraintestinal manifestations are a common finding in adults. The gold standard of diagnosis is the serological detection of specific antibodies (the serum tissue transglutaminase IgA antibodies) in combination with a typical histological finding from a duodenal biopsy. Causal treatment is a lifelong gluten-free diet. Strict adherence to gluten-free diet will reduce the risk of serious complications (intestinal T-cell lymphoma). In the following case report we present a case of a 58-year-old patient, who have been diagnosed with celiac disease at this age based on non-classical symptoms. Specifically, these were multiple pathological fractures from metabolic bone disease due to malabsorption of calcium and vitamin D and subsequent secondary hyperparathyroidism.

Recent data suggest that we are on the verge of a dementia pandemic. Hypertension is a significant risk factor for this so far untreatable irreversible condition. The attention of researchers is now focused on identifying individuals at increased risk of cognitive decline or with early-stage cognitive deficit. Apart from cognitive function tests and imaging studies, no suitable biomarkers to identify these individuals have been available as yet. Haemodynamic parameters could be potentially useful biomarkers. At the ESH 2022 Congress, Professor Cunha presented the current knowledge suggesting that cognitive decline could be related to visit-to-visit blood pressure variability, carotid artery intima media thickness, and aortic stiffness as measured by pulse wave velocity (PWV). Currently, the CEREBRO study is being conducted to evaluate the prevalence of cognitive dysfunction in patients with hypertension and to search for early vascular biomarkers that correlate with cognitive decline. In addition to early and tight control of blood pressure, early detection of cognitive impairment could be a way to reduce the prevalence of advanced stages of dementia in the future.

Systemic mastocytosis (SM) is a disease characterized by the proliferation of clonal mast cells. SM biologically include a wide spectrum, ranging from relatively benign indolent forms to mast cell leukemia. The clinical presentation varies from nearly asymptomatic forms, through various degrees of mediator syndrome, to a neoplastic syndrome associated with hepatosplenomegaly, lymphadenopathy, and constitutional symptoms. Diagnosis relies on morphological and histological evaluation of the bone marrow. Patients are classified based on diagnostic findings and symptomatology according to the WHO and ICC classifications, which determine the type of disease and subsequent therapy, which is strictly individualized and includes symptomatic, targeted, and cytoreductive therapy. Given the wide spectrum of symptoms, patients with SM may visit specialists in most internal medicine departments in addition to hematologists and allergologists. Raising awareness of this diagnosis within the medical community is crucial. Low awareness leads to delayed diagnosis and undertreatment, posing risks of life-threatening situations in patients liable to severe allergic reactions.

Cieľ: Zistiť stav výživy u hospitalizovaných geriatrických pacientov na internom oddelení; zistiť, či existujú štatisticky významné korelácie medzi vybranými socio-demografickými údajmi, zdravotnými charakteristikami a meracím nástrojom. Súbor a metódy. Geriatrickí pacienti vo veku ≥ 65 rokov hospitalizovaní na internom oddelení. Dizajn štúdie kvantitatívny, deskriptívny, korelačný. Výskumný protokol obsahoval sledované premenné: demografické údaje, zdravotné charakteristiky, laboratórne parametre a merací nástroj na posúdenie stavu výživy MNA®. Empirické údaje boli spracované metódami deskriptívnej a induktívnej štatistiky. Výsledky: V súbore n = 137 (100 %) pacientov bolo 48 % mužov a 52 % žien, priemerný vek súboru bol 76,2 roka. Podľa MNA®-FF malo 9 % pacientov normálny nutričný stav, až 74 % malo riziko podvýživy a 17 % malo podvýživu. Polymorbiditu malo 99 % a polyfarmakoterapiu 96 % pacientov. Štatistickú významnosť sme zistili medzi výsledným skóre MNA®-FF a BMI (p < 0,001) a úbytkom na hmotnosti za posledných 6 mesiacov (p < 0,001) a hodnotou hemoglobínu (p = 0,033). Záver: Hospitalizovaní geriatrickí pacienti majú vo zvýšenej miere prítomné riziko malnutrície alebo už prítomnú malnutríciu. Súčasťou komplexného posudzovania stavu výživy je aj administrácia valídneho a reliabilného meracieho nástroja, ktorý je schopný rýchlo detekovať poruchu výživy už pri príjme pacienta na hospitalizáciu. Včasná identifikácia tejto poruchy je východiskom pre cielenú nutričnú intervenciu.

Background: Thyrotoxic crisis is a medical emergency status needed rapid diagnostic and urgent treatment, presented by decompensation and multiorgan dysfunction. Amiodarone induced thyrotoxicosis (AIT) is one of the severe complications caused by amiodarone therapy. Aim: Analysis of patients suffered from thyrotoxic crisis induced by Amiodarone therapy, with focus on clinical picture, laboratory findings and therapeutic options. Methods and Results: A total of 39 consecutive patients were dispensed to the Endocrine outpatient clinic of the University Hospital Banská Bystrica, with AIT during the period of 2005-2021 year we performed retrospective analysis of 5 consecutive patients with thyrotoxic crisis, who have been hospitalized on department of Internal Medicine University Hospital Banska Bystrica. All of patients were men (mean age 56,0 ± 5,4 years), All of analysed patients (n = 5) have been treated for arterial hypertension, 20% (n = 1) ischemic heart disease, 60% (n = 3) had medical history of heart failure and 40% (n = 2) had implantable cardioverter defibrillator. Indication for Amiodarone therapy was atrial fibrillation (n = 2) and ventricular tachyarrhythmias (n = 3). The average time of use of amiodarone until development AIT was 1005 ± 199 days. Mean TSH in the time of diagnosis was 0,005 ± 0,008 mIU/L and mean free T4 was 52,1 ± 14,3 pmol/L. Mean volume of thyroid gland was 19,8 ± 5,8 ml and mean Burch-Wartofsky Score was 86 ± 18. Three patients have been diagnosed as mixed type AIT and the two as AIT type 2. Diagnosis was made on the basis of clinical, laboratory and imaging examinations. All of the patients (n=5) have been treated with antithyroid drugs and corticosteroids at the maximum recommended doses. 80% (n=4) underwent urgently thyroidectomy and one was threated conservatively. The thyroid papillary micro adenocarcinoma was histologically confirmed in 1 of the observed patients. Conclusion: Thyrotoxic crisis induced by Amiodarone is an endocrine emergency which is characterized by multiple organs failure due to sever thyrotoxicosis.

Antibiotics are one of the most frequently administered groups of drugs in intensive care. The treatment of critically ill patients with community and nosocomial infections has some significant specifics compared to the treatment of outpatients or patients hospitalized in wards. Septic patients must be treated in a timely manner with an appropriately chosen empiric antibiotic treatment in a sufficient dose and at adequately selected dosing intervals. Compared to less serious conditions, these patients cannot wait to start antibiotic therapy. Pharmacokinetics is very often changed in critically ill patients, and it also changes dynamically during the course of the disease, so it is advantageous to be able to monitor the levels of antibiotics in the blood and adjust their dosage accordingly. The chosen therapy should be reevaluated daily and possibly adjusted based on valid microbiological results. Appropriately chosen de-escalation is the right principle even for critically ill patients in intensive care units. The article will touch on all the mentioned aspects and try to outline the principles of optimally guided antibiotic therapy in intensive care settings, supported by the current knowledge of evidence-based medicine.

Syncope is a sudden transient loss of consciousness caused by short-term hypoperfusion of the brain. It is a common reason for patients to visit acute admissions, where it is crucial to distinguish life-threatening causes from benign conditions. In this case report, we present the case of a 71-year-old patient whose syncope was caused by rupture of a right coronary artery aneurysm, resulting in the formation of a bulky hematoma in the right-sided cardiac compartments. This mechanism led to recurrent syncope, which at first glance could be mistakenly attributed to orthostatic hypotension caused by newly administered antihypertensive drugs. The case highlights the importance of a comprehensive approach to the diagnosis of syncope and emphasizes the need to exclude serious cardiovascular causes, especially in cases of recurrent and unexplained syncope. This rare but life-threatening condition was promptly diagnosed and treated by urgent cardiac surgery.

The concept of functional revascularization based on proving ischemia has been strongly recommended in the practical guidelines of both European and Czech Societies of Cardiology. In daily practice, application of this concept decreases the rate of coronary interventions. Though the best clinical evidence has been provided in patients with chronic coronary syndromes, recent data strongly advocate its usage also in patients with acute coronary syndromes. Invasive pressure-derived indices: hyperemic FFRmyo (fractional flow reserve of myocardium) and resting iFR (instantaneous wave-free ratio) require an interventional procedure by wiring the diseased vessel. FFRmyo ≤ 0.80 and iFR ≤ 0.89 mean functionally significant coronary disease mostly indicated for revascularization. Besides that, there are several non-invasive functional tests that may be used for detecting ischemia: perfusion scintigraphy, cardiovascular magnetic resonance, positron emission tomography and recently developed FFRCT or quantitative flow ratio (QFR). In routine practice, the concept of functional revascularization avoids unneccessary coronary interventions and, in case of functionally non-significant disease/stenoses, the patients may be treated conservatively with a very good prognosis. Currently, the "functionally complete revascularization", instead of the anatomic one, might become the goal of our treatment as the all-in-one concept in the cathetrization laboratory.

Aim: Hidradenitis suppurativa (HS) is a pro-inflammatory condition associated with other comorbidities, such as obesity and an increased risk of cardiovascular (CV) disease. One of the prognostic markers of CV risk is the neutrophil-to-lymphocyte ratio (NLR), which is an inflammatory marker and a strong prognostic indicator for patients suffering from various diseases. The aim of this study was to confirm the increased cardiovascular risk in patients with moderate to severe HS based on an elevated NLR compared to a control group of healthy individuals. Materials and methods: In this study, we prospectively monitored laboratory parameters in 51 patients with moderate to severe HS, whose disease severity was determined using the IHS4 scoring system. We compared the group with a control group of 51 healthy individuals. Peripheral venous blood was collected from all patients in both groups, and the NLR was determined from the absolute values of neutrophils and lymphocytes in the blood count. These results were then compared between the group of patients with HS and the control group of healthy individuals using a paired t-test, with a statistical significance threshold (α) set at 0,05. Results: In descriptive statistics, the average number of neutrophils, lymphocytes, and NLR was higher in the examined group of patients with HS than in the control group of healthy individuals. Using a paired t-test, we demonstrated statistically significantly higher values for the averages of individual hematological markers monitored. Conclusion: The results of the study show that patients with HS have higher NLR values than healthy individuals, which may be associated with an increased risk of CV and other complications. Our results highlight the presence of systemic inflammation in individuals with HS and suggest that these markers of inflammation may be valuable in clinical practice for screening and monitoring the progression of HS.

Subclinical hypothyroidism is a relatively common condition characterized by elevated serum TSH levels, but normal free thyroxine levels. The risks associated with subclinical hypothyroidism are less severe compared to those with overt hypothyroidism, making it essential to carefully select patients who would benefit from the treatment. Factors such as the patient´s age, comorbidities, symptoms, and TSH concentration need to be considered in this selections proces. The therapy, if required, consists of levothyroxine substitution with carefull dose titration to avoid overtreatment. The goal is to normalize TSH levels. Untreated patients should be folowed up accordingly to their risk factors mainly the risk of progression to overt hypothyroidism. Aproach to each patient should be individulized and flexible.

Arterial hypertension affects nearly 20% of Czech population. Due to this high prevalence, arterial hypertension has become a diagnosis seen on daily basis by general practitioners in primary care as well by specialists in hospitals. Despite the amount of energy and time which doctors give into the treatment of hypertension, we can still find patients who are not treated in the best way. And because we can still find some space for improvement, we should take care about the treatment of hypertension even at patients who came to the hospital for other reasons. Hospitalisation on its own brings very good conditions for frequent blood pressure controls and for review of chronic pharmacotherapy.

Cushing's syndrome (CS) is a disease caused by excessive autonomous production of cortisol and its effects on cells, tissues and organs of the human body. The clinical feature of CS is very complex and directly threatens the lives of its carriers. Morbidity and mortality of patients with active CS is up to four times higher than in the reference population, mainly due to cardiovascular causes, but patients are at risk of a number of other complications. In addition, there is evidence that increased morbidity and mortality persist for many years even after successful treatment. Treatment of CS must be early and comprehensive. In all situations with persistent overproduction of cortisol, we must normalize its production, where pharmacological treatment has its place. The oral product Isturisa with the active substance osilodrostat (code LCI699) is indicated for the treatment of endogenous CS in adult patients. Its efficacy and safety have been and are being verified in the clinical trial program (LINC 1-7). Clinical studies phase III verified the efficacy and safety of osilodrostat. In vitro data indicate that neither osilodrostat nor its major metabolite inhibit enzymes and transporters at clinically relevant levels. Drug interactions do not appear likely. The most serious adverse event was adrenal insufficiency.

Chronic myeloid leukemia (CML) is a clonal myeloproliferative neoplasia that is characterised by Philadelphia chromosome (Ph1 chromosome) and/or fusion gene BCR-ABL1 in bone marrow. Interpheron α and bone marrow transplantation used to be the main treatment modalities for patients with CML 20 years ago. Due to the introduction of imatinib mesylate since the year 2000 the outcome of CML patients has dramatically improved. The survival of both younger and elderly patients in the case of an optimal response has been prolonged and currently is close to survival of healthy population. Although, one third of patients does not respond well to first line imatinib and needs to change the treatment to second line tyrosine kinase inhibitors (TKI: bosutinib, dasatinib and nilotinib). Younger patients without cardiologic and metabolic disorders and those with poor risk profile score may have benefit from TKI of 2nd generation as a 1^st line treatment option with the aim of reaching deeper molecular response and the chance of treatment free remission (TFR) in future. By older patients with severe comorbidities and in patients with good risk profile score imatinib as a 1^st line treatment option can be used. For patients who are resistant simultaneously to 2^nd generation TKI and for patients with mutation T315I ponatinib - TKI of 3^rd generation can be used effectively. Intolerance and toxicity of TKI´s are the main barriers of effective CML treatment. TKI selection for each patient should be individual. Patient´s cooperation with medical team is crucial and inevitable in long time treatment process. The chance for TFR has become feasible for approximately 40-60 % CML patients in deep and durable molecular remission and represents a further important milestone in the management of CML patients.

Levothyroxine is a synthetic levoisomer of thyroxine. Currently, it is one of the most commonly prescribed drugs worldwide. The main indication for levothyroxine treatment is hypothyroidism of any type. It is also used for suppression therapy in patients with thyroid cancer. The therapeutic dose depends on the residual thyroid secretion, the weight of the patient, and the purpose of the treatment. The initial dose typically ranges from 25 to 50 μg daily, with further adjustment according to the level of thyroid-stimulating hormone (TSH). Initial dose titration is not recommended during postoperative replacement therapy and in pregnant women with hypothyroidism. Most of the plasma thyroxine is bound to transport proteins. However, only the free thyroxin is biologically active. Thyroxine is mainly a prohormone which is metabolized to the more active triiodothyronine. Properly managed levothyroxine treatment is safe with minimal adverse effects. Palpitations and other symptoms of hyperthyroidism may occur with overdose. For proper absorption, levothyroxine should be taken on an empty stomach, separately from other medications, at least 30 minutes before breakfast. Absorption may be impaired by other medications, especially by those increasing the pH of gastric acid.

PCSK9 inhibitors are modern and effective hypolipidemic drugs for lowering LDL-cholesterol, which belong to the "biological therapy". Their prescription is limited to specialized centers and to the fulfillment of other conditions set by SÚKL. This article lists the current valid criteria under which they can be indicated for reimbursement from public health insurance, and comments conditions and limitations in terms of the possibility of their fulfillment in clinical practice.

Introduction: Single stage thoracoscopic radiofrequency ablation (RFA) is a treatment method for persistent and long-term persistent atrial fibrillation (AF) offering the possibility for patients otherwise inconsolable by conventional catheter RFA. We present a pilot group of patients after the introduction of the new method at our clinical center. Patients group: A total of 52 patients aged 61.82 ± 9.7 years underwent single stage hybrid ablation (thoracoscopic isolation of pulmonary veins and box lesion followed by catheter verification of the surgical procedure effectivness) for symptomatic persistent and long-term persistent AF with significantly dilated left atrium 57.9 ± 11.0mm in the period September 2016-March 2019. Results: The median duration of the procedure was 232 minutes and the median duration of hospitalization was 10 days. At discharge, 52 patients (100%) had sinus rhythm. 48 of 52 patients (92.3%) had a 6-month follow-up. 41 of 48 (85.4%) and 38 of 44 (86.4%) of patients were AF free at 3-month and 6-month follow-up, respectively. Acute complications were: one left atrial perforation resolved successfully by suture and one transient ischaemic attack without permanent sequelae. Late complications involved one massive pulmonary embolization and an atrioesophageal fistula. There was no periprocedural myocardial infarction or stroke with permanent sequelae. Conclusion: Hybrid thoracoscopic-catheter ablation performed during one procedure is an effective and relatively safe mini-invasive method of treatment for long-term persistent atrial fibrillation.

Uric acid (UA) is predominantly formed in the liver, intestine and vascular endothelium as an end product of the metabolism of purines derived from food and endogenously from damaged or dead cells. The kidneys play a major role in the excretion of UA, eliminating about 70 % of the daily production. The remainder (approximately 30 %) is excreted by the intestine. If the production of UA exceeds the capacity of its excretion, hyperuricaemia results. Overexpression of urate transporter 1 (URAT1), glucose transporter 9 (GLUT9) and impaired glycolysis due to insulin resistance may be related to the development of hyperuricaemia in metabolic syndrome. Hyperuricemia is associated with the development and severity of metabolic syndrome. Previously, hyperuricaemia was thought to be the main cause of gout and gouty arthritis only. It was also assumed that hyperuricemia in patients with renal disease was a consequence of inadequate UA excretion due to renal failure and therefore was not a target for intensive treatment. Basic scientific evidence now suggests that hyperuricemia plays a pathogenic role in the development of chronic kidney disease and cardiovascular disease by causing endothelial dysfunction, vascular smooth muscle cell proliferation, and activation of the renin- angiotensin system. Lowering UA levels is an effective method for improving the condition, but not all UA lowering agents work the same. In clinical practice, these agents should be used with caution. Further accumulating data suggest that UA-lowering therapy slows the progression of these diseases.

With the increasing number of diabetics in the population, there is also a rise in both microvascular and macrovascular complications. Kidney damage represents one of the leading causes of mortality in patients with diabetes. The classification of diabetic nephropathy is based on the glomerular filtration rate and the degree of albuminuria, categorizing patients into risk groups according to their mortality risk. The treatment of these patients is based on data from large multicenter studies, which have demonstrated cardiovascular benefits, particularly with the use of gliflozins. Therefore, gliflozins and statins, together with metformin, are among the first-line treatment options for patients with type 2 diabetes mellitus and renal impairment. Comprehensive care for these patients should also include regular dietary consultations, physical activity, and psychological support. The situation is different for patients with type 1 diabetes mellitus, where the use of gliflozins is not recommended. In this group, the cornerstone of pharmacotherapy remains ACE inhibitors or sartans, along with adequate diabetes management. In advanced stages of the disease, it is crucial to refer patients to specialists in a timely manner for the evaluation of transplantation therapy.