The Impact of Convertase Subtilisin/Kexin Type 9 Monoclonal Antibodies with and without Apheresis on Platelet Aggregation in Familial Hypercholesterolemia.

BACKGROUND AND AIMS: It is well known that elevated cholesterol is associated with enhanced platelet aggregation and patients suffering from familial hypercholesterolemia (FH) have a high risk of thrombotic cardiovascular events. Although decreasing cholesterol level is associated with attenuation of platelet hyperactivity, there are currently no data on the effect of convertase subtilisin/kexin type 9 monoclonal antibodies (PCSK9ab) on platelet reactivity in FH. The aim of the study was to analyse the impact of different therapies including PCSK9ab on platelet aggregation in FH. METHODS: This study enrolled all 15 patients treated in the University Hospital Hradec Králové for FH. PCSK9ab have been administered in 12 of 15 patients while 8 patients were also undergoing lipid apheresis. Blood samples from all patients including pre- and post-apheresis period were tested for platelet aggregation triggered by 7 inducers, and the effect of 3 clinically used drugs (acetylsalicylic acid, ticagrelor and vorapaxar) was compared as well. RESULTS: Although apheresis decreased the reactivity of platelets in general, platelet responses were not different between non-apheresis patients treated with PCSK9ab and apheresis patients (post-apheresis values) with the exception of ristocetin. However, when compared to age-matched healthy population, FH patients had significantly lower platelet aggregation responses to 4 out of 7 used inducers and higher profit from 2 out of 3 used antiplatelet drugs even after exclusion of FH patients regularly receiving conventional antiplatelet treatment. CONCLUSION: This study showed for the first time the suitability of PCSK9ab treatment for reduction of platelet reactivity in FH patients.

The world apheresis association registry, 2023 update.

The WAA apheresis registry contains data on more than 140,000 apheresis procedures conducted in 12 different countries. The aim is to give an update of indications, type and number of procedures and adverse events (AEs). MATERIAL AND METHODS: The WAA-registry is used for registration of apheresis procedures and is free of charge. The responsible person for a center can apply at the site www.waa-registry.org RESULTS: Data includes reported AEs from 2012 and various procedures and diagnoses during the years 2018-2022; the latter in total from 27 centers registered a total of 9500 patients (41% women) that began therapeutic apheresis (TA) during the period. A total of 58,355 apheresis procedures were performed. The mean age was 50 years (range 0-94). The most common apheresis procedure was stem cell collection for which multiple myeloma was the most frequent diagnosis (51%). Donor cell collection was done in 14% and plasma exchange (PEX) in 28% of patients; In relation to all performed procedures PEX, using a centrifuge (35%) and LDL-apheresis (20%) were the most common. The main indication for PEX was TTP (17%). Peripheral veins were used in 56% as the vascular access. The preferred anticoagulant was ACD. AEs occurred in 2.7% of all procedures and were mostly mild (1%) and moderate 1.5% (needed supportive medication) and, only rarely, severe (0.15%). CONCLUSION: The data showed a wide range of indications and variability in apheresis procedures with low AE frequency.

Using the World Apheresis Association Registry Helps to Improve the Treatment Quality of Therapeutic Apheresis.

Therapeutic apheresis (TA) is prescribed to patients that suffer from a severe progressive disease that is not sufficiently treated by conventional medications. A way to gain more knowledge about this treatment is usually by the local analysis of data. However, the use of large quality assessment registries enables analyses of even rare findings. Here, we report some of the recent data from the World Apheresis Association (WAA) registry. Data from >104,000 procedures were documented, and TA was performed on >15,000 patients. The main indication for TA was the collection of autologous stem cells (45% of patients) as part of therapy for therapy. Collection of stem cells from donors for allogeneic transplantation was performed in 11% of patients. Patients with indications such as neurological diseases underwent plasma exchange (28%). Extracorporeal photochemotherapy, lipid apheresis, and antibody removal were other indications. Side effects recorded in the registry have decreased significantly over the years, with approximately only 10/10,000 procedures being interrupted for medical reasons. CONCLUSION: Collection of data from TA procedures within a multinational and multicenter concept facilitates the improvement of treatment by enabling the analysis of and feedback on indications, procedures, effects, and side effects.

The serine protease inhibitors and SERPINE1/2 disrupt prostaglandin E2 production and hyaluronic acid retention in FSH-stimulated pig cumulus-oocyte complexes.

The serine proteases, tissue- and urokinase-type plasminogen activators (PLAT and PLAU) and their inhibitors SERPINE1/2 are regulators of plasminogen to plasmin conversion. They are widely expressed in ovarian tissues, including granulosa and cumulus cells, and their expression is regulated by gonadotropins. The aim of this work was to assess the effect of serine protease inhibitors (aprotinin and AEBSF) and SERPINE1/2 on FSH-induced cumulus cell expansion, the production of prostaglandin E2 (PGE2) and retention of hyaluronic acid (HA) in expanding cumulus. The serine protease activity proved to be essential for the production of PGE2 and also for the retention of HA; the inhibition of plasminogen activators by SERPINE1/2 had the same effect. Collectively, these data indicate that plasmin is required for proper function of expanding cumulus cells in vitro and presumably also in vivo in the pre-ovulatory follicles.

[The role of PCSK9-inhibitors and of lipoprotein apheresis in the treatment of homozygous and severe heterozygous familial hypercholesterolemia: A rivalry, or are things quite different?] / Postavení inhibitoru PCSK9 a lipoproteinové aferézy v lécbe homozygotní a závazné heterozygotní familiární hypercholesterolemie: Kdo z koho, nebo je to jinak?

PCSK9-inhibitors belong to the new class of hypolipidemic agents. They enhance catabolism of low density lipoprotein cholesterol (LDL-C) through inhibiting activity of proprotein convertase subtilisin/kexin type 9 (PCSK9). They are monoclonal antibodies (alirocumab, evolocumab etc). Under clinical development are also other types of PCSK9-inhibitors which act at a subcellular level. The treatment with PCSK9-inhibitors can be beneficially combined with lipoprotein apheresis (LA). If such treatment using PCSK9-inhibitors is possible with regard to an individual patients genotype, the combination of LA and PCSK9-inhibitors leads to slowing the space of LDL-C increase between individual procedures of apheresis and enables attaining of the lowest possible values of LDL-cholesterolemia for the longest possible period of time. Due to high efficiency of PCSK9-inhibitors lowering LDL-C, but also their lower cost as compared to therapeutic LA, PCSK9-inhibitors now take precedence over the use of extracorporeal lipoprotein apheresis which, nonetheless, still remains the final method for hypolipidemic treatment of patients with severe hypercholesterolemia, who are resistant to conventional therapy while not reaching the target lipid values and at high cardiovascular risk. They belong to extracorporeal elimination methodologies which remove low density lipoprotein (LDL) cholesterol from circulating blood. LA in combination with higher doses of statins and ezetimib currently represents the most efficient method of treatment of homozygous and statin-refractory heterozygous familial hypercholesterolemia (FH). Residual cardiovascular risk in these patients still remains high, in particular because, despite the aforementioned treatment, the target values for lipids according to present recommendations cannot be reached. The combination of LA with the new drugs is promising, primarily due to its potential for further lowering of LDL-cholesterolemia between the individual apheresis procedures. Preliminary results of the ongoing studies indicate that the new hypolipidemic drugs in combination with LA, or when used separately, will substantially enrich and improve the treatment of refractory FH.Key words: alirocumab - atherosclerosis - evolocumab - hypercholesterolemia - cardiovascular disease - lipoprotein apheresis.

Significance of epidermal growth factor receptor signaling for acquisition of meiotic and developmental competence in mammalian oocytes.

The surge in luteinizing hormone (LH) in preovulatory ovarian follicles triggers the resumption of oocyte meiosis accompanied by expansion of surrounding cumulus cells and ovulation of cumulus-oocyte complexes (COCs) into the oviduct. Over the last 15 years, substantial progress has been made in elucidating the key pathways by which the LH signal spreads within the preovulatory follicle and in identifying the molecules responsible for maintaining oocyte arrest and meiosis resumption. It is now clear that the adenylcyclase-mediated rise in intracellular cyclic adenosine monophosphate leads to activation of the epidermal growth factor receptor (EGFR) network in granulosa and cumulus cells. This signaling network can control the transcription of key genes required for cell metabolism, cumulus expansion, and oocyte meiosis resumption. In addition, EGFR signaling is involved in the regulation of gap junctional communication within follicular somatic cells, and in this way it can control the diffusion of meiosis-arresting molecules as well as energy substrates into the oocyte. Thus, the proper functioning of the follicular EGFR network is a vital precondition for the production of matured and developmentally competent oocytes. However, most current in vitro maturation systems are based on a culture of COCs isolated from growing follicles, in which function of the EGFR network may be insufficient for promoting oocyte meiotic and developmental competence. This review focuses on research identifying the importance of the EGFR signaling in somatic follicular cells for oocyte meiotic and developmental competence, and on special approaches to the culture of COCs isolated from growing follicles to promote oocyte quality.

Depression and Smoking Cessation: Evidence from a Smoking Cessation Clinic with 1-Year Follow-Up.

BACKGROUND: Smoking is more prevalent among people with depression. Depression may make cessation more difficult and cessation may affect depression symptoms. PURPOSE: The aims of this study were to assess the associations between (1) baseline depression and 1-year smoking abstinence and (2) abstinence and change in depression. METHODS: Observational study using data collected routinely in a smoking cessation clinic in the Czech Republic from 2008 to 2014. Aim 1: N = 3775 patients; 14.3% reported mild and 15.4% moderate/severe baseline depression levels measured using Beck's Depression Inventory (BDI-II). Logistic regressions assessed if depression level predicted 1-year biochemically verified abstinence while adjusting for patient and treatment characteristics. Aim 2: N = 835 patients abstinent at 1 year; change in depression was analysed using Chi-square statistics, t test and mixed method analyses of variance. RESULTS: Rate of abstinence was lower for patients with mild (32.5%, OR = 0.68; 95% CI: 0.54 to 0.87, p = 0.002) and moderate/severe depression (25.8%; OR = 0.57, 95% CI: 0.45 to 0.74, p < 0.001) compared with patients without depression (40.5%). Across abstinent patients, the majority with baseline depression reported lower depression levels at follow-up. Overall mean (SD) BDI-II scores improved from 9.2 (8.6) to 5.3 (6.1); t(834) = 14.6, p < 0.001. There were significant main effects of time (F(1832) = 880.8, p < 0.001, partial η2 = 0.51) and baseline depression level (F(2832) = 666.4, p < 0.001, partial η2 = 0.62) on follow-up depression and a significant depression * time interaction (F(2832) = 296.5, p < 0.001, partial η2 = 0.42). CONCLUSIONS: In this effective smoking cessation clinic, depression at the start of treatment predicted reduced smoking abstinence 1 year later. Patients abstinent from smoking experienced considerable improvement in depression.

Prostaglandin E2 stimulates the expression of cumulus expansion-related genes in pigs: the role of protein kinase B.

The production of prostaglandin E2 (PGE2) seems to play an important role in the ovulation process. PGE2 was found to induce cumulus expansion and meiosis resumption in mice, but little is known about its role in pigs. The goals of this study were (a) to assess the effect of PGE2 on the expression levels of cumulus expansion-related genes, (b) to define the signaling pathways that drive the PGE2-stimulated expression of cumulus expansion-related genes, (c) to measure the effect of PGE2 on the activation of key signaling molecules (MAPK3/1, PKB) and on hyaluronan production in cumulus cells, and (d) to assess the effect of PGE2 on meiosis resumption. We documented that PGE2 is able to induce the expression of cumulus expansion-related genes (HAS2, TNFAIP6) as well as genes involved in steroidogenesis (CYP11A1) or prostaglandin production (PTGS2). PGE2 is able to activate PKB and MAPK3/1 and induce mild cumulus expansion and meiosis resumption, but less efficiently than FSH.

Weight Concerns Associated With Delay in Quit Date But Not Treatment Outcomes: A Czech Republic Experience.

BACKGROUND: Weight concerns are prevalent in smokers and may reduce the success rate of quitting. This concept has been primarily studied on US populations and it is unknown how weight concerns may differ cross-culturally. This study examined the role of weight concern in European smokers wishing to stop smoking. METHODS: A sample of 593 smokers (299 men and 294 women, mean age 38 years) utilizing the Centre for Tobacco-Dependent in Prague, Czech Republic, between 2010 and 2013 were studied. Weight concerns were assessed at baseline prior to treatment by evidence-based stop smoking methods. Abstinence was evaluated at 12 months post baseline. RESULTS: Approximately 34% of all patients (204/593) were classified as weight concerned (by indicating on the Weight Concern Scale that they would return to smoking after any weight gain) at the time they sought treatment. Among all men, 19.4% (58/299) were weight concerned and among all women, 49.7% (146/294) were weight concerned. Among females, weight-concerned smokers were of similar weight, but younger (p < .001), and had been smoking cigarettes for fewer years (p = .002) compared with those without weight concerns, whereas the male weight-concerned smokers were significantly (p = .030) heavier than those without weight concerns. Although the presence of weight concern was associated with a delay in setting a quit date (log-rank test p = .019), it was not associated with abstinence at one year. CONCLUSION: The quit success rate of weight-concerned smokers in Czech Republic did not differ from those without weight concern when utilizing an individualized smoking cessation treatment program. Individually tailored tobacco dependence treatment could help to prevent weight concern from affecting successful quitting. IMPLICATIONS: This study adds the new cross-cultural aspect of post-cessation weight concern. Weight concern has been studied primarily on US populations and our sample consists of European sample of smokers. Additionally, we have found that the presence of weight concern lead to delay in setting a quit date, but the success rate of those weight concerned did not differ from those without weight concern. Thus, it is possible, that this individualized evidence-based tobacco treatment program was able to prevent weight concern impact towards successful quitting.

Colorectal cancer in patients under the age of 40 years: experience from a tertiary care centre in the Czech Republic.

INTRODUCTION: Colorectal cancer (CRC) in young patients is not an uncommon disease. Reports on its behaviour in young patients are conflicting. The aim of this study was to investigate patient and tumour characteristics, treatment and prognosis of this disease. METHODS: Our study group comprised all patients under the age of 40 years treated with CRC at the Department of Surgery at Motol University Hospital in Prague between the years 2005 and 2015. RESULTS: Thirty-eight patients under 40 years of age diagnosed with CRC were included in the study. Five patients had Lynch syndrome and six had first-degree relatives with CRC. There were 22 rectal tumours. All but four patients underwent resection of the primary tumour, all patients received chemotherapy and 13 patients received biological therapy. Disease recurrence occurred in 25.8%. Five-year survival was 47.9%. Advanced disease and adverse histological subtypes were identified as poor prognostic factors. CONCLUSIONS: Colorectal cancer in young patients has a high incidence of predisposing conditions, aggressive histological features and advanced disease. Young patients are of a good state of health and thus should receive aggressive therapy. Clinicians should pay more attention to symptoms of CRC in young patients to be able to initiate early treatment.

Cyclic guanosine monophosphate does not inhibit gonadotropin-induced activation of mitogen-activated protein kinase 3/1 in pig cumulus-oocyte complexes.

BACKGROUND: Recent results indicate a key role for cyclic guanosine monophosphate (cGMP) in the regulation of oocyte meiotic arrest in preovulatory mammalian follicles. The aim of our study was to determine whether the resumption of oocyte meiosis and expansion of cumulus cells in isolated pig cumulus-oocyte complexes (COCs) can be blocked by a high intracellular concentration of cGMP, and whether this effect is mediated by a cGMP-dependent inhibition of mitogen-activated protein kinase 3/1 (MAPK3/1). METHODS: The COCs were isolated from ovaries of slaughtered gilts and cultured in vitro in M199 supplemented with 5% fetal calf serum. The expression levels of the C-type natriuretic peptide (CNP) precursor (NPPC) and its receptor (NPR2) mRNAs during the culture of COCs were determined by real-time RT-PCR. To control the intracellular concentration of cGMP in the COCs, the culture medium was further supplemented with CNP or various concentrations of synthetic cGMP analogues; the concentration of cGMP in COCs was then assessed by ELISA. The effect of the drugs on oocyte maturation was assessed after 24 and 44 h of culture by determining nuclear maturation. The expansion of cumulus cells was assessed by light microscopy and the expression of cumulus expansion-related genes by real-time RT-PCR. A possible effect of cGMP on FSH-induced activation of MAPK3/1 was assessed by immunoblotting the COC proteins with phospho-specific and total anti-Erk1/2 antibodies. RESULTS: The COCs expressed NPPC and NPR2, the key components of cGMP synthesis, and produced a large amount of cGMP upon stimulation with exogenous CNP, which lead to a significant (P < 0.05) delay in oocyte meiotic resumption. The COCs also responded to cGMP analogues by inhibiting the resumption of oocyte meiosis. The inhibitory effect of cGMP on meiotic resumption was reversed by stimulating the COCs with FSH. However, high concentration of intracellular cGMP was not able to suppress FSH-induced activation of MAPK3/1 in cumulus cells, cumulus expansion and expression of expansion-related genes (P > 0.05). CONCLUSIONS: The findings of this study indicate that high cGMP concentrations inhibit the maturation of pig oocytes in vitro but the inhibitory mechanism does not involve the suppression of MAPK3/1 activation in cumulus cells.

Gene expression analysis of pig cumulus-oocyte complexes stimulated in vitro with follicle stimulating hormone or epidermal growth factor-like peptides.

BACKGROUND: The gonadotropin-induced resumption of oocyte meiosis in preovulatory follicles is preceded by expression of epidermal growth factor (EGF)-like peptides, amphiregulin (AREG) and epiregulin (EREG), in mural granulosa and cumulus cells. Both the gonadotropins and the EGF-like peptides possess the capacity to stimulate resumption of oocyte meiosis in vitro via activation of a broad signaling network in cumulus cells. To better understand the rapid genomic actions of gonadotropins (FSH) and EGF-like peptides, we analyzed transcriptomes of cumulus cells at 3 h after their stimulation. METHODS: We hybridized aRNA from cumulus cells to a pig oligonucleotide microarray and compared the transcriptomes of FSH- and AREG/EREG-stimulated cumulus cells with untreated control cells and vice versa. The identified over- and underexpressed genes were subjected to functional genomic analysis according to their molecular and cellular functions. The expression pattern of 50 selected genes with a known or potential function in ovarian development was verified by real-time qRT-PCR. RESULTS: Both FSH and AREG/EREG increased the expression of genes associated with regulation of cell proliferation, cell migration, blood coagulation and extracellular matrix remodeling. FSH alone induced the expression of genes involved in inflammatory response and in the response to reactive oxygen species. Moreover, FSH stimulated the expression of genes closely related to some ovulatory events either exclusively or significantly more than AREG/EREG (AREG, ADAMTS1, HAS2, TNFAIP6, PLAUR, PLAT, and HSD17B7). In contrast to AREG/EREG, FSH also increased the expression of genes coding for key transcription factors (CEBPB, FOS, ID1/3, and NR5A2), which may contribute to the differing expression profiles of FSH- and AREG/EREG-treated cumulus cells. CONCLUSIONS: The impact of FSH on cumulus cell gene transcription was higher than the impact of EGF-like factors in terms of the number of cell functions affected as well as the number of over- and underexpressed genes. Both FSH and EGF-like factors overexpressed genes involved in the post-ovulatory switch in steroidogenesis and tissue remodelling. However, FSH was remarkably more efficient in the up-regulation of several specific genes essential for ovulation of matured oocytes and also genes that been reported to play an important role in maturation of cumulus-enclosed oocytes in vitro.

Regulation of mitogen-activated protein kinase 3/1 activity during meiosis resumption in mammals.

In vivo, resumption of oocyte meiosis occurs in large ovarian follicles after the preovulatory surge of luteinizing hormone (LH). The LH surge leads to the activation of a broad signaling network in mural granulosa cells equipped with LH receptors. The signals generated in the mural granulosa cells are further augmented by locally produced peptides or steroids and transferred to the cumulus cell compartment and the oocyte itself. Over the last decade, essential progress has been made in the identification of molecular events associated with the final maturation and ovulation of mammalian oocytes. All new evidence argues for a multiple roles of mitogen-activated protein kinase 3/1 (MAPK3/1) in the gonadotropin-induced ovulation processes. However, the knowledge of gonadotropin-induced signaling pathways leading to MAPK3/1 activation in follicular cells seems limited. To date, only the LH-induced transactivation of the epidermal growth factor receptor/MAPK3/1 pathway has been described in granulosa/cumulus cells even though other mechanisms of MAPK3/1 activation have been detected in other types of cells. In this review, we aimed to summarize recent advances in the elucidation of gonadotropin-induced mechanisms leading to the activation of MAPK3/1 in preovulatory follicles and cultured cumulus-oocyte complexes and to point out a specific role of this kinase in the processes accompanying final maturation of the mammalian oocyte.

Extracorporeal Elimination of Circulating Pegylated Liposomal Doxorubicin (PLD) to Enhance the Benefit of Cytostatic Therapy in Platinum-Resistant Ovarian Cancer Patients.

Ovarian cancer is the fifth most common malignancy in the world's female population and with the highest lethality index among gynecological tumors. The prognosis of metastatic disease is usually poor, especially in platinum-resistant cases. There are several options for the treatment of metastatic disease resistant to platinum derivates (e.g. paclitaxel, topotecan and pegylated liposomal doxorubicin), all of which are considered equipotent. Pegylated liposomal doxorubicin (PLD) is a liposomal form of the anthracycline antibiotic doxorubicin. It is characterized by more convenient pharmacokinetics and a different toxicity profile. Cardiotoxicity, the major adverse effect of conventional doxorubicin, is reduced in PLD as well as hematotoxicity, alopecia, nausea and vomiting. Skin toxicity and mucositis, however, emerge as serious issues since they represent dose and schedule-limiting toxicities. The pharmacokinetics of PLD (prolonged biological half-life and preferential distribution into tumor tissue) provide new possibilities to address these toxicity issues. The extracorporeal elimination of circulating liposomes after PLD saturation in the tumor tissue represents a novel and potent strategy to diminish drug toxicity. This article intends to review PLD characteristics and the importance of extracorporeal elimination to enhance treatment tolerance and benefits.

[Position of lipoprotein apheresis in present]. / Postavení lipoproteinové aferézy v soucasnosti.

Lipoprotein apheresis (LA) is an effective treatment method the patients with severe hypercholesterolemia, resistant to the standard therapy. LA is an extracorporeal elimination technique, which specifically removes low density lipoprotein (LDL) cholesterol from the circulation. At present, lipoprotein apheresis, combined with high-dose statin and ezetimibe therapy, is the best available means of treating patients with homozygous and statin refractory heterozygous familial hypercholesterolaemia (FH). However, the extent of cholesterol-lowering achieved is often insufficient to meet the targets set by current guidelines. The recent advent of new classes of lipid-lowering agents provides new hope that the latter objective may now be achievable. These compounds act either by reducing low density lipoprotein (LDL) cholesterol production by inhibiting apolipoprotein B synthesis with an antisense oligonucleotide (mipomersen), or by inhibiting microsomal triglyceride transfer protein (lomitapid), or by enhancing LDL catabolism via monoclonal antibody-mediated inhibition of the activity of proprotein convertase subtilisin/kexin 9 (PCSK9-alirocumab, evolocumab etc). The promising is the combination of LDL-apheresis with new drugs, namely for its potential to further decrease of LDL-cholesterol between apheresis. Depending on the outcome of current trials, it seems likely that these compounds, used alone or combined with lipoprotein apheresis, will markedly improve the management of refractory FH.

[The role of learning curve on the results of aortic valve implantation for severe aortic stenosis]. / Vliv zkusenosti na výsledky katetrové implantace aortální chlopne v lécbe významné aortální stenózy.

INTRODUCTION: Patients with serious aortic stenoses treated by conservative therapy have significantly worse life expectancy. Besides the surgical aortic valve replacement (AVR) as the gold standard of therapy, the transcatheter aortic valve implantation (TAVI) is indicated in patients at very high risk or who are contraindicated to AVR. The role of learning-curve in TAVI has to be established. AIM: Assessment of the results of consecutive TAVI procedures based on the experience of the team. METHODS: 58 high-risk consecutive patients with the average age of 82.2 years were divided into 3 groups based on the TAVI order ( 20., 21.-40., 41.-58.). After the Edwards SAPIEN implantation via transfemoral or transapical approaches, all patients were followed for minimum 30 days. Data from the national registry (Czech TAVI Registry) were used for the retrospective analysis. Comparison of the groups was done by using the Kruskal-Wallis test, Mann-Whitney U test and χ2 test. RESULTS: Significantly shorter procedural time (p < 0.001), hospitalization (p = 0.033) and a lower amount of contrast medium (p < 0.001) was observed during the time. There was no difference in the rate of clinical complications at 30 days. CONCLUSIONS: Increasing experience of the TAVI implantation team is associated with significantly shorter procedural time, hospitalization and a lower amount of contrast medium. Overall very good clinical results during 30 days were not affected by the team experience.

[LDL-apheresis in the treatment familial hypercholesterolemia]. / LDL-aferéza v lécbe familiárních hyperlipoproteinemií

LDL-apheresis is an extracorporeal elimination technique, which specifically removes LDL-cholesterol from the circulation. There are six methods for the selective LDL-cholesterol removal these days. The main indications for LDL-apheresis are the diagnosis of homozygous familial hypercholesterolemia, heterozygous familial hypercholesterolemia which is refractory the standard care and intolerance of routine care, and also patients with lipoprotein(a) increase resistant to the farmacotherapy. There is still debate which LDL-cholesterolemia is indication for LDL-apheresis therapy, and the recommendation differs among various countries. Despite large randomized trials are missing, there are several good quality studies to conclude, that the beneficial cardiovascular effects of LDL-apheresis in severe hypercholesterolemia are important and beneficial.

[The user´s reporting from the national registry of catheter aortic valve implantations (Czech TAVI Registry): the possibilities of the analytical reports based on the database system TrialDB2]. / Uzivatelské výstupy z národního registru katetrových implantací aortální chlopne (Czech TAVI Registry): moznosti analytických výstupu zalozených na databázovém systému TrialDB2.

Assessment of the treatment procedures and their results is increasingly important in current medicine. The emphasis is put on an effective use of the health technologies (HTA). Unlike randomised studies, which involve strictly selected groups of patients who meet inclusion and exclusion criterias, the multicentre clinical registries provide a real-life picture of the treatment safety and effectiveness. Well prepared registries involve both research database and a friendly user interface enabling collection of parametric and easily analyzable data. Although there are some technological aspects aiming to ensure a maximum quality of entered data, cooperation with the users and data managers is essential. Such a registry, otherwise meaningful, must provide answers to previously defined medical hypotheses. Regular feedback to users (so called benchmarking or reporting) is considered to be of key importance. The Czech TAVI Registry (CTR) is a good example of reaching all of the above defined criterias. This registry contains data of approximately 95 % of all transcatheter aortic valve implantations (TAVI) performed in the Czech Republic. It is based on a general system aimed at the design of clinical trials, namely the TrialDB2 (a database system for clinical registries developed by the Institute of Biostatistics and Analyses at the Masaryk University (IBA MU). CTR has been run as an English-language version under the auspices of the Czech Society of Cardiology and represents one of the top-quality registries maintained by IBA MU. This paper presents the currently available database systems and some reports from this particular registry.

Tobacco treatment outcomes in patients with and without a history of depression, Czech Republic, 2005-2010.

INTRODUCTION: Higher prevalence of smoking among depressed patients, as well as the risk of depression in smokers, is well documented. The proportion of patients with a history of depression among those seeking intensive treatment of tobacco dependence is also high. In contrast, evidence of treatment success in this subgroup of patients is controversial. The aim of this study was to compare smoking abstinence rates after tobacco treatment in smokers with and without a history of depression. METHODS: We reviewed retrospective data from 1,730 smokers seeking treatment in Prague, Czech Republic. History of depression was defined as past diagnosis of depression or current treatment of depression. After a 1-year, self-reported smoking status was validated by expired-air carbon monoxide. We used logistic regression to analyze associations between abstinence rates, history of depression, and other factors (eg, age, sex, tobacco dependence). RESULTS: Of 1,730 smokers treated, 289 (16.7%) had a history of depression. The smoking abstinence rate at 1 year was 32.5% for smokers with a history of depression and 38.7% for those with no history (P = .048). Among women, abstinence did not differ between groups (35.0% vs 35.7%; P = .86). However, among men, those with a history of depression had lower rates of abstinence (27.4% vs 41.3%; P = .009). After adjustment for baseline covariates, history of depression was not significantly associated with smoking abstinence in men or women. CONCLUSION: Intensive outpatient tobacco treatment programs can achieve abstinence rates among smokers with a history of depression similar to rates among the general population.

Project I-COP - architecture of software tool for decision support in oncology.

This article briefly describes the development of the I-COP tool, which is designed to promote education and decision making of clinical oncologists. It is based on real data from medical facilities, which are processed, stored in database, analyzed and finally displayed in an interactive software application. Used data sources are shortly described in individual sections together with the functionality of developed tools. The final goal of this project is to provide support for work and education within each involved partner center. Clinical oncologists are therefore supposed to be the authors and users at the same time.