Familial hypercholesterolemia (FH) is a relatively rare genetic disease associated with high serum cholesterol levels but also with abnormalities in blood coagulation. Novel pharmacotherapeutic approaches in FH including proprotein convertase subtilisin/kexin type 9 antibodies (PCSK9Ab) are very efficient in decreasing cholesterol levels but their impact on coagulation in FH is not yet established. Therefore, we hypothesized that these novel antidyslipidemic drugs can positively impact blood coagulation due to their more potent effect on cholesterol. A total of 15 healthy volunteers and all 15 available patients with severe FH treated at the University Hospital Hradec Králové were enrolled, coagulation was assessed by mechanic coagulometer, and the impact of four clinically used direct anticoagulants was analyzed ex vivo. FH patients were treated effectively as their total cholesterol was 4.11 ± 1.57 mM and LDL cholesterol was 2.44 ± 1.46 mM, which were even lower values than detected in our generally healthy controls. Twelve from the 15 FH patients were finally analyzed as 3 were treated with anticoagulants. Coagulation in FH patients was prolonged more extensively by dabigatran and rivaroxaban, when compared to healthy controls. Treatment with PCSK9Ab or lipid apheresis did not seem to have a significant effect on coagulation. The latter procedure however significantly decreased serum levels of one vitamin K form, MK4. Shorter coagulation time was associated with higher levels of LDL, non-HDL, and total cholesterol. Current treatment of FH seems to improve the effects of direct anticoagulants beyond known effects on LDL cholesterol levels.

• MeSH
• anticholesteremika terapeutické užití   MeSH
• antikoagulancia * terapeutické užití   farmakologie   MeSH
• cholesterol krev   MeSH
• dabigatran terapeutické užití   farmakologie   MeSH
• dospělí MeSH
• hemokoagulace * účinky léků   MeSH
• hyperlipoproteinemie typ II * krev   farmakoterapie   MeSH
• hypolipidemika * terapeutické užití   farmakologie   MeSH
• LDL-cholesterol krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• PCSK9 inhibitory MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• rivaroxaban terapeutické užití   farmakologie   MeSH
• studie případů a kontrol MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Age-related macular degeneration (AMD) is a progressive chronic disease causing visual impairment or central vision loss in the elderly. We hypothesized that successful rheopheresis would be associated with positive changes in soluble endoglin (sENG), PSCK9, alpha-2-macroglobulin (A2M), and hs-CRP levels. 31 elderly patients with the dry form of AMD, treated with rheopheresis with a follow-up period of at least 5 years and an average age of 68 ± 4 years, were evaluated. Each treated patient received a series of 8 procedures in 10 weeks and, after the 2-year period, another 2 procedures within 1 week. Then, the patients were followed up every 6 months and divided into the successfully treated and therapeutic failure group according to best-corrected visual acuity (BCVA), size of the drusen area, and the drusenoid pigment epithelium detachment (DPED). Based on the ophthalmological assessment, rheopheresis treatment was successful in 73% of AMD patients. The therapy was associated with a significant decrease in total cholesterol, LDL-C, HDL-C, apoprotein B, lipoprotein (a) levels, and rheologically important parameters, irrespective of the therapy's success or failure. The success of rheopheresis therapy was exclusively related to a significant decrease in sENG and A2M levels. Over the long term, rheopheresis prevented the decline of BCVA, reduced the DPED and area of macular drusen, and improved the preservation of an intact photoreceptor ellipsoid zone in most patients. Moreover, we showed for the first time that sENG and A2M could be potentially sensitive biomarkers of successful rheopheresis procedure, irrespective of lipid parameters changes.

• MeSH
• biologické markery * krev   MeSH
• endoglin * krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• makulární degenerace * terapie   krev   MeSH
• senioři MeSH
• výsledek terapie MeSH
• zraková ostrost MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Východisko: Lipoproteinová aferéza (LA) je velmi účinná, časově náročná a nákladná metoda snižování hladin LDL-cholesterolu (Low Denzity Lipoprotein Cholesterol – LDL-C), lipoproteinu(a) – Lp(a) a dalších apoB obsahujících lipoproteinů, včetně na triglyceridy bohatých lipoproteinů. Tato metoda byla poprvé použita téměř před 50 lety a dlouho byla terapií „poslední možnosti“ pro dyslipidemie, které jinak nelze řešit. V posledních letech jsou vyvíjena nová, velmi účinná hypolipidemika a účelem tohoto přehledu je definovat roli lipoproteinové aferézy v současném kontextu. Rozbor problematiky: Lipoproteinová aferéza stále hraje důležitou roli v léčbě pacientů s homozygotní familiární hypercholesterolemií (HoFH) a některých pacientů s dalšími formami hypercholesterolemie a aterosklerotickými kardiovaskulárními chorobami (ASKVO). Zejména pacienti, kteří nedosahují léčebných cílů navzdory moderní hypolipidemické farmakoterapii, ať už proto, že ji netolerují nebo je terapeutická odpověď nedostatečná. Lp(a) je vedle LDL-C další důležitý kardiovaskulární rizikový faktor a lipoproteinová aferéza je taktéž využívána ke snížení koncentrací lipoproteinu(a) u pacientů s významným zvýšením Lp(a) a kardiovaskulárním onemocněním. Existuje však značná heterogenita v doporučeních vědeckých autorit ohledně toho, které skupiny pacientů by měly být léčeny lipoproteinovou aferézou. Závěr: Doporučení odborných společností indikují léčbu klasickými i moderními hypolipidemiky před zahájením léčby lipoproteinovou aferézou a současně také s aferézou s cílem snížení a dosažení cílových hladin LDL-C. LA nemusí předcházet farmakoterapii, naopak klinické studie ukázaly možnost weaningu z LA při použití testovaných nových léčiv. Kombinované použití lipoproteinové aferézy a nových hypolipidemik (inhibitorů PCSK9, lomitapidu a evinakumabu) nabízí cenný terapeutický přístup u pacientů s obtížně kontrolovatelnými hladinami LDL-C. Lipoproteinová aferéza zůstává důležitým nástrojem pro terapii pacientů se závažnými dyslipidemiemi rezistentními na léčbu, zejména pacientů s homozygotní FH.

Background: Lipoprotein apheresis (LA) is a very effective, time-consuming and costly method of lowering low-density lipoprotein cholesterol (LDL-C), lipoprotein(a) – Lp(a) and other apoB-containing lipoproteins, including triglyceride-rich lipoproteins. This method was first used almost 50 years ago and has long been a “last resort” therapy for dyslipidemias that cannot otherwise be addressed. In recent years, new, highly effective hypolipidemic agents have been developed and the purpose of this review is to define the role of lipoprotein apheresis in the current context. Discussion of the problem: Lipoprotein apheresis still plays an important role in the treatment of patients with homozygous familial hypercholesterolemia (HoFH) and some patients with other forms of hypercholesterolemia and atherosclerotic cardiovascular disease (ASCVD). In particular, patients who fail to achieve therapeutic goals despite modern hypolipidemic drug therapy, either because they are intolerant or the therapeutic response is inadequate. Lp(a) is another important cardiovascular risk factor besides LDL-C, and lipoprotein apheresis is also used to reduce lipoprotein(a) concentrations in patients with significant elevations of Lp(a) and cardiovascular disease. However, there is considerable heterogeneity in the recommendations of scientific authorities regarding which groups of patients should be treated with lipoprotein apheresis. Conclusion. Recommendations of professional societies indicate treatment with conventional and modern hypolipidemic agents before starting lipoprotein apheresis therapy and simultaneously with apheresis to reduce and achieve target LDL-C levels. LA does not need to precede drug therapy; on the contrary, clinical trials have shown the possibility of weaning from LA when using investigational new drugs. The combined use of lipoprotein apheresis and novel hypolipidemics (PCSK9 inhibitors, lomitapide and evinacumab) offers a valuable therapeutic approach for patients with difficult-to-control LDL-C levels. Lipoprotein apheresis remains an important tool for the treatment of patients with severe treatment-resistant dyslipidemias, especially those with homozygous FH.

• Klíčová slova
• lipoproteinová aferéza,
• MeSH
• ateroskleróza terapie   MeSH
• dyslipidemie * terapie   MeSH
• humanizované monoklonální protilátky aplikace a dávkování   MeSH
• hypercholesterolemie terapie   MeSH
• hypolipidemika aplikace a dávkování   farmakologie   MeSH
• kardiovaskulární nemoci terapie   MeSH
• LDL-cholesterol krev   účinky léků   MeSH
• lidé MeSH
• lipoprotein (a) krev   účinky léků   MeSH
• PCSK9 inhibitory terapeutické užití   MeSH
• rizikové faktory kardiovaskulárních chorob MeSH
• separace krevních složek * metody   přístrojové vybavení   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• práce podpořená grantem MeSH
• přehledy MeSH

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.

• MeSH
• agregace trombocytů * účinky léků   MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II * krev   terapie   farmakoterapie   MeSH
• inhibitory agregace trombocytů * terapeutické užití   farmakologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• monoklonální protilátky terapeutické užití   farmakologie   MeSH
• PCSK9 inhibitory * MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 * imunologie   MeSH
• senioři MeSH
• separace krevních složek * MeSH
• trombocyty účinky léků   metabolismus   imunologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

• Publikační typ
• abstrakt z konference MeSH

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.

• MeSH
• dárci tkání MeSH
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• novorozenec MeSH
• plazmaferéza MeSH
• předškolní dítě MeSH
• registrace MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• separace krevních složek * metody   MeSH
• výměna plazmy škodlivé účinky   MeSH
• Check Tag
• dítě MeSH
• dospělí MeSH
• kojenec MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• novorozenec MeSH
• předškolní dítě MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The aim of this study was to compare trends in mortality and incidence, clinicopathological features and survival of patients diagnosed with pancreatic ductal adenocarcinoma under 50 years of age (early-onset pancreatic cancer [EOPC]) with patients diagnosed over 50 years of age (late-onset pancreatic cancer [LOPC]). METHODS: The national oncological registry of the Czech Republic was reviewed to identify all patients with histologically confirmed pancreatic ductal adenocarcinoma diagnosed between the years 1985 and 2015. Incidence, mortality, clinicopathological and survival data were analyzed and compared between patients with EOPC and LOPC. RESULTS: From a total of 18 888 patients included in the study, 1324 patients were under the age of 50 years (7.0%). The average annual percentage changes (AAPC) in incidence of all patients with EOPC was -1.0%. The APPC for male patients with EOPC was -2.0% and for female patients was +0.6%. The AAPC in incidence for LOPC was +1.3%. There were no differences in tumor stage, grade or location between EOPC and LOPC. Young patients were more frequently male (64.4% vs. 52.9%), more frequently underwent treatment and had better overall survival. The median survival interval for EOPC was 5.9 months and for LOPC was 4.5 months (p < .001). CONCLUSIONS: The clinicopathological features of pancreatic ductal adenocarcinoma were similar in patients under and over the age of 50 years. Patients with EOPC survived longer than patients with LOPC. Continued efforts should be made to diagnose early and treat young patients aggressively.

• MeSH
• duktální karcinom slinivky břišní * epidemiologie   terapie   MeSH
• incidence MeSH
• lidé středního věku MeSH
• lidé MeSH
• nádory slinivky břišní * epidemiologie   terapie   diagnóza   MeSH
• registrace MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Geografické názvy
• Česká republika MeSH

• MeSH
• COVID-19 * epidemiologie   mortalita   MeSH
• hospitalizace statistika a číselné údaje   MeSH
• lidé MeSH
• riziko MeSH
• vakcinace statistika a číselné údaje   MeSH
• věkové faktory MeSH
• Check Tag
• lidé MeSH
• Geografické názvy
• Česká republika MeSH

Lipoprotein apheresis (LA) is a therapeutic option for patients with severe hypercholesterolemia who have persistently elevated LDL-C levels despite attempts at drug therapy. MicroRNAs (miRNAs), important posttranscriptional gene regulators, are involved in the pathogenesis of atherosclerosis. Our study aimed to monitor the dynamics of twenty preselected circulating miRNAs in patients under long-term apheresis treatment. Plasma samples from 12 FH patients (men = 50%, age = 55.3 ± 12.2 years; mean LA overall treatment time = 13.1 ± 7.8 years) were collected before each apheresis therapy every sixth month over the course of four years of treatment. Eight complete follow-up (FU) samples were measured in each patient. Dynamic changes in the relative quantity of 6 miRNAs (miR-92a, miR-21, miR-126, miR-122, miR-26a, and miR-185; all p < 0.04) during FU were identified. Overall apheresis treatment time influenced circulating miR-146a levels (p < 0.04). In LDLR mutation homozygotes (N = 5), compared to heterozygotes (N = 7), we found higher plasma levels of miR-181, miR-126, miR-155, and miR-92a (all p < 0.03). Treatment with PCSK9 inhibitors (N = 6) affected the plasma levels of 7 miRNAs (miR-126, miR-122, miR-26a, miR-155, miR-125a, miR-92a, and miR-27a; all p < 0.04). Long-term monitoring has shown that LA in patients with severe familial hypercholesterolemia influences plasma circulating miRNAs involved in endothelial dysfunction, cholesterol homeostasis, inflammation, and plaque development. The longer the treatment using LA, the better the miRNA milieu depicting the potential cardiovascular risk.

• MeSH
• cirkulující mikroRNA * genetika   MeSH
• dospělí MeSH
• hyperlipoproteinemie typ II * genetika   terapie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mikro RNA * genetika   MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 genetika   MeSH
• senioři MeSH
• separace krevních složek * MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• Publikační typ
• abstrakt z konference MeSH