Investigation of factor VIII and von Willebrand factor levels in patients with atrial fibrillation and ischemic stroke

Bevezetés: A cardio- és cerebrovascularis betegségek népegészségügyi jelentőségük miatt intenzíven kutatottak, mégis, kihívást jelent patomechanizmusuk jobb megértése, továbbá a kialakulásuk rizikóját előrejelző és/vagy a kimenetel szempontjából prognosztikai értékkel bíró biomarkerek azonosítása. Betegek és módszerek: Munkánk során két obszervációs klinikai tanulmányban vizsgáltuk az egyes haemostasis és fibrinolitikus faktorok szintjét, különös tekintettel a VIII-as faktorra (FVIII) és a von Willebrand faktorra (VWF) pitvarfibrilláló betegekben, továbbá akut ischaemiás stroke-on átesett betegekben. Az első vizsgálatba összesen 24, pitvarfibrillációban szenvedő beteg és 14, egyéb supraventricularis tachycardiában szenvedő kontroll került be. Mindkét csoport esetén a vérvétel az elektív katéterabláció során a beavatkozás előtt történt három mintavételi helyről: v. femoralis, bal pitvar és bal fülcse. A vérmintákból elvégeztük a FVIII aktivitás, VWF antigén szint, fibrinogén, XIII-as faktor, α2 plazmin inhibitor aktivitás, trombin-antitrombin (TAT) -komplex, kvantitatív fibrin monomer (FM) szint, plazminogén, plazmin-α2 antiplazmin (PAP) -komplex, PAI-1 aktivitás, D-dimer teszteket. A másik tanulmányban 131, ischaemiás stroke miatt trombolízisen átesett beteg vérmintájából határoztuk meg a FVIII aktivitás és VWF antigén szinteket a rekombináns szöveti faktor terápia beadása előtt, közvetlenül a terápia után és 24 órával a lízist követően. Eredményeinket összevetettük a stroke súlyosságával és a terápia rövid-és hosszú-távú kimenetelével. Eredmények: Pitvarfibrilláló betegekben a FVIII aktivitás és a VWF antigén szint szignifikánsan emelkedett volt az intracardialis és perifériás vérmintákban a nem pitvarfibrilláló kontrollokhoz képest. A haemostasis lokális aktivációjára az emelkedett TAT-komplex, FM, PAP-komplex és D-dimer szintek utaltak, azonban ezek az eltérések nem voltak specifikusak pitvarfibrillációra nézve. Az ischaemiás stroke-ban szenvedő betegek vizsgálata során a súlyosabb stroke-ot elszenvedett betegekben szignifikánsan magasabb VWF antigénszintet detektáltunk. Logisztikus regressziós modellt alkalmazva igazoltuk, hogy a trombolízist követően emelkedett FVIII és VWF antigén szintek a rossz hosszú távú kimenetel független rizikótényezői (lízis után közvetlenül FVIII: OR:7,1, 95% CI: 1,7-28,4, p=0,006; VWF: OR: 6,31, 95% CI: 1,8-21,7, p=0,003). Konklúzió: Az emelkedett FVIII és VWF szintek jelezhetik a pitvarfibrillációval társuló thromboemboliás rizikót, míg az ischaemiás stroke trombolízis terápiája után mért emelkedett FVIII és VWF szintek a kedvezőtlen hosszú távú kimenetel független prediktorai.Introduction. Cardiovascular and cerebrovascular diseases, as the leading causes of mortality and long-term morbidity are intensively investigated disorders. Still, today the understanding of their pathomechanism as well as the identification of biomarkers as potential risk factors and/or prognostic markers remain a challenge. Patients and methods. We have carried out two observational clinical studies in order to investigate the levels of certain hemostasis and fibrinolytic factors, particularly factor VIII (FVIII) and von Willebrand factor (VWF) in patients with atrial fibrillation and acute ischemic stroke. The first patient group consisted of 24 patients with atrial fibrillation and 14 patients with other supraventricular tachycardia (controls) undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein, left atrium and left atrial appendage before the ablation procedure. FVIII activity, VWF antigen level, fibrinogen, factor XIII, α2 plasmin inhibitor activity, thrombin-antithrombin (TAT) complex, quantitative fibrin monomer (FM), plasminogen, plasmin-α2 antiplasmin (PAP) complex, PAI-1 activity, and D-dimer were measured from all samples. The other study population included 131 consecutive acute ischemic stroke patients who underwent i.v. thrombolysis with recombinant tissue plasminogen activator (rt-PA). Blood samples were taken on admission, 1 and 24 h after rt-PA administration to measure FVIII activity and VWF antigen levels. Results were compared to stroke severity and to short- and long-term clinical outcomes. Results. In atrial fibrillation patients, FVIII activity and VWF antigen levels were significantly elevated in intracardiac and peripheral blood samples as compared to controls. TAT complex, FM, PAP complex and D-dimer levels were significantly elevated in the intracardiac samples of both groups, indicating a temporary thrombotic risk associated with the catheterization procedure. When investigating ischemic stroke patients, significantly elevated VWF levels were detected on admission in case of more severe stroke. In a binary backward logistic regression analysis elevated FVIII and VWF levels after thrombolysis were independently associated with poor long-term functional outcomes (immediately after thrombolysis FVIII: OR:7.1, 95% CI: 1.7-28.4, p=0.006; VWF: OR: 6.31, 95% CI: 1.8-21.7, p=0.003). Conclusions. Elevated FVIII and VWF levels might predict increased thromboembolic risk in atrial fibrillation patients, while in case of ischemic stroke patients, elevated FVIII and VWF levels after thrombolysis are independent predictors of poor long-term functional outcomes

Markers of Coagulation and Fibrinolysis Predicting the Outcome of Acute Ischemic Stroke Thrombolysis Treatment: a Review of the Literature

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Markers of coagulation and fibrinolysis predicting the outcome of acute ischemic stroke thrombolysis treatment: a review of the literature

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Comparative analysis of EZH2, p16 and p53 expression in uterine carcinosarcomas

Introduction: The role of p16 and p53 immunohistochemistry in the diagnosis of rare and aggressive uterine carcinosarcoma (UCS) has been well established. However, enhancer of zeste homolog 2 (EZH2), a histone methyltransferase and a member of the polycomb group family is a relatively new biomarker, with limited published data on its significance in this tumor type. The goal of this study was to examine EZH2 expression in UCS and its components, in correlation with morphological features, and p16 and p53 staining patterns.Methods: Twenty-eight UCSs were included in the study. EZH2, p16 and p53 immunoreactivity were assessed independently by two pathologists in both tumor components (epithelial and mesenchymal). EZH2 and p16 immunostains were scored semiquantitatively: based on the percentage and intensity of tumor cell staining a binary staining index (“high- or low-expressing”) was calculated. The p53 staining pattern was evaluated as wild-type or aberrant (diffuse nuclear, null, or cytoplasmic expression). Statistical tests were used to evaluate the correlation between staining patterns for all three markers and the different tumor components and histotypes.Results: High EZH2 and p16 expression and aberrant p53 patterns were present in 89.3% 78.6% and 85.7% of the epithelial component and in 78.6%, 62.5% and 82.1% of the mesenchymal component, respectively. Differences among these expression rates were not found to be significant (p > 0.05). Regarding the epithelial component, aberrant p53 pattern was found to be significantly (p = 0.0474) more frequent in the serous (100%) than in endometrioid (66.6%) histotypes. Within the mesenchymal component, p53 null expression pattern occurred significantly (p = 0.0257) more frequently in heterologous sarcoma components (71.4%) compared to the homologous histotype (18.8%).Conclusion: In conclusion, EZH2, p16 and p53 seem to play a universal role in the pathogenesis of UCS; however, a distinctive pattern of p53 expression appears to exist between the serous and endometrioid carcinoma components and also between the homologous and heterologous sarcoma components

Adaptation to recent outcomes attenuates the lasting effect of initial experience on risky decisions

Both primarily and recently encountered information have been shown to influence experience-based risky decision making. The primacy effect predicts that initial experience will influence later choices even if outcome probabilities change and reward is ultimately more or less sparse than primarily experienced. However, it has not been investigated whether extended initial experience would induce a more profound primacy effect upon risky choices than brief experience. Therefore, the present study tested in two experiments whether young adults adjusted their risk-taking behavior in the Balloon Analogue Risk Task after an unsignaled and unexpected change point. The change point separated early "good luck" or "bad luck" trials from subsequent ones. While mostly positive (more reward) or mostly negative (no reward) events characterized the early trials, subsequent trials were unbiased. In Experiment 1, the change point occurred after one-sixth or one-third of the trials (brief vs. extended experience) without intermittence, whereas in Experiment 2, it occurred between separate task phases. In Experiment 1, if negative events characterized the early trials, after the change point, risk-taking behavior increased as compared with the early trials. Conversely, if positive events characterized the early trials, risk-taking behavior decreased after the change point. Although the adjustment of risk-taking behavior occurred due to integrating recent experiences, the impact of initial experience was simultaneously observed. The length of initial experience did not reliably influence the adjustment of behavior. In Experiment 2, participants became more prone to take risks as the task progressed, indicating that the impact of initial experience could be overcome. Altogether, we suggest that initial beliefs about outcome probabilities can be updated by recent experiences to adapt to the continuously changing decision environment

Low factor XIII levels after intravenous thrombolysis predict short-term mortality in ischemic stroke patients

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Intracardiac hemostasis and fibrinolysis parameters in patients with atrial fibrillation

Aims. To identify intracardiac hemostasis or fibrinolysis abnormalities, which are associated with atrial fibrillation (AF) and increase the risk of thromboembolism. Patients and Methods. Patient group consisted of 24 patients with AF and control group included 14 individuals with other supraventricular tachycardia undergoing transcatheter radiofrequency ablation. Blood samples were drawn from the femoral vein (FV), left atrium (LA), and left atrial appendage (LAA) before the ablation procedure. Fibrinogen, factor VIII (FVIII) and factor XIII activity, von Willebrand factor (VWF) antigen, thrombin-antithrombin (TAT) complex, quantitative fibrin monomer (FM), plasminogen, α2-plasmin inhibitor, plasmin-α2-antiplasmin (PAP) complex, PAI-1 activity, and D-dimer were measured from all samples. Results. Levels of FVIII and VWF were significantly elevated in the FV and LA of AF patients as compared to controls. TAT complex, FM, PAP complex, and D-dimer levels were significantly elevated in the LA as compared to FV samples in case of both groups, indicating a temporary thrombotic risk associated with the catheterization procedure. Conclusions. None of the investigated hemostasis or fibrinolysis parameters showed significant intracardiac alterations in AF patients as compared to non-AF controls. AF patients have elevated FVIII and VWF levels, most likely due to endothelial damage, presenting at both intracardiac and systemic level

Intracardiac Fibrinolysis and Endothelium Activation Related to Atrial Fibrillation Ablation with Different Techniques

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A magyar tüdőtranszplantációs program indulása és első eredményei

Absztrakt: Magyarországon az első tüdőtranszplantációt 2015. 12. 12-én végeztük el az Országos Onkológiai Intézet és a Semmelweis Egyetem együttműködésével. Cikkünkben az elmúlt két és fél év eredményeit összegezzük. 2018 augusztusáig 55 tüdőtranszplantációra került sor. Az adatfeldolgozást retrospektív módszerrel végeztük. A várólistára helyezés a Tüdő Transzplantációs Bizottság javaslatára történt. A donortüdők agyhalott donorokból származtak. A posztoperatív gondozás a Semmelweis Egyetemen folytatódott. 2015. 12. 12. és 2018. 07. 31. között 76 szervkivételen vettünk részt: 45 magyar, 23 Eurotransplant-, 8 Eurotransplanton kívüli országban, ezekből 54 kétoldali és 1 egyoldali tüdőtranszplantáció valósult meg. A műtéteket egyoldali (n = 1), kétoldali thoracotomiából (n = 1) vagy ’clamshell’ betolásból (n = 53), venoarterialis extrakorporális membránoxigenizáció-támogatással végeztük. Három esetben az extrakorporális membránoxigenizáció-támogatást a posztoperatív szakban prolongáltuk, másik két betegnél extrakorporális membránoxigenizáció-bridge terápiát követően végeztük el a transzplantációt. Egy kombinált tüdő-vese transzplantáció is történt. A recipiensek alapbetegsége krónikus obstruktív tüdőbetegség (n = 28); fibrotizáló tüdőbetegség (n = 8); cystás fibrosis (n = 12); elsődleges pulmonalis hypertonia (n = 2); histiocytosis-X (n = 1); bronchiectasia (n = 2); lymphangioleiomyomatosis (n = 1) és bronchiolitis obliterans szindróma miatti retranszplantáció (n = 1) volt. Átlagéletkoruk 47,5 ± 15,18 év volt. A legfiatalabb beteg 13 éves volt. A várólistán 12 beteg hunyt el. A betegek átlagosan 24,6 ± 18,18 napot töltöttek az intenzív osztályon. A korai posztoperatív időszakban 2 beteget vesztettünk el. Tartós lélegeztetési igény miatt tracheostomát 13 esetben készítettünk. A betegek 1 éves túlélése 82,96% volt. A hazai tüdőtranszplantációs programban gyorsan emelkednek az esetszámok, ami más centrumok indulásához képest kivételes eredmény. A szövődmények és halálozások aránya más, nagy esetszámú centrumok számainak megfelel. A jövőben a várólista bővítését, az esetszámok további növelését, és az ’ex vivo lung perfusion’ (EVLP-) rendszer használatának bevezetését szeretnénk megvalósítani. Orv Hetil. 2018; 159(46): 1859–1868. | Abstract: The first lung transplantation in Hungary was performed on 12th of December, 2015. It was a joint effort of the National Institute of Oncology and the Semmelweis University. Hereby we summarise the results and experiences from the first three years. Until August, 2018, 55 lung transplantations were performed in Hungary. This was a retrospective analysis. All patients were listed according to the recommendation of the Lung Transplantation Committee. All implanted lungs have been procured from brain dead donors. Postoperative treatment and rehabilitation of the patients were continued at the Semmelweis University. Between 12. 12. 2015 and 31. 07. 2018, our team performed 76 organ retrievals: out of 45 Hungarian offers, 23 came from Eurotransplant countries and 8 outside of the Eurotransplant region. From these donations, 54 double and 1 single side transplantations were successfully performed. The surgical approach was single side thoracotomy (n = 1), bilateral thoracotomy (n = 1) and in the majority of the cases clamshell incision (n = 53). For the intraoperative veno-arterial extracorporeal membrane oxygenation support was used. The extracorporeal membrane oxygenation support had to be prolonged in 3 patients into the early postoperative period, two other recipients were bridged to transplant with extracorporeal membrane oxygenation. In the same time period, one combined lung-kidney transplantation was also performed. The distribution of recipients according to the underlying disease was: chronic obstructive pulmonary disease (n = 28); idiopathic pulmonary fibrosis (n = 8); cystic fibrosis (n = 12); primary pulmonary hypertension (n = 2); hystiocytosis-X (n = 1); bronchiectasis (n = 2); lymphangioleiomyomatosis (n = 1); and re-transplantation following bronchiolitis obliterans syndrome (n = 1), respectively. The mean age of recipients was 47.5 ± 15.18 years. The youngest recipient was 13 years old. We unfortunately lost 12 patients on our waiting list. The mean intensive care unit stay was 24.6 ± 18.18 days. Two patients were lost in the early postoperative phase. Tracheostomy was necessary in 13 cases due to the need of prolonged ventilation. 1-year survival of the recipients was 82.96% (until 31. 07. 2018). When looking at the first three years of the program, the case numbers elevated quickly throughout the years which is rather unique when compared to other centres in their starting period. Perioperative mortality and morbidity is comparable with high-volume lung transplantation centres. In the future we would like to increase the number of patients on the waiting list, thus increasing the total number of transplantations performed, and we are also planning to implement the use of the ex vivo lung perfusion system (EVLP) in our program. Orv Hetil. 2018; 159(46): 1859–1868

The factor XIII-A Val34Leu polymorphism decreases whole blood clot mass at high fibrinogen concentrations

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