106 results on '"P. Wadowski"'
Search Results
2. Synthesis, anticancer activity, and molecular docking of half-sandwich iron(II) cyclopentadienyl complexes with maleimide and phosphine or phosphite ligands
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Das, Sujoy, Strachanowska, Marcelina, Wadowski, Piotr, Juszczak, Michał, Tokarz, Paulina, Kosińska, Aneta, Palusiak, Marcin, Rybarczyk-Pirek, Agnieszka J., Wzgarda-Raj, Kinga, Vasudevan, Saranya, Chworos, Arkadiusz, Woźniak, Katarzyna, and Rudolf, Bogna
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- 2024
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3. Synthesis, anticancer activity, and molecular docking of half-sandwich iron(II) cyclopentadienyl complexes with maleimide and phosphine or phosphite ligands
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Sujoy Das, Marcelina Strachanowska, Piotr Wadowski, Michał Juszczak, Paulina Tokarz, Aneta Kosińska, Marcin Palusiak, Agnieszka J. Rybarczyk-Pirek, Kinga Wzgarda-Raj, Saranya Vasudevan, Arkadiusz Chworos, Katarzyna Woźniak, and Bogna Rudolf
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Medicine ,Science - Abstract
Abstract In these studies, we designed and investigated the potential anticancer activity of five iron(II) cyclopentadienyl complexes bearing different phosphine and phosphite ligands. All complexes were characterized with spectroscopic analysis viz. NMR, FT–IR, ESI–MS, UV–Vis, fluorescence, XRD (for four complexes) and elemental analyses. For biological studies, we used three types of cells—normal peripheral blood mononuclear (PBM) cells, leukemic HL-60 cells and non-small-cell lung cancer A549 cells. We evaluated cell viability and DNA damage after cell incubation with these complexes. We observed that all iron(II) complexes were more cytotoxic for HL-60 cells than for A549 cells. The complex CpFe(CO)(P(OPh)3)(η1-N-maleimidato) 3b was the most cytotoxic with IC50 = 9.09 µM in HL-60 cells, IC50 = 19.16 µM in A549 and IC50 = 5.80 µM in PBM cells. The complex CpFe(CO)(P(Fu)3)(η1-N-maleimidato) 2b was cytotoxic only for both cancer cell lines, with IC50 = 10.03 µM in HL-60 cells and IC50 = 73.54 µM in A549 cells. We also found the genotoxic potential of the complex 2b in both types of cancer cells. However, the complex CpFe(CO)2(η1-N-maleimidato) 1 which we studied previously, was much more genotoxic than complex 2b, especially for A549 cells. The plasmid relaxation assay showed that iron(II) complexes do not induce strand breaks in fully paired ds-DNA. The DNA titration experiment showed no intercalation of complex 2b into DNA. Molecular docking revealed however that complexes CpFe(CO)(PPh3) (η1-N-maleimidato) 2a, 2b, 3b and CpFe(CO)(P(OiPr)3)(η1-N-maleimidato) 3c have the greatest potential to bind to mismatched DNA. Our studies demonstrated that the iron(II) complex 1 and 2b are the most interesting compounds in terms of selective cytotoxic action against cancer cells. However, the cellular mechanism of their anticancer activity requires further research.
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- 2024
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4. Myocardial Oedema as a Consequence of Viral Infection and Persistence—A Narrative Review with Focus on COVID-19 and Post COVID Sequelae
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Noel G. Panagiotides, Michael Poledniczek, Martin Andreas, Martin Hülsmann, Alfred A. Kocher, Christoph W. Kopp, Aleksandra Piechota-Polanczyk, Annika Weidenhammer, Noemi Pavo, and Patricia P. Wadowski
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myocardial oedema ,glycocalyx ,coronavirus disease 2019 ,microcirculation ,platelets ,Microbiology ,QR1-502 - Abstract
Microvascular integrity is a critical factor in myocardial fluid homeostasis. The subtle equilibrium between capillary filtration and lymphatic fluid removal is disturbed during pathological processes leading to inflammation, but also in hypoxia or due to alterations in vascular perfusion and coagulability. The degradation of the glycocalyx as the main component of the endothelial filtration barrier as well as pericyte disintegration results in the accumulation of interstitial and intracellular water. Moreover, lymphatic dysfunction evokes an increase in metabolic waste products, cytokines and inflammatory cells in the interstitial space contributing to myocardial oedema formation. This leads to myocardial stiffness and impaired contractility, eventually resulting in cardiomyocyte apoptosis, myocardial remodelling and fibrosis. The following article reviews pathophysiological inflammatory processes leading to myocardial oedema including myocarditis, ischaemia-reperfusion injury and viral infections with a special focus on the pathomechanisms evoked by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. In addition, clinical implications including potential long-term effects due to viral persistence (long COVID), as well as treatment options, are discussed.
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- 2024
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5. Platelet activation and aggregation in different centrifugal-flow left ventricular assist devices
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Maximilian Tscharre, Franziska Wittmann, Daniela Kitzmantl, Silvia Lee, Beate Eichelberger, Patricia P. Wadowski, Günther Laufer, Dominik Wiedemann, Birgit Forstner-Bergauer, Cihan Ay, Simon Panzer, Daniel Zimpfer, and Thomas Gremmel
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lvad ,heartmate 3 ,hvad ,platelet activation ,platelet aggregation ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Left-ventricular assist devices (LVADs) improve outcomes in end-stage heart failure patients. Two centrifugal-flow LVAD systems are currently approved, HeartMate 3 (HM3) and Medtronic/Heartware HVAD (HVAD). Clinical findings suggest differences in thrombogenicity between both systems. We compared markers of platelet activation and aggregation between HM3 and HVAD. We prospectively included 59 LVAD patients (40 HM3, 19 HVAD). Platelet P-selectin expression, activated glycoprotein (GP) IIb/IIIa and monocyte-platelet aggregates (MPA) were assessed by flow-cytometry. Platelet aggregation was measured by light-transmission aggregometry (LTA) and multiple-electrode aggregometry (MEA). Von-Willebrand factor (VWF) antigen (VWF:Ag), VWF activity (VWF:Ac), and VWF multimer pattern analysis were determined. Soluble P-selectin (sP-selectin) was measured with an enzyme-linked immunoassay. P-selectin, GPIIb/IIIa and MPA levels in vivo and in response to arachidonic acid, adenosine diphosphate, and thrombin receptor activating peptide were similar between HM3 and HVAD (all p > .05). Likewise, agonist-inducible platelet aggregation by LTA and MEA did not differ between HM3 and HVAD (all p > .05). VWF:Ag levels and FVIII:C were similar between both systems (both p > .05), but patients with HVAD had significantly lower VWF:Ac (p = .011) and reduced large VWF multimers (p = .013). Finally, sP-selectin levels were similar in patients with HVAD and HM3 (p = .845). In conclusion, on-treatment platelet activation and aggregation are similar in HM3 and HVAD patients. Potential clinical implications of observed differences in VWF profiles between both LVAD systems need to be addressed in future clinical trials.
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- 2022
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6. Micro- and Macrovascular Effects of Inflammation in Peripheral Artery Disease—Pathophysiology and Translational Therapeutic Approaches
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Michael Poledniczek, Christoph Neumayer, Christoph W. Kopp, Oliver Schlager, Thomas Gremmel, Alicja Jozkowicz, Michael E. Gschwandtner, Renate Koppensteiner, and Patricia P. Wadowski
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atherosclerosis ,inflammation ,peripheral artery disease ,glycocalyx ,endothelial dysfunction ,Biology (General) ,QH301-705.5 - Abstract
Inflammation has a critical role in the development and progression of atherosclerosis. On the molecular level, inflammatory pathways negatively impact endothelial barrier properties and thus, tissue homeostasis. Conformational changes and destruction of the glycocalyx further promote pro-inflammatory pathways also contributing to pro-coagulability and a prothrombotic state. In addition, changes in the extracellular matrix composition lead to (peri-)vascular remodelling and alterations of the vessel wall, e.g., aneurysm formation. Moreover, progressive fibrosis leads to reduced tissue perfusion due to loss of functional capillaries. The present review aims at discussing the molecular and clinical effects of inflammatory processes on the micro- and macrovasculature with a focus on peripheral artery disease.
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- 2023
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7. Toll-like Receptors as Pro-Thrombotic Drivers in Viral Infections: A Narrative Review
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Benjamin Panzer, Christoph W. Kopp, Christoph Neumayer, Renate Koppensteiner, Alicja Jozkowicz, Michael Poledniczek, Thomas Gremmel, Bernd Jilma, and Patricia P. Wadowski
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toll-like receptors ,glycocalyx ,SARS-CoV-2 infection ,platelet activation ,micro-thrombosis ,Cytology ,QH573-671 - Abstract
Toll-like receptors (TLRs) have a critical role in the pathogenesis and disease course of viral infections. The induced pro-inflammatory responses result in the disturbance of the endovascular surface layer and impair vascular homeostasis. The injury of the vessel wall further promotes pro-thrombotic and pro-coagulatory processes, eventually leading to micro-vessel plugging and tissue necrosis. Moreover, TLRs have a direct role in the sensing of viruses and platelet activation. TLR-mediated upregulation of von Willebrand factor release and neutrophil, as well as macrophage extra-cellular trap formation, further contribute to (micro-) thrombotic processes during inflammation. The following review focuses on TLR signaling pathways of TLRs expressed in humans provoking pro-thrombotic responses, which determine patient outcome during viral infections, especially in those with cardiovascular diseases.
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- 2023
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8. Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Acute Coronary Syndrome: Implications for Platelet Reactivity?
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Tscharre, Maximilian, Wadowski, Patricia P., Weikert, Constantin, Pultar, Joseph, Eichelberger, Beate, Panzer, Simon, and Gremmel, Thomas
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- 2021
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9. Comparison of coenzyme Q10 or fish oil for prevention of intermittent hypoxia-induced oxidative injury in neonatal rat lungs
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Christina D’Agrosa, Charles L. Cai, Faisal Siddiqui, Karen Deslouches, Stephen Wadowski, Jacob V. Aranda, and Kay D. Beharry
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Coenzyme Q10 ,Fish oil ,Intermittent hypoxia ,Lung injury ,Oxidative stress ,Diseases of the respiratory system ,RC705-779 - Abstract
Abstract Background Neonatal intermittent hypoxia (IH) results in oxidative distress in preterm infants with immature antioxidant systems, contributing to lung injury. Coenzyme Q10 (CoQ10) and fish oil protect against oxidative injury. We tested the hypothesis that CoQ10 is more effective than fish oil for prevention of IH-induced lung injury in neonatal rats. Methods Newborn rats were exposed to two clinically relevant IH paradigms at birth (P0): (1) 50% O2 with brief hypoxia (12% O2); or (2) room air (RA) with brief hypoxia (12% O2), until P14 during which they were supplemented with daily oral CoQ10, fish oil, or olive oil from P0 to P14. Pups were studied at P14 or placed in RA until P21 with no further treatment. Lungs were assessed for histopathology and morphometry; biomarkers of oxidative stress and lipid peroxidation; and antioxidants. Results Of the two neonatal IH paradigms 21%/12% O2 IH resulted in the most severe outcomes, evidenced by histopathology and morphometry. CoQ10 was effective for preserving lung architecture and reduction of IH-induced oxidative stress biomarkers. In contrast, fish oil resulted in significant adverse outcomes including oversimplified alveoli, hemorrhage, reduced secondary crest formation and thickened septae. This was associated with elevated oxidants and antioxidants activities. Conclusions Data suggest that higher FiO2 may be needed between IH episodes to curtail the damaging effects of IH, and to provide the lungs with necessary respite. The negative outcomes with fish oil supplementation suggest oxidative stress-induced lipid peroxidation.
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- 2021
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10. Effect of the Addition of Re on the Microstructure and Phase Composition of Haynes 282: Ab Initio Modelling and Experimental Investigation of Additively Manufactured Specimens
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Antoni Wadowski, Jan S. Wróbel, Milena Koralnik, and Ryszard Sitek
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ab initio calculation ,short-range ordering ,rhenium effect ,nickel alloys ,additive manufacturing ,Technology ,Electrical engineering. Electronics. Nuclear engineering ,TK1-9971 ,Engineering (General). Civil engineering (General) ,TA1-2040 ,Microscopy ,QH201-278.5 ,Descriptive and experimental mechanics ,QC120-168.85 - Abstract
Interactions in a multicomponent Ni-Cr-Mo-Al-Re model alloy were determined by ab initio calculations in order to investigate the Re doping effect on Haynes 282 alloys. Simulation results provided an understanding of short-range interactions in the alloy and successfully predicted the formation of a Cr and Re-rich phase. The Haynes 282 + 3 wt% Re alloy was manufactured using the additive manufacturing direct metal laser sintering (DMLS) technique, in which the presence of the (Cr17Re6)C6 carbide was confirmed by an XRD study. The results provide useful information about the interactions between Ni, Cr, Mo, Al, and Re as a function of temperature. The designed five-element model can lead to a better understanding of phenomena that occur during the manufacture or heat treatment of modern, complex, multicomponent Ni-based superalloys.
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- 2023
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11. Platelet-to-Lymphocyte Ratio as Marker of Platelet Activation in Patients on Potent P2Y Inhibitors
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Patricia P. Wadowski MD, PhD, Joseph Pultar, Constantin Weikert, Beate Eichelberger, Maximilian Tscharre MD, PhD, Renate Koppensteiner MD, Simon Panzer MD, and Thomas Gremmel MD, MBA
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Diseases of the circulatory (Cardiovascular) system ,RC666-701 ,Therapeutics. Pharmacology ,RM1-950 - Abstract
A high platelet-to-lymphocyte ratio (PLR) has recently been associated with ischemic outcomes in cardiovascular disease. Increased platelet reactivity and leukocyte-platelet aggregate formation are directly involved in the progress of atherosclerosis and have been linked to ischemic events following percutaneous coronary intervention (PCI). In order to understand the relation of PLR with platelet reactivity, we assessed PLR as well as agonist-inducible platelet aggregation and neutrophil-platelet aggregate (NPA) formation in 182 acute coronary syndrome (ACS) patients on dual antiplatelet therapy with aspirin and prasugrel (n = 96) or ticagrelor (n = 86) 3 days after PCI. PLR was calculated from the blood count. Platelet aggregation was measured by multiple electrode aggregometry and NPA formation was determined by flow cytometry, both in response to ADP and SFLLRN. A PLR ≥91 was considered as high PLR based on previous data showing an association of this threshold with adverse ischemic outcomes. In the overall cohort and in prasugrel-treated patients, high PLR was associated with higher SFLLRN-inducible platelet aggregation (67 AU [50-85 AU] vs 59.5 AU [44.3-71.3 AU], P = .01, and 73 AU [50-85 AU] vs 61.5 AU [46-69 AU], P = .02, respectively). Further, prasugrel-treated patients with high PLR exhibited higher ADP- (15% [11%-23%] vs 10.9% [7.6%-15.9%], P = .007) and SFLLRN-inducible NPA formation (64.3% [55.4%-73.8%] vs 53.8% [44.1%-70.1%], P = .01) as compared to patients with low PLR. These differences were not seen in ticagrelor-treated patients. In conclusion, high PLR is associated with increased on-treatment platelet reactivity in prasugrel-treated patients, but not in patients on ticagrelor.
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- 2022
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12. Growth Differentiation Factor 15 Is Associated with Platelet Reactivity in Patients with Acute Coronary Syndrome
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David Mutschlechner, Maximilian Tscharre, Patricia P. Wadowski, Joseph Pultar, Constantin Weikert, Silvia Lee, Beate Eichelberger, Simon Panzer, Thomas Perkmann, and Thomas Gremmel
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growth differentiation factor 15 ,acute coronary syndrome ,prasugrel ,ticagrelor ,platelet reactivity ,Medicine - Abstract
Bleeding events in patients with acute coronary syndrome (ACS) are a risk factor for adverse outcomes, including mortality. We investigated the association of growth differentiation factor (GDF)-15, an established predictor of bleeding complications, with on-treatment platelet reactivity in ACS patients undergoing coronary stenting receiving prasugrel or ticagrelor. Platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to adenosine diphosphate (ADP), arachidonic acid (AA), thrombin receptor-activating peptide (TRAP, a protease-activated receptor-1 (PAR-1) agonist), AYPGKF (a PAR-4 agonist) and collagen (COL). GDF-15 levels were measured using a commercially available assay. GDF-15 correlated inversely with MEA ADP (r = −0.202, p = 0.004), MEA AA (r = −0.139, p = 0.048) and MEA TRAP (r = −0.190, p = 0.007). After adjustment, GDF-15 was significantly associated with MEA TRAP (β = −0.150, p = 0.044), whereas no significant associations were detectable for the other agonists. Patients with low platelet reactivity in response to ADP had significantly higher GDF-15 levels (p = 0.005). In conclusion, GDF-15 is inversely associated with TRAP-inducible platelet aggregation in ACS patients treated with state-of-the-art antiplatelet therapy and significantly elevated in patients with low platelet reactivity in response to ADP.
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- 2023
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13. Microvascular Thrombosis as a Critical Factor in Severe COVID-19
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Patricia P. Wadowski, Benjamin Panzer, Alicja Józkowicz, Christoph W. Kopp, Thomas Gremmel, Simon Panzer, and Renate Koppensteiner
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capillaries ,coronavirus disease 2019 ,glycocalyx ,microcirculation ,platelets ,thromboinflammation ,Biology (General) ,QH301-705.5 ,Chemistry ,QD1-999 - Abstract
Platelet–endothelial interactions have a critical role in microcirculatory function, which maintains tissue homeostasis. The subtle equilibrium between platelets and the vessel wall is disturbed by the coronavirus disease 2019 (COVID-19), which affects all three components of Virchow’s triad (endothelial injury, stasis and a hypercoagulable state). Endotheliitis, vasculitis, glycocalyx degradation, alterations in blood flow and viscosity, neutrophil extracellular trap formation and microparticle shedding are only few pathomechanisms contributing to endothelial damage and microthrombosis resulting in capillary plugging and tissue ischemia. In the following opinion paper, we discuss major pathological processes leading to microvascular endothelial activation and thrombosis formation as a possible major adverse factor driving the deterioration of patient disease course in severe COVID-19.
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- 2023
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14. Decreased Platelet Inhibition by Thienopyridines in Hyperuricemia
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Lee, Silvia, Wadowski, Patricia P., Hoberstorfer, Timothy, Weikert, Constantin, Pultar, Joseph, Kopp, Christoph W., Panzer, Simon, and Gremmel, Thomas
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- 2021
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15. Comparison of coenzyme Q10 or fish oil for prevention of intermittent hypoxia-induced oxidative injury in neonatal rat lungs
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D’Agrosa, Christina, Cai, Charles L., Siddiqui, Faisal, Deslouches, Karen, Wadowski, Stephen, Aranda, Jacob V., and Beharry, Kay D.
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- 2021
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16. Does case-based blended-learning expedite the transfer of declarative knowledge to procedural knowledge in practice?
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Bela Turk, Sebastian Ertl, Guoruey Wong, Patricia P. Wadowski, and Henriette Löffler-Stastka
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Competence ,Performance ,Case-based learning ,Case-based blended learning ,Bloom’s taxonomy ,Special aspects of education ,LC8-6691 ,Medicine - Abstract
Abstract Background Case-Based Learning (CBL) has seen widespread implementation in undergraduate education since the early 1920s. Ample data has shown CBL to be an enjoyable and motivational didactic tool, and effective in assisting the expansion of declarative and procedural knowledge in academia. Although a plethora of studies apply multiple choice questions (MCQs) in their investigation, few studies measure CBL or case-based blended learning (CBBL)-mediated changes in students’ procedural knowledge in practice or employ comparison or control groups in isolating causal relationships. Methods Utilizing the flexibilities of an e-learning platform, a CBBL framework consisting of a) anonymized patient cases, b) case-related textbook material and online e-CBL modules, and c) simulated patient (SP) contact seminars, was developed and implemented in multiple medical fields for undergraduate medical education. Additionally, other fields saw a solo implementation of e-CBL in the same format. E- cases were constructed according to the criteria of Bloom’s taxonomy. In this study, Objective Structured Clinical Examination (OSCE) results from 1886 medical students were analyzed in total, stratified into the following groups: medical students in 2013 (n = 619) before CBBL implementation, and after CBBL implementation in 2015 (n = 624) and 2016 (n = 643). Results A significant improvement (adjusted p = .002) of the mean OSCE score by 1.02 points was seen between 2013 and 2015 (min = 0, max = 25). Conclusion E-Case-Based Learning is an effective tool in improving performance outcomes and may provide a sustainable learning platform for many fields of medicine in future.
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- 2019
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17. Ritmo abstrato: a música visual no filme absoluto
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Vitor Droppa Wadowski Fonseca
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artes ,cinema experimental ,música visual ,filme absoluto ,Arts in general ,NX1-820 ,Special aspects of education ,LC8-6691 - Abstract
A definição mais recorrente de Música Visual desponta do cinema de vanguarda emergente na Alemanha durante a década de 1920 e remete aos Filmes Absolutos produzidos por Walter Ruttman, Hans Richter, Viking Eggeling e Oskar Fischinger. O estudo desenvolvido nesta pesquisa constrói uma análise de suas obras, conceitos e processos artísticos a fim de compreender como as linguagens sonoras e visuais foram articuladas para a criação da Música Visual em seus filmes. A partir do contraponto entre os trabalhos cinematográficos analisados, o artigo apresenta uma perspectiva sobre o conceito de Música Visual no Filme Absoluto que contempla e correlaciona as diferentes concepções fomentadas por seus precursores.
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- 2019
18. The Catholic Church in Poland, Her Faithful, and the Restrictions on Freedom to Practise Religion during the First Wave of the COVID-19 Pandemic
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Piotr Stanisz, Dariusz Wadowski, Justyna Szulich-Kałuża, Małgorzata Nowak, and Mirosław Chmielewski
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freedom of religion ,COVID-19 ,Catholic Church ,communication ,faithful ,canon law ,Religions. Mythology. Rationalism ,BL1-2790 - Abstract
In response to the rapid spread of the coronavirus epidemic, the state authorities in Poland—as in other countries—decided to introduce various restrictions on rights and freedoms, including the freedom to practise religion. The purpose of this study is to analyse and evaluate the position taken by the ministers of the Catholic Church in Poland and her faithful towards these restrictions during the first wave of the pandemic. An analysis of source material, including documents published by representatives of the Conference of Polish Bishops and diocesan bishops (or curial deputy officials), leads to the conclusion that, in their official messages, the bishops virtually unanimously supported the restrictions imposed by the state, often granting them the sanction of canon law, or introducing even more restrictive solutions in their own dioceses. Moreover, an analysis of the media coverage of the first wave of the pandemic, as well as sociological opinion research focusing on Poland’s Catholic faithful, concludes that both the faithful and ‘rank-and-file’ clergy exhibited a polarised assessment of the stance adopted by the bishops towards the restrictions. However, this analysis allows for the refutation of the claim expressed in the literature, and shared by some of the faithful, about the bishops’ excessive submissiveness to the state authorities. Our research proves that this claim somewhat distorts the reality. Rather, the attitude of the hierarchs of the Church needs to be seen as an expression of their responsibility for the common good. More deserving of criticism, on the other hand, is the excessive focus of the ecclesiastical message of this period on the restrictions on the freedom to practise religion, while the right of the faithful to the spiritual goods of the Church was relegated to the background (Can. 213 CIC-1983). In adopting the research framework developed by Joseph Cardijn (‘see–judge–act’), our analysis concludes with the recommendation that, should a similar crisis arise in the future, the institution of the Church should rather focus its message to the faithful on securing the said right in the context of the state-imposed restrictions, by adopting the attitude typical of that of an addressee of legal norms, in line with the conclusions drawn from its own autonomy and independence as underlying principles of the State-Church relationship in both Church teachings and Polish law.
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- 2022
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19. Ticagrelor Inhibits Toll-Like and Protease-Activated Receptor Mediated Platelet Activation in Acute Coronary Syndromes
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Wadowski, Patricia P., Weikert, Constantin, Pultar, Joseph, Lee, Silvia, Eichelberger, Beate, Koppensteiner, Renate, Lang, Irene M., Panzer, Simon, and Gremmel, Thomas
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- 2020
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20. Case-based blended eLearning scenarios—adequate for competence development or more?
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Wadowski, Patricia Pia, Litschauer, Brigitte, Seitz, Tamara, Ertl, Sebastian, and Löffler-Stastka, Henriette
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- 2019
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21. Immune Microenvironment and Genetics in Malignant Pleural Mesothelioma
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Benjamin Wadowski, Raphael Bueno, and Assunta De Rienzo
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mesothelioma ,genomics ,transcriptomics ,immune ,checkpoint ,microenvironment ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Malignant pleural mesothelioma (MPM) is a rare and aggressive malignancy with limited therapeutic options beyond surgery and cytotoxic chemotherapy. The success of immune checkpoint inhibition has been found to correlate with expression of immune-related genes such as CD274 (PD-L1) in lung and other solid cancers. However, only a small subset of MPM patients respond to checkpoint inhibition, and this response has been varied and unpredictable across several clinical trials. Recent advances in next-generation sequencing (NGS) technology have improved our understanding of the molecular features of MPM, also with respect to its genetic signature and how this impacts the immune microenvironment. This article will review current evidence surrounding the interplay between MPM genetics, including epigenetics and transcriptomics, and the immune response.
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- 2021
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22. Protease‐activated receptor‐mediated platelet aggregation in acute coronary syndrome patients on potent P2Y12 inhibitors
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Patricia P. Wadowski, Joseph Pultar, Constantin Weikert, Beate Eichelberger, Benjamin Panzer, Kurt Huber, Irene M. Lang, Renate Koppensteiner, Simon Panzer, and Thomas Gremmel
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antiplatelet therapy ,protease‐activated receptor 1 ,protease‐activated receptor 4 ,prasugrel ,ticagrelor ,platelet aggregation ,Diseases of the blood and blood-forming organs ,RC633-647.5 - Abstract
Abstract Background Despite the increasing use of potent P2Y12 inhibitors, further atherothrombotic events still impair the prognosis of many acute coronary syndrome (ACS) patients. This may in part be attributable to intact platelet aggregation via the human thrombin receptors protease‐activated receptor (PAR)‐1 and PAR‐4. Objective We studied PAR mediated platelet aggregation in ACS patients following percutaneous coronary intervention (PCI) with stent implantation in a cross‐sectional study. Methods Platelet aggregation to ADP as well as to the PAR‐1 agonist SFLLRN and the PAR‐4 agonist AYPGKF was assessed by multiple electrode aggregometry in 194 ACS patients on dual antiplatelet therapy with aspirin and either prasugrel (n = 114) or ticagrelor (n = 80) 3 days after PCI. Results Based on the consensus cutoff value, high on‐treatment residual platelet reactivity to ADP (HRPR ADP) was observed in only 2 prasugrel‐treated patients. Both patients with HRPR ADP had also a normal response to SFLLRN and AYPGKF. Among the 112 prasugrel‐treated patients with adequate P2Y12 inhibition, 50 patients (45%) still had a normal response to SFLLRN, and 70 patients (63%) still had a normal response to AYPGKF. Among the 80 ticagrelor‐treated patients with adequate P2Y12 inhibition, 25 patients (31%) still had a normal response to SFLLRN, and 50 (63%) still had a normal response to AYPGKF. Conclusion Normal platelet aggregation via PAR‐1 and PAR‐4 is preserved in many patients with adequate P2Y12 inhibition by prasugrel and ticagrelor. The present findings may at least in part explain adverse ischemic events despite potent P2Y12 inhibition.
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- 2019
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23. Growth Differentiation Factor-15 Correlates Inversely with Protease-Activated Receptor-1-Mediated Platelet Reactivity in Patients with Left Ventricular Assist Devices
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Maximilian Tscharre, Franziska Wittmann, Daniela Kitzmantl, Silvia Lee, Beate Eichelberger, Patricia P. Wadowski, Günther Laufer, Dominik Wiedemann, Simon Panzer, Thomas Perkmann, Daniel Zimpfer, and Thomas Gremmel
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LVAD ,GDF-15 ,multiple electrode aggregometry ,GPIIb/IIIa ,PAR-1 ,Medicine ,Pharmacy and materia medica ,RS1-441 - Abstract
Growth differentiation factor (GDF)-15 inhibits platelet activation, prevents thrombus formation, and has been linked to bleeding events. This was a prospective study including 51 left-ventricular assist device (LVAD) patients on aspirin and phenprocoumon. Platelet surface expression of activated glycoprotein (GP) IIb/IIIa was assessed by flow cytometry, and platelet aggregation was measured by multiple electrode aggregometry (MEA) in response to arachidonic acid (AA), adenosine diphosphate (ADP), and thrombin receptor-activating peptide (TRAP), a protease-activated-receptor-1 (PAR-1) agonist. GDF-15 was determined with a commercially-available assay. There was a trend towards an inverse correlation of GDF-15 with activated GPIIb/IIIa in response to TRAP (r = −0.275, p = 0.0532) but not in response to AA and ADP. Moreover, GDF-15 correlated with MEA TRAP (r = −0.326, p = 0.0194), whereas it did not correlate with MEA ADP and MEA AA. In a second step, GDF-15 levels in the fourth quartile were defined as high GDF-15. Patients with high GDF-15 showed significantly lower TRAP-inducible platelet aggregation by MEA compared to patients in the first quartile (63 AU vs. 113 AU, p = 0.0065). In conclusion, in LVAD patients receiving state-of-the-art antithrombotic therapy, GDF-15 correlates inversely with residual platelet reactivity via PAR-1.
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- 2022
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24. Glycocalyx as Possible Limiting Factor in COVID-19
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Patricia P. Wadowski, Bernd Jilma, Christoph W. Kopp, Sebastian Ertl, Thomas Gremmel, and Renate Koppensteiner
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glycocalyx ,heparan sulfate ,complement ,SARS-CoV-2 ,COVID-19 ,Immunologic diseases. Allergy ,RC581-607 - Published
- 2021
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25. Oral antiplatelet agents in cardiovascular disease
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Pultar, Joseph, Wadowski, Patricia P., Panzer, Simon, and Gremmel, Thomas
- Abstract
Abstract.Antiplatelet agents significantly reduce mortality and morbidity in ischemic heart disease, cerebrovascular disease and peripheral artery disease (PAD), and are therefore part of guideline-driven daily medical treatment in these patients. Due to its beneficial effects in the secondary prevention of atherothrombotic events, aspirin remains the most frequently prescribed antiplatelet agent in cardiovascular disease. In patients with acute coronary syndromes (ACS) and in those undergoing angioplasty with stent implantation dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist is indicated. The development of the newer ADP P2Y12inhibitors prasugrel and ticagrelor has further improved prognosis in ACS patients compared to clopidogrel. Moreover, vorapaxar allows the inhibition of platelet activation by thrombin via protease-activated receptor-1 and has been approved for the use in patients with PAD and in those with a history of myocardial infarction. This review article summarizes the current evidence on oral antiplatelet agents in cardiovascular disease.Keywords:Aspirin, clopidogrel, prasugrel, ticagrelor, vorapaxar, cardiovascular disease
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- 2024
- Full Text
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26. Regulation of histamine and diamine oxidase in patients undergoing orthotopic liver transplantation
- Author
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Schiefer, Judith, Baron-Stefaniak, Joanna, Boehm, Thomas, Wadowski, Patricia, Berlakovich, Gabriela, Kuessel, Lorenz, Mühlbacher, Jakob, Jilma-Stohlawetz, Petra, Schwameis, Michael, Jilma, Bernd, and Faybik, Peter
- Published
- 2020
- Full Text
- View/download PDF
27. Does case-based blended-learning expedite the transfer of declarative knowledge to procedural knowledge in practice?
- Author
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Turk, Bela, Ertl, Sebastian, Wong, Guoruey, Wadowski, Patricia P., and Löffler-Stastka, Henriette
- Published
- 2019
- Full Text
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28. Association of RERG Expression with Female Survival Advantage in Malignant Pleural Mesothelioma
- Author
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Assunta De Rienzo, Melissa H. Coleman, Beow Y. Yeap, David T. Severson, Benjamin Wadowski, Corinne E. Gustafson, Roderick V. Jensen, Lucian R. Chirieac, William G. Richards, and Raphael Bueno
- Subjects
malignant pleural mesothelioma ,RERG ,sex ,estrogen ,survival ,Neoplasms. Tumors. Oncology. Including cancer and carcinogens ,RC254-282 - Abstract
Sex differences in incidence, prognosis, and treatment response have been described for many cancers. In malignant pleural mesothelioma (MPM), a lethal disease associated with asbestos exposure, men outnumber women 4 to 1, but women consistently live longer than men following surgery-based therapy. This study investigated whether tumor expression of genes associated with estrogen signaling could potentially explain observed survival differences. Two microarray datasets of MPM tumors were analyzed to discover estrogen-related genes associated with survival. A validation cohort of MPM tumors was selected to balance the numbers of men and women and control for competing prognostic influences. The RAS like estrogen regulated growth inhibitor (RERG) gene was identified as the most differentially-expressed estrogen-related gene in these tumors and predicted prognosis in discovery datasets. In the sex-matched validation cohort, low RERG expression was significantly associated with increased risk of death among women. No association between RERG expression and survival was found among men, and no relationship between estrogen receptor protein or gene expression and survival was found for either sex. Additional investigations are needed to elucidate the molecular mechanisms underlying this association and its sex specificity.
- Published
- 2021
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29. Functional capillary impairment in patients with ventricular assist devices
- Author
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Wadowski, Patricia P., Steinlechner, Barbara, Zimpfer, Daniel, Schlöglhofer, Thomas, Schima, Heinrich, Hülsmann, Martin, Lang, Irene M., Gremmel, Thomas, Koppensteiner, Renate, Zehetmayer, Sonja, Weikert, Constantin, Pultar, Joseph, and Jilma, Bernd
- Published
- 2019
- Full Text
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30. Prolonged Ischemia Increases Complications Among High- and Low-Volume Centers in Lung Transplantation.
- Author
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Wadowski, Benjamin J., Wang, Simeng, Angel, Luis F., Geraci, Travis C., Chan, Justin C.Y., and Chang, Stephanie H.
- Abstract
The effect of prolonged allograft ischemic time on lung transplant outcomes remains controversial, with most studies associating it with increased mortality, but this effect is partly mitigated by center volume. This study sought to evaluate the mechanism of these findings and clarify the impact of ischemic time on short-term outcomes in a national sample. Data on lung transplants (January 2010-Janary 2017) were extracted from the Scientific Registry of Transplant Recipients database. Ischemic time was dichotomized as prolonged ischemic time (PIT) or no PIT (N-PIT) at 6 hours. High-volume centers were defined as the top quintile. The primary outcome was 30-day, 1-year, and 3-year mortality; secondary outcomes included in-hospital complications and 72-hour oxygenation. Among 11,809 records, there were significant differences between PIT and N-PIT recipients by demographics, lung allocation score, and donor organ metrics. In a 1:1 propensity score–matched cohort (n = 6422), PIT recipients had reduced survival compared with N-PIT at 3 years (66.5% vs 68.8%, P =.031). On multivariable analysis, this effect persisted among low-volume but not high-volume centers. PIT recipients were more likely to require reintubation, prolonged (>5 days) mechanical ventilation, hemodialysis, longer stay, and acute rejection (all P <.01). Except for reintubation, these disparities were present at both high- and low-volume centers independently. Ischemic time had no effect on 72-hour oxygenation. PIT remains associated with higher rates of postoperative complications and reduced short-term survival. While center volume ameliorated the survival impact, this was not achieved by reducing postoperative complications. Further research is warranted before broadening ischemic time thresholds among low-volume centers. [ABSTRACT FROM AUTHOR]
- Published
- 2023
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31. Disaggregation Following Agonist-Induced Platelet Activation in Patients on Dual Antiplatelet Therapy
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Wadowski, Patricia P., Eichelberger, Beate, Kopp, Christoph W., Pultar, Joseph, Seidinger, Daniela, Koppensteiner, Renate, Lang, Irene M., Panzer, Simon, and Gremmel, Thomas
- Published
- 2017
- Full Text
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32. Cardiovascular Disease Management in the Context of Global Crisis
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Patricia P. Wadowski, Aleksandra Piechota-Polańczyk, Martin Andreas, and Christoph W. Kopp
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Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health - Abstract
The outbreak of coronavirus disease 2019 (COVID-19) initiated a pandemic that has deteriorated health care access and thus disadvantaged vulnerable populations [...]
- Published
- 2022
33. Impact of ABO Blood Group on Thromboembolic and Bleeding Complications in Patients with Left Ventricular Assist Devices
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Maximilian Tscharre, Franziska Wittmann, Daniela Kitzmantl, Thomas Schlöglhofer, Philip Cichra, Silvia Lee, Beate Eichelberger, Patricia P. Wadowski, Günther Laufer, Dominik Wiedemann, Simon Panzer, Daniel Zimpfer, and Thomas Gremmel
- Subjects
Hematology - Abstract
Background The ABO blood group system is linked to hemostasis via its relationship with von Willebrand factor (VWF) and factor VIII (FVIII). In the current study, we investigated the association of the ABO system with clinical outcomes as well as VWF and platelet function in patients with left ventricular assist devices (LVADs). Methods Bleeding and thromboembolic complications were assessed in 111 patients during 1 year after LVAD implantation. In 67 LVAD patients, VWF antigen, VWF activity, VWF ristocetin cofactor, VWF collagen-binding, and FVIII activity were assessed. Platelet surface P-selectin and activated glycoprotein IIb/IIIa were determined by flow cytometry, and soluble P-selectin was measured with an enzyme-linked immunoassay. Platelet aggregation was assessed by light transmission and impedance aggregometry. Results Thirty-six patients (32.4%) experienced a bleeding and 22 patients (19.8%) a thromboembolic event. In univariate analyses, patients with blood group O had numerically more bleeding complications and less thromboembolic events as compared to patients with blood group non-O (both p ≥ 0.05). After multivariable adjustment, blood group O was significantly associated with a higher risk of bleeding (hazard ratio 2.42 [95% confidence interval 1.03–5.70], p = 0.044) but not linked to thromboembolic complications. Conclusion Patients with blood group O had significantly lower levels of VWF and FVIII (all p
- Published
- 2022
34. Platelet-to-lymphocyte and Neutrophil-to-lymphocyte Ratios Predict Target Vessel Restenosis after Infrainguinal Angioplasty with Stent Implantation
- Author
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Silvia Lee, Timothy Hoberstorfer, Patricia P. Wadowski, Christoph W. Kopp, Simon Panzer, and Thomas Gremmel
- Subjects
peripheral artery disease ,ratios ,target vessel restenosis ,target vessel reocclusion ,platelet reactivity ,neutrophil-platelet aggregates ,Medicine - Abstract
Platelet-to-lymphocyte (PLR), neutrophil-to-lymphocyte (NLR) and lymphocyte-to-monocyte (LMR) ratios are associated with the occurrence of critical limb ischemia in peripheral artery disease (PAD). We therefore investigated whether PLR, NLR or LMR are linked to target vessel restenosis (TVR) following infrainguinal angioplasty and stenting. Moreover, we studied on-treatment platelet reactivity and neutrophil-platelet aggregate (NPA) formation as potential underlying mechanisms. Platelet, neutrophil, lymphocyte and monocyte counts were determined one day after angioplasty and stenting in 95 stable PAD patients. Platelet reactivity and NPA formation in response to protease-activated receptor−1 stimulation were measured by light transmission aggregometry (LTA) and flow cytometry, respectively. PLR and NLR were significantly higher in patients who subsequently developed TVR (both p < 0.05). In contrast, LMR did not differ significantly between patients without and with TVR (p = 0.28). A PLR ≥ 91 and NLR ≥2.75 were identified as the best thresholds to predict TVR, providing sensitivities of 87.5% and 81.3%, and specificities of 34.9% and 50.8%, respectively, and were therefore defined as high PLR and high NLR. TVR occurred significantly more often in patients with high PLR and high NLR than in those with lower ratios (both p < 0.05). Patients with high PLR and high NLR exhibited significantly increased on-treatment platelet aggregation compared to those with lower ratios, and patients with high PLR had higher levels of NPA formation (all p < 0.01). In conclusion, PLR and NLR predict TVR after infrainguinal angioplasty with stent implantation. Platelet activation and neutrophil-platelet interaction may be involved in the underlying pathomechanisms
- Published
- 2020
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35. A Rare Case of Bilateral Upper Extremity Hypercalcinosis in Systemic Sclerosis Requiring Multiple Radical Debridements
- Author
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Jordan D. Frey, Benjamin Wadowski, and Sheel Sharma
- Subjects
Surgery ,RD1-811 - Published
- 2016
- Full Text
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36. Impact of body size on platelet function in patients with acute coronary syndrome on dual antiplatelet therapy
- Author
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Benjamin Panzer, Patricia P. Wadowski, Kurt Huber, Simon Panzer, and Thomas Gremmel
- Subjects
Pharmacology ,Ticagrelor ,Percutaneous Coronary Intervention ,Treatment Outcome ,Physiology ,Purinergic P2Y Receptor Antagonists ,Molecular Medicine ,Body Size ,Humans ,Acute Coronary Syndrome ,Prasugrel Hydrochloride ,Platelet Aggregation Inhibitors - Abstract
Patients undergoing acute percutaneous coronary intervention receive dual antiplatelet therapy for secondary prevention. Recurrent myocardial infarction or bleedings are possibly due to under- or overdosing of antiplatelet therapy in relation to body size.We correlated residual platelet aggregation with body mass index, body surface area, lean body mass and blood volume in 220 patients on prasugrel (n = 121) or ticagrelor (n = 99).Platelet aggregation outside the recommended window was recorded in 85 patients, but not correlated with any of the body indices.Body size does not affect platelet response to prasugrel or ticagrelor at the guideline-recommended fixed dosages.
- Published
- 2022
37. Protease‐activated receptor‐mediated platelet aggregation in patients with type 2 diabetes on potent <scp>P2Y</scp> 12 inhibitors
- Author
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Benjamin Panzer, Patricia P. Wadowski, Kurt Huber, Simon Panzer, and Thomas Gremmel
- Subjects
Endocrinology ,Endocrinology, Diabetes and Metabolism ,Internal Medicine - Published
- 2022
38. Protease-activated receptor-mediated platelet aggregation in patients with type 2 diabetes on potent P2Y
- Author
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Benjamin, Panzer, Patricia P, Wadowski, Kurt, Huber, Simon, Panzer, and Thomas, Gremmel
- Subjects
Ticagrelor ,Adenosine ,Percutaneous Coronary Intervention ,Diabetes Mellitus, Type 2 ,Platelet Aggregation ,Receptors, Proteinase-Activated ,Purinergic P2Y Receptor Antagonists ,Humans ,Acute Coronary Syndrome ,Prasugrel Hydrochloride ,Platelet Aggregation Inhibitors - Abstract
Antiplatelet therapy is a cornerstone in the secondary prevention of ischemic events following percutaneous coronary intervention (PCI). The new P2YWe compared P2YOverall, there were no differences of P2YPrasugrel and ticagrelor inhibit P2Y
- Published
- 2022
39. Circulating MicroRNAs and Monocyte–Platelet Aggregate Formation in Acute Coronary Syndrome
- Author
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Patrick Haider, Joseph Pultar, Johann Wojta, Svitlana Demyanets, Patricia P. Wadowski, Simon Panzer, Beate Eichelberger, Stefan Stojkovic, Silvia Lee, Constantin Weikert, Christian Hengstenberg, and Thomas Gremmel
- Subjects
Blood Platelets ,Male ,0301 basic medicine ,Ticagrelor ,Acute coronary syndrome ,Prasugrel ,030204 cardiovascular system & hematology ,Pharmacology ,Monocytes ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,P2Y12 ,medicine ,Humans ,Platelet ,Platelet activation ,Acute Coronary Syndrome ,Aged ,Aspirin ,business.industry ,Hematology ,Middle Aged ,Platelet Activation ,medicine.disease ,Receptors, Purinergic P2Y12 ,MicroRNAs ,Adenosine diphosphate ,030104 developmental biology ,chemistry ,Purinergic P2Y Receptor Antagonists ,Female ,business ,Prasugrel Hydrochloride ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Background Monocyte–platelet aggregates (MPAs) are a sensitive marker of in vivo platelet activation in acute coronary syndrome (ACS) and associated with clinical outcomes. MicroRNAs (miRs) play an important role in the regulation of platelet activation, and may influence MPA formation. Both, miRs and MPA, could be influenced by the type of P2Y12 inhibitor. Aim To study the association of platelet-related miRs with MPA formation in ACS patients on dual antiplatelet therapy (DAPT), and to compare miRs and MPA levels between prasugrel- and ticagrelor-treated patients. Methods and Results We analyzed 10 circulating platelet-related miRs in 160 consecutive ACS patients on DAPT with low-dose aspirin and either prasugrel (n = 80) or ticagrelor (n = 80). MPA formation was measured by flow cytometry without addition of platelet agonists and after simulation with the toll-like receptor (TLR)-1/2 agonist Pam3CSK4, adenosine diphosphate (ADP), or arachidonic acid (AA). In multivariate regression analyses, we identified miR-21 (β = 9.50, 95% confidence interval [CI]: 1.60–17.40, p = 0.019) and miR-126 (β = 7.50, 95% CI: 0.55–14.44, p = 0.035) as independent predictors of increased MPA formation in vivo and after TLR-1/2 stimulation. In contrast, none of the investigated miRs was independently associated with MPA formation after stimulation with ADP or AA. Platelet-related miR expression and MPA formation did not differ significantly between prasugrel- and ticagrelor-treated patients. Conclusion Platelet-related miR-21 and miR-126 are associated with MPA formation in ACS patients on DAPT. miRs and MPA levels were similar in prasugrel- and ticagrelor-treated patients.
- Published
- 2021
40. WASTE MANAGEMENT IN THE MINDS OF YOUNG PEOPLE
- Author
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Monika STĘPIEŃ, Mateusz WADOWSKI, and Zbigniew ŻURAKOWSKI
- Subjects
waste management ,segregation of waste ,municipal infrastructure ,environment ,Production management. Operations management ,TS155-194 - Abstract
The aim of the paragraph was to study young people's awareness on waste management; their attitude towards the amendment of statute on cleanliness and order in municipalities which is coming into effect now; and people's attitude towards waste segregation. The analysis showed that young people do not have sufficient knowledge about waste segregation in their own area, neither about the waste processing machines. They have not acquired enough knowledge about current alteration in this topic as well. However, young people still try to protect environment and have positive attitude towards the issue of waste segregation.
- Published
- 2013
41. A Case of Autoimmune Small Fiber Neuropathy as Possible Post COVID Sequelae
- Author
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Noel G. Panagiotides, Fritz Zimprich, Klaus Machold, Oliver Schlager, Markus Müller, Sebastian Ertl, Henriette Löffler-Stastka, Renate Koppensteiner, and Patricia P. Wadowski
- Subjects
Health, Toxicology and Mutagenesis ,Public Health, Environmental and Occupational Health - Abstract
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is reported to induce and augment autoimmune processes. Moreover, postinfectious effects of coronavirus disease 2019 (COVID-19) are still poorly understood and often resemble symptoms of the acute infection phase. A patient with swollen extremities was presented to the Department of Angiology at the Medical University of Vienna with complaints of muscle and joint pain, paresthesia, and arterial hypertension with intense headache. Prior to these complaints, she had been suffering from various symptoms since November 2020, following a SARS-CoV-2 infection in the same month. These included recurrent sore throat, heartburn, dizziness, and headache. Paresthesia and muscle and joint pain started in temporal relation to a human papillomavirus (HPV) vaccination. Since the patient was suffering from severe pain, intensive pain management was performed. Skin and nerve biopsies revealed autoimmune small fiber neuropathy. The patient’s condition could be related to COVID-19, as her first symptoms began in temporal relation to the SARS-CoV-2 infection. Furthermore, in the disease course, antinuclear (ANA) and anti-Ro antibodies, as well as anti-cyclic citrullinated peptide (anti-CCP) antibodies, could be detected. Together with the symptoms of xerophthalmia and pharyngeal dryness, primary Sjögren’s syndrome was diagnosed. In conclusion, though biopsy results could not distinguish a cause of the disease, SARS-CoV-2 infection can be discussed as a likely trigger for the patient’s autoimmune reactions.
- Published
- 2023
42. Decreased Platelet Inhibition by Thienopyridines in Hyperuricemia
- Author
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Joseph Pultar, Thomas Gremmel, Timothy Hoberstorfer, Constantin Weikert, Silvia Lee, Patricia P. Wadowski, Christoph W. Kopp, and Simon Panzer
- Subjects
Male ,Ticagrelor ,medicine.medical_specialty ,Acute coronary syndrome ,Ticlopidine ,Prasugrel ,Genotype ,Thienopyridines ,medicine.medical_treatment ,Comorbidity ,Hyperuricemia ,chemistry.chemical_compound ,P2Y12 ,Internal medicine ,Humans ,Medicine ,Pharmacology (medical) ,Prospective Studies ,Acute Coronary Syndrome ,Aged ,Cytochrome P-450 CYP2C9 ,Pharmacology ,business.industry ,Angioplasty ,Percutaneous coronary intervention ,General Medicine ,Middle Aged ,Platelet Activation ,medicine.disease ,Clopidogrel ,Uric Acid ,Adenosine Diphosphate ,chemistry ,Purinergic P2Y Receptor Antagonists ,Cardiology ,Uric acid ,Female ,Stents ,Original Article ,Platelet reactivity ,Cardiology and Cardiovascular Medicine ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Purpose Hyperuricemia carries an increased risk of atherothrombotic events in acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI). This may at least in part be due to inadequate P2Y12 inhibition. The aim of this study was to prospectively investigate the potential association between hyperuricemia and decreased platelet inhibition by P2Y12 antagonists. Methods Levels of uric acid as well as on-treatment residual platelet reactivity in response to adenosine diphosphate (ADP) were assessed in 301 clopidogrel-treated patients undergoing elective angioplasty and stenting, and in 206 prasugrel- (n = 118) or ticagrelor-treated (n = 88) ACS patients following acute PCI. Cut-off values for high on-treatment residual ADP-inducible platelet reactivity (HRPR) were based on previous studies showing an association of test results with clinical outcomes. Results Hyperuricemia was significantly associated with increased on-treatment residual ADP-inducible platelet reactivity in clopidogrel- and prasugrel-treated patients in univariate analyses and after adjustment for differences in patient characteristics by multivariate regression analyses. In contrast, ticagrelor-treated patients without and with hyperuricemia showed similar levels of on-treatment residual platelet reactivity to ADP. HRPR occurred more frequently in clopidogrel- and prasugrel-treated patients with hyperuricemia than in those with normal uric acid levels. In contrast, hyperuricemic patients receiving ticagrelor did not have a higher risk of HRPR compared with those with normal uric acid levels. Conclusion Hyperuricemia is associated with decreased platelet inhibition by thienopyridines but a normal response to ticagrelor. It remains to be established if lowering uric acid increases the antiplatelet effects of clopidogrel and prasugrel in hyperuricemic patients with HRPR.
- Published
- 2020
43. Protease-Activated Receptor-Mediated Platelet Aggregation In Patients With Type 2 Diabetes On Potent P2Y12 Inhibitors
- Author
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Simon Panzer, Kurt Huber, Benjamin Panzer, Thomas Gremmel, and Patricia P. Wadowski
- Subjects
P2Y12 ,Platelet aggregation ,Chemistry ,medicine ,Protease-activated receptor ,In patient ,Type 2 diabetes ,Pharmacology ,medicine.disease - Abstract
Background: Dual antiplatelet therapy is a cornerstone in the secondary prevention of ischemic events following percutaneous coronary intervention (PCI) with stent implantation. The new, more potent adenosine diphosphate (ADP) P2Y12 receptor inhibitors prasugrel and ticagrelor have been shown to improve patients’ outcomes. Whether or not these drugs have equal efficacy in diabetic as in non-diabetic individuals is disputed. Furthermore, platelets can be activated by thrombin, which is, at least in part, independent of ADP-inducible activation. Protease-activated receptor (PAR)-1 and -4 are thrombin receptors on human platelets activated by the agonists SFLLRN and AYPGKF, respectively. In the current study, we sought to compare the in vitro efficacy of prasugrel (n=121) and ticagrelor (n=99) to inhibit PAR-mediated platelet activation in patients with type 2 diabetes (n=55).Materials and Methods: We compared P2Y12-, PAR-1- and PAR-4-mediated platelet aggregation as assessed by multiple electrode platelet aggregometry between prasugrel- and ticagrelor-treated patients without and with type 2 diabetes who underwent acute PCI. Results: There were no significant differences of on-treatment platelet aggregation in response to ADP, SFLLRN and AYPGKF between patients on prasugrel or on ticagrelor. Diabetic and non-diabetic patients responded equally. There was no significant correlation between either; ADP-, SFLLRN-, or AYPGKF-inducible platelet aggregation and levels of HbA1c or the body mass index. However, we observed patients with high residual platelet reactivity to SFLLRN and AYPGKF in all cohorts.Conclusion: Prasugrel and ticagrelor inhibit platelet aggregation in diabetic and non-diabetic patients to a similar extent.
- Published
- 2021
44. From clinical reasoning to effective clinical decision making – new training methods
- Author
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Patricia Pia Wadowski, Barbara eSteinlechner, Arno eSchiferer, and Henriette eLöffler-Stastka
- Subjects
e-learning ,residency ,clinical reasoning ,Teaching case ,acute thrombocytopenia ,Psychology ,BF1-990 - Published
- 2015
- Full Text
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45. Sex-specific platelet activation through protease-activated receptor-1 in patients undergoing cardiac catheterization
- Author
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Joseph Pultar, Alan D. Michelson, Thomas Gremmel, Andrew L. Frelinger, Constantin Weikert, Simon Panzer, Silvia Lee, Maximilian Tscharre, and Patricia P. Wadowski
- Subjects
Blood Platelets ,Male ,medicine.medical_specialty ,Acute coronary syndrome ,Cardiac Catheterization ,Platelet Aggregation ,medicine.medical_treatment ,Platelet Glycoprotein GPIIb-IIIa Complex ,Gastroenterology ,Flow cytometry ,Thrombin ,Internal medicine ,medicine ,Humans ,Platelet ,Receptor, PAR-1 ,Platelet activation ,Receptor ,Cardiac catheterization ,medicine.diagnostic_test ,business.industry ,Percutaneous coronary intervention ,medicine.disease ,Platelet Activation ,Female ,Cardiology and Cardiovascular Medicine ,business ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Background and aims Protease-activated receptor (PAR)-1-mediated platelet activation may vary according to sex and clinical situation. In order to investigate sex-specific platelet activation through PAR-1, we assessed platelet response to thrombin receptor-activating peptide (TRAP) in 562 patients undergoing cardiac catheterization without (Group 1A) and with (Group 1B) acute coronary syndrome (ACS). Subsequently, we sought to confirm our findings in 287 patients undergoing elective (Group 2A) or acute (Group 2B) percutaneous coronary intervention. Methods TRAP-stimulated platelet surface expression of P-selectin and activated glycoprotein IIb/IIIa (GPIIb/IIIa) were measured by flow cytometry in Group 1. Light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) in response to TRAP were assessed in Group 2. Results In Group 1A, platelet activation in response to TRAP was significantly higher in women compared to men (P-selectin: 511 MFI [443–597 MFI] vs. 471 MFI [393–552 MFI]; GPIIb/IIIa: 84 MFI [58–119 MFI] vs. 70 MFI [47–103 MFI]; both p ≤ 0.002). In contrast, in Group 1B, TRAP-stimulated P-selectin and activated GPIIb/IIIa were similar in men and women (both p ≥ 0.3). Likewise, TRAP-stimulated platelet aggregation was significantly higher in female patients in Group 2A (LTA: 66% [54–76%] vs. 51% [41–65%]; MEA: 78 AU [66–107 AU] vs. 62 AU [52–88 AU]; both p ≤ 0.02), whereas men and women in Group 2 B had similar platelet aggregation (p = 0.5). The occurrence of ischemic endpoints did not differ significantly between men and women in Group 1A and Group 1B. Conclusions Platelet PAR-1 signaling is more pronounced in women than in men without ACS. In ACS, however, PAR-1-mediated platelet activation is similar in male and female patients.
- Published
- 2021
46. Impact of ABO Blood Group on Thromboembolic and Bleeding Complications in Patients with Left Ventricular Assist Devices
- Author
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Tscharre, Maximilian, Wittmann, Franziska, Kitzmantl, Daniela, Schlöglhofer, Thomas, Cichra, Philip, Lee, Silvia, Eichelberger, Beate, Wadowski, Patricia P., Laufer, Günther, Wiedemann, Dominik, Panzer, Simon, Zimpfer, Daniel, and Gremmel, Thomas
- Published
- 2023
- Full Text
- View/download PDF
47. Oral antiplatelet agents in cardiovascular disease
- Author
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Thomas Gremmel, Joseph Pultar, Simon Panzer, and Patricia P. Wadowski
- Subjects
medicine.medical_specialty ,Adenosine ,Ticlopidine ,Prasugrel ,Administration, Oral ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,P2Y12 ,Internal medicine ,medicine ,Humans ,cardiovascular diseases ,030212 general & internal medicine ,Vorapaxar ,Aspirin ,Prasugrel Hydrochloride ,business.industry ,Clopidogrel ,Cardiovascular Diseases ,Cardiology ,Cardiology and Cardiovascular Medicine ,business ,Ticagrelor ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Abstract. Antiplatelet agents significantly reduce mortality and morbidity in ischemic heart disease, cerebrovascular disease and peripheral artery disease (PAD), and are therefore part of guideline-driven daily medical treatment in these patients. Due to its beneficial effects in the secondary prevention of atherothrombotic events, aspirin remains the most frequently prescribed antiplatelet agent in cardiovascular disease. In patients with acute coronary syndromes (ACS) and in those undergoing angioplasty with stent implantation dual antiplatelet therapy with aspirin and an adenosine diphosphate (ADP) receptor antagonist is indicated. The development of the newer ADP P2Y12 inhibitors prasugrel and ticagrelor has further improved prognosis in ACS patients compared to clopidogrel. Moreover, vorapaxar allows the inhibition of platelet activation by thrombin via protease-activated receptor-1 and has been approved for the use in patients with PAD and in those with a history of myocardial infarction. This review article summarizes the current evidence on oral antiplatelet agents in cardiovascular disease. Keywords: Aspirin, clopidogrel, prasugrel, ticagrelor, vorapaxar, cardiovascular disease
- Published
- 2019
48. Platelet activation and aggregation in different centrifugal-flow left ventricular assist devices
- Author
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Cihan Ay, Thomas Gremmel, Daniela Kitzmantl, Günther Laufer, Silvia Lee, Franziska Wittmann, Patricia P. Wadowski, Simon Panzer, Dominik Wiedemann, Birgit Forstner-Bergauer, Daniel Zimpfer, Maximilian Tscharre, and Beate Eichelberger
- Subjects
0301 basic medicine ,Male ,medicine.medical_specialty ,Platelet aggregation ,Platelet Aggregation ,030204 cardiovascular system & hematology ,03 medical and health sciences ,0302 clinical medicine ,Internal medicine ,Medicine ,Humans ,Platelet ,Platelet activation ,Prospective Studies ,Aged ,business.industry ,Hematology ,General Medicine ,Middle Aged ,equipment and supplies ,medicine.disease ,Platelet Activation ,030104 developmental biology ,Heart failure ,Cardiology ,Female ,Heart-Assist Devices ,business - Abstract
Left-ventricular assist devices (LVADs) improve outcomes in end-stage heart failure patients. Two centrifugal-flow LVAD systems are currently approved, HeartMate 3 (HM3) and Medtronic/Heartware HVAD (HVAD). Clinical findings suggest differences in thrombogenicity between both systems. We compared markers of platelet activation and aggregation between HM3 and HVAD. We prospectively included 59 LVAD patients (40 HM3, 19 HVAD). Platelet
- Published
- 2021
49. Angiotensin-Converting Enzyme Inhibitors and Angiotensin Receptor Blockers in Acute Coronary Syndrome: Implications for Platelet Reactivity?
- Author
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Maximilian Tscharre, Joseph Pultar, Patricia P. Wadowski, Thomas Gremmel, Beate Eichelberger, Constantin Weikert, and Simon Panzer
- Subjects
Male ,Acute coronary syndrome ,Prasugrel ,Ticlopidine ,Platelet Aggregation ,Platelet Function Tests ,medicine.medical_treatment ,Angiotensin-Converting Enzyme Inhibitors ,030204 cardiovascular system & hematology ,Pharmacology ,Acute coronary syndromes ,03 medical and health sciences ,chemistry.chemical_compound ,Angiotensin Receptor Antagonists ,0302 clinical medicine ,medicine ,Humans ,Multiple electrode aggregometry ,Pharmacology (medical) ,030212 general & internal medicine ,Acute Coronary Syndrome ,Aged ,Aspirin ,biology ,business.industry ,Dual Anti-Platelet Therapy ,Percutaneous coronary intervention ,Angiotensin-converting enzyme ,General Medicine ,Middle Aged ,medicine.disease ,Angiotensin receptor blockers ,Blockade ,Clopidogrel ,Adenosine diphosphate ,chemistry ,biology.protein ,Female ,Original Article ,Cardiology and Cardiovascular Medicine ,business ,Platelet reactivity ,Ticagrelor ,medicine.drug - Abstract
Background In patients with acute coronary syndrome (ACS), angiotensin-converting enzyme (ACE) inhibitors are preferred over angiotensin receptor blockers (ARBs). However, in a recent pilot study, treatment with ACE inhibitors was associated with increased platelet reactivity compared to ARBs. Therefore, we sought to investigate the impact of renin-angiotensin-aldosterone system (RAAS) blockade with ACE inhibitors and ARBs on platelet aggregation in patients with ACS undergoing percutaneous coronary intervention. Methods On-treatment residual platelet reactivity in response to arachidonic acid (AA), adenosine diphosphate (ADP), SFLLRN, AYPGKF, and collagen was assessed by multiple electrode aggregometry (MEA) in 197 ACS patients on dual antiplatelet therapy (DAPT) with aspirin and either prasugrel or ticagrelor. Results One hundred sixty-five (83.7%) patients were treated with ACE inhibitors, 32 (16.3%) with ARBs. On-treatment residual AA- and ADP-inducible platelet reactivity was significantly higher in patients with ACE inhibitors (both p p = 0.036) and there was a trend for higher AYPGKF- and collagen-inducible platelet reactivity (p = 0.053 and p = 0.082). The incidence of high on-treatment residual platelet reactivity AA was significantly higher in patients with ACE inhibitors (52 [31.5%] vs. 3 [9.4%] patients; p = 0.019). Conclusion ACE inhibitors are associated with increased on-treatment residual platelet reactivity in ACS patients with potent DAPT. Further clinical trials are needed to elucidate the role of RAAS blockade with ACE inhibitors and ARBs in ACS patients treated according to current standards.
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- 2020
50. Comparison of Light Transmission Aggregometry With Impedance Aggregometry in Patients on Potent P2Y12 Inhibitors
- Author
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Joseph Pultar, Patricia P. Wadowski, Irene M. Lang, Renate Koppensteiner, Constantin Weikert, Beate Eichelberger, Thomas Gremmel, and Simon Panzer
- Subjects
Male ,Acute coronary syndrome ,Ticagrelor ,Prasugrel ,Platelet Function Tests ,030204 cardiovascular system & hematology ,Pharmacology ,Sensitivity and Specificity ,antiplatelet therapy ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,P2Y12 ,multiple electrode aggregometry ,Clinical Studies ,medicine ,Humans ,Pharmacology (medical) ,In patient ,030212 general & internal medicine ,high on-treatment residual platelet reactivity ,Aged ,Aspirin ,business.industry ,Dual Anti-Platelet Therapy ,food and beverages ,Middle Aged ,medicine.disease ,Adenosine diphosphate ,chemistry ,Purinergic P2Y Receptor Antagonists ,Arachidonic acid ,Female ,P2Y12 antagonists ,Cardiology and Cardiovascular Medicine ,business ,light transmission aggregometry ,Prasugrel Hydrochloride ,Platelet Aggregation Inhibitors ,medicine.drug - Abstract
Since data on the agreement between light transmission aggregometry (LTA) and multiple electrode aggregometry (MEA) in patients on the more potent P2Y12 inhibitors are missing so far, we investigated if the evaluation of the responsiveness to therapy by LTA can be replaced by MEA in 160 acute coronary syndrome (ACS) patients on dual antiplatelet therapy with aspirin and prasugrel or ticagrelor (n = 80 each). Cut-off values for high on-treatment residual platelet reactivity (HRPR) in response to adenosine diphosphate (ADP) or arachidonic acid (AA) were defined according to previous studies showing an association of HRPR with the occurrence of adverse ischemic outcomes. ADP- inducible platelet aggregation was 33% and 37% ( P = 0.07) by LTA and 19 AU and 20 AU ( P = 0.38) by MEA in prasugrel- and ticagrelor-treated patients, respectively. AA- inducible platelet aggregation was 2% and 3% by LTA and 15 AU and 16 AU by MEA, (all P ≥ 0.3) in patients on prasugrel and ticagrelor, respectively. By LTA, HRPR ADP and HRPR AA were seen in 5%/5% and in 4%/ 13% of patients receiving prasugrel- and ticagrelor, respectively. By MEA, HRPR ADP and HRPR AA were seen in 3%/ 25% and 0%/24% of prasugrel- and ticagrelor-treated patients, respectively. ADP-inducible platelet reactivity by MEA correlated significantly with LTA ADP in prasugrel-treated patients (r = 0.4, P < 0.001), but not in those receiving ticagrelor (r = 0.09, P = 0.45). AA-inducible platelet aggregation by LTA and MEA did not correlate in prasugrel- and ticagrelor-treated patients. Sensitivity/specificity of HRPR by MEA to detect HRPR by LTA were 25%/99% for MEA ADP and 100%/79% for MEA AA in prasugrel-treated patients, and 0%/100% for MEA ADP and 70%/83% for MEA AA in ticagrelor-treated patients. In conclusion, on-treatment residual ADP-inducible platelet reactivity by LTA and MEA shows a significant correlation in prasugrel- but not ticagrelor-treated patients. However, in both groups LTA and MEA revealed heterogeneous results regarding the classification of patients as responders or non-responders to P2Y12 inhibition.
- Published
- 2020
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