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1. Sarcopenia and adipose tissue evaluation by artificial intelligence predicts the overall survival after TAVI

Author

Matej Pekař, Otakar Jiravský, Jan Novák, Piotr Branny, Jakub Balušík, Daniel Daniš, Jan Hečko, Marek Kantor, Robert Prosecky, Lubomir Blaha, and Radek Neuwirth

Subjects
Sarcopenia, Artificial intelligence, Visceral adipose tissue, Subcutaneous adipose tissue, Survival, TAVI, Medicine, Science
Abstract

Abstract Sarcopenia is a serious systemic disease that reduces overall survival. TAVI is selectively performed in patients with severe aortic stenosis who are not indicated for open cardiac surgery due to severe polymorbidity. Artificial intelligence-assisted body composition assessment from available CT scans appears to be a simple tool to stratify these patients into low and high risk based on future estimates of all-cause mortality. Within our study, the segmentation of preprocedural CT scans at the level of the lumbar third vertebra in patients undergoing TAVI was performed using a neural network (AutoMATiCA). The obtained parameters (area and density of skeletal muscles and intramuscular, visceral, and subcutaneous adipose tissue) were analyzed using Cox univariate and multivariable models for continuous and categorical variables to assess the relation of selected variables with all-cause mortality. 866 patients were included (median(interquartile range)): age 79.7 (74.9–83.3) years; BMI 28.9 (25.9–32.6) kg/m2. Survival analysis was performed on all automatically obtained parameters of muscle and fat density and area. Skeletal muscle index (SMI in cm2/m2), visceral (VAT in HU) and subcutaneous adipose tissue (SAT in HU) density predicted the all-cause mortality in patients after TAVI expressed as hazard ratio (HR) with 95% confidence interval (CI): SMI HR 0.986, 95% CI (0.975–0.996); VAT 1.015 (1.002–1.028) and SAT 1.014 (1.004–1.023), all p

Published
2024
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3. Flavonoids against the SARS-CoV-2 induced inflammatory storm

Author

Alena Liskova, Marek Samec, Lenka Koklesova, Samson M. Samuel, Kevin Zhai, Raghad Khalid Al-Ishaq, Mariam Abotaleb, Vladimir Nosal, Karol Kajo, Milad Ashrafizadeh, Ali Zarrabi, Aranka Brockmueller, Mehdi Shakibaei, Peter Sabaka, Ioana Mozos, David Ullrich, Robert Prosecky, Giampiero La Rocca, Martin Caprnda, Dietrich Büsselberg, Luis Rodrigo, Peter Kruzliak, and Peter Kubatka

Subjects
SARS-CoV-2, COVID-19, Inflammation, Cytokine storm, Phytochemicals, Flavonoids, Therapeutics. Pharmacology, RM1-950
Abstract

The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities.

Published
2021
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6. 36-month clinical outcomes of patients with venous thromboembolism

Author

Alexander G.G. Turpie, Alfredo E. Farjat, Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Shinya Goto, Pantep Angchaisuksiri, Gloria Kayani, Renato D. Lopes, Chern-En Chiang, Harry Gibbs, Eric Tse, Peter Verhamme, Hugo ten Cate, Juan Muntaner, Sebastian Schellong, Henri Bounameaux, Paolo Prandoni, Uma Maheshwari, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool-Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera-Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann-Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau-Chung Wu, Cheng Hock Toh, Chevrier Elisa, Chien-Hsun Hsia, Chien-Lung Huang, Chi-Hang Kevin Kwok, Chih-Cheng Wu, Chi-Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret-Gris, Chung Yin Ha, Chun-Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, David - Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs-Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala-Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia-Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye-Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean-Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans-Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho-Young Yhim, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik-Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M. De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer-Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen-Yuan Kuo, Jhih-Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jørn Nielsen, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou-Gi Shyu, Kristel Vandenbosch, Kuan-Cheng Chang, Kuan-Ming Chiu, Kubina Jean-Manuel, Kwan Jing Wern, Kwo-Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool-Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El-Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon-Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan-Keim, Remedios Otero, Renate Murena-Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung-Hyun Nam, Sevestre-Pietri Marie-Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe-Nana Jean-Léopold, Somchai Wongkhantee, Soo-Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel-Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting-Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei-Hsiang Lin, Weihua Zhang, Wei-Kung Tseng, Wen-Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won Il Choi, Yang-Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung-Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Pulmonary Medicine, Clinical Genetics, Internal Medicine, Vascular Medicine, ACS - Pulmonary hypertension & thrombosis, ARD - Amsterdam Reproduction and Development, ACS - Diabetes & metabolism, VU University medical center, Interne Geneeskunde, MUMC+: MA Alg Interne Geneeskunde (9), and RS: Carim - B04 Clinical thrombosis and Haemostasis

Subjects
History, Anticoagulation, Registry, Polymers and Plastics, SDG 3 - Good Health and Well-being, Deep vein thrombosis, Pulmonary embolism, Hematology, Business and International Management, Industrial and Manufacturing Engineering, Venous thromboembolism
Abstract

BACKGROUND: Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary embolism (PE), is a leading cause of morbidity and mortality worldwide. METHODS: GARFIELD-VTE is a prospective, non-interventional observational study of real-world treatment practices. We aimed to capture the 36-month clinical outcomes of 10,679 patients with objectively confirmed VTE enrolled between May 2014 and January 2017 from 415 sites in 28 countries. FINDINGS: A total of 6582 (61.6 %) patients had DVT alone, 4097 (38.4 %) had PE ± DVT. At baseline, 98.1 % of patients received anticoagulation (AC) with or without other modalities of therapy. The proportion of patients on AC therapy decreased over time: 87.6 % at 3 months, 73.0 % at 6 months, 54.2 % at 12 months and 42.0 % at 36 months. At 12-months follow-up, the incidences (95 % confidence interval [CI]) of all-cause mortality, recurrent VTE and major bleeding were 6.5 (7.0-8.1), 5.4 (4.9-5.9) and 2.7 (2.4-3.0) per 100 person-years, respectively. At 36-months, these decreased to 4.4 (4.2-4.7), 3.5 (3.2-2.7) and 1.4 (1.3-1.6) per 100 person-years, respectively. Over 36-months, the rate of all-cause mortality and major bleeds were highest in patients treated with parenteral therapy (PAR) versus oral anti-coagulants (OAC) and no OAC, and the rate of recurrent VTE was highest in patients on no OAC versus those on PAR and OAC. The most frequent cause of death after 36-month follow-up was cancer (n = 565, 48.6 %), followed by cardiac (n = 94, 8.1 %), and VTE (n = 38, 3.2 %). Most recurrent VTE events were DVT alone (n = 564, 63.3 %), with the remainder PE, (n = 236, 27.3 %), or PE in combination with DVT (n = 63, 7.3 %). INTERPRETATION: GARFIELD-VTE provides a global perspective of anticoagulation patterns and highlights the accumulation of events within the first 12 months after diagnosis. These findings may help identify treatment gaps for subsequent interventions to improve patient outcomes in this patient population. ispartof: THROMBOSIS RESEARCH vol:222 pages:31-39 ispartof: location:United States status: published

Published
2023

9. Cisplatin treatment reduces vasoconstriction to angiotensin II associated with altering expression of angiotensin type II receptors

Author

Kristen Renee McSweeney, Laura Kate Gadanec, Peter Kubatka, Martin Caprnda, Ludovit Gaspar, Robert Prosecky, Delian Delev, Peter Kruzliak Peter Kruzliak, Vasso Apostolopoulos, and Anthony Zulli

Abstract

The renin angiotensin system is a key regulator of blood pressure homeostasis. Angiotensin type 1 (AT1R) and 2 receptors (AT2R) have been investigated as targets for cisplatin-induced acute kidney injury; however, their therapeutic potential remains inconclusive. We determined the effect that acute cisplatin treatment had on angiotensin II (AngII)-mediated vasoconstriction in blood vessels and expression profiles of AT1R and AT2R in mouse arteries and kidneys. 18-week-old male C57BL/6 mice (n = 8) were treated with vehicle or bolus dose of cisplatin (12.5 mg/kg). Thoracic aorta (TA), adnominal aorta (AA), brachiocephalic arteries (BC), iliac arteries (IL) and kidneys were collected for isometric tension analysis and immunohistochemistry analysis. Cisplatin treatment reduced IL vasoconstriction to AngII at all doses; AngII [10-8.0 M] (vehicle: 19.61 3.49 % vs. cisplatin: 0.43 0.09 %, ** p < 0.01) to AngII [10-5.0 M] (vehicle: 27.57 3.22 % vs. cisplatin: 3.26 1.26 %, *** p < 0.001); but did not induce constriction in TA, AA or BC after vehicle or cisplatin treatment. Following cisplatin treatment AT1R expression was significantly upregulated (arbitrary units) in the IL vessels when compared to the TA (IL: 0.014 ± 0.004 vs TA: 0.0013 ± 0.0006, * p < 0.05) and the AA (IL: 0.014 ± 0.004 vs AA: 0.0014 ± 0.0008, * p < 0.05). AT2R expression was downregulated in the media of cisplatin treated IL vessels compared to both TA (IL: 0.0223 ± 0.0052 vs TA: 0.072 ± 0.005, *** p < 0.001) and AA IL: 0.022 ± 0.005 vs AA: 0.060 ± 0.002, ** p < 0.01). AT1R (vehicle: 0.003 0.001 vs cisplatin 0.019 0.002, ** p < 0.01) and AT2R (vehicle: 0.016 0.004 vs cisplatin 0.037 0.004, * p < 0.05) in renal tubules were both upregulated following cisplatin treatment. Herein we report that cisplatin reduces AngII mediated vasoconstriction in IL. This accompanied by an absence of normal counterregulatory expression of AT1R and AT2R, indicating other factors are involved.

Published
2022

11. Flavonoids exert potential in the management of hypertensive disorders in pregnancy

Author

Alena Mazurakova, Lenka Koklesova, Marek Samec, Erik Kudela, Jana Sivakova, Terezia Pribulova, Martin Jozef Pec, Martin Pec, Martin Kello, Dietrich Büsselberg, Olga Golubnitschaja, Ludovit Gaspar, Martin Caprnda, Mariusz Adamek, Robert Prosecky, Elmira Eminova, Denis Baranenko, Peter Kruzliak, Peter Kubatka, and Kamil Biringer

Subjects
Flavonoids, Pre-Eclampsia, Tea, Pregnancy, Vegetables, Internal Medicine, Obstetrics and Gynecology, Humans, Female, Hypertension, Pregnancy-Induced, Child
Abstract

Hypertensive disorders in pregnancy represent severe complications of pregnancy, which, if not treated, can result in serious health consequences for the mother and the child. Flavonoids are bioactive secondary metabolites commonly found in fruits, vegetables, green tea, whole grains, and medicinal plants. Flavonoids exert potent protective efficacy in experimental models of hypertensive disorders in pregnancy, especially preeclampsia, demonstrated through their capacity to modulate inflammatory responses, oxidative stress, and vascular dysfunction. In addition to their potential as therapeutics, flavonoids or flavonoid-rich food could be helpful to decrease the risk of hypertensive disorders in pregnancy when included in the diet pattern before and during pregnancy. However, the clinical evaluation of the potential capacity of flavonoids in hypertensive disorders in pregnancy is insufficient. Due to promising results from experimental studies, we highlight the need for the evaluation of flavonoids also in an appropriate clinical setting, which can be, together with proper preventive strategies, helpful in the overall management of hypertensive disorders in pregnancy.

Published
2022

12. The role of plant-derived natural substances as immunomodulatory agents in carcinogenesis

Author

Pavol Zubor, Taeg Kyu Kwon, Martin Caprnda, Dietrich Büsselberg, Luis Rodrigo, Peter Kruzliak, Radovan Murín, Rachele Ciccocioppo, Samson Mathews Samuel, Marek Samec, Jan Bujnak, Lenka Koklesova, Alena Liskova, Peter Kubatka, and Robert Prosecky

Subjects
0301 basic medicine, Cancer Research, Carcinogenesis, Preclinical and clinical research, animal diseases, Phytochemicals, chemical and pharmacologic phenomena, Biology, medicine.disease_cause, Immune tolerance, Immunomodulation, 03 medical and health sciences, 0302 clinical medicine, Immune system, Neoplasms, Immune Tolerance, medicine, Humans, Cancer, Immune escape, General Medicine, biochemical phenomena, metabolism, and nutrition, medicine.disease, Acquired immune system, Immunity, Innate, 030104 developmental biology, Oncology, Phytochemical, 030220 oncology & carcinogenesis, Cancer research, Cytokines, bacteria, Cancer development
Abstract

The role of immune system in carcinogenesis represents fundamental events associated with cancer eradication; however, tumor evolution is connected with various mechanisms of tumor evasion and progression of cancer. Based on recent evidence, phytochemicals are directly associated with immunomodulation of the innate and adaptive immunity via different mechanisms of action including stimulation and amplification of immune cells, humoral compartments, and associated molecules. This comprehensive study focuses on immunomodulating potential of phytochemicals (mixture in plants or separately such as individual phytochemical) and their impact on regulation of immune response during cancer development, immune tolerance, and immune escape. Clinical application of phytochemicals as modulators of host immunity against cancer may represent perspective approach in anticancer therapy.

Published
2020

14. Kinetics of platelet adhesion to a fibrinogen‐coated surface in whole blood under flow conditions

Author

Ioana Mozos, Yuliya Avtaeva, Nadezhda I. Zozulya, Peter Kruzliak, Martin Caprnda, Luis Rodrigo, Sergey Okhota, I. S. Mel’nikov, Robert Prosecky, and Zufar Gabbasov

Subjects
Blood Platelets, Microbiology (medical), medicine.medical_specialty, Platelet Aggregation, Clinical Biochemistry, Platelet Glycoprotein GPIIb-IIIa Complex, 030204 cardiovascular system & hematology, Fibrinogen, Autoimmune thrombocytopenia, 03 medical and health sciences, Platelet Adhesiveness, 0302 clinical medicine, Internal medicine, medicine, Von Willebrand disease, Humans, Immunology and Allergy, Platelet, Receptor, Research Articles, 030304 developmental biology, Whole blood, 0303 health sciences, Chemistry, whole blood, Biochemistry (medical), Public Health, Environmental and Occupational Health, flow conditions, Hematology, Adhesion, Blood flow, recording of a scattered laser light signal from a fibrinogen‐covered surface, medicine.disease, Healthy Volunteers, 3. Good health, Kinetics, Medical Laboratory Technology, Endocrinology, Platelet Glycoprotein GPIb-IX Complex, platelet adhesion, fibrinogen‐coated surface, Platelet Aggregation Inhibitors, Research Article, medicine.drug
Abstract

Aim To test a novel method of assessment of platelet adhesion to a fibrinogen‐coated surface in whole blood under flow conditions. Methods We developed a fluidic device that mimics blood flow in vessels. The method of detection of platelet adhesion is based on recording of a scattered laser light signal from a fibrinogen‐covered surface. Testing was performed in platelet‐rich plasma (PRP) and whole blood of healthy volunteers. Control measurements were performed, followed by tests with inhibition of platelet GPIIa/IIIb and GPIb receptors. Then, the same testing sequence was performed in whole blood of persons with autoimmune thrombocytopenia and type 3 von Willebrand disease. Results The change in intensity of scattered light was 2.7 (2.4; 4.1) times higher in whole blood (0.2 ± 0.08V, n = 7) than in PRP (0.05 ± 0.02 V, n = 7), p, The laser optical system for recording of platelet adhesion to protein‐coated surfaces under flow conditions. The illustration of the flow chamber with the flat glass surface coated with a monolayer of cell‐adhesive molecules. The glass surface was coated with fibrinogen. The reflected light evanesces into the blood sample beyond the reflection zone to a depth of approximately 400–600 nm. Platelets or other blood cells in the flow do not interact with this laser radiation, which evanesces to such a small depth. The laser light can interact with platelets only when they are strongly attached to or spread onto the glass surface.

Published
2021

15. Prevalence and significance of M541L single nucleotide polymorphism in the central European cohort of gastrointestinal stromal tumor patients

Author

Szépe P, Robert Prosecky, Ivana Kasubova, Tatiana Burjanivova, Peter Kruzliak, Bibiana Malicherova, Zora Lasabova, Rachele Ciccocioppo, Andrea Stanclova, Marian Grendar, Lukáš Plank, Karin Jasek, and Luis Rodrigo

Subjects
0301 basic medicine, Oncology, Adult, Male, Cancer Research, medicine.medical_specialty, Adolescent, Gastrointestinal Stromal Tumors, Single-nucleotide polymorphism, PDGFRA, Polymorphism, Single Nucleotide, 03 medical and health sciences, symbols.namesake, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Biomarkers, Tumor, Humans, Clinical significance, Stromal tumor, Aged, Gastrointestinal Neoplasms, Retrospective Studies, Sanger sequencing, Aged, 80 and over, Hematology, GiST, business.industry, General Medicine, Middle Aged, Prognosis, digestive system diseases, Europe, Survival Rate, Proto-Oncogene Proteins c-kit, 030104 developmental biology, 030220 oncology & carcinogenesis, Cohort, symbols, Female, business, Follow-Up Studies
Abstract

Single nucleotide polymorphisms can create a genetic microenvironment in some tumors that affects the course of treatment, resistance, etc. Whether single nucleotide polymorphisms have an impact on gastrointestinal stromal tumor (GIST) development and disease progression is not yet accurately verified. KIT SNPM541L in exon 10 correlates with a worse prognosis of many cancers. The impact of KIT SNPM541L in GISTs is relatively unknown and, therefore, its analyses could have potential in patient therapy and could provide more detailed information on tumor character, clinical presentation, or tumor behavior in treatment. The aim of the study was the analysis of the biological and clinical significance of the KIT SNPM541L polymorphism in exon 10. Paraffin sample tissues were obtained from the National GIST Register in Martin. Retrospective samples from 177 GIST patients were divided into several groups. Detection of SNPM541L was performed by Sanger sequencing. Statisitical analyses were performed to determine the prevalence of KIT SNPM541L in the Slovak GIST cohort, to search for correlation between c-KIT status and clinicopathological, molecular and biological data. Overall, 29 samples out of 177 showed KIT SNPM541L polymorphism. Our results do not support the association between KIT SNPM541L and increased risk of relapse in localized primary GISTs. Additionally, we found a positive correlation between KIT SNPM541L occurrence and earlier onset of relapse in PDGFRa and WT subgroup of GISTs.

Published
2020

16. Flavonoids against the SARS-CoV-2 induced inflammatory storm

Author

Karol Kajo, Robert Prosecky, Ioana Mozos, Raghad Khalid Al-Ishaq, Peter Kubatka, Ali Zarrabi, Kevin Zhai, Mehdi Shakibaei, Milad Ashrafizadeh, Giampiero La Rocca, Peter Kruzliak, Lenka Koklesova, Alena Liskova, Martin Caprnda, Dietrich Büsselberg, Mariam Abotaleb, Vladimir Nosal, Peter Sabaka, David Ullrich, Aranka Brockmueller, Marek Samec, Luis Rodrigo, Samson Mathews Samuel, Liskova A., Samec M., Koklesova L., Samuel S.M., Zhai K., Al-Ishaq R.K., Abotaleb M., Nosal V., Kajo K., Ashrafizadeh M., Zarrabi A., Brockmueller A., Shakibaei M., Sabaka P., Mozos I., Ullrich D., Prosecky R., La Rocca G., Caprnda M., Busselberg D., Rodrigo L., Kruzliak P., and Kubatka P.

Subjects
Settore BIO/17 - Istologia, 0301 basic medicine, Phytochemicals, Anti-Inflammatory Agents, Anti-inflammatory effects, Inflammation, RM1-950, Review, Cytokine storm, Proinflammatory cytokine, Immunomodulation, Endothelial activation, 03 medical and health sciences, 0302 clinical medicine, Immune system, Animals, Humans, Medicine, Dipeptidyl peptidase-4, Flavonoids, Pharmacology, SARS-CoV-2, business.industry, fungi, COVID-19, food and beverages, Inflammasome, General Medicine, medicine.disease, COVID-19 Drug Treatment, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Immunology, Therapeutics. Pharmacology, medicine.symptom, Signal transduction, Cytokine Release Syndrome, business, medicine.drug
Abstract

The disease severity of COVID-19, especially in the elderly and patients with co-morbidities, is characterized by hypercytokinemia, an exaggerated immune response associated with an uncontrolled and excessive release of proinflammatory cytokine mediators (cytokine storm). Flavonoids, important secondary metabolites of plants, have long been studied as therapeutic interventions in inflammatory diseases due to their cytokine-modulatory effects. In this review, we discuss the potential role of flavonoids in the modulation of signaling pathways that are crucial for COVID-19 disease, particularly those related to inflammation and immunity. The immunomodulatory ability of flavonoids, carried out by the regulation of inflammatory mediators, the inhibition of endothelial activation, NLRP3 inflammasome, toll-like receptors (TLRs) or bromodomain containing protein 4 (BRD4), and the activation of the nuclear factor erythroid-derived 2-related factor 2 (Nrf2), might be beneficial in regulating the cytokine storm during SARS-CoV-2 infection. Moreover, the ability of flavonoids to inhibit dipeptidyl peptidase 4 (DPP4), neutralize 3-chymotrypsin-like protease (3CLpro) or to affect gut microbiota to maintain immune response, and the dual action of angiotensin-converting enzyme 2 (ACE-2) may potentially also be applied to the exaggerated inflammatory responses induced by SARS-CoV-2. Based on the previously proven effects of flavonoids in other diseases or on the basis of newly published studies associated with COVID-19 (bioinformatics, molecular docking), it is reasonable to assume positive effects of flavonoids on inflammatory changes associated with COVID-19. This review highlights the current state of knowledge of the utility of flavonoids in the management of COVID-19 and also points to the multiple biological effects of flavonoids on signaling pathways associated with the inflammation processes that are deregulated in the pathology induced by SARS-CoV-2. The identification of agents, including naturally occurring substances such as flavonoids, represents great approach potentially utilizable in the management of COVID-19. Although not clinically investigated yet, the applicability of flavonoids against COVID-19 could be a promising strategy due to a broad spectrum of their biological activities., Graphical Abstract ga1

Published
2021

17. Matrix metalloproteinase-3 gene polymorphism (rs3025058) affects markers atherosclerosis in type 2 diabetes mellitus

Author

Eduard Curilla, Ales Pleskovic, Peter Kruzliak, Jovana Nikolajević Starčević, Daniel Petrovič, Marija Šantl Letonja, Martin Caprnda, Andreja Cokan Vujkovac, Ioana Mozos, and Robert Prosecky

Subjects
Carotid Artery Diseases, Male, 0301 basic medicine, Pathology, Time Factors, Cross-sectional study, Coronary Artery Disease, Coronary Angiography, Carotid Intima-Media Thickness, Severity of Illness Index, Gastroenterology, Coronary artery disease, 0302 clinical medicine, Gene Frequency, Risk Factors, Prospective Studies, Prospective cohort study, Subclinical infection, Middle Aged, Prognosis, Phenotype, Matrix Metalloproteinase 9, Female, Matrix Metalloproteinase 3, Cardiology and Cardiovascular Medicine, medicine.medical_specialty, Polymorphism, Single Nucleotide, 03 medical and health sciences, Internal medicine, medicine, Humans, Genetic Predisposition to Disease, Allele frequency, Genotyping, Genetic Association Studies, Aged, Chi-Square Distribution, business.industry, Coronary Stenosis, Type 2 Diabetes Mellitus, medicine.disease, Cross-Sectional Studies, 030104 developmental biology, Diabetes Mellitus, Type 2, Asymptomatic Diseases, Multivariate Analysis, Linear Models, Gene polymorphism, business, 030217 neurology & neurosurgery
Abstract

Abstract. Background: The study was designed to test the possible association between either polymorphisms of the matrix metalloproteinase-9 (MMP-9) gene (rs17576, rs3918242) or the MMP-3 5A/6A gene polymorphism (rs3025058) with markers of carotid atherosclerosis in patients with type 2 diabetes mellitus (T2DM). The second aim of the study was to demonstrate an association between either the rs17576, rs3918242 or rs3025058 and subclinical markers of coronary artery disease in the same subset of patients with T2DM. Patients and methods: A total of 595 subjects with T2DM and 200 subjects without T2DM (control group) were enrolled in the prospective study. Subclinical markers of carotid atherosclerosis were assessed ultrasonographically. Additionally, in a subset of subjects with T2DM a coronary computed tomography angiography (CCTA) was performed for diagnostic purposes. Genotyping of all three polymorphisms (rs17576, rs3918242, rs3025058) was performed with real-time PCR systems. Results: The comparison of atherosclerosis parameters was performed with regard to different genotypes of MMP-9 rs17576, rs3918242, and MMP-3 rs3025058 polymorphisms upon enrolment and during follow-up. In our study, we found an association between the MMP-3 rs3025058 and CIMT at the time of recruitment. Multiple linear regression analysis revealed the association of either the A- allele or the A- genotypes of the rs3025058 (MMP-3) with carotid intima media thickness (CIMT) progression in a 3.8-year follow-up. We demonstrated the effect of the rs3025058 on subclinical markers of coronary atherosclerosis (coronary calcium score, number of coronary arteries with more than 50 % stenosis, and presence of at least one vessel with more than 50 % stenosis). Conclusions: We found an association between the MMP-3 rs3025058 and subclinical markers of carotid (CIMT) and coronary atherosclerosis at the time of recruitment. Moreover, we demonstrated the effect of the MMP-3 rs3025058 on CIMT progression in the 3.8-year follow-up in patients with T2DM.

Published
2017

18. The therapeutic effect of B-type natriuretic peptides in acute decompensated heart failure

Author

Aleksandras Laucevičius, Robert Staffa, Jozef Dragasek, Andrius Berukstis, Peter Kruzliak, Haaris A. Shiwani, Vanda Valentova, Robert Prosecky, Slavomira Filipova, Peter Kubatka, Anthony Zulli, Ioana Mozos, Emmanuel E. Egom, Katarina Gazdikova, I Rihácek, Vladimir Krasnik, and Martin Caprnda

Subjects
0301 basic medicine, medicine.medical_specialty, Acute decompensated heart failure, Physiology, medicine.drug_class, Diuresis, Natriuresis, law.invention, 03 medical and health sciences, 0302 clinical medicine, Atrial natriuretic peptide, Randomized controlled trial, law, Physiology (medical), Internal medicine, Natriuretic Peptide, Brain, Natriuretic peptide, Medicine, Humans, Pharmacology, Heart Failure, business.industry, Therapeutic effect, medicine.disease, 3. Good health, 030104 developmental biology, 030220 oncology & carcinogenesis, Heart failure, Acute Disease, Cardiology, business, hormones, hormone substitutes, and hormone antagonists
Abstract

B-type natriuretic peptide (BNP) exhibits roles in natriuresis and diuresis, making it an ideal drug that may aid in diuresing a fluid-overloaded patient with poor or worsening renal function. Several randomized clinical trials have tested the hypothesis that infusions of pharmacological doses of BNP to acute heart failure (HF) patients may enhance decongestion and preserve renal function in this clinical setting. Unfortunately, none of these have demonstrated beneficial outcomes. The current challenge for BNP research in acute HF lies in addressing a failure of concept and a reluctance to abandon an ineffective research model. Future success will necessitate a detailed understanding of the mechanism of action of BNP, as well as better integration of basic and clinical science.

Published
2019

19. MicroRNA-15a tissue expression is a prognostic marker for survival in patients with clear cell renal cell carcinoma

Author

Robert Prosecky, Lesia Tumanovska, Peter Urdzík, D. O. Stroy, Yuriy Borys, Victor E. Dosenko, Yulian Mytsyk, Luis Rodrigo, Askold Kucher, Katarina Gazdikova, and Peter Kruzliak

Subjects
0301 basic medicine, Oncology, Male, medicine.medical_specialty, medicine.medical_treatment, Kidney, Nephrectomy, General Biochemistry, Genetics and Molecular Biology, 03 medical and health sciences, 0302 clinical medicine, Renal cell carcinoma, Internal medicine, medicine, Biomarkers, Tumor, Humans, Carcinoma, Renal Cell, Survival analysis, Retrospective Studies, business.industry, Cancer, General Medicine, medicine.disease, Prognosis, Survival Analysis, Kidney Neoplasms, Up-Regulation, Gene Expression Regulation, Neoplastic, Clear cell renal cell carcinoma, MicroRNAs, 030104 developmental biology, Real-time polymerase chain reaction, Treatment Outcome, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Biomarker (medicine), Female, business, Clear cell
Abstract

None of the currently investigated molecular markers demonstrated sufficient accuracy in prognostication of the renal cell carcinoma (RCC) oncologic outcomes; thus, none of them has been recommended for the application in the routine clinical practice. The role of miR-15a as a potential prognostic marker for RCC is still not unveiled. The aim of our study was to assess the expression of miR-15a in tumor tissues of the patients with RCC and to evaluate the possibility of its usage as a prognostic molecular biomarker of this disease. The retrospective included 64 adult patients with clear cell RCC (ccRCC) in whom radical or partial nephrectomy was conducted. After deparaffinization of formalin-fixed paraffin-embedded (FFPE) ccRCC specimens, the tissue expression of miR-15a was measured using the reverse transcription and quantitative polymerase chain reaction in the real time. For the reference, the expression of miR-15a was estimated in 15 FFPE tissue specimens of the normal renal parenchyma. Survival analysis involved all cases of non-metastatic RCCs (n = 57). Five-year cancer-specific survival (CSS) was estimated by means of the Kaplan–Meier method and was calculated from the date of surgery to the date of death. Patients with the RCC were characterized by significantly upregulated tumor tissue mean levels of miR-15a compared to the healthy controls: 0.10 ± 2.62 relative units (RU) versus 4.84E − 03 ± 3.11E − 03 RU (p

Published
2019

20. Anticoagulation therapy patterns for acute treatment of venous thromboembolism in GARFIELD-VTE patients

Author

Sylvia Haas, Walter Ageno, Jeffrey I. Weitz, Samuel Z. Goldhaber, Alexander G.G. Turpie, Shinya Goto, Pantep Angchaisuksiri, Joern Dalsgaard Nielsen, Gloria Kayani, Audrey Zaghdoun, Alfredo E. Farjat, Sebastian Schellong, Henri Bounameaux, Lorenzo G. Mantovani, Paolo Prandoni, Ajay K. Kakkar, Ab Loualidi, Abdurrahim Colak, Abraham Bezuidenhout, Abu Abdool‐Carrim, Addala Azeddine, Adriaan Beyers, Adriaan Dees, Ahmed Mohamed, Ahmet Aksoy, Akihiko Abiko, Akinori Watanabe, Alan Krichell, Alberto Alfredo Fernandez, Alberto Tosetto, Alexey Khotuntsov, Alisha Oropallo, Alison Slocombe, Allan Kelly, Amanda Clark, Amr Gad, Amy Arouni, Andor Schmidt, Andrea Berni, Andres Javier Kleiban, Andrew Machowski, Andrey Kazakov, Angel Galvez, Ann Lockman, Anna Falanga, Anoop Chauhan, Antoni Riera‐Mestre, Antonino Mazzone, Armando D'Angelo, Artur Herdy, Atsushi Kato, Ayman Abd Elhamid Ebrahim, Mahmoud Salem, Azlan Husin, Barbara Erdelyi, Barry Jacobson, Beatrice Amann‐Vesti, Bektas Battaloglu, Benedicte Wilson, Benilde Cosmi, Bergmann Jean Francois, Berremeli Toufek, Beverley Hunt, Bhavesh Natha, Bisher Mustafa, Bonnie Chi Shan Kho, Boulon Carine, Brian Zidel, Brisot Dominique, Brousse Christophe, Bruno Trimarco, Canhua Luo, Carlos Alberto Cuneo, Carlos Jerjes Sanchez Diaz, Carsten Schwencke, Cas Cader, Celal Yavuz, Cesar Javier Zaidman, Charles Lunn, Chau‐Chung Wu, Cheng Hock Toh, Chern‐En Chiang, Chevrier Elisa, Chien‐Hsun Hsia, Chien‐Lung Huang, Chi‐Hang Kevin Kwok, Chih‐Cheng Wu, Chi‐Hung Huang, Chris Ward, Christian Opitz, Christina Jeanneret‐Gris, Chung Yin Ha, Chun‐Yao Huang, Claude Luyeye Bidi, Clifford Smith, Cornelia Brauer, Corrado Lodigiani, Couturaud Francis, Cynthia Wu, Daniel Staub, Daniel Theodoro, Daniela Poli, Riesco Acevedo, David Adler, David Jimenez, David Keeling, David Scott, Davide Imberti, Desmond Creagh, Desmurs‐Clavel Helene, Dirk Hagemann, Dirk Le Roux, Dirk Skowasch, Dmitry Belenky, Dmitry Dorokhov, Dmitry Petrov, Dmitry Zateyshchikov, Domenico Prisco, Dorthe Møller, Dusan Kucera, Ehab M. Esheiba, Elizaveta Panchenko, Elkouri Dominique, Emre Dogan, Emre Kubat, Enrique Diaz Diaz, Eric Wai Choi Tse, Erik Yeo, Erman Hashas, Ernst Grochenig, Eros Tiraferri, Erwin Blessing, Escande Orthlieb Michèle, Esther Usandizaga, Ettore Porreca, Fabian Ferroni, Falvo Nicolas, Félix Ayala‐Paredes, Firas Koura, Fitjerald Henry, Franco Cosmi, Frans Erdkamp, Gadel Kamalov, Garcia‐Bragado Dalmau, Garrigues Damien, Garry Klein, Gaurand Shah, Geert Hollanders, Geno Merli, Georg Plassmann, George Platt, Germain Poirier, German Sokurenko, Ghassan Haddad, Gholam Ali, Giancarlo Agnelli, Gin Gin Gan, Grace Kaye‐Eddie, Gregoire Le Gal, Gregory Allen, Guillermo Antonio Llamas Esperón, Guillot Jean‐Paul, Hagen Gerofke, Hallah Elali, Hana Burianova, Hans‐Juergen Ohler, Haofu Wang, Harald Darius, Harinder S. Gogia, Harry Striekwold, Harry Gibbs, Hatice Hasanoglu, Hatice Turker, Hendrik Franow, Herbert De Raedt, Herman Schroe, Hesham Salah ElDin, Hesham Zidan, Hiroaki Nakamura, Ho Young Kim, Holger Lawall, Hong Zhu, Hongyan Tian, Ho‐Young Yhim, Hugo ten Cate, Hun Gyu Hwang, Hyeok Shim, Igor Kim, Igor Libov, Igor Sonkin, Igor Suchkov, Ik‐Chan Song, Ilker Kiris, Ilya Staroverov, Irene Looi, Isabel M De La Azuela Tenorio, Ismail Savas, Ivan Gordeev, Ivo Podpera, Jae Hoon Lee, Jameela Sathar, James Welker, Jan Beyer‐Westendorf, Jan Kvasnicka, Jan Vanwelden, JangYong Kim, Jaromira Svobodova, Jaspal Gujral, Javier Marino, Javier Tristan Galvar, Jeannine Kassis, Jen‐Yuan Kuo, Jhih‐Yuan Shih, JiHyun Kwon, Jin Hyun Joh, Jin Hyun Park, Jin Seok Kim, Jinghua Yang, Jiri Krupicka, Jiri Lastuvka, Jiri Pumprla, Jiri Vesely, Joan Carlos Souto, João Antônio Correa, Johan Duchateau, John Perry Fletcher, Jorge del Toro, Jorge Guillermo Chavez Paez, Jose Dalmo Araujo Filho, Jose Saraiva, Jose Antonio Diaz Peromingo, Jose Gomez Lara, Jose Luis Fedele, Jose Maria Surinach, Joseph Chacko, Juan Antonio Muntaner, Juan Carlos Álvarez Benitez, Juan Moreno Hoyos Abril, Julian Humphrey, Julio Bono, Junji Kanda, Juree Boondumrongsagoon, Kai Hang Yiu, Kanchana Chansung, Karin Boomars, Kate Burbury, Katsuhiro Kondo, Kemal Karaarslan, Kensuke Takeuchi, Knut Kroeger, Konstantin Zrazhevskiy, Koscál Svatopluk, Kou‐Gi Shyu, Kristel Vandenbosch, Kuan‐Cheng Chang, Kuan‐Ming Chiu, Kubina Jean‐Manuel, Kwan Jing Wern, Kwo‐Chang Ueng, Lalita Norasetthada, Laure Binet, Lee Ping Chew, Lei Zhang, Leone Maria Cristina, Lidwine Tick, Lilia Beatriz Schiavi, Lily Lee Lee Wong, Lohana Borges, Louis Botha, Luc Capiau, Luc Timmermans, Luciano Eduardo López, Luigi Ria, Luis Manuel Hernandez Blasco, Luis Alberto Guzman, Luis Flota Cervera, Mahe Isabelle, Manuel Monreal Bosch, Manuel de los Rios Ibarra, Manuel Núñez Fernandez, Marc Carrier, Marcelo Raul Barrionuevo, Marco Antonio Alcocer Gamba, Marco Cattaneo, Marco Moia, Margaret Bowers, Mariam Chetanachan, Mario Alberto Berli, Mark Fixley, Markus Faghih, Markus Stuecker, Marlin Schul, Martin Banyai, Martin Koretzky, Martin Myriam, Mary Elizabeth Gaffney, Masao Hirano, Masashi Kanemoto, Mashio Nakamura, Mersel Tahar, Messas Emmanuel, Michael Kovacs, Michael Leahy, Michael Levy, Michael Munch, Michael Olsen, Michel De Pauw, Michel Gustin, Michiel Van Betsbrugge, Mikhail Boyarkin, Miroslav Homza, Modise Koto, Mohamed Abdool‐Gaffar, Mohamed Ayman Fakhry Nagib, Mohamed El‐Dessoki, Mohamed Khan, Monniaty Mohamed, Moo Hyun Kim, Moon‐Hee Lee, Mosaad Soliman, Mostafa Shawky Ahmed, Mostafa Soliman Abd el Bary, Moustafa A. Moustafa, Muhammad Hameed, Muhip Kanko, Mujibur Majumder, Nadezhda Zubareva, Nicola Mumoli, Nik Azim Nik Abdullah, Nisa Makruasi, Nishen Paruk, Nonglak Kanitsap, Norberto Duda, Nordiana Nordin, Ole Nyvad, Olga Barbarash, Orcun Gurbuz, Oscar Gomez Vilamajo, Oscar Nandayapa Flores, Ozcan Gur, Oztekin Oto, Pablo Javier Marchena, Patrick Carroll, Pavel Lang, Peter MacCallum, Peter Baron von Bilderling, Peter Blombery, Peter Verhamme, Petr Jansky, Peuch Bernadette, Philippe De Vleeschauwer, Philippe Hainaut, Piera Maria Ferrini, Piriyaporn Iamsai, Ponchaux Christian, Pongtep Viboonjuntra, Ponlapat Rojnuckarin, Prahlad Ho, Pramook Mutirangura, Rachel Wells, Rafael Martinez, Raimundo Tirado Miranda, Ralf Kroening, Rapule Ratsela, Raquel Lopez Reyes, Raul Franco Diaz de Leon, Raymond Siu Ming Wong, Raz Alikhan, Reinhold Jerwan‐Keim, Remedios Otero, Renate Murena‐Schmidt, Reto Canevascini, Richard Ferkl, Richard White, Rika Van Herreweghe, Rita Santoro, Robert Klamroth, Robert Mendes, Robert Prosecky, Roberto Cappelli, Rudolf Spacek, Rupesh Singh, Sam Griffin, Sang Hoon Na, Sanjeev Chunilal, Saskia Middeldorp, Satoshi Nakazawa, See Guan Toh, Seinturier Christophe, Selim Isbir, Selma Raymundo, Seng Kiat Ting, Serge Motte, Serir Ozkan Aktogu, Servaas Donders, Seung Ick Cha, Seung‐Hyun Nam, Sevestre‐Pietri Marie‐Antoinette, Shaun Maasdorp, Shenghua Sun, Shenming Wang, Sherif Mohamed Essameldin, Sherif Mohamed Sholkamy, Shintaro Kuki, Shuichi Yoshida, Shunzo Matsuoka, Simon McRae, Simon Watt, Siriwimon Patanasing, Siwe‐Nana Jean‐Léopold, Somchai Wongkhantee, Soo‐Mee Bang, Sophie Testa, Stanislav Zemek, Steffen Behrens, Stephan Dominique, Stuart Mellor, Suaran Singh Gurcharan Singh, Sudip Datta, Sunee Chayangsu, Susan Solymoss, Tamara Everington, Tarek Ahmed Adel Abdel‐Azim, Tawatchai Suwanban, Taylan Adademir, Terence Hart, Terriat Béatrice, Thifhelimbilu Luvhengo, Thomas Horacek, Thomas Zeller, Tim Boussy, Tim Reynolds, Tina Biss, Ting‐Hsing Chao, Tomas Smith Casabella, Tomoya Onodera, Tontanai Numbenjapon, Victor Gerdes, Vladimir Cech, Vladimir Krasavin, Vladimir Tolstikhin, W.A. Bax, Wagih Fawzy Abdel Malek, Wai Khoon Ho, Walter Pharr, Weihong Jiang, Wei‐Hsiang Lin, Weihua Zhang, Wei‐Kung Tseng, Wen‐Ter Lai, Wilfried De Backer, Wilhelm Haverkamp, Winston Yoshida, Wolfgang Korte, Won II Choi, Yang‐Ki Kim, Yasuhiro Tanabe, Yasushi Ohnuma, Yeung‐Chul Mun, Yohan Balthazar, Yong Park, Yoshisato Shibata, Yuriy Burov, Yuriy Subbotin, Zdenek Coufal, Zhenwen Yang, Zhicheng Jing, Zhongqi Yang, Haas, S, Ageno, W, Weitz, J, Goldhaber, S, Turpie, A, Goto, S, Angchaisuksiri, P, Dalsgaard Nielsen, J, Kayani, G, Zaghdoun, A, Farjat, A, Schellong, S, Bounameaux, H, Mantovani, L, Prandoni, P, and Kakkar, A

Subjects
Male, pulmonary embolism, Time Factors, Deep vein, direct oral anticoagulant, Practice Patterns, 030204 cardiovascular system & hematology, heparin, Direct oral anticoagulants, 0302 clinical medicine, Pregnancy, Deep vein thrombosis, 80 and over, Registries, Practice Patterns, Physicians', ddc:616, Aged, 80 and over, Venous Thrombosis, Anticoagulant, Hematology, Heparin, Middle Aged, Thrombosis, Pulmonary embolism, medicine.anatomical_structure, Treatment Outcome, Practice Guidelines as Topic, Female, Guideline Adherence, medicine.drug, medicine.medical_specialty, medicine.drug_class, venous thromboembolism, direct oral anticoagulants, deep vein thrombosis, Aged, Anticoagulants, Blood Coagulation, Drug Utilization, Healthcare Disparities, Humans, Pulmonary Embolism, Venous Thromboembolism, 03 medical and health sciences, Thromboembolism, Internal medicine, medicine, In patient, cardiovascular diseases, Rivaroxaban, Physicians', business.industry, deep vein thrombosi, deep vein thrombosis, direct oral anticoagulants, heparin, pulmonary embolism, venous thromboembolism, equipment and supplies, Venous, medicine.disease, business, Venous thromboembolism
Abstract

Background Parenteral anticoagulants and vitamin K antagonists (VKAs) have constituted the cornerstone of venous thromboembolism (VTE) treatment. Meanwhile, direct oral anticoagulants (DOACs) provide physicians with an alternative. The Global Anticoagulant Registry in the FIELD (GARFIELD)-VTE observes real-world treatment practices. Objectives Describe initial anticoagulation (AC) treatment patterns in VTE patients who received parenteral AC, VKAs, and/or DOACs within ±30 days of diagnosis. Methods VTE patients were categorized into parenteral AC only, parenteral AC with transition to VKA, VKA only, parenteral AC with transition to DOAC, and DOAC only. Results A total of 9647 patients were initiated on AC treatment alone. 4781 (49.6%) patients received DOACs ± parenteral ACs; 3187 (33.0%), VKA ± parenteral ACs; and 1679 (17.4%) parenteral ACs alone. Rivaroxaban was the most frequently used DOAC (79.4%). DOACs were more frequently used in North America/Australia (58.1%), Europe (52.2%), and Asia (47.6%) than in Latin America (29.7%) and the Middle East/South Africa (32.5%). In patients with suspected VTE, most received parenteral AC monotherapy (67.7%). Patients with deep vein thrombosis were more likely to receive DOACs alone than those with pulmonary embolism with or without deep vein thrombosis (36.2% vs 25.9%). Active cancer patients received parenteral AC alone (58.9%), with 25.5% receiving DOAC ± parenteral AC and 12.8% parenteral AC and VKA. A total of 46.5% of pregnant patients received parenteral AC monotherapy, 34.0% were treated with VKA ± parenteral AC, and 19.5% received a DOAC (± parenteral AC). Conclusion AC treatment patterns vary by patient population, geographic region and site of VTE. Guidelines for AC therapy are not always adhered to.

Published
2019

21. Atherogenic index of plasma is positively associated with the risk of all-cause death in elderly women : A 10-year follow-up

Author

Robert Prosecky, Peter Kruzliak, Maria Bisahova, Andrej Dukát, Daniel Petrovič, Martin Caprnda, Peter Sabaka, Ruth Baneszova, Matej Bendzala, Andrea Komornikova, and Luis Rodrigo

Subjects
medicine.medical_specialty, Slovakia, 030204 cardiovascular system & hematology, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, High-density lipoprotein, Diabetes mellitus, Internal medicine, medicine, Humans, 030212 general & internal medicine, Myocardial infarction, Prospective Studies, Prospective cohort study, Stroke, Triglycerides, Aged, Cholesterol, business.industry, nutritional and metabolic diseases, General Medicine, Cholesterol, LDL, Middle Aged, medicine.disease, Atherosclerosis, Lipoproteins, LDL, Endocrinology, chemistry, Low-density lipoprotein, Hypertension, lipids (amino acids, peptides, and proteins), Female, business, Lipoproteins, HDL, Algorithms, Lipoprotein
Abstract

The blood concentrations of total cholesterol and low-density lipoprotein (LDL) do not predict survival in patients older than 60 years. The atherogenic index of plasma (AIP) is a logarithm of the triacylglycerol to high-density lipoprotein (HDL) ratio and a surrogate for the concentration of small dense LDL. It might be a better reflection of the risk of all-cause death in elderly patients. We conducted a prospective observational study of patients with arterial hypertension older than 60 years. The concentrations of total cholesterol, LDL, HDL and triacylglycerol were measured at the time of the recruitment and the patients were observed for 10 years. Cox regression analysis was performed to assess the effects of lipoproteins and AIP on survival. A total of 500 patients were recruited and 473 of them (226 men, 247 women) either died or successfully completed the 10-year follow-up and were included in the analysis. The AIP was positively associated, while HDL concentration was negatively associated with the risk of all-cause death adjusted for age, smoking habits, statin use, history of diabetes mellitus, myocardial infarction, stroke and peripheral artery occlusive disease (PAOD) in elderly women but not in men. The LDL, total cholesterol, triacylglycerol and non-HDL concentrations were not associated with the risk of death in both sexes. The AIP is positively associated with the risk of all-cause death in elderly women with arterial hypertension independent of age, smoking habits, statin therapy and comorbidities.

Published
2017

22. Immunomodulatory effects of stem cells: Therapeutic option for neurodegenerative disorders

Author

Dario Siniscalco, Nazarii Kobyliak, Vanda Valentova, Nadezda Stollárová, Iveta Gasparova, Luis Rodrigo, Martin Caprnda, Dietrich Büsselberg, Jozef Dragasek, Robert Prosecky, Ioana Mozos, Peter Kubatka, Katarina Gazdikova, Giampiero La Rocca, Peter Kruzliak, Caprnda, M., Kubatka, P., Gazdikova, K., Gasparova, I., Valentova, V., Stollarova, N., LA ROCCA, G., Kobyliak, N., Dragasek, J., Mozos, I., Prosecky, R., Siniscalco, D., Busselberg, D., Rodrigo, L., and Kruzliak, P.

Subjects
0301 basic medicine, Settore BIO/17 - Istologia, Pathology, medicine.medical_specialty, medicine.medical_treatment, Regenerative medicine, Models, Biological, 03 medical and health sciences, medicine, Animals, Humans, Immunologic Factors, Induced pluripotent stem cell, Pharmacology, Stem cell therapy, business.industry, Multiple sclerosis, Stem Cells, Mesenchymal stem cell, Neurodegenerative Diseases, General Medicine, Stem-cell therapy, Neurodegenerative disorder, medicine.disease, Embryonic stem cell, Neural stem cell, 030104 developmental biology, Stem cell, business, Neuroscience, Stem Cell Transplantation
Abstract

Stem cells have the capability of self-renewal and can differentiate into different cell types that might be used in regenerative medicine. Neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), multiple sclerosis (MS), and amyotrophic lateral sclerosis (ALS) currently lack effective treatments. Although stem cell therapy is still on the way from bench to bedside, we consider that it might provide new hope for patients suffering with neurodegenerative diseases. In this article, we will give an overview of recent studies on the potential therapeutic use of mesenchymal stem cells (MSCs), neural stem cells (NSCs), embryonic stem cells (ESCs), induced pluripotent stem cells (iPSCs), and perinatal stem cells to neurodegenerative disorders and we will describe their immunomodulatory mechanisms of action in specific therapeutic modalities.

Published
2017

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