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2. Response evaluation of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus using 18F-FDG PET/MRI

Author

Sazan Rasul, Barbara Katharina Geist, Helmut Brath, Pascal Baltzer, Lalith Kumar Shiyam Sundar, Verena Pichler, Markus Mitterhauser, and Marcus Hacker

Subjects
Diseases of the endocrine glands. Clinical endocrinology, RC648-665
Abstract

IntroductionInhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(18F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI.MethodsPET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DMbaseline) and 2 weeks after initiation of therapy with SGLT2i (T2DMSGLT2i). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls.ResultsMTT in T2DMbaseline was significantly higher than in healthy controls (5.7 min vs 4.3 min, p=0.012) and significantly decreased to 4.4 min in T2DMSGLT2i (p=0.004). GRP of T2DMSGLT2i was higher than of T2DMbaseline (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DMbaseline and T2DMSGLT2i (122 vs 92 and 86 mL/min/1.73 m², respectively; p

Published
2020
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3. Prevalence and Correlates of Smoking and Readiness to Quit Smoking in People Living with HIV in Austria and Germany.

Author

Helmut Brath, Igor Grabovac, Horst Schalk, Olaf Degen, and Thomas E Dorner

Subjects
Medicine, Science
Abstract

We aimed to investigate the prevalence and correlates of smoking in people living with HIV (PLWHIV) in Germany and Austria and their readiness to quit. A total of 447 consecutive patients with confirmed positive HIV status who were treated in different outpatient HIV centres in Austria and Germany were included. Nicotine dependence and stages of change were assessed by standardized questionnaires, and this was confirmed by measuring exhaled carbon monoxide. Prevalence of smoking was 49.4%. According to a multivariate logistic regression analysis, higher age (for each year of life OR = 0.96; 95% CI 0.92-1.00) and tertiary education level (OR = 0.43; 95% CI 0.15-0.79) were associated with a lower chance, and occasional (OR = 3.75; 95% CI 1.74-8.07) and daily smoking of the partner (OR 8.78; 95% CI 4.49-17.17) were significantly associated with a higher chance of smoking. Moderate (OR = 3.41; 95% CI = 1.30-9.05) and higher nicotine dependency level (OR = 3.40; 95% CI 1.46-7.94), were significantly associated with higher chance, and older age (for each year of life OR = 0.95; 95% CI = 0.91-0.99), with lower chance for readiness to quit smoking. Those results may be used to address preventive measures to quit smoking aimed at PLWHIV and the importance of addressing smoking habits.

Published
2016
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4. Oxidative Stress, DNA Damage and DNA Repair in Female Patients with Diabetes Mellitus Type 2.

Author

Annemarie Grindel, Bianca Guggenberger, Lukas Eichberger, Christina Pöppelmeyer, Michaela Gschaider, Anela Tosevska, George Mare, David Briskey, Helmut Brath, and Karl-Heinz Wagner

Subjects
Medicine, Science
Abstract

BACKGROUND:Diabetes mellitus type 2 (T2DM) is associated with oxidative stress which in turn can lead to DNA damage. The aim of the present study was to analyze oxidative stress, DNA damage and DNA repair in regard to hyperglycemic state and diabetes duration. METHODS:Female T2DM patients (n = 146) were enrolled in the MIKRODIAB study and allocated in two groups regarding their glycated hemoglobin (HbA1c) level (HbA1c≤7.5%, n = 74; HbA1c>7.5%, n = 72). In addition, tertiles according to diabetes duration (DD) were created (DDI = 6.94±3.1 y, n = 49; DDII = 13.35±1.1 y, n = 48; DDIII = 22.90±7.3 y, n = 49). Oxidative stress parameters, including ferric reducing ability potential, malondialdehyde, oxidized and reduced glutathione, reduced thiols, oxidized LDL and F2-Isoprostane as well as the activity of antioxidant enzymes superoxide dismutase, catalase and glutathione peroxidase were measured. Damage to DNA was analyzed in peripheral blood mononuclear cells and whole blood with single cell gel electrophoresis. DNA base excision repair capacity was tested with the modified comet repair assay. Additionally, mRNA expressions of nine genes related to base excision repair were analyzed in a subset of 46 matched individuals. RESULTS:No significant differences in oxidative stress parameters, antioxidant enzyme activities, damage to DNA and base excision repair capacity, neither between a HbA1c cut off />7.5%, nor between diabetes duration was found. A significant up-regulation in mRNA expression was found for APEX1, LIG3 and XRCC1 in patients with >7.5% HbA1c. Additionally, we observed higher total cholesterol, LDL-cholesterol, LDL/HDL-cholesterol, triglycerides, Framingham risk score, systolic blood pressure, BMI and lower HDL-cholesterol in the hyperglycemic group. CONCLUSION:BMI, blood pressure and blood lipid status were worse in hyperglycemic individuals. However, no major disparities regarding oxidative stress, damage to DNA and DNA repair were present which might be due to good medical treatment with regular health checks in T2DM patients in Austria.

Published
2016
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5. Sex-specific trends in smoking prevalence over seven years in different Austrian populations: results of a time-series cross-sectional analysis

Author

Thomas Dorner, Alexandra Kautzky-Willer, and Helmut Brath

Subjects
Adult, Male, medicine.medical_specialty, Adolescent, Cross-sectional study, Population, Logistic regression, preventive medicine, Risk Factors, general medicine (see internal medicine), Diabetes mellitus, Epidemiology, medicine, Prevalence, Humans, education, Preventive healthcare, education.field_of_study, business.industry, Public health, general diabetes, Smoking, public health, health policy, General Medicine, Middle Aged, medicine.disease, Obesity, Cross-Sectional Studies, Austria, Medicine, Female, epidemiology, business, Demography
Abstract

ObjectivesAim of this study was to examine trends over time in smoking status in men and women, and in subgroups, in Austria, a country with poor smoking regulation policies.Design and participantsTwo cross-sectional surveys (Austrian Health Interview Surveys for 2007 and 2014), each with more than 15 000 participants from the general population, aged ≥15 years.Outcome measuresPrevalence of self-reported daily smoking. ORs for daily smoking in subgroups, presented as results of logistic regression models, adjusted for sociodemographic variables and presence of chronic diseases.ResultsPrevalence of daily cigarette smoking was 26.0% for men in both years, and increased from 19.1% to 22.0% (pConclusionsThere has been a remarkable increase in smoking prevalence over the 7-year period in women in Austria, especially for those with chronic diseases, higher age, lower education and a migration background. Better political and clinical efforts are needed to reduce the high tobacco use in Austria.

Published
2020

6. Response evaluation of SGLT2 inhibitor therapy in patients with type 2 diabetes mellitus using 18F-FDG PET/MRI

Author

Lalith Kumar Shiyam Sundar, Alexandra Kautzky-Willer, Helmut Brath, Markus Mitterhauser, Verena Pichler, Barbara Katharina Geist, Pascal A. T. Baltzer, Marcus Hacker, and Sazan Rasul

Subjects
medicine.medical_specialty, Endocrinology, Diabetes and Metabolism, Urology, Renal function, 030209 endocrinology & metabolism, Type 2 diabetes, FDG-Positron Emission Tomography, Diseases of the endocrine glands. Clinical endocrinology, 03 medical and health sciences, 0302 clinical medicine, Diabetes mellitus, PET (positive emission tomography), Medicine, Humans, 030212 general & internal medicine, Sodium-Glucose Transporter 2 Inhibitors, Glycemic, business.industry, renal function, Type 2 Diabetes Mellitus, Glucose analog, Emerging Technologies, Pharmacology and Therapeutics, RC648-665, medicine.disease, Magnetic Resonance Imaging, Glucose, Diabetes Mellitus, Type 2, Positron-Emission Tomography, type 2 diabetes, SGLT2 Inhibitor, sodium glucose cotransporter, business
Abstract

IntroductionInhibitors of sodium-glucose linked transporter-2 (SGLT2i) are enhancing glucose excretion in the proximal renal tubules, and thus are increasingly used to lower blood glucose levels in patients with type 2 diabetes mellitus (T2DM). The glucose analog 2-deoxy-2-(18F) fluoro-D-glucose (FDG) can be used to quantify renal function in vivo, and due to an affinity for SGLT2 could also provide information about SGLT2 transporter function. Our objectives in this study were, therefore, to assess the impact of SGLT2i on renal function parameters in patients with T2DM and identify predictive parameters of long-term response to SGLT2i using dynamic FDG positron emission tomography (PET)/MRI.MethodsPET FDG renal function measures such as mean transit time (MTT) and general renal performance (GRP) together with glomerular filtration rate (GFR) were determined in 20 patients with T2DM before (T2DMbaseline) and 2 weeks after initiation of therapy with SGLT2i (T2DMSGLT2i). Additionally, dynamic FDG PET data of 24 healthy subjects were used as controls.ResultsMTT in T2DMbaseline was significantly higher than in healthy controls (5.7 min vs 4.3 min, p=0.012) and significantly decreased to 4.4 min in T2DMSGLT2i (p=0.004). GRP of T2DMSGLT2i was higher than of T2DMbaseline (5.2 vs 4.7, p=0.02) and higher but not significantly than of healthy individuals (5.2 vs 5.1, p=0.34). Expectedly, GFR of healthy participants was significantly higher than of T2DMbaseline and T2DMSGLT2i (122 vs 92 and 86 mL/min/1.73 m², respectively; pSGLT2i, the lower was the glycated hemoglobin level 3 months after therapy initiation.ConclusionMTT and GRP values of patients with T2DM shifted significantly toward values of healthy control 2 weeks after therapy with SGLT2i begins. GRP in T2DMSGLT2i was associated with better long-term glycemic response 3 months after initiation of therapy.Trial registration numberNCT03557138.

Published
2020

7. Ticagrelor in patients with diabetes and stable coronary artery disease with a history of previous percutaneous coronary intervention (THEMIS-PCI): a phase 3, placebo-controlled, randomised trial

Author

Deepak L Bhatt, Philippe Gabriel Steg, Shamir R Mehta, Lawrence A Leiter, Tabassome Simon, Kim Fox, Claes Held, Marielle Andersson, Anders Himmelmann, Wilhelm Ridderstråle, Jersey Chen, Yang Song, Rafael Diaz, Shinya Goto, Stefan K James, Kausik K Ray, Alexander N Parkhomenko, Mikhail N Kosiborod, Darren K McGuire, Robert A Harrington, Vladimir Santos, Ashit Jain, Irina Lendel, Michael Russo, W H Haught, Manuel Bouza, Harinder Gogia, Supratim Banerjee, George Kichura, Louis Kantaros, Francisco Padron, Rakesh Passi, Jay Stone, Michael Pursley, Michael D'Urso, Timothy Gardner, James Bennett, Khaled Nour, Satinder Saini, Wenwu Zhang, Dharam Kumbhani, Dustin Thomas, Dominick Angiolillo, Barry Bertolet, Amaury Roman-Miranda, Robert Black, Ramin Manshadi, Carlos Vaca, Antonio Blanco, Mark Napoli, David Brabham, Ayim Akyea-Djamson, Pratik Desai, Sudhir Prasada, Ajit Khaira, Leslie Forgosh, Ira Lieber, Guillermo Umpierrez, Dinesh Singal, Juan Londono, Neil Fraser, Jose Ruiz, Damaris Vega, Lilia Rodriguez, Christopher Brown, Faizullah Syed, Guarav Aggarwala, William Eaves, Michael Foster, Dinesh Gupta, David Avino, Wail Asfour, Glen Tonnessen, Xue-Qiao Zhao, Narendra Singh, Andrew Brockmyre, Norman Lepor, Nicolas Shammas, David Blick, Steven Hearne, John Prodafikas, Edgar Carell, Mark Izzo, Amin Karim, Bosh Zakhary, Mahmoud Atieh, Steven Leichter, Charles Meadows, David Hotchkiss, Mazen Abu-Fadel, Alan Wiseman, Jeffrey Bander, Mahesh Shah, Subhash Banerjee, Ricky Ganim, Karen Sopko, Misal Khan, Ramon Lloret, Troy Weirick, Rajendra Mehta, Udho Thadani, Anuj Bhargava, Mikhail Kosiborod, Jaynier Moya, Cezar Staniloae, Yamirka D Guerra, Anil Chhabra, Douglas Kosmicki, Wassim Shaheen, Akber Mohammed, J'Cinda Bitters, Jan Pattanayak, Julian Javier, Sunny Srivastava, Roland Phillips, Jessie Al-Amin, Michael Lillestol, Patrick Simpson, Lydie Hazan, Amit Amin, Gopi Shah, Denes Korpas, Bruce Platt, Jim Dickert, Orlando Puente, Louis Hiotis, Timothy Doyle, Raj Rajan, Alan Meholick, Christian Gring, Elie Hage-Korban, Robert Feldman, Harry Colfer, Samuel Butman, Malcolm Foster, Terence Hart, Randall Huling, Shervin Eshaghian, Ofsman Quintana, Deanna Cheung, Franklin Handel, Mara Rodriguez, David Suh, Paul Gordon, Gregg Pressman, Michael Bauer, William French, Mark Barettella, Sridhar Chatrathi, Damodhar Suresh, Ronald Goldberg, Mark Huth, Liwa Younis, Aref Rahman, Richard Mascolo, Michelle Welch, Randeep Suneja, Stephen Smith, Scott Shurmur, John Agaiby, Ahmad Jingo, Janice Johnston, Mary Beth, Anthony Vlastaris, Susan Kemp, Hamid Taheri, Edward Pereira, Michael Deyoung, Zafir Hawa, Ray Smith, Thomas Galski, Samer Garas, M Reddy, Susheel Sharma, Joeseph Hargrove, Charles Treasure, Ronald Emerson, Tariq Haddad, Kathryn Rohr, Larry Levinson, Raul Gaona, Barry Uretsky, Hiralal Maheshwari, Denny Lee, Stephanie Kinnaman, Robert Singal, Jeffrey Geohas, Osvaldo Gigliotti, Ajit Raisinghani, Charanjit Khurana, Brent Hella, Michael Kelberman, Steven Voyce, Sanjay Singh, Eric Lo, Pradeep Singh, Ross Goodfellow, Stuart Fischer, Richard Lorraine, Traci Turner, Jeffrey Shanes, Robert Busch, Robert Broker, Michelle Zaniewski, Kevin Pounds, Giselle Debs-Perez, Stephen Ong, Brad Frandsen, Douglas Fullington, Naseem Jaffrani, Ahtaram Khan, Marcus Lee, Joe Pouzar, George Revtyak, Julian Gonzalez, Samer Nakhle, Abel Murillo, Douglas Young, Sashi Makam, Mushtaq Syed, Kevin Woolf, Paul Grena, Sarab Alfata, Sharan Mahal, David Hoffman, Tinoy Kizhakekuttu, Joseph Deering, Janak Bhavsar, Scott Mikesell, William Wilson, Vance Wilson, Salah El, Francis Spinale, Vinod Kannarkat, Sunder Rao, Lenita Hanson, John Bertsch, Elena Gonzalez-Ortiz, Norma Severino, John Willis, Joel Schock, Ladan Bakhtari, Raul Gazmuri, Saadat Ansari, Jason Hall, Arvind Mehta, Neal Shealy, Stuart Zarich, Deovrat Singh, Kishor Vora, Nabil Andrawis, Darron Molter, David Maron, Jose Cardona, Ronald D'Agostino, Tamjeed Arshad, Rodney Samaan, David Jones, Dale Presser, John Heath, Sandy Green, George Bittar, Sheldon Henry, David Korn, John Schmedtje, Venkatesh Nadar, Bruce Graham, Ajay Labroo, Leonardo Clavijo, Hal Roseman, Gilbert Ledesma, Robert Rosen, Isaac Dor, William Kirby, Jennefer Sutton, Frank Eder, Bruce Iteld, Jose Gomez-Cortes, Maurice Buchbinder, Joseph Kasper, Antonio Terrelonge, Gustavo Torres, Ted Jagielo, Jose Alvarez, Yehuda Handelsman, Mario Guillen, Randall Richwine, Lorena Lewy-Alterbaum, Clinton Corder, Moogali Arvind, David Bolshoun, Magdy Mikhail, Stephen Minton, Odilon Alvarado, J Abbott, Brett Cauthen, Ryan Welter, Randy Mintz, John Cox, Annette Quick, Melvin Weiss, Johnny Dy, James Zebrack, Glenn Gandelman, Vinayak Hegde, Marc Silver, Michele DeGregorio, William Lawson, Christopher Paa, Anna Bortnick, Merrill Krolick, Rodolfo Sotolongo, Jorge Cheirif, Priya Kumar, Preetham Jetty, Ambar Patel, Mariusz Kruk, Iwona Kobielusz-Gembala, Barbara Rewerska, Adam Madrzejewski, Krzysztof Milewski, Jerzy Cygler, Joanna Petryka-Mazurkiewicz, Waldemar Jastrzebski, Janusz Korecki, Wojciech Fil, Janusz Prokopczuk, Anna Bochenek, Marek Wujkowski, Robert Witek, Piotr Konczakowski, Pawel Miekus, Marcin Szczasny, Wlodzimierz Musial, Krzysztof Cymerman, Jacek Lampart, Jacek Mikosinski, Slawomir Szynal, Issa Fares, Grzegorz Opolski, Stanislaw Mazur, Beata Wozakowska-Kaplon, Renata Bijata-Bronisz, Lukasz Wierucki, Beata Losa, Grzegorz Drelich, Marek Konieczny, Pawel Starczewski, Lidia Pawlowicz, Pawel Jesionowski, Jaroslaw Jurowiecki, Jacek Gniot, Mariusz Czyzycki, Karol Stania, Izabela Kucharczyk-Bauman, Benita Busz-Papiez, Agnieszka Karczmarczyk, Wanda Sudnik, Alina Koszek, Piotr Kolodziej, Bartosz Skwarna, Nicolás Jaramillo, Maciej Jankowski, Wojciech Czochra, Leszek Kinasz, Beata Miklaszewicz, Teresa Stasinska, Wladyslaw Pluta, Marcin Basiak, Teresa Rusicka, Izabela Niedbal-Yahfouf, Grazyna Popenda, Romuald Korzeniak, Agnieszka Mirek, Rafal Mariankowski, Lukasz Wojnowski, Marek Korol, Jacek Baszak, Piotr Podolec, Wojciech Piesiewicz, Aleksander Zurakowski, Carlos Luengas, Marek Skura, Piotr Pilecki, Piotr Majchrzak, Ewa Krzyzagórska, Marcin Drozd, Barbara Kaczmarek, Teresa Sliwinska, Katarzyna Zelazowska, Rafal Sztembis, Katarzyna Landa, Lidia Matyszczak-Toniak, Krzysztof Strojek, Marek Piepiorka, Robert Malinowski, Maria Górska, Edyta Stolarczyk-Sowa, Leszek Romanowski, Elzbieta Zinka, Zygfryd Reszka, Joanna Skierkowska, Anna Uzunow, Ewa Laskowska-Derlaga, Ekaterina Puntus, Elena D Kosmacheva, Natalia Koziolova, Prokhor Pavlov, Tatiana Supryadkina, Yury Didenko, Philipp Kopylov, Andrei Kazakov, Sergei Aksentiev, Elena Vishneva, Alexey Repin, Olga Smolenskaya, Olga Mantserova, Oleg Khrustalev, Elena Privalova, Vladimir Konstantinov, Svetlana Boldueva, Andrey Ezhov, Alexander Chernyavsky, Gadel Kamalov, Albert Galyavich, Galina Zubeeva, Galina Nechaeva, Sergey Shustov, Nino Dzhaiani, Tatiana Treshkur, Nataliya Osokina, Alexey Panov, Elena Shutemova, Valeriy Makukhin, Tatiana Kropotina, Larisa Tsyba, Yuri Karpov, J M Sizova, Marina Ballyuzek, Nikolay Tarasov, Elena Demchenko, Olga Barbarash, Valentin Moiseev, Valentin Markov, Vadim Kuznetsov, Inna Viktorova, Igor Sergienko, Lyudmila Ermoshkina, Niyaz Khasanov, Tatiana Khlevchuk, Andrey Baglikov, Sergey Shalaev, Elena Zonova, Elena Reznik, Larisa Haisheva, Tatyana Morugova, Nikita Lomakin, Alexander Vishnevsky, Yuri Shvarts, Olga Magnitskaya, Marina Mikhailusova, Elena Pavlysh, Igor Libov, Anna Zateyschikova, Victor Kostenko, Anton Edin, Yaroslava Khovaeva, Konstantin Zakharov, Raisa Stryuk, Vladimir Khirmanov, Sergey Kanorskiy, Sergey Yakushin, Anna Barabashkina, Hongwei Li, Qiang Zhao, Jian Zhang, Jianhua Ma, Yong He, Ming Luo, Aidong Zhang, Ningru Zhang, Yingru Chai, Genshan Ma, Hao Wang, Zhigang Liu, Lanjie He, Zhifang Song, Xiaolin Dong, Liang Tao, Zhanquan Li, Xi Su, Xiangqing Kong, Heping Niu, Junbo Ge, Zhurong Luo, Wenjun Huang, Daoquan Peng, Zuyi Yuan, Maria Milanova, Doncho Tenev, Antoni Gogov, Dimitar Karageorgiev, Todor Kolchev, Nikolay Rusev, Nikolina Georgieva, Rumen Kondov, Veselin Rusinov, Ivo Petrov, Georgi Stanchev, Mariana Konteva, Adriana Dincheva, Zdravka Yaneva, Ralitsa Vatova, Katya Ilieva, Nikolai Runev, Borislav Kolomanov, Ivan Petrov, Nikolay Iliev, Snezhanka Tisheva, Boryana Chompalova, Maria Tokmakova, Dimitar Raev, Kolyo Byanov, Dimitar Markov, Lenko Mihov, Atanas Mihov, Nora Milcheva, Milen Minchev, Mihail Mollov, Borislav Borisov, Tihomir Tihchev, Venelin Karakolev, Bojidar Dimov, Svetoslav Georgiev, Lachezar Smilov, Bon K Koo, Taehoon Ahn, Soon J Hong, Junghan Yoon, Seok K Oh, Myung H Jeong, Doo-Il Kim, Kiyuk Chang, Weon Kim, Joo-Yong Hahn, Kwang S Cha, Jung-Hee Lee, Si-Wan Choi, Chang-Wook Nam, In-Ho Chae, Yong H Park, Seung-Jea Tahk, Won-Yong Shin, Jei-Keon Chae, Byung J Kim, Jang-Whan Bae, Woo J Park, Seung W Rha, Young J Choi, Jin-Yong Hwang, Hun S Park, Luciano Baracioli, Fabio Guimaraes, Eduardo Vasconcellos, José Saraiva, Adamastor Pereira, Queulla Santos, Paulo Rossi, Lilia Maia, Miguel Madeira, Marcio Pereira, Roberto Botelho, Gilmar Reis, Freddy Eliaschewitz, Joao Borges, Carlos Nascimento, Jose A Fortes, Weimar de Souza, Pedro Pimentel, Miguel Hissa, Marcos Franchetti, Dalton Precoma, Costantino Ortiz, Mauro Hernandes, Wladmir Saporito, Fabio R dos Santos, Adrian Kormann, Fernando Neuenschwander, Oscar Dutra, Nelson Rassi, Luiz Tanajura, Juliana Souza, Delcio S Junior, Paulo Leaes, Adriana Forte, Teresa C Bonansea, Jose Marin, Bruno Machado, Maria J Cerqueira, Frederico Silva, Yorghos Michalaros, Euler Manenti, Cintia Cercato, Estevao Figueiredo, Ming-En Liu, Yi-Chih Wang, Tsung-Ming Lee, Chih Fang, Yen-Wen Wu, Kwo-Chang Ueng, Huey-Herng Sheu, Wen T Lai, I-Chang Hsieh, Zhih-Cherng Chen, Mu-Jang Lee, Chern Chiang, Kou-Gi Shyu, Chien-Hsun Hsia, Guang-Yuan Mar, Shih-Hung Chan, Chih-Cheng Wu, Wei-Kung Tseng, Kuan-Cheng Chang, Hung-I Yeh, Ji-Hung Wang, Charles Hou, Inna Sorokina, Maryna Dolzhenko, Olha Horoshko, Oleksandr Karpenko, Leonid Rudenko, Igor Vakaliuk, Anna Kulyk, Olena Levchenko, Oleksandr Prokhorov, Dmytro Reshotko, Mykhaylo Sorokivskyy, Nataliia Velichko, Valentyn Maslovskyi, Zinaida Teliatnikova, Sergiy Dotsenko, Olena Krakhmalova, Igor Kraiz, Viktoria Zharinova, Larysa Bula, Igor Kaydashev, Valeriy Molodtsov, Lesya Rasputina, Viktoriya Pidlisna, Olena Lysunets, Anatoliy Kravchenko, Liubomyr Glushko, Tetyana Khomazyuk, Yevgeniya Svyshchenko, Oleksandr Parkhomenko, Boris Mankovsky, Orest Abrahamovych, Andriy Yagensky, Mykola Stanislavchuk, Larisa Vasilyeva, Liubov Sokolova, Oleg Sychov, Vira Tseluyko, Igor Kyrychenko, Mykola Rishko, Sergiy Furkalo, Richard Gallo, Olivier Bertrand, Shamir Mehta, Christian Constance, Bruce Sussex, Remo Zadra, Simon Kouz, Raja Chehayeb, Amritanshu Pandey, Danielle Dion, Gordon Bailey, Laurie Hill, Krishnan Ramanathan, Micha Dorsch, Alykhan Nanji, Mohan Babapulle, Martine Montigny, Gilbert Gosselin, Payam Dehghani, Dennis Rupka, Michel Le May, Francis Pichette, Francois St-Maurice, Patrick Teefy, Samer Mansour, Saleem Kassam, Stephen Cheung, Anthony D Siega, Dennis O'Keefe, Eric Sabbah, Alan Bell, Guy Chouinard, Brian Wong, Mark Miller, Daniel Gaudet, Pierre Lachance, Iqbal Bata, Robert Petrella, Denis Gossard, Richard Dumas, Douglas Ing, Hagop Boyrazian, Ricardo Bessoudo, Thao T Huynh, Randy Hart, Jasmin Belle-Isle, Dinkar Shukla, Allan Kelly, Giuseppe Mazza, James Cha, Sam Henein, Andre Frechette, Saul Vizel, Joanne F Liutkus, Michael O'Mahony, Frank Halperin, Jacobus Kooy, John Graham, Allan Bailey, Ronald Wojcik, Igor Wilderman, Tibor Turi, Ákos Motyovszki, Béla Merkely, Csaba Király, Péter Andrássy, Zsolt Sárszegi, Tibor Fülöp, Zsolt Zilahi, István Édes, Andras Papp, Gábor Müller, Anna Czigány, Szilárd Zólyomi, László Korányi, János Takács, Ferenc Juhász, Bela Benczur, Sándor Kancz, András Földi, András C Nagy, Judit Bakai, István Greschik, László Püski, László Nagy, Róbert Kirschner, Roman Kuchar, Petr Hajek, Ladislav Busak, Daniel Michalik, Ivo Matyasek, Ivana Marusincova, Dusan Kucera, Ondrej Jerabek, Michaela Honkova, Vratislav Dedek, Ivan Rihacek, Pavel Kos, Josef Slaby, Martina Machkova, Eva Zidkova, Lubomir Elbl, Hana Grunfeldova, Jiri Carda, Vladimir Mrozek, Jiri Maly, Richard Milkovic, Jan Malecha, Hana Skalicka, Ivo Oral, Eva Krcova, Libor Lisa, Jan Belohlavek, Roman Miklik, Ondrej Cermak, Jana Bednarova, Zdenek Peroutka, Jindrich Spinar, Andreas Wilke, Karl-Friedrich Appel, Jens Taggeselle, Andreas Förster, Nicole Toursarkissian, Ekkehard Schmidt, Jochen Bott, Ayham Al-Zoebi, Dirk Hennig, Sabine Fischer, Norbert Schön, Joachim Sauter, Gregor Simonis, Ruth Nischik, Werner Rieker, Isabelle Schenkenberger, Thomas Behnke, Gerhard Klausmann, Michael Jeserich, Dietmar Trenk, Ingo Weigmann, Hannes Reuter, Reinhard Rummel, Candy von Münchhausen, Charlotte von Engelhardt, Eishun Horibe, Taro Shibasaki, Tomohiko Sato, Tsunekazu Kakuta, Ichiro Michishita, Michinao Tan, Ryoji Ishiki, Takahiko Aoyama, Shinichi Higashiue, Yawara Niijima, Akira Idogaki, Toru Hasegawa, Arihiro Kiyosue, Yoshiaki Tomobuchi, Katsunori Kawamitsu, Satsuki Kawasaki, Yoshiki Hata, Kazuki Fukui, Kozaburo Seki, Takashi Takenaka, Mitsuru Abe, Noriaki Utsu, Atsuyuki Oono, Kazuhisa Mitsuo, Atsushi Sueyoshi, Atsushi Hirohata, Mitsuru Tsujimoto, Osamu Ueda, Shinichi Takase, Masahiro Suzuki, Satoru Sakuragi, Fumi Yamamoto, Noritaka Fujimoto, Shigeo Kakinoki, Tatsushi Sugiura, Hiroshi Sugino, Toshihiro Nakamura, Toshiaki Kadokami, Hiroki Uehara, Masahiro Ono, Koichi Yokoya, Akihiro Koike, Sei Komatsu, Masahiro Sonoda, Hideki Ueno, Tomofumi Doi, Yuichiro Takagi, Kazuteru Fujimoto, Yutaka Eki, Munenori Okubo, Kenichiro Sasaki, Martijn van Eck, Eelko Ronner, Salem The, Ruud van de Wal, Pieter Nierop, Cornelis de Nooijer, Henri Werner, Iris Westendorp, Coen van der Zwaan, Hendrikus Crijns, Jan H Cornel, Sipke Strikwerda, Robert Bos, Edwin de Melker, Adrianus Kuijper, Hans Louwerenburg, Jacobus Plomp, Jan-Melle Dantzig, Francisco Prins, Henricus van Kesteren, Frank Willems, Giovanni Amoroso, Gabriela Carnero, Ernesto Duronto, Diego Besada, Carolina Chacon, Pedro Zangroniz, Silvana Solis, Alberto Liberman, Virginia Sernia, Andres Alvarisqueta, Laura Maffei, Oscar G Vilamajo, Celso García, Maximiliano Sicer, Juan Muntaner, Anselmo Bordonava, Juan Albisu, Alejandra Zanini, Lucas Rista, Miguel Hominal, José N Estrada, Aldo Prado, Diego M Gosparini, Beatriz Schiavi, Armando G Castillo, José G Ruíz, Guillermo R Martinez, Víctor G López, Enrique L Rosas, Gabriel R Lopez, Elias G Cantu, Manuel de los Ríos Ibarra, Francisco P Padilla, Jose P Carrasco, Luis V Carrillo, Joel D García, Alfredo N Askar, Carlos A Salinas, Marco A Gamba, Carlos G Sanchez, Arnulfo G Cantú, Raul V Sánchez, Jaime C Madrigal, Rafael H Urbano, Andrés Í Romo, José R González Juanatey, Paolo Racugno, Angel C Fillat, José M de la Torre Hernández, Juan A Peláez, Jorge B Cortada, Pablo G Pavia, Manuel J Navarro, Roberto M Asenjo, Francisco F Díaz, Eduard B Peligero, Fernando A Manterola, Antonio F Ortiz, Juan D Mediavilla García, Francisco M Ortuño, Tomás R Vera, Alfonso S González, Jaime A Viñas, Francisco J Fernández Portales, Petra S Mayordomo, Francisco B Ojeda, Antonio R Domínguez, Rosa S González, Diego B Guerrero, Juan M Ruiz Nodar, Xavier G Marimon, José G Margáez, Roberto M Aguilera, José F Díaz Fernández, José L Zamorano Gómez, Vicente B González, Bruno G del Blanco, Ignacio P Pérez, Mercé R Moreno, Ainhoa R Ereño, José A García Lledó, Juan Prieto, Alex Villablanca, Carlos Raffo, Christian Pincetti, Carlos Conejeros, Oscar Roman, Manuel Rodriguez, Paola Varleta, Cindy Goldberg, Jorge Sandoval, German Arriagada, Lucio Leon, Sergio Potthoff, Jorge Cobos, Christian Figueroa, Ellen Makotoko, Nyda Fourie, Lesley Burgess, Hendrik Nortje, Rust Theron, Perumal Pillai, Naresh Ranjith, Julien Trokis, Soobramoney Pillay, Jeevren Reddy, Theema Nunkoo, Cornelia Kapp, Dorothea Urbach, Lawrence Distiller, Adrian Horak, Louis van Zyl, Kathleen Coetzee, Zelda Punt, Junaid Bayat, Saleem Dawood, Ismail Mitha, Trevenesan Padayachee, Farzana Hoosen, Anthony Dalby, null Prabhavathi, Prakash Gowdaiah, Vimal Mehta, Milan Chag, Milind Gadkari, Kannaiyan Ramamurthee, Asit Das, Jitendra S Sawhney, Suvro Banerjee, Prachee Sathe, Srilakshmi Adhyapak, Tuan Nguyen, Vinh Pham, Huan Do, Anh Nguyen, Hien Nguyen, Binh Truong, Shahnaz Jamil-Copley, Chim Lang, Alastair Pell, Azfar Zaman, Robert Storey, Neil Swanson, Simon Smith, David Sharman, Denise Braganza, Peter Hammond, Andrew Moriarty, Stephen Bain, Maurice Pye, Andrew Sharp, Mark Blagden, Harpal Randeva, Timothy Myhill, Girish Viswanathan, Philip Keeling, Piers Clifford, Manish Saxena, Kristopher Lyons, John McMurray, Feeroz Jaafar, Clare Murphy, Simon Cartwright, Kamal Abouglila, Lubomir Antalik, Peter Krajci, Miroslav Urban, Frantisek Fazekas, Daniel Pella, Daniel Koleny, Tatiana Vykoukalova, Vladimir Macek, Daniela Vinanska, Livia Jamriskova, Slavomir Such, Peter Fulop, Stefan Farsky, Viliam Bugan, Jaroslava Strbova, Karol Micko, Juraj Palka Jr, Vladimir Sivak, Dalby Kristensen, Jens Refsgaard, Lene Holmvang, Ulrik Dixen, Henrik Nielsen, Kenneth Egstrup, Lisette O Jensen, Roman Sykulski, Ole Rasmussen, Alin Andries, Anders Luckow, Gitte Nielsen, Torben Sørensen, Chaiyasith Wongvipaporn, Noppadol Chamnarnphol, Suphot Srimahachota, Nakarin Sansanayudh, Srun Kuanprasert, Damras Tresukosol, Bancha Sookananchai, Mehmet Kanadasi, Turkay Ozcan, Murathan Kucuk, Zeki Ongen, Ertugrul Okuyan, Alev Arat, Sadik Acikel, Ahmet Yalcin, Umit Guray, Ceyhun Ceyhan, Necla Ozer, Sakir Arslan, Oskar Angerås, Nina Johnston, Ann-Charlotte Weiderman, Stellan Bandh, Ole Hansen, Hans Larnefeldt, Dawid Kusiak, Carl-Johan Lindholm, Anders Hedman, David Erlinge, Dan Curiac, Pia Lundman, Roberto Zucconi-Mazzini, Layth Aladellie, Jens Jensen, Jan Verwerft, Mathias Vrolix, Dirk Faes, Harry Striekwold, Peter Sinnaeve, Patrick Timmermans, Antoine Guedes, Marc Delforge, Jan Nimmegeers, Francis Stammen, Ian Buysschaert, Etienne Hoffer, Geert Hollanders, Geert Vervoort, Patrick Coussement, Stefan de Maeseneire, Luc Janssens, Stein A Gravdal, Knut Risberg, Lars Gullestad, Ola D Hofseth, Dennis Nilsen, Knut T Lappegård, Christian van den Heuvel, Charlotte Gibbs, Alamdar Khusrawi, Satish Arora, Tadeusz Tomala, Thorbjørn Kjærnli, Jan Berg-Johansen, Robert Hagemeier, Gunnar Skjelvan, David Colquhoun, John Amerena, Claire Morbey, Christopher Hammett, Anthony Dart, Ronald Lehman, Andrew Hamilton, Matthew Worthley, Peter Purnell, Alan Whelan, Richard MacIsaac, Ktut Arya, Sultan Linjawi, Joseph Proietto, Lakshman Prasad, Aldo Rodriguez, Armando Godoy, Victor Rodriguez, Percy Berrospi, Carlos Chavez, Sandra Negron, Javier Heredia, Felix Medina, Helard Manrique, Walter Cabrera, Fernando Cordova, Trinidad Quinteros, Jaime M Haro, Susana Regalado, Javier Guitton, Hugo Arbanil, Michel Pansieri, Eric Decoulx, Pascal Goube, Axel de Labriolle, Jean N Labeque, Gregoire Range, Yves Cottin, Gilles Montalescot, Guillaume Cayla, Nicolas Danchin, Denis Angoulvant, Emile Ferrario, Meyer Elbaz, Olivier Dubreuil, Philippe G Steg, Caroline Fontaine, Emmanuel Sorbets, Hafiz Omer, Shukri Al-Saif, Hussam Al-Faleh, Abdullah Al-Shehri, Halia Alshehri, Rasha Bazari, Pak Hei, Man Ying, Michael Chan, Michelle Wong, Ronald Ma, Shing C Siu, Chiu C Tsang, Maurizio Ferrario, Emilio Assanelli, Michele Senni, Piermarco Piatti, Paolo Calabrò, Stefano Urbinati, Massimo Michisanti, Ferdinando Varbella, Salvatore de Cosmo, Roberto Trevisan, Sandro Bellotti, Giuseppe Di Pasquale, Angelo S Bongo, Massimo Uguccioni, Edoardo Mannucci, Ciro Mauro, Mauro Ragonese, Claudio Fresco, Maurizio Turturo, Rossella Marcucci, Manuel J Lievano Triana, Camilo Arana, Jose Accini, Rodrigo Botero, Marlena Muzyk-Osikowicz, Fredy T Dada, Gregorio S Vallejo, Fernando Manzur, Daniel Isaza, Dora Molina, Juan G Mesa, Alvaro Quintero, Kai Nyman, Jyrki Mäkelä, Jorma Strand, Sakari Nieminen, Jyrki Taurio, Matti Kuusela, Timo Valle, Mikko Pietilä, Sakari Kekki, Timo Strandberg, Marc Klutstein, Gabriel Greenberg, Yoseph Rozenman, Ehud Chorin, Ariel Roguin, Basil Lewis, Amir Bashkin, Edgar Tan, Jose P Prado, Arthur Ferrolino, Noe Babilonia, Benny Barbas, Generoso Matiga, Raul M Coching, Heinz Drexel, Helmut Brath, Christoph Schnack, Ursula Hanusch, Evelyn Fließer-Görzer, Bernhard Paulweber, Christoph Ebenbichler, Rudolf Prager, Kurt Huber, Michael Wolzt, Johann Auer, Rudolf Berger, Gerit-Holger Schernthaner, Gabriela Stanciulescu, Mihai Creteanu, Marilena Spiridon, Viorica Dobreanu, Dragos Vinereanu, Laura C Iosipescu, Octavian Istratoaie, Ioan Coman, Constantin Militaru, Mircea Cinteza, Peter R Sinnaeve, José C Nicolau, José F Kerr Saraiva, Ramón Corbalán, Petr Widimský, Steen D Kristensen, Juha Hartikainen, Harald Darius, Hung F Tse, Robert G Kiss, Prem Pais, Eli Lev, Leonardo de Luca, Gabriel A Ramos López, Frederic Kontny, Noe A Babilonia, Dmitry A Zateyshchikov, Mikhail Ruda, Omer Elamin, František Kovář, Anthony J Dalby, Héctor Bueno, Chern-En Chiang, Alexander Parkhomenko, Tuan Q Nguyen, Maria Leonsson-Zachrisson, Herrada, Anthony, Brigham & Women’s Hospital [Boston] (BWH), Harvard Medical School [Boston] (HMS), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Recherche Vasculaire Translationnelle (LVTS (UMR_S_1148 / U1148)), Université Paris 13 (UP13)-Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Royal Brompton Hospital, McMaster University [Hamilton, Ontario], Keenan Research Centre of the Li Ka Shing Knowledge Institute [Toronto], St. Michael's Hospital, University of Toronto, Service de Pharmacologie médicale = service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Sorbonne Université (SU), National Heart and Lung Institute [London] (NHLI), Imperial College London-Royal Brompton and Harefield NHS Foundation Trust, Uppsala University Hospital, Uppsala Universitet [Uppsala], AstraZeneca, Tokai University, Uppsala University, Imperial College London, Saint Luke's Mid America Heart Institute, University of Missouri [Kansas City] (UMKC), University of Missouri System, University of New South Wales [Sydney] (UNSW), University of Texas Southwestern Medical Center [Dallas], Stanford University, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Université de Montpellier (UM), Bhatt, D, Steg, P, Mehta, S, Leiter, L, Simon, T, Fox, K, Held, C, Andersson, M, Himmelmann, A, Ridderstrale, W, Chen, J, Song, Y, Diaz, R, Goto, S, James, S, Ray, K, Parkhomenko, A, Kosiborod, M, Mcguire, D, Harrington, R, Santos, V, Jain, A, Lendel, I, Russo, M, Haught, W, Bouza, M, Gogia, H, Banerjee, S, Kichura, G, Kantaros, L, Padron, F, Passi, R, Stone, J, Pursley, M, D'Urso, M, Gardner, T, Bennett, J, Nour, K, Saini, S, Zhang, W, Kumbhani, D, Thomas, D, Angiolillo, D, Bertolet, B, Roman-Miranda, A, Black, R, Manshadi, R, Vaca, C, Blanco, A, Napoli, M, Brabham, D, Akyea-Djamson, A, Desai, P, Prasada, S, Khaira, A, Forgosh, L, Lieber, I, Umpierrez, G, Singal, D, Londono, J, Fraser, N, Ruiz, J, Vega, D, Rodriguez, L, Brown, C, Syed, F, Aggarwala, G, Eaves, W, Foster, M, Gupta, D, Avino, D, Asfour, W, Tonnessen, G, Zhao, X, Singh, N, Brockmyre, A, Lepor, N, Shammas, N, Blick, D, Hearne, S, Prodafikas, J, Carell, E, Izzo, M, Karim, A, Zakhary, B, Atieh, M, Leichter, S, Meadows, C, Hotchkiss, D, Abu-Fadel, M, Wiseman, A, Bander, J, Shah, M, Ganim, R, Sopko, K, Khan, M, Lloret, R, Weirick, T, Mehta, R, Thadani, U, Bhargava, A, Moya, J, Staniloae, C, Guerra, Y, Chhabra, A, Kosmicki, D, Shaheen, W, Mohammed, A, Bitters, J, Pattanayak, J, Javier, J, Srivastava, S, Phillips, R, Al-Amin, J, Lillestol, M, Simpson, P, Hazan, L, Amin, A, Shah, G, Korpas, D, Platt, B, Dickert, J, Puente, O, Hiotis, L, Doyle, T, Rajan, R, Meholick, A, Gring, C, Hage-Korban, E, Feldman, R, Colfer, H, Butman, S, Hart, T, Huling, R, Eshaghian, S, Quintana, O, Cheung, D, Handel, F, Rodriguez, M, Suh, D, Gordon, P, Pressman, G, Bauer, M, French, W, Barettella, M, Chatrathi, S, Suresh, D, Goldberg, R, Huth, M, Younis, L, Rahman, A, Mascolo, R, Welch, M, Suneja, R, Smith, S, Shurmur, S, Agaiby, J, Jingo, A, Johnston, J, Beth, M, Vlastaris, A, Kemp, S, Taheri, H, Pereira, E, Deyoung, M, Hawa, Z, Smith, R, Galski, T, Garas, S, Reddy, M, Sharma, S, Hargrove, J, Treasure, C, Emerson, R, Haddad, T, Rohr, K, Levinson, L, Gaona, R, Uretsky, B, Maheshwari, H, Lee, D, Kinnaman, S, Singal, R, Geohas, J, Gigliotti, O, Raisinghani, A, Khurana, C, Hella, B, Kelberman, M, Voyce, S, Singh, S, Lo, E, Singh, P, Goodfellow, R, Fischer, S, Lorraine, R, Turner, T, Shanes, J, Busch, R, Broker, R, Zaniewski, M, Pounds, K, Debs-Perez, G, Ong, S, Frandsen, B, Fullington, D, Jaffrani, N, Khan, A, Lee, M, Pouzar, J, Revtyak, G, Gonzalez, J, Nakhle, S, Murillo, A, Young, D, Makam, S, Syed, M, Woolf, K, Grena, P, Alfata, S, Mahal, S, Hoffman, D, Kizhakekuttu, T, Deering, J, Bhavsar, J, Mikesell, S, Wilson, W, Wilson, V, El, S, Spinale, F, Kannarkat, V, Rao, S, Hanson, L, Bertsch, J, Gonzalez-Ortiz, E, Severino, N, Willis, J, Schock, J, Bakhtari, L, Gazmuri, R, Ansari, S, Hall, J, Mehta, A, Shealy, N, Zarich, S, Singh, D, Vora, K, Andrawis, N, Molter, D, Maron, D, Cardona, J, D'Agostino, R, Arshad, T, Samaan, R, Jones, D, Presser, D, Heath, J, Green, S, Bittar, G, Henry, S, Korn, D, Schmedtje, J, Nadar, V, Graham, B, Labroo, A, Clavijo, L, Roseman, H, Ledesma, G, Rosen, R, Dor, I, Kirby, W, Sutton, J, Eder, F, Iteld, B, Gomez-Cortes, J, Buchbinder, M, Kasper, J, Terrelonge, A, Torres, G, Jagielo, T, Alvarez, J, Handelsman, Y, Guillen, M, Richwine, R, Lewy-Alterbaum, L, Corder, C, Arvind, M, Bolshoun, D, Mikhail, M, Minton, S, Alvarado, O, Abbott, J, Cauthen, B, Welter, R, Mintz, R, Cox, J, Quick, A, Weiss, M, Dy, J, Zebrack, J, Gandelman, G, Hegde, V, Silver, M, Degregorio, M, Lawson, W, Paa, C, Bortnick, A, Krolick, M, Sotolongo, R, Cheirif, J, Kumar, P, Jetty, P, Patel, A, Kruk, M, Kobielusz-Gembala, I, Rewerska, B, Madrzejewski, A, Milewski, K, Cygler, J, Petryka-Mazurkiewicz, J, Jastrzebski, W, Korecki, J, Fil, W, Prokopczuk, J, Bochenek, A, Wujkowski, M, Witek, R, Konczakowski, P, Miekus, P, Szczasny, M, Musial, W, Cymerman, K, Lampart, J, Mikosinski, J, Szynal, S, Fares, I, Opolski, G, Mazur, S, Wozakowska-Kaplon, B, Bijata-Bronisz, R, Wierucki, L, Losa, B, Drelich, G, Konieczny, M, Starczewski, P, Pawlowicz, L, Jesionowski, P, Jurowiecki, J, Gniot, J, Czyzycki, M, Stania, K, Kucharczyk-Bauman, I, Busz-Papiez, B, Karczmarczyk, A, Sudnik, W, Koszek, A, Kolodziej, P, Skwarna, B, Jaramillo, N, Jankowski, M, Czochra, W, Kinasz, L, Miklaszewicz, B, Stasinska, T, Pluta, W, Basiak, M, Rusicka, T, Niedbal-Yahfouf, I, Popenda, G, Korzeniak, R, Mirek, A, Mariankowski, R, Wojnowski, L, Korol, M, Baszak, J, Podolec, P, Piesiewicz, W, Zurakowski, A, Luengas, C, Skura, M, Pilecki, P, Majchrzak, P, Krzyzagorska, E, Drozd, M, Kaczmarek, B, Sliwinska, T, Zelazowska, K, Sztembis, R, Landa, K, Matyszczak-Toniak, L, Strojek, K, Piepiorka, M, Malinowski, R, Gorska, M, Stolarczyk-Sowa, E, Romanowski, L, Zinka, E, Reszka, Z, Skierkowska, J, Uzunow, A, Laskowska-Derlaga, E, Puntus, E, Kosmacheva, E, Koziolova, N, Pavlov, P, Supryadkina, T, Didenko, Y, Kopylov, P, Kazakov, A, Aksentiev, S, Vishneva, E, Repin, A, Smolenskaya, O, Mantserova, O, Khrustalev, O, Privalova, E, Konstantinov, V, Boldueva, S, Ezhov, A, Chernyavsky, A, Kamalov, G, Galyavich, A, Zubeeva, G, Nechaeva, G, Shustov, S, Dzhaiani, N, Treshkur, T, Osokina, N, Panov, A, Shutemova, E, Makukhin, V, Kropotina, T, Tsyba, L, Karpov, Y, Sizova, J, Ballyuzek, M, Tarasov, N, Demchenko, E, Barbarash, O, Moiseev, V, Markov, V, Kuznetsov, V, Viktorova, I, Sergienko, I, Ermoshkina, L, Khasanov, N, Khlevchuk, T, Baglikov, A, Shalaev, S, Zonova, E, Reznik, E, Haisheva, L, Morugova, T, Lomakin, N, Vishnevsky, A, Shvarts, Y, Magnitskaya, O, Mikhailusova, M, Pavlysh, E, Libov, I, Zateyschikova, A, Kostenko, V, Edin, A, Khovaeva, Y, Zakharov, K, Stryuk, R, Khirmanov, V, Kanorskiy, S, Yakushin, S, Barabashkina, A, Li, H, Zhao, Q, Zhang, J, Ma, J, He, Y, Luo, M, Zhang, A, Zhang, N, Chai, Y, Ma, G, Wang, H, Liu, Z, He, L, Song, Z, Dong, X, Tao, L, Li, Z, Su, X, Kong, X, Niu, H, Ge, J, Luo, Z, Huang, W, Peng, D, Yuan, Z, Milanova, M, Tenev, D, Gogov, A, Karageorgiev, D, Kolchev, T, Rusev, N, Georgieva, N, Kondov, R, Rusinov, V, Petrov, I, Stanchev, G, Konteva, M, Dincheva, A, Yaneva, Z, Vatova, R, Ilieva, K, Runev, N, Kolomanov, B, Iliev, N, Tisheva, S, Chompalova, B, Tokmakova, M, Raev, D, Byanov, K, Markov, D, Mihov, L, Mihov, A, Milcheva, N, Minchev, M, Mollov, M, Borisov, B, Tihchev, T, Karakolev, V, Dimov, B, Georgiev, S, Smilov, L, Koo, B, Ahn, T, Hong, S, Yoon, J, Oh, S, Jeong, M, Kim, D, Chang, K, Kim, W, Hahn, J, Cha, K, Lee, J, Choi, S, Nam, C, Chae, I, Park, Y, Tahk, S, Shin, W, Chae, J, Kim, B, Bae, J, Park, W, Rha, S, Choi, Y, Hwang, J, Park, H, Baracioli, L, Guimaraes, F, Vasconcellos, E, Saraiva, J, Pereira, A, Santos, Q, Rossi, P, Maia, L, Madeira, M, Pereira, M, Botelho, R, Reis, G, Eliaschewitz, F, Borges, J, Nascimento, C, Fortes, J, de Souza, W, Pimentel, P, Hissa, M, Franchetti, M, Precoma, D, Ortiz, C, Hernandes, M, Saporito, W, dos Santos, F, Kormann, A, Neuenschwander, F, Dutra, O, Rassi, N, Tanajura, L, Souza, J, Junior, D, Leaes, P, Forte, A, Bonansea, T, Marin, J, Machado, B, Cerqueira, M, Silva, F, Michalaros, Y, Manenti, E, Cercato, C, Figueiredo, E, Liu, M, Wang, Y, Lee, T, Fang, C, Wu, Y, Ueng, K, Sheu, H, Lai, W, Hsieh, I, Chen, Z, Chiang, C, Shyu, K, Hsia, C, Mar, G, Chan, S, Wu, C, Tseng, W, Yeh, H, Wang, J, Hou, C, Sorokina, I, Dolzhenko, M, Horoshko, O, Karpenko, O, Rudenko, L, Vakaliuk, I, Kulyk, A, Levchenko, O, Prokhorov, O, Reshotko, D, Sorokivskyy, M, Velichko, N, Maslovskyi, V, Teliatnikova, Z, Dotsenko, S, Krakhmalova, O, Kraiz, I, Zharinova, V, Bula, L, Kaydashev, I, Molodtsov, V, Rasputina, L, Pidlisna, V, Lysunets, O, Kravchenko, A, Glushko, L, Khomazyuk, T, Svyshchenko, Y, Parkhomenko, O, Mankovsky, B, Abrahamovych, O, Yagensky, A, Stanislavchuk, M, Vasilyeva, L, Sokolova, L, Sychov, O, Tseluyko, V, Kyrychenko, I, Rishko, M, Furkalo, S, Gallo, R, Bertrand, O, Constance, C, Sussex, B, Zadra, R, Kouz, S, Chehayeb, R, Pandey, A, Dion, D, Bailey, G, Hill, L, Ramanathan, K, Dorsch, M, Nanji, A, Babapulle, M, Montigny, M, Gosselin, G, Dehghani, P, Rupka, D, Le May, M, Pichette, F, St-Maurice, F, Teefy, P, Mansour, S, Kassam, S, Cheung, S, Siega, A, O'Keefe, D, Sabbah, E, Bell, A, Chouinard, G, Wong, B, Miller, M, Gaudet, D, Lachance, P, Bata, I, Petrella, R, Gossard, D, Dumas, R, Ing, D, Boyrazian, H, Bessoudo, R, Huynh, T, Hart, R, Belle-Isle, J, Shukla, D, Kelly, A, Mazza, G, Cha, J, Henein, S, Frechette, A, Vizel, S, Liutkus, J, O'Mahony, M, Halperin, F, Kooy, J, Graham, J, Bailey, A, Wojcik, R, Wilderman, I, Turi, T, Motyovszki, A, Merkely, B, Kiss, R, Kiraly, C, Andrassy, P, Sarszegi, Z, Fulop, T, Zilahi, Z, Edes, I, Papp, A, Muller, G, Czigany, A, Zolyomi, S, Koranyi, L, Takacs, J, Juhasz, F, Benczur, B, Kancz, S, Foldi, A, Nagy, A, Bakai, J, Greschik, I, Puski, L, Nagy, L, Kirschner, R, Kuchar, R, Hajek, P, Busak, L, Michalik, D, Matyasek, I, Marusincova, I, Kucera, D, Jerabek, O, Honkova, M, Dedek, V, Rihacek, I, Kos, P, Slaby, J, Machkova, M, Zidkova, E, Elbl, L, Grunfeldova, H, Carda, J, Mrozek, V, Maly, J, Milkovic, R, Malecha, J, Skalicka, H, Oral, I, Krcova, E, Lisa, L, Belohlavek, J, Miklik, R, Cermak, O, Bednarova, J, Peroutka, Z, Spinar, J, Wilke, A, Appel, K, Taggeselle, J, Forster, A, Toursarkissian, N, Schmidt, E, Bott, J, Al-Zoebi, A, Hennig, D, Schon, N, Sauter, J, Simonis, G, Nischik, R, Rieker, W, Schenkenberger, I, Behnke, T, Klausmann, G, Jeserich, M, Trenk, D, Weigmann, I, Reuter, H, Rummel, R, von Munchhausen, C, von Engelhardt, C, Horibe, E, Shibasaki, T, Sato, T, Kakuta, T, Michishita, I, Tan, M, Ishiki, R, Aoyama, T, Higashiue, S, Niijima, Y, Idogaki, A, Hasegawa, T, Kiyosue, A, Tomobuchi, Y, Kawamitsu, K, Kawasaki, S, Hata, Y, Fukui, K, Seki, K, Takenaka, T, Abe, M, Utsu, N, Oono, A, Mitsuo, K, Sueyoshi, A, Hirohata, A, Tsujimoto, M, Ueda, O, Takase, S, Suzuki, M, Sakuragi, S, Yamamoto, F, Fujimoto, N, Kakinoki, S, Sugiura, T, Sugino, H, Nakamura, T, Kadokami, T, Uehara, H, Ono, M, Yokoya, K, Koike, A, Komatsu, S, Sonoda, M, Ueno, H, Doi, T, Takagi, Y, Fujimoto, K, Eki, Y, Okubo, M, Sasaki, K, van Eck, M, Ronner, E, The, S, van de Wal, R, Nierop, P, de Nooijer, C, Werner, H, Westendorp, I, van der Zwaan, C, Crijns, H, Cornel, J, Strikwerda, S, Bos, R, de Melker, E, Kuijper, A, Louwerenburg, H, Plomp, J, Dantzig, J, Prins, F, van Kesteren, H, Willems, F, Amoroso, G, Carnero, G, Duronto, E, Besada, D, Chacon, C, Zangroniz, P, Solis, S, Liberman, A, Sernia, V, Alvarisqueta, A, Maffei, L, Vilamajo, O, Garcia, C, Sicer, M, Muntaner, J, Bordonava, A, Albisu, J, Zanini, A, Rista, L, Hominal, M, Estrada, J, Prado, A, Gosparini, D, Schiavi, B, Castillo, A, Martinez, G, Lopez, V, Rosas, E, Lopez, G, Cantu, E, de los Rios Ibarra, M, Padilla, F, Carrasco, J, Carrillo, L, Garcia, J, Askar, A, Salinas, C, Gamba, M, Sanchez, C, Cantu, A, Sanchez, R, Madrigal, J, Urbano, R, Romo, A, Gonzalez Juanatey, J, Racugno, P, Fillat, A, de la Torre Hernandez, J, Pelaez, J, Cortada, J, Pavia, P, Navarro, M, Asenjo, R, Diaz, F, Peligero, E, Manterola, F, Ortiz, A, Mediavilla Garcia, J, Ortuno, F, Vera, T, Gonzalez, A, Vinas, J, Fernandez Portales, F, Mayordomo, P, Ojeda, F, Dominguez, A, Gonzalez, R, Guerrero, D, Ruiz Nodar, J, Marimon, X, Margaez, J, Aguilera, R, Diaz Fernandez, J, Zamorano Gomez, J, Gonzalez, V, del Blanco, B, Perez, I, Moreno, M, Ereno, A, Garcia Lledo, J, Prieto, J, Villablanca, A, Raffo, C, Pincetti, C, Conejeros, C, Roman, O, Varleta, P, Goldberg, C, Sandoval, J, Arriagada, G, Corbalan, R, Leon, L, Potthoff, S, Cobos, J, Figueroa, C, Makotoko, E, Fourie, N, Burgess, L, Nortje, H, Theron, R, Pillai, P, Ranjith, N, Trokis, J, Pillay, S, Reddy, J, Nunkoo, T, Kapp, C, Urbach, D, Distiller, L, Horak, A, van Zyl, L, Coetzee, K, Punt, Z, Bayat, J, Dawood, S, Mitha, I, Padayachee, T, Hoosen, F, Dalby, A, Prabhavathi, Gowdaiah, P, Mehta, V, Chag, M, Gadkari, M, Ramamurthee, K, Das, A, Sawhney, J, Sathe, P, Adhyapak, S, Nguyen, T, Pham, V, Do, H, Nguyen, A, Nguyen, H, Truong, B, Jamil-Copley, S, Lang, C, Pell, A, Zaman, A, Storey, R, Swanson, N, Sharman, D, Braganza, D, Hammond, P, Moriarty, A, Bain, S, Pye, M, Sharp, A, Blagden, M, Randeva, H, Myhill, T, Viswanathan, G, Keeling, P, Clifford, P, Saxena, M, Lyons, K, Mcmurray, J, Jaafar, F, Murphy, C, Cartwright, S, Abouglila, K, Antalik, L, Krajci, P, Urban, M, Fazekas, F, Pella, D, Koleny, D, Vykoukalova, T, Macek, V, Vinanska, D, Jamriskova, L, Such, S, Fulop, P, Farsky, S, Bugan, V, Strbova, J, Micko, K, Palka Jr, J, Sivak, V, Kristensen, D, Refsgaard, J, Holmvang, L, Dixen, U, Nielsen, H, Egstrup, K, Jensen, L, Sykulski, R, Rasmussen, O, Andries, A, Luckow, A, Nielsen, G, Sorensen, T, Wongvipaporn, C, Chamnarnphol, N, Srimahachota, S, Sansanayudh, N, Kuanprasert, S, Tresukosol, D, Sookananchai, B, Kanadasi, M, Ozcan, T, Kucuk, M, Ongen, Z, Okuyan, E, Arat, A, Acikel, S, Yalcin, A, Guray, U, Ceyhan, C, Ozer, N, Arslan, S, Angeras, O, Johnston, N, Weiderman, A, Bandh, S, Hansen, O, Larnefeldt, H, Kusiak, D, Lindholm, C, Hedman, A, Erlinge, D, Curiac, D, Lundman, P, Zucconi-Mazzini, R, Aladellie, L, Jensen, J, Verwerft, J, Vrolix, M, Faes, D, Striekwold, H, Sinnaeve, P, Timmermans, P, Guedes, A, Delforge, M, Nimmegeers, J, Stammen, F, Buysschaert, I, Hoffer, E, Hollanders, G, Vervoort, G, Coussement, P, de Maeseneire, S, Janssens, L, Gravdal, S, Risberg, K, Gullestad, L, Hofseth, O, Nilsen, D, Lappegard, K, van den Heuvel, C, Gibbs, C, Khusrawi, A, Arora, S, Tomala, T, Kjaernli, T, Berg-Johansen, J, Hagemeier, R, Skjelvan, G, Colquhoun, D, Amerena, J, Morbey, C, Hammett, C, Dart, A, Lehman, R, Hamilton, A, Worthley, M, Purnell, P, Whelan, A, Macisaac, R, Arya, K, Linjawi, S, Proietto, J, Prasad, L, Rodriguez, A, Godoy, A, Rodriguez, V, Berrospi, P, Chavez, C, Negron, S, Heredia, J, Medina, F, Manrique, H, Cabrera, W, Cordova, F, Quinteros, T, Haro, J, Regalado, S, Guitton, J, Arbanil, H, Pansieri, M, Decoulx, E, Goube, P, de Labriolle, A, Labeque, J, Range, G, Cottin, Y, Montalescot, G, Cayla, G, Danchin, N, Angoulvant, D, Ferrario, E, Elbaz, M, Dubreuil, O, Fontaine, C, Sorbets, E, Omer, H, Al-Saif, S, Al-Faleh, H, Al-Shehri, A, El-Amin, O, Alshehri, H, Bazari, R, Hei, P, Ying, M, Chan, M, Wong, M, Ma, R, Siu, S, Tsang, C, Ferrario, M, Assanelli, E, Senni, M, Piatti, P, Calabro, P, Urbinati, S, Michisanti, M, Varbella, F, de Cosmo, S, Trevisan, R, Bellotti, S, Di Pasquale, G, Bongo, A, Uguccioni, M, Mannucci, E, Mauro, C, Ragonese, M, Fresco, C, Turturo, M, Marcucci, R, Lievano Triana, M, Arana, C, Accini, J, Botero, R, Muzyk-Osikowicz, M, Dada, F, Vallejo, G, Manzur, F, Isaza, D, Molina, D, Mesa, J, Quintero, A, Nyman, K, Makela, J, Strand, J, Nieminen, S, Taurio, J, Kuusela, M, Valle, T, Pietila, M, Kekki, S, Strandberg, T, Klutstein, M, Greenberg, G, Rozenman, Y, Chorin, E, Roguin, A, Lewis, B, Bashkin, A, Tan, E, Prado, J, Ferrolino, A, Babilonia, N, Barbas, B, Matiga, G, Coching, R, Drexel, H, Brath, H, Schnack, C, Hanusch, U, Fliesser-Gorzer, E, Paulweber, B, Ebenbichler, C, Prager, R, Huber, K, Wolzt, M, Auer, J, Berger, R, Schernthaner, G, Stanciulescu, G, Creteanu, M, Spiridon, M, Dobreanu, V, Vinereanu, D, Iosipescu, L, Istratoaie, O, Coman, I, Militaru, C, Cinteza, M, Nicolau, J, Kerr Saraiva, J, Widimsky, P, Kristensen, S, Hartikainen, J, Darius, H, Tse, H, Pais, P, Lev, E, de Luca, L, Ramos Lopez, G, Kontny, F, Zateyshchikov, D, Ruda, M, Elamin, O, Kovar, F, Bueno, H, Leonsson-Zachrisson, M, Université Paris Diderot - Paris 7 (UPD7)-Université Paris 13 (UP13)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de pharmacologie - Dosage de médicaments [CHU Saint-Antoine], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Saint-Antoine [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Sorbonne Université (SU), and Royal Brompton and Harefield NHS Foundation Trust-Imperial College London

Subjects
Male, Platelet Aggregation Inhibitors/therapeutic use, THEMIS Steering Committee and Investigators, medicine.medical_treatment, Vascular damage Radboud Institute for Health Sciences [Radboudumc 16], 030204 cardiovascular system & hematology, Coronary Angiography, Stroke/epidemiology, Coronary artery disease, DOUBLE-BLIND, 0302 clinical medicine, Hemorrhage/chemically induced, acetylsalicylic acid, antidiabetic agent, placebo, ticagrelor, Secondary Prevention, Medicine, 030212 general & internal medicine, Myocardial infarction, Coronary Artery Bypass, Cardiovascular Diseases/mortality, 11 Medical and Health Sciences, OUTCOMES, Aspirin, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, General Medicine, Middle Aged, Clopidogrel, 3. Good health, Ticagrelor/therapeutic use, DRUG-ELUTING STENTS, CLOPIDOGREL, Cardiology, PLATELET INHIBITION, Drug Therapy, Combination, Female, Life Sciences & Biomedicine, Ticagrelor, TIMI, medicine.drug, Coronary Artery Disease/complications, medicine.medical_specialty, Hypoglycemic Agents/therapeutic use, POOLED ANALYSIS, 03 medical and health sciences, Medicine, General & Internal, Percutaneous Coronary Intervention, Double-Blind Method, General & Internal Medicine, Internal medicine, Myocardial Infarction/epidemiology, Humans, Aged, Science & Technology, ANTIPLATELET THERAPY, business.industry, Diabetes Mellitus, Type 2/complications, ELEVATION MYOCARDIAL-INFARCTION, RIVAROXABAN, Percutaneous coronary intervention, medicine.disease, ASPIRIN, Coronary Stenosis/diagnostic imaging, Aspirin/therapeutic use, Conventional PCI, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Contains fulltext : 215333.pdf (Publisher’s version ) (Closed access) BACKGROUND: Patients with stable coronary artery disease and diabetes with previous percutaneous coronary intervention (PCI), particularly those with previous stenting, are at high risk of ischaemic events. These patients are generally treated with aspirin. In this trial, we aimed to investigate if these patients would benefit from treatment with aspirin plus ticagrelor. METHODS: The Effect of Ticagrelor on Health Outcomes in diabEtes Mellitus patients Intervention Study (THEMIS) was a phase 3 randomised, double-blinded, placebo-controlled trial, done in 1315 sites in 42 countries. Patients were eligible if 50 years or older, with type 2 diabetes, receiving anti-hyperglycaemic drugs for at least 6 months, with stable coronary artery disease, and one of three other mutually non-exclusive criteria: a history of previous PCI or of coronary artery bypass grafting, or documentation of angiographic stenosis of 50% or more in at least one coronary artery. Eligible patients were randomly assigned (1:1) to either ticagrelor or placebo, by use of an interactive voice-response or web-response system. The THEMIS-PCI trial comprised a prespecified subgroup of patients with previous PCI. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke (measured in the intention-to-treat population). FINDINGS: Between Feb 17, 2014, and May 24, 2016, 11 154 patients (58% of the overall THEMIS trial) with a history of previous PCI were enrolled in the THEMIS-PCI trial. Median follow-up was 3.3 years (IQR 2.8-3.8). In the previous PCI group, fewer patients receiving ticagrelor had a primary efficacy outcome event than in the placebo group (404 [7.3%] of 5558 vs 480 [8.6%] of 5596; HR 0.85 [95% CI 0.74-0.97], p=0.013). The same effect was not observed in patients without PCI (p=0.76, pinteraction=0.16). The proportion of patients with cardiovascular death was similar in both treatment groups (174 [3.1%] with ticagrelor vs 183 (3.3%) with placebo; HR 0.96 [95% CI 0.78-1.18], p=0.68), as well as all-cause death (282 [5.1%] vs 323 [5.8%]; 0.88 [0.75-1.03], p=0.11). TIMI major bleeding occurred in 111 (2.0%) of 5536 patients receiving ticagrelor and 62 (1.1%) of 5564 patients receiving placebo (HR 2.03 [95% CI 1.48-2.76], p

Published
2019

8. Association of Genomic Instability with HbA1c levels and Medication in Diabetic Patients

Author

Armen Nersesyan, Karl-Heinz Wagner, Annemarie Grindel, Helmut Brath, and Siegfried Knasmueller

Subjects
0301 basic medicine, Genome instability, musculoskeletal diseases, Adult, medicine.medical_specialty, endocrine system diseases, medicine.medical_treatment, Buccal swab, Gastroenterology, Article, Genomic Instability, Cancer prevention, 03 medical and health sciences, Hba1c level, Diabetes mellitus, Internal medicine, medicine, Humans, Hypoglycemic Agents, Micronuclei, Chromosome-Defective, Aged, Aged, 80 and over, Glycated Hemoglobin, Multidisciplinary, business.industry, Insulin, Mouth Mucosa, Type 2 diabetes, Middle Aged, medicine.disease, 030104 developmental biology, Diabetes Mellitus, Type 2, Risk factors, Case-Control Studies, Micronucleus test, Etiology, Female, Micronucleus, business
Abstract

Diabetes Mellitus type 2 (DM2) is associated with increased cancer risk. Instability of the genetic material plays a key role in the aetiology of human cancer. This study aimed to analyse genomic instability with the micronucleus cytome assay in exfoliated buccal cells depending on glycated haemoglobin (HbA1c) levels and medication in 146 female DM2 patients. The occurrence of micronuclei was significantly increased in DM2 patients compared to healthy controls. Furthermore, it was doubled in DM2 patients with HbA1c > 7.5% compared to subjects with HbA1c ≤ 7.5%. Positive correlations were found between micronuclei frequencies and HbA1c as well as fasting plasma glucose. Patients under insulin treatment showed a two-fold increase in micronuclei frequencies compared to subjects under first-line medication (no drugs or monotherapy with non-insulin medication). However, after separation of HbA1c (cut-off 7.5%) only patients with severe DM2 characterised by high HbA1c and insulin treatment showed higher micronuclei frequencies but not patients with insulin treatment and low HbA1c. We demonstrated that the severity of DM2 accompanied by elevated micronuclei frequencies predict a possible enhanced cancer risk among female DM2 patients. Therapy, therefore, should focus on a strict HbA1c control and personalised medical treatments.

Published
2017
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9. Effectiveness of vildagliptin versus other oral antidiabetes drugs as add-on to sulphonylurea monotherapy: Post hoc analysis from the EDGE study

Author

Helmut Brath, U Phadke, K M Prasanna Kumar, Chantal Mathieu, Päivi M. Paldánius, and A Gawai

Subjects
Blood Glucose, Male, Pyrrolidines, Time Factors, Endocrinology, Diabetes and Metabolism, Administration, Oral, Adamantane, 030204 cardiovascular system & hematology, Weight Gain, 0302 clinical medicine, Risk Factors, Odds Ratio, Clinical endpoint, Vildagliptin, Prospective Studies, Prospective cohort study, Nutrition and Dietetics, Sulphonylurea, Middle Aged, Metformin, Treatment Outcome, Tolerability, Drug Therapy, Combination, Female, Family Practice, medicine.drug, Adult, medicine.medical_specialty, India, 030209 endocrinology & metabolism, 03 medical and health sciences, Internal medicine, Diabetes mellitus, Nitriles, Post-hoc analysis, Internal Medicine, medicine, Humans, Hypoglycemic Agents, Real-life setting, Aged, Glycated Hemoglobin, Dipeptidyl-Peptidase IV Inhibitors, business.industry, Odds ratio, medicine.disease, Logistic Models, Sulfonylurea Compounds, Endocrinology, Diabetes Mellitus, Type 2, Hyperglycemia, Multivariate Analysis, business, Biomarkers
Abstract

AimIn this post hoc analysis of the EDGE study, we assessed the effectiveness and safety of vildagliptin versus other oral antidiabetes drugs (OADs) as add-on to first-line sulphonylurea (SU) therapy in patients who did not receive metformin in a real-life setting.MethodsThe primary endpoint was odds of achieving an HbA1c reduction of >0.3% without tolerability issues. Secondary endpoint was odds of achieving HbA1c

Published
2016

10. Effectiveness and tolerability of second-line therapy with vildagliptin vs. other oral agents in type 2 diabetes: A real-life worldwide observational study (EDGE)

Author

Wolfgang Kothny, Emmanouil Pagkalos, R Göke, Nicolaas C. Schaper, J J de Castro, Helmut Brath, E Márquez Rodriguez, Ignacio Conget, Chantal Mathieu, P. M. Nilsson, S K Wangnoo, A Penfornis, Giovanni Bader, Anthony H. Barnett, MUMC+: MA Endocrinologie (9), Interne Geneeskunde, and RS: CARIM School for Cardiovascular Diseases

Subjects
Male, medicine.medical_specialty, Pyrrolidines, METFORMIN, Administration, Oral, Adamantane, Type 2 diabetes, Medicine, General & Internal, Pharmacotherapy, Endocrinology, General & Internal Medicine, Internal medicine, Nitriles, medicine, Humans, Hypoglycemic Agents, Vildagliptin, Pharmacology & Pharmacy, Prospective Studies, COMBINATION, Prospective cohort study, Glycated Hemoglobin, COMPLICATIONS, Science & Technology, BLOOD-GLUCOSE CONTROL, business.industry, ADVERSE DRUG-REACTIONS, General Medicine, Odds ratio, Middle Aged, EFFICACY, medicine.disease, Hypoglycemia, Surgery, PROPENSITY SCORE, Regimen, Tolerability, Diabetes Mellitus, Type 2, SAFETY, Cohort, PIOGLITAZONE, Drug Therapy, Combination, Female, business, Life Sciences & Biomedicine, CLINICAL-TRIALS, medicine.drug
Abstract

Aim Real-life studies are needed to confirm the clinical relevance of findings from randomised controlled trials (RCTs). This study aimed to assess the effectiveness and tolerability of vildagliptin add-on vs. other oral antihyperglycaemic drugs (OADs) added to OAD monotherapy in a real-life setting, and to explore the advantages and limitations of large-scale ‘pragmatic’ trials. Methods EDGE was a prospective, 1-year, worldwide, real-life observational study in which 2957 physicians reported on the effects of second-line OADs in 45,868 patients with T2DM not reaching glycaemic targets with monotherapy. Physicians could add any OAD, and patients entered either vildagliptin or (pooled) comparator cohort. The primary effectiveness and tolerability end-point (PEP) evaluated proportions of patients decreasing HbA1c > 0.3%, without hypoglycaemia, weight gain, peripheral oedema or gastrointestinal side effects. The most clinically relevant secondary end-point (SEP 3) was attainment of end-point HbA1c

Published
2013

11. Vitamin and antioxidant rich diet increases MLH1 promoter DNA methylation in DMT2 subjects

Author

Karl-Heinz Wagner, Helmut Brath, Eva Aumüller, Olivier J. Switzeny, Alexander G. Haslberger, and Elisabeth Müllner

Subjects
Vitamin, medicine.medical_specialty, Antioxidant, lcsh:QH426-470, medicine.medical_treatment, lcsh:Medicine, Biology, MLH1, medicine.disease_cause, chemistry.chemical_compound, Internal medicine, Genetics, medicine, Epigenetics, Molecular Biology, Genetics (clinical), DNA methylation, Nutritional intervention, Research, Diabetes, lcsh:R, Pyrosequencing, ROS, Impaired fasting glucose, medicine.disease, digestive system diseases, Demethylation, lcsh:Genetics, Endocrinology, chemistry, DNA mismatch repair, Oxidative stress, Developmental Biology
Abstract

Background Oxidative stress may lead to an increased level of unrepaired cellular DNA damage, which is discussed as one risk for tumor initiation. Mismatch repair (MMR) enzymes act as proofreading complexes that maintain the genomic integrity and MMR-deficient cells show an increased mutation rate. One important gene in the MMR complex is the MutL homolog 1 (MLH1) gene. Since a diet rich in antioxidants has the potential to counteract harmful effects by reactive oxygen species (ROS), we investigated the impact of an antioxidant, folate, and vitamin rich diet on the epigenetic pattern of MLH1. These effects were analyzed in individuals with non-insulin depended diabetes mellitus type 2 (NIDDM2) and impaired fasting glucose (IFG). Methods In this post-hoc analysis of a randomized trial we analyzed DNA methylation of MLH1, MSH2, and MGMT at baseline and after 8 weeks of intervention, consisting of 300 g vegetables and 25 ml plant oil rich in polyunsaturated fatty acids per day. DNA methylation was quantified using combined bisulfite restriction enzyme analysis (COBRA) and pyrosequencing. MLH1 and DNMT1 mRNA expression were investigated by qRT-PCR. DNA damage was assessed by COMET assay. Student’s two-tailed paired t test and one-way ANOVA with Scheffé corrected Post hoc test was used to determine significant methylation and expression differences. Two-tailed Pearson test was used to determine correlations between methylation level, gene expression, and DNA strand break amount. Results The intervention resulted in significantly higher CpG methylation in two particular MLH1 promoter regions and the MGMT promoter. DNA strand breaks and methylation levels correlated significantly. The expression of MLH1, DNMT1, and the promoter methylation of MSH2 remained stable. CpG methylation levels and gene expression did not correlate. Conclusion This vitamin and antioxidant rich diet affected the CpG methylation of MLH1. The higher methylation might be a result of the ROS scavenging antioxidant rich diet, leading to lower activity of DNA demethylating enzymes. Our results suggest the hypothesis of CpG demethylation via DNA repair enzymes under these circumstances. NIDDM2 and IFG patients benefit from this simple dietary intervention involving epigenetic and DNA repair mechanisms.

Published
2012

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