Article
Cardiac & Cardiovascular Systems
Elizabeth J. Rowe, Tyler Shugg, Reynold C. Ly, Santosh Philips, Marc B. Rosenman, John T. Callaghan, Milan Radovich, Brian R. Overholser, Bryan P. Schneider, James E. Tisdale, Todd C. Skaar
Summary: This study demonstrates that prescriptions for QT-prolonging drugs were associated with longer QTc measurements and increased odds of being excluded from cancer clinical trials.
FRONTIERS IN CARDIOVASCULAR MEDICINE
(2022)
Article
Pharmacology & Pharmacy
Zheng Zequn, Wu Yujia, Qian Dingding, Lian Jiangfang
Summary: COVID-19, caused by SARS-CoV2, poses challenges to the medical system due to lack of safe and effective treatment methods; some old drugs may cause cardiotoxicity by blocking hERG channels; understanding drug interactions with hERG channels is crucial for developing safer and more effective drugs.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Pharmacology & Pharmacy
Talip E. Eroglu, Carlo A. Barcella, Marieke T. Blom, Grimur H. Mohr, Patrick C. Souverein, Christian Torp-Pedersen, Fredrik Folke, Mads Wissenberg, Anthonius de Boer, Peter J. Schwartz, Gunnar H. Gislason, Hanno L. Tan
Summary: In clinical practice, non-cardiac QT-prolonging drugs are associated with a higher risk of out-of-hospital cardiac arrest (OHCA) compared to cardiac QT-prolonging drugs. Despite users of cardiac QT-prolonging drugs having a higher a priori risk, they have a lower OHCA risk likely due to risk mitigation measures surrounding their prescription.
BRITISH JOURNAL OF CLINICAL PHARMACOLOGY
(2022)
Review
Pharmacology & Pharmacy
Hugo M. Vargas, Michael G. Rolf, Todd A. Wisialowski, William Achanzar, Anthony Bahinski, Alan Bass, Charles T. Benson, Khuram W. Chaudhary, Nicolas Couvreur, Corina Dota, Michael J. Engwall, C. Michael Foley, David Gallacher, Andrea Greiter-Wilke, Jean-Michel Guillon, Brian Guth, Herbert M. Himmel, Christa Hegele-Hartung, Maki Ito, Stephen Jenkinson, Katsuyoshi Chiba, Armando Lagrutta, Paul Levesque, Eric Martel, Yoshiko Okai, Ravikumar Peri, Amy Pointon, Yusheng Qu, Ard Teisman, Martin Traebert, Takashi Yoshinaga, Gary A. Gintant, Derek J. Leishman, Jean-Pierre Valentin
Summary: Efficient assessment of drug-induced QTc prolongation remains a concern of drug developers and regulators worldwide. While successful, nonclinical evaluations currently have minimal impact on clinical QTc prolongation assessment. Fully integrating nonclinical and clinical data can simplify drug development processes.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Article
Clinical Neurology
Gudrun Hefner, Martina Hahn, Christoph Hiemke, Sermin Toto, Jan Wolff, Sibylle C. Roll, Ansgar Klimke
Summary: The study analyzed the prevalence and type of pharmacodynamic drug-drug interactions between QT-prolonging drugs in psychiatry. Results showed a high prevalence of QT-prolonging drugs use in psychiatric patients, with some patients using multiple drugs with lethal risks concurrently. Replacing high-risk drugs with more tolerable options could enhance the tolerability of psychopharmacological treatment.
JOURNAL OF NEURAL TRANSMISSION
(2021)
Article
Psychology, Multidisciplinary
Ashley M. Goodwin, Danielle Miller, Stefani D'Angelo, Alexandra Perrin, Ruby Wiener, Brittney Greene, Anne-Marie N. Romain, Lindsay Arader, Thevaa Chandereng, Ying Kuen Cheung, Karina W. Davidson, Mark Butler
Summary: Stress is a significant public health burden in the United States, and personalized treatment methods have shown promise in effectively managing stress. This trial aims to evaluate the effectiveness of personalized treatments in reducing stress and providing guidance for clinicians in choosing the best stress management techniques for individuals.
FRONTIERS IN PSYCHOLOGY
(2023)
Article
Oncology
Terutsugu Koya, Kenichi Yoshida, Misa Togi, Yo Niida, Sumihito Togi, Hiroki Ura, Shuichi Mizuta, Tomohisa Kato Jr, Sohsuke Yamada, Takeo Shibata, Yi-Chang Liu, Shyng-Shiou Yuan, Deng-Chyang Wu, Hirohito Kobayashi, Taiju Utsugisawa, Hitoshi Kanno, Shigetaka Shimodaira
Summary: This study developed highly potent human platelet lysate-induced antigen-presenting cells (HPL-APCs) and aimed to verify the safety, tolerability, and immunoinducibility of HPL-APCs loaded with cancer candidate antigens. Interim analysis confirmed safety and tolerability in three patients and immune response in two completed cases. This study demonstrates the feasibility and immunoinducibility of personalized cancer vaccines using HPL-APCs and highlights the potential for further antitumor activity through optimized combination therapies.
Review
Pharmacology & Pharmacy
Lydia M. Seed, Timothy J. Hearn
Summary: Diurnal oscillations in human cardiac electrophysiology are controlled by the endogenous circadian clock. This study focuses on Long QT syndrome (LQTS) and the diurnal variation in arrhythmic events. It also examines the impact of timing information on the interpretation of drug trials. The findings suggest that there is a need for better incorporation of time of day information in LQTS trial design and provide a visual portal to aid trial designers and clinicians.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Cardiac & Cardiovascular Systems
Talip E. Eroglu, Marieke T. Blom, Patrick C. Souverein, Anthonius de Boer, Hanno L. Tan
Summary: Non-cardiac QT-prolonging drugs (QT drugs) increase the risk of out-of-hospital cardiac arrest. However, there is currently no stratified analysis of the risk associated with category 1 and category 2 QT drugs.
Article
Cell Biology
Konstantinos Leventogiannis, Evdoxia Kyriazopoulou, Nikolaos Antonakos, Antigone Kotsaki, Iraklis Tsangaris, Dimitra Markopoulou, Inge Grondman, Nikoleta Rovina, Vassiliki Theodorou, Eleni Antoniadou, Ioannis Koutsodimitropoulos, George Dalekos, Glykeria Vlachogianni, Karolina Akinosoglou, Vassileios Koulouras, Apostolos Komnos, Theano Kontopoulou, Athanassios Prekates, Antonia Koutsoukou, Jos W. M. van der Meer, George Dimopoulos, Miltiades Kyprianou, Mihai G. Netea, Evangelos J. Giamarellos-Bourboulis
Summary: This study investigates the role of immune activation in guiding targeted immunotherapy for sepsis. Using biomarkers such as ferritin and HLA-DR/CD14, sepsis patients were classified into three immune classifications: macrophage activation-like syndrome (MALS), immunoparalysis, and intermediate. The results show that MALS and immunoparalysis are associated with higher mortality rates, while immunotherapy can improve patient survival.
CELL REPORTS MEDICINE
(2022)
Article
Cell Biology
Bou-Yue Peng, Abhinay Kumar Singh, Ching-Yu Tsai, Chun-Hao Chan, Yue-Hua Deng, Chi-Ming Wu, Yen-Ru Chou, Wen Tsao, Chia-Yu Wu, Win-Ping Deng
Summary: This study highlights the therapeutic potential of the hPRP and HA combination for TMJ-OA therapy, with detailed evidence from bench to bedside. Clinical trials show that the treatment promotes cartilage regeneration, inhibits inflammation, reduces pain, and increases joint function in TMJ-OA.
JOURNAL OF BIOMEDICAL SCIENCE
(2023)
Article
Hematology
Nicola Giesen, Manik Chatterjee, Christof Scheid, Alexandra M. Poos, Britta Besemer, Kaya Miah, Axel Benner, Nicole Becker, Thomas Moehler, Ivana Metzler, Cyrus Khandanpour, Andrea Seidel-Glaetzer, Karolin Trautmann-Grill, K. Martin Kortuem, Carsten Mueller-Tidow, Gunhild Mechtersheimer, Benjamin Goeppert, Albrecht Stenzinger, Niels Weinhold, Hartmut Goldschmidt, Katja Weisel, Marc S. Raab
Summary: This article reports a clinical trial targeting patients with BRAFV600E-mutated relapsed/refractory multiple myeloma (RRMM), using the combination of BRAF/MEK inhibitors encorafenib and binimetinib. The results demonstrate that this treatment approach is highly effective and safe in RRMM patients.
Article
Medicine, General & Internal
Rod W. Hunt, Helen G. Liley, Deepika Wagh, Rachel Schembri, Katherine J. Lee, Andrew D. Shearman, Samantha Francis-Pester, Koert DeWaal, Jeanie Y. L. Cheong, Monika Olischar, Nadia Badawi, Flora Y. Wong, David A. Osborn, Victor Samuel Rajadurai, Peter A. Dargaville, Bevan Headley, Ian Wright, Paul B. Colditz
Summary: This randomized clinical trial aimed to determine whether active management of electrographic and clinical seizures in encephalopathic term or near-term neonates improved survival free of severe disability at 2 years compared with only treating clinically detected seizures. The study found that treating electrographic and clinical seizures with currently used anticonvulsants did not significantly reduce the rate of death or disability at 2 years in a heterogeneous group of neonates with seizures. Additionally, there was evidence that cognitive outcomes were worse in the group where both types of seizures were actively managed.
Review
Hematology
Chi Keung Lam, Joseph C. Wu
Summary: Drug-induced cardiotoxicity poses a significant challenge in healthcare, while identifying susceptible populations and developing personalized treatment strategies are crucial. The utility of induced pluripotent stem cells provides researchers with a powerful tool to identify patients who can predict adverse cardiovascular effects.
ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
(2021)
Article
Immunology
Stephen M. Bart, John J. Farley, Shukal Bala, Thushi Amini, Edward Cox
Summary: As drug development becomes more globalized, geographical recruitment trends for recent antibacterial clinical trials vary by indication, but demographic characteristics and microbiology are broadly similar across regions, alleviating concerns about generalizability due to shifting enrollment trends.
CLINICAL INFECTIOUS DISEASES
(2021)
Article
Toxicology
Dakshesh Patel, Jayna Stohlman, Qianyu Dang, David G. Strauss, Ksenia Blinova
TOXICOLOGICAL SCIENCES
(2019)
Article
Multidisciplinary Sciences
Marcello Panagia, Jing Yang, Eric Gale, Huan Wang, Ivan Luptak, Howard H. Chen, Dakshesh Patel, Dominique Croteau, David Richard Pimentel, Markus Michael Bachschmid, Wilson S. Colucci, Chongzhao Ran, David E. Sosnovik
SCIENTIFIC REPORTS
(2020)
Article
Cell & Tissue Engineering
John W. Ostrominski, Ravi Chandra Yada, Noriko Sato, Michael Klein, Ksenia Blinova, Dakshesh Patel, Racquel Valadez, Maryknoll Palisoc, Stefania Pittaluga, Kah-Whye Peng, Hong San, Yongshun Lin, Falguni Basuli, Xiang Zhang, Rolf E. Swenson, Mark Haigney, Peter L. Choyke, Jizhong Zou, Manfred Boehm, So Gun Hong, Cynthia E. Dunbar
STEM CELLS TRANSLATIONAL MEDICINE
(2020)
Article
Physiology
Tromondae K. Feaster, Maura Casciola, Akshay Narkar, Ksenia Blinova
Summary: The study demonstrated significant enhancement in contractility and calcium handling of hiPSC-CMs with CCM stimulation. Electrophysiological properties were also altered leading to shortened action potential duration. This study provides a comprehensive characterization of CCM effects on hiPSC-CMs, offering an in vitro model for future assessment of cardiac electrophysiology medical devices.
PHYSIOLOGICAL REPORTS
(2021)
Article
Biochemistry & Molecular Biology
Akshay Narkar, James M. Willard, Ksenia Blinova
Summary: This review focuses on recent advances in chronic cardiotoxicity assessment using cardiomyocytes differentiated from human induced pluripotent stem cells. The review summarizes studies on chronic cardiotoxicity induced by various drugs, including anticancer agents, antibiotics, anti-HCV drugs, and antidiabetic drugs. The review also highlights the use of hiPSC-CMs in investigating the chronic effects of non-pharmaceutical cardiotoxicants and the development of biomarker assays. The comprehensive investigation of long-term repeated exposure-induced effects on cardiomyocytes can provide mechanistic insights and recapitulate drug and environmental cardiotoxicity.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Physiology
Maura Casciola, Devin Keck, Tromondae K. Feaster, Ksenia Blinova
Summary: This study compared the effects of pulse electric field-based ablation using two different human cellular models, showing cell type specificity in electric field thresholds. Additionally, it highlighted the potential risks of increased temperature and thermal tissue damage associated with PEF treatment.
PHYSIOLOGICAL REPORTS
(2022)
Article
Physiology
Akshay Narkar, Tromondae K. Feaster, Maura Casciola, Ksenia Blinova
Summary: This study developed an in vitro neurocardiac coculture model system to study the interaction between the heart and the nervous system. It was found that the effects and kinetics of cardiac medical devices were more pronounced in coculture, and part of the mechanism of action could be attributed to peripheral nervous system stimulation.
PHYSIOLOGICAL REPORTS
(2022)
Article
Physiology
Tromondae K. Feaster, Nicole Feric, Isabella Pallotta, Akshay Narkar, Maura Casciola, Michael P. Graziano, Roozbeh Aschar-Sobbi, Ksenia Blinova
Summary: This study extends the evaluation of standard CCM pulse parameters to human 3D microphysiological systems, providing a robust model for assessing various clinical CCM pulse parameters. It was found that 3D human engineered cardiac tissues (ECTs) displayed a strong CCM contractile response, while conventional 2D monolayer cells showed no response. Additionally, the 3D ECTs exhibited enhanced contractility in a CCM pulse parameter-dependent manner.
FRONTIERS IN PHYSIOLOGY
(2022)
Article
Physiology
Maura Casciola, Tromondae K. Feaster, Michael J. Caiola, Devin Keck, Ksenia Blinova
Summary: Pulsed electric field (PEF) cardiac ablation is a technique used to treat drug resistant atrial fibrillation. The lack of comprehensive studies to select PEF parameters for safe and effective treatments hinders device development and regulatory decision-making. Human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) are proposed as an alternative to evaluate cardiac electrophysiology safety.
FRONTIERS IN PHYSIOLOGY
(2023)
Article
Multidisciplinary Sciences
Tromondae K. Feaster, Maura Casciola, Akshay Narkar, Ksenia Blinova
Summary: This paper describes a novel method to evaluate the contractile properties of cardiac medical devices using human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) and a flexible hydrogel substrate. The method allows for the quantification of the effects of cardiac electrophysiology device signals on human cardiac function with standard laboratory equipment. The results showed significantly enhanced contractile properties of the hiPSC-CMs exposed to the device signals, indicating the potential of this method for cardiac medical device safety assessment and effectiveness testing.
JOVE-JOURNAL OF VISUALIZED EXPERIMENTS
(2022)
Proceedings Paper
Engineering, Biomedical
Kenneth Aycock, Ksenia Blinova, Maura Casciola, Brent Craven, Matthew Di Prima, Gavin D'Souza, Nandini Duraiswamy, Masoud Farahmand, Prasanna Hariharan, Luke Herbertson, Megan Jamiolkowski, Qijin Lu, Richard Malinauskas, Mehulkumar Patel, Jean Rinaldi, Shiril Sivan, Oleg Vesnovsky, Jason Weaver
Summary: The Cardiovascular Research Program at FDA's OSEL aims to drive innovation in cardiovascular device technology through the development and standardization of pre-clinical test methods, with the goal of improving regulatory review processes and accelerating patient access to safe and effective cardiovascular medical devices.
PROCEEDINGS OF THE 2021 DESIGN OF MEDICAL DEVICES CONFERENCE (DMD2021)
(2021)
Article
Multidisciplinary Sciences
Phu N. Tran, Jiansong Sheng, Aaron L. Randolph, Claudia Alvarez Baron, Nicolas Thiebaud, Ming Ren, Min Wu, Lars Johannesen, Donna A. Volpe, Dakshesh Patel, Ksenia Blinova, David G. Strauss, Wendy W. Wu
Review
Medicine, Legal
Gary Gintant, Emily Pfeiffer Kaushik, Tromondae Feaster, Sonja Stoelzle-Feix, Yasunari Kanda, Tomoharu Osada, Godfrey Smith, Katherine Czysz, Ralf Kettenhofen, Hua Rong Lu, Beibei Cai, Hong Shi, Todd Joseph Herron, Qianyu Dang, Francis Burton, Li Pang, Martin Traebert, Yama Abassi, Jennifer Beck Pierson, Ksenia Blinova
REGULATORY TOXICOLOGY AND PHARMACOLOGY
(2020)