ABSTRACT
Safety pharmacology is an essential part of drug development aiming to identify, evaluate and investigate undesirable pharmacodynamic properties of a drug primarily prior to clinical trials. In particular, cardiovascular adverse drug reactions (ADR) have halted many drug development programs. Safety pharmacology has successfully implemented a screening strategy to detect cardiovascular liabilities, but there is room for further refinement. In this setting, we present the INSPIRE project, a European Training Network in safety pharmacology for Early Stage Researchers (ESRs), funded by the European Commission's H2020-MSCA-ITN programme. INSPIRE has recruited 15 ESR fellows that will conduct an individual PhD-research project for a period of 36 months. INSPIRE aims to be complementary to ongoing research initiatives. With this as a goal, an inventory of collaborative research initiatives in safety pharmacology was created and the ESR projects have been designed to be complementary to this roadmap. Overall, INSPIRE aims to improve cardiovascular safety evaluation, either by investigating technological innovations or by adding mechanistic insight in emerging safety concerns, as observed in the field of cardio-oncology. Finally, in addition to its hands-on research pillar, INSPIRE will organize a number of summer schools and workshops that will be open to the wider community as well. In summary, INSPIRE aims to foster both research and training in safety pharmacology and hopes to inspire the future generation of safety scientists.
PMID:32565326 | DOI:10.1016/j.vascn.2020.106889
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PubMed articles on: Cancer & VTE/PE
Prevention and treatment of venous thromboembolism in cancer patients
Spehlmann ME, et al. Herz 2020 - Review.
ABSTRACT
Deep vein thrombosis and pulmonary artery embolism are common and serious concomitant diseases in patients with cancer. The prophylaxis and therapy of such venous thromboembolic events (VTE) in oncology have so far been achieved with low-molecular-weight heparins. An increasing number of studies show evidence of the use of direct oral anticoagulants. However, since none of the possible options were shown to have a clear advantage in all patients, the individual decision to use a drug should be made depending on its effectiveness in preventing VTE, the risk of bleeding, the nature of the cancer, the interactions with other medications, the route of administration, and finally the cost of treatment.
PMID:32564097 | DOI:10.1007/s00059-020-04961-9
03:15
PubMed articles on: Cardio-Oncology
Cardioprotective Strategies to Prevent Cancer Treatment-Related Cardiovascular Toxicity: a Review
03:15
PubMed articles on: Cardio-Oncology
Pluripotent Stem Cell Modeling of Anticancer Therapy-Induced Cardiotoxicity
03:15
PubMed articles on: Cancer & VTE/PE
Effectiveness and Safety of Apixaban and Rivaroxaban for Acute Venous Thromboembolism Therapy in Patients with Extremes in Body Weight (ClinicalTrials.gov: NCT03504007)
03:16
PubMed articles on: Cardio-Oncology
Establishing an oncocardiology service
Lehmann LH and Totzeck M. Herz 2020 - Review.
ABSTRACT
Oncocardiology is an emerging field in cardiovascular healthcare. Besides establishing surveillance and follow-up strategies for cancer patients, it will be essential to set up specialized oncocardiology services. However, there is a lack of clinical studies to give evidence-based recommendations regarding cardiological diagnostic and therapeutic approaches for cancer patients. An oncocardiology service is a patient-centered structure that aims to integrate research and interdisciplinary patient care to bridge this gap. We discuss the current challenges in developing an oncocardiology service and review the literature on this topic. We further provide an overview of the essential diagnostic tools and upcoming ethical issues to be considered in the management of oncology patients.
PMID:32572500 | PMC:PMC7306932 | DOI:10.1007/s00059-020-04952-w
03:16
PubMed articles on: Cardio-Oncology
Whole milk consumption is associated with lower risk of coronary artery calcification progression: evidences from the Multi-Ethnic Study of Atherosclerosis
Ghosh S, et al. Eur J Nutr 2020.
ABSTRACT
PURPOSE: Coronary artery calcification (CAC) progression is a strong predictor of cardiovascular disease (CVD) morbidity and mortality. However, the association between whole milk and CAC progression remains unknown. Recent studies highlighted beneficial effects of short chain fatty acids (SCFA) from whole milk on CVD. In this study, we attempted to investigate the relationship between whole milk consumption and CAC progression, and the potential effect of SCFA in it.
METHODS: We analyzed a population-based cohort with 5273 participants from the Multi-Ethnic Study of Atherosclerosis (MESA) who completed a dietary questionnaire at baseline. CAC was measured at baseline and subsequent follow-up examinations by multi-detector computed tomography (MDCT) scans with Agatston scores. CAC progression was defined as increased CAC scores in the follow-up from the baseline exam.
RESULTS: Participants consuming whole milk exhibited lower baseline CAC and CAC progression than those who never/rarely consumed whole milk (P < 0.001 and P = 0.010, respectively). Moreover, multivariable logistic regression analysis demonstrated that whole milk intake was independently associated with lower CAC progression (OR 0.765; 95% CI 0.600-0.977; P = 0.032), especially in males, participants with age ≤ 64 years and with body mass index (BMI) ≤ 25 kg/m2. Mediation analysis further showed that caproic acid, one kind of SCFA, partly mediated protective effects of whole milk on CAC progression.
CONCLUSIONS: Self-reported whole milk consumption was inversely associated with CAC progression in community-dwelling participants, especially in those at relatively low cardiovascular risks. The beneficial effect was partially mediated by SCFA. Therefore, whole milk can be incorporated into part of a cardio-protective diet. Regarding this, future studies may target SCFA to provide insight into more mechanistic views.
PMID:32583016 | DOI:10.1007/s00394-020-02301-5
03:16
PubMed articles on: Cancer & VTE/PE
Guidance on diagnosis, prevention and treatment of thromboembolic complications in COVID-19: a position paper of the Brazilian Society of Thrombosis and Hemostasis and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy
Orsi FA, et al. Hematol Transfus Cell Ther 2020 - Review.
ABSTRACT
Hemostatic abnormalities and thrombotic risk associated with coronavirus disease 2019 (COVID-19) are among the most discussed topics in the management of this disease. The aim of this position paper is to provide the opinion of Brazilian experts on the thromboprophylaxis and management of thrombotic events in patients with suspected COVID-19, in the sphere of healthcare in Brazil. To do so, the Brazilian Society of Thrombosis and Hemostasis (BSTH) and the Thrombosis and Hemostasis Committee of the Brazilian Association of Hematology, Hemotherapy and Cellular Therapy (ABHH) have constituted a panel of experts to carefully review and discuss the available evidence about this topic. The data discussed in this document was reviewed by May 9, 2020. Recommendations and suggestions reflect the opinion of the panel and should be reviewed periodically as new evidence emerges.
PMID:32565232 | PMC:PMC7293502 | DOI:10.1016/j.htct.2020.06.001
03:16
PubMed articles on: Cardio-Oncology
Positron emission tomography imaging in cardiovascular disease
Tarkin JM, et al. Heart 2020 - Review.
ABSTRACT
Positron emission tomography (PET) imaging is useful in cardiovascular disease across several areas, from assessment of myocardial perfusion and viability, to highlighting atherosclerotic plaque activity and measuring the extent of cardiac innervation in heart failure. Other important roles of PET have emerged in prosthetic valve endocarditis, implanted device infection, infiltrative cardiomyopathies, aortic stenosis and cardio-oncology. Advances in scanner technology, including hybrid PET/MRI and total body PET imaging, as well as the development of novel PET tracers and cardiac-specific postprocessing techniques using artificial intelligence will undoubtedly continue to progress the field.
PMID:32571959 | DOI:10.1136/heartjnl-2019-315183
03:16
PubMed articles on: Cardio-Oncology
Cardiac Imaging in Oncology Patients in Europe: a Model for Advancement of CV Safety and Development of Comprehensive CV Care
López-Fernández T. J Cardiovasc Transl Res 2020 - Review.
ABSTRACT
Cancer therapy-related cardiovascular events are widely recognized as a global problem, and cardio-oncology has been proposed as a new approach to coordinate preventive strategies in oncologic patients. Cardiac imaging plays a critical role in this process. This article summarizes current practices and future needs in cardiac imaging to improve the cardiovascular surveillance of cancer patients.
PMID:32583314 | PMC:PMC7314619 | DOI:10.1007/s12265-020-10028-1
03:16
PubMed articles on: Cardio-Oncology
Cardio-oncology: the new frontier of clinical and preventive cardiology
Paris S, et al. Monaldi Arch Chest Dis 2020.
ABSTRACT
Even if cancer and cardiovascular diseases are considered two distinct diseases, an intricate interconnection between these conditions has been established. Increased risk of malignancy has been identified in patients with cardiovascular disease, as well as a greater propensity to the development of cardiovascular diseases has been observed in patients with cancer. The development of cardiotoxicity following exposure to certain anticancer drugs only partially explains this relationship. Shared risk factors and common pathogenic mechanisms suggest the existence of a common biology and a complex interplay between these two conditions. Due to improving longevity and therapeutic advances, the number of patients affected or potentially at risk of developing these two diseases is constantly increasing and currently, several drugs against cancer from anthracyclines to checkpoint inhibitors, can also cause a wide range of unexpected cardiovascular side effects. Management of these issues in clinical practice is an emerging challenge for cardiologists and oncologists, and led to the development of a new dedicated discipline called cardio-oncology. Surveillance and prevention strategies as well as interventions to reduce cardiovascular risk and prevent cardiotoxicities are the primary objectives of cardio-oncology. In this review, we explore the etiopathogenesis common to cardiovascular disease and cancer and the complex interplay between them. We also report the main characteristics of the drugs responsible for cardiotoxicity, highlighting the available strategies for optimal patient management based on a multidisciplinary approach in the cardio-oncology setting.
PMID:32571000 | DOI:10.4081/monaldi.2020.1348
03:16
PubMed articles on: Cancer & VTE/PE
Direct oral anticoagulants and cancer-associated VTE: good for all, or just some?
Carrier M and Wang TF. Blood 2020.
ABSTRACT
Venous thromboembolism (VTE) is associated with significant mortality and morbidity in patients with cancer. Therefore, tailoring anticoagulation is of utmost importance in order to decrease the risk of recurrent VTE while minimizing the risk of bleeding. Direct oral anticoagulants have been recently compared to low-molecular-weight heparin for the management of acute cancer-associated thrombosis. Although direct oral anticoagulants are a welcome addition, clinicians need to incorporate clinical characteristics, drug-drug interactions and patient preference in decision making.
PMID:32575112 | DOI:10.1182/blood.2019004177
03:16
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PubMed articles on: Cardio-Oncology
Breast Cancer Survivorship, Quality of Life, and Late Toxicities
Nardin S, et al. Front Oncol 2020 - Review.
ABSTRACT
Breast cancer is the most frequent cancer in women: in 2018, almost two million cases have been diagnosed all over the world and it represents the principal cause of death from a neoplastic disease in women. In the past years, breast cancer prognosis has significantly improved over time: currently 5-year survival rates are in the range of 90%, and 10-year survival is about 80%. This improvement has been mostly observed in western countries, due to high coverage and compliance with screening programs, leading to early diagnosis, i.e., when the disease is at a subclinical level, and to an improvement in tumor molecular characterization and innovative systemic treatments. Yet the identification of different biological breast cancer subtypes prompted the development of innovative targeted agents and improved treatment personalization. On the other hand, longer survival rates and increasing proportions of cured patients require dedicated strategies to manage long-term sequelae of breast cancer treatments, with particular attention to quality of life. This review analyzes the most important issues, potentially occurring with cancer treatments, concerning long-term sequelae and quality of life, to define a global approach to breast cancer survivorship.
PMID:32612947 | PMC:PMC7308500 | DOI:10.3389/fonc.2020.00864
03:16
PubMed articles on: Cancer & VTE/PE
End of an era of administering erythropoiesis stimulating agents among Veterans Administration cancer patients with chemotherapy-induced anemia
Hoque S, et al. PLoS One 2020.
ABSTRACT
Erythropoisis stimulating agent (ESA) use was addressed in Food and Drug Administration (FDA) Oncology Drug Advisory Committee (ODAC) meetings between 2004 and 2008. FDA safety-focused regulatory actions occurred in 2007 and 2008. In 2007, black box warnings advised of early death and venous thromboembolism (VTE) risks with ESAs in oncology. In 2010, a Risk Evaluation Strategies (REMS) was initiated, with cancer patient consent that mortality and VTE risks were noted with ESAs. We report warnings and REMS impacts on ESA utilization among Veterans Administration (VA) cancer patients with chemotherapy-induced anemia (CIA). Data were from Veterans Affairs database (2003-2012). Epoetin and darbepoetin use were primary outcomes. Segmented linear regression was used to estimate changes in ESA use levels and trends, clinical appropriateness, and adverse events (VTEs) among chemotherapy-treated cancer patients. To estimate changes in level of drug prescription rate after policy actions, model-specific indicator variables as covariates based on specific actions were included. ESA use fell by 95% and 90% from 2005, for epoetin and darbepoetin, from 22% and 11%, respectively, to 1% and 1%, respectively, among cancer patients with CIA, respectively (p<0.01).<0.01).
PMID:32584835 | PMC:PMC7316310 | DOI:10.1371/journal.pone.0234541
03:16
PubMed articles on: Cardio-Oncology
Rosuvastatin based novel 3-substituted isocoumarins / 3-alkylidenephthalides: Ultrasound assisted synthesis and identification of new anticancer agents
Kumar JS, et al. Eur J Med Chem 2020.
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