Articles de revues : « Cardioncologia »

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Penna, Claudia. « Redox and Nitrosative Signaling and Stress ». Antioxidants 9, n^o 12 (7 décembre 2020) : 1237. http://dx.doi.org/10.3390/antiox9121237.

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Todaro, Maria Chiara, Lilia Oreto, Rubina Qamar, Timothy E. Paterick, Scipione Carerj et Bijoy K. Khandheria. « Cardioncology : State of the heart ». International Journal of Cardiology 168, n^o 2 (septembre 2013) : 680–87. http://dx.doi.org/10.1016/j.ijcard.2013.03.133.

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Chatterjee, Shambhabi, Shashi Kumar Gupta, Christian Bär et Thomas Thum. « Noncoding RNAs : potential regulators in cardioncology ». American Journal of Physiology-Heart and Circulatory Physiology 316, n^o 1 (1 janvier 2019) : H160—H168. http://dx.doi.org/10.1152/ajpheart.00418.2018.

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Cancer is the leading cause of morbidity and mortality in the United States and globally. Owing to improved early diagnosis and advances in oncological therapeutic options, the number of cancer survivors has steadily increased. Such efficient cancer therapies have also lead to alarming increase in cardiovascular complications in a significant proportion of cancer survivors, due to adverse cardiovascular effects such as cardiotoxicity, cardiac atrophy, and myocarditis. This has emerged as a notable concern in healthcare and given rise to the new field of cardioncology, which aims at understanding the processes that occur in the two distinct disorders and how they interact to influence the progression of each other. A key player in both cancer and heart failure is the genome, which is predominantly transcribed to noncoding RNAs (ncRNAs). Since the emergence of ncRNAs as master regulators of gene expression, several reports have shown the relevance of ncRNAs in cancer and cardiovascular disorders. However, the knowledge is quite limited regarding the relevance of ncRNAs in cardioncology. The objective of this review is to summarize the current knowledge of ncRNAs in the context of cardioncology. Furthermore, the therapeutic strategies as well as the prospective translational applications of these ncRNA molecules to the clinics are also discussed.

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Cardinale, Daniela, Vincenzo Caruso et Carlo M. Cipolla. « The breast cancer patient in the cardioncology unit ». Journal of Thoracic Disease 10, S35 (décembre 2018) : S4306—S4322. http://dx.doi.org/10.21037/jtd.2018.10.06.

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Lestuzzi, C. « Cardioncology, oncocardiology. Are we barking up the wrong tree ? » International Journal of Cardiology 167, n^o 2 (juillet 2013) : 307–9. http://dx.doi.org/10.1016/j.ijcard.2013.04.148.

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Printz, Carrie. « International Cardioncology Society tackles heart problems in cancer patients ». Cancer 117, n^o 9 (20 avril 2011) : 1785–87. http://dx.doi.org/10.1002/cncr.26155.

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Throndson, K., D. Grantham et B. Laurila. « Nursing Collaboration to Improve Management of CardiOncology In-Patient Population ». Canadian Journal of Cardiology 32, n^o 10 (octobre 2016) : S330. http://dx.doi.org/10.1016/j.cjca.2016.07.582.

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Printz, Carrie. « Cardioncology pioneer sees promise in new drugs, case management approaches ». Cancer 117, n^o 9 (20 avril 2011) : 1787. http://dx.doi.org/10.1002/cncr.26157.

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Chazova, I. E., E. V. Oschepkova, M. Yu Kirillova et G. Ch Sharipova. « Cardioncology : management of arterial hypertension in patients with cancer on chemotherapy ». Systemic Hypertension 12, n^o 2 (15 juin 2015) : 6–7. http://dx.doi.org/10.26442/sg29054.

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Tarantini, L., A. Camerini, M. L. Canale, I. Bisceglia, D. Gabrielli, F. Colvicchi, M. M. Gulizia et A. Navazio. « THROUGH AND BEYOND COVID-19 PANDEMIC : A NEW SCENARIO FOR CARDIONCOLOGY ». Annals of Research in Oncology 01, n^o 04 (décembre 2021) : 303. http://dx.doi.org/10.48286/aro.2021.27.

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Sonaglioni, Andrea, Adriana Albini, Emanuela Fossile, Maria Adelaide Pessi, Gian Luigi Nicolosi, Michele Lombardo, Claudio Anzà et Giuseppe Ambrosio. « Speckle-Tracking Echocardiography for Cardioncological Evaluation in Bevacizumab-Treated Colorectal Cancer Patients ». Cardiovascular Toxicology 20, n^o 6 (9 juin 2020) : 581–92. http://dx.doi.org/10.1007/s12012-020-09583-5.

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Zamaldinov, N. D., S. A. Malamagomedova et A. O. Kelin. « Cardioncology of children’s patients : an interdisciplinary approach to treatment and supportive therapy ». CARDIOMETRY, n^o 23 (20 août 2022) : 54–57. http://dx.doi.org/10.18137/cardiometry.2022.23.5457.

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The paper investigates the features of an interdisciplinary approach in the field of treatment and supportive therapy of pediatric patients with oncological diagnoses having concomitant problems in the field of cardiology. The authors note that the formation of an interdisciplinary approach in the field of prevention and treatment of cardiopathologies in children with cancer will eliminate gaps in the knowledge of specialists and improve the results of treatment of children with cancer. Early detection of cardiovascular diseases and preventive initiation of drug treatment improves the quality of life as well as increases the long-term survival rates of such children.

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Федорец, Виктор Николаевич, София Фатхутдиновна Вершинина, Ирина Владиславовна Вологдина, Разифа Мидхатовна Жабина, Лариса Анатольевна Красильникова, Игорь Владимирович Овчинников et Владимир Станиславович Василенко. « Past, present and development possibility of cardiooncology ». Medicine : theory and practice, n^o 1 (16 mai 2022) : 3–12. http://dx.doi.org/10.56871/6211.2022.35.75.001.

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Материал посвящен новому междисциплинарному направлению «Кардиоонкология». Пациенты с онкологическими заболеваниями имеют повышенный риск развития сердечно -сосудистых осложнений, связанных с проводимой противоопухолевой терапией. В статье описаны исторические этапы применения противоопухолевого лечения, сопровождающегося возможным эффектом кардиотоксичности, представлено современное состояние проблемы и рассмотрены перспективы дальнейшего развития. Приведены данные российских и зарубежных исследований в этой области. The material is devoted to a new interdisciplinary direction “Cardioncology”. Patients with oncological diseases have an increased risk of developing cardiovascular complications associated with antitumor therapy. The article describes the historical stages of the use of antitumor treatment leading to the development of cardiotoxicity, presents the current state of the problem and considers the prospects for further development. The data of russian and foreign studies in this area are presented.

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Zambelli, Alberto, Matteo Della Porta et Vittorio Rosti. « From cancer patients to cancer survivors : The issue of Cardioncology – A biological perspective ». European Journal of Cancer 46, n^o 4 (mars 2010) : 697–702. http://dx.doi.org/10.1016/j.ejca.2009.12.011.

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Minotti, Giorgio. « The International Cardioncology Society–ONE trial : Not all that glitters is for cardioncologists only ». European Journal of Cancer 97 (juillet 2018) : 27–29. http://dx.doi.org/10.1016/j.ejca.2018.04.003.

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Kogoniya, L. M., M. O. Rusanov et V. E. Shikina. « Cardiotoxicity of anticancer drugs and radiotherapy in patients with hematologic malignancies and solid tumors ». Oncohematology 17, n^o 3 (20 juillet 2022) : 127–36. http://dx.doi.org/10.17650/1818-8346-2022-17-3-127-136.

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Cardioncology has emerged as a new field at the intersection of cardiology and oncology. Despite the fact that improving efficiency of antitumor treatment increased the survival of oncological hematological patients, the long-term cardiovascular consequences of this treatment have become more clinically significant.Despite the effectiveness of modern methods of treatment, some drugs, such as Bcr-Abl kinase inhibitors, anthracyclines, HER2/Erbb2 inhibitors, vascular endothelial growth factor inhibitors, fluoropyrimidines, as well as radiation therapy can have a pronounced effect on the cardiovascular system. These toxic effects lead to cardiac arrhythmia, heart failure, vascular toxicity and even death. It is important for hematologists, oncologists and cardiologists to understand the basic diagnostic and treatment strategies that should be used in the event of toxicity of this kind. At a time when, due to the developed cardiotoxicity, antitumor therapy should be discontinued, in some cases, it is possible to consider continuing treatment with caution and careful monitoring.

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Quagliariello, Vincenzo, Annamaria Bonelli, Antonietta Caronna, Gabriele Conforti, Martina Iovine, Andreina Carbone, Massimiliano Berretta, Gerardo Botti et Nicola Maurea. « SARS-CoV-2 Infection and Cardioncology : From Cardiometabolic Risk Factors to Outcomes in Cancer Patients ». Cancers 12, n^o 11 (10 novembre 2020) : 3316. http://dx.doi.org/10.3390/cancers12113316.

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The coronavirus disease-2019 (COVID-19) is a highly transmissible viral illness caused by SARS-CoV-2, which has been defined by the World Health Organization as a pandemic, considering its remarkable transmission speed worldwide. SARS-CoV-2 interacts with angiotensin-converting enzyme 2 and TMPRSS2, which is a serine protease both expressed in lungs, the gastro-intestinal tract, and cardiac myocytes. Patients with COVID-19 experienced adverse cardiac events (hypertension, venous thromboembolism, arrhythmia, myocardial injury, fulminant myocarditis), and patients with previous cardiovascular disease have a higher risk of death. Cancer patients are extremely vulnerable with a high risk of viral infection and more negative prognosis than healthy people, and the magnitude of effects depends on the type of cancer, recent chemotherapy, radiotherapy, or surgery and other concomitant comorbidities (diabetes, cardiovascular diseases, metabolic syndrome). Patients with active cancer or those treated with cardiotoxic therapies may have heart damages exacerbated by SARS-CoV-2 infection than non-cancer patients. We highlight the cardiovascular side effects of COVID-19 focusing on the main outcomes in cancer patients in updated perspective and retrospective studies. We focus on the main cardio-metabolic risk factors in non-cancer and cancer patients and provide recommendations aimed to reduce cardiovascular events, morbidity, and mortality.

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Lenihan, Daniel J., Daniela Cardinale et Carlo M. Cipolla. « The Compelling Need for a Cardiology and Oncology Partnership and the Birth of the International CardiOncology Society ». Progress in Cardiovascular Diseases 53, n^o 2 (septembre 2010) : 88–93. http://dx.doi.org/10.1016/j.pcad.2010.06.002.

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Quagliariello, Vincenzo, Irma Bisceglia, Massimiliano Berretta, Martina Iovine, Maria Laura Canale, Carlo Maurea, Vienna Giordano, Andrea Paccone, Alessandro Inno et Nicola Maurea. « PCSK9 Inhibitors in Cancer Patients Treated with Immune-Checkpoint Inhibitors to Reduce Cardiovascular Events : New Frontiers in Cardioncology ». Cancers 15, n^o 5 (22 février 2023) : 1397. http://dx.doi.org/10.3390/cancers15051397.

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Cancer patients treated with immune checkpoint inhibitors (ICIs) are exposed to a high risk of atherosclerosis and cardiometabolic diseases due to systemic inflammatory conditions and immune-related atheroma destabilization. Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a key protein involved in metabolism of low-density lipoprotein (LDL) cholesterol. PCSK9 blocking agents are clinically available and involve monoclonal antibodies, and SiRNA reduces LDL levels in high-risk patients and atherosclerotic cardiovascular disease events in multiple patient cohorts. Moreover, PCSK9 induces peripheral immune tolerance (inhibition of cancer cell- immune recognition), reduces cardiac mitochondrial metabolism, and enhances cancer cell survival. The present review summarizes the potential benefits of PCSK9 inhibition through selective blocking antibodies and siRNA in patients with cancer, especially in those treated with ICIs therapies, in order to reduce atherosclerotic cardiovascular events and potentially improve ICIs-related anticancer functions.

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Lenihan, Daniel J., Gregory Hartlage, Jeanne DeCara, Anne Blaes, J. Emanuel Finet, Alexander R. Lyon, Robert F. Cornell et al. « Cardio-Oncology Training : A Proposal From the International Cardioncology Society and Canadian Cardiac Oncology Network for a New Multidisciplinary Specialty ». Journal of Cardiac Failure 22, n^o 6 (juin 2016) : 465–71. http://dx.doi.org/10.1016/j.cardfail.2016.03.012.

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Semeraro, Gennaro Carmine, Carlo Maria Cipolla et Daniela Maria Cardinale. « Role of Cardiac Biomarkers in Cancer Patients ». Cancers 13, n^o 21 (29 octobre 2021) : 5426. http://dx.doi.org/10.3390/cancers13215426.

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In patients with cancer—and especially some specific subtypes—the heart can be pathologically affected due to the direct action of the tumor or its secretion products or due to the toxicity of some oncological treatments. Cardiac biomarkers have been investigated as inexpensive and easily accessible tools for prediction, early diagnosis, monitoring, or prognosis of various forms of cancer-related cardiac diseases. However, their clinical usefulness was not always clearly demonstrated in every area of cardioncology. For the identification of anthracycline related cardiotoxicity in the very early stages troponins proved to be more efficient detectors than imaging methods. Nevertheless, the lack of a standardized dosage methodology and of cardiotoxicity specific thresholds, do not yet allow to outline the precise way to employ them in clinical routine and to incorporate them into appropriate diagnostic or managing algorithms. Cardiac biomarkers proved also effective in patients with primary cardiac amyloidosis, in which both troponins and natriuretic peptides were able to predict adverse outcome, and carcinoid heart disease, where a precise diagnostic cut-off for N-terminal prohormone of brain natriuretic peptide (NT-proBNP) was identified to screen patients with valvular involvement. Likewise, NT-proBNP proved to be an excellent predictor of postoperative atrial fibrillation (POAF). On the contrary, evidence is still not sufficient to promote the routine use of cardiac biomarkers to early diagnose myocarditis due to immune check points inhibitors (ICIs), radiotherapy induced cardiotoxicity and cardiac complications related to androgenetic deprivation. In this review we present all the evidence gathered so far regarding the usefulness and limitations of these relatively inexpensive diagnostic tools in the field of cardio-oncology.

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Maurea, Nicola, irma bisceglia, Andrea Paccone, Simona Buccolo, Martina Iovine et Vincenzo Quagliariello. « DAPAGLIFLOZIN REDUCES SYSTEMIC PCSK9 LEVELS IN PRECLINICAL MODELS OF SHORT-TERM DOXORUBICIN CARDIOTOXICITY THROUGH NLRP3 INFLAMMASOME/IL-1β : A FIRST EVIDENCE OF SGLT-2/PCSK9 CROSS-TALK IN CARDIONCOLOGY ». Journal of the American College of Cardiology 81, n^o 8 (mars 2023) : 2269. http://dx.doi.org/10.1016/s0735-1097(23)02713-4.

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Quagliariello, Vincenzo, Manuela Giovanna Basilicata, Giacomo Pepe, Raffaele De Anseris, Annabella Di Mauro, Giosuè Scognamiglio, Giuseppe Palma et al. « Combination of Spirulina platensis, Ganoderma lucidum and Moringa oleifera Improves Cardiac Functions and Reduces Pro-Inflammatory Biomarkers in Preclinical Models of Short-Term Doxorubicin-Mediated Cardiotoxicity : New Frontiers in Cardioncology ? » Journal of Cardiovascular Development and Disease 9, n^o 12 (28 novembre 2022) : 423. http://dx.doi.org/10.3390/jcdd9120423.

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Anthracyclines are essential adjuvant therapies for a variety of cancers, particularly breast, gastric and esophageal cancers. Whilst prolonging cancer-related survival, these agents can induce drug-related cardiotoxicity. Spirulina, Reishi (Ganoderma lucidum) and Moringa are three nutraceuticals with anti-inflammatory effects that are currently used in cancer patients as complementary and alternative medicines to improve quality of life and fatigue. We hypothesize that the nutraceutical combination of Spirulina, Reishi and Moringa (Singo) could reduce inflammation and cardiotoxicity induced by anthracyclines. Female C57Bl/6 mice were untreated (Sham, n = 6) or treated for 7 days with short-term doxorubicin (DOXO, n = 6) or Singo (Singo, n = 6), or pre-treated with Singo for 3 days and associated with DOXO for remaining 7 days (DOXO–Singo, n = 6). The ejection fraction and radial and longitudinal strain were analyzed through transthoracic echocardiography (Vevo 2100, Fujifilm, Tokyo, Japan). The myocardial expressions of NLRP3, DAMPs (galectin-3 and calgranulin S100) and 13 cytokines were quantified through selective mouse ELISA methods. Myocardial fibrosis, necrosis and hypertrophy were analyzed through immunohistochemistry (IHC). Human cardiomyocytes were exposed to DOXO (200 nM) alone or in combination with Singo (at 10, 25 and 50 µg/mL) for 24 and 48 h. Cell viability and inflammation studies were also performed. In preclinical models, Singo significantly improved ejection fraction and fractional shortening. Reduced expressions of myocardial NLRP3 and NF-kB levels in cardiac tissues were seen in DOXO–Singo mice vs. DOXO (p < 0.05). The myocardial levels of calgranulin S100 and galectin-3 were strongly reduced in DOXO–Singo mice vs. DOXO (p < 0.05). Immunohistochemistry analysis indicates that Singo reduces fibrosis and hypertrophy in the myocardial tissues of mice during exposure to DOXO. In conclusion, in the preclinical model of DOXO-induced cardiotoxicity, Singo is able to improve cardiac function and reduce biomarkers involved in heart failure and fibrosis.

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Madeira Timóteo Dias, Isabela Carolina, Eloá Carneiro Carvalho, Ana Lúcia Cascardo Marins, Andrezza Serpa Franco, Norma Valéria Dantas de Oliveira Souza et Karla Biancha Silva de Andrade. « Avaliação de risco para tromboembolismo venoso : estudo bibliométrico para a prática clínica de cardioncologia ». Revista Enfermagem Atual In Derme 96, n^o 39 (15 septembre 2022). http://dx.doi.org/10.31011/reaid-2022-v.96-n.39-art.1438.

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Objetivo: identificar as produções científicas acerca das estratégias de avaliação de risco para tromboembolismo venoso, para aplicação pelo enfermeiro no cuidado ao paciente oncológico. Métodos: trata-se de uma pesquisa de revisão, tipo bibliométrica, de natureza descritiva e abordagem quantitativa. Resultados: foram encontradas 133 publicações e selecionados 34 textos após análise conforme os critérios de inclusão. Dos 34 artigos que participaram da pesquisa, 23 (67,6%) trabalharam com aplicação de escalas de avaliação de risco para tromboembolismo venoso, onde 14 (41,2%) abordavam o escore de Khorana. Conclusão: Apesar de existir produção científica sobre as estratégias de avaliação de risco para tromboembolismo venoso, a diversidade de modelos e biomarcadores de predição de risco pode dificultar a escolha pelo profissional enfermeiro no cuidado ao paciente oncológico

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« Cardioncology and Cardiotoxicity ». European Heart Journal Supplements 21, Supplement_J (1 décembre 2019) : J39—J44. http://dx.doi.org/10.1093/eurheartj/suz248.

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Cardinale, Daniela, Michela Salvatici et Maria T. Sandri. « Role of biomarkers in cardioncology ». Clinical Chemistry and Laboratory Medicine (CCLM) 49, n^o 12 (1 janvier 2011). http://dx.doi.org/10.1515/cclm.2011.692.

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AbstractCardiotoxicity is a serious adverse effect of anticancer drugs, impacting on quality of life and overall survival of cancer patients. According to the current standard for monitoring cardiac function, cardiotoxicity is usually detected only when a functional impairment has already occurred, precluding any chance of preventing its development. Over the last decade, however, a new approach, based on the use of cardiac biomarkers, has emerged, and has proven to be an effective alternative strategy for early detection of subclinical cardiac injury. In particular, the role of troponin I in identifying patients at risk of cardiotoxicity and of angiotensin-converting enzyme inhibitors in preventing left ventricular ejection fraction reduction and late cardiac events represent an effective tool for the prevention of this complication.

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Chazova, I. E., E. V. Oschepkova, M. Yu Kirillova et G. Ch Sharipova. « Cardioncology : management of arterial hypertension in patients with cancer on chemotherapy ». Systemic Hypertension 12, n^o 2 (2015). http://dx.doi.org/10.26442/2075-082x_12.2.6-7.

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Tlegenova, Zhenisgul, et Saule Balmagambetova. « Comments on new 2022 European Society of Cardiology guidelines on cardioncology ». Heart, Vessels and Transplantation, Ahead of Print (21 janvier 2023). http://dx.doi.org/10.24969/hvt.2023.370.

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Magnesa, Michele, Grazia Casavecchia, Roberta Barone, Mariolina Riccardo, Delia Corbo et Natale Daniele Brunetti. « 682 Cardioncology : is it time to spread the need for dedicated management ? » European Heart Journal Supplements 23, Supplement_G (1 décembre 2021). http://dx.doi.org/10.1093/eurheartj/suab130.001.

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Abstract Case report A 56-year-old man affected by micromolecular multiple myeloma was treated by several cycles of different chemotherapy drugs from September 2015 to December 2020. The chemotherapy regimen included 4-cycle first-line therapy with Bortezomib, Thalidomide, and Dexamethasone; 19-cycle second-line therapy with Carfilzomib, Revlimid, and Dexamethasone; 8-cycle third-line therapy with Daratumumab, Revlimid, and Dexamethasone; finally, he was started on therapy with Pomalidomide and Endoxan. During the various treatments, the patient did not follow a dedicated cardiological follow-up programme. In November 2020, he was hospitalized in the Intensive Care Unit for acute pulmonary oedema and subsequently discharged with a diagnosis of mild left ventricular systolic dysfunction (LVEF 50%). One month later, due to the worsening of dyspnoea, the patient was finally referred to our Cardioncology Unit for the medical assessment. The echocardiographic examination revealed a global and severe left ventricular dysfunction (FE 40%) with significant reduction in left ventricular global longitudinal strain (GLS −10%). For these reasons, we referred the patient to coronary angiography. Conclusions This case report wants to underline how important a dedicated cardiological follow-up is in patients undergoing chemotherapy drugs, especially if used at high doses and for many cycles.

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Cardinale, Daniela, Gina Biasillo et Carlo Maria Cipolla. « Curing Cancer, Saving the Heart : A Challenge That Cardioncology Should Not Miss ». Current Cardiology Reports 18, n^o 6 (23 avril 2016). http://dx.doi.org/10.1007/s11886-016-0731-z.

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Chianca, Michela, Iacopo Fabiani, Annamaria Del Franco, Chrysanthos Grigoratos, Alberto Aimo, Giorgia Panichella, Alberto Giannoni et al. « Management and treatment of cardiotoxicity due to anticancer drugs : 10 questions and answers ». European Journal of Preventive Cardiology, 8 août 2022. http://dx.doi.org/10.1093/eurjpc/zwac170.

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Abstract Since the introduction of anthracyclines into clinical practice in the 1960s, chemotherapy have always been associated to cardiotoxicity. Patients on cardiotoxic drugs can develop a wide range of cardiovascular diseases, including left ventricular (LV) systolic dysfunction and heart failure (HF), arrhythmias, hypertension, and coronary artery disease (CAD). The rising number of cancer patients, population aging, and the frequent overlap of cardiovascular and oncological diseases have highlighted the importance of close collaboration between cardiologists and oncologists. As a result, in 1995, cardiologists at the IEO (European Institute of Oncology) coined the term cardioncology, a new discipline focused on the dynamics of cardiovascular disease in cancer patients. Given the complex scenario characterized by a constant dialogue between the oncological condition and cardiovascular comorbidity, it is essential for the clinician to get the knowledge to properly fulfill the needs of the oncological patient under cardiotoxic treatment. Through the answer to 10 questions, we aim to describe the complex issue of cardiotoxicity by addressing the main critical points and current evidence related to the assessment, management, treatment and surveillance of cancer patients under chemotherapy.

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Fabiani, Iacopo, Carlo Maria Cipolla, Nicola Colombo et Daniela Cardinale. « Cardioncological Approach for Trastuzumab Therapy in Breast Cancer Patients With Cardiotoxicity : Impact on Adherence and Clinical Outcome ». Frontiers in Pharmacology 11 (4 août 2020). http://dx.doi.org/10.3389/fphar.2020.01190.

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Di Lisi, Daniela, Cristina Madaudo, Alfredo Ruggero Galassi et Giuseppina Novo. « Higher Incidence of Chemotherapy-Related Cardiac Dysfunction after Third Wave COVID-19 Pandemic : A Single Cardioncology Centre Experience ». SSRN Electronic Journal, 2022. http://dx.doi.org/10.2139/ssrn.4055863.

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Quagliariello, Vincenzo, Margherita Passariello, Annabella Di Mauro, Ciro Cipullo, Andrea Paccone, Antonio Barbieri, Giuseppe Palma et al. « Immune checkpoint inhibitor therapy increases systemic SDF-1, cardiac DAMPs Fibronectin-EDA, S100/Calgranulin, galectine-3, and NLRP3-MyD88-chemokine pathways ». Frontiers in Cardiovascular Medicine 9 (8 septembre 2022). http://dx.doi.org/10.3389/fcvm.2022.930797.

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BackgroundImmune checkpoint inhibitors (ICIs) have significantly changed the oncology clinic in recent years, improving survival expectations in cancer patients. ICI therapy have a broad spectrum of side effects from endocrinopathies to cardiovascular diseases. In this study, pro-inflammatory and pro-fibrotic effects of short-term ICIs therapy in preclinical models were analyzed.MethodsFirstly, in a human in vitro model, human cardiomyocytes co-cultured with hPBMC were exposed to ICIs (with CTLA-4 or PD-1 blocking agents, at 200 nM) for 72 h. After treatment, production of DAMPs and 12 cytokines were analyzed in the supernatant through colorimetric and enzymatic assays. C57/Bl6 mice were treated with CTLA-4 or PD-1 blocking agents (15 mg/kg) for 10 days. Before (T0), after three days (T3) and after treatments (T10), ejection fraction, fractional shortening, radial and longitudinal strain were calculated by using bidimensional echocardiography (Vevo 2100, Fujfilm). Fibrosis, necrosis, hypertrophy and vascular NF-kB expression were analyzed through Immunohistochemistry. Myocardial expression of DAMPs (S100- Calgranulin, Fibronectin and Galectine-3), MyD88, NLRP3 and twelve cytokines have been analyzed. Systemic levels of SDF-1, IL-1β, and IL-6 were analyzed before, during and after ICIs therapy.ResultsRadial and longitudinal strain were decreased after 10 days of ICIs therapy. Histological analysis of NF-kB expression shows that short-term anti-CTLA-4 or anti-PD-1 treatment increased vascular and myocardial inflammation. No myocardial hypertrophy was seen with the exception of the pembrolizumab group. Myocardial fibrosis and expression of galectin-3, pro-collagen 1-α and MMP-9 were increased after treatment with all ICIs. Both anti-CTLA-4 or anti-PD-1 treatments increased the expression of DAMPs, NLRP3 inflammasome and MyD88 and induced both in vitro and in vivo the secretion of IL-1β, TNF-α and IL-6. Systemic levels of SDF-1, IL-1β and IL-6 were increased during and after treatment with ICIs.ConclusionsShort therapy with PD-1 and CTLA-4 blocking agents increases vascular expression of NF-kB, systemic SDF-1, IL-1β, IL-6 levels and myocardial NLRP3, MyD88 and DAMPs expression in preclinical models. A pro-inflammatory cytokine storm was induced in myocardial tissues and in cultured cardiac cells after ICIs therapy. The overall picture of the study suggests new putative biomarkers of ICIs-mediated systemic and myocardial damages potentially useful in clinical cardioncology.

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Quagliariello, Vincenzo, Margherita Passariello, Annabella Di Mauro, Ciro Cipullo, Andrea Paccone, Antonio Barbieri, Giuseppe Palma et al. « 201 CTLA-4 AND PD-1 BLOCKING AGENTS INCREASES SYSTEMIC SDF-1, CARDIAC DAMPS FIBRONECTIN EDA, S-100 CALGRANULIN, GALECTINE-3 AND NLRP-3/MYD-88 CHEMOKINE PATHWAYS ». European Heart Journal Supplements 24, Supplement_K (14 décembre 2022). http://dx.doi.org/10.1093/eurheartjsupp/suac121.133.

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Abstract Background Immune checkpoint inhibitors (ICIs) have significantly changed the oncology clinic in recent years, improving survival expectations in cancer patients. ICI therapy have a broad spectrum of side effects from endocrinopathies to cardiovascular diseases.In this study, pro-inflammatory and pro-fibrotic effects of short-term ICIs therapy in preclinical models were analyzed. Methods Firstly, in a human in vitro model, human cardiomyocytes co-cultured with hPBMC were exposed to ICIs (with CTLA-4 or PD-1 blocking agents, at 200 nM) for 72h. After treatment, production of DAMPs and 12 cytokines were analyzed in the supernatant through colorimetric and enzymatic assays. C57/Bl6 mice were treated with CTLA-4 or PD-1 blocking agents (15 mg/kg) for 10 days. Before (T0), after three days (T3) and after treatments (T10), ejection fraction, fractional shortening, radial and longitudinal strain were calculated by using bidimensional echocardiography (Vevo 2100,Fujfilm). Fibrosis, necrosis, hypertrophy and vascular NF-kB expression were analyzed through Immunohistochemistry. Myocardial expression of DAMPs (S100- Calgranulin, Fibronectin and Galectine-3), MyD88, NLRP3 and twelve cytokines have been analyzed. Systemic levels of SDF-1, IL-1β and IL-6 were analyzed before, during and after ICIs therapy. Results Radial and longitudinal strain were decreased after 10 days of ICIs therapy. Histological analysis of NF-kB expression shows that short-term anti-CTLA-4 or anti-PD-1 treatment increased vascular and myocardial inflammation. No myocardial hypertrophy was seen with the exception of the pembrolizumab group. Myocardial fibrosis and expression of galectin-3, pro-collagen 1-α and MMP-9 were increased after treatment with all ICIs. Both anti-CTLA-4 or anti-PD-1 treatments increased the expression of DAMPs, NLRP3 inflammasome and MyD88 and induced both in vitro and in vivo the secretion of IL-1β, TNF-α and IL-6. Systemic levels of SDF-1, IL-1β and IL-6 were increased during and after treatment with ICIs. Conclusions Short therapy with PD-1 and CTLA-4 blocking agents increases vascular expression of NF-kB, systemic SDF-1, IL-1β, IL-6 levels and myocardial NLRP3, MyD88 and DAMPs expression in preclinical models. A pro-inflammatory cytokine storm was induced in myocardial tissues and in cultured cardiac cells after ICIs therapy. The overall picture of the study suggests new putative biomarkers of ICIs-mediated systemic and myocardial damages potentially useful in clinical cardioncology.

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