Skip to main content

Cardiotoxicity of novel anti-cancer therapies

The cardiotoxicity of cancer treatments is a significant research space in the cardio-oncology field. 

For this Cardio-Oncology article collection, we welcome submissions examining cardiotoxicity caused by chemotherapy, radiotherapy, molecular-targeted agents, and immune-modulating agents. Manuscripts investigating cardiotoxicity related to novel cancer treatments will be highly appreciated.

Submissions can be made through the journal's editorial management system. 
Articles published in the collection have already gone through the systematic peer review process of the journal.

New Content Item

 

Page 1 of 2

  1. Breast cancer is estimated to comprise about 290,560 new cases in 2022. Aromatase inhibitors (AIs) are recommended as adjuvant treatment for estrogen-receptor positive (ER+) breast carcinoma in postmenopausal ...

    Authors: Adnan Shaaban, Ashley Petersen, Heather Beckwith, Natalia Florea, David A. Potter, Douglas Yee, Rachel I. Vogel, Daniel Duprez and Anne H. Blaes
    Citation: Cardio-Oncology 2024 10:27
    Content type: Research Published on:

  2. Anthracyclines can cause left ventricular (LV) dysfunction. There is little data about right ventricular (RV) damage during chemotherapy.

    Authors: Ludovico Rossetto, Daniela Di Lisi, Cristina Madaudo, Francesco Paolo Sinagra, Antonio Di Palermo, Oreste Fabio Triolo, Grazia Gambino, Antonella Ortello, Alfredo Ruggero Galassi and Giuseppina Novo
    Citation: Cardio-Oncology 2024 10:24
    Content type: Research Published on:

  3. Panitumumab is a human immunoglobulin monoclonal antibody designed to target the epidermal growth factor receptor (EGFR) which is used in the treatment of metastatic colorectal cancer alone or in combination w...

    Authors: Isabelle Senechal, Nikolaos Vogiatzakis, Maria Sol Andres, Jieli Tong, Sivatharshini Ramalingam, Stuart D Rosen, Alexander R Lyon and Muhummad Sohaib Nazir
    Citation: Cardio-Oncology 2024 10:23
    Content type: Case Report Published on:

  4. Chimeric Antigen Receptor-T (CAR-T) cell infusion is a rapidly evolving antitumor therapy; however, cardiovascular (CV) complications, likely associated with cytokine release syndrome (CRS) and systemic inflam...

    Authors: Massimiliano Camilli, Marcello Viscovo, Tamara Felici, Luca Maggio, Federico Ballacci, Giacomo Carella, Alice Bonanni, Priscilla Lamendola, Lorenzo Tinti, Antonio Di Renzo, Giulia Coarelli, Eugenio Galli, Giovanna Liuzzo, Francesco Burzotta, Rocco Antonio Montone, Federica Sorà…
    Citation: Cardio-Oncology 2024 10:18
    Content type: Research Published on:

  5. Capecitabine, a pro-drug of 5-fluorouracil, is commonly used in the treatment of breast and colorectal cancer. Its side effects, including nausea, vomiting, diarrhea, fatigue, loss of appetite, and bone marrow...

    Authors: Maciej Kabat, Roma Padalkar, Sara Hazaveh, Vladimir Joseph, David Feigenblum and Sean Sadikot
    Citation: Cardio-Oncology 2024 10:11
    Content type: Case Report Published on:

  6. Cardiotoxicity is one of the most common adverse events of the chemotherapy. Physical exercise was shown to be cardioprotective. We aim to estimate the efficacy and safety of exercise in cancer patients receiv...

    Authors: Ahmed Mazen Amin, Yehya Khlidj, Mohamed Abuelazm, Ahmed A. Ibrahim, Mohammad Tanashat, Muhammad Imran, Abubakar Nazir, Hosam Shaikhkhalil and Basel Abdelazeem
    Citation: Cardio-Oncology 2024 10:10
    Content type: Review Published on:

  7. This article provides an up-to-date overview of pericardial effusion in oncological practice and a guidance on its management. Furthermore, it addresses the question of when malignancy should be suspected in c...

    Authors: S. Mori, M. Bertamino, L. Guerisoli, S. Stratoti, C. Canale, P Spallarossa, I. Porto and P. Ameri
    Citation: Cardio-Oncology 2024 10:8
    Content type: Review Published on:

  8. Early identification of patients susceptible to chemotherapy-induced cardiotoxicity could lead to targeted treatment to reduce cardiac dysfunction. Rats treated with doxorubicin (DOX), a chemotherapeutic agent...

    Authors: Julia Matzenbacher dos Santos, Aby Joiakim, David A. Putt, Marielle Scherrer-Crosbie and Hyesook Kim
    Citation: Cardio-Oncology 2023 9:47
    Content type: Research Published on:

  9. Antineoplastic monoclonal antibodies (mAbs), such as trastuzumab, bevacizumab, and pertuzumab have been the mainstay of therapy in cancer patients. Despite proven efficacy of the monoclonal antibodies, cardiov...

    Authors: Abdulrazaq S. Al-Jazairi, Nahlah Bahammam, Dhai Aljuaid, Lama Almutairi, Shroog Alshahrani, Norah Albuhairan, Peter M. B. Cahusac and Ghazwa B. Korayem
    Citation: Cardio-Oncology 2023 9:35
    Content type: Research Published on:

  10. Immune checkpoint inhibitor (ICI) myocarditis is associated with significant mortality risk. Electrocardiogram (ECG) changes in ICI myocarditis have strong prognostic value. However the impact of complete hear...

    Authors: Michael P. O’Shea, Suganya Arunachalam Karikalan, Ali Yusuf, Timothy Barry, Eiad Habib, John O’Shea, Michael Killian, Eman Baqal, Srishti Nayak, Rajeev Masson, Joerg Hermann, Shimoli Shah, Chadi Ayoub and Hicham El Masry
    Citation: Cardio-Oncology 2023 9:34
    Content type: Research Published on:

  12. Biomarkers represent a potential tool to identify individuals at risk for anthracycline-induced cardiotoxicity (AICT) prior to symptom onset or left ventricular dysfunction.

    Authors: Matthew Dean, Min Jung Kim, Sharon Dimauro, Susan Tannenbaum, Garth Graham, Bruce T. Liang and Agnes S. Kim
    Citation: Cardio-Oncology 2023 9:23
    Content type: Research Published on:

  14. Many ca. survivors exhibit signs of IR, an important risk factor for the development of CAD. CAC scans offer a risk assessment of CV disease before cardiac damage has occurred. We investigated how IR affects C...

    Authors: N. Jacobi, S. Ortman, L. Buda and Daniel Duprez
    Citation: Cardio-Oncology 2023 9:21
    Content type: Research Published on:

  15. Despite the cardiotoxic effect of anthracycline on the left ventricle (LV) was totally identified. The assessment of the anthracycline effect on the right ventricle(RV) by conventional echocardiography was a c...

    Authors: Wafaa S. El-Sherbeny, Nesreen M. Sabry, Shaimaa B. El-Saied and Basma Elnagar
    Citation: Cardio-Oncology 2023 9:20
    Content type: Research Published on:

  16. Chimeric antigen receptor T- Cell (CAR-T) immunotherapy has been a breakthrough treatment for various hematological malignancies. However, cardiotoxicities such as new-onset heart failure, arrhythmia, acute co...

    Authors: Dae Hyun Lee, Sanjay Chandrasekhar, Michael D. Jain, Rahul Mhaskar, Kayla Reid, Sae Bom Lee, Salvatore Corallo, Melanie J. Hidalgo-Vargas, Abhishek Kumar, Julio Chavez, Bijal Shah, Aleksandr Lazaryan, Farhad Khimani, Taiga Nishihori, Christina Bachmeier, Rawan Faramand…
    Citation: Cardio-Oncology 2023 9:18
    Content type: Research Published on:

  17. Cancer patients receiving chemotherapy have an increased risk of cardiovascular complications. This limits the widespread use of lifesaving therapies, often necessitating alternate lower efficacy regimens, or ...

    Authors: Ali Mir, Yasra Badi, Seif Bugazia, Anas Zakarya Nourelden, Ahmed Hashem Fathallah, Khaled Mohamed Ragab, Mohammed Alsillak, Sarah Makram Elsayed, Abdulrahman Ibrahim Hagrass, Sawyer Bawek, Mohamad Kalot and Zachary L. Brumberger
    Citation: Cardio-Oncology 2023 9:10
    Content type: Review Published on:

  18. Prostate cancer has a very high prevalence among elder men, and this could potentially increase as longevity in many parts of the world is increasing. Early stages of prostate cancer can have surgical options,...

    Authors: Aswini Kumar, Aswanth Reddy and Arjun Sekar
    Citation: Cardio-Oncology 2023 9:9
    Content type: Case Report Published on:

  19. Immune checkpoint inhibitors (ICI) are associated with immune-mediated adverse effects, potentially involving any organ. ICI has also been associated with an increased risk of cardiovascular disease in cancer ...

    Authors: Charlie Wang, Sophia Zoungas, Mabel Yan, Rory Wolfe, Andrew Haydon, Mark Shackleton, Mark Voskoboynik, Maggie Moore, Miles C. Andrews, Stephen J. Nicholls and Victoria Mar
    Citation: Cardio-Oncology 2022 8:23
    Content type: Research Published on:

  20. The full range of cardiovascular complications related to the use of Immune checkpoint inhibitors (ICI) is not fully understood. We aim to describe the spectrum of cardiovascular adverse events (cvAEs) by pres...

    Authors: Maria Sol Andres, Sivatharshini Ramalingam, Stuart D. Rosen, John Baksi, Rajdeep Khattar, Yulia Kirichenko, Kate Young, Nadia Yousaf, Alicia Okines, Robert Huddart, Kevin Harrington, Andrew J.S. Furness, Samra Turajlic, Lisa Pickering, Sanjay Popat, James Larkin…
    Citation: Cardio-Oncology 2022 8:21
    Content type: Research Published on:

  21. We report the case of a 59-year-old female patient with no previous cardiovascular disease treated for Breast cancer with Capecitabine. Shortly after starting treatment, she developed recurrent angina. An exer...

    Authors: George B. Strobel, Shiva P. Ponamgi, Attila Roka and Ahmed S. A. Aboeata
    Citation: Cardio-Oncology 2022 8:19
    Content type: Case Report Published on:

  22. Acute pericarditis is caused by the inflammation of the pericardium which can result in an effusion around the heart. Proton beam therapy causing radiation-induced pericarditis is not a well-known cause of per...

    Authors: Rahul Gupta, Muling Lin, Gary M. Freedman, Deborah W. Sundlof and Cheri Silverstein Fadlon
    Citation: Cardio-Oncology 2022 8:9
    Content type: Correspondence Published on:

  23. Androgen deprivation therapy (ADT) and radiotherapy (RT) are the mainstay treatment for localized prostate cancer and recurrence after surgery. Cardiovascular (CV) toxicity of ADT is increasingly recognized, a...

    Authors: Youquan Li, Whee Sze Ong, Ma Than Than Shwe, Nelson Ling Fung Yit, Sheriff Zhan Hong Quek, Eric Pei Ping Pang, Wen Shen Looi, Wen Long Nei, Michael Lian Chek Wang, Melvin Lee Kiang Chua, Terence Wee Kiat Tan, Eu Tiong Chua, Choon Ta Ng and Jeffrey Kit Loong Tuan
    Citation: Cardio-Oncology 2022 8:4
    Content type: Research Published on:

  24. Checkpoint-inhibitor immunotherapies have had a profound effect in the treatment of cancer by inhibiting down-regulation of T-cell response to malignancy. The cardiotoxic potential of these agents was first de...

    Authors: Zachary L. Brumberger, Mary E. Branch, Max W Klein, Austin Seals, Michael D. Shapiro and Sujethra Vasu
    Citation: Cardio-Oncology 2022 8:3
    Content type: Research Published on:

  25. Ibrutinib is a Bruton’s tyrosine kinase inhibitor used in the treatment of hematological malignancies. The most common cardiotoxicity associated with ibrutinib is atrial arrhythmia (atrial fibrillation and flu...

    Authors: Juan Carlo Avalon, Jacob Fuqua, Tyler Miller, Seth Deskins, Chelby Wakefield, Austin King, Sonya Inderbitzin-Brooks, Christopher Bianco, Lauren Veltri, Wei Fang, Michael Craig, Abraham Kanate, Kelly Ross, Midhun Malla and Brijesh Patel
    Citation: Cardio-Oncology 2021 7:38
    Content type: Research Published on:

  26. Gilteritinib is a novel FMS-like tyrosine kinase 3 inhibitor recently approved by the United States Food and Drug Administration in 2018 for relapsed or refractory acute myeloid leukemia. However, gilteritinib...

    Authors: Lisa Kim, Brian Fowler, Courtney M. Campbell, Jeremy Slivnick, Haseeb Nawaz, Yaquta Kaka, Patrick Ruz, Ajay Vallakati, Ragavendra Baliga, Sumithira Vasu and Daniel Addison
    Citation: Cardio-Oncology 2021 7:36
    Content type: Case report Published on:

  27. Recent advances in the treatment algorithms of early breast cancer have markedly improved overall survival. However, anthracycline- and trastuzumab-associated cardiotoxicity may lead to dose-reduction or halt ...

    Authors: A Mecinaj, G Gulati, SL Heck, E Holte, MW Fagerland, AI Larsen, E.S Blix, J Geisler, T Wethal and T Omland
    Citation: Cardio-Oncology 2021 7:33
    Content type: Research Published on:

  28. Modern therapies in oncology have increased cancer survivorship, as well as the incidence of cardiovascular adverse events. While immune checkpoint inhibitors have shown significant clinical impact in several ...

    Authors: Jessica Castrillon Lal, Sherry-Ann Brown, Patrick Collier and Feixiong Cheng
    Citation: Cardio-Oncology 2021 7:19
    Content type: Research Published on:

  29. The CBR3 V244M single nucleotide polymorphism has been linked to the risk of anthracycline-related cardiomyopathy in survivors of childhood cancer. There have been limited prospective studies examining the impact...

    Authors: Jennifer K. Lang, Badri Karthikeyan, Adolfo Quiñones-Lombraña, Rachael Hageman Blair, Amy P. Early, Ellis G. Levine, Umesh C. Sharma, Javier G. Blanco and Tracey O’Connor
    Citation: Cardio-Oncology 2021 7:17
    Content type: Research Published on:

  30. Breast cancer is the most common female cancer worldwide. Effective therapies including doxorubicin and trastuzumab have improved survival, but are associated with a substantial risk of cardiovascular disease....

    Authors: Rebecca K. Hoffman, Bang-Jin Kim, Payal D. Shah, Joseph Carver, Bonnie Ky and Sandra Ryeom
    Citation: Cardio-Oncology 2021 7:15
    Content type: Research Published on:

  31. Trastuzumab reduces risk of breast cancer recurrence but carries risk of cardiotoxicity that may be reversible upon treatment cessation and institution of left ventricular (LV) enhancement therapies (LVETx). W...

    Authors: Ren Jie Robert Yao, Jordan Gibson, Christine Simmons and Margot K. Davis
    Citation: Cardio-Oncology 2021 7:12
    Content type: Research Published on:

  32. Immune checkpoint inhibitors (ICIs) are a novel class of anticancer agents that have demonstrated clinical response for both solid and hematological malignancies. ICIs are associated with development of immune...

    Authors: Nida Waheed, Michael G. Fradley, David L. DeRemer, Ahmad Mahmoud, Chintan P. Shah, Taimour Y. Langaee, Gloria P. Lipori, Keith March, Carl J. Pepine, Rhonda M. Cooper-DeHoff, Yonghui Wu and Yan Gong
    Citation: Cardio-Oncology 2021 7:10
    Content type: Research Published on:

  33. Cancer therapy-related cardiac dysfunction (CTRD) is a major source of morbidity and mortality in long-term cancer survivors. Decreased GLS predicts decreased left ventricular ejection fraction (LVEF) in patie...

    Authors: Raquel Araujo-Gutierrez, Kalyan R. Chitturi, Jiaqiong Xu, Yuanchen Wang, Elizabeth Kinder, Alpana Senapati, L. Bindu Chebrolu, Mahwash Kassi and Barry H. Trachtenberg
    Citation: Cardio-Oncology 2021 7:4
    Content type: Research Published on:

  34. Trastuzumab-induced cardiotoxicity (TIC) can lead to early discontinuation of adjuvant therapy, however there is limited evidence on long-term survival outcomes in patients with operable human epidermal growth...

    Authors: Sagar Sardesai, Jasmine Sukumar, Mahmoud Kassem, Marilly Palettas, Julie Stephens, Evan Morgan, Daniel Addison, Ragavendra Baliga, Daniel G. Stover, Jeffrey VanDeusen, Nicole Williams, Mathew Cherian, Maryam Lustberg, Robert Wesolowski and Bhuvaneswari Ramaswamy
    Citation: Cardio-Oncology 2020 6:26
    Content type: Research Published on:

  35. Cancer therapy-related cardiac dysfunction (CTRCD) is a critical problem with an impact on both oncological and cardiovascular prognosis, especially when it prevents patients from receiving cancer treatment. S...

    Authors: Vanesa Gregorietti, Teresa Lopez Fernandez, Diego Costa, Elías Ortega Chahla and Andrés J. Daniele
    Citation: Cardio-Oncology 2020 6:24
    Content type: Research Published on:

    The Short communication to this article has been published in Cardio-Oncology 2020 6:25

  36. Proteasome inhibitors such as carfilzomib are indicated in multiple myeloma patients showing relapse and/or refractoriness of clonal activity. However, this therapy has been associated with a significant incid...

    Authors: Arnold Méndez-Toro, Cándida Díaz-Brochero and Estivalis Acosta-Gutiérrez
    Citation: Cardio-Oncology 2020 6:17
    Content type: Short communication Published on:

  37. Doxorubicin remains one of the most common causes of cardiotoxicity in patients with lymphoma, leading to significant morbidity and mortality. Early decline in left ventricular (LV) ejection fraction predicts ...

    Authors: Maria Isabel Camara Planek, Ahmad Manshad, Kyaw Hein, Mohamad Hemu, Fatima Ballout, Rajiv Varandani, Parameswaran Venugopal and Tochukwu Okwuosa
    Citation: Cardio-Oncology 2020 6:10
    Content type: Research Published on:

  38. Anthracyclines are a mainstay of chemotherapy. However, a relatively frequent adverse outcome of anthracycline treatment is cardiomyopathy. Multiple genetic studies have begun to dissect the complex genetics u...

    Authors: Timothy N. McOwan, Lauren A. Craig, Anne Tripdayonis, Kathy Karavendzas, Michael M. Cheung, Enzo R. Porrello, Rachel Conyers and David A. Elliott
    Citation: Cardio-Oncology 2020 6:5
    Content type: Research Published on:

  39. Irradiation of the heart during cancer radiotherapy is associated with a dose-dependent risk of heart failure. Animal studies have demonstrated that irradiation leads to an inflammatory response within the hea...

    Authors: Justin M. Canada, Georgia K. Thomas, Cory R. Trankle, Salvatore Carbone, Hayley Billingsley, Benjamin W. Van Tassell, Ronald K. Evans, Ryan Garten, Elisabeth Weiss and Antonio Abbate
    Citation: Cardio-Oncology 2020 6:2
    Content type: Short communication Published on:

  40. Continuous infusion of doxorubicin or dexrazoxane pre-treatment prior to bolus doxorubicin are proven strategies to protect against doxorubicin-induced cardiotoxicity. Recently, global longitudinal peak systol...

    Authors: Jieli Li, Hui-Ming Chang, Jose Banchs, Dejka M. Araujo, Saamir A. Hassan, Elizabeth A. Wagar, Edward T. H. Yeh and Qing H. Meng
    Citation: Cardio-Oncology 2020 6:1
    Content type: Research Published on:

  41. Cancer diagnostics and therapies have improved steadily over the last few decades, markedly increasing life expectancy for patients at all ages. However, conventional and newer anti-neoplastic therapies can ca...

    Authors: Neha Bansal, M. Jacob Adams, Sarju Ganatra, Steven D. Colan, Sanjeev Aggarwal, Rudolf Steiner, Shahnawaz Amdani, Emma R. Lipshultz and Steven E. Lipshultz
    Citation: Cardio-Oncology 2019 5:18
    Content type: Review Published on:

  42. Dexrazoxane protects from lower-cumulative-dose doxorubicin cardiotoxicity, but the effect of dexrazoxane in children with sarcoma treated with higher-cumulative-dose doxorubicin is unknown.

    Authors: Lisa M. Kopp, Richard B. Womer, Cindy L. Schwartz, David H. Ebb, Vivian I. Franco, David Hall, Donald A. Barkauskas, Mark D. Krailo, Holcombe E. Grier, Paul A. Meyers, Leonard H. Wexler, Neyssa M. Marina, Katherine A. Janeway, Richard Gorlick, Mark L. Bernstein and Steven E. Lipshultz
    Citation: Cardio-Oncology 2019 5:15
    Content type: Research Published on:

  43. 5-Fluorouracil (5-FU) is an antimetabolite chemotherapy used for a variety of solid tumors. It has the potential to cause a wide spectrum of cardiotoxicity, ranging from asymptomatic electrocardiographic chang...

    Authors: Cai Yuan, Hiral Parekh, Carmen Allegra, Thomas J. George and Jason S. Starr
    Citation: Cardio-Oncology 2019 5:13
    Content type: Review Published on:

  44. Cardiotoxicity is a potential complication of anticancer therapy. While guidelines have been developed to assist practitioners, an effective, evidence based clinical pathway for the treatment of cardiotoxicity...

    Authors: Robyn A. Clark, Tania S. Marin, Alexandra L. McCarthy, Julie Bradley, Suchi Grover, Robyn Peters, Christos S. Karapetis, John J. Atherton and Bogda Koczwara
    Citation: Cardio-Oncology 2019 5:14
    Content type: Research Published on:

  45. Cardiovascular disease (CVD) is the leading non-malignant cause of death in childhood cancer survivors. Heightened risk of CVD is often attributable to treatment with anthracycline chemotherapy. Anthracycline-...

    Authors: Treya M. Long, Channa E. Marsh, Lawrence G. Dembo, Philip Watson, Karen E. Wallman, Thomas S. Walwyn, Catherine S. Choong and Louise H. Naylor
    Citation: Cardio-Oncology 2019 5:11
    Content type: Research Published on:

  46. Cardiotoxicity is an adverse effect of trastuzumab (TRA) in the treatment of human epidermal growth factor 2 positive (HER2+) breast cancer. Current literature on the cardioprotective effects of agents targete...

    Authors: Melissa Y. Y. Moey, Darla K. Liles and Blase A. Carabello
    Citation: Cardio-Oncology 2019 5:9
    Content type: Research Published on:

  47. Early identification of cardiac dysfunction by non-invasive imaging in HER2-positive breast cancer patients treated with trastuzumab is challenging. In particular multigated acquisition (MUGA) scan, which is m...

    Authors: Nathalie I. Bouwer, Crista Liesting, Marcel J. M. Kofflard, Sylvia M. Sprangers-van Campen, Jasper J. Brugts, Jos J. E. M. Kitzen, Michael A. Fouraux, Mark-David Levin and Eric Boersma
    Citation: Cardio-Oncology 2019 5:4
    Content type: Research Published on:

  48. Anthracycline chemotherapy is an effective and widely used treatment for solid tumors and hematological malignancies regardless of its known cardiotoxicity. The mechanisms of the cardiotoxicity are not fully u...

    Authors: Amanda J. Favreau-Lessard, Hagen Blaszyk, Michael A. Jones, Douglas B. Sawyer and Ilka M. Pinz
    Citation: Cardio-Oncology 2019 5:2
    Content type: Research Published on:

  49. Cardiotoxicity associated with anthracycline-based chemotherapies has limited their use in patients with preexisting cardiomyopathy or heart failure. Dexrazoxane protects against the cardiotoxic effects of ant...

    Authors: Sarju Ganatra, Anju Nohria, Sachin Shah, John D. Groarke, Ajay Sharma, David Venesy, Richard Patten, Krishna Gunturu, Corrine Zarwan, Tomas G. Neilan, Ana Barac, Salim S. Hayek, Sourbha Dani, Shantanu Solanki, Syed Saad Mahmood and Steven E. Lipshultz
    Citation: Cardio-Oncology 2019 5:1
    Content type: Research Published on:

  50. Doxorubicin chemotherapy is used across a range of adult and pediatric malignancies. Cardiac toxicity is common, and dysfunction develops over time in many patients. Biomarkers used for predicting late cardiac...

    Authors: Andrew Poklepovic, Yuesheng Qu, Molly Dickinson, Michael C. Kontos, Maciej Kmieciak, Elizabeth Schultz, Dipankar Bandopadhyay, Xiaoyan Deng and Rakesh C. Kukreja
    Citation: Cardio-Oncology 2018 4:7
    Content type: Research Published on: