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In cancer, a patient is considered a survivor from the time of initial diagnosis until the end of life. With improvements in early diagnosis and treatment, the number of cancer survivors (CS) has grown considerably and includes: (1) Patients cured and free from cancer who may be at risk of late-onset cancer therapy-related cardiovascular toxicity (CTR-CVT); (2) Patients with long-term control of not-curable cancers in whom CTR-CVT may need to be addressed. This paper highlights the importance of the cancer care continuum, of a patient-centered approach and of a prevention-oriented policy. The ultimate goal is a personalized care of CS, achievable only through a multidisciplinary-guided survivorship care plan, one that replaces the fragmented management of current healthcare systems. Collaboration between oncologists and cardiologists is the pillar of a framework in which primary care providers and other specialists must be engaged and in which familial, social and environmental factors are also taken into account., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Bisceglia, Canale, Silvestris, Gallucci, Camerini, Inno, Camilli, Turazza, Russo, Paccone, Mistrulli, De Luca, Di Fusco, Tarantini, Lucà, Oliva, Moreo, Maurea, Quagliariello, Ricciardi, Lestuzzi, Fiscella, Parrini, Racanelli, Russo, Incorvaia, Calabrò, Curigliano, Cinieri, Gulizia, Gabrielli, Oliva and Colivicchi.)

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 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., 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., Competing Interests: Authors MP and CD were employed by Ceinge-Biotecnologie Avanzate. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Quagliariello, Passariello, Di Mauro, Cipullo, Paccone, Barbieri, Palma, Luciano, Buccolo, Bisceglia, Canale, Gallucci, Inno, De Lorenzo and Maurea.)

The pathophysiology of some non-communicable diseases (NCDs) such as hypertension, cardiovascular disease (CVD), diabetes, and cancer includes an alteration of the endothelial function. COVID-19 is a pulmonary and vascular disease with a negative impact on patients whose damaged endothelium is particularly vulnerable. The peculiar SARS-CoV-2-induced "endothelitis" triggers an intriguing immune-thrombosis that affects both the venous and arterial vascular beds. An increased liability for infection and an increased likelihood of a worse outcome have been observed during the pandemic in patients with active cancer and in cancer survivors. "Overlapping commonalities" between COVID-19 and Cardio-Oncology have been described that include shared phenotypes of cardiovascular toxicities such as left ventricular dysfunction, ischemic syndromes, conduction disturbances, myocarditis, pericarditis and right ventricular failure; shared pathophysiologic mechanisms such as inflammation, release of cytokines, the renin-angiotensin-aldosterone-pathway, coagulation abnormalities, microthrombosis and endothelial dysfunction. For these features and for the catalyst role of NCDs (mainly CVD and cancer), we should refer to COVID-19 as a "syndemic." Another challenging issue is the persistence of the symptoms, the so-called "long COVID" whose pathogenesis is still uncertain: it may be due to persistent multi-organ viral attacks or to an abnormal immune response. An intensive vaccination campaign is the most successful pharmacological weapon against SARS-CoV-2, but the increasing number of variants has reduced the efficacy of the vaccines in controlling SARS-CoV-2 infections. After a year of vaccinations we have also learned more about efficacy and side-effects of COVID-19 vaccines. An important byproduct of the COVID-19 pandemic has been the rapid expansion of telemedicine platforms across different care settings; this new modality of monitoring cancer patients may be useful even in a post pandemic era. In this paper we analyze the problems that the cardio-oncologists are facing in a pandemic scenario modified by the extensive vaccination campaign and add actionable recommendations derived from the ongoing studies and from the syndemic nature of the infection., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Bisceglia, Canale, Gallucci, Turazza, Lestuzzi, Parrini, Russo, Maurea, Quagliariello, Oliva, Di Fusco, Lucà, Tarantini, Trambaiolo, Moreo, Geraci, Gabrielli, Gulizia, Oliva and Colivicchi.)