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PURPOSE: Despite great success as a targeted breast cancer therapy, trastuzumab use may be complicated by heart failure and loss of left ventricular contractile function. This review summarizes the risk factors, imaging, and prevention of cardiotoxicity associated with trastuzumab and other HER2-targeted therapies. FINDINGS: Cardiovascular disease risk factors, advanced age, and previous anthracycline treatment predispose to trastuzumab-induced cardiotoxicity (TIC), with anthracycline exposure being the most significant risk factor. Cardiac biomarkers such as troponins and pro-BNP and imaging assessments such as echocardiogram before and during trastuzumab therapy may help in early identification of TIC. Initiation of beta-adrenergic antagonists and angiotensin converting enzyme inhibitors may prevent TIC. Cardiotoxicity rates of other HER2-targeted treatments, such as pertuzumab, T-DM1, lapatinib, neratinib, tucatinib, trastuzumab deruxtecan, and margetuximab, appear to be significantly lower as reported in the pivotal trials which led to their approval. CONCLUSIONS: Risk assessment for TIC should include cardiac imaging assessment and should incorporate prior anthracycline use, the strongest risk factor for TIC. Screening and prediction of cardiotoxicity, referral to a cardio-oncology specialist, and initiation of effective prophylactic therapy may all improve prognosis in patients receiving HER2-directed therapy. Beta blockers and ACE inhibitors appear to mitigate risk of TIC. Anthracycline-free regimens have been proven to be efficacious in early HER2-positive breast cancer and should now be considered the standard of care for early HER2-positive breast cancer. Newer HER2-directed therapies appear to have significantly lower cardiotoxicity compared to trastuzumab, but trials are needed in patients who have experienced TIC and patients with pre-existing cardiac dysfunction.
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Neoplasias da Mama , Cardiotoxicidade , Feminino , Humanos , Oxazóis , Piridinas , Quinazolinas , Receptor ErbB-2 , Fatores de Risco , TrastuzumabRESUMO
OBJECTIVE: To analyze trends in management and outcomes of patients infected with the human immunodeficiency virus (HIV) undergoing percutaneous coronary intervention (PCI) for an acute myocardial infarction (AMI) in the United States. BACKGROUND: Infection with HIV is an independent risk factor for accelerated atherosclerosis associated with higher rates of AMI. Current trends and outcomes of HIV-infected individuals presenting with AMI in the United States remain unknown. METHODS: Using the Healthcare Cost and Utilization Project National Inpatient Sample database we identified HIV-infected individuals who underwent PCI for an AMI from 2002 to 2013. Multivariable logistic regression and propensity-score matching were performed to analyze outcomes. RESULTS: We identified a total of 59 194 patients of which 7841 underwent PCI during index hospitalization (13.3%). Most patients were men (71%), ≥50 years of age (82%), and white (74%). ST-elevation myocardial infarction was present in 21% of cases. Charlson comorbidity index (CCI) was 5.67 ± 0.4. Predictors of post-procedural complications included female sex, black race, higher CCI, and placement of a bare metal stent, whereas predictors of mortality included occurrence of a complication, ST-elevation myocardial infarction, age ≥70 years, and higher CCI. Conversely, placement of a drug-eluting stent was associated with a reduced risk of complications and mortality. After propensity-score matching, HIV-infected individuals were less likely to undergo PCI and receive a drug-eluting stent, while having longer length of stay, higher hospitalization costs, and higher in-hospital mortality when compared to non-infected individuals. CONCLUSION: Significant disparities continue to affect HIV-infected individuals undergoing PCI for AMI in the United States.
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Infecções por HIV/complicações , Infarto do Miocárdio/cirurgia , Intervenção Coronária Percutânea , Idoso , Idoso de 80 Anos ou mais , Bases de Dados Factuais , Feminino , Custos Hospitalares , Mortalidade Hospitalar , Hospitalização/economia , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/virologia , Pontuação de Propensão , Fatores de Risco , Stents , Resultado do Tratamento , Estados UnidosRESUMO
Acute cardiac manifestions of COVID-19 have been well described, while chronic cardiac sequelae remain less clear. Various studies have shown conflicting data on the prevalence of new or worsening cardiovascular disease, myocarditis or cardiac dysrhythmias among patients recovered from COVID-19. Data are emerging that show that patients recovering from COVID-19 have an increased incidence of myocarditis and arrhythmias after recovery from COVID-19 compared with the control groups without COVID-19. The incidence of myocarditis after COVID-19 infection is low but is still significantly greater than the incidence of myocarditis from a COVID-19 vaccine. There have been several studies of athletes who underwent a variety of screening protocols prior to being cleared to return to exercise and competition. The data show possible, probable or definite myocarditis or cardiac injury among 0.4-3.0% of the athletes studied. Recent consensus statements suggest that athletes with full recovery and absence of cardiopulmonary symptoms may return to exercise and competition without cardiovascular testing. In conclusion, patients with COVID-19 may be expected to have an increased risk of cardiovascular disease, myocarditis or arrhythmias during the convalescent phase. Fortunately, the majority of patients, including athletes may return to their normal activity after recovery from COVID 19, in the absence of persisting cardiovascular symptoms.
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COVID-19 , Miocardite , Humanos , Miocardite/diagnóstico , Miocardite/epidemiologia , COVID-19/epidemiologia , Vacinas contra COVID-19 , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/epidemiologia , Arritmias Cardíacas/terapia , AtletasRESUMO
INTRODUCTION/PURPOSE: SARS-CoV-2 infection (COVID-19) can result in myocarditis. Protocols were developed to allow competitive athletes to safely return to play (RTP) after a COVID-19 infection, but the financial impact of these protocols is unknown. Our objective was to determine the differential cost of post-COVID-19 RTP protocols for competitive collegiate athletes. METHODS: This multicenter retrospective cohort study of clinical evaluation of 295 athletes after COVID-19 infection was performed at four institutions with three RTP protocols. Costs were calculated using adjusted Center for Medicare and Medicaid Services pricing. All athletes underwent electrocardiogram and clinical evaluation. A tiered approach performed cardiac imaging and biomarker analysis for major symptoms. A universal transthoracic echocardiogram (TTE) approach performed TTE and biomarkers for all athletes. A universal exercise stress echocardiogram (ESE) approach performed ESE and biomarkers for all athletes. RESULTS: The cost per athlete was $632.51 ± 651.80 ($44,908 total) in tiered group (n = 71), $1,072.30 ± 517.93 ($87,928 total) in the universal TTE group (n = 82), and $1357.38 ± 757.05 ($192,748 total) in the universal ESE group (n = 142) (P < 0.001). Extrapolated national costs for collegiate athletes would be $39 to 64 million higher for universal imaging approaches versus a tiered approach. Only seven athletes had probable/possible myocarditis with no significant difference between approaches. CONCLUSIONS: Cardiac screening in collegiate athletes after COVID-19 infection resulted in significant cost to the health care system. A tiered-based approach was more economical, and a universal exercise echocardiogram group detected slightly more myocardial abnormalities by cardiac magnetic resonance imaging. The clinical consequences of these approaches are unknown.
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COVID-19 , Miocardite , Idoso , Atletas , Biomarcadores , Humanos , Medicare , Estudos Multicêntricos como Assunto , Estudos Retrospectivos , Volta ao Esporte , SARS-CoV-2 , Estados UnidosRESUMO
Up to 20%-30% of patients hospitalized with coronavirus disease 2019 (COVID-19) have evidence of myocardial involvement. Acute cardiac injury in patients hospitalized with COVID-19 is associated with higher morbidity and mortality. There are no data on how acute treatment of COVID-19 may affect the convalescent phase or long-term cardiac recovery and function. Myocarditis from other viral pathogens can evolve into overt or subclinical myocardial dysfunction, and sudden death has been described in the convalescent phase of viral myocarditis. This raises concerns for patients recovering from COVID-19. Some patients will have subclinical and possibly overt cardiovascular abnormalities. Patients with ostensibly recovered cardiac function may still be at risk of cardiomyopathy and cardiac arrhythmias. Screening for residual cardiac involvement in the convalescent phase for patients recovered from COVID-19-associated cardiac injury is needed. The type of testing and therapies for post COVID-19 myocardial dysfunction will need to be determined. Therefore, now is the time to plan for appropriate registries and clinical trials to properly assess these issues and prepare for long-term sequelae of "post-COVID-19 cardiac syndrome."
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Arritmias Cardíacas , Doenças Cardiovasculares , Convalescença , Infecções por Coronavirus , Pandemias , Pneumonia Viral , Arritmias Cardíacas/diagnóstico , Arritmias Cardíacas/etiologia , Arritmias Cardíacas/virologia , Betacoronavirus/patogenicidade , COVID-19 , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/virologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/fisiopatologia , Programas de Triagem Diagnóstica , Necessidades e Demandas de Serviços de Saúde , Humanos , Pneumonia Viral/complicações , Pneumonia Viral/fisiopatologia , SARS-CoV-2 , Análise de Sobrevida , SobreviventesRESUMO
Melanomas demonstrate chromosomal instability (CIN). In fact, CIN can be used to differentiate melanoma from benign nevi. The exact molecular mechanisms that drive CIN in melanoma have yet to be fully elucidated. Cancer/testis antigens are a unique group of germ cell proteins that are found to be primarily expressed in melanoma as compared to benign nevi. The abnormal expression of these germ cell proteins, normally expected only in the testis and ovaries, in somatic cells may lead to interference with normal cellular pathways. Germ cell proteins that may be particularly critical in CIN are meiosis proteins. Here, we review pathways unique to meiosis with a focus on how the aberrant expression of meiosis proteins in normal mitotic cells "meiomitosis" could impact chromosomal instability in melanoma and other cancers.
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Early diagnosis gives melanoma patients the best chance for long term survival. However discrimination of an early melanoma from an unusual/atypical benign nevus can represent a significant challenge. There are no current pathological markers to definitively define malignant potential in these indeterminate lesions. Thus, there is a need for improved diagnostic tools. Chromosomal instability (CIN) is a hallmark of cancer and is markedly prevalent in melanoma. Advances in genomics have opened the door for the development of molecular tools to better segregate benign and malignant lesions. This paper focuses on CIN in melanoma and the role of current diagnostic approaches.
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Germ cell protein expression in melanoma has been shown to correlate with malignancy, severity of disease and to serve as an immunologic target for therapy. However, very little is known about the role that germ cell proteins play in cancer development. Unique germ cell pathways include those involved in immortalization, genetic evolution, and energy metabolism. There is an ever increasing recognition that within tumors there is a subpopulation of cells with stem-cell-like characteristics that play a role in driving tumorgenesis. Stem cell and germ cell biology is intertwined. Given the enormous potential and known expression of germ cell proteins in melanoma, it is possible that they represent a largely untapped resource that may play a fundamental role in tumor development and progression. The purpose of this paper is to provide an update on the current value of germ cell protein expression in melanoma diagnosis, prognosis, and therapy, as well as to review critical germ cell pathways and discuss the potential roles these pathways may play in malignant transformation.