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Purpose of ReviewHER2-targeted therapies have led to improved clinical outcomes in early and advanced breast cancer (BC). We review the long-term cardiotoxicity of HER2-targeted therapy in early and advanced BC, our current knowledge of cardiotoxicity of novel HER2-targeted therapies, and propose a cardiac monitoring (CM) strategy for this population.Recent FindingsLong-term data from studies with HER2-targeted therapy in the adjuvant setting have failed to demonstrate an increase in cardiotoxicity over time, and rates of cardiotoxicity seen with novel HER2 agents remain low. Despite over a decade of experience with HER2-targeted therapy, CM in clinical practice is inconsistent in patients with early BC and almost non-existent in advanced BC.SummaryLong-term follow-up of clinical trials with HER2-targeted agents in early and advanced BC has failed to demonstrate increased rates of cardiotoxicity over time, attesting to the long-term safety of this class of drugs for the majority of patients, although the long-term cardiac safety of newer HER2 agents in the non-clinical trial setting is largely unknown. We propose CM incorporating clinical history, cardiac imaging, and biomarkers.

Breast cancer survivors have an increased risk of colorectal cancer (CRC) and those with chronic diseases are more likely to experience poor mental and physical health. For this study, we examined the mediating effects of mental and physical health on the association between chronic disease conditions and guideline-concordant colorectal cancer (CRC) screening among breast cancer survivors. We included 1,885 breast cancer survivors aged 45-75 years who were eligible for CRC screening in 2016, 2018, and 2020 Behavioral Risk Factor Surveillance System. The exposure was chronic diseases defined as prevalent diabetes, coronary heart disease/myocardial infarction, stroke, chronic obstructive pulmonary disease, emphysema/chronic bronchitis, arthritis, depressive disorders, or kidney diseases. The outcome was receipt of guideline-concordant CRC screening. Mediators were defined as self-reported frequent poor mental/physical health in the past 30 days (14-30 vs. 0-13 days). Multivariable logistic regression models were adjusted for sociodemographic and cancer-related factors. We used the methods proposed by Valeri & VanderWeele for the mediation analyses. Breast cancer survivors with chronic diseases were 1.7-fold more likely to have CRC screening compared to those without any chronic diseases (OR, 1.68; 95% CI, 1.27-2.21). In mediation analysis, we found that frequent poor mental health mediated the association between chronic disease conditions and CRC screening utilization (-4.4% mediated; p-value = 0.035). We also observed a reduction through frequent poor physical health by 10.5% (p-value = 0.008). Frequent poor mental and physical health negatively mediated the association between the presence of chronic diseases and CRC screening utilization with a higher estimate for those with poor physical health. Effective implementation of integrated follow-up care is needed among breast cancer survivors to address chronic disease management and prioritize mental and physical health so that all patients receive guideline concordant CRC screening recommendations.

Breast cancer survivors have an increased risk of colorectal cancer (CRC) and those with chronic diseases are more likely to experience poor mental and physical health. For this study, we examined the mediating effects of mental and physical health on the association between chronic disease conditions and guideline-concordant colorectal cancer (CRC) screening among breast cancer survivors. We included 1,885 breast cancer survivors aged 45-75 years who were eligible for CRC screening in 2016, 2018, and 2020 Behavioral Risk Factor Surveillance System. The exposure was chronic diseases defined as prevalent diabetes, coronary heart disease/myocardial infarction, stroke, chronic obstructive pulmonary disease, emphysema/chronic bronchitis, arthritis, depressive disorders, or kidney diseases. The outcome was receipt of guideline-concordant CRC screening. Mediators were defined as self-reported frequent poor mental/physical health in the past 30 days (14-30 vs. 0-13 days). Multivariable logistic regression models were adjusted for sociodemographic and cancer-related factors. We used the methods proposed by Valeri & VanderWeele for the mediation analyses. Breast cancer survivors with chronic diseases were 1.7-fold more likely to have CRC screening compared to those without any chronic diseases (OR, 1.68; 95% CI, 1.27-2.21). In mediation analysis, we found that frequent poor mental health mediated the association between chronic disease conditions and CRC screening utilization (-4.4% mediated; p-value = 0.035). We also observed a reduction through frequent poor physical health by 10.5% (p-value = 0.008). Frequent poor mental and physical health negatively mediated the association between the presence of chronic diseases and CRC screening utilization with a higher estimate for those with poor physical health. Effective implementation of integrated follow-up care is needed among breast cancer survivors to address chronic disease management and prioritize mental and physical health so that all patients receive guideline concordant CRC screening recommendations.

The purpose of this review is to provide a framework for the cardiovascular evaluation and management of patients undergoing hematopoietic cell transplantation (HCT). To accomplish this, we have performed an extensive literature review, critically analyzed the available evidence, and developed a set of recommendations to guide best practice. Herein, we discuss the cardiovascular risk profile of patients undergoing HCT along with putative mechanisms of HCT-induced cardiovascular injury. We then present an algorithm for cardiovascular testing and risk mitigation of potential recipients. Last, we address the management of the most prevalent cardiovascular conditions associated with HCT recipients.

The protein corona formed on nanoparticles (NPs) has potential as a valuable diagnostic tool for improving plasma proteome coverage. Here, we show that spiking small molecules, including metabolites, lipids, vitamins, and nutrients into plasma can induce diverse protein corona patterns on otherwise identical NPs, significantly enhancing the depth of plasma proteome profiling. The protein coronas on polystyrene NPs when exposed to plasma treated with an array of small molecules allows for the detection of 1793 proteins marking an 8.25-fold increase in the number of quantified proteins compared to plasma alone (218 proteins) and a 2.63-fold increase relative to the untreated protein corona (681 proteins). Furthermore, we discovered that adding 1000 µg/ml phosphatidylcholine could singularly enable the detection of 897 proteins. At this specific concentration, phosphatidylcholine selectively depletes the four most abundant plasma proteins, including albumin, thus reducing the dynamic range of plasma proteome and enabling the detection of proteins with lower abundance. Employing an optimized data-independent acquisition approach, the inclusion of phosphatidylcholine leads to the detection of 1436 proteins in a single plasma sample. Our molecular dynamics results reveal that phosphatidylcholine interacts with albumin via hydrophobic interactions, H-bonds, and water bridges. The addition of phosphatidylcholine also enables the detection of 337 additional proteoforms compared to untreated protein corona using a top-down proteomics approach. Given the critical role of plasma proteomics in biomarker discovery and disease monitoring, we anticipate the widespread adoption of this methodology for the identification and clinical translation of biomarkers. The protein corona on nanoparticles has potential for application in protein diagnostics. Here, the authors report on the use of small molecules to change the protein and proteoform patterns of protein corona on otherwise identical nanoparticles, which can be leveraged to significantly enhance the depth of plasma proteome profiling.

BackgroundFour-factor prothrombin complex concentrate (PCC) is frequently used as a reversal agent for major bleeding in patients on factor Xa inhibitors. Piran et al. reviewed its safety and efficacy for the first time in 2018. However, more studies have been published on the matter since then. The aim of this study is to investigate the efficacy and safety of this use and update this review.MethodsWe systematically searched in Medline, Scopus, and the Cochrane Library from 1/1/2018 to 6/19/2020. A random effects model meta-analysis of proportions was used to study the efficacy of PCC on major bleeding control, mortality and thrombosis incidence.Results33 studies (n = 2568 patients), with the majority of studies being uncontrolled retrospective cohort studies, were included; atrial fibrillation was the main factor Xa inhibitors indication and approximately 62% of patients presented with intracranial hemorrhage. We estimated the pooled proportion outcomes for hemostasis (80%, CI 0.75–0.84), mortality (15%, CI 0.11–0.19) and thromboembolic adverse events (3%, CI 0.02–0.05). High versus low dose PCC did not affect hemostasis or thrombosis. Patients with ICH had higher mortality rates (22%, CI 0.13–0.32). Heterogeneity was significant (Ι2 > 50% with p < 0.05) for all pooled proportional outcomes. The quality of evidence was low given that included studies were not randomized or controlled.ConclusionOur study demonstrates the efficacy and safety of the off label use of 4F PCC in major bleeding associated with factor Xa inhibitors. Our data require further validation with future randomized clinical trials.

Purpose of ReviewCancer and heart disease are the leading causes of mortality in the USA. Advances in cancer therapies, namely, the development and use of chemotherapeutic agents alone or in combination, are becoming increasingly prevalent.Recent FindingsMany chemotherapeutic agents have been associated with adverse cardiovascular manifestations. The mechanisms of these sequelae remain incompletely understood. In particular, microtubule inhibitor (MTI) agents have been related to the development of heart failure, myocardial ischemia, and conduction abnormalities. At present, there are no guidelines for patients undergoing MTI therapy as it pertains to both preventative and mitigatory strategies for cardiovascular complications. We conducted a literature review focusing on content related to the use of MTIs and their effect on the cardiovascular system.SummaryMTIs have been associated with various forms of cardiotoxicity, and fatal cardiotoxicities are rare. The most well-described cardiotoxicities are brady- and tachyarrhythmias. The co-administration of anthracycline-based agents with MTIs can increase the risk of cardiotoxicity.

Cardiac magnetic resonance (CMR) global longitudinal strain and circumferential strain abnormalities have been associated with left ventricular ejection fraction (LVEF) reduction and cardiotoxicity from oncologic therapy. However, few studies have evaluated the associations of strain and cardiovascular outcomes. To assess CMR circumferential and global longitudinal strain (GLS) correlations with cardiovascular outcomes including myocardial infarction, systolic dysfunction, diastolic dysfunction, arrhythmias and valvular disease in breast cancer patients treated with and without anthracyclines and/or trastuzumab therapy. Breast cancer patients with a CMR from 2013-2017 at Yale New Haven Hospital were included. Patient co-morbidities, medications, and cardiovascular outcomes were obtained from chart review. Biostatistical analyses, including Pearson correlations, competing risk regression model, and competing risk survival curves comparing the two groups were analyzed. 116 breast cancer with CMRs were included in our analysis to assess differences between Anthracycline/Trastuzumab (AT) (62) treated versus non anthracycline/trastuzumab (NAT) (54) treated patients in terms of imaging characteristics and outcomes. More AT patients 17 (27.4%) developed systolic heart failure compared to the NAT group 6 (10.9%), p = 0.025. Statin use was associated with a significant reduction in future arrhythmias (HR 0.416; 95% CI 0.229-0.755, p = 0.004). In a sub-group of 13 patients that underwent stress CMR, we did not find evidence of microvascular dysfunction by sub-endocardial/sub-epicardial myocardial perfusion index ratio after adjusting for ischemic heart disease. In our study, CMR detected signs of subclinical cardiotoxicity such as strain abnormalities despite normal LV function and abnormal circumferential strain was associated with adverse cardiovascular outcomes such as valvular disease and systolic heart failure. Thus, CMR is an important tool during and after cancer treatment to identity and prognosticate cancer treatment-related cardiotoxicity.

In the United States, both cannabis use disorder (CUD) and opioid use disorder (OUD) have increased in prevalence. The prevalence, demographics, and costs of CUD and OUD are not well known in heart failure (HF) admissions. This study aimed to use a national database to examine the prevalence, demographics, and costs associated with CUD and OUD in HF. This study used the National Inpatient Sample from 2008 to 2018 to identify all primary HF admissions with and without the co-diagnosis of OUD or CUD using International Classification for Diagnosis, diagnosis codes. Demographics, costs, and trends were examined. Between 2008 and 2018, we identified 11,692,995 admissions for HF of which 84,796 (0.8%) had a co-diagnosis of CUD only, and 67,137 (0.6%) had a co-diagnosis of OUD only. The proportion of HF admissions with CUD significantly increased from 0.3% in 2008 to 1.3% in 2018 (p<0.001). The proportion of HF admissions with OUD significantly increased from 0.2% in 2008 to 1.1% in 2018 (p<0.001). Patients admitted with HF and either CUD or OUD were younger, more likely to be Black, and from lower socioeconomic backgrounds (p<0.001, all). HF admissions with OUD or CUD had higher median costs compared to HF admissions without associated substance abuse diagnoses ( $8,611 vs. $ 8,337 for CUD HF and$10,019 vs. $ 8,337 for OUD HF, p<0.001 for both). Among discharge records for HF, CUD and OUD are increasing in prevalence, significantly affect underserved populations and are associated with higher costs of stay. Future research is essential to better delineate the cause of these increased costs and create interventions, particularly in underserved populations.

Background: Breast cancer (BC) patients have heightened risks of atrial fibrillation (AF) and ischemic stroke (IS). Standard IS scores are poorly validated in cancer, omit cancer-specific factors, and guidelines offer no cancer-tailored management. Objectives: To develop and validate a novel score to predict IS risk in BC patients with AF. Methods: Data sources: UH Seidman Cancer Center (derivation; 40% set aside for internal validation) and MCG Cancer Center (external validation). Adults ≥ 18 years old with DCIS or stage I–IV BC who developed AF after diagnosis were included. Variable selection by LASSO Cox regression; continuous predictors dichotomized via cubic splines; points assigned from multivariable hazards to form B-S2CALED. Continuous scores were split into risk groups. Discrimination of categorized B-S2CALED versus CHA2DS2-VASc was assessed with the concordance index (C-index) and net reclassification improvement (NRI). Results: In the internal validation cohort (n = 935), 87 patients experienced IS/TIA. The B-S2CALED score achieved a C-index of 0.64 (95% CI 0.59–0.70) compared with 0.54 (95% CI: 0.51–0.56) for CHA2DS2-VASc, yielding a total NRI of 0.188. In the external validation cohort (n = 95), 8 patients developed IS/TIA. The B-S2CALED score produced a C-index of 0.77 (95% CI: 0.72–0.83) versus 0.53 (95% CI: 0.51–0.56) for CHA2DS2-VASc, with a total NRI of 0.563. Similar advantages were observed when the score was treated as a continuous variable. Conclusions: The BC-specific B-S2CALED score outperformed CHA2DS2-VASc for predicting thromboembolic events in BC patients with AF. Validation in larger datasets is needed before clinical adoption.