RESUMEN
BACKGROUND: Patients born with single ventricle anatomy typically undergo surgical palliation in three stages, culminating in the Fontan procedure. Assessment of flow across a Fontan fenestration by Doppler ultrasound theoretically allows for non-invasive estimation of the transpulmonary gradient (TPG). Our objective was to determine the relationship between Doppler-derived mean fenestration gradient (mFG) and direct catheter-based measurements of TPG in patients with fenestrated Fontans. METHODS: We performed a single-center retrospective cohort study of 59 patients with fenestrated Fontans completed between 2000 and 2022. The primary outcome was catheter-based measurement of TPG and the primary predictor was mFG from echo performed within 6 months of the catheterization. Linear regression and R2 were used to determine the relationship between predictors and outcomes. RESULTS: Catheter-based measurements of TPG and mFG were weakly correlated (R2 = 0.382, p < 0.001); the regression coefficient was 0.550, with a standard error of 0.09 for every increase in mFG (Cath TPG = 0.55 [mFG] + 1.92). mFG had a slightly better predictive relationship with cath-derived TPG in patients with systemic left ventricles with R2 of 0.47, p < 0.004. CONCLUSION: mFG accounts for approximately 38% of the variance in catheter-derived TPG. Although mFG is non-invasive and intuitive, mFG in Fontan patients should be interpreted with caution and direct measurement by cardiac catheterization should be considered.
RESUMEN
Biomarkers play a crucial role in the diagnosis, prognosis, and therapeutics of cancer. We use biomarkers to identify, image, monitor, and target cancer. In many respects, the discovery of pertinent biomarkers that distinguish fulminant from indolent neoplasms and sensitive from refractory malignancies would be a holy grail of cancer research and therapy. We propose that a stem cell versus genetic theory of cancer may not only enable us to track and trace the biological evolution of cancer but also empower us to attenuate its clinical course and optimize the clinical outcome of patients with cancer. Hence, a biomarker that identifies cancer stem cells (CSCs) and distinguishes them from non-CSCs may serve to elucidate inter-tumoral and intra-tumoral heterogeneity, elevate the values and utility of current prognostic and predictive tests, and enhance drug versus therapy development in cancer care. From this perspective, we focus on CSC biomarkers and discuss stemness or stem-like biomarkers in the context of a unified theory and a consideration of stem cell versus genetic origin. We review their role in primary and mixed tumors, in the elaboration of tumor subtypes, and in the imaging and monitoring of minimal residual diseases. We investigate how scientific theories influence the direction of scientific research and interpretation of experimental results, and how genomics and epigenomics affect the dynamics and trajectories of biomarkers in the conduct of cancer research and in the practice of cancer care.
RESUMEN
Doxorubicin (DOX)-induced cardiotoxicity is a major limitation to its clinical application. Cardiotoxicity of DOX is dose-dependent that begins with the first dose. Oxidative stress and inflammation are involved in DOX-related cardiotoxicity. This study aimed to determine whether multiple markers of inflammation, hypercoagulability and endothelial injury correlate with the risk of early DOX-induced cardiotoxicity in breast cancer patients. Blood samples of 51 breast cancer patients treated with DOX-based chemotherapy were collected before (baseline) and after the first cycle of chemotherapy. The risk of cardiotoxicity was defined as an asymptomatic reduction of cardiac left ventricle ejection fraction (LVEF) >10% at completion of chemotherapy versus baseline. Plasma samples were examined for multiple biomarkers of inflammation, hypercoagulability and endothelial dysfunction, including C-reactive protein (CRP), thrombomodulin (TM), thrombin-antithrombin complex (TAT), myeloperoxidase (MPO), von Willebrand factor (vWF) and P-selectin. Surrogate markers of neutrophil extracellular traps (NETs) nucleosomes and double stranded DNA (dsDNA) were also measured. Patients with abnormal decline of LVEF >10% (n=21) had significantly elevated levels of MPO and TM both at baseline, and after the first dose of DOX-based chemotherapy relative to patients with normal LVEF (n=30) after adjusting for race, age, BMI and type of breast cancer. The first dose of DOX also induced significantly higher circulating levels of TAT complex and nucleosomes in patients at risk of cardiotoxicity in comparison with patients without. The comparison between the means of the biomarkers in after-before DOX-based chemotherapy of the two groups of patients showed significant differences for MPO, TAT complex and CRP. The results from this study suggest that the risk of DOX-induced cardiotoxicity in breast cancer is associated with endothelial dysfunction, inflammation and prothrombotic state before and after the first dose of chemotherapy.