Cardio-oncology for the general physician: 'old' and 'new' cardiovascular toxicities and how to manage them

Cardio-oncology is the care of cancer patients with cardiovascular disease. The need for a dedicated subspecialty emerged to address heart failure caused by drugs such as anthracyclines and anti-human epidermal growth factor receptor 2 (HER2) therapies, but over time has expanded into an exciting subspecialty with widening horizons. While still dealing with a lot of commonly recognised toxicities, such as heart failure, hypertension and coronary disease, new and revolutionary cancer therapies have been associated with challenging cardiovascular complications, requiring specialist input to manage effectively. Echocardiography is a key investigation, with advanced techniques such as three-dimensional and strain assessment allowing more accurate diagnosis and earlier detection of subtle changes. Cardiac magnetic resonance and biomarkers are useful adjuncts to aid diagnosis and management. With increasing cancer incidence and improved cancer survival rates, it is important that general cardiologists and physicians are aware of cardiac complications associated with cancer and how to manage them

Assessing Competence of NHS Consultants: Challenges and Possible Solutions

Even a mention of formal assessment of senior clinicians can be a contentious issue, to say least, when revalidation is said to be firmly in place in NHS-UK for almost half a decade. Since revalidation is accepted as a standard modality of assessment of performance, some colleagues in NHS wonder ‘stir up a hornets’ nest,’ when the authors allude to limitations of revalidation because poorly performing senior NHS clinicians may ‘slip through the net.’ NHS consultants have clinical as well as training roles. Fundamentally, this assessment (revalidation) is meant to ensure the safety of the public and mitigates the risk of disciplinary action by the GMC. Unfortunately, a disciplinary action is often the first sign of underperformance. In fact, the Bristol and Shipman inquiries have underscored the importance of the non-clinical and behavioural skills like communication, teamworking, personal organization and leadership are as important as clinical skills. Rather than considered an assessment tool, an annual appraisal is aimed to facilitate and improve the way NHS consultants work and provide services. The authors have to wait for five years, to assess the efficacy of the system that was introduced with much ‘fanfare’ since it was projected as a panacea for poor performance by ’bad doctors.’ The objectives of this article are to contextualize the issue of the underperformance among senior clinicians in the current NHS environment and to conceptualize the idea that their performance as trainers is directly related to their performance as clinicians. It is worth identifying the underlying factors of that are related to, or even better, can predict underperformance and will help evolve a strategy to help those consultants who are underperforming

Prediction of the Atomization Energy of Molecules Using Coulomb Matrix and Atomic Composition in a Bayesian Regularized Neural Networks

Exact calculation of electronic properties of molecules is a fundamental step for intelligent and rational compounds and materials design. The intrinsically graph-like and non-vectorial nature of molecular data generates a unique and challenging machine learning problem. In this paper we embrace a learning from scratch approach where the quantum mechanical electronic properties of molecules are predicted directly from the raw molecular geometry, similar to some recent works. But, unlike these previous endeavors, our study suggests a benefit from combining molecular geometry embedded in the Coulomb matrix with the atomic composition of molecules. Using the new combined features in a Bayesian regularized neural networks, our results improve well-known results from the literature on the QM7 dataset from a mean absolute error of 3.51 kcal/mol down to 3.0 kcal/mol.Comment: Under review ICANN 201

Hypertensive Cardiotoxicity in Cancer Treatment-Systematic Analysis of Adjunct, Conventional Chemotherapy, and Novel Therapies-Epidemiology, Incidence, and Pathophysiology

Cardiotoxicity is the umbrella term for cardiovascular side effects of cancer therapies. The most widely recognized phenotype is left ventricular dysfunction, but cardiotoxicity can manifest as arrhythmogenic, vascular, myocarditic and hypertensive toxicities. Hypertension has long been regarded as one of the most prevalent and modifiable cardiovascular risk factors in the general population, but its relevance during the cancer treatment journey may be underestimated. Hypertensive cardiotoxicity occurs de novo in a substantial proportion of treated cancer patients. The pathology is incompletely characterized—natriuresis and renin angiotensin system interactions play a role particularly in conventional treatments, but in novel therapies endothelial dysfunction and the interaction between the cancer and cardiac kinome are implicated. There exists a treatment paradox in that a significant hypertensive response not only mandates anti-hypertensive treatment, but in fact, in certain cancer treatment scenarios, hypertension is a predictor of cancer treatment efficacy and response. In this comprehensive review of over 80,000 patients, we explored the epidemiology, incidence, and mechanistic pathophysiology of hypertensive cardiotoxicity in adjunct, conventional chemotherapy, and novel cancer treatments. Conventional chemotherapy, adjunct treatments, and novel targeted therapies collectively caused new onset hypertension in 33–68% of treated patients. The incidence of hypertensive cardiotoxicity across twenty common novel therapies for any grade hypertension ranged from 4% (imatinib) to 68% (lenvatinib), and high grade 3 or 4 hypertension in <1% (imatinib) to 42% (lenvatinib). The weighted average effect was all-grade hypertension in 24% and grade 3 or 4 hypertension in 8%

Opportunities for improved cardiovascular disease prevention in oncology patients

PURPOSE OF REVIEW: Cancer patients often have cardiovascular risk factors at the time of cancer diagnosis, which are known to increase the risk of cardiotoxicity. Cancer survivors have significantly higher cardiovascular risk. Current cardiovascular disease prevention guidelines are based on studies that largely excluded these patients. We reviewed recent data regarding cardiovascular disease prevention in this population. RECENT FINDINGS: Nonpharmacologic therapies aiming to reduce 'lifestyle toxicity' produced by cancer treatments have demonstrated potential to decrease the incidence of adverse outcomes. Exercise before, during and after cancer treatment not only promotes higher quality of life and cardiorespiratory fitness but also reduces adverse cardiovascular outcomes. Lipid and cardiometabolic disease management is paramount but predominantly based on data that excludes these populations of cancer patients and survivors. SUMMARY: A comprehensive approach including medical evaluation, prescriptive exercise, cardiac risk factor modification, education, counseling, pharmacologic and behavioral interventions are needed in cancer patients. These interventions constitute the core of cardio-oncology rehabilitation programs, which if implemented appropriately may help reduce cardiovascular events in this population. Knowledge gaps in these areas are starting to be addressed by ongoing clinical trials

Socio-Economic Burden of Myocardial Infarction Among Cancer Patients

Cancer patients face a higher risk of future myocardial infarction (MI), even after completion of anticancer therapies. MI is a critical source of physical and financial stress in non-cancer patients, but its impacts associated with cancer patients also saddled with the worry (stress) of potential reoccurrence is unknown. Therefore, we aimed to quantify MI's stress and financial burden after surviving cancer and compare to those never diagnosed with cancer. Utilizing cross-sectional national survey data from 2013-2018 derived from publicly available U.S. datasets, the National Health Interview Survey (NHIS), and economic data from the National Inpatient Sample (NIS), we compared the socio-economic outcomes among those with MI by cancer-status. We adjusted for social, demographic, and clinical factors. Overall, 19,504 (10.2%) of the 189,836 NHIS survey responders reported having cancer for more than 1 year. There was an increased prevalence of MI among cancer survivors compared to non-cancer patients (8.8% vs. 3.2%, P0.05). There was no difference in annual residual family income by cancer status; however, 3 lowest deciles of residual income representing 21.1% cancer-survivor with MI had a residual income of <$9,000. Myocardial infarction continues to represent an immense source of financial and perceived stress. In conclusion, although cancer patients face a higher risk of subsequent MI, this does not appear to advance their reported stress significantly

Spectroscopic investigation of quantum confinement effects in ion implanted silicon-on-sapphire films

Crystalline Silicon-on-Sapphire (SOS) films were implanted with boron (B$^+$) and phosphorous (P$^+$) ions. Different samples, prepared by varying the ion dose in the range $10^{14}$ to 5 x $10^{15}$ and ion energy in the range 150-350 keV, were investigated by the Raman spectroscopy, photoluminescence (PL) spectroscopy and glancing angle x-ray diffraction (GAXRD). The Raman results from dose dependent B$^+$ implanted samples show red-shifted and asymmetrically broadened Raman line-shape for B$^+$ dose greater than $10^{14}$ ions cm$^{-2}$. The asymmetry and red shift in the Raman line-shape is explained in terms of quantum confinement of phonons in silicon nanostructures formed as a result of ion implantation. PL spectra shows size dependent visible luminescence at $\sim$ 1.9 eV at room temperature, which confirms the presence of silicon nanostructures. Raman studies on P$^+$ implanted samples were also done as a function of ion energy. The Raman results show an amorphous top SOS surface for sample implanted with 150 keV P$^+$ ions of dose 5 x $10^{15}$ ions cm$^{-2}$. The nanostructures are formed when the P$^+$ energy is increased to 350 keV by keeping the ion dose fixed. The GAXRD results show consistency with the Raman results.Comment: 9 Pages, 6 Figures and 1 Table, \LaTex format To appear in SILICON(SPRINGER

Molecular cytogenetics (FISH, GISH) of Coccinia grandis: A ca. 3 myr-old species of Cucurbitaceae with the largest Y/autosome divergence in flowering plants

The independent evolution of heteromorphic sex chromosomes in 19 species from 4 families of flowering plants permits studying X/Y divergence after the initial recombination suppression. Here, we document autosome/Y divergence in the tropical Cucurbitaceae Coccinia grandis, which is ca. 3 myr old. Karyotyping and C-value measurements show that the C. grandis Y chromosome has twice the size of any of the other chromosomes, with a male/female C-value difference of 0.094 pg or 10% of the total genome. FISH staining revealed 5S and 45S rDNA sites on autosomes but not on the Y chromosome, making it unlikely that rDNA contributed to the elongation of the Y chromosome; recent end-to-end fusion also seems unlikely given the lack of interstitial telomeric signals. GISH with different concentrations of female blocking DNA detected a possible pseudo-autosomal region on the Y chromosome, and C-banding suggests that the entire Y chromosome in C. grandis is heterochromatic. During meiosis, there is an end-to-end connection between the X and the Y chromosome, but the X does not otherwise differ from the remaining chromosomes. These findings and a review of plants with heteromorphic sex chromosomes reveal no relationship between species age and degree of sex chromosome dimorphism. Its relatively small genome size (0.943 pg/2C in males), large Y chromosome, and phylogenetic proximity to the fully sequenced Cucumis sativus make C. grandis a promising model to study sex chromosome evolution. Copyright © 2012 S. Karger AG, Base