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

Anthracyclines and Biomarkers of Myocardial Injury: The Effect of Remote Ischemic Conditioning

Background: Remote ischemic conditioning (RIC) has been beneficial in laboratory studies of anthracycline cardiotoxicity, but its effects in patients is not established. Objectives: The authors studied the effect of RIC on cardiac biomarkers and function during and after anthracycline chemotherapy. Methods: The ERIC-Onc study (Effect of Remote Ischaemic Conditioning in Oncology Patients; NCT02471885) was a randomized, single-blind, sham-controlled study of RIC at each chemotherapy cycle. The primary endpoint was troponin T (TnT) during chemotherapy and up to 1 year. Secondary outcomes included cardiac function, major adverse cardiovascular events (MACE), and MACE or cancer death. Cardiac myosin-binding-protein C (cMyC) was investigated in parallel with TnT. Results: The study was prematurely halted after the evaluation of 55 patients (RIC n = 28, sham n = 27). Biomarkers increased from baseline to cycle 6 of chemotherapy for all patients (median TnT 6 [IQR: 4-9] ng/L to 33 [IQR: 16-36)] ng/L; P ≤ 0.001; cMyC 3 (IQR: 2-5) ng/L to 47 (IQR: 18-49) ng/L; P ≤ 0.001). Mixed-effects regression analysis for repeated measures showed no difference in TnT between the 2 groups (RIC vs sham, mean difference 3.15 ng/L; 95% CI: −0.04 to 6.33; P = 0.053), or cMyC (RIC vs sham, mean difference 4.17 ng/L; 95% CI: −0.12 to 8.45; P = 0.056). There were more MACE and cancer deaths in the RIC group (11 vs 3; HR: 0.25; 95% CI: 0.07-0.90; P = 0.034), with more cancer deaths (8 vs 1; HR: 0.21; 95% CI: 0.04-0.95; P = 0.043) at 1 year. Conclusions: TnT and cMyC significantly increased during anthracycline chemotherapy with 81% having a TnT ≥14 ng/L at cycle 6. RIC did not affect the rise in biomarkers, but there was a small increase in early cancer deaths, possibly related to the greater proportion of patients with metastatic disease randomized to the RIC group (54%vs 37%). (Effect of Remote Ischaemic Conditioning in Oncology Patients [ERIC-ONC]; NCT02471885

Modelling of gas–solid turbulent channel flow with non-spherical particles with large Stokes numbers

AbstractThis paper describes a complete framework to predict the behaviour of interacting non-spherical particles with large Stokes numbers in a turbulent flow. A summary of the rigid body dynamics of particles and particle collisions is presented in the framework of Quaternions. A particle-rough wall interaction model to describe the collisions between non-spherical particles and a rough wall is put forward as well. The framework is coupled with a DNS-LES approach to simulate the behaviour of horizontal turbulent channel flow with 5 differently shaped particles: a sphere, two types of ellipsoids, a disc, and a fibre. The drag and lift forces and the torque on the particles are computed from correlations which are derived using true DNS.The simulation results show that non-spherical particles tend to locally maximise the drag force, by aligning their longest axis perpendicular to the local flow direction. This phenomenon is further explained by performing resolved direct numerical simulations of an ellipsoid in a flow. These simulations show that the high pressure region on the acute sides of a non-spherical particle result in a torque if an axis of the non-spherical particle is not aligned with the flow. This torque is only zero if the axis of the particle is perpendicular to the local direction of the flow. Moreover, the particle is most stable when the longest axis is aligned perpendicular to the flow.The alignment of the longest axis of a non-spherical particle perpendicular to the local flow leads to non-spherical particles having a larger average velocity compared to spherical particles with the same equivalent diameter. It is also shown that disc-shaped particles flow in a more steady trajectory compared to elongated particles, such as elongated ellipsoids and fibres. This is related to the magnitude of the pressure gradient on the acute side of the non-spherical particles. Finally, it is shown that the effect of wall roughness affects non-spherical particles differently than spherical particles. Particularly, a collision of a non-spherical particle with a rough wall induces a significant amount of rotational energy, whereas a corresponding collision with a spherical particle results in mostly a change in translational motion

Modelling of gas–solid turbulent channel flow with non-spherical particles with large Stokes numbers

AbstractThis paper describes a complete framework to predict the behaviour of interacting non-spherical particles with large Stokes numbers in a turbulent flow. A summary of the rigid body dynamics of particles and particle collisions is presented in the framework of Quaternions. A particle-rough wall interaction model to describe the collisions between non-spherical particles and a rough wall is put forward as well. The framework is coupled with a DNS-LES approach to simulate the behaviour of horizontal turbulent channel flow with 5 differently shaped particles: a sphere, two types of ellipsoids, a disc, and a fibre. The drag and lift forces and the torque on the particles are computed from correlations which are derived using true DNS.The simulation results show that non-spherical particles tend to locally maximise the drag force, by aligning their longest axis perpendicular to the local flow direction. This phenomenon is further explained by performing resolved direct numerical simulations of an ellipsoid in a flow. These simulations show that the high pressure region on the acute sides of a non-spherical particle result in a torque if an axis of the non-spherical particle is not aligned with the flow. This torque is only zero if the axis of the particle is perpendicular to the local direction of the flow. Moreover, the particle is most stable when the longest axis is aligned perpendicular to the flow.The alignment of the longest axis of a non-spherical particle perpendicular to the local flow leads to non-spherical particles having a larger average velocity compared to spherical particles with the same equivalent diameter. It is also shown that disc-shaped particles flow in a more steady trajectory compared to elongated particles, such as elongated ellipsoids and fibres. This is related to the magnitude of the pressure gradient on the acute side of the non-spherical particles. Finally, it is shown that the effect of wall roughness affects non-spherical particles differently than spherical particles. Particularly, a collision of a non-spherical particle with a rough wall induces a significant amount of rotational energy, whereas a corresponding collision with a spherical particle results in mostly a change in translational motion

Early Spatial Memory Impairment in a Double Transgenic Model of Alzheimer’s Disease TgF-344 AD

Before the course of Alzheimer’s disease fully manifests itself and largely impairs a patient’s cognitive abilities, its progression has already lasted for a considerable time without being noticed. In this project, we mapped the development of spatial orientation impairment in an active place avoidance task—a highly sensitive test for mild hippocampal damage. We tested vision, anxiety and spatial orientation performance at four age levels of 4, 6, 9, and 12 months across male and female TgF-344 AD rats carrying human genes for presenilin-1 and amyloid precursor protein. We found a progressive deterioration of spatial navigation in transgenic animals, beginning already at the age of 4 months, that fully developed at 6 months of age across both male and female groups, compared to their age-matched controls. In addition, we described the gradual vision impairment that was accentuated in females at the age of 12 months. These results indicate a rather early onset of cognitive impairment in the TgF-344 AD Alzheimer’s disease model, starting earlier than shown to date, and preceding the reported development of amyloid plaques