Enhancing oncolytic virotherapy by extracellular vesicle mediated microRNA reprograming of the tumour microenvironment.

Background: There has been limited success of cancer immunotherapies in the treatment of ovarian cancer (OvCa) to date, largely due to the immunosuppressive tumour microenvironment (TME). Tumour-associated macrophages (TAMs) are a major component of both the primary tumour and malignant ascites, promoting tumour growth, angiogenesis, metastasis, chemotherapy resistance and immunosuppression. Differential microRNA (miRNA) profiles have been implicated in the plasticity of TAMs.

Efficacy of coxsackievirus A21 against drug-resistant neoplastic B cells.

Primary drug resistance and minimal residual disease are major challenges in the treatment of B cell neoplasms. Therefore, this study aimed to identify a novel treatment capable of eradicating malignant B cells and drug-resistant disease. Oncolytic viruses eradicate malignant cells by direct oncolysis and activation of anti-tumor immunity, have proven anti-cancer efficacy, and are safe and well tolerated in clinical use.

Past, Present and Future of Oncolytic Reovirus.

Oncolytic virotherapy (OVT) has received significant attention in recent years, especially since the approval of talimogene Laherparepvec (T-VEC) in 2015 by the Food and Drug administration (FDA). Mechanistic studies of oncolytic viruses (OVs) have revealed that most, if not all, OVs induce direct oncolysis and stimulate innate and adaptive anti-tumour immunity. With the advancement of tumour modelling, allowing characterisation of the effects of tumour microenvironment (TME) components and identification of the cellular mechanisms required for cell death (both direct oncolysis and anti-tumour immune responses), it is clear that a "one size fits all" approach is not applicable to all OVs, or indeed the same OV across different tumour types and disease locations.

Predictors of Long-Term Outcomes in Asymptomatic Patients With Severe Aortic Stenosis and Preserved Left Ventricular Systolic Function Undergoing Exercise Echocardiography.

Background: In asymptomatic patients with severe aortic stenosis and preserved left ventricular ejection fraction, we sought to assess incremental prognostic utility of exercise stress echocardiography.

Methods And Results: We studied 533 such patients (age, 66±13 years; 78% men; 31% with coronary artery disease) who underwent exercise stress echocardiography between 2001 and 2012. Clinical, echocardiographic, and exercise variables (metabolic equivalents [METs], % of age-sex-predicted METs and heart rate recovery at first minute post exercise) were recorded.

Synergistic Utility of Brain Natriuretic Peptide and Left Ventricular Strain in Patients With Significant Aortic Stenosis.

Background: In aortic stenosis (AS), symptoms and left ventricular (LV) dysfunction represent a later disease state, and objective parameters that identify incipient LV dysfunction are needed. We sought to determine prognostic utility of brain natriuretic peptide (BNP) and left ventricular global longitudinal strain (LV-GLS) in patients with aortic valve area <1.3 cm(2).

Outcomes of surgical aortic valve replacement for severe aortic stenosis: Incorporation of left ventricular systolic function and stroke volume index.

Objectives: We sought to assess predictors of mortality in consecutive patients with severe aortic stenosis undergoing aortic valve replacement and to determine whether there are differences in mortality, separated on the basis of different aortic stenosis subtypes and left ventricular stroke volume index.

Methods: We studied 875 patients (aged 69 ± 12 years, 67% were men) with severe aortic stenosis (aortic valve area ≤ 1 cm(2)) who underwent aortic valve replacement between January 2007 and December 2008 (excluding other severe valve disease, balloon aortic valvuloplasty, and transcatheter aortic valve replacement). Clinical and echocardiographic data were recorded.

Impact of duration of mitral regurgitation on outcomes in asymptomatic patients with myxomatous mitral valve undergoing exercise stress echocardiography.

Background: Significant mitral regurgitation (MR) typically occurs as holosystolic (HS) or mid-late systolic (MLS), with differences in volumetric impact on the left ventricle (LV). We sought to assess outcomes of degenerative MR patients undergoing exercise echocardiography, separated based on MR duration (MLS versus HS).

Methods And Results: We included 609 consecutive patients with ≥III+myxomatous MR undergoing exercise echocardiography: HS (n=487) and MLS (n=122).

Incremental prognostic value of left ventricular global longitudinal strain in patients with aortic stenosis and preserved ejection fraction.

Background: We sought to assess the utility of left ventricular global longitudinal strain (LV-GLS) in predicting mortality in moderate to severe and paradoxical severe aortic stenosis (AS) patients with preserved ejection fraction.

Methods And Results: We studied 395 AS patients (70 ± 14 years, 57% men) with aortic valve area <1.3 cm(2) evaluated between January to June 2008 (excluding severe other valve disease and LV ejection fraction <50%).

Importance of exercise capacity in predicting outcomes and determining optimal timing of surgery in significant primary mitral regurgitation.

Background: In primary mitral regurgitation (MR), exercise echocardiography aids in symptom evaluation and timing of mitral valve (MV) surgery. In patients with grade ≥3 primary MR undergoing exercise echocardiography followed by MV surgery, we sought to assess predictors of outcomes and whether delaying MV surgery adversely affects outcomes.

Methods And Results: We studied 576 consecutive such patients (aged 57±13 years, 70% men, excluding prior valve surgery and functional MR).

Predictors of long-term outcomes in patients with significant myxomatous mitral regurgitation undergoing exercise echocardiography.

Background: Significant myxomatous mitral regurgitation leads to progressive left ventricular (LV) decline, resulting in congestive heart failure and death. Such patients benefit from mitral valve surgery. Exercise echocardiography aids in risk stratification and helps decide surgical timing.