Publications by authors named "Simon Newsome"

Article Synopsis
  • The study found that big clinical trials for a type of cancer called diffuse large B-cell lymphoma have confusing and different definitions for what they are trying to measure.
  • This makes it hard to understand and compare the results from these studies because they may be looking at different things.
  • The authors suggest that people involved in these trials should talk more to clearly define what they want to find out and the best ways to measure it.
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Background: Dilated cardiomyopathy (DCM) is a final common manifestation of heterogenous etiologies. Adverse outcomes highlight the need for disease stratification beyond ejection fraction.

Objectives: The purpose of this study was to identify novel, reproducible subphenotypes of DCM using multiparametric data for improved patient stratification.

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Background: Patient outcomes are poor for aggressive B-cell non-Hodgkin's lymphomas not responding to or progressing within 12 months after first-line therapy. Tisagenlecleucel is an anti-CD19 chimeric antigen receptor T-cell therapy approved for diffuse large B-cell lymphoma after at least two treatment lines.

Methods: We conducted an international phase 3 trial involving patients with aggressive lymphoma that was refractory to or progressing within 12 months after first-line therapy.

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When an entire cohort of patients receives a treatment, it is difficult to estimate the treatment effect in the treated because there are no directly comparable untreated patients. Attempts can be made to find a suitable control group (e.g.

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Objectives: This study aims to investigate the prognostic significance of late gadolinium enhancement (LGE) in patients without coronary artery disease and with normal range left ventricular (LV) volumes and ejection fraction.

Background: Nonischemic patterns of LGE with normal LV volumes and ejection fraction are increasingly detected on cardiovascular magnetic resonance, but their prognostic significance, and consequently management, is uncertain.

Methods: Patients with midwall/subepicardial LGE and normal LV volumes, wall thickness, and ejection fraction on cardiovascular magnetic resonance were enrolled and compared to a control group without LGE.

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Article Synopsis
  • Heart failure (HF) in patients with hypertrophic cardiomyopathy (HCM) significantly affects health outcomes, and the study aimed to identify predictors of HF using cardiovascular magnetic resonance (CMR) imaging.
  • Among 543 patients studied, 94 experienced severe outcomes related to HF, and over a median follow-up of 5.6 years, 39 patients (8.7%) reached the composite endpoint of HF death, transplantation, or severe functional decline.
  • Key independent predictors of HF included left ventricular end-systolic volume, the percentage of late gadolinium enhancement, age, and presence of mitral regurgitation, while the presence of inducible perfusion defects did not predict HF outcomes.
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Atrial fibrillation (AF) in hypertrophic cardiomyopathy (HC) is associated with significant symptomatic deterioration, heart failure, and thromboembolic disease. There is a need for better mechanistic insight and improved identification of at risk patients. We used cardiovascular magnetic resonance (CMR) to assess predictors of AF in HC, in particular the role of myocardial fibrosis.

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Objective: With increasing age, the prevalence of aortic stenosis grows exponentially, increasing left heart pressures and potentially leading to myocardial hypertrophy, myocardial fibrosis and adverse outcomes. To identify patients who are at greatest risk, an outpatient model for risk stratification would be of value to better direct patient imaging, frequency of monitoring and expeditious management of aortic stenosis with possible earlier surgical intervention. In this study, a relatively simple model is proposed to identify myocardial fibrosis in patients with a diagnosis of moderate or severe aortic stenosis.

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Aims: There is an important need for better biomarkers to predict left ventricular (LV) remodelling in dilated cardiomyopathy (DCM). We undertook a comprehensive assessment of cardiac structure and myocardial composition to determine predictors of remodelling.

Methods And Results: Prospective study of patients with recent-onset DCM with cardiovascular magnetic resonance (CMR) assessment of ventricular structure and function, extracellular volume (T1 mapping), myocardial strain, myocardial scar (late gadolinium enhancement) and contractile reserve (dobutamine stress).

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Objectives: This study sought to quantify myocardial blood flow (MBF) and myocardial perfusion reserve (MPR) in dilated cardiomyopathy (DCM) and examine the relationship between myocardial perfusion and adverse left ventricular (LV) remodeling.

Background: Although regarded as a nonischemic condition, DCM has been associated with microvascular dysfunction, which is postulated to play a role in its pathogenesis. However, the relationship of the resulting perfusion abnormalities to myocardial fibrosis and the degree of LV remodeling is unclear.

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Background: Patients with dilated cardiomyopathy whose symptoms and cardiac function have recovered often ask whether their medications can be stopped. The safety of withdrawing treatment in this situation is unknown.

Methods: We did an open-label, pilot, randomised trial to examine the effect of phased withdrawal of heart failure medications in patients with previous dilated cardiomyopathy who were now asymptomatic, whose left ventricular ejection fraction (LVEF) had improved from less than 40% to 50% or greater, whose left ventricular end-diastolic volume (LVEDV) had normalised, and who had an N-terminal pro-B-type natriuretic peptide (NT-pro-BNP) concentration less than 250 ng/L.

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Background: Myocardial fibrosis, identified by late gadolinium enhancement cardiovascular magnetic resonance, predicts outcomes in chronic heart failure (HF). Its prognostic significance in new-onset HF and reduced left ventricular ejection fraction (LVEF) is unclear. We investigated whether the pattern and extent of fibrosis predict survival in new-onset HF and reduced LVEF of initially uncertain pathogenesis.

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Left ventricular myocardial fibrosis in patients with aortic stenosis (AS) confers worse prognosis. Plasma osteoprotegerin (OPG), a cytokine from the TNF receptor family, correlates with the degree of valve calcification in AS, reflecting the activity of the tissue RANKL/RANK/OPG (receptor activator of nuclear factor κΒ ligand/RANK/osteoprotegerin) axis, and is associated with poorer outcomes in AS. Its association with myocardial fibrosis is unknown.

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Objectives: This study sought to investigate the association between the extent, location, and pattern of late gadolinium enhancement (LGE) and outcome in a large dilated cardiomyopathy (DCM) cohort.

Background: The relationship between LGE and prognosis in DCM is incompletely understood.

Methods: The authors examined the association between LGE and all-cause mortality and a sudden cardiac death (SCD) composite based on the extent, location, and pattern of LGE in DCM.

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Background: Personalized external aortic root support (PEARS) was introduced in 2004 for prevention of aortic root dilatation in Marfan patients. The individual's aortic root is replicated by 3-dimensional printing. A polymer mesh sleeve is manufactured, which is implanted with the aim to support and stabilize the aortic wall.

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Aim: To evaluate the relationship between sex, age and outcome in dilated cardiomyopathy (DCM).

Methods And Results: We used proportional hazard modelling to examine the association between sex, age and all-cause mortality in consecutive patients with DCM. Overall, 881 patients (290 women, median age 52 years) were followed for a median of 4.

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In the presence of time-dependent confounding, there are several methods available to estimate treatment effects. With correctly specified models and appropriate structural assumptions, any of these methods could provide consistent effect estimates, but with real-world data, all models will be misspecified and it is difficult to know if assumptions are violated. In this paper, we investigate five methods: inverse probability weighting of marginal structural models, history-adjusted marginal structural models, sequential conditional mean models, g-computation formula, and g-estimation of structural nested models.

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Background:: Atrial fibrillation (AF) is associated with increased morbidity in acute coronary syndrome patients, but impact on outcomes beyond 1 year is unclear.

Methods:: This was a post-hoc analysis from the long-tErm follow-uP of antithrombotic management patterns In acute CORonary syndrome patients (EPICOR) registry (NCT01171404), a prospective, observational study conducted in Europe and Latin America, which enrolled acute coronary syndrome survivors at discharge. Antithrombotic management patterns, mortality, a composite endpoint of death/new non-fatal myocardial infarction/stroke and bleeding events were assessed after 2 years of follow-up in patients with or without AF.

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Background: Improved understanding of dilated cardiomyopathy (DCM) due to titin truncation (TTNtv) may help guide patient stratification.

Objectives: The purpose of this study was to establish relationships among TTNtv genotype, cardiac phenotype, and outcomes in DCM.

Methods: In this prospective, observational cohort study, DCM patients underwent clinical evaluation, late gadolinium enhancement cardiovascular magnetic resonance, TTN sequencing, and adjudicated follow-up blinded to genotype for the primary composite endpoint of cardiovascular death, and major arrhythmic and major heart failure events.

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Background: Long-term risk of post-discharge mortality associated with acute coronary syndrome remains a concern. The development of a model to reliably estimate two-year mortality risk from hospital discharge post-acute coronary syndrome will help guide treatment strategies.

Methods: EPICOR (long-tErm follow uP of antithrombotic management patterns In acute CORonary syndrome patients, NCT01171404) and EPICOR Asia (EPICOR Asia, NCT01361386) are prospective observational studies of 23,489 patients hospitalized for an acute coronary syndrome event, who survived to discharge and were then followed up for two years.

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Background: Aortic stenosis is the most common age-related valvular pathology. Patients with aortic stenosis and myocardial fibrosis have worse outcome but the underlying mechanism is unclear. Lipoprotein(a) is associated with adverse cardiovascular risk and is elevated in patients with aortic stenosis.

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Background: Current guidelines only recommend the use of an implantable cardioverter defibrillator in patients with dilated cardiomyopathy for the primary prevention of sudden cardiac death (SCD) in those with a left ventricular ejection fraction (LVEF) <35%. However, registries of out-of-hospital cardiac arrests demonstrate that 70% to 80% of such patients have an LVEF >35%. Patients with an LVEF >35% also have low competing risks of death from nonsudden causes.

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