Patients in epitypes with stem-cell-like methylation features showed inferior overall survival along with up-regulated stem cell gene expression signatures. We further identified a DNA methylation signature involving STAT motifs associated with FLT3-ITD mutations. Finally, DNA methylation signatures were stable at relapse for the large majority of patients, and rare epitype switching accompanied loss of the dominant epitype mutations and reversion to stem-cell-like methylation patterns. These results show that DNA methylation-based classification integrates important molecular features of AML to reveal the diverse pathogenic and biological aspects of the disease.
To determine the incidence, risk predictors and relative mortality risk of incident heart failure (HF) in patients following atrial fibrillation (AF) hospitalisation.
The Western Australian Hospitalisation Morbidity Data Collection was used to identify patients aged 25-94 years with index (first-in-period) AF hospitalisation, but without a prior HF admission, between 2000 and 2013. We evaluated the risk of incident HF hospitalisation within 3 years after AF admission, and the impact of HF hospitalisation on all-cause mortality.
The cohort comprised 52 447 patients, 57.5% men, with a median age of 73.1 (IQR 63.2-80.8) years. At 3 years after AF discharge, the cumulative incidence of HF (n=6153) was 11.7% (95% CI 11.5% to 12.0%) and all-cause death (n=9702) was 18.5% (95% CI 18.2% to 18.8%). Independent predictors of incident HF included advancing age, any history of myocardial infarction (MI), peripheral vascular disease, valvular heart disease, chronic kidney disease, chronic obstructive pulmonary disease, hypertension, diabetes, obesity and excessive alcohol use (all p<0.001). Patients hospitalised for first-ever HF compared with those without HF hospitalisation had an adjusted HR of 3.3 (95% CI 3.1 to 3.4) for all-cause mortality (p<0.001). Independent predictors of HF were also shared with those for mortality, with the exception of hypertension.
Hospitalisation for new HF is common in patients with AF and independently associated with a 3-fold hazard for death. The clinical predictors of incident HF emphasise the importance of integrated management of common comorbid conditions and lifestyle risk factors in patients with AF to reduce their morbidity and mortality.
Hospitalisation for new HF is common in patients with AF and independently associated with a 3-fold hazard for death. click here The clinical predictors of incident HF emphasise the importance of integrated management of common comorbid conditions and lifestyle risk factors in patients with AF to reduce their morbidity and mortality.
To date, long-term graft dysfunction, an important cause of death after heart transplantation, has been defined as a left ventricular ejection fraction (LVEF) of ≤40% or right atrial pressure (RAP) of ≥15 mm Hg. Empirical associations between measures of cardiac function and mortality post-transplant remain, however, unestablished.
We conducted a retrospective two-centre cohort study of consecutive adults who underwent heart transplant between 2002 and 2017. We evaluated the association between LVEF and RAP and mortality, including rejection and cardiac allograft vasculopathy as additional time-dependent covariates using Cox proportional hazard models. We applied restricted cubic splines to both LVEF and RAP.
Of 590 eligible heart transplant recipients, of whom 72% were male with a mean age of 49 years, 410 received their transplant at Toronto General Hospital and 180 at Rigshospitalet. We observed a 5% absolute risk increase for 1-year mortality, from 11% to 16%, when the LVEF dropped to 53% (HR 1.71 for LVEF of 53% compared with 60%, 95% CI 1.36 to 2.14) or when the RAP increased to 12 mm Hg (HR 1.49 for RAP of 12 mm Hg compared with 5 mm Hg, 95% CI 1.04 to 2.13).
In this study, we observed that small changes in graft function at any time post-transplant are associated with an increased mortality. Our results suggest that the current definition of graft dysfunction may underestimate patient risk of adverse outcomes.
In this study, we observed that small changes in graft function at any time post-transplant are associated with an increased mortality. Our results suggest that the current definition of graft dysfunction may underestimate patient risk of adverse outcomes.
It has been speculated that the SARS-CoV-2 was already widespread in western countries before February 2020.
We gauged this hypothesis by analysing the nasal swab of infants with either bronchiolitis or a non-infectious disease admitted to the Ospedale Maggiore, Milan (one of the first epicentres of SARS-CoV-2 outbreak in Europe) from November 2019.
The SARS-CoV-2 RNA was never detected in 218 infants with bronchiolitis (95 females, median age 4.9 months) and 49 infants (22 females, median age 5.6 months) with a non-infectious disease between November 2019 and February 2020. On the contrary, two infants hospitalised for bronchiolitis between March and April 2020 tested positive for SARS-CoV-2.
This study does not support the hypothesis that SARS-CoV-2 was already circulating among infants before the official outbreak of SARS-CoV-2 infection. However, it shows for the first time that SARS-CoV-2 might cause bronchiolitis requiring hospitalisation.
This study does not support the hypothesis that SARS-CoV-2 was already circulating among infants before the official outbreak of SARS-CoV-2 infection. However, it shows for the first time that SARS-CoV-2 might cause bronchiolitis requiring hospitalisation.
To identify factors associated with hypertension control among treated middle-aged UK adults.
A cross-sectional population-based study including 99 468 previously diagnosed, treated hypertensives enrolled in the UK Biobank. Hypertension control was defined as systolic blood pressure <140 mm Hg and diastolic blood pressure <90 mm Hg.
Median age was 62.3 years (IQR 57.3 to 66.0), 45.9% female, 92.0% white, 40.1% obese, 9.3% current smokers and 19.4% had prior cardiovascular disease. 38.1% (95% CI 37.8% to 38.4%) were controlled. In multivariable logistic regression, associations with lack of hypertension control included older age (OR 0.61, 95% CI 0.58 to 0.64 for 60-69 years compared with age 40-50 years), higher alcohol use (OR 0.61, 95% CI 0.58 to 0.64, for consuming >30 units per week compared with none), black ethnicity (OR 0.73, 95% CI 0.65 to 0.82 compared with white), obesity (OR 0.73, 95% CI 0.71 to 0.76 compared with normal body mass index). The strongest positive association with control was having ≥3 comorbidities (OR 2.click here