Dabrafenib, alone or in combination with trametinib, in BRAF V600-mutated pediatric Langerhans cell histiocytosis.

Langerhans cell histiocytosis (LCH) is a rare, heterogenous, neoplastic disorder primarily affecting children. BRAF mutations have been reported in >50% of patients with LCH. The selective BRAF inhibitor, dabrafenib, in combination with the MEK1/2 inhibitor, trametinib, has been approved in select BRAF V600-mutant solid tumors.

Long-term outcomes of osilodrostat in Cushing's disease: LINC 3 study extension.

Objective: To investigate the long-term efficacy and tolerability of osilodrostat, a potent oral 11β-hydroxylase inhibitor, for treating Cushing's disease (CD).

Design/methods: A total of 137 adults with CD and mean 24-h urinary free cortisol (mUFC) > 1.5 × upper limit of normal (ULN) received osilodrostat (starting dose 2 mg bid; maximum 30 mg bid) during the prospective, Phase III, 48-week LINC 3 (NCT02180217) core study.

Randomized Trial of Osilodrostat for the Treatment of Cushing Disease.

Context: Cushing disease, a chronic hypercortisolism disorder, is associated with considerable morbidity and mortality. Normalizing cortisol production is the primary treatment goal.

Objective: We aimed to evaluate the safety and efficacy of osilodrostat, a potent, orally available 11βhydroxylase inhibitor, compared with placebo in patients with Cushing disease.

Is Cardiomegaly an Indication of "Heart-Sparing Effect" in Small Fetuses?

Introduction: This study aimed to test the hypothesis that cardiac size is maintained in small fetuses presenting with cardiomegaly.

Materials And Methods: We identified singleton fetuses with estimated fetal weight <10th centile and with cardiomegaly without another more likely cardiac or extra-cardiac cause. We used Z-scores for cardiac and thoracic circumferences normalized for gestational age (GA), biparietal diameter (BPD), head circumference (HC), and femur length (FL), obtained from 188 normally grown fetuses.

Six-minute walk test: prognostic value and effects of nebivolol versus placebo in elderly patients with heart failure from the SENIORS trial.

Background: There is limited information about the 6-min walk test (6MWT) in elderly patients with heart failure. We evaluated 6MWT and the effect of nebivolol on 6MWT from the SENIORS trial.

Methods And Results: The SENIORS trial evaluated nebivolol versus placebo on death and hospitalisation in patients aged ≥ 70 years with heart failure.

Long-term efficacy and safety of once-monthly pasireotide in Cushing's disease: A Phase III extension study.

Objectives: Many patients with Cushing's disease (CD) require chronic pharmacotherapy to control their hypercortisolism. We evaluated the efficacy and safety of long-acting pasireotide during a long-term extension study in patients with CD.

Design: Open-label extension to a 12-month Phase III study of long-acting pasireotide in CD (N = 150; NCT01374906).

Long-term safety and efficacy of subcutaneous pasireotide in patients with Cushing's disease: interim results from a long-term real-world evidence study.

Purpose: Clinical trials have demonstrated the favorable efficacy/safety profile of pasireotide in patients with Cushing's disease (CD). We report interim long-term results of an ongoing real-world evidence study of subcutaneous pasireotide in patients with CD.

Methods: Adults with CD receiving pasireotide, initiated before (prior-use) or at study entry (new-use), were monitored for ≤ 3 years during a multicenter observational study ( http://clinicaltrials.

Efficacy and safety of once-monthly pasireotide in Cushing's disease: a 12 month clinical trial.

Background: Cushing's disease is a rare debilitating endocrine disorder for which few prospective interventional studies have been done. We report results of the first phase 3 trial assessing long-acting intramuscular pasireotide in patients with Cushing's disease.

Methods: In this phase 3 clinical trial we recruited patients aged 18 years or older with persistent, recurrent, or de-novo (non-surgical candidates) Cushing's disease who had a mean urinary free cortisol (mUFC) concentration (from three 24 h samples) of 1·5-5·0 times the upper limit of normal (ULN), a normal or greater than normal morning plasma adrenocorticotropic hormone concentration, and a pituitary source of Cushing's syndrome, from 57 sites across 19 countries.

Prevalence and Prognostic Significance of Right Ventricular Systolic Dysfunction in Patients Undergoing Transcatheter Aortic Valve Implantation.

Background: Cardiovascular magnetic resonance (CMR) can provide important structural information in patients undergoing transcatheter aortic valve implantation. Although CMR is considered the standard of reference for measuring ventricular volumes and mass, the relationship between CMR findings of right ventricular (RV) function and outcomes after transcatheter aortic valve implantation has not previously been reported.

Methods And Results: A total of 190 patients underwent 1.

Clinical and economic consequences of non-cardiac incidental findings detected on cardiovascular computed tomography performed prior to transcatheter aortic valve implantation (TAVI).

Transcatheter aortic valve implantation (TAVI) is an effective treatment option for patients with severe degenerative aortic valve stenosis who are high risk for conventional surgery. Computed tomography (CT) performed prior to TAVI can detect pathologies that could influence outcomes following the procedure, however the incidence, cost, and clinical impact of incidental findings has not previously been investigated. 279 patients underwent CT; 188 subsequently had TAVI and 91 were declined.

Systemic right ventricular fibrosis detected by cardiovascular magnetic resonance is associated with clinical outcome, mainly new-onset atrial arrhythmia, in patients after atrial redirection surgery for transposition of the great arteries.

Background: We hypothesized that fibrosis detected by late gadolinium enhancement (LGE) cardiovascular magnetic resonance predicts outcomes in patients with transposition of the great arteries post atrial redirection surgery. These patients have a systemic right ventricle (RV) and are at risk of arrhythmia, premature RV failure, and sudden death.

Methods And Results: Fifty-five patients (aged 27±7 years) underwent LGE cardiovascular magnetic resonance and were followed for a median 7.

Utility of the SENIORS elderly heart failure risk model applied to the RICA registry of acute heart failure.

Background: Heart failure (HF) is predominantly a disease of the elderly. Reliable risk stratification would help in the management of this population, but no model has been well evaluated in elderly HF patients in both acute and chronic settings and not being restricted by ejection fraction. To evaluate the utility of the SENIORS risk model, developed from a clinical trial of elderly patients with chronic HF, in an independent cohort (National Spanish Registry: RICA) of elderly acute HF patients.

Coronary microvascular ischemia in hypertrophic cardiomyopathy - a pixel-wise quantitative cardiovascular magnetic resonance perfusion study.

Background: Microvascular dysfunction in HCM has been associated with adverse clinical outcomes. Advances in quantitative cardiovascular magnetic resonance (CMR) perfusion imaging now allow myocardial blood flow to be quantified at the pixel level. We applied these techniques to investigate the spectrum of microvascular dysfunction in hypertrophic cardiomyopathy (HCM) and to explore its relationship with fibrosis and wall thickness.

Calibration of myocardial T2 and T1 against iron concentration.

Background: The assessment of myocardial iron using T2* cardiovascular magnetic resonance (CMR) has been validated and calibrated, and is in clinical use. However, there is very limited data assessing the relaxation parameters T1 and T2 for measurement of human myocardial iron.

Methods: Twelve hearts were examined from transfusion-dependent patients: 11 with end-stage heart failure, either following death (n=7) or cardiac transplantation (n=4), and 1 heart from a patient who died from a stroke with no cardiac iron loading.

Influence of systolic blood pressure on clinical outcomes in elderly heart failure patients treated with nebivolol: data from the SENIORS trial.

Aims: There is limited information about the effects of beta-blockers in heart failure (HF) stratified by blood pressure, especially in the elderly and those with preserved EF. We evaluate the effects of nebivolol on outcomes in elderly patients with HF stratified by baseline systolic blood pressure (SBP) and EF.

Methods And Results: The SENIORS trial evaluated the effects of nebivolol and enrolled 2128 patients ≥ 70 years of age with HF.

Does manual therapy provide additional benefit to breathing retraining in the management of dysfunctional breathing? A randomised controlled trial.

Purpose: Dysfunctional breathing (DB) is associated with an abnormal breathing pattern, unexplained breathlessness and significant patient morbidity. Treatment involves breathing retraining through respiratory physiotherapy. Recently, manual therapy (MT) has also been used, but no evidence exists to validate its use.

Role of late gadolinium enhancement cardiovascular magnetic resonance in the risk stratification of hypertrophic cardiomyopathy.

Objective: Myocardial fibrosis identified by late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) in patients with hypertrophic cardiomyopathy (HCM) is associated with adverse cardiovascular events, but its value as an independent risk factor for sudden cardiac death (SCD) is unknown. We investigated the role of LGE-CMR in the risk stratification of HCM.

Methods: We conducted a prospective cohort study in a tertiary referral centre.

Biopsy-based calibration of T2* magnetic resonance for estimation of liver iron concentration and comparison with R2 Ferriscan.

Background: There is a need to standardise non-invasive measurements of liver iron concentrations (LIC) so clear inferences can be drawn about body iron levels that are associated with hepatic and extra-hepatic complications of iron overload. Since the first demonstration of an inverse relationship between biopsy LIC and liver magnetic resonance (MR) using a proof-of-concept T2* sequence, MR technology has advanced dramatically with a shorter minimum echo-time, closer inter-echo spacing and constant repetition time. These important advances allow more accurate calculation of liver T2* especially in patients with high LIC.

Effects of nebivolol on biomarkers in elderly patients with heart failure.

Background: Heart failure activates neurohormones, and elevated levels of brain natriuretic peptide (BNP) are associated with adverse outcomes. The SENIORS trial showed that nebivolol, a highly selective beta-1 antagonist with vasodilating properties, reduced the composite outcome of all cause mortality or cardiovascular hospital admissions in older patients with heart failure. We explored the effects of nebivolol on a range of neurohormones, cytokines and markers of nitric oxide activity in heart failure.

Organizational index mapping to identify focal sources during persistent atrial fibrillation.

Introduction: Localized rotors have been implicated in the mechanism of persistent atrial fibrillation (AF). Although regions of highest dominant frequency (DF) on spectral analysis of the left atrium (LA) have been said to identify rotors, other mechanisms such as wavefront collisions will sporadically also generate an inconsistent distribution of high DF. We hypothesized that if drivers of AF were present, their distinctive spectral characteristics would result more from their temporal stability than their high frequency.

Inflammatory bowel disease in the UK: is quality of care improving?

Objective: A national audit conducted in 2005/6 showed unacceptable quality of care for inpatients with inflammatory bowel disease (IBD) in the UK. This was re-audited in 2007/8 and 2010/11. The aim of this study is to examine the quality of care provided for inpatients with IBD in the UK.

The prevalence and prognostic significance of right ventricular systolic dysfunction in nonischemic dilated cardiomyopathy.

Background: Cardiovascular magnetic resonance is the gold-standard technique for the assessment of ventricular function. Although left ventricular volumes and ejection fraction are strong predictors of outcome in dilated cardiomyopathy (DCM), there are limited data regarding the prognostic significance of right ventricular (RV) systolic dysfunction (RVSD). We investigated whether cardiovascular magnetic resonance assessment of RV function has prognostic value in DCM.

International survey of T2* cardiovascular magnetic resonance in β-thalassemia major.

Accumulation of myocardial iron is the cause of heart failure and early death in most transfused thalassemia major patients. T2* cardiovascular magnetic resonance provides calibrated, reproducible measurements of myocardial iron. However, there are few data regarding myocardial iron loading and its relation to outcome across the world.

Prognostic value of cardiovascular magnetic resonance in patients with suspected arrhythmogenic right ventricular cardiomyopathy.

Background: Early recognition and accurate risk stratification are important in the management of arrhythmogenic right ventricular cardiomyopathy (ARVC). Identification of predictors of outcome by cardiovascular magnetic resonance (CMR) in patients undergoing evaluation for ARVC is limited. We investigated the predictive value of morphological abnormalities detected by CMR for major clinical events in patients with suspected ARVC.

Associations between the organisation of stroke services, process of care, and mortality in England: prospective cohort study.

Objective: To estimate the relations between the organisation of stroke services, process measures of care quality, and 30 day mortality in patients admitted with acute ischaemic stroke.

Design: Prospective cohort study.

Setting: Hospitals (n=106) admitting patients with acute stroke in England and participating in the Stroke Improvement National Audit Programme and 2010 Sentinel Stroke Audit.