Discovering Distinct Phenotypical Clusters in Heart Failure Across the Ejection Fraction Spectrum: a Systematic Review.

REVIEW PURPOSE: This systematic review aims to summarise clustering studies in heart failure (HF) and guide future clinical trial design and implementation in routine clinical practice. FINDINGS: 34 studies were identified (n = 19 in HF with preserved ejection fraction (HFpEF)). There was significant heterogeneity invariables and techniques used. However, 149/165 described clusters could be assigned to one of nine phenotypes: 1) young, low comorbidity burden; 2) metabolic; 3) cardio-renal; 4) atrial fibrillation (AF); 5) elderly female AF; 6) hypertensive-comorbidity; 7) ischaemic-male; 8) valvular disease; and 9) devices. There was room for improvement on important methodological topics for all clustering studies such as external validation and transparency of the modelling process. The large overlap between the phenotypes of the clustering studies shows that clustering is a robust approach for discovering clinically distinct phenotypes. However, future studies should invest in a phenotype model that can be implemented in routine clinical practice and future clinical trial design. HF = heart failure, EF = ejection fraction, HFpEF = heart failure with preserved ejection fraction, HFrEF = heart failure with reduced ejection fraction, CKD = chronic kidney disease, AF = atrial fibrillation, IHD = ischaemic heart disease, CAD = coronary artery disease, ICD = implantable cardioverter-defibrillator, CRT = cardiac resynchronization therapy, NT-proBNP = N-terminal pro b-type natriuretic peptide, BMI = Body Mass Index, COPD = Chronic obstructive pulmonary disease.

Talar Fractures in Children: A Possible Injury After Go-Karting Accidents.

Go-karting is an increasingly popular high-energy sport enjoyed by both children and adults. Because of the speeds involved, accidents involving go-karts can lead to serious injury. We describe 6 talar fractures in 4 patients that resulted from go-karting accidents. Talar fractures can cause severe damage to the tibiotalar joint, talocalcaneal or subtalar joint, and the talonavicular joint. This damage can, in turn, lead to complications such as avascular necrosis, arthritis, nonunion, delayed union, and neuropraxia, which have the potential to cause long-term disability in a child.

Identifying distinct clinical clusters in heart failure with mildly reduced ejection fraction.

INTRODUCTION: Heart failure (HF) is a heterogeneous syndrome, and the specific sub-category HF with mildly reduced ejection fraction (EF) range (HFmrEF; 41-49% EF) is only recently recognised as a distinct entity. Cluster analysis can characterise heterogeneous patient populations and could serve as a stratification tool in clinical trials and for prognostication. The aim of this study was to identify clusters in HFmrEF and compare cluster prognosis. METHODS AND RESULTS: Latent class analysis to cluster HFmrEF patients based on their characteristics was performed in the Swedish HF registry (n = 7316). Identified clusters were validated in a Dutch cross-sectional HF registry-based dataset CHECK-HF (n = 1536). In Sweden, mortality and hospitalisation across the clusters were compared using a Cox proportional hazard model, with a Fine-Gray sub-distribution for competing risks and adjustment for age and sex. Six clusters were discovered with the following prevalence and hazard ratio with 95% confidence intervals (HR [95%CI]) vs. cluster 1: 1) low-comorbidity (17%, reference), 2) ischaemic-male (13%, HR 0.9 [95% CI 0.7-1.1]), 3) atrial fibrillation (20%, HR 1.5 [95% CI 1.2-1.9]), 4) device/wide QRS (9%, HR 2.7 [95% CI 2.2-3.4]), 5) metabolic (19%, HR 3.1 [95% CI 2.5-3.7]) and 6) cardio-renal phenotype (22%, HR 2.8 [95% CI 2.2-3.6]). The cluster model was robust between both datasets. CONCLUSION: We found robust clusters with potential clinical meaning and differences in mortality and hospitalisation. Our clustering model could be valuable as a clinical differentiation support and prognostic tool in clinical trial design.

Are on-scene blood transfusions by a helicopter emergency medical service useful and safe? A multicentre case-control study.

INTRODUCTION: In the prehospital setting, crystalloid fluids are frequently used, but only erythrocytes are capable of transporting oxygen to tissues. The aim of this study was to establish the efficacy and safety of the prehospital use of uncross matched type O rhesus-negative packed red blood cells (URBC) by the Dutch physician-staffed helicopter emergency medical service. We hypothesized that prehospital URBC transfusions are safe and more effective with respect to survival than resuscitations with crystalloids. METHODS: The effects of prehospital URBC transfusions were studied by comparing a cohort of patients (>18 years) who were treated with a combination of URBC and crystalloid fluids with a matched control group of patients who received crystalloid fluids alone. RESULTS: Among 73 adults who received prehospital URBC transfusions, 50 (68%) patients were included. No transfusion reactions were observed. No effect of prehospital transfusion on 24-h or 30-day survival was found. Haemoglobin levels at presentation to the emergency department were higher in the URBC cohort. The two groups had similar cumulative erythrocyte requirements within the first 24 h. CONCLUSION: Neither survival benefits nor a decreased incidence of shock on admission were observed after prehospital helicopter emergency medical service URBC transfusions. There were no prehospital transfusion reactions in this study; therefore, URBC transfusions were deemed to be safe. A prospective randomized study is warranted to evaluate the effect of early URBC transfusions and transfusions with preheated URBC on the survival of patients with severe prehospital haemorrhagic shock.

Factors contributing to improved local control after mastectomy in patients with breast cancer aged 40 years or younger.

Long-term local control rates were studied in a series of 659 patients with invasive breast cancer aged 40 years or younger, who underwent mastectomy in general hospitals in the southern part of the Netherlands between 1988 and 2005. During a median follow-up time of 6.0 years, 34 patients developed a local recurrence in the chest wall without previous or simultaneous evidence of distant disease. The 5- and 10-year actuarial local recurrence rates for the total group were 5.6% (95% confidence interval [95% CI], 3.5-7.7%) and 7.3% (95% CI, 4.7-9.9%), respectively. A multivariate analysis showed that patients receiving radiotherapy (hazards ratio [HR], 0.29; 95% CI, 0.10-0.96) or adjuvant systemic treatment (HR 0.23; 95% CI, 0.08-0.65) had a significantly lower risk of local recurrence. It is concluded that excellent local control rates can be obtained with mastectomy in young women with breast cancer, especially in those who receive adjuvant systemic treatment and/or radiotherapy.