Validation and Potential Mechanisms of Red Cell Distribution Width as a Prognostic Marker in Heart Failure

Adverse outcomes have recently been linked to elevated red cell distribution width (RDW) in heart failure. Our study sought to validate the prognostic value of RDW in heart failure and to explore the potential mechanisms underlying this association

Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Iatrogenic Axillary Pseudoaneurysm Caused by Ultrasound-guided, Vacuum-assisted Biopsy of the Axillary Lymph Node: A Case Report

Arterial pseudoaneurysms are contained ruptures of the arterial wall that require prompt intervention. Iatrogenic pseudoaneurysms may result from various diagnostic and therapeutic procedures. Iatrogenic axillary pseudoaneurysms are quite rare, with few reported cases in the literature. We report a case of a 45-year-old woman who sustained an axillary pseudoaneurysm after an ultrasound-guided, vacuum-assisted biopsy of the axillary lymph node. An arteriovenous fistula developed concomitantly. Despite two image-guided treatments, thrombin injection and endovascular coil embolization, the pseudoaneurysm had persistent flow and was ultimately surgically resected at the time when the patient underwent mastectomy for breast cancer

Iatrogenic Axillary Pseudoaneurysm Caused by Ultrasound-guided, Vacuum-assisted Biopsy of the Axillary Lymph Node: A Case Report

Arterial pseudoaneurysms are contained ruptures of the arterial wall that require prompt intervention. Iatrogenic pseudoaneurysms may result from various diagnostic and therapeutic procedures. Iatrogenic axillary pseudoaneurysms are quite rare, with few reported cases in the literature. We report a case of a 45-year-old woman who sustained an axillary pseudoaneurysm after an ultrasound-guided, vacuum-assisted biopsy of the axillary lymph node. An arteriovenous fistula developed concomitantly. Despite two image-guided treatments, thrombin injection and endovascular coil embolization, the pseudoaneurysm had persistent flow and was ultimately surgically resected at the time when the patient underwent mastectomy for breast cancer

Accuracy of whole-body HDP SPECT/CT, FDG PET/CT, and their combination for detecting bone metastases in breast cancer:an intra-personal comparison

New generation SPECT/CT scanners allow rapid whole-body imaging, and potentially facilitate significantly improved diagnostic accuracy. Thus, the aim of this study was to compare the diagnostic accuracy of whole-body Tc-99m-HDP SPECT/CT, F-18-FDG PET/CT, and their combination for detecting bone metastases in breast cancer. Women with biopsy-proven breast cancer that were referred for whole-body SPECT/CT and FDG PET/CT were consecutively included in this retrospective study. Two blinded readers independently interpreted all scans. In a per-patient analysis, the diagnostic performances of whole-body SPECT/CT, FDG PET/CT, and their combination were compared using receiver operating characteristic (ROC) analysis. In a per-lesion analysis, the performances were compared using figures of merit (FoM) differences in Jackknife alternative free-response ROC analysis, which considers the location information. Follow-up served as reference standard. Overall, 25 consecutive women (median age: 55; range 38-82) with 117 lesions were included. The median follow-up was 21 months (2-46 months). The per-patient analysis revealed no significant differences in diagnostic performance (P = 0.16), while the per-lesion analysis revealed a diagnostic superiority of whole-body SPECT/CT over FDG PET/CT (P = 0.004). Specifically, the PET/CT FoM was significantly lower than the SPECT/CT FoM (FoM difference = -0.11, 95% CI [-0.21; -0.02], P = 0.021). No significant difference was observed between SPECT/CT and the combination of SPECT/CT and PET/CT. The per-lesion analysis suggest that SPECT/CT has a higher diagnostic accuracy than FDG PET/CT for the detection of bone metastases. Thus, SPECT/CT may be a useful adjunct to FDG PET/CT for staging of breast cancer patients

Aberrant regulation of a poison exon caused by a non-coding variant in a mouse model of Scn1a-associated epileptic encephalopathy.

Dravet syndrome (DS) is a developmental and epileptic encephalopathy that results from mutations in the Nav1.1 sodium channel encoded by SCN1A. Most known DS-causing mutations are in coding regions of SCN1A, but we recently identified several disease-associated SCN1A mutations in intron 20 that are within or near to a cryptic and evolutionarily conserved "poison" exon, 20N, whose inclusion is predicted to lead to transcript degradation. However, it is not clear how these intron 20 variants alter SCN1A expression or DS pathophysiology in an organismal context, nor is it clear how exon 20N is regulated in a tissue-specific and developmental context. We address those questions here by generating an animal model of our index case, NM_006920.4(SCN1A):c.3969+2451G>C, using gene editing to create the orthologous mutation in laboratory mice. Scn1a heterozygous knock-in (+/KI) mice exhibited an ~50% reduction in brain Scn1a mRNA and Nav1.1 protein levels, together with characteristics observed in other DS mouse models, including premature mortality, seizures, and hyperactivity. In brain tissue from adult Scn1a +/+ animals, quantitative RT-PCR assays indicated that ~1% of Scn1a mRNA included exon 20N, while brain tissue from Scn1a +/KI mice exhibited an ~5-fold increase in the extent of exon 20N inclusion. We investigated the extent of exon 20N inclusion in brain during normal fetal development in RNA-seq data and discovered that levels of inclusion were ~70% at E14.5, declining progressively to ~10% postnatally. A similar pattern exists for the homologous sodium channel Nav1.6, encoded by Scn8a. For both genes, there is an inverse relationship between the level of functional transcript and the extent of poison exon inclusion. Taken together, our findings suggest that poison exon usage by Scn1a and Scn8a is a strategy to regulate channel expression during normal brain development, and that mutations recapitulating a fetal-like pattern of splicing cause reduced channel expression and epileptic encephalopathy