Device profile of the Impella 5.0 and 5.5 system for mechanical circulatory support for patients with cardiogenic shock: overview of its safety and efficacy.

INTRODUCTION: Trans-valvular micro-axial flow pumps such as Impella are increasingly utilized in patients with cardiogenic shock [CS]. A number of different Impella devices are now available providing a wide range of cardiac output. Among these, the Impella 5.0 and recently introduced Impella 5.5 pumps can provides 5.55 L/min of flow, enabling complete left ventricular support with more favorable hemodynamic effects on myocardial oxygen consumption and left ventricular unloading. These devices require placement of a surgical conduit graft for endovascular delivery, but are increasingly being used in patients with CS due to acutely decompensated heart failure [ADHF], acute myocardial infarction [AMI] and after cardiac surgery as a bridge to transplant or durable ventricular assist device surgery or myocardial recovery. AREAS COVERED: This review focuses on the device profile and use of the Impella 5.0 and 5.5 systems in patients with CS. Specifically; we reviewed the published literature for Impella 5.0 device to summarize data regarding safety and efficacy. EXPERT OPINION: The Impella 5.0 and 5.5 are trans-valvular micro-axial flow pumps for which the current data suggest excellent safety and efficacy profiles as approaches to provide circulatory support, myocardial unloading, and axillary placement enabling patient mobilization and rehabilitation. ABBREVIATIONS: pMCS, Percutaneous mechanical circulatory support devices; CS, Cardiogenic shock; ADHF, Acute decompensated heart failure; AMI, Acute myocardial infarction; LVAD, Left ventricular assist deviceI; ABP, Intra-aortic balloon pump; VA-ECLS, Veno-arterial extracorporeal life support.

Genome-Scale CRISPR-Mediated Control of Gene Repression and Activation.

While the catalog of mammalian transcripts and their expression levels in different cell types and disease states is rapidly expanding, our understanding of transcript function lags behind. We present a robust technology enabling systematic investigation of the cellular consequences of repressing or inducing individual transcripts. We identify rules for specific targeting of transcriptional repressors (CRISPRi), typically achieving 90%-99% knockdown with minimal off-target effects, and activators (CRISPRa) to endogenous genes via endonuclease-deficient Cas9. Together they enable modulation of gene expression over a ∼1,000-fold range. Using these rules, we construct genome-scale CRISPRi and CRISPRa libraries, each of which we validate with two pooled screens. Growth-based screens identify essential genes, tumor suppressors, and regulators of differentiation. Screens for sensitivity to a cholera-diphtheria toxin provide broad insights into the mechanisms of pathogen entry, retrotranslocation and toxicity. Our results establish CRISPRi and CRISPRa as powerful tools that provide rich and complementary information for mapping complex pathways.