Among patients with STEMI undergoing primary percutaneous coronary intervention, adverse events are markedly increased in those with LVEF <40% during the index revascularization procedure. Nevertheless, these high-risk patients experience substantial clinical benefits from bivalirudin and PES.

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Respiratory distress syndrome (RDS) and bronchopulmonary dysplasia (BPD) contribute significantly to neonatal morbidity and mortality. Pulmonary function depends on the interaction between alveolar microvasculature and airspace development. While it has been shown in various animal models that vascular endothelial growth factor (VEGF) and its receptors increase in normal animal lung development, its pathophysiological role in neonatal respiratory failure is not yet entirely clear. Current animal and human studies exhibit controversial results. Though animal models are invaluable tools in the study of human lung disease, inherent differences in physiology mandate clarification of the timing of these studies to ensure that they appropriately correlate with the human stages of lung development. The purpose of this review article is to highlight the importance of considering the temporal relationship of VEGF and lung development in human neonates and developmentally-appropriate animal models with RDS and BPD.

Transcatheter aortic valve replacement (TAVR) is increasingly used to treat patients with aortic stenosis deemed high or extreme surgical risk candidates. Despite improved survival and quality of life following the procedure, TAVR is not without its complications. Stroke is a major source of morbidity and mortality in patients undergoing the procedure, with rates similar to and often higher than those associated with surgery. Most studies show a consistent link between TAVR and embolic lesions visualized on diffusion-weighted magnetic resonance imaging. The question of whether these lesions lead to long-term cognitive consequences remains open, but given the large literature on silent strokes and cognition, this association is probable. Initial studies implementing cerebral embolic protection devices in TAVR have yielded promising results with decreased neurological complications and appearance of new lesions on imaging. In this article, we will review the evidence linking silent stroke with cognitive decline, and potential therapeutic options to prevent stroke related to TAVR, including cerebral protection devices currently under investigation.

The Rho family small GTPase Cdc42 has been implicated in a wide range of cellular functions including the establishment of cell polarity and the remodeling of the actin cytoskeletal architecture, resulting in the tight regulation of cell growth and survival during developmental processes. The complete knock-out of Cdc42 in the mouse is embryonic-lethal, and its targeted deletion in various tissues has been shown to disrupt tissue homeostasis. Thus far, in most studies, the targeted deletion of Cdc42 occurred during embryogenesis. Here, we have used a conditional gene deletion strategy in mice to probe the specific role of Cdc42 during adult mammary gland function. Cdc42 conditional-knock-out females were unable to adequately nourish their pups, due to a disorganized epithelial compartment within their mammary glands. A closer examination showed that their mammary epithelial cells were not able to maintain functional alveolar lumens, due to an inability to establish normal apical/basal epithelial polarity, as well as proper cell-cell contacts. Loss of these essential epithelial characteristics led to a premature sloughing off of the Cdc42-null epithelial cells. Overall our findings demonstrate that Cdc42 plays essential roles in mammary gland function post pregnancy, where it helps to establish proper epithelial cell polarity and tissue homeostasis during lactation.

The risk of the composite endpoint did not differ significantly between those undergoing CAS versus CEA. The stenting group demonstrated a higher rate of periprocedural stroke, which was also apparent when patients were stratified by stenting department. These differences were likely driven by variation in baseline medical comorbidities and symptom status. © 2016 Wiley Periodicals, Inc.

BackgroundNeurological events associated with transcatheter aortic valve implantation are major contributors to morbidity and mortality. Choosing an appropriate endpoint to determine neuroprotection device efficacy is a key difficulty inhibiting the translation of the innovation from the laboratory to the bedside. Cost and sample size limitations inhibit the feasibility of using the rate of clinical (such as stroke or other cerebral) events as the primary efficacy endpoint. This paper focuses on consensus opinions from the 2013 Yale-University College London (UCL) Device Innovation Summit.DiscussionNeuroimaging, specifically diffusion-weighted magnetic resonance imaging (DW MRI), may serve as a surrogate endpoint for clinical studies detecting cerebral events in which cost and sample-size limitations prohibit the use of clinical outcomes. A major limitation of using imaging to prove efficacy in cardiac device studies is that no standardized endpoint exists. Ongoing trials investigating cerebral protection devices for transcatheter aortic valve implantation are utilizing and reporting various qualitative and quantitative DW MRI values; however, single lesion volume, number of new lesions, and total lesion volume have been found to be the most reproducible and prognostically important imaging measures.SummaryDW MRI may be a useful surrogate endpoint for clinical studies detecting cerebral events to determine the device’s success in neurological protection. Consensus from the 2013 Yale-UCL Device Innovation Summit specifically recommends the reporting of mean single lesion volume, number of new lesions, and total volume, and encourages European Union (EU)-US regulatory consensus in the guidance of implementing this endpoint.

Percutaneous carotid artery stenting (CAS) has emerged as a less invasive alternative to carotid endarterectomy for the treatment of carotid atherosclerotic disease. The main risk of CAS is the occurrence of neuro-vascular complications; however, carotid artery stenting-related dysautonomia (CAS-D) (hypertension, hypotension, and bradycardia) is the most frequently reported problem occurring in the periprocedural period. Alterations in autonomic homeostasis result from baroreceptor stimulation, which occurs particularly at the time of balloon inflation in the region of the carotid sinus. The response can be profound enough to induce asystole or even complete cessation of postganglionic sympathetic nerve activity. Frequency and factors predisposing a patient to CAS-D have been investigated in several studies; however, there are significant discrepancies in results among reports. Lack of consistent findings may arise from using different methods and definitions, as well as other factors discussed in detail in this review. Furthermore, a correlation of CAS-D with short and long-term outcomes has been investigated only in small and mostly retrospective studies, explaining why its prognostic significance remains uncertain. In this manuscript, we have focused on risk factors, pathophysiology and management of periprocedural autonomic dysfunction. As there is no standardized approach to the treatment of CAS-D, we present an algorithm for the periprocedural management of patients undergoing CAS. The proposed algorithm was developed based on our procedural experience as well as data from the available literature. The Yale Algorithm was successfully implemented at our institution and we are currently collecting data for short- and long-term safety. © 2014 Wiley Periodicals, Inc.