Sonothrombolysis Before and After Percutaneous Coronary Intervention Provides the Largest Myocardial Salvage in ST Segment Elevation Myocardial Infarction.

Background: Sonothrombolysis is a therapeutic application of ultrasound with ultrasound contrast for patients with ST elevation myocardial infarction (STEMI). Recent trials demonstrated that sonothrombolysis, delivered before and after primary percutaneous coronary intervention (pPCI), increases infarct vessel patency, improves microvascular flow, reduces infarct size, and improves ejection fraction. However, it is unclear whether pre-pPCI sonothrombolysis is essential for therapeutic benefit.

Safety of Same-Day Hospital Discharge Post Patent Foramen Ovale Closure: Findings from a Multicenter Study.

Transcatheter patent foramen ovale (PFO) closure is indicated for patients with cryptogenic stroke. Although procedural safety is well established, there are limited data on the safety of same-day (SD) discharge. We aimed to review the outcomes of PFO closure with SD.

Structural Heart Interventions in the Elderly Population.

Aortic stenosis is the most common valvular heart disease in the elderly population. Since the advent of transcatheter aortic valve implantation (TAVI) in 2002, the clinical indications for this alternative to a surgical replacement have continually expanded. While the treatment of octo- and nonagenarians can present significant challenges, here we present a case of TAVI in an elderly patient.

A Complex Tricuspid Clip: Bridging the Decision.

We present this case of a 22-year-old woman with congenital heart disease as the youngest reported patient, to the best of our knowledge, to successfully undergo treatment of medically refractory torrential tricuspid regurgitation with the MitraClip system as an adjunct to guideline directed therapy. ().

Outcomes of transcatheter aortic valve replacement in end stage liver and renal disease.

Objectives: This study evaluates in-hospital, 30-day, and 1-year outcomes post-transcatheter aortic valve replacement (TAVR) in end stage liver disease (ESLD) and/or end stage renal disease (ESRD) compared with patients without these comorbidities.

Background: TAVR is an alternative to surgical aortic valve replacement in patients with ESLD and ESRD, though current outcomes data are limited.

Methods: We compared 309 patients (N = 29 ESLD and/or ESRD, N = 280 control) age > 18 who underwent transfemoral TAVR from 2014 to 2020 have been compared.

IL-18 mediates sickle cell cardiomyopathy and ventricular arrhythmias.

Previous reports indicate that IL18 is a novel candidate gene for diastolic dysfunction in sickle cell disease (SCD)-related cardiomyopathy. We hypothesize that interleukin-18 (IL-18) mediates the development of cardiomyopathy and ventricular tachycardia (VT) in SCD. Compared with control mice, a humanized mouse model of SCD exhibited increased cardiac fibrosis, prolonged duration of action potential, higher VT inducibility in vivo, higher cardiac NF-κB phosphorylation, and higher circulating IL-18 levels, as well as reduced voltage-gated potassium channel expression, which translates to reduced transient outward potassium current (Ito) in isolated cardiomyocytes.

A Multicenter, Randomized, Double-blind, Placebo-controlled Trial of Saccharomyces boulardii in Infants and Children With Acute Diarrhea.

Aim: This study was designed to assess the efficacy and safety of Saccharomyces cerevisiae variant boulardii CNCM I-3799 (S. boulardii CNCM I-3799) in the management of acute diarrhea in children.

Methods: A total of 100 infants and children 3-36 months of age with acute diarrhea received medical care according to the World Health Organization guidelines on the management of acute diarrhea in children and were randomly allocated to the probiotic group (S.

An Industry Perspective on Risks and Mitigation Strategies Associated with Post Conduct Phase of Clinical Trial.

Objective: To discuss the potential risks and their mitigation strategies in the post-conduct phase of the trial.

Background: Risk management is very important for the clinical trial (CT) to ensure that the trial delivers its desired outcome(s) in terms of achieving protocol objective and regulatory compliance.

Methodology: Experienced members of the clinical operation team of a pharmaceutical major underwent a series of sessions to identify risks associated with the post-conduct phase of CT and developed mitigation strategies based on own experiences and guidance documents.

Radial Percutaneous Coronary Intervention in Complex Arm and Chest Vasculature: Tips and Tricks.

Purpose Of Review: The purpose of this review is to identify the anatomical difficulties an operator may encounter during the transradial approach for cardiac catheterization and to offer tips and tricks to overcome those challenges.

Recent Findings: With increasing implementation of the transradial approach for cardiac catheterization, many new techniques have been utilized to overcome anatomical challenges. This article also discusses the difficulties faced during transradial approach in patients with prior coronary artery bypass grafting (CABG).

Effect of Food on the Pharmacokinetics of Saroglitazar Magnesium, a Novel Dual PPARαγ Agonist, in Healthy Adult Subjects.

Background And Objective: Peroxisome proliferator-activated receptors (PPARs) have recently become a focus of interest for their important roles in glucose and lipid metabolism. In humans, PPAR activation causes a decrease in plasma triglyceride (TG) levels, enhancement of high-density lipoprotein cholesterol (HDL-C) and simultaneous enhancement of very-low-density lipoprotein (VLDL) lipolysis, whereas PPARγ agonists act as insulin sensitizers and improve insulin resistance, which is very useful in patients with type 2 diabetes mellitus (T2DM). Saroglitazar magnesium is a dual PPAR agonist with potent predominant PPAR and moderate PPAR activity and the first glitazar to be granted marketing authorization in India.

Phase I Clinical Study of ZYAN1, A Novel Prolyl-Hydroxylase (PHD) Inhibitor to Evaluate the Safety, Tolerability, and Pharmacokinetics Following Oral Administration in Healthy Volunteers.

Objective: This phase I study of ZYAN1 was conducted to evaluate the safety, tolerability, and pharmacokinetics following oral administration in healthy volunteers.

Methods: The study was a randomized, double-blind, placebo-controlled phase I study carried out in two parts in addition to a third part involving an open-label study to evaluate the food/sex effect. A total of 100 subjects were enrolled into the study as follows: part I-single-dose study with ZYAN1 10, 25, 50, 100, 150, 200, and 300 mg (n = 56); part II-multiple-dose study with every other day dosing of ZYAN1 100, 150, 200, and 300 mg (n = 32); and part III-sex and food effect study with ZYAN1 150 mg (n = 12; open-label).

Associations of Prolonged QTc in Sickle Cell Disease.

Sudden death is a leading cause of mortality in sickle cell disease, implicating ventricular tachyarrhythmias. Prolonged QTc on an electrocardiogram (ECG), commonly seen with myocardial ischemia, is a known risk for polymorphic ventricular tachycardia (VT). We hypothesized that prolonged QTc is associated with mortality in sickle cell disease.

Safety and efficacy of rescue angioplasty for ST-elevation myocardial infarction with high utilization rates of glycoprotein IIb/IIIa inhibitors.

Background: Fibrinolytic therapies remain widely used for ST-elevation myocardial infarction, and for "failed reperfusion," rescue percutaneous coronary intervention (PCI) is guideline recommended to improve outcomes. However, these recommendations are based on data from an earlier era of pharmacotherapy and procedural techniques.

Methods And Results: To determine factors affecting prognosis after rescue PCI, we studied 241 consecutive patients (median age 55 years, interquartile range [IQR] 48-65) undergoing procedures between 2001 and 2009 (53% anterior ST-elevation myocardial infarction and 78% transferred).

High on treatment platelet reactivity and stent thrombosis.

Background: Stent thrombosis (ST) remains a major adverse outcome of percutaneous coronary intervention (PCI). We examined potential associations between high on treatment platelet reactivity and the risk of ST and assessed the effects of increased antiplatelet dosage on platelet inhibition.

Methods: Differences in clinical characteristics and the effect of aspirin and clopidogrel on platelet reactivity were determined after angiographically proven ST in 16 patients and in 40 patients without ST.

Abciximab as an adjunctive therapy for patients undergoing percutaneous coronary interventions.

Introduction: Platelets play a central role in the pathophysiology of acute coronary syndromes (ACS) and activation of platelet glycoprotein (GP) IIb/IIIa receptor is critical to platelet aggregation. Abciximab, a human murine chimeric antibody to the GPIIb/IIIa receptor, is an important biological therapy in the management of patients presenting with ACS.

Areas Covered: The objective of this review is to define the role of abciximab in the management of ACS by interpreting the available data from randomized clinical trials using abciximab in various clinical scenarios, particularly in percutaneous coronary intervention (PCI).

Ultrasound-mediated delivery of echogenic immunoliposomes to porcine vascular smooth muscle cells in vivo.

Vascular smooth muscle cells (VSMCs) are important targets in the treatment of atherosclerosis. However, the arterial media, where the majority of VSMCs reside, have proven to be a difficult target for drug/gene delivery. We have demonstrated that ultrasound enhances drug/gene delivery to VSMCs in vitro by using echogenic immunoliposomes (ELIPs) as the vector.

Lipid contribution to the affinity of antigen association with specific antibodies conjugated to liposomes.

Immunoliposomes, directed to clinically relevant cell-surface molecules with antibodies, antibody fragments or peptides, are used for site-specific diagnostic evaluation or delivery of therapeutic agents. We have developed intrinsically echogenic liposomes (ELIP) covalently linked to fibrin(ogen)-specific antibodies and Fab fragments for ultrasonic imaging of atherosclerotic plaques. In order to determine the effect of liposomal conjugation on the molecular dynamics of fibrinogen binding, we studied the thermodynamic characteristics of unconjugated and ELIP-conjugated antibody molecules.

Fibrin targeting of tissue plasminogen activator-loaded echogenic liposomes.

We recently reported entrapment of tissue-plasminogen activator (tPA) into echogenic liposomes (ELIP) with retention of echogenicity and thrombolytic effect. Integral to the potential of this agent for ultrasound-detectable local drug delivery is the specific binding of tPA-ELIP to clots. tPA contains fibrin-binding sites; we hypothesized that tPA when associated with ELIP, will maintain fibrin binding properties, rendering further manipulation for targeting of the tPA-ELIP unnecessary.

Increased systemic catecholamines in complex regional pain syndrome and relationship to psychological factors: a pilot study.

We have demonstrated that subjects with complex regional pain syndrome (CRPS) have asymmetric venous pool plasma concentrations of norepinephrine (NE) when affected and unaffected limbs are compared, with most demonstrating decreased NE levels in the affected limb. This pilot study explored whether systemic venous plasma catecholamine levels in CRPS subjects with sympathetically maintained pain (SMP) differ from those found in healthy volunteers. We also explored whether catecholamine levels were correlated with scores on psychometric measures of depression, anxiety, and personality.

Structural and functional imaging of 3D microfluidic mixers using optical coherence tomography.

To achieve high mixing efficiency in microfluidic devices, complex designs are often required. Microfluidic devices have been evaluated with light and confocal microscopy, but fluid-flow characteristics at different depths are difficult to separate from the en face images produced. By using optical coherence tomography (OCT), an imaging modality capable of imaging 3D microstructures at micrometer-scale resolutions over millimeter-size scales, we obtained 3D dynamic functional and structural data for three representative microfluidic mixers: a Y channel mixer, a 3D serpentine mixer, and a vortex mixer.