Young adults with acute coronary syndrome undergoing percutaneous coronary intervention: Insights from the Houston Methodist Young ACS-PCI Registry.

Background: Limited data exist on the risk profile and prognosis of young patients undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS). This study sheds light on the burden of cardiovascular risk factors and outcomes in this population.

Methods: The Houston Methodist Young ACS-PCI registry is a retrospective analysis of young adults (18 to 50 years) undergoing PCI for ACS between 2010 and 2022.

Brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease: A 12-week, active-treatment, extension trial.

Background: A 12-week randomized controlled trial demonstrated that brexpiprazole is efficacious for treating agitation in patients with dementia due to Alzheimer's disease.

Objective: To assess the long-term safety and tolerability of brexpiprazole for the treatment of agitation associated with dementia due to Alzheimer's disease.

Methods: This 12-week, active-treatment (oral brexpiprazole 2 or 3 mg/day) extension trial ran from October 2018-September 2022 at 66 sites in Europe/US.

Novel purine derivatives as selective CDK2 inhibitors with potential anticancer activities: Design, synthesis and biological evaluation.

Purine analogues were discovered to be inhibitors of CDK2, suggesting a potential therapeutic scaffold. This paper addresses the design, synthesis, and anticancer evaluation of purine analogues as kinase inhibitors. In the early stages of the investigation, the designed compounds demonstrated a promising docking score and greater protein-ligand stability in MD simulation than the standard, indicating a higher affinity against CDK2.

Percutaneous coronary intervention before transcatheter aortic valve implantation: A propensity score matched analysis.

Background: The role of percutaneous coronary intervention (PCI) in patients with stable coronary artery disease (CAD) who subsequently undergo transcatheter aortic valve replacement (TAVR) remains uncertain. Therefore, we conducted this study to assess the association of PCI before TAVR with mortality and cardiovascular outcomes.

Methods: We used the TriNetX database (Jan 2012 - Aug 2022) and grouped patients into PCI (3 months or less) before TAVR and no PCI.

Fragment-Based Discovery of Allosteric Inhibitors of SH2 Domain-Containing Protein Tyrosine Phosphatase-2 (SHP2).

The ubiquitously expressed protein tyrosine phosphatase SHP2 is required for signaling downstream of receptor tyrosine kinases (RTKs) and plays a role in regulating many cellular processes. Genetic knockdown and pharmacological inhibition of SHP2 suppresses RAS/MAPK signaling and inhibit the proliferation of RTK-driven cancer cell lines. Here, we describe the first reported fragment-to-lead campaign against SHP2, where X-ray crystallography and biophysical techniques were used to identify fragments binding to multiple sites on SHP2.

Intravascular imaging guided versus coronary angiography guided percutaneous coronary intervention: systematic review and meta-analysis.

Objective: To assess the absolute treatment effects of intravascular imaging guided versus angiography guided percutaneous coronary intervention in patients with coronary artery disease, considering their baseline risk.

Design: Systematic review and meta-analysis.

Data Sources: PubMed/Medline, Embase, and Cochrane Library databases up to 31 August 2023.

Outcomes With Intravascular Ultrasound and Optical Coherence Tomography Guidance in Percutaneous Coronary Intervention.

Intracoronary imaging has become an important tool in the treatment of complex lesions with percutaneous coronary intervention (PCI). This retrospective cohort study identified 1,118,475 patients with PCI from the Nationwide Readmissions Database from 2017 to 2019. Intravascular ultrasound (IVUS) and optical coherence tomography (OCT) were identified with appropriate International Classification of Diseases, Tenth Revision codes.

A commentary on the use of pharmacoenhancers in the pharmaceutical industry and the implication for DMPK drug discovery strategies.

Paxlovid, a drug combining nirmatrelvir and ritonavir, was designed for the treatment of COVID-19 and its rapid development has led to emergency use approval by the FDA to reduce the impact of COVID-19 infection on patients.In order to overcome potentially suboptimal therapeutic exposures, nirmatrelvir is dosed in combination with ritonavir to boost the pharmacokinetics of the active product.Here we consider examples of drugs co-administered with pharmacoenhancers.

Assessment of Repeat Revascularization in Percutaneous Coronary Intervention Randomized Controlled Trials as a Surrogate for Mortality: A Meta-Regression Analysis.

The association of repeat revascularization after percutaneous coronary intervention (PCI) with mortality is uncertain. To assess the association of repeat revascularization after PCI with mortality in patients with coronary artery disease (CAD). We identified randomized controlled trials comparing PCI with coronary artery bypass graft (CABG) or optimal medical therapy (OMT) using electronic databases through January 1, 2022.

Spontaneous Coronary Artery Dissection: An Elusive Disease of the Coronaries.

The articles in our Points to Remember column highlight important "need to know" facts about conditions that cardiovascular healthcare professionals may encounter. These may come from any medical specialty, such as nephrology or neurology. The article in this issue is provided by Swaminathan Perinkulam Sathyanarayanan, MD, Department of Internal Medicine, University of South Dakota, and Smitha Narayana Gowda, MD, and Alpesh Shah, MD, Houston Methodist DeBakey Heart & Vascular Center, Houston Methodist.

Clinical Positioning of the IAP Antagonist Tolinapant (ASTX660) in Colorectal Cancer.

Inhibitors of apoptosis proteins (IAPs) are intracellular proteins, with important roles in regulating cell death, inflammation, and immunity. Here, we examined the clinical and therapeutic relevance of IAPs in colorectal cancer. We found that elevated expression of cIAP1 and cIAP2 (but not XIAP) significantly correlated with poor prognosis in patients with microsatellite stable (MSS) stage III colorectal cancer treated with 5-fluorouracil (5FU)-based adjuvant chemotherapy, suggesting their involvement in promoting chemoresistance.

Discovery of ASTX029, A Clinical Candidate Which Modulates the Phosphorylation and Catalytic Activity of ERK1/2.

Aberrant activation of the mitogen-activated protein kinase pathway frequently drives tumor growth, and the ERK1/2 kinases are positioned at a key node in this pathway, making them important targets for therapeutic intervention. Recently, a number of ERK1/2 inhibitors have been advanced to investigational clinical trials in patients with activating mutations in B-Raf proto-oncogene or Ras. Here, we describe the discovery of the clinical candidate ASTX029 () through structure-guided optimization of our previously published isoindolinone lead ().

ASTX029, a Novel Dual-mechanism ERK Inhibitor, Modulates Both the Phosphorylation and Catalytic Activity of ERK.

The MAPK signaling pathway is commonly upregulated in human cancers. As the primary downstream effector of the MAPK pathway, ERK is an attractive therapeutic target for the treatment of MAPK-activated cancers and for overcoming resistance to upstream inhibition. ASTX029 is a highly potent and selective dual-mechanism ERK inhibitor, discovered using fragment-based drug design.

Outcomes of patients with moderate-to-severe Ischemia excluded from the ischemia trial.

Background: The International Study of Comparative Health Effectiveness with Medical and Invasive Approaches (ISCHEMIA) trial showed no difference in outcomes between medical therapy vs coronary revascularization in the management of patients with stable coronary artery disease. We aimed to determine the percentage of patients with at least moderate ischemia that would have been eligible for enrollment and evaluate the outcomes of those who would not.

Methods: Consecutive patients who underwent cardiac single-photon emission computed tomography (SPECT) between April 2016 and September 2019 were identified and all-cause mortality was determined.

Impact of adherence to the hybrid algorithm for initial crossing strategy selection in chronic total occlusion percutaneous coronary intervention.

Introduction And Objectives: The hybrid algorithm was designed to assist with initial and subsequent crossing strategy selection in chronic total occlusion (CTO) percutaneous coronary interventions (PCIs). However, the success of the initially selected strategy has received limited study.

Methods: We examined the impact of adherence to the hybrid algorithm recommendation for initial CTO crossing technique selection in 4178 CTO PCIs from a large multicenter registry.

Follow-up Outcomes After Chronic Total Occlusion Percutaneous Coronary Intervention in Patients With and Without Prior Coronary Artery Bypass Graft Surgery: Insights From the PROGRESS-CTO Registry.

Background: Long-term outcomes of patients with prior coronary artery bypass graft (CABG) surgery undergoing chronic total occlusion (CTO) percutaneous coronary intervention (PCI) have received limited study.

Methods: We compared the clinical and angiographic characteristics and procedural and follow-up outcomes of patients with and without prior CABG in a multicenter international registry.

Results: Of the 1572 patients included in this analysis, a total of 498 (32%) had prior CABG.

C-reactive protein and prognosis after percutaneous coronary intervention and bypass graft surgery for left main coronary artery disease: Analysis from the EXCEL trial.

Background: The prognostic impact of high-sensitivity C-reactive protein (CRP) levels in patients with left main coronary artery disease (LMCAD) treated with percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG) is unknown. We sought to determine the effect of elevated baseline CRP levels on the 3-year outcomes after LMCAD revascularization and to examine whether CRP influenced the relative outcomes of PCI versus CABG.

Methods: In the EXCEL trial, patients with LMCAD and Synergy between PCI with Taxus and Cardiac Surgery (SYNTAX) scores ≤32 were randomized to PCI versus CABG.

Chronic Total Occlusion Coronary Intervention: In Search of a Definitive Benefit.

Percutaneous coronary intervention (PCI) of chronic coronary total occlusion is the latest frontier in percutaneous intervention. There are vast improvements in the initial success and safety of the procedure as well as a better understanding of appropriateness and benefits. Advances in technology and skill allow for increased utilization of PCI in cases of chronic coronary total occlusion, with benefits regarding symptoms and quality of life.

Guidewire and microcatheter utilization patterns during antegrade wire escalation in chronic total occlusion percutaneous coronary intervention: Insights from a contemporary multicenter registry.

Objectives: We sought to describe contemporary guidewire and microcatheter utilization for antegrade wire escalation (AWE) during chronic total occlusion (CTO) percutaneous coronary intervention (PCI).

Background: Equipment utilization for AWE has been variable and evolving over time.

Methods: We examined device utilization during 694 AWE attempts in 679 patients performed at 15 experienced US centers between May 2012 and April 2015.

Incidence and influence of posterior capsule striae on the development of posterior capsule opacification after 1-piece hydrophobic acrylic intraocular lens implantation.

Purpose: To determine the incidence of intraoperative posterior capsule striae after implantation of a 1-piece hydrophobic acrylic intraocular lens (IOL), study the clinical impact on the patients' vision, and assess whether the presence of posterior capsule striae increases the risk for posterior capsule opacification (PCO).

Setting: Iladevi Cataract & IOL Research Centre, Ahmedabad, India.

Design: Case-control study.

Comparison of posterior capsule opacification with hydrophobic acrylic and hydrophilic acrylic intraocular lenses.

Purpose: To compare posterior capsule opacification (PCO) 3 years postoperatively in contralateral eyes with a single-piece hydrophobic acrylic and 1 of 2 single-piece hydrophilic acrylic intraocular lenses (IOLs) with different configurations.

Setting: Iladevi Cataract and IOL Research Institute, Ahmedabad, India.

Design: Prospective randomized clinical trial.