Inclisiran as a siRNA Inhibitor of Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9); Past, Present, and Future.

Reducing low-density lipoprotein cholesterol (LDL-C) levels has been shown to reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Statins are the foundation of LDL-C lowering therapy with other non-statin agents used in circumstances where goal LDL-C levels are not reached or owing to intolerance to adverse effects of statins. In 2003, the discovery of the role of the proprotein convertase subtilisin/kexin type 9 (PCSK9) system in promoting elevated LDL-C levels led to new avenues of drug development to achieve target LDL-C.

Genome-Wide European Ancestry Study Identifies Coronary Artery Disease-Associated Loci Through Gene-Sex Hormone Interaction.

Background: Although sex differences in coronary artery disease (CAD) risk have been observed, little is known about the role of sex hormones in CAD genetics. Accounting for sex hormone levels may help identify CAD-risk loci and extend our knowledge of its genetic architecture.

Methods And Results: A total of 365 662 individuals of European ancestry enrolled in the UK Biobank were considered.

Enhancing negative control selection: A comparative analysis of random and targeted sampling techniques for obtaining High-Quality RNA from normal breast tissue.

Molecular profiling is a crucial aspect of cancer therapy selection, underscoring the necessity for representative sampling of both tumor and normal tissues. While much attention has been given to representative tumor sampling, there has been a notable lack of exploration into the issue of poor RNA quality in normal breast tissue processing. Normal breast tissue from the same patient is often used as a negative control for most "-omics" experiments.

Association of Lipoprotein(a) With Major Adverse Cardiovascular Events Across hs-CRP: A Systematic Review and Meta-Analysis.

Background: Lipoprotein(a) [Lp(a)] is an independent risk factor for atherosclerotic cardiovascular disease. The relationship between Lp(a) and major adverse cardiovascular events (MACE) in the context of high-sensitivity C-reactive protein (hs-CRP) levels remains controversial due to conflicting results from previous studies.

Objectives: This systematic review and meta-analysis aimed to clarify the association between Lp(a) and risk of MACE across different hs-CRP levels in both primary and secondary prevention settings.

Association of circulating ketone bodies with cognitive performance and dementia in the Multi-Ethnic Study of Atherosclerosis (MESA).

Introduction: Growing interest centers on the association between circulating ketone bodies (KB) and cognitive function, notably in aging and neurodegenerative diseases.

Methods: Associations of plasma KB with incident dementia and cognitive performances were examined among Multi-Ethnic Study of Atherosclerosis (MESA) participants. KB were measured using plasma samples collected following an overnight fasting at Exam 1 (2000-02) and detailed cognitive testing at Exam 5 (2010-2012,  = 4392), Exam 6 (2016-2018,  = 1838), and in MESA-MIND (2019-2021,  = 2060).

The future of hypertension pharmacotherapy: Ongoing and future clinical trials for hypertension.

Hypertension is among the most prevalent diagnoses across the world and increases the risk of many serious health problems, such as stroke, heart disease, and kidney disease. Pharmacological approaches to treat hypertension are often required and reduce blood pressure through mechanisms such as vasodilation, inhibition of the renin-angiotensin-aldosterone pathway, and increased urine output to reduce blood volume, among other mechanisms. Further research is ongoing to find novel pathways and mechanisms to treat hypertension, which we summarize in this review.

SALL4 and C-kit positive malignant extrarenal rhabdoid tumor of the pelvis in a child: A diagnostic and therapeutic challenge.

Extrarenal rhabdoid tumors (ERRTs) are highly aggressive pediatric tumors with very few cases reported in the literature. These tumors, similar to their renal counterparts, are characterized by inactivating mutations of the SMARCB1/INI-1 gene, a member of the SWI/SNF chromatin remodeling pathway. Diagnosis of ERRTs appears challenging owing to its rarity, varied morphological profile with a higher tendency for rhabdoid differentiation, and overlapping features with other SMARCB-1 deficient tumors.

Coronary Artery Calcium for Risk Stratification Among Persons With Very High HDL Cholesterol.

Background: Compared to normal high-density lipoprotein (HDL) cholesterol values, very high HDL cholesterol is associated with a higher incidence of mortality and atherosclerotic cardiovascular disease (ASCVD). As such, clinical risk stratification among persons with very high HDL cholesterol is challenging.

Objectives: Among persons with very high HDL cholesterol, the purpose was to determine the prevalence of coronary artery calcium (CAC) and compare the association between traditional risk factors vs CAC for all-cause mortality and ASCVD.

Incretin hormone agonists: Current and emerging pharmacotherapy for obesity management.

Obesity continues to be a significant global health challenge, affecting over 800 million individuals worldwide. Traditional management strategies, including dietary, exercise, and behavioral interventions, often result in insufficient and unsustainable weight loss. Lifestyle modification remains the cornerstone of obesity management, providing the foundation for other strategies.

Solitary fibrous tumor of the brain: A report of 3 cases.

Solitary fibrous tumor of the central nervous system (CNS) accounts for <1% of all primary CNS tumors. These tumors are typically dura-based and are graded using a three-tiered system based on cellularity, mitotic activity and necrosis. Extracranial metastasis of this disease is rare.

: A Novel ROS1 Oncogenic Fusion Detected on Next Generation Sequencing.

Advanced Non-Small Cell Lung Carcinoma (NSCLC) patients with gene rearrangement have shown significant therapeutic responses to tyrosine kinase inhibitors approved by the US Food and Drug Administration, with approximately 40 fusion partners documented in the existing literature. Our report highlights a novel fusion partner of that has demonstrated a conclusive response to the current standard of treatment.

Spindle epithelial tumor with thymus-like elements (SETTLE): a diagnostic challenge with distinct therapeutic implication; case report.

Spindle epithelial tumor with thymus-like elements (SETTLE) is a rare malignant neoplasm of the thyroid gland which is believed to arise from intrathyroidal thymic tissue. It predominantly affects young adults and children presenting with a thyroid mass of variable duration and rarely occurs in adults. It has a high overall survival with a tendency for delayed metastasis.

A study on beneficial impact of the use of medium-molecular-weight hydroxyethyl starch in granulocyte apheresis using continuous-flow cell separator Spectra Optia: A retrospective single-center study at a tertiary care oncology center.

Introduction: Granulocyte transfusion is one of the best therapeutic modalities in prolonged neutropenic patients with severe bacterial/fungal infections. Granulocyte harvest using conventional acid citrate dextrose (ACD) anticoagulant (ACD-A) by apheresis is not satisfactory in comparison to the use of hydroxyethyl starch (HES), but the latter is associated with various adverse events, especially with high-molecular-weight HES.

Aims And Objective: This study aimed to assess the beneficial impact of the use of medium-molecular-weight (MMW)-HES and trisodium citrate combination over ACD-A in granulocyte apheresis when using Spectra Optia.

Genetics and Pathophysiological Mechanisms of Lipoprotein(a)-Associated Cardiovascular Risk.

Elevated lipoprotein(a) is a genetically transmitted codominant trait that is an independent risk driver for cardiovascular disease. Lipoprotein(a) concentration is heavily influenced by genetic factors, including kringle IV-2 domain size, single-nucleotide polymorphisms, and interleukin-1 genotypes. Apolipoprotein(a) is encoded by the gene and contains 10 subtypes with a variable number of copies of kringle -2, resulting in >40 different apolipoprotein(a) isoform sizes.

The prognostic value of metabolic dysfunction-associated steatotic liver disease in acute myocardial infarction: A propensity score-matched analysis.

Aim: Patients with metabolic dysfunction-associated steatotic liver disease (MASLD) are at increased risk of incident cardiovascular disease. However, the clinical characteristics and prognostic importance of MASLD in patients presenting with acute myocardial infarction (AMI) have yet to be examined.

Methods: This study compared the characteristics and outcomes of patients with and without MASLD presenting with AMI at a tertiary centre in Singapore.

All we need to know about lipoprotein(a).

Lipoprotein(a) [Lp(a)], a genetically determined macromolecular complex, is independently and causally associated with atherosclerotic cardiovascular disease (ASCVD) and calcific aortic stenosis via proposed proinflammatory, prothrombotic, and proatherogenic mechanisms. While Lp(a) measurement standardization issues are being resolved, several guidelines now support testing Lp(a) at least once in each adult's lifetime for ASCVD risk prediction which can foster implementation of more aggressive primary or secondary prevention therapies. Currently, there are several emerging targeted Lp(a) lowering therapies in active clinical investigation for safety and cardiovascular benefit among both primary and secondary prevention populations.