Predicting Major Adverse Cardiovascular Events Following Carotid Endarterectomy Using Machine Learning.

Background Carotid endarterectomy (CEA) is a major vascular operation for stroke prevention that carries significant perioperative risks; however, outcome prediction tools remain limited. The authors developed machine learning algorithms to predict outcomes following CEA. Methods and Results The National Surgical Quality Improvement Program targeted vascular database was used to identify patients who underwent CEA between 2011 and 2021.

Inverse relationship between amount and tumor CD274 (PD-L1) expression in colorectal carcinoma.

Objectives: The CD274 (programmed cell death 1 ligand 1, PD-L1)/PDCD1 (programmed cell death 1, PD-1) immune checkpoint axis is known to regulate the antitumor immune response. Evidence also supports an immunosuppressive effect of . We hypothesised that tumor CD274 overexpression might be inversely associated with abundance of in colorectal carcinoma.

Single- Versus Dual-Chamber Implantable Cardioverter-Defibrillator for Primary Prevention of Sudden Cardiac Death in the United States.

Background Routine addition of an atrial lead during an implantable cardioverter-defibrillator (ICD) implantation for primary prevention of sudden cardiac death, in patients without pacing indications, was not shown beneficial in contemporary studies. We aimed to investigate the use and safety of single- versus dual-chamber ICD implantations in these patients. Methods and Results Using the National Inpatient Sample database, we identified patients with no pacing indications who underwent primary-prevention ICD implantation in the United States between 2015 and 2019.

A Phase I Randomized Trial of Once-Daily Versus Twice-Daily Recombinant Human Parathyroid Hormone (1-84) for Hypoparathyroidism.

Recombinant human parathyroid hormone (1-84), rhPTH(1-84), is an approved adjunctive treatment to oral calcium and active vitamin D for adult patients with hypoparathyroidism; however, there is limited information on the effect of twice daily (BID) dosing of rhPTH(1-84). This was a phase I, open-label, randomized, crossover, multicenter study conducted in adult patients with chronic hypoparathyroidism. The primary objective was to assess the pharmacokinetic profile and pharmacodynamic effects of 1 day of treatment with rhPTH(1-84) administered subcutaneously at 25 μg BID, 50 μg BID, and 100 μg once daily (QD) with or without supplemental oral calcium.

Birth Weight Is Associated With Clonal Hematopoiesis of Indeterminate Potential and Cardiovascular Outcomes in Adulthood.

Background High and low birth weight are independently associated with increased cardiovascular disease risk in adulthood. Clonal hematopoiesis of indeterminate potential (CHIP), the age-related clonal expansion of hematopoietic cells with preleukemic somatic mutations, predicts incident cardiovascular disease independent of traditional cardiovascular risk factors. Whether birth weight predicts development of CHIP later in life is unknown.

Optimized Risk Score to Predict Mortality in Patients With Cardiogenic Shock in the Cardiac Intensive Care Unit.

Background Mortality prediction in critically ill patients with cardiogenic shock can guide triage and selection of potentially high-risk treatment options. Methods and Results We developed and externally validated a checklist risk score to predict in-hospital mortality among adults admitted to the cardiac intensive care unit with Society for Cardiovascular Angiography & Interventions Shock Stage C or greater cardiogenic shock using 2 real-world data sets and Risk-Calibrated Super-sparse Linear Integer Modeling (RiskSLIM). We compared this model to those developed using conventional penalized logistic regression and published cardiogenic shock and intensive care unit mortality prediction models.

Impact of Diabetes on Outcomes in Patients Hospitalized With Acute Myocardial Infarction: Insights From the Atherosclerosis Risk in Communities Study Community Surveillance.

Background Diabetes is associated with increased risk of acute myocardial infarction (AMI). The demographic trends, clinical presentation, management, and outcomes of patients with diabetes who are hospitalized with AMI have not been recently reported. Methods and Results The ARIC (Atherosclerosis Risk in Communities) study conducted hospital surveillance of AMI in 4 US communities.

Association Between Life's Simple 7 and Biomarkers of Cardiovascular Disease: Aldosterone, Interleukin-6, C-Reactive Protein.

Background To promote ideal cardiovascular health, the American Heart Association recommends adhering to Life's Simple 7 (LS7)-achieving healthy targets for body mass index, physical activity, dietary intake, blood pressure, fasting plasma glucose, and cholesterol, along with smoking abstinence. Poorer achievement of LS7 (lower score) has been associated with the development of hypertension and cardiovascular disease. However, less is known about the associations between LS7 and specific biomarkers linked to cardiovascular health: aldosterone, CRP (C-reactive protein), and IL-6 (interleukin-6).

Association of Accelerometer-Measured Physical Activity and Sedentary Behavior With Incident Cardiovascular Disease, Myocardial Infarction, and Ischemic Stroke: The Women's Health Study.

Background Few studies have investigated associations of acclerometer-based assessments of physical activity (PA) and sedentary behavior (SB) with incidence of cardiovascular disease (CVD) and its components. This prospective cohort study assessed the associations of accelerometer-measured PA and SB with total CVD, myocardial infarction, and ischemic stroke (IS). Methods and Results The authors included 16 031 women aged 62 years and older, free of CVD, with adherent accelerometer wear (≥10 hours/day for ≥4 days) from the Women's Health Study (mean age, 71.

Structural rationalization of GSPT1 and IKZF1 degradation by thalidomide molecular glue derivatives.

Thalidomide and its derivatives are molecular glues that bind cereblon (CRBN), a component of an E3 ubiquitin ligase complex, and mediate protein interactions with neosubstrates resulting in their polyubiquitination and proteasomal degradation. The structural features of neosubstrate binding have been elucidated that highlight key interactions with a β-hairpin degron containing a glycine, which is present in a wide-range of proteins, including zinc-finger transcription factors such as IKZF1, and the translation termination factor GSPT1. Here, we profile 14 closely-related thalidomide derivatives in CRBN occupancy, and IKZF1 and GSPT1 degradation cell-based assays, and use crystal structures, computational docking and molecular dynamics to delineate subtle structure-activity relationships.

NLRP3 Inflammasome Activation in Peripheral Arterial Disease.

Background Peripheral arterial disease (PAD) is estimated to affect 7% of the adult population in the United States; however, there is currently little understanding of the key cellular and molecular pathways at play. With PAD characterized by vascular inflammation and associated calcification, the current study set out to elucidate the role of NLRP3 (nucleotide oligomerization domain-like receptor family, pyrin domain containing 3) inflammasome activation in the current cohort. Methods and Results Global proteomics of human vessels with and without PAD from a total of 14 donors revealed an increase of proinflammatory associated ontologies, specifically acute phase and innate immunity.

Incident Atrial Fibrillation and Risk of Dementia in a Diverse, Community-Based Population.

Background Atrial fibrillation (AF) is the most common, clinically relevant arrhythmia in adults and associated with ischemic stroke and premature death. However, data are conflicting on whether AF is independently associated with risk of dementia, particularly in diverse populations. Methods and Results We identified all adults from 2 large integrated health care delivery systems between 2010 and 2017 and performed a 1:1 match of incident AF: no AF by age at index date, sex, estimated glomerular filtration rate category, and study site.

Spontaneous idiopathic spinal subdural hemorrhage in a 16-year-old boy: A rare case in pediatrics and review of literature.

Idiopathic spinal subdural hematoma (SSDH) is a rare phenomenon. Here, we present a 16-year-old-boy who presented with acute sudden onset weakness and brown squared syndrome; the cervical MRI findings showed acute subdural hematoma from C2 to C6. Emergent surgical intervention was performed, and significant improvement was seen in follow-ups.

Covalent drugs targeting histidine - an unexploited opportunity?

Covalent drugs and chemical probes often possess pharmacological advantages over reversible binding ligands, such as enhanced potency and pharmacodynamic duration. The highly nucleophilic cysteine thiol is commonly targeted using acrylamide electrophiles, but the amino acid is rarely present in protein binding sites. Sulfonyl exchange chemistry has expanded the covalent drug discovery toolkit by enabling the rational design of irreversible inhibitors targeting tyrosine, lysine, serine and threonine.