Glucagon-like peptide-1 (GLP-1) receptor agonists are incretin analogues that promote glucose-mediated insulin release and are used to treat type 2 diabetes mellitus and obesity. GLP-1 receptor agonists and GLP-1 and glucose-dependent insulinotropic peptide agonists have several mechanisms of action, including reduction of gastric emptying, inhibition of glucagon secretion, beneficial changes in the intestinal microbiome, and direct effects on hypothalamic nuclei to enhance satiety (which promotes weight loss). Beyond the impressive effects of GLP-1 receptor agonists on blood glucose levels and body weight, large-scale randomized, controlled trials have shown that GLP-1 receptor agonists reduce cardiovascular risk and slow progression to renal failure in persons at high risk and those with type 2 diabetes. Adverse side effects from GLP-1 receptor agonists are mostly gastrointestinal but may also include loss of muscle and bone mass. Questions remain about long-term adherence, weight regain after discontinuation of treatment, and the functional implications of the loss of muscle and bone mass. Recent and ongoing targeted studies suggest the possibility of additional uses for GLP-1 receptor agonists.

Renizgamglogene autogedtemcel (reni-cel) is an investigational clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a gene-edited autologous hematopoietic stem-cell therapy. The therapy was designed to disrupt the BCL11A binding sites in the HBG1 and HBG2 promoters to reactivate fetal hemoglobin production for the treatment of transfusion-dependent β-thalassemia.

Renizgamglogene autogedtemcel (reni-cel) is an investigational clustered regularly interspaced short palindromic repeats (CRISPR)-Cas12a gene-edited autologous hematopoietic stem-cell therapy. The therapy was designed to disrupt the BCL11A binding sites in the HBG1 and HBG2 promoters to reactivate fetal hemoglobin production for the treatment of sickle cell disease.

Sickle cell disease is characterized by chronic hemolytic anemia and recurrent severe vaso-occlusive crises. Ristoglogene autogetemcel (risto-cel) includes autologous CD34+ hematopoietic stem and progenitor cells that have been base-edited to target the HBG1 and HBG2 promoters and inhibit BCL11A binding without altering BCL11A expression, yielding a switch in hemoglobin production from sickle hemoglobin (HbS) to antisickling fetal hemoglobin (HbF).

Whether sirolimus-coated balloon angioplasty for infrainguinal artery disease reduces the incidence of major adverse limb events remains unknown.

Percutaneous coronary intervention (PCI) is increasingly used for revascularization of unprotected left main coronary artery disease. Whether intravascular ultrasonographic (IVUS) guidance during PCI results in better clinical outcomes than conventional angiographic guidance alone is uncertain.

Intravascular ultrasound (IVUS) guidance during percutaneous coronary intervention (PCI) has been associated with increased stent optimization and reduced adverse events among patients with complex coronary-artery lesions, but adoption of this strategy in Western countries remains low. Although practice guidelines recommend intracoronary imaging for anatomically complex lesions, evidence from current European practice is limited.

The role of long-term beta-blocker therapy after a myocardial infarction in patients without left ventricular systolic dysfunction or heart failure is unclear in the era of contemporary coronary-artery reperfusion and secondary prevention interventions.

Overactivation of the alternative complement pathway contributes to IgA nephropathy and glomerular inflammation. In the 9-month interim analysis of this phase 3 trial, iptacopan, a complement factor B inhibitor, led to a significant reduction of 38.3% in the 24-hour urinary protein-to-creatinine ratio as compared with placebo and had an acceptable safety profile.

Approved pharmacologic therapies for pediatric hypertrophic cardiomyopathy are lacking, and surgical intervention may be indicated in patients with left ventricular outflow tract obstruction. The efficacy and safety of mavacamten, a cardiac myosin inhibitor that is available for adults, warrant evaluation in adolescents.

Assessing intermediate coronary lesions with an intracoronary pressure wire improves clinical outcomes in patients undergoing cardiac catheterization and percutaneous coronary intervention (PCI). However, clinical use of pressure-wire-based physiological assessment remains low. Measurement of fractional flow reserve (FFR) derived from coronary angiographic images alone correlates well with pressure-wire-based FFR measurements and may simplify procedures, but its effect on clinical outcomes is unknown.

Current society guidelines recommend physiological assessment of intermediate coronary lesions to guide revascularization. Data regarding revascularization guided by vessel fractional flow reserve (vFFR), derived from three-dimensional quantitative coronary angiography without the need for a pressure wire or hyperemic agent, as compared with pressure-wire-based fractional flow reserve (FFR), are lacking.

Complex percutaneous coronary intervention (PCI) in patients with severely impaired left ventricular function carries a high risk of death and complications. Whether percutaneous left ventricular unloading improves outcomes remains unclear.

For patients with atrial fibrillation, the use of oral anticoagulant therapy to prevent stroke is limited by the risk of bleeding. Left atrial appendage closure is considered for patients who are unsuitable candidates for long-term anticoagulation, but its role in patients who are eligible for anticoagulants has not been established.

Whether anticoagulation alone is an adequate treatment for acute, intermediate-risk pulmonary embolism is uncertain.

Brepocitinib is a first-in-class, oral, selective TYK2-JAK1 inhibitor that blocks cytokine signaling, which has been implicated in dermatomyositis.

Despite guideline recommendations, evidence from randomized trials evaluating the appropriate low-density lipoprotein (LDL) cholesterol target for secondary prevention in patients with atherosclerotic cardiovascular disease remains limited.

Minipuberty refers to a specific period in early postnatal life with high activity of the hypothalamic-pituitary-gonadal (HPG) hormone axis. In infant boys 1 to 3 months of age, high concentrations of follicle-stimulating hormone and luteinizing hormone are released, which results in high levels of gonadal hormones from testicular Leydig cells (testosterone and insulin-like 3) and Sertoli cells (inhibin B and antimüllerian hormone). The HPG axis is also active in infant girls, who have adult levels of follicle-stimulating hormone and luteinizing hormone during this period. Immediately after minipuberty, the HPG axis is silenced for approximately 10 years and is reactivated only with the onset of puberty. Thus, minipuberty represents an early window for diagnosing disorders of sexual differentiation and rare endocrine disorders, such as congenital hypogonadotropic hypogonadism, and may help guide dosing of therapeutic interventions including gonadotropin therapy. Of note, minipuberty predicts adult reproductive capacity.

Among asymptomatic patients with severe aortic stenosis, a previous analysis showed that the risk of a composite of death during surgery or within 30 days after surgery (called operative mortality) or death from cardiovascular causes was significantly lower with early surgery than with conservative care. However, the long-term survival benefit of early surgery, as compared with conservative care, remains unclear.

Standard adjuvant chemotherapy for stage III colon cancer consists of a fluoropyrimidine-plus-oxaliplatin regimen. Whether the addition of atezolizumab (an anti-programmed death ligand 1 agent) to a modified FOLFOX6 regimen (fluorouracil, oxaliplatin, and leucovorin; called mFOLFOX6) would improve outcomes in patients with stage III colon cancer with mismatch repair-deficient (dMMR) status is unclear.