Restoring mitochondrial quantity and quality to reverse the Warburg effect and drive neuroblastoma differentiation.

Reduced mitochondrial quality and quantity in tumors is associated with dedifferentiation and increased malignancy. However, it remains unclear how to restore mitochondrial quantity and quality in tumors and whether mitochondrial restoration can drive tumor differentiation. Our study shows that restoring mitochondrial function using retinoic acid (RA) to boost mitochondrial biogenesis and a mitochondrial uncoupler to enhance respiration synergistically drives neuroblastoma differentiation and inhibits proliferation.

Novel Approach for Assessing Outcomes of Type 1 Diabetes Prevention Trials Over a Fixed Time Interval.

Challenges in time to event type 1 diabetes (T1D) prevention trial design can yield negative results even for treatments that may actually improve disease pathology. We evaluated whether a binary metabolic end point for 12-month change from baseline to 1 year postrandomization could be useful in T1D prevention trials. This approach detected treatment effects at least as well as standard primary end points with shorter follow-up.

The rapidly increasing incidence of type 2 diabetes and macrovascular and microvascular complications disproportionately affects younger age groups: A decade of evidence from an international federated database.

Aims: To characterise recent trends in incidence and prevalence of type 2 diabetes (T2D) associated complications, and their relative impact across the lifespan.

Methods: We conducted a retrospective cohort study using the TriNetX global federated database. Incidence and prevalence of T2D and associated complications: ischaemic heart disease (IHD), heart failure, cerebral infarction, neuropathy, nephropathy, and retinopathy were assessed between 2012 and 2023.

Comparative Efficacy of Tirzepatide, Liraglutide, and Semaglutide in Reduction of Risk of Major Adverse Cardiovascular Events in Patients with Obstructive Sleep Apnea and Type 2 Diabetes: Real-World Evidence.

Glucagon-like peptide-1 (GLP-1) receptor agonists (liraglutide, semaglutide) and dual glucose-dependent insulinotropic polypeptide (GLP-1/GIP) receptor agonists (tirzepatide) are approved for treatment of type 2 diabetes (T2D) and obesity. To compare the relative efficacy of tirzepatide, liraglutide, and semaglutide in reducing major adverse cardiovascular events (MACEs) in patients with obstructive sleep apnea (OSA) and T2D. We performed a retrospective cohort analysis in a large global federated database of patients with OSA and T2D.

A Randomized, Double-Blind, Placebo-Controlled Trial of Abatacept for the Treatment of Relapsing, Nonsevere Granulomatosis With Polyangiitis.

Objective: To compare the efficacy of abatacept to placebo for the treatment of relapsing, nonsevere granulomatosis with polyangiitis (GPA).

Methods: In this multicenter trial, eligible patients with relapsing, nonsevere GPA were randomized to receive abatacept 125 mg subcutaneously once a week or placebo, both together with prednisone 30 mg/day (or equivalent), tapered and discontinued at week 12. Patients already taking methotrexate, azathioprine, mycophenolate, or leflunomide continued this medication at a stable dose.