α-Ketoglutarate-Mediated DNA Demethylation Sustains T-Acute Lymphoblastic Leukemia upon TCA Cycle Targeting.

Despite the development of metabolism-based therapy for a variety of malignancies, resistance to single-agent treatment is common due to the metabolic plasticity of cancer cells. Improved understanding of how malignant cells rewire metabolic pathways can guide the rational selection of combination therapy to circumvent drug resistance. Here, we show that human T-ALL cells shift their metabolism from oxidative decarboxylation to reductive carboxylation when the TCA cycle is disrupted.

Influence of inpatient opioid consumption on persistent use following total knee arthroplasty.

Background: Total knee arthroplasty (TKA) is associated with a high incidence of continued opioid use beyond the expected period of recovery. The aim of this study was to determine the influence of inpatient opioid consumption on the development of persistent use.

Methods: Opioid-naïve patients undergoing primary, uncomplicated TKA were included in a prospective, observational study at a single institution.