Sex disparities in outcomes after carotid artery interventions: A systematic review.

This systematic review aimed to identify sex-specific outcomes in men and women after carotid endarterectomy (CEA) and carotid artery stenting (CAS), including transfemoral and transcarotid. A search of literature published from January 2000 through December 2022 was conducted using key terms attributed to carotid interventions on PubMed. Studies comparing outcome metrics post intervention (ie, myocardial infarction [MI], cerebral vascular accident [CVA] or stroke, and long-term mortality) among male and female patients were reviewed. Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. Overall, all studies reported low rates of perioperative complications. Among the studies that did not stratify outcomes by the preoperative symptom status, there were no significant sex differences in rates of perioperative strokes or MIs. Two studies, however, noted a higher rate of 30-day mortality in male patients undergoing CEA than in female patients. Analysis of asymptomatic patients undergoing CEA revealed no difference in perioperative MIs (female: 0% to 1.8% v male: 0.4% to 4.3%), similar rates of CVAs (female: 0.8% to 5% v male: 0.8% to 4.9%), and no significant differences in the long-term mortality outcomes. Alternatively, symptomatic patients undergoing CEA reported a higher rate of CVAs in female patients vs. male patients (7.7% v 6.2%) and showed a higher rate of death in female patients (1% v 0.7%). Among studies that did not stratify outcome by symptomatology, there was no difference in the 30-day outcomes between sexes for patients undergoing CAS. Asymptomatic patients undergoing CAS demonstrated similar incident rates across perioperative MIs (female: 0% to 5.9% v male: 0.28% to 3.3%), CVAs (female: 0.5% to 4.1% v male: 0.4% to 6.2%), and long-term mortality outcomes (female: 0% to 1.75% v male: 0.2% to 1.5%). Symptomatic patients undergoing CAS similarly reported higher incidences of perioperative MIs (female: 0.3% to 7.1% v male: 0% to 5.5%), CVAs (female: 0% to 9.9% v male: 0% to 7.6%), and long-term mortality outcomes (female: 0.6% to 7.1% v male: 0.5% to 8.2%). Sex-specific differences in outcomes after major vascular procedures are well recognized. Our review suggests that symptomatic female patients have a higher incidence of neurologic and cardiac events after carotid interventions, but that asymptomatic patients do not.

Dihydroceramide desaturase 1 (DES1) promotes anchorage-independent survival downstream of HER2-driven glucose uptake and metabolism.

Oncogenic reprogramming of cellular metabolism is a hallmark of many cancers, but our mechanistic understanding of how such dysregulation is linked to tumor behavior remains poor. In this study, we have identified dihydroceramide desaturase (DES1)-which catalyzes the last step in de novo sphingolipid synthesis-as necessary for the acquisition of anchorage-independent survival (AIS), a key cancer enabling biology, and establish DES1 as a downstream effector of HER2-driven glucose uptake and metabolism. We further show that DES1 is sufficient to drive AIS and in vitro tumorigenicity and that increased DES1 levels-found in a third of HER2+ breast cancers-are associated with worse survival outcomes. Taken together, our findings reveal a novel pro-tumor role for DES1 as a transducer of HER2-driven glucose metabolic signals and provide evidence that targeting DES1 is an effective approach for overcoming AIS. Results further suggest that DES1 may have utility as a biomarker of aggressive and metastasis-prone HER2+ breast cancer.