The role of endoplasmic reticulum stress in promoting aerobic glycolysis in cancer cells: An overview.

Aerobic glycolysis, also known as the Warburg effect, is a metabolic phenomenon frequently observed in cancer cells, characterized by the preferential utilization of glucose through glycolysis, even under normal oxygen conditions. This metabolic shift provides cancer cells with a proliferative advantage and supports their survival and growth. While the Warburg effect has been extensively studied, the underlying mechanisms driving this metabolic adaptation in cancer cells remain incompletely understood. In recent years, emerging evidence has suggested a potential link between endoplasmic reticulum (ER) stress and the promotion of aerobic glycolysis in cancer cells. The ER is a vital organelle involved in protein folding, calcium homeostasis, and lipid synthesis. Various cellular stresses, such as hypoxia, nutrient deprivation, and accumulation of misfolded proteins, can lead to ER stress. In response, cells activate the unfolded protein response (UPR) to restore ER homeostasis. However, prolonged or severe ER stress can activate alternative signaling pathways that modulate cellular metabolism, including the promotion of aerobic glycolysis. This review aims to provide an overview of the current understanding regarding the influence of ER stress on aerobic glycolysis in cancer cells to shed light on the complex interplay between ER stress and metabolic alterations in cancer cells. Understanding the intricate relationship between ER stress and the promotion of aerobic glycolysis in cancer cells may provide valuable insights for developing novel therapeutic strategies targeting metabolic vulnerabilities in cancer.

Is there a benefit of aspirin therapy for primary prevention to reduce the risk of atherosclerotic cardiovascular disease in patients with elevated Lipoprotein (a)-A review of the evidence.

Aspirin has long been recognized as a beneficial treatment for atherosclerotic cardiovascular disease (ASCVD) due to its antiplatelet effects. However, there is a need to more precisely identify individuals who would benefit from aspirin therapy for primary prevention in order to reduce the risk of ASCVD. Those with elevated lipoprotein (a) [Lp(a)] levels are at increased risk of ASCVD. In this article, we provide an overview of studies that have explored the use of aspirin therapy in individuals with elevated Lp(a). We discuss the potential mechanisms by which aspirin therapy may reduce ASCVD risk, and present a review of the data on the effectiveness of aspirin therapy in reducing ASCVD risk in individuals with elevated Lp(a). The presented evidence suggests that individuals with elevated Lp(a) benefit more from aspirin therapy for reduction of ASCVD events than the general population.

Outcomes of Mechanical Thrombectomy Compared With Systemic Thrombolysis in Pulmonary Embolism: A Comprehensive Evaluation From the National Inpatient Sample Database.

BACKGROUND: Systemic thrombolysis (ST) may not be ideal for many patients with acute pulmonary embolism (PE) due to bleeding risk. In this analysis, we evaluated the safety and effectiveness of mechanical thrombectomy (MT) as an alternative to ST for acute PE. METHODS: Patients aged ≥18 years who underwent MT and/or ST for PE were identified from the National Inpatient Sample database from 2016 to 2017. Patients who underwent catheter-directed thrombolysis were excluded. We compared in-hospital outcomes of both groups in this retrospective study. RESULTS: Of 16 890 patients who received an intervention for acute PE, 1380 (8.2%) received MT and 15 510 (91.8%) received ST. There was no difference in age between both groups. In-hospital mortality was significantly lower in patients who received MT than that in those who received ST (11.9% vs 20.6%, odds ratio [OR]: 0.52, 95% confidence interval [CI]: 0.29-0.93, p=0.028). There was no statistically significant difference in terms of periprocedural bleeding, intracranial hemorrhage, and acute kidney injury between the 2 groups (p≥0.608 for all). Patients who received MT had a higher rate of respiratory complications (19.0% vs 11.6%, OR: 1.79, 95% CI: 1.06-3.03, p=0.030) and discharge to an outside facility (34.1% vs 19.2%, OR: 2.18, 95% CI: 1.41-3.37, p<0.001) than those who received ST. CONCLUSION: Mortality was significantly lower with MT than that with ST, but larger randomized studies are needed to validate this. The use of MT should be individualized on the basis of the patients' clinical presentation, risk profile, and local resources. CLINICAL IMPACT: In this study, we utilized the National Inpatient Sample database to study the in-hospital outcomes of pulmonary embolism patients who underwent mechanical thrombectomy compared to those who underwent systemic thrombolysis. We found that the patients who were diagnosed with pulmonary embolism and underwent mechanical thrombectomy had significantly lower mortality compared to those who were treated using systemic thrombolysis. This study was the first of its kind, utilizing the national inpatient sample database for evaluation of mechanical thrombectomy in comparison with the standard of care. These result would direct further randomized controlled trials for better evaluation of the utilization of mechanical thrombectomy in the correct clinical context. Furthermore, our study demonstrated comparable peri-operative complications between the mechanical thrombectomy group and the systemic thrombolysis group. These results would direct clinicians to consider mechanical thrombectomy if clinically indicated given the promising results.