Antithrombotic therapy is essential to prevent adverse ischemic events, especially stent thrombosis and reinfarction during and after primary percutaneous coronary intervention (PCI) in patients with acute myocardial infarction (AMI).^1-4 The benefits of antithrombotic agents must be weighed against their risk of hemorrhagic complications, the occurrence of which has been strongly associated with subsequent mortality.^5-8

Background: The relationship between the systemic immune inflammatory index (SII) and the prognosis of hypertensive patients is unclear. This study aims to explore the association of SII with all-cause and cause-specific mortality in patients with hypertension.Methods: This study included 8524 adults with hypertension from the National Health and Nutritional Examination Surveys (NHANES) 2011–2018, and followed for survival through December 31, 2019. Cox proportional hazards models were used to investigate the associations between SII and mortality from all causes, cardiovascular disease (CVD), and cancer. Restricted cubic spline, piecewise linear regression, subgroup and sensitivity analyses were also used.Results: During a median follow-up of 4.58 years, 872 all-cause deaths occurred. After adjusting for covariates, higher SII was significantly associated with an elevated risk of CVD mortality. There was a 102% increased risk of CVD mortality per one-unit increment in natural log-transformed SII (lnSII) (P < 0.001). Consistent results were also observed when SII was examined as categorical variable (quartiles). The associations of SII with all-cause and cancer mortality were detected as U-shaped with threshold values of 5.97 and 6.18 for lnSII respectively. Below thresholds, higher SII was significantly associated with lower all-cause mortality (HR=0.79, 95%CI=0.64-0.97) and cancer mortality (HR=0.73, 95%CI=0.53-1.00). Above thresholds, SII was significantly positive associated with all-cause mortality (HR=1.93, 95%CI=1.55-2.40) and cancer mortality (HR=1.93, 95%CI=1.22-3.05). The results were robust in subgroup and sensitivity analyses.Conclusion: Higher SII (either as a continuous or categorical variable) were significantly associated with a higher risk of CVD mortality. The U-shaped associations were observed between SII and all-cause and cancer mortality.

Background: The continued success of oncological therapeutics is dependent on the mitigation of treatment-related adverse events, particularly cardiovascular toxicities. As such, there is an important need to understand the basic mechanisms of drug toxicities in the process of antitumor therapy. Our aim in this study was to elucidate the underlying mechanisms of sorafenib (sor)-induced cardiomyocyte damage.

Background: Guidelines have classified patients with acute coronary syndrome (ACS) and diabetes as a special population, with specific sections presented for the management of these patients considering their extremely high risk. However, in China up-to-date information is lacking regarding the burden of diabetes in patients with ACS and the potential impact of diabetes status on the in-hospital outcomes of these patients. This study aims to provide updated estimation for the burden of diabetes in patients with ACS in China and to evaluate whether diabetes is still associated with excess risks of early mortality and major adverse cardiovascular and cerebrovascular events (MACCE) for ACS patients. Methods: The Improving Care for Cardiovascular Disease in China-ACS Project was a collaborative study of the American Heart Association and the Chinese Society of Cardiology. A total of 63,450 inpatients with a definitive diagnosis of ACS were included. Prevalence of diabetes was evaluated in the overall study population and subgroups. Multivariate logistic regression was performed to examine the association between diabetes and in-hospital outcomes, and a propensity-score-matched analysis was further conducted. Results: Among these ACS patients, 23,880 (37.6%) had diabetes/possible diabetes. Both STEMI and NSTE-ACS patients had a high prevalence of diabetes/possible diabetes (36.8% versus 39.0%). The prevalence of diabetes/possible diabetes was higher in women (45.0% versus 35.2%, p < 0.001). Even in patients younger than 45 years, 26.9% had diabetes/possible diabetes. While receiving comparable treatments for ACS, diabetes/possible diabetes was associated with a twofold higher risk of all-cause death (adjusted odds ratio 2.04 [95% confidence interval 1.78–2.33]) and a 1.5-fold higher risk of MACCE (adjusted odds ratio 1.54 [95% confidence interval 1.39–1.72]). Conclusions: Diabetes was highly prevalent in patients with ACS in China. Considerable excess risks for early mortality and major adverse cardiovascular events were found in these patients. Trial registration NCT02306616. Registered December 3, 2014

Exosomes are important for intercellular communication, but the role of exosomes in the communication between adipose tissue (AT) and the liver remains unknown. The aim of this study is to determine the contribution of AT-derived exosomes in nonalcoholic fatty liver disease (NAFLD). Exosome components, liver fat content, and liver function were monitored in AT in mice fed a high-fat diet (HFD) or treated with metformin or GW4869 and with AMPKα1-floxed (Prkaα1^fl/fl/wild-type [WT]), Prkaα1^−/−, liver tissue-specific Prkaα1^−/−, or AT-specific Prkaα1^−/− modification. In cultured adipocytes and white AT, the absence of AMPKα1 increased exosome release and exosomal proteins by elevating tumor susceptibility gene 101 (TSG101)–mediated exosome biogenesis. In adipocytes treated with palmitic acid, TSG101 facilitated scavenger receptor class B (CD36) sorting into exosomes. CD36-containing exosomes were then endocytosed by hepatocytes to induce lipid accumulation and inflammation. Consistently, an HFD induced more severe lipid accumulation and cell death in Prkaα1^−/− and AT-specific Prkaα1^−/− mice than in WT and liver-specific Prkaα1^−/− mice. AMPK activation by metformin reduced adipocyte-mediated exosome release and mitigated fatty liver development in WT and liver-specific Prkaα1^−/− mice. Moreover, administration of the exosome inhibitor GW4869 blocked exosome secretion and alleviated HFD-induced fatty livers in Prkaα1^−/− and adipocyte-specific Prkaα1^−/− mice. We conclude that HFD-mediated AMPKα1 inhibition promotes NAFLD by increasing numbers of AT CD36-containing exosomes.