Clinical characteristics, management, and outcome of incidental pulmonary embolism in cancer patients.

Incidental pulmonary embolisms (IPEs) are common in cancer patients. Examining the characteristics and outcomes of IPEs in cancer patients can help to ensure proper management, promoting better outcomes. To determine the clinical characteristics, management, and outcomes of IPEs for cancer patients, we conducted a 1:2 ratio case-control study and identified all consecutive patients with IPE who visited the emergency department at The University of Texas MD Anderson Cancer Center between 1 January 2006 and 1 January 2016. Each IPE case was matched with 2 controls using a propensity score obtained using logistic regression for IPE status with other factors affecting overall survival. A total of 904 confirmed cases were included in the analysis. IPE frequently occurred during the first year after cancer diagnosis (odds ratio [OR], 2.79; 95% confidence interval [95% CI], 2.37-3.29; P < .001). Patients receiving cytotoxic chemotherapy had a nearly threefold greater risk of developing IPE (OR, 2.87; 95% CI, 2.42-3.40; P < .001). In-hospital mortality was 1.9%. The 7- and 30-day mortality rates among the cases were 1.8% and 9.9%, respectively, which was significantly higher than in the control groups: 0.2% and 3.1%, respectively (P < .001). IPE was associated with reduced overall survival (hazard ratio [HR], 1.93; 95% CI, 1.74-2.14; P < .001). Concurrent incidental venous thromboembolism was identified in 189 of the patients (20.9%) and was also associated with reduced overall survival (HR, 1.65; 95% CI, 1.21-2.25; P = .001). Our results show that IPE events are associated with poor outcomes in cancer patients. Proper management plans similar to those of symptomatic pulmonary embolisms are essential.

HIV-1 viral protein R (Vpr) induces fatty liver in mice via LXRα and PPARα dysregulation: implications for HIV-specific pathogenesis of NAFLD.

HIV patients develop hepatic steatosis. We investigated hepatic steatosis in transgenic mice expressing the HIV-1 accessory protein Vpr (Vpr-Tg) in liver and adipose tissues, and WT mice infused with synthetic Vpr. Vpr-Tg mice developed increased liver triglyceride content and elevated ALT, bilirubin and alkaline phosphatase due to three hepatic defects: 1.6-fold accelerated de novo lipogenesis (DNL), 45% slower fatty acid ß-oxidation, and 40% decreased VLDL-triglyceride export. Accelerated hepatic DNL was due to coactivation by Vpr of liver X receptor-α (LXRα) with increased expression of its lipogenic targets Srebp1c, Chrebp, Lpk, Dgat, Fasn and Scd1, and intranuclear SREBP1c and ChREBP. Vpr enhanced association of LXRα with Lxrα and Srebp1c promoters, increased LXRE-LXRα binding, and broadly altered hepatic expression of LXRα-regulated lipid metabolic genes. Diminished hepatic fatty acid ß-oxidation was associated with decreased mRNA expression of Pparα and its targets Cpt1, Aox, Lcad, Ehhadh, Hsd10 and Acaa2, and blunted VLDL export with decreased expression of Mttp and its product microsomal triglyceride transfer protein. With our previous findings that Vpr circulates in HIV patients (including those with undetectable plasma HIV-1 RNA), co-regulates the glucocorticoid receptor and PPARγ and transduces hepatocytes, these data indicate a potential role for Vpr in HIV-associated fatty liver disease.