Functional and cognitive impairment, social functioning, frailty and adverse health outcomes in older patients with esophageal cancer, a systematic review.

BACKGROUND: Older patients with esophageal cancer are at high risk of adverse health outcomes, but the association of geriatric assessment with adverse health outcomes in these patients has not been systematically evaluated. The aim of this systematic review was to study the association of functional and cognitive impairment, social environment and frailty with adverse health outcomes in patients diagnosed with esophageal cancer. METHODS: We searched Pubmed, Embase, Web of Science and Cochrane Library for original studies reporting on associations of functional or cognitive impairment, social environment and frailty with adverse outcomes (mortality, functional or cognitive decline, adverse events during treatment, prolonged length of hospitalization (LOS) and health related quality of life (HRQoL)) after follow-up in patients with esophageal cancer. RESULTS: Of 1.391 identified citations, nineteen articles were included that reported on 53 associations. The median sample size of the included studies was 110 interquartile range (IQR 91-359). Geriatric conditions were prevalent: between 14 and 67% of the included participants were functionally impaired, around 42% had depressive symptoms and between 5 and 23% did not have a partner. In nineteen of 53 (36%) associations functional or cognitive impairment or frailty were significant associated with adverse health outcomes, but the studies were small. In four out of six (67%) associations with the largest sample size (n ≥ 359), functional impairment or social environment were significant associated with adverse health outcomes. CONCLUSION: Functional and cognitive impairment, depression and social isolation are prevalent in patients with esophageal cancer, and associate with adverse health outcomes. Geriatric measurements may guide decision-making and customize treatments, but more large studies are needed to explore the clinical usability.

Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis.

BACKGROUND AND AIMS: Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation would be accelerated by concomitant statin treatment, thereby further reducing hypercholesterolemia and atherosclerosis. METHODS: APOE*3-Leiden.CETP mice were fed a Western-type diet and treated without or with the selective ß3-adrenergic receptor (AR) agonist CL316,243 that activates BAT, atorvastatin (statin) or both. RESULTS: ß3-AR agonism increased energy expenditure as a result of an increased fat oxidation by activated BAT, which was not further enhanced by statin addition. Accordingly, statin treatment neither influenced the increased uptake of triglyceride-derived fatty acids from triglyceride-rich lipoprotein-like particles by BAT nor further lowered plasma triglyceride levels induced by ß3-AR agonism. Statin treatment increased the hepatic uptake of the formed cholesterol-enriched remnants generated by ß3-AR agonism. Consequently, statin treatment further lowered plasma cholesterol levels. Importantly, statin, in addition to ß3-AR agonism, also further reduced the atherosclerotic lesion size as compared to ß3-AR agonism alone, without altering lesion severity and composition. CONCLUSIONS: Statin treatment accelerates the hepatic uptake of remnants generated by BAT activation, thereby increasing the lipid-lowering and anti-atherogenic effects of BAT activation in an additive fashion. We postulate that, in clinical practice, combining statin treatment with BAT activation is a promising new avenue to combat hyperlipidemia and cardiovascular disease.