Improving 30-day mortality after PEG tube placement in England from 2007 to 2019: a retrospective national cohort analysis of 87,862 patients.

BACKGROUND AND AIMS: PEG has been associated with poor case selection and high mortality. We examined indications, 30-day mortality, and 7-day adverse events in a national cohort undergoing PEG tube insertion. METHODS: Adult patients undergoing their first PEG tube insertion from 2007 to 2019 were identified in the Hospital Episode Statistics database. Indications and adverse events were identified using International Statistical Classification of Diseases and Related Health Problems, 10th Revision codes. Multivariable logistic regression modeling examined factors associated with mortality. RESULTS: Of 87,682 patients identified, 58% were men and median age was 69 years (interquartile range, 57-79). The number of patients with dementia or stroke as the indication for PEG fell from 2007 to 2019 (dementia, from 147 to 28 [P < .001]; stroke, from 2851 to 1781 [P < .001]). The median interval from stroke admission to PEG tube insertion increased from 21 (interquartile range, 12-36) to 28 (interquartile range, 13-45) days (P < .001). Aspiration pneumonia within 7 days of PEG fell from 10.2% to 8.6% (P = .04). Thirty-day mortality fell from 13.2% to 5.3% (P < .001), with associated factors of increasing age (≥82 years quintile odds ratio [OR], 4.44; 95% confidence interval [CI], 4.01-4.92), PEG tube insertion during emergency admission (OR, 2.10; 95% CI, 1.97-2.25), Charlson comorbidity score ≥5 (OR, 1.67; 95% CI, 1.53-1.82), and dementia (OR, 1.46; 95% CI, 1.26-1.71). Female sex (OR, .81; 95% CI, .77-.85), least-deprived quintile (OR, .88; 95% CI, .81-.95), and more recent years of PEG tube insertion (2019; OR, .44; 95% CI, .39-.51) were negatively associated with mortality. CONCLUSIONS: Thirty-day mortality after PEG tube insertion has fallen 60% over 13 years. Dementia or stroke as an indication for PEG fell, and the time interval from stroke to PEG tube insertion increased. These findings may be attributable to improved patient selection and timing for PEG tube insertion.

Growth hormone induces hepatic production of fibroblast growth factor 21 through a mechanism dependent on lipolysis in adipocytes.

Fibroblast growth factor (FGF) 21 and growth hormone (GH) are metabolic hormones that play important roles in regulating glucose and lipid metabolism. Both hormones are induced in response to fasting and exert their actions on adipocytes to regulate lipolysis. However, the molecular interaction between these two hormones remains unclear. Here we demonstrate the existence of a feedback loop between GH and FGF21 on the regulation of lipolysis in adipocytes. A single bolus injection of GH into C57 mice acutely increases both mRNA and protein expression of FGF21 in the liver, thereby leading to a marked elevation of serum FGF21 concentrations. Such a stimulatory effect of GH on hepatic FGF21 production is abrogated by pretreatment of mice with the lipolysis inhibitor niacin. Direct incubation of either liver explants or human HepG2 hepatocytes with GH has no effect on FGF21 expression. On the other hand, FGF21 production in HepG2 cells is significantly induced by incubation with the conditioned medium harvested from GH-treated adipose tissue explants, which contains high concentrations of free fatty acids (FFA). Further analysis shows that FFA released by GH-induced lipolysis stimulates hepatic FGF21 expression by activation of the transcription factor PPARα. In FGF21-null mice, both the magnitude and duration of GH-induced lipolysis are significantly higher than those in their wild type littermates. Taken together, these findings suggest that GH-induced hepatic FGF21 production is mediated by FFA released from adipose tissues, and elevated FGF21 in turn acts as a negative feedback signal to terminate GH-stimulated lipolysis in adipocytes.