No abstract

Journal of Gastroenterology and Hepatology Researchwere analyzed. Patient characteristics, quantity and type of fluid administered, change in serum sodium, and 6-month mortality were recorded. RESULTS: A total of 146 eligible patients were identified, of which 62% (91/146) received primarily crystalloid and 38% (55/146) primarily albumin resuscitative fluid. Those within the albumin cohort were more likely to receive diuretics (82% vs 56%, p = 0.001), have a history of refractory ascites (56% vs 21%, p < 0.001), ascites on admission (96% vs 60%, p < 0.001), higher admission body mass (81.6 kg vs 75.5 kg, p = 0.04), higher creatinine (152.9 µmol/L vs 130.8 µmol/L, p = 0.03), and higher model for end-stage liver disease (MELD) score (23.0 vs 18.9, p = 0.002) compared to those in the crystalloid cohort. Fluid selection did not impact sodium correction (p = 0.67). In multivariate analysis, receiving albumin and having higher baseline serum albumin were both associated with reduced 6-month mortality, odds ratio of 0.06 (p = 0.013) and 0.13 (p = 0.035), respectively. CONCLUSIONS: Fluid selection in patients with cirrhosis and hyponatremia insignificantly impacted sodium correction. Albumin infusion was associated with reduced 6-month mortality. Larger prospective trials are required to investigate this relationship.

Context The selective progesterone modulator ulipristal acetate (ulipristal) offers a much-needed therapeutic option for the clinical management of uterine fibroids. Although ulipristal initially passed safety evaluations in Europe, postmarketing analysis identified cases of hepatic injury and failure, leading to restrictions on the long-term use of ulipristal. One of the factors potentially contributing to significant side effects with the selective progesterone modulators is cross-reactivity with other steroid receptors. Objective To determine whether ulipristal can alter the activity of the endogenous glucocorticoid receptor (GR) in relevant cell types. Design Immortalized human uterine fibroid cells (UtLM) and hepatocytes (HepG2) were treated with the synthetic glucocorticoid dexamethasone and/or ulipristal. Primary uterine fibroid tissue was isolated from patients undergoing elective gynecological surgery and treated ex vivo with dexamethasone and/or ulipristal. In vivo ulipristal exposure was performed in C57Bl/6 mice to measure the effect on basal gene expression in target tissues throughout the body. Results Dexamethasone induced the expression of established glucocorticoid-target genes period 1 (PER1), FK506 binding protein 51 (FKBP5), and glucocorticoid-induced leucine zipper (GILZ) in UtLM and HepG2 cells, whereas cotreatment with ulipristal blocked the transcriptional response to glucocorticoids in a dose-dependent manner. Ulipristal inhibited glucocorticoid-mediated phosphorylation, nuclear translocation, and DNA interactions of GR. Glucocorticoid stimulation of PER1, FKBP5, and GILZ was abolished by cotreatment with ulipristal in primary uterine fibroid tissue. The expression of glucocorticoid-responsive genes was decreased in the lung, liver, and uterus of mice exposed to 2 mg/kg ulipristal. Interestingly, transcript levels of Fkbp5 and Gilz were increased in the hippocampus and pituitary. Conclusions These studies demonstrate that ulipristal inhibits endogenous glucocorticoid signaling in human fibroid and liver cells, which is an important consideration for its use as a long-term therapeutic agent.

No abstract