Ursodeoxycholic acid and COVID-19 outcomes: a cohort study and data synthesis of state-of-art evidence.

BACKGROUND: The potential of ursodeoxycholic acid (UDCA) in inhibiting angiotensin-converting enzyme 2 was demonstrated. However, conflicting evidence emerged regarding the association between UDCA and COVID-19 outcomes, prompting the need for a comprehensive investigation. RESEARCH DESIGN AND METHODS: Patients diagnosed with COVID-19 infection were retrospectively analyzed and divided into two groups: the UDCA-treated group and the control group. Kaplan-Meier recovery analysis and Cox proportional hazards models were used to evaluate the recovery time and hazard ratios. Additionally, study-level pooled analyses for multiple clinical outcomes were performed. RESULTS: In the 115-patient cohort, UDCA treatment was significantly associated with a reduced recovery time. The subgroup analysis suggests that the 300 mg subgroup had a significant (adjusted hazard ratio: 1.63 [95% CI, 1.01 to 2.60]) benefit with a shorter duration of fever. The results of pooled analyses also show that UDCA treatment can significantly reduce the incidence of severe/critical diseases in COVID-19 (adjusted odds ratio: 0.68 [95% CI, 0.50 to 0.94]). CONCLUSIONS: UDCA treatment notably improves the recovery time following an Omicron strain infection without observed safety concerns. These promising results advocate for UDCA as a viable treatment for COVID-19, paving the way for further large-scale and prospective research to explore the full potential of UDCA.

IL-18 expression in clinical human pituitary adenoma.

BACKGROUND: IL-18 is known as an interferon-inducing factor that belongs to the IL-1 family, and is synthesized as an inactive precursor protein. OBJECTIVE: The present study aims to investigate the expression of IL-18, IL-18R, R and IL-18 binding protein (BP) mRNA in various types of human pituitary tumors, such as adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), thyroid stimulating hormone (TSH)-producing adenomas and non-function adenomas. METHODS: Pituitary adenoma tissues were obtained during the surgery of 41 patients: nine patients had ACTH-producing pituitary adenomas, nine patients had GH-producing pituitary adenomas, five patients had TSH-producing pituitary adenomas, seven patients had PRL-producing pituitary adenomas, and 11 patients had non-functioning adenomas. The mRNA expression levels of IL-18, IL-18BP, IL-18R and IL-18R were quantified using real-time quantitative PCR. RESULTS: The mRNA expression of IL-18 was significantly higher in ACTH-, GH- and PRL-producing adenomas, when compared to non-function tumors. Similarly, a significantly higher mRNA expression of IL-18BP and IL-18R was observed in ACTH-, GH- and PRL-producing adenomas, when compared with non-functional adenomas. In contrast, no upregulation of IL-18R mRNA was observed in any of the pituitary adenomas. CONCLUSIONS: The mRNA levels of IL-18, IL-18BP and IL-18R are significantly elevated in clinical pituitary tumors, such as ACTH-, GH- and PRL-producing adenomas, when compared to non-functional adenomas. These present results suggest the possibility that IL-18 may be involved in the pathogenesis of pituitary adenoma.

Pooled Analysis of Gastric Emptying in Patients With Obesity: Implications for Oral Absorption Projection.

PURPOSE: Gastric emptying time is one of limiting factors that determines the pharmacokinetic properties of drugs administered by mouth. Despite the high prevalence of obesity worldwide, modifications in gastric emptying time have not been systematically addressed in this set of patients. The current analysis aims to quantitatively address obesity-related changes in gastric emptying time of solids, semisolids, and liquids compared with lean individuals, highlighting the relevant pharmacokinetic implications of oral drug absorption in patients with obesity. METHODS: We searched the Cochrane Library, PubMed, Web of Science, and Embase for all relevant articles published until November 1, 2020. Differences in gastrointestinal variables in relation to gastric emptying between obese and lean individuals were quantified by weighted mean difference (WMD) and ratio of means (RoM). Robustness of the analyses was evaluated by subgroup analysis and publication bias test. FINDINGS: A total of 17 studies with 906 participants were included. The gastric half-emptying time of solids (WMD, -10.4 minutes; P = 0.001; RoM, 0.90; P = 0.01) and liquids (WMD, -6.14 minutes; P < 0.001; RoM, 0.83, P = 0.03) was significantly shorter in individuals with obesity compared with lean individuals. These findings were confirmed by the subgroup analyses and publication bias tests. IMPLICATIONS: Our pooled analysis systemically quantifies the differences in gastric half-emptying time between individuals with obesity and lean individuals, facilitating better understanding and prediction of drug absorption in individuals with obesity through physiologically based pharmacokinetic approaches. Obesity is associated with a faster transit of both solids and liquids through the stomach.