PURPOSE: Oral ondansetron is a safe and effective antiemetic drug to facilitate oral rehydration therapy in acute gastroenteritis (AGE) with mild dehydration. We investigated the effect of oral ondansetron therapy on intravenous (IV) hydration frequency and emergency department length of stay (EDLOS) in dehydrated children with AGE. METHODS: We reviewed 15,813 children aged 12-60 months with primary diagnosis of AGE who visited a tertiary care university-affiliated hospital emergency department. The enrolled children were divided into the pre- (from January 2009 to June 2011) and post- (from January 2016 to June 2018) ondansetron groups according to the implementation of oral ondansetron therapy in the emergency department. As primary outcomes, IV hydration frequency, EDLOS, and hospitalization rate were compared between the 2 groups. As secondary outcomes, EDLOS and hospitalization rate were compared between the children in the post-ondansetron group who underwent the therapy, and those who did not. RESULTS: Of 7,990 enrolled children, 3,300 (41.3%) were designated as the post-ondansetron group, and among them 1,093 (33.1%) underwent oral ondansetron therapy. This group showed a lower IV hydration frequency, a shorter median EDLOS compared to the other group (55.8% vs. 61.9%, P < 0.001; 175.0 vs. 223.0 minutes, P < 0.001, respectively), and a higher hospitalization rate (9.9% vs. 7.9%, P < 0.001). The children in the post-ondansetron group who underwent the therapy showed a shorter median EDLOS and a lower hospitalization rate compared to those who did not (142.0 vs. 205.0 minutes, P < 0.001; 2.9% vs. 13.4%, P < 0.001, respectively). CONCLUSION: Oral ondansetron therapy may reduce IV hydration frequency and EDLOS in dehydrated children with AGE, and can be considered in those having severe vomiting.
Child ; Dehydration ; Diagnosis ; Emergencies ; Emergency Service, Hospital ; Fluid Therapy ; Gastroenteritis ; Hospitalization ; Humans ; Length of Stay ; Ondansetron ; Tertiary Healthcare ; Vomiting

Background: Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. Methods: Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. Results: Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. Conclusion These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.

Background: Fabry disease is a rare X-linked genetic lysosomal disorder caused by mutations in the GLA gene encoding alpha-galactosidase A. Despite some data showing that profibrotic and proinflammatory cytokines and oxidative stress could be involved in Fabry disease-related renal injury, the pathogenic link between metabolic derangement within cells and renal injury remains unclear. Methods: Renal fibrosis was triggered by unilateral ureteral obstruction (UUO) in mice with Fabry disease to investigate the pathogenic mechanism leading to fibrosis in diseased kidneys. Results: Compared to kidneys of wild-type mice, lamellar inclusion bodies were recognized in proximal tubules of mice with Fabry disease. Sirius red and trichrome staining revealed significantly increased fibrosis in all UUO kidneys, though it was more prominent in obstructed Fabry kidneys. Renal messenger RNA levels of inflammatory cytokines and profibrotic factors were increased in all UUO kidneys compared to sham-operated kidneys but were not significantly different between UUO control and UUO Fabry mice. Protein levels of Nox2, Nox4, NQO1, catalase, SOD1, SOD2, and Nrf2 were not significantly different between UUO control and UUO Fabry kidneys, while the protein contents of LC3-II and LC3-I and expression of Beclin1 were significantly decreased in UUO kidneys of Fabry disease mouse models compared with wild-type mice. Notably, TUNEL-positive cells were elevated in obstructed kidneys of Fabry disease mice compared to wild-type control and UUO mice. Conclusion These findings suggest that impaired autophagy and enhanced apoptosis are probable mechanisms involved in enhanced renal fibrosis under the stimulus of UUO in Fabry disease.