Pancreatitis in pre-adolescent children: a 10 year experience in the pediatric emergency department.

BACKGROUND: The diagnosis of pediatric pancreatitis has been increasing over the last 15 years but the etiology of this is uncertain. The population of pre-adolescent patients with pancreatitis in the emergency department has not been specifically described. Our objective was to determine the characteristics of these patients to illuminate this population and disease in order to better identify them and avoid a delay in diagnosis and treatment. METHODS: This was a retrospective descriptive study of consecutive pediatric patients under the age of 13 years between 2006 and 2016 who presented to our pediatric emergency department with a diagnosis of atraumatic pancreatitis. Patient characteristics, lab and imaging results, identified etiology of pancreatitis, and recurrence rates were recorded and evaluated. RESULTS: There were 139 visits, of which 85 were for a first episode of acute pancreatitis, and 54 were patients with an episode of recurrent pancreatitis. The median age for all visits was 8 years (IQ range 5-11). Of the acute cases, 26% had uncertain or undetermined etiologies of which half were thought to likely be viral related; 20% had systemic inflammatory or autoimmune diseases; 19% were associated with medications, with the most common being valproic acid; 16% were cholelithiasis-related; and 15% were found to have a genetic, congenital or structural etiology. No patients had elevated triglycerides. Those with cholelithiasis and genetic or structural defects were found to have a higher recurrence rate than those with other etiologies. There were only four patients diagnosed with chronic pancreatitis. CONCLUSIONS: The etiology of pancreatitis in pre-adolescent children has a different distribution than in adolescents and adults, with gallstone disease less frequent and concurrent contributing illness more common. Patients on pancreatitis-causing medications or with known genetic risk or structural pancreatic problems should be tested for pancreatitis if presenting with concerning symptoms. Hypertriglyceridemia and chronic pancreatitis with evidence of pancreatic exocrine insufficiency is uncommon in this population.

Brain-targeted (pro)renin receptor knockdown attenuates angiotensin II-dependent hypertension.

The (pro)renin receptor is a newly discovered member of the brain renin-angiotensin system. To investigate the role of brain (pro)renin receptor in hypertension, adeno-associated virus-mediated (pro)renin receptor short hairpin RNA was used to knockdown (pro)renin receptor expression in the brain of nontransgenic normotensive and human renin-angiotensinogen double-transgenic hypertensive mice. Blood pressure was monitored using implanted telemetric probes in conscious animals. Real-time PCR and immunostaining were performed to determine (pro)renin receptor, angiotensin II type 1 receptor, and vasopressin mRNA levels. Plasma vasopressin levels were determined by ELISA. Double-transgenic mice exhibited higher blood pressure, elevated cardiac and vascular sympathetic tone, and impaired spontaneous baroreflex sensitivity. Intracerebroventricular delivery of (pro)renin receptor short-hairpin RNA significantly reduced blood pressure, cardiac and vasomotor sympathetic tone, and improved baroreflex sensitivity compared with the control virus treatment in double-transgenic mice. (Pro)renin receptor knockdown significantly reduced angiotensin II type 1 receptor and vasopressin levels in double-transgenic mice. These data indicate that (pro)renin receptor knockdown in the brain attenuates angiotensin II-dependent hypertension and is associated with a decrease in sympathetic tone and an improvement of the baroreflex sensitivity. In addition, brain-targeted (pro)renin receptor knockdown is associated with downregulation of angiotensin II type 1 receptor and vasopressin levels. We conclude that central (pro)renin receptor contributes to the pathogenesis of hypertension in human renin-angiotensinogen transgenic mice.