Cannabinoid Hyperemesis Syndrome in Pediatrics: An Emerging Problem.

Cannabis use has been evolving in both recreational drug use and medicinal uses, in part due to the recent introduction of various strains and components. With increasing use, we have seen emergence of a hyperemesis syndrome called cannabinoid hyperemesis syndrome characterized as intractable vomiting, nausea, and abdominal pain in the context of prolonged cannabinoid use. Although the antiemetic properties of cannabis have been known for years, the paradoxical effect of hyperemesis has yet to be elucidated. Herein we discuss the current research, epidemiology, and diagnosis and treatment of cannabinoid hyperemesis syndrome. Without timely diagnosis and treatment, patients may experience significant physical and emotional distress, as well as place unnecessary financial burden on the medical system.

TNF Receptor 1 Promotes Early-Life Immunity and Protects against Colitis in Mice.

Neutralization of tumor necrosis factor (TNF) represents a widely used therapeutic strategy for autoimmune diseases including inflammatory bowel disease (IBD). However, the fact that many patients with IBD are non-responsive to anti-TNF therapies suggests the need for a better understanding of TNF signaling in IBD. Here, we show that co-deletion of TNF receptor 1 (TNFR1, Tnfrsf1a) in the Il10-/- spontaneous colitis model exacerbates disease, resulting in very-early-onset inflammation after weaning. The disease can be interrupted by treatment with antibiotics. The single deletion of TNFR1 induces subclinical colonic epithelial dysfunction and mucosal immune abnormalities, including accumulation of neutrophils and depletion of B cells. During the pre-disease period (before weaning), both Tnfr1-/- and Il10-/-Tnfr1-/- animals exhibit impaired expression of pro-inflammatory cytokines compared with wild-type and Il10-/- controls, respectively. Collectively, these results demonstrate the net anti-inflammatory functions of TNF/TNFR1 signaling through the regulation of colonic immune homeostasis in early life.

A Novel Case of Biliary Atresia in a Premature Neonate With 1p36 Deletion Syndrome.

We describe the case of a premature male neonate diagnosed with biliary atresia who was found to have chromosome 1p36 deletion syndrome. Our patient was born prematurely, at a gestational age of 28 weeks. Pregnancy was complicated by advanced maternal age, gestational hypertension, and intrauterine growth restriction. Physical examination revealed several dysmorphic features, prompting a genetic evaluation, which revealed chromosome 1p36 deletion syndrome. At week 7 of life, he was found to have acholic stools. Direct bilirubin was found to be elevated despite discontinuation of total parenteral nutrition at 3 weeks of life, thus raising the suspicion for biliary atresia. Biliary atresia was confirmed by constellation of clinical, imaging and intraoperative findings. First reported in 1996, 1p36 deletion syndrome has been researched increasingly and several new phenotypic associations have been reported over the years. While attempts at linking specific phenotypic abnormalities with individual gene(s) deletion(s) are being made, deletion patterns that would affect specific organ system or function remain to be fully understood. Thus, clinicians currently rely on reports of previously identified abnormalities. To our knowledge, our patient is the first report of biliary atresia in a patient with chromosome 1p36 deletion syndrome. It is important to determine the etiology of the cholestasis, when present, while caring for premature neonates with 1p36 deletion syndrome. This is necessary to avoid assuming that the cholestasis is arising from total parenteral nutrition administration and not from other gastrointestinal anomalies including biliary atresia, which is a time-sensitive diagnosis.

A prognostic tool to predict severe acute pancreatitis in pediatrics.

BACKGROUND/OBJECTIVES: Approximately 15-20% of pediatric patients with acute pancreatitis (AP) develop severe disease. Severity scoring tools were developed for adult patients, but have limitations when applied in children. We aimed to identify early predictors of severe acute pancreatitis (SAP) on hospital admission for early risk stratification of patients. METHODS: Retrospective review of AP admissions was conducted. The derivation cohort included cases at Cincinnati Children's Hospital Medical Center (CCHMC) between 2009 and 2013. Clinical data collected during the first 24 h of admission were analyzed and a predictive model was derived through statistical analysis. The performance of the model was evaluated in a validation cohort from 2 more institutions other than CCHMC. RESULTS: In the derivation cohort 19% of the 284 admissions were SAP. A generalized linear mixed effect model analysis revealed that lipase, albumin and white blood count (WBC) play a role in the development of SAP (area under the receiver operating curve (AUROC 0.76)). In the validation cohort of 165 AP cases, SAP ranged from 8 to 20% at the three institutions. Performance of the model in this cohort was comparable to the derivation model (AUROC 0.77). There were 369 encounters in the combined derivation and validation pool (AUROC 0.76). CONCLUSIONS: The prognostic severity tool with 3 variables (lipase, albumin, and WBC) obtained within 24 h of admission can be applied to predict SAP in pediatric patients.

Hepatopulmonary syndrome associated with nodular regenerative hyperplasia after liver transplantation in a child.

HPS is a significant complication of portal hypertension in children with chronic liver disease and is an established indication for LT. It is characterized clinically by the triad of pulmonary vascular dilatation causing hypoxemia in the setting of advanced liver disease. NRH, a cause of non-cirrhotic portal hypertension, is characterized by diffuse benign transformation of the hepatic parenchyma into small regenerative nodules with minimal or no fibrosis. Development of NRH and HPS in pediatric LT recipients has not been reported, although occasional cases have been reported in adult LT recipients. In this report, we discuss a case of a three-yr-old male who developed HPS, two yr after LT. Pulmonary and cardiac causes for hypoxemia were ruled out by appropriate investigations including a chest X ray, echocardiogram, cardiac catheterization, and a CT angiographic study. The diagnosis of HPS was confirmed via bubble echocardiogram that demonstrated intrapulmonary shunting. Open liver biopsy revealed marked NRH. The patient underwent liver retransplantation that resulted in complete reversal of his pulmonary symptoms and normal oxygen saturations within three months after LT.

Definitions of pediatric pancreatitis and survey of present clinical practices.

OBJECTIVES: There is limited literature on acute pancreatitis (AP), acute recurrent pancreatitis (ARP), and chronic pancreatitis (CP) in children. The International Study Group of Pediatric Pancreatitis: In Search for a Cure (INSPPIRE) consortium was formed to standardize definitions, develop diagnostic algorithms, investigate disease pathophysiology, and design prospective multicenter studies in pediatric pancreatitis. METHODS: Subcommittees were formed to delineate definitions of pancreatitis, and a survey was conducted to analyze present practice. RESULTS: AP was defined as requiring 2 of the following: abdominal pain compatible with AP, serum amylase and/or lipase values ≥3 times upper limits of normal, and imaging findings of AP. ARP was defined as ≥2 distinct episodes of AP with intervening return to baseline. CP was diagnosed in the presence of typical abdominal pain plus characteristic imaging findings, or exocrine insufficiency plus imaging findings, or endocrine insufficiency plus imaging findings. We found that children with pancreatitis were primarily managed by pediatric gastroenterologists. Unless the etiology was known, initial investigations included serum liver enzymes, triglycerides, calcium, and abdominal ultrasound. Further investigations (usually for ARP and CP) included magnetic resonance or other imaging, sweat chloride, and genetic testing. Respondents' future goals for INSPPIRE included determining natural history of pancreatitis, developing algorithms to evaluate and manage pancreatitis, and validating diagnostic criteria. CONCLUSIONS: INSPPIRE represents the first initiative to create a multicenter approach to systematically characterize pancreatitis in children. Future aims include creation of patient database and biologic sample repository.