Assuring Quality for Non-hospital-based Biologic Infusions in Pediatric Inflammatory Bowel Disease: A Clinical Report From the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition.

The primary aim of this Clinical Report by the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition is to provide formal guidance to pediatric gastroenterologists and clinicians, health systems, and insurance payers regarding home- and office-based infusions for biologic therapies in pediatric inflammatory bowel disease. Patients in North America are increasingly denied coverage by payers based on "place of service" codes at hospital-based infusion units where the treating clinicians primarily provide care. A task force with topic expertise generated 8 best practice recommendations to ensure quality of care for pediatric patients with inflammatory bowel disease receiving non-hospital-based biologic infusions. Pragmatic considerations discussed in this report include patient safety, pediatric-trained nurse availability, care coordination, patient-centeredness, shared liability, administrative support, clinical governance, and costs of care.

Pulmonary Manifestations in Adolescents With Inflammatory Bowel Disease.

Objectives. The available literature on pulmonary disease in pediatric inflammatory bowel disease is limited. We evaluated the prevalence of pulmonary manifestations in pediatric inflammatory bowel disease and their association with disease severity. Methods. Patients completed the St. George's Respiratory Questionnaire (SGRQ), a self-reported measure of quality of life in patients with pulmonary disease. Chart review provided demographic information and Pediatric Crohn's Disease Activity Index (PCDAI) and Pediatric Ulcerative Colitis Activity Index scores. Regression models were utilized to evaluate associations between SGRQ score and clinical risk factors. Results. The prevalence of pulmonary manifestations was 9.62% (95% confidence interval = 5.48% to -15.36%). PCDAI scores in Crohn's disease patients with pulmonary symptoms were significantly higher (SGRQ mean = 10.71 ± 10.94) than in patients without such symptoms. SGRQ score was also higher in patients with indeterminate colitis (8.64, 95% confidence interval = 0.72-16.57, P = .03), when compared with Crohn's disease. Conclusions. Additional investigations including pulmonary function tests and imaging could provide further insight into this issue.

VEGFR-2 silencing by small interference RNA (siRNA) suppresses LPA-induced epithelial ovarian cancer (EOC) invasion.

BACKGROUND: The VEGF-VEGF receptor (VEGFR) signaling axis has emerged as a promising target for cancer therapy, attributing to its vital role in tumor angiogenesis and growth. We have previously reported the regulation of epithelial ovarian cancer (EOC) invasion and migration by VEGF and the implication of VEGF-VEGFR-2 axis in lysophosphatidic acid (LPA)-induced EOC invasion. However, the expression profile of VEGF and VEGFRs in EOC, their association with tumor aggressiveness, and their regulation by LPA remain unclear. OBJECTIVES AND METHODS: In this study, we examined the expression of VEGFR-1, VEGFR-2, neuropilin-1 (NRP-1), NRP-2, VEGF(121), and VEGF(165) in established EOC cell lines and assessed their correlation with cell invasiveness. Moreover, using an ovarian cancer tissue qPCR array, we analyzed VEGFR-2 expression across a panel of 48 tissues with different disease stages and histological grades. We also tested the effect of LPA on VEGF and VEGFR-2 expression and examined whether blocking VEGFR-2 by RNA interference (RNAi) affects LPA-induced EOC invasion. RESULTS: We show that VEGF and VEGFR-2 expression correlates with cell invasiveness and VEGFR-2 expression in ovarian cancer tissues correlate with tumor grade. In addition, LPA, at 20 muM, significantly induced the expression of VEGF(121), VEGF(165), and VEGFR-2 in SKOV3 and DOV13 cells (P<0.05). VEGFR-2 small interference RNA (siRNA) transfection remarkably decreased LPA's invasion-promoting effect (P<0.001) in SKOV3 cells without significantly decreasing SKOV3 cells' basal invasiveness. In DOV13 cells, VEGFR-2 silencing significantly decreases both the basal level cell invasion and LPA's invasion promoting effect (P<0.001). CONCLUSION: These results suggest that decreasing VEGFR-2 expression by RNAi may prove to be an effective method to reduce the metastatic potential of EOC cells exposed to elevated levels of LPA.

Esophageal IgE, IgG4, and mucosal eosinophilia in individuals with dysphagia.

BACKGROUND: Eosinophilic esophagitis (EoE) is an inflammatory disease of the esophagus, producing failure to thrive in infants and dysphagia with food impaction in older children and adults. Although most people with EoE manifest atopic/allergic disease, the specific allergens to which immunoglobulin E (IgE) is directed, if any, have not yet been characterized. METHODS: Mucosal brush biopsy (MBB) and solid tissue biopsy (STB) specimens were prospectively obtained from 25 individuals with dysphagia and suspicion of EoE. Specific IgE (sIgE) against 112 epitopes from airborne and food proteins, antigens known to cause a polyclonal IgE response and IgG4 to food allergens, were measured. RESULTS: There was no difference in total IgE harvested between the 2 biopsy methods (p > 0.05) or between the EoE-positive (N = 12) and EoE-negative (N = 13) groups (p > 0.05). None of the samples in either group contained measurable serum IgE to any of the airborne or food proteins tested, but low levels of IgE specific to Candida and Staphylococcus enterotoxins were detected. Low levels of IgG4 specific to wheat, soy, peanut, and egg were also detected. CONCLUSIONS: Both MBB and STB are able to harvest measureable levels of IgE and IgG4 from the esophageal mucosa. Low levels of serum-specific IgE suggest that other inflammatory mechanisms, besides type I, IgE-mediated, allergen-specific hypersensitivity, may act as the primary catalyst for mucosal eosinophilia. Clarifying the role of both IgE-mediated and non-IgE-mediated inflammatory mechanisms will help identify more targeted diagnostic and treatment strategies for individuals who present with dysphagia and esophageal eosinophilia.

Health Care Maintenance for the Pediatric Patient With Inflammatory Bowel Disease.

Nearly one-quarter of patients with inflammatory bowel disease (IBD) are younger than 20 years of age at diagnosis. Furthermore, the incidence of IBD in children continues to increase. Nevertheless, variation in management exists within the care of patients with IBD with regards to disease screening and preventive care. A multidisciplinary approach that involves the general practitioner and pediatric gastroenterologist is needed to routinely monitor growth, bone health, vitamin and mineral deficiencies, vaccination status, and endoscopic surveillance. It is also important to monitor for extraintestinal manifestations of IBD that may affect the liver, joints, skin, and eyes. The purpose of this article is to provide an updated overview of comprehensive care for pediatric patients with IBD.

Cerebral venous thrombosis in inflammatory bowel disease.

Cerebral venous thrombosis (CVT) is a rare but devastating complication of inflammatory bowel disease (IBD). Here we describe six IBD patients with cerebral venous thrombosis. The patients presented with hours to days of headache and were found to have venous thrombosis on imaging. Four of the six patients had ulcerative colitis and two had Crohn's disease. All six patients were treated with therapeutic anticoagulation. There were two deaths; one patient became comatose and died despite anticoagulation while the other recovered well from the sinus thrombosis but died after a bowel perforation 3 weeks later. This case series demonstrates the critical need for early recognition of neurological symptoms in patients with IBD during disease flares. It is important to recognize the clinical signs in order to start anticoagulation expeditiously and improve neurological outcomes.

Transcription factors specifying dopamine phenotype are decreased in cocaine users.

During development, survival of midbrain dopamine neurons and specification of their phenotype are dependent upon the intracellular expression of a number of transcription factors, including Engrailed 1, Pitx3, and Nurr1. The role of these transcription factors in the maintenance of the dopaminergic phenotype is less clear. In the present study, we show that each of these transcription factors is robustly expressed in adult dopamine neurons in human midbrain, and that cocaine abuse is associated with a significant decrease in the abundance of Nurr1 and Pitx3 in these cells. These data suggest that cocaine abuse leads to a partial loss of dopaminergic phenotype.

The prevalence of abnormal liver enzymes and metabolic syndrome in obese adolescent females with polycystic ovary syndrome.

OBJECTIVES: We sought to determine the prevalence of abnormal liver enzymes suggestive of nonalcoholic steatohepatitis and metabolic syndrome in obese adolescent females with polycystic ovary syndrome. DESIGN: A retrospective chart review. PARTICIPANTS: Patients included 39 obese (body mass index Z score >/= 2) adolescent females with a diagnosis of polycystic ovary syndrome. Clinical and biochemical data in these patients were reviewed. MAIN OUTCOME MEASURES: Aspartate and alanine aminotransferase levels, lipid panel, blood pressure, body mass index, and glucose intolerance were the main outcome measures of the study. RESULTS: The study showed that 15.4 % (6 of 39) of patients had elevated aminotransferase levels, suggestive of nonalcoholic steatohepatitis, and 43.6 % (17 of 39) of patients qualified as having metabolic syndrome. Finally, 10.2 % (4 of 39) of patients were found to have both liver dysfunction and metabolic syndrome. CONCLUSION: Liver dysfunction consistent with nonalcoholic steatohepatitis and metabolic syndrome are prevalent in obese adolescent females with polycystic ovary syndrome. Therefore, early screening and further work-up for both disease states are warranted in cases of young adolescent females with polycystic ovary syndrome.