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Abbreviations GERD Gastroesophageal reflux disease GI Gastroenterology H2RA H2 antagonist PCP Primary care physician PPI Proton pump inhibitor Many infants with fussiness or spitting-up are prescribed acid suppression therapy with proton pump inhibitors (PPIs) and H2 antagonists (H2RAs) despite data suggesting these therapies do not improve symptoms over placebo.1,2 Furthermore, there are risks with acid suppression treatment, including increasing rates of gastroenteritis, pneumonia and necrotising enterocolitis.3 In 2018, the North American Society of Pediatric Gastroenterology, Hepatology and Nutrition (NASPGHAN) and the European Society of Pediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN) released updated clinical practice guidelines for the management of gastroesophageal reflux disease (GERD) for infants.4 The guidelines recommend thickening and trial of hypoallergenic formula as first-line therapies for the treatment of GERD in infants, as well as referral to gastroenterology (GI) clinician prior to starting acid suppression. Also, the patients in this study had severe enough symptoms to require referral to GI clinic; thus, our data does not capture changes made by primary care providers for patients who had symptom resolution. [Extracted from the article]

Importance: Proton pump inhibitors (PPI) are commonly prescribed to children with oropharyngeal dysphagia and resultant aspiration based on the assumption that these patients are at greater risk for reflux-related lung disease. There is little data to support this approach and the potential risk for increased infections in children treated with PPI may outweigh any potential benefit., Objective: The aim of this study was to determine if there is an association between hospitalization risk in pediatric patients with oropharyngeal dysphagia and treatment with PPI., Design, Setting, and Participants: We performed a retrospective cohort study to compare the frequency and length of hospitalizations for children who had abnormal results on videofluoroscopic swallow studies that were performed between January 1, 2015, and December 31, 2015, and who were or were not treated with PPI, with follow-up through December 31, 2016. Records were reviewed for children who presented for care at Boston Children's Hospital, a tertiary referral center. Participants included 293 children 2 years and younger with evidence of aspiration or penetration on videofluoroscopic swallow study., Exposures: Groups were compared based on their exposure to PPI treatment., Main Outcomes and Measures: The primary outcomes were hospital admission rate and hospital admission nights and these were measured as incident rates. Multivariable analyses were performed to determine predictors of hospitalization risk after adjusting for comorbidities. Kaplan-Meier curves were created to determine the association of PPI prescribing with time until first hospitalization., Results: A total of 293 patients with a mean (SD) age of 8.8 (0.4) months and a mean (SD) follow-up time of 18.15 (0.20) months were included in the analysis. Patients treated with PPI had higher admission rates (Incidence rate ratio [IRR], 1.77; 95% CI, 1.16-2.68) and admission nights (IRR, 2.51; 95% CI, 1.36-4.62) even after adjustment for comorbidities. Patients with enteral tubes who were prescribed PPIs were at the highest risk for admission (hazard ratio [HR], 2.31; 95% CI, 1.24-4.31)., Conclusions and Relevance: Children with aspiration who are treated with PPI have increased risk of hospitalization compared with untreated patients. These results support growing concern about the risks of PPI use in children.

Background: The extracellular matrix (ECM) is a critical determinant of neovessel integrity., Materials and Methods: Thirty-six (polyglycolic acid + polycaprolactone and poly lactic acid) tissue-engineered vascular grafts seeded with syngeneic bone marrow mononuclear cells were implanted as inferior vena cava interposition grafts in C57BL/6 mice. Specimens were characterized using immunohistochemical staining and qPCR for representative ECM components in addition to matrix metalloproteinases (MMPs). Total collagen, elastin, and glycosaminoglycan (GAG) contents were determined. MMP activity was measured using zymography., Results: Collagen production on histology demonstrated an initial increase in type III at 1 week followed by type I production at 2 weeks and type IV at 4 weeks. Gene expression of both type I and type III peaked at 2 weeks, whereas type IV continued to increase over the 4-week period. Histology demonstrated fibrillin-1 deposition at 1 week followed by elastin production at 4 weeks. Elastin gene expression significantly increased at 4 weeks, whereas fibrillin-1 decreased at 4 weeks. GAG demonstrated abundant production at each time point on histology. Gene expression of decorin significantly increased at 4 weeks, whereas versican decreased over time. Biochemical analysis showed that total collagen production was greatest at 2 weeks, and there was a significant increase in elastin and GAG production at 4 weeks. Histological characterization of MMPs showed abundant production of MMP-2 at each time point, while MMP-9 decreased over the 4-week period. Gene expression of MMP-2 significantly increased at 4 weeks, whereas MMP-9 significantly decreased at 4 weeks., Conclusions: ECM production during neovessel formation is characterized by early ECM deposition followed by extensive remodeling., (Copyright © 2011 S. Karger AG, Basel.)