conditional-reprogramming-pediatric-human-esophageal-epithelial-cells

Conditional Reprogramming of Pediatric Human Esophageal Epithelial Cells for Use in Tissue Engineering and Disease Investigation

Identifying and expanding patient-specific cells in culture for use in tissue engineering and disease investigation can be very challenging. Utilizing ...

Connecticut Children's Medical Center

Eosinophilic esophagitis (EE) is a clinical entity that is recognized increasingly in children. The treatment of EE has been debated since its identification as a clinical entity separate from reflux esophagitis. We hypothesize that the treatment with a high-dose proton pump inhibitor (HDPPI) helps differentiate EE from noneosinophilic esophagitis (NEE).

Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis.

Forty-one children with a variety of gastrointestinal complaints were diagnosed with Clostridium difficile infections as part of a routine screen over 3 years. The infection had not been suspected prior to the screen. Each child responded to treatment with metronidazole with resolution of their symptoms. These data suggest that community-associated C difficile is increasing and may produce atypical disease and lead to misdiagnosis.

Increasing incidence of community-associated atypical Clostridium difficile disease in children.

Objectives. To our knowledge, the occurrence of esophagitis in children with celiac disease (CD) has never been evaluated. The aim of this study is to determine the prevalence of esophagitis in children with CD. Patients and Methods. Between 2003 and 2007, children with biopsy confirmed CD were retrospectively identified. Biopsy reports were reviewed for esophageal inflammation. Biopsy reports of 2218 endoscopies performed during the same period were also evaluated for inflammation. Results. Forty-nine children diagnosed with CD (47% boys). Nineteen of 49 (39%) patients with CD had esophagitis (95% CI 0.23-0.5). Thirty percent of boys and 46% of girls with CD had esophagitis (95% CI 0.12-0.40). Overall, 45% of patients who underwent upper endoscopy had esophagitis. The prevalence of esophagitis in CD (39%) compared to the prevalence of esophagitis (45%) in our practice was not significantly different, P = 0.2526. Conclusion. There was no difference in the prevalence of esophagitis between children diagnosed with CD at the time of their diagnostic EGD and the prevalence of esophagitis in children without CD. A prospective study to determine whether the esophagitis should be treated with acid suppression or whether the esophagitis heals with the gluten-free diet is warranted.

Esophagitis in children with celiac disease.

The aim of the present study was to review postoperative complications of pediatric patients undergoing colectomy for ulcerative colitis (UC) or inflammatory bowel disease-unspecified (IBD-U) with a focus on preoperative immunosuppression including exposure to infliximab.

Preoperative immunosuppression is not associated with increased postoperative complications following colectomy in children with colitis.

Gastric outlet obstruction (GOO) in children is most commonly caused by idiopathic hypertrophic pyloric stenosis. Prior to proton pump inhibitors and H2 blockers, peptic ulcer disease (PUD) secondary to H. pylori was a cause of GOO. Both patients presented with a history of weight loss, vomiting, and abdominal pain. Their diagnosis of PUD and GOO was made by EGD and UGI. H. pylori testing was negative for both on multiple occasions but still received H. pylori eradication therapy. Patient 1 after failing pharmaceutical management underwent surgery for definitive treatment. Patient 2 underwent six therapeutic pyloric dilations before undergoing surgery as definitive treatment. These cases suggest that GOO secondary to PUD occurs in the absence of H. pylori infection and surgical management can provide definitive therapy.

Two Cases of Helicobacter pylori-Negative Gastric Outlet Obstruction in Children.

Enterourachal fistulas are exceedingly rare in Crohn's patients. We report a case of a presumed enterourachal fistula that led to an infected urachal cyst. Preoperative medical treatment obliterated the fistula and avoided the need to resect bowel at the time of operation. We recommend consideration of this diagnosis in a Crohn's patient with a midline abdominal mass.

Infected urachal cyst secondary to a Crohn's enterourachal fistula.

A tissue-engineered esophagus offers an alternative for the treatment of pediatric patients suffering from severe esophageal malformations, caustic injury, and cancer. Additionally, adult patients suffering from carcinoma or trauma would benefit.

Biomimetic and synthetic esophageal tissue engineering.

Oral immunotherapy for peanut allergy induces eosinophilic esophagitis: three pediatric case reports.

AGEs are a heterogeneous group of molecules formed from the nonenzymatic reaction of reducing sugars with free amino groups of proteins, lipids, and/or nucleic acids. AGEs have been shown to play a role in various conditions including cardiovascular disease and diabetes. In this study, we hypothesized that AGEs play a role in the "multiple hit hypothesis" of nonalcoholic fatty liver disease (NAFLD) and contribute to the pathogenesis of hepatosteatosis. We measured the effects of various mouse chows containing high or low AGE in the presence of high or low fat content on mouse weight and epididymal fat pads. We also measured the effects of these chows on the inflammatory response by measuring cytokine levels and myeloperoxidase activity levels on liver supernatants. We observed significant differences in weight gain and epididymal fat pad weights in the high AGE-high fat (HAGE-HF) versus the other groups. Leptin, TNF-α, IL-6, and myeloperoxidase (MPO) levels were significantly higher in the HAGE-HF group. We conclude that a diet containing high AGEs in the presence of high fat induces weight gain and hepatosteatosis in CD-1 mice. This may represent a model to study the role of AGEs in the pathogenesis of hepatosteatosis and steatohepatitis.

Advanced Glycation End Products Induce Obesity and Hepatosteatosis in CD-1 Wild-Type Mice.

Eosinophilic esophagitis (EoE) is an emerging allergic, IgE- and non-IgE (Th2 cell)-mediated disease. There are major gaps in the understanding of the basic mechanisms that drive the persistence of EoE. We investigated whether esophageal biopsies from children with EoE demonstrate an inflammatory response that is distinct from normal controls. We prospectively enrolled 84 patients, of whom 77 were included in our analysis, aged 4-17 years (12.8±3.8 years; 81% males). Five esophageal biopsies were collected from each patient at the time of endoscopy. Intramucosal lymphocytes were isolated, phenotyped and stimulated with phorbol 12-myristate 13-acetate/ionomycin to measure their potential to produce cytokines via flow cytometry. We also performed cytokine arrays on 72-h biopsy culture supernatants. CD8(+) T cells, compared with CD4(+) T cells, synthesized more TNF-α and interferon (IFN)-γ after mitogen stimulation in the EoE-New/Active vs EoE-Remission group (P=0.0098; P=0.02) and controls (P=0.0008; P=0.03). Culture supernatants taken from explant esophageal tissue contained 13 analytes that distinguished EoE-New/Active from EoE-Remission and Controls. Principal component analysis and cluster analysis based on these analytes distinctly separated EoE-New/Active from EoE-Remission and Controls. In summary, we have identified a previously unappreciated role for CD8(+) T lymphocytes with potential to produce TNF-α and IFN-γ in EoE. Our results suggest that CD8(+) T cells have a role in the persistence or progression of EoE. We have also identified a panel of analytes produced by intact esophageal biopsies that differentiates EoE-New/Active from EoE-Remission and controls. Our results suggest that esophageal epithelial cells may have specific immune effector functions in EoE that control the type and amplitude of inflammation.

Article	Year
Treatment with high-dose proton pump inhibitors helps distinguish eosinophilic esophagitis from noneosinophilic esophagitis. Journal of pediatric gastroenterology and nutrition\| PubMed ID: 19633574	2009
Increasing incidence of community-associated atypical Clostridium difficile disease in children. Clinical pediatrics\| PubMed ID: 20150212	2010
Esophagitis in children with celiac disease. ISRN gastroenterology\| PubMed ID: 21991513	2011
Preoperative immunosuppression is not associated with increased postoperative complications following colectomy in children with colitis. Journal of pediatric gastroenterology and nutrition\| PubMed ID: 22395189	2012
Two Cases of Helicobacter pylori-Negative Gastric Outlet Obstruction in Children. Case reports in gastrointestinal medicine\| PubMed ID: 22606426	2011
Infected urachal cyst secondary to a Crohn's enterourachal fistula. Journal of pediatric surgery\| PubMed ID: 23217916	2012
Biomimetic and synthetic esophageal tissue engineering. Biomaterials\| PubMed ID: 25916501	2015
Oral immunotherapy for peanut allergy induces eosinophilic esophagitis: three pediatric case reports. Pediatric allergy and immunology : official publication of the European Society of Pediatric Allergy and Immunology\| PubMed ID: 26888330	2016
Advanced Glycation End Products Induce Obesity and Hepatosteatosis in CD-1 Wild-Type Mice. BioMed research international\| PubMed ID: 26942201	2016
Characterizing the inflammatory response in esophageal mucosal biopsies in children with eosinophilic esophagitis. Clinical & translational immunology\| PubMed ID: 27525061	2016
Ulcer of the Duodenum Caused by a Pancreatic Neuroendocrine Tumor in an Adolescent. Clinical gastroenterology and hepatology : the official clinical practice journal of the American Gastroenterological Association\| PubMed ID: 27613258	2017

Wael Sayej

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