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A series of well-regulated cellular and molecular events result in the compartmentalization of the anterior foregut into the esophagus and trachea. Disruption of the compartmentalization process leads to esophageal atresia/tracheoesophageal fistula (EA/TEF). The cause of EA/TEF remains largely unknown. Therefore, to mimic the early development of the esophagus and trachea, we differentiated iPSCs from EA/TEF patients and iPSCs and embryonic stem cells from healthy individuals into mature 3-dimensional esophageal organoids. CXCR4, SOX17, and GATA4 expression was similar in both patient and healthy endodermal cells. Key transcription factor SOX2 was significantly lower in patient-derived anterior foregut. We also observed an abnormal expression of NKX2.1 in the patient-derived mature esophageal organoids. At the anterior foregut stage, RNA sequencing revealed critical genes GSTM1 and RAB37 to be significantly lower in patient-derived anterior foregut. We therefore hypothesize that a transient dysregulation of SOX2 and the abnormal expression of NKX2.1 in patient-derived cells could be responsible for the abnormal foregut compartmentalization.

Background A recent meta-analysis of 48 studies, showed an equal prevalence of AP (16%) among the following etiologies; systemic disease, alcohol, medication, genetics, gallstones and infection in North American hospitalized and ambulatory pediatric patients. However, data on the epidemiology of severe pediatric acute pancreatitis (AP) in Canada are lacking. Purpose We aim to evaluate the clinical presentation, etiologies, comorbidities and outcome of pediatric patients with AP admitted to a tertiary hospital in Quebec, Canada. Method A retrospective observational cohort study (January 2014-December 2021) was performed at the CHU Sainte-Justine. Descriptive analyses were performed with SAS statistical softwar Result(s) Among the 214 patients included (110 (51%) males), 58 (27.1%) were already hospitalized at time of AP diagnosis (AP as secondary diagnosis) while 156 (72.9%) were admitted from the emergency room mainly with a presentation of abdominal pain (AP as primary diagnosis). Thirty-two patients (15.0%) were transferred to the ICU due to hemodynamic instability or respiratory failure. Comorbidities included cancer (38 patients (17.7%)), obesity (17 (7.9%)) and inflammatory bowel disease (15 (7.0%)). The three most commonly identified etiologies were medication (19.6%), biliary disease (16.3%) and infection (14,9%). Despite extensive investigations, 26.2% of cases were idiopathic. The main complications were, ascites (48 patients (22.4%)), necrotic pancreatitis (10 (4.6%)) and pancreatic pseudocyst (10 (4.6%)). The median duration of hospitalization for AP as a primary diagnosis was 4 days (interquartile range (IQR) 2-7) as compared to 22 (11-37) for AP as a secondary diagnosis. Conclusion(s) Approximately one third of hospitalized patients had an underlying condition requiring treatments that could cause AP, which explains the high prevalence of drug-induced AP in this report. The longest hospitalizations were associated with AP as secondary diagnosis. Ongoing work will identify factors associated with disease severity and outcome in particular in primary AP. Please acknowledge all funding agencies by checking the applicable boxes below None Disclosure of Interest None Declared

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