Long-term functional outcomes and multidisciplinary management after ileorectal Duhamel pull-through for total colonic aganglionosis- 20-year experience in a tertiary surgical center

Introduction Management of patients with total colonic aganglionosis (TCA) is challenging for paediatric surgeons. The purpose of this study was to review our institution's 20-year experience regarding long-term outcomes and multidisciplinary team management of these patients after an Ileorectal Duhamel pull-through procedure. Materials and Methods Retrospective review was conducted for all patients diagnosed with TCA in our tertiary institution. Data was collected on demographics, clinical presentation, complications, need for additional surgery and long-term effects on bowel function. Results Of a total of 202 patients with Hirschsprung's disease (HSCR), 13 were diagnosed with TCA (6.4 %). Clinical presentation was variable. 11 presented in neonatal period with distal bowel obstruction and 2 presented with constipation in early infancy. Ileorectal Duhamel pull-through was performed in all patients. Median follow up was 13 years. 11 are toilet trained, of whom 5 are fully continent. 6 continue to have problems with bowel continence or constipation. 1 developed recurrent episode of Hirschsprung's associated enterocolitis (HAEC). 2 patients had stoma re-established. Patients experiencing difficulties in bowel function are jointly managed by a multidisciplinary team consisting of surgeons, gastroenterologists, paediatric psychologists, and clinical nurse specialists. Conclusions TCA can be associated with significant long-term morbidity. Nearly half of the patients in this series have ongoing problems with bowel continence requiring a permanent stoma in some. Diligent follow-up coupled with inputs of a multidisciplinary team has greatly helped manage these complex patients in our institution

ERNICA Consensus Conference on the Management of Patients with Esophageal Atresia and Tracheoesophageal Fistula: Diagnostics, Preoperative, Operative, and Postoperative Management

\u2003INTRODUCTION: \u2003Many aspects of the management of esophageal atresia (EA) and tracheoesophageal fistula (TEF) are controversial and the evidence for decision making is limited. Members of the European Reference Network for Rare Inherited Congenital Anomalies (ERNICA) conducted a consensus conference on the surgical management of EA/TEF based on expert opinions referring to the latest literature. MATERIALS AND METHODS: \u2003Nineteen ERNICA representatives from nine European countries participated in the conference. The conference was prepared by item generation, item prioritization by online survey, formulation of a final list containing the domains diagnostics, preoperative, operative, and postoperative management, and literature review. The 2-day conference was held in Berlin in October 2018. Anonymous voting was conducted via an internet-based system. Consensus was defined when 75% of the votes scored 6 to 9. RESULTS: \u2003Fifty-two items were generated with 116 relevant articles of which five studies (4.3%) were assigned as level-1evidence. Complete consensus (100%) was achieved on 20 items (38%), such as TEF closure by transfixing suture, esophageal anastomosis by interrupted sutures, and initiation of feeding 24 hours postoperatively. Consensus 6575% was achieved on 37 items (71%), such as routine insertion of transanastomotic tube or maximum duration of thoracoscopy of 3 hours. Thirteen items (25%) were controversial (range of scores, 1-9). Eight of these (62%) did not reach consensus. CONCLUSION: \u2003Participants of the conference reached significant consensus on the management of patients with EA/TEF. The consensus may facilitate standardization and development of generally accepted guidelines. The conference methodology may serve as a blueprint for further conferences on the management of congenital malformations in pediatric surgery

Engineered Tissue-Stent Biocomposites as Tracheal Replacements

Here we report the creation of a novel tracheal construct in the form of an engineered, acellular tissue-stent biocomposite trachea (TSBT). Allogeneic or xenogeneic smooth muscle cells are cultured on polyglycolic acid polymer-metal stent scaffold leading to the formation of a tissue comprising cells, their deposited collagenous matrix, and the stent material. Thorough decellularization then produces a final acellular tubular construct. Engineered TSBTs were tested as end-to-end tracheal replacements in 11 rats and 3 nonhuman primates. Over a period of 8 weeks, no instances of airway perforation, infection, stent migration, or erosion were observed. Histological analyses reveal that the patent implants remodel adaptively with native host cells, including formation of connective tissue in the tracheal wall and formation of a confluent, columnar epithelium in the graft lumen, although some instances of airway stenosis were observed. Overall, TSBTs resisted collapse and compression that often limit the function of other decellularized tracheal replacements, and additionally do not require any cells from the intended recipient. Such engineered TSBTs represent a model for future efforts in tracheal regeneration

Age-specific nasal epithelial responses to SARS-CoV-2 infection.

Funder: Microscopy was performed at the Light Microscopy Core Facility, UCL GOS Institute of Child Health supported by the NIHR GOSH BRC award 17DD08.Funder: This project has been made possible in part by grants 2017-174169 and 2019-202654 from the Chan Zuckerberg Foundation and Sanger core grant WT206194.Children infected with SARS-CoV-2 rarely progress to respiratory failure. However, the risk of mortality in infected people over 85 years of age remains high. Here we investigate differences in the cellular landscape and function of paediatric (70 years) ex vivo cultured nasal epithelial cells in response to infection with SARS-CoV-2. We show that cell tropism of SARS-CoV-2, and expression of ACE2 and TMPRSS2 in nasal epithelial cell subtypes, differ between age groups. While ciliated cells are viral replication centres across all age groups, a distinct goblet inflammatory subtype emerges in infected paediatric cultures and shows high expression of interferon-stimulated genes and incomplete viral replication. In contrast, older adult cultures infected with SARS-CoV-2 show a proportional increase in basaloid-like cells, which facilitate viral spread and are associated with altered epithelial repair pathways. We confirm age-specific induction of these cell types by integrating data from in vivo COVID-19 studies and validate that our in vitro model recapitulates early epithelial responses to SARS-CoV-2 infection