43 research outputs found

    Lessons learned from pre-clinical testing of xenogeneic decellularized esophagi in a rabbit model

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    Summary Decellularization of esophagi from several species for tissue engineering is well described, but successful implantation in animal models of esophageal replacement has been challenging. The purpose of this study was to assess feasibility and applicability of esophageal replacement using decellularized porcine esophageal scaffolds in a new pre-clinical model. Following surgical replacement in rabbits with a vascularizing muscle flap, we observed successful anastomoses of decellularized scaffolds, cues of early neovascularization, and prevention of luminal collapse by the use of biodegradable stents. However, despite the success of the surgical procedure, the long-term survival was limited by the fragility of the animal model. Our results indicate that transplantation of a decellularized porcine scaffold is possible and vascular flaps may be useful to provide a vascular supply, but long-term outcomes require further pre-clinical testing in a different large animal model

    Adaptable haemodynamic endothelial cells for organogenesis and tumorigenesis

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    Endothelial cells adopt tissue-specific characteristics to instruct organ development and regeneration1,2. This adaptability is lost in cultured adult endothelial cells, which do not vascularize tissues in an organotypic manner. Here, we show that transient reactivation of the embryonic-restricted ETS variant transcription factor 2 (ETV2)3 in mature human endothelial cells cultured in a serum-free three-dimensional matrix composed of a mixture of laminin, entactin and type-IV collagen (LEC matrix) ‘resets’ these endothelial cells to adaptable, vasculogenic cells, which form perfusable and plastic vascular plexi. Through chromatin remodelling, ETV2 induces tubulogenic pathways, including the activation of RAP1, which promotes the formation of durable lumens4,5. In three-dimensional matrices—which do not have the constraints of bioprinted scaffolds—the ‘reset’ vascular endothelial cells (R-VECs) self-assemble into stable, multilayered and branching vascular networks within scalable microfluidic chambers, which are capable of transporting human blood. In vivo, R-VECs implanted subcutaneously in mice self-organize into durable pericyte-coated vessels that functionally anastomose to the host circulation and exhibit long-lasting patterning, with no evidence of malformations or angiomas. R-VECs directly interact with cells within three-dimensional co-cultured organoids, removing the need for the restrictive synthetic semipermeable membranes that are required for organ-on-chip systems, therefore providing a physiological platform for vascularization, which we call ‘Organ-On-VascularNet’. R-VECs enable perfusion of glucose-responsive insulin-secreting human pancreatic islets, vascularize decellularized rat intestines and arborize healthy or cancerous human colon organoids. Using single-cell RNA sequencing and epigenetic profiling, we demonstrate that R-VECs establish an adaptive vascular niche that differentially adjusts and conforms to organoids and tumoroids in a tissue-specific manner. Our Organ-On-VascularNet model will permit metabolic, immunological and physiochemical studies and screens to decipher the crosstalk between organotypic endothelial cells and parenchymal cells for identification of determinants of endothelial cell heterogeneity, and could lead to advances in therapeutic organ repair and tumour targeting

    Pleurodesis with povidone–iodine for refractory chylothorax in newborns: Personal experience and literature review

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    Introduction: Refractory chylothorax is a severe clinical issue, particularly in neonates. Conventional primary approach is based on diet with medium-chain fatty acids and/or total parenteral nutrition. In nonresponders, proposed second line treatments include chemical or surgical pleurodesis, thoracic duct ligation, pleuroperitoneal shunting and pleurectomy but none of these have been shown to be superior to other in terms of resolution rate and safety. Our aim is to report our experience on povidone-iodine use for chemical pleurodesis in newborn infants with chylothorax unresponsive to conservative treatment.Our aim is to report our experience on povidone-iodine use for chemical pleurodesis in newborn infants with chylothorax unresponsive to conservative treatment.Methods: Since 2013, povidone-iodine pleurodesis was attempted in all patients with persistent chylothorax who failed conservative treatment (no response to at least 10 days of total parenteral nutrition and maximum dosage of intravenous octreotide). Pleurodesis consisted in the injection of 2 ml/kg of a 4% povidone-iodine solution inside the pleural space, leaving the pleural tube clamped for the subsequent 4 hours.Results: Five patients were treated with chemical pleurodesis of persistent chylothorax. Four of 5 patients had their pleural effusion treated by one single povidone-iodine infusion. Median time for resolution was 4 days. A patient with massive superior vena cava thrombosis did not benefit from pleurodesis. None of the patients experienced long term side effects of the treatment.Conclusion: Our data suggest that povidone-iodine pleurodesis may be considered a safe and effective option to treat refractory chylothorax in newborns. (C) 2015 Elsevier Inc. All rights reserved

    Comparison of outcomes following radiological reduction of intussusception with or without sedation

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    Background: Non-operative radiological reduction (NORR) is usually the first line treatment in pediatric ileo-colic intussusception. The aim of our study was to compare outcomes of NORR with or without sedation. Methods: All patients undergoing to contrast enema NORR for intussusception between 01.01.2015 to 31.12.2020 in two hospitals were included: in one centre patients were sedated (A) while in the other patients were awake (B). Primary outcome was the rate of radiological reduction. Secondary outcomes were length-of-stay, complications and recurrence rate. Results: Seventy-seven and 49 patients were included in group A and B respectively. Successful reduction rate was 72.7% in group A and 61.2% in group B (P>0.05). There were no complications related to the procedure among the 2 groups. Adverse events to sedation were observed in 3 patients. Conclusions: NORR has similar success rate when performed under sedation or awake, despite the former being graved by additional anesthesiologic risks and thus warrant careful indications

    ERCP with intracholedocal biopsy for the diagnosis of biliary tract rhabdomyosarcoma in children

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    Rhabdomyosarcoma is the most common tumor of the biliary tract in children. Although some features at preoperative radiographic studies (ultrasound, CT, MRI) may be suggestive of BT-RMS, until few years ago the final diagnosis was obtained by either operative or transcutaneous biopsy, thus exposing to a risk of regional dissemination. More recent and still anecdotal, is the histological diagnosis on tissue obtained by transluminal biopsy either during transhepatic cholangiography or endoscopic retrograde cholangio-pancreatography (ERCP), the latter having the major advantage of a much lower risk of loco-regional dissemination. We present two cases of BT-RMS that were histologically diagnosed by intracholedocal biopsy performed during ERCP, after being suspected at conventional imaging

    Parasitological and Molecular Observations on a Little Family Outbreak of Human Fasciolosis Diagnosed in Italy

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    In the year 2010, three children who were born in a Romanian cattle farmer family went to Italy to join their mother. One of them was admitted to an Italian pediatric hospital for severe anemia that, when she was in her country, had been treated with blood transfusion. Blood tests and an abdominal ultrasound study triggered the suspicion of biliary parasitosis. The child underwent a cholangiopancreatography that caused the release of parasitic material microscopically identified as Fasciola hepatica. All children and their mother were submitted to coproparasitological analyses, which identified F. hepatica eggs only in the patient and in her twin sister. Parasitic materials recovered and flatworm specimens by us ad hoc obtained from Italian and Romanian cattle were genetically (ITS and COI genes) analyzed, and their sequences were compared with those deposited in GenBank. Specimens from children clustered with the Romanian strain examined and showed remarkable genetic differences with flatworm specimens from Italy. Anamnesis, parasite biology, and genetic data strongly suggest that twin sisters became infected in Romania; however, human fasciolosis is an emerging sanitary problem, favored by climate changes and global drivers; therefore, it deserves more attention on behalf of physicians working in both developing and developed countries
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