Hepatic tissue engineering using decellularized scaffolds is a potential therapeutic alternative to conventional transplantation. However, scaffolds are usually obtained using decellularization protocols that destroy the extracellular matrix (ECM) and hamper clinical translation. We aim to develop a decellularization technique that reliably maintains hepatic microarchitecture and ECM components. Isolated rat livers were decellularized by detergent-enzymatic technique with (EDTA-DET) or without EDTA (DET). Histology, DNA quantification and proteomics confirmed decellularization with further DNA reduction with the addition of EDTA. Quantification, histology, immunostaining, and proteomics demonstrated preservation of extracellular matrix components in both scaffolds with a higher amount of collagen and glycosaminoglycans in the EDTA-DET scaffold. Scanning electron microscopy and X-ray phase contrast imaging showed microarchitecture preservation, with EDTA-DET scaffolds more tightly packed. DET scaffold seeding with a hepatocellular cell line demonstrated complete repopulation in 14 days, with cells proliferating at that time. Decellularization using DET preserves microarchitecture and extracellular matrix components whilst allowing for cell growth for up to 14 days. Addition of EDTA creates a denser, more compact matrix. Transplantation of the scaffolds and scaling up of the methodology are the next steps for successful hepatic tissue engineering.
Tissue engineering of autologous lung tissue aims to become a therapeutic alternative to transplantation. Efforts published so far in creating scaffolds have used harsh decellularization techniques that damage the extracellular matrix (ECM), deplete its components and take up to 5 weeks to perform. The aim of this study was to create a lung natural acellular scaffold using a method that will reduce the time of production and better preserve scaffold architecture and ECM components. Decellularization of rat lungs via the intratracheal route removed most of the nuclear material when compared to the other entry points. An intermittent inflation approach that mimics lung respiration yielded an acellular scaffold in a shorter time with an improved preservation of pulmonary micro-architecture. Electron microscopy demonstrated the maintenance of an intact alveolar network, with no evidence of collapse or tearing. Pulsatile dye injection via the vasculature indicated an intact capillary network in the scaffold. Morphometry analysis demonstrated a significant increase in alveolar fractional volume, with alveolar size analysis confirming that alveolar dimensions were maintained. Biomechanical testing of the scaffolds indicated an increase in resistance and elastance when compared to fresh lungs. Staining and quantification for ECM components showed a presence of collagen, elastin, GAG and laminin. The intratracheal intermittent decellularization methodology could be translated to sheep lungs, demonstrating a preservation of ECM components, alveolar and vascular architecture. Decellularization treatment and methodology preserves lung architecture and ECM whilst reducing the production time to 3 h. Cell seeding and in vivo experiments are necessary to proceed towards clinical translation.
3 November 2012 in Pediatric Surgery International
‘Payment by results’ (PbR) remuneration for healthcare services relies on the accurate conversion of diagnoses into Healthcare Resource Group (HRG) codes that are then reimbursed. Inconsistencies in documentation can result in inaccuracies in this process, with consequent implications for measuring activity, disease incidence and organisational performance.
1 February 2021 in International Journal of Surgery
During the Covid-19 pandemic, non-operative management for acute appendicitis (AA) was implemented in the UK. The aim of this study was to determine the efficacy and outcomes of conservative versus surgical management of AA during the pandemic. We conducted an observational study in a tertiary referral centre. Data was collected from all patients (≥16 years) with a diagnosis of AA between November 1, 2019 to March 10, 2020 (pre-COVID period) and March 10, 2020 to July 5, 2020 (COVID period). A total of 116 patients in the pre-COVID period were included versus 91 in the COVID period. 43.1% (n = 50) of patients pre-COVID were classified as ASA 2 compared to 26.4% (n = 24) during the COVID period (p-value = 0.042). 72.5% (n = 66) of the patients during the COVID period scored as high risk using the Alvarado score compared to 24.1% (n = 28) in the pre-COVID period (p-value<0.001). We observed a significant increase in radiological evaluation, 69.8% versus 87.5% of patients had a CT in the pre-COVID and COVID periods respectively (p-value = 0.008). 94.9% of patients were managed operatively in the pre-COVID period compared to 60.4% in the COVID period (p-value<0.001). We observed more open appendicectomies (37.3% versus 0.9%; p-value<0.001) during the COVID period compared to the pre-COVID period. More abscess formation and free fluid were found intraoperatively in the COVID period (p-value = 0.021 and 0.023 respectively). Re-attendance rate due to appendicitis-related issues was significantly higher in the COVID period (p = 0.027). Radiological diagnosis of AA was more frequent during the COVID period. More conservative management for AA was employed during the COVID-19 pandemic, and for those managed operatively an open approach was preferred. Intra-operative findings were suggestive of delayed presentation during the COVID period without this affecting the length of hospital stay.