INTRODUCTION: Limited literature exists on oncological chest wall reconstruction in the paediatric population, with the field still largely undecided on the best surgical reconstructive techniques to employ. The use of biological grafts/meshes is gaining popularity in certain adult surgical procedures but their use in paediatric procedures is rarely reported in the literature. We present the outcomes of our institution's multidisciplinary approach to managing paediatric chest wall tumours as well as our experience with the use of biological grafts for chest wall reconstruction following oncological resections. METHODS: Data were analysed retrospectively from eight paediatric patients who were treated for primary chest wall tumours between 2010 and 2018. RESULTS: The tumours comprised two lipoblastomas, three Ewing's sarcomas, an undifferentiated sarcoma with osteosarcomatous differentiation, a high grade undifferentiated sarcoma and a myofibroma. Seven of the eight patients underwent chest wall reconstruction with a biological graft. There were no postoperative mortalities and no evidence of recurrence in any of the patients in the series. No further chest wall operations were required and there were no postoperative infection related complications. CONCLUSIONS: We support the use of biological grafts for chest wall reconstruction after oncological resections and maintain that a multidisciplinary approach is essential for the management of paediatric chest wall tumours.
\n \n\n \n \nStoma formation is a common paediatric surgical procedure and yet, there is no low-cost stoma model for technical skills training. We describe a low-cost low-fidelity simulator for stoma formation made from simple easily available materials using porcine bowel and skin. The model was introduced at a regional training day for paediatric surgical registrars. All the trainees rated it as excellent and life-like. We describe an inexpensive stoma model for simulation-based training in technical skills especially in low-middle-income countries (LMICs) due to the cost benefit.
\n \n\n \n \nBACKGROUND: Surgical simulation is an important aspect of competency-based training. Recent trends in paediatric surgical simulations have migrated towards high-fidelity simulation with advanced technology resulting in models which are expensive and largely inaccessible in low- and middle-income countries. METHODS: This article describes four wet simulation models of common surgical procedures in paediatric population created with animal tissue from local abattoir. The models are designed to provide a framework for others to make the models and benefit from the training opportunity they provide especially in low-middle-income countries. RESULTS: The models created in the wet laboratory are neonatal bowel anastomosis, duodenoduodenostomy for discrepancy anastomosis, gastrostomy and pyeloplasty. These models are easily reproducible in resource-challenged healthcare setting as they are low cost, utilise locally available resources and require only a basic set of surgical instruments with which to perform the procedures. CONCLUSION: These models provide locally accessible material for sustainable training programmes which are fundamental in developing safe and affordable surgical care worldwide.
\n \n\n \n \nBicycles are a common cause of blunt abdominal trauma causing 5%-14% of injuries. However, impalement or shear injuries from low-velocity mechanism of injury are rare. We report a case of a 14-year-old boy presenting with an extensive left groin injury sustained while cycling one-handed along the pavement at walking pace. The laceration ran for 12-14\u2009cm from the left groin across the pubis to the right and 10\u2009cm inferiorly into the perineum. This inverted the left scrotum and partially degloved the penis. The corpus cavernosa and tunica vaginalis were exposed up to the level of the superficial inguinal ring. Literature on handlebar-impalement injuries is sparse and the majority of penile degloving injuries described in the literature result from alternative mechanisms. This unusual case demonstrates the potential forces involved, and potential damage resulting from handlebar injuries even at low velocity.
\n \n\n \n \nOBJECTIVES: Intraoperative fluorescence imaging is currently used in a variety of surgical fields for four main purposes: assessing tissue perfusion; identifying/localizing cancer; mapping lymphatic systems; and visualizing anatomy. To establish evidence-based guidance for research and practice, understanding the state of research on fluorescence imaging in different surgical fields is needed. We evaluated the evidence on fluorescence imaging for perfusion assessments using the Idea, Development, Exploration, Assessment, Long Term Study (IDEAL) framework, which was designed for describing the stages of innovation in surgery and other interventional procedures. DESIGN: Narrative literature review with analysis of IDEAL stage of each field of study. SETTING: All publications on intraoperative fluorescence imaging for perfusion assessments reported in PubMed through 2019 were identified for six surgical procedures: coronary artery bypass grafting (CABG), upper gastrointestinal (GI) surgery, colorectal surgery, solid organ transplantation, reconstructive surgery, and cerebral aneurysm surgery. MAIN OUTCOME MEASURES: The IDEAL stage of research evidence was determined for each specialty field using a previously described approach. RESULTS: 196 articles (15\u2009003 cases) were selected for analysis. Current status of research evidence was determined to be IDEAL Stage 2a for upper GI and transplantation surgery, IDEAL 2b for CABG, colorectal and cerebral aneurysm surgery, and IDEAL Stage 3 for reconstructive surgery. Using the technique resulted in a high (up to 50%) rate of revisions among surgical procedures, but its efficacy improving postoperative outcomes has not yet been demonstrated by randomized controlled trials in any discipline. Only one possible adverse reaction to intravenous indocyanine green was reported. CONCLUSIONS: Using fluorescence imaging intraoperatively to assess perfusion is feasible and appears useful for surgical decision making across a range of disciplines. Identifying the IDEAL stage of current research knowledge aids in planning further studies to establish the potential for patient benefit.
\n \n\n \n \nBACKGROUND: The WHO Surgical Safety Checklist has been shown to reduce perioperative morbidity and mortality worldwide. There is evidence to suggest that sign-out is the most poorly performed phase of the checklist as it coincides with a period of high workload for team members. This study aimed to see whether modification of this process might result in greater compliance. METHODS: A controlled longitudinal (before and after) study was performed to evaluate the effect of a modified checklist sign-out on compliance in a single surgical department. Checklist quality was evaluated by measurement of checklist completion, active participation, and team member presence. Workload assessment was performed to identify the optimal moment for the sign-out process. The sign-out process was modified through an iterative multidisciplinary approach, informed by results from the workload assessment. Feedback was obtained through staff surveys. RESULTS: A total of 185 operations were used, with an intervention group in vascular surgery and a control group in orthopaedics. The optimal timing for sign-out was identified as after final wound closure. The modified sign-out process improved active participation of team members (21 of 34 versus 31 of 34; P\u2009=\u20090.010). In the control group, complete compliance improved (48 of 76 versus 30 of 41; P\u2009=\u20090.041). However, active participation decreased (53 of 76 versus 19 of 41; P\u2009=\u20090.022). No differences were noted between groups in team member presence. Eighteen of 21 staff questioned viewed the modifications positively. CONCLUSION: The optimal sign-out timing was identified as immediately after final wound closure prior to undraping the patient.
\n \n\n \n \nIrradiation of the wrong patient or wrong site is a reportable adverse event for hospitals. Improvement efforts to date have been narrowly targeted, often without consideration of wider contextual factors. This study applied a systems human factors/ergonomics (HFE) approach in an NHS trust to develop interventions across micro, unit and organisation levels. At the micro level, the workspace was adapted to reduce distractions during safety critical work. At the unit level a standard operating procedure for patient identification was designed with staff alongside the introduction of wristband barcode scanners. At the organisation level safety workshops were run for staff in the radiology directorate. These introduced a systems approach to managing risk, encouraged near miss reporting and employed scenario-based exercises to raise discussion of risk-efficiency trade-offs. Following implementation interruptions in the control rooms decreased by 34% (from a mean of 4.91/10 min). Interrupted time series analysis showed that the interventions were associated with a decrease in patient identification incidents (rate ratio = 0.37), and an increase in near miss reporting (rate ratio = 2.5), representing an additional 4.7 reports/month. The workshops raised a wide range of system components that influenced the imaging task and provided examples of situated and structural resilience attributes. The safe provision of imaging across different modalities and physical locations is a challenge for many radiology departments; this study indicates that a multi-level systems approach can reduce risk.
\n \n\n \n \nThe immune system presents a significant challenge to the success of clinical transplantation. For the majority of patients, treatment with a combination of immunosuppressive drugs are essential to prevent rejection. Tissue injury caused by organ retrieval and implantation triggers an innate immune response, which in turn, activates the adaptive immune system capable of responding to both major and minor histocompatibility antigens mismatched between the organ donor and the recipient. Advances in immunosuppressive strategies using small molecules and biological agents have revolutionized the management and outcomes of solid organ transplantation.
\n \n\n \n \nPURPOSE: Using RNA sequencing, we recently developed the 52-gene-based Oxford classifier of carcinoma of the ovary (Oxford Classic, OxC) for molecular stratification of serous ovarian cancers (SOCs) based on the molecular profiles of their cell of origin in the fallopian tube epithelium. Here, we developed a 52-gene NanoString panel for the OxC to test the robustness of the classifier. EXPERIMENTAL DESIGN: We measured the expression of the 52 genes in an independent cohort of prospectively collected SOC samples (n = 150) from a homogenous cohort who were treated with maximal debulking surgery and chemotherapy. We performed data mining of published expression profiles of SOCs and validated the classifier results on tissue arrays comprising 137 SOCs. RESULTS: We found evidence of profound nongenetic heterogeneity in SOCs. Approximately 20% of SOCs were classified as epithelial-to-mesenchymal transition-high (EMT-high) tumors, which were associated with poor survival. This was independent of established prognostic factors, such as tumor stage, tumor grade, and residual disease after surgery (HR, 3.3; P = 0.02). Mining expression data of 593 patients revealed a significant association between the EMT scores of tumors and the estimated fraction of alternatively activated macrophages (M2; P < 0.0001), suggesting a mechanistic link between immunosuppression and poor prognosis in EMT-high tumors. CONCLUSIONS: The OxC-defined EMT-high SOCs carry particularly poor prognosis independent of established clinical parameters. These tumors are associated with high frequency of immunosuppressive macrophages, suggesting a potential therapeutic target to improve clinical outcome.
\n \n\n \n \nINTRODUCTION: Regulatory T cell (Treg) therapy has been demonstrated to facilitate long-term allograft survival in preclinical models of transplantation and may permit reduction of immunosuppression and its associated complications in the clinical setting. Phase 1 clinical trials have shown Treg therapy to be safe and feasible in clinical practice. Here we describe a protocol for the TWO study, a phase 2b randomised control trial of Treg therapy in living donor kidney transplant recipients that will confirm safety and explore efficacy of this novel treatment strategy. METHODS AND ANALYSIS: 60 patients will be randomised on a 1:1 basis to Treg therapy (TR001) or standard clinical care (control). Patients in the TR001 arm will receive an infusion of autologous polyclonal ex vivo expanded Tregs 5 days after transplantation instead of standard monoclonal antibody induction. Maintenance immunosuppression will be reduced over the course of the post-transplant period to low-dose tacrolimus monotherapy. Control participants will receive a standard basiliximab-based immunosuppression regimen with long-term tacrolimus and mycophenolate mofetil immunosuppression. The primary endpoint is biopsy proven acute rejection over 18 months; secondary endpoints include immunosuppression burden, chronic graft dysfunction and drug-related complications. ETHICS AND DISSEMINATION: Ethical approval has been provided by the National Health Service Health Research Authority South Central-Oxford A Research Ethics Committee (reference 18/SC/0054). The study also received authorisation from the UK Medicines and Healthcare products Regulatory Agency and is being run in accordance with the principles of Good Clinical Practice, in collaboration with the registered trials unit Oxford Clinical Trials Research Unit. Results from the TWO study will be published in peer-reviewed scientific/medical journals and presented at scientific/clinical symposia and congresses. TRIAL REGISTRATION NUMBER: ISRCTN: 11038572; Pre-results.
\n \n\n \n \nA number of immune regulatory cellular therapies, including regulatory T cells and mesenchymal stromal cells, have emerged as novel alternative therapies for the control of transplant alloresponses. Clinical studies have demonstrated their feasibility and safety, however developing our understanding of the impact of cellular therapeutics in vivo requires advanced immune monitoring strategies. To accurately monitor the immune response, a combination of complementary methods is required to measure the cellular and molecular phenotype as well as the function of cells involved. In this review we focus on the current immune monitoring strategies and discuss which methods may be utilized in the future.
\n \n\n \n \nHumanized immune system (HIS) mouse models are useful tools for the in vivo investigation of human hematopoiesis. However, the majority of HIS models currently in use are biased towards lymphocyte development and fail to support long-term multilineage leucocytes and erythrocytes. Those that achieve successful multilineage reconstitution often require preconditioning steps which are expensive, cause animal morbidity, are technically demanding, and poorly reproducible. In this study, we address this challenge by using HSPC-NBSGW mice, in which NOD,B6.SCID IL-2r\u03b3 -/-KitW41/W41 (NBSGW) mice are engrafted with human CD133+ hematopoietic stem and progenitor cells (HSPCs) without the need for preconditioning by sublethal irradiation. These HSPCs are enriched in long-term hematopoietic stem cells (LT-HSCs), while NBSGW mice are permissive to human hematopoietic stem cell (HSC) engraftment, thus reducing the cell number required for successful HIS development. B cells reconstitute with the greatest efficiency, including mature B cells capable of class-switching following allogeneic stimulation and, within lymphoid organs and peripheral blood, T cells at a spectrum of stages of maturation. In the thymus, human thymocytes are identified at all major stages of development. Phenotypically distinct subsets of myeloid cells, including dendritic cells and mature monocytes, engraft to a variable degree in the bone marrow and spleen, and circulate in peripheral blood. Finally, we observe human erythrocytes which persist in the periphery at high levels following macrophage clearance. The HSPC-NBSGW model therefore provides a useful platform for the study of human hematological and immunological processes and pathologies.
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