Evolving role of staging CT scans during CT-angiography for DIEP flap reconstruction planning.

BACKGROUND: Preoperative planning with CT-angiography (CTA) in deep inferior epigastric perforator (DIEP) flap reconstruction is an essential preoperative tool. The aim of this study was to describe the management of the incidental findings following the introduction and further modification of a combined CTA and CT-staging preoperative protocol which includes chest, abdomen, pelvis, and musculoskeletal system. MATERIAL AND METHODS: A retrospective case series of 292 patients (Group 1) with breast cancer who underwent DIEP flap between 2015 and 2019. This was followed by a re-assessment between 2019 and 2021 of 101 patients (Group 2) following modification of the staging-CT protocol to include only those patients who received chemotherapy. Group 1 included immediate and delayed reconstruction; whereas Group 2 included only the high-risk delayed reconstruction cases. Both groups had CT staging. RESULT: Overall, 30% of Group 1, most likely those who had the delayed reconstruction, had findings which were recommended for further follow-up. This led to a change in staging of the high-risk patients only at the end of 2019 to those who underwent chemotherapy and had delayed reconstruction. Briefly, 56.4% of Group 2 demonstrated incidental findings, 42.1% of them required repeat scanning, 7% were referred to other specialties, and 47.4% did not require further action. There were no cases of occult metastatic breast cancer in either series; however, 1% were diagnosed with de novo primary cancers at non breast sites only in the first series. CONCLUSION: The screening of patients with asymptomatic breast cancer as part of CTA scanning prior to autologous reconstruction is not universally practiced and not supported by the NICE guidelines. This unit changed the practice to stop preoperative staging for low-risk patients by the end of 2019, and reserved it for the high-risk patient groups to reduce cost.

A Metastatic Well-differentiated Squamous Cell Carcinoma in a Patient with an Arteriovenous Fistula.

Patients receiving hemodialysis have an increased risk of developing nonmelanoma skin cancers, such as cutaneous squamous cell carcinoma (SCC). Management of SCC usually relies on complete surgical excision of the primary tumor and may require regional lymph node dissection due to lymphatic spread. An 81-year-old man with an arteriovenous fistula (AVF) presented with an unusually aggressive metastatic well-differentiated SCC, necessitating an axillary dissection for lymph node metastasis. He had been referred for radiotherapy to complete his oncological treatment following excision of the primary SCC on his forearm. An AVF site is subjected to significant changes in circulatory pressure, leading to reduced lymphatic drainage and likely focal immunosuppression. Increased lymphatic burden, combined with repeated trauma to the fistula in an immunosuppressed patient, potentially precipitated the development of an SCC on the affected limb. The individual risk factors for SCC such as sites of chronic inflammation and repeated trauma, host immunosuppression, and renal disease are well established. This patient demonstrates the perfect storm of all these risk factors, leading to a highly malignant metastatic SCC. As the standards of renal care improve and the number of patients with AVF increases, we must remain vigilant in the management of SCCs in these patients.

Rapid redesign and effect on clinical workload of a supra-regional burns and plastic surgery service during the COVID-19 pandemic.

INTRODUCTION: In March 2020, South Wales experienced the most significant COVID-19 outbreak in the UK outside of London. We share our experience of the rapid redesign and subsequent change in activity in one of the busiest supra-regional burns and plastic surgery services in the UK. METHODS: A time-matched retrospective service evaluation was completed for a 7-week "COVID-19" study period and the equivalent weeks in 2018 and 2019. The primary aim of this study was to evaluate plastic surgery theatre use and the impact of service redesign. Comparison between study periods was tested for statistical significance using two-tailed t-tests. RESULTS: Operation numbers reduced by 64% and total operating time by 70%. General anaesthetic cases reduced from 41% to 7% (p<0.0001), and surgery was mainly carried out in ringfenced daycase theatres. Emergency surgery decreased by 84% and elective surgery by 46%. Cancer surgery as a proportion of total elective operating increased from 51% to 96% (p<0.0001). The absolute number of cancer-related surgeries undertaken was maintained despite the pandemic. CONCLUSION: Rapid development of COVID-19 SOPs minimised inpatient admissions. There was a significant decrease in operating while maintaining emergency and cancer surgery. Our ringfenced local anaesthetic Plastic Surgery Treatment Centre was essential in delivering a service. COVID-19 acted as a catalyst for service innovations and the uptake of activities such as telemedicine, virtual MDTs, and online webinars. Our experiences support the need for a core burns and plastic service during a pandemic, and show that the service can be effectively redesigned at speed.

Candidate Bioinks for Extrusion 3D Bioprinting-A Systematic Review of the Literature.

Purpose: Bioprinting is becoming an increasingly popular platform technology for engineering a variety of tissue types. Our aim was to identify biomaterials that have been found to be suitable for extrusion 3D bioprinting, outline their biomechanical properties and biocompatibility towards their application for bioprinting specific tissue types. This systematic review provides an in-depth overview of current biomaterials suitable for extrusion to aid bioink selection for specific research purposes and facilitate design of novel tailored bioinks. Methods: A systematic search was performed on EMBASE, PubMed, Scopus and Web of Science databases according to the PRISMA guidelines. References of relevant articles, between December 2006 to January 2018, on candidate bioinks used in extrusion 3D bioprinting were reviewed by two independent investigators against standardised inclusion and exclusion criteria. Data was extracted on bioprinter brand and model, printing technique and specifications (speed and resolution), bioink material and class of mechanical assessment, cell type, viability, and target tissue. Also noted were authors, study design (in vitro/in vivo), study duration and year of publication. Results: A total of 9,720 studies were identified, 123 of which met inclusion criteria, consisting of a total of 58 reports using natural biomaterials, 26 using synthetic biomaterials and 39 using a combination of biomaterials as bioinks. Alginate (n = 50) and PCL (n = 33) were the most commonly used bioinks, followed by gelatin (n = 18) and methacrylated gelatin (GelMA) (n = 16). Pneumatic extrusion bioprinting techniques were the most common (n = 78), followed by piston (n = 28). The majority of studies focus on the target tissue, most commonly bone and cartilage, and investigate only one bioink rather than assessing a range to identify those with the most promising printability and biocompatibility characteristics. The Bioscaffolder (GeSiM, Germany), 3D Discovery (regenHU, Switzerland), and Bioplotter (EnvisionTEC, Germany) were the most commonly used commercial bioprinters (n = 35 in total), but groups most often opted to create their own in-house devices (n = 20). Many studies also failed to specify whether the mechanical data reflected pre-, during or post-printing, pre- or post-crosslinking and with or without cells. Conclusions: Despite the continued increase in the variety of biocompatible synthetic materials available, there has been a shift change towards using natural rather than synthetic bioinks for extrusion bioprinting, dominated by alginate either alone or in combination with other biomaterials. On qualitative analysis, no link was demonstrated between the type of bioink or extrusion technique and the target tissue, indicating that bioprinting research is in its infancy with no established tissue specific bioinks or bioprinting techniques. Further research is needed on side-by-side characterisation of bioinks with standardisation of the type and timing of biomechanical assessment.

Facial Cartilaginous Reconstruction-A Historical Perspective, State-of-the-Art, and Future Directions.

Importance: Reconstruction of facial deformity poses a significant surgical challenge due to the psychological, functional, and aesthetic importance of this anatomical area. There is a need to provide not only an excellent colour and contour match for skin defects, but also a durable cartilaginous structural replacement for nasal or auricular defects. The purpose of this review is to describe the history of, and state-of-the-art techniques within, facial cartilaginous surgery, whilst highlighting recent advances and future directions for this continually advancing specialty. Observations: Limitations of synthetic implants for nasal and auricular reconstruction, such as silicone and porous polyethylene, have meant that autologous cartilage tissue for such cases remains the current gold standard. Similarly, tissue engineering approaches using unrelated cells and synthetic scaffolds have shown limited in vivo success. There is increasing recognition that both the intrinsic and extrinsic microenvironment are important for tissue engineering and synthetic scaffolds fail to provide the necessary cues for cartilage matrix secretion. Conclusions and Relevance: We discuss the first-in-man studies in the context of biomimetic and developmental approaches to engineering durable cartilage for clinical translation. Implementation of engineered autologous tissue into clinical practise could eliminate donor site morbidity and represent the next phase of the facial reconstruction evolution.

Role of hydrogen peroxide in intra-operative wound preparation based on an in vitro fibrin clot degradation model.

Three per cent hydrogen peroxide (H2O2) is widely used to irrigate acute and chronic wounds in the surgical setting and clinical experience tells us that it is more effective at removing dried-on blood than normal saline alone. We hypothesise that this is due to the effect of H2O2 on fibrin clot architecture via fibrinolysis. We investigate the mechanisms and discuss the clinical implications using an in vitro model. Coagulation assays with normal saline (NaCl), 1% and 3% concentrations of H2O2 were performed to determine the effect on fibrin clot formation. These effects were confirmed by spectrophotometry. The effects of 1%, 3% and 10% H2O2 on the macroscopic and microscopic features of fibrin clots were assessed at set time intervals and compared to a NaCl control. Quantitative analysis of fibrin networks was undertaken to determine the fibre length, diameter, branch point density and pore size. Fibrin clots immersed in 1%, 3% and 10% H2O2 demonstrated volume losses of 0.09-0.25mm3/min, whereas those immersed in the normal saline gained in volume by 0.02±0.13 mm3/min. Quantitative analysis showed that H2O2 affects the structure of the fibrin clot in a concentration-dependent manner, with the increase in fibre length, diameter and consequently pore sizes. Our results support our hypothesis that the efficacy of H2O2 in cleaning blood from wounds is enhanced by its effects on fibrin clot architecture in a concentration- and time-dependent manner. The observed changes in fibre size and branch point density suggest that H2O2 is acting on the quaternary structure of the fibrin clot, most likely via its effect on cross-linking of the fibrin monomers and may therefore be of benefit for the removal of other fibrin-dependent structures such as wound slough.

Reduced S100 Protein Expression in Malignant Ossifying Fibromyxoid Tumors: A Case Report.

Ossifying fibromyxoid tumor of soft parts (OFMT) is a rare mesenchymal neoplasm of uncertain lineage. OMFT normally has a benign clinical course, and malignant variants are considered unusual. Criteria defining malignancy have not yet been clearly identified and universally accepted, and there is diagnostic uncertainty between pathologists as to how best to recognize a malignant variant. We present the case of a 68-year-old male patient who, following initial diagnosis of typical OFMT in the left scapular region, presented to the sarcoma service 9 years later with a short history of a solid lesion in the right calf. Biopsy confirmed metastatic OFMT and further imaging identified three other radiologically similar but distant lesions, which were later resected. The histology of the initial biopsy was reviewed, and the original observations were found to be accurate and due to current diagnostic criteria, the specimen was reported as typical. We propose that this case report contributes to a growing body of literature suggesting that negative S100 expression may be a useful feature in identifying and characterizing malignant OFMT.

Innovation in a Time of Crisis: A Systematic Review of Three-Dimensional Printing in the COVID-19 Pandemic.

The coronavirus (COVID-19) global pandemic resulted in the breakdown of traditional supply chains responsible for providing essential equipment to hospitals and personal protective equipment (PPE) for health and social care workers. The three-dimensional (3D) printing community has responded to emerging need by recognizing shortages across health care systems and providing innovative solutions in real time, circumventing short-term global supply issues. A systematic review was undertaken to investigate the role of 3D printing in the COVID-19 pandemic in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines using the MEDLINE, EMBASE, and World Health Organization (WHO) COVID-19 databases. Newspaper and internet article sources were identified using the NEXIS media database. All studies and articles on the application of 3D printed solutions during the peak of the COVID-19 pandemic were included. The literature search identified 26 related articles, and 13 studies met inclusion criteria and were suitable for full-text review. One thousand two hundred and one unique digital media articles were identified; after removal of duplicates and screening of headlines for the inclusion and exclusion criteria, 460 articles were suitable for full-text review. The cross-collaboration between the 3D printing community and health care systems has aided in the provision of innovative solutions to combat the COVID-19 crisis. The applications for 3D printing ranged from oxygenation equipment to noninvasive and invasive ventilatory parts and innovative solutions for infection control and quarantine hubs. This review has identified that 3D printing technology has made the biggest contribution to the production of PPE in particular face shields, mirroring the areas of greatest shortage and need. Additive manufacturing has played a pivotal role in aligning disciplines in engineering, science, and medicine for the greater good. We have witnessed the rapid reconfiguration of traditional supply chains to circumvent global shortages, while making advancements in effort to limit the impact of this and future pandemics.

Facial Reconstruction: A Systematic Review of Current Image Acquisition and Processing Techniques.

Introduction: Plastic and reconstructive surgery is based on a culmination of technological advances, diverse techniques, creative adaptations and strategic planning. 3D imaging is a modality that encompasses several of these criteria while encouraging the others. Imaging techniques used in facial imaging come in many different modalities and sub-modalities which is imperative for such a complex area of the body; there is a clear clinical need for hyper-specialized practice. However, with this complexity comes variability and thus there will always be an element of bias in the choices made for imaging techniques. Aims and Objectives: The aim of this review is to systematically analyse the imaging techniques used in facial reconstruction and produce a comprehensive summary and comparison of imaging techniques currently available, including both traditional and novel methods. Methods: The systematic search was performed on EMBASE, PubMed, Scopus, Web of Science and Cochrane reviews using keywords such as "image technique/acquisition/processing," "3-Dimensional," "Facial," and "Reconstruction." The PRISMA guidelines were used to carry out the systematic review. Studies were then subsequently collected and collated; followed by a screening and exclusion process with a final full-text review for further clarification in regard to the selection criteria. A risk of bias assessment was also carried out on each study systematically using the respective tool in relation to the study in question. Results: From the initial 6,147 studies, 75 were deemed to fulfill all selection criteria and selected for meta-analysis. The majority of papers involved the use of computer tomography, though the use of magnetic resonance and handheld scanners using sonography have become more common in the field. The studies ranged in patient population, clinical indication. Seminal papers were highlighted within the group of papers for further analysis. Conclusions: There are clearly many factors that affect the choice of image acquisition techniques and their potential at being ideal for a given role. Ultimately the surgical team's choice will guide much of the decision, but it is crucial to be aware of not just the diagnostic ability of such modalities, but their treatment possibilities as well.

3D Bioprinting and the Future of Surgery.

Introduction: The disciplines of 3D bioprinting and surgery have witnessed incremental transformations over the last century. 3D bioprinting is a convergence of biology and engineering technologies, mirroring the clinical need to produce viable biological tissue through advancements in printing, regenerative medicine and materials science. To outline the current and future challenges of 3D bioprinting technology in surgery. Methods: A comprehensive literature search was undertaken using the MEDLINE, EMBASE and Google Scholar databases between 2000 and 2019. A narrative synthesis of the resulting literature was produced to discuss 3D bioprinting, current and future challenges, the role in personalized medicine and transplantation surgery and the global 3D bioprinting market. Results: The next 20 years will see the advent of bioprinted implants for surgical use, however the path to clinical incorporation will be fraught with an array of ethical, regulatory and technical challenges of which each must be surmounted. Previous clinical cases where regulatory processes have been bypassed have led to poor outcomes and controversy. Speculated roles of 3D bioprinting in surgery include the production of de novo organs for transplantation and use of autologous cellular material for personalized medicine. The promise of these technologies has sparked an industrial revolution, leading to an exponential growth of the 3D bioprinting market worth billions of dollars. Conclusion: Effective translation requires the input of scientists, engineers, clinicians, and regulatory bodies: there is a need for a collaborative effort to translate this impactful technology into a real-world healthcare setting and potentially transform the future of surgery.

Cutaneous manifestations of NAXD deficiency - A case report.

Metabolism is a tightly regulated sequence of events, supported by key reactions between enzymes and enzyme-specific substrates. These reactions have the potential to produce metabolic side products that can have deleterious effects to further key metabolic reactions. The nicotinamide repair system consists of two partner enzymes, NAD(P)HX epimerase (NAXE) and NAD(P)HX dehydratase (NAXD). These enzymes regulate the levels of metabolic side products. Here we present a case of an 11-month old child who presented to our paediatric department with pyrexia, lethargy and multiple cutaneous lesions on the background of NAXD deficiency, a lethal neurometabolic disorder of early childhood. Despite early intervention with intravenous antibiotics, the patient failed to improve and subsequently passed away. The skin lesions were thought to be a consequence of systemic disease rather than a propagator of infection. Clinicians should be aware of this incredibly rare metabolic disease, its potential to cause widespread systemic dysfunction and the developing avenues for management.

Using 3D Printing Technology to Teach Cartilage Framework Carving for Ear Reconstruction.

Objective: The aim of this study was to determine the validity of using a carvable 3D printed rib model in combination with a 3D printed auricular framework to facilitate the teaching, training and planning of auricular reconstruction. Design: 3D printed costal cartilages from ribs 6-9 were produced using a FormLabs Form3 Printer and used to make negative molds. 2:1 silicone-cornstarch mixture was added to each mold to make 12 simulated 6-9th costal cartilages suitable for carving. 3D printed auricular frameworks were produced in polylactic acid using an Ultimaker 3 3D printer to demonstrate the component parts and constructed framework of an auricular reconstruction. Participants: Twelve plastic surgery trainees attended a workshop in which they each attempted auricular reconstruction using the carvable models and 3D printed plastic models as a guide. All candidates completed a pre- and post-training questionnaire to assess confidence and comprehension of auricular reconstruction, and the suitability of the models for facilitating this teaching. Results: Only 42% of trainees (n = 5) had observed an ear reconstruction in theater prior to the training course. Statistically significant improvements in the appreciation of the different components that make an auricular framework (p < 0.0001) and confidence in carving and handling costal cartilage (p < 0.0001) were noted following completion of the training. Highly significant improvements in comprehension of the approach to ear reconstruction (p = 0.006) and locating the subunits of a reconstructed ear from costal cartilage (p = 0.003) were also noted. 100% of participants felt the 3D printed teaching aids directly enhanced their learning. Conclusions: Ear reconstruction is a complex, time consuming multi-stage operation demanding significant amounts of experience, planning and an appreciation of the 3D chondrocutaneous structure. In this study we have demonstrated the value of 3D printing in producing a suitable simulated costal cartilage model and as an adjunct to comprehending and planning a framework for auricular reconstruction.

Could Vitamins Help in the Fight Against COVID-19?

There are limited proven therapeutic options for the prevention and treatment of COVID-19. The role of vitamin and mineral supplementation or "immunonutrition" has previously been explored in a number of clinical trials in intensive care settings, and there are several hypotheses to support their routine use. The aim of this narrative review was to investigate whether vitamin supplementation is beneficial in COVID-19. A systematic search strategy with a narrative literature summary was designed, using the Medline, EMBASE, Cochrane Trials Register, WHO International Clinical Trial Registry, and Nexis media databases. The immune-mediating, antioxidant and antimicrobial roles of vitamins A to E were explored and their potential role in the fight against COVID-19 was evaluated. The major topics extracted for narrative synthesis were physiological and immunological roles of each vitamin, their role in respiratory infections, acute respiratory distress syndrome (ARDS), and COVID-19. Vitamins A to E highlighted potentially beneficial roles in the fight against COVID-19 via antioxidant effects, immunomodulation, enhancing natural barriers, and local paracrine signaling. Level 1 and 2 evidence supports the use of thiamine, vitamin C, and vitamin D in COVID-like respiratory diseases, ARDS, and sepsis. Although there are currently no published clinical trials due to the novelty of SARS-CoV-2 infection, there is pathophysiologic rationale for exploring the use of vitamins in this global pandemic, supported by early anecdotal reports from international groups. The final outcomes of ongoing trials of vitamin supplementation are awaited with interest.

Isolation and characterisation of nasoseptal cartilage stem/progenitor cells and their role in the chondrogenic niche.

BACKGROUND: Since cartilage-derived stem/progenitor cells (CSPCs) were first identified in articular cartilage using differential adhesion to fibronectin, their self-renewal capacity and niche-specific lineage preference for chondrogenesis have propelled their application for cartilage tissue engineering. In many adult tissues, stem/progenitor cells are recognised to be involved in tissue homeostasis. However, the role of nasoseptal CSPCs has not yet been elucidated. Our aim was to isolate and characterise nasoseptal CSPCs alongside nasoseptal chondrocyte populations and determine chondrogenic capacity. METHODS: Here, we isolated nasoseptal CSPCs using differential adhesion to fibronectin and assessed their colony forming efficiency, proliferation kinetics, karyotype and trilineage potential. CSPCs were characterised alongside non-fibronectin-adherent nasoseptal chondrocytes (DNCs) and cartilage-derived cells (CDCs, a heterogenous combination of DNCs and CSPCs) by assessing differences in gene expression profiles using PCR Stem Cell Array, immunophenotype using flow cytometry and chondrogencity using RT-PCR and histology. RESULTS: CSPCs were clonogenic with increased gene expression of the neuroectodermal markers NCAM1 and N-Cadherin, as well as Cyclins D1 and D2, compared to DNCs. All three cell populations expressed recognised mesenchymal stem cell surface markers (CD29, CD44, CD73, CD90), yet only CSPCs and CDCs showed multilineage differentiation potential. CDC populations expressed significantly higher levels of type 2 collagen and bone morphogenetic protein 2 genes, with greater cartilage extracellular matrix secretion. When DNCs were cultured in isolation, there was reduced chondrogenicity and higher expression of type 1 collagen, stromal cell-derived factor 1 (SDF-1), CD73 and CD90, recognised markers of a fibroblast-like phenotype. CONCLUSIONS: Fibronectin-adherent CSPCs demonstrate a unique gene expression profile compared to non-fibronectin-adherent DNCs. DNCs cultured in isolation, without CSPCs, express fibroblastic phenotype with reduced chondrogenicity. Mixed populations of stem/progenitor cells and chondrocytes were required for optimal chondrogenesis, suggesting that CSPCs may be required to retain phenotypic stability and chondrogenic potential of DNCs. Crosstalk between DNCs and CSPCs is proposed based on SDF-1 signalling.

Author Correction: Morphological and biomechanical characterization of immature and mature nasoseptal cartilage.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Deep inferior epigastric perforator flap demonstrating the triple response of Lewis phenomenon - A case report and insights into aetiology.

Dermatographism, also known as skin writing, is an immunological response that remains an enigma. It occurs when normal skin is stroked with a dull object causing it to become raised and inflamed, and assume the shape of the stroke. Here we present a case of dermatographia in a denervated deep inferior epigastric perforator flap used to reconstruct breast tissue following mastectomy.

Morphological and biomechanical characterization of immature and mature nasoseptal cartilage.

Nasoseptal cartilage has been assumed to be isotropic, unlike the well-defined zonal organization of articular cartilage attributed to postnatal biomechanical loading. We know from clinical experience that malrotation of surgical nasoseptal cartilage grafts can lead to increased graft absorption. Other studies have also suggested directionally dependent compressive stiffness suggesting anisotropy, but morphological investigations are lacking. This study characterizes immature and mature native bovine nasoseptal cartilage using a combination of immunohistochemistry, biomechanical testing and structural imaging. Our findings indicate that there is extensive postnatal synthesis and reorganization of the extracellular matrix in bovine nasoseptal cartilage, independent of joint loading forces responsible for articular cartilage anisotropy. Immature nasoseptal cartilage is more cellular and homogenous compared to the zonal organization of cells and extracellular matrix of mature cartilage. Mature samples also exhibited greater glycosaminoglycan content and type II collagen fibre alignment compared to immature cartilage and this correlates with greater compressive stiffness. Engineered neocartilage often consists of immature, isotropic, homogenous tissue that is unable to meet the functional and mechanical demands when implanted into the native environment. This study demonstrates the importance of anisotropy on biomechanical tissue strength to guide future cartilage tissue engineering strategies for surgical reconstruction.