Introduction At present, vaccines form the only mode of prophylaxis against COVID-19. The time needed to achieve mass global vaccination and the emergence of new variants warrants continued research into other COVID-19 prevention strategies. The severity of COVID-19 infection is thought to be associated with the initial viral load, and for infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus and attach to the host cell surface receptors. Carrageenan, a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a wide range of viruses in clinical trials through the prevention of viral entry into respiratory host cells. Carrageenan has also demonstrated in vitro activity against SARS-CoV-2. Methods and analysis A single-centre, randomised, double-blinded, placebo-controlled phase III trial was designed. Participants randomised in a 1:1 allocation to either the treatment arm, verum Coldamaris plus (1.2 mg iota-carrageenan (Carragelose®), 0.4 mg kappa-carrageenan, 0.5% sodium chloride and purified water), or placebo arm, Coldamaris sine (0.5% sodium chloride) spray applied daily to their nose and throat for 8 weeks, while completing a daily symptom tracker questionnaire for a total of 10 weeks. Primary outcome Acquisition of COVID-19 infection as confirmed by a positive PCR swab taken at symptom onset or seroconversion during the study. Secondary outcomes include symptom type, severity and duration, subsequent familial/household COVID-19 infection and infection with non-COVID-19 upper respiratory tract infections. A within-trial economic evaluation will be undertaken, with effects expressed as quality-adjusted life years. Discussion This is a single-centre, phase III, double-blind, randomised placebo-controlled clinical trial to assess whether carrageenan nasal and throat spray reduces the risk of development and severity of COVID-19. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Trial registration NCT04590365; ClinicalTrials.gov NCT04590365. Registered on 19 October 2020.
Abstract Introduction The severity of Covid-19 infection is associated with viral load. For infection to occur, viruses including SARS-CoV-2 must first penetrate the respiratory mucus to attach to the host cell surface receptors. Iota-carrageenan (I-C), a sulphated polysaccharide extracted from red edible seaweed, has shown efficacy against a range of viruses in clinical trials, through prevention of viral entry into respiratory host cells and in-vitro activity against SARS-CoV-2. Our aim, as an academic surgical department, was to design and implement a clinical trial to investigate whether I-C nasal and throat sprays are effective in reducing the rate and severity of Covid-19 infection. Method The study is a single centre, double-blinded randomised controlled trial. Recruitment of 480 participants aged ≥18 years without previous Covid-19 infection and who have not yet been vaccinated, commenced in December 2020. Participants are randomised to either the treatment (0.12% I-C in 0.5% saline spray) or placebo (0.5% saline spray) arm and will prophylactically apply the spray to their nose and throat while completing a daily symptom tracker for a total of 10 weeks. The primary outcome is the acquisition of Covid-19 infection. Secondary outcomes include symptom type, severity and duration, subsequent familial/household Covid-19 infection and infection with non-Covid-19 upper respiratory tract infections. Discussion Our hypothesis is that I-C sprays will reduce SARS-CoV-2 attachment to the naso- and oropharyngeal mucosal epithelial cells thus reducing the effective viral infective dose. If proven effective, the self-administered prophylactic spray would have wider utility for key workers and the general population. Trial registration number NCT04590365
Abstract Introduction In a regional centre for plastic surgery, it had been noted that operations were being delayed due to lack of pre-operative investigations. A pre-operative investigation checklist was developed between anaesthetic and surgical staff for semi-elective plastic trauma surgery patients, based on NICE guidelines. The checklist recommends which blood, radiology and cardiopulmonary tests would be appropriate based upon age, ASA grade and co-morbidity. Method A complete cycle audit was used to evaluate the checklist. All patients having GA/block for plastic surgery trauma in a 2-week window were included. Data was collected retrospectively via electronic operative records, anaesthetic assessments, and clinical notes. A minimum of 15 patients was collected per cycle. A single page pre-operative checklist was created for pre-operative investigations were introduced after the first cycle. Results The first audit cycle had 16 patients, ASA1 (5), ASA 2(6) ASA 3 (5). 75% had appropriate pre-op investigations. In the second cycle 22 patients, ASA 1 (8), ASA 2 (9), ASA 3 (3), ASA 4 (1). 100% of patients had appropriate pre-operative investigations. Conclusions There was increased awareness of pre-operative investigations in medical and nursing staff after the introduction of the checklist. It has helped streamline the delivery of semi-elective trauma surgery in our unit.
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.
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 comple x, 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.
Modern three-dimensional (3D) bioprinting promises the creation of bespoke tissue-engineered constructs that would herald the end of donor site morbidity, creation of solid complex organs “made to order,” and facilitate a revolution in both biological sciences and medical research. Biotechnology companies along with major laboratories worldwide, in response to this potential, have invested decades and millions of dollars in the development of printing technology and its applications across a number of disciplines. The relatively simple core principle of stereolithography developed in the 1980s has sparked a materials and technological revolution that has seen the development of more precise printers, intelligent bioinks, and scaffold materials capable of supporting de novo tissue growth. The original aims of producing solid 3D polymer models have been superseded, and today 3D bioprinting is used in a range of scientific and commercial fields such as in drug delivery systems, cosmetic testing, and in the printing of customized 3D scaffolds to support tissue growth [1–3]. While much of the activity worldwide is research based, there is already a significant commercial element, which incorporates these new technologies into modern practice. The current uses of 3D printing include the creation of devices and implants which have been available for a number of years and allow the production of personalized implants to augment operative technique and bespoke 3D prosthesis for reconstruction [4–6].
Recent advances in microsurgery, imaging, and transplantation have led to significant refinements in autologous reconstructive options; however, the morbidity of donor sites remains. This would be eliminated by successful clinical translation of tissue-engineered solutions into surgical practice. Plastic surgeons are uniquely placed to be intrinsically involved in the research and development of laboratory engineered tissues and their subsequent use. In this article, we present an overview of the field of tissue engineering, with the practicing plastic surgeon in mind. The Medical Research Council states that regenerative medicine and tissue engineering "holds the promise of revolutionizing patient care in the twenty-first century." The UK government highlighted regenerative medicine as one of the key eight great technologies in their industrial strategy worthy of significant investment. The long-term aim of successful biomanufacture to repair composite defects depends on interdisciplinary collaboration between cell biologists, material scientists, engineers, and associated medical specialties; however currently, there is a current lack of coordination in the field as a whole. Barriers to translation are deep rooted at the basic science level, manifested by a lack of consensus on the ideal cell source, scaffold, molecular cues, and environment and manufacturing strategy. There is also insufficient understanding of the long-term safety and durability of tissue-engineered constructs. This review aims to highlight that individualized approaches to the field are not adequate, and research collaboratives will be essential to bring together differing areas of expertise to expedite future clinical translation. The use of tissue engineering in reconstructive surgery would result in a paradigm shift but it is important to maintain realistic expectations. It is generally accepted that it takes 20-30 years from the start of basic science research to clinical utility, demonstrated by contemporary treatments such as bone marrow transplantation. Although great advances have been made in the tissue engineering field, we highlight the barriers that need to be overcome before we see the routine use of tissue-engineered solutions.
Photography provides an unsurpassed method of communicating accurate visual pathologies to both patients and colleagues. 1 Starr J.C. Integrating digital image management software for improved patient care and optimal practice management. Dermatol Surg. 2006; 32: 834-840 PubMed Google Scholar It has become the standard of practice for documenting pre-operative, operative and post-operative clinical findings in a number of medical specialities, including Plastic and Reconstructive Surgery. In some areas of the world, electronic notes systems are commonly used to incorporate photographs and to create clinical letters, however in our experience this is not the norm. Digital technology has revolutionised photography, simplifying the process of capturing and recording images. Modern digital cameras, such as those in smartphones, are user friendly, portable, produce high definition images and are relatively inexpensive.
Despite the increasing laboratory research in the growing field of 3D bioprinting, there are few reports of successful translation into surgical practice. This review outlines the principles of 3D bioprinting including software and hardware processes, biocompatible technological platforms and suitable bioinks. The advantages of 3D bioprinting over traditional tissue engineering techniques in assembling cells, biomaterials and biomolecules in a spatially controlled manner to reproduce native tissue macro-, micro- and nanoarchitectures are discussed, together with an overview of current progress in bioprinting tissue types relevant for plastic and reconstructive surgery. If successful, this platform technology has the potential to biomanufacture autologous tissue for reconstruction, obviating the need for donor sites or immunosuppression. The biological, technological and regulatory challenges are highlighted, with strategies to overcome these challenges by using an integrated approach from the fields of engineering, biomaterial science, cell biology and reconstructive microsurgery.
The potential use of stem cell-based therapies for the repair and regeneration of various tissues and organs offers a paradigm shift in plastic and reconstructive surgery. The use of either embryonic stem cells (ESC) or induced pluripotent stem cells (iPSC) in clinical situations is limited because of regulations and ethical considerations even though these cells are theoretically highly beneficial. Adult mesenchymal stem cells appear to be an ideal stem cell population for practical regenerative medicine. Among these cells, adipose-derived stem cells (ADSC) have the potential to differentiate the mesenchymal, ectodermal and endodermal lineages and are easy to harvest. Additionally, adipose tissue yields a high number of ADSC per volume of tissue. Based on this background knowledge, the purpose of this review is to summarise and describe the proliferation and differentiation capacities of ADSC together with current preclinical data regarding the use of ADSC as regenerative tools in plastic and reconstructive surgery.
Recent advances in regenerative medicine place us in a unique position to improve the quality of engineered tissue. We use auricular cartilage as an exemplar to illustrate how the use of tissue-specific adult stem cells, assembly through additive manufacturing and improved understanding of postnatal tissue maturation will allow us to more accurately replicate native tissue anisotropy. This review highlights the limitations of autologous auricular reconstruction, including donor site morbidity, technical considerations and long-term complications. Current tissue-engineered auricular constructs implanted into immune-competent animal models have been observed to undergo inflammation, fibrosis, foreign body reaction, calcification and degradation. Combining biomimetic regenerative medicine strategies will allow us to improve tissue-engineered auricular cartilage with respect to biochemical composition and functionality, as well as microstructural organization and overall shape. Creating functional and durable tissue has the potential to shift the paradigm in reconstructive surgery by obviating the need for donor sites.
The evolution of breast reconstruction and management of breast cancer has evolved significantly since the earliest descriptions in the Edwin Smith Papyrus (3,000 BC). The development of surgical and scientific expertise has changed the way that women are managed, and plastic surgeons are now able to offer a wide range of reconstructive options to suit individual needs. Beyond the gold standard autologous flap based reconstructions, regenerative therapies promise the elimination of donor site morbidity whilst providing equivalent aesthetic and functional outcomes. Future research aims to address questions regarding ideal cell source, optimisation of scaffold composition and interaction of de novo adipose tissue in the microenvironment of breast cancer.