Scaffold Biomaterials in Tissue Regeneration in Surgery

This chapter will focus on the subject of tissue regeneration in a variety of different surgical fields and operations. We will explore the use of acellular dermal matrices, stem cell-based therapies, gene regulation, emerging 3D printing techniques and their potential applications in surgery. Acellular dermal matrices (ADMs) are biological materials derived from human or animal tissue through complicated and expensive decellularisation processes, leading to acellular material that can be used to aid tissue healing. ADMs were first introduced for the treatment of burn injuries, but are now widely used in a variety of surgical fields, including abdominal wall and breast reconstruction. A wide range of materials can be used to produce ADMs, but usually include bovine, porcine or human tissues (e.g., dermis and pericardium). ADMs act as scaffolds onto which human tissue can incorporate, allowing for an innovative, yet a very effective way to aid tissue regeneration. Stem cell therapies also hold promise in aiding tissue regeneration in the coming years and we will also explore techniques that are currently being researched by prominent scientists all across the world. For example, adipose tissue-derived stem cells (ASCs) are a potentially revolutionary therapy in regenerative medicine. We will review the current evidence available and consider the possible clinical applications of ASCs, including their potential to treat ischaemic diseases and their role in healing chronic wounds. ASCs are adult stem cells, which display similar morphology and differentiation properties to adult mesenchymal stem cells (MSCs). The multiple linage pathways displayed by ASCs allows a variety of tissues to be repaired and maintained. Moreover, adipose tissue is abundant, easily accessible and is able to be repeatedly harvested with low morbidity. Previously, autologous fat grafting was more commonly utilised for managing volume defects in reconstructive and plastic surgery; however, recent literature has revealed promising therapeutic effects of ASCs in tissue regeneration. Finally, gene regulation, which holds promise in musculoskeletal diseases, and 3D printed scaffolds that aid neural regeneration will also be discussed in this chapter as emerging, and potentially very promising, tissue regeneration techniques

Resurgence and order effects in humans

Latent behaviours are learned behaviours that have not been recently observed in an individual’s behavioural history. These behaviours can reappear under many different conditions. Resurgence refers to the reappearance of latent behaviour during extinction. Resurgence is one of the behavioural effects which increases behavioural variability during extinction. This increase in behavioural variability contributes to the complex responses produced in problem solving situations. In typical resurgence research there are three phases: a training phase, an alternative reinforcement phase and a resurgence phase. However, in real-life situations, people often have more extensive learning histories and multiple behaviours may reappear when extinction occurs. The aim of this study was to research whether the order that behaviours were acquired in, for either three or four behaviours, would affect their prevalence during extinction. University students were randomly assigned into one of two groups. The first group took part in a four-phase resurgence procedure and learnt three responses sequentially before transitioning to the extinction phase. The second group learnt an additional response before transitioning to the extinction phase. A primacy and recency effect was found in the three response group; the first trained response and the last trained response were the most prevalent trained responses during extinction. This was consistent with previous research. The behaviours of the participants in the second, four-response, group were more idiosyncratic and no order effects were observed. This study contributes to the research of how different aspects of an individual’s behavioural history can affect resurgence

A paper-based simulation model for teaching inguinal hernia anatomy

Background: Inguinal hernias remain a challenging area of learning for medical students due to its relatively complex anatomy. Modern curriculum delivery methods are conventionally limited to didactic lectures and demonstration of anatomy intraoperatively. These strategies have limitations; lectures are inherently descriptive and based on 2-dimensional models, while intraoperative teaching is often unstructured and opportunistic. Methods: A paper-based model was developed comprising three overlapping paper panels simulating the anatomical layers of the inguinal canal which can be modified readily to further simulate various hernia pathologies and their surgical repair. These models were incorporated into a timetabled structured learning session for 3rd- and 4th-year medical students. Learners responded to fully anonymised surveys before and after the learning session. Findings: A total of 45 students participated in these sessions over a period of 6 months. Pre-learning session mean ratings for the learners’ confidence in their understanding of the layers of the inguinal canal, identifying indirect and direct inguinal hernias and in naming the contents of the inguinal canal were 2.5, 3.3 and 2.9, while post-learning session mean ratings were 8.0, 9.4 and 8.2, respectively. Paired samples Student’s t-tests for all three questions were statistically significant (p < 0.001). The mean rating for usefulness of the session was 9.6/10. Free comments from students emphasised the models’ usefulness as a visual learning aid. Discussion and Conclusion: Our novel, low-cost paper model was associated with an improvement in learners’ perceived knowledge and understanding of inguinal canal anatomy and pathology

Are we meeting current standards in medicines reconciliation? A study in a district general hospital.

Introduction: Inadequate medicines reconciliation on admission is often identified as a major cause of patient morbidity, with poor access to patient's regular medications often cited as a barrier to care. In the surgical admission unit of our district general hospital, drug charts are completed by junior doctors who do not have access to the Emergency Care Summary (ECS) thus making it difficult to accurately complete admission drug charts. Methods: Our initial measurement of all acute surgical admissions revealed that 49% of patients had an accurate medicines reconciliation upon admission, increasing to 75% within 24 hours of admission. It was clear from this data that our current practice needed improvement in order to ensure patient safety. Resultantly the junior medical staff were provided with ECS accounts and teaching to aid the process of medicines reconciliation. Results: Following the introduction of access to ECS and junior doctor education, a further two data cycles were completed. On the first cycle, the number of accurately completed drug charts increased to 62% on admission and 86% at 24 hours. After the second cycle 57% were complete on admission increasing to 84% at 24 hours. Conclusion: Our project has shown that by providing junior doctors with medicines reconciliation education and access to patients’ pre-admission medications through a nationwide electronic system resulted in a considerable increase in the completion of medicine reconciliation

Quinolone-resistant gyrase mutants demonstrate decreased susceptibility to triclosan

Objectives: Cross-resistance between antibiotics and biocides is a potentially important driver of MDR. A relationship between susceptibility of Salmonella to quinolones and triclosan has been observed. This study aimed to: (i) investigate the mechanism underpinning this; (ii) determine whether the phenotype is conserved in Escherichia coli; and (iii) evaluate the potential for triclosan to select for quinolone resistance. Methods: WT E. coli, Salmonella enterica serovar Typhimurium and gyrA mutants were used. These were characterized by determining antimicrobial susceptibility, DNA gyrase activity and sensitivity to inhibition. Expression of stress response pathways (SOS, RpoS, RpoN and RpoH) was measured, as was the fitness of mutants. The potential for triclosan to select for quinolone resistance was determined. Results: All gyrase mutants showed increased triclosan MICs and altered supercoiling activity. There was no evidence for direct interaction between triclosan and gyrase. Identical substitutions in GyrA had different impacts on supercoiling in the two species. For both, there was a correlation between altered supercoiling and expression of stress responses. This was more marked in E. coli, where an Asp87Gly GyrA mutant demonstrated greatly increased fitness in the presence of triclosan. Exposure of parental strains to low concentrations of triclosan did not select for quinolone resistance. Conclusions: Our data suggest gyrA mutants are less susceptible to triclosan due to up-regulation of stress responses. The impact of gyrA mutation differs between E. coli and Salmonella. The impacts of gyrA mutation beyond quinolone resistance have implications for the fitness and selection of gyrA mutants in the presence of non-quinolone antimicrobials

Current practice and surgical outcomes of neoadjuvant chemotherapy for early breast cancer : UK NeST study

Funding Information: This work was funded by a grant from the Association of Breast SurgeryPeer reviewedPublisher PD

Effects of hospital facilities on patient outcomes after cancer surgery: an international, prospective, observational study

Background Early death after cancer surgery is higher in low-income and middle-income countries (LMICs) compared with in high-income countries, yet the impact of facility characteristics on early postoperative outcomes is unknown. The aim of this study was to examine the association between hospital infrastructure, resource availability, and processes on early outcomes after cancer surgery worldwide.Methods A multimethods analysis was performed as part of the GlobalSurg 3 study-a multicentre, international, prospective cohort study of patients who had surgery for breast, colorectal, or gastric cancer. The primary outcomes were 30-day mortality and 30-day major complication rates. Potentially beneficial hospital facilities were identified by variable selection to select those associated with 30-day mortality. Adjusted outcomes were determined using generalised estimating equations to account for patient characteristics and country-income group, with population stratification by hospital.Findings Between April 1, 2018, and April 23, 2019, facility-level data were collected for 9685 patients across 238 hospitals in 66 countries (91 hospitals in 20 high-income countries; 57 hospitals in 19 upper-middle-income countries; and 90 hospitals in 27 low-income to lower-middle-income countries). The availability of five hospital facilities was inversely associated with mortality: ultrasound, CT scanner, critical care unit, opioid analgesia, and oncologist. After adjustment for case-mix and country income group, hospitals with three or fewer of these facilities (62 hospitals, 1294 patients) had higher mortality compared with those with four or five (adjusted odds ratio [OR] 3.85 [95% CI 2.58-5.75]; p<0.0001), with excess mortality predominantly explained by a limited capacity to rescue following the development of major complications (63.0% vs 82.7%; OR 0.35 [0.23-0.53]; p<0.0001). Across LMICs, improvements in hospital facilities would prevent one to three deaths for every 100 patients undergoing surgery for cancer.Interpretation Hospitals with higher levels of infrastructure and resources have better outcomes after cancer surgery, independent of country income. Without urgent strengthening of hospital infrastructure and resources, the reductions in cancer-associated mortality associated with improved access will not be realised

The NeST (Neoadjuvant systemic therapy in breast cancer) study: National Practice Questionnaire of United Kingdom multi-disciplinary decision making

Abstract: Background: Neoadjuvant systemic therapy (NST) is increasingly used in the treatment of breast cancer, yet it is clear that there is significant geographical variation in its use in the UK. This study aimed to examine stated practice across UK breast units, in terms of indications for use, radiological monitoring, pathological reporting of treatment response, and post-treatment surgical management. Methods: Multidisciplinary teams (MDTs) from all UK breast units were invited to participate in the NeST study. A detailed questionnaire assessing current stated practice was distributed to all participating units in December 2017 and data collated securely usingREDCap. Descriptive statistics were calculated for each questionnaire item. Results: Thirty-nine MDTs from a diverse range of hospitals responded. All MDTs routinely offered neoadjuvant chemotherapy (NACT) to a median of 10% (range 5–60%) of patients. Neoadjuvant endocrine therapy (NET) was offered to a median of 4% (range 0–25%) of patients by 66% of MDTs. The principal indication given for use of neoadjuvant therapy was for surgical downstaging. There was no consensus on methods of radiological monitoring of response, and a wide variety of pathological reporting systems were used to assess tumour response. Twenty-five percent of centres reported resecting the original tumour footprint, irrespective of clinical/radiological response. Radiologically negative axillae at diagnosis routinely had post-NACT or post-NET sentinel lymph node biopsy (SLNB) in 73.0 and 84% of centres respectively, whereas 16% performed SLNB pre-NACT. Positive axillae at diagnosis would receive axillary node clearance at 60% of centres, regardless of response to NACT. Discussion: There is wide variation in the stated use of neoadjuvant systemic therapy across the UK, with general low usage of NET. Surgical downstaging remains the most common indication of the use of NAC, although not all centres leverage the benefits of NAC for de-escalating surgery to the breast and/or axilla. There is a need for agreed multidisciplinary guidance for optimising selection and management of patients for NST. These findings will be corroborated in phase II of the NeST study which is a national collaborative prospective audit of NST utilisation and clinical outcomes