Elizabeth Ratcliffe

Background/Objectives: The incidence of acute kidney injury (AKI) following advanced epithelial ovarian cancer (EOC) surgery has not been extensively studied. This study aimed to investigate the incidence of AKI and identify preoperative and intraoperative predictors in patients undergoing advanced EOC cytoreduction using both traditional statistics and Artificial Intelligence (AI) modelling. Methods: Retrospective data was collected for 134 patients with a suspected or confirmed diagnosis of advanced EOC (FIGO Stage III-IV) who underwent surgical cytoreduction between January 2021 and December 2022 at a UK tertiary referral centre. AKI was diagnosed according to the KDIGO criteria. Data on 22 patient variables were extracted, including age, Charlson Comorbidity Index (CCI), procedure length, surgical complexity, and length of hospital stay. Logistic regression analysis was used for feature selection to identify AKI predictors, and an extreme gradient boost (XGBoost) model was applied to all variables related to AKI events. Results: The incidence of postoperative AKI was 6.72% (n=9). Predictive factors for AKI included younger age (OR = 0.942, p=0.037), lower CCI (OR = 0.415, p=0.015), longer procedure duration (OR = 1.006, p=0.019), and greater surgical effort (OR = 1.427, p=0.007). Patients with perioperative AKI experienced a doubling in the length of hospital stay (p=0.008). Mortality rates were similar between patients with and without AKI. AI-driven algorithms highlighted the complexity of AKI prediction and provided individual risk profiles, enabling future stratification and prompting different frequencies of AKI monitoring following cytoreduction. Conclusions: Predicting AKI is a complex task. This study found a lower-than-expected incidence of AKI following advanced EOC cytoreductive surgery. AKI is linked to heightened surgical risk-taking, underscoring the need for improved guidelines focusing on postoperative monitoring for targeted patients. Artificial Intelligence offers the potential for personalized AKI prediction.

Chronic wounds are becoming an increasing burden on healthcare services, as they have extended healing times and are susceptible to infection, with many failing to heal, which can lead ultimately to amputation. Due to the additional rise in antimicrobial resistance and emergence of difficult-to-treat Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. (ESKAPE pathogens), novel treatments will soon be required asides from traditional antibiotics. Many natural substances have been identified as having the potential to aid in both preventing infection and increasing the speed of wound closure processes. Manuka honey is already in some cases used as a topical treatment in the form of ointments, which in conjunction with dressings and fish skin grafts are an existing US Food and Drug Administration-approved treatment option. These existing treatment options indicate that fatty acids from fish oil and manuka honey are well tolerated by the body, and if the active components of the treatments were better understood, they could make valuable additions to topical treatment options. This review considers two prominent natural substances with established manufacturing and global distribution—marine based fatty acids (including their metabolites) and manuka honey—their function as antimicrobials and how they can aid in wound repair, two important aspects leading to resolution of chronic wounds.

Both honey and fish oil have been historically used in medicine and identified as having antimicrobial properties. Although analyses of the substances have identified different components within them, it is not fully understood how these components interact and contribute to the observed effect. With the increase in multi-drug resistant strains of bacteria found in infections, new treatment options are needed. This study aimed to assess the antimicrobial abilities of fish oil components, including docosahexaenoic acid (DHA), eicosapentaenoic acid (EPA), and derived resolvins (RvE1, RvD2, and RvD3), as well as two varieties of manuka honey, against a panel of medically relevant microorganisms and antimicrobial resistant organisms, such as Methicillin Resistant Staphylococcus aureus (MRSA) and carbapenem-resistant Escherichia coli. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were identified; further minimum biofilm eradication concentrations (MBEC) were investigated for responsive organisms, including S. aureus, E. coli, Staphylococcus epidermidis, Klebsiella pneumoniae, and Pseudomonas aeruginosa. Concurrent with the existing literature, manuka honey was found to be a broad-spectrum antimicrobial with varied potency according to methylglyoxal content. DHA and EPA were both effective against Gram-positive and negative bacteria, but some drug-resistant strains or pathogens were not protected by a capsule. Only E. coli was inhibited by the resolvins.

Synthetic biology is an emerging area of research that combines the investigative nature of biology with the constructive nature of engineering. Despite the field being in its infancy, it has already aided the development of a myriad of industrially and pharmaceutically useful compounds, devices and therapies and is now being applied within the field of regenerative medicine. By combining synthetic biology with regenerative medicine, the engineering of cells and organisms offers potential avenues for applications in tissue engineering, bioprocessing, biomaterial and scaffold development, stem cell therapies and even gene therapies. This review aims to discuss how synthetic biology has been applied within these distinct areas of regenerative medicine, the challenges it faces and any future possibilities this exciting new field may hold.

It is well documented that cryopreservation and resuscitation of human embryonic stem cells (hESCs) is complex and ill-defined, and often suffers poor cell recovery and increased levels of undesirable cell differentiation. In this study we have applied Quality-by-Design (QbD) concepts to the critical processes of slow-freeze cryopreservation and resuscitation of hESC colony cultures. Optimized subprocesses were linked together to deliver a controlled complete process. We have demonstrated a rapid, high-throughput, and stable system for measurement of cell adherence and viability as robust markers of in-process and postrecovery cell state. We observed that measurement of adherence and viability of adhered cells at 1 h postseeding was predictive of cell proliferative ability up to 96 h in this system. Application of factorial design defined the operating spaces for cryopreservation and resuscitation, critically linking the performance of these two processes. Optimization of both processes resulted in enhanced reattachment and post-thaw viability, resulting in substantially greater recovery of cryopreserved, pluripotent cell colonies. This study demonstrates the importance of QbD concepts and tools for rapid, robust, and low-risk process design that can inform manufacturing controls and logistics.

Academic centers, hospitals and small companies, as typical development settings for UK regenerative medicine assets, are significant contributors to the development of autologous cell-based therapies. Often lacking the appropriate funding, quality assurance heritage or specialist regulatory expertise, qualifying aseptic cell processing facilities for GMP compliance is a significant challenge. The qualification of a new Cell Therapy Manufacturing Facility with automated processing capability, the first of its kind in a UK academic setting, provides a unique demonstrator for the qualification of small-scale, automated facilities for GMP-compliant manufacture of autologous cell-based products in these settings. This paper shares our experiences in qualifying the Cell Therapy Manufacturing Facility, focusing on our approach to streamlining the qualification effort, the challenges, project delays and inefficiencies we encountered, and the subsequent lessons learned.

There is a dearth of technology and methods to aid process characterization, control and scale‐up of complex culture platforms that provide niche micro‐environments for some stem cell‐based products. We have demonstrated a novel use of 3d in vivo imaging systems to visualize medium flow and cell distribution within a complex culture platform (hollow fiber bioreactor) to aid characterization of potential spatial heterogeneity and identify potential routes of bioreactor failure or sources of variability. This can then aid process characterization and control of such systems with a view to scale‐up. Two potential sources of variation were observed with multiple bioreactors repeatedly imaged using two different imaging systems: shortcutting of medium between adjacent inlet and outlet ports with the potential to create medium gradients within the bioreactor, and localization of bioluminescent murine 4T1‐luc2 cells upon inoculation with the potential to create variable seeding densities at different points within the cell growth chamber. The ability of the imaging technique to identify these key operational bioreactor characteristics demonstrates an emerging technique in troubleshooting and engineering optimization of bioreactor performance. © 2013 American Institute of Chemical Engineers Biotechnol. Prog., 30:256–260, 2014

Apart from haematopoietic stem cell transplantation for haematological disorders many stem cell-based therapies are experimental. However, with only 12 years between human embryonic stem cell isolation and the first clinical trial, development of stem cell products for regenerative medicine has been rapid and numerous clinical trials have begun to investigate their therapeutic potential. This review summarizes key clinical trial data, current and future perspectives on stem cell-based products undergoing clinical trials, based on literature search and author research. It is widely recognized that the ability to stimulate stem cell differentiation into specialized cells for use as cellular therapies will revolutionize health care and offer major hope for numerous diseases for which there are limited or no therapeutic options. Stem cell-based products are unique and cover a large range of disorders to be treated; therefore, there is significant potential for variation in cell source, type, processing manipulation, the bioprocessing approach and scalability, the cost and purity of manufacture, final product quality and mode of action. As such there are gaps in regulatory and manufacturing frameworks and technologies, only a small number of products are currently within late phase clinical trials and few products have achieved commercialization. Recent developments are encouraging acceleration through the difficulties encountered en route to clinical trials and commercialization of stem cell therapies. The field is growing year on year with the first clinical trial using induced pluripotent stem cells anticipated by end 2013.