ORCID Profile
0000-0001-9188-7097
Current Organisations
Australian National Phenome Centre, Murdoch University
,
Murdoch University
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Publisher: American Chemical Society (ACS)
Date: 24-02-2023
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.BURNS.2022.08.021
Abstract: Surgical wound excision is a necessary procedure for burn patients that require the removal of eschar. The extent of excision is currently guided by clinical judgement, with excessinto healthy tissue potentially leading to excessive scar, or inadequate debridement increasing risk of infection. Thus, an objective real-time measure to facilitate accurate excision could support clinical judgement and improve this surgical procedure. This study was designed to investigate the potential use of Rapid evaporative ionisation mass spectrometry (REIMS) as a tool to support data-driven objective tissue excision. Data were acquired using a multi-platform approach that consisted of both Rapid Evaporative Ionisation Mass Spectrometry (REIMS) performed on intact skin, and comprehensive liquid chromatography-mass spectrometry (LC-MS/MS) lipidomics performed on homogenised skin tissue extracts. Data were analysed using principal components analysis (PCA) and multivariate orthogonal projections to latent squares discriminant analysis (OPLS-DA) and logistic regression to determine the predictability of the models. PCA and OPLS-DA models of the REIMS and LC-MS/MS lipidomics data reported separation of excised and healthy tissue. Molecular fingerprints generated from REIMS analysis of healthy skin tissue revealed a high degree of heterogeneity, however, intra-in idual variance was smaller than inter-in idual variance. Both platforms indicated high levels of skin classification accuracy. In addition, OPLS-DA of the LC-MS/MS lipidomic data revealed significant differences in specific lipid classes between healthy control and excised skin s les including lower free fatty acids (FFA), monoacylglycerols (MAG), lysophosphatidylglycerol (LPG) and lysophosphatidylethanolamines (LPE) in excised tissue and higher lactosylceramides (LCER) and cholesterol esters (CE) compared to healthy control tissue. Having established the heterogeneity in the biochemical composition of healthy skin using REIMS and LC-MS/MS, our data show that REIMS has the potential to distinguish between excied and healthy skin tissue s les. This pilot study suggests that REIMS may be an effective tool to support accurate tissue excision during burn surgery.
Publisher: MDPI AG
Date: 20-07-2021
Abstract: Improved methods are required for investigating the systemic metabolic effects of SARS-CoV-2 infection and patient stratification for precision treatment. We aimed to develop an effective method using lipid profiles for discriminating between SARS-CoV-2 infection, healthy controls, and non-SARS-CoV-2 respiratory infections. Targeted liquid chromatography–mass spectrometry lipid profiling was performed on discovery (20 SARS-CoV-2-positive 37 healthy controls 22 COVID-19 symptoms but SARS-CoV-2negative) and validation (312 SARS-CoV-2-positive 100 healthy controls) cohorts. Orthogonal projection to latent structure-discriminant analysis (OPLS-DA) and Kruskal–Wallis tests were applied to establish discriminant lipids, significance, and effect size, followed by logistic regression to evaluate classification performance. OPLS-DA reported separation of SARS-CoV-2 infection from healthy controls in the discovery cohort, with an area under the curve (AUC) of 1.000. A refined panel of discriminant features consisted of six lipids from different subclasses (PE, PC, LPC, HCER, CER, and DCER). Logistic regression in the discovery cohort returned a training ROC AUC of 1.000 (sensitivity = 1.000, specificity = 1.000) and a test ROC AUC of 1.000. The validation cohort produced a training ROC AUC of 0.977 (sensitivity = 0.855, specificity = 0.948) and a test ROC AUC of 0.978 (sensitivity = 0.948, specificity = 0.922). The lipid panel was also able to differentiate SARS-CoV-2-positive in iduals from SARS-CoV-2-negative in iduals with COVID-19-like symptoms (specificity = 0.818). Lipid profiling and multivariate modelling revealed a signature offering mechanistic insights into SARS-CoV-2, with strong predictive power, and the potential to facilitate effective diagnosis and clinical management.
Publisher: American Chemical Society (ACS)
Date: 19-05-2021
Publisher: Cold Spring Harbor Laboratory
Date: 28-04-2023
DOI: 10.1101/2023.04.24.537960
Abstract: Globally, burns are a significant cause of injury that can cause substantial acute trauma as well as lead to increased incidence of chronic co-morbidity and disease. To date, research has primarily focused on the systemic response to severe injury, with little in the literature reported on impact of non-severe injuries ( % total burn surface area TBSA). To elucidate the metabolic consequences of non-severe burn injury, longitudinal plasma was collected from adults (n=35) who presented at hospital with a non-severe burn injury at admission, and at 6 week follow up. A cross-sectional baseline s le was also collected from non-burn control participants (n=14). S les underwent multiplatform metabolic phenotyping using 1 H nuclear magnetic resonance spectroscopy and liquid chromatography-mass spectrometry to quantify 112 lipoprotein and glycoproteins signatures and 852 lipid species from across 20 subclasses. Multivariate data modelling (Orthogonal projection to latent structures-discriminate analysis) revealed alterations in lipoprotein and lipid metabolism when comparing baseline control to hospital admission s les, with the phenotypic signature found to be sustained at follow up. Univariate (Mann-Whitney U) testing and OPLS-DA indicated specific increases in GlycB (p-value .0e -4 ), low density lipoprotein-2 subfractions (Variable importance in projection score VIP .83e -1 ) and monoacyglyceride (20:4)(p-value .0e -4 ) and decreases in circulating anti-inflammatory high-density lipoprotein-4 subfractions (VIP .75e -1 ), phosphatidylcholines, phosphatidylglycerols, phosphatidylinositols and phosphatidylserines. The results indicate a persistent systemic metabolic phenotype that occurs even in cases of non-severe burn injury. The phenotype is indicative of an acute inflammatory profile which continues to be sustained post-injury, suggesting an impact on systems health beyond the site of injury. The phenotypes contained metabolic signatures consistent with chronic inflammatory states reported to have elevated incidence post-burn injury. Such phenotypic signatures may provide patient stratification opportunities, to identify in idual responses to injury, personalise intervention strategies and improve acute care, reducing risk of chronic co-morbidity.
Publisher: American Chemical Society (ACS)
Date: 16-03-2021
Publisher: Cold Spring Harbor Laboratory
Date: 30-07-2023
DOI: 10.1101/2023.07.28.550938
Abstract: Impaired wound healing in burn injuries can lead to complications such as skin graft loss, infection, and increased risk of scarring, which impacts long-term patient outcomes and quality of life. While wound repair in severe burns has received substantial research attention, poor wound outcomes in cases of non- severe burns (classified as % of the total body surface area (TBSA)) remain relatively understudied despite also having considerable physiological impact and constituting the majority of hospital admissions for burns. Predicting outcomes in the early stages of healing would decrease financial and patient burden, and aid in preventing long-term complications from poor wound healing. Lipids have been implicated in inflammation and tissue repair processes and may play essential roles in burn wound healing. Longitudinal plasma s les were collected from patients (n=20) with non-severe ( % TBSA) flame or scald burns over a 6-week period including timepoints pre- and post-surgical intervention. S les were analysed using liquid chromatography-tandem mass spectrometry and nuclear magnetic resonance spectroscopy to detect 850 lipid species and 112 lipoproteins. Statistical analyses, including orthogonal projection to latent structures-discriminant analysis was performed to identify changes associated with either re-epithelialisation or delayed wound re-epithelisation. The results demonstrated that the plasma lipid and lipoprotein profiles at admission could predict wound re-epithelisation outcomes at two weeks post-surgery, and that these discriminatory profiles were maintained over a 6-week period. Triacylglycerides, diacylglycerides (DAG) and low density lipoprotein (LDL) subfractions were associated with delayed wound closure, with DAG(18:2_18:3) and LDL/High density lipoprotein (HDL) ratio having the most influence (p-value 0.02, Cliff’s delta 0.7), while HDL subfractions, phosphatidylinositols, phosphatidylcholines (PC), and phosphatidylserines were associated with re-epithelisation at two weeks post-surgery, with PC(16:0_18:1) and HDL-2 apolipoprotein-A1 showing the greatest influence on the model (p-value 0.01, Cliff’s delta -0.7). We demonstrate clinical prediction of wound re-epithelisation in non-severe burn patients using lipid and lipoprotein profiling. Further validation of the models will potentially lead to personalised intervention strategies to enhance injury outcomes, reducing the risk of chronic complications post-burn injury. Demonstration of wound healing prediction from time of hospital admission for non-severe burns. Plasma lipid and lipoprotein profiles within 48 hours of admission to hospital with non-severe burn injury are distinctly different between patients whose wounds re-epithelialized within two weeks and those with delayed re-epithelisation. Patients with delayed wound re-epithelisation have a persistent lipid and lipoprotein signature from burns admission up to six weeks post-injury.
Location: Australia
No related grants have been discovered for Monique Ryan.