ORCID Profile
0000-0002-2946-8841
Current Organisations
South Western Sydney Local Health District
,
Liverpool Hospital
Does something not look right? The information on this page has been harvested from data sources that may not be up to date. We continue to work with information providers to improve coverage and quality. To report an issue, use the Feedback Form.
Publisher: Cold Spring Harbor Laboratory
Date: 25-12-2021
DOI: 10.1101/2021.12.20.21267962
Abstract: Clinicians and researchers utilize subjective classification systems based on clinical parameters to stratify lower extremity ulcer infections for treatment and research. This study compared clinical infection classifications (mild to severe) of lower extremity ulcers (n = 44) with transcriptomic profiles and direct measurement of bacterial RNA signatures by RNA-sequencing. S les demonstrating similar transcriptomes were clustered and characterized by transcriptomic fingerprint. Clinical infection severity did not explain the major sources of variability among the s les and s les with the same clinical classification demonstrated high inter-s le variability. High proportions of bacterial RNA, however, resulted in a strong effect on transcription and increased expression of genes associated with immune response and inflammation. K-means clustering identified two clusters of s les, one of which contained all of the s les with high levels of bacterial RNA. A support vector classifier identified a fingerprint of 20 genes, including immune-associated genes such as CXCL8, GADD45B , and HILPDA , which accurately identified s les with signs of infection via cross-validation. This suggests that stratification of infection states based on a transcriptomic fingerprint may be a useful tool for studying host-bacterial interactions in these ulcers, as well as an objective classification method to identify the severity of infection. Clinicians and researchers utilize classification schemes based on clinically measurable parameters to describe infection severity in lower extremity ulcers. However, here we show that the local host gene expression is often discordant to clinical classification scores. We observed this inconsistency is explained by the increased presence of bacteria, which promotes increased immune and inflammatory responses. Two groups of host gene expression, predominantly differentiated by the levels of bacterial RNA, could be classified with less than 20 genes. These results provide significant insights into host response to bacterial infection where bacteria are directly observed, rather than implied from clinical observation, and illustrated the limitations of clinical observations to stratify lower extremity ulcers.
Publisher: Cold Spring Harbor Laboratory
Date: 23-02-2023
DOI: 10.1101/2023.02.23.529664
Abstract: Hidradenitis Suppurativa is a chronic inflammatory disease of which the pathogenesis is incompletely understood. Dermal fibroblasts have been previously identified as a major source of inflammatory cytokines, however information pertaining to the characteristics of subpopulations of fibroblasts in HS remains unexplored. Using in silico-deconvolution of whole-tissue RNAseq, Nanostring gene expression panels and confirmatory immunohistochemistry we identified fibroblast subpopulations in HS tissue and their relationship to disease severity and lesion morphology. Gene signatures of SFRP2+ fibroblast subsets were increased in lesional tissue, with gene signatures of SFRP1+ fibroblast subsets decreased. SFRP2+ and CXCL12+ fibroblast numbers, measured by IHC, were increased in HS tissue, with greater numbers associated with epithelialized tunnels and Hurley Stage 3 disease. Pro-inflammatory CXCL12+ fibroblasts were also increased, with reductions in SFRP1+ fibroblasts compared to healthy controls. Evidence of Epithelial Mesenchymal Transition was seen via altered gene expression of SNAI2 and altered protein expression of ZEB1, TWIST1, Snail/Slug, E-Cadherin and N-Cadherin in HS lesional tissue. The greatest dysregulation of EMT associated proteins was seen in biopsies containing epithelialized tunnels. The use of the oral Spleen tyrosine Kinase inhibitor Fostamatinib significantly reduced expression of genes associated with chronic inflammation, fibroblast proliferation and migration suggesting a potential role for targeting fibroblast activity in HS.
Publisher: Wiley
Date: 22-03-2020
DOI: 10.1111/AJD.13274
Publisher: Oxford University Press (OUP)
Date: 19-05-2022
DOI: 10.1111/BJD.21612
Abstract: Human epithelia are constantly exposed to microorganisms present in the environment or residing as part of commensal flora. Despite this exposure, infections involving the skin and subcutaneous tissue in healthy in iduals are, fortunately, quite rare. Many of the wounds that afflict the human body occur in in iduals of ill health and/or where the mechanism of wounding is impeded by host immunological, physiological or regenerative dysfunction. The interplay between microorganisms and host immunity is complex and remains ill defined however, the interpretation of downstream manifestations of the host response to invading microorganisms is still based largely on the clinical signs and symptoms of an active infectious process. In this review article we will provide a brief overview of the current challenges clinicians face in diagnosing wound infections, how chronic infections caused by biofilms are a major challenge, and how there have been minimal advancements in developing new diagnostics or therapeutics in the identification and management of wound infections.
Publisher: Wiley
Date: 31-07-2023
DOI: 10.1111/EXD.14894
Abstract: Mast cells have traditionally been associated with allergic inflammatory responses however, they play important roles in cutaneous innate immunity and wound healing. The Hidradenitis Suppurativa tissue transcriptome is associated with alterations in innate immunity and wound healing‐associated pathways however, the role of mast cells in the disease is unexplored. We demonstrate that mast cell‐associated gene expression (using whole tissue RNAseq) is upregulated, and in‐silico cellular deconvolution identifies activated mast cells upregulated and resting mast cells downregulated in lesional tissue. Tryptase/Chymase positive mast cells (identified using IHC) localize adjacent to epithelialized tunnels, fibrotic regions of the dermis and at perivascular sites associated with Neutrophil Extracellular Trap formation and TNF‐alpha production. Treatment with Spleen Tyrosine Kinase antagonist (Fostamatinib) reduces the expression of mast cell‐associated gene transcripts, associated biochemical pathways and the number of tryptase/chymase positive mast cells in lesional hidradenitis suppurativa tissue. This data indicates that although mast cells are not the most abundant cell type in Hidradenitis Suppurativa tissue, the dysregulation of mast cells is paralleled with B cell lasma cell inflammation, inflammatory epithelialized tunnels and epithelial budding. This provides an explanation as to the mixed inflammatory activation signature seen in HS, the correlation with dysregulated wound healing and potential pathways involved in the development of epithelialized tunnels.
Publisher: Springer Science and Business Media LLC
Date: 28-01-2021
DOI: 10.1186/S13047-021-00448-W
Abstract: To utilise the 2019 International Working Group on the Diabetic Foot (IWGDF) - diabetic foot infection (DFI) guidelines as an audit tool for clinical practice in patients with diabetes attending a High-Risk Foot Service. Data from 93 consecutive patients were collected over a 19-month period in patients attending a High-Risk Foot Service. The diagnosis and management of each patient in the s le were compared against the 2019 IWGDF DFI guidelines, grouped into four categories: Diagnosis, Microbiology, Treatment of soft tissue infection, and Surgical treatment and osteomyelitis. Deficits in performance were recorded using the recommendations as a benchmark standard. There were 109 DFI events. Nineteen (63%) of the recommendations were met, 7 (24%) were partially met, and four (13%) recommendations were not met. Fourteen of the s le had no documented requests for full blood counts. Tissue was obtained for culture in 32 (29%) of the s le. No percutaneous bone biopsies were performed. Only 13 (28%) patients had intraoperative bone specimens sent for culture and sensitivities, with no bone specimens sent for histopathology. Modification of antibiotic therapy following available culture results was low, occurring in 12 out of 63 possible occasions (19%). The duration of antibiotic regimens in PEDIS 2 infections and osteomyelitis was greater than that recommended. Utilising the IWGDF DFI guidelines to benchmark clinical practice is a useful tool to identify gaps in clinical performance or service delivery and may help to improve patient care.
Location: United Kingdom of Great Britain and Northern Ireland
Location: United Kingdom of Great Britain and Northern Ireland
No related grants have been discovered for matthew malone.