Publications by authors named "Edward Giles"

Background: Adolescents with inflammatory bowel disease (IBD) transitioning to adult care is often deemed a challenging period for patients, their carers, and practitioners. The use of structured transition programs is increasingly incorporated into standards of care, yet the optimal format remains unknown. The aim of this study is to carry out a systematic review of structured transition programs and their components to assess the impact on disease-specific and transition-related outcomes.

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Background: The incidence of pediatric inflammatory bowel disease (IBD) is rising, and there is an increasing need to support adolescents when they transition to adult care. Evidence supports the use of a structured transition process but there is great variation across Australasia. The study aim was to develop evidence and expert opinion-based consensus statements to guide transitional care services in IBD.

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Background And Aim: Children and adolescents account for approximately 14% of inflammatory bowel disease (IBD) diagnoses. At an appropriate age and level of development adolescents with IBD have their care transferred from the pediatric to adult clinical team during a process termed "transition". The study aim was to survey pediatric gastroenterologists throughout Australasia to identify commonality in the transition process to contribute to standardized guideline development.

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Background: Crohn's Colitis Care is an adult inflammatory bowel disease eHealth system. Crohn's Colitis Care required additional pediatric functionality to enable life-long records and mitigate transition inadequacies.

Aim: This study describes and evaluates a consensus method developed to ensure consumer needs were met.

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Background & Aims: Type I interferon (T1IFN) signalling is crucial for maintaining intestinal homeostasis. We previously found that the novel T1IFN, IFNε, is highly expressed by epithelial cells of the female reproductive tract, where it protects against pathogens. Its function has not been studied in the intestine.

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Many gut microorganisms critical to human health rely on nutrients produced by each other for survival; however, these cross-feeding interactions are still challenging to quantify and remain poorly characterized. Here, we introduce a Metabolite Exchange Score (MES) to quantify those interactions. Using metabolic models of prokaryotic metagenome-assembled genomes from over 1600 individuals, MES allows us to identify and rank metabolic interactions that are significantly affected by a loss of cross-feeding partners in 10 out of 11 diseases.

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Abnormal immune responses to the resident gut microbiome can drive inflammatory bowel disease (IBD). Here, we combine high-resolution, culture-based shotgun metagenomic sequencing and analysis with matched host transcriptomics across three intestinal sites (terminal ileum, cecum, rectum) from pediatric IBD (PIBD) patients (n = 58) and matched controls (n = 42) to investigate this relationship. Combining our site-specific approach with bacterial culturing, we establish a cohort-specific bacterial culture collection, comprising 6,620 isolates (170 distinct species, 32 putative novel), cultured from 286 mucosal biopsies.

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Aim: Deamidated gliadin peptide-IgG (DGP-IgG) antibody serology testing is widely utilised in screening for coeliac disease in Australia; however, it is used sparingly in Europe. The aim of this study was to assess the diagnostic value of a positive DGP-IgG in the setting of a negative tissue transglutaminase-IgA (tTG-IgA) for gastrointestinal pathology among paediatric patients.

Methods: We conducted a retrospective cohort study of all children with an elevated DGP-IgG in the setting of a negative tTG-IgA who underwent gastroscopy over a 48-month period (January 2015-December 2018) at a tertiary paediatric centre.

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Background: From consumption of fermented foods and probiotics to emerging applications of faecal microbiota transplantation, the health benefit of manipulating the human microbiota has been exploited for millennia. Despite this history, recent technological advances are unlocking the capacity for targeted microbial manipulation as a novel therapeutic.

Aim: This review summarises the current developments in microbiome-based medicines and provides insight into the next steps required for therapeutic development.

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Aim: The transition from paediatric to adult care for patients with inflammatory bowel disease (IBD) is associated with an increased risk of treatment non-adherence, hospitalizations and emergency department (ED) use. We established a new young adult IBD clinic (YAC) in Melbourne to capture this at-risk population. We aimed to assess patient satisfaction as well as clinical outcomes.

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Aim: Magnet ingestion has become more frequent in children as magnetic toys and jewellery have been popularised, with the potential to cause significant morbidity. Our aim was to describe our experience at a tertiary paediatric surgical centre.

Methods: Retrospective review of patients admitted with multiple magnet ingestion (January 2011-December 2020).

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Repeated infections drive the development of clinical immunity to malaria in humans; however, the immunological mechanisms that underpin this response are only partially understood. We investigated the impact of repeated infections on human γδ T cells in the context of natural infection in Malian children and adults, as well as serial controlled human malaria infection (CHMI) of U.S.

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Unlike conventional αβ T cells, γδ T cells typically recognize nonpeptide ligands independently of major histocompatibility complex (MHC) restriction. Accordingly, the γδ T cell receptor (TCR) can potentially recognize a wide array of ligands; however, few ligands have been described to date. While there is a growing appreciation of the molecular bases underpinning variable (V)δ1 and Vδ2 γδ TCR-mediated ligand recognition, the mode of Vδ3 TCR ligand engagement is unknown.

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Big data has become a central part of medical research, as well as modern life generally. "Omics" technologies include genomics, proteomics, microbiomics and increasingly other omics. These have been driven by rapid advances in laboratory techniques and equipment.

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Gastrostomy tube (GT) complications are often managed in the Emergency Department (ED). We aimed to characterize and compare the pattern of ED presentations of GT complications in adults and children. A retrospective chart review of patients with GT complications presenting to 3 Australian EDs in 2 years was undertaken.

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Microbiome in health and disease.

J Paediatr Child Health

November 2020

There has been an exponential rise in research into the microbiota of the human gastrointestinal tract, particularly of the genomic content (the microbiome). The vast number of micro-organisms residing in our gut has an integral role in essential processes, including growth and development. Probiotics, live micro-organisms with putative benefits on health have become ubiquitous as treatments for many conditions, despite often limited robust clinical trial data.

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Background And Aim: Pediatric Crohn's disease (CD) has been shown to have a high recurrence rate following surgical resection. Risk factors for postoperative CD recurrence in children are not well known. The aim of this study was to identify factors influencing postoperative recurrence in pediatric CD.

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T cell receptors (TCRs) recognize antigens presented by major histocompatibility complex (MHC) and MHC class I-like molecules. We describe a diverse population of human γδ T cells isolated from peripheral blood and tissues that exhibit autoreactivity to the monomorphic MHC-related protein 1 (MR1). The crystal structure of a γδTCR-MR1-antigen complex starkly contrasts with all other TCR-MHC and TCR-MHC-I-like complex structures.

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Objectives: Paediatric endoscopy is an important diagnostic tool; however, there is little published data to guide clinicians in selecting patients for endoscopy. This study aimed to evaluate a single centre's experience of newly presenting children focusing on presenting symptoms, investigations, and diagnostic yield.

Methods: Clinical factors and endoscopic plus histological findings over a 6-month period were assessed.

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The human gut is in constant complex interaction with the external environment. Although much is understood about the composition and function of the microbiota, much remains to be learnt about the mechanisms by which these organisms interact with the immune system in health and disease. Type 1 interferon (T1IFN), a ubiquitous and pleiotropic family of cytokines, is a critical mediator of the response to viral, bacterial, and other antigens sampled in the intestine.

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Tumor-derived and bacterial phosphoantigens are recognized by unconventional lymphocytes that express a Vγ9Vδ2 T cell receptor (Vδ2 T cells) and mediate host protection against microbial infections and malignancies. Vδ2 T cells are absent in rodents but readily populate the human intestine, where their function is largely unknown. Here, we assessed Vδ2 T cell phenotype and function by flow cytometry in blood and intestinal tissue from Crohn's disease patients (CD patients) and healthy controls.

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Objectives: To study innate immune pathways in patients undergoing hepatopancreaticobiliary surgery to understand mechanisms leading to enhanced inflammatory responses and identifying biomarkers of adverse clinical consequences.

Background: Patients undergoing major abdominal surgery are at risk of life-threatening systemic inflammatory response syndrome (SIRS) and sepsis. Early identification of at-risk patients would allow tailored postoperative care and improve survival.

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Background & Aims: Reduced generation of all-trans retinoic acid (RA) by CD103(+) intestinal dendritic cells (DCs) is linked to intestinal inflammation in mice. However, the role of RA in intestinal inflammation in humans is unclear. We investigated which antigen-presenting cells (APCs) produce RA in the human intestine and whether generation of RA is reduced in patients with Crohn's disease (CD).

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